bluuebunny/crossref_metadata_2025 huggingface dataset:
Entry of antiepileptic drugs (valproate and lamotrigine) into the developing rat brain
Authors: Toll Samuel J. , Qiu Fiona , Huang Yifan , Habgood Mark D. , Dziegielewska Katarzyna M. , Nie Shuai , Saunders Norman R.
Published: July 2021

Background: Women with epilepsy face difficult choices whether to continue antiepileptic drug treatment during pregnancy, as uncontrolled seizures carry great risk to mother and fetus but continuing treatment may have adverse effects on baby’s development. This study aimed at evaluating antiepileptic drug entry into developing brain.

Methods: Anaesthetised pregnant, non-pregnant adult females, postnatal and fetal rats were injected intraperitoneally with different doses, single or in combinations, of valproate and lamotrigine, within clinical range. Injectate included 3H-labelled drug. After 30min, CSF, blood and brain samples were obtained; radioactivity measured using liquid scintillation counting. Some animals were also exposed to valproate in feed throughout pregnancy and into neonatal period. Drug levels measured by liquid chromatography coupled to mass spectrometry (LC-MS). Results given as CSF or tissue/plasma% as index of drug entry.

Results: Entry of valproate into brain and CSF was higher at E19 and P4 compared to adult and was dose-dependent except at E19; placental transfer increased significantly at highest dose of 100mg/kg. Lamotrigine entry into the brain was dose dependent only at E19. Chronic valproate treatment, or combination of valproate and lamotrigine had little effect on either drug entry, except for reduced valproate brain entry in adult brain with chronic treatment. Placental transfer decreased significantly after chronic valproate treatment. LC-MS measurement of valproate in adults confirmed that rat plasma values were within the clinical range and CSF/plasma and brain/plasma ratios for LC-MS and 3H-valproate were similar.

Conclusion: Results suggest that entry of valproate may be higher in developing brain, the capacity of barrier mechanism is mostly unaffected by doses within the clinical range, with or without addition of lamotrigine. Chronic valproate exposure may result in upregulation in cellular mechanisms restricting its entry into the brain. Entry of lamotrigine was little different at different ages and was not dose dependent.
Rapid detection of herpes simplex virus 2: a SYBR-Green-based real-time PCR assay
Authors: Shaha Modhusudon , Roy Bithi , Islam Mohammad Ariful
Published: July 2021

The prevalence of Herpes simplex virus 2 (HSV2) is increasing at an alarming rate in the world. Most of the HSV2 cases are not diagnosed properly, although a range of molecular and serological diagnoses exist. Herein, we have reported a very rapid detection method specific for HSV2 using real-time PCR. The primers specific for HSV2 were designed using the Primer-BLAST tool and 120 base pairs of the polymerase gene were amplified using real-time PCR with SYBR Green dye. The designed primer pair was found highly efficient in detecting only HSV2 DNA, but not HSV1. The threshold cycle (Ct) value for HSV2 reactions by designed primers was found to be an average of 22.55 for a standard copy number of viral DNA that may denote the efficiency of the primers. The melting temperature (Tm) of the amplicon using designed primers (82.60C) was also higher than that using reference primers (about 780C), indicating the high GC content of the amplified template. The designed primer pair will help clinicians to detect the HSV2 DNA specifically and diagnose the associated disease rapidly.
Evaluation of the convalescent plasma therapy effectiveness and the factors that influence the therapeutic outcome in hospitalized COVID-19 patients: A retrospective cohort study.
Authors: Ibadi Zainab , Assad Hayder , Fawzi Hayder
Published: July 2021

Background: As an effective antiviral therapy is not available for the treatment of the current rapidly and continuously spreading coronavirus disease (COVID-19), it is very crucial to find an alternative treatment strategy. Convalescent plasma (CP) therapy has been used for prevention and treatment of many emerging infectious diseases, however, the results of current studies on CP in COVID-19 are not consistent. Therefore, this study aimed to evaluate the effectiveness of CP therapy in hospitalized patients with COVID-19, while evaluating patient and donor-related factors that might influence the therapeutic outcome. Methods: We conducted a retrospective cohort study on 312 patients with either severe or critical COVID-19, who were admitted to Al-Hakeem and Al-Amal hospitals in Al-Najaf city, Iraq from June to August 2020.  The patients were allocated to either the plasma therapy group (152 patients) who received CP combined with standard therapy or the standard therapy group (160 patients). The outcome measures were the 21-day mortality rate and time to clinical improvement. Results: The overall cumulative survival rate was significantly higher in patients who received CP compared to standard therapy alone at 21 days (68.3% vs. 46.8%, p-value = 0.010), with mean survival at 17.6 vs. 15.3 days, (p-value = 0.010). In multivariate analysis, the plasma therapy effect was an independent predictor of survival (adjusted hazard ratio, 95% confidence interval: 0.368, 0.177 – 0.765). In terms of clinical improvement, the use of CP resulted in shorter clinical improvement (median duration of improvement: 8 vs. 11 days, p-value = 0.007), with 74.3% improvement rate after 21 days in CP compared to 65.0% in standard therapy. Conclusions: Therapy with CP in combination with standard therapy, independently improved survival in hospitalized patient with severe or critical COVID-19.
Long-term effect of full-body pulsed electromagnetic field and exercise protocol in the treatment of men with osteopenia or osteoporosis: A randomized placebo-controlled trial
Authors: Ebid Anwar , El-boshy Mohamed , El-Shamy Shamekh , Thabet Ali , Abedalla Mohamed , Ali Tariq
Published: July 2021

Background: Osteoporosis is the most prevalent metabolic disease affecting bones. Objective: To investigate the long-term effect of pulsed electromagnetic field (PEMF) combined with exercise protocol on bone mineral density (BMD) and bone markers in men with osteopenia or osteoporosis. Methods: Ninety-five males with osteopenia or osteoporosis (mean age, 51.26 ± 2.41 years; mean height, 176 ± 2.02 cm; mean weight, 83.08 ± 2.60 kg; mean body–mass index (BMI), 26.08 ± 1.09 kg/m2) participated in the study, and they were randomly assigned to one of three groups: Group 1 received a full-body PEMF and exercise protocol (PEMF +EX), Group 2 received a placebo full-body PEMF and exercise protocol (PPEMF +EX), and Group 3 received a full-body PEMF alone (PEMF). PEMF was applied for the whole body using a full-body mat three times per week for 12 weeks, with an exercise protocol that includes flexibility, aerobic exercise, strengthening, weight-bearing, and balance exercises followed by whole-body vibration (WBV) training. Outcome measures include BMD of total hip and lumbar spine and bone markers [serum osteocalcin (s-OC), Serum amino-terminal cross-linking telopeptide of type I collagen (s-NTX), Serum carboxy-terminal cross-linking telopeptide of type I collagen (s-CTX), Parathyroid hormones (PTH), Bone-specific Alkaline Phosphatase (BSAP), and 25-hydroxy vitamin D (Vit D)]. Results: The BMD of total hip and lumbar spine was significantly increased post-treatment in all groups, and more so in Group 1 and Group 2 than Group 3. There was a significant difference in bone markers in all groups, more so in Group 1 and Group 2 than in Group 3. Conclusion: PEMF combined with exercise protocol exerts a potent role for treating OP, is more effective than exercise and PEMF alone for increasing BMD and enhancing bone formation, and suppresses bone-resorption markers after 12-weeks of treatment with the impact lasting up to 6 months.
RNfuzzyApp: an R shiny RNA-seq data analysis app for visualisation, differential expression analysis, time-series clustering and enrichment analysis
Authors: Haering Margaux , Habermann Bianca H
Published: July 2021

RNA sequencing (RNA-seq) is a widely adopted affordable method for large scale gene expression profiling. However, user-friendly and versatile tools for wet-lab biologists to analyse RNA-seq data beyond standard analyses such as differential expression, are rare. Especially, the analysis of time-series data is difficult for wet-lab biologists lacking advanced computational training. Furthermore, most meta-analysis tools are tailored for model organisms and not easily adaptable to other species.

With RNfuzzyApp, we provide a user-friendly, web-based R shiny app for differential expression analysis, as well as time-series analysis of RNA-seq data. RNfuzzyApp offers several methods for normalization and differential expression analysis of RNA-seq data, providing easy-to-use toolboxes, interactive plots and downloadable results. For time-series analysis, RNfuzzyApp presents the first web-based, fully automated pipeline for soft clustering with the Mfuzz R package, including methods to aid in cluster number selection, cluster overlap analysis, Mfuzz loop computations, as well as cluster enrichments.

RNfuzzyApp is an intuitive, easy to use and interactive R shiny app for RNA-seq differential expression and time-series analysis, offering a rich selection of interactive plots, providing a quick overview of raw data and generating rapid analysis results. Furthermore, its orthology assignment, enrichment analysis, as well as ID conversion functions are accessible to non-model organisms.
Identifying priorities for the collection and use of data related to community first response and out-of-hospital cardiac arrest: protocol for a nominal group technique study
Authors: Keegan Dylan , Heffernan Eithne , McSharry Jenny , Barry Tomás , Masterson Siobhán
Published: July 2021

Introduction: Out-of-hospital cardiac arrest (OHCA) is a devastating health event that affects over 2000 people each year in Ireland. Survival rate is low, but immediate intervention and initiation of cardiopulmonary resuscitation (CPR) and administration of an automated external defibrillator (AED) can increase chances of survival. It is not always possible for the emergency medical services (EMS) to reach OHCA cases quickly. As such, volunteers, including lay and professional responders (e.g. off-duty paramedics and fire-fighters), trained in CPR and AED use, are mobilised by the EMS to respond locally to prehospital medical emergencies (e.g. OHCA and stroke). This is known as community first response (CFR).

Data on the impact of CFR interventions are limited. This research aims to identify the most important CFR data to collect and analyse, the most important uses of CFR data, as well as barriers and facilitators to data collection and use. This can inform policies to optimise the practice of CFR in Ireland.

Methods: The nominal group technique (NGT) is a structured consensus process where key stakeholders (e.g. CFR volunteers, clinicians, EMS personnel, and patients/relatives) develop a set of prioritised recommendations. This study will employ the NGT, incorporating an online survey and online consensus meeting, to develop a priority list for the collection and use of CFR data in Ireland. Stakeholder responses will also identify barriers and facilitators to data collection and use, as well as indicators that improvements to these processes have been achieved. The maximum sample size for the NGT will be 20 participants to ensure sufficient representation from stakeholder groups.

Discussion: This study, employing the NGT, will consult key stakeholders to establish CFR data collection, analysis, and use priorities. Results from this study will inform CFR research, practice, and policy, to improve the national CFR service model and inform international response programs.
Modeling of dangerous internal forces in the calculation by the mixed method of statically indeterminate frames with bars of a given stiffness
Authors: Sazonova Svetlana , Asminin Viktor , Zvyaginceva Alla
Published: July 2021

The features of using the mixed method for calculating internal forces in statically indeterminate frames with rods of a given stiffness are considered. The substantiation of the choice for the calculation of frames of the mixed method, methods of forces or displacements is given. The condition of equivalence of the main and the given systems is provided. The calculations took into account the mechanical meaning of the canonical equations and individual terms of the canonical equations of the mixed method. The corresponding reactions and displacements have been determined. It has been substantiated which part of the frame when calculating by the mixed method is more rational to calculate by the method of displacement, and which part by the method of forces. Used "tabular" data in the process of calculating the frame by the mixed method. If necessary, frame parts are designed to be statically determinate.
BRASH syndrome: more than just syncope
Authors: Vangipuram Divya , Nugent Kenneth
Published: July 2021

The pentad of bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia describes the BRASH syndrome, a newly recognized phenomenon in which accumulation of potassium and renally excreted atrioventricular nodal blockers cause a cycle of bradycardia, hypoperfusion, and worsening renal function. Here, we describe a case of BRASH in an elderly woman whose medications had recently changed, and who presented with bradycardia, anuria, and hypotension. Resolution of symptoms occurred over hours after the right treatment was started. Furthermore, we review case reports written in recent years for common BRASH syndrome patient characteristics.
Orbital Cellulitis in West Texas
Authors: Clarke Cameron Levi , Mitchell Kelly Thrush
Published: July 2021

Purpose: Identify the risk factors, microbiology, complications, and treatment outcomes of orbital cellulitis in West Texas
Study type: Retrospective chart review
Main findings: 46 patients over a 10-year period were treated for orbital cellulitis. The majority of patients were adult and male. The most common causative organisms were staphylococcus aureus and polymicrobial infections. Abscess formation, either subperiosteal or intraorbital, were the most common complications. The majority of patients regained normal visual acuity following resolution of the infection.
Conclusion: Prompt treatment of orbital cellulitis results in limited complications and resolution of visual loss
Hydroxyzine revealing acquired neuromuscular weakness in a patient with COVID-19 disease
Authors: Bahi Mohamed , Aissaoui Younes , Belhadj Ayoub , Qamouss Youssef , Seddiki Rachid
Published: July 2021

Acquired neuromuscular weakness often develops in patients with an acute respiratory distress syndrome (ARDS), in particular in patients who are ventilated and sedated for long periods. This has been rarely described in the literature on ARDS secondary to SARS-CoV-2 infection. Our clinical case revealed the existence of these neuromuscular manifestations in the COVID-19 disease after the use of hydroxyzine, an antihistamine whose respiratory side-effects are unknown.
Keywords: Neuromuscular weakness, COVID-19, hydroxyzine, hypercapnia.
Management of post-operative Junctional Ectopic Tachycardia in symptomatic neonates and infants at a tertiary care center in a developing country: Lessons learned!
Authors: Abohelwa Mostafa , Refaat Marwan , Gharamti Amal , Ahmed Mohamed , Elgehiny Amr , El-Rassi Issam , Bitar Fadi , Arabi Mariam
Published: July 2021

Purpose: Junctional ectopic tachycardia (JET) is an uncommon form of arrhythmia that occurs after surgical correction of congenital heart defects. Data on neonates and infants are rare. This study highlights the epidemiology, incidence, and management of neonates and infants with JET at a tertiary care center in Lebanon.
Methods: We conducted a retrospective chart review between January 1, 2013, and December 31, 2017. All Patients with documented symptomatic junctional ectopic tachycardia on electrocardiogram who required medical treatment post-surgery were included.
Results: A total of 9 patients were included. The median age was 18 days, and six were males. Six out of nine (66.67%) were successfully treated with cooling and amiodarone on the initial attempt. The other three cases failed initial treatment with adenosine. However, they were successfully treated with cooling and amiodarone as second-line therapy. All cases of junctional ectopic tachycardia occurred post-surgery at an average of 1.67 ± 1.11 days.
Conclusion: Junctional ectopic tachycardia mostly occurs after corrective cardiac surgery and can be successfully treated with cooling and amiodarone. Timely diagnosis significantly affects the outcome.
Cause of death in fatal cases associated with positive COVID-19 PCR tests
Authors: Peterson Christopher , Fanous John , Mallah Haneen , Yang Shengping , Berdine Gilbert
Published: July 2021

The response to the COVID-19 pandemic is heavily influenced by reported fatalities from the virus and, by implication, the criteria used to determine those fatalities. Given complications, such as the presence of comorbidities and limitations in testing, the World Health Organization (WHO) guidelines recommend counting both confirmed and suspected COVID-19 deaths as fatalities. While easily implementable, this method does little to indicate the degrees of certainty for a COVID-19 death, and thus concerns have arisen that this may overcount the number of COIVD-19 fatalities. In response, we developed and implemented a scoring system to determine the likelihood that COVID-19 contributed to patient death. Three reviewers independently assessed records of 47 patients who reportedly died from COVID-19. Greatest consensus was observed at the ends of the scoring spectrum, with twelve patients having complete consensus among reviewers. Intraclass correlation among the three reviewers was 0.52 (95% CI, 0.25-0.72). Middle scores had the greatest variability, possibly due to plausible alternative diagnoses, suggesting the potential for variability in death certification and the need for a scoring system that reports degrees of certainty. Although scoring rules can guide reviewers toward greater consensus about cause of death, in the absence of an objective criteria for COVID-19 disease, the determination of cause of death in paitents with positive PCR tests for SARS-CoV-2 who also have significant comorbid conditions will remain subjective.
Keywords: COVID-19; fatality; cause of death
Yes! We’re open. Open science and the future of academic practices in translation and interpreting studies
Authors: Olalla-Soler Christian
Published: July 2021

This article offers an overview of open science and open-science practices and their applications to translation and interpreting studies (TIS). Publications on open science in different disciplines were reviewed in order to define open science, identify academic publishing practices emerging from the core features of open science, and discuss the limitations of such practices in the humanities and the social sciences. The compiled information was then contextualised within TIS academic publishing practices based on bibliographic and bibliometric data. The results helped to identify what open-science practices have been adopted in TIS, what problems emerge from applying some of these practices, and in what ways such practices could be fostered in our discipline. This article aims to foster a debate on the future of TIS publishing and the role that open science will play in the discipline in the upcoming years.
Leadership Styles and Labor Market Conditions
Authors: Dur Robert , Kvaløy Ola , Schöttner Anja
Published: July 2021

Why do some leaders use praise as a means to motivate workers, whereas other leaders use social punishment? This paper develops a simple economic model to examine how leadership styles depend on the prevailing labor market conditions for workers. We show that the existence of a binding wage floor for workers (e.g., due to trade union wage bargaining, minimum wage legislation, or limited-liability protection) can make it attractive for firms to hire a leader who makes use of social punishment. Although the use of social punishments generally is socially inefficient, it lessens the need for high bonus pay, which allows the firm to extract rents from the worker. In contrast, firms hire leaders who provide praise to workers only if it is socially efficient to do so. Credible use of leadership styles requires either repeated interaction or a leader with the right social preferences. In a single-period setting, only moderately altruistic leaders use praise as a motivation tool, whereas only moderately spiteful leaders use social punishment. Lastly, we show that when the leaders’ and workers’ reservation utilities give rise to a bigger income gap between leaders and workers, attracting spiteful leaders becomes relatively less costly and unfriendly leadership becomes more prevalent.

This paper was accepted by Axel Ockenfels, behavioral economics and decision analysis.
Memory colors and the assessment of color quality in lighting applications
Authors: Babilon Sebastian , Klabes Julian , Myland Paul , Khanh Tran Quoc
Published: July 2021

Due to their potential use as an internal reference, memory colors may provide an excellent approach for the color rendition evaluation of white light sources in terms of predicting visual appreciation. Because of certain limitations in the design of existing memory-related color quality measures, a new metric based on the outcome of a series of recently conducted memory color appearance rating experiments is proposed in this work. In order to validate its predictive performance, a meta-correlation analysis on a comprehensive set of preference rating data collected from literature is performed. Results indicate that the new metric proposal outperforms established color quality measures and is capable of correctly predicting the rank order of light sources in different lighting scenarios. The future inclusion of this new metric into a comprehensive lighting quality model may serve as a valuable tool for the lighting designer to create optimally lit environments for humans that do not only support the visual task fulfillment but also increase the users’ well-being and emotional comfort by rendering the perceived space in such a way that it complies with the people’s inherent memory references.
Broadband responsivity enhancement of Si photodiodes by a plasmonic antireflection bilayer
Authors: Park Jongcheol , Kang Il-Suk , Sim Gapseop , Kim Tae Hyun , Lee Jong-Kwon
Published: July 2021

Randomly distributed plasmonic Ag nanoparticles (NPs) with various sizes were fabricated by a reflow process to an island-shaped Ag thin-film deposited on a Si photodiode. These NPs conformally enclosed by an antireflective (AR)-type SiNx/SiO2 bilayer reveal significantly diminished reflectance in a broad wavelength (500 nm - 1100 nm) as compared to the cases of Ag NPs or SiO2 layer enclosing Ag NPs on the Si substrate. Accordingly, the forward scattering and the total reflection along with wide-angle interference in between the dielectric bilayer incorporating the Ag NPs induce highly increased light absorption in the Si substrate. The fabricated Si photodiode adopting the plasmonic AR bilayer shows the responsivity peak value of 0.72 A/W at 835 nm wavelength and significant responsivity enhancement up to 40% relative to a bare Si photodiode in a wavelength range of 500 nm to 1000 nm.
Theoretical analysis of thermal-lensing effect in a high power exciplex pumped Cs vapor laser
Authors: Su Chenyi , Xu Xingqi , Huang Jinghua , Pan Bailiang
Published: July 2021

Considering the kinetic and fluid dynamic processes in the gain medium, a theoretical model is established to describe the mechanism of thermal-lensing effect in an exciplex pumped Cs vapor laser. The three-dimensional distribution of temperature and index of refraction in the gain medium are depicted. The effective focal length and radius of thermal lens are predicted. Our simulation results show the thermal lens plays a non-negligible role in high-power XPCsLs and can be significantly aggravated in higher wall temperature, buffer pressure and pump intensity. The divergence of laser beam influenced by thermal lens is also made in detail. This model is helpful for in-depth understanding of the thermal-lensing effect in XPALs.
Optical see-through augmented reality displays with wide field of view and hard-edge occlusion by using paired conical reflectors
Authors: Zhang Yan , Hu Xiaodan , Kiyokawa Kiyoshi , Isoyama Naoya , Sakata Nobuchika , Hua Hong
Published: July 2021

Optical see-through head-mounted displays are actively developed in
recent years. An appropriate method for mutual occlusion is essential
to provide a decent user experience in many application scenarios of
augmented reality. However, existing mutual occlusion methods fail to
work well with a large field of view (FOV). In this Letter, we propose
a double-parabolic-mirror structure that renders hard-edge occlusion
within a wide FOV. The parabolic mirror increases the numerical
aperture of the system significantly, and the usage of paired
parabolic mirrors eliminates most optical aberrations. A liquid
crystal on silicon device is introduced as the spatial light modulator
for imaging a bright see-through view and rendering sharp occlusion
patterns. A loop structure is built to eliminate vertical parallax.
The system is designed to obtain a maximum monocular FOV of

H

114
∘

×

V

95
∘

with hard-edge occlusion, and a FOV
of

H

83.5
∘

×

V

53.1
∘

is demonstrated with our bench-top
prototype.
Temperature-compensated distributed refractive index sensor based on an etched multi-core fiber in optical frequency domain reflectometry
Authors: Zhu Zongda , Ba Dexin , Liu Lu , Qiu Liqiang , Dong Yongkang
Published: July 2021

We proposed a temperature-compensated distributed refractive index (RI) sensor using an etched multi-core fiber (MCF) in optical frequency domain reflectometry. The MCF contains inner and outer cores and is etched until the outer core is exposed. Therefore, the outer core can be used for distributed RI sensing, and the inner core can be used for temperature compensation. The sensing length of 19 cm and the spatial resolution of 5.3 mm are achieved in the experiment. The RI sensing range is as wide as 1.33–1.44 refractive index units (RIU), and the maximum sensitivity of 47 nm/RIU is obtained around 1.44 RIU. Additionally, the temperature sensitivity is 9.8 pm/°C. Using this sensor, we successfully detected the glycerol diffusion process in water.
Lensless phase retrieval based on deep learning used in holographic data storage
Authors: Hao Jianying , Lin Xiao , Lin Yongkun , Song Haiyang , Chen Ruixian , Chen Mingyong , Wang Kun , Tan Xiaodi
Published: July 2021

This paper proposes a lensless phase retrieval method based on deep learning (DL) used in holographic data storage. By training an end-to-end convolutional neural network between the phase-encoded data pages and the corresponding near-field diffraction intensity images, the new unknown phase data page can be predicted directly from the intensity image by the network model without any iterations. The DL-based phase retrieval method has a higher storage density, lower bit-error-rate (BER), and higher data transfer rate compared to traditional iterative methods. The retrieval optical system is simple, stable, and robust to environment fluctuations which is suitable for holographic data storage. Besides, we studied and demonstrated that the DL method has a good suppression effect on the dynamic noise of the holographic data storage system.
Experimental generation of perfect optical vortices through strongly scattering media
Authors: Yuan Weiming , Xu Yi , Zheng Kanpei , Fu Songnian , Wang Yuncai , Qin Yuwen
Published: July 2021

Perfect optical vortices enable the unprecedented optical multiplexing utilizing orbital angular momentum of light, which, however, suffer from distortion when they propagate in inhomogeneous media. Herein, we report on the experimental demonstration of perfect optical vortice generation through strongly scattering media. The transmission-matrix-based point-spread-function engineering is applied to encode the targeted mask in the Fourier domain before focusing. We experimentally demonstrate the perfect optical vortice generation either through a multimode fiber or a ground glass, where the numerical results agree well with the measured one. Our results might facilitate the manipulation of orbital angular momentum of light through disordered scattering media and shed new light on the optical multiplexing utilizing perfect optical vortices.
Compact tomographic near-eye display using a MEMS scanning mirror
Authors: Kim Minkwan , Lee Seungjae , Jo Youngjin , Lee Siwoo , Lee Byoungho
Published: July 2021

We propose a compact tomographic near-eye display by combining a micro–electro–mechanical systems (MEMS) scanning mirror device, focus tunable lens, and a single light-emitting diode source. A holographic optical element was used to elaborately focus the light source into the MEMS scanning mirror while providing further miniaturization. We implemented a drastically downsized multifocal display system that expresses a depth range of 4.8 D with eight focal planes by synchronizing these modules. Furthermore, the planar images are optimized to achieve correct retinal scenes at each accommodation state. The simulated and experimental results verify that the suggested near-eye display system can provide three-dimensional virtual images while showing physical feasibility.
Ultrafast optical rotation in chiral molecules with ultrashort and tightly focused beams
Authors: Ayuso David , Ordonez Andres F. , Ivanov Misha , Smirnova Olga
Published: July 2021

Sculpting the subcycle temporal structure of optical waveforms allows one to image and even control the electronic clouds of atoms, molecules, and solids. Here, we show how the transverse spin component arising upon spatial confinement of such optical waveforms enables extremely efficient chiral recognition and control of ultrafast chiral dynamics. When an intense and ultrashort linearly polarized laser pulse is tightly focused into a medium of randomly oriented chiral molecules, the medium generates light that is elliptically polarized, with opposite helicities and opposite rotations of the polarization ellipse in media of opposite handedness. In contrast to conventional optical activity of chiral media, this new nonlinear optical activity is driven by purely electric–dipole interactions. It leads to giant enantio-sensitivity in the near VIS–UV domain, where optical instrumentation is readily available, already in optically thin media. Adding a polarizer turns the rotation of the polarization ellipse into a highly enantio-sensitive intensity of nonlinear optical response. We also show that subcycle optical control of the incident light wave enables full control over the enantio-sensitive response. The proposed all-optical method not only enables chiral discrimination with extreme enantio-efficiency, but also ultrafast imaging and control of chiral dynamics using commercially available optical technology.
Phonon dephasing and spectral diffusion of quantum emitters in hexagonal boron nitride
Authors: White Simon , Stewart Connor , Solntsev Alexander S. , Li Chi , Toth Milos , Kianinia Mehran , Aharonovich Igor
Published: July 2021

Quantum emitters in hexagonal boron nitride (hBN) are emerging as bright and robust sources of single photons for applications in quantum optics. In this work we present detailed studies on the limiting factors to achieve Fourier transform limited spectral lines. Specifically, we study phonon dephasing and spectral diffusion of quantum emitters in hBN via resonant excitation spectroscopy at cryogenic temperatures. We show that the linewidths of hBN quantum emitters are phonon broadened, even at 5 K, with typical values of the order of

∼

1

G
H
z

. While spectral diffusion dominates at increasing pump powers, it can be minimized by working well below saturation excitation power. Our results are important for future utilization of quantum emitters in hBN for quantum interference experiments.
Proteases Regulate Cancer Stem Cell Properties and Remodel Their Microenvironment
Authors: Habič Anamarija , Novak Metka , Majc Bernarda , Lah Turnšek Tamara , Breznik Barbara
Published: July 2021

Proteolytic activity is perturbed in tumors and their microenvironment, and proteases also affect cancer stem cells (CSCs). CSCs are the therapy-resistant subpopulation of cancer cells with tumor-initiating capacity that reside in specialized tumor microenvironment niches. In this review, we briefly summarize the significance of proteases in regulating CSC activities with a focus on brain tumor glioblastoma. A plethora of proteases and their inhibitors participate in CSC invasiveness and affect intercellular interactions, enhancing CSC immune, irradiation, and chemotherapy resilience. Apart from their role in degrading the extracellular matrix enabling CSC migration in and out of their niches, we review the ability of proteases to modulate CSC properties, which prevents their elimination. When designing protease-oriented therapies, the multifaceted roles of proteases should be thoroughly investigated.
Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era
Authors: Prem Kiesha , Zandvoort Kevin van , Klepac Petra , Eggo Rosalind M. , Davies Nicholas G. ,   Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Cook Alex R. , Jit Mark
Published: July 2021

Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices for populations up to age 80 with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.
Dimeric allostery mechanism of the plant circadian clock photoreceptor ZEITLUPE
Authors: Trozzi Francesco , Wang Feng , Verkhivker Gennady , Zoltowski Brian D. , Tao Peng
Published: July 2021

In Arabidopsis thaliana, the Light-Oxygen-Voltage (LOV) domain containing protein ZEITLUPE (ZTL) integrates light quality, intensity, and duration into regulation of the circadian clock. Recent structural and biochemical studies of ZTL indicate that the protein diverges from other members of the LOV superfamily in its allosteric mechanism, and that the divergent allosteric mechanism hinges upon conservation of two signaling residues G46 and V48 that alter dynamic motions of a Gln residue implicated in signal transduction in all LOV proteins. Here, we delineate the allosteric mechanism of ZTL via an integrated computational approach that employs atomistic simulations of wild type and allosteric variants of ZTL in the functional dark and light states, together with Markov state and supervised machine learning classification models. This approach has unveiled key factors of the ZTL allosteric mechanisms, and identified specific interactions and residues implicated in functional allosteric changes. The final results reveal atomic level insights into allosteric mechanisms of ZTL function that operate via a non-trivial combination of population-shift and dynamics-driven allosteric pathways.
Explaining distortions in metacognition with an attractor network model of decision uncertainty
Authors: Atiya Nadim A. A. , Huys Quentin J. M. , Dolan Raymond J. , Fleming Stephen M.
Published: July 2021

Metacognition is the ability to reflect on, and evaluate, our cognition and behaviour. Distortions in metacognition are common in mental health disorders, though the neural underpinnings of such dysfunction are unknown. One reason for this is that models of key components of metacognition, such as decision confidence, are generally specified at an algorithmic or process level. While such models can be used to relate brain function to psychopathology, they are difficult to map to a neurobiological mechanism. Here, we develop a biologically-plausible model of decision uncertainty in an attempt to bridge this gap. We first relate the model’s uncertainty in perceptual decisions to standard metrics of metacognition, namely mean confidence level (bias) and the accuracy of metacognitive judgments (sensitivity). We show that dissociable shifts in metacognition are associated with isolated disturbances at higher-order levels of a circuit associated with self-monitoring, akin to neuropsychological findings that highlight the detrimental effect of prefrontal brain lesions on metacognitive performance. Notably, we are able to account for empirical confidence judgements by fitting the parameters of our biophysical model to first-order performance data, specifically choice and response times. Lastly, in a reanalysis of existing data we show that self-reported mental health symptoms relate to disturbances in an uncertainty-monitoring component of the network. By bridging a gap between a biologically-plausible model of confidence formation and observed disturbances of metacognition in mental health disorders we provide a first step towards mapping theoretical constructs of metacognition onto dynamical models of decision uncertainty. In doing so, we provide a computational framework for modelling metacognitive performance in settings where access to explicit confidence reports is not possible.
Bridging cell-scale simulations and radiologic images to explain short-time intratumoral oxygen fluctuations
Authors: Kingsley Jessica L. , Costello James R. , Raghunand Natarajan , Rejniak Katarzyna A.
Published: July 2021

Radiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a macroscopic scale (average value per voxel) and are not able to capture microscopic scale (cell-level) phenomena. Nevertheless, to examine the causes of frequent fast fluctuations in tissue oxygenation, models simulating individual cells’ behavior are needed. Here, we provide a link between the average data values recorded for radiologic images and the cellular and vascular architecture of the corresponding tissues. Using hybrid agent-based modeling, we generate a set of tissue morphologies capable of reproducing oxygenation levels observed in radiologic images. We then use these in silico tissues to investigate whether oxygen fluctuations can be explained by changes in vascular oxygen supply or by modulations in cellular oxygen absorption. Our studies show that intravascular changes in oxygen supply reproduce the observed fluctuations in tissue oxygenation in all considered regions of interest. However, larger-magnitude fluctuations cannot be recreated by modifications in cellular absorption of oxygen in a biologically feasible manner. Additionally, we develop a procedure to identify plausible tissue morphologies for a given temporal series of average data from radiology images. In future applications, this approach can be used to generate a set of tissues comparable with radiology images and to simulate tumor responses to various anti-cancer treatments at the tissue-scale level.
A fast and robust Bayesian nonparametric method for prediction of complex traits using summary statistics
Authors: Zhou Geyu , Zhao Hongyu
Published: July 2021

Genetic prediction of complex traits has great promise for disease prevention, monitoring, and treatment. The development of accurate risk prediction models is hindered by the wide diversity of genetic architecture across different traits, limited access to individual level data for training and parameter tuning, and the demand for computational resources. To overcome the limitations of the most existing methods that make explicit assumptions on the underlying genetic architecture and need a separate validation data set for parameter tuning, we develop a summary statistics-based nonparametric method that does not rely on validation datasets to tune parameters. In our implementation, we refine the commonly used likelihood assumption to deal with the discrepancy between summary statistics and external reference panel. We also leverage the block structure of the reference linkage disequilibrium matrix for implementation of a parallel algorithm. Through simulations and applications to twelve traits, we show that our method is adaptive to different genetic architectures, statistically robust, and computationally efficient. Our method is available athttps://github.com/eldronzhou/SDPR.
Cost-effectiveness of dengue vaccination in Puerto Rico
Authors: España Guido , Leidner Andrew J. , Waterman Stephen H. , Perkins T. Alex
Published: July 2021

An effective and widely used vaccine could reduce the burden of dengue virus (DENV) around the world. DENV is endemic in Puerto Rico, where the dengue vaccine CYD-TDV is currently under consideration as a control measure. CYD-TDV has demonstrated efficacy in clinical trials in vaccinees who had prior dengue virus infection. However, in vaccinees who had no prior dengue virus infection, the vaccine had a modestly elevated risk of hospitalization and severe disease. The WHO therefore recommended a strategy of pre-vaccination screening and vaccination of seropositive persons. To estimate the cost-effectiveness and benefits of this intervention (i.e., screening and vaccination of seropositive persons) in Puerto Rico, we simulated 10 years of the intervention in 9-year-olds using an agent-based model. Across the entire population, we found that 5.5% (4.6%-6.3%) of dengue hospitalizations could be averted. However, we also found that 0.057 (0.045–0.073) additional hospitalizations could occur for every 1,000 people in Puerto Rico due to DENV-naïve children who were vaccinated following a false-positive test results for prior exposure. The ratio of the averted hospitalizations among all vaccinees to additional hospitalizations among DENV-naïve vaccinees was estimated to be 19 (13–24). At a base case cost of vaccination of 382 USD, we found an incremental cost-effectiveness ratio of 122,000 USD per QALY gained. Our estimates can provide information for considerations to introduce the CYD-TDV vaccine in Puerto Rico.
UV decontamination of personal protective equipment with idle laboratory biosafety cabinets during the COVID-19 pandemic
Authors: Weaver Davis T. , McElvany Benjamin D. , Gopalakrishnan Vishhvaan , Card Kyle J. , Crozier Dena , Dhawan Andrew , Dinh Mina N. , Dolson Emily , Farrokhian Nathan , Hitomi Masahiro , Ho Emily , Jagdish Tanush , King Eshan S. , Cadnum Jennifer L. , Donskey Curtis J. , Krishnan Nikhil , Kuzmin Gleb , Li Ju , Maltas Jeff , Mo Jinhan , Pelesko Julia , Scarborough Jessica A. , Sedor Geoff , Tian Enze , An Gary C. , Diehl Sean A. , Scott Jacob G.
Published: July 2021

Personal protective equipment (PPE) is crucially important to the safety of both patients and medical personnel, particularly in the event of an infectious pandemic. As the incidence of Coronavirus Disease 2019 (COVID-19) increases exponentially in the United States and many parts of the world, healthcare provider demand for these necessities is currently outpacing supply. In the midst of the current pandemic, there has been a concerted effort to identify viable ways to conserve PPE, including decontamination after use. In this study, we outline a procedure by which PPE may be decontaminated using ultraviolet (UV) radiation in biosafety cabinets (BSCs), a common element of many academic, public health, and hospital laboratories. According to the literature, effective decontamination of N95 respirator masks or surgical masks requires UV-C doses of greater than 1 Jcm−2, which was achieved after 4.3 hours per side when placing the N95 at the bottom of the BSCs tested in this study. We then demonstrated complete inactivation of the human coronavirus NL63 on N95 mask material after 15 minutes of UV-C exposure at 61 cm (232 μWcm−2). Our results provide support to healthcare organizations looking for methods to extend their reserves of PPE.
Methodology of emergency medical logistics for multiple epidemic areas in public health emergency
Authors: Hou Chunxia , Jiang Huiyuan
Published: July 2021

Coronavirus disease 2019(COVID-19) has brought great disasters to humanity, and its influence continues to intensify. In response to the public health emergencies, prompt relief supplies are key to reduce the damage. This paper presents a method of emergency medical logistics to quick response to emergency epidemics. The methodology includes two recursive mechanisms: (1) the time-varying forecasting of medical relief demand according to a modified susceptible-exposed-infected- Asymptomatic- recovered (SEIAR) epidemic diffusion model, (2) the relief supplies distribution based on a multi-objective dynamic stochastic programming model. Specially, the distribution model addresses a hypothetical network of emergency medical logistics with considering emergency medical reserve centers (EMRCs), epidemic areas and e-commerce warehousing centers as the rescue points. Numerical studies are conducted. The results show that with the cooperation of different epidemic areas and e-commerce warehousing centers, the total cost is 6% lower than without considering cooperation of different epidemic areas, and 9.7% lower than without considering cooperation of e-commerce warehousing centers. Particularly, the total cost is 20% lower than without considering any cooperation. This study demonstrates the importance of cooperation in epidemic prevention, and provides the government with a new idea of emergency relief supplies dispatching, that the rescue efficiency can be improved by mutual rescue between epidemic areas in public health emergency.