Supertough MXene/Sodium Alginate Composite Fiber Felts Integrated with Outstanding Electromagnetic Interference Shielding and Heating Properties.

The development of multifunctional MXene-based fabrics for smart textiles and portable devices has garnered significant attention. However, very limited studies have focused on their structure design and associated mechanical properties. Here, the supertough MXene fiber felts composed of MXene/sodium alginate (SA) fibers were fabricated. The fracture strength and bending stiffness of felts can be up to 97.8 MPa and 1.04 N mm2, respectively. Besides, the fracture toughness of felts was evaluated using the classic Griffith theory, yielding to a critical stress intensity factor of 1.79 MPam. In addition, this kind of felt presents outstanding electrothermal conversion performance (up to 119 °C at a voltage of 2.5 V), high cryogenic and high-temperature tolerance of photothermal conversion performance (-196 to 160 °C), and excellent electromagnetic interference (EMI) shielding effectiveness (54.4 dB in the X-band). This work provides new structural design concepts for high-performance MXene-based textiles, broadening their future applications.

Oxytocin is not associated with postpartum hemorrhage in labor augmentation in a retrospective cohort study in the United States.

BACKGROUND: Previous studies reported conflicting results on the relationship between oxytocin use for labor augmentation and the risk of postpartum hemorrhage, probably because it is rather challenging to disentangle oxytocin use from labor dystocia. OBJECTIVE: This study aimed to investigate the independent association between oxytocin use for augmentation and the risk of postpartum hemorrhage by using advanced statistical modeling to control for labor patterns and other covariates. STUDY DESIGN: We used data from 20,899 term, cephalic, singleton pregnancies of patients with spontaneous onset of labor and no previous cesarean delivery from Intermountain Healthcare in Utah in the Consortium on Safe Labor. Presence of postpartum hemorrhage was identified on the basis of a clinical diagnosis. Propensity scores were calculated using a generalized linear mixed model for oxytocin use for augmentation, and covariate balancing generalized propensity score was applied to obtain propensity scores for the duration and total dosage of oxytocin augmentation. A weighted generalized additive mixed model was used to depict dose-response curves between the duration and total dosage of oxytocin augmentation and the outcomes. The average treatment effects of oxytocin use for augmentation on postpartum hemorrhage and estimated blood loss (mL) were assessed by inverse probability weighting of propensity scores. RESULTS: The odds of both postpartum hemorrhage and estimated blood loss increased modestly when the duration and/or total dosage of oxytocin used for augmentation increased. However, in comparison with women for whom oxytocin was not used, oxytocin augmentation was not clinically or statistically significantly associated with estimated blood loss (6.5 mL; 95% confidence interval, 2.5-10.3) or postpartum hemorrhage (adjusted odds ratio, 1.02; 95% confidence interval, 0.82-1.24) when rigorously controlling for labor pattern and potential confounders. The results remained consistent regardless of inclusion of women with an intrapartum cesarean delivery. CONCLUSION: The odds of postpartum hemorrhage and estimated blood loss increased modestly with increasing duration and total dosage of oxytocin augmentation. However, in comparison with women for whom oxytocin was not used and after controlling for potential confounders, there was no clinically significant association between oxytocin use for augmentation and estimated blood loss or the risk of postpartum hemorrhage.

Causal mediation analysis with a three-dimensional image mediator.

Causal mediation analysis is increasingly abundant in biology, psychology, and epidemiology studies and so forth. In particular, with the advent of the big data era, the issue of high-dimensional mediators is becoming more prevalent. In neuroscience, with the widespread application of magnetic resonance technology in the field of brain imaging, studies on image being a mediator emerged. In this study, a novel causal mediation analysis method with a three-dimensional image mediator is proposed. We define the average casual effects under the potential outcome framework, explore several sufficient conditions for the valid identification, and develop techniques for estimation and inference. To verify the effectiveness of the proposed method, a series of simulations under various scenarios is performed. Finally, the proposed method is applied to a study on the causal effect of mother's delivery mode on child's IQ development. It is found that cesarean section may have a negative effect on intellectual performance and that this effect is mediated by white matter development. Additional prospective and longitudinal studies may be necessary to validate these emerging findings.

Comparative analysis of codon usage patterns in the chloroplast genomes of nine forage legumes.

Leguminosae is one of the three largest families of angiosperms after Compositae and Orchidaceae. It is widely distributed and grows in a variety of environments, including plains, mountains, deserts, forests, grasslands, and even waters where almost all legumes can be found. It is one of the most important sources of starch, protein and oil in the food of mankind and also an important source of high-quality forage material for animals, which has important economic significance. In our study, the codon usage patterns and variation sources of the chloroplast genome of nine important forage legumes were systematically analyzed. Meanwhile, we also constructed a phylogenetic tree based on the whole chloroplast genomes and protein coding sequences of these nine forage legumes. Our results showed that the chloroplast genomes of nine forage legumes end with A/T bases, and seven identical high-frequency (HF) codons were detected among the nine forage legumes. ENC-GC3s mapping, PR2 analysis, and neutral analysis showed that the codon bias of nine forage legumes was influenced by many factors, among which natural selection was the main influencing factor. The codon usage frequency showed that the Nicotiana tabacum and Saccharomyces cerevisiae can be considered as receptors for the exogenous expression of chloroplast genes of these nine forage legumes. The phylogenetic relationships of the chloroplast genomes and protein coding genes were highly similar, and the nine forage legumes were divided into three major clades. Among the clades Melilotus officinalis was more closely related to Medicago sativa, and Galega officinalis was more closely related to Galega orientalis. This study provides a scientific basis for the molecular markers research, species identification and phylogenetic studies of forage legumes. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01421-0.

Calycosin protects against oxidative stress-induced cardiomyocyte apoptosis by activating aldehyde dehydrogenase 2.

Myocardial infarction (MI) is the leading cause of death worldwide, and oxidative stress is part of the process that causes MI. Calycosin, a naturally occurring substance with cardioprotective properties, is one of the major active constituents in Radix Astragali. In this study, effect of Calycosin was investigated in vivo and in vitro to determine whether it could alleviate oxidative stress and oxidative stress-induced cardiac apoptosis in neonatal cardiomyocytes (NCMs) via activation of aldehyde dehydrogenase 2 (ALDH2). Calycosin protected against oxidative stress and oxidative stress-induced apoptosis in NCMs. Molecular docking revealed that the ALDH2-Calycosin complex had a binding energy of -9.885 kcal/mol. In addition, molecular docking simulations demonstrated that the ALDH2-Calycosin complex was stable. Using BLI assays, we confirmed that Calycosin could interact with ALDH2 (KD  = 1.9 × 10-4 M). Furthermore, an ALDH2 kinase activity test revealed that Calycosin increased ALDH2 activity, exhibiting an EC50 of 91.79 µM. Pre-incubation with ALDH2 inhibitor (CVT-10216 or disulfiram) reduced the cardio-protective properties Calycosin. In mice with MI, Calycosin therapy substantially reduced myocardial apoptosis, oxidative stress, and activated ALDH2. Collectively, our findings clearly suggest that Calycosin reduces oxidative stress and oxidative stress-induced apoptosis via the regulation of ALDH2 signaling, which supports potential therapeutic use in MI.

Causal effect estimation for multivariate continuous treatments.

Causal inference is widely used in various fields, such as biology, psychology, and economics, etc. In observational studies, balancing the covariates is an important step in estimating the causal effect. This study extends the one-dimensional entropy balancing method to multiple dimensions to balance the covariates. Both parametric and nonparametric methods are proposed to estimate the causal effect of multivariate continuous treatments and theoretical properties of the two estimations are provided. Furthermore, the simulation results show that the proposed method is better than other methods in various cases. Finally, the proposed method is applied to analyze the impact of the duration and frequency of smoking on medical expenditure. The results from the parametric method indicate that the frequency of smoking increases medical expenditure while the duration of smoking does not. The results from the nonparametric method indicate that there is a short-term downward trend and then a long-term upward trend as the duration and frequency of smoking increase.

Analysis of risk factors associated with acute respiratory infections among under-five children in Uganda.

BACKGROUND: Globally, infectious diseases are the major cause of death in children under the age of 5 years. Sub-Saharan Africa and South Asia account for 95% of global child mortalities every year, where acute respiratory infections (ARI) remain the leading cause of child morbidity and mortality. The aim of this study is to analyze the risk factors of ARI disease symptoms among children under the age of 5 years in Uganda. METHODS: A cross-sectional design was used to analyze 2016 Uganda Demographic and Health Survey (UDHS) data collected on 13,493 children under the age of 5 years in Uganda. Various methods, such as logistic regression, elastic net logistic regression, decision tree, and random forest, were compared and used to predict 75% of the symptom outcomes of ARI disease. Well-performing methods were used to determine potential risk factors for ARI disease symptoms among children under the age of 5 years. RESULTS: In Uganda, about 40.3% of children were reported to have ARI disease symptoms in the 2 weeks preceding the survey. Children under the age of 24 months were found to have a high prevalence of ARI disease symptoms. By considering 75% of the sample, the random forest was found to be a well-performing method (accuracy = 88.7%; AUC = 0.951) compared to the logistic regression method (accuracy = 62.0%; AUC = 0.638) and other methods in predicting childhood ARI symptoms. In addition, one-year old children (OR: 1.27; 95% CI: 1.12-1.44), children whose mothers were teenagers (OR: 1.28; 95% CI: 1.06-1.53), and farm workers (1.25; 95% CI: 1.11-1.42) were most likely to have ARI disease symptoms than other categories. Furthermore, children aged 48-59 months (OR: 0.69; 95% CI: 0.60-0.80), breastfed children (OR: 0.83; 95% CI: 0.76-0.92), usage of charcoal in cooking (OR: 0.77; 95% CI: 0.69-0.87), and the rainy season effect (OR: 0.66; 95% CI: 0.61-0.72) showed a low risk of developing ARI disease symptoms among children under the age of 5 years in Uganda. CONCLUSION: Policy-makers and health stakeholders should initiate target-oriented approaches to address the problem regarding poor children's healthcare, improper environmental conditions, and childcare facilities. For the sake of early child care, the government should promote child breastfeeding and maternal education.

Combined strategy of knowledge-based rule selection and historical data percentile-based range determination to improve an autoverification system for clinical chemistry test results.

BACKGROUND: Current autoverification, which is only knowledge-based, has low efficiency. Regular historical data analysis may improve autoverification range determination. We attempted to enhance autoverification by selecting autoverification rules by knowledge and ranges from historical data. This new system was compared with the original knowledge-based system. METHODS: New types of rules, extreme values, and consistency checks were added and the autoverification workflow was rearranged to construct a framework. Criteria for creating rules for extreme value ranges, limit checks, consistency checks, and delta checks were determined by analyzing historical Zhongshan laboratory data. The new system's effectiveness was evaluated using pooled data from 20 centers. Efficiency improvement was assessed by a multicenter process. RESULTS: Effectiveness was evaluated by the true positive rate, true negative rate, and overall consistency rate, as compared to manual verification, which were 77.55%, 78.53%, and 78.3%, respectively for the new system. The original overall consistency rate was 56.2%. The new pass rates, indicating efficiency, were increased by 19%-51% among hospitals. Further customization using individualized data increased this rate. CONCLUSIONS: The improved system showed a comparable effectiveness and markedly increased efficiency. This transferable system could be further improved and popularized by utilizing historical data from each hospital.

Serum ß-catenin changes vary among different stages of osteonecrosis of the femoral head: an exploratory biomarker study.

BACKGROUND: Wnt/ß-catenin signaling pathway is closely related to the pathogenesis Osteonecrosis of the femoral head (ONFH). ß-catenin, as a major component of Wnt signaling pathway, plays a vital role in the proliferation of osteoblasts. But the effect of altering ß-catenin level on the early diagnosis and staging of ONFH has not been studied. Our purpose is to investigate the role of ß-catenin level in the progress of ONFH. METHOD: One hundred and one patients with three stages of ONFH and fifty healthy controls were recruited between May 2016 and November 2016. We divided the patients into 32 cases of stage II, 41 cases of stage III and 28 cases of stage IV according to the Association Research Circulation Osseous (ARCO) classification. We evaluated the clinical bone histomorphology, expression position and level of ß-catenin as well as the plasma ß-catenin level. We investigated the level of ß-catenin from the serum and tissue samples using ELISA and Western Blot assay. We also evaluated the expression of ß-catenin in bone tissue by immunohistochemistry. Data were analyzed by independent t-test and ANOVA. RESULTS: We found that the mean (± SD) serum level of ß-catenin was 66.99 ± 3.032 ng/ml in the ONFH patients, which was higher than 20.14 ± 1.715 ng/ml observed in the control group (P < 0.001). Moreover, the ß-catenin levels were 49.30 ± 4.649 ng/ml, 72.54 ± 4.864 ng/ml and 79.10 ± 4.773 ng/ml in the ONFH patients with ARCO stage II, stage III and stage IV respectively, showing significant difference among them (P < 0.001). We also found that the area under the curve (AUC) calculated by ROC curve analysis to determine the values for ß-catenin levels in ONFH compared with those in the control group was 0.9358 (P < 0.001), where the sensitivity was 77.23% and specificity was 98.00%. CONCLUSION: Our results indicate that the increased ß-catenin may play a vital role in the progress of ONFH and the level of ß-catenin is correlated with ARCO stages. The cut-off concentration may be used as one of the sensitive marks to assess the disease process of ONFH.

A case of bacteremia caused by Slackia exigua in a patient with liver abscess, which caused by fish puncture through the stomach wall.

We present a case of hepatic abscess caused by a fish puncture through the gastric wall and the development of Slackia exigua infection.

Magnolol, a natural aldehyde dehydrogenase-2 agonist, inhibits the proliferation and collagen synthesis of cardiac fibroblasts.

Inhibiting myocardial fibrosis can help prevent cardiovascular diseases, including heart failure. Magnolol (Mag), a natural component of Magnoliae officinalis, has been reported to inhibit fibrosis. However, the mechanism of Mag activity and its effects on myocardial fibrosis remain unclear. Here, we investigated the involvement of ALDH2, an endogenous protective agent against myocardial fibrosis, in the Mag-mediated inhibition of cardiac fibroblast proliferation and collagen synthesis. We found that Mag significantly inhibited cardiac fibroblast proliferation and collagen synthesis, based on the results of MTT, EdU and western blot assays. Moreover, molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) assays showed that Mag could bind directly and stably to ALDH2. Further analysis of the mechanism of these effects indicated that treatment with Mag dose-dependently enhanced ALDH2 activity without altering protein expression. Mag could enhance the activity of recombinant human ALDH2 proteins with a half-maximal effective concentration of 5.79 × 10-5 M. In addition, ALDH2 activation via Alda-1 inhibited cardiac fibroblast proliferation and collagen synthesis, while ALDH2 inhibition via daidzin partially blocked the suppressive effects of Mag. In summary, Mag may act as a natural ALDH2 agonist and inhibit cardiac fibroblast proliferation and collagen synthesis.

Diagnostic Value of Serum Cytokeratin 18, Carcinoembryonic Antigen, and Thyroglobulin in Patients with Papillary Thyroid Carcinoma.

BACKGROUND: The current study aims to explore the expression and diagnostic value of cytokeratin 18 (CK) in patients with papillary thyroid carcinoma (PTC). METHODS: Patients diagnosed with thyroid tumor, including 127 cases of PTC and 60 cases of benign tumors and 50 healthy controls were included. Serum CK 18, carcinoembryonic antigen (CEA) and thyroglobulin (Tg) were detected using enzyme-linked immunosorbent assay (ELISA). The diagnostic value of serum CK 18, CEA, and Tg for PTC was analyzed by receiver-operating characteristic (ROC) curve. RESULTS: We showed novel data that the level of serum CK 18 was higher in PTC patients than that in controls. Upregulation of serum CK 18 correlated with aggressive clinicopathologic characteristics of PTC, including lymph node metastasis, high ASA risk classification, advanced TNM stage, and larger tumor size. Furthermore, serum CEA and Tg levels of thyroid cancer patients were significantly higher than those of the benign group. More importantly, the AUC-ROC of combined serum CEA, Tg, and CK 18 was higher than that of CEA, Tg, and CK 18 alone, indicating the combination of serum CEA, Tg, and CK 18 significantly improved the diagnostic efficiency in PTC patients. CONCLUSIONS: Altogether, combined use of serum CK 18, Tg, and CEA may be a promising biomarker in screening benign and malignant thyroid tumors.

Combined effects of weight change trajectories and eating behaviors on childhood adiposity status: A birth cohort study.

Previous studies have suggested that infant rapid weight change can be associated with an increased weight later in life. However, the weight change trajectory in early life over time and which childhood lifestyle behaviors may modify the risk of rapid weight change have not been characterized. Using our ongoing birth cohort study, we have addressed these issues. Nine follow-up time points (birth, 3, 6, 9, 12, 18, 24, 36, and 48 months) were used to calculate the change between two adjacent weight-for-age z-scores (WAZ-change), and then WAZ-change trajectories were defined via group-based trajectory modeling. The solitary, independent and combined effects of WAZ-change trajectories and each lifestyle factor (eating behaviors, physical activity, media exposure time and total sleep duration) on childhood adiposity measures at age 4 years were determined using multivariate regression analysis. Overall, 84 (38%) children had a steady growth trajectory from birth to 4 years, while the other 137 (62%) children had an early infancy rapid growth trajectory, particularly in the first three months. Compared to children with steady growth, children with early infancy rapid growth had a significantly higher body mass index, waist circumference, and subcutaneous fat. Moreover, weight change trajectory and three eating behaviors (i.e. food responsiveness, satiety responsiveness and food fussiness), not only had independent effects, but also combined (synergistic) effects on the majority of adiposity measures. Our results extend the current literature and provide a potentially valuable model to aid clinicians and health professionals in designing early-life interventions targeting specific populations, specific ages and specific lifestyle behaviors to prevent childhood overweight/obesity.

Physical activity and atrial tachyarrhythmia recurrence in atrial fibrillation patients after catheter ablation.

BACKGROUND: The association between physical activity (PA) and atrial tachyarrhythmia (AT) recurrence after ablation for atrial fibrillation (AF) remains unclear. METHODS: We consecutively enrolled 496 patients treated with AF ablation therapy in Beijing Anzhen Hospital. After excluding six patients with valvular heart disease, seven patients with congenital heart disease, 33 patients lost to follow-up, and 14 patients who did not provide PA level during follow-ups, 436 patients had their PA level assessed by the International Physical Activity Questionnaire-Short Form before ablation and each time of follow-up. The association between PA level (measured at the time closest to AT recurrence, or the end of 12-month follow-up if no AT recurrence), as well as active PA during follow-up, and postablation AT recurrence was tested by multivariate logistic regression. RESULTS: Of the enrolled patients, 134 (30.7%) patients experienced AT recurrence in the first 12 months postablation. Compared to patients with low PA, patients with moderate or high PA had a lower risk of AT recurrence (odds ratio [OR] = .44; 95% confidence interval [CI], .25-.80; P = .01 for patients with moderate PA; and OR = .43 [95% CI, .21-.85], P = .02 for patients with high PA). Compared to patients without active PA, patients with active PA had a lower risk of AT recurrence (OR = .44 [95% CI, .27-.70], P < .01). CONCLUSIONS: Moderate and high PA are associated with a lower risk of AT recurrence after AF ablation. Active PA during follow-up is also associated with a significantly lower risk of AT recurrence in the postablation AF population.

An Analysis of Clinical Efficacy of Microsurgical Resection of Intradural Neoplasm by Unilateral Approach with Caspar Retractors.

OBJECTIVE: This study aims to investigate the clinical efficacy of minimally invasive microsurgical resection of intraspinal tumors with the aid of Caspar retractors. MATERIALS AND METHODS: A total of 125 intraspinal tumor patients with lesions smaller than 6 cm, who were treated at the Neurosurgery Department of our hospital from March 2010 to March 2016, were retrospectively analyzed. Among these, 73 patients underwent microsurgical resection of intraspinal tumors with the aid of Caspar retractors, while 52 patients underwent conventional laminectomy for resection of intraspinal tumors. Relevant indicators between both groups of patients were compared, including length of surgical incision, duration of surgery, postoperative drainage volume, time to first out-of-bed activity after surgery, postoperative hospitalization period, visual analog score (VAS) score, and Japanese Orthopedic Association (JOA) score, at 1 month after surgery. RESULTS: Compared with the conventional laminectomy group, patients who underwent microsurgical resection with the aid of Caspar retractors had better outcomes in terms of length of surgical incision, postoperative drainage volume, time to first out-of-bed activity after surgery, postoperative hospitalization period, and VAS scores (p < 0.05). However, JOA scores at 1 month after surgery did not have any significant differences (p > 0.05). CONCLUSIONS: The microsurgical resection of intraspinal tumors with the aid of Caspar retractors has advantages of small trauma, less bleeding, and faster recovery. It is a safe and efficacious method for treating small intraspinal tumors.

Prevalence of modifiable risk factors and relation to stroke and death in patients with atrial fibrillation: A report from the China atrial fibrillation registry study.

BACKGROUND: Lifestyle and risk factor management may improve outcomes in patients with atrial fibrillation (AF). We aim to evaluate the prevalence of modifiable risk factors and how these factors impact clinical outcomes in patients with AF. METHODS AND RESULTS: Data on 17 898 AF cohort patients with AF enrolled between 2011 and 2016 was analyzed. A healthy lifestyle was defined as not smoking, not drinking, a healthy body mass index (BMI), untreated total cholesterol less than 200 mg/dL, untreated blood pressure (BP) less than 120/80 mm Hg, and untreated fasting plasma glucose (FPG) less than 100 mg/dL. The association between risk factors and risk of the composite endpoint of all-cause mortality and nonfatal ischemic stroke were assessed using Cox proportional hazards regression model. Only 4.0% of patients achieved a healthy lifestyle. In multivariate analysis, current smoking, a low BMI, not well-controlled FPG were independently and significantly associated with higher risk of all-cause mortality and nonfatal ischemic stroke, with corresponding hazard ratio (HR) estimates 1.22 (95% confidence interval [CI], 1.00-1.47), HR = 1.72 (95% CI, 1.34-2.20), and HR = 1.25 (95% CI, 1.06-1.46), respectively. High BP was also associated with higher risk with the outcomes (HR = 1.15, 95% CI, 1.00-1.34). Compared with patients with no risk factor, those who failed to maintained or achieved optimal risk factor control had a progressively higher risk of death and nonfatal ischemic stroke (HR for 1 risk factor = 1.44; 95% CI, 1.07-1.92; and more than 2 risk factors = 1.75; 95% CI, 0.99-3.09). CONCLUSIONS: Maintenance of well-controlled risk factors may substantially lower the risk of death and ischemic stroke in patients with AF.

Control of Anticoagulation Therapy in Patients with Atrial Fibrillation Treated with Warfarin: A Study from the Chinese Atrial Fibrillation Registry.

BACKGROUND Several factors determine the efficacy of warfarin anticoagulation in patients with non-valvular atrial fibrillation (NVAF). This study aimed to use data from the Chinese Atrial Fibrillation Registry study to assess the control of anticoagulation therapy in Chinese patients with NVAF treated with warfarin. MATERIAL AND METHODS From the Chinese Atrial Fibrillation Registry study the anticoagulant use and dosing, the time in therapeutic range (TTR) of the international normalized ratio (INR), and standard deviation of the observed INR values (SDINR), and their influencing factors were evaluated. RESULTS The median INR and SDINR were 2.04 (IQR 1.71-2.41) and 0.50 (IQR, 0.35-0.69), respectively. The median TTR was 51.7% (IQR, 30.6-70.1%) and only 25.1% had a TTR ≥70%. Age was ≥70 years (OR, 0.72; 95% CI, 0.55-0.94; P=0.015), bleeding history (OR 0.48; 95% CI, 0.23-0.89; P=0.029), the use of a single drug (OR, 0.62; 95% CI, 0.42-0.92; P=0.016), more than drug (OR, 0.60; 95% CI, 0.41-0.88; P=0.009), and lack of assessment of bleeding risk (OR, 0.72; 95% CI, 0.54-0.97; P=0.033) were associated with TTR <70% (INR 2.0-3.0). Coronary heart disease (CHD) and peripheral artery disease (PAD) (OR, 0.69; 95% CI, 0.52-0.90; P=0.007) and diabetes mellitus (OR, 0.79; 95% CI, 0.62-0.99; P=0.044) were associated with increased variability in INR (SDINR ≥0.5). CONCLUSIONS In Chinese patients with NVAF, warfarin anticoagulation was associated with lower TTR and less stable anticoagulation than in current guidelines, and risk factors for reduced safety and efficacy were identified.

Profile clustering in clinical trials with longitudinal and functional data methods.

Repeated measurements are widely encountered in medical or pharmaceutical studies, which can be analyzed by both longitudinal data and functional data analysis methods, particularly when the underlying process is continuous and the number of measurement points is not too small. Motivated by real problems of clustering patient profiles in clinical trials, this paper gives an overview of the clustering methods for repeated measurement data and compares three longitudinal data methods and two functional data methods with extensive simulation studies. Methods with appropriate properties are applied to the real data to produce interpretable results.

Association of reduced sclerostin expression with collapse process in patients with osteonecrosis of the femoral head.

PURPOSE: Sclerostin is an osteocyte-derived protein that has a potent inhibitory effect on osteoblast activity. The osteocyte apoptosis induced by various causes of osteonecrosis of the femoral head (ONFH) plays a key role in the promotion of femoral head collapse. But the effect of altering sclerostin level on the collapse of ONFH has not been studied. Our aim was to assess the role of sclerostin level in the collapse of ONFH. METHODS: Between May 2016 and November 2016, 236 subjects were enrolled in the present study. The patients were classified according to the Association Research Circulation Osseous (ARCO) classification. The clinical bone histomorphology, the expression position, and level of sclerostin as well as the plasma sclerostin level were evaluated. RESULTS: The sclerostin level was significantly lower in the non-traumatic ONFH group than those in the healthy control group (P = 0.002). The sclerostin level was negatively associated with ARCO stages (r = - 0.239, P = 0.009) and significantly lower in the postcollapse group (P = 0.025). CONCLUSIONS: The reduced expression of sclerostin may play a key role in the collapse process of ONFH and be predictive of the disease progression of ONFH.

Migraine and the risk of stroke: an updated meta-analysis of prospective cohort studies.

Dozens of observational studies and two meta-analyses have investigated the association of migraine with the risk of stroke, but their results are inconsistent. We aimed to quantitatively evaluate the relationship between migraine and stroke risk by performing a meta-analysis of prospective cohort studies. PubMed and Embase were searched through July 2016 to identify studies that met pre-stated inclusion criterion and reference lists of retrieved articles were also reviewed. Information on the characteristics of the included study, risk estimates, and control for possible confounding factors were extracted independently by two authors. The random-effects model was used to calculate the pooled risk estimates. Eleven prospective cohort studies involving 3371 patients with stroke and 2,221,888 participants were included in this systematic review. Compared with non-migraineurs, the pooled relative risks of total stroke, hemorrhagic stroke, and ischemic stroke for migraineurs were 1.55 [95% confidence interval (CI) 1.38-1.75], 1.15 (95% CI 0.85-1.56), and 1.64 (95% CI 1.22-2.20), respectively. Exception of any single study did not materially alter the combined risk estimate. Integrated epidemiological evidence supports that migraine should be associated with the increased risk of total stroke and ischemic stroke, but the relationship between migraine and the risk of hemorrhagic stroke is not of certainty.