bluuebunny/crossref_metadata_2025 huggingface dataset:
Design of a sparse array for a one-dimensional non-uniform optical phased array
Authors: Du Kunyang , Wang Rui , Guo Jin , Jiang Ruitao , Kan Dongbin , Zhang Yaoyuan
Published: February 2022

To effectively improve the far-field scanning range of an optical phased array (OPA), we propose a genetic algorithm using double fitness functions to optimize the array element arrangement of a one-dimensional non-uniform OPA and simulate a one-dimensional OPA with different array element numbers. The results show that the non-uniform OPA with more array elements exhibits an improved grating lobe suppression effect, and the optimized antenna array pattern exhibits improved comprehensive performance upon employing the double fitness function of grating lobe suppression and beam steering. Considering 128 array elements as an example, the sidemode suppression ratio (SMSR) exhibits a 2.8-dB improvement in the steering process, which verifies the importance of incorporating the novel fitness function of steering optimization. In addition, we further analyze the influence of manufacturing errors such as emission intensity and array position on the SMSR; it is found that the OPA obtained by simulation is sufficiently robust. Our research lays a theoretical foundation for the development of a one-dimensional non-uniform OPA sparse array.
Λ-enhanced gray molasses in a tetrahedral laser beam geometry
Authors: Barker D. S. , Norrgard E. B. , Klimov N. N. , Fedchak J. A. , Scherschligt J. , Eckel S.
Published: February 2022

We report the observation of sub-Doppler cooling of lithium using an
irregular-tetrahedral laser beam arrangement, which is produced by a
nanofabricated diffraction grating. We are able to capture 11(2)%
of the lithium atoms from a grating magneto-optical trap into
Λ-enhanced D1 gray molasses. The
molasses cools the captured atoms to a radial temperature of 60(9)
μK and an axial temperature of 23(3) μK. In contrast to results
from conventional counterpropagating beam configurations, we do not
observe cooling when our optical fields are detuned from Raman
resonance. An optical Bloch equation simulation of the cooling
dynamics agrees with our data. Our results show that grating
magneto-optical traps can serve as a robust source of cold atoms for
tweezer-array and atom-chip experiments, even when the atomic species
is not amenable to sub-Doppler cooling in bright optical molasses.
Optimized multilayer structure for sensitive THz characterization of thin-film glucose solutions
Authors: Ding Xuefei , Hernandez-Serrano A. I. , Lindley-Hatcher Hannah , Stantchev Rayko I. , Zhou Jun , Pickwell-MacPherson Emma
Published: February 2022

Terahertz time-domain spectroscopy (THz-TDS) has shown promise in biomedical sample characterization and high characterization sensitivity is in demand due to the thin-film (TF) feature of the sample. This paper proposes an optimized multilayer structure for sensitive characterization of TF aqueous solutions in reflection THz-TDS. Theoretical simulations are conducted for structural optimization and the 75 µm window-sample-mirror structure displays the best sensitivity compared to other sandwich structures and traditional THz measurement geometries. 0-20% TF glucose solutions are then measured; and a spectral peak introduced by the proposed structure is observed to result in the high sensitivity. Our work provides a new way of customizing multilayer structure for THz thin-film characterization.
Experimental investigation in nodal aberration theory (NAT): separation of astigmatic figure error from misalignments in a Cassegrain telescope
Authors: Karcı Özgür , Yeşiltepe Meltem , Arpa Eray , Wu Yuchen , Ekinci Mustafa , Rolland Jannick P.
Published: February 2022

We present simulations and experimental validations for separating astigmatic figure error from misalignments in Nodal Aberration Theory (NAT) with a high-precision Cassegrain telescope. Both the primary mirror figure error and the secondary mirror misalignments induce binodal astigmatism for the telescope systems. The separation of these two aberration factors plays a crucial role in the telescope alignment process. In this study, the figure error of the aspheric primary mirror of the Cassegrain telescope induced by the mirror mounts was measured interferometrically utilizing a computer-generated hologram (CGH). According to the primary mirror figure error, the astigmatic node locations in the image plane were simulated using real raytracing. The center of the nodes was located on the field center, and the nodes were placed symmetrically with respect to the field center in the image plane. The telescope's alignment was performed using the simulation results, and the node locations were measured on a grid of field points interferometrically. Thereafter, secondary mirror misalignments around the coma-free pivot point were introduced into the optical system, and the node's center was shifted from the field center in the image plane as predicted by NAT. The simulations and interferometric field measurements were performed and compared on a grid of field points for the misaligned state in the presence of primary mirror figure error. The experimental results confirm the predictions from NAT. Statistical analysis was also performed to confirm the accuracy and stability of the measurements.
Controllable perfect optical vortex generated by complex amplitude encoding
Authors: Yang Rui , Jiang Xiaotong , Yu Junjie , Han Jing , Li Zhigang , Zhang Dengying , Shi Qiang , Zhu Linwei
Published: February 2022

We propose a new paradigm for generating the perfect optical vortex (POV) with a controlled structure and orbital angular momentum (OAM) distribution in the focal region of a tightly focused system. The superiority of the proposed technique is demonstrated with an experiment involving the dynamic manipulation of small particles. This technique for creating the POV could open new routes to optical manipulation based on OAM.
Faraday isolator based on crystalline silicon for 2-µm laser radiation
Authors: Snetkov Ilya , Yakovlev Alexey
Published: February 2022

The magneto-optical properties of single-crystal silicon were investigated as a function of wavelength and temperature. A bulk free-space traditional Faraday isolator for the radiation with a wavelength of 1940 nm (magnetic field ∼2.8 Т) was implemented. The negative value of the piezo-optical anisotropy ratio of the used material allowed for the development of a Faraday isolator with compensation of thermally induced depolarization without a reciprocal rotator. The potential of single-crystal silicon as a magneto-optical material for Faraday isolators operating at room as well as at cryogenic temperatures in high-power laser radiation was considered. It was shown that single-crystal silicon is highly promising for the development of Faraday devices, including ones for next-generation laser interferometers aimed at detecting gravitational waves.
Timing jitter reduction of silicon hybrid harmonically mode-locked ring laser using an integrated sampled-grating DBR
Authors: Shekarpour Mohammad , Yavari Mohammad Hasan
Published: February 2022

An integrated sampled-grating silicon hybrid mode-locked ring laser is proposed for 20-GHz super-mode noise suppression. The dynamics, phase noise, and timing jitter are investigated using a delay differential equation (DDE) model. The results show that the 20-GHz harmonic regime of the proposed structure is significantly increased when the sampled-grating structure is included. Additionally, a better selectivity of the optical modes by a sampled-grating distributed Bragg reflector (SGDBR) leads to more suppression of super-mode noise compared to the long-ring structures with a spectral filter which were previously reported. Compared to previous works, the phase noise is improved by approximately 6 dB and the timing jitter is decreased to less than a third.
>10 GHz femtosecond fiber laser system at 2.0 μm
Authors: Liang Zhaoheng , Lin Wei , Wu Jingfeng , Chen Xuewen , Guo Yuankai , Ling Lin , Wei Xiaoming , Yang Zhongmin
Published: February 2022

We demonstrate a high-power 2.0-μm fiber laser system delivering femtosecond pulses with a fundamental repetition rate of >10 GHz, the highest value so far, to the best of our knowledge. The seed is a self-started fundamentally mode-locked Tm-doped fiber laser that has excellent power and spectral stabilities. The laser system can provide an average power of >600 mW, and the use of soliton-effect-based pulse compression allows the achievement of a pulse duration of 163 fs, leading to a compression factor of ∼ 13. It is anticipated that this new high-power femtosecond fiber laser with a 10-GHz-level fundamental repetition rate can serve as a promising light source for various applications, including laser surgery, micromachining, frequency comb spectroscopy, and nonlinear frequency conversion.
Optical random micro-phase-shift DropConnect in a diffractive deep neural network
Authors: Xiao Yong-Liang , Li Sikun , Situ Guohai , Zhong Jianxin
Published: February 2022

The formulation and training of unitary neural networks is the basis of
an active modulation diffractive deep neural network. In this Letter,
an optical random phase DropConnect is implemented on an optical
weight to manipulate a jillion of optical connections in the form of
massively parallel sub-networks, in which a micro-phase assumed as an
essential ingredient is drilled into Bernoulli holes to enable
training convergence, and malposed deflections of the geometrical
phase ray are reformulated constantly in epochs, allowing for
enhancement of statistical inference. Optically, the random
micro-phase-shift acts like a random phase sparse griddle with respect
to values and positions, and is operated in the optical path of a
projective imaging system. We investigate the performance of the
full-drilling and part-drilling phenomena. In general, random
micro-phase-shift part-drilling outperforms its full-drilling
counterpart both in the training and inference since there are more
possible recombinations of geometrical ray deflections induced by
random phase DropConnect.
Integrating two epsilon-near-zero materials into planar multilayer metamaterial structure for broadband near-perfect mid-IR absorption
Authors: Almossalami Hossam A. , Liang Sen , Zheng Jun , Ye Hui
Published: February 2022

Absorptive metamaterials composed of antimony-doped-germanium of different epsilon-near-zero wavelengths and germanium films are designed and fabricated for broadband perfect light absorption around the epsilon-near-zero wavelengths. By integrating two bilayers separated by a semiconductor spacer into a metamaterial structure backed by substrate and gold thick ground plane, we realize more than 93% P-polarized light absorption over a wavelength range of 1.8 microns for an angle of incidence of 40° and a flat-top 75% absorption over a wideband of 1.74 microns for an angle of incidence of 50° in the middle wave infrared region.
Optical Fiber: Through the Looking Glass
Authors: Ballato John
Published: February 2022

The UN International Year of Glass, celebrated throughout 2022,
offers an opportunity to reflect on the enabling role of glass in fiber
optics—and on their entangled futures.
Averaging approaches for highly accurate image-based edge localization
Authors: Aslani Valese , Guerra Flavio , Steinitz Adriana , Wilhelm Philipp , Haist Tobias
Published: February 2022

We introduce an optical and a digital averaging technique that considerably improves edge localization performance. Especially for high quality images, the optical method achieves measurement uncertainties down to levels of millipixels. The approach uses an optical replication scheme based on a computer-generated hologram to reduce noise and discretization errors. The second method is based on a neural network denoising architecture and is especially suited for high levels of photon noise. Edge localization can be improved by up to 60% while preserving high lateral and temporal resolution. The methods are first tested using high quality images obtained by a scientific CMOS sensor imaging a razor blade mounted on a mechanical stage. Then, the laboratory results are tested for larger distances to validate the methods for building deformation measurements.
Real-time X-ray phase-contrast imaging using SPINNet—a speckle-based phase-contrast imaging neural network
Authors: Qiao Zhi , Shi Xianbo , Yao Yudong , Wojcik Michael J. , Rebuffi Luca , Cherukara Mathew J. , Assoufid Lahsen
Published: February 2022

X-ray phase-contrast imaging has become indispensable for visualizing samples with low absorption contrast. In this regard, speckle-based techniques have shown significant advantages in spatial resolution, phase sensitivity, and implementation flexibility compared with traditional methods. However, the computational cost associated with data inversion has hindered their wider adoption. By exploiting the power of deep learning, we developed a speckle-based phase-contrast imaging neural network (SPINNet) that significantly improves the imaging quality and boosts the phase retrieval speed by at least 2 orders of magnitude compared to existing methods. To achieve this performance, we combined SPINNet with a coded-mask-based technique, an enhanced version of the speckle-based method. Using this scheme, we demonstrate the simultaneous reconstruction of absorption and phase images on the order of 100 ms, where a traditional correlation-based analysis would take several minutes even with a cluster. In addition to significant improvement in speed, our experimental results show that the imaging and phase retrieval quality of SPINNet outperform existing single-shot speckle-based methods. Furthermore, we successfully demonstrate SPINNet application in x-ray optics metrology and 3D x-ray phase-contrast tomography. Our result shows that SPINNet could enable many applications requiring high-resolution and fast data acquisition and processing, such as in situ and in operando 2D and 3D phase-contrast imaging and real-time at-wavelength metrology and wavefront sensing.
Characterising metabolomic signatures of lipid-modifying therapies through drug target mendelian randomisation
Authors: Richardson Tom G. , Leyden Genevieve M. , Wang Qin , Bell Joshua A. , Elsworth Benjamin , Davey Smith George , Holmes Michael V.
Published: February 2022

Large-scale molecular profiling and genotyping provide a unique opportunity to systematically compare the genetically predicted effects of therapeutic targets on the human metabolome. We firstly constructed genetic risk scores for 8 drug targets on the basis that they primarily modify low-density lipoprotein (LDL) cholesterol (HMGCR, PCKS9, and NPC1L1), high-density lipoprotein (HDL) cholesterol (CETP), or triglycerides (APOC3, ANGPTL3, ANGPTL4, and LPL). Conducting mendelian randomisation (MR) provided strong evidence of an effect of drug-based genetic scores on coronary artery disease (CAD) risk with the exception of ANGPTL3. We then systematically estimated the effects of each score on 249 metabolic traits derived using blood samples from an unprecedented sample size of up to 115,082 UK Biobank participants. Genetically predicted effects were generally consistent among drug targets, which were intended to modify the same lipoprotein lipid trait. For example, the linear fit for the MR estimates on all 249 metabolic traits for genetically predicted inhibition of LDL cholesterol lowering targets HMGCR and PCSK9 was r2 = 0.91. In contrast, comparisons between drug classes that were designed to modify discrete lipoprotein traits typically had very different effects on metabolic signatures (for instance, HMGCR versus each of the 4 triglyceride targets all had r2 < 0.02). Furthermore, we highlight this discrepancy for specific metabolic traits, for example, finding that LDL cholesterol lowering therapies typically had a weak effect on glycoprotein acetyls, a marker of inflammation, whereas triglyceride modifying therapies assessed provided evidence of a strong effect on lowering levels of this inflammatory biomarker. Our findings indicate that genetically predicted perturbations of these drug targets on the blood metabolome can drastically differ, despite largely consistent effects on risk of CAD, with potential implications for biomarkers in clinical development and measuring treatment response.
Predicting drug polypharmacology from cell morphology readouts using variational autoencoder latent space arithmetic
Authors: Chow Yuen Ler , Singh Shantanu , Carpenter Anne E. , Way Gregory P.
Published: February 2022

A variational autoencoder (VAE) is a machine learning algorithm, useful for generating a compressed and interpretable latent space. These representations have been generated from various biomedical data types and can be used to produce realistic-looking simulated data. However, standard vanilla VAEs suffer from entangled and uninformative latent spaces, which can be mitigated using other types of VAEs such as β-VAE and MMD-VAE. In this project, we evaluated the ability of VAEs to learn cell morphology characteristics derived from cell images. We trained and evaluated these three VAE variants—Vanilla VAE, β-VAE, and MMD-VAE—on cell morphology readouts and explored the generative capacity of each model to predict compound polypharmacology (the interactions of a drug with more than one target) using an approach called latent space arithmetic (LSA). To test the generalizability of the strategy, we also trained these VAEs using gene expression data of the same compound perturbations and found that gene expression provides complementary information. We found that the β-VAE and MMD-VAE disentangle morphology signals and reveal a more interpretable latent space. We reliably simulated morphology and gene expression readouts from certain compounds thereby predicting cell states perturbed with compounds of known polypharmacology. Inferring cell state for specific drug mechanisms could aid researchers in developing and identifying targeted therapeutics and categorizing off-target effects in the future.
IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data
Authors: Heydari Tiam , A. Langley Matthew , Fisher Cynthia L. , Aguilar-Hidalgo Daniel , Shukla Shreya , Yachie-Kinoshita Ayako , Hughes Michael , M. McNagny Kelly , Zandstra Peter W.
Published: February 2022

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs allow simulation of fundamental hypotheses governing developmental programs and help accelerate the design of strategies to control stem cell fate. We first describe the architecture of IQCELL. Next, we apply IQCELL to scRNA-seq datasets from early mouse T-cell and red blood cell development, and show that the platform can infer overall over 74% of causal gene interactions previously reported from decades of research. We will also show that dynamic simulations of the generated GRN qualitatively recapitulate the effects of known gene perturbations. Finally, we implement an IQCELL gene selection pipeline that allows us to identify candidate genes, without prior knowledge. We demonstrate that GRN simulations based on the inferred set yield results similar to the original curated lists. In summary, the IQCELL platform offers a versatile tool to infer, simulate, and study executable GRNs in dynamic biological systems.
Separable roles for RNAi in regulation of transposable elements and viability in the fission yeast Schizosaccharomyces japonicus
Authors: Chapman Elliott , Taglini Francesca , Bayne Elizabeth H.
Published: February 2022

RNA interference (RNAi) is a conserved mechanism of small RNA-mediated genome regulation commonly involved in suppression of transposable elements (TEs) through both post-transcriptional silencing, and transcriptional repression via heterochromatin assembly. The fission yeast Schizosaccharomyces pombe has been extensively utilised as a model for studying RNAi pathways. However, this species is somewhat atypical in that TEs are not major targets of RNAi, and instead small RNAs correspond primarily to non-coding pericentromeric repeat sequences, reflecting a specialised role for the pathway in promoting heterochromatin assembly in these regions. In contrast, in the related fission yeast Schizosaccharomyces japonicus, sequenced small RNAs correspond primarily to TEs. This suggests there may be fundamental differences in the operation of RNAi pathways in these two related species. To investigate these differences, we probed RNAi function in S. japonicus. Unexpectedly, and in contrast to S. pombe, we found that RNAi is essential in this species. Moreover, viability of RNAi mutants can be rescued by mutations implicated in enhancing RNAi-independent heterochromatin propagation. These rescued strains retain heterochromatic marks on TE sequences, but exhibit derepression of TEs at the post-transcriptional level. Our findings indicate that S. japonicus retains the ancestral role of RNAi in facilitating suppression of TEs via both post-transcriptional silencing and heterochromatin assembly, with specifically the heterochromatin pathway being essential for viability, likely due to a function in genome maintenance. The specialised role of RNAi in heterochromatin assembly in S. pombe appears to be a derived state that emerged after the divergence of S. japonicus.
Effects of socioeconomic factors and booking time on the WHO recommended eight antenatal care contacts in Liberia
Authors: Ekholuenetale Michael , Nzoputam Chimezie Igwegbe , Barrow Amadou
Published: February 2022

Antenatal care (ANC) is an important intervention that has been linked to reduce maternal and newborn adverse outcomes. However, the long years of war in Liberia may have contributed to the poor health indices including the uptake of maternal health care services. The objective of this study was to determine the marginal interaction effects between booking time and socioeconomic factors in eight or more ANC contacts. A total sample of 4,185 women who had given birth were included in this study. The 2020 Liberia Demographic and Health Survey (LDHS) dataset was analyzed. The outcome variable was eight or more ANC contacts. Percentage and Chi-square test were used in univariate and bivariate analyses respectively. The marginal interaction effects between booking time and socioeconomic factors of eight or more ANC contacts were estimated. The statistical significance was determined at 5%. The weighted prevalence of eight or more ANC contacts was 26.6% (95% CI: 23.8%, 29.6%). The uptake of eight or more ANC contacts increased steadily by increasing women’s level of education and household wealth index. Women with higher educational attainment had a prevalence of 49.0% (95%CI: 36.5%, 61.6%) and those in the richest households had an estimated prevalence of 31.4% (95%CI: 24.9%, 38.8%) respectively. Furthermore, the urban dwellers had a weighted eight or more ANC contacts prevalence of 29.0% (95%CI: 24.6%, 34.0%). The key finding is increased marginal interaction effects for higher education and early booking (48.4%), richest households and early booking (35.4%), and urban residential status and early booking (36.2%) respectively. Overall, the prevalence of eight or more ANC contacts was low. However, we found higher coverage of eight or more ANC contacts among women who initiated ANC within the first trimester and among those with higher socioeconomic status. We recommend the Liberian government to design and/or support programmes targeted at promoting early ANC initiation and supporting the disadvantaged women such as the uneducated, poor and those living in rural or remote settings.
The relationship between congenital heart disease and cancer in Swedish children: A population-based cohort study
Authors: Kampitsi Christina-Evmorfia , Mogensen Hanna , Feychting Maria , Tettamanti Giorgio
Published: February 2022

Background

Birth defects have been consistently associated with elevated childhood cancer risks; however, the relationship between congenital heart disease (CHD) and childhood cancer remains conflicting. Considering the increasing patient population with CHD after improvements in their life expectancies, insights into this relationship are particularly compelling. Thus, we aimed to determine the relationship between CHD and cancer in Swedish children.

Methods and findings

All individuals registered in the Swedish Medical Birth Register (MBR) between 1973 and 2014 were included in this population–based cohort study (n = 4,178,722). Individuals with CHD (n = 66,892) were identified from the MBR and National Patient Register, whereas cancer diagnoses were retrieved from the Swedish Cancer Register. The relationship between CHD and childhood cancer (<20 years at diagnosis) was evaluated using Cox proportional hazards regression models. We observed increased risks of cancer overall, leukemia, lymphoma, and hepatoblastoma in children with CHD, but after adjustment for Down syndrome, only the increased lymphoma (hazard ratio (HR) = 1.64, 95% confidence interval (CI) 1.11 to 2.44) and hepatoblastoma (HR = 3.94, 95% CI 1.83 to 8.47) risk remained. However, when restricting to CHD diagnoses from the MBR only, i.e., those diagnosed around birth, the risk for childhood cancer overall (HR = 1.45, 95% CI 1.23 to 1.71) and leukemia (HR = 1.41, 95% CI 1.08 to 1.84) was more pronounced, even after controlling for Down syndrome. Finally, a substantially elevated lymphoma risk (HR = 8.13, 95% CI 4.06 to 16.30) was observed in children with complex CHD. Limitations of the study include the National Patient Register not being nationwide until 1987, in addition to the rareness of the conditions under study providing limited power for analyses on the rarer cancer subtypes.

Conclusions

We found associations between CHD and childhood lymphomas and hepatoblastomas not explained by a diagnosis of Down syndrome. Stronger associations were observed in complex CHD.
Intuition, reflection, and prosociality: Evidence from a field experiment
Authors: Grehl Sascha , Tutić Andreas
Published: February 2022

Are humans instinctively good or is it only our capacity for reflection that enables us to restrain our selfish traits and behave prosocially? Against the background of dual-process theory, the question of whether people tend to behave prosocially on intuitive grounds has been debated controversially for several years. Central to this debate is the so-called social heuristic hypothesis (SHH), which states that subjects orient their behavior more closely to their deeply ingrained norms and attitudes when the behavior comes about in an intuitive rather than reflective manner. In this paper, we apply the SHH to a novel setting and investigate whether its implications hold true in a non-reactive field experiment, in which subjects are unaware that they are part of a study. We test whether subjects report a misdirected email or try to use the opportunity to reap a monetary benefit. Since all subjects participated six months prior to the field experiment in a lab experiment, we have solid measures of the subjects’ general tendency to behave intuitively and their prosocial attitudes. In addition, participants were asked in a follow-up survey to self-report their intuitiveness at the time of the decision. While we observe a significant and positive effect on prosocial behavior for self-reported intuitiveness (but not for general intuitiveness) in the bivariate analyses, this effect becomes insignificant when controlling for interaction effects with attitudes. In addition, for both forms of intuitiveness, we find a significant and positive interaction effect with subjects’ prosocial attitudes on prosocial behavior. Hence, this study confirms previous findings from laboratory as well as online studies and provides external validity by demonstrating that the SHH applies in a real-life situation.
Subcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial
Authors: Branch-Elliman Westyn , Ferguson Ryan , Doros Gheorghe , Woods Patricia , Leatherman Sarah , Strymish Judith , Datta Rupak , Goswami Rekha , Jankowich Matthew D. , Shah Nishant R. , Taylor Thomas H. , Page Sarah T. , Schiller Sara J. , Shannon Colleen , Hau Cynthia , Flynn Maura , Holmberg Erika , Visnaw Karen , Dhond Rupali , Brophy Mary , Monach Paul A.
Published: February 2022

Importance and objective

The aim of this pragmatic, embedded, adaptive trial was to measure the effectiveness of the subcutaneous anti-IL-6R antibody sarilumab, when added to an evolving standard of care (SOC), for clinical management of inpatients with moderate to severe COVID-19 disease.

Design

Two-arm, randomized, open-label controlled trial comparing SOC alone to SOC plus sarilumab. The trial used a randomized play-the-winner design and was fully embedded within the electronic health record (EHR) system.

Setting

5 VA Medical Centers.

Participants

Hospitalized patients with clinical criteria for moderate to severe COVID-19 but not requiring mechanical ventilation, and a diagnostic test positive for SARS-CoV-2.

Interventions

Sarilumab, 200 or 400 mg subcutaneous injection. SOC was not pre-specified and could vary over time, e.g., to include antiviral or other anti-inflammatory drugs.

Main outcomes and measures

The primary outcome was intubation or death within 14 days of randomization. All data were extracted remotely from the EHR.

Results

Among 162 eligible patients, 53 consented, and 50 were evaluated for the primary endpoint of intubation or death. This occurred in 5/20 and 1/30 of participants in the sarilumab and SOC arms respectively, with the majority occurring in the initial 9 participants (3/4 in the sarilumab and 1/5 in the SOC) before the sarilumab dose was increased to 400 mg and before remdesivir and dexamethasone were widely adopted. After interim review, the unblinded Data Monitoring Committee recommended that the study be stopped due to concern for safety: a high probability that rates of intubation or death were higher with addition of sarilumab to SOC (92.6%), and a very low probability (3.4%) that sarilumab would be found to be superior.

Conclusions and relevance

This randomized trial of patients hospitalized due to respiratory compromise from COVID-19 but not mechanical ventilation found no benefit from subcutaneous sarilumab when added to an evolving SOC. The numbers of patients and events were too low to allow definitive conclusions to be drawn, but this study contributes valuable information about the role of subcutaneous IL-6R inhibition in the treatment of hospitalized COVID-19 patients. Methods developed and piloted during this trial will be useful in conducting future studies more efficiently.

Trial registration

Clinicaltrials.gov—NCT04359901; https://clinicaltrials.gov/ct2/show/NCT04359901?cond=NCT04359901&draw=2&rank=1.
Sex-specific and concentration-dependent influence of Cremophor RH 40 on ampicillin absorption via its effect on intestinal membrane transporters in rats
Authors: Yin Heyue , Shao Haibin , Liu Jing , Qin Yujia , Deng Wenbin
Published: February 2022

Pharmaceutical excipients are the basic materials and important components of pharmaceutical preparations, and play an important role in improving the efficacy of drugs and reducing adverse reactions. Therefore, selecting suitable excipients for dosage form is an important step in formulation development. An increasing number of studies have revealed that the traditionally regarded "inert" excipients can, however, influence the bioavailability of drugs. Moreover, these effects on the bioavailability of drugs caused by pharmaceutical excipients may differ in between males and females. In this study, the in situ effect of the widely-used pharmaceutical excipient Cremophor RH 40 spanning from 0.001% to 0.1% on the intestinal absorption of ampicillin in male and female rats using closed-loop models was investigated. Cremophor RH 40 ranging from 0.03% to 0.07% increased the absorption of ampicillin in females, however, was decreased in male rats. The mechanism of such an effect on drug absorption is suggested to be due to the interaction between Cremophor RH 40 and two main membrane transporters P-gp and PepT1. Cremophor RH 40 altered the PepT1 protein content in a sex-dependent manner, showing an increase in female rats but a decrease in males. No modification on the PepT1 mRNA abundance was found with Cremophor RH 40, indicating that the excipient may regulate the protein recruitment of the plasma membrane from the preformed cytoplasm pool to alter the PepT1 function. This influence, however, may differ between males and females. As such, the study herein shows that supposedly inert excipient Cremophor RH 40 can influence membrane fluidity, uptake and efflux transporters in a sex- and concentration-dependent manner. These findings, therefore, highlight the need for sex-specific studies in the application of solubilizing excipients in drug formulation development.
Spatial distribution and determinant factors of intimate partner violence among reproductive age group women in Ethiopia: Using generalized structural equation modeling
Authors: Tusa Biruk Shalmeno , Kebede Sewnet Adem , Weldesenbet Adisu Birhanu
Published: February 2022

Introduction

Intimate Partner Violence (IPV) is the most serious and pervasive yet under-recognized human rights violation in the world, particularly in Ethiopia. Hence, the objective of this study was to find the spatial distribution of IPV and its determinant factors in Ethiopia.

Methods

Secondary data analysis was conducted among 2,687 reproductive age group women (15–49 years). The distribution of IPV across the country was observed by ArcGIS software. In SaTScan software, the Bernoulli model was fitted by Kulldorff methods to identify the purely spatial clusters of IPV. Besides, Generalized Structural Equation Model (GSEM) was used to determine factors associated with each domain of IPV (physical, emotional & sexual violence).

Result

The spatial distribution of IPV was found to be clustered in Ethiopia with Global Moran’s I 0.09 (p < 0.001), and the highest IPV cluster was observed in Oromia (p < 0.001), Somali (p < 0.001) and SNNP (p<0.001) regions. Watching television and not having attitudes toward wife beating were negatively associated with physical violence. Being rich and nonsmoker were inversely associated with emotional violence. The odds of experiencing sexual violence were high among pregnant women and wives of uneducated husbands/partners. In addition, women’s decision-making autonomy and husband/partner drinking alcohol have positive and negative associations with all domains of IPV respectively.

Conclusion

There was a significant clustering of IPV in Ethiopia and the highest IPV cluster was observed in Oromia, Somali and SNNP regions. Being rich, watching television, not having attitudes toward wife beating, women’s decision-making autonomy, and husband’s/partner’s high education and non-alcohol drinker status were negatively associated with IPV. The likelihood of experiencing IPV was also high among smokers and pregnant women. Thus, we recommend that improving the economic status of the household through social protection and empowerment of women in decision-making autonomy by education and employment and increasing community awareness about the consequences of IPV with particular emphasis on Oromia, Somali and SNNP regions is essential.
How large of a grant size is appropriate? Evidence from the National Natural Science Foundation of China
Authors: Duan Peixin
Published: February 2022

Under the current universal trend towards larger grant sizes in research funding systems, we focus on how large of a grant size is appropriate. We study the directional returns to scale (RTS) to assess whether current grant sizes are the most productive. We take the General Program of the National Natural Science Foundation of China (NSFC) as an example and select three samples of physics, geography and management for an empirical study. We find that the optimal input direction and the most productive grant size scale is different for the three disciplines; based on the current grant size, physics should not expand the grant size and team size input, geography should further increase the grant size to improve performance and management should further expand the team size rather than the grant size. In this paper, we demonstrate a new method to calculate the optimal direction, which is the lowest rate of congestion, according to the characteristics of the General Program. Based on these results, we also calculate the most productive scale size. This method has certain value for project management.
Quantification of the calcium signaling deficit in muscles devoid of triadin
Authors: Manno Carlo , Tammineni Eshwar , Figueroa Lourdes , Marty Isabelle , Ríos Eduardo
Published: February 2022

Triadin, a protein of the sarcoplasmic reticulum (SR) of striated muscles, anchors the calcium-storing protein calsequestrin to calcium release RyR channels at the junction with t-tubules, and modulates these channels by conformational effects. Triadin ablation induces structural SR changes and alters the expression of other proteins. Here we quantify alterations of calcium signaling in single skeletal myofibers of constitutive triadin-null mice. We find higher resting cytosolic and lower SR-luminal [Ca2+], 40% lower calsequestrin expression, and more CaV1.1, RyR1 and SERCA1. Despite the increased CaV1.1, the mobile intramembrane charge was reduced by ~20% in Triadin-null fibers. The initial peak of calcium release flux by pulse depolarization was minimally altered in the null fibers (revealing an increase in peak calcium permeability). The “hump” phase that followed, attributable to calcium detaching from calsequestrin, was 25% lower, a smaller change than expected from the reduced calsequestrin content and calcium saturation. The exponential decay rate of calcium transients was 25% higher, consistent with the higher SERCA1 content. Recovery of calcium flux after a depleting depolarization was faster in triadin-null myofibers, consistent with the increased uptake rate and lower SR calsequestrin content. In sum, the triadin knockout determines an increased RyR1 channel openness, which depletes the SR, a substantial loss of calsequestrin and gains in other couplon proteins. Powerful functional compensations ensue: activation of SOCE that increases [Ca2+]cyto; increased SERCA1 activity, which limits the decrease in [Ca2+]SRand a restoration of SR calcium storage of unknown substrate. Together, they effectively limit the functional loss in skeletal muscles.
The perceptions of different professionals on school absenteeism and the role of school health care: A focus group study conducted in Finland
Authors: Melander Katja , Kortteisto Tiina , Hermanson Elina , Kaltiala Riittakerttu , Mäki-Kokkila Katariina , Kaila Minna , Kosola Silja
Published: February 2022

Purpose of the study

School absenteeism and school dropout jeopardize the future health and wellbeing of students. Reports on the participation of school health care in absenteeism reduction are infrequent, although physical and mental health problems are the most common causes of school absenteeism. Our aim was to explore what reasons different professionals working in schools recognize for absenteeism and which factors either promote or inhibit the inclusion of school health care in absenteeism reduction.

Materials and methods

Data for this qualitative study was gathered from ten focus groups conducted in two municipalities in southern Finland. The groups included (vice) principals, special education/resource/subject teachers, guidance counselors, school social workers, school psychologists, school nurses, school doctors, and social workers working in child protective services. Data analysis was predominantly inductive but the categorization of our results was based on existing literature.

Results

Study participants identified student-, family-, and school-related reasons for absenteeism but societal reasons went unmentioned. A number of reasons promoting the inclusion of school health care in absenteeism reduction arose, such as expertise in health-related issues and the confidentiality associated with health care. Inclusion of school health care was hindered by differences in work culture and differing perceptions regarding the aims of school health care.

Conclusion

Professionals working in schools were knowledgeable about the different causes of school absenteeism. Clarifying both the aims of school health care and the work culture of different professionals could facilitate the inclusion of school health care in absenteeism reduction.
Genome-wide analysis of sucrose synthase family in soybean and their expression in response to abiotic stress and seed development
Authors: Ahmad Muhammad Zulfiqar , Ahmad Hafiz Ishfaq , Gul Asma , Shah Zamarud , Ahmad Bushra , Ahmed Shakeel , Al-Ghamdi Abdullah Ahmed , S. Elshikh Mohamed , Jamil Arshad , Nasir Jamal Abdul , Dvořáčková Helena , Dvořáček Jan
Published: February 2022

The sucrose synthase (SS) is an important enzyme family which play a vital role in sugar metabolism to improve the fruit quality of the plants. In many plant species, the members of SS family have been investigated but the detailed information is not available in legumes particularly and Glycine max specifically. In the present study, we found thirteen SS members (GmSS1-GmSS13) in G. max genome. High conserved regions were present in the GmSS sequences that may due to the selection pressure during evolutionary events. The segmental duplication was the major factor to increase the number of GmSS family members. The identified thirteen GmSS genes were divided into Class I, Class II and Class III with variable numbers of genes in each class. The protein interaction of GmSS gave the co-expression of sucrose synthase with glucose-1-phosphate adenylyltransferase while SLAC and REL test found number of positive sites in the coding sequences of SS family members. All the GmSS family members except GmSS7 and few of class III members, were highly expressed in all the soybean tissues. The expression of the class I members decreased during seed development, whireas, the class II members expression increased during the seed developing, may involve in sugar metabolism during seed development. Solexa sequencing libraries of acidic condition (pH 4.2) stress samples showed that the expression of class I GmSS genes increased 1- to 2-folds in treated samples than control. The differential expression pattern was observed between the members of a paralogous. This study provides detailed genome-wide analysis of GmSS family in soybean that will provide new insights for future evolutionary and soybean breeding to improve the plant growth and development.
Suvorexant and mirtazapine improve chronic pain-related changes in parameters of sleep and voluntary physical performance in mice with sciatic nerve ligation
Authors: Ito Hisakatsu , Tsuneki Hiroshi , Sasaoka Toshiyasu , Toyooka Naoki , Matsuo Mitsuhiro , Yamazaki Mitsuaki
Published: February 2022

Both chronic pain and sleep disorders are associated with a reduction in the quality of life. They can be both a cause and a consequence of each other, and should therefore be simultaneously treated. However, optimal treatments for chronic pain-related sleep disorders are not well established. Here, we aimed to investigate the effects of suvorexant, a novel sleep drug, and mirtazapine, a noradrenergic and specific serotonergic antidepressant, on pain-related changes in sleep parameters in a preclinical chronic pain mice model, by partial sciatic nerve ligation. We evaluated the quantity, duration, and depth of sleep by analyzing the electroencephalogram and voluntary activity by counting the number of wheel rotations to determine various symptoms of sleep disorders, including reduced total sleep time, fragmentation, low quality, and impaired activity in the daytime. Suvorexant and mirtazapine normalized the reduction in sleep time and fragmented sleep, further regaining the sleep depth at sleep onset in the chronic pain state in nerve-ligated mice. Mirtazapine also increased the percentage of rapid eye movement sleep in mice. Suvorexant decreased voluntary activity, which was prolonged after administration; however, mirtazapine did not decrease it. Although the effects of suvorexant and mirtazapine on sleep and activity are different, both suvorexant and mirtazapine could be potential therapeutic agents for chronic pain-related sleep disorders.
Prevalence of chronic kidney disease stages 3–5 in low- and middle-income countries in Asia: A systematic review and meta-analysis
Authors: Suriyong Pongpan , Ruengorn Chidchanok , Shayakul Chairat , Anantachoti Puree , Kanjanarat Penkarn
Published: February 2022

Chronic kidney disease (CKD) is a major public health problem in low- and middle-income countries (LMICs). Although CKD prevalence has been rapidly increasing in LMICs, particularly in Asia, quantitative studies on the current epidemiology of CKD in this region are limited. This study aimed to identify the prevalence of CKD stages 3–5 in LMICs in Asia, by subregion, country economy classification, identification of CKD, traditional and non-traditional risk factors. A systematic review and meta-analysis of observational studies was conducted through a literature search of seven electronic databases and grey literature search published until November 2021. The Newcastle-Ottawa quality assessment scale (NOS) was used to assess the risk of bias of each study. A random-effects model was used to estimate pooled prevalence. The protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO CRD42019120519). Of 4,548 potentially relevant records, 110 studies with moderate and high quality were included with 4,760,147 subjects. The average prevalence (95% CI) of CKD stages 3–5 in 14 LMICs in Asia was 11.2% (9.3–13.2%). The prevalence of CKD stages 3–5 was varied among subregions and country economic classification. CKD prevalence was 8.6% (7.2–10.2%) in east Asia, 12.0% (7.7–17.0%) in south-east Asia, 13.1% (8.7–18.2%) in western Asia, and 13.5% (9.5–18.0%) in south Asia. CKD prevalence was 9.8% (8.3–11.5%) in upper-middle-income countries and 13.8% (9.9–18.3%) in lower-middle-income countries. Prevalence of CKD stage 3–5 in LMICs in Asia is comparable to global prevalence. High level of heterogeneity was observed. Study of factors and interventions that lead to the delay of CKD progression is needed.
Influence of interaction of cerebral fluids on ventricular deformation: A mathematical approach
Authors: Valova Galina , Bogomyakova Olga , Tulupov Andrey , Cherevko Alexander
Published: February 2022

This paper describes the effects of the interaction of cerebral fluids (arterial, capillary and venous blood, cerebrospinal fluid) on ventricular wall displacement and periventricular pressure using a mathematical multiphase poroelasticity model for the cerebral parenchyma. The interaction of cerebral fluids is given by a set of four numerical coefficients. A multiple linear regression with interaction is constructed that allows us to quantify the effect of these coefficients on the average ventricular wall displacement. The prevailing influence of an arterial-liquor component was observed. The sets of coefficients associated with such pathological conditions were found: normal pressure hydrocephalus, intracranial hypertension, and replacement ventriculomegaly under a prolonged hypoperfusion.