bluuebunny/crossref_metadata_2025 huggingface dataset:
CD6-mediated inhibition of T cell activation via modulation of Ras
Authors: Henriques Sónia N. , Oliveira Liliana , Santos Rita F. , Carmo Alexandre M.
Published: November 2022

Background

CD6 is one of many cell surface receptors known to regulate signal transduction upon T cell activation. However, whether CD6 mediates costimulatory or inhibitory signals is controversial. When T cells engage with antigen presenting cells (APCs), CD6 interacts with its ligand CD166 at the cell–cell interface while the cytosolic tail assembles a complex signalosome composed of adaptors and effector enzymes, that may either trigger activating signaling cascades, or instead modulate the intensity of signaling. Except for a few cytosolic adaptors that connect different components of the CD6 signalosome, very little is known about the mechanistic effects of the cytosolic effectors that bind CD6.

Methods

Jurkat model T cells were transfected to express wild-type (WT) CD6, or a cytoplasmic truncation, signaling-disabled mutant, CD6Δcyt. The two resulting cell lines were directly activated by superantigen (sAg)-loaded Raji cells, used as APCs, to assess the net signaling function of CD6. The Jurkat cell lines were further adapted to express a FRET-based unimolecular HRas biosensor that reported the activity of this crucial GTPase at the immunological synapse.

Results

We show that deletion of the cytosolic tail of CD6 enhances T-cell responses, indicating that CD6 restrains T-cell activation. One component of the CD6-associated inhibitory apparatus was found to be the GTPase activating protein of Ras (RasGAP), that we show to associate with CD6 in a phosphorylation-dependent manner. The FRET HRas biosensor that we developed was demonstrated to be functional and reporting the activation of the T cell lines. This allowed to determine that the presence of the cytosolic tail of CD6 results in the down-regulation of HRas activity at the immunological synapse, implicating this fundamental GTPase as one of the targets inhibited by CD6.

Conclusions

This study provides the first description of a mechanistic sequence of events underlying the CD6-mediated inhibition of T-cell activation, involving the modulation of the MAPK pathway at several steps, starting with the coupling of RasGAP to the CD6 signalosome, the repression of the activity of Ras, and culminating in the reduction of ERK1/2 phosphorylation and of the expression of the T-cell activation markers CD69 and IL-2R α chain.
RETRACTED ARTICLE: The prevalence of electronic cigarettes vaping globally: a systematic review and meta-analysis
Authors: Tehrani Hadi , Rajabi Abdolhalim , Ghelichi- Ghojogh Mousa , Nejatian Mahbobeh , Jafari Alireza
Published: November 2022

Background

The purpose of this systematic review study was to determine the national, regional, and global prevalence of electronic cigarettes (e-cigarettes) vaping.

Method

The articles were searched in July 2020 without a time limit in Web of Science (ISI), Scopus, PubMed, and Ovid-MEDLINE. At first, the titles and abstracts of the articles were reviewed, and if they were appropriate, they entered the second stage of screening. In the second stage, the whole articles were reviewed and articles that met the inclusion criteria were selected. In this study, search, selection of studies, qualitative evaluation, and data extraction were performed by two authors independently, and any disagreement between the two authors was reviewed and corrected by a third author.

Results

In this study, the lifetime and current prevalence of e-cigarettes vaping globally were 23% and 11%, respectively. Lifetime and current prevalence of e-cigarettes vaping in women were 16% and 8%, respectively. Also, lifetime and current prevalence of e-cigarettes vaping in men were 22% and 12%, respectively. In this study, the current prevalence of e-cigarettes vaping in who had lifetime smoked conventional cigarette was 39%, and in current smokers was 43%. The lifetime prevalence of e-cigarettes vaping in the Continents of America, Europe, Asia, and Oceania were 24%, 26%, 16%, and 25%, respectively. The current prevalence of e-cigarettes vaping in the Continents of America, Europe, Asia, and Oceania were 10%, 14%, 11%, and 6%, respectively.

Conclusions

Based on the results of this study, it can be concluded that the popularity of e-cigarettes is increasing globally. Therefore, it is necessary for countries to have more control over the consumption and distribution of e-cigarettes, as well as to formulate the laws prohibiting about the e-cigarettes vaping in public places. There is also a need to design and conduct information campaigns to increase community awareness about e-cigarettes vaping.
Quantum computer-assisted global optimization in geophysics illustrated with stack-power maximization for refraction residual statics estimation
Authors: Dukalski Marcin , Rovetta Diego , van der Linde Stan , Möller Matthias , Neumann Niels , Phillipson Frank
Published: November 2022

Much of recent progress in geophysics can be attributed to the adaptation of heterogeneous high-performance computing architectures. It is projected that the next major leap in many areas of science, and hence hopefully in geophysics too, will be due to the emergence of quantum computers. Finding a right combination of hardware, algorithms, and a use case, however, proves to be a very challenging task — especially when looking for a relevant application that scales efficiently on a quantum computer and is difficult to solve using classical means. We find that maximizing stack power for residual statics correction, an NP-hard combinatorial optimization problem, appears to naturally fit a particular type of quantum computing known as quantum annealing. We express the underlying objective function as a quadratic unconstrained binary optimization, which is a quantum-native formulation of the problem. We choose some solution space and define a proper encoding to translate the problem variables into qubit states. We find that these choices can have a significant impact on the maximum problem size that can fit on the quantum annealer and on the fidelity of the final result. To improve the latter, we embed the quantum optimization step in a hybrid classical-quantum workflow, which aims to increase the frequency of finding the global, rather than some local, optimum of the objective function. Finally, we find that a generic, black-box, hybrid classical-quantum solver also could be used to solve stack-power maximization problems proximal to industrial relevance and capable of surpassing deterministic solvers prone to cycle skipping. A custom-built workflow capable of solving larger problems with an even higher robustness and greater control of the user appears to be within reach in the very near future.
Psychiatry's need for Vergangenheitsbewältigung: ‘culture wars’, cognitive dissonance and coming to terms with the past
Authors: Lepping Peter , Poole Rob
Published: November 2022

UK psychiatry's sense of self rests on being part of a socially progressive national tradition. This makes it difficult to engage with more critical narratives. The process of analysing and accepting psychiatry's past can help our profession to get closer to its real self and on a path to a better future.
Levothyroxine: Conventional and Novel Drug Delivery Formulations
Authors: Liu Hanqing , Li Wei , Zhang Wen , Sun Shengrong , Chen Chuang
Published: November 2022

Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues some strategies have been developed. Novel formulations (liquid solutions and soft gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.
IL1B gene variants, but not TNF, CXCL8, IL6 and IL10, modify the course of cystic fibrosis in Polish patients.
Authors: Zakerska-Banaszak Oliwia , Gozdzik-Spychalska Joanna , Gabryel Marcin , Zuraszek Joanna , Skrzypczak-Zielinska Marzena , Slomski Ryszard , Dobrowolska Agnieszka , Piorunek Tomasz , Batura-Gabryel Halina
Published: November 2022

Background: The main aim of this study was to evaluate whether selected polymorphic variants in genes from the inflammatory pathway can be predictors of pulmonary or digestive manifestation of cystic fibrosis, as well as of severity of lung disease.

Materials and methods: Using pyrosequencing and sequencing we have genotyped 12 variants in TNF (rs361525, rs1800629), CXCL8 (rs4073, rs2227306, rs2227307, rs188378669), IL1B (rs16944, rs1143634, rs1142639, rs1143627), IL6 (rs1800795) and IL10 (rs1800896) genes in a cohort of 55 Polish patients with diagnosed cystic fibrosis and controls. In our study group, a pulmonary manifestation of disease revealed 44 of subjects (80%), and digestive symptoms dominated in 11 (20%) of analyzed individuals. Severe lung dysfunction has occurred in 20 (36.4%) of patients.

Results: We proved, that two promoter variants of IL1B, rs1143627 (c.-118G > A) and rs16944 (c.-598T > C) are presented significantly more often  in patients with severe character of lung disease compared to mild (82.5% vs. 62.8%, p-value 0.030, and 87.5% vs. 64.3%, p-value 0.008, respectively) in cystic fibrosis course. Haplotype AC formed by both changes had also a higher frequency (80%) in patients with severe course compared to the mild character (61.4%) of disease. However, the frequency of promoter variant TNF c.-308C > T (rs1800629) was presented at a significantly lower level in the patient’s group compared to healthy controls (2.7% vs. 15%, p-value 0.001). Furthermore, the presence of methicillin-resistant Staphylococcus aureus significantly correlated with the lower FEV1% in patients (p-value 0.01).

Conclusions: Genetic variants, rs1143627 and rs16944, of IL1B are promising candidates as predictors of the severe character of lung disease in Polish patients with cystic fibrosis.
Financial distress, earning management, financial statement fraud and audit quality as a moderating variable: listed companies on the Indonesia Stock Exchange
Authors: Mukhtaruddin Mukhtaruddin , Chairunnisa Widya Zahra , Patmawati Patmawati , Saftiana Yulia
Published: November 2022

Background: Accounting practices, profit bubbles, information manipulation and deception, and earning management are all examples of fraudulent financial statement cases. Companies create fraudulent financial statements for a variety of reasons, including financial challenges and debt payment delays. Financial fraud is created by five factors: pressure, opportunity, rationalization, capability, and arrogance.

Methods: The purpose of this study is to see whether audit quality (AQ) has a moderating effect on the relationship between financial distress (FD) and earning management (EM) to financial statement fraud (FSF) in infrastructure, utility, and transportation companies listed on the Indonesia Stock Exchange during the years 2015 to 2019. The data sources are the www.idx.go.id and the company’s annual reports. Purposive sampling was used to collect data from thirty companies over the course of five years, totaling 150 observations. Moderating regression analysis (MRA) was used in data analysis.

Result and conclusions: The hypothesis testing revealed that FD and EM have a significant impact on FSF.  AQ is able to moderate the relationship between FD to FSF but unable to moderate the relationship between EM to FSF.
Harnessing the disruption on medical trainee education due to COVID-19 in New South Wales, Australia
Authors: Van Es Simone L. , Tan Aaron J.H. , Vial Toni , Burnand Jo , Blizard Claire M.
Published: November 2022

The coronavirus disease (COVID-19) pandemic has caused disruption and uncertainty for junior medical doctor training and education. This has compounded the existing stress experienced by this cohort. However, by choosing appropriate educational models, as well as using novel educational approaches and advancing our online technology capabilities, we may be able to provide acceptable and even, superior solutions for educational training moving forward, as well as promote trainee wellbeing during these uncertain times.
Mentalização em Professoras de Berçário
Authors: Recktenvald Karina , Donelli Tagma Marina Schneider
Published: November 2022

Mentalização é a habilidade de interpretar os próprios comportamentos e os de outros em termos de estados mentais. No presente estudo exploratório, objetivou-se avaliar a capacidade de mentalização de professoras de berçário que atuam com bebês entre quatro e dezoito meses de idade, em escolas de Educação Infantil. Participaram do estudo quatro professoras que atuam em Porto Alegre e região Metropolitana, três delas na rede pública e uma na rede privada. Utilizaram-se os instrumentos: Ficha de Dados Sociodemográficos e Profissionais e Entrevista de História de Vida e Relações Atuais – essa analisada através do Checklist for the clinical assessment of mentalizing. A classificação da capacidade de mentalização das participantes variou entre "boa" e "muito alta" nos quatro contextos avaliados pelo Checklist. Conclui-se que o resultado é positivo, pois uma boa capacidade de mentalização dos cuidadores está atrelada à oferta de cuidados de qualidade e à possibilidade de o professor pensar sobre como se relaciona com as crianças. Também contribui para o desenvolvimento da capacidade de mentalização delas. Indica-se a necessidade de novas pesquisas que validem instrumentos de avaliação da capacidade de mentalização no país, criem e testem intervenções que visem promovê-la, inclusive, em contextos diversos do escolar.
Encontros e Desencontros de Judith Butler com a Psicanálise
Authors: Bonfim Flavia Gaze , Vidal Paulo Eduardo Viana
Published: November 2022

A proposta deste artigo é apresentar algumas considerações sobre o pensamento da filósofa Judith Butler, suas críticas à teoria de Lacan, bem como alguns contrapontos a seus argumentos críticos, com o objetivo de demarcar os encontros e desencontros de Butler com a psicanálise. Nesse percurso, identificamos que as críticas da autora se restringem ao primeiro ensino lacaniano, não levando em considerações os avanços das fórmulas quânticas da sexuação e a noção de sinthoma, como arranjo singular do falasser com o gozo. Além disso, constatamos também que seu questionamento em relação à psicanálise não impossibilitou que, para pensar o gênero, Butler se servisse do aparato conceitual da metapsicologia freudiana e lacaniana, especialmente da noção de pulsão. Concluímos que as críticas de Butler à psicanálise não precisam ser tomadas como um problema ou um entrave, visto que elas promovem uma exigência frutífera de precisão teórico-clínica, que irrompe na atualidade, para avançarmos no debate sobre as novas ordenações da sexualidade.
Intersecções entre Gênero, Raça e Pobreza na vida de Mulheres no Nordeste do Brasil
Authors: Barbosa Vilkiane Natercia Malherme , Moura Júnior James Ferreira
Published: November 2022

A análise interseccional dos marcadores de raça, classe, gênero tem sido uma importante ferramenta ética e metodológica para a compreensão das condições de opressão vividas pelas pessoas em situação de pobreza. Reconhece-se que esses marcadores podem gerar tanto opressões como processos de resistências que afetam seus modos de vida. Assim, o objetivo deste trabalho é analisar os impactos das intersecções do gênero, da raça, e da pobreza no modo de vida das mulheres de uma comunidade no Nordeste do Brasil. A proposta foi realizada a partir de uma perspectiva qualitativa, com entrevistas semi-estruturadas com sete mulheres pretas. Elas são moradoras de uma comunidade em situação de pobrezas em cidade com menos de 30 mil habitantes. Foi realizada análise de conteúdo do material produzido. Identificou-se que as estruturas macrossociais patriarcais, classistas e racistas exercem influência sobre os modos de vida destas mulheres. Como consequências, observou-se a existência de trajetórias de violências e de pobreza, fomentando processos específicos de opressão, por vezes reproduzidos pelas próprias mulheres. Contudo, é relevante pontuar que estas mulheres também têm produzido dissonâncias, permitindo experimentar resistências e novas formas de agenciamentos para a produção de novos modos de vida que desvelam possibilidade de enfrentamento destas mazelas sociais.
Alfabetização e Letramento: Uma Discussão sobre Gêneros Textuais Digitais
Authors: Moya Paula Tamyris , Arrais Luciana Figueiredo Lacanallo , Lucas Maria Angélica Olivo Francisco
Published: November 2022

Este artigo tem o objetivo de discutir contribuições do uso de gêneros textuais digitais no processo de alfabetização e letramento. Em situações vivenciadas em sala de aula é notável que as novas tecnologias trazem grande motivação aos alunos. Tal observação assinala a possibilidade de empregar ferramentas tecnológicas como recursos didáticos que potencializem os processos de alfabetização e de letramento. Diante disso, questionamos: os gêneros textuais digitais podem fomentar a aprendizagem da linguagem escrita no início do processo de escolarização? Para responder a essa questão, buscamos embasamento na Teoria Histórico-Cultural e em princípios da teoria bakhtiniana. Inicialmente, analisamos o papel do professor diante do processo de ensino e aprendizagem da linguagem escrita. Na sequência, discorremos a respeito dos processos de alfabetização e letramento. Posteriormente, apresentamos algumas reflexões a respeito da possibilidade de gêneros discursivos digitais promoverem tais processos. Esperamos que tais reflexões auxiliem o leitor a pensar a organização do ensino da linguagem escrita, buscando assegurar a todos os alunos a apropriação desse conhecimento, condição para o pleno desenvolvimento.
Exascale integrated modeling of low-order wavefront sensing and control for the Roman Coronagraph instrument
Authors: Dube Brandon D. , Riggs A. J. , Kern Brian D. , Cady Eric J. , Krist John E. , Zhou Hanying , Nemati Bijan , Seo Byoung-Joon , Steeves John , Arndt David , Mandić Milan , Shields Joel , Boussalis Dhemetrios , Valverde Alfredo , Rahman Zahidul , Fathpour Nanaz
Published: November 2022

Astronomical instruments to detect exoplanets require extreme wavefront
stability. For these missions to succeed, comprehensive and precise
modeling is required to design and analyze suitable coronagraphs and
their wavefront control systems. In this paper, we describe techniques
for integrated modeling at scale that is, to the best of our
knowledge, 1000 times faster than previously published works. We show
how this capability has been used to validate performance and perform
uncertainty quantification for the Roman Coronagraph instrument.
Finally, we show how this modeling capacity may be necessary to design
and build the next generation of space-based coronagraph
instruments.
Dominated mode switching and nanoparticle detection at exceptional points
Authors: Wang Zijie , Zhang Xiaobei , Zhang Qi , Chen Yiqi , Wang Yang , Yu Yang , Yang Yong , Wang Tingyun
Published: November 2022

We present a theoretical investigation of dominated mode switching and nanoparticle detection at a wavelength of 2 µm that uses coupled whispering gallery mode (WGM) resonators operating at exceptional points (EPs). The simulations show that with assisted gain and loss the system can be steered to operate at EPs by adjusting the nanoparticle-introduced backscattering. The unbalanced contributions of the clockwise and counterclockwise modes can be observed when the system approaches the EPs, and the dominated mode is switchable by transiting the system from one EP to another. Owing to the square root topology of EPs, the enhanced frequency splitting can be obtained when the system is subjected to a perturbation, which results in a more than five times sensitivity enhancement compared to a traditional sensor. Furthermore, a simulation also reveals that an increased gain–loss contrast in the resonators contributes to an enhanced frequency splitting, and thus a higher sensitivity enhancement factor. Our investigations validate the feasibility of a WGM resonator operating at EPs for unidirectional laser emitting and nanoparticle sensing.
Non-photochemical quenching estimates from in situ spectroradiometer measurements: implications on remote sensing of sun-induced chlorophyll fluorescence in lakes
Authors: Gupana Remika S. , Damm Alexander , Rahaghi Abolfazl Irani , Minaudo Camille , Odermatt Daniel
Published: November 2022

Quantum yield of fluorescence (ϕ
F
) is key to interpret remote measurements of sun-induced fluorescence (SIF), and whether the SIF signal is governed by photochemical quenching (PQ) or non-photochemical quenching (NPQ). Disentangling PQ from NPQ allows using SIF estimates in various applications in aquatic optics. However, obtaining ϕ
F
is challenging due to its high temporal and physiological variability, and the combined measurements needed to enclose all relevant optical paths. In inland waters, this type of data is scarce and information on diurnal and seasonal ϕ
F
dynamics are almost unknown. Using an autonomous hyperspectral Thetis profiler in Lake Geneva, we demonstrate how to estimate ϕ
F
using an ensemble of in-situ measurements acquired between 2018 to 2021. We use vertical and temporal changes in retrieved ϕ
F
to determine NPQ and PQ conditions. We observed NPQ in 36% of the total daytime profiles used in the ϕ
F
analysis. While downwelling irradiance is a significant contributor to ϕ
F
, its role cannot be easily interpreted. Other factors such as phytoplankton photoregulation and assemblages also likely play significant roles in quenching mechanisms. We conclude that an adapted approach exploiting in-situ data is suitable to determine diurnal and seasonal NPQ occurrence, and helps develop future remote sensing algorithms.
Deep ultraviolet spontaneous emission enhanced by layer dependent black phosphorus plasmonics
Authors: Sikder Bejoy , Nayem Suzit Hasan , Uddin Shiekh Zia
Published: November 2022

Although graphene has been the primary material of interest recently for spontaneous emission engineering through the Purcell effect, it features isotropic and thickness-independent optical properties. In contrast, the optical properties of black Phosphorus (BP) are in-plane anisotropic; which supports plasmonic modes and are thickness-dependent, offering an additional degree of freedom for control. Here we investigate how the anisotropy and thickness of BP affect spontaneous emission from a Hydrogenic emitter. We find that the spontaneous emission enhancement rate i.e. Purcell factor (PF) depends on emitter orientation, and PF at a particular frequency and distance can be controlled by BP thickness. At lower frequencies, PF increases with increasing thickness due to infrared (IR) plasmons, which then enhances visible and UV far-field spectra, even at energies greater than 10 eV. By leveraging the thickness and distance-dependent PF, deep UV emission can be switched between 103 nm or 122 nm wavelength from a Hydrogenic emitter. Additionally, we find that doping can significantly tune the PF near BP and this alteration depends on the thickness of the BP. Our work shows that BP is a promising platform for studying strong plasmon-induced light-matter interactions tunable by varying doping levels, emitter orientation, and thickness.
Single thin-plate compression of multi-TW laser pulses to 3.9 fs
Authors: Tóth Szabolcs , Nagymihály Roland S. , Seres Imre , Lehotai Levente , Csontos János , Tóth László Tamás , Geetha Prabhash Prasannan , Somoskői Tamás , Kajla Barna , Abt Dániel , Pajer Viktor , Farkas Arnold , Mohácsi Árpád , Börzsönyi Ádám , Osvay Károly
Published: November 2022

Post-compression of 12-fs laser pulses with multi-TW peak power from an optical parametric chirped pulse amplification (OPCPA) system was performed by using a single thin fused silica plate in a vacuum. By optimizing the input pulses in both spatial and temporal domains, after compression with customized chirped mirrors, we achieved pulses as short as 3.87 fs, in combination with 12-mJ energy. The spatio-spectral quality of the post-compressed pulses was thoroughly analyzed. The generated 1.4-cycle pulses pave the way for next generation attosecond and particle acceleration experiments.
Gain-switched Ho:YAG laser with a 3.35-ns pulse duration
Authors: Bach Yechiel , Nahear Rotem , Noach Salman
Published: November 2022

This paper presents a gain-switched Ho:YAG laser at 2090 nm, pumped by a passively Q switched Tm:YLF. A pulse duration of 3.35 ns is achieved with a pulse energy of 0.7 mJ at 1.3-kHz repetition rate, corresponding to 209-kW peak power. The pump energy is 2.8 mJ, corresponding to 25% conversion efficiency with 37% slope efficiency. This laser performance with its compact design can be implemented in applications that require short pulse durations that have not been addressed to date.
Low coercivity magnetoplasmonic crystal based on a thin permalloy film for magnetic field sensing applications
Authors: Murzin Dmitry V. , Frolov Aleksandr Yu. , Mamian Karen A. , Belyaev Victor K. , Fedyanin Andrey A. , Rodionova Valeria V.
Published: November 2022

This research is devoted to the fabrication of 5-nm thick permalloy film-based magnetoplasmonic crystal for magnetic field sensing applications. Optical and magneto-optical activity of the magnetoplasmonic crystal is studied with the means of numerical modeling and spectroscopy techniques. The studied sample achieves sensitivity to an external DC magnetic field of 7.5 mOe in the 5.1 Oe required modulation AC magnetic field. Obtained experimental and modeling results can be used for the fabrication of cheaper and more energy-efficient sensing elements for magnetoplasmonic crystal-based magnetic field sensors due to the reduction of required ferromagnetic material and modulation magnetic field.
Bifacial-metasurface-enabled pancake metalens with polarized space folding
Authors: Chen Chen , Ye Xin , Sun Jiacheng , Chen Yuxin , Huang Chunyu , Xiao Xingjian , Song Wange , Zhu Shining , Li Tao
Published: November 2022

Replacing traditional refractive lenses with metalenses that have ultrathin and flat architecture could make imaging systems more compact. However, the space between the lens and image is usually the dominating factor in determining the bulkiness, and it cannot be shortened just by using thinner lenses. Here, we propose a pancake metalens that folds the optical path at will using a metacavity consisting of a spin-dependent bifacial metasurface and a mirror. We first verify the asymmetric and independent functions of this bifacial metasurface, and then demonstrate the polarized space-folding effect of the metacavity. Imparted with specifically designed phase, we demonstrate a pancake metalens with on-demand (e.g., 2/3 and 4/5) reduction of imaging distance and relatively good imaging performance. This pancake metaoptics framework could enable miniaturization of imaging systems and would provide insights for metadevice applications.
Exploring the mono-/bistability range of positively autoregulated signaling systems in the presence of competing transcription factor binding sites
Authors: Gao Rong , Brokaw Samantha E. , Li Zeyue , Helfant Libby J. , Wu Ti , Malik Muhammad , Stock Ann M.
Published: November 2022

Binding of transcription factor (TF) proteins to regulatory DNA sites is key to accurate control of gene expression in response to environmental stimuli. Theoretical modeling of transcription regulation is often focused on a limited set of genes of interest, while binding of the TF to other genomic sites is seldom considered. The total number of TF binding sites (TFBSs) affects the availability of TF protein molecules and sequestration of a TF by TFBSs can promote bistability. For many signaling systems where a graded response is desirable for continuous control over the input range, biochemical parameters of the regulatory proteins need be tuned to avoid bistability. Here we analyze the mono-/bistable parameter range for positively autoregulated two-component systems (TCSs) in the presence of different numbers of competing TFBSs. TCS signaling, one of the major bacterial signaling strategies, couples signal perception with output responses via protein phosphorylation. For bistability, competition for TF proteins by TFBSs lowers the requirement for high fold change of the autoregulated transcription but demands high phosphorylation activities of TCS proteins. We show that bistability can be avoided with a low phosphorylation capacity of TCSs, a high TF affinity for the autoregulated promoter or a low fold change in signaling protein levels upon induction. These may represent general design rules for TCSs to ensure uniform graded responses. Examining the mono-/bistability parameter range allows qualitative prediction of steady-state responses, which are experimentally validated in the E. coli CusRS system.
Simultaneous depletion of RB, RBL1 and RBL2 affects endoderm differentiation of human embryonic stem cells
Authors: Nakanoh Shota , Kadiwala Juned , Pinte Laetitia , Morell Carola Maria , Lenaerts An-Sofie , Vallier Ludovic
Published: November 2022

RB is a well-known cell cycle regulator controlling the G1 checkpoint. Previous reports have suggested that it can influence cell fate decisions not only by regulating cell proliferation and survival but also by interacting with transcription factors and epigenetic modifiers. However, the functional redundancy of RB family proteins (RB, RBL1 and RBL2) renders it difficult to investigate their roles during early development, especially in human. Here, we address this problem by generating human embryonic stem cells lacking RB family proteins. To achieve this goal, we first introduced frameshift mutations in RBL1 and RBL2 genes using the CRISPR/Cas9 technology, and then integrated the shRNA-expression cassette to knockdown RB upon tetracycline treatment. The resulting RBL1/2_dKO+RB_iKD cells remain pluripotent and efficiently differentiate into the primary germ layers in vitro even in the absence of the RB family proteins. In contrast, we observed that subsequent differentiation into foregut endoderm was impaired without the expression of RB, RBL1 and RBL2. Thus, it is suggested that RB proteins are dispensable for the maintenance and acquisition of cell identities during early development, but they are essential to generate advanced derivatives after the formation of primary germ layers. These results also indicate that our RBL1/2_dKO+RB_iKD cell lines are useful to depict the detailed molecular roles of RB family proteins in the maintenance and generation of various cell types accessible from human pluripotent stem cells.
Manipulating risk of infection and appeal to public benefit increase compliance with infection control measures in a hypothetical pandemic scenario
Authors: Bjørkheim Sebastian , Sætrevik Bjørn
Published: November 2022

To limit an infectious outbreak, the public must be informed about the infection risk and be motivated to comply with infection control measures. Perceiving a situation as threatening and seeing benefits to complying may be necessary to motivate for compliance. The current study used a preregistered survey experiment with a 2-by-2 between-subject design to investigate if emphasizing high infection risk and appealing to societal benefits impacted intention to comply with infection control measures. The results from a representative Norwegian sample (N = 2533) show that describing a high (as opposed to low) personal risk scenario had a small main effect on compliance. Further, appealing to public (as opposed to self-interested) benefits also had a small main effect. There was no interaction between risk scenario and motivational emphasis. The results suggest that to maximize compliance, information about disease outbreak should emphasize the individual risk of contracting the disease, and could also underline the public value of limiting infection spread. These findings can inform health authorities about the motives underlying compliance with infection control measures during an infectious disease outbreak.
Impact of HPV mRNA types 16, 18, 45 detection on the risk of CIN3+ in young women with normal cervical cytology
Authors: Al-Shibli Khalid , Mohammed Hiba Abdul Latif , Maurseth Ramona , Fostervold Mikkel , Werner Sebastian , Sørbye Sveinung Wergeland
Published: November 2022

Background

Despite a well-established cervical cancer (CC) screening program in Norway, the incidence of CC in young women is increasing, peaking at 35 years of age. 25 percent of all women diagnosed with CC had normal cytology within 3 years prior to cancer diagnosis, addressing the need to improve the screening programme to further reduce cancer incidences missed by cytology.

Objective

We wanted to investigate the detection rate of CIN3+ in women 25–39 years with normal cytology by using a 3-type HPV mRNA test as a targeted quality assurance measure. The control group is women with normal cytology.

Methods

During 2014–2017, samples from 13,021 women 25–39 years of age attending cervical cancer screening were analysed at Nordlandssykehuset, Bodø, Norway, including 1,896 women with normal cytology and HPV mRNA test (intervention group), and 11,125 women with cytology only (control group). The HPV mRNA testing was performed using a 3-type HPV E6/E7 mRNA test (PreTect SEE; direct genotyping 16, 18 and 45). The women were followed-up according to national guidelines throughout December 2021.

Results

Of the 13,021 women, 429 women (3.3%) had CIN3+ confirmed by biopsy in the follow-up, including 13 cases of invasive cervical cancer. Of the 1,896 women with normal cytology and HPV mRNA test (intervention group), 49 women (2.6%) had a positive test. The risks of CIN3+ among women with either a positive or negative HPV mRNA test were 28.6% (14/49) and 0.8% (14/1847). None of the women in the intervention group developed cervical cancer during follow-up. Of the 11,125 women with cytology only (control group), 712 women (6.4%) had abnormal cytology (ASC-US+). The risks of CIN3+ among women with abnormal and normal cytology were 17.7% (126/712) and 2.6% (275/10,413).

Conclusion

By testing women 25–39 years of age with a normal cytology result using a specific 3-type HPV mRNA test, an increase in screening programme sensitivity can be achieved without an excessive additional workload. Women with normal cytology and a negative HPV mRNA test have a very low risk of cervical cancer.
Maximum knee extension velocity without external load is a stronger determinant of gait function than quadriceps strength in the early postoperative period following total knee arthroplasty
Authors: Iwata Akira , Sano Yuki , Wanaka Hideyuki , Kobayashi Shingo , Okamoto Kensuke , Yamahara Jun , Inaba Masaki , Konishi Yuya , Inoue Junji , Kanayama Atsuki , Yamamoto Saki , Iwata Hiroshi
Published: November 2022

Objective

Quadriceps weakness is considered the primary determinant of gait function after total knee arthroplasty (TKA). However, many patients have shown a gap in improvement trends between gait function and quadriceps strength in clinical situations. Factors other than quadriceps strength in the recovery of gait function after TKA may be essential factors. Because muscle power is a more influential determinant of gait function than muscle strength, the maximum knee extension velocity without external load may be a critical parameter of gait function in patients with TKA. This study aimed to identify the importance of knee extension velocity in determining the gait function early after TKA by comparing the quadriceps strength.

Methods

This prospective observational study was conducted in four acute care hospitals. Patients scheduled for unilateral TKA were recruited (n = 186; age, 75.9 ± 6.6 years; 43 males and 143 females). Knee extension velocity was defined as the angular velocity of knee extension without external load as quickly as possible in a seated position. Bilateral knee function (knee extension velocity and quadriceps strength), lateral knee function (pain and range of motion), and gait function (gait speed and Timed Up and Go test (TUG)) were evaluated before and at 2 and 3 weeks after TKA.

Results

Both bilateral knee extension velocities and bilateral quadriceps strengths were significantly correlated with gait function. The knee extension velocity on the operation side was the strongest predictor of gait function at all time points in multiple regression analysis.

Conclusion

These findings identified knee extension velocity on the operation side to be a more influential determinant of gait function than impairments in quadriceps strength. Therefore, training that focuses on knee extension velocity may be recommended as part of the rehabilitation program in the early postoperative period following TKA.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR) UMIN000020036.
The effectiveness of problem based learning in improving critical thinking, problem-solving and self-directed learning in first-year medical students: A meta-analysis
Authors: Manuaba Ida Bagus Amertha Putra , -No Yi , Wu Chien-Chih
Published: November 2022

Background

The adaptation process for first-year medical students is an important problem because it significantly affects educational activities. The previous study showed that 63% of students had difficulties adapting to the learning process in their first year at medical school. Therefore, students need the most suitable learning style to support the educational process, such as Problem-based learning (PBL). This method can improve critical thinking skills, problem-solving and self-directed learning. Although PBL has been adopted in medical education, the effectiveness of PBL in first-year medical students is still not yet clear. The purpose of this meta-analysis is to verify whether the PBL approach has a positive effect in improving knowledge, problem-solving and self-directed learning in first-year medical students compared with the conventional method.

Methods

We searched PubMed, ScienceDirect, Cochrane, and Google Scholar databases until June 5, 2021. Search terms included problem-based learning, effectiveness, effectivity, and medical student. We excluded studies with the final-year medical student populations. All analyses in our study were carried out using Review Manager version 5.3 (RevMan Cochrane, London, UK).

Result

Seven eligible studies (622 patients) were included. The pooled analysis demonstrated no significant difference between PBL with conventional learning method in critical thinking/knowledge assessment (p = 0.29), problem-solving aspect (p = 0.47), and self-directed learning aspect (p = 0.34).

Conclusion

The present study concluded that the PBL approach in first-year medical students appeared to be ineffective in improving critical thinking/knowledge, problem-solving, and self-directed compared with the conventional teaching method.
Study on the central neural pathway and the relationship between the heart and small intestine via a dual neural tracer
Authors: ZHANG Fan , WU Li-bin , HU Ling , WU Zi-jian , CUI Shuai , YU Qing , CAI Rong-lin
Published: November 2022

Despite very different functions, studies increasingly report that there may be a potential central nervous anatomical connection between the heart and the small intestine. In this study, the central nervous anatomical relationship between the heart and small intestine was studied via a viral tracer. Pseudorabies virus (PRV) syngeneic strains with different fluorescent reporter genes (eGFP or mRFP) were microinjected into the heart walls and small intestinal walls of male C57BL/6J using glass microelectrode. The results showed that the co-labeled nuclei in the brain were lateral periaqueductal gray (LPAG) and ventrolateral periaqueductal gray (VLPAG) in the midbrain, mesencephalic trigeminal nucleus (Me5), and motor trigeminal nucleus anterior digastric Part (5Adi) in the pons. The co-labeled sites in the spinal cord were intermediolateral column (IML) in the second thoracic vertebra, IML and lamina 7 of the spinal gray (7SP) in the third thoracic vertebra, and IML in the fourth thoracic vertebra. Our data show that there is a neuroanatomical connection between the small intestine and the heart in the central nervous system (CNS). Neuroanatomical integration of the heart and small intestine may provide a basis for revealing the physiological and pathological interactions between the circulatory and digestive systems. The interactions may be mediated more effectively through sympathetic nerves.
Uptake and effect of universal test-and-treat on twelve months retention and initial virologic suppression in routine HIV program in Kenya
Authors: Kimanga Davies O. , Oramisi Violet A. , Hassan Amin S. , Mugambi Mary K. , Miruka Frederick O. , Muthoka Kennedy J. , Odhiambo Jacob O. , Yegon Peter K. , Omoro Gonza O. , Mbaire Catherine , Masamaro Kenneth M. , Njogo Susan M. , Barker Joseph L , Ngugi Catherine N.
Published: November 2022

Early combination antiretroviral therapy (cART), as recommended in WHO’s universal test-and-treat (UTT) policy, is associated with improved linkage to care, retention, and virologic suppression in controlled studies. We aimed to describe UTT uptake and effect on twelve-month non-retention and initial virologic non-suppression (VnS) among HIV infected adults starting cART in routine HIV program in Kenya. Individual-level HIV service delivery data from 38 health facilities, each representing 38 of the 47 counties in Kenya were analysed. Adults (>15 years) initiating cART between the second-half of 2015 (2015HY2) and the first-half of 2018 (2018HY1) were followed up for twelve months. UTT was defined based on time from an HIV diagnosis to cART initiation and was categorized as same-day, 1–14 days, 15–90 days, and 91+ days. Non-retention was defined as individuals lost-to-follow-up or reported dead by the end of the follow up period. Initial VnS was defined based on the first available viral load test with >400 copies/ml. Hierarchical mixed-effects survival and generalised linear regression models were used to assess the effect of UTT on non-retention and VnS, respectively. Of 8592 individuals analysed, majority (n = 5864 [68.2%]) were female. Same-day HIV diagnosis and cART initiation increased from 15.3% (2015HY2) to 52.2% (2018HY1). The overall non-retention rate was 2.8 (95% CI: 2.6–2.9) per 100 person-months. When compared to individuals initiated cART 91+ days after a HIV diagnosis, those initiated cART on the same day of a HIV diagnosis had the highest rate of non-retention (same-day vs. 91+ days; aHR, 1.7 [95% CI: 1.5–2.0], p<0.001). Of those included in the analysis, 5986 (69.6%) had a first viral load test done at a median of 6.3 (IQR, 5.6–7.6) months after cART initiation. Of these, 835 (13.9%) had VnS. There was no association between UTT and VnS (same-day vs. 91+ days; aRR, 1.0 [95% CI: 0.9–1.2], p = 0.664). Our findings demonstrate substantial uptake of the UTT policy but poor twelve-month retention and lack of an association with initial VnS from routine HIV settings in Kenya. These findings warrant consideration for multi-pronged program interventions alongside UTT policy for maximum intended benefits in Kenya.
Effect of an illegal open dump in an urban forest on landscape appreciation
Authors: Bielinis Ernest , Janeczko Emilia , Korcz Natalia , Janeczko Krzysztof , Bielinis Lidia
Published: November 2022

Rubbish in a forest environment is a great threat to this ecosystem, but this threat may also apply to the lost benefits for visitors to the forest. Previous studies proved that forest areas have a positive effect on obtaining psychological relaxation in the people visiting them. However, it was not known whether this restorative experience could be disturbed in any way by the presence of an open dump in the forest. To check how the presence of a landfill affects the visitors, an experiment was planned in which the respondents observed a forest area with a landfill and a forest landscape without a landfill for 15 minutes (control). The respondents then assessed the landscape using the semantic differential method and the Perceived Restorativeness Scale (PRS). An analysis of these observations showed that the presence of a landfill in the forest significantly changed the appreciation of the landscape by the respondents, the values of positive experiences decreased, and the negative experiences increased. Restorativeness was also reduced. Based on the results, it can be concluded that the presence of garbage in the forest may interrupt the restorative experience of its visitors.
Tele-Rapid Response Team (Tele-RRT): The effect of implementing patient safety network system on outcomes of medical patients–A before and after cohort study
Authors: Balshi Ahmed N. , Al-Odat Mohammed A. , Alharthy Abdulrahman M. , Alshaya Rayan A. , Alenzi Hanan M. , Dambung Alhadzia S. , Mhawish Huda , Altamimi Saad M. , Aletreby Waleed Th.
Published: November 2022

Background

Rapid Response Teams were developed to provide interventions for deteriorating patients. Their activation depends on timely detection of deterioration. Automated calculation of warning scores may lead to early recognition, and improvement of RRT effectiveness.

Method

This was a “Before” and “After” study, in the “Before” period ward nurses activated RRT after manually recording vital signs and calculating warning scores. In the “After” period, vital signs and warning calculations were automatically relayed to RRT through a wireless monitoring network.

Results

When compared to the before group, the after group had significantly lower incidence and rate of cardiopulmonary resuscitation (CPR) (2.3 / 1000 inpatient days versus 3.8 / 1000 inpatient days respectively, p = 0.01), significantly shorter length of hospital stay and lower hospital mortality, but significantly higher number of RRT activations. In multivariable logistic regression model, being in the “After” group decreases odds of CPR by 33% (OR = 0.67 [95% CI: 0.46–0.99]; p = 0.04). There was no difference between groups in ICU admission.

Conclusion

Automated activation of the RRT significantly reduced CPR events and rates, improved CPR success rate, reduced hospital length of stay and mortality, but increased the number of RRT activations. There were no differences in unplanned ICU admission or readmission.