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We synthesized three efficient blue emitting Eu(ii) complexes with narrow full width at half maximums and fabricated the first deep blue OLEDs based on an Eu(ii) complex.

Background: Triglyceride glucose (TyG) index is a good surrogate biomarker to evaluate insulin resistance (IR). The study aimed to investigate whether the TyG index is related to the severity of diabetic foot ulcers (DFUs) in patients with type2 diabetes mellitus (T2DM). Methods: A total of 1059 T2DM patients were enrolled in this observational, retrospective, single-center study. TyG index was calculated as ln[fasting triglycerides (mg/dl)×fasting glucose (mg/ dl)/2]. The severity of DFUs was classified into mild-to-moderate DFUs (Wagner grade score Results: Compared with the reference lowest TyG tertile (T1), the highest tertile (T3) was associated with 0.377-fold increased risk of prevalence of severe DFUs (odds ratio [OR] 1.377, 95% confidence interval [CI] 1.017-1.865) (P =0.039). After adjusting for potential confounders, the multivariable-adjusted OR and 95% CI were 1.506 (1.079-2.103) (P =0.016) in patients with highest tertile. Moreover, subgroup analyses indicated that the association was stronger among men, patients with age ≥ 65 years, duration of diabetes more than 10 years, or without PAD. Conclusions: Elevated TyG index is independently associated with severity of DFUs even after adjusting conventional confounders.

Background & Aims: Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death. Methods: Risk predictions for CRC and competing causes of death from a large community-based cohort were used to stratify individuals into risk groups. A microsimulation model was used to optimize colonoscopy screening for each risk group by varying the start age (40–60 years), end age (70–85 years), and screening interval (5–15 years). The outcomes included personalized screening ages and intervals and cost-effectiveness compared with uniform colonoscopy screening (ages 45–75, every 10 years). Key assumptions were varied in sensitivity analyses. Results: Risk-stratified screening resulted in substantially different screening recommendations, ranging from a one-time colonoscopy at age 60 for low-risk individuals to a colonoscopy every 5 years from ages 40 to 85 for high-risk individuals. Nevertheless, on a population level, risk-stratified screening would increase net quality-adjusted life years gained (QALYG) by only 0.7% at equal costs to uniform screening or reduce average costs by 1.2% for equal QALYG. The benefit of risk-stratified screening improved when it was assumed to increase participation or costs less per genetic test. Conclusions: Personalized screening for CRC, accounting for competing causes of death risk, could result in highly tailored individual screening programs. However, average improvements across the population in QALYG and cost-effectiveness compared with uniform screening are small.

Type 1 diabetes mellitus (T1DM)-induced cognitive dysfunction is common, but its underlying mechanisms are still poorly understood. In this study, we found that knockout of conventional protein kinase C (cPKC)γ significantly increased the phosphorylation of Tau at Ser214 and neurofibrillary tangles, but did not affect the activities of GSK-3β and PP2A in the hippocampal neurons of T1DM mice. cPKCγ deficiency significantly decreased the level of autophagy in the hippocampal neurons of T1DM mice. Activation of autophagy greatly alleviated the cognitive impairment induced by cPKCγ deficiency in T1DM mice. Moreover, cPKCγ deficiency reduced the AMPK phosphorylation levels and increased the phosphorylation levels of mTOR in vivo and in vitro. The high glucose-induced Tau phosphorylation at Ser214 was further increased by the autophagy inhibitor and was significantly decreased by an mTOR inhibitor. In conclusion, these results indicated that cPKCγ promotes autophagy through the AMPK/mTOR signaling pathway, thus reducing the level of phosphorylated Tau at Ser214 and neurofibrillary tangles.

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expanded PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS were 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1,681-3,651 cases and 8,696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They were significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values

Research shows that socioeconomic status (SES) factors are closely associated with children’s higher-order cognitive development such as executive function (EF) skills in early years (e.g., Vandenbroucke et al., 2016; Vrantisidis et al., 2020). The general pattern of the association is that advantageous socioeconomic background contributes to better child outcomes (e.g., Noble et al., 2007). However, inconsistent findings were yielded in terms of the unique association between each socioeconomic status factor such as mother’s education, father’s education, income and children’s EF, i.e., some factors appear to have stronger links with EF than others (e.g., Last et al., 2018). Also, it is unclear how SES factors are linked to different components of children’s EF. Although it is argued that early childhood EF should be conceptualized as a unidimensional construct, it is possible that in the preschooler sample, the diversity of EF is emerging and the subcomponents of EF would be associated with SES factors differently. Futhermore, most previous studies in this direction were conducted in the West. Less empirical attention has been paid to the context where there are huge gaps in the regional economic development such as mianland China. Apart from family SES factors, regional SES may contribute to children’s cognitive development because high regional SES indicates richer educational resources and better overall living environements. However, this impact has rarely been examined before. Last but not least, few studies have examined how SES factors and age interact to impact preschoolers’ EF. It is possible that the impact of SES would exceed age on EF development, which would highlight the considerable influence of SES on child development. The present study utilises the data collected for the PhD study of Jiayin Zheng (link here) and some of the data will be shared with several studies linked to the Ready-or-Not project. The Ready-or-Not project is a large-scale, cross-cultural study led by Prof Claire Hughes at the Centre for Family Research, University of Cambridge. The present study aims to investigate the associations between different socioeconomic status (SES) factors and preschoolers’ executive function (EF) skills in mainland China, and the interaction effect between age and SES in impacting executive function skills. The data were collected in different geographical regions in mainland China and the noticeable gaps in the regional economic development of those areas were detected. The present study aims to address the following research questions: 1. How are family SES factors and regional SES (indicated by the regional economic development of the areas where participants were recruited) associated with Chinese preschoolers’ executive function skills? 1.1 How are different family SES indicators (mother’s education, father’s education, family income, subjective social ladder) associated with the latent EF of Chinese preschoolers? 1.2 How are family SES indicators associated with different components (working memory, inhibition, and behavioural self-regulation) of Chinese preschoolers’ EF? 1.3 How is regional SES associated with the latent EF of children? 1.4 How is regional SES associated with different components (working memory, inhibition, and behavioural self-regulation) of Chinese preschoolers’ EF? 2. How do age and school year interact with family and regional SES factors in the associations with Chinese preschoolers’ EF?

The COVID-19 pandemic regulations have resulted in the limited investigation of potential between-country contrasts in children’s development, as schools in many countries faced ongoing challenges that limit the feasibility of research visits. Consequently, child assessments have become virtual. Nonetheless, this shift to remote assessments has widened the contexts for cross-cultural comparisons. Against this background, the current study presents a comparison of an online, home-based assessment of executive function (EF) in Hong Kong, mainland China, and the United Kingdom in a sample population of 5 to 6-year old children. Existing cross-cultural work on EF has found that children in East Asia appear to outperform their Western counterparts on executive function (EF) tasks; a recent systematic review indicates this advantage persists from preschool to adolescence (Schirmbeck et al., 2020). However, while EF are traditionally viewed as stable traits, there is growing evidence that EF task performance shows short-term fluctuations, with studies highlighting multiple proximal influences, which include assessment contexts (Doebel, 2020). This, in light of the fact that differences in school climate across cultures may influence the extent to which children engage with the task, motivates our aim to examine group differences in EF across Hong Kong, mainland China, and the United Kingdom which is based on an online, home-based assessment of EF.

Summary of the Research: Kindergarten is an essential stage for children’s development of executive function (EF) skills, which are strong predictors of individual well-being and accomplishment in a long run (e.g., Diamond et al., 2013; Zelazo et al., 2003). Under the Bioecological System of Human Development framework, children’s higher-order cognitive development is reciprocally associated with a series of contextual factors including proximal process factors (e.g., interpersonal relationships) and distal process factors (e.g., physical environment). In family settings, socioeconomic status (SES) factors such as parental education and family income are associated with child development since higher socioeconomic status indicates more appropriate parenting practices, richer nutritional and educational resources, and a more cognitively stimulating family environment. In school settings, multiple factors can influence young children’s ways to explore, learn, interact, and accordingly, develop, which include proximal process factors that are mostly person-centred variables and distal process factors that are more related to the physical environment. For kindergarten children, the family setting and school setting work together to influence their cognitive development. Therefore, it should be informative to investigate how family process factors and school process factors interact to shape kindergarten children’s higher-order cognitive abilities such as executive function. The present project has several research aims: 1) investigate how socioeconomic status factors contribute to kindergarten children’s executive function skills in mainland China; 2) investigate how a series of school process factors, including the characteristics of the dyadic teacher-child relationships, teachers’ professional wellbeing, classroom environment, and school type are associated with kindergarten children’s executive function skills in mainland China; 3) investigate how socioeconomic status factors interact with school process factors in the associations with kindergarten children’s executive function skills in mainland China. The rationale of the present project is multi-fold: 1) the majority of this line of research was carried out in the West, much less empirical attention has been paid to a context like mainland China which is characteristic of huge regional economic development variations and a Confucian sociocultural context; 2) the previous studies do not agree on how each socioeconomic status factor contributes to child development specifically; 3) the previous studies yielded inconsistent findings regarding how some of the school process factors such as the quality of teacher-child relationships are associated with kindergarten children’s executive function and few studies have taken into account different school process factors simultaneously; 4) few previous studies have particularly investigated how family process factors (socioeconomic status in the current context) interact with school process factors to impact children’s executive function skills. The present study is situated in mainland China where a large demographically diverse sample has been recruited and contributes particularly to the mainland China site of an ongoing project titled Ready-or-Not (readyornotstudy.com) led by Professor Claire Hughes at the Centre of Family Research, University of Cambridge. We collected socioeconomic status data and other related demographic information from our kindergarten children sample. Children’s executive function skills were evaluated with behavioural tasks either virtually or onsite. We also collected data on a series of school process factors via teacher questionnaires. In addition, I integrated the commonly-used teacher survey and a child interview translated from English by myself to examine teachers’ and children’s perceptions of teacher-child relationships separately. This multi-informant approach can depict the patterns of teacher-child relationships in mainland China comprehensively. The dataset will be analysed through multiple types of analyses, mainly including confirmatory factor analysis, structural equation modelling, and some exploratory methods if applicable. Advanced statistical methods such as full information maximum likelihood estimation to deal with the missing data issue will be applied to the current dataset. The present study aims to address the following research questions and test the appropriateness of data analysis approaches. Research Questions: 1) How do kindergarten children’s executive function skills develop with age in mainland China? 2) How are family SES factors associated with kindergarten children’s EF skills in mainland China? 3) How are school process factors including teacher-child relationship, teachers’ professional well-being, classroom environment, and school type associated with kindergarten children’s EF skills in mainland China? 4) Would the school process factors moderate the associations between SES and kindergarten children’s EF skills in mainland China (i.e., would school process factors interact with SES factors to impact kindergarten children’s EF skills in mainland China)?

The present study utilises the data collected for the PhD study of Jiayin Zheng and some of the data will be shared with several studies linked to the Ready-or-Not project. The Ready-or-Not project is a large-scale, cross-cultural study led by Prof Claire Hughes at the Centre for Family Research, University of Cambridge. The present study is linked to another pre-registered study titled “Age, socioeconomic status, and children’s executive function development: The empirical evidence from a Chinese sample” (I will refer to it as Study 1 in the current pre-registration report) and the current research questions are associated with the inquiries in Study 1. The present study aims to draw on the associations between socioeconomic status factors and Chinese preschoolers’ cognitive abilities which are the focus of Study 1, and investigate how a series of school process factors contribute to these associations. The school process factors include not only the proximal factors such as teacher-child relationships and teachers’ professional well-being (indexed by teacher professional burnout) but the comparatively more distal factors such as classroom environment (indexed by classroom chaos) and school type. The present study is interested in how school factors and family factors can interact to impact early childhood development. The present study aims to address the following research questions: 1. How are the proximal and distal school process factors including teacher-child relationship, teachers’ professional well-being, classroom environment, and school type associated with Chinese preschoolers’ executive function? 2. Would the school process factors moderate the associations between socioeconomic status and Chinese preschoolers’ executive function? 2.1 Would the proximal school factors, i.e., teacher-child relationship and teachers’ professional well-being moderate the associations between socioeconomic status and preschoolers’ executive function? 2.2 Would the distal school factors, i.e., classroom environment and school type moderate the associations between socioeconomic status and preschoolers’ executive function?

A wealth of previous studies have tested a strong association between family socioeconomic status (SES) and the development of children’s executive function (EF) skills. A significant proportion of the studies paid empirical attention to the factors in the family context/process that mediate this association. This pre-registered study is a review of the empirical studies written between 2000 and 2023 which investigated the mediators of the association between family SES and children’s EF. The purposes of this review are four-folded: (1) to identify the factors in the family process which mediate the long-founded link between SES and EF; (2) to explore the nuanced impacts of these mediators; (3) to chart the problems of the existing mediation studies; (4) to inform the future EF studies.

Background:Polygenic risk scores (PRS) which summarize individuals’ genetic risk profile may enhance targeted colorectal cancer screening. A critical step towards clinical implementation is rigorous external validations in large community-based cohorts. This study externally validated a PRS-enhanced colorectal cancer risk model comprising 140 known colorectal cancer loci to provide a comprehensive assessment on prediction performance.Methods:The model was developed using 20,338 individuals and externally validated in a community-based cohort (n = 85,221). We validated predicted 5-year absolute colorectal cancer risk, including calibration using expected-to-observed case ratios (E/O) and calibration plots, and discriminatory accuracy using time-dependent AUC. The PRS-related improvement in AUC, sensitivity and specificity were assessed in individuals of age 45 to 74 years (screening-eligible age group) and 40 to 49 years with no endoscopy history (younger-age group).Results:In European-ancestral individuals, the predicted 5-year risk calibrated well [E/O = 1.01; 95% confidence interval (CI), 0.91–1.13] and had high discriminatory accuracy (AUC = 0.73; 95% CI, 0.71–0.76). Adding the PRS to a model with age, sex, family and endoscopy history improved the 5-year AUC by 0.06 (P < 0.001) and 0.14 (P = 0.05) in the screening-eligible age and younger-age groups, respectively. Using a risk-threshold of 5-year SEER colorectal cancer incidence rate at age 50 years, adding the PRS had a similar sensitivity but improved the specificity by 11% (P < 0.001) in the screening-eligible age group. In the younger-age group it improved the sensitivity by 27% (P = 0.04) with similar specificity.Conclusions:The proposed PRS-enhanced model provides a well-calibrated 5-year colorectal cancer risk prediction and improves discriminatory accuracy in the external cohort.Impact:The proposed model has potential utility in risk-stratified colorectal cancer prevention.

The Chinese Medical Doctor Association has initiated metabolic management center (MMC) program for 6 years since 2016 nationwide. It is worth investigating the level of control metabolic outcomes in patients with type2 diabetes (T2DM) after MMC model in Yan'an, northwest China. Patients with T2DM was admitted to MMC in Yan'an University Affiliated Hospital from November 2018 to July 2021. They were asked to revisit hospital every 3 months. Blood glucose, blood pressure and blood lipids at baseline were compared to its counterparts after 1 year MMC management. Glycosylated hemoglobin and low density lipoprotein cholesterol (LDL-C) level in T2DM patients after 1 year management were lower than their baseline level (glycosylated hemoglobin 7.74 ± 1.94% vs 8.63 ± 2.26%, P .001; LDL-C 1.81 ± 0.73mmol/L vs 2.18 ± 1.49mmol/L, P .001). Mean HOMA-β increased after management (65.89 ± 90.81% vs 128.38 ± 293.93%, P .05). After 1 year of management, patients in high school or above group achieved higher control rate of body mass index than those in middle school or below group (71.82% vs 28.18%, P = .043). high density lipoprotein cholesterol control rate was higher in high income group (42.86% vs 34.97%, 16.28%, P = .012), while LDL-C control rate was higher in low-income group (97.67% vs 78.57%, 84.51%, P = .018). fasting plasma glucose control rate in new diagnosis group was higher than that of the middle and long course groups (71.43% vs 52.38%, 42.44%, P = .002). The comprehensive control rate increased from 9.83% at baseline to 26.15% after 1 year MMC management. The metabolic outcomes and their control rate in T2DM patients were improved after 1 year MMC management. It indicated that patients may achieve more benefits with MMC management.

Accurate risk assessment is critical in clinical decision-making. It entails the projected risk based on a risk prediction model agreeing with the observed risk in the target cohort. However, the model often over- or under-estimates the risk. Building a new model for the target cohort would be ideal but costly. It is therefore of great interest to recalibrate an existing model for the target cohort. Existing methods have been proposed to recalibrate the model by leveraging the disease incidence rates from the target cohort. However, they assume the same covariate distribution across cohorts and when the assumption is violated, the recalibrated model can be substantially biased. Further, recalibration is also complicated by the two-phase sampling design that is commonly used for developing risk prediction models. In this paper, we develop a weighted estimating-equation approach accounting for the two-phase design and combine it with a weighted empirical likelihood that leverages the summary information on both disease incidence rates and covariates from the target cohort. We provide a resampling-based inference procedure. Our extensive simulation results show that using the summary information from the target population, the proposed recalibration method yields nearly unbiased risk estimates under a wide range of scenarios. An application to a colorectal cancer study also illustrates that the proposed method yields a well-calibrated model in the target cohort.

Ischemic stroke, which accounts for nearly 80% of all strokes, leads to white matter injury and neurobehavioral dysfunction, but relevant therapies to inhibit demyelination or promote remyelination after white matter injury are still unavailable. In this study, the middle cerebral artery occlusion/reperfusion (MCAO/R) in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro were used to establish the ischemic models. We found that Eph receptor A4 (EphA4) had no effect on the apoptosis of oligodendrocytes using TUNEL staining. In contrast, EphA4 promoted proliferation of oligodendrocyte precursor cells (OPCs), but reduced the numbers of mature oligodendrocytes and the levels of myelin-associated proteins (MAG, MOG, and MBP) in the process of remyelination in ischemic models in vivo and in vitro as determined using PDGFRα-EphA4-shRNA and LV-EphA4 treatments. Notably, conditional knockout of EphA4 in OPCs (EphA4

The development of fibrosis in nonalcoholic fatty liver disease (NAFLD) is influenced by genetics, sex, and menopausal status, but whether genetic susceptibility to fibrosis is influenced by sex and reproductive status is unclear. Our aim was to identify metabolism‐related single nucleotide polymorphisms (SNPs), whose effect on NAFLD fibrosis is significantly modified by sex and menopausal status. We performed a cross‐sectional, proof‐of‐concept study of 616 patients in the Duke NAFLD Clinical Database and Biorepository. The primary outcome was nonalcoholic steatohepatitis–Clinical Research Network (NASH–CRN) fibrosis stage. Menopause status was self‐reported; age 51 years was used as a surrogate for menopause in patients with missing menopause data. The Metabochip was used to obtain 98,359 SNP genotypes in known metabolic pathway genes for each patient. We used additive genetic models to characterize sex and menopause‐specific effects of SNP genotypes on NAFLD fibrosis stage. In the main effects analysis, none of the SNPs were associated with fibrosis at P

Background Multiple missense mutations in DCTN1 gene have been linked to Perry syndrome (PS), a rare neurodegenerative disease clinically manifested with parkinsonism, mental depression, and central hypoventilation. DCTN1 encodes dynactin p150Glued protein, the largest subunit of dynactin motor protein complex. The PS-related mutations are concentrated at the amino-terminal cytoskeleton-associated protein and glycine-rich (CAP-Gly) domain, which mediates the association of p150Glued with microtubules. Degeneration of nigrostriatal dopaminergic neurons (DANs) was reported in the postmortem brains of PS patients. However, how the dysfunction of p150Glued affects the function and survival of DANs remains to be determined. Methods Using Cre-LoxP genetic manipulation, we crossbred Dctn1 knock-in (KI) mice with Th-Cre mice to generate Dctn1 conditional knockout (cKO) mice for genetic deletion of p150Glued protein in catecholaminergic neurons, including midbrain DANs. We also crossbred the Dctn1 KI mice with Cre/Esr1 mice to generate pups for primary culture of Dctn1 cKO cells. We then performed series of biochemical, neurochemical, cell biology, behavioral and neuropathological studies on the Dctn1 cKO mice or cells to investigate the underlying pathological mechanisms. Results While both Dctn1 control and cKO mice showed deterioration of rotarod motor performance during aging, the process was greatly accelerated in the cKO mice. The loss of p150Glued led to progressive degeneration of axon fibers and then cell bodies of midbrain DANs. In addition to neurodegeneration, abnormal accumulation of a-synuclein was found in the soma and nuclei of DANs in aged cKO mice. Moreover, before the onset of axon atrophy, both dopamine transporter (DAT) levels and activity were reduced in the DAN axon terminals of cKO mice. Further studies revealed unusually large spheric structures in the axons and dendrites of cKO DANs. Interestingly, endoplasmic reticulum (ER) stress protein BiP was abnormally accumulated in the dendritic spheroids and soma of cKO DANs. Accordingly, the Dctn1 cKO cells displayed impaired ER export and increased unfolded protein response (UPR). As a result, the Dctn1 cKO DANs were more vulnerable to ER stress-induced cell death. Conclusion Our findings demonstrate that p150Glued is important in maintaining the function and survival of midbrain DANs during aging. We particularly highlighted the role of p150Glued in stabilizing the molecular machinery for ER export, suggesting that the PS-related p150Glued dysfunction may render the midbrain DANs more susceptible to UPR and ER stress.

Background: Fusobacterium nucleatum (F. nucleatum) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis. Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer–specific survival. We conducted deep sequencing of nusA, nusG, and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer–specific mortality, and somatic mutations. Results: F. nucleatum, which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis. Presence of F. nucleatum was associated with higher colorectal cancer–specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07–3.45; P = 0.029). Only F. nucleatum subspecies animalis, the main subspecies detected (65.8%), was associated with colorectal cancer–specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations. Conclusions: F. nucleatum, and particularly subspecies animalis, was associated with a higher colorectal cancer–specific mortality and specific somatic mutated genes. Impact: Our findings identify the F. nucleatum subspecies animalis as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance.

For review and approval of drug products, a 95% confidence interval approach for evaluation of new drugs is commonly used, while a 90% confidence interval approach is considered for assessment of generic drugs and biosimilar products. In the past decade, FDA has been challenged for adopting different standards (i.e., 5% type-I error rate for new drugs and 10% type-I error rate for generics/biosimilars) for regulatory submissions of drugs and biologics. This note intends to clarify the confusion by pointing out the fundamental differences between (i) the concepts of point hypotheses and interval hypotheses, and (ii) the concepts of interval hypotheses testing and confidence interval approach. In general, the method of interval hypotheses testing is not equivalent to the confidence interval approach although they may be operationally equivalent under certain conditions.

In analytical similarity assessment of a biosimilar product, key quality attributes of the test and reference products need to be shown statistically similar. When there were multiple references, similarity among the reference products is also required. We proposed a simultaneous confidence approach based on the fiducial inference theory as an alternative to the pairwise comparison method. Three versions with two types of simultaneous confidence intervals for each version were proposed based on different assumptions of the population variance. We conducted extensive simulation studies to compare the performance of our proposed method and the pairwise method, and provided examples to illustrate the concern of using pairwise method.

Supplemental digital content is available in the text. Colorectal cancer is a leading cause of cancer death within the United States. Identification of previously identified colon cancer and large colon polyps at the time of surgery and repeat endoscopy is crucial to allow for accurate assessment and resection. This study reports actual and reported colonic tattooing practices as well as their impact on surgical and endoscopic evaluation at a tertiary medical center., Objectives Accurate localization of a colonic lesion is crucial to successful resection. Although colonic tattooing is a widely accepted technique to mark lesions for future identification surgery or repeat colonoscopy, no consensus guidelines exist. The objective of this study was to determine whether the current tattooing practice at a tertiary medical center differs from recommendations in the literature and self-reported provider practice. Methods The study consisted of an observational retrospective chart review of patients who received colonic tattoos, as well as a provider survey of reported tattooing practices at a tertiary academic medical center. A total of 747 patients older than 18 years of age who underwent colonoscopy with tattoo were included. Forty-four gastroenterologists performing endoscopy were surveyed on tattooing techniques. Results In the majority of cases, neither the number of tattoos, location of the tattoo nor the distance from the lesion was specified within the report. Following the index procedure, a tattoo was detected in 75% of surgical resections and 73% of endoscopies. At the time of surgery, however, the tattoo and/or the lesion was detected approximately 94% of the time. Twenty-five endoscopists (56.8%) completed the survey. Differences were seen the between the chart review and reported practice. Most providers report placing ≥2 marks (87.2%); however, chart review revealed that only 56.2 % were tattooed with ≥2 marks. Conclusions Variation exists between the reported tattooing practice and actual practice. Despite this, most tattoos are identified at the time of surgery or repeat endoscopy. Further research is needed to determine whether a standardized approach to tattooing and reporting could improve localization at repeat endoscopy.

Online drug reviews are increasingly available for drug users and medical professionals to collect first-hand patient experiences on drugs. The challenge is, however, to provide them with quick and accurate access to the helpful reviews mingled with an extensive amount of less helpful ones. One way to facilitate information access to helpful reviews is helpfulness prediction. By analyzing the features extracted from reviews, the helpfulness of a review can be objectively evaluated. However, the user sentiments and opinions contained in drug reviews, compared with the ones in other product reviews, are exceedingly complicated to be analyzed due to the differences in users’ physical and mental conditions. Hence, in this paper, we proposed a mechanism that combines medical-domain features (medical word sentiments, proportion of medical words in reviews) into a helpfulness prediction model. Besides, we noticed that the number of useful counts received by a review cannot sufficiently validate its helpfulness since useful counts are significantly influenced by the length of duration it was exposed to readers and total read times. Hence, to address this selection bias issue, we proposed four methods and examined their performances. Our findings show 1) the added medical features significantly elevated the accuracy of helpfulness prediction results. 2) readability, proportion of medical words and proportion of nouns are the three features showing the highest importance in helpfulness prediction. 3) the method to select sample based on useful counts achieves the best performance possibly because the sample data generated by this method contains more unbiased feature characteristics of review helpfulness.

Predicting risks of chronic diseases has become increasingly important in clinical practice. When a prediction model is developed in a given source cohort, there is often a great interest to apply the model to other cohorts. However, due to potential discrepancy in baseline disease incidences between different cohorts and shifts in patient composition, the risk predicted by the original model often under- or over-estimates the risk in the new cohort. The remedy of such a poorly calibrated prediction is needed for proper medical decision-making. In this article, we assume the relative risks of predictors are the same between the two cohorts, and propose a novel weighted estimating equation approach to re-calibrating the projected risk for the targeted population through updating the baseline risk. The recalibration leverages the knowledge about the overall survival probabilities for the disease of interest and competing events, and the summary information of risk factors from the targeted population. The proposed re-calibrated risk estimators gain efficiency if the risk factor distributions are the same for both the source and target cohorts, and are robust with little bias if they differ. We establish the consistency and asymptotic normality of the proposed estimators. Extensive simulation studies demonstrate that the proposed estimators perform very well in terms of robustness and efficiency in finite samples. A real data application to colorectal cancer risk prediction also illustrates that the proposed method can be used in practice for model recalibration.

Background: This study reports a case series of transforaminal endoscopic decompression for symptomatic intraspinal gout treatment.Methods: In the past three years, the technique of transforaminal endoscopic decompression has been applied for the treatment of symptomatic intraspinal gout, and detailed information on 8 consecutive patients pre- and postoperatively has been recorded for further research.Results: Here, we present a consecutive series of 8 patients who underwent transforaminal endoscopic decompression for the treatment of intraspinal gout in our hospital from 2016 to 2019. These 8 patients all suffered from low back and leg pain and varying degrees of neurologic deficits. After at least 1 year of follow-up, the modified Japanese Orthopedic Association (m-JOA) score and the MOS 36-Item Short-from Health Survey (SF-36) score were significantly improved compared with before surgery. All patients were satisfied with the results of the operation, and no complications were experienced.Conclusion: Transforaminal endoscopic decompression may be a unique approach to treat intraspinal gout because of its small trauma, rapid recovery, and reliable effect.