bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Frequency Scaling of a Single-Core Processor Using Machine Learning Paradigms
Authors: Thethi Sukhmani K , Kumar Ravi
Published: July 2020

Dynamic frequency scaling (DFS) is one of the most important approaches for on-the-fly power optimization in modern-day processors. Owing to the trend of chip size shrinkage and increasing the complexity of system design, the problem of achieving an efficient DFS depends upon multi-parametric, non-linear optimization. Hence, it becomes extremely important to identify an optimal underclocking frequency on-the-fly, which depends upon numerous parameters that do not share direct relationship amongst each other. This paper proposes a machine learning approach to DFS of a ubiquitous single-core processor. Several performance parameters of the processor were monitored under an application of a number of clocking frequencies. The dataset thus generated was used to train four artificial neural networks (ANNs) viz. generalized regression (GRNN), decision tree classifier, random forest classifier and backpropagation technique. Under changing parametric conditions of the proposed network, the modes were fit to data while running three applications, i.e. 64- and 1024-point fast fourier transform (FFT) and basicmath applications. The performance of all ANNs was found to be promising and good generalization was obtained with all datasets. In the view of optimizing both speed and power of a system, the results indicate towards suitability of trained GRNN for on-chip deployment for implementing DFS.
Considering Fine-Grained and Coarse-Grained Information for Context-Aware Recommendations
Authors: Luo Yiqin , Sun Yanpeng , Chang Liang , Gu Tianlong , Bin Chenzhong , Li Long
Published: July 2020

In context-aware recommendation systems, most existing methods encode users’ preferences by mapping item and category information into the same space, which is just a stack of information. The item and category information contained in the interaction behaviours is not fully utilized. Moreover, since users’ preferences for a candidate item are influenced by the changes in temporal and historical behaviours, it is unreasonable to predict correlations between users and candidates by using users’ fixed features. A fine-grained and coarse-grained information based framework proposed in our paper which considers multi-granularity information of users’ historical behaviours. First, a parallel structure is provided to mine users’ preference information under different granularities. Then, self-attention and attention mechanisms are used to capture the dynamic preferences. Experiment results on two publicly available datasets show that our framework outperforms state-of-the-art methods across the calculated evaluation metrics.
Theorizing News Literacy Behaviors
Authors: Vraga Emily K , Tully Melissa , Maksl Adam , Craft Stephanie , Ashley Seth
Published: July 2020

Despite renewed interest in news literacy (NL) as a way to combat mis- and dis-information, existing scholarship is plagued by insufficient theory building and inadequate conceptualization of both “NL” and its application. We address this concern by offering a concise definition of NL and suggest five key knowledge and skill domains that comprise this literacy. We distinguish NL from its application to behaviors that communication scholars have been interested in, including news exposure, verification, and identifying misinformation. We propose an adapted Theory of Planned Behavior (TPB) to include NL in addition to the existing components (attitudes towards the behavior, social norms, perceived behavioral control) when modeling NL Behaviors. We discuss how this model can unite scholars across subfields and propose a research agenda for moving scholarship forward.
Multimodality cardiac evaluation in children and young adults with multisystem inflammation associated with COVID-19
Authors: Theocharis Paraskevi , Wong James , Pushparajah Kuberan , Mathur Sujeev K , Simpson John M , Pascall Emma , Cleary Aoife , Stewart Kirsty , Adhvaryu Kaitav , Savis Alex , Kabir Saleha R , Uy Mirasol Pernia , Heard Hannah , Peacock Kelly , Miller Owen
Published: July 2020

Aims

Following the peak of the UK COVID-19 epidemic, a new multisystem inflammatory condition with significant cardiovascular effects emerged in young people. We utilized multimodality imaging to provide a detailed sequential description of the cardiac involvement.

Methods and Results

Twenty consecutive patients (mean age 10.6 ± 3.8 years) presenting to our institution underwent serial echocardiographic evaluation on admission (median day 5 of illness), the day coinciding with worst cardiac function (median day 7), and the day of discharge (median day 15). We performed cardiac computed tomography (CT) to assess coronary anatomy (median day 15) and cardiac magnetic resonance imaging (CMR) to assess dysfunction (median day 20). On admission, almost all patients displayed abnormal strain and tissue Doppler indices. Three-dimensional (3D) echocardiographic ejection fraction (EF) was <55% in half of the patients. Valvular regurgitation (75%) and small pericardial effusions (10%) were detected. Serial echocardiography demonstrated that the mean 3D EF deteriorated (54.7 ± 8.3% vs. 46.4 ± 8.6%, P = 0.017) before improving at discharge (P = 0.008). Left main coronary artery (LMCA) dimensions were significantly larger at discharge than at admission (Z score –0.11 ± 0.87 vs. 0.78 ± 1.23, P = 0.007). CT showed uniform coronary artery dilatation commonly affecting the LMCA (9/12). CMR detected abnormal strain in all patients with global dysfunction (EF <55%) in 35%, myocardial oedema in 50%, and subendocardial infarct in 5% (1/20) patients.

Conclusions

Pancarditis with cardiac dysfunction is common and associated with myocardial oedema. Patients require close monitoring due to coronary artery dilatation and the risk of thrombotic myocardial infarction.
Ventricular tachycardia storm management in a COVID-19 patient: a case report
Authors: Mitacchione Gianfranco , Schiavone Marco , Gasperetti Alessio , Forleo Giovanni B
Published: July 2020

Background

Coronavirus disease 2019 (COVID-19) has been associated with myocardial involvement. Among cardiovascular manifestations, cardiac arrhythmias seem to be fairly common, although no specifics are reported in the literature. An increased risk of malignant ventricular arrhythmias and electrical storm (ES) has to be considered.

Case summary

We describe a 68-year-old patient with a previous history of coronary artery disease and severe left ventricular systolic disfunction, who presented to our emergency department describing cough, dizziness, fever, and shortness of breath. She was diagnosed with COVID-19 pneumonia, confirmed after three nasopharyngeal swabs. Ventricular tachycardia (VT) storm with multiple implantable cardioverter defibrillator (ICD) shocks was the presenting manifestation of cardiac involvement during the COVID-19 clinical course. A substrate-based VT catheter ablation procedure was successfully accomplished using a remote navigation system. The patient recovered from COVID-19 and did not experience further ICD interventions.

Discussion

To date, COVID-19 pneumonia associated with a VT storm as the main manifestation of cardiac involvement has never been reported. This case highlights the role of COVID-19 in precipitating ventricular arrhythmias in patients with ischaemic cardiomyopathy who were previously stable.
Self-reported treatment burden in patients with atrial fibrillation: quantification, major determinants, and implications for integrated holistic management of the arrhythmia
Authors: Potpara Tatjana S , Mihajlovic Miroslav , Zec Nevena , Marinkovic Milan , Kovacevic Vladan , Simic Jelena , Kocijancic Aleksandar , Vajagic Leona , Jotic Aleksandra , Mujovic Nebojsa , Stankovic Goran R
Published: July 2020

Aims 

Treatment burden (TB) refers to self-perceived cumulative work patients do to manage their health. Using validated tools, TB has been documented in several chronic conditions, but not atrial fibrillation (AF). We measured TB and analysed its determinants and impact on quality of life (QoL) in an AF cohort.

Methods and results 

A single-centre study prospectively included consecutive adult AF patients and non-AF controls managed from 1 April to 21 June 2019, who voluntarily and anonymously answered the TB questionnaire (TBQ) and 5-item EQ-5D QoL questionnaire; TB was calculated as a sum of TBQ points (maximum 170) and expressed as proportion of the maximum value. Of 514 participants, 331 (64.4%) had AF. The mean self-reported TB was 27.6% among AF patients and 24.3% among controls, P = 0.011. The mean TB was significantly higher in patients taking vitamin K antagonists (VKAs) vs. those taking non-VKA antagonist oral anticoagulants (NOAC; 29.5% vs. 24.7%, P = 0.006). The highest item-specific TB was reported for healthcare system organization-related items (e.g. visit appointment), diet, and physical activity modifications. On multivariable analyses, female sex, younger age, and permanent AF were associated with a higher TB, whereas NOACs and electrical AF cardioversion exhibited an inverse association; TB was an independent predictor of decreased QoL (all P < 0.05).

Conclusion 

Our study provided clinically relevant insights into self-perceived TB among AF patients. Approximately one in four patients with AF have a high TB. Specific AF treatments and optimization of healthcare system-required patient activities may reduce the self-perceived TB in AF patients.
Scattering of SH waves around circular canyon in inhomogeneous wedge space
Authors: Yang Zailin , Li Xinzhu , Song Yunqiu , Jiang Guanxixi , Sun Menghan , Fang Xueqian
Published: July 2020

Scattering of SH waves around a circular canyon in radial inhomogeneous wedge space is investigated in this paper. Based on the complex function method, the governing equation with variable coefficients is transformed into a standard Helmholtz equation and the corresponding analytical solution to this problem is derived. The unknown coefficients in the wavefield is obtained by enforcing the stress-free condition in the circular canyon, then the incident, reflected and scattering waves in the total wavefield are all acquired. Through the calculation and analysis of the parameters that affect the ground motion, the influence of the circular canyon on the ground motion in the radial inhomogeneous wedge space is obtained. Moreover, combined with graphical results, the effects by inhomogeneous parameter on ground motion with circular canyon in wedge space are conspicuous.
Patterns of CAG repeat instability in the central nervous system and periphery in Huntington’s disease and in spinocerebellar ataxia type 1
Authors: Mouro Pinto Ricardo , Arning Larissa , Giordano James V , Razghandi Pedram , Andrew Marissa A , Gillis Tammy , Correia Kevin , Mysore Jayalakshmi S , Grote Urtubey Debora-M , Parwez Constanze R , von Hein Sarah M , Clark H Brent , Nguyen Huu Phuc , Förster Eckart , Beller Allison , Jayadaev Suman , Keene C Dirk , Bird Thomas D , Lucente Diane , Vonsattel Jean-Paul , Orr Harry , Saft Carsten , Petrasch-Parwez Elisabeth , Wheeler Vanessa C
Published: July 2020

The expanded HTT CAG repeat causing Huntington’s disease (HD) exhibits somatic expansion proposed to drive the rate of disease onset by eliciting a pathological process that ultimately claims vulnerable cells. To gain insight into somatic expansion in humans, we performed comprehensive quantitative analyses of CAG expansion in ~50 central nervous system (CNS) and peripheral postmortem tissues from seven adult-onset and one juvenile-onset HD individual. We also assessed ATXN1 CAG repeat expansion in brain regions of an individual with a neurologically and pathologically distinct repeat expansion disorder, spinocerebellar ataxia type 1 (SCA1). Our findings reveal similar profiles of tissue instability in all HD individuals, which, notably, were also apparent in the SCA1 individual. CAG expansion was observed in all tissues, but to different degrees, with multiple cortical regions and neostriatum tending to have the greatest instability in the CNS, and liver in the periphery. These patterns indicate different propensities for CAG expansion contributed by disease locus-independent trans-factors and demonstrate that expansion per se is not sufficient to cause cell type or disease-specific pathology. Rather, pathology may reflect distinct toxic processes triggered by different repeat lengths across cell types and diseases. We also find that the HTT CAG length-dependent expansion propensity of an individual is reflected in all tissues and in cerebrospinal fluid. Our data indicate that peripheral cells may be a useful source to measure CAG expansion in biomarker assays for therapeutic efforts, prompting efforts to dissect underlying mechanisms of expansion that may differ between the brain and periphery.
Elevated Blood Mitochondrial DNA in Early Life Among Uninfected Children Exposed to Human Immunodeficiency Virus and Combination Antiretroviral Therapy in utero
Authors: Ajaykumar Abhinav , Zhu Mayanne , Kakkar Fatima , Brophy Jason , Bitnun Ari , Alimenti Ariane , Soudeyns Hugo , Saberi Sara , Albert Arianne Y K , Money Deborah M , Côté Hélène C F ,   CIHR Team in Cellular Aging and HIV Comorbidities in Women and Children (Children and Women: AntiRetrovirals and Markers of Aging [CARMA]), Pick Neora , Murray Melanie , Janssen Patricia , Singer Joel , Lapointe Normand , Prior Jerilynn , Silverman Michael , Lou Smith Mary
Published: July 2020

Background

Combination antiretroviral therapy (cART) during pregnancy prevents vertical transmission, but many antiretrovirals cross the placenta and several can affect mitochondria. Exposure to maternal human immunodeficiency virus (HIV) and/or cART could have long-term effects on children who are HIV exposed and uninfected (CHEU). Our objective was to compare blood mitochondrial DNA (mtDNA) content in CHEU and children who are HIV unexposed and uninfected (CHUU), at birth and in early life.

Methods

Whole-blood mtDNA content at birth and in early life (age 0–3 years) was compared cross-sectionally between CHEU and CHUU. Longitudinal changes in mtDNA content among CHEU was also evaluated.

Results

At birth, CHEU status and younger gestational age were associated with higher mtDNA content. These remained independently associated with mtDNA content in multivariable analyses, whether considering all infants, or only those born at term. Longitudinally, CHEU mtDNA levels remained unchanged during the first 6 months of life, and gradually declined thereafter. A separate age- and sex-matched cross-sectional analysis (in 214 CHEU and 214 CHUU) illustrates that the difference in mtDNA between the groups remains detectable throughout the first 3 years of life.

Conclusion

The persistently elevated blood mtDNA content observed among CHEU represents a long-term effect, possibly resulting from in utero stresses related to maternal HIV and/or cART. The clinical impact of altered mtDNA levels is unclear.
COVID-19 calls for virtue ethics
Authors: Bellazzi Francesca , Boyneburgk Konrad v
Published: July 2020

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 19 (COVID-19) has led to the imposition of severely restrictive measures by governments in the Western hemisphere. We feel a contrast between these measures and our freedom. This contrast, we argue, is a false perception. It only appears to us because we look at the issue through our contemporary moral philosophy of utilitarianism and an understanding of freedom as absence of constraints. Both these views can be substituted with more sophisticated alternatives, namely an ethics of virtue and a notion of freedom of the will. These offer a fuller picture of morality and enable us to cooperate with the current restrictions by consciously choosing to adhere to them instead of perceiving them as draconian and immoral. We ask whether we should collaborate with the restrictions and argue that considerations of virtue will lead to an affirmative answer. More broadly, virtue ethics permits to deal with the practical concerns about how an individual should behave during this pandemic, given the current lockdown measures or lack thereof.

In section 1, we present how utilitarianism and a notion of freedom as negative liberty support the opposition to restrictive measures. In section 2, we outline an alternative based on an ethics of virtue and a more elaborated notion of free will. In the concluding section 3, we argue that considerations of virtue should guide the individual and public response to the emergency.
Examining the Functionality of the MATADOC With the CRS-R: A Pilot Study
Authors: Bodine Caitlyn E , Seu Alika , Roth Edward A , Wegener Erin E , Magee Wendy L
Published: July 2020

Prolonged disorders of consciousness (PDOC) following acquired brain injury affect a person’s awareness of self and the environment. Motor, communication, sensory, and cognitive deficits challenge assessment. Rigorously tested behavioral assessments, sensitive to detecting awareness, are critical for discerning a prognosis for recovery and access to treatment. The Coma Recovery Scale-Revised (CRS-R) is considered the gold standard in PDOC diagnostic assessments. This study explored preliminary concurrent validity of the Music Therapy Assessment Tool for Awareness in Disorders of Consciousness (MATADOC) with the CRS-R. The MATADOC and CRS-R were administered concurrently to 8 participants utilizing a repeated measures design. Correlations for diagnosis and item functionality were explored between and within the 2 measures. There was an adequate level of agreement between the 2 measures for overall diagnosis. Significant positive correlations were found between measures for all domains utilizing the MATADOC repeated administrations design. Within-measure relationships were significant for each of the auditory and communication domains with diagnosis for both measures, and additionally for each of the visual and arousal domains with diagnosis on the MATADOC. Both measures yielded significant inter-item relationships for auditory–visual domains, communication–visual domains, arousal–auditory domains, and arousal–visual domains. The MATADOC yielded an additional significant correlation for the auditory-communication domains. The findings have positive implications for the MATADOC as a diagnostic measure and companion assessment in cases of questionable diagnosis. Research with a larger sample is warranted. Generally, higher arousal scores on the MATADOC support music as effective in eliciting arousal, giving patients the opportunity to perform at their optimal level of function.
Changes in the home range sizes of terrestrial vertebrates in response to urban disturbance: a meta-analysis
Authors: O’Donnell Kate , delBarco-Trillo Javier
Published: July 2020

The unprecedented growth rate in human population and the increasing movement of people to urban areas is causing a rapid increase in urbanisation globally. Urban environments may restrict or affect the behaviour of many animal species. Importantly, urban populations may change their spatial movement, particularly decreasing their home ranges in response to habitat fragmentation, the presence of landscape barriers and the availability and density of resources. Several species-specific studies suggest that urban animals decrease their home ranges compared with their non-urban counterparts; however, it remained unclear whether this pattern is widespread across taxa or is instead restricted to specific taxonomic groups. Consequently, we conducted a meta-analysis, collecting 41 sets of data comparing home ranges in both natural and urban environments in 32 species of reptiles, birds and mammals. We calculated effect sizes as the difference in animal home range sizes between natural and urban environments. We found that the home ranges were smaller in urban environments compared with natural environments (mean effect size = −0.844), and we observed a similar result when considering birds and mammals separately. We also found that home range sizes were not significantly affected when disturbance in urban areas was minimal, which suggests that many species may be able to tolerate low levels of disturbance without changing their movement patterns. Our study thus indicates that increasing levels of urbanisation restrict the spatial movement of species across taxa; this information is relevant for ecological studies of further urban species as well as for the development of management strategies for urban populations.
Initial results from a real-time FRB search with the GBT
Authors: Agarwal Devansh , Lorimer D R , Surnis M P , Pei X , Karastergiou A , Golpayegani G , Werthimer D , Cobb J , McLaughlin M A , White S , Armour W , MacMahon D H E , Siemion A P V , Foster G
Published: July 2020

We present the data analysis pipeline, commissioning observations, and initial results from the greenburst fast radio burst (FRB) detection system on the Robert C. Byrd Green Bank Telescope (GBT) previously described by Surnis et al., which uses the 21-cm receiver observing commensally with other projects. The pipeline makes use of a state-of-the-art deep learning classifier to winnow down the very large number of false-positive single-pulse candidates that mostly result from radio frequency interference. In our observations, totalling 156.5 d so far, we have detected individual pulses from 20 known radio pulsars that provide an excellent verification of the system performance. We also demonstrate, through blind injection analyses, that our pipeline is complete down to a signal-to-noise threshold of 12. Depending on the observing mode, this translates into peak flux sensitivities in the range 0.14–0.89 Jy. Although no FRBs have been detected to date, we have used our results to update the analysis of Lawrence et al. to constrain the FRB all-sky rate to be $1150^{+200}_{-180}$ per day above a peak flux density of 1 Jy. We also constrain the source count index α = 0.84 ± 0.06, which indicates that the source count distribution is substantially flatter than expected from a Euclidean distribution of standard candles (where α = 1.5). We discuss this result in the context of the FRB redshift and luminosity distributions. Finally, we make predictions for detection rates with greenburst, as well as other ongoing and planned FRB experiments.
Conceptual Truth, Necessity, and Negation
Authors: Narboux Jean-Philippe
Published: July 2020

Throughout his philosophical career, Hilary Putnam was preoccupied with the question of what survives of the traditional notion of a priori truth in light of the recurring historical phenomenon, made prominent by the scientific revolutions of the early decades of the twentieth century, through which “something that was literally inconceivable has turned out to be true” (1962b). Impugning the analytic-synthetic dichotomy, Putnam’s redefinition of “conceptual truth” in terms of “quasi-necessity relative to a conceptual scheme” is meant to accommodate the possibility of transitions of just this sort. In this essay, I trace the origins and development of Putnam’s account of “quasi-necessity.” I try to defend it against some objections naturally arising in connection with the interplay of modality and negation. My main contention is that the main tenets of Putnam’s semantic externalism inform his reconception of conceptual truth, and that they must be recognized to hold of such basic logical notions as those of judgment and negation.
Multiomics profiling of paired primary and recurrent glioblastoma patient tissues
Authors: Dekker Lennard J M , Kannegieter Nynke M , Haerkens Femke , Toth Emma , Kros Johan M , Steenhoff Hov Dag Are , Fillebeen Julien , Verschuren Lars , Leenstra Sieger , Ressa Anna , Luider Theo M
Published: July 2020

Background

Despite maximal therapy with surgery, chemotherapy, and radiotherapy, glioblastoma (GBM) patients have a median survival of only 15 months. Almost all patients inevitably experience symptomatic tumor recurrence. A hallmark of this tumor type is the large heterogeneity between patients and within tumors itself which relates to the failure of standardized tumor treatment. In this study, tissue samples of paired primary and recurrent GBM tumors were investigated to identify individual factors related to tumor progression.

Methods

Paired primary and recurrent GBM tumor tissues from 8 patients were investigated with a multiomics approach using transcriptomics, proteomics, and phosphoproteomics.

Results

In the studied patient cohort, large variations between and within patients are observed for all omics analyses. A few pathways affected at the different omics levels partly overlapped if patients are analyzed at the individual level, such as synaptogenesis (containing the SNARE complex) and cholesterol metabolism. Phosphoproteomics revealed increased STMN1(S38) phosphorylation as part of ERBB4 signaling. A pathway tool has been developed to visualize and compare different omics datasets per patient and showed potential therapeutic drugs, such as abobotulinumtoxinA (synaptogenesis) and afatinib (ERBB4 signaling). Afatinib is currently in clinical trials for GBM.

Conclusions

A large variation on all omics levels exists between and within GBM patients. Therefore, it will be rather unlikely to find a drug treatment that would fit all patients. Instead, a multiomics approach offers the potential to identify affected pathways on the individual patient level and select treatment options.
Towards understanding residual and dilated dense neural networks via convolutional sparse coding
Authors: Zhang Zhiyang , Zhang Shihua
Published: July 2020

Convolutional neural network (CNN) and its variants have led to many state-of-the-art results in various fields. However, a clear theoretical understanding of such networks is still lacking. Recently, a multilayer convolutional sparse coding (ML-CSC) model has been proposed and proved to equal such simply stacked networks (plain networks). Here, we consider the initialization, the dictionary design and the number of iterations to be factors in each layer that greatly affect the performance of the ML-CSC model. Inspired by these considerations, we propose two novel multilayer models: the residual convolutional sparse coding (Res-CSC) model and the mixed-scale dense convolutional sparse coding (MSD-CSC) model. They are closely related to the residual neural network (ResNet) and the mixed-scale (dilated) dense neural network (MSDNet), respectively. Mathematically, we derive the skip connection in the ResNet as a special case of a new forward propagation rule for the ML-CSC model. We also find a theoretical interpretation of dilated convolution and dense connection in the MSDNet by analyzing the MSD-CSC model, which gives a clear mathematical understanding of each. We implement the iterative soft thresholding algorithm and its fast version to solve the Res-CSC and MSD-CSC models. The unfolding operation can be employed for further improvement. Finally, extensive numerical experiments and comparison with competing methods demonstrate their effectiveness.
Effectiveness of various methods of home fortification in under-5 children: where they work, where they do not. A systematic review and meta-analysis
Authors: Nikooyeh Bahareh , Neyestani Tirang R
Published: July 2020

Context

The common approaches of home fortification (HF) for prevention and/or treatment of micronutrient deficiencies are micronutrient powders (MNPs), foodlets, and lipid-based nutrient supplements (LNSs). There are mixed results for the impact of HF on growth and nutritional status of young children.

Objective

This systematic review was prepared in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to evaluate current evidence from randomized controlled trials including children younger than 5 years to assess the effect of strategies of HF on growth and micronutrient status.

Methods

The MEDLINE, PubMed, Embase, Cochrane Library, and Google Scholar databases were searched to July 2018. A total of 1301 studies were found in a preliminary search. After screening of titles and abstracts, 30 studies were selected.

Results

Treatment with MNPs, foodlets, and LNSs effectively increased hemoglobin concentrations by at least 2.52 g/L, 4.59 g/L, and 4.4 g/dL, respectively, as compared with a control. There was a significant decrease in risk of anemia development after foodlet intervention compared with a control or iron drops (odds ratio, 0.27; 95%CI, 0.10–0.74; P = 0.01). However, these interventions did not result in any significant improvement in z-scores for changes of height for age, weight for age, and weight for height. The results indicated that MNP (7.16; 95%CI, 0.31–14.01; P = 0.04) and foodlet treatment (4.92; 95%CI, 0.28–9.57; P = 0.04) could increase serum zinc levels. However, none of the home fortification methods improved vitamin A status in the target group.

Conclusion

Home fortification can be used as an effective method to improve hemoglobin, iron, and zinc status, although in this study it had no effect on vitamin A or anthropometric indicators of the target population. More investigations are warranted for newer approaches of HF to improve a broader range of micronutrients as well as child growth indices and for evaluation of the coverage, compliance, and consistency of such interventions at the population level.

PROSPERO Registration No

CRD42018109279
Assessing Complexity Among Patients With Tuberculosis in California, 1993–2016
Authors: Vaisman Alon , Barry Pennan , Flood Jennifer
Published: July 2020

Background

Although the number of patients with active tuberculosis (TB) has decreased in the last 25 years, anecdotal reports suggest that the complexity of these patients has increased. However, this complexity and its components have never been quantified or defined. We therefore aimed to describe the complexity of patients with active TB in California during 1993–2016.

Methods

We analyzed data on patient comorbidities, clinical features, and demographics from the California Department of Public Health TB Registry. All adult patients who were alive at the time of TB diagnosis in California during 1993–2016 were included in the analyses. Factors deemed by an expert panel to increase complexity (ie, increased resources or expertise requirement for successful management) were analyzed and included the following: age >75 years, HIV infection, multidrug resistance (MDR), and extrapulmonary TB disease. Second, using additional information on other comorbidities available starting in 2010, we performed exploratory factor analysis on 25 variables in order to define the dimensions of complexity.

Results

Among the 67 512 patients analyzed, the proportion of patients with extrapulmonary disease, age >75 years, or MDR-TB each increased over the study period (P < .001), while the proportion of patients with HIV decreased. Furthermore, the proportion of patients with at least 1 factor of those increased, rising from 38.8% to 45.3% (P < .001) from 1993 to 2016. Dimensions of complexity identified in the exploratory factor analysis included the following: race/immigration, social features, elderly/institutionalized, advanced TB, comorbidity, and drug resistance risk.

Conclusions

In this first description of complexity in the setting of TB, we found that the complexity of patients with active TB has risen over the last 25 years in California. These findings suggest that despite the overall decline in active TB cases, effective management of more complex patients may require additional attention and resource investment.
The Bruce–Roberts Number of A Function on A Hypersurface with Isolated Singularity
Authors: Nuño-Ballesteros J J , Oréfice-Okamoto B , Lima-Pereira B K , Tomazella J N
Published: July 2020

Let $(X,0)$ be an isolated hypersurface singularity defined by $\phi \colon ({\mathbb{C}}^n,0)\to ({\mathbb{C}},0)$ and $f\colon ({\mathbb{C}}^n,0)\to{\mathbb{C}}$ such that the Bruce–Roberts number $\mu _{BR}(f,X)$ is finite. We first prove that $\mu _{BR}(f,X)=\mu (f)+\mu (\phi ,f)+\mu (X,0)-\tau (X,0)$, where $\mu $ and $\tau $ are the Milnor and Tjurina numbers respectively of a function or an isolated complete intersection singularity. Second, we show that the logarithmic characteristic variety $LC(X,0)$ is Cohen–Macaulay. Both theorems generalize the results of a previous paper by some of the authors, in which the hypersurface $(X,0)$ was assumed to be weighted homogeneous.
Exploring European-funded project-based networks in ICT and their links with regional total factor productivity: The FP7 and the CIP
Authors: Vicente María Rosalía , García-Muñiz Ana Salomé , Billón Margarita
Published: July 2020

The research evaluation community has devoted multiple efforts to analyze the effects of Framework Programmes. However, there is little empirical evidence on their impact on economic performance. This article presents an empirical analysis of the research project-based networks created by 7th Framework Programme in the field of Information and Communication Technologies and investigates their links with regional total factor productivity. For comparison purposes, the diffusion network created by the Competitiveness and Innovation Framework Programme is also studied. Our results allow us to assess whether (or not) there are any common patterns in the research and diffusion links established by regions in these two European-supported networks and evaluate their (potentially) different connection with productivity. We use tools from Social Network Analysis and, specifically, the novel measure of bridging centrality, which takes into account territories’ internal microstructure.
Real-Time Functional Magnetic Resonance Imaging Neurofeedback for the Relief of Distressing Auditory-Verbal Hallucinations: Methodological and Empirical Advances
Authors: Humpston Clara , Garrison Jane , Orlov Natasza , Aleman André , Jardri Renaud , Fernyhough Charles , Allen Paul
Published: July 2020

Auditory-verbal hallucinations (AVH) are often associated with high levels of distress and disability in individuals with schizophrenia-spectrum disorders. In around 30% of individuals with distressing AVH and diagnosed with schizophrenia, traditional antipsychotic drugs have little or no effect. Thus, it is important to develop mechanistic models of AVH to inform new treatments. Recently a small number of studies have begun to explore the use of real-time functional magnetic resonance imaging neurofeedback (rtfMRI-NF) for the treatment of AVH in individuals with schizophrenia. rtfMRI-NF protocols have been developed to provide feedback about brain activation in real time to enable participants to progressively achieve voluntary control over their brain activity. We offer a conceptual review of the background and general features of neurofeedback procedures before summarizing and evaluating existing mechanistic models of AVH to identify feasible neural targets for the application of rtfMRI-NF as a potential treatment. We consider methodological issues, including the choice of localizers and practicalities in logistics when setting up neurofeedback procedures in a clinical setting. We discuss clinical considerations relating to the use of rtfMRI-NF for AVH in individuals distressed by their experiences and put forward a number of questions and recommendations about best practice. Lastly, we conclude by offering suggestions for new avenues for neurofeedback methodology and mechanistic targets in relation to the research and treatment of AVH.
The Great Recession and Ethno-Racial Disparities in Access to Mortgage Credit
Authors: Loya José , Flippen Chenoa
Published: July 2020

The mortgage industry has long been central to racially and ethnically stratified access to homeownership. Liberalized access to credit during the 1990s and early 2000s targeted subprime and other high-cost loans to individuals and communities of color. This article draws on annual data from the Home Mortgage Disclosure Act (HMDA) from 2004 through 2017 to assess short-term variation in racial and ethnic disparities in loan outcomes associated with the Great Recession. We show that, relative to the boom, this period is associated with a reduction in disparities in loan outcomes between non-Hispanic whites and Asians on the one hand and blacks and Latinos on the other. This is particularly true for the disproportionate channeling of black and Latino applicants into high-cost loans, and in communities with higher minority concentrations. As the economy and access to credit improved, particularly after 2011, black and Latino over-representation in high-cost loans began to rebound, though ethno-racial disparities in loan rejection continued well below levels observed during the boom years. The return of inequality in high-cost lending is particularly troubling in light of the sharp drop in minority applications. Implications for ethno-racial stratification are discussed.
ApoC-III helical structure determines its ability to bind plasma lipoproteins and inhibit Lipoprotein Lipase-mediated triglyceride lipolysis
Authors: Vitali Cecilia , Stankov Sylvia , Khetarpal Sumeet A. , Millar John , Mayne Leland , Englander S. Walter , Hand Nicholas J. , Lund-Katz Sissel , Phillips Michael C. , Rader Daniel J.
Published: July 2020

In humans, apolipoprotein C-III (apoC-III) plasma levels have been associated with increased risk of cardiovascular disease. This association is in part explained by the effects of apoC-III on triglyceride (TG) metabolism; apoC-III raises plasma TG by increasing very low density lipoprotein (VLDL) secretion, inhibiting lipoprotein lipase (LPL)-mediated TG lipolysis, and impairing the removal of triglyceride-rich lipoprotein (TRL) remnants from the circulation. In this study, we explored the structure-function relationship the interaction of apoC-III with plasma lipoproteins and its ultimate impact on LPL activity. The structural and functional properties of wild-type (WT) apoC-III were compared with two missense variants previously associated with lower (A23T) and higher (Q38K) plasma TG. ApoC-III in the lipid-free state is unstructured but its helix content and stability increases when bound to lipid. Lipid-bound apoC-III contains two alpha helices spanning residues amino acids 11 - 38 (helix 1) and 44 – 64 (helix 2). Investigation of the structural and functional consequences of the A23T and Q38K variants showed that these amino acid substitutions within helix 1 do not significantly alter the stability of the helical structure but affect its hydrophilic-lipophilic properties. The A23T substitution impairs lipoprotein binding capacity, reduces LPL inhibition, and ultimately leads to lower plasma TG levels. Conversely, the Q to K substitution at position 38 enhances the lipid affinity of helix 1, increases TRL binding capacity and LPL inhibition, and is associated with hypertriglyceridemia. This study indicates that structural modifications that perturb the hydrophilic/lipophilic properties of the alpha helices can modulate the hypertriglyceridemic effects of apoC-III.
Ultra-Fast Homomorphic Encryption Models enable Secure Outsourcing of Genotype Imputation
Authors: Kim Miran , Harmanci Arif , Bossuat Jean-Philippe , Carpov Sergiu , Cheon Jung Hee , Chillotti Ilaria , Cho Wonhee , Froelicher David , Gama Nicolas , Georgieva Mariya , Hong Seungwan , Hubaux Jean-Pierre , Kim Duhyeong , Lauter Kristin , Ma Yiping , Ohno-Machado Lucila , Sofia Heidi , Son Yongha , Song Yongsoo , Troncoso-Pastoriza Juan , Jiang Xiaoqian
Published: July 2020

Genotype imputation is a fundamental step in genomic data analysis such as GWAS, where missing variant genotypes are predicted using the existing genotypes of nearby ‘tag’ variants. Imputation greatly decreases the genotyping cost and provides high-quality estimates of common variant genotypes. As population panels increase, e.g., the TOPMED Project, genotype imputation is becoming more accurate, but it requires high computational power. Although researchers can outsource genotype imputation, privacy concerns may prohibit genetic data sharing with an untrusted imputation service. To address this problem, we developed the first fully secure genotype imputation by utilizing ultra-fast homomorphic encryption (HE) techniques that can evaluate millions of imputation models in seconds. In HE-based methods, the genotype data is end-to-end encrypted, i.e., encrypted in transit, at rest, and, most importantly, in analysis, and can be decrypted only by the data owner. We compared secure imputation with three other state-of-the-art non-secure methods under different settings. We found that HE-based methods provide full genetic data security with comparable or slightly lower accuracy. In addition, HE-based methods have time and memory requirements that are comparable and even lower than the non-secure methods. We provide five different implementations and workflows that make use of three cutting-edge HE schemes (BFV, CKKS, TFHE) developed by the top contestants of the iDASH19 Genome Privacy Challenge. Our results provide strong evidence that HE-based methods can practically perform resource-intensive computations for high throughput genetic data analysis. In addition, the publicly available codebases provide a reference for the development of secure genomic data analysis methods.
Assessing methods for geometric distortion compensation in 7T gradient echo fMRI data
Authors: Schallmo Michael-Paul , Weldon Kimberly B. , Burton Philip C. , Sponheim Scott R. , Olman Cheryl A.
Published: July 2020

Echo planar imaging (EPI) is widely used in functional and diffusion-weighted MRI, but suffers from significant geometric distortions in the phase encoding direction caused by inhomogeneities in the static magnetic field (B0). This is a particular challenge for EPI at very high field (≥ 7T), as distortion increases with higher field strength. A number of techniques for distortion correction exist, including those based on B0field mapping and acquiring EPI scans with opposite phase encoding directions. However, few quantitative comparisons of distortion compensation methods have been performed using human EPI data, especially at very high field. Here, we compared distortion compensation using B0field maps and opposite phase encoding scans in two different software packages (FSL and AFNI) applied to 7T gradient echo (GE) EPI data from 31 human participants. We assessed distortion compensation quality by quantifying alignment to anatomical reference scans using Dice coefficients and mutual information. Performance between FSL and AFNI was equivalent. In our whole-brain analyses, we found superior distortion compensation using GE scans with opposite phase encoding directions, versus B0field maps or spin echo (SE) opposite phase encoding scans. However, SE performed better when analyses were limited to ventromedial prefrontal cortex, a region with substantial dropout. Matching the type of opposite phase encoding scans to the EPI data being corrected (e.g., SE-to-SE) also yielded better distortion correction. While the ideal distortion compensation approach likely varies depending on methodological differences across experiments, this study provides a framework for quantitative comparison of different distortion compensation methods.
SMAD6 Integrates Endothelial Cell Homeostatic Flow Responses Downstream of Notch
Authors: Ruter Dana L , Liu Ziqing , Ngo Kimlynn M , Shaka X , Marvin Allison , Buglak Danielle B , Kidder Elise J , Bautch Victoria L
Published: July 2020

Laminar shear stress regulates blood vessel morphogenesis and subsequent quiescence, leading to vascular homeostasis. Although important for vessel function, how vascular homeostasis is set up and maintained is poorly understood. SMAD6, a scaffold for several signaling pathways, is expressed in developing arteries and its expression is flow-regulated. We found that SMAD6 is essential for endothelial cell flow-mediated responses downstream of the mechanosensor Notch1. Endothelial cells with reduced SMAD6 levels failed to align under homeostatic laminar shear flow, while forced SMAD6 expression rescued misalignment induced by reduced Notch1 signaling. SMAD6-dependent homeostatic laminar flow responses required the Notch ligand Dll4 and Notch transcriptional activity. Mechanistically, neither the N-terminal nor the C-terminal domain of SMAD6 alone rescued flow alignment upon loss of Notch signaling. Endothelial cells with reduced Smad6 levels had compromised barrier function, and RNA profiling revealed upregulation of proliferation-associated genes and down regulation of junction-associated genes. Among junction-related genes affected by SMAD6 levels, the proto-cadherin PCDH12 was upregulated by homeostatic flow and required for proper flow-mediated endothelial cell alignment. Thus, SMAD6 is a critical integrator of flow-mediated signaling inputs downstream of Notch1, as vessels transition from an angiogenic to a homeostatic phenotype.
Zinc Determines Dynamical Properties and Aggregation Kinetics of Human Insulin
Authors: Pounot K. , Grime G. W. , Longo A. , Zamponi M. , Noferini D. , Cristiglio V. , Seydel T. , Garman E. F. , Weik M. , Foderà V. , Schirò G.
Published: July 2020

Protein aggregation is a widespread process leading to deleterious consequences in the organism, with amyloid aggregates being important not only in biology but also for drug design and biomaterial production. Insulin is a protein largely used in diabetes treatment and its amyloid aggregation is at the basis of the so-called insulin-derived amyloidosis. Here we uncover the major role of zinc in both insulin dynamics and aggregation kinetics at low pH, where the formation of different amyloid superstructures (fibrils and spherulites) can be thermally induced. Amyloid aggregation is accompanied by zinc release and the suppression of water-sustained insulin dynamics, as shown by particle-induced X-ray emission and X-ray absorption spectroscopy and by neutron spectroscopy, respectively. Our study shows that zinc binding stabilizes the native form of insulin by facilitating hydration of this hydrophobic protein and suggests that introducing new binding sites for zinc can improve insulin stability and tune its aggregation propensity.

Statement of Significance

Localized amyloidosis occurs at insulin injection sites for diabetes treatment, leading to deleterious inflammations known as insulin-derived amyloidosis. Amyloid superstructures are also promising candidates in the field of biomaterials. Here we revealed that zinc, coordinated to insulin in the native form, is released upon amyloid aggregation, when insulin forms superstructures known as fibrils and spherulites. Zinc release leads to a full suppression of functionally essential protein dynamics through a modification of the protein’s hydration properties and completely modifies insulin amyloid kinetics. The results suggest that changes in protein hydration upon zinc binding/release modifies both stability and dynamics of insulin and might then be a general strategy to control protein stability and tune protein aggregation into amorphous and ordered superstructures.