bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ensemble modeling highlights importance of understanding parasite-host behavior in preclinical antimalarial drug development
Authors: Burgert Lydia , Rottmann Matthias , Wittlin Sergio , Gobeau Nathalie , Krause Andreas , Dingemanse Jasper , Möhrle Jörg J. , Penny Melissa A. 
Published: March 2020

AbstractEmerging drug resistance and high-attrition rates in early and late stage drug development necessitate accelerated development of antimalarial compounds. However, systematic and meaningful translation of drug efficacy and host-parasite dynamics between preclinical testing stages is missing. We developed an ensemble of mathematical within-host parasite growth and antimalarial action models, fitted to extensive data from four antimalarials with different modes of action, to assess host-parasite interactions in two preclinical drug testing systems of murine parasite P. berghei in mice, and human parasite P. falciparum in immune-deficient mice. We find properties of the host-parasite system, namely resource availability, parasite maturation and virulence, drive P. berghei dynamics and drug efficacy, whereas experimental constraints primarily influence P. falciparum infection and drug efficacy. Furthermore, uninvestigated parasite behavior such as dormancy influences parasite recrudescence following non-curative treatment and requires further investigation. Taken together, host-parasite interactions should be considered for meaningful translation of pharmacodynamic properties between murine systems and for predicting human efficacious treatment.
Serum microRNA in patients undergoing atrial fibrillation ablation
Authors: Kiliszek Marek , Maciak Karolina , Maciejak Agata , Krzyżanowski Krystian , Wierzbowski Robert , Gora Monika , Burzynska Beata , Segiet Agnieszka , Skrobowski Andrzej 
Published: March 2020

AbstractMicroRNAs mediate posttranscriptional gene regulation. The aim of the study was to find a microRNA predictor of successful atrial fibrillation (AF) ablation. A total of 109 patients undergoing first-time AF ablation were included. Nineteen patients were selected to undergo serum microRNA sequencing (study group). The sequencing data were used to select several microRNAs that correlated with 12-month recurrences after AF ablation. Those microRNAs were validated by digital droplet PCR in samples from remaining 90 patients. All patients underwent pulmonary vein isolation (RF ablation, contact force catheter, electroanatomical system). The endpoint of the study was the 12-month AF recurrence rate; the overall recurrence rate was 42.5%. In total, levels of 34 miRNAs were significantly different in sera from patients with AF recurrence compared to patients without AF recurrence. Six microRNAs (miR-183-5p, miR-182-5p, miR-32-5p, miR-107, miR-574-3p, and miR-144-3p) were validated in the whole group. Data from the validation group did not confirm the observations from the study group, as no significant differences were found between miRNAs serum levels in patients with and without recurrences 12 months after AF ablation.
Sources of variation in the 3dMDface and Vectra H1 3D facial imaging systems
Authors: White Julie D. , Ortega-Castrillon Alejandra , Virgo Ciara , Indencleef Karlijne , Hoskens Hanne , Shriver Mark D. , Claes Peter 
Published: March 2020

AbstractAs technology advances and collaborations grow, our ability to finely quantify and explore morphological variation in 3D structures can enable important discoveries and insights into clinical, evolutionary, and genetic questions. However, it is critical to explore and understand the relative contribution of potential sources of error to the structures under study. In this study, we isolated the level of error in 3D facial images attributable to four sources, using the 3dMDface and Vectra H1 camera systems. When the two camera systems are used separately to image human participants, this analysis finds an upper bound of error potentially introduced by the use of the 3dMDface or Vectra H1 camera systems, in conjunction with the MeshMonk registration toolbox, at 0.44 mm and 0.40 mm, respectively. For studies using both camera systems, this upper bound increases to 0.85 mm, on average, and there are systematic differences in the representation of the eyelids, nostrils, and mouth by the two camera systems. Our results highlight the need for careful assessment of potential sources of error in 3D images, both in terms of magnitude and position, especially when dealing with very small measurements or performing many tests.
High-fidelity scaling relationships for determining dissipative particle dynamics parameters from atomistic molecular dynamics simulations of polymeric liquids
Authors: Nafar Sefiddashti M. H. , Boudaghi-Khajehnobar M. , Edwards B. J. , Khomami B. 
Published: March 2020

AbstractAn optimized Dissipative Particle Dynamics (DPD) model with simple scaling rules was developed for simulating entangled linear polyethylene melts. The scaling method, which can be used for mapping dimensionless (reduced units) DPD simulation data to physical units, was based on scaling factors for three fundamental physical units; namely, length, time, and viscosity. The scaling factors were obtained as ratios of equilibrium Molecular Dynamics (MD) simulation data in physical units and equivalent DPD simulation data for relevant quantities. Specifically, the time scaling factor was determined as the ratio of longest relaxation times, the length scaling factor was obtained as the ratio of the equilibrium end-to-end distances, and the viscosity scaling factor was calculated as the ratio of zero-shear viscosities, each as obtained from the MD (in physical units) and DPD (reduced units) simulations. The scaling method was verified for three MD/DPD model liquid pairs under several different nonequilibrium conditions, including transient and steady-state simple shear and planar elongational flows. Comparison of the MD simulation results with those of the scaled DPD simulations revealed that the optimized DPD model, expressed in terms of the proposed scaling method, successfully reproduced the computationally expensive MD results using relatively cheaper DPD simulations.
Hidden Hypocalcemia as a Risk Factor for Cardiovascular Events and All-Cause Mortality among Patients Undergoing Incident Hemodialysis
Authors: Yamaguchi Satoshi , Hamano Takayuki , Doi Yohei , Oka Tatsufumi , Kajimoto Sachio , Kubota Keiichi , Yasuda Seiichi , Shimada Karin , Matsumoto Ayumi , Hashimoto Nobuhiro , Sakaguchi Yusuke , Matsui Isao , Isaka Yoshitaka 
Published: March 2020

AbstractLower corrected calcium (cCa) levels are associated with a better prognosis among incident dialysis patients. However, cCa frequently overestimates ionized calcium (iCa) levels. The prognostic importance of the true calcium status defined by iCa remains to be revealed. We conducted a retrospective cohort study of incident hemodialysis patients. We collected data of iCa levels immediately before the first dialysis. We divided patients into three categories: apparent hypocalcemia (low iCa; <1.15 mmol/L and low cCa; <8.4 mg/dL), hidden hypocalcemia (low iCa despite normal or high cCa), and normocalcemia (normal iCa). The primary outcome was the composite of all-cause death and cardiovascular diseases after hospital discharge. Among the enrolled 332 patients, 75% of the patients showed true hypocalcemia, defined as iCa <1.15 mmol/L, 61% of whom showed hidden hypocalcemia. In multivariate Cox models including other potential risk factors, true hypocalcemia was a significant risk factor (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.03–5.34), whereas hypocalcemia defined as corrected calcium <8.4 mg/dL was not. Furthermore, hidden hypocalcemia was significantly associated with an increased risk of the outcome compared with normocalcemia (HR, 2.56; 95% CI, 1.11–5.94), while apparent hypocalcemia was not. Patients with hidden hypocalcemia were less likely to receive interventions to correct hypocalcemia, such as increased doses of active vitamin D or administration of calcium carbonate, than patients with apparent hypocalcemia (odds ratio, 0.45; 95% CI, 0.23–0.89). Hidden hypocalcemia was a strong predictor of death and cardiovascular events, suggesting the importance of measuring iCa.
Surgery for synchronous and metachronous single-organ metastasis of pancreatic cancer: a SEER database analysis and systematic literature review
Authors: Liu Qiaofei , Zhang Ronghua , Michalski Christoph W. , Liu Bing , Liao Quan , Kleeff Jorg 
Published: March 2020

AbstractSurgery for metastatic pancreatic cancer remains controversial as the survival benefit is questionable. The aim of the present study was to analyze the survival of these patients using data extracted from the surveillance, epidemiology, and end results (SEER) program database. Further, studies on resection for metastatic disease to the lung were systematically reviewed. A total of 11,541 cases with synchronous distant metastasis were analyzed. The median survival of single-organ metastasis was better than of multi-organ metastasis (single-organ 4.0 ± 0.07 months, two-organs 3.0 ± 0.13 months, three/four-organs 2.0 ± 0.19 months; p < 0.0001). Single organ lung metastasis had longer median survival times compared to the other sites (lung 6.0 ± 0.32 months, HR 0.87, 95% CI 0.78–0.97; p = 0.013). Resection of the primary tumor was associated with longer survival in synchronous single-organ metastasis to the lung compared to no resection (14.0 ± 1.93 months vs 6.0 ± 0.31 months, p < 0.0001). A systematic literature review identified 79 cases of metachronous lung metastasis with a survival of 120.0 ± 6.32 months and 83.0 ± 24.84 months following resection of the primary tumor and metastasis, respectively. Lower TNM staging, longer interval to metastasis, and single metastatic lesion correlated with better survival. Resection in highly selected pancreatic cancer patients with synchronous and metachronous lung only metastasis might confer a survival benefit and should be considered on an individual basis.
Seeing other perspectives: evaluating the use of virtual and augmented reality to simulate visual impairments (OpenVisSim)
Authors: Jones Pete R. , Somoskeöy Tamás , Chow-Wing-Bom Hugo , Crabb David P. 
Published: March 2020

AbstractSimulations of visual impairment are used to educate and inform the public. However, evidence regarding their accuracy remains lacking. Here we evaluated the effectiveness of modern digital technologies to simulate the everyday difficulties caused by glaucoma. 23 normally sighted adults performed two everyday tasks that glaucoma patients often report difficulties with: a visual search task in which participants attempted to locate a mobile phone in virtual domestic environments (virtual reality (VR)), and a visual mobility task in which participants navigated a physical, room-scale environment, while impairments were overlaid using augmented reality (AR). On some trials, a gaze-contingent simulated scotoma—generated using perimetric data from a real patient with advanced glaucoma—was presented in either the superior or inferior hemifield. The main outcome measure was task completion time. Eye and head movements were also tracked and used to assess individual differences in looking behaviors. The results showed that the simulated impairments substantially impaired performance in both the VR (visual search) and AR (visual mobility) tasks (both P < 0.001). Furthermore, and in line with previous patient data: impairments were greatest when the simulated Visual Field Loss (VFL) was inferior versus superior (P < 0.001), participants made more eye and head movements in the inferior VFL condition (P < 0.001), and participants rated the inferior VFL condition as more difficult (P < 0.001). Notably, the difference in performance between the inferior and superior conditions was almost as great as the difference between a superior VFL and no impairment at all (VR: 71%; AR: 70%). We conclude that modern digital simulators are able to replicate and objectively quantify some of the key everyday difficulties associated with visual impairments. Advantages, limitations, and possible applications of current technologies are discussed. Instructions are also given for how to freely obtain the software described (OpenVisSim).
PORTAL: Three-dimensional polarized (sub)millimeter line radiative transfer
Authors: Lankhaar Boy , Vlemmings Wouter 
Published: March 2020

Context. Magnetic fields are important to the dynamics of many astrophysical processes and can typically be studied through polarization observations. Polarimetric interferometry capabilities of modern (sub)millimeter telescope facilities have made it possible to obtain detailed velocity resolved maps of molecular line polarization. To properly analyze these for the information they carry regarding the magnetic field, the development of adaptive three-dimensional polarized line radiative transfer models is necessary.
Aims. We aim to develop an easy-to-use program to simulate the polarization maps of molecular and atomic (sub)millimeter lines in magnetized astrophysical regions, such as protostellar disks, circumstellar envelopes, or molecular clouds.
Methods. By considering the local anisotropy of the radiation field as the only alignment mechanism, we can model the alignment of molecular or atomic species inside a regular line radiative transfer simulation by only making use of the converged output of this simulation. Calculations of the aligned molecular or atomic states can subsequently be used to ray trace the polarized maps of the three-dimensional simulation.
Results. We present a three-dimensional radiative transfer code, POlarized Radiative Transfer Adapted to Lines (PORTAL), that can simulate the emergence of polarization in line emission through a magnetic field of arbitrary morphology. Our model can be used in stand-alone mode, assuming LTE excitation, but it is best used when processing the output of regular three-dimensional (nonpolarized) line radiative transfer modeling codes. We present the spectral polarization map of test cases of a collapsing sphere and protoplanetary disk for multiple three-dimensional magnetic field morphologies.
Rehabilitation seltener Erkrankungen:
Ochronose/Alkaptonurie
Authors: Gehlen Martin , Mahn Karin , Schwarz-Eywill Michael , Gerß Lisa , Siebers-Renelt Ulrike , Önder Nuri , Maier Anna 
Published: March 2020

ZusammenfassungEine Alkaptonurie ist eine seltene Stoffwechselerkrankung, die zu dem klinischen
Bild der Ochronose führt. Durch einen genetisch terminierten Enzymdefekt
treten bräunliche Pigmentablagerungen in bradytrophen Geweben auf.
Klinisch stehen schwere degenerative Gelenk- und
Wirbelsäulenveränderungen, eine Osteoporose und
Herzklappenvitien im Vordergrund. Dieser Artikel gibt einen Überblick
über klinische Manifestationen und multimodale
Therapiemöglichkeiten im Rahmen einer stationären
Rehabilitation.
A Conceptual Framework of Social Communication: Clinical Applications to Pediatric Traumatic Brain Injury
Authors: Wiseman-Hakes Catherine , Kakonge Lisa , Doherty Meghan , Beauchamp Miriam 
Published: March 2020

AbstractSocial communication impairments are common following pediatric traumatic brain injury (TBI) and can lead to social isolation, and poor social outcomes. Social communication has been documented as a persistent area of need in terms of proper assessment and intervention; however, this is not consistently addressed in clinical practice. While there is a body of evidence regarding social communication impairments and pediatric TBI, this area is not yet fully understood and remains underrecognized. To meet this gap, we provide a conceptual framework of social communication from a neurodevelopmental perspective, which can be applied to better understand the social communication impairments associated with pediatric TBI. We propose a general model of social communication with component constructs and consideration of internal factors such as sex and gender. These can inform considerations, clinical applications, and future research in assessment and evidence-based interventions within the domain of social communication.
Piotroski’s FSCORE: international evidence
Authors: Walkshäusl Christian 
Published: March 2020

AbstractAlmost 20 years after its publication, Piotroski’s (J Account Res 38:1–41, 2000) FSCORE, the composite measure of the firm’s fundamental strength remains a strong predictor of subsequent stock returns and future profitability in international markets over the 2000–2018 period. Across developed non-US countries as well as emerging countries, high-FSCORE firms significantly outperform low-FSCORE firms by about 10% per year. Furthermore, FSCORE preserves its return-predictive power in all size segments after controlling for established cross-sectional return determinants, such as firm size, book-to-market, momentum, operating profitability, and investment. The findings are consistent with the view that fundamental information is only gradually incorporated into prices by investors.
High-throughput, combinatorial synthesis of multimetallic nanoclusters
Authors: Yao Yonggang , Huang Zhennan , Li Tangyuan , Wang Hang , Liu Yifan , Stein Helge S. , Mao Yimin , Gao Jinlong , Jiao Miaolun , Dong Qi , Dai Jiaqi , Xie Pengfei , Xie Hua , Lacey Steven D. , Takeuchi Ichiro , Gregoire John M. , Jiang Rongzhong , Wang Chao , Taylor Andre D. , Shahbazian-Yassar Reza , Hu Liangbing 
Published: March 2020

Significance
Multielement nanomaterials hold great promise for various applications due to their widely tunable surface chemistry, yet it remains challenging to efficiently study this multidimensional space. Conventional approaches are typically slow and depend on serendipity, while a robust and general synthesis is still lacking among increasingly complex compositions. We report a high-throughput technique for combinatorial compositional design (formulation in solution phases) and rapid synthesis (within seconds) of ultrafine multimetallic nanoclusters with a homogeneous alloy structure. We synthesized and screened the PtPdRhRuIrFeCoNi compositional space using scanning droplet cell electrochemistry, with two promising catalysts quickly identified and further verified in a rotating disk setup. The reported high-throughput approach establishes a facile and reliable pipeline to significantly accelerate material discovery in multimetallic nanomaterials.
Disruption of cellular proteostasis by H1N1 influenza A virus causes α-synuclein aggregation
Authors: Marreiros Rita , Müller-Schiffmann Andreas , Trossbach Svenja V. , Prikulis Ingrid , Hänsch Sebastian , Weidtkamp-Peters Stefanie , Moreira Ana Raquel , Sahu Shriya , Soloviev Irina , Selvarajah Suganya , Lingappa Vishwanath R. , Korth Carsten 
Published: March 2020

Significance
Synucleinopathies such as Parkinson’s disease feature deposition of misfolded α-synuclein. It is likely that cellular proteostasis compensates for misfolded α-synuclein to some extent, but, once exhausted, α-synuclein can form seeds for a prion-like spread in the brain. Here, we demonstrate that, in human dopaminergic neurons and in mouse brain, H1N1 influenza virus induces aggregation of α-synuclein by blocking protein degradation pathways. Following intranasal instillation, H1N1 spreading along the olfactory route into brain areas mimics α-synuclein deposits in synucleinopathies. H1N1 may therefore be considered a risk factor for synucleinopathies that could potentially be minimized by regular vaccination. On the contrary, H1N1 tropism for olfactory epithelium suggests that live attenuated virus vaccines should be investigated for possible long-term effects on protein misfolding.
Spatiotemporal gating of SIRT1 functions by O-GlcNAcylation is essential for liver metabolic switching and prevents hyperglycemia
Authors: Chattopadhyay Tandrika , Maniyadath Babukrishna , Bagul Hema P. , Chakraborty Arindam , Shukla Namrata , Budnar Srikanth , Rajendran Abinaya , Shukla Arushi , Kamat Siddhesh S. , Kolthur-Seetharam Ullas 
Published: March 2020

Significance
Emerging literature indicates that, besides circadian inputs, fed–fast cycles are vital for maintaining physiological homeostasis. While several studies have highlighted the importance of feeding and state-specific molecular signatures, information regarding mechanisms that bring about efficient fed–fast–refed transitions is sparse. Here we show how a glucose-derived modification (glycosylation) of SIRT1, a master regulator of transcription and insulin signaling, regulates this metabolic switch in the liver by restricting SIRT1 functions during fasted-to-refed transition. SIRT1 glycosylation orchestrates molecular interactions to suppress fasting genes, derepress fed genes, and activate insulin signaling upon refeeding. We show that aberrant SIRT1 glycosylation causes hepatic dysfunctions resulting in a diabetes-like state and is also associated with aging and obesity.
Splice variant of growth hormone-releasing hormone receptor drives esophageal squamous cell carcinoma conferring a therapeutic target
Authors: Xiong Xiao , Ke Xiurong , Wang Lu , Yao Zhimeng , Guo Yi , Zhang Xianyang , Chen Yuping , Pang Chi Pui , Schally Andrew V. , Zhang Hao 
Published: March 2020

Significance
An explanation has been lacking for the suppressive action of antagonists of growth hormone-releasing hormone receptors (GHRH-Rs) on cancers that do not express GHRH-Rs, an established target of the antagonists. We demonstrate here that esophageal squamous cell carcinoma (ESCC), a representative cancer type that barely expresses GHRH-Rs, responds to GHRH-R antagonists. Hypoxia induces GHRH-R splice variant 1 (SV1) and activates a key glycolytic enzyme. Glycolytic metabolism and tumor progression are promoted by activation of SV1 and reversed by the GHRH-R antagonist MIA-602. A high expression of SV1 in ESCC patients predicts a poor prognosis. These findings document the importance of SV1 as a target of GHRH-R antagonists and underline the therapeutic potential of GHRH-R antagonists against SV1-expressing cancers.
Trait evolution is reversible, repeatable, and decoupled in the soldier caste of turtle ants
Authors: Powell Scott , Price Shauna L. , Kronauer Daniel J. C. 
Published: March 2020

SignificanceSpecialized castes are seen as phenotypic innovations necessary for ecological and evolutionary success in social insects. Nevertheless, how castes evolve adaptively as a lineage fills ecological space has remained unaddressed. Recent work with turtle ants has established that head shape and size in the iconic soldier caste, specialized for nest entrance defense, determine two key aspects of nesting ecology. Here species-level comparative analyses reveal that the evolution of head shape and size is extensively reversible, repeatable, and decoupled within the soldier caste and relative to the queen caste, underpinning the lineage’s diverse nesting ecology. These findings reshape our understanding of caste evolution, rejecting a stable, directional process in favor of a dynamic process of adaptive fitting between phenotype and environment.
Fluctuation–response inequality out of equilibrium
Authors: Dechant Andreas , Sasa Shin-ichi 
Published: March 2020

Significance
Inequalities play a central role in physics: They allow us to state universal relations between different quantities. Starting from information-theoretic concepts, we derive an inequality for stochastic dynamics, called fluctuation–response inequality (FRI). The FRI connects the response of a physical observable to a change in the dynamics and the fluctuations of the observable in a reference dynamic. We argue that the FRI can serve as a starting point to discover many previously unknown inequalities between different physical observables. To demonstrate this point, we derive a relation between mobility and diffusion in particle transport. We further rederive the thermodynamic uncertainty relation and use the FRI to extend it to a much broader class of dynamics.