bluuebunny/crossref_metadata_2025 huggingface dataset:
Weight-Related Information Avoidance Prospectively Predicts Poorer Self-Monitoring and Engagement in a Behavioral Weight Loss Intervention
Authors: Schumacher Leah M , Martinelli Mary K , Convertino Alexandra D , Forman Evan M , Butryn Meghan L
Published: June 2020

Background

Self-monitoring is a key component of behavioral weight loss (BWL) interventions. Past research suggests that individuals may avoid self-monitoring in certain contexts (e.g., skipping self-weighing after higher-than-usual calorie intake). However, no studies have attempted to quantify individuals’ inclination to avoid information about their weight control (“weight-related information avoidance”; WIA) or prospectively examined its implications for treatment engagement and outcomes in BWL programs.

Purpose

Characterize WIA using a validated questionnaire among adults enrolled in BWL treatment and examine whether WIA prospectively predicts self-monitoring adherence, session attendance, treatment discontinuation, or weight loss.

Methods

Participants (N = 87; MBMI = 34.9 kg/m2, 83% female) completed a measure of WIA prior to starting a 12 week, group-based BWL intervention. Participants were given digital self-monitoring tools and instructed to self-monitor their food intake daily, physical activity daily, and body weight weekly (Weeks 1–10) and then daily (Weeks 11–12). Session attendance and treatment discontinuation were recorded. Weight was measured in-clinic pretreatment and posttreatment.

Results

While mean WIA was low (M = 2.23, standard deviation [SD] = 0.95; potential scale range: 1–7), greater WIA predicted poorer attendance (r = −.23; p = .03) and poorer self-monitoring of physical activity (r = −.28; p = .009) and body weight (r = −.32; p = .003). WIA did not predict food monitoring (p = .08), treatment discontinuation (p = .09), or 12 week weight loss (p = .91).

Conclusions

Greater WIA, as assessed via a brief questionnaire, may place individuals at risk for poorer self-monitoring and treatment engagement during BWL. Further research on the implications of WIA in the context of weight management is warranted, including evaluation of correlates, moderators, and mechanisms of action of WIA.

Clinical Trial Registration

NCT03337139.
Prime Movers: Effects of Subliminal Primes, Music, and Music Video on Psychological Responses to Exercise
Authors: Pottratz Suzanne T , Hutchinson Jasmin C , Karageorghis Costas I , Mullin Elizabeth M , Zenko Zachary
Published: June 2020

Background

Priming is a process in which exposure to a stimulus activates relevant mental representations that are given increased weight in subsequent judgment tasks. Affective primes can influence affective evaluations and associations. Such influence has meaningful implications for the promotion of exercise behavior, yet there is scant research on priming effects in exercise settings.

Purpose

The purpose of the present pair of studies was to examine the efficacy of music (M), music video (MV), and music video with affective primes (PRIME) in modulating psychological responses during and immediately following an exercise bout among two distinct populations.

Methods

In Study 1, physically active participants completed a brisk walking task on a treadmill under four conditions: M, MV, PRIME, and control. Affective valence and rating of perceived exertion (RPE) were assessed during exercise and remembered/forecasted pleasure was measured immediately following each exercise bout. In Study 2, largely inactive and overweight participants completed a brisk walking task on a treadmill under two conditions: MV and PRIME. Affective valence was assessed during exercise, while exercise enjoyment and remembered/forecasted pleasure were assessed postexercise.

Results

In Study 1, PRIME yielded more positively valenced affect, remembered/forecasted pleasure, and lower RPE when compared to the other conditions (MCohen’s d for all DVs = 0.91). In Study 2, PRIME elicited more positively valenced affect, greater enjoyment, and enhanced remembered/forecasted pleasure when compared to MV (MCohen’s d for all DVs = 0.64).

Conclusions

Subliminal primes embedded in music video can elicit positive changes in psychological responses during and immediately following exercise.
Mutations in transmembrane proteins: diseases, evolutionary insights, prediction and comparison with globular proteins
Authors: Zaucha Jan , Heinzinger Michael , Kulandaisamy A , Kataka Evans , Salvádor Óscar Llorian , Popov Petr , Rost Burkhard , Gromiha M Michael , Zhorov Boris S , Frishman Dmitrij
Published: June 2020

Membrane proteins are unique in that they interact with lipid bilayers, making them indispensable for transporting molecules and relaying signals between and across cells. Due to the significance of the protein’s functions, mutations often have profound effects on the fitness of the host. This is apparent both from experimental studies, which implicated numerous missense variants in diseases, as well as from evolutionary signals that allow elucidating the physicochemical constraints that intermembrane and aqueous environments bring. In this review, we report on the current state of knowledge acquired on missense variants (referred to as to single amino acid variants) affecting membrane proteins as well as the insights that can be extrapolated from data already available. This includes an overview of the annotations for membrane protein variants that have been collated within databases dedicated to the topic, bioinformatics approaches that leverage evolutionary information in order to shed light on previously uncharacterized membrane protein structures or interaction interfaces, tools for predicting the effects of mutations tailored specifically towards the characteristics of membrane proteins as well as two clinically relevant case studies explaining the implications of mutated membrane proteins in cancer and cardiomyopathy.
ccNetViz: a WebGL-based JavaScript library for visualization of large networks
Authors: Saska Ales , Tichy David , Moore Robert , Rasquinha Achilles , Akdas Caner , Zhao Xiaodong , Fabbri Renato , Jeličić Ana , Grover Gaurav , Jotwani Himanshu , Shadab Mohamed , Helikar Resa M , Helikar Tomáš
Published: June 2020

Visualizing a network provides a concise and practical understanding of the information it represents. Open-source web-based libraries help accelerate the creation of biologically based networks and their use. ccNetViz is an open-source, high speed and lightweight JavaScript library for visualization of large and complex networks. It implements customization and analytical features for easy network interpretation. These features include edge and node animations, which illustrate the flow of information through a network as well as node statistics. Properties can be defined a priori or dynamically imported from models and simulations. ccNetViz is thus a network visualization library particularly suited for systems biology.

Availability and implementation

The ccNetViz library, demos and documentation are freely available at http://helikarlab.github.io/ccNetViz/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Preclinical contraceptive development for men and women
Authors: Johnston Daniel S , Goldberg Erwin
Published: June 2020

This manuscript endeavors to present research considerations for the preclinical development of non-hormonal contraceptives. Topics include (1) how advances in genomics and bioinformatics impact the identification of novel targets for non-hormonal contraception, (2) the importance of target validation prior to investment in a contraceptive development campaign, (3) considerations on targeting gametogenesis vs gamete maturation/function, (4) how targets from the male reproductive system are expanding women’s options for ‘on demand’ contraception, and (5) some emerging non-hormonal methods that are not based on a specific molecular target. Also presented are ideas for developing a pipeline of non-hypothalamic-pituitary-gonadal-acting contraceptives for men and women while balancing risk and innovation, and our perspective on the pros and cons of industry and academic environments on contraceptive development. Three product development programs are highlighted that are biologically interesting, innovative, and likely to influence the field of contraceptive development in years to come.
Conceptual Links between Landscape Diversity and Diet Diversity: A Roadmap for Transdisciplinary Research
Authors: Gergel Sarah E , Powell Bronwen , Baudron FrÉdÉric , Wood Sylvia L R , Rhemtulla Jeanine M , Kennedy Gina , Rasmussen Laura V , Ickowitz Amy , Fagan Matthew E , Smithwick Erica A H , Ranieri Jessica , Wood Stephen A , Groot Jeroen C J , Sunderland Terry C H
Published: June 2020

Malnutrition linked to poor quality diets affects at least 2 billion people. Forests, as well as agricultural systems linked to trees, are key sources of dietary diversity in rural settings. In the present article, we develop conceptual links between diet diversity and forested landscape mosaics within the rural tropics. First, we summarize the state of knowledge regarding diets obtained from forests, trees, and agroforests. We then hypothesize how disturbed secondary forests, edge habitats, forest access, and landscape diversity can function in bolstering dietary diversity. Taken together, these ideas help us build a framework illuminating four pathways (direct, agroecological, energy, and market pathways) connecting forested landscapes to diet diversity. Finally, we offer recommendations to fill remaining knowledge gaps related to diet and forest cover monitoring. We argue that better evaluation of the role of land cover complexity will help avoid overly simplistic views of food security and, instead, uncover nutritional synergies with forest conservation and restoration.
Safe Haven or Dangerous Place? Stereotype Amplification and Americans’ Perceived Risk of Terrorism, Violent Street Crime, and Mass Shootings
Authors: Haner Murat , Sloan Melissa M , Pickett Justin T , Cullen Francis T
Published: June 2020

People overestimate the risk of some events, such as terrorist attacks and immigrant crimes, but not of others. Stereotype amplification theory indicates that politicized, out-group stereotypes may be to blame. We examine Americans’ perceptions of the risk that different forms of violence—out-group, in-group and non-racialized—will occur in their local communities. We hypothesize that negative stereotypes of immigrants and Muslims will increase the perceived risk of out-group violence but not of other forms of violence. Analyses of original survey data from a sample of 1,068 Americans reveal four findings: (1) most Americans accurately perceive home-grown violence to be more likely than violence by foreigners, (2) political identification and ideology strongly predict out-group stereotypes, (3) out-group stereotypes strongly predict the perceived risk of out-group violence but are not significantly associated with risk perceptions for other forms of violence and (4) vulnerability factors predict risk perceptions for all forms of violence.
Social Work Scholarship on Forced Migration: A Scoping Review
Authors: Gonzalez Benson Odessa , Wachter Karin , Lee Jessica , Nichols Darlene , Hylton Erica
Published: June 2020

This scoping review identifies and analyses historical to present–day contributions of social work scholarship on forced migration, with the aim of reviewing trends and identifying priority areas for the discipline moving forward. This review examined 331 articles related to forced migration published in 40 social work journals over four decades (1978 to 2019). Findings illustrate notable trends in temporal, methodological, topical and geographical dimensions and how those vary by first authors' locations, research sites and study populations. Temporally, the number of articles has been increasing, quadrupling between 2001–2010 and 2011–2019, with 20 social work journals doubling their number of articles. Methodologically, the large majority of articles were qualitative and/or conceptual. Topically, the most common were practice, intervention, health and mental health, while the least common topics included human rights, social justice, poverty, religion, violence, history and theory. Geographically, social work scholarship was mainly focused on refugees in the Global North and third-country resettlement contexts, and authored by scholars in the Global North. Findings thus reveal critical gaps in topics and geographical biases, raising questions related to issues of ethics, power and the production of knowledge about forced migration in the social work academy.
Outcome of total hip and total knee arthroplasty and vitamin D homeostasis
Authors: Brambilla Lorenzo , Peretti Giuseppe Maria , Sirtori Paolo , Maffulli Nicola , Mangiavini Laura
Published: June 2020

Background

Low levels of vitamin D are common in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA), but it is still unclear whether the outcome of such surgery is related to vitamin D levels.

Sources of data

Publicly available electronic databases were systematically reviewed to update knowledge about the role of vitamin D in THA and TKA patients, and to appraise the correlation between vitamin D levels before surgery and post-surgical outcomes. Eight studies were included in our review: six employed prospective observational designs, two reported retrospective database interrogations. Six prospective observational studies and two retrospective database interrogations matched inclusion and exclusion criteria.

Areas of agreement

Patients undergoing THA and TKA have a high prevalence of hypovitaminosis D. Five of eight studies (62.5%) report a statistically significant association between low vitamin D status and worse outcomes after THA and TKA.

Areas of controversy

Different explanations have been proposed for vitamin D insufficiency, but some authors have questioned the correctness of the methods used to measure the vitamin D levels.

Growing points

A trial focusing on the role of vitamin D supplementation on safety and outcomes of patients undergoing THA and TKA with low vitamin D status is ongoing.

Areas timely for developing research

Further studies should explore the possible causal relationship between vitamin D status and outcomes of THA and TKA and verify the laboratory methods to analyse it.
Clinical courses and outcomes of five patients with primary lung cancer surgically treated while affected by Severe acute respiratory syndrome coronavirus 2
Authors: Gonfiotti Alessandro , Gatteschi Lavinia , Salvicchi Alberto , Bongiolatti Stefano , Lavorini Federico , Voltolini Luca
Published: June 2020

OBJECTIVES

There is currently a lack of clinical data on the novel beta-coronavirus infection [caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] and concomitant primary lung cancer. Our goal was to report our experiences with 5 patients treated for lung cancer while infected with SARS-CoV-2.

METHODS

We retrospectively evaluated 5 adult patients infected with SARS-CoV-2 who were admitted to our thoracic surgery unit between 29 January 2020 and 4 March 2020 for surgical treatment of a primary lung cancer. Clinical data and outcomes are reported.

RESULTS

All patients were men with a mean age of 74.0 years (range 67–80). Four of the 5 patients (80%) reported chronic comorbidities. Surgery comprised minimally invasive lobectomy (2 patients) and segmentectomy (1 patient), lobectomy with en bloc chest wall resection (1 patient) and pneumonectomy (1 patient). Mean chest drain duration was 12.4 days (range 8–22); mean hospital stay was 33.8 days (range 21–60). SARS-CoV-2-related symptoms were fever (3 patients), persistent cough (3 patients), diarrhoea (2 patients) and syncope (2 patients); 1 patient reported no symptoms. Morbidity related to surgery was 60%; 30-day mortality was 40%. Two patients (1 with a right pneumonectomy, 74 years old; 1 with a lobectomy with chest wall resection and reconstruction, 70 years old), developed SARS-CoV-2-related lung failure leading to death 60 and 32 days after surgery, respectively.

CONCLUSIONS

Lung cancer surgery may represent a high-risk factor for developing a severe case of coronavirus disease 2019, particularly in patients with advanced stages of lung cancer. Additional strategies are needed to reduce the risk of morbidity and mortality from SARS-CoV-2 infection during treatment for lung cancer.
Comparison of pain perception, anxiety, and impacts on oral health-related quality of life between patients receiving clear aligners and fixed appliances during the initial stage of orthodontic treatment
Authors: Gao Meiya , Yan Xinyu , Zhao Rui , Shan Yue , Chen Yiyin , Jian Fan , Long Hu , Lai Wenli
Published: June 2020

Background and Objectives

Clear aligner is an advanced orthodontic method with benefits of comfort, aesthetics, and convenience. This study aimed to compare pain perception, anxiety, and impacts on oral health-related quality of life (OHRQoL) between adult patients receiving clear aligners and fixed appliances during the initial stage of orthodontic treatments.

Material and Methods

The two groups were well matched by ages, gender, and levels of malocclusion severity. Pain perception, anxiety, and OHRQoL were assessed through visual analogue scale, state-trait anxiety inventory, and oral health impact profile-14 (OHIP-14), respectively. And the comparison of above scores was performed by two-way analysis of variance.

Results

A total of 110 patients (55 pairs) were enrolled in this study. Orthodontic pain levels peaked on the first day and decreased gradually afterwards in both groups, which were significantly higher in the fixed group on the first, second, fourth, and fifth days. Likewise, anxiety levels peaked on the first day and decreased thereafter, with significant difference on the 1st, 3d, 5th, 7th, and 14th days. Moreover, the OHIP-14 scores increased and peaked on the first day and then gradually decreased for both groups, which were also significantly higher in the fixed group on the 1st, 7th, and 14th days.

Limitations

More malocclusion types should be used for group matching. The effect of exclusion of small groups should be taken into consideration in sample size calculation. Income was significantly unbalanced between two groups due to higher cost of clear aligners, and random assignment of treatment modalities was unfeasible.

Conclusions

Patients treated with clear aligners experienced lower pain levels, less anxiety, and higher OHRQoL as compared to those receiving fixed appliances.
Cell wall homeostasis in lactic acid bacteria: threats and defences
Authors: Martínez Beatriz , Rodríguez Ana , Kulakauskas Saulius , Chapot-Chartier Marie-Pierre
Published: June 2020

Lactic acid bacteria (LAB) encompasses industrially relevant bacteria involved in food fermentations as well as health-promoting members of our autochthonous microbiota. In the last years, we have witnessed major progresses in the knowledge of the biology of their cell wall, the outermost macrostructure of a Gram-positive cell, which is crucial for survival. Sophisticated biochemical analyses combined with mutation strategies have been applied to unravel biosynthetic routes that sustain the inter- and intra-species cell wall diversity within LAB. Interplay with global cell metabolism has been deciphered that improved our fundamental understanding of the plasticity of the cell wall during growth. The cell wall is also decisive for the antimicrobial activity of many bacteriocins, for bacteriophage infection and for the interactions with the external environment. Therefore, genetic circuits involved in monitoring cell wall damage have been described in LAB, together with a plethora of defence mechanisms that help them to cope with external threats and adapt to harsh conditions. Since the cell wall plays a pivotal role in several technological and health-promoting traits of LAB, we anticipate that this knowledge will pave the way for the future development and extended applications of LAB.
Macular Ganglion Cell-Inner Plexiform Layer as a Marker of Cognitive and Sensory Function in Midlife
Authors: Merten Natascha , Paulsen Adam J , Pinto A Alex , Chen Yanjun , Dillard Lauren K , Fischer Mary E , Huang Guan-Hua , Klein Barbara E K , Schubert Carla R , Cruickshanks Karen J
Published: June 2020

Background

Neurodegenerative diseases are public health challenges in aging populations. Early identification of people at risk for neurodegeneration might improve targeted treatment. Noninvasive, inexpensive screening tools are lacking but are of great potential. Optical coherence tomography (OCT) measures the thickness of nerve cell layers in the retina, which is an anatomical extension of the brain and might be indicative of common underlying neurodegeneration. We aimed to determine the association of macular ganglion cell-inner plexiform layer (mGCIPL) thickness with cognitive and sensorineural function in midlife.

Method

This cross-sectional study included 1,880 Beaver Dam Offspring Study participants (aged 27–93 years, mean 58) who participated in the 10-year follow-up examination. We assessed cognitive function and impairment, hearing sensitivity thresholds and impairment, central auditory processing, visual impairment, and olfactory impairment. We measured mGCIPL using the Cirrus 5000 HD-OCT Macular Cube Scan. Multivariable linear and logistic regression models adjusted for potential confounders were used to determine associations between mGCIPL thickness and cognitive and sensorineural functions, as well as for comparing participants with a thin mGCIPL (1 SD below average) to the remainder in those functions.

Results

Thinner mGCIPL was associated with worse cognitive function, worse central auditory function, and visual impairment. We found an association of mGCIPL thickness with hearing sensitivity in women only and no association with impairment in hearing, olfaction, and cognition. Results on the thin group comparisons were consistent.

Conclusions

mGCIPL thickness is associated with cognitive and sensorineural function and has the potential as a marker for neurodegeneration in middle-aged adults.
Influenza Infection has Fiber Type-Specific Effects on Cellular and Molecular Skeletal Muscle Function in Aged Mice
Authors: Straight Chad R , Ringham Olivia R , Bartley Jenna M , Keilich Spencer R , Kuchel George A , Haynes Laura , Miller Mark S
Published: June 2020

Skeletal muscle myopathies represent a common non-pulmonary manifestation of influenza infection, leading to reduced physical function and hospitalization in older adults. However, underlying mechanisms remain poorly understood. Our study examined the effects of influenza virus A pulmonary infection on contractile function at the cellular (single fiber) and molecular (myosin-actin interactions and myofilament properties) levels in soleus and extensor digitorum longus muscles of aged (20 months) C57BL/6 male mice that were healthy or flu-infected for 7 (7-days post-infection; 7-DPI) or 12 days (12-DPI). Cross-sectional area (CSA) of myosin heavy chain (MHC) IIA and IIB fibers was reduced at 12-DPI relative to 7-DPI and healthy. Maximal isometric force in MHC IIA fibers was also reduced at 12-DPI relative to 7-DPI and healthy, resulting in no change in specific force (maximal isometric force divided by CSA). In contrast, MHC IIB fibers produced greater isometric force and specific force at 7-DPI compared to 12-DPI or healthy. The increased specific force in MHC IIB fibers was likely due to greater myofilament lattice stiffness and/or an increased number or stiffness of strongly bound myosin-actin cross-bridges. At the molecular level, cross-bridge kinetics were slower in MHC IIA fibers with infection, while changes in MHC IIB fibers were largely absent. In both fiber types, greater myofilament lattice stiffness was positively related to specific force. This study provides novel evidence that cellular and molecular contractile function is impacted by influenza infection in a fiber type-specific manner, suggesting potential molecular mechanisms to help explain the impact of flu-induced myopathies.
Iterative hard thresholding in genome-wide association studies: Generalized linear models, prior weights, and double sparsity
Authors: Chu Benjamin B , Keys Kevin L , German Christopher A , Zhou Hua , Zhou Jin J , Sobel Eric M , Sinsheimer Janet S , Lange Kenneth
Published: June 2020

Background

Consecutive testing of single nucleotide polymorphisms (SNPs) is usually employed to identify genetic variants associated with complex traits. Ideally one should model all covariates in unison, but most existing analysis methods for genome-wide association studies (GWAS) perform only univariate regression.

Results

We extend and efficiently implement iterative hard thresholding (IHT) for multiple regression, treating all SNPs simultaneously. Our extensions accommodate generalized linear models, prior information on genetic variants, and grouping of variants. In our simulations, IHT recovers up to 30% more true predictors than SNP-by-SNP association testing and exhibits a 2–3 orders of magnitude decrease in false-positive rates compared with lasso regression. We also test IHT on the UK Biobank hypertension phenotypes and the Northern Finland Birth Cohort of 1966 cardiovascular phenotypes. We find that IHT scales to the large datasets of contemporary human genetics and recovers the plausible genetic variants identified by previous studies.

Conclusions

Our real data analysis and simulation studies suggest that IHT can (i) recover highly correlated predictors, (ii) avoid over-fitting, (iii) deliver better true-positive and false-positive rates than either marginal testing or lasso regression, (iv) recover unbiased regression coefficients, (v) exploit prior information and group-sparsity, and (vi) be used with biobank-sized datasets. Although these advances are studied for genome-wide association studies inference, our extensions are pertinent to other regression problems with large numbers of predictors.
Overexpression of Staufen1 in DM1 mouse skeletal muscle exacerbates dystrophic and atrophic features
Authors: Crawford Parks Tara E , Marcellus Kristen A , Péladeau Christine , Jasmin Bernard J , Ravel-Chapuis Aymeric
Published: June 2020

In myotonic dystrophy type 1 (DM1), the CUG expansion (CUGexp) in the 3′ untranslated region of the dystrophia myotonica protein kinase messenger ribonucleic acid affects the homeostasis of ribonucleic acid-binding proteins, causing the multiple symptoms of DM1. We have previously reported that Staufen1 is increased in skeletal muscles from DM1 mice and patients and that sustained Staufen1 expression in mature mouse muscle causes a progressive myopathy. Here, we hypothesized that the elevated levels of Staufen1 contributes to the myopathic features of the disease. Interestingly, the classic DM1 mouse model human skeletal actin long repeat (HSALR) lacks overt atrophy while expressing CUGexp transcripts and elevated levels of endogenous Staufen1, suggesting a lower sensitivity to atrophic signaling in this model. We report that further overexpression of Staufen1 in the DM1 mouse model HSALR causes a myopathy via inhibition of protein kinase B signaling through an increase in phosphatase tensin homolog, leading to the expression of atrogenes. Interestingly, we also show that Staufen1 regulates the expression of muscleblind-like splicing regulator 1 and CUG-binding protein elav-like family member 1 in wild-type and DM1 skeletal muscle. Together, data obtained from these new DM1 mouse models provide evidence for the role of Staufen1 as an atrophy-associated gene that impacts progressive muscle wasting in DM1. Accordingly, our findings highlight the potential of Staufen1 as a therapeutic target and biomarker.
Example of Adverse Outcome Pathway Concept Enabling Genome-to-Phenome Discovery in Toxicology
Authors: Gust Kurt A , Ji Qing , Luo Xiao
Published: June 2020

Synopsis

The following article represents a mini-review of an intensive 10-year progression of genome-to-phenome (G2P) discovery guided by the adverse outcome pathway (AOP) concept. This example is presented as a means to stimulate crossover of this toxicological concept to enhance G2P discovery within the broader biological sciences community. The case study demonstrates the benefits of the AOP approach for establishing causal linkages across multiple levels of biological organization ultimately linking molecular initiation (often at the genomic scale) to organism-level phenotypes of interest. The case study summarizes a US military effort to identify the mechanism(s) underlying toxicological phenotypes of lethargy and weight loss in response to nitroaromatic munitions exposures, such as 2,4,6-trinitrotoluene. Initial key discoveries are described including the toxicogenomic results that nitrotoluene exposures inhibited expression within the peroxisome proliferator activated receptor α (PPARα) pathway. We channeled the AOP concept to test the hypothesis that inhibition of PPARα signaling in nitrotoluene exposures impacted lipid metabolic processes, thus affecting systemic energy budgets, ultimately resulting in body weight loss. Results from a series of transcriptomic, proteomic, lipidomic, in vitro PPARα nuclear signaling, and PPARα knock-out investigations ultimately supported various facets of this hypothesis. Given these results, we next proceeded to develop a formalized AOP description of PPARα antagonism leading to body weight loss. This AOP was refined through intensive literature review and polished through multiple rounds of peer-review leading to final international acceptance as an Organisation for Economic Cooperation and Development-approved AOP. Briefly, that AOP identifies PPARα antagonist binding as the molecular initiating event (MIE) leading to a series of key events including inhibition of nuclear transactivation for genes controlling lipid metabolism and ketogenesis, inhibition of fatty acid beta-oxidation and ketogenesis dynamics, negative energy budget, and ultimately the adverse outcome (AO) of body-weight loss. Given that the PPARα antagonism MIE represented a reliable indicator of AO progression within the pathway, a phylogenetic analysis was conducted which indicated that PPARα amino acid relatedness generally tracked species relatedness. Additionally, PPARα amino acid relatedness analysis using the Sequence Alignment to Predict Across Species Susceptibility predicted susceptibility to the MIE across vertebrates providing context for AOP extrapolation across species. Overall, we hope this illustrative example of how the AOP concept has benefited toxicology sows a seed within the broader biological sciences community to repurpose the concept to facilitate enhanced G2P discovery in biology.
Remedies for algorithmic tacit collusion
Authors: Beneke Francisco , Mackenrodt Mark-Oliver
Published: June 2020

There is growing evidence that tacit collusion can be autonomously achieved by machine learning technology, at least in some real-life examples identified in the literature and experimental settings. Although more work needs to be done to assess the competitive risks of widespread adoption of autonomous pricing agents, this is still an appropriate time to examine which possible remedies can be used in case competition law shifts towards the prohibition of tacit collusion. This is because outlawing such conduct is pointless unless there are suitable remedies that can be used to address the social harm. This article explores how fines and structural and behavioural remedies can serve to discourage collusive results while preserving the incentives to use efficiency-enhancing algorithms. We find that this could be achieved if fines and remedies can target structural conditions that facilitate collusion. In addition, the problem of unfeasibility of injunctions to remedy traditional price coordination changes with the use of pricing software, which in theory can be programmed to avoid collusive outcomes. Finally, machine-learning methods can be used by the authorities themselves as a tool to test the effects of any given combination of remedies and to estimate a more accurate competitive benchmark for the calculation of the appropriate fine.
Normative Values of High-Sensitivity Cardiac Troponin T and N-Terminal pro-B-Type Natriuretic Peptide in Children and Adolescents: A Study from the CALIPER Cohort
Authors: Lam Emily , Higgins Victoria , Zhang Liyong , Chan Man Khun , Bohn Mary Kathryn , Trajcevski Karin , Liu Peter , Adeli Khosrow , Nathan Paul C
Published: June 2020

Background

Cardiac troponin (cTn) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are increasingly used clinically to evaluate and prognosticate acute myocardial infarction and heart failure, respectively. Pediatric reference intervals and cut-offs have not been established for Roche’s Elecsys Troponin T hs (high sensitive) assay. Although pediatric reference intervals exist for NT-proBNP, cut-off values do not exist. In this study, we report reference intervals and 99th percentile cut-offs in a large, healthy Canadian pediatric population using the CALIPER cohort.

Methods

Blood samples from 484 healthy children and adolescents between 0 and <19 years old were recruited from hospital outpatient clinics and community settings. Serum samples were analyzed using Roche’s Cobas e411 and evaluated for high-sensitivity cTnT (hs-cTnT) and NT-proBNP concentrations. 95% reference intervals and 99th percentile cut-off values were established.

Results

Three hs-cTnT age partitions were established (0 to <6 months, 6 months to <1 year, and 1 to <19 years) with highest concentrations observed in children under 1 year. Two NT-proBNP age partitions were established (0 to <1 year, and 1 to <19 years), also with higher concentrations in infants under 1 year of age. For each of these age partitions, the 99th percentile cut-off, 95% reference interval, and proportion of detectable concentrations were determined.

Conclusions

This is the first study to examine hs-cTnT and NT-proBNP reference values together in a healthy pediatric cohort without other clinical indications. We present 99th percentile cut-offs, which will allow clinicians to appropriately evaluate cardiovascular disease in children and adolescents.
Assessing the enrichment of dietary supplement coverage in the Unified Medical Language System
Authors: Vasilakes Jake , Bompelli Anusha , Bishop Jeffrey R , Adam Terrence J , Bodenreider Olivier , Zhang Rui
Published: June 2020

Objective

We sought to assess the need for additional coverage of dietary supplements (DS) in the Unified Medical Language System (UMLS) by investigating (1) the overlap between the integrated DIetary Supplements Knowledge base (iDISK) DS ingredient terminology and the UMLS and (2) the coverage of iDISK and the UMLS over DS mentions in the biomedical literature.

Materials and Methods

We estimated the overlap between iDISK and the UMLS by mapping iDISK to the UMLS using exact and normalized strings. The coverage of iDISK and the UMLS over DS mentions in the biomedical literature was evaluated via a DS named-entity recognition (NER) task within PubMed abstracts.

Results

The coverage analysis revealed that only 30% of iDISK terms can be matched to the UMLS, although these cover over 99% of iDISK concepts. A manual review revealed that a majority of the unmatched terms represented new synonyms, rather than lexical variants. For NER, iDISK nearly doubles the precision and achieves a higher F1 score than the UMLS, while maintaining a competitive recall.

Discussion

While iDISK has significant concept overlap with the UMLS, it contains many novel synonyms. Furthermore, almost 3000 of these overlapping UMLS concepts are missing a DS designation, which could be provided by iDISK. The NER experiments show that the specialization of iDISK is useful for identifying DS mentions.

Conclusions

Our results show that the DS representation in the UMLS could be enriched by adding DS designations to many concepts and by adding new synonyms.
Importance of Preanalytical Factors in Measuring Cr and Co Levels in Human Whole Blood: Contamination Control, Proper Sample Collection and Long-Term Storage Stability
Authors: Sommer Yuliya L , Ward Cynthia D , Georgi Joaudimir Castro , Cheng Po-Yung , Jones Robert L
Published: June 2020

A number of errors with potentially significant consequences may be introduced at various points in the analytical process, which result in skewed, erroneous analytical results. Precautionary procedures such as contamination control, following established sample collection protocols, and having a complete understanding of the long-term stability of the elements of interest can minimize or eliminate these errors. Contamination control is critical in the quantification of Cr and Co in human whole blood. Cr and Co levels in most biological samples are low, but these elements occur naturally in the environment and are often found in commercial and consumer products, which increases the risk of contamination. In this paper, we demonstrated that lot screening process in which we pre-screen a sub-set of manufactured lots used in collecting, analyzing and storing blood samples is a critical step in controlling Cr and Co contamination. Stainless steel needles are often utilized in blood collection but are considered as a potential source of introducing metal contamination to the patient sample. We conducted two studies to determine if there is a possibility of Cr or Co leaching into the human whole blood from the needles during blood collection. We analyzed blood collected from 100 donors and blood collected in vitro in the laboratory from designated vessel containing spiked blood with higher levels of Cr and Co. Two blood tubes were consecutively collected through one needle. In both studies, Cr and Co concentration levels in the two consecutively collected tubes were compared. Based on the results from donor and in vitro blood collection studies, we concluded that there was no Cr and Co leaching from the limited sets of stainless steel needles used in these studies. Furthermore, we demonstrated that Cr and Co human whole blood samples are stable for 1 year stored at temperatures of −70, −20 and 4°C and 6 months at room temperature.
Coronavirus Disease 2019 in Children Cared for at Texas Children’s Hospital: Initial Clinical Characteristics and Outcomes
Authors: Foster Catherine E , Moulton Elizabeth A , Munoz Flor M , Hulten Kristina G , Versalovic James , Dunn James , Revell Paula , Koy Tjin H , Arrington Amy S , Marquez Lucila , Campbell Judith
Published: June 2020

We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19.
Delayed clinical presentation of Plasmodium falciparum malaria after leaving an endemic area: a tale of two patients
Authors: Pennington Kaylin , Ives Samuel T , Frosch Anne E P , Shaughnessy Megan K
Published: June 2020

Malaria due to Plasmodium falciparum (Pf) may be missed if patients present with symptoms outside of the expected incubation period. We describe two patients who developed Pf malaria more than one year after visiting malaria-endemic countries. Both worked at an international airport, but no source of infection was identified.
Unraveling the mechanisms of chemotherapy-induced damage to human primordial follicle reserve: road to developing therapeutics for fertility preservation and reversing ovarian aging
Authors: Szymanska Katarzyna J , Tan Xiujuan , Oktay Kutluk
Published: June 2020

Among the investigated mechanisms of chemotherapy-induced damage to human primordial follicle reserve are induction of DNA double-strand breaks (DSBs) and resultant apoptotic death, stromal–microvascular damage and follicle activation. Accumulating basic and translational evidence suggests that acute exposure to gonadotoxic chemotherapeutics, such as cyclophosphamide or doxorubicin, induces DNA DSBs and triggers apoptotic death of primordial follicle oocytes within 12–24 h, resulting in the massive loss of ovarian reserve. Evidence also indicates that chemotherapeutic agents can cause microvascular and stromal damage, induce hypoxia and indirectly affect ovarian reserve. While it is possible that the acute reduction of the primordial follicle reserve by massive apoptotic losses may result in delayed activation of some primordial follicles, this is unlikely to be a predominant mechanism of loss in humans. Here, we review these mechanisms of chemotherapy-induced ovarian reserve depletion and the potential reasons for the discrepancies among the studies. Based on the current literature, we propose an integrated hypothesis that explains both the acute and delayed chemotherapy-induced loss of primordial follicle reserve in the human ovary.
Prognostic models for chronic kidney disease: a systematic review and external validation
Authors: van Rijn Marieke H C , van de Luijtgaarden Moniek , van Zuilen Arjan D , Blankestijn Peter J , Wetzels Jack F M , Debray Thomas P A , van den Brand Jan A J G
Published: June 2020

Background

Accurate risk prediction is needed in order to provide personalized healthcare for chronic kidney disease (CKD) patients. An overload of prognosis studies is being published, ranging from individual biomarker studies to full prediction studies. We aim to systematically appraise published prognosis studies investigating multiple biomarkers and their role in risk predictions. Our primary objective was to investigate if the prognostic models that are reported in the literature were of sufficient quality and to externally validate them.

Methods

We undertook a systematic review and appraised the quality of studies reporting multivariable prognosis models for end-stage renal disease (ESRD), cardiovascular (CV) events and mortality in CKD patients. We subsequently externally validated these models in a randomized trial that included patients from a broad CKD population.

Results

We identified 91 papers describing 36 multivariable models for prognosis of ESRD, 50 for CV events, 46 for mortality and 17 for a composite outcome. Most studies were deemed of moderate quality. Moreover, they often adopted different definitions for the primary outcome and rarely reported full model equations (21% of the included studies). External validation was performed in the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners trial (n = 788, with 160 events for ESRD, 79 for CV and 102 for mortality). The 24 models that reported full model equations showed a great variability in their performance, although calibration remained fairly adequate for most models, except when predicting mortality (calibration slope >1.5).

Conclusions

This review shows that there is an abundance of multivariable prognosis models for the CKD population. Most studies were considered of moderate quality, and they were reported and analysed in such a manner that their results cannot directly be used in follow-up research or in clinical practice.
Consensus recommendations for a dynamic susceptibility contrast MRI protocol for use in high-grade gliomas
Authors: Boxerman Jerrold L , Quarles Chad C , Hu Leland S , Erickson Bradley J , Gerstner Elizabeth R , Smits Marion , Kaufmann Timothy J , Barboriak Daniel P , Huang Raymond H , Wick Wolfgang , Weller Michael , Galanis Evanthia , Kalpathy-Cramer Jayashree , Shankar Lalitha , Jacobs Paula , Chung Caroline , van den Bent Martin J , Chang Susan , Al Yung W K , Cloughesy Timothy F , Wen Patrick Y , Gilbert Mark R , Rosen Bruce R , Ellingson Benjamin M , Schmainda Kathleen M ,   Jumpstarting Brain Tumor Drug Development Coalition Imaging Standardization Steering Committee, Arons David F , Kingston Ann , Sandak David , Wallace Max , Musella Al , Haynes Chas
Published: June 2020

Despite the widespread clinical use of dynamic susceptibility contrast (DSC) MRI, DSC-MRI methodology has not been standardized, hindering its utilization for response assessment in multicenter trials. Recently, the DSC-MRI Standardization Subcommittee of the Jumpstarting Brain Tumor Drug Development Coalition issued an updated consensus DSC-MRI protocol compatible with the standardized brain tumor imaging protocol (BTIP) for high-grade gliomas that is increasingly used in the clinical setting and is the default MRI protocol for the National Clinical Trials Network. After reviewing the basis for controversy over DSC-MRI protocols, this paper provides evidence-based best practices for clinical DSC-MRI as determined by the Committee, including pulse sequence (gradient echo vs spin echo), BTIP-compliant contrast agent dosing (preload and bolus), flip angle (FA), echo time (TE), and post-processing leakage correction. In summary, full-dose preload, full-dose bolus dosing using intermediate (60°) FA and field strength-dependent TE (40–50 ms at 1.5 T, 20–35 ms at 3 T) provides overall best accuracy and precision for cerebral blood volume estimates. When single-dose contrast agent usage is desired, no-preload, full-dose bolus dosing using low FA (30°) and field strength-dependent TE provides excellent performance, with reduced contrast agent usage and elimination of potential systematic errors introduced by variations in preload dose and incubation time.
The interplay of cell cycle and DNA repair gene alterations in upper tract urothelial carcinoma: predictive and prognostic implications
Authors: Vlachostergios Panagiotis J
Published: June 2020

Upper tract urothelial carcinoma (UTUC) is rare but can occur sporadically outside the context of Lynch syndrome. In these cases, knowing whether non-mismatch repair (MMR), DNA damage response and repair (DDR), and cell cycle gene alterations may predict responses to chemotherapy or immunotherapy and survival is of clinical importance. This study examined the germline and somatic mutational landscape of two UTUC patients with differential responses to programmed death 1 (PD-1)/PD-ligand 1 (PD-L1) immune checkpoint inhibitors and queried three independent UTUC cohort studies for co-occurrence of key cell cycle and DDR genes, as well as for their associations with overall survival (OS). TP53 and RB1 emerged as potential determinants of shorter OS in UTUC cohort patients, regardless of concurrent DDR alterations, and if prospectively assessed in larger studies they might also explain resistance to PD-1/PD-L1 blockade despite PD-L1 expression.
Jewish Ethics Regarding Vaccination
Authors: Rashi Tsuriel
Published: June 2020

In recent years, more and more religious communities have been refusing to vaccinate their children, and in so doing are allowing diseases to spread. These communities justify resistance to vaccination on various religious grounds and make common cause with nonreligious communities who oppose vaccination for their own reasons. Today this situation is reflected primarily in the spread of measles, and vaccine hesitancy was identified by the World Health Organization as 1 of the top 10 global health threats of 2019. The present article presents the religious and ethical arguments for the obligation within Jewish tradition to vaccinate all children. Apart from the obligation on parents to vaccinate their own children, it includes the ethical arguments based on Judaism that call for parents to become organized and force schools to refuse to accept children who have not been vaccinated and demand vaccination of those who have not been inoculated.