bluuebunny/crossref_metadata_2025_split huggingface dataset:
Boolean dynamic modeling of cancer signaling networks: Prognosis, progression, and therapeutics
Authors: Sherekar Shubhank , Viswanathan Ganesh A. 
Published: May 2021

AbstractCancer is a multifactorial disease. Aberrant functioning of the underlying complex signaling network that orchestrates cellular response to external or internal cues governs incidence, progression, and recurrence of cancer. Detailed understanding of cancer's etiology can offer useful insights into arriving at novel therapeutic and disease management strategies. Such an understanding for most cancers is currently limited due to unavailability of a predictive large‐scale, integrated signaling model accounting for all tumor orchestrating factors. We suggest that the potential of Boolean dynamic (BD) modeling approaches, though qualitative, can be harnessed for developing holistic models capturing multi‐scale, multi‐cellular signaling processes involved in cancer incidence and progression. We believe that constraining such an integrated BD model with variety of omics data at different scales from laboratory and clinical settings could offer deeper insights into causal mechanisms governing the disease leading to better prognosis. We review the recent literature employing different BD modeling strategies to model variety of cancer signaling programs leading to identification of cancer‐specific prognostic markers such as SMAD proteins, which may also serve as early predictors of tumor cells hijacking the epithelial‐mesenchymal plasticity program.In silicosimulations of BD models of different cancer signaling networks combined with attractor landscape analysis and validated with experimental data predicted the nature of short‐ and long‐term response of standard targeted therapeutic agents such as Nutlin‐3, a small molecule inhibitor for p53‐MDM2 interaction. BD simulations also offered a mechanistic view of emerging resistance to drugs such as Trastuzumab for HER+ breast cancer, analysis of which suggested new combination therapies to circumvent them. We believe future improvements in BD modeling techniques, and tools can lead to development of a comprehensive platform that can drive holistic approaches toward better decision‐making in the clinical settings, and thereby help identify novel therapeutic strategies for improved cancer treatment at personalised levels.
Full closed loop open‐source algorithm performance comparison in pigs with diabetes
Authors: Lal Rayhan A. , Maikawa Caitlin L. , Lewis Dana , Baker Sam W. , Smith Anton A. A. , Roth Gillie A. , Gale Emily C. , Stapleton Lyndsay M. , Mann Joseph L. , Yu Anthony C. , Correa Santiago , Grosskopf Abigail K. , Liong Celine S. , Meis Catherine M. , Chan Doreen , Garner Joseph P. , Maahs David M. , Buckingham Bruce A. , Appel Eric A. 
Published: May 2021

AbstractUnderstanding how automated insulin delivery (AID) algorithm features impact glucose control under full closed loop delivery represents a critical step toward reducing patient burden by eliminating the need for carbohydrate entries at mealtimes. Here, we use a pig model of diabetes to compare AndroidAPS and Loop open‐source AID systems without meal announcements. Overall time‐in‐range (70–180 mg/dl) for AndroidAPS was 58% ± 5%, while time‐in‐range for Loop was 35% ± 5%. The effect of the algorithms on time‐in‐range differed between meals and overnight. During the overnight monitoring period, pigs had an average time‐in‐range of 90% ± 7% when on AndroidAPS compared to 22% ± 8% on Loop. Time‐in‐hypoglycemia also differed significantly during the lunch meal, whereby pigs running AndroidAPS spent an average of 1.4% (+0.4/−0.8)% in hypoglycemia compared to 10% (+3/−6)% for those using Loop. As algorithm design for closed loop systems continues to develop, the strategies employed in the OpenAPS algorithm (known as oref1) as implemented in AndroidAPS for unannounced meals may result in a better overall control for full closed loop systems.
Negative frequency‐dependent selection maintains shell banding polymorphisms in two marine snails (Littorina fabalis and Littorina saxatilis)
Authors: Estévez Daniel , Galindo Juan , Rolán‐Alvarez Emilio 
Published: May 2021

AbstractThe presence of shell bands is common in gastropods. Both the marine snails Littorina fabalis and Lttorina saxatilis are polymorphic for this trait. Such polymorphism would be expected to be lost by the action of genetic drift or directional selection, but it appears to be widespread at relatively constant frequencies. This suggests it is maintained by balancing selection on the trait or on a genetically linked trait. Using long time series of empirical data, we compared potential effects of genetic drift and negative frequency‐dependent selection (NFDS) in the two species. The contribution of genetic drift to changes in the frequency of bands in L. fabalis was estimated using the effective population size estimated from microsatellite data, while the effect of genetic drift in L. saxatilis was derived from previously published study. Frequency‐dependent selection was assessed by comparing the cross‐product estimator of fitness with the frequency of the polymorphism across years using a regression analysis. Both studied species showed patterns of NFDS. In addition, in L. fabalis, contributions from genetic drift could explain some of the changes in banding frequency. Overdominance and heterogeneous selection did not fit well to our data. The possible biological explanations resulting in the maintenance of the banding polymorphism are discussed.
Illegal harvesting and livestock grazing threaten the endangered orchid Dactylorhiza hatagirea (D. Don) Soó in Nepalese Himalaya
Authors: Chapagain Deep Jyoti , Meilby Henrik , Baniya Chitra Bahadur , Budha‐Magar Shanta , Ghimire Suresh Kumar 
Published: May 2021

AbstractHarvesting of orchids for medicine and salep production is a traditional practice, and increasing market demand is spurring illegal harvest. Ethno‐ecological studies in combination with the effect of anthropogenic disturbance are lacking for orchids. We compared population density and structure, and tuber biomass of Dactylorhiza hatagirea (D. Don) Soó for three years in two sites: Manang, where harvesting of medicinal plants was locally regulated (protected), and Darchula, where harvesting was locally unregulated (unprotected). Six populations were studied along an elevation gradient by establishing 144 temporary plots (3 × 3 m2) from 3,400 to 4,600 m elevations. Mean density of D. hatagirea was significantly higher in the locally protected (1.31 ± 0.17 plants/m2) than in the unprotected (0.72 ± 0.06 plants/m2) site. The protected site showed stable population density with high reproductive fitness and tuber biomass over the three‐year period. A significant negative effect (p < .1) of relative radiation index (RRI) on the density of the adult vegetative stage and a positive effect of herb cover on juvenile and adult vegetative stages were found using mixed zero‐inflated Poisson (mixed ZIP) models. The densities of different life stages were highly sensitive to harvesting and livestock grazing. Significant interactions between site and harvesting and grazing indicated particularly strong negative effects of these disturbances on densities of juvenile and adult reproductive stages in the unprotected site. Semi‐structured interviews were conducted with informants (n = 186) in the villages and at the ecological survey sites. Our interview results showed that at the protected site people are aware of the conservation status and maintain sustainable populations, whereas the opposite was the case at the unprotected site where the populations are threatened. Sustainability of D. hatagirea populations, therefore, largely depends on controlling illegal and premature harvesting and unregulated livestock grazing, thus indicating the need for permanent monitoring of the species.
Hormone‐mediated foraging strategies in an uncertain environment: Insights into the at‐sea behavior of a marine predator
Authors: DeRango Eugene J. , Schwarz Jonas F. L. , Piedrahita Paolo , Páez‐Rosas Diego , Crocker Daniel E. , Krüger Oliver 
Published: May 2021

Abstract

Hormones are extensively known to be physiological mediators of energy mobilization and allow animals to adjust behavioral performance in response to their environment, especially within a foraging context.

Few studies, however, have narrowed focus toward the consistency of hormonal patterns and their impact on individual foraging behavior. Describing these relationships can further our understanding of how individuals cope with heterogeneous environments and exploit different ecological niches.

To address this, we measured between‐ and within‐individual variation of basal cortisol (CORT), thyroid hormone T3, and testosterone (TEST) levels in wild adult female Galápagos sea lions (Zalophus wollebaeki) and analyzed how these hormones may be associated with foraging strategies. In this marine predator, females exhibit one of three spatially and temporally distinct foraging patterns (i.e., “benthic,” “pelagic,” and “night” divers) within diverse habitat types.

Night divers differentiated from other strategies by having lower T3 levels. Considering metabolic costs, night divers may represent an energetically conservative strategy with shorter dive durations, depths, and descent rates to exploit prey which migrate up the water column based on vertical diel patterns.

Intriguingly, CORT and TEST levels were highest in benthic divers, a strategy characterized by congregating around limited, shallow seafloors to specialize on confined yet reliable prey. This pattern may reflect hormone‐mediated behavioral responses to specific risks in these habitats, such as high competition with conspecifics, prey predictability, or greater risks of predation.

Overall, our study highlights the collective effects of hormonal and ecological variation on marine foraging. In doing so, we provide insights into how mechanistic constraints and environmental pressures may facilitate individual specialization in adaptive behavior in wild populations.
Top predators govern multitrophic diversity effects in tritrophic food webs
Authors: Ceulemans Ruben , Guill Christian , Gaedke Ursula 
Published: May 2021

AbstractIt is well known that functional diversity strongly affects ecosystem functioning. However, even in rather simple model communities consisting of only two or, at best, three trophic levels, the relationship between multitrophic functional diversity and ecosystem functioning appears difficult to generalize, because of its high contextuality. In this study, we considered several differently structured tritrophic food webs, in which the amount of functional diversity was varied independently on each trophic level. To achieve generalizable results, largely independent of parametrization, we examined the outcomes of 128,000 parameter combinations sampled from ecologically plausible intervals, with each tested for 200 randomly sampled initial conditions. Analysis of our data was done by training a random forest model. This method enables the identification of complex patterns in the data through partial dependence graphs, and the comparison of the relative influence of model parameters, including the degree of diversity, on food‐web properties. We found that bottom‐up and top‐down effects cascade simultaneously throughout the food web, intimately linking the effects of functional diversity of any trophic level to the amount of diversity of other trophic levels, which may explain the difficulty in unifying results from previous studies. Strikingly, only with high diversity throughout the whole food web, different interactions synergize to ensure efficient exploitation of the available nutrients and efficient biomass transfer to higher trophic levels, ultimately leading to a high biomass and production on the top level. The temporal variation of biomass showed a more complex pattern with increasing multitrophic diversity: while the system initially became less variable, eventually the temporal variation rose again because of the increasingly complex dynamical patterns. Importantly, top predator diversity and food‐web parameters affecting the top trophic level were of highest importance to determine the biomass and temporal variability of any trophic level. Overall, our study reveals that the mechanisms by which diversity influences ecosystem functioning are affected by every part of the food web, hampering the extrapolation of insights from simple monotrophic or bitrophic systems to complex natural food webs.
Parathormone levels add prognostic ability to N‐terminal pro‐brain natriuretic peptide in stable coronary patients
Authors: Gutiérrez‐Landaluce Carlos , Aceña Álvaro , Pello Ana , Martínez‐Milla Juan , González‐Lorenzo Óscar , Tarín Nieves , Cristóbal Carmen , Blanco‐Colio Luis M. , Martín‐Ventura José Luis , Huelmos Ana , López‐Castillo Marta , Alonso Joaquín , López Bescós Lorenzo , Alonso‐Pulpón Luis , González‐Parra Emilio , Egido Jesús , Mahíllo‐Fernández Ignacio , Lorenzo Óscar , González‐Casaus María Luisa , Tuñón José 
Published: May 2021

AbstractAimsThere are controversial data on the ability of the components of mineral metabolism (vitamin D, phosphate, parathormone [PTH], fibroblast growth factor‐23 [FGF23], and klotho) to predict cardiovascular events. In addition, it is unknown whether they add any prognostic value to other well‐known biomarkers.Methods and resultsIn 969 stable coronary patients, we determined plasma levels of all the aforementioned components of mineral metabolism with a complete set of clinical and biochemical variables, including N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity troponin I (hs‐TnI), and high‐sensitivity C‐reactive protein. Secondary outcomes were ischaemic events (any acute coronary syndrome, stroke, or transient ischaemic attack) and heart failure or death. The primary outcome was a composite of the secondary outcomes. Median follow‐up was 5.39 years. Age was 60 (52–72) years. Median glomerular filtration rate was 80.4 (65.3–93.1) mL/min/1.73 m2. One‐hundred and eighty‐five patients developed the primary outcome. FGF23, PTH, hs‐TnI, and NT‐proBNP were directly related with the primary outcome on univariate Cox analysis, while Klotho and calcidiol were inversely related. On multivariate analysis, only PTH (HR 1.058 [CI 1.021–1.097]; P = 0.002) and NT‐proBNP (HR 1.020 [CI 1.012–1.028]; P < 0.001) were independent predictors of the primary outcome but also for the secondary outcome of heart failure or death (HR 1.066 [CI 1.016–1.119]; P = 0.009 and HR 1.024 [CI 1.014–1.034]; P < 0.001, respectively). PTH was the only biomarker that predicted ischaemic events (HR 1.052 [1.010–1.096]; P = 0.016). Patients were divided in two subgroups according to FGF23 plasma levels. PTH retained its prognostic value only in patients with FGF23 levels above the median (>85.5 RU/mL) (P < 0.001) but not in patients with low FGF23 levels (P = 0.551). There was a significant interaction between FGF23 and PTH (P = 0.002). However, there was no significant interaction between PTH and both klotho and calcidiol levels.ConclusionsParathormone is an independent predictor of cardiovascular events in coronary patients, adding complimentary prognostic information to NT‐proBNP plasma levels. This predictive value is restricted to patients with high FGF23 plasma levels. This should be considered in the design of future studies in this field.
Wearable cardioverter‐defibrillator: friend or foe in suspected myocarditis?
Authors: Blaschke Florian , Lacour Philipp , Dang Phi Long , Parwani Abdul Shokor , Hohendanner Felix , Walter Thula , Klingel Karin , Kühl Uwe , Heinzel Frank R. , Sherif Mohammad , Boldt Leif‐Hendrik , Pieske Burkert , Tschöpe Carsten 
Published: May 2021

AbstractAimWearable cardioverter defibrillator (WCD, LifeVest, and Zoll) therapy has become a useful tool to bridge a temporarily increased risk for sudden cardiac death. However, despite extensive use, there is a lack of evidence whether patients with myocarditis and impaired LVEF may benefit from treatment with a WCD.Methods and resultsWe conducted a single‐centre retrospective observational study analysing patients with a WCD prescribed between September 2015 and April 2020 at our institution. In total, 135 patients were provided with a WCD, amongst these 76 patients (mean age 48.9 ± 13.7 years; 84.2% male) for clinically suspected myocarditis. Based on the results of the endomyocardial biopsy and, where available cardiac magnetic resonance imaging, 39 patients (51.3%) were diagnosed with myocarditis and impaired LVEF and 37 patients (48.7%) with dilated cardiomyopathy (DCM) without evidence of cardiac inflammation. The main immunohistopathological myocarditis subtype was lymphocytic myocarditis in 36 (92.3%) patients, and four patients (10.3%) of this group had an acute myocarditis. Three patients had cardiac sarcoidosis (7.7%). Ventricular tachycardia occurred in seven myocarditis (in total 41 VTs; 85.4% non‐sustained) and one DCM patients (in total one non‐sustained ventricular tachycardia). Calculated necessary WCD wearing time until ventricular tachycardia occurrence is 86.41 days in myocarditis compared with 6.46 years in DCM patients.ConclusionsOur data suggest that myocarditis patients may benefit from WCD therapy. However, as our study is not powered for outcome, further randomized studies powered for the outcome morbidity and mortality are necessary.
Frequency, predictors, and prognosis of heart failure with improved left ventricular ejection fraction: a single‐centre retrospective observational cohort study
Authors: Li Qing , Qiao Yu , Tang Jiong , Guo Yulong , Liu Ke , Yang Bangguo , Zhou Yingqiu , Yang Kai , Shen Shuqin , Guo Tao , Guo Jinrui 
Published: May 2021

AbstractAimsAn improved left ventricular ejection fraction (HFiEF) was observed across heart failure (HF) patients with a reduced or mid‐range ejection fraction (HFrEF or HFmrEF, respectively). We postulated that HFiEF patients are clinically distinct from non‐HFiEF patients.Methods and resultsA total of 447 patients hospitalized due to a clinical diagnosis of HF (LVEF <50% at baseline) were enrolled from September 2017 to September 2019. Echocardiogram re‐evaluation was conducted repeatedly over 6 months of follow‐up after discharge. The primary endpoint included the composite of HF hospitalization and all‐cause mortality. Subjects (n = 184) with HFiEF (defined as an absolute LVEF improvement≥10%) were compared with 263 non‐HFiEF (defined by <10% improvement in LVEF) subjects. Multivariable Cox regression was performed and identified younger age, smaller left ventricular end diastolic dimension (LVEDD), beta‐blocker use, AF ablation and cardiac resynchronization therapy (CRT) as independent predictors of HFiEF. According to Kaplan–Meier analysis, HFiEF subjects had lower cardiac composite outcomes (P = 0.002) and all‐cause mortality (P = 0.003) than non‐HFiEF subjects. Multivariate Cox survival analysis revealed that non‐HFiEF (compared with HFiEF) was an independent predictor of both the primary endpoints (HR = 0.679, 95% CI: 0.451–0.907, P = 0.012), which was driven by all‐cause mortality (HR = 0.504, 95% CI: 0.256–0.991, P = 0.047).ConclusionsThese data confirm that compared with non‐HFiEF, HFiEF is a distinct HF phenotype with favourable clinical outcomes.
Inhalation of publicly available indoor insecticide spray caused myocardial infarction type II: a case report
Authors: Habedank Dirk , Stubbe Beate , Ewert Ralf , Kroll Alexandra , Atmowihardjo Iskandar , Habedank Birgit 
Published: May 2021

AbstractWe report on a 70‐year‐old woman who tried to eliminate ants from her kitchen by applying a publicly available insecticide spray. Immediately afterwards, she felt dyspnoea, superseded by heavy chest pain. High‐sensitivity troponin concentration increased from 33 to 149 ng/L (cut‐off 50 ng/L). Significant coronary stenosis was excluded by coronary angiography, and the myocardial damage was classified as myocardial infarction type II. After exclusion of other potential mechanisms, we consider a cardiotoxic effect of the insecticide mixture of cypermethrin, tetramethrin, and piperonyl butoxide possible. We conclude that consumer information has to be improved. This concerns sustainable control measures adapted to the target insect species (in this case, the black garden ant Lasius niger), and differentiation between authorized and non‐authorized but notified products. The instructions for use should give clear information on vulnerable groups and recommend personal protective equipment. Physicians and authorities should be alert to cardiac side‐effects of insecticides.
Multisource evidence theory‐based fraud risk assessment of China's listed companies
Authors: Qiu Shi , Luo Yuansheng , Guo Hongwei 
Published: May 2021

AbstractFinancial fraud has great negative impact on capital markets. It misleads investors and the government and will hurt the development of the capital market in China. To detect corporate fraud, an artificial intelligence‐based method is proposed to evaluate the fraud risk. A new model for assessing the fraud risk of listed companies in China is put forward. The proposed approach collects multisource evidence from inside and outside listed companies. The internal evidence for fraud risk assessment is gathered by a machine‐learning method. The external evidence for fraud risk assessment is obtained by a web crawler. An evidence theory‐based is employed for integrating the multisource evidence. The Fraud Risk Assessment Model based on Multisource Evidence Theory is established. The proposed model is applied to assess the fraud risk of the listed companies in China. The results indicate that the proposed model is effective at evaluating the fraud risk of listed companies, and it also has a higher precision, recall, and F‐1 measure than the traditional probability model.
Interest rates forecasting: Between Hull and White and the CIR#—How to make a single‐factor model work
Authors: Orlando Giuseppe , Bufalo Michele 
Published: May 2021

AbstractIn this work, we present our findings of the so‐called CIR#, which is a modified version of the Cox, Ingersoll, and Ross (CIR) model, turned into a forecasting tool for any term structure. The main feature of the CIR# model is its ability to cope with negative interest rates, cluster volatility, and jumps. By considering a dataset composed of money market interest rates during turmoil and calmer periods, we show how the CIR# performs in terms of directionality of rates and forecasting error. Comparison is carried out with a revamped version of the CIR model (denoted
), the Hull and White model, and the exponentially weighted moving average (EWMA) which is often adopted whenever no structure in data is assumed. To confirm the analysis, testing and validation is performed on both historical and ad hoc data with different metrics and clustering criteria.