bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bringing proportional recovery into proportion: Bayesian modelling of post-stroke motor impairment
Authors: Bonkhoff Anna K , Hope Thomas , Bzdok Danilo , Guggisberg Adrian G , Hawe Rachel L , Dukelow Sean P , Rehme Anne K , Fink Gereon R , Grefkes Christian , Bowman Howard 
Published: May 2020

AbstractAccurate predictions of motor impairment after stroke are of cardinal importance for the patient, clinician, and healthcare system. More than 10 years ago, the proportional recovery rule was introduced by promising that high-fidelity predictions of recovery following stroke were based only on the initially lost motor function, at least for a specific fraction of patients. However, emerging evidence suggests that this recovery rule is subject to various confounds and may apply less universally than previously assumed. Here, we systematically revisited stroke outcome predictions by applying strategies to avoid confounds and fitting hierarchical Bayesian models. We jointly analysed 385 post-stroke trajectories from six separate studies—one of the largest overall datasets of upper limb motor recovery. We addressed confounding ceiling effects by introducing a subset approach and ensured correct model estimation through synthetic data simulations. Subsequently, we used model comparisons to assess the underlying nature of recovery within our empirical recovery data. The first model comparison, relying on the conventional fraction of patients called ‘fitters’, pointed to a combination of proportional to lost function and constant recovery. ‘Proportional to lost’ here describes the original notion of proportionality, indicating greater recovery in case of a more severe initial impairment. This combination explained only 32% of the variance in recovery, which is in stark contrast to previous reports of &gt;80%. When instead analysing the complete spectrum of subjects, ‘fitters’ and ‘non-fitters’, a combination of proportional to spared function and constant recovery was favoured, implying a more significant improvement in case of more preserved function. Explained variance was at 53%. Therefore, our quantitative findings suggest that motor recovery post-stroke may exhibit some characteristics of proportionality. However, the variance explained was substantially reduced compared to what has previously been reported. This finding motivates future research moving beyond solely behaviour scores to explain stroke recovery and establish robust and discriminating single-subject predictions.
Global CNS correction in a large brain model of human alpha-mannosidosis by intravascular gene therapy
Authors: Yoon Sea Young , Hunter Jacqueline E , Chawla Sanjeev , Clarke Dana L , Molony Caitlyn , O’Donnell Patricia A , Bagel Jessica H , Kumar Manoj , Poptani Harish , Vite Charles H , Wolfe John H 
Published: May 2020

Abstract
Intravascular injection of certain adeno-associated virus vector serotypes can cross the blood–brain barrier to deliver a gene into the CNS. However, gene distribution has been much more limited within the brains of large animals compared to rodents, rendering this approach suboptimal for treatment of the global brain lesions present in most human neurogenetic diseases. The most commonly used serotype in animal and human studies is 9, which also has the property of being transported via axonal pathways to distal neurons. A small number of other serotypes share this property, three of which were tested intravenously in mice compared to 9. Serotype hu.11 transduced fewer cells in the brain than 9, rh8 was similar to 9, but hu.32 mediated substantially greater transduction than the others throughout the mouse brain. To evaluate the potential for therapeutic application of the hu.32 serotype in a gyrencephalic brain of larger mammals, a hu.32 vector expressing the green fluorescent protein reporter gene was evaluated in the cat. Transduction was widely distributed in the cat brain, including in the cerebral cortex, an important target since mental retardation is an important component of many of the human neurogenetic diseases. The therapeutic potential of a hu.32 serotype vector was evaluated in the cat homologue of the human lysosomal storage disease alpha-mannosidosis, which has globally distributed lysosomal storage lesions in the brain. Treated alpha-mannosidosis cats had reduced severity of neurological signs and extended life spans compared to untreated cats. The extent of therapy was dose dependent and intra-arterial injection was more effective than intravenous delivery. Pre-mortem, non-invasive magnetic resonance spectroscopy and diffusion tensor imaging detected differences between the low and high doses, and showed normalization of grey and white matter imaging parameters at the higher dose. The imaging analysis was corroborated by post-mortem histological analysis, which showed reversal of histopathology throughout the brain with the high dose, intra-arterial treatment. The hu.32 serotype would appear to provide a significant advantage for effective treatment of the gyrencephalic brain by systemic adeno-associated virus delivery in human neurological diseases with widespread brain lesions.
Cardiomyocyte ageing and cardioprotection: consensus document from the ESC working groups cell biology of the heart and myocardial function
Authors: Ruiz-Meana Marisol , Bou-Teen Diana , Ferdinandy Péter , Gyongyosi Mariann , Pesce Maurizio , Perrino Cinzia , Schulz Rainer , Sluijter Joost P G , Tocchetti Carlo G , Thum Thomas , Madonna Rosalinda 
Published: May 2020

Abstract
Advanced age is a major predisposing risk factor for the incidence of coronary syndromes and comorbid conditions which impact the heart response to cardioprotective interventions. Advanced age also significantly increases the risk of developing post-ischaemic adverse remodelling and heart failure after ischaemia/reperfusion (IR) injury. Some of the signalling pathways become defective or attenuated during ageing, whereas others with well-known detrimental consequences, such as glycoxidation or proinflammatory pathways, are exacerbated. The causative mechanisms responsible for all these changes are yet to be elucidated and are a matter of active research. Here, we review the current knowledge about the pathophysiology of cardiac ageing that eventually impacts on the increased susceptibility of cells to IR injury and can affect the efficiency of cardioprotective strategies.
“Simple” Biomechanical Model for Ants Reveals How Correlated Evolution among Body Segments Minimizes Variation in Center of Mass as Heads Get Larger
Authors: Anderson Philip S L , Rivera Michael D , Suarez Andrew V 
Published: May 2020

Synopsis
The field of comparative biomechanics strives to understand the diversity of the biological world through the lens of physics. To accomplish this, researchers apply a variety of modeling approaches to explore the evolution of form and function ranging from basic lever models to intricate computer simulations. While advances in technology have allowed for increasing model complexity, insight can still be gained through the use of low-parameter “simple” models. All models, regardless of complexity, are simplifications of reality and must make assumptions; “simple” models just make more assumptions than complex ones. However, “simple” models have several advantages. They allow individual parameters to be isolated and tested systematically, can be made applicable to a wide range of organisms and make good starting points for comparative studies, allowing for complexity to be added as needed. To illustrate these ideas, we perform a case study on body form and center of mass stability in ants. Ants show a wide diversity of body forms, particularly in terms of the relative size of the head, petiole(s), and gaster (the latter two make-up the segments of the abdomen not fused to thorax in hymenopterans). We use a “simple” model to explore whether balance issues pertaining to the center of mass influence patterns of segment expansion across major ant clades. Results from phylogenetic comparative methods imply that the location of the center of mass in an ant’s body is under stabilizing selection, constraining the center of mass to the middle segment (thorax) over the legs. This is potentially maintained by correlated rates of evolution between the head and gaster on either end. While these patterns arise from a model that makes several assumptions/simplifications relating to shape and materials, they still offer intriguing insights into the body plan of ants across ∼68% of their diversity. The results from our case study illustrate how “simple,” low-parameter models both highlight fundamental biomechanical trends and aid in crystalizing specific questions and hypotheses for more complex models to address.
Evaluation of an artificial intelligence clinical trial matching system in Australian lung cancer patients
Authors: Alexander Marliese , Solomon Benjamin , Ball David L , Sheerin Mimi , Dankwa-Mullan Irene , Preininger Anita M , Jackson Gretchen Purcell , Herath Dishan M 
Published: May 2020

Abstract

Objective
The objective of this technical study was to evaluate the performance of an artificial intelligence (AI)-based system for clinical trials matching for a cohort of lung cancer patients in an Australian cancer hospital.

Methods
A lung cancer cohort was derived from clinical data from patients attending an Australian cancer hospital. Ten phases I–III clinical trials registered on clinicaltrials.gov and open to lung cancer patients at this institution were utilized for assessments. The trial matching system performance was compared to a gold standard established by clinician consensus for trial eligibility.

Results
The study included 102 lung cancer patients. The trial matching system evaluated 7252 patient attributes (per patient median 74, range 53–100) against 11 467 individual trial eligibility criteria (per trial median 597, range 243–4132). Median time for the system to run a query and return results was 15.5 s (range 7.2–37.8). In establishing the gold standard, clinician interrater agreement was high (Cohen’s kappa 0.70–1.00). On a per-patient basis, the performance of the trial matching system for eligibility was as follows: accuracy, 91.6%; recall (sensitivity), 83.3%; precision (positive predictive value), 76.5%; negative predictive value, 95.7%; and specificity, 93.8%.

Discussion and Conclusion
The AI-based clinical trial matching system allows efficient and reliable screening of cancer patients for clinical trials with 95.7% accuracy for exclusion and 91.6% accuracy for overall eligibility assessment; however, clinician input and oversight are still required. The automated system demonstrates promise as a clinical decision support tool to prescreen a large patient cohort to identify subjects suitable for further assessment.
Artificial intelligence-based conversational agent to support medication prescribing
Authors: Preininger Anita M , South Brett , Heiland Jeff , Buchold Adam , Baca Mya , Wang Suwei , Nipper Rex , Kutub Nawshin , Bohanan Bryan , Jackson Gretchen Purcell 
Published: May 2020

Abstract

Objective
This article describes the system architecture, training, initial use, and performance of Watson Assistant (WA), an artificial intelligence-based conversational agent, accessible within Micromedex®.

Materials and methods
The number and frequency of intents (target of a user’s query) triggered in WA during its initial use were examined; intents triggered over 9 months were compared to the frequency of topics accessed via keyword search of Micromedex. Accuracy of WA intents assigned to 400 queries was compared to assignments by 2 independent subject matter experts (SMEs), with inter-rater reliability measured by Cohen’s kappa.

Results
In over 126 000 conversations with WA, intents most frequently triggered involved dosing (N = 30 239, 23.9%) and administration (N = 14 520, 11.5%). SMEs with substantial inter-rater agreement (kappa = 0.71) agreed with intent mapping in 247 of 400 queries (62%), including 16 queries related to content that WA and SMEs agreed was unavailable in WA. SMEs found 57 (14%) of 400 queries incorrectly mapped by WA; 112 (28%) queries unanswerable by WA included queries that were either ambiguous, contained unrecognized typographical errors, or addressed topics unavailable to WA. Of the queries answerable by WA (288), SMEs determined 231 (80%) were correctly linked to an intent.

Discussion
A conversational agent successfully linked most queries to intents in Micromedex. Ongoing system training seeks to widen the scope of WA and improve matching capabilities.

Conclusion
WA enabled Micromedex users to obtain answers to many medication-related questions using natural language, with the conversational agent facilitating mapping to a broader distribution of topics than standard keyword searches.
You Will Not Remember This: How Memory Efficacy Influences Virtuous Behavior
Authors: Touré-Tillery Maferima , Kouchaki Maryam 
Published: May 2020

AbstractThe present article explores the effect of memory efficacy on consumer behavior—particularly on consumer’s likelihood to behave “virtuously,” that is, in line with standards, such as ideals, values, morals, and social expectations. Memory efficacy refers to people’s general belief that they will be able to remember in the future the things they are experiencing or doing in the present. We hypothesize and find across five studies that when consumers have low-memory efficacy (vs. control), they are less likely to behave virtuously because their actions seem less consequential for their self-concept (i.e., less self-diagnostic). Using two different experimental manipulations of memory efficacy, we examine its effect on virtuous behavior in the context of prosocial choices—that is, charitable giving (study 1A) and volunteering (studies 1B and 2). We then explore our proposed underlying mechanism (perceptions of self-diagnosticity) using causal-chain mediation (studies 3A and 3B) and moderation approaches (studies 4 and 5) in the context of food choices. We conclude with a discussion of the practical and theoretical implications of our findings.
Comparing Populations of Western Corn Rootworm (Coleoptera: Chrysomelidae) in Regions With and Without a History of Injury to Cry3 Corn
Authors: St. Clair Coy R , Head Graham P , Gassmann Aaron J 
Published: May 2020

Abstract
Transgenic corn expressing insecticidal proteins derived from the bacterium Bacillus thuringiensis (Bt) is an important pest management tool. Western corn rootworm, Diabrotica virgifera virgifera LeConte, is a key pest of corn in the midwestern United States that has developed field-evolved resistance to all available Bt traits. The first Bt trait to be commercialized for management of rootworm was Cry3Bb1 in 2003, and field-evolved resistance appeared in 2009. In this study, we examined fields in counties where greater-than-expected injury to Cry3 (Cry3Bb1 or mCry3A) corn roots (&gt;1 node) had previously been reported (problem counties) and counties where injury had not been reported (non-problem counties). Four to eight fields were sampled per county in 2015, 2016, and 2017 to quantify rootworm abundance, root injury, Cry3Bb1resistance, and rootworm management strategies. Rootworm abundance, root injury, and resistance to Cry3Bb1 did not differ between county types. Management tactics differed between county types, with problem counties growing more corn, using more soil insecticide, and growing more Cry34/35Ab1 corn. Additionally, a comparison of root injury to Bt and non-Bt corn within fields indicated that farmers derived an economic benefit from planting Bt corn to manage corn rootworm. Our results suggest that rootworm populations are similar between problem and non-problem counties in Iowa due to similar levels of selection pressure on Cry3 corn, but problem county fields have applied more management tactics due to previous rootworm issues in the area.
Single-Index Expectile Models for Estimating Conditional Value at Risk and Expected Shortfall
Authors: Jiang Rong , Hu Xueping , Yu Keming 
Published: May 2020

Abstract
This article develops a single-index approach for modeling the expectile-based value at risk (EVaR). EVaR has an advantage over the conventional quantile-based VaR (QVaR) of being more sensitive to the magnitude of extreme losses. EVaR can also be used for calculating QVaR and expected shortfall (ES) by exploiting the one-to-one mapping from expectiles to quantiles and the relationship between VaR and ES. We develop an asymmetric least squares technique for estimating the unknown regression parameter and link function in a single-index model, and establish the asymptotic normality of the resultant estimators. Simulation studies and real data applications are conducted to illustrate the finite sample performance of the proposed methods.
Pronghorn population genomics show connectivity in the core of their range
Authors: LaCava Melanie E F , Gagne Roderick B , Stowell Sierra M Love , Gustafson Kyle D , Buerkle C Alex , Knox Lee , Ernest Holly B 
Published: May 2020

AbstractPreserving connectivity in the core of a species’ range is crucial for long-term persistence. However, a combination of ecological characteristics, social behavior, and landscape features can reduce connectivity among wildlife populations and lead to genetic structure. Pronghorn (Antilocapra americana), for example, exhibit fluctuating herd dynamics and variable seasonal migration strategies, but GPS tracking studies show that landscape features such as highways impede their movements, leading to conflicting hypotheses about expected levels of genetic structure. Given that pronghorn populations declined significantly in the early 1900s, have only partially recovered, and are experiencing modern threats from landscape modification, conserving connectivity among populations is important for their long-term persistence in North America. To assess the genetic structure and diversity of pronghorn in the core of their range, we genotyped 4,949 genome-wide single-nucleotide polymorphisms and 11 microsatellites from 398 individuals throughout the state of Wyoming. We found no evidence of genetic subdivision and minimal evidence of isolation by distance despite a range that spans hundreds of kilometers, multiple mountain ranges, and three interstate highways. In addition, a rare variant analysis using putatively recent mutations found no genetic division between pronghorn on either side of a major highway corridor. Although we found no evidence that barriers to daily and seasonal movements of pronghorn impede gene flow, we suggest periodic monitoring of genetic structure and diversity as a part of management strategies to identify changes in connectivity.
Trends in the Incidence of Pancreatic Adenocarcinoma in All 50 United States Examined Through an Age-Period-Cohort Analysis
Authors: da Costa Wilson L , Oluyomi Abiodun O , Thrift Aaron P 
Published: May 2020

Abstract

Background
Pancreatic ductal adenocarcinoma is a major contributor to cancer-related mortality in the United States. We aimed to investigate trends in incidence rates from all 50 states from 2001 to 2016, overall and by race, sex, and state and using age-period-cohort analyses.

Methods
Age-adjusted incidence rates and trends in adults aged 35 years and older were calculated using data from the US Cancer Statistics registry. We used joinpoint regression to compute annual percent changes (APC) and average annual percent changes. We also analyzed incidence trends by age groups and birth cohorts through age-period-cohort modeling.

Results
Age-standardized incidence rates increased by 1.23% (95% confidence interval [CI] = 0.92% to 1.54%) annually between 2001 and 2008 but were stable between 2008 and 2016 (APC = 0.11%, 95% CI = -0.13% to 0.35%). APCs and inflection points were no different for men and women. Rates increased statistically significantly among non-Hispanic whites (NHW) and non-Hispanic blacks between 2001 and 2007 and between 2001 and 2008, respectively, but, in later years, rates increased slowly among NHWs (APC = 0.36%, 95% CI = 0.12% to 0.60%), and were stable among non-Hispanic blacks (APC = -0.40%, 95% CI = -0.89% to 0.10%). The number of states with age-standardized incidence rates no less than 20.4 per 100 000 increased from 16 in 2001–2003 to 40 by 2015–2016. We found a strong birth cohort effect in both men and women and increasing rates among successive birth cohorts of NHWs.

Conclusions
The incidence of pancreatic ductal adenocarcinoma has consistently increased in the United States, albeit at slower rates recently. We observed notable increases among NHWs and in some states in the central and southern part of the country.
Multiple Whole Chromosomal Gains Define Angiomatous Meningiomas and Are Absent From the Tumor Vasculature
Authors: Ahrendsen Jared T , Hsu Nancy , Wolf Zena , Bryke Christine , Varma Hemant 
Published: May 2020

Abstract
Angiomatous meningioma is a variant with prominent vascularity that can mimic other highly vascularized tumors and present diagnostic challenges. Unlike most meningioma variants, where NF2 gene loss on chromosome 22 is the most common genetic abnormality, angiomatous meningiomas are unique in having multiple whole chromosome gains (polysomies). We analyzed 38 meningiomas, 9 angiomatous (including 2 atypical and 1 anaplastic), and 29 nonangiomatous meningiomas, using array comparative genomic hybridization (aCGH). Angiomatous meningiomas showed multiple chromosomal alterations including polysomies and copy neutral loss of heterozygosity in comparison to nonangiomatous variants. The most frequent gains were of chromosomes 5 and 20 (100% and 89% of cases, respectively); none showed chromosome 22 loss. Furthermore, using fluorescence in situ hybridization we show that the vasculature lacked chromosomal polysomy. While generally benign, we present 2 grade II and the first cytogenetically confirmed grade III angiomatous meningioma, demonstrating their potentially aggressive behavior. Thus, multiple polysomies define angiomatous meningioma and aCGH can distinguish this variant from nonangiomatous meningiomas and other histological mimics in diagnostically challenging cases. Furthermore, the prominent vasculature is not neoplastic and likely induced by angiogenic factors. Together, these findings suggest a distinct tumorigenic pathway in angiomatous meningiomas.