bluuebunny/crossref_metadata_2025 huggingface dataset:
Occurrence of severe hypoglycaemic events among US youth and young adults with type 1 or type 2 diabetes
Authors: Saydah Sharon , Imperatore Giuseppina , Divers Jasmin , Bell Ronny , Henkin Leora , Mayer‐Davis Elizabeth , Zhong Victor W. , Dabelea Dana , Lawrence Jean M. , Pihoker Catherine
Published: January 2019

Objective

Although severe hypoglycaemia (SH) can lead to adverse health outcomes, little is known about its occurrence and re‐occurrence among youth with type 1 or type 2 diabetes.

Methods

This study included 2740 participants aged <20 years at diabetes diagnosis and 5‐14 years diabetes duration from the SEARCH for Diabetes in Youth Cohort Study. Participants reported SH events in the past 6 months. Differences in SH events by demographic and clinical factors were tested using logistic regression models.

Results

Severe hypoglycaemia in the past 6 months was more common among youth with type 1 (7.0%, 168 of 2399) than with type 2 diabetes (2.6%, nine of 341) (P < 0.002). The median number of SH events per youth who had at least one SH event in the past 6 months was 1 for both type 1 type 2 diabetes. For youth with type 1 diabetes, those who reported SH events were older, were more likely to have obesity or to be physically active, and had lower HbA1c. After adjustments, one unit increase in HbA1c was associated with 16% lower likelihood (OR 0.84, 95% CI 0.75, 0.94) and being physically active was associated with an 87% higher likelihood (OR 1.87, 95% CI 1.23, 2.86) of reporting a SH event. There were too few SH events among youth with type 2 diabetes to analyse further.

Conclusions

In youth with diabetes, SH was common even within a short 6‐month window. Better understanding the causes of SH may help prevent them from occurring.
Haemodynamic profiles in adult Fontan patients: associated haemodynamics and prognosis
Authors: Miranda William R. , Borlaug Barry A. , Hagler Donald J. , Connolly Heidi M. , Egbe Alexander C.
Published: January 2019

Aims

The Fontan operation is associated with significant long‐term morbidity and mortality, posing challenges in management. No haemodynamic classification has been established to aid management and prognostication of patients with Fontan palliation. Our aim was to assess haemodynamic profiles for Fontan patients and evaluate their relationships to prognosis.

Methods and results

Eighty‐four adult Fontan patients without obstruction or significant valve disease undergoing cardiac catheterization for Fontan‐related co‐morbidities were divided into four different haemodynamic profiles based on normal/high Fontan pressures (FP) (< 15 or ≥ 15 mmHg) and low/normal cardiac index (CI) (< 2.5 or ≥ 2.5 L/min/m2). Fourteen patients had low CI/high FP (17%), 24 low CI/normal FP (29%), 20 normal CI/high FP (24%), and 26 normal CI/normal FP (31%). Demographic and clinical data were similar among groups except for a trend towards a higher prevalence of cirrhosis in the normal CI/high FP (50%) group. Systemic vascular afterload, assessed by systemic vascular resistance and effective arterial elastance, was higher in patients with low CI/high FP and low CI/normal FP as compared to normal CI profiles. Pulmonary vascular resistance indices were higher in patients with low CI/high FP than all other profiles. The normal CI/high FP haemodynamic profile was an independent predictor of mortality (hazard ratio 4.1, 95% confidence interval 1.2–11.5). Heterotaxy and protein‐losing enteropathy were also predictors of mortality on the multivariate model.

Conclusion

The proposed haemodynamic classification provides prognostic information in adults post‐Fontan with patients in the normal CI/high FP profile having worse survival. Whether this classification can guide management in these patients deserves further investigation.
Optimization of Solution Condition for an Effective Electrochemical Reduction of N2O
Authors: Kwon Oh Sung , Baek Seungyeon , Kim Hyeonsu , Choi Insoo , Kwon Oh Joong , Kim Jae Jeong
Published: January 2019

An effective electrochemical reduction of nitrous oxide (N2O) is established by controlling solution compositions in this study. N2O was electrochemically reduced varying solvent composition and supporting electrolytes (K2SO4 and Na2SO4) concentrations. The differences in reduction current density and solution resistance were analyzed via linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS), respectively, depending on solution conditions. UV‐Vis spectroscopy was adopted to measure the solubility of N2O. As a result, among the conditions investigated in this study, 300 mM of K2SO4 and aqueous based solution were revealed as an optimum condition for the electrochemical N2O reduction. At 300 mM of K2SO4, the highest current density was obtained due to a high conductance of the electrolyte and a moderate solubility of N2O.
Selective detection of cytochrome C by microchip electrophoresis based on an aptamer strategy
Authors: Zhu Luqi , Luo Feifei , Li Zhi , Dai Ge , He Pingang , Wang Qingjiang , Chen Qiming
Published: January 2019

The release of cytochrome C (Cyt C) plays an important role in apoptosis. In this study, selective and sensitive detection of Cyt C based on an aptamer strategy coupled with MCE was developed. Following the binding of a specific aptamer to Cyt C, the aptamer exhibited an irregular state, reducing the binding affinity of a fluorescent probe, and thus preventing the aptamer‐Cyt C complexes from detection within the MCE. The height of the detection peak of the residual aptamer linearly decreased, and therefore, the difference in peak height of residual aptamer compared to that of the initial aptamer was used to quantify the captured protein concentration. Experimental conditions such as incubation time, pH, temperature, and ionic strength were optimized. A measurement of Cyt C concentration by MCE was achieved within 135 s, with a limit of detection as low as 0.4 nM. The proposed method has high selectivity and good stability for the detection of Cyt C. The experimental results demonstrate that this method is quick, consumes only a small quantity of sample, is highly selectivity and exhibits high sensitivity.
Design of a high‐efficiency synthetic system for l‐asparaginase production in Bacillus subtilis
Authors: Li Xu , Xu Shuqin , Zhang Xian , Xu Meijuan , Yang Taowei , Wang Li , Zhang Huiling , Fang Haitian , Osire Tolbert , Yang Shangtian , Rao Zhiming
Published: January 2019

l‐asparaginase has high application value in medicine and food industry, but the low yield limits its application. In this study, we designed a synthetic system in Bacillus subtilis to produce l‐asparaginase by improving gene expression and optimizing the fermentation agitation speed. Gene expression was improved by respectively increasing transcription levels and translation speeds through screening promoters and RBS sequences. With the optimal promoter, P43, and the synthetic RBS sequence, the yield obtained in a shake flask was 371.87 U/mL, which was 2.09 times that with the original strain. To further enhance production in a 5‐L fermenter, a multistage agitation speed control strategy was adopted, involving agitation at 600 rpm for the first 12 h, followed by a gradual increase in speed to 900 rpm, which resulted in the highest yield of l‐asparaginase, 5321 U/mL, after 42 h of fermentation.
Microbial quality of reduced‐sodium napa cabbage kimchi and its processing
Authors: Song Won‐Jae , Chung Ha‐Yull , Kang Dong‐Hyun , Ha Jae‐Won
Published: January 2019

This study evaluated the microbial safety of reduced‐sodium napa cabbage kimchi products by comparing with conventional kimchi samples. Five commercial kimchi samples were collected from different manufacturers in Korea. Total aerobic plate counts and coliforms counts between regular and reduced‐sodium kimchi were not significantly (p > 0.05) different and major foodborne pathogens, including Escherichia coli O157:H7, Salmonella spp., Listeria monocytogenes, Staphylococcus aureus, and Yersinia enterocolitica were not detected in any sample. Bacillus cereus contamination among all kimchi samples was less than the regulation level (3.0 log CFU/g). However, high levels of coliforms were observed in both types of samples. To investigate microbial hazards of kimchi processing, we analyzed specific kimchi production processes and found five control points which can reduce coliform levels in kimchi samples. The results of this study could be helpful for the kimchi industry to produce safe reduced‐sodium kimchi products.
Effects of 1‐methylcyclopropene on the quality attributes of harvested Chinese mushroom (Volvariella volvacea) fruiting bodies
Authors: Chen Bingzhi , Wu Guohong , Li Ling , Wei Qi , Zhong Qiangui , Chen Xiaoning , Xiao Kaiqian , Xie Baogui , Jiang Yuji
Published: January 2019

The effects of paper containing different concentrations of 1‐methylcyclopropene (1‐MCP) on the quality of Chinese mushrooms were investigated. Mushrooms were first stored with paper containing 0, 0.25, 0.50, 0.75, 1.00, or 1.25 μl L−1 1‐MCP at 15 ± 1°C for 12 hr and then continued for up to 8 days. 1‐MCP reduced the respiratory peak, weight loss, degree of cap browning, relative leakage rate, and soluble solid content, and delayed the change in the surface hue angle. Mushrooms exposed to paper containing 1‐MCP maintained firmness and sensory attributes. The storage time of Chinese mushrooms treated with 1‐MCP at the best concentration (0.75 μl L−1) was 8 days, which was 4 days longer than that of the control. Browning in mushrooms was related to the vitamin C content, total phenol content, and polyphenol oxidase activity. The results would be very useful to the mushroom industry and provide a theoretical basis for the potential researches of the mechanisms maturation and senescence in Chinese mushrooms.
A large‐scale exome array analysis of venous thromboembolism
Authors: Lindström Sara , Brody Jennifer A. , Turman Constance , Germain Marine , Bartz Traci M. , Smith Erin N. , Chen Ming‐Huei , Puurunen Marja , Chasman Daniel , Hassler Jeffrey , Pankratz Nathan , Basu Saonli , Guan Weihua , Gyorgy Beata , Ibrahim Manal , Empana Jean‐Philippe , Olaso Robert , Jackson Rebecca , Brækkan Sigrid K. , McKnight Barbara , Deleuze Jean‐Francois , O’Donnell Cristopher J. , Jouven Xavier , Frazer Kelly A. , Psaty Bruce M. , Wiggins Kerri L. , Taylor Kent , Reiner Alexander P. , Heckbert Susan R. , Kooperberg Charles , Ridker Paul , Hansen John‐Bjarne , Tang Weihong , Johnson Andrew D. , Morange Pierre‐Emmanuel , Trégouët David A. , Kraft Peter , Smith Nicholas L. , Kabrhel Christopher ,   on behalf of the INVENT Consortium
Published: January 2019

Although recent Genome‐Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome‐wide search for low‐frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta‐analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene‐based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] ~0.08%). We confirmed associations with previously identified VTE loci, including ABO,
F5,
F11, and
FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene‐based analysis. Given our sample size, we had greater than 80% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low‐frequency and rare variants associated with VTE risk.
Ethnic differences in cognition and age in people diagnosed with dementia: A study of electronic health records in two large mental healthcare providers
Authors: Mukadam Naaheed , Lewis Gemma , Mueller Christoph , Werbeloff Nomi , Stewart Robert , Livingston Gill
Published: January 2019

Objectives

Qualitative studies suggest that people from UK minority ethnic groups with dementia access health services later in the illness than white UK‐born elders, but there are no large quantitative studies investigating this. We aimed to investigate interethnic differences in cognitive scores and age at dementia diagnosis.

Methods

We used the Clinical Record Interactive Search (CRIS) applied to the electronic health records of two London mental health trusts to identify patients diagnosed with dementia between 2008 and 2016. We meta‐analysed mean Mini Mental State Examination (MMSE) and mean age at the time of diagnosis across trusts for the most common ethnic groups, and used linear regression models to test these associations before and after adjustment for age, sex, index of multiple deprivation, and marital status. We also compared percentage of referrals for each ethnic group with catchment census distributions.

Results

Compared with white patients (N = 9380), unadjusted mean MMSE scores were lower in Asian (−1.25; 95% CI −1.79, −0.71; N = 642) and black patients (−1.82, 95% CI −2.13, −1.52; N = 2008) as was mean age at diagnosis (Asian patients: −4.27 (−4.92, −3.61); black patients −3.70 (−4.13, −3.27) years). These differences persisted after adjustment. In general, ethnic group distributions in referrals did not differ substantially from those expected in the catchments.

Conclusions

People from black and Asian groups were younger at dementia diagnosis and had lower MMSE scores than white referrals.
The impact of apathy on cognitive performance in the elderly
Authors: Montoya‐Murillo Genoveva , Ibarretxe‐Bilbao Naroa , Peña Javier , Ojeda Natalia
Published: January 2019

Objectives

To examine the impact of apathy on cognitive performance in the elderly following the conceptual principles proposed by Marin1 and Stuss et al2 and to determine the role of the symptoms of apathy in different cognitive domains.

Methods

Cross‐sectional study with a cohort of healthy elderly subjects over 55 years old (n = 140). One hundred forty healthy‐elderly subjects (aged 79.24 ± 8.6 years old) were recruited from 12 day centers in Northern Spain. Participants underwent a neuropsychological battery, which evaluated Mini Mental State Examination (MMSE), attention, processing speed, verbal fluency, visual and verbal memory, working memory, and executive functioning. Apathy was assessed by the Lille Apathy Rating Scale (LARS), which is composed of four factors: intellectual curiosity, emotion, action initiation, and self‐awareness. Correlation and linear regression analyses were performed.

Results

In the correlational analysis, the LARS total score correlated negatively with global cognition, verbal fluency, and visual and verbal memory. The intellectual curiosity factor correlated negatively with all cognitive domains except attention. The emotion factor correlated negatively with visual memory. No correlation was found between the action initiation and self‐awareness factors or any of the cognitive variables. Multiple stepwise regression analysis showed that symptoms of apathy explained cognitive performance in attention, processing speed, verbal fluency, visual and verbal memory, working memory, executive functioning, and MMSE.

Conclusions

Apathy was significantly associated with cognitive performance, especially with the intellectual curiosity factor. Our results suggest that specific symptoms of apathy contribute differently to individual cognitive domains.
An average sliding window correlation method for dynamic functional connectivity
Authors: Vergara Victor M. , Abrol Anees , Calhoun Vince D.
Published: January 2019

Sliding window correlation (SWC) is utilized in many studies to analyze the temporal characteristics of brain connectivity. However, spurious artifacts have been reported in simulated data using this technique. Several suggestions have been made through the development of the SWC technique. Recently, it has been proposed to utilize a SWC window length of 100 s given that the lowest nominal fMRI frequency is 0.01 Hz. The main pitfall is the loss of temporal resolution due to a large window length. In this work, we propose an average sliding window correlation (ASWC) approach that presents several advantages over the SWC. One advantage is the requirement for a smaller window length. This is important because shorter lengths allow for a more accurate estimation of transient dynamicity of functional connectivity. Another advantage is the behavior of ASWC as a tunable high pass filter. We demonstrate the advantages of ASWC over SWC using simulated signals with configurable functional connectivity dynamics. We present analytical models explaining the behavior of ASWC and SWC for several dynamic connectivity cases. We also include a real data example to demonstrate the application of the new method. In summary, ASWC shows lower artifacts and resolves faster transient connectivity fluctuations, resulting in a lower mean square error than in SWC.
Impact of tumor‐associated macrophages and BRAFV600E mutation on clinical outcomes in patients with various thyroid cancers
Authors: Cho Jae Won , Kim Won Woong , Lee Yu‐mi , Jeon Min Ji , Kim Won Gu , Song Dong Eun , Park Yangsoon , Chung Ki‐Wook , Hong Suck Joon , Sung Tae‐Yon
Published: January 2019

Background

Tumor‐associated macrophages (TAMs) play a role in thyroid cancer tumor progression and metastasis. This study aimed to investigate the association of TAM density and cluster of differentiation 68 (CD68) expression with thyroid tumors as a prognostic marker and the relationship of these factors with BRAFV600E mutations.

Methods

This study included 275 thyroid specimen tissues, including benign and malignant lesions. We compared the clinicopathological features according to thyroid tumor types and evaluated the presence of CD68 expression and BRAFV600E mutations.

Results

CD68 positive expression increased with aggressiveness of thyroid tumor histologic grades (P < 0.001). In patients with poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), CD68 positivity was associated with aggressive adverse clinical outcomes such as extrathyroidal extension, cervical lymph node metastases, and distant metastases (P < 0.05).

Conclusions

CD68 positivity was more frequent in advanced and aggressive thyroid cancer types such as PDTC/ATC.
A critical analysis of the prognostic performance of the 8th edition American Joint Committee on Cancer staging for metastatic cutaneous squamous cell carcinoma of the head and neck
Authors: Sood Ashish , Wykes James , Roshan David , Wang Laura Y. , McGuinness John , Fowler Allan , Ebrahimi Ardalan
Published: January 2019

Background

The 8th edition AJCC staging of cutaneous squamous cell carcinoma of the head and neck (cSCCHN) incorporated extranodal extension (ENE) for the first time. This study compared the prognostic performance of the 7th and 8th edition staging for cSCCHN with nodal metastases.

Methods

Retrospective analysis of 96 patients with metastatic cSCCHN, comparing the ability of staging systems to predict disease‐specific and overall survival (OS) using the proportion of variation explained and Harrell's C‐index.

Results

In AJCC8, the N classification was upstaged in 77% of patients due to the presence of ENE and 88% of patients were classified as TNM stage IV. AJCC8 was inferior to AJCC7 in predicting disease‐specific survival for both N and TNM stages, and OS by TNM stage.

Conclusions

The majority of patients with metastatic cSCCHN have ENE and are classified as TNM stage IV based on the 8th edition staging, resulting in poor prognostic performance.
Bilateral vs ipsilateral adjuvant radiotherapy in patients with cancer of unknown primary of the head and neck: An analysis of the clinical outcome and radiation‐induced side effects
Authors: Le Nguyen‐Son , Janik Stefan , Simmel Helmut , Erovic Boban M.
Published: January 2019

Background

The purpose of this study was to analyze and compare ipsilateral and bilateral adjuvant radiotherapy in patients with cancer of unknown primary (CUP) of the head and neck.

Methods

Overall survival, recurrence‐free survival, and radiation‐induced side effects were assessed in 76 patients with CUP who underwent ipsilateral (n = 29) or bilateral (n = 47) radiotherapy.

Results

At a median follow‐up of 41 months, the 5‐year overall survival and recurrence‐free rate were 67.9% and 71.5%, respectively. No statistically significant difference between ipsilateral and bilateral radiotherapy could be found regarding 5‐year overall survival, recurrence‐free survival, occurrence of a primary tumor, and distant metastasis. The analysis of radiation‐induced acute side effects showed a significant benefit of ipsilateral radiotherapy.

Conclusion

As the main parameters of the study regarding the outcome and radiation‐induced side effects showed no advantages of bilateral radiotherapy, the strategy of ipsilateral radiotherapy can be recommended for the adjuvant treatment of CUP patients.
Circular RNA circ‐PRKCI functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR‐3680‐3p in esophageal squamous cell carcinoma
Authors: Shi Naiming , Shan Ben , Gu Biao , Song Yaqi , Chu Hongjun , Qian Long
Published: January 2019

Circular RNA (circRNA) is a new noncoding RNAs and plays an important role in many pathological processes. Recently, studies have shown that circular RNA_PRKCI (circ‐PRKCI) regulates cell proliferation and cell migration of tumor cells. Esophageal carcinoma is a highly malignant digestive tract tumor, which is divided into esophageal adenocarcinoma and esophageal squamous cell carcinoma. In this study, we studied whether circ‐PRKCI might influence cell proliferation and cell migration in esophageal squamous cell carcinoma. Quantitative reverse transcription PCR was performed to detect the relative expression of circ‐PRKCI in five cases of esophageal squamous cell carcinoma and five cases of paired adjacent normal tissues. RNA immunoprecipitation assay and Luciferase assay confirm the direct interaction between miR‐3680‐3p and AKT3 or circ‐PRKCI. Ethynyldeoxyuridine assays and cell counting Kit‐8 were performed to evaluate the effect of miR‐3680‐3p or circ‐PRKCI on cell proliferation, transwell assays were also performed to detect migration in vitro. We found circ‐PRKCI is obviously upregulated in esophageal squamous cell carcinoma and upregulation of circ‐PRKCI stimulated cell migration and proliferation of ESCC cells. In the mechanism, we confirm that circ‐PRKCI, as a molecular sponge of miR‐3680‐3p, upregulates the expression of AKT. In conclusion, our current studies have been revealing that circ‐PRKCI/miR‐3680‐3p/AKT3 regulatory network plays an important role in esophageal squamous cell carcinoma and that provide new insights into the pathogenesis of esophageal squamous cell carcinoma.
Progesterone ameliorates the endometrial polyp by modulating the signaling pathway of Wnt and β‐catenin via regulating the expression of H19 and miR‐152
Authors: Feng Meining , Zhang Tongmei , Ma Huiping
Published: January 2019

Background

MicroRNAs and long noncoding RNAs are believed to play important roles in the pathogenesis of various diseases. This study aimed to explore the potential mechanism of the involvement of H19 and miR‐152 in an endometrial polyp.

Methods

Luciferase assay was conducted to determine the effect of progesterone. Real‐time polymerase chain reaction (PCR) and western blot were performed to detect the influence of progesterone on miR‐152 and Wnt1. MTT assay and flow cytometry (FCM) were utilized to detect the effect of progesterone on cell proliferation and apoptosis. In silicon analysis, luciferase assay, real‐time PCR, and immunohistochemistry (IHC) were performed to explore the regulatory relationship between H19 and miR‐152 or miR‐152 and Wnt1.

Results

Progesterone dose‐dependently increased the H19 expression level through driving the promoter efficiency of H19. Then, progesterone upregulated Wnt1 level and downregulated miR‐152 in a dose‐dependent manner in ECC1 and HEC1A cells. Administration of progesterone inhibited cell viability and promoted cell apoptosis. H19 negatively regulated miR‐152 expression by binding to miR‐152. Furthermore, Wnt1 was identified as a virtual target gene of miR‐152 and was inhibited by miR‐152. Progesterone receptors mRNA and miR‐152 were lowly expressed in participants with an endometrial polyp, while the levels of H19 and Wnt1 were much higher in the endometrial polyp group compared with normal controls. H19 negatively regulated miR‐152 and miR‐152 negatively regulated Wnt1, with the negative correlation coefficients being −0.500 and −0.500, respectively. Using IHC, it was found that Wnt1 and Bcl‐2 protein were highly expressed in the endometrial polyp group compared with normal controls.

Conclusion

The results suggested that H19 was associated with endometrial polyp via mediating cell proliferation and apoptosis.
Long noncoding antisense RNA FAM83A‐AS1 promotes lung cancer cell progression by increasing FAM83A
Authors: Shi Rongxing , Jiao Zichen , Yu Ao , Wang Tao
Published: January 2019

The abnormal expression of long noncoding RNAs (lncRNAs) is closely associated with human cancers. As one special group of lncRNAs, natural antisense transcripts (NATs) can be transcribed from both DNA strands at the same locus but in the opposite direction from the gene transcript. Their expression levels are altered in many cancers, but their roles are poorly understood. We strove to find NATs involved in human non–small‐cell lung cancer (NSCLC) and to reveal their mechanism of action in cancer. We analysed the NATs in NSCLC from the TCGA database by circlncRNAnet. One NAT, family with sequence similarity 83 member A antisense RNA 1 (FAM83A‐AS1), was found to be markedly upregulated and positively correlated with its cognate sense counterpart, FAM83A, in NSCLC. Moreover, overexpression of FAM83A‐AS1 increased FAM38A protein levels and induced ERK1/2 phosphorylation downstream of FAM83A in cells. Finally, overexpression of FAM83A‐AS1 promoted LUAD cell proliferation and invasion. In summary, lncRNA FAM83A‐AS1 promotes LUAD by increasing FAM83A expression.
CHARMM‐GUI Nanodisc Builder for modeling and simulation of various nanodisc systems
Authors: Qi Yifei , Lee Jumin , Klauda Jeffery B. , Im Wonpil
Published: January 2019

Nanodiscs are discoidal protein–lipid complexes that have wide applications in membrane protein studies. Modeling and simulation of nanodiscs are challenging due to the absence of structures of many membrane scaffold proteins (MSPs) that wrap around the membrane bilayer. We have developed CHARMM‐GUI Nanodisc Builder (http://www.charmm-gui.org/input/nanodisc) to facilitate the setup of nanodisc simulation systems by modeling the MSPs with defined size and known structural features. A total of 11 different nanodiscs with a diameter from 80 to 180 Å are made available in both the all‐atom CHARMM and two coarse‐grained (PACE and Martini) force fields. The usage of the Nanodisc Builder is demonstrated with various simulation systems. The structures and dynamics of proteins and lipids in these systems were analyzed, showing similar behaviors to those from previous all‐atom and coarse‐grained nanodisc simulations. We expect the Nanodisc Builder to be a convenient and reliable tool for modeling and simulation of nanodisc systems. © 2019 Wiley Periodicals, Inc.
Epigenetics in osteoarthritis: Novel spotlight
Authors: Fathollahi Anwar , Aslani Saeed , Jamshidi Ahmadreza , Mahmoudi Mahdi
Published: January 2019

Osteoarthritis (OA) is the most common type of arthritis and no longer is considered as an absolute consequence of joint mechanical use (wear and tear); rather recent data demonstrate the pivotal role of inflammatory mediators in the development and progression of this disease. This multifactorial disease results from several environmental and inherited factors. Genetic cannot solely explain all the contribution share of inheritance and, this way, it is speculated that epigenetics can play a role, too. Moreover, environmental factors can induce local epigenetic changes. The epigenetic contribution to OA pathogenesis occurs at all of its levels, DNA methylation, histone modification, microRNA, and long noncoding RNA. In fact, during early phases of OA pathogenesis, environmental factors employ epigenetic mechanisms to provide a positive feedback for the OA‐related pathogenic mechanisms and pathways with an ultimate outcome of a well‐established clinical OA. These epigenetic changes stay during clinical disease and prevent the body natural healing and regenerative processes to work properly, resulting in an incurable disease condition. In this review article, we aimed to have an overview on the studies performed with regard to understanding the role of epigenetics in the etiopathogenesis of OA and highlighted the importance of such kind of regulatory mechanisms within this context.
MT1‐MMP downregulation via the PI3K/Akt signaling pathway is required for the mechanical stretching‐inhibited invasion of bone‐marrow‐derived mesenchymal stem cells
Authors: Fu Xiaorong , Halim Alexander , Tian Boren , Luo Qing , Song Guanbin
Published: January 2019

Mobilization from the bone marrow and the migration of bone‐marrow‐derived mesenchymal stem cells (BMSCs) through the peripheral circulation to injured tissue sites are regulated by multiple mechanical and chemical factors. We previously demonstrated that mechanical stretching promotes the migration but inhibits the invasion of BMSCs. However, the involved mechanisms, especially the mechanism of stretching‐inhibited BMSC invasion, have not been thoroughly elucidated to date. In this study, we found that mechanical stretching with a 10% amplitude at a 1‐Hz frequency for 8 hr significantly reduces BMSC invasion and downregulates the expression of membrane type‐1 matrix metalloproteinases (MT1‐MMP) at both the messenger RNA and protein levels. The overexpression of MT1‐MMP restores mechanical stretching‐reduced BMSC invasion. Moreover, phosphatidylinositol 3‐kinase (PI3K)‐dependent Akt phosphorylation in BMSCs was found to be inactivated by mechanical stretching. Pharmacological inhibitors of PI3K/Akt signaling (LY294002 or A443654) reduced the expression of MT1‐MMP and impaired BMSC invasion. In addition, the upregulation of Akt phosphorylation by a pharmacological activator (SC79) increased MT1‐MMP expression and suppressed mechanical stretching‐reduced BMSC invasion. Taken together, our results suggest that mechanical stretching inhibits BMSC invasion by downregulating MT1‐MMP expression by suppressing the PI3K/Akt signaling pathway.
Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human
Authors: Wong Yin Cheong , Centanni Maddalena , de Lange Elizabeth C. M.
Published: January 2019

Receptor occupancy (RO) is a translational biomarker for assessing drug efficacy and safety. We aimed to apply a physiologically based pharmacokinetic (PBPK) modeling approach to predict the brain dopamine D2 RO time profiles of antipsychotics. Clozapine and risperidone were modeled together with their active metabolites, norclozapine and paliperidone, First, in PK‐Sim a rat PBPK model was developed and optimized using literature plasma PK data. Then, blood‐brain barrier parameters including the expression and efflux transport kinetics of P‐glycoprotein were optimized using literature microdialysis data on brain extracellular fluid (brainECF), which were further adapted when translating the rat PBPK model into the human PBPK model. Based on the simulated drug and metabolite concentrations in brainECF, drug‐D2 receptor binding kinetics (association and dissociation rates) were incorporated in MoBi to predict RO. From an extensive literature search, 32 plasma PK data sets (16 from rat and 16 from human studies) and 23 striatum RO data sets (13 from rat and 10 from human studies) were prepared and compared with the model predictions. The rat PBPK‐RO model adequately predicted the plasma concentrations of the parent drugs and metabolites and the RO levels. The human PBPK‐RO model also captured the plasma PK and RO levels despite the large interindividual and interstudy variability, although it tended to underestimate the plasma concentrations and RO measured at late time points after risperidone dosing. The developed human PBPK‐RO model was successfully applied to predict the plasma PK and RO changes observed after risperidone dose reduction in a clinical trial in schizophrenic patients.
Removal of chlorobenzene using a sequential adsorption–plasma catalytic system over Ag‐, Ce‐ and Mn‐modified activated carbon catalysts
Authors: Jiang Liying , Cao Xiang , Chen Jianmeng , Guo Haiqian , Chen Zhong , Li Sha
Published: January 2019

BACKGROUND

A dielectric barrier discharge reactor coupled with a series of activated carbon (AC) catalysts was applied to remove low concentrations of chlorobenzene. The catalysts were prepared via an impregnation method and their adsorption capacity and plasma‐catalytic ability examined in a sequential adsorption–plasma oxidation process.

RESULTS

Ag/AC had the longest breakthrough time and highest breakthrough capacity among the catalysts studied. At the discharge stage, the Ag/AC catalyst had the highest CO2 yield, chlorobenzene mineralization rate and carbon balance, and the lowest emission of chlorobenzene when compared with the other catalysts under the same conditions. However, the Ag/AC catalyst exhibited the worst reducing ozone generation performance, while the Mn/AC catalyst showed the best ozone decomposition ability. The organic intermediates produced using Ag/AC and Ce/AC were simpler and in lower concentrations than those formed using Mn/AC. The adsorption capacity and catalytic activity of the Ag/AC catalyst showed no obvious decrease after five cycles. Fourier transform infrared and scanning electron microscopy–energy dispersive spectroscopy analyses after the reaction showed that some nitrogen organic intermediates and chlorine substances produced via the degradation of chlorobenzene were adsorbed onto the catalyst surface.

CONCLUSIONS

Ag/AC exhibited a longer breakthrough time, higher breakthrough capacity, higher CO2 yield, less chlorobenzene emission and better carbon balance when compared with the other catalysts. © 2019 Society of Chemical Industry
Enzyme immobilization on photopatterned temperature‐response poly (N‐isopropylacrylamide) for microfluidic biocatalysis
Authors: Zhu Lin‐Lin , Zhu Chang‐Tong , Xiong Meng , Jin Chuan‐Qi , Sheng Sheng , Wu Fu‐An , Wang Jun
Published: January 2019

BACKGROUND

Microfluidic chips have gained growing attention from the scientific community due to their large surface/interface area and fast mass transfer. However, their application is challenged by the instability of enzymes and time‐consuming catalytic process. Poly (N‐isopropylacrylamide) (PNIPAAm) coupled with photopatterning technology was applied to immobilize an enzyme on the microchannel surface to realize the biotransformation in this study.

RESULTS

The photopattern‐immobilized naringinase on a microchip achieved a yield of 93.63 ± 1.12% for isoquercitrin production within 5 min. The production of unit time per unit enzyme (g g−1 h−1) increased 2.1‐fold whereas the reaction time decreased to 1/12 of the time required in a batch reactor. The enzyme was absorbed and desorbed at 40 and 25 °C, respectively, and the release efficiency of immobilized naringinase reached 80.57%, indicating that most of the enzymes were replaced with fresh enzymes to proceed each enzymatic reaction. Six cycles of enzymatic hydrolysis reactions were completed successively, maintaining >60% of relative enzymatic activity.

CONCLUSION

The results indicated that using the immobilized enzyme on the photopatterned PNIPAAm in the enzymatic hydrolysis of rutin was an efficient and simple way to achieve a high yield of isoquercitrin. Thus, this approach represents a convenient and cost‐saving method to produce fine chemicals using microfluidic biocatalysis. © 2019 Society of Chemical Industry
Ankyrin repeat domain 1: A novel gene for cardiac septal defects
Authors: Yang Yongchao , Xia Yu , Wu Yueheng , Huang Shufang , Teng Yun , Liu Xiaobing , Li Ping , Chen Jimei , Zhuang Jian
Published: January 2019

Introduction

Cardiac septal defects account for more than 50% of congenital heart defects. Ankyrin repeat domain 1 (ANKRD1) is an important transcription factor that is mutated in multiple cardiac diseases; however, a relationship between the ANKRD1 mutation and cardiac septal defects has not been described.

Methods

We examined genetic mutations in a large family with three cardiac septal defect patients. Whole exome sequencing, bioinformatics and conservation analysis were utilized to predict the pathogenicity of candidate mutations. Dual luciferase reporter assay and nuclear localization experiments were performed to evaluate the influence of target mutation.

Results

A heterozygous, missense variant of ANKRD1 (MIM* 609599): NM_014391: exon6: c.C560T:p.S187F was identified at a highly conserved region. Sanger sequencing in extended family members demonstrated an incomplete inheritance model. When co‐activated with NKX2.5, ANKRD1 repressed ANF expression as assessed by a dual‐luciferase reporter assay, and p.S187F mutation enhanced the repressive effect (0.318 ± 0.018 versus 0.564 ± 0.048, p < 0.01). A real‐time polymerase chain reaction confirmed that p.S187F mutation of ANKRD1 decreased the expression of endogenous ANF (0.85 ± 0.05 versus 0.61 ± 0.04, p < 0.01). Furthermore, nuclear localization experiments demonstrated that the mutation significantly decreased the nuclear distribution of ANKRD1.

Conclusions

The present study is the first to identify the p.S187F mutant of ANKRD1, which is associated with cardiac septal defects.
Diffusion kurtosis imaging in mild traumatic brain injury and postconcussional syndrome
Authors: Karlsen Rune Hatlestad , Einarsen Cathrine , Moe Hans Kristian , Håberg Asta Kristine , Vik Anne , Skandsen Toril , Eikenes Live
Published: January 2019

Aims of this study were to investigate white matter (WM) and thalamus microstructure 72 hr and 3 months after mild traumatic brain injury (TBI) with diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI), and to relate DKI and DTI findings to postconcussional syndrome (PCS). Twenty‐five patients (72 hr = 24; 3 months = 23) and 22 healthy controls were recruited, and DKI and DTI data were analyzed with Tract‐Based Spatial Statistics (TBSS) and a region‐of‐interest (ROI) approach. Patients were categorized into PCS or non‐PCS 3 months after injury according to the ICD‐10 research criteria for PCS. In TBSS analysis, significant differences between patients and controls were seen in WM, both in the acute stage and 3 months after injury. Fractional anisotropy (FA) reductions were more widespread than kurtosis fractional anisotropy (KFA) reductions in the acute stage, while KFA reductions were more widespread than the FA reductions at 3 months, indicating the complementary roles of DKI and DTI. When comparing patients with PCS (n = 9), without PCS (n = 16), and healthy controls, in the ROI analyses, no differences were found in the acute DKI and DTI metrics. However, near‐significant differences were observed for several DKI metrics obtained in WM and thalamus concurrently with symptom assessment (3 months after injury). Our findings indicate a combined utility of DKI and DTI in detecting WM microstructural alterations after mild TBI. Moreover, PCS may be associated with evolving alterations in brain microstructure, and DKI may be a promising tool to detect such changes.
Information, beliefs, and motivation: The antecedents to human resource attributions
Authors: Hewett Rebecca , Shantz Amanda , Mundy Julia
Published: January 2019

Despite significant interest in the attributions employees make about their organization's human resource (HR) practices, there is little understanding of the antecedents of HR attributions. Drawing on attribution theory, we suggest that HR attributions are influenced by information (perceptions of distributive and procedural fairness), beliefs (organizational cynicism), and motivation (perceived relevance). We test a model through a two‐wave survey of 347 academic faculty in the United Kingdom, examining their attributions of the purpose of their institution's workload management framework. After two preliminary studies (an interview study and a cross‐sectional survey) to establish contextually relevant attributions, we find that fairness and cynicism are important for the formation of internal attributions of commitment but less so for cost‐saving or exploitation attributions. Fairness and cynicism also interact such that distributive fairness buffers the negative attributional effect of cynicism, and individuals are more likely to attribute fair procedures to external forces if they are cynical about their organization. This study furthers the application of attribution theory to the organizational domain while making significant contributions to our understanding of the HR‐performance process.
Extracellular expression of agarase rAgaM1 in Bacillus subtilis and its ability for neoagaro‐oligosaccharide production
Authors: Li Li , Qu Wu , Jin Min , Di Wenjie , Zeng Runying
Published: January 2019

An agarase gene (agaM1) was cloned, expressed and characterized by using Escherichia coli as host strain, revealing the outstanding properties of recombinant AgaM1 (rAgaM1) in agarose degradation and neoagaro‐oligosaccharides (NAs) production in our previous work. In current study, agaM1 was extracellularly expressed in Bacillus subtilis, and we aim to assess the ability of the supernatant of recombinant B. subtilis fermentation broth containing rAgaM1 to degrade agarose without protein purification, which would save the cost of purification and avoid the activity loss during purification. The pH and temperature optima for the supernatant were 7.0 and 50 °C, respectively. The supernatant containing rAgaM1 has outstanding stability against 40 °C and 50 °C. Besides, we detailedly studied the possible influence factors of rAgaM1 expression in the supernatant, including pH, temperature, isopropyl β‐D‐thiogalactoside (IPTG) concentration, initial optical density at a wavelength of 600 nm (OD600), and induction time, and the optimum conditions for rAgaM1 expression by B. subtilis were confirmed. Moreover, the supernatant was able to produce NAs by using the Gracilaria lemaneiformis, whose cells were broken by autoclaving, as substrate, and a total of 1.41 µmol ml−1 of NA, including neoagarotetraose and neoagarohexaose, was produced after degradation for 48 h. This ability could save the cost of substrates in NA production, although the method requires a further study. Our results reveal that the NAs with great potential in food and pharmaceutical industries could be inexpensive to make by the supernatant containing rAgaM1 of B. subtilis fermentation broth in the foreseeable future.
Nutrient flows and balances in intensively managed vegetable production of two West African cities
Authors: Akoto-Danso Edmund Kyei , Manka'abusi Delphine , Steiner Christoph , Werner Steffen , Haering Volker , Lompo Désiré J.-P. , Nyarko George , Marschner Bernd , Drechsel Pay , Buerkert Andreas
Published: January 2019

This study reports and analyzes nutrient balances in experimental vegetable production systems of the two West African cities of Tamale (Ghana) and Ouagadougou (Burkina Faso) over a two‐year period comprising thirteen and eleven crops, respectively. Nutrient‐use efficiency was also calculated. In Tamale and Ouagadougou, up to 2% (8 and 80 kg N ha−1) of annually applied fertilizer nitrogen were leached. While biochar application or wastewater irrigation on fertilized plots did not influence N leaching in both cities, P and K leaching, as determined with ion‐absorbing resin cartridges, were reduced on biochar‐amended plots in Tamale. Annual nutrient balances amounted to +362 kg N ha−1, +217 kg P ha−1, and –125 kg K ha−1 in Tamale, while Ouagadougou had balances of up to +692 kg N ha−1, +166 kg P ha−1, and –175 kg K ha−1 y−1. Under farmers' practice of fertilization, agronomic nutrient‐use efficiencies were generally higher in Tamale than in Ouagadougou, but declined in both cities during the last season. This was the result of the higher nutrient inputs in Ouagadougou compared to Tamale and relatively lower outputs. The high N and P surpluses and K deficits call for adjustments in local fertilization practices to enhance nutrient‐use efficiency and prevent risks of eutrophication.
Comparative assessment of drug‐induced sleep endoscopy scoring systems in pediatric sleep apnea
Authors: Tejan Joseph , Medina Melecio , Ulualp Seckin O.
Published: January 2019

Objectives/Hypothesis

A wide variety of drug‐induced sleep endoscopy (DISE) scoring systems has been used to evaluate sites of upper airway obstruction in children and adults; however, a universally accepted DISE scoring system dedicated to children has not been developed. We evaluated the utility of DISE scoring systems in the assessment of obstructive sleep apnea (OSA) using a single cohort of pediatric patients.

Study Design

Retrospective chart review.

Methods

The medical records of surgically naïve–healthy children with OSA who had undergone DISE were reviewed. Information about demographics, past medical history, and severity of OSA were obtained. A literature review was conducted to identify DISE scoring systems used in children with OSA. Recordings of DISE were analyzed without knowledge of patient information and severity of OSA. The effect of age, obesity, severity of OSA, and oxygen nadir on DISE score was assessed.

Results

Sixty‐eight patients (46 male, 22 female, age range: 19 months–18 years) were included. Forty‐three patients were obese and 25 were nonobese. The severity of OSA was mild in 12 patients, moderate in 13 patients, and severe in 43 patients. DISE scoring systems did not document differences among the groups of patients with mild OSA, moderate OSA, and severe OSA (P > .05). DISE scores were not different among the studied age and weight categories (P > .05).

Conclusions

The DISE scoring systems did not show differences in DISE scores in surgically naïve–healthy children with varying age, weight, and OSA severity categories. Our findings provide preliminary evidence for the need of a universally applicable pediatric DISE scoring system for OSA.

Level of Evidence

4

Laryngoscope, 129:2195–2198, 2019