bluuebunny/crossref_metadata_2025 huggingface dataset:
System-Technical Analysis of Technologies of Shrink Labels Manufacture
Authors: Гавенко Світлана Федорівна , Котмальова Олена Георгіївна , Лабецька Марта Тарасівна
Published: April 2022

Термозбіжна етикетка на сьогоднішній день є одним із передових інноваційних рішень в галузі маркування паковань. Термозбіжна плівка має механічну міцність, еластичність і вологозахисні властивості, легко змінює лінійні розміри під впливом температури, що дозволяє їй набувати форми запаковуваної продукції, запобігає від несанкціонованого відкриття і підробки, а також привертає увагу покупців за рахунок оригінальних дизайнерських рішень. Технологія термозбіжного етикетування продукції використовується в фармацевтиці, косметології, харчовій, молочній, кондитерській промисловості.
Для збереження продукцією свого належного товарного вигляду до закінчення терміну експлуатації, а також для можливості її декорування, друкування на термозбіжній етикетці виконується на внутрішній її стороні. Для нанесення зображення на термозбіжні етикетки в основному використовують технології глибокого і флексографічного друку. Специфіка технологічного процесу виготовлення термозбіжної етикетки обумовлює використання матеріалів з різними фізичними властивостями: прозорістю, блиском, товщиною, міцністю, коефіцієнтами тертя і розтягування, температурою, відсотком і часом усадки, що суттєво позначається на її кінцевій вартості. Найбільш широке застосування отримали ПЕТ і ПВХ-плівки. ПВХ-плівка деформується при більш низьких температурах і відрізняється більшою стійкістю до дії зовнішнього середовища, тоді як використання ПЕТ плівок дозволяє досягти кращих показників термоусадження і відповідно забезпечити вищу якість друкування. При нанесенні інформації на термозбіжну плівку можна використовувати фарби на водній основі, але тоді виникає ймовірність розмивання зображення при проходженні паковання через піч парового типу. Як альтернативу для друку на таких плівках застосовують фарби УФ закріплення, що дозволяє наносити багатоколірні складні зображення на будь-які види матеріалів, однак такий метод є досить дорогим, через високу вартість фарб та друкарського обладнання.
Тому важливим є проведення системо-технічного, економічного аналізу та визначення найбільш рентабельної і ефективної технології виготовлення термозбіжних етикеток.
LIMITADORES DO PROCESSO DE ENSINO E APRENDIZAGEM DOS CONCEITOS DE PROBABILIDADE
Authors: Rodrigues Soares José Ailton , De Souza Carvalho Euvaldo , Rodrigues Pereira Onésimo , Feliciano da Silva Roney , Alexandre Oliveira Paulo , Gramacho da Silva Warley , Aparecida de Souza Martins Glêndara
Published: April 2022

O trabalho apresentado debate a respeito dos principais limitadores que atuam como agentes que dificultam e minimizam a aprendizagem da temática Probabilidade no ensino médio. Inicialmente, descreve-se as habilidades e competências definidas para o ensino de Probabilidades segundo os Parâmetros Curriculares Nacionais (PCN). Em seguida, é apresentado uma pesquisa bibliográfica que demonstra a importância, juntamente com os obstáculos encontrados, para abordagem do tema. Realiza-se uma análise de estruturação e formulação de alguns problemas, destacando as situações que envolvem uma contextualização e interdisciplinaridade dos temos elencados. As considerações finais apontam limitadores relacionados à formação de professores, uso mecanizado de fórmulas e escolha de problemas sem contexto com a vivência dos alunos. Em caráter sugestivo, apresenta-se uma metodologia baseada na escolha de problemas que permite, de modo facilitador, o desenvolvimento do processo de ensino e aprendizagem da Probabilidade no ensino médio.
SEQUÊNCIA DIDÁTICA PARA O ESTUDO DA ELIPSOIDE COM O AUXILIO DO SOFTWARE WINPLOT
Authors: Teixeira Paulo Céber Mendonça , Vieira Carla Francisca e Sousa
Published: April 2022

Este trabalho tem como objetivo elaborar uma Sequência Didática para o estudo de Superfícies Quadráticas Elipsoides, com o auxílio do Software Winplot. Toda a intervenção pedagógica foi planejada baseada nas ideias e princípios pedagógicos da concepção construtivista de ensino e aprendizagem que consideram o papel ativo do sujeito e do meio e que tem o processo de aprendizagem como prioridade. Como recurso didático, optou-se por utilizar o software Winplot, por ser uma ferramenta educacional para o estudo de funções gráficas de livre acesso. Considera-se que a sequência didática elaborada possa ser uma alternativa para fugir do modelo tradicional de ensino e contribuir para o estudo da superfície quadrática elipsoide por oferecer condições favoráveis à construção do conhecimento de forma autônoma e consciente, por parte do aluno, levando em consideração o seu conhecimento prévio e respeitando a diversidade.
TENDÊNCIAS DE PESQUISAS SOBRE A ABORDAGEM DAS CAPACIDADES DE AMARTYA SEN: UM MAPEAMENTO DA PRODUÇÃO CIENTÍFICA POR MEIO DO ESTUDO BIBLIOMÉTRICO
Authors: Dezordi Ana Paula da Rosa , Zaluski Felipe Cavalheiro , Sausen Jorge Oneide , Mueller Airton Adelar
Published: April 2022

O estudo objetiva analisar as tendências da produção científica sobre a abordagem das Capacidades de Amartya Sen, por meio de um estudo bibliométrico na base Web of Science, dentre os anos de 1995-2019. Para isso, primeiramente, buscou-se identificar os periódicos e a evolução das publicações no período considerado. Após, analisou-se as instituições de origem e os principais autores dos artigos. Em seguimento, elucidou-se os tipos de pesquisa e os aspectos metodológicos adotados nos artigos. Por fim, efetuou-se uma análise dos hot topics relacionadas a Abordagem das Capacidades. Neste contexto, percebe-se o crescimento das publicações de artigos que buscam compreender e analisar a Abordagem das Capacidades e destaca os esforços em contribuir com o avanço da temática. Permite-se ponderar que, houve um crescente interesse acadêmico pelo tema nas duas últimas décadas, e que pode avançar nos próximos anos.
On the asymmetric effect of real exchange rate on growth: Evidence from Africa
Authors: Dada James Temitope
Published: April 2022

Purpose ― This study investigates the asymmetric effect of real exchange rates on the economic growth of twenty African countries for the period 2005 to 2019.
Design/Method/Approach ― A refined method of Granger and Yoon (2002) was used to decompose real exchange into appreciation and depreciation. To address the problem of endogeneity and cross-sectional dependence, a two-steps system generalized method of moments, Driscoll-Kraay estimator, and Augmented Mean group were used.
Findings ― This study established the presence of asymmetries in the real exchange rate in the region. Further, the study found that real exchange rate appreciation inhibits economic growth while real exchange rate depreciation is beneficial to growth in the region. The results are robust to different estimation techniques.
Practical Implications ― The outcome of this study supports the traditional view of exchange rates on macroeconomic variables. Hence, findings from this study can help investors and policymakers in the region to better understand the dynamics of the exchange rate and its effect on economic growth.
Originality/Value ― This study enriches the literature on the relationship between exchange rate and growth, especially in Africa using a refined approach to decompose exchange rate into appreciation and depreciation.
TGF-β as a Key Modulator of Astrocyte Reactivity
Authors: Luo Jian
Published: April 2022

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity. Genetic and pharmacological manipulation of TGF-β signaling pathway in animal models of CNS injury and disease alters pathological and functional outcomes. This review aims to provide recent understanding regarding astrocyte reactivity and TGF-β signaling in brain injury, aging, and neurodegeneration. Further, it explores how TGF-β signaling modulates astrocyte reactivity and function.
THE IMPACT OF FRAMING EFFECT: HOW FRAMING EFFECT AFFECTS STUDENTS IN CHOOSING UNIVERSITY’S MAJOR
Authors: Suroyo Suroyo , Putra Bima Maulana
Published: April 2022

Many students in choosing higher education majors are not in accordance with their abilities and interests. This will have an impact on students in making decisions on the choice of majors.  This research is qualitative survey study with all students of the University of Riau as the population in this study, with 556 samples covering eight departments and three faculties using representative sampling technique with criteria for early students (semester 1 and semester 3). The results of the study prove that in terms of practicality and knowledge possessed by students to choose majors, such as motivation, excelling, enjoyable, easeness, preference will affect decision making (thinking process, and ambiguity). The decision to choose a major that is not in accordance with the major can have a negative effect on the student. This is something that students should pay attention to.

Keywords: Decision-Making, Framing Effect, Major, Students

 

Abstrak

Banyak mahasiswa dalam memilih jurusan pendidikan tinggi tidak sesuai dengan kemampuan dan minatnya. Hal ini akan berdampak pada mahasiswa dalam mengambil keputusan pada pemilihan jurusan. Penelitian ini merupakan study qualitative berjenis survey dengan mahasiswa Universitas Riau sebagai populasi dalam penelitian ini, dengan 556 sampel yang meliputi delapan jurusan dan tiga fakultas dengan menggunakan teknik representative sampling dengan kriteria mahasiswa awal (semester 1 dan semester 3). Hasil penelitian membuktikan bahwa dalam hal praktis dan pengetahuan yang dimiliki oleh mahasiswa untuk memilih jurusan, seperti motivasi, exelling, enjoyable, easiness, preference akan berpengaruh terhadap pengambilan keputusan (proses berpikir, dan ambiguitas). Keputusan dalam memilih jurusan yang tidak sesuai dengan jurusan dapat memberikan efek negatif pada mahasiswa tersebut. hal ini yang harus menjadi perhatian oleh mahasiswa.  

 
Kata kunci: Framing Effect, Mahasiswa, Jurusan, Pengambilan Keputusan
Exploring the Impact and Acceptance of Wearable Sensor Technology for Pre- and Postoperative Rehabilitation in Knee Replacement Patients
Authors: Cooper D.M. , Bhuskute N. , Walsh G.
Published: April 2022

Background:

Knee replacement operations are common, highly successful procedures that are increasing in frequency. The COVID-19 pandemic has emphasized the need for innovative care pathways that reduce face-to-face appointments. We report on the impact of introducing a wearable sensor for pre- and postoperative rehabilitation of 21 knee replacement patients at 2 hospitals in the U.K.

Methods:

The sensor (BPMpathway; 270 Vision) was provided during joint school prior to knee replacement and stayed with the patient until a maximum of 9 weeks post-surgery. Participant progress and exercise were monitored remotely, with exercise regimens altered as required. Participants and clinicians could communicate remotely via the device.

Results:

The median range of motion during the first week post-surgery was 63° (interquartile range [IQR] = 21°) and increased to 136° (IQR = 16°) by week 7. The rate of participant compliance with exercises using the device was 32.3% for thrice-daily compliance and 52.4% for once-daily compliance. The 2-way communication channel was well utilized by both participants and clinicians. We report a 35.7% reduction in face-to-face physiotherapy appointments compared with standard practice. Finally, >80% of users who completed the feedback questionnaire reported a positive experience using the device, finding it easy to understand and reporting that it motivated them to perform their exercises.

Conclusions:

The use of BPMpathway was well received, effective, and reduced face-to-face physiotherapy appointments.

Clinical Relevance:

Remote monitoring can reduce the burden to the outpatient physiotherapy service by supporting the post-COVID-19 surgical service recovery plans of the National Health Service and allowing patients to recuperate at home.
FORMALIDADES ADUANERAS EN LA IMPORTACIÓN Y EXPORTACIÓN DESPUÉS DEL BREXIT
Authors:   Universidad Miguel Hernández de Elche, Ortega Giménez Alfonso , Choque Alarcón Daisi ,   Universidad Miguel Hernández de Elche
Published: April 2022

Una vez consolidado el Brexit sus efectos se reflejan con claridad en el comercio internacional, ahora las mercancías que se envíen o procedan de Reino Unido se trataran como exportaciones o importaciones de un tercer país, en el que se debe cumplir con todas las formalidades aduaneras establecidas por el código aduanero. Las empresas exportadoras e importadoras provenientes de Reino Unido deberán cumplir con la legislación europea en materia de calidad comercial, sanitaria y fitosanitaria establecida para el caso de los productos perecederos, sin dejar de lado los requisitos comunitarios de marcado y de puesta en conformidad con los requisitos esenciales de seguridad, determinada por la reglamentación de la UE.
Development of a New Progressive Nonintrusive Theory to Reduce Computation Time with Particle-in-Fluid Flow Application
Authors: Razavi Seyed Mahdi , Zargar Zeinab , Farouq Ali S. M. , Soliman Mohamed Y.
Published: April 2022

Solid-in-fluid flow studies and modeling approaches are categorized mainly based on the scale at which solid particles are modeled. Eulerian-Eulerian approaches treat solid at the same scale as fluid. These approaches are fast but suffer from improper physics and high dispersion effect due to averaging solid properties to upscale them to the fluid scale. Eulerian-Lagrangian methods try to solve the issue by modeling each particle individually. Modeling movement of each particle in fluid is complex, especially when modeling individual particle interaction with other particles and fluid is involved. Although such an approach is favorable due to its high accuracy in modeling solid behavior, it is computationally intensive and very time-consuming. It may take hours or even days to simulate a few seconds of a solid-in-fluid flow process when number of particles grows and goes beyond one thousand. In this paper, a theory is developed to reproduce and predict solid state variables such as location and velocity with a reasonable accuracy but at least four orders of magnitude faster. This solution uses the available information from previously finished simulations to build a progressive nonintrusive formulation based on the trajectory piecewise linearization (TPWL) theory that reproduces and predicts particles locations and velocities. Reproduction or prediction run accuracy is verified by comparing the results against a verification run and the reduction in computation time is also measured. The progressive nonintrusive formulation developed in this work is universal and is not limited to solid-in-fluid flow applications such as particle transport in wellbore or hydraulic fracture in petroleum engineering, and it can be applied to other engineering or science problems too.
Characterization of Agrobacterium-mediated co-transformation events in rice using green and red fluorescent proteins
Authors: Li Lihua , Tian Xudan , Wang Lanlan , Zhao Jianhua , Zhou Jie , He Haiyan , Dai Liangying , Qu Shaohong
Published: April 2022

Background Biotechnologists seeking to develop marker-free transgenic plants have established co-transformation methods. For co-transformation using mixed Agrobacterium strains, the mix ratio of Agrobacterium strains and selection scheme may influence co-transformation frequency. This study used fluorescent GFP and RFP markers to compose different selection schemes for observation of the selective dynamics of transformed rice cells and to investigate the factors affecting co-transformation efficiency.Methods and ResultsWe utilized GFP and RFP markers in co-transformation and tested the combinations of an antibiotic-selectable vector (pGFP-HPT) and a single RFP vector (pRFP) and of two antibiotic-selectable vectors (pGFP-HPT and pRFP-HPT) in rice. The pGFP-HPT/pRFP combination resulted in 70.9 % to 81.2 % of co-transformation frequencies while lower frequencies (56.6 % on average) were obtained with the pGFP-HPT/pRFP-HPT combination. Based on GFP/RFP segregation patterns, 55 % of the pGFP-HPT/pRFP co-transformants contained unlinked T-DNAs and segregated single RFP progeny, which simulated the selection process of marker-free transgenic plants that carry an actual gene of interest. Transgene expression levels in the rice lines varied as revealed by RT-PCR, and tandem-linked T-DNAs were detected in co-transformants, suggesting that transgene expression might be affected by duplicated T-DNA structures.ConclusionCo-transformation via mixed Agrobacterium strains is feasible, and approximately 55 % of the pGFP-HPT/pRFP co-transformants contained unlinked T-DNAs and segregated single RFP progeny. The pGFP-HPT/pRFP and the pGFP-HPT/pRFP-HPT vector combinations showed distinctive selective dynamics of transformed rice cells, suggesting that co-transformation efficiency depends on both vector system and selection scheme.
The predictive impact of socioeconomic status on the pattern of reproductive health in 35-70-year-old women in Ardabil: A Persian cohort study
Authors: Zandian Hamed , Pourfarzi Farhad , Mardi Afrouz , Zahirian Telma , Shadman Atefeh
Published: April 2022

BackgroundWomen often have many reproductive health problems in developing countries. Economic and social factors play an important role in health outcomes. The purpose of this study was to determine the predictive impact of socioeconomic status on reproductive health in Ardabil women aged 35 to 70.MethodA cross-sectional study was performed on the population of women aged 35 to 70 years who participated in the Ardabil Persian cohort study. Out of 9,000 eligible populations, 368 participants were randomly included in the study. A checklist was used to collect all patient information from the Ardabil Persian Cohort Center. Data analysis was performed using descriptive statistics, logistic regression and multivariate regression analysis.ResultsThe results showed that there was a significant statistical relationship between socioeconomic status and women reproductive health (p<0.001). Women with greater socioeconomic status had fewer reproductive health issues, such as infertility, tubectomy, abortion, stillbirth, atypical menopause, and hysterectomy.ConclusionsThe findings of the study indicated the relationship between socioeconomic status and women reproductive health. It should promote the health of women through fostering cross-sectoral collaboration and implementing government policies to empower and improve women's socioeconomic status.
Improvement in sensitivity for lateral flow immunoassay of ferritin using novel device design based on gold-enhanced gold nanoparticles
Authors: Ruecha Nipapan , Preechakasedkit Pattarachaya , Teekayupak Kanyapat , Citterio Daniel
Published: April 2022

This work introduces a low-cost adhesive tape combined with a hydroxylamine/polyvinyl alcohol/polyethylene oxide (HA/PVA/PEO) blend film to fabricate novel devices for improving sensitivity of gold nanoparticle (AuNP)-based lateral flow immunoassays (LFIAs) via two platforms: (1) LFIA device with integrated gold enhancement and (2) LFIA device with two independent sample inlets. The detection of ferritin has been used for proof-of-concept. The adhesive tape inserted in the devices assists to separate two solutions independently flowing from two different inlets toward a nitrocellulose membrane. On-device gold enhancement was achieved by the enlargement of AuNPs via the catalytic reaction of KAuCl4 and HA using the HA/PVA/PEO blend film easily prepared via a solution-casting technique, which could delay the flow of HA released from the film for 180 s and improve storage stability of the device. Under optimal conditions evaluated by naked eyes, the gold enhancement (LOD = 0.5 ng/mL) and double-sample inlet (LOD = 2 ng/mL) devices exhibited 20-fold and 5-fold higher sensitivity respectively than a conventional device, verifying the sensitivity improvement. Furthermore, the proposed device was successfully detected ferritin in human serum samples within 10 min via naked-eye observation, exhibiting rapidity and simplicity of use, and the capability to perform on-site assays.
Cleavage of histone H2A during embryonic stem cell differentiation destabilizes nucleosomes to counteract gene activation
Authors: Garcia Benjamin , Coradin Mariel , Cesare Joseph , Lan Yemin , Zhu Zhexin , Lund Peder , Sidoli Simone , Perez Yekaterina , Lu Congcong , Porter Elizabeth , Roberts Charles
Published: April 2022

Histone proteolysis is a poorly understood phenomenon in which the N-terminal tails of histones are irreversibly cleaved by intracellular proteases. During development, histone post-translational modifications are known to orchestrate gene expression patterns that ultimately drive cell fate decisions. Therefore, deciphering the mechanisms of histone proteolysis is necessary to enhance the understanding of cellular differentiation. Here we show that H2A is cleaved by the lysosomal protease Cathepsin L during ESCs differentiation. Using quantitative mass spectrometry (MS), we identified L23 to be the primary cleavage site that gives rise to the clipped form of H2A (cH2A), which reaches a maximum level of ~ 1% of total H2A after four days of differentiation. Using ChIP-seq, we found that preventing proteolysis leads to an increase in acetylated H2A at promoter regions in differentiated ES cells. We also identified novel readers of different acetylated forms of H2A in pluripotent ES cells, such as members of the PBAF remodeling complex. Finally, we showed that H2A proteolysis abolishes this recognition. Altogether, our data suggests that proteolysis serves as an efficient mechanism to silence pluripotency genes and destabilize the nucleosome core particle.
A Theory-Informed Systematic Review To Understand Physical Activity Among Women In GCC Countries
Authors: Osabi Lujain. A. , Klundert Joris , Alhurishi Sultana A , Cramm Jane M
Published: April 2022

Aim The aim of this systematic review is to identify health beliefs and modifying factors influencing physical (in)activity among adult women in the six countries of the Gulf Cooperation Council: Bahrain, Kuwait, Oman, Qatar, Saudi Arabia, and the United Arab Emirates.Methods A comprehensive literature search was conducted to locate published studies in the following databases; MEDLINE (Ovid), EMBASE, the Cochrane CENTRAL, Web of science, and the Google Scholar databases for studies published between 2009 to 2019. The quality of the included studies has been assessed using the Mixed Methods Appraisal Tool (MMAT). Based on the health belief model, the data collection and analysis systematically identified evidence on the relationships of health beliefs and modifying factors with physical activity.Results Six studies are from Saudi Arabia and five studies are from Oman. Two studies were reported from each of Qatar and Kuwait for a a total n=(15) studies. Reported physical ctivity prevalence is low, ranging from 50 percent to almost zero, depending on location, subpopulation and measurement instrument. The evidence on relationship of modifying factors and health beliefs with physical activity is scarce and sometimes inconclusive. Of the modifying factors, middle age and employment are positively associated with physical activity, whereas marital status, education, income, and BMI were not significantly associated with physical activity. Regarding health beliefs, the only conclusive evidence found was that lack of time was not significantly associated with physical activity, for the population of males and females combined. Lack of social support and lack of skills are the two beliefs reported significantly more frequently by female respondents and which therefore may explain the gender difference in physical activity prevalence. Differences in reporting of fear of injury and lack of willpower were non significant.ConclusionsRobust qualitatative and quantitative research on health beliefs and modifying factors explaining low prevalence of physical activity among female adults in the GCC is urgently needed. Current evidence reveals that unemployed women and women of age below 25 and elderly women are less likely to be physically active. Compared to male adults, female adults are more likely to believe to lack social support and skills for physical activity . Many of the known factors and health beliefs appear not to be significantly related to physical activity for adult women in GCC countries.
Information feedback provokes multi-peak dynamics in the modern world epidemic spreads
Authors: Lobov Sergey A. , Zharinov Alexey I. , Berdnikova Ekaterina S. , Kurganov Dmitry P. , Kazantsev Victor B.
Published: April 2022

We propose simple agent-based mathematical model of epidemic development capable to generate various multi-peak dynamics typical to COVID-19 pandemic. Agents are supplied with very simple kind behavior moving in a homogeneous interaction space with a constant speed. There is a probability of infection transmission if the agents meet with at certain distance. Next we assume that our agents get three features of intelligences called here: (i) information induced feedback, (ii) delay reaction on danger and (iii) danger adaptation. All these features are accounted in the model by the infection probability that becomes dynamic variable driven by additional differential equation. The information feedback means that this probability decreases with growing number of infected cases. It reflects facts that in modern world information media monitor the pandemic situation and with progressing infection around people start to protect them carefully that finally leads to the decrease of infected cases. Characteristic timings accounted in our model by delay reaction on the information feedback and danger adaptation time are also important in the probability dynamics. Surprisingly, but within these simple assumptions that did not touch any molecular specificity of COVID-19, except quite long exposure time, we immediately get a multi-peak dynamics of the pandemic development. Here, we show different conceptual cases of how such rhythmicity evolves under different parametric conditions.
The neuropeptide PACAP alleviates T. gondii infection-induced neuroinflammation and neuronal impairment
Authors: Figueiredo Caio Andreeta , Düsedau Henning Peter , Steffen Johannes , Ehrentraut Stefanie , Dunay Miklos P. , Toth Gabor , Reglödi Dora , Heimesaat Markus M. , Dunay Ildiko Rita
Published: April 2022

Background: Cerebral infection with the protozoan Toxoplasma gondii (T. gondii) is responsible for inflammation of the central nervous system (CNS) contributing to subtle neuronal alterations. Albeit essential for brain parasite control, continuous microglia activation and recruitment of peripheral immune cells entail distinct neuronal impairment upon infection-induced neuroinflammation. PACAP is an endogenous neuropeptide known to inhibit inflammation and promote neuronal survival. Since PACAP is actively transported into the CNS, we aimed to assess the impact of PACAP on the T. gondii-induced neuroinflammation and subsequent effects on neuronal homeostasis.Methods: Exogenous PACAP was administered intraperitoneally in the chronic stage of T. gondii infection, and brains were isolated for histopathological analysis and determination of pathogen levels. Immune cells from the brain, blood, and spleen were analyzed by flow cytometry, and the further production of inflammatory mediators was investigated by intracellular protein staining as well as expression levels by RT-qPCR. Neuronal and synaptic alterations were assessed on the transcriptional level, focusing on neurotrophins, neurotrophin-receptors and signature synaptic markers.Results: Here we reveal that PACAP administration reduced the inflammatory foci and the number of apoptotic cells in the brain parenchyma and restrained the activation of microglia and recruitment of monocytes. The neuropeptide reduced the expression of inflammatory mediators such as IFN-γ, IL-6, iNOS, and IL-1β. Moreover, PACAP diminished IFN-γ production by recruited CD4+ T cells in the CNS. Importantly, PACAP promoted neuronal health via increased expression of the neurotrophin BDNF and reduction of p75NTR, a receptor related to neuronal cell death. In addition, PACAP administration was associated with increased expression of transporters involved in glutamatergic and GABAergic signaling, that are particularly affected during cerebral toxoplasmosis.Conclusions: Together, our findings unravel the beneficial effects of exogenous PACAP treatment upon infection-induced neuroinflammation, highlighting the potential implication of neuropeptides against neuroinflammatory conditions.
C/EBP-β LAP regulates chemo-immuno-resistance in hypoxic non-small cell lung cancer
Authors: Riganti Chiara , Salaroglio Iris C. , Belisario Dimas Carolina , Akman Muhlis , Vecchia Sofia La , Godel Martina , Anobile Dario Pasquale , Ortone Giacomo , Digiovanni Sabrina , Fontana Simona , Costamagna Costanzo , Kopecka Joanna
Published: April 2022

Background. Solid tumors subjected to intermittent hypoxia are characterized by resistance to chemotherapy and immune-killing by effector T-lymphocytes, particularly tumor-infiltrating Vγ9Vδ2 T-lymphocytes. The molecular circuitries determining this double resistance are not known. Methods. We analyzed a panel of 28 human non-small cell lung cancer (NSCLC) lines, using an in vitro system simulating continuous and intermittent hypoxia. Chemosensitivity to cisplatin and docetaxel was evaluated by chemiluminescence, ex vivo Vγ9Vδ2 T-lymphocyte expansion and immune-killing by flow cytometry. Targeted transcriptomic identified efflux transporters and nuclear factors involved in this chemo-immuno-resistant phenotype. The molecular mechanism linking Hypoxia-inducible factor-1α (HIF-1α), CCAAT/Enhancer Binding Protein-β (C/EBP-β) isoforms LAP and LIP, ABCB1, ABCC1 and ABCA1 transporters were evaluated by immunoblotting, RT-PCR, RNA-IP, ChIP. Oxidative phosphorylation, mitochondrial ATP, ROS and depolarization were measured spectrofluorimetrically. The role of ROS/HIF-1α/LAP axis was validated in HIF-1α/LAP knocked-out or overexpressing cells, and in humanized (Hu-CD34+NSG) mice bearing LAP-overexpressing tumors. The clinical meaning of LAP was assessed in 60 NSCLC patients prospectively enrolled, treated with chemotherapy.Results. By up-regulating ABCB1 and ABCC1, and down-regulating ABCA1, intermittent hypoxia induced a stronger chemo-immuno-resistance than continuous hypoxia in NSCLC cells. Intermittent hypoxia impaired the electron transport chain, increasing mitochondrial ROS that favor the stabilization of C/EBP-β mRNA mediated by HIF-1α. HIF-1α/C/EBP-β mRNA binding increases the splicing of C/EBP-β toward the production of LAP isoform that transcriptionally induces ABCB1 and ABCC1, promoting the efflux of cisplatin and docetaxel. LAP also decreases ABCA1, limiting the efflux of isopentenyl pyrophosphate, i.e. the endogenous activator of Vγ9Vδ2 T-cells, and reducing the immune-killing. In NSCLC patients subjected to cisplatin-based chemotherapy, C/EBP-β LAP was abundant in hypoxic tumors and was associated with lower response to treatment and survival. LAP-overexpressing tumors implanted in Hu-CD34+NSG mice recapitulated the chemo-immuno-resistant phenotype of patients. Interestingly, the ROS scavenger mitoquinol induced chemo-immuno-sensitization in immuno-xenografts, by disrupting the ROS/HIF-1α/LAP cascade. Conclusions. The impairment of mitochondrial metabolism induced by intermittent hypoxia increases the ROS-dependent stabilization of HIF-1α/LAP complex in NSCLC, producing chemo-immuno-resistance. Clinically used mitochondrial ROS scavengers may counteract such double resistance. Moreover, we suggest C/EBP-β LAP as a new predictive and prognostic factor in NSCLC patients.
Differential expression of m5C RNA methyltransferase genes NSUN6 and NSUN7 in Alzheimer’s disease and Traumatic Brain Injury
Authors: Perezgrovas-Saltijeral Adriana , Rajkumar Anto Praveen , Knight Helen Miranda
Published: April 2022

Epigenetic processes have become increasingly relevant in understanding disease modifying mechanisms. 5-methylcytosine methylation of DNA (5mC) and RNA (m5C) have functional transcriptional and RNA translational consequences and are tightly regulated by writers, readers, and erasers effector proteins. To investigate the involvement of 5mC and m5C effector proteins contributing to the development of dementia neuropathology, RNA-sequencing data for 32 effector proteins across four brain regions was examined in 51 aged non-affected and 56 Alzheimer’s disease (AD) individuals obtained from the Aging, Dementia and Traumatic Brain Injury (TBI) study. Gene expression profiles were compared between AD and controls, neuropathological Braak and CERAD scores and in individuals with a history of TBI. We found an increase in DNA methylation writers DNMT1, DNMT3A, DNMT3B mRNA and reader UHRF1 mRNA in AD samples across three brain regions. While DNA methyltransferases erasers GADD45B and AICDA showed changes in mRNA abundance within neuropathological load groupings. RNA methylation writers NSUN6 and NSUN7 showed significant expression differences with AD and, along with the reader, ALYREF, differences in expression for neuropathologic ranking. A history of TBI was associated with a significant increase in ZBTB4 (p < 0.01) and decrease in NSUN6 (p < 0.005) mRNA. These findings implicate regulation of protein pathways disrupted in AD and TBI via multiple pre- and post- transcriptional mechanisms including potentially acting upon tRNAs, enhancer RNAs, as well as nuclear-cytoplasmic shuttling and cytoplasmic translational control. The targeting of such processes provide new therapeutic avenues for neurodegenerative brain conditions.
Evaluation of Medical Scribes’ effect on the Emergency Department’s productivity - A before-after cohort study
Authors: Noaimi Muje El , Linde Kristina Bengtsson , Petzold Max , Shakely Delér
Published: April 2022

Background
Emergency department length of stay is increasing in Sweden. One contributing factor for the accelerating emergency department length of stay, is the rise in administrative workload on the physicians. Prolonged patient waiting time and overcrowding leads to an unsafe environment. The aim of this study was to evaluate whether the productivity of physicians at the emergency department of Kungälv hospital increased following the introduction of medical scribes.
Method
We conducted a before-after study during 39 days at an emergency department. Data were collected from shifts worked by physicians with different work experience and medical specialties during two different summer periods, one period with medical scribes and the other without medical scribes. All patients visiting the emergency department and requiring healthcare during the period of medical scribes’ presence, were eligible. Patients were excluded from the study if they denied the presence of a medical scribe, or if the physician refused the medical scribe’s presence. We measured the physicians’ productivity by evaluating the mean number of assessed patients per hour per physician. Independent Samples t-test was used for statistical analysis.
Result
We documented a total of 584 physician-hours with a medical scribe and 584 hours without a medical scribe. A total number of 463 patients was assessed with a medical scribe during the period of 2018 compared to 362 patients assessed without a medical scribe in 2017. The physicians assessed significantly larger number of patients per hour with the assistance of a medical scribe, an increase of 0.22 (36%) patients per hour per physician, from 0.61 to 0.83 patients per hour per physician (95% CI 0.13–0.30).
Conclusion
We conclude that scribes do improve physicians’ productivity by increasing the number of assessed patients per hour per physician.
Predictors of root resorption in lateral incisors adjacent to maxillary impacted canines in CBCT images: A retrospective study
Authors: Moshfeghi Mahkameh , Hosseini Maryam , Eslamiamirabadi Negin , Biria Mina
Published: April 2022

Background: Diagnosis and early treatment of impacted teeth are crucial for preventing their pathological complications such as root resorption. This study aimed to assess the predictive factors of root resorption in lateral incisors adjacent to impacted maxillary canines using cone-beam computed tomography. Methods: In this retrospective descriptive-analytic study, 150 samples of impacted canines from 138 CBCT images were collected from the files of 12–35-year-old patients. The association between the severity and location of root resorption in lateral incisors adjacent to impacted maxillary canines and the patients’ age, sex, impacted canine’s angulation, position and follicle size was evaluated. Position and angulation of the impacted teeth were measured using the OnDemand3Dä software. Kruskal Wallis test, Fisher’s exact test, Mann-Whitney test, Kolmogorov-Smirnov test, Spearman’s rank correlation coefficient and multinomial logistic regression were used for data analysis.Results: The probability of resorption in the middle-third of the roots of lateral incisors decreased by 20% with each millimeter of increase in the distance between the impacted canines’ cusp tip from the occlusal plane (P=0.009). There was a significant association between the severity of lateral incisors’ root resorption and sex; root resorption was significantly more severe in females (P=0.029). No significant differences were observed between the lateral incisors’ root resorption and age, sagittal and transverse positions of the impacted canine, its follicle size, and the angle between the long axis of canines with the midline, occlusal plane and the long axis of lateral incisors (P>0.05).Conclusion: Among the evaluated variables, the vertical position of the impacted canine influenced the location of the lateral incisors’ root resorption. The severity of root resorption was higher in females.
Wayfinding artificial intelligence to detect uncertain spots of OCT image in retinal diseases
Authors: Sakamoto Taiji , Shiihara Hideki , Sonoda Shozo , Terasaki Hiroto , Fujiwara Kazuki , Funatsu Ryoh , Shiba Ryosuke , Kumagai Yoshiki , Honda Naoto
Published: April 2022

The purpose of this study is to develop an artificial intelligence (AI) algorithm to identify spots with uncertain retinal structure using optical coherence tomography (OCT). SD-OCT B-scan images were classified into 189 normal and 111 disease-affected images. They were automatically segmented using a boundary layer detection model using deep learning. During segmentation, the AI ​​model calculated the probability of the boundary surface of the layer for each A-scan. If this probability distribution is not biased toward one point, the layer detection is uncertain. This uncertainty was calculated by entropy and a value, referred to as the uncertainty index (UI), was calculated for each OCT image. The ability of the UI in classifying normal and disease images and the presence or absence of abnormalities in each layer of the retina were evaluated by area under curve (AUC). A heatmap that changes color according to the UI value was created. The UI of normal and disease-affected images (mean ± SD) were 1.76 ± 0.10 and 2.06 ± 0.22, respectively, showing a significant difference (p < 0.05). The AUC for the classification of normal and disease-affected images using UI was 0.93. The AUCs for the presence of abnormalities in each layer of the retina were: ILM: 0.588, NFL/GCL: 0.902, IPL/INL: 0.920, OPL/ONL: 0.882, EZ: 0.926, RPE/BM: 0.866. Our algorithm was able to identify retinal structural abnormalities on OCT with high accuracy, which may provide a basis for the diagnostic process as a new wayfinding AI method.
Neighbourhood environment and socioeconomic inequalities in cancer admissions: a prospective study using UK Biobank and linked administrative records
Authors: Mason Kate E. , Pearce Neil , Cummins Steven
Published: April 2022

Purpose: Neighbourhood environments may influence cancer risk. Average population effect estimates might mask differential effects by socioeconomic position. Improving neighbourhood environments could inadvertently widen health inequalities if important differences are overlooked. Methods: Using linked records of hospital admissions in UK Biobank, we assessed associations between admission with a primary diagnosis of cancer (any/breast/colorectal), and exposure to neighbourhood greenspace, physical activity facilities, and takeaway food stores, and whether household income and area deprivation modify these associations. We used adjusted Cox proportional hazards models, and estimated relative excess risks due to interaction (RERI) to assess effect modification. Results: Associations between neighbourhood exposures and cancer-related hospitalisations were weak to null overall, but with some evidence of effect modification. Most notably, more greenspace near home was associated with 16% lower hazard of cancer-related hospital admission in deprived areas (95%CI: 2%-29%). This was further pronounced for people in low-income households in deprived areas, and for breast cancer. Conclusions: In deprived neighbourhoods, increasing the amount of greenspace may help reduce cancer-related hospitalisations. Examining effect modification by multiple socioeconomic indicators can yield greater insight into how social and environmental factors interact to influence cancer incidence. This may help avoid perpetuating cancer inequalities when designing neighbourhood environment interventions.
Management of primary spontaneous pneumothorax in a third-level pediatric surgical center.
Authors: Spezzotto Giovanna , Boscarelli Alessandro , Giangreco Manuela , Ceschiutti Giulia , Codrich Daniela , Scarpa Maria-Grazia , Iaquinto Marianna , Olenik Damiana , Guida Edoardo , Schleef Jurgen
Published: April 2022

INTRODUCTION: The management of primary spontaneous pneumothorax (PSP) in pediatrics remains controversial. Due to a lack of standardized guidelines, it is based on evidence from adult patients. The aim of this study was to investigate difference in the length of stay (LOS) between various treatment options, the risk of recurrence after non-surgical treatment versus surgery, and the role of computed tomography (CT) in the management of PSP. METHODS: We retrospectively reviewed patients admitted to our Pediatric Surgery Unit for an episode of PSP between June 2009 and July 2020. Medical records including clinical presentation at admission, diagnostics, treatments, complications, and LOS were collected. RESULTS: Twenty-three patients (22 males and 1 female) were included in this study. Median age was 15.65 (range 9–18). Chest X-rays were performed in all patients and showed 5 small (22%) and 18 large (78%) PSP. Eleven patients (48%) were managed non-operatively with observation alone and a recurrence rate of 18%, chest drain was used in 11 patients with a recurrence rate of 36%, and surgery was deemed necessary as a first treatment choice in one case. Notably, surgery resulted in a longer LOS than other types of treatment (P = .001). Six patients (27%) had an episode of relapse after non-operative management or chest drain placement. Following surgery, a relapse occurred in 2 of the 6 patients. CONCLUSIONS: According to our experience, small PSP or clinically stable larger PSP can be treated conservatively with observation alone. Operative management should be taken into consideration in children with large symptomatic PSP, persistent air leak, and/or relapse after chest drain insertion.
Treatment for non-type 1 retinopathy of prematurity by intravitreal injection of anti-vascular endothelial growth factor drugs
Authors: Zhang Haitao , Yang Xin , Zheng Fangfang , Yin Xiangke , Wan Suhua , Xu Yingying
Published: April 2022

To explore clinical characteristics and treatment reasons for intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs in the treatment of non-type 1 retinopathy of prematurity (ROP). A retrospective study was conducted to screen the non-type 1 ROP from the collected ROP patients who received intravitreal injection of anti-VEGF drugs in Henan Eye Hospital from September 2018 to June 2021. A total of 138 ROP cases (262 eyes) were included in this study, including 39 cases (28.3%) 65 eyes (24.8%) were the non-type 1 ROP. Compared with the type 1 ROP group, the non-type 1 ROP group had slightly later treatment time (41.1±8.9 weeks vs 38.6±5.5 weeks, P<0.05) and a higher proportion of fusion protein drugs(87.2% vs 54.5%, P<0.05). After intravitreal injection of anti-VEGF drugs, 27 eyes (41.5%) were cured and 38 eyes (58.5%) were improved in the non-type 1 ROP group, without recurrence and aggravation cases. There were more lesions in zone II (63 eyes, 96.9%), stage 2 (41 eyes, 63.1%) and stage 3 (22 eyes, 33.8%), and 58 eyes (89.2%) showed pre-plus in the non-type 1 ROP group. Treatment reasons included pre-plus in 58 eyes (89.2%), ridge changes in 22 eyes (33.8%), simultaneous treatment of the contralateral eye in 9 eyes (13.8%), no regression of lesions in persistent stage 2 or 3 over 44 weeks of follow-up in 8 eyes (12.3%), and logistical considerations in 4 eyes (6.2%). Considering some peculiar clinical characteristic, personalized treatment by intravitreal injection of anti-VEGF drugs may be necessary for some non-type 1 ROP in critical conditions.
Network pharmacology and bioinformatics analyses identify the intersection genes and mechanism of Huangbai for Recurrent Aphthous Stomatitis
Authors: lai yingtao , tang lulu , lu shuting , ou weiwei , huang ling
Published: April 2022

Background: Recurrent aphthous stomatitis (RAS) are complex inflammatory diseases caused by multi-factors, which severely impact patient quality of life. However, there is still no effective treatment methods for RAS without side effects. Traditionally, Cortex Phellodendri has been known as “Huang Bai” for the treatment of gastroenteritis, abdominal pain, or diarrhea. Since “Huang Bai” is herb with antibacterial and anti-inflammatory functions. Our study aimed to explore the common genes and underlying mechanisms in “Huang Bai” for the treatment of RAS.Methods: Network pharmacology methods and bioinformatics analyses were utilized by incorporating target searching and fishing. Network analysis and silico validation were used to discover the pharmacological mechanisms of “Huang Bai” for the treatment of recurrent aphthous stomatitis. Results: Based on filtering criteria, 25 active ingredients in HB, 200 drug targets, and 578 differentially expressed genes (DEGs) between RAS and normal samples were obtained. The GO enrichment analysis revealed that the immune response was the most significantly enriched term within the DEGs. The KEGG pathway analysis identified 60 significant pathways, most of which involved in the inhibition of inflammation and regulation of immunological response. The functions are dependent on a multi-pathway, particularly the TNF signaling pathway and the HIF-1 signaling pathway. We identified six hub genes in the PPI network, most of which were validated as highly expressed in oral ulcers by DiseaseMeth databases. In addition, molecular docking displayed that the primary molecule combined well with the key targets. Conclusions: This study reflects the multi-component multi-target multi-pathway action characteristics of HB. Our study provides potential biomarkers or treatment targets for further research.