iEnhancer-DCSA: identifying enhancers via dual-scale convolution and spatial attention.

BACKGROUND: Due to the dynamic nature of enhancers, identifying enhancers and their strength are major bioinformatics challenges. With the development of deep learning, several models have facilitated enhancers detection in recent years. However, existing studies either neglect different length motifs information or treat the features at all spatial locations equally. How to effectively use multi-scale motifs information while ignoring irrelevant information is a question worthy of serious consideration. In this paper, we propose an accurate and stable predictor iEnhancer-DCSA, mainly composed of dual-scale fusion and spatial attention, automatically extracting features of different length motifs and selectively focusing on the important features. RESULTS: Our experimental results demonstrate that iEnhancer-DCSA is remarkably superior to existing state-of-the-art methods on the test dataset. Especially, the accuracy and MCC of enhancer identification are improved by 3.45% and 9.41%, respectively. Meanwhile, the accuracy and MCC of enhancer classification are improved by 7.65% and 18.1%, respectively. Furthermore, we conduct ablation studies to demonstrate the effectiveness of dual-scale fusion and spatial attention. CONCLUSIONS: iEnhancer-DCSA will be a valuable computational tool in identifying and classifying enhancers, especially for those not included in the training dataset.

A case of a common bile duct stone containing a metallic clip appearing after laparoscopic cholecystectomy.

Laparoscopic cholecystectomy (LC) is currently the standard procedure for the treatment of benign gallbladder diseases. Although the ligature clip may fall off and shift after surgery, relevant reports are rare. We describe the formation of common bile duct stone in an elderly female in which a metal clip displaced into the common bile duct 6 years after LC.

Chest circumference and sitting height among children and adolescents from Lhasa, tibet compared to other high altitude populations.

OBJECTIVES: The adaptation of human beings to a high altitude environment during growth has been reported in several populations but is less known for Tibetans. The objective of this study was to investigate similarities and differences of Tibetans in patterns and characteristics of physical growth and development in comparison to other high altitude populations. METHODS: We measured the stature, weight, chest circumference and sitting height of 2,813 healthy children and adolescents aged 6- to 21-year-old living at 3,658-4,500 m in Tibet, China, and compared them with published data from other high altitude populations. Eligible participants must have been born and raised in Tibet, and both their parents' families have to be Tibetan for at least the past three generations. RESULTS: The physical growth and development of children and adolescents in Tibet and the Andes followed similar patterns, such as delayed growth, short stature and sitting height, and large chest dimensions. Relative to stature, Tibetan sitting heights are similar to Andeans, but chest circumferences are smaller. CONCLUSIONS: Findings from this study reinforce the conclusion that Tibetan and Andean populations have adapted differently to high altitude hypoxia. The physical features of each population may result from unique adaptation to hypoxia, as well as socio-ecological factors, such as poor nutrition.

Cornell Assessment of Pediatric Delirium: a valid, rapid, observational tool for screening delirium in the PICU*.

OBJECTIVE: To determine validity and reliability of the Cornell Assessment of Pediatric Delirium, a rapid observational screening tool. DESIGN: Double-blinded assessments were performed with the Cornell Assessment of Pediatric Delirium completed by nursing staff in the PICU. These ratings were compared with an assessment by consultation liaison child psychiatrist using the Diagnostic and Statistical Manual IV criteria as the "gold standard" for diagnosis of delirium. An initial series of duplicate Cornell Assessment of Pediatric Delirium assessments were performed in blinded fashion to assess interrater reliability. Nurses recorded the time required to complete the Cornell Assessment of Pediatric Delirium screen. SETTING: Twenty-bed general PICU in a major urban academic medical center over a 10-week period, March-May 2012. PATIENTS: One hundred eleven patients stratified over ages ranging from 0 to 21 years and across developmental levels. INTERVENTION: Two hundred forty-eight paired assessments completed. MEASUREMENTS AND MAIN RESULTS: The Cornell Assessment of Pediatric Delirium had an overall sensitivity of 94.1% (95% CI, 83.8-98.8%) and specificity of 79.2% (95% CI, 73.5-84.9%). Overall Cronbach's α of 0.90 was observed, with a range of 0.87-0.90 for each of the eight items, indicating good internal consistency. A scoring cut point of 9 demonstrated good interrater reliability of the Cornell Assessment of Pediatric Delirium when comparing results of the screen between nurses (overall κ = 0.94; item range κ = 0.68-0.78). In patients without significant developmental delay, sensitivity was 92.0% (95% CI, 85.7-98.3%) and specificity was 86.5% (95% CI, 75.4-97.6%). In developmentally delayed children, the Cornell Assessment of Pediatric Delirium showed decreased specificity of 51.2% (95% CI, 24.7-77.8%) but sensitivity remained high at 96.2% (95% CI, 86.5-100%). The Cornell Assessment of Pediatric Delirium takes less than 2 minutes to complete. CONCLUSIONS: With an overall prevalence rate of 20.6% in our study population, delirium is a common problem in pediatric critical care. The Cornell Assessment of Pediatric Delirium is a valid, rapid, observational nursing screen that is urgently needed for the detection of delirium in PICU settings.

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder.

BACKGROUND: Hostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. METHODS: Data were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3-12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS-Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. RESULTS: Most patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [-0.93], disruptive-aggressive behavior [-0.79], combined [-1.75]; P ≤ 0.001 each), YMRS total score (-5.92, P ≤ 0.0001), and all individual YMRS items (-0.25 to -0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LIMITATIONS: Post hoc analysis. CONCLUSION: Cariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.

The Association between Obesity Susceptibility and Polymorphisms of MC4R, SH2B1, and NEGR1 in Tibetans.

Background: A high-altitude environment has inhibitory effects on obesity. Tibetans are not a high-risk population for obesity, but there are still obese individuals within that population. Obesity has become a worldwide health problem, and previous studies have found that obesity is closely associated with hereditary factors. Few studies have investigated obesity in Tibetans, and the association between gene polymorphisms and obesity in Tibetans remains unclear. Methods: Our study investigated the fat mass of 140 native Tibetan individuals (70 men and 70 women) from Lhasa and analyzed the associations between polymorphisms of melanocortin 4 receptor (MC4R), Src homology 2B adapter protein 1 (SH2B1), and neuronal growth regulator 1 (NEGR1) and obesity. Result: Among Tibetan individuals, there were differences in genotype and allele frequencies between those in the obesity group and those in the healthy group at MC4R (rs17782313) and SH2B1 (rs7359397). The polymorphisms of MC4R (rs17782313) were associated with fat mass and obesity in Tibetan men and women, and there was an association between SH2B1 (rs7359397) polymorphisms and fat mass and obesity in Tibetan men. However, polymorphisms of NEGR1 (rs3101336) were not associated with fat mass or obesity in Tibetan individuals. Conclusion: Among Tibetan individuals, polymorphisms of MC4R (rs17782313) and SH2B1 (rs7359397) were associated with obesity, but NEGR1 (rs3101336) polymorphisms were not associated with obesity.

Subject-level matching for imbalance in cluster randomized trials with a small number of clusters.

In a cluster randomized controlled trial (RCT), the number of randomized units is typically considerably smaller than in trials where the unit of randomization is the patient. If the number of randomized clusters is small, there is a reasonable chance of baseline imbalance between the experimental and control groups. This imbalance threatens the validity of inferences regarding post-treatment intervention effects unless an appropriate statistical adjustment is used. Here, we consider application of the propensity score adjustment for cluster RCTs. For the purpose of illustration, we apply the propensity adjustment to a cluster RCT that evaluated an intervention to reduce suicidal ideation and depression. This approach to adjusting imbalance had considerable bearing on the interpretation of results. A simulation study demonstrates that the propensity adjustment reduced well over 90% of the bias seen in unadjusted models for the specifications examined.

Two propensity score-based strategies for a three-decade observational study: investigating psychotropic medications and suicide risk.

The US Food and Drug Administration issued separate warnings for suicidality with antidepressants and antiepileptic drugs in the past 5 years. This study describes methods for examining the association of these agents with suicide attempts and suicide deaths in more broadly generalizable samples than examined by the US Food and Drug Administration. An observational study of mood disorders was examined that includes three decades of prospective assessments. Because of sample size differences, two distinct longitudinal implementations of the propensity adjustment are used in separate analyses of antidepressants and antiepileptic drugs. Propensity score quintile-stratified safety analyses were used with the large antidepressant data set; whereas, propensity score matched safety analyses were used with the smaller antiepileptic drug data because stratification was not feasible. In each case, mixed-effects survival models compared the safety of participants when receiving the respective class of medication to periods when they did not receive that medication. When participants were more severely ill, they were significantly more likely to receive either class of psychotropics. Propensity quintile-stratified safety analyses found that risk of suicide attempts or suicides was significantly reduced when participants received antidepressants. In contrast, propensity score matched safety analyses found neither significant risk nor protection from suicidality among participants receiving antiepileptics.

Performance of a propensity score adjustment in longitudinal studies with covariate-dependent representation.

Longitudinal observational studies provide rich opportunities to examine treatment effectiveness during the course of a chronic illness. However, there are threats to the validity of observational inferences. For instance, clinician judgment and self-selection play key roles in treatment assignment. To account for this, an adjustment such as the propensity score can be used if certain assumptions are fulfilled. Here, we consider a problem that could surface in a longitudinal observational study and has been largely overlooked. It can occur when subjects have a varying number of distinct periods of therapeutic intervention. We evaluate the implications of baseline variables in the propensity model being associated with the number of post baseline observations per subject and refer to it as 'covariate-dependent representation'. An observational study of antidepressant treatment effectiveness serves as a motivating example. The analyses examine the first 20 years of follow-up data from the National Institute of Mental Health Collaborative Depression Study, a longitudinal, observational study. A simulation study evaluates the consequences of covariate-dependent representation in longitudinal observational studies of treatment effectiveness under a range of data specifications.The simulations found that estimates were adversely affected by underrepresentation when there was lower ICC among repeated doses and among repeated outcomes.

Extracorporeal membrane oxygenation for thyroid surgery in patients with severe tracheal stenosis.

Venovenous extracorporeal membrane oxygenation is effective for maintaining gas exchange in patients with respiratory failure or severe tracheal stenosis. Perioperative anesthetic management of severe airway obstruction can be associated with ventilation or intubation difficulties. Consequently, venovenous extracorporeal membrane oxygenation could be an option for treating such patients to avoid potential risks. However, only a limited number of similar cases have been reported. Therefore, we have summarized two cases to provide theoretical and practical references for treating patients with respiratory failure or severe tracheal stenosis using extracorporeal membrane oxygenation.

N-Nitro-1H-pyrrole-2-carboxamide.

In the title compound, C(5)H(5)N(3)O(3), the nitro group is twisted with respect to the amide group, with C-N-N-O torsion angles of 29.0 (2) and -153.66 (14)°. In the crystal, mol-ecules are linked through inter-molecular N-H⋯O and C-H⋯O hydrogen bonds, forming supra-molecular chains along the a axis. These chains stack in parallel and form distinct layer motifs in the (001) plane.

Exosomes from miR-29a-modified adipose-derived mesenchymal stem cells reduce excessive scar formation by inhibiting TGF-ß2/Smad3 signaling.

Pathological scars mainly refer to hypertrophic scars and keloids, and have a high incidence. Moreover, these scars seriously affect the patient's appearance and are associated with significant pain. The present study aimed to investigate the inhibitory effect of microRNA (miR)­29a from human adipose­derived mesenchymal stem cells (hADSCs) exosomes on scar formation. Firstly, the expression of miR­29a in thermal skin tissues of mice and human hypertrophic scar fibroblasts (HSFBs) was detected via reverse transcription­quantitative PCR. Exosomes derived from miR­29a­modified hADSCs were extracted and the influence of miR­29a­modified hADSCs­exo on the proliferation and function of HSFBs was determined. Lastly, the effect of miR­29a­modified hADSCs­exo on scar formation was determined using a thermal mouse model. The results demonstrated that miR­29a was downregulated in scar tissues after scalding and in HSFBs. After treating HSFBs with miR­29a­modified hADSC exosomes, miR­29a­overexpressing hADSC exosomes inhibited the proliferation and migration of HSFBs. Moreover, it was found that TGF­ß2 was the target of miR­29a, and that hADSC exosome­derived miR­29a inhibited the fibrosis of HSFBs and scar hyperplasia after scalding in mice by targeting the TGF­ß2/Smad3 signaling pathway. In summary, the current data indicated that miR­29a­modified hADSC exosome therapy can decrease scar formation by inhibiting the TGF­ß2/Smad3 signaling pathway via its derived exogenous miR­29a, and this may be useful for the future treatment of pathological scars by providing a potential molecular basis.

Enhancement of transdermal delivery of artemisinin using microemulsion vehicle based on ionic liquid and lidocaine ibuprofen.

A microemulsion system based on ionic liquid (IL) and deep eutectic compound was proposed to improve the transdermal delivery of artemisinin. Deep eutectic lidocaine ibuprofen (Lid·Ibu) was selected as the oil phase, and the imidazolium ionic liquid, 1-hydroxyethyl-3-methylimidazolium chloride ([HOEmim]Cl), was incorporated into the aqueous phase as a transdermal enhancer. The ingredients for the microemulsion in this study were selected, and their ratios were optimized. The optimal microemulsion carrier was composed of 45 wt% of water phase, 45 wt% surfactant phase (containing Tween-80, Span-20, and ethanol (co-surfactant) with the weight ratio of 1:1:1), and 10 wt% Lid·Ibu as the oil phase with artemisinin loading of 1.0 wt% (all the ratios were based on the total weight of microemulsion). Physical properties of this microemulsion, including particle size (41.95 ± 0.85 nm), viscosity (26.65 ± 0.13 mPa·s) and density (1.02 g/cm3), were measured. In-vitro transdermal assay showed a remarkable enhancement of artemisinin transport through the skin, with the permeation flux being 3-fold of the value for isopropyl myristate system in 6 h. The impact of IL-based microemulsion (ILME) on stratum corneum (SC) was investigated by DSC, ATR-FTIR and AFM, which unveiled that the ILME possesses the ability of reducing the SC barrier by disrupting the regular arrangement of keratin, resulting in enhancement of transdermal delivery of artemisinin. This current work suggested that the microemulsion proposed here had an excellent capability to promote the transdermal delivery of artemisinin, which might also be a promising vehicle for the skin delivery of other hydrophobic natural drugs.

Highly active Ce, Y, La-modified Cu/SiO2 catalysts for hydrogenation of methyl acetate to ethanol.

Rare earth element (Ce, Y, and La) modified Cu/SiO2 catalysts via hydrolysis precipitation and impregnation method were fabricated for the vapor-phase hydrogenation of methyl acetate to ethanol. LaO x showed the most pronounced promotion in the catalytic tests. After detailed characterizations, via N2 adsorption-desorption, XRD, N2O chemisorption, FTIR, H2-TPR, H2-TPD, TEM, XPS, and TG/DTA, we found that the addition of promoter LaO x can decrease the particle size while in turn, it can increase the dispersion of copper species. The strong interactions between copper and lanthanum atoms alter the surface chemical states of the copper species. This results in the generation of more Cu+ species and high S Cu + values, which are responsible for the excellent activity and stability during hydrogenation. In addition, the content of additive LaO x and reaction conditions (reaction temperature and LHSV) were optimized. Then, the long-term stability performance was evaluated over the selected catalyst in contrast with Cu/SiO2.

Manic/hypomanic symptom burden and cardiovascular mortality in bipolar disorder.

OBJECTIVES: To compare the risk for cardiovascular mortality between bipolar I and bipolar II subtypes and determine correlates of cardiovascular mortality. Bipolar disorder conveys an increased risk of cardiovascular mortality. METHODS: Participants with major affective disorders were recruited for the National Institute of Mental Health Collaborative Depression Study and followed prospectively for up to 25 years. A total of 435 participants met the diagnostic criteria for bipolar I (n = 288) or bipolar II (n = 147) disorder based on Research Diagnostic Criteria at intake and measures of psychiatric symptoms during follow-up. Diagnostic subtypes were contrasted by cardiovascular mortality risk using Cox proportional hazards regression. Affective symptom burden (the proportion of time with clinically significant manic/hypomanic or depressive symptoms) and treatment exposure were additionally included in the models. RESULTS: Thirty-three participants died from cardiovascular causes. Participants with bipolar I disorder had more than double the cardiovascular mortality risk of those with bipolar II disorder, after controlling for age and gender (hazard ratio = 2.35, 95% Confidence Interval = 1.04-5.33; p = .04). The observed difference in cardiovascular mortality between these subtypes was at least partially confounded by the burden of clinically significant manic/hypomanic symptoms which predicted cardiovascular mortality independent of diagnosis, treatment exposure, age, gender, and cardiovascular risk factors at intake. Selective serotonin uptake inhibitors seemed protective although they were introduced late in follow-up. Depressive symptom burden was not related to cardiovascular mortality. CONCLUSIONS: Participants with bipolar I disorder may face a greater risk of cardiovascular mortality than those with bipolar II disorder. This difference in cardiovascular mortality risk may reflect manic/hypomanic symptom burden.

Empirical typology of bipolar I mood episodes.

BACKGROUND: Much remains unknown about the phenomenology of bipolar I disorder. AIMS: To determine the type of bipolar I mood episodes that occur over time, and their relative frequency. METHOD: A total of 219 individuals with Research Diagnostic Criteria bipolar I disorder were prospectively followed for up to 25 years (median 20 years). Psychopathology was assessed with the Longitudinal Interval Follow-up Evaluation. RESULTS: Overall, 1208 mood episodes were prospectively observed. The episodes were empirically classified as follows: major depression, 30.9% (n = 373); minor depression, 13.0% (n = 157); mania, 20.4% (n = 246); hypomania, 10.4% (n = 126); cycling, 17.3% (n = 210); cycling plus mixed state, 7.8% (n = 94); and mixed, 0.2% (n = 2). CONCLUSIONS: Cycling episodes constituted 25% of all episodes. Work groups revising ICD-10 and DSM-IV should add a category for bipolar I cycling episode.

[Genetic polymorphism of 15 STR loci in Tibetan population].

The polymorphism distributions of 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, VWA, TPOX, D18S51, D5S818, and FGA) were investigated in a Tibetan population by multiplex PCR amplification using five fluorochromes (6FAM, VIC, NED, PET, LIZ). Gene frequency, discrimination power (DP), heterozygosity (H), polymorphism information content (PIC) and probability of paternity exclusion (EPP) were calculated, and all loci were tested for Hardy-Weinberg equilibrium. Results indicate that the gene frequency of these 15 STR loci is in Hardy-Weinberg equilibrium. The DP is at 0.7555-0.9602, H is at 0.5651-0.8530, PIC is at 0.5528-0.8456, and EPP is at 0.3811-0.8549. Cumulative DP of the 15 STR is 0.99999999, and cumulative EPP is 0.999999997. Therefore, these 15 STR loci can be used as genetic markers of Tibetan populations in anthropological studies, linkage analysis of genetic diseases, individual identification and paternity testing in forensic medicine.