bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of dietetic consultation for lowering blood lipid levels in the management of cardiovascular disease risk: A systematic review and meta‐analysis of randomised controlled trials
Authors: Ross Lynda J. , Barnes Katelyn A. , Ball Lauren E. , Mitchell Lana J. , Sladdin Ishtar , Lee Patricia , Williams Lauren T.
Published: February 2019

Aim

Evidence of the effectiveness of dietetic consultation for the management of cardiovascular disease (CVD) risk factors has not been previously synthesised. A systematic review and four meta‐analyses evaluated the effectiveness of dietetic consultation for lowering blood lipid levels in high‐risk individuals in primary health‐care settings.

Methods

Of the 4860 records identified, 10 eligible randomised controlled trials (RCTs, n = 1530) were evaluated for reporting blood lipid outcomes following dietetic consultation (DN)—defined as at least one exclusive individual face‐to‐face consultation with a dietitian and comparators (C)—defined as no nutrition intervention or usual or minimal care provided by physicians and/or nurses.

Results

DN groups were effective for lowering blood lipid levels across nine studies reporting total cholesterol (TC) and LDL; and across five of six studies reporting triglycerides (TG). Between‐group differences were not consistently assessed, with significance levels reported in four studies all in favour of DN, P < 0.05. Meta‐analyses for TC and LDL (seven studies) confirmed DN and C groups were equally effective, P > 0.05; and for TG (six studies) DN groups were significantly more effective than C groups, P < 0.05).

Conclusions

This review provides RCT evidence that dietetic counselling is effective for lowering TG levels and at least as effective as usual and minimal care for improving cholesterol levels in high‐risk individuals in primary health care. However, more adequate reporting of methods and greater consistency in timing interventions and data collection will enhance the quality of the evidence and increase confidence in the health benefits of dietetic counselling for the management of CVD risk.
The Role of Solid Support Bound Metal Chelators on System‐Dependent Synergy and Antagonism with Nisin
Authors: Herskovitz Joshua E. , Worobo Randy W. , Goddard Julie M.
Published: February 2019

Active packaging can enhance the performance of natural antimicrobials in controlling food spoilage and waste, while addressing consumer demands for cleaner labels. Yet, synergies are system dependent, with some conditions counterintuitively promoting antagonistic effects. In particular, metal chelators can improve performance of certain natural antimicrobials and have been incorporated in nonmigratory metal chelating active packaging technologies. However, the influence of chelating ligand chemistry on antimicrobial efficacy has not been investigated in microbial spoilage models. The effect of three commercial chelating resins on the growth of Alicyclobacillus acidoterrestris ATCC 49025, a thermoduric acidophilic spore‐former, in growth media and apple juice was investigated. Dowex MAC‐3, Chelex 100, and Lewatit TP260 were used as models for metal chelating active packaging containing carboxylic acid (CA), iminodiacetic acid (IDA), and aminomethylphosphonic acid (AMPA) ligands. Diameters (CA = 472.4 ± 117.2 μm, IDA = 132.93 ± 26.71 μm, and AMPA = 498.3 ± 29.24 μm), dissociation kinetics (CA = 6.44 ± 0.109, IDA = ‐0.977 ± 9.94, AMPA = 7.43 ± 0.193), and metal chelating capacities (CA = 1.16 × 10−4 mol/g, IDA = 1.52 × 10−3 mol/g, and AMPA = 4.67 × 10−4 mol/g) were used to distinguish differences in antimicrobial efficacies. Growth of A. acidoterrestris in acidified Potato Dextrose Broth over 24 hr with chelating resins indicated early death phase for CA and IDA resins and bactericidal for AMPA resin. However, viability in commercial apple juice with the inclusion of nisin and chelating resins was variable, with IDA resin significantly (P < 0.05) increasing viability while the effect of CA and AMPA resins remained elusive. This work emphasizes the importance of biological repeatability and correct statistical modeling in identifying conditions under which the antimicrobial intervention of nisin in real food systems, such as acidic beverages and juices, are synergistic or antagonistic.

Practical Application

New technologies to control microbial food spoilage and waste need to be explored to address consumers on‐going demands for reducing additive use.  Solid support bound metal chelators can both promote and control microbial growth when used in conjunction with nisin, a natural antimicrobial.  This work explores how system conditions can render a given technology either synergistic or antagonistic, and highlights the importance of sufficient biological replicates in experimental design.
Chronic Oral Administration of Tenebrio molitor Extract Exhibits Inhibitory Effect on Glucocorticoid Receptor Overexpression in the Hippocampus of Ovariectomy‐Induced Estrogen Deficient Mice
Authors: Kim Gwang‐Ho , Baek Hye Kyung , Lee Jong Suk , Kim Sung‐Jo , Yi Sun Shin
Published: February 2019

It has been reported that estrogen deficiency in female disrupts systemic endocrinologic regulatory mechanisms, finally leading to osteoporotic condition. Estrogen deficiency also down‐regulates brain functions due to its deficits of its original roles in a number of neurological events. Therefore, it is necessary to find alternative materials that can prevent osteoporotic condition and maintain normal brain functions to correct such hormone deficiency. In the present study, we found that novel compounds originated from larvae of Tenebrio molitor (TM) possessed anti‐osteoporotic effect. They could also prevent abnormal progressive brain function by deaccelerating enhanced HPA‐axis negative feedback while maintaining neurogenesis in hippocampus. We daily administered TM to ovariectomized (OVX) ddY mice for 4 weeks and then performed histological and hormonal evaluations for its anti‐osteoporotic effects. In addition, we investigated glucocorticoid receptor (GR) expression and neuroblast expression (DCX) in the hippocampal dentate gyrus morphologically by immunohistochemistry analysis. According to our results, TM has anti‐osteoporotic effects. It also tends to bring interfered brain environment back to normal condition.

These results suggest that TM might have anti‐osteoporosis effect and enhancing effects on enrichment of environment in brain by being antidestroyed hormonal deficiency simultaneously. This is the first study to report that TM can be used as source of bioactive substance to prevent decreased neurogenesis and impaired HPA axis driven by high GR expression in the hippocampus in hormonal deficient female animals.

Practical Application

Anti‐osteoporosis effect and stress resistance due to improved brain function caused by the ingestion of Tenebrio molitor extract were observed in postmenopausal women. T. molitor is available as a nutritional supplement for bone and brain health, which menopausal women need most.
Value of contrast‐enhanced harmonic endoscopic ultrasonography in differentiating between gastrointestinal stromal tumors: A meta‐analysis
Authors: Tang Jia Yue , Tao Ke Gong , Zhang Li Yuan , Wu Kai Ming , Shi Jian , Zeng Xin , Lin Yong
Published: February 2019

Objective

Contrast‐enhanced harmonic endoscopic ultrasonography (CH‐EUS) is a valuable device to diagnose and determine the malignant potential of gastrointestinal stromal tumors (GIST) as early as possible when making clinical therapeutic decisions. This study aimed to estimate the ability of CH‐EUS to discriminate between GIST and benign submucosal lesions (SML) and to predict their malignant potential.

Methods

PubMed, MEDLINE, EMBASE, the Web of Science, and Cochrane Central Register of Controlled Trials databases were screened. Using the data provided in the literatures, 2 × 2 tables were constructed to obtain the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. A receiver operating characteristic (ROC) curve was generated and the area under the ROC curve (AUROC) was calculated.

Results

Four studies with a total of 187 patients were identified to evaluate the value of CH‐EUS in discriminating between GIST and benign SML. The pooled sensitivity, specificity, and AUROC were 89% (95% CI 0.82‐0.93), 82% (95% CI 0.66‐0.92), and 0.89, respectively. Five studies including 143 patients were analyzed to assess the accuracy of CH‐EUS in determining the malignant potential of GIST. The pooled sensitivity, specificity, and AUROC curve of CH‐EUS were 96% (95% CI 0.90‐0.99), 53% (95% CI 0.40‐0.66), and 0.92, respectively.

Conclusions

CH‐EUS is a safe, noninvasive method that can distinguish between GIST and benign subepithelial lesions and to predict their malignant potential to a certain extent. Large‐scale, multicenter prospective studies are needed in the future.
Quantitative immunochemical fecal occult blood test for neoplasia in colon cancer screening
Authors: Yuan Si Yi , Wu Wei , Fu Jing , Lang Yi Xuan , Li Ji Chi , Guo Ye , Wang Ya Nan , Qian Jia Ming , Li Jing Nan
Published: February 2019

OBJECTIVE

To investigate the performance of the quantitative immunochemical fecal occult blood test (qFIT) and to determine the association between the fecal hemoglobin (Hb) level and the location and size of adenomas and the stages of colorectal cancer (CRC).

METHODS

A total of 692 participants were included in the study. Their fecal Hb level was measured using an OC‐SENSA MICRO qFIT. The colonoscopy results, including the location, size, and histological features of the adenomas, as well as the relationship between the Hb level and different characteristics were analyzed. Performance of the qFIT at various thresholds of fecal Hb levels was evaluated.

RESULTS

Advanced colorectal neoplasia (ACRN) was identified in 76 patients based on the colonoscopic and pathological examinations. Large adenomas (≥10 mm) had a higher fecal Hb level than small adenomas (<10 mm). Advanced adenomas located on the left side of the colon presented with a higher fecal Hb level than those on the right side (P = 0.022). Stage III‐IV CRC patients had a significantly higher Hb level than stage I‐II patients (P = 0.013). The sensitivity and specificity of qFIT for ACRN was 51.3% and 86.4%，respectively, with the best cut‐off level of 400 ng/mL. The sensitivity and specificity for CRC was 61.0% and 89.1%, with the best cut‐off level of 500 ng/mL.

CONCLUSIONS

qFIT has an acceptable sensitivity and specificity for ACRN detection. Furthermore, the qFIT results are associated with the location and size of adenomas as well as the grade of CRC.
The recent past and promising future for data integration methods to estimate species’ distributions
Authors: Miller David A. W. , Pacifici Krishna , Sanderlin Jamie S. , Reich Brian J.
Published: February 2019

With the advance of methods for estimating species distribution models has come an interest in how to best combine datasets to improve estimates of species distributions. This has spurred the development of data integration methods that simultaneously harness information from multiple datasets while dealing with the specific strengths and weaknesses of each dataset.

We outline the general principles that have guided data integration methods and review recent developments in the field. We then outline key areas that allow for a more general framework for integrating data and provide suggestions for improving sampling design and validation for integrated models.

Key to recent advances has been using point‐process thinking to combine estimators developed for different data types. Extending this framework to new data types will further improve our inferences, as well as relaxing assumptions about how parameters are jointly estimated. These along with the better use of information regarding sampling effort and spatial autocorrelation will further improve our inferences.

Recent developments form a strong foundation for implementation of data integration models. Wider adoption can improve our inferences about species distributions and the dynamic processes that lead to distributional shifts.
Differential gene expression and stereological analyses of the cerebellum following methamphetamine exposure
Authors: Eskandarian Boroujeni Mahdi , Peirouvi Tahmineh , Shaerzadeh Fatemeh , Ahmadiani Abolhasan , Abdollahifar Mohammad Amin , Aliaghaei Abbas
Published: February 2019

Methamphetamine (METH) is a highly addictive psychostimulant that profoundly aimed at monoaminergic systems in the brain. Despite the leading role of cerebellum in sensorimotor control as well as augmented locomotor activity under the influence of METH, there are few studies examining the effect of METH administration on gene expression profiling and structural consequences in the cerebellar region. Thus, we sought to explore the effects of METH on the cerebellum, from gene expression changes to structural alterations. In this respect, we investigated genome‐wide mRNA expression using high throughput RNA‐seq technology and confirmatory quantitative real‐time PCR, accompanied by stereological analysis of cerebellar layers along with identification of reactive astrogliosis by glial fibrillary acidic protein and behavioral assessment following METH exposure. According to our RNA‐seq data, 473 unique differentially expressed genes (DEG) were detected upon METH injections in which a large number of these genes engage basically in biological regulations and metabolic processes, chiefly located in nucleus and membrane. In addition, pathway analysis of METH‐induced DEG revealed several enriched signaling cascades related largely to immune response, neurotransmission, cell growth, and death. Further, METH induced a significant reduction in volumes of cerebellar layers (molecular, granular, and Purkinje) and a decrease in the white matter volume along with a rise in astrogliosis as well as increased locomotor activity. In conclusion, considering gene expression changes combined with structural alterations of the cerebellum in response to METH, these data suggest METH‐induced neurotoxicity in the cerebellar region.
Grass greenness and grass height promote the resource partitioning among reintroduced Burchell's zebra and blue wildebeest in southern Mozambique
Authors: Mandlate Luís Comissário , Arsenault Randal , Rodrigues Flávio H. G.
Published: February 2019

Differences in the selection of habitat and specific dietary items support resource partitioning and coexistence of sympatric African grazing herbivores, such as zebra and wildebeest. In Maputo Special Reserve (MSR), southern Mozambique, these two species were extirpated during the civil war (1977–1992); since 2010, they have been reintroduced into the Reserve. Identifying the resource selection by reintroduced species and how these species coexist, while utilising the same resources, is both of ecological interest and important for the management of wildlife communities and parks. This is a key application of our research. Therefore, the present study investigated resource partitioning between Burchell's zebra (Equus burchelli, Smuts 1832) and blue wildebeest (Connochaetes taurinus, Burchell 1823) in the MSR. We conducted the study from July 2016 to June 2017. The data were collected by direct observation, driving the vehicle along the reserve's roads that covered the vegetation communities where zebras and wildebeest are known to commonly occur. The composition of the diet and specific features of the grass grazed by the two species, including greenness, height, and the number of stems, were assessed. The widely available grass, Aristida barbicollis, contributed most to the diet of both herbivores. The dietary overlap between the two herbivores was higher during the dry season (95%) than wet season (86%). Resources partitioning appears to be determined, principally, by the height and greenness of the grass, with the zebra grazing taller grass, which may facilitate the access of the wildebeest to the greener, lower proportion of the forage. That results follow the expectation that, among native herbivores, overlap in resource use is not expected based on evolutionary segregation.
Oncologists' and pediatric oncologists' perspectives and challenges for fertility preservation
Authors: Lampic Claudia , Wettergren Lena
Published: February 2019

International guidelines recommend that health‐care providers initiate discussions about the impact of treatment on fertility with cancer patients of reproductive age, or with parents/legal guardians of children, as early as possible in the treatment process. Still, both physicians and patients confirm that this is not always the case. This literature review summarizes findings regarding oncologists' and pediatric oncologists' perspectives and challenges of providing fertility preservation care, and points out directions for development. The results concerning the challenges facing clinicians are consistent and encompass both internal and external factors. The internal factors relate to clinicians' characteristics and values and include their knowledge of fertility preservation, clinical experience, perceptions of patients' plans for children, and how comfortable they are to discuss sensitive issues. The external factors relate to the availability of health‐care services and the organization of care, including the clinicians' working conditions. Several strategies to overcome identified challenges for clinicians to provide high‐quality fertility preservation care are proposed. These include educational interventions to increase clinicians' knowledge about treatment‐induced fertility impairment and available fertility preservation measures, as well as interventions aimed to increase clinicians' readiness and competence to communicate with patients and their parents. In addition, different types of educational resources for patients have been suggested to improve patient‐provider communication about fertility preservation, such as age‐appropriate brochures and decision aids. Organizational approaches suggested to address the identified external factors include development and implementation of policies and guidelines as well as closer collaboration between oncological and fertility clinics. Also, modifications of electronic medical record systems may support clinicians by prompting the documentation of discussions about potential treatment impact on future fertility and about available fertility preservation options. The development and implementation of multifaceted oncofertility programs appears to be a promising way forward towards high‐quality fertility preservation care meeting patients' needs.
From bench to bedside: Current developments and future possibilities of artificial human ovary to restore fertility
Authors: Salama Mahmoud , Woodruff Teresa K.
Published: February 2019

Several fertility restoration options are not feasible for some cancer patients, poor responders and patients with premature ovarian failure who have diminished ovarian reserve. To preserve and restore fertility in such patients, new strategies should be offered including artificial human ovary technology. In this mini‐review, we explore from bench to bedside the current developments and future possibilities of artificial human ovary technology to restore fertility.
The EX‐PRESS glaucoma shunt versus nonpenetrating deep sclerectomy with Esnoper implant in combined surgery for open‐angle glaucoma: a prospective randomized study
Authors: Muñoz Marcos , Anton Alfonso , Castany Marta , Gil Alfonso , Martinez Alberto , Muñoz‐Negrete Francisco J. , Urcelay Jose , Moreno‐Montañes Javier
Published: February 2019

Purpose

To report 1‐year treatment outcomes of P50 EX‐PRESS implant versus nonpenetrating deep sclerectomy (NPDS) with Esnoper V2000 combined with phacoemulsification.

Design

Randomized, prospective and multicentre clinical trial.

Methods

Settings: Six clinical centres. Population: Patients 54–89 years of age without previous filtering surgery with cataract and glaucoma who required lower levels of intraocular pressure (IOP). Interventions: Phaco‐EX‐PRESS P50 or Phaco‐NPDS with Esnoper V2000, both groups with mitomycin C (0.2 mg/ml for 2 min). Main outcome measures: IOP, complete success rate (IOP: ≥6 and ≤18 mmHg), visual acuity, use of medical therapy and systematic assessment of complications and postoperative interventions.

Results

A total of 98 eyes were enrolled, including 50 in the EX‐PRESS group and 48 in the NPDS group. At 12 months, IOP (mean ± SD) was 13.9 ± 3.3 mmHg in EX‐PRESS group and 13.3 ± 3.6 mmHg in NPDS group (p = 0.38). Success rate was 75% and 80% in EX‐PRESS and NPDS groups, respectively (p = 0.53). The number of glaucoma medications (mean ± SD) was 0.2 ± 0.55 in EX‐PRESS group and 0.17 ± 0.44 in NPDS group (p = 1.00). The total number of complications was 66 in 35 subjects in EX‐PRESS group and 39 in 23 subjects in NPDS group (p = 0.02). The incidence of more than one complication was n = 13 (26%) versus n = 9 (18.8%) in EX‐PRESS and NPDS groups, respectively (p = 0.38). The total number of required postoperative interventions was 59 and 26 in EX‐PRESS and NPDS groups, respectively (p = 0.01). Visual acuity was similar in both groups at month 12 (p = 0.13). Surgical time (mean ± SD) was 52.6 ± 13.6 min in EX‐PRESS group and 63.3 ± 19.4 min in NPDS group (p = 0.01).

Conclusion

Phaco‐EX‐PRESS surgery had similar success rate compared to Phaco‐NPDS during 1 year of follow‐up. Both procedures were associated with similar IOP reduction and use of additional medical therapy at 12 months. EX‐PRESS surgery required more postoperative interventions and had more complications, but needed less surgical time compared to NPDS.
Retinal oxygen saturation in 1461 healthy children aged 7–19 and its associated factors
Authors: Liu Xiaoxiao , He Xiangui , Yin Yao , Zhang Bo , Sun Sifei , Zhu Jianfeng , Zou Haidong , Wang Ling , Xu Xun
Published: February 2019

Purpose

The aim of the present study was to investigate age‐specific normative retinal oxygen saturation values and explore the associated factors in healthy Chinese school‐aged children with different refractive statuses.

Design

Population‐based observational cross‐sectional study.

Methods

Children aged 7–19 years were enrolled. Each participant underwent a series of comprehensive ocular examinations, including axial length (AL), cycloplegic refraction and Oxymap T1 imagery following cycloplegia. The acquired oximetry images were measured, and the values of the retinal oxygen saturation parameters were calculated. The independent factors of the retinal oxygen saturation were analysed using multiple linear regression. The oxygen saturation of retinal arteries (SaO2) and veins (SvO2) as well as the differences between the arteries and veins (AVD) were measured as the main outcomes.

Results

In total, 1461 participants were included in the study. The mean age of the participants was 12.1 ± 3.2 years, and 53.0% were boys. The mean SaO2, SvO2 and AVD values were 83.7 ± 6.4%, 50.1 ± 5.4% and 33.6 ± 5.4%, respectively, and the values increased with age. Girls had higher SvO2 and lower AVD than boys (p < 0.05). The Pearson correlation coefficients among spherical equivalent (SE) and SaO2, SvO2 and AVD were −0.372, −0.203 and −0.240, respectively (all p < 0.001), while the correlations between AL and SaO2, SvO2 and AVD were 0.276, 0.106 and 0.221, respectively (all p < 0.001). The myopia group had significantly higher SaO2, SvO2 and AVD than the emmetropia and hyperopia groups (p < 0.001), but the high myopia group had lower SaO2 and SvO2 than the moderate myopia group. When age, gender, body mass index (BMI), intraocular pressure (IOP) and axial length (AL) were included as factors in the multiple regression, older age was associated with higher SaO2, SvO2 and AVD, while longer AL was associated with higher SaO2 and AVD. Gender was an independent factor predicting SvO2, while gender and BMI were the independent factors predicting AVD. Age explained more variance than AL in SaO2, SvO2 and AVD.

Conclusions

Our population‐based study provides age‐specific profiles of retinal oxygen saturation in Chinese children and adolescents. Older age and longer AL were important independent factors of increased retinal oxygen saturation.
Body mass index in early pregnancy and future risk of severe liver disease: a population‐based cohort study
Authors: Hagström Hannes , Höijer Jonas , Andreasson Anna , Bottai Matteo , Johansson Kari , Ludvigsson Jonas F. , Stephansson Olof
Published: February 2019

Background

In young men, high body mass index (BMI) has been linked to liver disease later in life, but it is unclear if this also applies to women.

Aim

To study the association between BMI early in life and development of liver disease later in life in women.

Methods

We obtained data on early pregnancy BMI from 1 139 458 Swedish women between 1992 and 2015. National registers were used to ascertain incident severe liver disease, defined as cirrhosis, decompensated liver disease (hepatocellular carcinoma, oesophageal varices, hepatorenal syndrome or hepatic encephalopathy) or liver failure. A Cox regression model was used to investigate associations of BMI with incident severe liver disease adjusting for maternal age, calendar year, country of birth, smoking, civil status and education.

Results

During an average follow‐up of 13.8 years, 774 women developed severe liver disease. Compared to women with a low normal BMI (18.5‐22.4), an increased risk of severe liver disease was found in women with BMI between 22.5 and 24.9 kg/m2 (adjusted hazard ratio [aHR] 1.25, 95% CI 1.04‐1.50), 25.0 and 29.9 kg/m2 (aHR 1.27, 95% CI 1.05‐1.53) and BMI ≥ 30 kg/m2 (aHR 1.77, 95% CI 1.40‐2.24). When examining BMI as a continuous variable, the aHR increased by 4% per kg/m2 (95% CI 1.02‐1.05). A diagnosis of diabetes was associated with an increased risk of severe liver disease independent of baseline BMI.

Conclusion

A high BMI early in life in women is associated with a dose‐dependent, increased risk for future severe liver disease.
Effect of different time intervals after feeding on plasma metabolites in growing pigs: an UPLC‐MS‐based metabolomics study
Authors: Liu Hu , Li Tiantian , Jiang Zhaoning , Wang Wenhui , Ming Dongxu , Chen Yifan , Wang Fenglai
Published: February 2019

A diet consumed by pigs provides the nutrients for the production of a large number of metabolites that, after first‐pass metabolism in the liver, circulate systemically where they may exert diverse physiologic influences on pigs. So far, little is known of how feeding elicits changes in metabolic profiles for growing pigs. This study investigated differences in plasma metabolites in growing pigs at several intervals after feeding using the technique of metabolomics. Ten barrows (22.5 ± 0.5 kg BW) were fed a corn‐soybean meal basal diet and were kept in metabolism crates for a period of 11 days. An indwelling catheter was inserted into the jugular vein of each pig before the experimental period. Plasmas before and 1, 4, and 8 hr after feeding were collected at day 11 and differential metabolites were determined using a metabolomics approach. Direct comparison at several intervals after feeding revealed differences in 14 compounds. Identified signatures were enriched in metabolic pathways related to linoleic acid metabolism, arginine and proline metabolism, lysine degradation, glycine, serine and threonine metabolism, and lysine biosynthesis. These results suggest that plasma metabolites of growing pigs after feeding were modulated through changes in linoleic acid metabolism and amino acid metabolism.
An Iterative Penalized Least Squares Approach to Sparse Canonical Correlation Analysis
Authors: Mai Qing , Zhang Xin
Published: February 2019

It is increasingly interesting to model the relationship between two sets of high-dimensional measurements with potentially high correlations. Canonical correlation analysis (CCA) is a classical tool that explores the dependency of two multivariate random variables and extracts canonical pairs of highly correlated linear combinations. Driven by applications in genomics, text mining, and imaging research, among others, many recent studies generalize CCA to high-dimensional settings. However, most of them either rely on strong assumptions on covariance matrices, or do not produce nested solutions. We propose a new sparse CCA (SCCA) method that recasts high-dimensional CCA as an iterative penalized least squares problem. Thanks to the new iterative penalized least squares formulation, our method directly estimates the sparse CCA directions with efficient algorithms. Therefore, in contrast to some existing methods, the new SCCA does not impose any sparsity assumptions on the covariance matrices. The proposed SCCA is also very flexible in the sense that it can be easily combined with properly chosen penalty functions to perform structured variable selection and incorporate prior information. Moreover, our proposal of SCCA produces nested solutions and thus provides great convenient in practice. Theoretical results show that SCCA can consistently estimate the true canonical pairs with an overwhelming probability in ultra-high dimensions. Numerical results also demonstrate the competitive performance of SCCA.
Aneuploidy in children with relapsed B‐cell precursor acute lymphoblastic leukaemia: clinical importance of detecting a hypodiploid origin of relapse
Authors: Groeneveld‐Krentz Stefanie , Schroeder Michael P. , Reiter Michael , Pogodzinski Malwine J. , Pimentel‐Gutiérrez Helia J. , Vagkopoulou Renia , Hof Jana , Chen‐Santel Christiane , Nebral Karin , Bradtke Jutta , Türkmen Seval , Baldus Claudia D. , Gattenlöhner Stefan , Haas Oskar A. , von Stackelberg Arend , Karawajew Leonid , Eckert Cornelia , Kirschner‐Schwabe Renate
Published: February 2019

Aneuploidy is common in paediatric B‐cell precursor acute lymphoblastic leukaemia (ALL). Specific subgroups, such as high hyperdiploidy (>50 chromosomes or DNA Index ≥1·16) and hypodiploidy (<45 chromosomes), predict outcome of patients after primary treatment. Whether aneuploidy has a prognostic value for relapsed disease is yet to be determined. Using DNA index and centromere screening by multiplex ligation‐dependent probe amplification, we investigated aneuploidy in 413 children treated for first relapse of B‐cell precursor ALL according to the ALL‐REZ BFM 2002 protocol. Ten‐year event‐free survival of patients with high hyperdiploid relapses approached 70%, whereas it was only 40% in low hyperdiploid relapses. Three patients with apparent hyperdiploid relapse had TP53 mutations. In these cases, array‐based allelotyping revealed a hypodiploid origin with absence of the hypodiploid founder clone (masked hypodiploidy). Collectively, patients with evident or masked hypodiploid relapses showed an extremely low event‐free survival rate of 9%. Importantly, the current relapse risk stratification did not identify cases with masked hypodiploidy as high‐risk patients, due to their favourable clinical presentation. In multivariate analysis, hypodiploidy proved to be an independent prognostic factor. This finding supports stratification of relapses with hypodiploid origin into high‐risk arms in future trials or allocation of patients to alternative treatment approaches.
Long‐term survivors of childhood, adolescent and young adult non‐Hodgkin lymphoma
Authors: Ehrhardt Matthew J. , Hochberg Jessica , Bjornard Kari L. , Brinkman Tara M.
Published: February 2019

Progress in overall survival rates for childhood non‐Hodgkin lymphoma (NHL) can be largely attributed to effective development and conduct of a number of international treatment studies. Knowledge gained from these studies has shifted the treatment paradigm from a “one‐size fits all” strategy to a histologically dependent approach. More specifically, many now adhere to a risk‐stratified approach, prescribing cumulative doses and intensities of chemotherapeutic exposures based upon the aggressiveness of disease. Moreover, recognition that high cure rates could be achieved without the use of radiation has eliminated the use of this modality in frontline settings for the majority of newly diagnosed children. These changes have contributed to the emergence of a heterogeneous group of NHL survivors. As the number of NHL survivors continues to increase, providers will encounter a wide spectrum of individuals whose risk for long‐term complications are accordingly diverse. The following review summarizes the existing literature surrounding late effects, such as chronic health conditions, functional and neurocognitive performance outcomes, and health‐related quality of life, that are unique to NHL survivors, as well as those extrapolated from the broader childhood cancer survivor population.
Risperidone effects on heterochromatin: the role of kinase signaling
Authors: Feiner B , Chase K A , Melbourne J K , Rosen C , Sharma R P
Published: February 2019

Epigenetic effects of anti-psychotic medications are poorly understood. We have appropriated a model whereby heterochromatin is established through 24- or 48-h lipopolysaccharide (LPS) treatment, and tested the epigenetic effects of risperidone along the adenylyl cyclase/protein kinase A (AC/PKA) pathway in human liposarcoma cells that express the LPS-sensitive Toll-like receptor (TLR)-4. Human SW872 cells were cultured with LPS and mRNA expression levels and epigenetic modifications of dimethylated lysine 9 of histone 2 (H3K9me2), geterochromatin protein 1γ (HP1γ) and phospho-H3S10 at promoters of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL1β were measured. Pharmacological manipulation of the AC/PKA pathway was achieved through treatment with a PKA inhibitor (H89), mitogen- and stress-activated kinase 1 (MSK1) inhibitor (SB-747651A) or forskolin. Twenty-four and 48-h LPS treatment establishes heterochromatin at selected promoters, corresponding to decreased mRNA expression. Concurrent risperidone treatment with LPS treatment can both ‘block’ and ‘reverse’ heterochromatin formation. Forskolin treatment resulted in a similar disassembling effect on heterochromatin. Conversely, inhibition of PKA by H89 or MSK1 both blocked ‘normalizing’ effects of risperidone on LPS-induced heterochromatin. Our results demonstrate that risperidone can disassemble heterochromatin, exerting this effect along the G-protein/AC/PKA pathway. This approach can also be utilized to investigate functional outcomes of single or combined pharmacological treatments on chromatin assemblies in human cells.
Bmp4 is an essential growth factor for the initiation of genital tubercle (GT) outgrowth
Authors: Kajioka Daiki , Suzuki Kentaro , Nakada Shoko , Matsushita Shoko , Miyagawa Shinichi , Takeo Toru , Nakagata Naomi , Yamada Gen
Published: February 2019

The external genitalia are appendage organs outgrowing from the posterior body trunk. Murine genital tubercle (GT), anlage of external genitalia, initiates its outgrowth from embryonic day (E) 10.5 as a bud structure. Several growth factors such as fibroblast growth factor (FGF), Wnt and Sonic hedgehog (Shh) are essential for the GT outgrowth. However, the mechanisms of initiation of GT outgrowth are poorly understood. We previously identified bone morphogenetic protein (Bmp) signaling as a negative regulator for GT outgrowth. We show here novel aspects of Bmp4 functions for GT outgrowth. We identified the Bmp4 was already expressed in cloaca region at E9.5, before GT outgrowth. To analyze the function of Bmp4 at early stage for the initiation of GT outgrowth, we utilized the Hoxa3‐Cre driver and Bmp4
flox/flox mouse lines. Hoxa3
Cre/+; Bmp4
flox/flox mutant mice showed the hypoplasia of GT with reduced expression of outgrowth promoting genes such as Wnt5a, Hoxd13 and p63, whereas Shh expression was not affected. Formation of distal urethral epithelium (DUE) marked by the Fgf8 expression is essential for controlling mesenchymal genes expression in GT and subsequent its outgrowth. Furthermore, Fgf8 expression was dramatically reduced in such mutant mice indicating the defective DUE formation. Hence, current results indicate that Bmp4 is an essential growth factor for the initiation of GT outgrowth independent of Shh signaling. Thus, Bmp4 positively regulates for the formation of DUE. The current study provides new insights into the function of Bmp signaling at early stage for the initiation of GT outgrowth.
Advances of tooth‐derived stem cells in neural diseases treatments and nerve tissue regeneration
Authors: Wang Dianri , Wang Yuhao , Tian Weidong , Pan Jian
Published: February 2019

Nerous system diseases, both central and peripheral, bring an incredible burden onto patients and enormously reduce their quality of life. Currently, there are still no effective treatments to repair nerve lesions that do not have side effects. Stem cell–based therapies, especially those using dental stem cells, bring new hope to neural diseases. Dental stem cells, derived from the neural crest, have many characteristics that are similar to neural cells, indicating that they can be an ideal source of cells for neural regeneration and repair. This review summarizes the neural traits of all the dental cell types, including DPSCs, PDLCs, DFCs, APSCs and their potential applications in nervous system diseases. We have summed up the advantages of dental stem cells in neural repair, such as their neurotrophic and neuroprotective traits, easy harvest and low rejective reaction rate, among others. Taken together, dental stem cells are an ideal cell source for neural tissue regeneration and repair.
Generalizability of glucagon‐like peptide‐1 receptor agonist cardiovascular outcome trials to the overall type 2 diabetes population in the United States
Authors: Boye Kristina S. , Riddle Matthew C. , Gerstein Hertzel C. , Mody Reema , Garcia‐Perez Luis‐Emilio , Karanikas Chrisanthi A. , Lage Maureen J. , Riesmeyer Jeffrey S. , Lakshmanan Mark C.
Published: February 2019

Aim

To examine the generalizability of results from glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) cardiovascular outcome trials (CVOTs) in the US type 2 diabetes (T2D) population.

Materials and methods

Patients enrolled or eligible for inclusion in four CVOTs (EXSCEL, LEADER, REWIND, and SUSTAIN‐6) were examined in reference to a retrospective clinical database weighted to match the age and sex distribution of the US adult T2D population. We descriptively compared key baseline characteristics of the populations enrolled in each trial to those of the reference population and estimated the proportions of individuals in the reference population represented by those in the trials for each characteristic. We also estimated the proportions of individuals in the reference population that might have been enrolled in each trial based upon meeting the trial inclusion and exclusion (I/E) criteria.

Results

No trial's enrolled population perfectly matched the reference population in key characteristics. The EXSCEL population most closely matched in mean age (62.7 vs. 60.5 years) and percentage with estimated glomerular filtration rate <60 (18.6 vs. 17.3%), while REWIND most closely matched in HbA1c, sex distribution, and proportion with a prior myocardial infarction. Based on I/E criteria, 42.6% of the reference population were eligible for enrolment in REWIND, versus 15.9% in EXSCEL, 13.0% in SUSTAIN‐6, and 12.9% in LEADER.

Conclusions

Although none of the trials are fully representative of the general population, among the four trials examined, results from baseline REWIND were found to be more generalizable to the US adult T2D population than those of other GLP‐1 RA CVOTs.
Continual Improvement of Online and Blended Teaching Using Relative Proximity Theory
Authors: MacLeod Kenneth R. , Swart William W. , Paul Ravi C.
Published: February 2019

This article applies Deming's Plan‐Do‐Study‐Act (PDSA) cycle of continual improvement to a course taught with both blended and online sections. It uses Relative Proximity Theory, an extension of the Theory of Transactional Distance, to measure the quality of online/blended learning as a function of the obstacles to a student's full engagement with a course. These obstacles can arise because of the student's transactions with fellow students, with the instructor, with the course content, or from the instructional technology used in the course. Using stepwise multiple regression, the most significant obstacles can be identified. Once the obstacles are known, strategies to reduce them are planned and implemented. Logistic regression is used to determine if the realized reductions are statistically significant and for setting the stage for further improvements.
Teaching Plan‐Do‐Study‐Act (PDSA) in a Supply Chain Context: A Paper Football In‐Class Activity
Authors: Brau Rebekah Inez , Gardner John W. , Webb G. Scott , McDonald Jason K.
Published: February 2019

We develop a single‐class period learning game for the Plan‐Do‐Study‐Act (PDSA) improvement cycle. The experiential activity walks teams through the PDSA problem‐solving process as they create paper American footballs and improve their performance using each step of the cycle. The game is one of the first to focus on PDSA. Key benefits include increased student attention, engagement, and learning. Empirical tests show that participant pre‐ and post‐test scores regarding their understanding of each phase of PDSA improved 21.2% after completing the game. Additionally, the treatment group performed 16.6% higher than the control group. In participant perception questions, 85% of participants felt the game was more effective than lecture or reading, 93% felt the game was fun, 95% felt the game improved their understanding of PDSA, and 98% felt the game was engaging.
Perceived stress and psychosis: The effect of perceived stress on psychotic‐like experiences in a community sample of adolescents
Authors: Turley Dan , Drake Richard , Killackey Eoin , Yung Alison R.
Published: February 2019

Aims

Psychotic‐like experiences (PLE) are sub‐threshold, non‐clinical forms of psychosis which can place an individual at greater risk of development of a psychotic disorder. Subtypes of PLE have also been shown to exist (bizarre experiences, persecutory ideation, perceptual abnormalities and magical thinking). Perceived stress relates to how two individuals may deal with the same objectively stressful event in different ways. The objective of our study was to investigate the extent to which perceived stress is associated with PLE in a community sample of adolescents, whether certain subtypes of PLE correlate more with perceived stress than others and to explore the role of depression with these associations.

Methods

A total of 655 students completed the community assessment of psychic experiences (CAPE) and perceived stress scale (PSS). Pearson's correlation was used to investigate the relationship between PSS and CAPE and also between perceived stress and the four subtypes of PLE. Regression then explored the effect of perceived stress on PLE when accounting for depressive symptomatology.

Results

Positive correlation was found between PSS and total CAPE (r = 0.405, P = 0.000). Positive significant correlation was also found between PSS and each subtype of PLE, with persecutory ideation correlating the strongest and magical thinking the least. Perceived stress was significantly associated with PLE even after adjusting for depression.

Conclusions

We recommend that more regular screening of perceived stress in adolescent populations could lead to earlier recognition of PLE. Early treatment has shown to reduce rates of transition to psychosis, and so could benefit our adolescent community in the future.
Self‐regulated learning strategies in world's first MOOC in implant dentistry
Authors: Lan Min , Hou Xiangyu , Qi Xinyu , Mattheos Nikos
Published: February 2019

Background

Massive Open Online Courses (MOOCs) have been often described as a major innovation Higher Education, but their application in the teaching of clinical disciplines is still very limited, while there is a lack of scientific evaluations in this domain. The aim of this study was to investigate learners' behaviours and correlate patterns of Self‐Regulated Learning (SRL) with performance and achievement during a MOOC in Implant Dentistry.

Methods

The clickstream data of learners from the first run of the MOOC Implant dentistry by The University of Hong Kong were modelled and quantified based on Zimmerman's SRL model. The data were quantitatively analysed by means of k‐means clustering for evidence of five SRL behavioural indicators of student activity. The clusters identified were then correlated with student engagement and learning performance.

Results

A total of 7608 individuals enrolled, 5014 engaged (active learners 65.90%), 1277 of them (25.47%) completed the course and 1232 purchased a certificate. Two major groups of learners emerged: Attentive (n = 1433) who were more likely to follow the prescribed pathway in the MOOC and Auditors (n = 3581) who accessed content selectively. There was significantly higher engagement, achievement and completion rates among Attentive than Auditors. Both groups included subcategories (Browser, Digger, Test‐driven, Sampler, Persistent) which might reflect different SRL strategies.

Conclusion

A MOOC in a clinical discipline can achieve high enrolment and completion rates as compared to current benchmarks. There appears to be a wide diversity of learning behaviours among learners, with two however dominant patterns. Learners with a linear learning pathway achieved significantly higher grades and completion rates than those who accessed content irregularly and selectively. Such differences however might be influenced by the demographic and professional background of the learner, as well as their motivation to attending the MOOC. Certain learning behaviours, in particular how learners access content in relation to assessments might be closer related to SRL.
Predicting coral community recovery using multi‐species population dynamics models
Authors: Kayal Mohsen , Lenihan Hunter S. , Brooks Andrew J. , Holbrook Sally J. , Schmitt Russell J. , Kendall Bruce E.
Published: February 2019

Predicting whether, how, and to what degree communities recover from disturbance remain major challenges in ecology. To predict recovery of coral communities we applied field survey data of early recovery dynamics to a multi‐species integral projection model that captured key demographic processes driving coral population trajectories, notably density‐dependent larval recruitment. After testing model predictions against field observations, we updated the model to generate projections of future coral communities. Our results indicated that communities distributed across an island landscape followed different recovery trajectories but would reassemble to pre‐disturbed levels of coral abundance, composition, and size, thus demonstrating persistence in the provision of reef habitat and other ecosystem services. Our study indicates that coral community dynamics are predictable when accounting for the interplay between species life‐history, environmental conditions, and density‐dependence. We provide a quantitative framework for evaluating the ecological processes underlying community trajectory and characteristics important to ecosystem functioning.