bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidentally identified ductus arteriosus aneurysm in eight adults: a case series
Authors: Yukimoto Mayo , Okuma Tomohisa , Sohgawa Etsuji , Nakano Mariko M , Shimono Taro , Miki Yukio
Published: March 2021

Ductus arteriosus aneurysm (DAA) in adulthood is a rare entity. We retrospectively reviewed our medical records from the past 10 years and identified 8 cases of adult DAA (6 males and 2 females aged between 69 and 89 years; mean, 76 years), using multiplanar reconstruction and three-dimensional reconstruction CT images. The aneurysm was suspected incidentally in all cases based on the results of chest radiographic screening or post-operative follow-up CT for lung or colon cancer. All eight patients were asymptomatic but had a history of or concurrent hypertension (n = 5, 62.5%), diabetes mellitus (n = 3, 37.5%), cerebrovascular disease (n = 3, 37.5%), ischemic heart disease (n = 1, 12.5%), and cardiac failure (n = 1). All patients had no history of trauma (n = 8, 100%). Six had a history of cigarette smoking. The aneurysm size ranged from 2.0 × 4.0 to 6.3 × 5.3 cm (mean, 3 × 5 cm). The surgical procedures used were four cases of total arch replacement and two cases of thoracic endovascular aortic repair. Two patients were not surgically treated. The median follow-up was 14.5 months (range, 2 months to 9 years). In the two patients who were not surgically treated, the aneurysm enlarged in one, and remained unchanged in the other. Of the six surgically managed cases, one was lost to follow-up, and another patient died of an unrelated cause. The remaining four cases had no enlargement of the aneurysm. No ruptures were reported in any of the cases. DAA should be considered when a saccular aneurysm is located in the minor curvature of the aortic arch and extending toward the left pulmonary trunk in adult patients. Differentiating adult DAA is important, because it is associated with a high risk of rupture due to the fragile nature of true aneurysms.
Identification of monetary shocks through the yield curve: Evidence for Brazil
Authors: Da Costa Filho Adonias Evaristo
Published: March 2021

This paper derives a new measure of monetary shock for Brazil based on the yield curve. First, the Diebold and Li (2006) model is estimated with nominal yields. The changes of the latent variables of this model surrounding monetary policy meetings are used to analyze the effects on the Brazilian economy. Monetary policy decisions associated with steeper yield curves lead to higher future economic activity.
Robust optimization of time series momentum portfolios
Authors: Fague Jeremy , Almeida Caio
Published: March 2021

Mean-Variance Optimization (MVO) is well-known to be extremely sensitive to slight differences in the expected returns and covariances: if these measures change day to day, MVO can specify very different portfolios. Making wholesale changes in portfolio composition can cause the incremental gains to be negated by trading costs. We present a method for regularizing portfolio turnover by using the ℓ1 penalty, with the amount of penalization informed by recent historical data. We find that this method dramatically reduces turnover, while preserving the efficiency of mean-variance optimization in terms of risk-adjusted return. Factoring in reasonable estimates of transaction costs, the turnover-regularized MVO portfolio substantially outperforms a leverage-constrained MVO approach, in terms of risk-adjusted return.
Application of genus Cassia in the treatment of Constipation: A systematic review
Authors: Aslam Muhammad Shahzad
Published: March 2021

Purpose:  Role of genus cassia in the treatment of Constipation

Methods: Methodological analysis, systematic review, and meta-analysis of identified studies using RevMan

Result and Discussion: Cassia fistula was partially effected in treating constipation however there is a need for improvement in the protocol of studies to reduce biases. These results were only limited to one species so it cannot be generalized among all species of Cassia.

Conclusion: Cassia fistula is partially effective in reducing the pain and consistency of stool during constipation among children.
Computing Sensitivities for Distortion Risk Measures
Authors: Glynn Peter W. , Peng Yijie , Fu Michael C. , Hu Jian-Qiang
Published: March 2021

Distortion risk measure, defined by an integral of a distorted tail probability, has been widely used in behavioral economics and risk management as an alternative to expected utility. The sensitivity of the distortion risk measure is a functional of certain distribution sensitivities. We propose a new sensitivity estimator for the distortion risk measure that uses generalized likelihood ratio estimators for distribution sensitivities as input and establish a central limit theorem for the new estimator. The proposed estimator can handle discontinuous sample paths and distortion functions.
Time Is the Wisest Counselor of All: The Value of Provider–Patient Engagement Length in Home Healthcare
Authors: Song Hummy , Andreyeva Elena , David Guy
Published: March 2021

Home healthcare is a rapidly growing area of the health sector in the United States. We study its role in the shift toward value-based care, as it is viewed as an avenue for achieving reductions in the cost and utilization of expensive downstream healthcare services. Using a novel data set on home healthcare visits, we examine whether and how the amount of time that a provider spends during a home health visit with a recently discharged patient impacts the patient’s likelihood of being readmitted to the hospital. Because unobserved patient health status may influence both the length of a home health visit and the likelihood of hospital readmission, we use the within-provider average visit length of all other episodes’ visits conducted by each provider in the 30-day period before and after the focal visit as an instrument for visit length. Using this instrumental variable approach and controlling for operational, demographic, and patient condition-related characteristics, we find the following: on average, an extra minute during a focal home health visit is associated with a 1.39% decrease in the likelihood of readmission to the hospital following that visit. Our finding suggests that a 10% increase in visit length would decrease the likelihood of readmission following a home health visit by 6%. We document heterogeneity in this effect across different patient types and visit types. We conduct a cost–benefit analysis that suggests that the cost of investing in additional home health capacity is outweighed by the cost savings arising from fewer hospitalizations.

This paper was accepted by Stefan Scholtes, healthcare management.
Financial Uncertainty with Ambiguity and Learning
Authors: Liu Hening , Zhang Yuzhao
Published: March 2021

We examine a production-based asset pricing model with regime-switching productivity growth, learning, and ambiguity. Both the mean and volatility of the growth rate of productivity are assumed to follow a Markov chain with an unobservable state. The agent’s preferences are characterized by the generalized recursive smooth ambiguity utility function. Our calibrated benchmark model with modest risk aversion can match moments of the variance risk premium in the data and reconcile empirical relations between the risk-neutral variance and macroeconomic quantities and their respective volatilities. We show that the interplay between productivity volatility risk and ambiguity aversion is important for pricing variance risk in returns.

This paper was accepted by Tomasz Piskorski, finance.
Health-related quality of life and sagittal balance at two to 25 years after posterior transfixation for high-grade dysplastic spondylolisthesis
Authors: Schlösser Tom P C. , Garrido Enrique , Tsirikos Athanasios I. , McMaster Michael J.
Published: March 2021

Aims

High-grade dysplastic spondylolisthesis is a disabling disorder for which many different operative techniques have been described. The aim of this study is to evaluate Scoliosis Research Society 22-item (SRS-22r) scores, global balance, and regional spino-pelvic alignment from two to 25 years after surgery for high-grade dysplastic spondylolisthesis using an all-posterior partial reduction, transfixation technique.

Methods

SRS-22r and full-spine lateral radiographs were collected for the 28 young patients (age 13.4 years (SD 2.6) who underwent surgery for high-grade dysplastic spondylolisthesis in our centre (Scottish National Spinal Deformity Service) between 1995 and 2018. The mean follow-up was nine years (2 to 25), and one patient was lost to follow-up. The standard surgical technique was an all-posterior, partial reduction, and S1 to L5 transfixation screw technique without direct decompression. Parameters for segmental (slip percentage, Dubousset’s lumbosacral angle) and regional alignment (pelvic tilt, sacral slope, L5 incidence, lumbar lordosis, and thoracic kyphosis) and global balance (T1 spino-pelvic inclination) were measured. SRS-22r scores were compared between patients with a balanced and unbalanced pelvis at final follow-up.

Results

SRS-22r domain and total scores improved significantly from preoperative to final follow-up, except for the mental health domain that remained the same. Slip percentage improved from 75% (SD 15) to 48% (SD 19) and lumbosacral angle from 70° (SD 11) to 101° (SD 11). Preoperatively, 35% had global imbalance, and at follow-up all were balanced. Preoperatively, 63% had an unbalanced pelvis, and at final follow-up this was 32%. SRS-22r scores were not different in patients with a balanced or unbalanced pelvis. However, postoperative pelvic imbalance as measured by L5 incidence was associated with lower SRS-22r self-image and total scores (p = 0.029).

Conclusion

In young patients with HGDS, partial reduction and transfixation improves local lumbosacral alignment, restores pelvic, and global balance and provides satisfactory long-term clinical outcomes. Higher SRS-22r self-image and total scores were observed in the patients that had a balanced pelvis (L5I < 60°) at two to 25 years follow-up. Cite this article: Bone Jt Open 2021;2(3):163–173.
Digital Hydraulic Technology for Linear Actuation: A State of the Art Review
Authors: Donkov Viktor Hristov , Andersen Torben , Linjama Matti , Ebbesen Morten
Published: March 2021

This paper analyses the current state of the art in linear actuation with digital hydraulics. Based on the differences in their aims the paper partitions the area into four actuation concepts – parallel valve solutions, single switching valve solutions, multi-chamber cylinders, and multi-pressure cylinders. The concepts are evaluated based on accuracy and smoothness of motion, switching load, reliability, efficiency and the number of components required.
The impact of laparoscopy on emergency surgery for adhesional small bowel obstruction: prospective single centre cohort study
Authors: Darbyshire AR , Kostakis I , Pucher PH , Toh SKC , Mercer SJ
Published: March 2021

Introduction

Laparoscopic adhesiolysis is increasingly being used to treat adhesional small bowel obstruction (ASBO) as it has been associated with reduced postoperative length of stay (LOS) and faster recovery. However, concerns regarding limited working space, iatrogenic bowel injury and failure to relieve the obstruction have limited its uptake. This study reports our centre’s experience of adopting laparoscopy as the standard operative approach.

Methods

A single-centre prospective cohort study was performed incorporating local data from the National Emergency Laparotomy Audit Database; January 2015 to December 2019. All patients undergoing surgery for ASBO were included. Patient demographic, operative and inhospital outcomes data were compared between different surgical approaches. Linear regression analysis was performed for LOS.

Results

A total of 299 cases were identified. Overall, 76.3% of cases were started laparoscopically and 52.2% were completed successfully. Patients treated laparoscopically had lower Portsmouth – Physiological and Operative Severity Score for the enuMeration of Mortality and morbidity (P-POSSUM) predicted mortality (median 2.1 (interquartile range (IQR) 1.3–5.0) vs 5.7 (IQR 2.0–12.4), p=<0.001) and shorter postoperative LOS compared with open (median 4.2 days (IQR 2.5–8.2) vs 11.3 days (IQR 7.3–16.6), p=0.000). Inhospital mortality was lower in the laparoscopic group (2 vs 7 deaths, p=<0.001). In regression analysis, laparoscopic surgery was found to have the strongest association with postoperative LOS (β −8.51 (−13.87 to −3.16) p=0.002) compared with open surgery.

Conclusions

Laparoscopy is a safe and feasible approach for adhesiolysis in the majority of patients with ASBO. It is associated with reduced LOS with no impact on complications or mortality.
Diversion, resection, or stenting as a bridge to surgery for acute neoplastic left-sided colonic obstruction: a systematic review and network meta-analysis of studies with curative intent
Authors: Gavriilidis P , de’Angelis N , Wheeler J , Askari A , Di Saverio S , Davies JR
Published: March 2021

Introduction

The debate on the best surgical management strategy for acute malignant left-sided colonic obstruction is ongoing. Decompressing colostomy (DC) and stenting as a bridge to surgery (SBTS) are the currently proposed alternative approaches to emergency colectomy (EC). However, the results of a traditional meta-analysis were inconclusive. Therefore, a network meta-analysis (NMA) was conducted to compare the three approaches for acute left-sided colonic obstruction.

Methods

A systematic literature search of Embase, PubMed, Google Scholar and the Cochrane library was performed. A traditional meta-analysis and subsequent NMA were conducted.

Findings

A significantly greater number of primary anastomoses were performed in the DC cohort than in the EC and SBTS cohorts. The 90-day mortality rate was significantly lower in the DC cohort than in the EC and SBTS cohorts. Higher costs were associated with the SBTS cohort (by US$2,000) than with the EC cohort. The locoregional recurrence rate was higher for the SBTS cohort than for the EC cohort.

Conclusions

Evidence from the first NMA suggests there may be some clinical advantages associated with DC as an alternative approach to the EC and SBTS approaches for adequately selected patients with malignant large bowel obstruction.
Unconventional Imaging: introduction to the feature issue
Authors: Liu Jung-Ping , Cheng Chau-Jern , Hayasaki Yoshio , Tanida Jun , Tsang Peter W. M.
Published: March 2021

This feature issue of Applied Optics is dedicated to the international meeting of Information Photonics 2020 (IP’20), which was held September 11–12, 2020, in Taipei, Taiwan. IP’20 covered a broad range of topics, including advanced display techniques, optical computing, and optical storage. This feature issue, however, limits topics to unconventional imaging techniques, such as digital holography, artificial-intelligence associated imaging, compressive imaging, and single-pixel imaging.
Imaging of electron transition and bond breaking in the photodissociation of H2+ via ultrafast X-ray photoelectron diffraction
Authors: Sun Zhaopeng , Yao Hongbin , Ren Xianghe , Liu Yunquan , Wang Dehua , Zhao Wenkai , Wang Chunyang , Yang Chuanlu
Published: March 2021

We theoretically investigate the photodissociation dynamics of H

2
+

using the methodology of ultrafast X-ray photoelectron diffraction (UXPD). We use a femtosecond infrared pulse to prompt a coherent excitation from the molecular vibrational state (v = 9) of the electronic ground state (1sσ
g
) and then adopt another time-delayed attosecond X-ray pulse to probe the dynamical properties. We have calculated photoionization momentum distributions by solving the non-Born-Oppenheimer time-dependent Schrödinger equation (TDSE). We unambiguously identify the phenomena associated with the g − u symmetry breakdown in the time-resolved photoelectron diffraction spectra. Using the two-center interference model, we can determine the variation in nuclear spacing with high accuracy. In addition, we use a strong field approximation (SFA) model to interpret the UXPD profile, and the SFA simulations can reproduce the TDSE results in a quantitative way.
Efficient microwave-to-optical single-photon conversion with a single flying circular Rydberg atom
Authors: Liu Yu-Guo , Xia Keyu , Zhu Shi-Liang
Published: March 2021

We propose a scheme for converting a microwave (mw) single photon in a mw cavity to a flying optical photon. The conversion is realized by using a flying circular Rydberg atom, which plays a role of the “data bus” as an excellent memory to connect the mw and optical cavities. To link the energy levels of atom in optical domain and mw domain, we use fast decircularization method and three-photon Raman transition method. Thank to these low loss processes and the super long lifetime of circular Rydberg states, this scheme can efficiently convert single mw photons into the optical domain. Based on existing experiments and data, the conversion efficiency is simulated as 60%. The theoretical limit of the conversion efficiency is about 87%.
Influence of polarization directions of the IR+XUV two-color laser fields on angle-resolved photoelectron energy spectrum
Authors: Jin Facheng , Yang Huihui , Zhang Hongdan , Wang Bingbing , Yang Weifeng
Published: March 2021

By employing the frequency-domain theory, we investigate the influence of polarization directions on angle-resolved photoelectron energy spectrum in the above-threshold ionization (ATI) process of atoms exposed to the IR+XUV two-color laser fields, which shows the multiplateau structures. When the ionized electron is emitted along the IR laser’s polarization direction, the width of each plateau keeps a certain energy range, and the jet structures and main lobes are determined by both the emission angle relative to the polarization direction of the XUV laser field and the number of the XUV photons absorbed by the electron. While when the ionized electron is emitted along the XUV laser’s polarization direction, the width of each plateau depends on the polarization direction of the IR laser field, and the angular distribution of the ionized electron exhibits the isotropic characteristics. These results show that the ATI spectrum may be effectively controlled by changing the angle between the two laser fields’ polarization directions.
Plasmonic optical trapping of nanoparticles using T-shaped copper nanoantennas
Authors: Li Rengang , Zhao Yaqian , Li Ruyang , Liu Haiwei , Ge Yuan , Xu Zhe
Published: March 2021

We demonstrate the optical trapping of single dielectric nanoparticles in a microfluidic chamber using a coupled T-shaped copper plasmonic nanoantenna for studying light–matter interaction. The nanoantenna is composed of two identical copper elements separated by a 50 nm gap and each element is designed with two nanoblocks. Our nanoantenna inherits three different advantages compared to previous plasmonic nanoantennas, which are usually made of gold. First, copper is a very promising plasmonic material with its very similar optical properties as gold. Second, copper is comparably cheap, which is compatible with industry-standard fabrication processes and has been widely used in microelectronics. Third, the trapping area of tweezers is expanded due to the intrinsic Fabry–Perot cavity with two parallel surfaces. We present finite element method simulations of the near-field distribution and photothermal effects. And we perform Maxwell stress tensor simulations of optical forces exerted on an individual nanoparticle in the vicinity of the nanoantenna. In addition, we examine how the existence of an oxide layer of cupric oxide and the heat sink substrate influence the optical trapping properties of copper nanoantennas. This work demonstrates that the coupled T-shaped copper nanoantennas are a promising means as optical nanotweezers to trap single nanoparticles in solution, opening up a new route for nanophotonic devices in optical information processing and on-chip biological sensing.
Ghost-induced exact degeneracies
Authors: Debnath Sanjay , Khan Emroz , Narimanov Evgenii E.
Published: March 2021

We show that ghost waves—a special class of nonuniform waves in biaxial dielectric media—can lead to exact frequency degeneracies in guided modes. These degeneracies offer a new way of controlling mode interactions with a broad range of potential applications, from integrated waveguides to nonlinear optics and optical sensing.
Enantioselection and chiral sorting of single microspheres using optical pulling forces
Authors: Ali Rfaqat , Dutra R. S. , Pinheiro F. A. , Maia Neto P. A.
Published: March 2021

We put forward a novel, twofold scheme that enables, at the same time, all-optical enantioselection and sorting of single multipolar chiral microspheres based on optical pulling forces exerted by two non-collinear, non-structured, circularly polarized light sources. Our chiral resolution method can be externally controlled by varying the angle between their incident wavevectors, allowing for fine-tuning of the range of chiral indices for enantioselection. Enantioselectivity is achieved by choosing angles such that only particles with the same handedness of the light sources are pulled. This proposal allows one to achieve all-optical sorting of chiral microspheres with arbitrarily small chiral parameters, thus outperforming current optical methods.
Phase retrieval using 3D Fourier transforms of volume diffraction pattern
Authors: Pedrini Giancarlo , Claus Daniel
Published: March 2021

In this Letter, we describe a method for retrieving the phase of a wavefield from a volume diffraction pattern. We show at first that the magnitude of the 3D Fourier transform of a diffracted volume wavefield is concentrated around a paraboloid. For the phase retrieval, we apply iteratively the constraints of the measured intensity and the paraboloid (sparsity) constraint in the 3D Fourier domain. Experimental validations and comparisons to other methods are presented.
Using image data to numerically correct the jitter in polarization depth encoding PS-OCT
Authors: Liu Xinyu , Jiang Liqin , Ke Mengyuan , Schmetterer Leopold , Barathi Veluchamy Amutha
Published: March 2021

In swept source polarization depth encoding polarization sensitive optical coherence tomography (PS-OCT), the laser jitter induces additional noise to the polarization sensitive measurement. In this Letter, we developed a numerical algorithm to correct the jitter phases based on the image data using the Mueller matrix calculus. The algorithm was demonstrated on in vivo retina imaging of a guinea pig with a custom-built PS-OCT system. The performance of the proposed algorithm was almost comparable to the conventional method of using a physical calibration signal. By not requiring a hardware generated calibration signal and

k

-clock, the proposed algorithm is useful to reduce the complexity and the cost of a polarization depth encoding PS-OCT system.
Electro-optic comb pumped optical parametric oscillator with flexible repetition rate at GHz level
Authors: Ye Hanyu , Freysz Valerian , Bello-Doua Ramatou , Pontagnier Lilia , Santarelli Giorgio , Cormier Eric , Freysz Eric
Published: March 2021

We present a gigahertz (GHz)-repetition-rate optical parametric oscillator (OPO) pumped by an electro-optic comb at 1.03 µm, delivering sub-picosecond signal pulses across 1.5–1.7 µm from a MgO-doped periodically poled

L
i
N
b

O

3

crystal. Using a pump power of 5 W at 14.2 GHz repetition rate, 378 mW of signal power is obtained at 1.52 µm from a subharmonic cavity, corresponding to a signal extraction efficiency of 7.6%. By cascading a Mach–Zehnder modulator, the pump pulse repetition rate can be divided by any integer number from one to 14, allowing the OPO to operate with a flexible repetition rate from 1 to 14.2 GHz. A strategy leading to quasi-continuous repetition rate tunability of the OPO is also discussed.
Sprouty2 positively regulates T cell function and airway inflammation through regulation of CSK and LCK kinases
Authors: Sripada Anand , Sirohi Kapil , Michalec Lidia , Guo Lei , McKay Jerome T. , Yadav Sangya , Verma Mukesh , Good James , Rollins Donald , Gorska Magdalena M. , Alam Rafeul
Published: March 2021

The function of Sprouty2 (Spry2) in T cells is unknown. Using 2 different (inducible and T cell–targeted) knockout mouse strains, we found that Spry2 positively regulated extracellular signal-regulated kinase 1/2 (ERK1/2) signaling by modulating the activity of LCK. Spry2−/−CD4+T cells were unable to activate LCK, proliferate, differentiate into T helper cells, or produce cytokines. Spry2 deficiency abrogated type 2 inflammation and airway hyperreactivity in a murine model of asthma. Spry2 expression was higher in blood and airway CD4+T cells from patients with asthma, and Spry2 knockdown impaired human T cell proliferation and cytokine production. Spry2 deficiency up-regulated the lipid raft protein caveolin-1, enhanced its interaction with CSK, and increased CSK interaction with LCK, culminating in augmented inhibitory phosphorylation of LCK. Knockdown of CSK or dislodgment of caveolin-1–bound CSK restored ERK1/2 activation in Spry2−/−T cells, suggesting an essential role for Spry2 in LCK activation and T cell function.
Protein sequence optimization with a pairwise decomposable penalty for buried unsatisfied hydrogen bonds
Authors: Coventry Brian , Baker David
Published: March 2021

In aqueous solution, polar groups make hydrogen bonds with water, and hence burial of such groups in the interior of a protein is unfavorable unless the loss of hydrogen bonds with water is compensated by formation of new ones with other protein groups. For this reason, buried “unsatisfied” polar groups making no hydrogen bonds are very rare in proteins. Efficiently representing the energetic cost of unsatisfied hydrogen bonds with a pairwise-decomposable energy term during protein design is challenging since whether or not a group is satisfied depends on all of its neighbors. Here we describe a method for assigning a pairwise-decomposable energy to sidechain rotamers such that following combinatorial sidechain packing, buried unsaturated polar atoms are penalized. The penalty can be any quadratic function of the number of unsatisfied polar groups, and can be computed very rapidly. We show that inclusion of this term in Rosetta sidechain packing calculations substantially reduces the number of buried unsatisfied polar groups.
BARcode DEmixing through Non-negative Spatial Regression (BarDensr)
Authors: Chen Shuonan , Loper Jackson , Chen Xiaoyin , Vaughan Alex , Zador Anthony M. , Paninski Liam
Published: March 2021

Modern spatial transcriptomics methods can target thousands of different types of RNA transcripts in a single slice of tissue. Many biological applications demand a high spatial density of transcripts relative to the imaging resolution, leading to partial mixing of transcript rolonies in many voxels; unfortunately, current analysis methods do not perform robustly in this highly-mixed setting. Here we develop a new analysis approach, BARcode DEmixing through Non-negative Spatial Regression (BarDensr): we start with a generative model of the physical process that leads to the observed image data and then apply sparse convex optimization methods to estimate the underlying (demixed) rolony densities. We apply BarDensr to simulated and real data and find that it achieves state of the art signal recovery, particularly in densely-labeled regions or data with low spatial resolution. Finally, BarDensr is fast and parallelizable. We provide open-source code as well as an implementation for the ‘NeuroCAAS’ cloud platform.
A multiscale model via single-cell transcriptomics reveals robust patterning mechanisms during early mammalian embryo development
Authors: Cang Zixuan , Wang Yangyang , Wang Qixuan , Cho Ken W. Y. , Holmes William , Nie Qing
Published: March 2021

During early mammalian embryo development, a small number of cells make robust fate decisions at particular spatial locations in a tight time window to form inner cell mass (ICM), and later epiblast (Epi) and primitive endoderm (PE). While recent single-cell transcriptomics data allows scrutinization of heterogeneity of individual cells, consistent spatial and temporal mechanisms the early embryo utilize to robustly form the Epi/PE layers from ICM remain elusive. Here we build a multiscale three-dimensional model for mammalian embryo to recapitulate the observed patterning process from zygote to late blastocyst. By integrating the spatiotemporal information reconstructed from multiple single-cell transcriptomic datasets, the data-informed modeling analysis suggests two major processes critical to the formation of Epi/PE layers: a selective cell-cell adhesion mechanism (via EphA4/EphrinB2) for fate-location coordination and a temporal attenuation mechanism of cell signaling (via Fgf). Spatial imaging data and distinct subsets of single-cell gene expression data are then used to validate the predictions. Together, our study provides a multiscale framework that incorporates single-cell gene expression datasets to analyze gene regulations, cell-cell communications, and physical interactions among cells in complex geometries at single-cell resolution, with direct application to late-stage development of embryogenesis.
Thermodynamic and sequential characteristics of phase separation and droplet formation for an intrinsically disordered region/protein ensemble
Authors: Chu Wen-Ting , Wang Jin
Published: March 2021

Liquid–liquid phase separation (LLPS) of some IDPs/IDRs can lead to the formation of the membraneless organelles in vitro and in vivo, which are essential for many biological processes in the cell. Here we select three different IDR segments of chaperon Swc5 and develop a polymeric slab model at the residue-level. By performing the molecular dynamics simulations, LLPS can be observed at low temperatures even without charge interactions and disappear at high temperatures. Both the sequence length and the charge pattern of the Swc5 segments can influence the critical temperature of LLPS. The results suggest that the effects of the electrostatic interactions on the LLPS behaviors can change significantly with the ratios and distributions of the charged residues, especially the sequence charge decoration (SCD) values. In addition, three different forms of swc conformation can be distinguished on the phase diagram, which is different from the conventional behavior of the free IDP/IDR. Both the packed form (the condensed-phase) and the dispersed form (the dilute-phase) of swc chains are found to be coexisted when LLPS occurs. They change to the fully-spread form at high temperatures. These findings will be helpful for the investigation of the IDP/IDR ensemble behaviors as well as the fundamental mechanism of the LLPS process in bio-systems.
Force variability is mostly not motor noise: Theoretical implications for motor control
Authors: Nagamori Akira , Laine Christopher M. , Loeb Gerald E. , Valero-Cuevas Francisco J.
Published: March 2021

Variability in muscle force is a hallmark of healthy and pathological human behavior. Predominant theories of sensorimotor control assume ‘motor noise’ leads to force variability and its ‘signal dependence’ (variability in muscle force whose amplitude increases with intensity of neural drive). Here, we demonstrate that the two proposed mechanisms for motor noise (i.e. the stochastic nature of motor unit discharge and unfused tetanic contraction) cannot account for the majority of force variability nor for its signal dependence. We do so by considering three previously underappreciated but physiologically important features of a population of motor units: 1) fusion of motor unit twitches, 2) coupling among motoneuron discharge rate, cross-bridge dynamics, and muscle mechanics, and 3) a series-elastic element to account for the aponeurosis and tendon. These results argue strongly against the idea that force variability and the resulting kinematic variability are generated primarily by ‘motor noise.’ Rather, they underscore the importance of variability arising from properties of control strategies embodied through distributed sensorimotor systems. As such, our study provides a critical path toward developing theories and models of sensorimotor control that provide a physiologically valid and clinically useful understanding of healthy and pathologic force variability.
Complementary phase responses via functional differentiation of dual negative feedback loops
Authors: Uriu Koichiro , Tei Hajime
Published: March 2021

Multiple feedback loops are often found in gene regulations for various cellular functions. In mammalian circadian clocks, oscillations ofPeriod1(Per1) andPeriod2(Per2) expression are caused by interacting negative feedback loops (NFLs) whose protein products with similar molecular functions repress each other. However,Per1expression peaks earlier thanPer2in the pacemaker tissue, raising the question of whether the peak time difference reflects their different dynamical functions. Here, we address this question by analyzing phase responses of the circadian clock caused by light-induced transcription of bothPer1andPer2mRNAs. Through mathematical analyses of dual NFLs, we show that phase advance is mainly driven by light inputs to the repressor with an earlier expression peak asPer1, whereas phase delay is driven by the other repressor with a later peak asPer2. Due to the complementary contributions to phase responses, the ratio of light-induced transcription rates betweenPer1andPer2determines the magnitude and direction of phase shifts at each time of day. Specifically, strongerPer1light induction thanPer2results in a phase response curve (PRC) with a larger phase advance zone than delay zone as observed in rats and hamsters, whereas strongerPer2induction causes a larger delay zone as observed in mice. Furthermore, the ratio of light-induced transcription rates required for entrainment is determined by the relation between the circadian and light-dark periods. Namely, if the autonomous period of a circadian clock is longer than the light-dark period, a larger light-induced transcription rate ofPer1thanPer2is required for entrainment, and vice versa. In short, the time difference betweenPer1andPer2expression peaks can differentiate their dynamical functions. The resultant complementary contributions to phase responses can determine entrainability of the circadian clock to the light-dark cycle.
A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes’ interactions points to Neutrophil extracellular traps as mediators of thrombosis in COVID-19
Authors: Ding Jun , Hostallero David Earl , El Khili Mohamed Reda , Fonseca Gregory Joseph , Milette Simon , Noorah Nuzha , Guay-Belzile Myriam , Spicer Jonathan , Daneshtalab Noriko , Sirois Martin , Tremblay Karine , Emad Amin , Rousseau Simon
Published: March 2021

Abnormal coagulation and an increased risk of thrombosis are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis in severe COVID-19 in children and adults. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic and metabolic disorders.
The evolutionary origin of the universal distribution of mutation fitness effect
Authors: Barlukova Ayuna , Rouzine Igor M.
Published: March 2021

An intriguing fact long defying explanation is the observation of a universal exponential distribution of beneficial mutations in fitness effect for different microorganisms. To explain this effect, we use a population model including mutation, directional selection, linkage, and genetic drift. The multiple-mutation regime of adaptation at large population sizes (traveling wave regime) is considered. We demonstrate analytically and by simulation that, regardless of the inherent distribution of mutation fitness effect across genomic sites, an exponential distribution of fitness effects emerges in the long term. This result follows from the exponential statistics of the frequency of the less-fit alleles,f, that we predict to evolve, in the long term, for both polymorphic and monomorphic sites. We map the logarithmic slope of the distribution onto the previously derived fixation probability and demonstrate that it increases linearly in time. Our results demonstrate a striking difference between the distribution of fitness effects observed experimentally for naturally occurring mutations, and the "inherent" distribution obtained in a directed-mutagenesis experiment, which can have any shape depending on the organism. Based on these results, we develop a new method to measure the fitness effect of mutations for each variable residue using DNA sequences sampled from adapting populations. This new method is not sensitive to linkage effects and does not require the one-site model assumptions.
The role of livestock movements in the spread of Rift Valley fever virus in animals and humans in Mayotte, 2018–19
Authors: Kim Younjung , Métras Raphaëlle , Dommergues Laure , Youssouffi Chouanibou , Combo Soihibou , Le Godais Gilles , Pfeiffer Dirk U. , Cêtre-Sossah Catherine , Cardinale Eric , Filleul Laurent , Youssouf Hassani , Subiros Marion , Fournié Guillaume
Published: March 2021

Rift Valley fever (RVF) is a vector-borne viral disease of major animal and public health importance. In 2018–19, it caused an epidemic in both livestock and human populations of the island of Mayotte. Using Bayesian modelling approaches, we assessed the spatio-temporal pattern of RVF virus (RVFV) infection in livestock and human populations across the island, and factors shaping it. First, we assessed if (i) livestock movements, (ii) spatial proximity from communes with infected animals, and (iii) livestock density were associated with the temporal sequence of RVFV introduction into Mayotte communes’ livestock populations. Second, we assessed whether the rate of human infection was associated with (a) spatial proximity from and (b) livestock density of communes with infected animals. Our analyses showed that the temporal sequence of RVFV introduction into communes’ livestock populations was associated with livestock movements and spatial proximity from communes with infected animals, with livestock movements being associated with the best model fit. Moreover, the pattern of human cases was associated with their spatial proximity from communes with infected animals, with the risk of human infection sharply increasing if livestock in the same or close communes were infected. This study highlights the importance of understanding livestock movement networks in informing the design of risk-based RVF surveillance programs.
The effect of human mobility and control measures on traffic safety during COVID-19 pandemic
Authors: Zhang Jie , Feng Baoheng , Wu Yina , Xu Pengpeng , Ke Ruimin , Dong Ni
Published: March 2021

As mobile device location data become increasingly available, new analyses are revealing the significant changes of mobility pattern when an unplanned event happened. With different control policies from local and state government, the COVID-19 outbreak has dramatically changed mobility behavior in affected cities. This study has been investigating the impact of COVID-19 on the number of people involved in crashes accounting for the intensity of different control measures using Negative Binomial (NB) method. Based on a comprehensive dataset of people involved in crashes aggregated in New York City during January 1, 2020 to May 24, 2020, people involved in crashes with respect to travel behavior, traffic characteristics and socio-demographic characteristics are found. The results show that the average person miles traveled on the main traffic mode per person per day, percentage of work trip have positive effect on person involved in crashes. On the contrary, unemployment rate and inflation rate have negative effects on person involved in crashes. Interestingly, different level of control policies during COVID-19 outbreak are closely associated with safety awareness, driving and travel behavior, and thus has an indirect influence on the frequency of crashes. Comparing to other three control policies including emergence declare, limits on mass gatherings, and ban on all nonessential gathering, the negative relationship between stay-at-home policy implemented in New York City from March 20, 2020 and the number of people involved crashes is found in our study.
Deuterium-depletion has no significant impact on the mutation rate of Escherichia coli, deuterium abundance therefore has a probabilistic, not deterministic effect on spontaneous mutagenesis
Authors: Ajibola Walliyulahi , Karcagi Ildikó , Somlyai Gábor , Somlyai Ildikó , Fehér Tamás
Published: March 2021

Deuterium (D), the second most abundant isotope of hydrogen is present in natural waters at an approximate concentration of 145–155 ppm (ca. 1.5E-4 atom/atom). D is known to influence various biological processes due to its physical and chemical properties, which significantly differ from those of hydrogen. For example, increasing D-concentration to >1000-fold above its natural abundance has been shown to increase the frequency of genetic mutations in several species. An interesting deterministic hypothesis, formulated with the intent of explaining the mechanism of D-mutagenicity is based on the calculation that the theoretical probability of base pairs to comprise two adjacent D-bridges instead of H-bridges is 2.3E-8, which is equal to the mutation rate of certain species. To experimentally challenge this hypothesis, and to infer the mutagenicity of D present at natural concentrations, we investigated the effect of a nearly 100-fold reduction of D concentration on the bacterial mutation rate. Using fluctuation tests, we measured the mutation rate of threeEscherichia coligenes (cycA,ackAandgalK) in media containing D at either <2 ppm or 150 ppm concentrations. Out of 15 pair-wise fluctuation analyses, nine indicated a significant decrease, while three marked the significant increase of the mutation/culture value upon D-depletion. Overall, growth in D-depleted minimal medium led to a geometric mean of 0.663-fold (95% confidence interval: 0.483–0.911) change in the mutation rate. This falls nowhere near the expected 10,000-fold reduction, indicating that in our bacterial systems, the effect of D abundance on the formation of point mutations is not deterministic. In addition, the combined results did not display a statistically significant change in the mutation/culture value, the mutation rate or the mutant frequency upon D-depletion. The potential mutagenic effect of D present at natural concentrations onE.coliis therefore below the limit of detection using the indicated methods.
Variety-seeking, learning and performance
Authors: Cattani Gino , Kim Ji-hyun
Published: March 2021

According to thevariance hypothesis, variety-seeking or exploration is a critical condition for improving learning and performance over time. Extant computational learning models support this hypothesis by showing how individuals who are exposed to diverse knowledge sources are more likely to find superior solutions to a particular problem. Yet this research provides no precise guidelines about how broadly individuals should search. Our goal in this paper is to elucidate the conditions under which variety-seeking in organizations is beneficial. To this end, we developed a computational model in which individuals learn as they interact with other individuals, and update their knowledge as a result of this interaction. The model reveals how the type of learning environment (performance landscape) in which the learning dynamic unfolds determines when the benefits of variety-seeking outweigh the costs. Variety-seeking is performance-enhancing only when the knowledge of the chosen learning targets (i.e., individuals to learn from) provide useful information about the features of the performance landscape. The results further suggest that superior knowledge might be available locally, i.e., in the proximity of an individual’s current location. We also identify the point beyond which variety-seeking causes a sharp performance decline and show how this point depends on the type of landscape in which the learning dynamic unfolds and the degree of specialization of individual knowledge. The presence of this critical point explains why exploration becomes very costly. The implications of our findings for establishing the boundaries of exploration are discussed.
Impact of different dietary fat sources on blood pressure in Chinese adults
Authors: Liu Qiaoling
Published: March 2021

Objectives

To investigate the association between the source of dietary fat and blood pressure for Chinese people aged between 30–59 with the aim of elucidating methods of hypertension prevention.

Design

Prospective cohort study using national survey data.

Participants

1,104 adults aged between 30–59 with normal blood pressures in 2006 were included in the study. Adults with history of prehypertension, hypertension, or were taking hypertension drugs in 2006 were excluded. Participants with implausibly high or low daily total energy intakes (<600 kcal/d or >5000 kcal/d) were excluded. Pregnant women, breastfeeding women, and people with motor impairment were excluded.

Results

People with abnormal blood pressure ingested a lower percent of dietary fat taken from seafood (P< 0.001) and a higher percent of dietary fat taken from fast food (P< 0.001). Dietary fat obtained from seafood and dairy products can be protective against abnormal blood pressure with a RR = 0.01 (95% CI: 0.001 to 0.25;P= 0.004) for seafood, and RR = 0.14 (95% CI: 0.04 to 0.44;P= 0.001) for egg, milk, and dairy products.

Conclusion

Seafood, egg, milk, and dairy products can be recommended as sources of dietary fat to reduce the incidence of hypertension and prehypertension while fast food should be avoided.