bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of an invasive strategy in the elderly hospitalized with acute coronary syndrome with emphasis on the nonagenarians
Authors: Couture Etienne L. , Farand Paul , Nguyen Michel , Allard Catherine , Wells George A. , Mansour Samer , Rinfret Stéphane , Afilalo Jonathan , Eisenberg Mark , Montigny Martine , Kouz Simon , Afilalo Marc , Lauzon Claude , Dery Jean‐Pierre , L'Allier Philippe , Schampaert Erick , Tardif Jean‐Claude , Huynh Thao
Published: September 2018

Background

Published data about nonagenarians with acute coronary syndrome (ACS) were mainly descriptive and limited by small sample sizes and unadjusted outcomes. We aim to describe the characteristics, management, and the impact of an invasive strategy on major adverse events in elderly patients hospitalized with ACS with focus on the nonagerians.

Methods and Results

We analyzed data collected as part of the AMI‐OPTIMA study, a cluster‐randomized study of knowledge translation intervention versus usual care on optimal discharge medications in patients admitted with ACS at 24 Canadian hospitals. To determine whether an invasive strategy improved outcomes in the elderly, we used inverse probability weighting to adjust for confounders between patients who underwent invasive versus conservative strategies. Of 4,569 consecutive patients: 2,395 (52%) were <70 years old, 1,031 (23%) were septuagenarians, 941 (21%) were octogenarians, and 202 (4.4%) were nonagenarians. An invasive strategy was associated with reduced in‐hospital all‐cause mortality in all age groups: 1.1% versus 3.8% in patients <70 years old (P < 0.001), 2.9% versus 7.4% in septuagenarians (P < 0.001), 5.1% versus 14.7% in octogenarians (P < 0.001), and 12.0% versus 25.1% in nonagenarians (P = 0.001). An invasive strategy was also associated with higher thrombolysis in myocardial infarction major bleeds in the nonagenarians (9.0% vs. 2.0%; P = 0.003).

Conclusions

The reduction in in‐hospital mortality associated with an invasive strategy in elderly and nonagenarians presented with ACS is generating hypothesis and merits further studies to confirm these benefits and to guide clinicians in the management of these high‐risk patients.
All's well that ends well? A test of the peak‐end rule in couples’ conflict discussions
Authors: Sels Laura , Ceulemans Eva , Kuppens Peter
Published: September 2018

Despite its importance for well‐being, surprisingly little is known about what determines how couples feel after a conflict. Using the peak‐end rule, we examined whether partners’ post‐conflict affect was mainly predicted by their most aversive or pleasant emotional experience (peaks) during the conflict, or by the emotional tone at the end of the interaction. One hundred and one couples engaged in a conflict interaction and afterwards evaluated their momentary affect during the interaction. Post‐conflict affect (in terms of positive and negative feelings, and perceived partner responsiveness) was assessed immediately after the conflict, after a subsequent positive discussion, and upon returning to daily life (here, rumination about the relationship was assessed as well). Our results showed that the negative and positive peaks, but not the end emotion, predicted immediate and partly extended post‐conflict affect in individuals. This finding has clinical implications for the mediation of couple conflict.
Form‐based river restoration decreases wetland hyporheic exchange: Lessons learned from the Upper Colorado River
Authors: Sparacino Matthew S. , Rathburn Sara L. , Covino Timothy P. , Singha Kamini , Ronayne Michael J.
Published: October 2018

Restoration of river–wetland systems to recover lost ecosystem services and restore consistent flood regimes is commonly directed at modifying in‐channel storage and hyporheic exchange. Here, we monitored the hydrologic response to channel realignment in a montane river–wetland system by comparing pre‐ and post‐restoration measurements. In 2015, an earthen berm and 190 m segment of the Upper Colorado River were constructed to consolidate flow from multiple channels into the historic thalweg. We injected a sodium chloride tracer during baseflow and used mass‐balance calculations and electrical resistivity imaging to assess changes in near‐channel hyporheic exchange. Results indicate a decrease in hyporheic exchange within the wetland due to lost complexity along the consolidated flow path. Subsurface complexity appears to control hyporheic exchange more than surface complexity. Flow consolidation increased the area‐adjusted wetland water yield by 231 mm, indicating a loss of wetland water storage capacity. One year of post‐restoration monitoring suggests that the form‐based channel restoration directed at consolidating flow into a single thread adversely affected the hyporheic exchange functioning in the pre‐restoration system. Results from this case study are applicable to restoration planners as they consider the effects of form‐based projects on water storage capacity in similar systems. © 2018 John Wiley & Sons, Ltd.
The antinutritional and vitamin composition of high‐quality yam flour as affected by yam specie, pretreatment, and drying method
Authors: Adebowale Abdul‐Rasaq A. , Wahab Abimbola B. , Sobukola Philip O. , Obadina Adewale O. , Kajihausa Ester O. , Adegunwa Olanike M. , Sanni Oladimeji L. , Tomlins Keith
Published: October 2018

Fresh yams are not shelf stable due to its high susceptibility to physiological deterioration; hence, its conversion into a more stable product like flour can stimulate its industrial application as a substitute to wheat flour. The influence of yam species, pretreatment, and drying method on the antinutritional factor and vitamin composition of high‐quality yam flour (HQYF) was determined. Four different yam species were pretreated with 0.28% potassium metabisulphite for 15 min and blanching at 70°C for 15 min. The differently pretreated slices were thereafter dried with cabinet dryer at 60°C for 48 h and open sun for 3 days, then milled into flour. The flour samples were analyzed for antinutritional and vitamin contents using standard laboratory procedures. The antinutritional factors in the high‐quality yam flour were significantly (p < .05) affected by yam specie, pretreatment, and drying methods. The low level of alkaloids (0.02 mg/100 g) and phytates (13.43 mg/100 g) in the flour samples from D. rotundata in this study underscores its safety for absorption in the body when consumed/used as food formulations. The main and interactive effect of specie of specie, pretreatment, and drying methods influenced the vitamin content of the high‐quality yam flour significantly (p < 0.05). The appreciable level of vitamin C (20.87–30.91 mg/100 g) recorded in all the HQYF could indicate the product of good nutritional quality for the consumers.
Spontaneous regression of a renal mass and multiple lung nodules after methotrexate cessation
Authors: Iwaki Takuya , Sugihara Toru , Omura Shota , Yoshizaki Uran , Honda Sachi , Azuma Takeshi , Kume Haruki
Published: September 2018

Introduction

Methotrexate has been reported to increase the risk of lymphoproliferative disorders. We report a rare case who was clinically diagnosed with methotrexate‐associated lymphoproliferative disorders of the kidney.

Case presentation

A 77‐year‐old patient with rheumatoid arthritis had taken low‐dose methotrexate for 13 years. The patient developed left renal mass 3 cm in size and multiple pulmonary nodules. Initially, renal malignant tumor with lung metastases was considered and the renal biopsy was planned. However, under possible diagnosis of methotrexate‐related lymphoproliferative disorder, we withdrew methotrexate treatment at first and then observed spontaneous regression of the tumorous lesions of the kidney and lungs.

Conclusion

Although methotrexate‐related lymphoproliferative disorder in kidneys is very rare, our case advocates the importance of a relevant differential diagnosis of methotrexate‐related lymphoproliferative disorder under the setting of long‐term treatment of methotrexate for rheumatoid arthritis.
Identification of long noncoding RNAs biomarkers for diagnosis and prognosis in patients with colon adenocarcinoma
Authors: Huang Wei , Liu Zhen , Li Yu , Liu Lilong , Mai Gang
Published: September 2018

Background

In the study, we aimed to find key long noncoding RNAs (lncRNAs) significantly associated with the diagnosis of colon adenocarcinoma (COAD) and lncRNA signatures to provide survival risk prognosis for patients with COAD.

Methods

The lncRNA and messenger RNA (mRNA) expression profiles and clinical information of patients with COAD were obtained from the Cancer Genome Atlas database. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) between COAD and normal tissues were identified. The optimal diagnostic and prognostic lncRNA biomarkers for COAD were identified by using feature selection procedure and classification model. Functional enrichment analysis revealed the possible roles of mRNAs coexpressed with lncRNAs in some cancer‐related biological processes and pathways. Receiver operating characteristic curve of these lncRNA biomarkers were obtained by using 10‐fold cross‐validation. Univariate and multivariate Cox regression analysis for these DElncRNAs were performed to obtain the lncRNAs related to overall survival time. The expression levels of selected DElncRNAs were validated by quantitative real time polymerase chain reaction (qRT‐PCR).

Results

A total of 169 DElncRNAs (60 downregulated and 109 upregulated) and 1236 DEmRNAs (708 downregulated and 528 upregulated) between COAD and normal tissues were identified. Eight lncRNAs of XXbac‐B476C20.9, PP7080, CDKN2B‐AS1, LINC00092, CA3‐AS1, HAND2‐AS1, CTD‐2269F5.1, and LINC01082 were selected as optimal diagnostic lncRNA biomarkers for COAD. The expression of eight optimal diagnostic lncRNA biomarkers in qRT‐PCR validation was consistent with our integrated analysis. Among them, XXbac‐B476C20.9 was not only one of the eight optimal diagnostic lncRNA biomarkers, but also related to the prognosis of COAD.

Conclusion

Our study demonstrated the promising potential of XXbac‐B476C20.9 as an independent biomarker for diagnosis and prognosis of patients with COAD.
MiR‐330‐3p suppresses phosphoglycerate mutase family member 5 ‐inducted mitophagy to alleviate hepatic ischemia‐reperfusion injury
Authors: Sun Xiang‐Li , Zhang Yan‐Le , Xi Shou‐Min , Ma Ling‐Jun , Li Shi‐Peng
Published: September 2018

Mitochondrial dysfunction plays a central role in hepatic ischemia‐reperfusion injury (IRI). The significance of mitophagy in hepatic IRI remains poorly understood. The mechanisms that cause IRI are complex, and many factors are involved in the injury formation process. The miR‐330‐3p mediates cell proliferation, cell death, and metabolism in various organisms. In this study, the levels of miR‐330‐3p were significantly downregulated in hepatic IRI, and the number of autophagosomes was increased in response to IRI as obtained under both in vivo and in vitro conditions. These results demonstrate that a reduction in miR‐330‐3p expression represents an important factor involved with promoting hepatic IRI. Moreover, we found that miR‐330‐3p interacted with phosphoglycerate mutase family member 5 (PGAM5) to regulate mitophagy. In specific, an overexpression of miR‐330‐3p diminished PGAM5 levels, which promoted mitophagy in response to IRI. In contrast, a downregulation of miR‐330‐3p was associated with increased PGAM5 levels leading to increased mitophagy. In conclusion, miR‐330‐3p suppresses PGAM5‐induced mitophagy to alleviate hepatic IRI. Such findings not only reveal some of the mechanistic basis for this microRNA in liver injury, but also provide a foundation for new therapeutic approaches in the treatment of this condition.
Development and Psychometric Testing of the Rate and Accumulation Concept Inventory
Authors: Flynn Carli D. , Davidson Cliff I. , Dotger Sharon
Published: September 2018

Background

Because a fundamental understanding of rate and accumulation principles is important for engineering students across all subdisciplines, a method is needed to assess their understanding of these principles.

Purpose/Hypothesis

This article discusses the development of the Rate and Accumulation Concept Inventory (RACI) instrument and provides an analysis of its validity and reliability. The RACI is designed to test students’ (1) overall mastery of rate and accumulation concepts and (2) mastery of specific rate and accumulation concepts (e.g., mathematics, mass flow, and heat flow).

Design/Methods

Exploratory findings of students’ conceptual understanding prompted the development of a preliminary RACI instrument. Two pilot studies were conducted, with adjustments made to the instrument between each. Data from the second pilot were used to assess evidence of validity and reliability through classical test theory, item response theory, and structural equation modeling.

Results

Validity and reliability evidence indicates that the RACI can be used to measure students’ overall understanding of the concepts identified, though several items require revision or removal. Issues of potential construct underrepresentation were found in two of the conceptual categories.

Conclusions

The evidence of reliability and validity indicates the appropriateness of the RACI for assessing engineering students’ overall understanding of rate and accumulation principles. Additional research is needed to further enhance the validity and reliability of the RACI as a diagnostic tool, particularly in measuring students’ understanding of rate and accumulation concepts in particular physical contexts.
On perfect matchings in matching covered graphs
Authors: He Jinghua , Wei Erling , Ye Dong , Zhai Shaohui
Published: October 2018

A graph is matching‐covered if every edge of is contained in a perfect matching. A matching‐covered graph is strongly coverable if, for any edge of , the subgraph is still matching‐covered. An edge subset of a matching‐covered graph is feasible if there exist two perfect matchings and such that , and an edge subset with at least two edges is an equivalent set if a perfect matching of contains either all edges in or none of them. A strongly matchable graph does not have an equivalent set, and any two independent edges of form a feasible set. In this paper, we show that for every integer , there exist infinitely many ‐regular graphs of class 1 with an arbitrarily large equivalent set that is not switching‐equivalent to either or , which provides a negative answer to a problem of Lukot’ka and Rollová. For a matching‐covered bipartite graph , we show that has an equivalent set if and only if it has a 2‐edge‐cut that separates into two balanced subgraphs, and is strongly coverable if and only if every edge‐cut separating into two balanced subgraphs and satisfies and .
The 1‐2‐3‐conjecture holds for dense graphs
Authors: Zhong Liang
Published: October 2018

This paper confirms the 1‐2‐3‐conjecture for graphs that can be edge‐decomposed into cliques of order at least 3. Furthermore we combine this with a result by Barber, Kühn, Lo, and Osthus to show that there is a constants such that every graph with and , where is the minimum degree of satisfying the 1‐2‐3‐conjecture.
Improved sleep and rehabilitation in a post‐traumatic stress disorder patient after commencement of prazosin
Authors: Lourens Helen
Published: September 2018

Background

First‐line treatment of post‐traumatic stress disorder (PTSD) is trauma‐focused psychotherapy. If drug treatment is indicated, then selective serotonin reuptake inhibitors are the first choice. Other drugs studied include prazosin, antipsychotics and anti‐seizure medications.

Aim

A case report of the marked improvement in the patient's rehabilitation following appropriately treating PTSD symptoms with prazosin.

Clinical details

A 28‐year‐old man was admitted to the Rehabilitation Ward, at Redcliffe Hospital, with a right quadricep tendon rupture which had been repaired 3 months previously. The patient was not able to weight‐bear and was admitted in a wheelchair. Past medical history included epilepsy and PTSD treated with quetiapine to assist sleep. Since quetiapine was not managing the PTSD symptoms it was ceased and prazosin was commenced to decrease PTSD nightmares.

Outcomes

Sleep quality and decreased trauma nightmares were significantly improved after commencement of prazosin. The patient progressed from being wheelchair‐bound to being more ambulant on discharge.

Conclusion

Prazosin is effective for enhanced sleep quality, reduction in trauma nightmares and marked reduction in PTSD symptoms. Better control of PTSD symptoms may have an impact on recovery and rehabilitation.
High‐Frequency Ultrasound Investigation of Port‐Wine Stains: Hemodynamic Features Revealed By 10‐ and 22‐MHz Transducers
Authors: Gong Xia , Yu Wenxin , Li Jia , Ding Angang , Xiong Ping , Lin Xiaoxi
Published: October 2018

Objectives

The hemodynamics of the ultrasound (US) features of port‐wine stains (PWSs) have not been reported. The purpose of this study was to evaluate the high‐frequency US findings of PWSs.

Methods

We retrospectively reviewed 98 PWS cases and categorized them into 4 groups based on clinical manifestations and pathologic findings (14 nodular, 28 thickened, 52 flattened, and 4 acquired). We evaluated the US findings with 10‐ and 22‐MHz transducers.

Results

For nodular PWSs, the mean thickened skin ± SD was 0.6 ± 0.5 mm, and the nodule thickness was 5.7 ± 3.3 mm; 63.6% of skin lesions showed vessel density of 2.16 ± 0.93/cm2 with venous flow of 4.6 ± 1.1 cm/s, and all nodules showed vessel density of 6.14 ± 1.92/cm2 with arterial and venous flow of 26.6 ± 17.9 and 9.9 ± 5.1 cm/s, respectively. The thickened skin of the thickened type was 1.4 ± 2.7 mm; 76.5% of skin lesions showed vessel density of 3.81 ± 1.98/cm2 with venous flow 4.6 ± 2.1 cm/s. The thickened skin of 36 flattened lesions was 0.1 ± 0.1 mm; 91.7% of skin lesions showed vessel density of 1.08 ± 0.28/cm2. The thickened skin of 4 acquired lesions was 0.7 ± 0.4 mm; 50% showed vessel density of 1.08 ± 0.28/cm2. The thickened skin and vessel density of nodular and thickened PWSs were thicker and higher than those of the flattened ones. The 22‐MHz transducer produced clearer contrast and higher vessel density than the 10‐MHz transducer.

Conclusions

These results showed differences in US findings of PWSs, which may be useful for clinical diagnosis.
Real‐time ultrasound elastography evaluation of achilles tendon properties in patients with mild hemiplegic stroke after rehabilitation training
Authors: Shao Yu‐Hong , Peng Ze , Kong Xun , Wang Bin , Zhang Hui
Published: October 2018

Objective

This study aims to evaluate the Achilles tendon's properties after rehabilitation training in patients with stroke using real‐time ultrasound elastography.

Methods

A total of 24 patients with mild hemiplegic stroke in the past 6 to 12 months and unilateral lower limb movement disorder were prospectively enrolled. All patients accepted 9‐week rehabilitation training with the same schema. The 2‐dimensional elastography and real‐time elastography findings in the impaired and contralateral normal Achilles tendon were measured at pretraining and at 3, 6, and 9 weeks after training, which included tendon length, thickness, elasticity score (grade 1–3), and strain ratio of fat to tendon. The functional properties, which include the 10‐meter walk test and timed up‐and‐go scores, were evaluated before and after the 9‐week training.

Results

The impaired Achilles tendon had a longer length (P = .002), lower frequency of grade 1 (P = .012), and lower strain ratio (P = .009) than the contralateral tendon before training. The impaired tendons at the third, sixth, and ninth weeks after training were compared to ones before training, respectively, which revealed shorter length, increased frequency of grade 1, and increased strain ratio. The first statistically significant changes in the length were observed at the sixth week, while such changes in elasticity score and strain ratio were observed at the ninth week.

Conclusions

Two‐dimensional elastography and real‐time elastography can provide valuable imaging markers for quantitatively evaluating the Achilles tendon's properties after rehabilitation training in patients with stroke.
A compact microstrip crossover using NRI‐TL metamaterial lines
Authors: Abbasi Muhammad Ali Babar , Antoniades Marco A. , Nikolaou Symeon
Published: October 2018

A practical implementation of a miniaturized crossover is presented using negative‐refractive‐index transmission‐line (NRI‐TL) metamaterial lines. NRI‐TL metamaterial theory has demonstrated that by loading a conventional transmission line with lumped LC elements, a large phase shift per‐unit‐length can be achieved. Employing this technique, the conventional microstrip transmission lines in a three‐section branch‐line coupler crossover are replaced with 90° NRI‐TL lines, and thus a compact NRI‐TL crossover with an area 47 times smaller than the area of its conventional counterpart is demonstrated. Measured results demonstrate that the proposed NRI‐TL metamaterial crossover exhibits a −10 dB |S11| bandwidth of 33% and a |3 dB| |S31| bandwidth of 26% around 1 GHz.
A novel MRI segmentation method using CNN‐based correction network for MRI‐guided adaptive radiotherapy
Authors: Fu Yabo , Mazur Thomas R. , Wu Xue , Liu Shi , Chang Xiao , Lu Yonggang , Li H. Harold , Kim Hyun , Roach Michael C. , Henke Lauren , Yang Deshan
Published: September 2018

Purpose

The purpose of this study was to expedite the contouring process for MRI‐guided adaptive radiotherapy (MR‐IGART), a convolutional neural network (CNN) deep‐learning (DL) model is proposed to accurately segment the liver, kidneys, stomach, bowel and duodenum in 3D MR images.

Methods

Images and structure contours for 120 patients were collected retrospectively. Treatment sites included pancreas, liver, stomach, adrenal gland, and prostate. The proposed DL model contains a voxel‐wise label prediction CNN and a correction network which consists of two sub‐networks. The prediction CNN and sub‐networks in the correction network each includes a dense block which consists of twelve densely connected convolutional layers. The correction network was designed to improve the voxel‐wise labeling accuracy of a CNN by learning and enforcing implicit anatomical constraints in the segmentation process. Its sub‐networks learn to fix the erroneous classification of its previous network by taking as input both the original images and the softmax probability maps generated from its previous sub‐network. The parameters of each sub‐network were trained independently using piecewise training. The model was trained on 100 datasets, validated on 10 datasets and tested on the remaining 10 datasets. Dice coefficient, Hausdorff distance (HD) were calculated to evaluate the segmentation accuracy.

Results

The proposed DL model was able to segment the organs with good accuracy. The correction network outperformed the conditional random field (CRF), a most comparable method that is usually applied as a post‐processing step. For the 10 testing patients, the average Dice coefficients were 95.3 ± 0.73, 93.1 ± 2.22, 85.0 ± 3.75, 86.6 ± 2.69, and 65.5 ± 8.90 for liver, kidneys, stomach, bowel, and duodenum, respectively. The mean Hausdorff Distance (HD) were 5.41 ± 2.34, 6.23 ± 4.59, 6.88 ± 4.89, 5.90 ± 4.05, and 7.99 ± 6.84 mm, respectively. Manual contouring, as to correct the automatic segmentation results, was four times as fast as manual contouring from scratch.

Conclusion

The proposed method can automatically segment the liver, kidneys, stomach, bowel, and duodenum in 3D MR images with good accuracy. It is useful to expedite the manual contouring for MR‐IGART.
Orientation dependence and decay characteristics of T2* relaxation in the human meniscus studied with 7 Tesla MR microscopy and compared to histology
Authors: Hager Benedikt , Walzer Sonja M. , Deligianni Xeni , Bieri Oliver , Berg Andreas , Schreiner Markus M. , Zalaudek Martin , Windhager Reinhard , Trattnig Siegfried , Juras Vladimir
Published: September 2018

Purpose

To evaluate: (1) the feasibility of MR microscopy T2* mapping by performing a zonal analysis of spatially matched T2* maps and histological images using microscopic in‐plane pixel resolution; (2) the orientational dependence of T2* relaxation of the meniscus; and (3) the T2* decay characteristics of the meniscus by statistically evaluating the quality of mono‐ and biexponential model.

Methods

Ultrahigh resolution T2* mapping was performed with ultrashort echo time using a 7 Tesla MR microscopy system. Measurement of one meniscus was performed at three orientations to the main magnetic field (0, 55, and 90°). Histological assessment was performed with picrosirius red staining and polarized light microscopy. Quality of mono‐ and biexponential model fitting was tested using Akaike Information Criteria and F‐test.

Results

(1) The outer laminar layer, connective tissue fibers from the joint capsule, and the highly organized tendon‐like structures were identified using ultra‐highly resolved MRI. (2) Highly organized structures of the meniscus showed considerable changes in T2* values with orientation. (3) No significant biexponential decay was found on a voxel‐by‐voxel–based evaluation. On a region‐of‐interest–averaged basis, significant biexponential decay was found for the tendon‐like region in a fiber‐to‐field angle of 0°.

Conclusion

The MR microscopy approach used in this study allows the identification of meniscus substructures and to quantify T2* with a voxel resolution approximately 100 times higher than previously reported. T2* decay showed a strong fiber‐to‐field angle dependence reflecting the anisotropic properties of the meniscal collagen fibers. No clear biexponential decay behavior was found for the meniscus substructures.
Sleep duration, timing, variability and measures of adiposity among 8‐ to 12‐year‐old children with obesity
Authors: Zhou M. , Lalani C. , Banda J. A. , Robinson T. N.
Published: October 2018

Objectives

Sleep disruption in laboratory studies increases adiposity and decreases glucose tolerance. However, few epidemiological studies have used objective measures of sleep. This study aims to assess associations between sleep duration, timing and regularity with measures of adiposity.

Methods

This is a cross‐sectional study of 188 children with obesity (age: 10.50 ± 1.39 years; body mass index: 29.24 ± 5.04 kg m−2). Nightly sleep duration, bedtime and wake time were measured by multiple‐day actigraphy and parent reports. Per cent overweight (per cent over median body mass index for age and sex) was chosen as the primary measure of obesity status. Objective measures of height, weight, waist circumference, blood pressure, fasting blood lipids, glucose, insulin, glycated haemoglobin and C‐reactive protein were obtained. Television screen time and total caloric intake were assessed via parent questionnaire.

Results

Each hour later in weekday bedtime was associated with an additional 6.17 per cent overweight (95% confidence interval [CI]: 1.42–10.92). Each hour greater in day‐to‐day variability in weekday bedtime and weekday wake time was associated with an additional 10.20 (95% CI: 0.50–19.91) and 10.02 (95% CI: 1.55–18.50) per cent overweight, respectively. Associations were similar after controlling for other obesity‐related behaviours (television screen time, total caloric intake and physical activity.)

Conclusions

Among children with obesity, later bedtime and greater variability in bedtime and wake time are associated with greater adiposity, independent of other obesity‐related behaviours. Early bedtime and wake time and consistent day‐to‐day sleep timing may be strategies to reduce adiposity in high‐risk children.
Serum-Free Medium Enhances the Immunosuppressive and Antifibrotic Abilities of Mesenchymal Stem Cells Utilized in Experimental Renal Fibrosis
Authors: Yoshida Ken , Nakashima Ayumu , Doi Shigehiro , Ueno Toshinori , Okubo Tomoe , Kawano Ki-ichiro , Kanawa Masami , Kato Yukio , Higashi Yukihito , Masaki Takao
Published: September 2018

Serum used in culture medium brings risks of immune reactions or infections and thus may hinder using ex vivo expanded mesenchymal stem cells (MSCs) for medical treatment. Here, we cultured MSCs in a serum-free medium (SF-MSCs) and in a medium containing 10% fetal bovine serum (10%MSCs) and investigated their effects on inflammation and fibrosis. MSC-conditioned medium suppressed transforming growth factor-β1–induced phosphorylation of Smad2 in HK-2 cells, with no significant difference between the two MSCs. This finding suggests that the direct antifibrotic effect of SF-MSCs is similar to that of 10%MSCs. However, immunohistochemistry revealed that renal fibrosis induced by unilateral ureteral obstruction in rats was more significantly ameliorated by the administration of SF-MSCs than by that of 10%MSCs. Coculture of MSCs and monocytic THP-1 cell-derived macrophages using a Transwell system showed that SF-MSCs significantly induced polarization from the proinflammatory M1 to the immunosuppressive M2 phenotype macrophages, suggesting that SF-MSCs strongly suppress the persistence of inflammation. Furthermore, the gene expression of tumor necrosis factor-α–induced protein 6 (TSG-6), which inhibits the recruitment of inflammatory cells, was higher in SF-MSCs than in 10%MSCs, and TSG-6 knockdown in SF-MSCs attenuated the anti-inflammatory responses in unilateral ureteral obstruction rats. These findings imply that SF culture conditions can enhance the immunosuppressive and antifibrotic abilities of MSCs and the administration of ex vivo expanded SF-MSCs has the potential to be a useful therapy for preventing the progression of renal fibrosis.
Limited Endothelial Plasticity of Mesenchymal Stem Cells Revealed by Quantitative Phenotypic Comparisons to Representative Endothelial Cell Controls
Authors: Antonyshyn Jeremy A. , McFadden Meghan J. , Gramolini Anthony O. , Hofer Stefan O.P. , Santerre J. Paul
Published: September 2018

Considerable effort has been directed toward deriving endothelial cells (ECs) from adipose-derived mesenchymal stem cells (ASCs) since 2004, when it was first suggested that ECs and adipocytes share a common progenitor. While the capacity of ASCs to express endothelial markers has been repeatedly demonstrated, none constitute conclusive evidence of an endothelial phenotype as all reported markers have been detected in other, non-endothelial cell types. In this study, quantitative phenotypic comparisons to representative EC controls were used to determine the extent of endothelial differentiation being achieved with ASCs. ASCs were harvested from human subcutaneous abdominal white adipose tissue, and their endothelial differentiation was induced using well-established biochemical stimuli. Reverse transcription quantitative real-time polymerase chain reaction and parallel reaction monitoring mass spectrometry were used to quantify their expression of endothelial genes and corresponding proteins, respectively. Flow cytometry was used to quantitatively assess their uptake of acetylated low-density lipoprotein (AcLDL). Human umbilical vein, coronary artery, and dermal microvascular ECs were used as positive controls to reflect the phenotypic heterogeneity between ECs derived from different vascular beds. Biochemically conditioned ASCs were found to upregulate their expression of endothelial genes and proteins, as well as AcLDL uptake, but their abundance remained orders of magnitude lower than that observed in the EC controls despite their global proteomic heterogeneity. The findings of this investigation demonstrate the strikingly limited extent of endothelial differentiation being achieved with ASCs using well-established biochemical stimuli, and underscore the importance of quantitative phenotypic comparisons to representative primary cell controls in studies of differentiation. Stem Cells Translational Medicine  2019;8:35–45
Neutrino masses and gauged U(1)ℓ lepton number
Authors: Chang We-Fu , Ng John N.
Published: October 2018

Abstract

We investigate the tree-level neutrino mass generation in the gauged U(1)
ℓ
lepton model recently proposed by us [1]. With the addition of one Standard Model(SM) singlet, ϕ
1(Y = 0, ℓ = 1), and one SM triplet scalar, T (Y = −1, ℓ = 0), realistic lepton masses can be accommodated. The resulting magnitude of neutrino mass is given by ∼ v

t

3
/v

L

2
, where v

t
and v

L
are the vacuum expectation values of T and ϕ
1, respectively, and it is automatically of the inverse see-saw type. Since v

L
is the lepton number violation scale we take it to be high, i.e. O ≳ (TeV). Moreover, the induced lepton flavor violating processes and the phenomenology of the peculiar triplet are studied. An interesting bound, 0.1 ≲ v

t
≲ 24.1 GeV, is obtained when taking into account the neutrino mass generation, Br(μ → eγ), and the limits from oblique parameters, ΔS and ΔT. Collider phenomenology of the SM triplets is also discussed.
Going Vertical
Authors: Toyne J. Marla , Anzellini Armando , Epstein Mičulka Lori , Mejías Pitti Ismael , Puig Castell Jordi , Guinot Castelló Salvador
Published: October 2018

Most archaeological practice involves horizontal excavations of ancient occupations and cemeteries, but the Chachapoya of Peru's eastern montane built tombs along narrow cliff ledges, which require innovative methods of investigation. Many of these sites are becoming exposed and threatened due to increased deforestation. The La Petaca mortuary complex includes 125 constructed platforms, modified ledges, mausoleums, and caves containing human remains across one section of an exposed rock face approximately 200 m across by approximately 80 m high. While the site has been looted and damaged due to various taphonomic processes (including ecological, geological, and cultural), we argue that there are recoverable details, especially in relation to how the ancient Chachapoya people created and accessed these vertical spaces. Through collaboration with technical professionals, we identified and documented many tombs using vertical progression techniques. This valuable partnership between spelunkers and archaeologists allowed us to develop techniques for “vertical archaeology,” including safe access in order to be able to document, sample, and make detailed observations of building methods and burial contents.
Release and speciation of carbon from Zircaloy-4 in anaerobic and highly alkaline conditions: Comparison of simple immersion and potentiostatic corrosion tests
Authors: Caes Sebastien , Druyts Frank , Thomas Peter
Published: October 2018

The gas release and speciation of carbon species from irradiated and unirradiated Zircaloy-4 samples, representative for the fuel cladding as used in Belgian nuclear power plants, were studied in a saturated Ca(OH)2 solution in anaerobic conditions. This environment is relevant for the Belgian Supercontainer design, as perceived for the geological disposal of high-level nuclear waste. To achieve this, we performed simple immersion and potentiostatic corrosion tests. Potentiodynamic polarization curves, recorded prior to the potentiostatic tests, revealed that irradiation seems to induce changes on the Zircaloy-4 corrosion behavior, such as a shift of the corrosion potential. Potentiostatic corrosion tests on unirradiated Zircaloy-4 provided a corrosion rate of ~54 nm/yr over a 7 day-experiment, whilst a corrosion rate of only ~4 nm/yr was calculated for the irradiated sample. Gas chromatography revealed that during simple immersion tests, which lasted 195 days, hydrogen, methane, ethane, and CO2 were produced, with methane being the major compound. Assuming that all carbon released from the metal was transformed into gaseous compounds, this yields to a corrosion rate ranging from 57 to 84 nm/yr for the irradiated sample. However, caution has to be taken on these corrosion rate and more tests should be performed to confirm these results.
Radical conservatism and global order: international theory and the new right
Authors: Drolet Jean-François , Williams Michael C
Published: October 2018

The rise of the radical ‘New Right’ (NR) across much of the global political landscape is one of the most striking political developments of recent years. This article seeks to foster international theory’s critical engagement with the NR by providing an overview of its thinking about world politics and the challenges it presents. We argue that in many ways international theory is in fact uniquely positioned to provide such an engagement, and that it is essential that international theory comes to terms more fully with its political vision and theoretical claims if it is to engage effectively with this increasingly potent and often deeply troubling intellectual and political movement.
Chronic lymphocytic leukemia treatment algorithm 2018
Authors: Parikh Sameer A.
Published: October 2018

Abstract

The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as ibrutinib, idelalisib, and venetoclax), and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in CLL, even among patients with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes. Each of these treatments is associated with a unique toxicity profile; in the absence of randomized data, the choice of one type of treatment over another depends on the co-morbidities of the patient. Chemoimmunotherapy still plays an important role in the management of previously untreated CLL patients, particularly among young fit patients who have standard risk FISH profile and mutated IGHV genes. Richter’s transformation of CLL remains a difficult complication to treat, although therapy with programmed death 1 inhibitors such as pembrolizumab and nivolumab has shown impressive responses in a subset of patients. Our ability to risk stratify CLL patients continues to evolve; the CLL-International Prognostic Index (CLL-IPI) is the best validated tool in predicting time to first therapy among previously untreated patients. This review summarizes the current approach to risk stratification and management of CLL patients.
Hydroxypropyl-beta and -gamma cyclodextrins rescue cholesterol accumulation in Niemann–Pick C1 mutant cell via lysosome-associated membrane protein 1
Authors: Singhal Ashutosh , Szente Lajos , Hildreth James E. K. , Song Byeongwoon
Published: October 2018

Niemann–Pick type C (NPC) disease is a fatal hereditary neurodegenerative disorder characterized by a massive accumulation of cholesterol in lysosomes and late endosomes due to a defect in intracellular cholesterol trafficking. Dysfunction in intracellular cholesterol trafficking is responsible for about 50 rare inherited lysosomal storage disorders including NPC. The lysosomal proteins NPC1 and NPC2 play a crucial role in trafficking of cholesterol from late endosomes and lysosomes to other cellular compartments. However, the detailed mechanisms of cholesterol trafficking at the late endosomes/lysosomes (LE/LY) are poorly understood. Studies showed that 2-hydroxypropyl-β-cyclodextrin (HPβCD) alleviates the cholesterol accumulation defect in animal model and has been approved for a phase 2b/3 clinical trial for NPC. HPβCD is known to bind cholesterol; however, the mechanisms how HPβCD mediates the exit of cholesterol from the LE/LY compartments are still unknown. Further, another cyclodextrin (CD) derivative, 2-hydroxypropyl-γ-cyclodextrin (HPγCD), was shown to reduce intracellular cholesterol accumulation in NPC patient cells and NPC mice model. Herein, we identified a number of candidate proteins differentially expressed in NPC patient-derived cells compared to cells derived from a healthy donor using a proteomic approach. Interestingly, both HPβCD and HPγCD treatments modulated the expression of most of these NPC-specific proteins. Data showed that treatment with both CDs induces the expression of the lysosome-associated membrane protein 1 (LAMP-1) in NPC patient-derived cells. Remarkably, LAMP-1 overexpression in HeLa cells rescued U18666A-induced cholesterol accumulation suggesting a role of LAMP-1 in cholesterol trafficking. We propose that HPβCD and HPγCD facilitate cholesterol export from the LE/LY compartments via the LAMP-1 protein, which may play a crucial role in cholesterol trafficking at the LE/LY compartments when there is no functional NPC1 protein. Together, this study uncovers new cellular mechanisms for cholesterol trafficking, which will contribute to development of novel therapeutic approaches for lysosomal storage diseases.
LncRNA-MEG3 inhibits activation of hepatic stellate cells through SMO protein and miR-212
Authors: Yu Fujun , Geng Wujun , Dong Peihong , Huang Zhiming , Zheng Jianjian
Published: October 2018

Activation of hepatic stellate cells (HSCs), a pivotal event in liver fibrosis, is considered as an epithelial–mesenchymal transition (EMT) process. Deregulation of long noncoding RNAs (lncRNAs) has been reported to be involved in a series of human diseases. LncRNA-maternally expressed gene 3 (MEG3) functions as a tumor suppressor in cancers and has been shown to play a vital role in EMT process. However, the biological role of MEG3 in liver fibrosis is largely unknown. In this study, MEG3 was reduced in vivo and in vitro during liver fibrosis. Restoring of MEG3 expression led to the suppression of liver fibrosis, with a reduction in α-SMA and type I collagen. Notably, MEG3 overexpression inhibited HSC activation through EMT, associated with an increase in epithelial markers and a reduction in mesenchymal markers. Further studies showed that Hedgehog (Hh) pathway-mediated EMT process was involved in the effects of MEG3 on HSC activation. Smoothened (SMO) is a member of Hh pathway. Using bioinformatic analysis, an interaction between MEG3 and SMO protein was predicted. This interaction was confirmed by the results of RNA immunoprecipitation and deletion-mapping analysis. Furthermore, MEG3 was confirmed as a target of microRNA-212 (miR-212). miR-212 was partly responsible for the effects of MEG3 on EMT process. Interestingly, MEG3 was also reduced in chronic hepatitis B (CHB) patients with liver fibrosis when compared with healthy controls. MEG3 negatively correlated with fibrosis stage in CHB patients. In conclusion, we demonstrate that MEG3 inhibits Hh-mediated EMT process in liver fibrosis via SMO protein and miR-212.
Exceptional catalytic effects of black phosphorus quantum dots in shuttling-free lithium sulfur batteries
Authors: Xu Zheng-Long , Lin Shenghuang , Onofrio Nicolas , Zhou Limin , Shi Fangyi , Lu Wei , Kang Kisuk , Zhang Qiang , Lau Shu Ping
Published: October 2018

Lithium sulfur batteries with high energy densities are promising next-generation energy storage systems. However, shuttling and sluggish conversion of polysulfides to solid lithium sulfides limit the full utilization of active materials. Physical/chemical confinement is useful for anchoring polysulfides, but not effective for utilizing the blocked intermediates. Here, we employ black phosphorus quantum dots as electrocatalysts to overcome these issues. Both the experimental and theoretical results reveal that black phosphorus quantum dots effectively adsorb and catalyze polysulfide conversion. The activity is attributed to the numerous catalytically active sites on the edges of the quantum dots. In the presence of a small amount of black phosphorus quantum dots, the porous carbon/sulfur cathodes exhibit rapid reaction kinetics and no shuttling of polysulfides, enabling a low capacity fading rate (0.027% per cycle over 1000 cycles) and high areal capacities. Our findings demonstrate application of a metal-free quantum dot catalyst for high energy rechargeable batteries.
Long non-coding RNA CCRR controls cardiac conduction via regulating intercellular coupling
Authors: Zhang Yong , Sun Lihua , Xuan Lina , Pan Zhenwei , Hu Xueling , Liu Hongyu , Bai Yunlong , Jiao Lei , Li Zhange , Cui Lina , Wang Xiaoxue , Wang Siqi , Yu Tingting , Feng Bingbing , Guo Ying , Liu Zonghong , Meng Weixin , Ren Hequn , Zhu Jiyuan , Zhao Xuyun , Yang Chao , Zhang Ying , Xu Chaoqian , Wang Zhiguo , Lu Yanjie , Shan Hongli , Yang Baofeng
Published: October 2018

Long non-coding RNAs (lncRNAs) have emerged as a new class of gene expression regulators playing key roles in many biological and pathophysiological processes. Here, we identify cardiac conduction regulatory RNA (CCRR) as an antiarrhythmic lncRNA. CCRR is downregulated in a mouse model of heart failure (HF) and in patients with HF, and this downregulation slows cardiac conduction and enhances arrhythmogenicity. Moreover, CCRR silencing induces arrhythmias in healthy mice. CCRR overexpression eliminates these detrimental alterations. HF or CCRR knockdown causes destruction of intercalated discs and gap junctions to slow longitudinal cardiac conduction. CCRR overexpression improves cardiac conduction by blocking endocytic trafficking of connexin43 (Cx43) to prevent its degradation via binding to Cx43-interacting protein CIP85, whereas CCRR silence does the opposite. We identified the functional domain of CCRR, which can reproduce the functional roles and pertinent molecular events of full-length CCRR. Our study suggests CCRR replacement a potential therapeutic approach for pathological arrhythmias.
Cryo-EM structure of the hibernating Thermus thermophilus 100S ribosome reveals a protein-mediated dimerization mechanism
Authors: Flygaard Rasmus Kock , Boegholm Niels , Yusupov Marat , Jenner Lasse B.
Published: October 2018

In response to cellular stresses bacteria conserve energy by dimerization of ribosomes into inactive hibernating 100S ribosome particles. Ribosome dimerization in Thermus thermophilus is facilitated by hibernation-promoting factor (TtHPF). In this study we demonstrate high sensitivity of Tt100S formation to the levels of TtHPF and show that a 1:1 ratio leads to optimal dimerization. We report structures of the T. thermophilus 100S ribosome determined by cryo-electron microscopy to average resolutions of 4.13 Å and 4.57 Å. In addition, we present a 3.28 Å high-resolution cryo-EM reconstruction of a 70S ribosome from a hibernating ribosome dimer and reveal a role for the linker region connecting the TtHPF N- and C-terminal domains in translation inhibition by preventing Shine−Dalgarno duplex formation. Our work demonstrates that species-specific differences in the dimerization interface govern the overall conformation of the 100S ribosome particle and that for Thermus thermophilus no ribosome-ribosome interactions are involved in the interface.