bluuebunny/crossref_metadata_2025 huggingface dataset:
A Community‐Based Intervention Program's Effects on Dietary Intake Behaviors
Authors: Chang Mei‐Wei , Brown Roger , Nitzke Susan
Published: October 2017

Objective

To evaluate the effect of a community‐based lifestyle behavioral intervention on intakes of fat, fruits, vegetables, fast foods, and beverages in low‐income young mothers with overweight or obesity.

Methods

Participants were randomly assigned to an intervention (watching video lessons at home plus peer support group teleconferences) or a comparison group. General linear mixed model analyses were utilized to determine mean differences between the groups (212 intervention, 126 comparison) immediately following and 3 months (196 intervention, 115 comparison) after the intervention.

Results

Immediately after the intervention, the intervention group had significantly lower mean scores in intakes of fat (effect size [d] = 0.24), fast foods (d = 0.33), and non–sugar‐sweetened beverages (d = 0.27) than the comparison group. No significant group differences were observed for intakes of fruits, vegetables, or sugar‐sweetened beverages. Three months after the intervention, no significant group differences were observed for intakes of fat, fruits, vegetables, fast foods, and both sugar‐ and non–sugar‐sweetened beverages.

Conclusions

The intervention group improved dietary intakes of fat and fast foods but not fruits, vegetables, or beverages over the short term. Our intervention had no long‐term effect on dietary intake behaviors.
The Food Environment, Preference, and Experience Modulate the Effects of Exendin‐4 on Food Intake and Reward
Authors: Mella Ricardo , Schmidt Camila B. , Romagnoli Pierre‐Paul , Teske Jennifer A. , Perez‐Leighton Claudio
Published: October 2017

Objective

The obesogenic food environment facilitates access to multiple palatable foods. Exendin‐4 (EX4) is a glucagon‐like peptide 1 receptor (GLP1R) agonist that inhibits food intake and has been proposed as an obesity therapy. This study tested whether the composition of the food environment and experience with palatable foods modulate the effects of EX4 on food intake and reward.

Methods

Mice fed a cafeteria (CAF) or control diet were tested for the anorectic effects of EX4 when simultaneously offered foods of varying individual preference and in a conditioned place preference (CPP) test for chocolate. Plasma glucagon‐like peptide 1 (GLP1) and hypothalamic GLP1R mRNA were analyzed post mortem.

Results

Mice fed a CAF diet developed individual food preference patterns. Offering mice either novel or highly preferred foods decreased the potency of EX4 to inhibit food intake compared to low preference foods or chow. Compared to the control diet, CAF diet intake blocked the decrease in chocolate CPP caused by EX4 and decreased the expression of hypothalamic GLP1R mRNA without altering the plasma GLP1 concentration.

Conclusions

The composition of the food environment, food preference, and experience modulate the ability of EX4 to inhibit food intake and reward. These data highlight the significance of modeling the complexity of the human food environment in preclinical obesity studies.
Characteristics of Weight Loss Trajectories in a Comprehensive Lifestyle Intervention
Authors: Marek Ryan J. , Coulon Sandra M. , Brown Joshua D. , Lydecker Janet A. , Marek Scott , Malcolm Robert , O'Neil Patrick M.
Published: October 2017

Objective

Focusing on average weight loss (WL) from interventions provides useful efficacy data but masks large variability across patients. In this study, parameters of weight loss trajectories were determined that differentiated individuals during a 15‐week clinical lifestyle intervention.

Methods

Patients (n = 595) were in a fee‐for‐service WL lifestyle program with a partial meal replacement diet and lifestyle change counseling. Parameters used in latent class analyses were percent WL (%WL), weight nadir, number of weekly weight gains, maximum weekly percent weight gain, standard deviation of weekly weight changes, linear slope values, and change in slope.

Results

Average %WL was 9.73%. Latent class analyses revealed three groups with considerable overlap in %WL ranges but differing significantly on all trajectory parameters (Ps < 0.001). Group 1 had the most variable and least successful pattern of weight changes. Group 3 had the least variable and most successful pattern of weight changes. Group 2 fell between the others on all parameters.

Conclusions

Emphasis on average WL likely obscures considerable variability in individual courses of weight change. Moreover, patients with similar %WL can have different WL trajectories. Identification of behavioral/physiological characteristics associated with different weight loss trajectories may facilitate the development of more tailored interventions, particularly for trajectories associated with less optimal outcomes.
Binge Eating and Weight Loss Outcomes in Individuals with Type 2 Diabetes: 4‐Year Results from the Look AHEAD Study
Authors: Chao Ariana M. , Wadden Thomas A. , Gorin Amy A. , Shaw Tronieri Jena , Pearl Rebecca L. , Bakizada Zayna M. , Yanovski Susan Z. , Berkowitz Robert I.
Published: October 2017

Objective

This study aims to assess whether an intensive lifestyle intervention (ILI) for weight reduction precipitates binge eating (BE) and whether BE attenuates 4‐year weight loss among participants with type 2 diabetes and overweight or obesity.

Methods

Participants (N = 4,901) were from Look AHEAD, a randomized controlled trial that compared ILI to diabetes support and education (DSE). Annual assessments of measured weight and self‐reported BE were used. By using the yearly time points when a person endorsed BE, participants were classified as no BE, remitted BE, incident BE, inconsistent BE (2‐3 years, including baseline), and consistent BE (≥ 4 years, including baseline). Cox regression and mixed‐effects models were used for analyses.

Results

ILI participants were marginally more likely to report incident BE at year 4 than those in DSE (P = 0.06). At year 4, ILI participants with remitted BE lost more weight (4.7 ± 0.8%) than those with consistent BE (1.9 ± 1.0%; P = 0.03). ILI participants with no BE lost more weight (4.6 ± 0.2%) than those with incident BE (3.1 ± 0.6%; P = 0.02) and consistent BE (P = 0.01). DSE participants with remitted BE lost more weight than those with incident and consistent BE.

Conclusions

Preexisting BE did not seem to be a contraindication for ILI, although persistent BE attenuated weight loss. Patients who report new or ongoing BE may need additional treatment.
Effect of Exercise Type During Intentional Weight Loss on Body Composition in Older Adults with Obesity
Authors: Beavers Kristen M. , Ambrosius Walter T. , Rejeski W. Jack , Burdette Jonathan H. , Walkup Michael P. , Sheedy Jessica L. , Nesbit Beverly A. , Gaukstern Jill E. , Nicklas Barbara J. , Marsh Anthony P.
Published: October 2017

Objective

To examine the long‐term effects of exercise modality during weight loss on body composition and associations between body composition and physical function changes.

Methods

Two hundred forty‐nine older adults (66.9 ± 4.7 years, 71% women, 32% African American, BMI: 34.4 ± 3.7 kg/m2) were randomized to weight loss (WL; n = 82), WL plus aerobic training (WL + AT; n = 86), or WL plus resistance training (WL + RT; n = 81) for 18 months. Dual‐energy x‐ray absorptiometry–acquired body composition, 400‐m walk time, and knee extensor strength were measured at baseline and at 6 and 18 months.

Results

Total body mass loss was enhanced when WL was combined with exercise (WL: −5.7 ± 0.7 kg, WL + AT: −8.5 ± 0.7 kg, WL + RT: −8.7 ± 0.7 kg; P < 0.01). Total body fat mass loss was significantly greater in WL + AT (−6.8 ± 0.6 kg, −16.4%) and WL + RT (−7.8 ± 0.5 kg, −19.0%) than WL (−4.8 ± 0.6 kg, −10.9%); both P < 0.01. Lean mass loss was greatest in WL + AT (−1.6 ± 0.3 kg, −3.1%) compared with WL + RT (−0.8 ± 0.3 kg, −1.5%) or WL (−1.0 ± 0.3 kg; −2.0%); both P ≤ 0.02. Change in 400‐m walk time was associated with change in fat mass (β/SD = +6.1 s; P < 0.01), while change in knee extensor strength was associated with change in lean mass (β/SD = +1.6 Nm; P < 0.01).

Conclusions

WL + RT results in less lean mass lost than WL + AT; WL plus exercise yields greater fat mass loss than WL alone.
American Society of Clinical Oncology Summit on Addressing Obesity Through Multidisciplinary Provider Collaboration: Key Findings and Recommendations for Action
Authors: Ligibel Jennifer A. , Alfano Catherine M. , Hershman Dawn L. , Merrill Janette K. , Basen‐Engquist Karen , Bloomgarden Zachary T. , Demark‐Wahnefried Wendy , Dixon Suzanne , Hassink Sandra G. , Jakicic John M. , Morton John Magaña , Okwuosa Tochi M. , Powell‐Wiley Tiffany M. , Rothberg Amy E. , Stephens Mark , Streett Sarah E. , Wild Robert A. , Westman Eric A. , Williams Ronald J. , Wollins Dana S. , Hudis Clifford A.
Published: October 2017

Objective

Given the increasing evidence that obesity increases the risk of developing and dying from malignancy, the American Society of Clinical Oncology (ASCO) launched an Obesity Initiative in 2013 that was designed to increase awareness among oncology providers and the general public of the relationship between obesity and cancer and to promote research in this area. Recognizing that the type of societal change required to impact the obesity epidemic will require a broad‐based effort, ASCO hosted the “Summit on Addressing Obesity through Multidisciplinary Collaboration” in 2016.

Methods

This meeting was held to review current challenges in addressing obesity within the respective health care provider communities and to identify priorities that would most benefit from a collective and cross‐disciplinary approach.

Results

Efforts focused on four key areas: provider education and training; public education and activation; research; and policy and advocacy. Summit attendees discussed current challenges in addressing obesity within their provider communities and identified priorities that would most benefit from multidisciplinary collaboration.

Conclusions

A synopsis of recommendations to facilitate future collaboration, as well as examples of ongoing cooperative efforts, provides a blueprint for multidisciplinary provider collaboration focused on obesity prevention and treatment.
Low‐Calorie Sweeteners: Disturbing the Energy Balance Equation in Adolescents?
Authors: Sylvetsky Allison C. , Jin Yichen , Mathieu Kevin , DiPietro Loretta , Rother Kristina I. , Talegawkar Sameera A.
Published: October 2017

Objective

The aim of this study was to investigate the relationship between low‐calorie sweeteners (LCSs), energy intake, and weight in US youth.

Methods

Data were collected from individuals aged 2 to 19 years who participated in the National Health and Nutrition Examination Survey (NHANES) 2009–2010 (n  =  3,296), 2011–2012 (n  =  3,139), and 2013–2014 (n  =  3,034). Logistic regression, unadjusted and adjusted for age, sex, race/ethnicity, income, energy intake, and physical activity, was used to estimate the odds of obesity in LCS consumers versus nonconsumers, both overall and across product categories (foods vs. beverages) and sociodemographic subgroups.

Results

Among adolescents, the odds of obesity were 55% and 70% higher in LCS beverage consumers than in nonconsumers in unadjusted and adjusted models, respectively. Energy intakes did not differ based on LCS consumption. In contrast, associations between LCS consumption and obesity risk were not statistically significant among children (2‐11 y old), except in boys and those who self‐identified as Hispanic.

Conclusions

LCS consumption is associated with increased odds of obesity among adolescents. This relationship is strikingly independent of total energy intake. Although findings should be interpreted cautiously because of the limitations of self‐reported dietary intake and the cross‐sectional nature of this analysis, the observational analysis in this study supports the need to investigate the mechanisms by which LCS may influence body weight, independently of changes in energy intake.
A Systematic Review of the Effect of Lifestyle Interventions on Adipose Tissue Gene Expression: Implications for Carcinogenesis
Authors: Campbell Kristin L. , Landells Catherine E. , Fan Jeremy , Brenner Darren R.
Published: October 2017

Objective

The mechanisms driving the associations between body weight and physical activity levels and multiple types of cancer are not yet well understood. The purpose of this review was to examine the effects of lifestyle interventions on proposed biomarkers of lifestyle and cancer risk at the level of adipose tissue in humans.

Methods

Embase, MEDLINE, and CINAHL were searched by using keywords relating to exercise or diet interventions, adipose tissue biology, and outcomes of interest. Eligible studies included randomized clinical trials of exercise and/or dietary interventions in humans compared with control or other interventions, reporting the collection of subcutaneous abdominal adipose tissue.

Results

Nineteen studies met criteria for inclusion. Eight studies modified dietary intake, five altered exercise levels, and six studies used a combination of both. Change in subcutaneous adipose tissue gene expression was most commonly observed with dietary weight loss, with a pattern of decrease in leptin, tumor necrosis factor alpha, and interleukin 6, along with an increase in adiponectin. There was limited change with exercise‐only interventions or study arms.

Conclusions

Interventions leading to weight loss result in an altered gene expression of adipokines and inflammatory markers in subcutaneous adipose tissue, while less change in gene expression was noted with exercise alone.
Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting
Authors: Anton Stephen D. , Moehl Keelin , Donahoo William T. , Marosi Krisztina , Lee Stephanie A. , Mainous Arch G. , Leeuwenburgh Christiaan , Mattson Mark P.
Published: October 2017

Objective

Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on a recurring basis. This review is focused on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch: the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake).

Results and Conclusions

Emerging findings suggest that the metabolic switch from glucose to fatty acid‐derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty acid‐derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and of the magnitude of negative energy balance during the fasting period.
Two Arabidopsis late pollen transcripts are detected in cytoplasmic granules
Authors: Scarpin María R. , Sigaut Lorena , Temprana Silvio G. , Boccaccio Graciela L. , Pietrasanta Lía I. , Muschietti Jorge P.
Published: October 2017

Many of mRNAs synthesized during pollen development are translated after germination, and we hypothesize that they are stored in cytoplasmic granules. We analyzed the cellular localization of the SKS14 and AT59 Arabidopsis mRNAs, which are orthologues of the tobacco NTP303 and tomato LAT59 pollen mRNAs, respectively, by artificially labeling the transcripts with a MS2‐GFP chimera. A MATLAB‐automated image analysis helped to identify the presence of cytoplasmic SKS14 and AT59 mRNA granules in mature pollen grains. These mRNA granules partially colocalized with VCS and DCP1, two processing body (PB) proteins. Finally, we found a temporal correlation between SKS14 protein accumulation and the disappearance of SKS14 mRNA granules during pollen germination. These results contribute to unveil a mechanism for translational regulation in Arabidopsis thaliana pollen.
ALUMINUM RESISTANCE TRANSCRIPTION FACTOR 1 (ART1) contributes to natural variation in aluminum resistance in diverse genetic backgrounds of rice (O. sativa)
Authors: Arbelaez Juan D. , Maron Lyza G. , Jobe Timothy O. , Piñeros Miguel A. , Famoso Adam N. , Rebelo Ana Rita , Singh Namrata , Ma Qiyue , Fei Zhangjun , Kochian Leon V. , McCouch Susan R.
Published: October 2017

Transcription factors (TFs) regulate the expression of other genes to indirectly mediate stress resistance mechanisms. Therefore, when studying TF‐mediated stress resistance, it is important to understand how TFs interact with genes in the genetic background. Here, we fine‐mapped the aluminum (Al) resistance QTL Alt12.1 to a 44‐kb region containing six genes. Among them is ART1, which encodes a C2H2‐type zinc finger TF required for Al resistance in rice. The mapping parents, Al‐resistant cv Azucena (tropical japonica) and Al‐sensitive cv IR64 (indica), have extensive sequence polymorphism within the ART1 coding region, but similar ART1 expression levels. Using reciprocal near‐isogenic lines (NILs) we examined how allele‐swapping the Alt12.1 locus would affect plant responses to Al. Analysis of global transcriptional responses to Al stress in roots of the NILs alongside their recurrent parents demonstrated that the presence of the Alt12.1 from Al‐resistant Azucena led to greater changes in gene expression in response to Al when compared to the Alt12.1 from IR64 in both genetic backgrounds. The presence of the ART1 allele from the opposite parent affected the expression of several genes not previously implicated in rice Al tolerance. We highlight examples where putatively functional variation in cis‐regulatory regions of ART1‐regulated genes interacts with ART1 to determine gene expression in response to Al. This ART1–promoter interaction may be associated with transgressive variation for Al resistance in the Azucena × IR64 population. These results illustrate how ART1 interacts with the genetic background to contribute to quantitative phenotypic variation in rice Al resistance.
Diverse contributions of MYC2 and EIN3 in the regulation of Arabidopsis jasmonate‐responsive gene expression
Authors: Zheng Yuyu , Lan Yiheng , Shi Tieliu , Zhu Ziqiang
Published: October 2017

Derepression of transcription factors is the key mechanism for triggering plant jasmonate (JA) responses. Unlike regulating certain physiological functions for the majority of transcription factors in JA signaling, MYC2 and EIN3 control more diverse aspects. MYC2 predominantly participates in wounding response, metabolism, and root growth inhibition, while EIN3 (and its closest homolog EIL1) regulates defense gene expression and root hair development. Recently, it was reported that MYC2 and EIN3/EIL1 proteins mutually interact with each other and suppress their interaction partner's transcriptional activities. To understand their contributions in the modulation of transcriptomic network, we initially identified 1,495 differentially expressed jasmonate (JA)‐responsive genes in wild‐type Arabidopsis through RNA‐seq analysis. Among them, 25% or 4.2% were independently regulated by EIN3/EIL1 or MYC2, respectively. Further analysis showed that EIN3/EIL1 and MYC2 interdependently regulate 16.3% of the JA‐regulated transcriptome, including downregulation of three auxin‐related genes, which might confer JA‐inhibited root elongation. Lastly, we found that <30 genes were antagonistically regulated by MYC2 and EIN3/EIL1. We conclude that EIN3/EIL1 play a dominant role while MYC2 largely relies on EIN3/EIL1 for executing its transcriptional activity, either synergistically or antagonistically.
High‐throughput profiling and analysis of plant responses over time to abiotic stress
Authors: Veley Kira M. , Berry Jeffrey C. , Fentress Sarah J. , Schachtman Daniel P. , Baxter Ivan , Bart Rebecca
Published: October 2017

Sorghum (Sorghum bicolor (L.) Moench) is a rapidly growing, high‐biomass crop prized for abiotic stress tolerance. However, measuring genotype‐by‐environment (G x E) interactions remains a progress bottleneck. We subjected a panel of 30 genetically diverse sorghum genotypes to a spectrum of nitrogen deprivation and measured responses using high‐throughput phenotyping technology followed by ionomic profiling. Responses were quantified using shape (16 measurable outputs), color (hue and intensity), and ionome (18 elements). We measured the speed at which specific genotypes respond to environmental conditions, in terms of both biomass and color changes, and identified individual genotypes that perform most favorably. With this analysis, we present a novel approach to quantifying color‐based stress indicators over time. Additionally, ionomic profiling was conducted as an independent, low‐cost, and high‐throughput option for characterizing G x E, identifying the elements most affected by either genotype or treatment and suggesting signaling that occurs in response to the environment. This entire dataset and associated scripts are made available through an open‐access, user‐friendly, web‐based interface. In summary, this work provides analysis tools for visualizing and quantifying plant abiotic stress responses over time. These methods can be deployed as a time‐efficient method of dissecting the genetic mechanisms used by sorghum to respond to the environment to accelerate crop improvement.
Spatial spread‐skill relationship in terms of agreement scales for precipitation forecasts in a convection‐allowing ensemble
Authors: Chen Xi , Yuan Huiling , Xue Ming
Published: October 2017

Verification of precipitation is one of the major issues in evaluating numerical weather prediction. In this study, a recently developed neighbourhood‐based method in terms of agreement scales is applied to characterize the scale‐dependent spatial spread‐skill relationship of precipitation forecasts in a 3 km convection‐allowing ensemble prediction system (EPS) over the Yangtze‐Huaihe river basin of China. Thirty cases during the Meiyu season of 2013 are classified into two weather regimes, large coverage (LC) and small coverage (SC), based on the precipitation fractional coverage. Overall, precipitation distributions for these two weather regimes are reasonably forecast by the EPS. The results show that the spatial spread‐skill relationship depends highly on the weather regime. The spatial spread‐skill relationship under SC is poorer and shows more diurnal variation compared to that under LC. In addition, this article extends the neighbourhood‐based method to investigate the relative influence of precipitation intensity and placement on the spatial spread‐skill relationship. With increasing precipitation threshold, the relative impact of precipitation intensity on the relationship gradually decreases, and the influence of precipitation placement becomes dominant.
Superior clinical pregnancy rates after microsurgical epididymal sperm aspiration
Authors: Hibi Hatsuki , Sumitomo Makoto , Fukunaga Noritaka , Sonohara Megumi , Asada Yoshimasa
Published: October 2017

Purpose

To assess normal fertilization, clinical pregnancy, and live birth rates after the use of microscopic epididymal sperm aspiration (MESA).

Methods

One‐hundred‐and‐sixty azoospermic participants who underwent MESA were evaluated. The MESA was performed by using a micropuncture method with a micropipette. In cases in which motile sperm were not obtained after the MESA, conventional or micro‐testicular sperm extraction (TESE) was completed.

Results

Adequate motile sperm were retrieved in 71 participants by using MESA and in 59 out of 89 participants by using TESE. Of the total number of patients, 123 underwent intracytoplasmic sperm injection. After MESA, the normal fertilization rate was 73.5% and the clinical pregnancy rate per case was 95.7%. Healthy deliveries resulted after MESA in 65 (92.9%) cases and after TESE in 38 (71.7%) cases.

Conclusion

The MESA specimen collection does not have any special requirements, such as mincing tissue disposition. The MESA also can reduce the amount of laboratory work that is needed for cryopreservation. In the authors' experience, MESA is a beneficial procedure and should be given priority over TESE.
Epidermal Growth Factor and Granulocyte Colony Stimulating Factor Signaling Are Synergistic for Hematopoietic Regeneration
Authors: Piryani Sadhna O. , Kam Angel Y. F. , Kliassov Evelyna G. , Chen Benny J. , Spector Neil L. , Chute John P. , Hsu David S. , Chao Nelson J. , Doan Phuong L.
Published: October 2017

Hematopoietic regeneration following chemotherapy may be distinct from regeneration following radiation. While we have shown that epidermal growth factor (EGF) accelerates regeneration following radiation, its role following chemotherapy is currently unknown. We sought to identify EGF as a hematopoietic growth factor for chemotherapy-induced myelosuppression. Following 5-fluorouracil (5-FU), EGF accelerated hematopoietic stem cell regeneration and prolonged survival compared with saline-treated mice. To mitigate chemotherapy-induced injury to endothelial cells in vivo, we deleted Bax in VEcadherin+ cells (VEcadherinCre;BaxFL/FL mice). Following 5-FU, VEcadherinCre;BaxFL/FL mice displayed preserved hematopoietic stem/progenitor content compared with littermate controls. 5-FU and EGF treatment resulted in increased cellular proliferation, decreased apoptosis, and increased DNA double-strand break repair by non-homologous end-joining recombination compared with saline-treated control mice. When granulocyte colony stimulating factor (G-CSF) is given with EGF, this combination was synergistic for regeneration compared with either G-CSF or EGF alone. EGF increased G-CSF receptor (G-CSFR) expression following 5-FU. Conversely, G-CSF treatment increased both EGF receptor (EGFR) and phosphorylation of EGFR in hematopoietic stem/progenitor cells. In humans, the expression of EGFR is increased in patients with colorectal cancer treated with 5-FU compared with cancer patients not on 5-FU. Similarly, EGFR signaling is responsive to G-CSF in humans in vivo with both increased EGFR and phospho-EGFR in healthy human donors following G-CSF treatment compared with donors who did not receive G-CSF. These data identify EGF as a hematopoietic growth factor following myelosuppressive chemotherapy and that dual therapy with EGF and G-CSF may be an effective method to accelerate hematopoietic regeneration.
Diallyl trisulfide suppresses doxorubicin‐induced cardiomyocyte apoptosis by inhibiting MAPK/NF‐κB signaling through attenuation of ROS generation
Authors: Wen Su‐Ying , Tsai Cheng‐Yen , Pai Pei‐Ying , Chen Yi‐Wei , Yang Yao‐Chih , Aneja Ritu , Huang Chih‐Yang , Kuo Wei‐Wen
Published: October 2017

Background

Doxorubicin (Dox) is an effective anticancer agent. However, its effectiveness is limited by its cardiotoxic effects. It has also been reported that the mitogen‐activated protein kinase family and NF‐κB can be activated by Dox treatment. DATS has been shown to be a potent antioxidant with cardioprotective effects. We investigate whether Dox induces cardiac apoptosis through JNK‐ and ERK‐dependent NF‐κB upregulation that can be reduced by DATS treatment.

Methods and Material

H9c2 cells were treated with 0.5–1.5 μM Dox for 24 hours. Dox promoted apoptosis and ROS generation and inhibited viability in a dose‐dependent manner. Then, the phosphorylation levels of JNK, ERK, and NF‐κB evaluated by western blot were elevated. We used inhibitors of JNK, ERK, and NF‐κB to determine which of these proteins were involved in Dox‐induced apoptosis. Furthermore, Dox‐exposed cells were treated with DATS at doses of 1, 5, and 10 μM, and the data demonstrated that ROS generation and apoptotic proteins were decreased and that ERK and NF‐κB were downregulated in a dose‐dependent manner. Additionally, six‐week‐old rats were divided into three groups (n = 6 per group) designed as an eight‐week study. Normal, Dox (at dose 3.75 mg/kg by ip) administered with or without DATS (at dose 40 mg/kg by gavage) treatment groups. The results indicate that cardiac dysfunction, apoptosis, and JNK, ERK, and NF‐κB activation by Dox were reversed by treatment with DATS.

Conclusion

DATS appears to suppress Dox‐induced cardiomyocyte apoptosis by inhibiting NADPH oxidase‐related ROS production and the downstream JNK/ERK/NF‐κB signaling pathway; DATS may possess clinical therapeutic potential by blocking Dox‐induced cardiotoxicity.
Utility of Different Adherence Measures for PrEP: Patterns and Incremental Value
Authors: Abaasa Andrew , Hendrix Craig , Gandhi Monica , Anderson Peter , Kamali Anatoli , Kibengo Freddie , Sanders Eduard J. , Mutua Gaudensia , Bumpus Namandjé N. , Priddy Frances , Haberer Jessica E.
Published: October 2017

Measuring PrEP adherence remains challenging. In 2009–2010, the International AIDS Vaccine Initiative randomized phase II trial participants to daily tenofovir disoproxil fumarate/emtricitabine or placebo in Uganda and Kenya. Adherence was measured by electronic monitoring (EM), self-report (SR), and drug concentrations in plasma and hair. Each adherence measure was categorised as low, moderate, or high and also considered continuously; the incremental value of combining measures was determined. Forty-five participants were followed over 4 months. Discrimination for EM adherence by area under receiver operating curves (AROC) was poor for SR (0.53) and best for hair (AROC 0.85). When combining hair with plasma or hair with self-report, discrimination was improved (AROC > 0.9). Self-reported adherence was of low utility by itself. Hair level was the single best PK measure to predict EM-assessed adherence; the other measurements had lower discrimination values. Combining short-term (plasma) and long-term (hair) metrics could be useful to assess patterns of drug-taking in the context of PrEP.
Erratum to: Surface functionalization of nanofibrillated cellulose using click-chemistry approach in aqueous media
Authors: Pahimanolis Nikolaos , Hippi Ulla , Johansson Leena-Sisko , Saarinen Tapio , Houbenov Nikolay , Ruokolainen Janne , Seppälä Jukka
Published: October 2017

The article “Surface functionalization of nanofibrillated cellulose using click-chemistry approach in aqueous media”, written by Nikolaos Pahimanolis, Ulla Hippi, Leena-Sisko Johansson, Tapio Saarinen, Nikolay Houbenov, Janne Ruokolainen and Jukka Seppälä, was originally published Online First without open access.
A point projection approach for improving the accuracy of the multilevel B-spline approximation
Authors: Moon Seonghyeon , Ko Kwanghee
Published: October 2017

In this study, we present a method for improving the accuracy of the multilevel B-spline approximation (MBA) method. We combine a point projection method with the MBA method for reducing the approximation error by directly adjusting the control points in the local area. An initial surface is generated by the MBA method, and grid points are produced on the surface. These grid points are projected onto the scattered point set, and the distances between the grid points and the projected points are computed. The control points are then modified based on the distances. The proposed method shows better approximations even with the same number of control points and ensures C2-continuity. The experimental results with examples verify the validity of the proposed method.

Highlights We propose a method for improving the multilevel B-spline approximation method. We use a point projection method for computing the amount of errors. The computed errors are directly applied to the control points for reducing the approximation error.
Use of Mental Health Services by Adolescents After Traumatic Brain Injury: A Secondary Analysis of a Randomized Controlled Trial
Authors: Huebner Andrea R.S. , Cassedy Amy , Brown Tanya M. , Taylor H. Gerry , Stancin Terry , Kirkwood Michael W. , Wade Shari L.
Published: October 2017

Background

Mental health problems are common after pediatric traumatic brain injury (TBI). Many patients in need of mental health services do not receive them, but studies have not consistently used prospective and objective methods or followed samples for more than 1 year.

Objective

To examine adolescents' use of mental health services after TBI.

Design

Secondary analysis from multicenter prospective randomized controlled trial.

Setting

Five level 1 U.S. trauma centers.

Participants

Adolescents aged 12‐17 years with moderate‐to‐severe TBI were recruited for a randomized clinical trial (n = 132 at baseline, 124 at 6 months, 113 at 12 months, and 101 at 18 months).

Methods

Participants were randomly assigned to counselor‐assisted problem‐solving or Internet resource comparison. Follow‐up assessments were completed at 6, 12, and 18 months after baseline. Generalized estimating equations with a logit link were used to examine use of mental health services. Treatment group and participant impairment were examined as predictors of use.

Main Outcome Measurements

Mental health care use was measured with the Service Assessment for Children and Adolescents; daily functioning and clinical outcome with the Child and Adolescent Functional Assessment Scale; behavioral and emotional functioning with the Child Behavior Checklist; and executive dysfunction with the Behavior Rating Inventory of Executive Function.

Results

Use of mental health services ranged from 22% to 31% in the 2 years post‐TBI. Participants with impairments were about 3 times more likely than those without impairments to receive services (odds ratio 4.61; 95% confidence interval 2.61‐8.14; P < .001). However, 50%‐68% of patients identified as impaired had unmet mental health care needs.

Conclusions

Less than one half of adolescents with behavioral health needs after TBI received mental health services. Future studies are needed to examine barriers associated with seeking services after TBI and psychoeducation as preventive care for this population.

Level of Evidence

II
The Effects of an 8‐Week Stabilization Exercise Program on Lumbar Multifidus Muscle Thickness and Activation as Measured With Ultrasound Imaging in Patients With Low Back Pain: An Exploratory Study
Authors: Larivière Christian , Gagnon Dany H. , Henry Sharon M. , Preuss Richard , Dumas Jean‐Pierre
Published: October 2017

Background

Lumbar stabilization exercise programs (LSEP) produce positive effects on clinical outcomes, but the underlying mechanisms remain relatively unexplored. Psychological and neuromuscular mechanisms can be involved, such as a better activation of the lumbar multifidus, which represents one possibility.

Objectives

To determine the following: (1) the effect of an LSEP on lumbar multifidus muscle thickness and activation, as measured with rehabilitative ultrasound imaging (RUSI), in patients with low back pain (LBP); (2) the correlation between RUSI measures and any change in clinical outcomes following the LSEP; and (3) the reliability of RUSI measures in control subjects over 8 weeks.

Design

One‐arm clinical trial with healthy subjects as a control group; reliability study.

Setting

LSEP delivered in a clinical setting; outcomes measured in a laboratory setting.

Participants

A total of 34 patients with nonacute LBP and 28 healthy control subjects.

Methods

Outcomes were measured before and after an 8‐week LSEP in patients with LBP, and at the same time interval (without treatment, to assess reliability) in control subjects.

Main Outcome Measurements

Pain numeric rating scale, Oswestry Disability Index (function), as well as RUSI measures for the lumbar multifidus (LM) muscles at 3 vertebral levels (L5‐S1, L4‐5, and L3‐4) during rest (static) and dynamic contractions (percent thickness change).

Results

Patients did not show systematic changes in RUSI measures relative to controls, even though RUSI impairments were observed at baseline (dynamic measure at L5‐S1) and even though patients had significant improvements in pain and disability. Correlational analyses with these clinical outcomes suggested that patients had reduced muscle thickness at baseline that was associated with a greater reduction in disability following LSEP; however, LM activation measured at baseline showed the opposite. Static RUSI measures showed excellent reliability at the L4‐5 and L3‐4 levels, whereas dynamic measures were not reliable.

Conclusions

Patients showed less muscle activation than controls at baseline (L5‐S1 level), but the LSEP did not normalize this impairment. The links between RUSI measures and the change in clinical outcomes during LSEP should be further explored.

This clinical trial has been recorded in the International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry (ID: ISRCTN94152969).

Level of Evidence

II
Equilibrium-Informed Trading with Relative Performance Measurement
Authors: Qiu Zhigang
Published: October 2017

This article analyzes the informative trading of professional money managers within a rational-expectations equilibrium model in which managers care about their performance relative to their peer group. I find that the existence of uninformed managers causes informed managers with relative performance concerns to trade less informatively, engendering less informative prices. When managers are differentially informed, they need to forecast the average performance based on private signals, and each manager may place more weight on the private signal if the signal provides good information about the average performance. The price aggregates those signals and thus becomes more informative.
Economic Risk Premia in the Fixed-Income Markets: The Intraday Evidence
Authors: Balduzzi Pierluigi , Moneta Fabio
Published: October 2017

We use high-frequency data to precisely estimate bond price reactions to macroeconomic announcements and the associated compensation for macro risks. We find evidence of a single factor summarizing the reaction of bond prices to different announcements. Before the financial crisis, the factor risk premium is substantial, significant, and mainly earned before announcement releases. After the crisis, the stock–bond covariance becomes negative and the preannouncement factor risk premium becomes insignificant. Our empirical results are consistent with information leakages that take place ahead of announcement releases and with the implications of a long-run risks model of bond risk premia.
CoMargin
Authors: Cruz Lopez Jorge A. , Harris Jeffrey H. , Hurlin Christophe , Pérignon Christophe
Published: October 2017

We present CoMargin, a new methodology to estimate collateral requirements in derivatives central counterparties (CCPs). CoMargin depends on both the tail risk of a given market participant and its interdependence with other participants. Our approach internalizes trading externalities and enhances the stability of CCPs, thus reducing systemic risk concerns. We assess our methodology using proprietary data from the Canadian Derivatives Clearing Corporation that include daily observations of the actual trading positions of all of its members from 2003 to 2011. We show that CoMargin outperforms existing margining systems by stabilizing the probability and minimizing the shortfall of simultaneous margin-exceeding losses.
Observing Life near the Ocean’s Surface with Satellites
Authors: Stuart Venetia
Published: October 2017

Third International Ocean Colour Science (IOCS) Meeting; Lisbon, Portugal, 15–19 May 2017
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Authors: Liao Chen-Yu , Anderson Sydney S , Chicoine Nicole H , Mayfield Jarrott R , Garrett Brittany J , Kwok Charlotte S , Academia Emmeline C , Hsu Yueh-Mei , Miller Delana M , Bair Amanda M , Wilson Joy A , Tannady Gabriella , Stewart Erin M , Adamson Stuart S , Wang Junying , Withers Dominic J , Kennedy Brian K
Published: October 2017

The mechanistic target of rapamycin (mTOR) signaling pathway plays a central role in aging and a number of different disease states. Rapamycin, which suppresses activity of the mTOR complex 1 (mTORC1), shows preclinical (and sometimes clinical) efficacy in a number of disease models. Among these are Lmna−/− mice, which serve as a mouse model for dystrophy-associated laminopathies. To confirm that elevated mTORC1 signaling is responsible for the pathology manifested in Lmna−/− mice and to decipher downstream genetic mechanisms underlying the benefits of rapamycin, we tested in Lmna−/− mice whether survival could be extended and disease pathology suppressed either by reduced levels of S6K1 or enhanced levels of 4E-BP1, two canonical mTORC1 substrates. Global heterozygosity for S6K1 ubiquitously extended lifespan of Lmna−/− mice (Lmna−/−S6K1+/− mice). This life extension is due to improving muscle, but not heart or adipose, function, consistent with the observation that genetic ablation of S6K1 specifically in muscle tissue also extended survival of Lmna−/− mice. In contrast, whole-body overexpression of 4E-BP1 shortened the survival of Lmna−/− mice, likely by accelerating lipolysis. Thus, rapamycin-mediated lifespan extension in Lmna−/− mice is in part due to the improvement of skeletal muscle function and can be phenocopied by reduced S6K1 activity, but not 4E-BP1 activation.
Molecular evidence strongly supports deadwood-inhabiting fungi exhibiting unexpected tree species preferences in temperate forests
Authors: Purahong Witoon , Wubet Tesfaye , Krüger Dirk , Buscot François
Published: October 2017

Wood-inhabiting fungi have essential roles in the regulation of carbon stocks and nutrient cycling in forest ecosystems. However, knowledge pertaining to wood-inhabiting fungi is only fragmentary and controversial. Here we established a large-scale deadwood experiment with 11 tree species to investigate diversity and tree species preferences of wood-inhabiting fungi using next-generation sequencing. Our results contradict existing knowledge based on sporocarp surveys and challenge current views on their distribution and diversity in temperate forests. Analyzing α-, β- and γ-diversity, we show that diverse fungi colonize deadwood at different spatial scales. Specifically, coniferous species have higher α- and γ-diversity than the majority of analyzed broadleaf species, but two broadleaf species showed the highest β-diversity. Surprisingly, we found nonrandom co-occurrence (P<0.001) and strong tree species preferences of wood-inhabiting fungi, especially in broadleaf trees (P<0.01). Our results indicate that the saprotrophic fungal community is more specific to tree species than previously thought.
Changes in bacterioplankton community structure during early lake ontogeny resulting from the retreat of the Greenland Ice Sheet
Authors: Peter Hannes , Jeppesen Erik , De Meester Luc , Sommaruga Ruben
Published: October 2017

Retreating glaciers and ice sheets are among the clearest signs of global climate change. One consequence of glacier retreat is the formation of new meltwater-lakes in previously ice-covered terrain. These lakes provide unique opportunities to understand patterns in community organization during early lake ontogeny. Here, we analyzed the bacterial community structure and diversity in six lakes recently formed by the retreat of the Greenland Ice Sheet (GrIS). The lakes represented a turbidity gradient depending on their past and present connectivity to the GrIS meltwaters. Bulk (16S rRNA genes) and putatively active (16S rRNA) fractions of the bacterioplankton communities were structured by changes in environmental conditions associated to the turbidity gradient. Differences in community structure among lakes were attributed to both, rare and abundant community members. Further, positive co-occurrence relationships among phylogenetically closely related community members dominate in these lakes. Our results show that environmental conditions along the turbidity gradient structure bacterial community composition, which shifts during lake ontogeny. Rare taxa contribute to these shifts, suggesting that the rare biosphere has an important ecological role during early lakes ontogeny. Members of the rare biosphere may be adapted to the transient niches in these nutrient poor lakes. The directionality and phylogenetic structure of co-occurrence relationships indicate that competitive interactions among closely related taxa may be important in the most turbid lakes.
Genome-wide genetic and epigenetic analyses of pancreatic acinar cell carcinomas reveal aberrations in genome stability
Authors: Jäkel Cornelia , Bergmann Frank , Toth Reka , Assenov Yassen , van der Duin Daniel , Strobel Oliver , Hank Thomas , Klöppel Günter , Dorrell Craig , Grompe Markus , Moss Joshua , Dor Yuval , Schirmacher Peter , Plass Christoph , Popanda Odilia , Schmezer Peter
Published: October 2017

Pancreatic acinar cell carcinoma (ACC) is an aggressive exocrine tumor with largely unknown biology. Here, to identify potential targets for personalized treatment, we perform integrative genome-wide and epigenome-wide analyses. The results show frequently aberrant DNA methylation, abundant chromosomal amplifications and deletions, and mutational signatures suggesting defective DNA repair. In contrast to pancreatic ductal adenocarcinoma, no recurrent point mutations are detected. The tumor suppressorsID3,ARID1A,APC, andCDKN2Aare frequently impaired also on the protein level and thus potentially affect ACC tumorigenesis. Consequently, this work identifies promising therapeutic targets in ACC for drugs recently approved for precision cancer therapy.
Mapping and phasing of structural variation in patient genomes using nanopore sequencing
Authors: Cretu Stancu Mircea , van Roosmalen Markus J. , Renkens Ivo , Nieboer Marleen M. , Middelkamp Sjors , de Ligt Joep , Pregno Giulia , Giachino Daniela , Mandrile Giorgia , Espejo Valle-Inclan Jose , Korzelius Jerome , de Bruijn Ewart , Cuppen Edwin , Talkowski Michael E. , Marschall Tobias , de Ridder Jeroen , Kloosterman Wigard P.
Published: October 2017

Despite improvements in genomics technology, the detection of structural variants (SVs) from short-read sequencing still poses challenges, particularly for complex variation. Here we analyse the genomes of two patients with congenital abnormalities using the MinION nanopore sequencer and a novel computational pipeline—NanoSV. We demonstrate that nanopore long reads are superior to short reads with regard to detection of de novo chromothripsis rearrangements. The long reads also enable efficient phasing of genetic variations, which we leveraged to determine the parental origin of all de novo chromothripsis breakpoints and to resolve the structure of these complex rearrangements. Additionally, genome-wide surveillance of inherited SVs reveals novel variants, missed in short-read data sets, a large proportion of which are retrotransposon insertions. We provide a first exploration of patient genome sequencing with a nanopore sequencer and demonstrate the value of long-read sequencing in mapping and phasing of SVs for both clinical and research applications.