bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiling of synthesis‐related impurities of the synthetic cannabinoid Cumyl‐5F‐PINACA in seized samples of e‐liquids via multivariate analysis of UHPLC−MSn data
Authors: Münster‐Müller Sascha , Matzenbach Isabelle , Knepper Thomas , Zimmermann Ralf , Pütz Michael
Published: July 2019

Vaping of synthetic cannabinoids via e‐cigarettes is growing in popularity. In the present study, we tentatively identified 12 by‐products found in a pure sample of the synthetic cannabinoid Cumyl‐5F‐PINACA (1‐(5‐fluoropentyl)‐N‐(2‐phenylpropan‐2‐yl)‐1H‐indazole‐3‐carboxamide), a prevalent new psychoactive substance (NPS) in e‐liquids, via high‐resolution mass spectrometry fragmentation experiments (HRMS/MS). Furthermore, we developed a procedure to reproducibly extract this synthetic cannabinoid and related by‐products from an e‐liquid matrix via chloroform and water. The extracts were submitted to flash chromatography (F‐LC) to isolate the by‐products from the main component. The chromatographic impurity signature was subsequently assessed by ultra‐high‐performance liquid chromatography coupled to mass spectrometry (UHPLC–MS) and evaluated by automated integration. The complete sample preparation sequence (F‐LC + UHPLC–MS) was validated by comparing the semi‐quantitative signal integrals of the chromatographic impurity signatures of five self‐made e‐liquids with varying concentrations of Cumyl‐5F‐PINACA [0.1, 0.2, 0.5, 0.7 and 1.0% (w/w)], giving an average relative standard deviation of 6.2% for triplicate measurements of preparations of the same concentration and 10.5% between the measurements of the five preparations with different concentrations. Lastly, the chromatographic signatures of 14 e‐liquid samples containing Cumyl‐5F‐PINACA from police seizures and Internet test purchases were evaluated via hierarchical cluster analysis for potential links. For the e‐liquid samples originating from test purchases, it was found that the date of purchase, the identity of the online shop, and the brand name are the critical factors for clustering of samples.
Budesonide use and misuse in sports: Elimination profiles of budesonide and metabolites after intranasal, high‐dose inhaled and oral administrations
Authors: Coll Sergi , Monfort Núria , Matabosch Xavier , Papakonstantinou Katerina , Pérez‐Mañá Clara , Mateus Julian A. , Ventura Rosa
Published: July 2019

Budesonide (BUD) is a glucocorticoid (GC) widely used in therapeutics. In sports, the World Anti‐doping Agency (WADA) controls the use of GCs, and WADA‐accredited laboratories use a reporting level of 30 ng/mL for 6β‐hydroxy‐budesonide (6βOHBUD) to detect the systemic administration of BUD. In the present work, we examined the urinary excretion profile of 6βOHBUD, BUD, and 16α‐hydroxy‐prednisolone (16αOHPRED) after intranasal (INT), inhaled (INH) (at high doses) and oral administrations in male and female volunteers. BUD was administered to healthy volunteers using INT route (256 μg/day for three days, n = 4 males and 4 females), INH route (800 μg/day for three days, n = 4 males and 4 females, and 1600 μg/day for three days, n = 4 males) or oral route (3 mg, n = 8 females). Urine samples were collected before and after administration at different time periods, and were analyzed by liquid chromatography–tandem mass spectrometry. 6βOHBUD and BUD concentrations were very low after INT treatment (0.0–7.1 and 0.0–8.1 ng/mL, respectively), and higher after INH treatments (0.0–35.4 and 0.0–48.3 ng/mL, respectively). For 16αOHPRED, elevated concentrations were detected after INT and INH treatments (2.6–66.4 and 3.4–426.5 ng/mL, respectively). Concentrations obtained following oral administration were higher than after therapeutic administrations (2.8–80.6, 1.5–36.1, and 10.4–532.2 ng/mL for 6βOHBUD, BUD, and 16αOHPRED, respectively). After all administrations, concentrations were higher in males than in females. Results demonstrated that 6βOHBUD is the best discriminatory marker and a reporting level of 40 ng/mL was found to be the best criterion to distinguish allowed from forbidden administrations of BUD.
Targeted exome sequencing reveals a novel GLI3 mutation in a Chinese family with nonsyndromic polydactyly
Authors: Zhao Xiangyu , Xu Hongyan , Liu Xiaxia , Li Lin
Published: July 2019

Background

Polydactyly is a phenotypically and genetically highly heterogeneous limb malformation with preaxial, postaxial, and central subtypes. The aim of this study was to identify genetically pathogenic factor in a Chinese nonsyndromic polydactyly family.

Results

Seven family members and 100 healthy controls were recruited, and the genetically pathogenic factor of the polydactyly family was investigated by targeted exome sequencing. Targeted exome sequencing revealed a novel frameshift mutation c.2148delA (p.Gln716Hisfs*17) of GLI3 in the family. This GLI3 variant was absent in 100 healthy controls and predicted to be highly damaging to the function of the GLI3 by causing half truncation of the protein.

Conclusion

This novel variant extended the mutational and phenotypic spectra of GLI3 and demonstrated the feasibility of targeted exome sequencing in clinical application of molecular diagnosis.
Leadership and the contagion of affective phenomena: A systematic review and mini meta‐analysis
Authors: Clarkson Beth G. , Wagstaff Christopher R. D. , Arthur Calum A. , Thelwell Richard C.
Published: July 2019

We present a systematic review of literature examining leadership and the contagion of affective phenomena, namely emotion, mood, and affect. Specifically, an inductive thematic analysis approach was adopted to synthesize the findings from published studies. In addition, a mini meta‐analysis was conducted to quantify reported effects. A rigorous search identified 25 studies that fulfilled the inclusion criteria for further review. Results highlighted important relationships between leadership and contagion aligned with six themes: Charismatic and transformational leadership are conducive to contagion of leader and follower positive affective phenomena; greater contagion effects exists when there is congruence between leader and follower affective states; contagion of leader and follower affective phenomena is directly linked to leader effectiveness and performance; and, individual susceptibility to the contagion of affective phenomena can moderate these relationships. These findings have salient implications for conceptualization and measurement across multiple lines of inquiry and within numerous domains of application.
Natural Gas Infrastructure Development—Risks and Responsibilities
Authors: Tata Padma , DeCotis Paul A.
Published: July 2019

A key driver for investment in natural gas infrastructure is market demand, and as data shows, demand continues to increase across the United States (see Figure 1). To meet this demand in part, developers are proposing new inter‐ and intrastate pipeline projects. In recent years, however, there has been strong opposition to new pipeline proposals, which has resulted in their delay or complete abandonment. Opponents to pipeline development are concerned that as a fossil fuel, continued and greater use of natural gas will further contribute to the increasing impacts of climate change. There are also concerns related to siting of proposed pipelines—namely, environmental impacts from construction activities or potential releases. Yet decisions on natural gas availability, infrastructure development, and use should not be made through a single‐lens view.
Factors affecting accuracy in the quality control checking of fresh produce labels: A situational and laboratory‐based exploration
Authors: Smith‐Spark James H. , Katz Hillary B. , Wilcockson Thomas D. W. , Marchant Alexander P.
Published: July 2019

Manufacturing industries often rely on quality control staff to ensure mistakes are detected before products are shipped to customers. Undetected errors can result in large financial and environmental costs to packaging companies and supermarkets but the contributors to such error are underexplored. The research reported in this paper investigated human error in the quality control checking of information displayed on the labels which accompany packaged fresh produce. Initial work sought to understand the demands of label‐checking in the packhouse environment, through interviews with key quality control staff, in situ observations, and the study of historical error data held by a fresh produce packaging company. This study highlighted the dynamic and cognitively challenging environment in which label‐checking occurred, while the historical error data indicated both the scale of the packhouse's work and the infrequency of error occurring. In a separate strand of laboratory‐based research, experienced and novice label‐checkers were presented with a simulated label‐checking task and a battery of computerized and pen‐and‐paper tests. These tasks were administered to determine whether cognitive abilities could predict label‐checking accuracy in a controlled laboratory environment. Stronger abilities in two cognitive processes (information processing speed and inhibition) predicted greater overall accuracy and higher detection of labeling errors. In identifying potential contributors to human error in the quality control checking of product labels both in situ and in the laboratory, the results are relevant to manufacturing, wherever information is printed on labels, especially when labeling processes depend upon human data entry and human quality control checking.
Chrna2‐OLM interneurons display different membrane properties and h‐current magnitude depending on dorsoventral location
Authors: Hilscher Markus M. , Nogueira Ingrid , Mikulovic Sanja , Kullander Klas , Leão Richardson N. , Leão Katarina E.
Published: July 2019

The hippocampus is an extended structure displaying heterogeneous anatomical cell layers along its dorsoventral axis. It is known that dorsal and ventral regions show different integrity when it comes to functionality, innervation, gene expression, and pyramidal cell properties. Still, whether hippocampal interneurons exhibit different properties along the dorsoventral axis is not known. Here, we report electrophysiological properties of dorsal and ventral oriens lacunosum moleculare (OLM) cells from coronal sections of the Chrna2‐cre mouse line. We found dorsal OLM cells to exhibit a significantly more depolarized resting membrane potential compared to ventral OLM cells, while action potential properties were similar between the two groups. We found ventral OLM cells to show a higher initial firing frequency in response to depolarizing current injections but also to exhibit a higher spike‐frequency adaptation than dorsal OLM cells. Additionally, dorsal OLM cells displayed large membrane sags in response to negative current injections correlating with our results showing that dorsal OLM cells have more hyperpolarization‐activated current (Ih) compared to ventral OLM cells. Immunohistochemical examination indicates the h‐current to correspond to hyperpolarization‐activated cyclic nucleotide‐gated subunit 2 (HCN2) channels. Computational studies suggest that Ih in OLM cells is essential for theta oscillations in hippocampal circuits, and here we found dorsal OLM cells to present a higher membrane resonance frequency than ventral OLM cells. Thus, our results highlight regional differences in membrane properties between dorsal and ventral OLM cells allowing this interneuron to differently participate in the generation of hippocampal theta rhythms depending on spatial location along the dorsoventral axis of the hippocampus.
Glucose intolerance in the third trimester is not predictive of adverse outcomes
Authors: Fonseca Andreia , Lopes João , Clode Nuno
Published: July 2019

Objective

To evaluate the incidence of abnormal third trimester oral glucose tolerance tests (OGTT) results in non‐diabetic women and to compare the obstetric and neonatal outcomes with those of women with normal OGTT results.

Methods

Women with third trimester singleton pregnancies with negative gestational diabetes test results earlier in their pregnancy were enrolled into an observational prospective study at a tertiary care hospital between June 1, 2014 and September 30, 2017. All underwent an additional 75 g OGTT between 32 and 36 weeks and were classified as having normal or abnormal results. Healthcare professionals were blinded to the results. Pregnancy and perinatal outcomes were compared.

Results

Four hundred and sixty‐seven women agreed to participate and 334 fulfilled the inclusion criteria. Forty‐five (13.5%) had an abnormal third trimester OGTT result. In this group, post‐term induction of labor was more frequent (70.6% vs 38.1%, adjusted odds ratio (aOR) 4.28, 95% confidence interval (CI) 1.33–13.77, P=0.015) as was cesarean delivery (31.1% vs 15.2%, aOR 2.57, 95% CI 1.14–5.81, P=0.023), regardless of surgery indication. Macrosomia was more common, but not significantly after adjusting for confounders (17.8% vs 4.2%, aOR 3.80, 95% CI 0.60–24.17, P=0.157). No other significant differences were found.

Conclusion

Post‐term induction of labor and cesarean delivery were more frequent in women with an abnormal third trimester OGTT result, but there was no increased risk of serious maternal or perinatal adverse outcomes.
An immune infiltration signature to predict the overall survival of patients with colon cancer
Authors: Peng Dengfa , Wang Lianjun , Li Huqing , Cai Changsong , Tan Yong , Xu Bin , Le Hao
Published: July 2019

Immune infiltration of tumors has been increasingly accepted as a prognostic factor in colon cancer. Here, we aim to develop a novel immune signature, based on estimated immune landscape from tumor transcriptomes, to predict the overall survival of patients with colon cancer. The compositions of 22 immune cell subtypes from three microarray datasets were characterized with the CIBERSORT deconvolution algorithm. A prognostic immunoscore (PIS) model for overall survival prediction was established by using least absolute shrinkage and selection operator (LASSO) penalized regression analysis. A total of 17 immune cell markers were screened out in the LASSO model and were then aggregated to generate the PIS. In the training cohort (n = 490), patients with high PIS exhibited a remarkably poorer overall survival than those with low PIS. Similar results were obtained in patients with different TNM stages and in patients receiving adjunctive chemotherapy or not. Multivariate Cox regression indicated that the PIS was an independent predictor for overall survival in colon cancer (hazard ratio: 2.734, 95% confidence interval: 2.052–3.643, p < .001). The prognostic capability of PIS was also confirmed in the testing cohort (n = 245) and the entire cohort (n = 735). As for biological implications, the PIS was significantly associated with some immune checkpoints, inflammatory factors, epithelial–mesenchymal transformation regulators, and many known signaling pathways in cancer. The results of our study provide a novel and promising immune signature for overall survival prediction of patients with colon cancer.
Histogram analysis of en face scattering coefficient map predicts malignancy in human ovarian tissue
Authors: Zeng Yifeng , Nandy Sreyankar , Rao Bin , Li Shuying , Hagemann Andrea R. , Kuroki Lindsay K. , McCourt Carolyn , Mutch David G. , Powell Matthew A. , Hagemann Ian S. , Zhu Quing
Published: July 2019

Ovarian cancer is a heterogeneous disease at the molecular and histologic level. Optical coherence tomography (OCT) is able to map ovarian tissue optical properties and heterogeneity, which has been proposed as a feature to aid in diagnosis of ovarian cancer. In this manuscript, depth‐resolved en face scattering maps of malignant ovaries, benign ovaries, and benign fallopian tubes obtained from 20 patients are provided to visualize the heterogeneity of ovarian tissues. Six features are extracted from histograms of scattering maps. All features are able to statistically distinguish benign from malignant ovaries. Two prediction models were constructed based on these features: a logistic regression model (LR) and a support vector machine (SVM). The optimal set of features is mean scattering coefficient and scattering map entropy. The LR achieved a sensitivity and specificity of 97.0% and 97.8%, and SVM demonstrated a sensitivity and specificity of 99.6% and 96.4%. Our initial results demonstrate the feasibility of using OCT as an “optical biopsy tool” for detecting the microscopic scattering changes associated with neoplasia in human ovarian tissue.
Construction of direct Z‐scheme g‐C3N4/TiO2 nanorod composites for promoting photocatalytic activity
Authors: Liu Mei , Wei Shaojie , Chen Wei , Gao Li , Li Xiying , Mao Liqun , Dang Haifeng
Published: July 2019

Direct Z‐scheme g‐C3N4/TiO2 nanorod composites were prepared for enhancing photocatalytic activity for pollutant removal. The characterization revealed that the g‐C3N4/TiO2 nanorod composite formed a close interface contact between g‐C3N4 and TiO2 nanorods, which was of benefit for the charge transfer and resulted in its high photocatalytic activity. The g‐C3N4/TiO2 nanorod composites exhibited higher photocatalytic activity for degradation of Rhodamine B (RHB) than bare g‐C3N4 and TiO2 nanorods. The high photocatalytic activity of g‐C3N4/TiO2 nanorod composites is attributed to the formation of the direct Z‐scheme system, in which the electrons from the conduction band (CB) of TiO2 combine with the holes from the valence band (VB) of C3N4 while the electrons from the CB of C3N4 and holes from the VB of TiO2 with stronger redox ability are used to reduce and oxidize pollutants. Based on the radical‐trapping experiments, the main reactive species for RHB degradation are O2− and ·OH, which are produced by photoinduced electrons and holes with high redox ability. This work provides insights into the photocatalytic mechanism of composite materials for the photocatalytic removal of organic pollutants.
Serum KL‐6 level is a prognostic marker in patients with anti‐MDA5 antibody‐positive dermatomyositis associated with interstitial lung disease
Authors: Ye Yan , Fu Qiong , Wang Ran , Guo Qiang , Bao Chunde
Published: July 2019

Objective

This study aimed to investigate the clinical significance of Krebs von den Lungen‐6 (KL‐6) serum levels in patients with anti‐MDA5 antibody‐positive dermatomyositis (anti‐MDA5+ DM) having interstitial lung disease (ILD), especially in the amyopathic DM phenotype.

Methods

The serum KL‐6 level was measured using a chemiluminescence enzyme immunoassay (CLEIA) in patients with anti‐MDA5+ DM, including clinically amyopathic dermatomyositis (CADM)‐ILD and classic DM‐ILD, and healthy donors. The baseline and post‐treatment serum KL‐6 levels were determined in 39 patients with CADM‐ILD who experienced remission or acute exacerbation. The association between laboratory findings, high‐resolution computed tomography (HRCT) scores, pulmonary function tests (PFTs), and the predictive value of baseline KL‐6 level for death was analyzed.

Results

The serum KL‐6 levels were significantly higher in patients with CADM‐ILD (1339 ± 1329 U/mL) compared with DM‐ILD (642.3 ± 498.4 U/mL) and healthy donors (162.4 ± 54.01 U/mL). The KL‐6 levels correlated positively with chest HRCT scores, serum lactate dehydrogenase, serum ferritin levels, and PFTs, but not with erythrocyte sedimentation rate. During follow‐up, the post‐treatment serum KL‐6 levels significantly reduced in the remission/stable group, but increased in the acute exacerbation group. Higher levels of ferritin and KL‐6 and HRCT scores were independently associated with poor prognosis. The 1‐year survival rate was significantly lower in patients with high KL‐6 level than in those with low KL‐6 level.

Conclusion

The serum KL‐6 levels may be a useful marker for predicting and monitoring ILD in Chinese patients with anti‐MDA5+ DM, especially amyopathic DM phenotype.
Rapamycin attenuates the paraquat‐induced pulmonary fibrosis through activating Nrf2 pathway
Authors: Tai Wenlin , Deng Shuhao , Wu Wenjuan , Li ZhenKun , Lei Wen , Wang Yin , Vongphouttha Chanthasone , Zhang Tao , Dong Zhaoxing
Published: July 2019

Oxidative stress is a key regulator of idiopathic pulmonary fibrosis. Paraquat (PQ)‐induced pulmonary fibrosis seriously endangers people's health. Rapamycin has been reported to alleviate PQ‐induced pulmonary fibrosis, but its underlying mechanism is unclear. The nuclear factor E2‐related factor 2 (Nrf2) plays an important regulatory role in the antioxidant therapy of PQ‐induced pulmonary fibrosis. In this study, we tried to confirm that rapamycin attenuates PQ‐induced pulmonary fibrosis by regulating Nrf2 pathway. In vivo, we proved that rapamycin could inhibit the degree of PQ‐induced oxidant stress as well as enhanced the expression of Nrf2. In vitro, rapamycin decreased the upregulated effects of cell death and apoptosis, fibrosis‐related factors expression and fibroblast‐to‐myofibroblast transformation by PQ treatment. In vivo, rapamycin treatment reduced fibrosis degree and the expression of fibrosis‐related factors in lung tissues of rat treated PQ. Furthermore, we also found that Nrf2 knockdown reduced the inhibitory effect of rapamycin on PQ‐induced pulmonary fibrosis, as well as decreased Nrf2 transfer from the cytoplasm into the nucleus. Our findings demonstrated that the protective effect of rapamycin is associated with the activation of the Nrf2 pathway in pulmonary fibrosis induced by PQ poisoning.
Numerical scheme for solving singular fractional partial integro‐differential equation via orthonormal Bernoulli polynomials
Authors: Samadyar Nasrin , Mirzaee Farshid
Published: July 2019

In this paper, an efficient matrix method based on 2D orthonormal Bernoulli polynomials are developed to obtain numerical solution of weakly singular fractional partial integro‐differential equations (FPIDEs). Operational matrix of integration, almost operational matrix of integration, and product operational matrix are employed to transform the solution of Volterra singular FPIDEs to the system of linear or nonlinear algebraic equations. The obtained algebraic system can be easily solved by using an appropriate numerical method. Also, some useful theorems concerning the convergence and error analysis associated to the mentioned approach are proven in the current paper. Finally, some numerical examples are included to illustrate the accuracy, efficiency, and applicability of the proposed approach.
Modeling of carbon nanotube ISFETs with high‐κ gate dielectrics for biosensing applications
Authors: Thakur Hiranya Ranjan , Dutta Jiten Chandra
Published: July 2019

An electrochemical model for two fabricated CNT‐ISFETs has been developed by considering all chemical and physical parameters of the device and then simulated in MATLAB environment. Model has been developed by studying on some aspects of carbon nanotube‐based ion sensitive field effect transistor (CNT‐ISFET) with two high‐κ dielectric materials (HfO2 and ZrO2) fabricated by chemical solution process at low temperature. DC experiments have been performed on pH of the solution  to determine the dependence of surface potential, threshold voltage, and drain current. Sensitivities of the devices have also been determined experimentally and found to be 57.5 and 60 mV/pH compared with theoretical values of 56.6 and 58.6 mV/pH for HfO2 and ZrO2 CNT‐ISFETs, respectively in the pH range of 5 to 9. Time domain experiments have been performed to determine the memory effects of the devices. Experiments showed drift rate of 0.52 and 0.683 mV/h at pH 7 for HfO2 and ZrO2 as gate oxides, respectively. The hysteresis widths are found to be 5.88 and 5.26 mV in a pH loop of 7 → 9 → 7 → 5 → 7 for loop time of 60 minutes, respectively, for HfO2 and ZrO2 dielectrics. The simulated results of the developed model are compared with experimentally obtained data and found to be in good agreement.
Photoactivated disinfection in periodontal treatment: A randomized controlled clinical split‐mouth trial
Authors: Husejnagic Selma , Lettner Stefan , Laky Markus , Georgopoulos Apostolos , Moritz Andreas , Rausch‐Fan Xiaohui
Published: July 2019

Background

Photoactivated disinfection (PAD) could support the periodontal treatment outcome. The effect of the light emitting diode (LED) as an innovative light source in PAD is under discussion. The aim of this study was to evaluate the clinical and microbiological effect of adjunctive PAD in the treatment of periodontitis with a red LED as light source.

Methods

Twenty patients with periodontitis completed this split‐mouth study. The left and right side of the jaws were randomly assigned to either test or control group. After conservative periodontal treatment in both groups, the test group received two sessions of adjunctive PAD (red LED, 635 nm, photosensitive dye, 0.01% tolonium chloride), whereas the control group received no adjunctive PAD. The parameters of clinical periodontal examination—including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and microbiological assays (PCR) were evaluated before and after treatment.

Results

After 3 months, both treatment groups showed significant improvements regarding BOP, PD, and CAL compared to baseline, with no significant difference between control and treatment group. The recolonization of Porphyromonas gingivalis and Treponema denticola was reduced after adjuvant treatment, but not significantly.

Conclusions

The positive effect of adjunctive PAD regarding clinical parameters was reported in recent trials. In this study and with the current settings, both treatment groups showed similar clinical results after initial periodontal treatment, without beneficial effect of adjunctive PAD.
Coherency‐Broken Bragg Filters: Overcoming On‐Chip Rejection Limitations
Authors: Oser Dorian , Mazeas Florent , Le Roux Xavier , Pérez‐Galacho Diego , Alibart Olivier , Tanzilli Sébastien , Labonté Laurent , Marris‐Morini Delphine , Vivien Laurent , Cassan Éric , Alonso‐Ramos Carlos
Published: July 2019

Selective optical filters with high rejection levels are of fundamental importance for a wide range of advanced photonic circuits. However, the implementation of high‐rejection on‐chip optical filters is seriously hampered by phase errors arising from fabrication imperfections. Due to coherent interactions, unwanted phase‐shifts result in detrimental destructive interferences that distort the filter response, whatever the chosen strategy (resonators, interferometers, Bragg filters, etc.). State‐of‐the‐art high‐rejection filters partially circumvent the sensitivity to phase errors by means of active tuning, complicating device fabrication and operation. Here, a new approach based on coherency‐broken Bragg filters is proposed to overcome this fundamental limitation. Non‐coherent interaction among modal‐engineered waveguide Bragg gratings separated by single‐mode waveguides is exploited to yield effective cascading, even in the presence of phase errors. This technologically independent approach allows seamless combination of filter stages with moderate performance free of active control, providing a dramatic increase of on‐chip rejection. Based on this concept, on‐chip non‐coherent cascading of Si Bragg filters is experimentally demonstrated, achieving a light rejection exceeding 80 dB, the largest value reported for an all‐passive silicon filter.
Nutritional Assessment in Inpatients With Cirrhosis Can Be Improved After Training and Is Associated With Lower Readmissions
Authors: Reuter Bradley , Shaw Jawaid , Hanson Jennifer , Tate Victoria , Acharya Chathur , Bajaj Jasmohan S.
Published: July 2019

Malnutrition is widely prevalent in cirrhosis patients, which can worsen sarcopenia, hepatic encephalopathy (HE), and overall prognosis. We aimed to define the frequency of nutritional assessments of patients with cirrhosis in retrospective and prospective (after educational training) cohorts and to evaluate prospective changes along with their effects on 90‐day readmissions. This study was conducted in 2 phases. Retrospectively, records of hospitalized patients with cirrhosis from the university and Veterans Affairs Medical Center (VAMC) settings were reviewed to assess nutritional status, if a nutrition consultation occurred, the number of days patients were nil per os (npo) and received inadequate nutrition, and if nutritional management was guideline directed. In the prospective phase, after dedicated educational efforts directed at the stakeholders regarding nutritional guidelines for patients with cirrhosis, subsequently hospitalized cirrhosis patients had nutritional and 90‐day readmission data collected for comparison between groups. In total, 279 patients were included in the retrospective phase (150 university/129 VAMC), and 102 VAMC patients were in the prospective phase. Cirrhosis severity, reason for admission, and hospital course were similar between groups regardless of cohort, ie, prospective versus retrospective or VAMC versus university. The prospective group had significantly more nutritional consultations and assessments (74.5% versus 40.1%; P < 0.001) compared with the retrospective group regardless of comparisons between the VAMC and university cohorts. Both groups had a similar number of days npo, but the prospective group had fewer days of inadequate nutrition. The 90‐day readmission rate was significantly lower in the prospective group versus the retrospective group (39.4% versus 28.4%; P = 0.04), which was associated with greater nutrition outpatient follow‐up. In conclusion, nutritional consultation rates in inpatients with cirrhosis can be significantly improved after educational intervention and is associated with lower 90‐day readmission rates.
Addition Polyalkylnorbornenes: A Promising New Class of Si‐Free Membrane Materials for Hydrocarbons Separation
Authors: Wozniak Alyona I. , Bermesheva Evgeniya V. , Borisov Ilya L. , Petukhov Dmitrii I. , Bermeshev Maxim V. , Volkov Alexey V. , Finkelshtein Eugene Sh.
Published: July 2019

Nanoporous glassy polymers are perspective materials for the fabrication of gas separation membranes, especially for the application of gaseous hydrocarbon separation. However, the drawback of such materials is the pronounced physical aging resulting in the dramatic drop of gas transport properties due to relaxation of high‐free‐volume fraction in time. Herein, a novel and readily available group of such glassy polymers is reported based on 5‐alkylnorbornenes. These polymers are easily synthesized from dicyclopentadiene and α‐olefins by Diels‐Alder reaction and vinyl (addition) polymerization of the formed cycloadducts in the presence of ([(η3‐C3H5)PdCl]2/PCy3/Na+[B(3,5‐(CF3)2C6H3)4]− catalyst. The obtained polymers display low‐fraction free volume, stable gas permeability over time, and possess a unique feature for the glassy polymers—solubility controlled permeation of hydrocarbons and enhanced C4H10/CH4 selectivity.
Patients want WHO descriptions to capture lived experience
Authors: Canady Valerie A.
Published: July 2019

Observing a need to gain the perspective of service users across international contexts, U.K. and U.S. researchers found that mental health patients want diagnostic descriptions that better reflect what it feels like to live with their conditions. Those feelings should be included in the World Health Organization's (WHO's) global manual of diagnoses — the International Classification of Diseases (ICD), new research states.
Emergent dynamics of the first‐order stochastic Cucker‐Smale model and application to finance
Authors: Bae Hyeong‐Ohk , Ha Seung‐Yeal , Kim Doheon , Kim Yongsik , Lim Hyuncheul , Yoo Jane
Published: July 2019

In this paper, we study stochastic aggregation properties of the financial model for the N‐asset price process whose dynamics is modeled by the weakly geometric Brownian motions with stochastic drifts. For the temporal evolution of stochastic components of drift coefficients, we employ a stochastic first‐order Cucker‐Smale model with additive noises. The asset price processes are weakly interacting via the stochastic components of drift coefficients. For the aggregation estimates, we use the macro‐micro decomposition of the fluctuations around the average process and show that the fluctuations around the average value satisfies a practical aggregation estimate over a time‐independent symmetric network topology so that we can control the differences of drift coefficients by tuning the coupling strength. We provide numerical examples and compare them with our analytical results. We also discuss some financial implications of our proposed model.
Numerical investigation of dual‐pumped optical frequency combs based on silicon‐on‐insulator microring resonator
Authors: Wen Jin , Duan Lina , Ma Chengju , Fan Wei
Published: July 2019

Dual‐pumped optical frequency combs (OFCs) based on silicon‐on‐insulator (SOI) microring and their characteristics are numerically investigated. This indicates that a relative low pump power is required to generate the comb modes effectively due to the high Q factor and large nonlinearity of the SOI microring. The number of generated comb modes reaches to 28, and the spacing of comb modes is over 300 nm. As the pump power enhances to 12 dBm, the bandwidth of the OFCs (over 800 nm) and the number of the comb modes (over 64) ranged from the infrared to mid‐infrared wavelength region. Correspondingly, the field profile of the OFCs changes to irregular shape when the pump power increases. Meanwhile, it has been found that the intensity of the pedestal of the OFC is above −150 dBm when the Gaussian noise is introduced, which reduced the bandwidth and modes of the OFCs by affecting the pump powers' transferring efficiency. The OFCs based on SOI microring can be found applications in chip‐scale oscillations, waveform generation, and ultrafast spectroscopy.
Extracting tree structures in CT data by tracking multiple statistically ranked hypotheses
Authors: Selvan Raghavendra , Petersen Jens , Pedersen Jesper H. , de Bruijne Marleen
Published: July 2019

Purpose

In this work, we adapt a method based on multiple hypothesis tracking (MHT) that has been shown to give state‐of‐the‐art vessel segmentation results in interactive settings, for the purpose of extracting trees.

Methods

Regularly spaced tubular templates are fit to image data forming local hypotheses. These local hypotheses are then used to construct the MHT tree, which is then traversed to make segmentation decisions. Some critical parameters in the method, we base ours on, are scale‐dependent and have an adverse effect when tracking structures of varying dimensions. We propose to use statistical ranking of local hypotheses in constructing the MHT tree which yields a probabilistic interpretation of scores across scales and helps alleviate the scale dependence of MHT parameters. This enables our method to track trees starting from a single seed point.

Results

The proposed method is evaluated on chest computed tomography data to extract airway trees and coronary arteries and compared to relevant baselines. In both cases, we show that our method performs significantly better than the Original MHT method in semiautomatic setting.

Conclusions

The statistical ranking of local hypotheses introduced allows the MHT method to be used in noninteractive settings yielding competitive results for segmenting tree structures.
IC/BPS‐associated alterations of M2 and M3 muscarinic acetylcholine receptor trafficking in human detrusor
Authors: Berndt‐Paetz Mandy , Herbst Luise , Weimann Annett , Gonsior Andreas , Stolzenburg Jens‐Uwe , Neuhaus Jochen
Published: July 2019

Aims

To explore caveolae‐ and clathrin‐mediated internalization of muscarinic M2 and M3 receptors, recycling and degradation in formalin‐fixed paraffin‐embedded detrusor sections; to study alterations possibly involved in the pathophysiology of the bladder functional disorder, interstitial cystitis/bladder pain syndrome (IC/BPS).

Materials and Methods

Samples of IC/BPS (n = 11) and cystectomy patients (n = 11) were analyzed. Proximity ligation assay (PLA) was used to detect interactions of M2 and M3 with endocytotic regulators (Cav‐1, clathrin, Rab7, and Rab11) by Cy3 labeling. Analyses of three‐dimensional (3D)‐reconstructed z‐stacks (63 ×  Oil 1.4) were done with Huygens software. We determined the object density for quantification and assessed membrane localization.

Results

Receptor/protein complexes were detected as well‐demarcated 3D objects. Interactions of M2 with Cav‐1, clathrin, Rab11, and Rab7 were significantly increased in IC/BPS. M3/clathrin and M3/Rab11 complexes were higher in IC/BPS, while M3/Cav‐1 and M3/Rab7 were not. A significant shift of complexes from the membrane to cytoplasm was observed in conjunction with increased internalization via clathrin vesicles or caveolae in IC/BPS.

Conclusions

High numbers of M3/clathrin and M3/Rab11 complexes reflect the well‐documented clathrin‐mediated desensitization of M3 and speak in favor with enhanced receptor protein expression in IC/BPS. Increased amounts of M2/Cav‐1, M2/clathrin, and M2/Rab11 complexes represent altered M2 internalization and recycling leading to high abundance in IC/BPS. In this regard, caveolae‐localized M2 could be possibly associated with the activation of nitric oxide (NO) synthase and NO production.
The Role of Political Activity in the Formation of Online Identity Bubbles
Authors: Koivula Aki , Kaakinen Markus , Oksanen Atte , Räsänen Pekka
Published: July 2019

Increasing social media use has transformed political participation by creating social cliques and echo chambers, which involve interaction between like‐minded people. This article examines the relationship between online political activity and personal involvement in online identity bubbles. This study is the first to examine this phenomenon using nationally representative data; its data were derived from surveys targeted at 18–74‐year‐old Finns (N = 3,724). Measures included online political activity, the Identity Bubble Reinforcement Scale, and behavioral and demographic factors. The results show that online political activity was positively associated with online identity bubbles. This effect was strong even after controlling for behavioral and demographic factors. In addition to online political activity, general online activity, online network size, and basic sociodemographic background variables explained variation of involvement in online identity bubbles. However, neither political preference nor political interest had a systematic effect on involvement in these bubbles. The findings confirm the theoretical assumption that online bubbles can be captured using subjective survey measures. Political activity appears to be a key factor associated with the strength of the online bubble experience. This finding has significance in the contemporary information society, in which various mundane discussions and cultural disputes become politically tinged.
The cysteine‐free single mutant C32S of APEX2 is a highly expressed and active fusion tag for proximity labeling applications
Authors: Huang Meng‐Sen , Lin Wen‐Ching , Chang Jen‐Hsuan , Cheng Cheng‐Hung , Wang Han Ying , Mou Kurt Yun
Published: July 2019

APEX2, an engineered ascorbate peroxidase for high activity, is a powerful tool for proximity labeling applications. Owing to its lack of disulfides and the calcium‐independent activity, APEX2 can be applied intracellularly for targeted electron microscopy imaging or interactome mapping when fusing to a protein of interest. However, APEX2 fusion is often deleterious to the protein expression, which seriously hampers its wide utility. This problem is especially compelling when APEX2 is fused to structurally delicate proteins, such as multi‐pass membrane proteins. In this study, we found that a cysteine‐free single mutant C32S of APEX2 dramatically improved the expression of fusion proteins in mammalian cells without compromising the enzyme activity. We fused APEX2 and APEX2C32S to four multi‐transmembrane solute carriers (SLCs), SLC1A5, SLC6A5, SLC6A14, and SLC7A1, and compared their expressions in stable HEK293T cell lines. Except the SLC6A5 fusions expressing at decent levels for both APEX2 (70%) and APEX2C32S (73%), other three SLC proteins showed significantly better expression when fusing to APEX2C32S (69 ± 13%) than APEX2 (29 ± 15%). Immunofluorescence and western blot experiments showed correct plasma membrane localization and strong proximity labeling efficiency in all four SLC‐APEX2C32S cells. Enzyme kinetic experiments revealed that APEX2 and APEX2C32S have comparable activities in terms of oxidizing guaiacol. Overall, we believe APEX2C32S is a superior fusion tag to APEX2 for proximity labeling applications, especially when mismatched disulfide bonding or poor expression is a concern.
Circular zymogens of human ribonuclease 1
Authors: Windsor Ian W. , Graff Crystal J. , Raines Ronald T.
Published: July 2019

The endogenous production of enzymes as zymogens provides a means to control catalytic activities. Here, we describe the heterologous production of ribonuclease 1 (RNase 1), which is the most prevalent secretory ribonuclease in humans, as a zymogen. In folded RNase 1, the N and C termini flank the enzymic active site. By using intein‐mediated cis‐splicing, we created circular proteins in which access to the active site of RNase 1 is obstructed by an amino‐acid sequence that is recognized by the HIV‐1 protease. Installing a sequence that does not perturb the RNase 1 fold led to only modest inactivation. In contrast, the ancillary truncation of residues from each terminus led to a substantial decrease in the catalytic activity of the zymogen with the maintenance of thermostability. For optimized zymogens, activation by HIV‐1 protease led to a > 104‐fold increase in ribonucleolytic activity at a rate comparable to that for the cleavage of endogenous viral substrates. Molecular modeling indicated that these zymogens are inactivated by conformational distortion in addition to substrate occlusion. Because protease levels are elevated in many disease states and ribonucleolytic activity can be cytotoxic, RNase 1 zymogens have potential as generalizable prodrugs.
Effect of the Local Environment on the Magnetic Properties of Mn3Si: Hybrid Ab Initio and Model Study
Authors: Draganyuk Oksana N. , Zhandun Vyacheslav S. , Zamkova Natalia G.
Published: July 2019

The effect of the local environment on the formation of magnetic moments on Mn atoms in manganese silicide Mn3Si is studied by the combination of ab initio calculations and the model analysis. The suggested approach is related to the self‐consistent mapping of the results of ab initio calculations to a multiorbital model. The model analysis allows to reveal the role played by the local environment of the transition metal atoms on the magnetic moments formation. It is found that the formation of the magnetic moment is controlled rather by hopping parameters between Mn atoms, not by the number of Mn–Si nearest neighbors. Particularly, the formation of magnetic moment on MnI atom is mainly controlled by the hopping parameter between nearest Mn atoms, while the magnetic moment on MnII atom is primarily determined by the hoppings between next‐nearest Mn atoms. The obtained phase diagrams of the magnetic state show the presence of a sharp boundary with respect to the hopping between Mn atoms. This opens the opportunity to turn on or turn off the magnetic state by the external impacts. The ab initio calculations of Mn3Si well agree with the results of model consideration and confirm the model conclusions.
Statistical postprocessing of dual‐resolution ensemble precipitation forecasts across Europe
Authors: Gascón Estíbaliz , Lavers David , Hamill Thomas M. , Richardson David S. , Ben Bouallègue Zied , Leutbecher Martin , Pappenberger Florian
Published: July 2019

This article verifies 1‐ to 10‐day probabilistic precipitation forecasts in June, July, and August 2016 from an experimental dual‐resolution version of the European Centre for Medium‐Range Weather Forecasts (ECMWF) ensemble prediction system. Five different ensemble combinations were tested. These comprised subsets of the 51‐member operational ECMWF configuration (18‐km grid) and an experimental 201‐member lower‐resolution configuration (29‐km grid). The motivation of the dual‐resolution ensemble forecast is to trade some higher‐resolution members against a larger number of lower‐resolution members to increase the overall ensemble size at constant overall computational cost. Forecasts were verified against precipitation analyses over Europe. Given substantial systematic errors of precipitation forecasts, both raw and post‐processed dual‐resolution ensemble predictions were evaluated. Postprocessing consisted of quantile mapping, tested with and without an objective weighting of sorted ensemble members using closest‐member histogram statistics. Reforecasts and retrospective precipitation analyses were used as training data. However, the reforecast ensemble size and the dual‐resolution ensemble sizes differed, which motivated the development of a novel approach for developing closest‐member histogram statistics for the larger real‐time ensemble from the smaller reforecast ensemble. Results show that the most skilful combination was generally 40 ensemble members from the operational configuration and 40 from the lower‐resolution ensemble, evaluated by continuous ranked probability scores, Brier Scores at various thresholds, and reliability diagrams. This conclusion was generally valid with and without postprocessing. Reliability was improved by postprocessing, though the improvement of the resolution component is not so clear. The advantages of many members at higher resolution was diminished at longer lead times; predictability of smaller scale features was lost, and there is more benefit in increasing the ensemble size to reduce sampling uncertainty. This article evaluates only one aspect in deciding on any future ensemble configuration, and other skill‐related considerations need to be taken into account.
Identifying and interpreting subgroups in health care utilization data with count mixture regression models
Authors: Kurz Christoph F. , Hatfield Laura A.
Published: July 2019

Inpatient care is a large share of total health care spending, making analysis of inpatient utilization patterns an important part of understanding what drives health care spending growth. Common features of inpatient utilization measures such as length of stay and spending include zero inflation, overdispersion, and skewness, all of which complicate statistical modeling. Moreover, latent subgroups of patients may have distinct patterns of utilization and relationships between that utilization and observed covariates. In this work, we apply and compare likelihood‐based and parametric Bayesian mixtures of negative binomial and zero‐inflated negative binomial regression models. In a simulation, we find that the Bayesian approach finds the true number of mixture components more accurately than using information criteria to select among likelihood‐based finite mixture models. When we apply the models to data on hospital lengths of stay for patients with lung cancer, we find distinct subgroups of patients with different means and variances of hospital days, health and treatment covariates, and relationships between covariates and length of stay.