bluuebunny/crossref_metadata_2025 huggingface dataset:
The MEMIC is an ex vivo system to model the complexity of the tumor microenvironment
Authors: Janská Libuše , Anandi Libi , Kirchberger Nell C. , Marinkovic Zoran S. , Schachtner Logan T. , Guzelsoy Gizem , Carmona-Fontaine Carlos
Published: July 2021

There is an urgent need for accurate, scalable and cost-efficient models of the tumor microenvironment. Here, we detail how to fabricate and use the metabolic microenvironment chamber (MEMIC) – a 3D-printed ex vivo model of intratumoral heterogeneity. A major driver of the cellular and molecular diversity in tumors is accessibility to the blood stream. Whereas perivascular tumor cells have direct access to oxygen and nutrients, cells further from the vasculature must survive under progressively more ischemic environments. The MEMIC simulates this differential access to nutrients, allow co-culturing any number of cell types, and it is optimized for live imaging and other microscopy-based analyses. Owing to a modular design and full experimental control, the MEMIC provides insights into the tumor microenvironment that would be difficult to obtain via other methods. As proof of principle, we show that cells sense gradual changes in metabolite concentration leading to predictable molecular and cellular spatial patterns. We propose the MEMIC as a complement to standard in vitro and in vivo experiments, diversifying the tools available to accurately model, perturb and monitor the tumor microenvironment.
LFA-1 and kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors
Authors: Eidell Keith P. , Lovy Alenka , Sylvain Nicholas R. , Scangarello Frank A. , Muendlein Hayley I. , Ophir Michael J. , Nguyen Ken , Seminario Maria-Cristina , Bunnell Stephen C.
Published: July 2021

Integrin engagement within the immune synapse enhances T cell activation, but our understanding of this process is incomplete. In response to T cell receptor (TCR) ligation, SLP-76 (LCP2), ADAP (FYB1) and SKAP55 (SKAP1) are recruited into microclusters and activate integrins via the effectors talin-1 and kindlin-3 (FERMT3). We postulated that integrins influence the centripetal transport and signaling of SLP-76 microclusters via these linkages. We show that contractile myosin filaments surround and are co-transported with SLP-76 microclusters, and that TCR ligand density governs the centripetal movement of both structures. Centripetal transport requires formin activity, actomyosin contraction, microtubule integrity and dynein motor function. Although immobilized VLA-4 (α4β1 integrin) and LFA-1 (αLβ2 integrin) ligands arrest the centripetal movement of SLP-76 microclusters and myosin filaments, VLA-4 acts distally, while LFA-1 acts in the lamellum. Integrin β2, kindlin-3 and zyxin are required for complete centripetal transport, while integrin β1 and talin-1 are not. CD69 upregulation is similarly dependent on integrin β2, kindlin-3 and zyxin, but not talin-1. These findings highlight the integration of cytoskeletal systems within the immune synapse and reveal extracellular ligand-independent roles for LFA-1 and kindlin-3.

This article has an associated First Person interview with the first author of the paper.
Long-Term Patient Satisfaction and Quality of Life After Breast-Conserving Therapy: A Prospective Study Using the BREAST-Q
Authors: Stolpner Ilona , Heil Jörg , Riedel Fabian , Wallwiener Markus , Schäfgen Benedikt , Feißt Manuel , Golatta Michael , Hennigs André
Published: July 2021

Background

Poor patient-reported satisfaction after breast-conserving therapy (BCT) has been associated with impaired health-related quality of life (HRQOL) and subsequent depression in retrospective analysis. This prospective cohort study aimed to assess the HRQOL of patients who have undergone BCT using the BREAST-Q, and to identify clinical risk factors for lower patient satisfaction.

Methods

Patients with primary breast cancer undergoing BCT were asked to complete the BREAST-Q preoperatively (T1) for baseline evaluation, then 3 to 4 weeks postoperatively (T2), and finally 1 year after surgery (T3). Clinicopathologic data were extracted from the patients’ charts. Repeated measures analysis of variance (ANOVA) was used to determine significant differences in mean satisfaction and well-being levels among the test intervals. Multiple linear regression was used to evaluate risk factors for lower satisfaction.

Results

The study enrolled 250 patients. The lowest baseline BREAST-Q score was reported for “satisfaction with breast” (mean, 61 ± 19), but this increased postoperatively (mean, 66 ± 18) and was maintained at the 1 year follow-up evaluation (mean, 67 ± 21). “Physical well-being” decreased from T1 (mean, 82 ± 17) to T2 (mean, 28 ± 13) and did not recover much by T3 (mean, 33 ± 13), being the lowest BREAST-Q score postoperatively and in the 1-year follow-up evaluation. In multiple regression, baseline psychosocial well-being, body mass index (BMI), and type of incision were risk factors for lower “satisfaction with breasts.”

Conclusion

Both the aesthetic/surgery-related and psychological aspects are equally important with regard to “satisfaction with breasts” after BCT. The data could serve as the benchmark for future studies.
Structurally Strained Cyclic Xanthene Dimers: A Model for the Rigid Crown Ether Moiety in the Reduced Graphene Oxide Framework
Authors: Kishimoto Keita , Oda Kasane , Nishida Jun-ichi , Kitamura Chitoshi , Kawase Takeshi
Published: July 2021

Highly strained cyclic xanthene dimers, which serve as models for reduced graphene oxide (RGO), were synthesized by Ni(0) mediated homo-coupling reactions. The dimers are obtained as highly stable colorless solids. X-ray crystallographic analysis of a tetra-tert-butyl derivative demonstrates that it possesses a highly strained structure with an extremely short non-bonded O⋯O distance (2.5662(44) Å). The results of variable temperature NMR experiments show that no signal broadening occurs even at 398 K, indicating that conformational flipping requires considerably high energy.
Structure and Unique Functions of Anisotropic Hydrogels Comprising Uniaxially Aligned Lamellar Bilayers
Authors: Yue Youfeng , Gong Jian Ping
Published: July 2021

In this account, we provide an overview of unique anisotropic hydrogels comprising uniaxially aligned lamellar bilayers embedded in amorphous gel matrix. Owing to their unique structures, the lamellar gels exhibit many unique functions that cannot be obtained from conventional hydrogels featuring amorphous and isotropic structures. For example, the periodical multilayer structure having interlayer spacing of several hundreds of nanometers imparts beautiful structural colors to the gel that respond sensitively to mechanical and chemical stimuli, the water-impermeable nature of the bilayers imparts one-dimensional swelling and diffusion, and the hydrophobic association of the bilayers serves as sacrificial bonds to impart high mechanical strength and toughness during deformation. This work demonstrates the significant potential of hydrogel materials fabricated by introducing anisotropic ordered structures.
Interpreting estimates of coronavirus disease 2019 (COVID-19) vaccine efficacy and effectiveness to inform simulation studies of vaccine impact: a systematic review
Authors: Imai Natsuko , Hogan Alexandra B. , Williams Lucy , Cori Anne , Mangal Tara D. , Winskill Peter , Whittles Lilith K. , Watson Oliver J. , Knock Edward S. , Baguelin Marc , Perez-Guzman Pablo N. , Gaythorpe Katy A.M. , Sonabend Raphael , Ghani Azra C. , Ferguson Neil M.
Published: July 2021

Background: The multiple efficacious vaccines authorised for emergency use worldwide represent the first preventative intervention against coronavirus disease 2019 (COVID-19) that does not rely on social distancing measures. The speed at which data are emerging and the heterogeneities in study design, target populations, and implementation make it challenging to interpret and assess the likely impact of vaccine campaigns on local epidemics. We reviewed available vaccine efficacy and effectiveness studies to generate working estimates that can be used to parameterise simulation studies of vaccine impact.

Methods: We searched MEDLINE, the World Health Organization’s Institutional Repository for Information Sharing, medRxiv, and vaccine manufacturer websites for studies that evaluated the emerging data on COVID-19 vaccine efficacy and effectiveness. Studies providing an estimate of the efficacy or effectiveness of a COVID-19 vaccine using disaggregated data against SARS-CoV-2 infection, symptomatic disease, severe disease, death, or transmission were included. We extracted information on study population, variants of concern (VOC), vaccine platform, dose schedule, study endpoints, and measures of impact. We applied an evidence synthesis approach to capture a range of plausible and consistent parameters for vaccine efficacy and effectiveness that can be used to inform and explore a variety of vaccination strategies as the COVID-19 pandemic evolves.

Results: Of the 602 articles and reports identified, 53 were included in the analysis. The availability of vaccine efficacy and effectiveness estimates varied by vaccine and were limited for VOCs. Estimates for non-primary endpoints such as effectiveness against infection and onward transmission were sparse. Synthesised estimates were relatively consistent for the same vaccine platform for wild-type, but was more variable for VOCs.

Conclusions: Assessment of efficacy and effectiveness of COVID-19 vaccines is complex. Simulation studies must acknowledge and capture the uncertainty in vaccine effectiveness to robustly explore and inform vaccination policies and policy around the lifting of non-pharmaceutical interventions.
Pulmonary Involvement in Secondary Syphilis
Authors: Benainous Ruben , Alunji Mohanad , Brillet Pierre Yves , Dhote Robin
Published: July 2021

In secondary syphilis, Treponema pallidum can spread to the lungs. A new case is described of a patient with multiple excavated subpleural pulmonary nodules, a rare localization of secondary syphilis. Despite the numerous pulmonary samples analysed in the literature, T. pallidum is rarely visualised directly on bronchial fibroscopy or biopsy. The diagnosis of secondary syphilis is suspected from historical and physical findings and confirmed by high values obtained from non-treponemal tests.
Vertebrates visiting natural waterholes in a tropical seasonal habitat in central México
Authors: López-Téllez Concepción , Pérez-Irineo Gabriela , Mandujano Salvador , Ramírez-Carmona Geovanny , Hernández-Gómez Carlos A. , Flores-Ramírez Diana E.
Published: July 2021

La distribución espacial y temporal de la disponibilidad de agua impacta el comportamiento de las especies.  Particularmente en hábitats áridos, los pozos de agua son fuentes de agua para muchas especies.  Presentamos registros interesantes de vertebrados que visitaron pozos de agua naturales mediante cámaras-trampa durante la estación seca en un bosque tropical seco del centro de México.  Durante la estación seca (diciembre de 2015, mayo de 2016 y abril-mayo de 2019), colocamos siete cámaras-trampa durante 135 días en siete pozos de agua.  Este método utilizado fue parte de las actividades de monitoreo y conservación, implementadas dentro de una amplia unidad de manejo de vida silvestre en el centro de México.  Registramos 20 especies de vertebrados visitando los pozos de agua: 15 mamíferos, cuatro aves, y un reptil.  La co-ocurrencia entre especies sin interacciones negativas, y algunos registros de conducta incluyeron: eventos de juego, acicalamiento y frotamiento contra piedras; se observó a algunas especies esperando su turno para beber.  Pudimos identificar al menos cuatro individuos de Mephitis macroura.  Nuestro estudio también enfatiza un aspecto básico, pero quizás subestimado en los últimos años producto del uso de cámaras-trampa: la observación cualitativa de animales a través de fotografías.  Estas observaciones pueden revelar aspectos básicos e interesantes de la historia natural de las especies que permiten mejorar el conocimiento sobre la coexistencia en un mismo lugar.
Au nanobowtie on a SiO2 microsphere for optoplasmonic trapping
Authors: Wang Jihao , Wei Hua , Wang Chenyang , Huang Yingzhou , Chen Guo , Liu Anping
Published: July 2021

The combination of photonic and plasmonic elements with complementary optical properties has stimulated the development of optoplasmonic hybrid systems, in which photonic and plasmonic elements can interact synergistically, breaking through the limitations of traditional structures. In this paper, a new optoplasmonic tweezer is theoretically proposed by using the Au nanobowtie and

S
i

O

2

microsphere. The finite-difference time-domain simulation is used to study the influence of the size of the

S
i

O

2

microsphere and the

S
i

O

2

hemisphere in polydimethylsiloxane on the optical potential well. The simulation results show that the electric field intensity of the structure is increased by 6 times compared with the Au nanobowtie structure, and the gradient force and the trapping potential are also significantly improved.
Three-dimensional polymer mode (de)multiplexer with cascaded tapered couplers for on-board optical interconnects
Authors: Shang Yuling , Guo Wenjie , He Xiang , Zhou Jinzhuo , Yan Yaya , Liu Zhengwei , Li Chunquan
Published: July 2021

A three-dimensional polymer mode (de)multiplexer based on mode evolution is proposed. The proposed configuration is mainly composed of cascaded two tapered couplers where waveguides with different heights are inversely tapered to achieve mode conversions of the

E

11

,

E

21

, and

E

31

modes. The dimensional parameters and characteristics are analyzed by the beam propagation method. This mode (de)multiplexer exhibits the coupling ratio greater than 0.97, excess loss lower than 0.15 dB and extinction ratio higher than 20 dB for TE and TM polarizations over the wavelength range

1530

∼

1625

n
m

(the

C

+

L

band). This design has weak wavelength dependence and polarization dependence, which is promising to be applied to broadband on-board mode multiplexing.
Miniaturized optical fiber probe for prostate cancer screening
Authors: Iele Antonio , Ricciardi Armando , Pecorella Claudia , Cirillo Andrea , Ficuciello Fanny , Siciliano Bruno , La Rocca Roberto , Mirone Vincenzo , Consales Marco , Cusano Andrea
Published: July 2021

Tissue elasticity is universally recognized as a diagnostic and prognostic biomarker for prostate cancer. As the first diagnostic test, the digital rectal examination is used since malignancy changes the prostate morphology and affects its mechanical properties. Currently, this examination is performed manually by the physician, with an unsatisfactory positive predictive value of 42%. A more objective and spatially selective technique is expected to provide a better prediction degree and understanding of the disease. To this aim, here we propose a miniaturized probe, based on optical fiber sensor technology, for mechanical characterization of the prostate with sub-millimeter resolution. Specifically, the optical system incorporates a customized Fiber Bragg Grating, judiciously integrated in a metallic cannula and moved by a robotic arm. The probe enables the local measurement of the force upon tissue indentation with a resolution of 0.97 mN. The system has been developed in such a way to be potentially used directly in vivo. Measurements performed on phantom tissues mimicking different stages of the prostatic carcinoma demonstrated the capability of our device to distinguish healthy from diseased zones of the prostate. The study on phantoms has been complemented with preliminary ex vivo experiments on real organs obtained from radical surgeries. Our findings lay the foundation for the development of advanced optical probes that, when integrated inside biopsy needle, are able to perform in vivo direct mechanical measurements with high sensitivity and spatial resolution, opening to new scenarios for early diagnosis and enhanced diagnostic accuracy of prostate cancer.
Quantum dynamics of mixed polarization states: effects of environment-mediated intermode coupling
Authors: Gaidash Andrei , Kozubov Anton , Miroshnichenko George , Kiselev Alexei D.
Published: July 2021

We study the quantum dynamics of mixed polarization states represented by the two-mode boson system interacting with an environment. Using the form of general dynamical equations for averaged operators that preserve normal ordering, we show that the dynamical regimes of the averaged Stokes operators crucially depend on the anisotropy of the relaxation operator resulting from the intermode coupling induced by the anisotropic environment. We analyze how this coupling impacts the quantum bit error rate in the well-known single-photon polarization-coding quantum key distribution protocol BB84.
High-performance terahertz refractive index sensor based on a hybrid graphene Tamm structure
Authors: Hu Jinlei , Li Menghan , Wang Zexiang , Hu Zhengda , Wang Jicheng , Khakhomov Sergei , Semchenko Igor
Published: July 2021

In recent years, the research on tunable and high-performance terahertz devices has attracted widespread attention. In this paper, we propose a novel refractive index sensor consisting of monolayer graphene and multilayer photonic crystal with a defect layer. It is found that Tamm plasmon polaritons can be excited at the top graphene interface, which can strongly interact with the defect mode in this coupled structure. The results of numerical simulation demonstrate that the coupling can be either tuned by adjusting the geometric parameters or actively controlled by the chemical potential in graphene as well as the incident angle of light, allowing for tunable dual-band perfect absorption with strong interaction. Moreover, the resonance frequency of the defect mode is sensitive to the changes of the ambient refractive index. The sensitivity and figure of merit of this device as a sensor can reach 1.01 THz per refractive index unit (THz/RIU) and

631.2

R
I
U

−
1

, respectively. In addition to high performance, the sensor does not require phase- or polarization-matching devices, paving the way for the research of optical devices.
Flexible non-linear physical security coding scheme combined with chaotic neural network for OFDM-WDM-PON
Authors: Li Mingye , Ren Jianxin , Mao Yaya , Song Xiumin , Chen Shuaidong , Han Shun , Zhao Jianye , Wan Yibin , Tian Feng , Liu Bo
Published: July 2021

In this paper, a flexible physical security coding scheme integrating chaotic neural network (CNN) and non-linear encryption is proposed for orthogonal frequency division multiplexing wavelength division multiplexing passive optical network (OFDM-WDM-PON). The scheme improved the flexibility, adjustability and the key space of chaotic encryption system by introducing chaos into neural networks. The system will encrypt the bit series, probability shaping points, and subcarriers position of the OFDM signal through linear encryption and non-linear encryption concurrently. Results show that a key sensitivity of 10−15 and a key space of more than 10279 can be achieved. The encrypted system's Lyapunov is 5.2631, along with 12 parameters can be dynamically changed in the range of 0∼5. Furthermore, when the bit error rate (BER) is less than 3.8×10−3, probabilistic shaping (PS) technology decreases power loss by around 0.5 dB. A 20.454 Gb/s data transmission experiment was successfully verified for a span of 25 Km single-mode fiber. According to the experimental results, the proposed encryption scheme is likely to be used in future OFDM-WDM-PON transmission systems.
Practical generation of arbitrary high-order cylindrical vector beams by cascading vortex half-wave plates
Authors: Qi Junli , Yi Wenjun , Fu Meicheng , Zhu Mengjun , Liu Ju , Huang Guocheng , Pan Jinghan , Zhu Shuyue , Chen Xin , Tabg Wusheng , Zhang Hui , Shi Bo , Deng Haifei , Wang Weihua , Li Xiujian
Published: July 2021

A practical direct-view scheme for generating arbitrary high-order cylindrical vector (HCV) beams by cascading vortex half-wave plates (VHPs) is presented. The combination of odd number 2n-1 VHPs for n≥1 can realize (m2n-1-m2n-2+…+m1)-order CV beams, in which m is the order number of VHP and the corresponding subscript 2n-1 represents the arrangement number of VHPs, and the cascading of even number 2n ones can obtain (m2n-m2n-1+…+m2-m1)-order CV beams. All 1-12 order CV beams, including the high-order anti-vortex CV (ACV) beams, are generated only by selectively cascading the VHPs with m=1, 3 and 8. The polarization properties of the generated HCV beams are investigated by measuring the corresponding Stokes parameters. It is experimentally demonstrated that arbitrary HCV beams are effectively achieved by the proposed method. The order numbers of CV beams can be greatly expanded by cascading limited types of VHPs.
Impact of the boundary’s sharpness on temporal reflection in dispersive media
Authors: Zhang Junchi , Donaldson W. R. , Agrawal Govind P.
Published: July 2021

We investigate the impact of the finite rise time of a spatiotemporal boundary inside a dispersive medium used for reflection and refraction of optical pulses. We develop a matrix approach in the frequency domain for analyzing such spatiotemporal boundaries and use it to show that the frequency range over which reflection can occur is reduced as the rise time increases. We also show that total internal reflection can occur even for boundaries with long rise times. This feature suggests that spatiotemporal waveguides can be realized through cross-phase modulation even when pump pulses have relatively long rise and fall times.
Deep photothermal effect induced by stereotactic laser beams in highly scattering media
Authors: Baez-Castillo L. , Ortiz-Rascón E. , Carrillo-Torres R. C. , Bruce N. C. , Garduño-Mejía J. , Lucero-Acuña A. , Álvarez-Ramos M. E.
Published: July 2021

Plasmonic photothermal therapy (PPTT), as an increasingly studied treatment alternative, has been widely regarded mostly as a surface tissue treatment choice. Although some techniques have been implemented for interstitial tumors, these involve some grade of invasiveness, as the outer skin is usually broken to introduce light-delivering optical fibers or even catheters. In this work, we present a potential non-invasive strategy using the stereotactic approach, long employed in radiosurgery, by converging multiple near infrared laser beams for PPTT in tissue-equivalent optical phantoms that enclose small gel spheres and simulate interstitial tissue impregnated with plasmonic nanoparticles. The real-time in-depth monitoring of temperature increase is realized by an infrared camera face-on mounted over the phantom. Our results show that a significant reduction in the surface heating can be achieved with this configuration while remarkably increasing the interstitial reach of PPTT, assuring a

∼

6
∘

C

temperature increase for the simulated tumors at 10 mm depth and

∼

4
∘

C

at 15 mm depth and opening up new possibilities for future clinical applications.
Anapole enhanced on-chip routing of spin–valley photons in 2D materials for silicon integrated optical communication
Authors: Yao Qi , Bie Ya-Qing , Chen Jianfa , Li Jinyang , Li Feng , Cao Zhaolong
Published: July 2021

Controlling the propagation direction of polarized light is crucial for optical communications and functional optical components. However, all-dielectric on-chip technology exploiting valley photon emission in transition metal dichalcogenides with enhanced emission has yet to be fully explored. Here, we report a design for enhancing valley emission and manipulating valley photon propagation based on degenerate non-radiating anapole states. By placing circularly polarized dipoles on top of a

C

4

symmetric cross-slotted silicon disk, the rotating anapole state is excited with a Purcell factor up to two orders. In addition, the photon coupled to the preferred direction of the waveguide are about 2 times larger than that to the opposite direction. Our design could pave the way for realizing on-chip valley-dependent optical communication.
Transport of light in a moving photonic lattice via atomic coherence
Authors: Zhang Zhaoyang , Shen Yutong , Ning Shaohuan , Liang Shun , Feng Yuan , Li Changbiao , Zhang Yanpeng , Xiao Min
Published: July 2021

In this Letter, we have investigated experimentally the photonic realization of a moving lattice with an instantaneously tunable transverse velocity in a three-level

Λ

-type warm

85

R
b

atomic medium. The dynamic photonic lattice moving along the direction of its spatial periodicity was constructed by introducing a frequency difference (determining the velocity) between two coupling beams, whose interference pattern could optically induce a (spatial) periodic refractive index change inside the atomic vapor under electromagnetically induced transparency. When a Gaussian probe field is launched into this optically induced lattice, the output diffraction patterns can shift along the transverse direction, indicating dynamical features of induced photonic structures. The realization of this effectively controllable moving photonic lattice provides a new platform for guiding the transport of light.
Lattice light sheets generated with a firmly arranged dielectric regular hexagonal pyramid array
Authors: Liang Ning , Huang Zengxin , Yan Chao , Wang Kunpeng , Kuang Dengfeng
Published: July 2021

We present a firmly arranged dielectric regular hexagonal pyramid array to generate lattice light sheets with high conversion efficiency and low stray light. Both the size and working distance of the lattice light sheets can be modulated by changing the structural parameters. We experimentally recorded the lattice light sheets illumination, which is consistent with the corresponding simulation. To evaluate the imaging quality, we compared the light field generated with and without structure by using polystyrene fluorescent microspheres. This study provides a potential method for the building of light sheet fluorescence microscopy with high resolution and low phototoxicity.
Intense quasi-monochromatic resonant harmonic generation in the multiphoton ionization regime
Authors: Singh Mangaljit , Fareed Muhammad Ashiq , Strelkov Vasily , Grum-Grzhimailo Alexei N. , Magunov Alexander , Laramée Antoine , Légaré François , Ozaki Tsuneyuki
Published: July 2021

Resonant high-order harmonics, which result in quasi-monochromatic extreme ultraviolet light with coherent intensity enhancement involving autoionizing resonances, have been demonstrated from laser-ablated plumes in the tunnel-ionization regime. Here, we demonstrate resonant harmonics in the previously unexplored multiphoton-ionization regime. We demonstrate an intense resonant harmonic from gallium with an intensity enhancement ratio of 714 relative to the neighboring harmonics, achieved without the need for extreme ultraviolet filtering methods, thus preventing a typical photon flux loss of more than 70%. Three-dimensional time-dependent Schrödinger equation calculations reveal that this increase in the enhancement ratio is due to the low electron wave packet spreading in the multiphoton-ionization regime. These results reveal a method for increasing the intensity and monochromaticity of intense multimicrojoule femtosecond extreme ultraviolet light and will also facilitate understanding of the involvement of autoionizing resonances in generating resonant harmonics in the multiphoton-ionization regime.
Do psychiatric diseases follow annual cyclic seasonality?
Authors: Zhang Hanxin , Khan Atif , Chen Qi , Larsson Henrik , Rzhetsky Andrey
Published: July 2021

Seasonal affective disorder (SAD) famously follows annual cycles, with incidence elevation in the fall and spring. Should some version of cyclic annual pattern be expected from other psychiatric disorders? Would annual cycles be similar for distinct psychiatric conditions? This study probes these questions using 2 very large datasets describing the health histories of 150 million unique U.S. citizens and the entire Swedish population. We performed 2 types of analysis, using “uncorrected” and “corrected” observations. The former analysis focused on counts of daily patient visits associated with each disease. The latter analysis instead looked at the proportion of disease-specific visits within the total volume of visits for a time interval. In the uncorrected analysis, we found that psychiatric disorders’ annual patterns were remarkably similar across the studied diseases in both countries, with the magnitude of annual variation significantly higher in Sweden than in the United States for psychiatric, but not infectious diseases. In the corrected analysis, only 1 group of patients—11 to 20 years old—reproduced all regularities we observed for psychiatric disorders in the uncorrected analysis; the annual healthcare-seeking visit patterns associated with other age-groups changed drastically. Analogous analyses over infectious diseases were less divergent over these 2 types of computation. Comparing these 2 sets of results in the context of published psychiatric disorder seasonality studies, we tend to believe that our uncorrected results are more likely to capture the real trends, while the corrected results perhaps reflect mostly artifacts determined by dominantly fluctuating, health-seeking visits across a given year. However, the divergent results are ultimately inconclusive; thus, we present both sets of results unredacted, and, in the spirit of full disclosure, leave the verdict to the reader.
Immune selection suppresses the emergence of drug resistance in malaria parasites but facilitates its spread
Authors: Whitlock Alexander O. B. , Juliano Jonathan J. , Mideo Nicole
Published: July 2021

Although drug resistance inPlasmodium falciparumtypically evolves in regions of low transmission, resistance spreads readily following introduction to regions with a heavier disease burden. This suggests that the origin and the spread of resistance are governed by different processes, and that high transmission intensity specifically impedes the origin. Factors associated with high transmission, such as highly immune hosts and competition within genetically diverse infections, are associated with suppression of resistant lineages within hosts. However, interactions between these factors have rarely been investigated and the specific relationship between adaptive immunity and selection for resistance has not been explored. Here, we developed a multiscale, agent-based model ofPlasmodiumparasites, hosts, and vectors to examine how host and parasite dynamics shape the evolution of resistance in populations with different transmission intensities. We found that selection for antigenic novelty (“immune selection”) suppressed the evolution of resistance in high transmission settings. We show that high levels of population immunity increased the strength of immune selection relative to selection for resistance. As a result, immune selection delayed the evolution of resistance in high transmission populations by allowing novel, sensitive lineages to remain in circulation at the expense of the spread of a resistant lineage.

In contrast, in low transmission settings, we observed that resistant strains were able to sweep to high population prevalence without interference. Additionally, we found that the relationship between immune selection and resistance changed when resistance was widespread. Once resistance was common enough to be found on many antigenic backgrounds, immune selection stably maintained resistant parasites in the population by allowing them to proliferate, even in untreated hosts, when resistance was linked to a novel epitope. Our results suggest that immune selection plays a role in the global pattern of resistance evolution.
Neuron tracing and quantitative analyses of dendritic architecture reveal symmetrical three-way-junctions and phenotypes of git-1 in C. elegans
Authors: Yuval Omer , Iosilevskii Yael , Meledin Anna , Podbilewicz Benjamin , Shemesh Tom
Published: July 2021

Complex dendritic trees are a distinctive feature of neurons. Alterations to dendritic morphology are associated with developmental, behavioral and neurodegenerative changes. The highly-arborized PVD neuron of C. elegans serves as a model to study dendritic patterning; however, quantitative, objective and automated analyses of PVD morphology are missing. Here, we present a method for neuronal feature extraction, based on deep-learning and fitting algorithms. The extracted neuronal architecture is represented by a database of structural elements for abstracted analysis. We obtain excellent automatic tracing of PVD trees and uncover that dendritic junctions are unevenly distributed. Surprisingly, these junctions are three-way-symmetrical on average, while dendritic processes are arranged orthogonally. We quantify the effect of mutation in git-1, a regulator of dendritic spine formation, on PVD morphology and discover a localized reduction in junctions. Our findings shed new light on PVD architecture, demonstrating the effectiveness of our objective analyses of dendritic morphology and suggest molecular control mechanisms.
The effect of natural selection on the propagation of protein expression noise to bacterial growth
Authors: Krah Laurens H. J. , Hermsen Rutger
Published: July 2021

In bacterial cells, protein expression is a highly stochastic process. Gene expression noise moreover propagates through the cell and adds to fluctuations in the cellular growth rate. A common intuition is that, due to their relatively high noise amplitudes, proteins with a low mean expression level are the most important drivers of fluctuations in physiological variables. In this work, we challenge this intuition by considering the effect of natural selection on noise propagation. Mathematically, the contribution of each protein species to the noise in the growth rate depends on two factors: the noise amplitude of the protein’s expression level, and the sensitivity of the growth rate to fluctuations in that protein’s concentration. We argue that natural selection, while shaping mean abundances to increase the mean growth rate, also affects cellular sensitivities. In the limit in which cells grow optimally fast, the growth rate becomes most sensitive to fluctuations in highly abundant proteins. This causes abundant proteins to overall contribute strongly to the noise in the growth rate, despite their low noise levels. We further explore this result in an experimental data set of protein abundances, and test key assumptions in an evolving, stochastic toy model of cellular growth.
Highly conserved and cis-acting lncRNAs produced from paralogous regions in the center of HOXA and HOXB clusters in the endoderm lineage
Authors: Degani Neta , Lubelsky Yoav , Perry Rotem Ben-Tov , Ainbinder Elena , Ulitsky Igor
Published: July 2021

Long noncoding RNAs (lncRNAs) have been shown to play important roles in gene regulatory networks acting in early development. There has been rapid turnover of lncRNA loci during vertebrate evolution, with few human lncRNAs conserved beyond mammals. The sequences of these rare deeply conserved lncRNAs are typically not similar to each other. Here, we characterizeHOXA-AS3andHOXB-AS3, lncRNAs produced from the central regions of the HOXA and HOXB clusters. Sequence-similar orthologs of both lncRNAs are found in multiple vertebrate species and there is evident sequence similarity between their promoters, suggesting that the production of these lncRNAs predates the duplication of the HOX clusters at the root of the vertebrate lineage. This conservation extends to similar expression patterns of the two lncRNAs, in particular in cells transiently arising during early development or in the adult colon. Functionally, the RNA products ofHOXA-AS3andHOXB-AS3regulate the expression of their overlapping HOX5–7 genes both in HT-29 cells and during differentiation of human embryonic stem cells. Beyond production of paralogous protein-coding and microRNA genes, the regulatory program in the HOX clusters therefore also relies on paralogous lncRNAs acting in restricted spatial and temporal windows of embryonic development and cell differentiation.
The discovery of a novel series of compounds with single-dose efficacy against juvenile and adult Schistosoma species
Authors: Gardner J. Mark F. , Mansour Nuha R. , Bell Andrew S. , Helmby Helena , Bickle Quentin
Published: July 2021

Treatment and control of schistosomiasis depends on a single drug, praziquantel, but this is not ideal for several reasons including lack of potency against the juvenile stage of the parasite, dose size, and risk of resistance. We have optimised the properties of a series of compounds we discovered through high throughput screening and have designed candidates for clinical development. The best compounds demonstrate clearance of both juvenile and adult S. mansoni worms in a mouse model of infection from a single oral dose of < 10 mg/kg. Several compounds in the series are predicted to treat schistosomiasis in humans across a range of species with a single oral dose of less than 5 mg/kg.
Can situations awaken emotions? The compilation and evaluation of the Emotional Situation Sentence System (ESSS)
Authors: Zhao Yuan , Yin Ming , Zhu Chuanlin , Tan Chenghui , Hu Shengjie , Liu Dianzhi
Published: July 2021

We aimed to establish and evaluate a standardized emotional situation sentence system (ESSS) relevant to the lives of college students to supplement prior literature and adapt to the needs of emotional research. Two studies were designed for this research; study 1 examined the effect of words in the ESSS and study 2 involved the use of pictures. For Study 1, 778 items were selected by 607 college students and 15 experts. We then tested the scale with 80 undergraduate participants. The ESSS sentences were rated on their degree of valence, arousal, and dominance using a 9-point scale. Cronbach’s α (greater than 0.986) of the overall score as well as each sub-score in the three components confirmed the scale’s reliability. As seen on a scatter plot, the results suggest that negative emotions (fear, disgust, anger, sadness, anxiety) are convergent and different from the distribution of positive (happiness) and neutral emotions. Study 2 included 30 participants to compare the difference in valence and arousal between the ESSS and emotional pictures. The results indicate that the ESSS is a standardized, situational, and ecological emotional contextual text system, well-suited to invoke emotion in college students. The ESSS has significantly better arousal and potency than pictures; moreover, it can be applied to experimental studies of anxiety-related emotions. However, emotion pictures have shorter response times, and wider application ranges, and they can include more cross-cultural characteristics compared to words.
Dynamic linkages between renewable energy, carbon emissions and economic growth through nonlinear ARDL approach: Evidence from Iran
Authors: Karimi M. S. , Ahmad S. , Karamelikli H. , Dinç D. T. , Khan Y. A. , Sabzehei M. T. , Abbas S. Z.
Published: July 2021

This study examines the relationship between economic growth, renewable energy consumption, and carbon emissions in Iran between 1975–2017, and the bounds testing approach to cointegration and the asymmetric method was used in this study. The results reveal that in the long run increase in renewable energy consumption and CO2 emissions causes an increase in real GDP per capita. Meanwhile, the decrease in renewable energy has the same effect, but GDP per capita reacts more strongly to the rise in renewable energy than the decline. Besides, in the long run, a reduction of CO2 emissions has an insignificant impact on GDP per capita. Furthermore, the results from asymmetric tests suggest that reducing CO2 emissions and renewable energy consumption do not have an essential role in decreasing growth in the short run. In contrast, an increase in renewable energy consumption and CO2 emissions do contribute to boosting the growth. These results may be attributable to the less renewable energy in the energy portfolio of Iran. Additionally, the coefficients on capital and labor are statistically significant, and we discuss the economic implications of the results and propose specific policy recommendations.
Calculation and realization of new method grey residual error correction model
Authors: Xiao Lifang , Chen Xiangyang , Wang Hao
Published: July 2021

Aiming at the problem of prediction accuracy of stochastic volatility series, this paper proposes a method to optimize the grey model(GM(1,1)) from the perspective of residual error. In this study, a new fitting method is firstly used, which combines the wavelet function basis and the least square method to fit the residual data of the true value and the predicted value of the grey model(GM(1,1)). The residual prediction function is constructed by using the fitting method. Then, the prediction function of the grey model(GM(1,1)) is modified by the residual prediction function. Finally, an example of the wavelet residual-corrected grey prediction model (WGM) is obtained. The test results show that the fitting accuracy of the wavelet residual-corrected grey prediction model has irreplaceable advantages.
The effect of human mobility restrictions on the COVID-19 transmission network in China
Authors: Oka Tatsushi , Wei Wei , Zhu Dan
Published: July 2021

Background

COVID-19 poses a severe threat worldwide. This study analyzes its propagation and evaluates statistically the effect of mobility restriction policies on the spread of the disease.

Methods

We apply a variation of the stochastic Susceptible-Infectious-Recovered model to describe the temporal-spatial evolution of the disease across 33 provincial regions in China, where the disease was first identified. We employ Bayesian Markov Chain Monte-Carlo methods to estimate the model and to characterize a dynamic transmission network, which enables us to evaluate the effectiveness of various local and national policies.

Results

The spread of the disease in China was predominantly driven by community transmission within regions, which dropped substantially after local governments imposed various lockdown policies. Further, Hubei was only the epicenter of the early epidemic stage. Secondary epicenters, such as Beijing and Guangdong, had already become established by late January 2020. The transmission from these epicenters substantially declined following the introduction of mobility restrictions across regions.

Conclusions

The spatial transmission network is able to differentiate the effect of the local lockdown policies and the cross-region mobility restrictions. We conclude that both are important policy tools for curbing the disease transmission. The coordination between central and local governments is important in suppressing the spread of infectious diseases.
Concordance and timing in recording cancer events in primary care, hospital and mortality records for patients with and without psoriasis: A population-based cohort study
Authors: Trafford Alex M. , Parisi Rosa , Rutter Martin K. , Kontopantelis Evangelos , Griffiths Christopher E. M. , Ashcroft Darren M. ,   on behalf of the Global Psoriasis Atlas (GPA)
Published: July 2021

Background

The association between psoriasis and the risk of cancer has been investigated in numerous studies utilising electronic health records (EHRs), with conflicting results in the extent of the association.

Objectives

To assess concordance and timing of cancer recording between primary care, hospital and death registration data for people with and without psoriasis.

Methods

Cohort studies delineated using primary care EHRs from the Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases, with linkage to hospital episode statistics (HES), Office for National Statistics (ONS) mortality data and indices of multiple deprivation (IMD). People with psoriasis were matched to those without psoriasis by age, sex and general practice. Cancer recording between databases was investigated by proportion concordant, that being the presence of cancer record in both source and comparator datasets. Delay in recording cancer diagnoses between CPRD and HES records and predictors of discordance were also assessed.

Results

58,904 people with psoriasis and 350,592 comparison patients were included using CPRD GOLD; whereas 213,400 people with psoriasis and 1,268,998 comparison patients were included in CPRD Aurum. For all cancer records (excluding keratinocyte), concordance between CPRD and HES was greater than 80%. Concordance for same-site cancer records was markedly lower (<68% GOLD-linked data; <72% Aurum-linked data). Concordance of non-Hodgkin lymphoma and liver cancer recording between CPRD and HES was lower for people with psoriasis compared to those without.

Conclusions

Concordance between CPRD and HES is poor when restricted to cancers of the same site, with greater discordance in people with psoriasis for some cancers of specific sites. The use of linked patient-level data is an important step in reducing misclassification of cancer outcomes in epidemiological studies using routinely collected electronic health records.
Late antiretroviral refills and condomless sex in a cohort of HIV-seropositive pregnant and postpartum Kenyan women
Authors: Eastment McKenna C. , Kinuthia John , Wang Lei , Wanje George , Wilson Katherine , Kaggiah Anne , Simoni Jane M. , Mandaliya Kishorchandra , Poole Danielle N. , Richardson Barbra A. , Jaoko Walter , John-Stewart Grace , McClelland R. Scott
Published: July 2021

Introduction

The postpartum period can be challenging for women living with HIV. Understanding how the postpartum period impacts ART adherence and condomless sex could inform the development of comprehensive sexual and reproductive health and HIV services tailored to the needs of women living with HIV during this critical interval.

Methods

In a longitudinal cohort study of HIV-seropositive Kenyan women, late ART refills and self-reported condomless sex were compared between the woman’s pregnancy and the postpartum period. Analyses were conducted using generalized estimating equations and adjusted for alcohol use, depressive symptoms, intimate partner violence (IPV), and having a recent regular partner. Effect modification was explored for selected variables.

Results and discussion

151 women contributed visits. Late ART refills occurred at 7% (32/439) of pregnancy visits compared to 18% (178/1016) during the postpartum period (adjusted relative risk [aRR] 2.44, 95% confidence interval [CI] 1.62–3.67). This association differed by women’s education level. Women with ≥8 years of education had late ART refills more during the postpartum period than pregnancy (aRR 3.00, 95%CI 1.95–4.62). In contrast, in women with <8 years of education, late ART refills occurred similarly during pregnancy and the postpartum period (aRR 0.88, 95%CI 0.18–4.35). Women reported condomless sex at 10% (60/600) of pregnancy visits compared to 7% (72/1081) of postpartum visits (aRR 0.76, 95%CI 0.45–1.27). This association differed by whether women had experienced recent IPV. Women without recent IPV had a significant decline in condomless sex from pregnancy to postpartum (aRR 0.53, 95%CI 0.30–0.95) while women with recent IPV had no significant change in condomless sex from pregnancy to postpartum (aRR 1.76, 95%CI 0.87–3.55).

Conclusion

Improved support for ART adherence during the postpartum period and addressing IPV to limit condomless sex could improve HIV treatment and prevention outcomes for HIV-seropositive women as well as their infants and sexual partners.