bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis for polarized elongation of actin filaments
Authors: Zsolnay Vilmos , Katkar Harshwardhan H. , Chou Steven Z. , Pollard Thomas D. , Voth Gregory A.
Published: November 2020

Significance

Eukaryotic cells utilize actin filaments to move, change shape, divide, and transport cargo. Decades of experiments have established that actin filaments elongate and shorten significantly faster from one end than the other, but the underlying mechanism for this asymmetry has not been explained. We used molecular dynamics simulations to investigate the structures of the actin filament ends in the ATP, ADP plus γ-phosphate, and ADP nucleotide states. We characterize the structures of actin subunits at both ends of the filament, explain the mechanisms leading to these differences, and connect the divergent structural properties of the two ends to their distinct polymerization rate constants.
Estimating and forecasting spatial population dynamics of apex predators using transnational genetic monitoring
Authors: Bischof Richard , Milleret Cyril , Dupont Pierre , Chipperfield Joseph , Tourani Mahdieh , Ordiz Andrés , de Valpine Perry , Turek Daniel , Royle J. Andrew , Gimenez Olivier , Flagstad Øystein , Åkesson Mikael , Svensson Linn , Brøseth Henrik , Kindberg Jonas
Published: November 2020

Significance

We are experiencing the accelerated loss and reconfiguration of biological diversity. Meanwhile, those charged with natural resource management are struggling to meet the challenges of monitoring and managing wildlife populations across vast areas crisscrossed by political borders. What if, akin to weather maps, we could track and forecast the dynamics of wildlife populations across space and time? Using the world’s most extensive large carnivore monitoring program, we showcase the application of an effective tool for spatially explicit quantification of wildlife population dynamics at scales that are relevant to management and conservation.
Ultrahigh foraging rates of Baikal seals make tiny endemic amphipods profitable in Lake Baikal
Authors: Watanabe Yuuki Y. , Baranov Eugene A. , Miyazaki Nobuyuki
Published: November 2020

Significance

Despite being ubiquitous in aquatic environments, amphipods are rarely targeted by seals or toothed whales, likely because they contain too little energy to warrant catching individually. We report a remarkable case of Baikal seals in Lake Baikal, among the least studied seal species. Seals individually hunted tiny (<0.1 g) endemic amphipods (the world’s only freshwater planktonic species) at the highest rates ever recorded for aquatic mammals, primarily by following diel depth changes of amphipod swarms. Baikal seals have specialized comb-like cheek teeth, allowing them to expel water that enters the mouth during high-speed foraging. Thus, even tiny organisms can be important foods for aquatic mammals that catch prey individually, if the environment and predators’ adaptations allow high foraging rates.
Matriliny reverses gender disparities in inflammation and hypertension among the Mosuo of China
Authors: Reynolds Adam Z. , Wander Katherine , Sum Chun-Yi , Su Mingjie , Emery Thompson Melissa , Hooper Paul L. , Li Hui , Shenk Mary K. , Starkweather Kathrine E. , Blumenfield Tami , Mattison Siobhán M.
Published: November 2020

Significance

Greater autonomy afforded to women in matrilineal societies has been hypothesized to benefit women’s health. Among the Mosuo, a society with both matrilineal and patrilineal subpopulations, we found that gender disparities in chronic disease are not only ameliorated but reversed in matriliny compared with patriliny. Gender disparities in health and chronic disease can thus be tied directly to cultural influences on health, including inequalities in autonomy and resource access between men and women.
Maternally inherited peptides as strain-specific chemosignals
Authors: Kaba Hideto , Fujita Hiroko , Agatsuma Takeshi , Matsunami Hiroaki
Published: November 2020

Significance

For most mammals, olfaction plays an important role in individual recognition. The social chemosignals secreted by individual conspecifics are complex variable mixtures that are still poorly understood. Here we identify nonformylated, but notN-formylated, mitochondrially encoded peptides: That is, the nine N-terminal amino acids of NADH dehydrogenases 1 and 2 as reliable chemosignals for individual recognition by using a vomeronasal organ-mediated pregnancy block, known as the Bruce effect. Our findings also revealed that pregnancy-blocking chemosignals in the urine are maternally inherited. We propose that this individuality cue provides the molecular means to communicate an individual’s maternal lineage and strain.
The social patterning of autism diagnoses reversed in California between 1992 and 2018
Authors: Winter Alix S. , Fountain Christine , Cheslack-Postava Keely , Bearman Peter S.
Published: November 2020

Significance

Rates of autism diagnosis in the United States have historically been higher among more advantaged social groups—Whites and those of higher socioeconomic status (SES). Using data from all births in the state of California in 1992 through 2016, we find that these trends reversed during our study period. By 2018, diagnosed autism incidence rates for 3- to 6-y-old children were higher for children of Black and Asian mothers than children of non-Hispanic White mothers and were higher for children of lower SES than of higher SES parents. These reversals point to the fundamental role that access to knowledge and resources plays in driving increased autism prevalence and shifting patterns of autism cases over the past quarter-century.
HOS15 is a transcriptional corepressor of NPR1-mediated gene activation of plant immunity
Authors: Shen Mingzhe , Lim Chae Jin , Park Junghoon , Kim Jeong Eun , Baek Dongwon , Nam Jaesung , Lee Sang Yeol , Pardo Jose M. , Kim Woe-Yeon , Mackey David , Yun Dae-Jin
Published: November 2020

Significance

Immune responses protect organisms against biotic challenges but can also produce deleterious effects, such as inflammation and necrosis. This growth-defense trade-off necessitates fine control of immune responses, including the activation of defense gene expression. The transcriptional coactivator NPR1 is a key regulatory hub of immune activation in plant cells. Surprisingly, full activation of NPR1-activated defense genes requires proteasome-mediated degradation of NPR1 induced by a CUL3-based E3 ubiquitin ligase complex. Our work demonstrates that HOS15 is the specificity determinant of a CUL1-based E3 ubiquitin ligase complex that limits defense gene expression by targeting NPR1 for proteasome-mediated degradation. Thus, distinct ubiquitin-based degradation pathways coordinately modulate the timing and amplitude of transcriptional outputs during plant defense.
FoxO1 is a crucial mediator of TGF-β/TAK1 signaling and protects against osteoarthritis by maintaining articular cartilage homeostasis
Authors: Wang Cuicui , Shen Jie , Ying Jun , Xiao Ding , O’Keefe Regis J.
Published: November 2020

Significance

Osteoarthritis (OA) is the most prevalent joint disease and has reached epidemic proportions in the United States. Currently, there are no effective therapeutic approaches to treat OA. Thus, there is an urgent need to develop mechanistically-based therapeutic strategies to treat this disease. In this study, we identified FoxO1 as a crucial mediator of the TGF-β pathway. We also showed that loss of FoxO1 in articular cartilage leads to OA-like pathologies and gain of FoxO1 in cartilage protects against surgically and loss-of-TGF-β-induced OA. Our study defines FoxO1 as a key downstream target of TGF-β signaling and the requisite role in the maintenance of postnatal articular cartilage homeostasis and implicates modulation of FoxO1 levels/activity as a potential therapeutic strategy for OA.
Absolute ion hydration free energy scale and the surface potential of water via quantum simulation
Authors: Shi Yu , Beck Thomas L.
Published: November 2020

Significance

Establishing an absolute free energy scale for single-ion hydration has been an elusive goal of condensed-phase chemistry for nearly a century. In this paper, a zero for the free energy scale is determined by employing quasi-chemical theory and quantum mechanical simulations of the sodium ion in water. The simulation results produce an accurate estimate of the effective surface potential of water by comparison of the computed “bulk” hydration free energy with experimental values for the “real” hydration free energy. This work provides a firm quantitative footing for studies of interfacial specific ion structure, thermodynamics, and kinetics in fields as diverse as colloid science, electrochemistry, biophysics, and energy storage materials.
Structure of eukaryotic DNA polymerase δ bound to the PCNA clamp while encircling DNA
Authors: Zheng Fengwei , Georgescu Roxana E. , Li Huilin , O’Donnell Michael E.
Published: November 2020

Significance

The structure of the eukaryotic chromosomal replicase, DNA polymerase (Pol) δ, was determined in complex with its cognate proliferating cell nuclear antigen (PCNA) sliding clamp on primed DNA. The results show that the Pol3 catalytic subunit binds atop the PCNA ring, and the two regulatory subunits of Pol δ, Pol31, and Pol32, are positioned off to the side of the Pol3 clamp. The catalytic Pol3 binds DNA and PCNA such as to thread the DNA straight through the circular PCNA clamp. Considering the large diameter of the PCNA clamp, there is room for water between DNA and the inner walls of PCNA, indicating the clamp “waterskates” on DNA during function with polymerase.
Replisome bypass of a protein-based R-loop block by Pif1
Authors: Schauer Grant D. , Spenkelink Lisanne M. , Lewis Jacob S. , Yurieva Olga , Mueller Stefan H. , van Oijen Antoine M. , O’Donnell Michael E.
Published: November 2020

Significance

The replisome machine that duplicates the DNA genome encounters a variety of blocks to replication, such as DNA bound proteins, R-loops, and DNA lesions. Studies in bacterial systems demonstrate that replisome advance through blocks is facilitated by an accessory monomeric helicase that acts on the opposite strand from the replicative hexameric helicase. This report examines this issue in a eukaryotic system, using Pif1, a monomeric helicase that acts on the opposite strand from the replicative CMG helicase. The report shows that an inactive “dead” Cas9 (dCas9) protein R-loop block arrests the replisome, but Pif1 enables replisome bypass of the dCas9 R-loop block. Hence, use of monomeric helicases may have evolved to aid replisome bypass of protein-DNA and protein-bound R-loop blocks.
Intrinsic time gravity, heat kernel regularization, and emergence of Einstein’s theory
Authors: Ita Eyo Eyo , Soo Chopin , Yu Hoi Lai
Published: November 2020

The Hamiltonian of intrinsic time gravity is elucidated. The theory describes Schrödinger evolution of our universe with respect to the fractional change of the total spatial volume. Gravitational interactions are introduced by extending Klauder’s momentric variable with similarity transformations, and explicit spatial diffeomorphism invariance is enforced via similarity transformation with exponentials of spatial integrals. In analogy with Yang–Mills theory, a Cotton–York term is obtained from the Chern–Simons functional of the affine connection. The essential difference is the fundamental variable for geometrodynamics is the metric rather than a gauge connection; in the case of Yang–Mills, there is also no analog of the integral of the spatial Ricci scalar curvature. Heat kernel regularization is employed to isolate the divergences of coincidence limits; apart from an additional Cotton–York term, a prescription in which Einstein’s Ricci scalar potential emerges naturally from the positive-definite self-adjoint Hamiltonian of the theory is demonstrated.
Fast and stable deep-learning predictions of material properties for solid solution alloys**
Authors: Lupo Pasini Massimiliano , Li Ying Wai , Yin Junqi , Zhang Jiaxin , Barros Kipton , Eisenbach Markus
Published: November 2020

We present a novel deep learning (DL) approach to produce highly accurate predictions of macroscopic physical properties of solid solution binary alloys and magnetic systems. The major idea is to make use of the correlations between different physical properties in alloy systems to improve the prediction accuracy of neural network (NN) models. We use multitasking NN models to simultaneously predict the total energy, charge density and magnetic moment. These physical properties mutually serve as constraints during the training of the multitasking NN, resulting in more reliable DL models because multiple physics properties are correctly learned by a single model. Two binary alloys, copper–gold (CuAu) and iron–platinum (FePt), were studied. Our results show that once the multitasking NN’s are trained, they can estimate the material properties for a specific configuration hundreds of times faster than first-principles density functional theory calculations while retaining comparable accuracy. We used a simple measure based on the root-mean-squared errors to quantify the quality of the NN models, and found that the inclusion of charge density and magnetic moment as physical constraints leads to more stable models that exhibit improved accuracy and reduced uncertainty for the energy predictions.
High-pressure Raman investigation of high index facets bounded α-Fe2O3 pseudocubic crystals
Authors: Bushiri M Junaid , Gopi Divya Neravathu , Monteseguro Virginia , Sans Juan Angel
Published: November 2020

High index facet bounded α-Fe2O3 pseudocubic crystals has gained the attention of the scientific community due to its promising electrochemical sensing response towards aqueous ammonia. The structural stability of α-Fe2O3 pseudocubic crystals is investigated through high-pressure Raman spectroscopy up to 22.2 GPa, and those results are compared with our ab initio theoretical calculations. The symmetry of the experimental Raman-active modes has been assigned by comparison with theoretical data. In addition to the Raman-active modes, two additional Raman features are also detected, whose intensity increases with compression. The origin of these two additional peaks addressed in this study, reveals a strong dependence on the geometry and the low dimensionality as the most plausible explanation.
Review of x-ray exposure and safety issues arising from ultra-short pulse laser material processing
Authors: Legall Herbert , Bonse Jörn , Krüger Jörg
Published: November 2020

Laser processing with ultra-short laser pulses enables machining of materials with high accuracy and throughput. The development of novel laser technologies with laser pulse repetition rates up to the MHz range opened the way for industrial manufacturing processes. From a radiological point of view this evolution is important, because x-ray radiation can be generated as an unwanted side effect in laser material processing. Even if the emitted x-ray dose per pulse is comparably low, the x-ray dose can become hazardous to health at high laser repetition rates. Therefore, radiation protection must be considered. This article provides an overview on the generation and detection of x-rays in laser material processing, as well as on the handling of this radiation risk in the framework of radiological protection.
Characterization of defect states in Mg-doped GaN-on-Si p+n diodes using deep-level transient Fourier spectroscopy
Authors: Lechaux Y , Minj A , Méchin L , Liang H , Geens K , Zhao M , Simoen E , Guillet B
Published: November 2020

Mg-doped GaN-on-Si p+n diodes have been fabricated and characterized by static electrical and deep-level transient Fourier spectroscopy (DLTFS) measurements. From static capacitance-voltage (C–V) and current–voltage (I–V) characteristics, we estimated the diffusion barrier of the p+n diode close to the GaN band gap at room temperature. The temperature dependence of the capacitance showed freeze-out effect of the Mg-dopants at 200 K. From DLTFS measurements for various reverse bias and pulse voltages, two peaks were found and are composed of different defect states. The first peak with two components was related to diffusion of Mg p-type dopants in the n-GaN and VN-related defects. The two components have activation energies close to 0.25 eV, from valence band and conduction band with a capture cross-section of ∼10−16 cm2. The second peak with two components showed temperature shifts with the pulse height indicating a band-like behavior. This peak was commonly attributed to deep acceptor CN-related defects with an activation energy of E
V +0.88 eV and a capture cross-section of 10−13 cm2. A second acceptor level was found, with an activation energy of 0.70 eV and a capture cross-section of 10−15 cm2. This second component was previously attributed to native point defects in GaN.
Ga composition effects on the electrical parameters of (Al,Ga)Sb/InAs two-dimensional electron gas
Authors: Wei Qiqi , Wang Hailong , Tong Shucheng , Ma Jialin , Zhao Xupeng , Zhao Jianhua
Published: November 2020

The effects of Ga composition on the electrical parameters of (Al,Ga)Sb/InAs two-dimensional electron gas have been investigated. The (Al,Ga)Sb/InAs structures are grown on GaAs (001) substrate by molecular-beam epitaxy with various Ga compositions in Al1−x
Ga
x
Sb bottom barrier. The sheet resistance shows a crossover with the variation of temperature, and the temperature T* corresponding to this crossover decreases with increasing the Ga composition. The temperature dependence of the electron mobility is similar for the samples with different Ga compositions, while the temperature dependence of the carrier density is obviously different. Qualitative analyses reveal that the temperature dependent portion of carrier density is mainly determined by the interface-related donors. A thermal activation model is used to fit the temperature dependence of carrier density, and the fitting results imply that the thermal activation energies of the carriers are significantly affected by the Ga composition. Our results provide useful information for understanding the sources of carriers in the (Al,Ga)Sb/InAs systems, and provide one pathway for the modulation of the temperature dependent carrier density.
Improved performance of Ni/GaN Schottky barrier impact ionization avalanche transit time diode with n-type GaN deep level defects
Authors: Zhang Xiao-Yu , Yang Lin-An , Yang Wen-lu , Li Yang , Ma Xiao-Hua , Hao Yue
Published: November 2020

In this paper, the effects of n-type GaN deep level defects on the DC, small signal AC, and radio frequency (RF) characteristics of Ni/GaN Schottky barrier impact ionization avalanche transit time (IMPATT) diode are investigated. A double avalanche termination region (DATR) structural IMPATT diode is proposed to mitigate the influences caused by these deep level defects. Simulation results show that the internal electric field, carrier generation rate and carrier velocity of IMPATT diode are affected by these deep level defects. With the increase of deep level defects density, the maximum RF output power, DC-to-RF conversion efficiency and optimum frequency of the diode all show a tendency to degenerate correspondingly. Through adjusting the electric field property properly of the diode, the DATR structural IMPATT diode improves the performances of IMPATT diode. The negative peak conductance of the improved diode is 11.4 × 103 S cm−2 at 248 GHz, showing the lowest quality factor of 1.42, the improved maximum RF output power of 1.35 MW cm−2 and DC-to-RF conversion efficiency of 15.7% at 220 GHz under the same deep level defects density, these characteristics of the improved DATR structural IMPATT diode reach the level which the low deep level defects density original diode shows.
An intra-operative feature-based classification of microelectrode recordings to support the subthalamic nucleus functional identification during deep brain stimulation surgery
Authors: Coelli S , Levi V , Del Vecchio Del Vecchio J , Mailland E , Rinaldo S , Eleopra R , Bianchi A M
Published: November 2020

Objective. The subthalamic nucleus (STN) is the most selected target for the placement of the Deep Brain Stimulation (DBS) electrode to treat Parkinson’s disease. Its identification is a delicate and challenging task which is based on the interpretation of the STN functional activity acquired through microelectrode recordings (MERs). Aim of this work is to explore the potentiality of a set of 25 features to build a classification model for the discrimination of MER signals belonging to the STN. Approach. We explored the use of different sets of spike-dependent and spike-independent features in combination with an ensemble trees classification algorithm on a dataset composed of 13 patients receiving bilateral DBS. We compared results from six subsets of features and two dataset conditions (with and without standardization) using performance metrics on a leave-one-patient-out validation schema. Main results. We obtained statistically better results (i.e. higher accuracy p-value = 0.003) on the RAW dataset than on the standardized one, where the selection of seven features using a minimum redundancy maximum relevance algorithm provided a mean accuracy of 94.1%, comparable with the use of the full set of features. In the same conditions, the spike-dependent features provided the lowest accuracy (86.8%), while a power density-based index was shown to be a good indicator of STN activity (92.3%). Significance. Results suggest that a small and simple set of features can be used for an efficient classification of MERs to implement an intraoperative support for clinical decision during DBS surgery.
An Experimental Study on Self-Compacting Concrete Using Tyre Rubber and Recycled Aggregate
Authors: Mishra M. , Panda K. C.
Published: November 2020

The present study carried out for an experimental investigation on both fresh and hardened properties of self-compacting concrete (SCC) containing waste tyre rubber and recycled aggregate (RA). The tyre rubber replaced 5 % and 10 % with coarse aggregate by its weight. The recycled aggregate replaced 5 % and 10 % with coarse aggregate by its weight. Totally 7 mix were prepared including the combination of 5 % tyre rubber with 5 % recycled aggregate and 10 % tyre rubber with 10 % recycled aggregate. The 5 mm and 10 mm size of rubber chips are used. The M30 grade concrete mix design was adopted for the present work. For SCC preparation, the coarse aggregate amount decreased by 35 % and fine aggregate amount increased 35 % with water cement ratio (w/c) 0.43 and super plasticizer (SP) 0.4%. To obtain fresh properties slump flow test, T500 test, J - ring test, V - funnel test, L - box test and U - box test is conducted. For hardened concrete properties the compressive strength, flexural strength and split tensile strength tests are conducted. An attempt has been taken to identify the combine potential effect of tyre rubber and recycled aggregate in concrete and necessity of fresh and hardened properties for the SCC mix.
Determination of SSUT of HSC Beams with WASPAS Method
Authors: Charan Behera Gopal , Panda Subhasri
Published: November 2020

Distressed beams should be retrofitted rather than demolishing. Now a days there are so many retrofitting materials available. Retrofitting is to be done with materials those are easy to apply, economic and less time consuming. Engineers are more interested in ultimate strength of a structure. Strength is related to stiffness. Finding secant stiffness at ultimate torque of a suitable wrapping material for distressed concrete beams that is economic, long lasting, sustainable and appropriate to the common people is the main focus of this investigation. The paper progresses with search of different wrapping strategies and different materials available. Then the paper aims exploring sustainability options for torsional retrofitting with ferrocement. Aim of the paper is to evaluate SSUT of “U” wrapped beam with different methods. This study shows there is reduction of stiffness at ultimate stage of wrapped beams. Experimental, analytical and Soft computing method MARS and WASPAS were discussed here to predict the value of SSUT. Torsionally over reinforced sections are found with more stiffness at ultimate than all other types of beams. The predicted values are well within the acceptable limits.
Effect of Stone dust and Lime in the Geotechnical Properties of Clayey Soil
Authors: Samal Rasmiranjan , Mishra Ayan
Published: November 2020

Clayey soils are commonly stiff in dry state but lose their stiffness when saturated with water. Soft clays are characterized by low bearing capacity and high compressibility. In this research, stone dust obtained from stone processing area used for Stabilization of clayey soil with lime. Thus, the effectiveness of using stone powder and lime in stabilizing fine-grained clayey soil (CL) was investigated in the laboratory. The soil samples in natural state and when mixed with varying percentages of lime and waste stone powder were used for the laboratory tests that included Atterberg limits tests, standard Proctor compaction tests, unconfined compression tests and California bearing ratio tests. The value of maximum dry density, Unconfined Compressive Strength and California Bearing Ratio decreased with increase in % of stone dust and lime. The Optimum Moisture Content value remain same with increasing stone dust content and lime.
Venous thromboembolic events in patients with COVID-19: a systematic review and meta-analysis
Authors: Wu Ting , Zuo Zhihong , Yang Deyi , Luo Xuan , Jiang Liping , Xia Zanxian , Xiao Xiaojuan , Liu Jing , Ye Mao , Deng Meichun
Published: November 2020

Background

High incidence of venous thromboembolic complications in coronavirus disease 2019 (COVID-19) patients was noted recently.

Objective

This study aimed to explore the factors associated with prevalence of venous thromboembolism (VTE) in COVID-19 patients.

Methods

A literature search was conducted in several online databases. Fixed effects meta-analysis was performed for the factors associated with prevalence of VTE in COVID-19 patients.

Results

A total of 39 studies were analysed in this analysis. The incidence of pulmonary embolism and VTE in severe COVID-19 patients were 17% (95% CI, 13–21%) and 42% (95% CI, 25–60%), respectively. VTE were more common among individuals with COVID-19 of advance age. Male COVID-19 patients are more likely to experience VTE. Higher levels of white blood cell (WBC; WMD = 1.34 × 109/L; 95% CI, 0.84–1.84 × 109/L), D-dimer (WMD = 4.21 μg/ml; 95% CI, 3.77–4.66 μg/ml), activated partial thromboplastin time (APTT; WMD = 2.03 s; 95% CI, 0.83–3.24 s), fibrinogen (WMD = 0.49 μg/ml; 95% CI, 0.18–0.79 g/L) and C-reactive protein (CRP; WMD = 21.89 mg/L; 95% CI, 11.44–32.34 mg/L) were commonly noted in COVID-19 patients with VTE. Patients with lower level of lymphocyte (WMD = −0.15 × 109/L; 95% CI, −0.23-−0.07 × 109/L) was at high risk of developing VTE. The incidence of severe condition (OR = 2.66; 95% CI, 1.95–3.62) was more likely to occur among COVID-19 patients who developed VTE.

Conclusion

VTE is a common complication in severe COVID-19 patients and thromboembolic events are also associated with adverse outcomes.
Optimizing Aesthetic Outcomes in Breast Reconstruction After Nipple-Sparing Mastectomy
Authors: Choi Mihye , Frey Jordan D
Published: November 2020

Nipple-sparing mastectomy (NSM) has been associated with improved quality of life and patient satisfaction with similar oncologic outcomes compared with traditional mastectomy techniques. By conserving the nipple-areola complex and the majority of the breast skin envelope, NSM allows for improved aesthetic outcomes after breast reconstruction. However, the technique is also associated with a steep learning curve that must be considered to achieve optimal outcomes. It is important that the plastic surgeon functions in concert with the extirpative breast surgeon to optimize outcomes because the reconstruction is ultimately dependent on the quality of the overlying mastectomy flaps. Various other factors influence the complex interplay between aesthetic and reconstructive outcomes in NSM, including preoperative evaluation, specific implant- and autologous-based considerations, as well as techniques to optimize and correct nipple-areola complex position. Management strategies for complications necessary to salvage a successful reconstruction are also reviewed. Lastly, techniques to expand indications for NSM and maximize nipple viability as well as preshape the breast are discussed. Through thoughtful preoperative planning and intraoperative technique, ideal aesthetic results in NSM may be achieved.
Simulation of African and non-African low and high coverage whole genome sequence data to assess variant calling approaches
Authors: Alosaimi Shatha , van Biljon Noëlle , Awany Denis , Thami Prisca K , Defo Joel , Mugo Jacquiline W , Bope Christian D , Mazandu Gaston K , Mulder Nicola J , Chimusa Emile R
Published: November 2020

Current variant calling (VC) approaches have been designed to leverage populations of long-range haplotypes and were benchmarked using populations of European descent, whereas most genetic diversity is found in non-European such as Africa populations. Working with these genetically diverse populations, VC tools may produce false positive and false negative results, which may produce misleading conclusions in prioritization of mutations, clinical relevancy and actionability of genes. The most prominent question is which tool or pipeline has a high rate of sensitivity and precision when analysing African data with either low or high sequence coverage, given the high genetic diversity and heterogeneity of this data. Here, a total of 100 synthetic Whole Genome Sequencing (WGS) samples, mimicking the genetics profile of African and European subjects for different specific coverage levels (high/low), have been generated to assess the performance of nine different VC tools on these contrasting datasets. The performances of these tools were assessed in false positive and false negative call rates by comparing the simulated golden variants to the variants identified by each VC tool. Combining our results on sensitivity and positive predictive value (PPV), VarDict [PPV = 0.999 and Matthews correlation coefficient (MCC) = 0.832] and BCFtools (PPV = 0.999 and MCC = 0.813) perform best when using African population data on high and low coverage data. Overall, current VC tools produce high false positive and false negative rates when analysing African compared with European data. This highlights the need for development of VC approaches with high sensitivity and precision tailored for populations characterized by high genetic variations and low linkage disequilibrium.
GeneReg: a constraint-based approach for design of feasible metabolic engineering strategies at the gene level
Authors: Razaghi-Moghadam Zahra , Nikoloski Zoran
Published: November 2020

Motivation

Large-scale metabolic models are widely used to design metabolic engineering strategies for diverse biotechnological applications. However, the existing computational approaches focus on alteration of reaction fluxes and often neglect the manipulations of gene expression to implement these strategies.

Results

Here, we find that the association of genes with multiple reactions leads to infeasibility of engineering strategies at the flux level, since they require contradicting manipulations of gene expression. Moreover, we identify that all of the existing approaches to design gene knockout strategies do not ensure that the resulting design may also require other gene alterations, such as up- or downregulations, to match the desired flux distribution. To address these issues, we propose a constraint-based approach, termed GeneReg, that facilitates the design of feasible metabolic engineering strategies at the gene level and that is readily applicable to large-scale metabolic networks. We show that GeneReg can identify feasible strategies to overproduce ethanol in Escherichia coli and lactate in Saccharomyces cerevisiae, but overproduction of the TCA cycle intermediates is not feasible in five organisms used as cell factories under default growth conditions. Therefore, GeneReg points at the need to couple gene regulation and metabolism to design rational metabolic engineering strategies.

Availability and implementation

https://github.com/MonaRazaghi/GeneReg

Supplementary information

Supplementary data are available at Bioinformatics online.
Hypoxia in multiple sclerosis; is it the chicken or the egg?
Authors: Halder Sebok K , Milner Richard
Published: November 2020

Over the past 50 years, intense research effort has taught us a great deal about multiple sclerosis. We know that it is the most common neurological disease affecting the young-middle aged, that it affects two to three times more females than males, and that it is characterized as an autoimmune disease, in which autoreactive T lymphocytes cross the blood–brain barrier, resulting in demyelinating lesions. But despite all the knowledge gained, a key question still remains; what is the initial event that triggers the inflammatory demyelinating process? While most research effort to date has focused on the immune system, more recently, another potential candidate has emerged: hypoxia. Specifically, a growing number of studies have described the presence of hypoxia (both ‘virtual’ and real) at an early stage of demyelinating lesions, and several groups, including our own, have begun to investigate how manipulation of inspired oxygen levels impacts disease progression. In this review we summarize the findings of these hypoxia studies, and in particular, address three main questions: (i) is the hypoxia found in demyelinating lesions ‘virtual’ or real; (ii) what causes this hypoxia; and (iii) how does manipulation of inspired oxygen impact disease progression?
Risk Factors and Outcomes of Hospitalized Patients With Severe Coronavirus Disease 2019 (COVID-19) and Secondary Bloodstream Infections: A Multicenter Case-Control Study
Authors: Bhatt Pinki J , Shiau Stephanie , Brunetti Luigi , Xie Yingda , Solanki Kinjal , Khalid Shaza , Mohayya Sana , Au Pak Ho , Pham Christopher , Uprety Priyanka , Nahass Ronald , Narayanan Navaneeth
Published: November 2020

Background

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Clinical characteristics regarding secondary infections in patients with COVID-19 have been reported, but detailed microbiology, risk factors, and outcomes of secondary bloodstream infections (sBSIs) in patients with severe COVID-19 have not been well described.

Methods

We performed a multicenter case-control study including all hospitalized patients diagnosed with severe COVID-19 and blood cultures drawn from 1 March 2020 to 7 May 2020 at 3 academic medical centers in New Jersey. Data collection included demographics, clinical and microbiologic variables, and patient outcomes. Risk factors and outcomes were compared between cases (sBSI) and controls (no sBSI).

Results

A total of 375 hospitalized patients were included. There were 128 sBSIs during the hospitalization. For the first set of positive blood cultures, 117 (91.4%) were bacterial and 7 (5.5%) were fungal. Those with sBSI were more likely to have altered mental status, lower mean percentage oxygen saturation on room air, have septic shock, and be admitted to the intensive care unit compared with controls. In-hospital mortality was higher in those with an sBSI versus controls (53.1% vs 32.8%, P = .0001).

Conclusions

We observed that hospitalized adult patients with severe COVID-19 and sBSI had a more severe initial presentation, prolonged hospital course, and worse clinical outcomes. To maintain antimicrobial stewardship principles, further prospective studies are necessary to better characterize risk factors and prediction modeling to better understand when to suspect and empirically treat for sBSIs in severe COVID-19.
Text Summarization as a Multi-objective Optimization Task: Applying Harmony Search to Extractive Multi-Document Summarization
Authors: Bidoki M , Fakhrahmad M , Moosavi M R
Published: November 2020

Today, automated extractive text summarization is one of the most common techniques for organizing information. In extractive summarization, the most appropriate sentences are selected from the text and build a representative summary. Therefore, probing for the best sentences is a fundamental task.

This paper has coped with extractive summarization as a multi-objective optimization problem and proposed a language-independent, semantic-aware approach that applies the harmony search algorithm to generate appropriate multi-document summaries. It learns the objective function from an extra set of reference summaries and then generates the best summaries according to the trained function. The system also performs some supplementary activities for better achievements. It expands the sentences by using an inventive approach that aims at tuning conceptual densities in the sentences towards important topics. Furthermore, we introduced an innovative clustering method for identifying important topics and reducing redundancies. A sentence placement policy based on the Hamiltonian shortest path was introduced for producing readable summaries.

The experiments were conducted on DUC2002, DUC2006 and DUC2007 datasets. Experimental results showed that the proposed framework could assist the summarization process and yield better performance. Also, it was able to generally outperform other cited summarizer systems.
Effects of Larval Population Density and Food Type on the Life Cycle ofMusca domestica(Diptera: Muscidae)
Authors: Kökdener Meltem , Kiper Filiz
Published: November 2020

Larval density is an important factor modulating larval resource-acquisition, influencing development of insects. This study aimed to evaluate the effect of larval density and substrate content on some life-history parameters of Musca domestica Linnaeus, 1758 (Diptera: Muscidae). This research was carried out from March 2019 through September 2019 at Animal Physiology Laboratory of Ondokuz Mayıs University, Samsun, Turkey. Groups of 25, 100, 200, and 400 newly hatched M. domestica larvae were transferred to a polyethylene cup filled with different substrates (i.e., wheat bran, poultry meal, soybean meal) and kept at 25°C, 62% RH with a photoperiod of 12:12 (L:D) h. A two-way analysis of variance (Two way ANOVA) was used to analyze the data on the percentage of pupal and larval survival development time, pupal, and adult weight to evaluate the effect of density and rearing substrate. In this study, increasing larval density and nutrient content of food led to changes in the larval and pupal development time of M. domestica. The results also indicated that the weight of pupae and adult survival was negatively affected by increasing larval density. The wheat bran diet was superior to the other diets for all parameters tested. Our study indicated that life history parameters of Musca domestica are affected by the rearing conditions.
A concealed carcinoid cardiac metastasis uncovered by comprehensive cardiovascular magnetic resonance-based tissue characterization: a case report
Authors: Georgiopoulos Georgios , Mitropoulou Panagiota , Masci Pier Giorgio , Schwitter Juerg
Published: November 2020

Background

Cardiac metastases of carcinoid tumours are extremely rare, and their diagnosis poses a significant challenge. A variety of techniques has been reported in the literature for this purpose, ranging from echocardiogram to the Indium-111 Octreotide, positron emission tomography using specific tracers, and biopsy. Occasionally, the diagnosis is only made post-mortem. Recently, CMR (cardiovascular magnetic resonance) has been added to the diagnostic toolkit. This case report describes the CMR sequences that can be used to characterize cardiac metastases of carcinoid tumours.

Case summary

A 55-year-old woman with an antecedent history of resected carcinoid tumour of the ileocecal junction underwent whole-body In-111 Octreoscan single-photon emission computed tomography in the context of her follow-up. This raised the suspicion of pericardial involvement, which prompted a CMR study. Comprehensive CMR findings were consistent with isolated carcinoid tumour metastasis embedded within the anterior papillary muscle. We describe the CMR sequences that were used to characterize the metastasis.

Discussion

The rarity of cardiac metastasis of carcinoid tumour makes its diagnosis challenging and warrants a high level of clinical suspicion. Cardiovascular magnetic resonance imaging proves to be an indispensable tool in the tissue characterization of such tumours.
Delayed occurrence of an accelerated idioventricular rhythm with alternating bundle branch block after myocardial infarction as predictor of sudden cardiac arrest: a case report
Authors: Bettin Markus , Koopmann Matthias , Mönnig Gerold , Pott Christian
Published: November 2020

Background

Accelerated idioventricular rhythm (AIVR) is known as reperfusion arrhythmia in the setting of acute myocardial infarction (AMI). In healthy individuals, it is usually considered to be benign. Alternating bundle branch block (ABBB) often progresses to complete atrioventricular block requiring permanent pacemaker implantation. We report a case of delayed appearance of AIVR following myocardial infarction (MI) in combination with ABBB as precursor of sudden cardiac arrest due to ventricular fibrillation (VF).

Case summary

A 62-year-old male with pre-existing left bundle branch block (LBBB) was admitted with an acute non-ST segment elevation MI. He underwent successful percutaneous coronary intervention (PCI) of a subtotal proximal left anterior descending artery (LAD) stenosis. Before and after PCI the electrocardiogram (ECG) demonstrated sinus rhythm with LBBB. The patient was discharged 5 days after PCI, left ventricular function at this time was moderately reduced (ejection fraction of 40%). After another 5 days, the patient was admitted for elective cardiac rehabilitation. At this time, the ECG demonstrated an AIVR with right bundle branch block morphology. Due to ABBB, the patient was scheduled for permanent pacemaker implantation. Before pacemaker implantation could take place, the patient developed a sudden cardiac arrest due to VF and was successfully resuscitated. A follow-up coronary angiography revealed no novel lesions. A cardiac resynchronization therapy defibrillator was implanted for secondary prevention of sudden cardiac death.

Discussion

Delayed occurrence of AIVR in combination with ABBB following AMI could be a predictor of sudden cardiac death. These patients are probably at high risk for malignant ventricular arrhythmias.
Antithrombotic therapy according to baseline bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention: applying the PRECISE-DAPT score in RE-DUAL PCI
Authors: Costa Francesco , Valgimigli Marco , Steg Philippe Gabriel , Bhatt Deepak L , Hohnloser Stefan H , Ten Berg Jurrien M , Miede Corinna , Nordaby Matias , Lip Gregory Y H , Oldgren Jonas , Cannon Christopher P
Published: November 2020

Aims

Patients with atrial fibrillation undergoing coronary intervention are at higher bleeding risk due to the concomitant need for oral anticoagulation and antiplatelet therapy. The RE-DUAL PCI trial demonstrated better safety with dual antithrombotic therapy (DAT: dabigatran 110 or 150 mg b.i.d., clopidogrel or ticagrelor) compared to triple antithrombotic therapy (TAT: warfarin, clopidogrel or ticagrelor, and aspirin). We explored the impact of baseline bleeding risk based on the PRECISE-DAPT score for decision-making regarding DAT vs. TAT.

Methods and results

A score ≥25 points qualified high bleeding risk (HBR). Comparisons were made for the primary safety endpoint International Society of Thrombosis and Haemostasis major or clinically relevant non-major bleeding, and the composite efficacy endpoint of death, thrombo-embolic events, or unplanned revascularization, analysed by time-to-event analysis. PRECISE-DAPT was available in 2336/2725 patients, and 37.9% were HBR. Compared to TAT, DAT with dabigatran 110 mg reduced bleeding risk both in non-HBR [hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.31–0.57] and HBR (HR 0.70, 95% CI 0.52–0.94), with a greater magnitude of benefit among non-HBR (Pint = 0.02). Dual antithrombotic therapy with dabigatran 150 mg vs. TAT reduced bleeding in non-HBR (HR 0.60, 95% CI 0.45–0.80), with a trend toward less benefit in HBR patients (HR 0.92, 95% CI 0.63–1.34; Pint = 0.08). The risk of ischaemic events was similar on DAT with dabigatran (both 110 and 150 mg) vs. TAT in non-HBR and HBR patients (Pint = 0.45 and Pint = 0.56, respectively).

Conclusions

PRECISE-DAPT score appeared useful to identify AF patients undergoing PCI at further increased risk of bleeding complications and may help clinicians identifying the antithrombotic regimen intensity with the best benefit–risk ratio in an individual patient.
Impact of chronic kidney disease in 29 893 patients undergoing transcatheter or surgical aortic valve replacement from the German Aortic Valve Registry
Authors: Mas-Peiro Silvia , Faerber Gloria , Bon Dimitra , Herrmann Eva , Bauer Timm , Bleiziffer Sabine , Bekeredjian Raffi , Böning Andreas , Frerker Christian , Beckmann Andreas , Möllmann Helge , Vasa-Nicotera Mariuca , Ensminger Stephan , Hamm Christian W , Beyersdorf Friedhelm , Fichtlscherer Stephan , Walther Thomas ,   for the GARY-Executive Board, Beyersdorf Friedhelm , Hamm Christian W , Cremer Jochen , Kuck Karl-Heinz , Ince Hüseyin , Andresen Dietrich , Mohr Friedrich W , Sack Stefan , Walther Thomas , Ensminger Stephan , Haude Michael , Linke Axel , M—llmann Helge , Wahlers Thorsten , Welz Armin , Beckmann Andreas , Papoutsis Konstantinos
Published: November 2020

OBJECTIVES

Chronic kidney disease (CKD) is a key risk factor in patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). We analysed the impact of estimated glomerular filtration rate (eGFR) and CKD stages on their mid-term survival.

METHODS

Data from 29 893 patients enrolled in the German Aortic Valve registry from January 2011 to December 2015 receiving TAVI (n = 12 834) or SAVR (n = 17 059) at 88 sites were included. The impact of renal impairment, as measured by eGFR and CKD stages, was investigated. The primary end-point was 1-year cumulative all-cause mortality.

RESULTS

Higher CKD stages were significantly associated to lower in-hospital, 30-day- and 1-year survival rates. Both TAVI- and SAVR-treated patients in CKD 3a, 3b, 4 and 5 stages showed significant and gradually increasing HR values for 1-year all-cause mortality. The same trend persisted in multivariable analysis, although HR values for CKD 3a and 5 did not reach significance in TAVI patients, whereas CKD 4 + 5 did not reach statistical significance in SAVR. Likewise, eGFR as a continuous variable was a significant predictor for 1-year mortality, with the best cut-off points being 47.4 ml/min/1.73 m2 for TAVI and 59.8 ml/min/1.73 m2 for SAVR. Significant 8.6% and 9.0% increases in 1-year mortality were observed for every 5-ml reduction in eGFR for TAVI and SAVR, respectively.

CONCLUSIONS

CKD ≥3b and CKD ≥3a are the independent major risk factors for mortality in patients undergoing TAVI and SAVR, respectively. In the overall population of patients with severe aortic stenosis, an appropriate stratification based on CKD substage may contribute to a better selection of patients suitable for such therapies.