bluuebunny/crossref_metadata_2025 huggingface dataset:
A importância do farmacêutico na consulta à pacientes pediátricos em uso de medicamentos off-Label
Authors: Menese Daiane Pereira dos Santos , Marquez Carolinne de Oliveira
Published: November 2021

Os medicamentos tem papel fundamental na recuperação e manutenção da saúde, devendo ser seguros, eficazes, de qualidade e acessíveis para o paciente. A consulta farmacêutica aos pacientes pediátricos em uso de medicamentos off-Label cuja utilização se dá de forma diferente da descrita em seu rótulo ou bula, quando se fala em indicação, via de administração, posologia e faixa etária, tem o papel de auxiliar na farmacoterapia, minimizando os erros e as reações adversas ao medicamento indicados por médicos e prevenir problemas relacionados aos medicamentos (PRM’s). A administração de medicamentos de adultos em crianças é uma prática comum que deve ser tratada com cautela, pois a fisiologia da criança é distinta e os riscos de intoxicação são diversos. O objetivo desse estudo foi evidenciar a importância do farmacêutico no acompanhamento farmacoterapêutico à pacientes pediátricos em uso de medicamentos off-Label durante as consultas farmacêuticas. A busca ocorreu no banco de dados da Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) e no Scientific Eletronic Library Online (SciELO). Para delimitação dos conteúdos foram utilizados critérios de inclusão: artigos disponíveis na íntegra em português e inglês, no período de 2012 a 2021 com acesso gratuito e que tivessem pertinência com tema. Os resultados demonstraram que o farmacêutico é imprescindível no acompanhamento e na orientação dos pacientes que usam medicamentos off-Label, sendo necessária a adequada formação desse profissional sobre a temática. Nesse contexto, o farmacêutico surge como profissional que promove o uso correto dos fármacos em pediatria, contribuindo para uma farmacoterapia segura.
Desafios enfrentados pelos professores no cenário pandêmico e no pós pandemia: professores e os desafios encontrados em tempo de pandemia
Authors: Santos Dayane Rodrigues dos , Oliveira Keila Fernandes , Soares Zilma Cardoso Barros
Published: November 2021

O presente artigo tem como tema geral os desafios encontrados pelos professores em tempos de pandemia. Os obstáculos que a população encontrou por consequências da pandemia do novo Coronavírus afetou diversos setores da sociedade em especial a educação, mais de dois terços de estudantes no mundo sofreram com danos ao seu processo de ensino aprendizagem, com altos níveis de desigualdades nesse setor, a falta de acesso e apoio para com os estudantes e principalmente os professores foram sem precedentes. Diante do problema, objetivou-se analisar quais os desafios encontrados pelos professores em tempos de pandemia? Este trabalho trata-se de uma pesquisa com base teórica sendo fundamentada em artigos, revistas online e teses. Para que com esses recentes dados de pesquisas esse trabalho se torne relevante em discutir e entender de forma geral esses novos desafios na educação básica em tempos de pandemia.
Emergencies in diseases of the circulatory system of the adult population of the Khabarovsk krai: the current status and trends
Authors:   Postgraduate Institute for Public Health Workers under Health Ministry of Khabarovsk Krai, Topalov K.P. , Zaitseva T.V. ,   Khabarovsk Krai Clinical Hospital  No.1 named after professor S.I. Sergeev under Health Ministry of Khabarovsk Krai, Trembach T.G. ,   Medical Information and Analytical Center under the Health Ministry of Khabarovsk Krai
Published: November 2021

The indicators of morbidity of the adult population of the Khabarovsk Krai with diseases of the circulatory system and mortality caused by these diseases in 2002–2019 were studied. Special attention is paid to urgent pathology - acute coronary syndrome and acute disorders of cerebral circulation. It was found that acute coronary syndrome and acute disorders of cerebral circulation in the region account for about 75–85% of all newly diagnosed diseases of the circulatory system - ischemic heart disease, cerebrovascular diseases; they result in up to 32% of deaths from diseases of the circulatory system
Forensic medical examination in the system of assessing the quality and safety of medical services
Authors:   Postgraduate Institute for Public Health Workers under Health Ministry of Khabarovsk Krai, Savkova V.M. , Savkov D.S. ,   Far Eastern State Medical University under Health Ministry of Russia
Published: November 2021

The article analyzes the legislative acts regulating the process and use of forensic medical examination in civil proceedings in the so-called medical cases
Different Cinematic Interpretations of Ch’unhyangjŏn: The Same Korean Identity
Authors: Sebo Gabor
Published: November 2021

The article examines the classic Korean folklore fable, 춘향전 (春香傳), Ch’unhyangjŏn (The Fragrance of Spring), The Tale of Ch’unhyang, through the lens of three different successful movie adaptations produced in North and South Korea. Respectively, Yu Wŏn-chun and Yun Ryong-gyu portrayed The Tale of Ch’unhyang (1980) in its modest “Juche realist” North Korean film style, whereas Im Kwŏn-t’aek depicted his work, Ch’unhyang (2000), in a contemporary liberally and daringly revised version, while the romantic portrayal produced in North Korea by the South Korean film director, Shin Sang-ok, in Love, Love, My Love (1984), is performed from a human-oriented and entertaining perspective filled with musical ingredients and brave images of love. The study aims to demonstrate how the story is diversely interpreted through the two divided film cultures by highlighting differences between collectivism and individualism, noting also that all three interpretations emerge from similar roots of cultural and national identity.
Feminist Ethnography in South Korea: Documenting Conversion to Islam in “Multicultural” Korea and the Gendered Struggle for Belonging
Authors: Sheikh Farrah
Published: November 2021

This paper presents a feminist ethnographic account of the gendered struggle for belonging in “multicultural” Korea through an in-depth case study of a Korean Muslim woman convert and her family. Centering the informant and her family’s narratives, I explore the gendered implications linked to her conversion to Islam, her sense of belonging and how her inter-ethnic marriage challenges existing notions of labelled “multicultural families” in Korean society. This paper sheds light on the penalties associated with the case study’s religious conversion and marriage choice, demonstrating how she experiences exclusion from mainstream society and her own ethnic community. Far from being an isolated case, I will further convey how it is linked to several others in the literature, highlighting the urgent need for further field research.
Challenging the “Hierarchy of Nationhood”: Diasporic Entitlement and the Case of Korean Chinese (Chosŏnjok) in South Korea
Authors: Lim Timothy , Song Changzoo
Published: November 2021

With about 7.5 million people, the Korean diaspora is concentrated in China, Japan, North America, and the former Soviet Union. Since the 1990s, many ethnic Koreans have been “returning” to South Korea, their putative ethnic homeland. Significantly, their treatment by the state has been unequal: On issues of residency and employment rights, ethnic Koreans from China (Chosŏnjok) and the former Soviet Union were relegated to second-class status compared to those from North America. This inequality is encapsulated in the phrase, used by a number of scholars, the “hierarchy of nationhood.” Surprisingly, perhaps, the Chosŏnjok community challenged this unequal treatment by asserting rights based on colonial victimhood, ethnic sameness, and cultural authenticity. While such expressions of entitlement are not unusual among marginalized diasporic groups, the Chosŏnjok achieved something remarkable, namely, they succeeded in gaining political and economic rights initially denied by the Korean state. Simply put, they successfully challenged the hierarchy of nationhood. Using a discursive institutional framework, we endeavor to explain how and why entitlement claims by the Chosŏnjok were effective. More specifically, we argue that the struggle by Chosŏnjok to overturn the hierarchy of nationhood had little to nothing to do with a coercive, dyadic power struggle against the Korean state, but was instead a fundamentally discursive struggle, which itself is a product or reflection of discursive agency, both on the part of Chosŏnjok but also, crucially, on the part of their key allies—religious leaders and civic organizations—in South Korea.
Rethinking Hegemony and Neutralization in Korea: Multinational
Diplomatic Engagements in the Run-Up to the Russo-Japanese War (1903–1904)
Authors: Jin Sangpil
Published: November 2021

This article demonstrates that the Russo-Japanese rivalry, far from being just another example of imperialist competition during the Age of Imperialism, can also serve as a useful case study of a diplomatic contest over a periphery between hegemonic powers. During this diplomatic tug-of-war, the Korean peninsula became the focal point of a contest between Japan and Russia. The present study illuminates the interactive processes of major diplomatic engagements between multiple actors through careful use of multi-lingual archives, as well as locates the significant implications of these exchanges for contemporary geopolitical landscapes in the Far East. Ultimately, this research provides an analytical framework for a more in-depth understanding of diplomatic interactions and the impacts of hegemonic struggles in modern Korean history.
ЧИ БУДЕ LAWFARE ВИРІШАЛЬНИМ ЕЛЕМЕНТОМ У ЗБРОЙНИХ КОНФЛІКТАХ XXI СТОЛІТТЯ?
Authors: Задорожний Володимир Павлович , Польцев Ігор Вікторович
Published: November 2021

В статті розглянуті питання порушень норм міжнародного права у різних збройних конфліктах, різнопланового тлумачення застосування норм права  та їх наслідків для подальшої безпеки кожної із сторін конфліктів. На сьогодні дотримання правил ведення війни у міжнародному збройному конфлікті залежить від цілей ворогуючих сторін в даному конфлікті. Кожна сторона у збройному протистоянні вибирає те сприйняття і виконання тих норм права, яке їй вигідне у даний момент. Застосування  певних міжнародно-правових законодавчих актів однією стороною з метою тиску на іншу змушує діяти обидві сторони конфлікту відповідно до реалій військово-політичної обстановки. Таке різнобічне тлумачення правових норм у збройному конфлікті  є новою формою ведення «гібридної війни» або lawfare (лофеа). В статті також сформульовані шляхи вивчення питань інтеграції форми «гібридної війни» lawfare  і з правилами ведення війни та із визначенням важливості lawfare  як вирішального елемента у збройних конфліктах XXІ сторіччя.
ОБОРОННИЙ КОМПЛЕКС ЛІТОПИСНОГО ЗВЕНИГОРОДА
Authors: Терський Святослав Володимирович
Published: November 2021

Один із головних політичних центрів Галицького князівства – Звенигород, розташований поблизу галицько-волинського кордону на перетині стратегічних шляхів протягом ХІ – ХІІІ ст. відігравав важливу роль у військово-політичних подіях. На полях поряд із Звенигородом відбулося принаймні декілька великих битв за володіння Галичиною. Три битви – 1226, 1144 та 1227 рр. знайшли відображення в літописах. Однак конкретний перебіг цих подій доволі скупо відображений в писемних джерелах. В статті проаналізовано військово-топогра­фічну ситуацію на території Звенигородського князівства. Простежено роль укріплень Звенигорода на основних стратегічних шляхах, які перетиналися в цьому місці та вели до основних центрів Галицького та Волинського князівств.
Сьогодні літописний центр князівства локалізований на території одноймен­ного села біля Львова. В статті підбито підсумки багаторічних археологічних досліджень із вивчення військової інфраструктури Х–ХІІІ ст. в цьому районі. Враховано результати найновіших археологічних розвідок на території Звени­городського князівства. Проведеними роботами встановлено датування решток давніх фортець. Проаналізовано зчислені знахідки середньовічного озброєння, які додатково ілюструють стан військової інфраструктури літописного Звенигорода.
ПРЕДМЕТИ ЗБРОЇ, ЕЛЕМЕНТИ СПОРЯДЖЕННЯ ТА ОБМУНДИРУВАННЯ З ПРИВАТНОЇ ЗБІРКИ ЗИГМУНТА РОЗВАДОВСЬКОГО У МУЗЕЙНИХ КОЛЕКЦІЯХ
Authors: Прокіп Андрій Володимирович , Михальський Юрій Володимирович
Published: November 2021

У статті розглянуто, систематизовано та подано характеристику окремих предметів зброї, елементів спорядження, військового обмундирування, що походять з приватної збірки Зигмунта Розвадовського (1870 – 1950) – художника-баталіста, сценографа, педагога, а також і колекціонера – збирача предметів старовини. Аналіз інвентарних книг колишнього Національного музею ім. короля Яна ІІІ у Львові дозволив з’ясувати, що 1935 р. музей придбав у З. Розвадовського      58 одиниць зброї (як холодної, так і вогнепальної), а також елементів військо­вого спорядження та обмундирування. Деякі з цих предметів згодом увійшли до колекції Львівського історичного музею.
ТЕХНОЛОГІЯ ГІБРИДНОЇ ВІЙНИ РОСІЇ ПРОТИ УКРАЇНИ (НА ПРИКЛАДІ ДОНЕЧЧИНИ)
Authors: Бенчук Віталій Олександрович , Трофимович Володимир Васильович
Published: November 2021

У статті розглядається технологія військової агресії Росії проти України на прикладі Донеччини. Її динаміка й еволюція прослідковуються в суспільно-політичних і військових процесах, які відбувалися під час так званої російської весни 2014 р. Відзначено, що на початковому етапі була спроба сценарію «народного заколоту», втім через низку причин він не спрацював. Через те під керівництвом службових осіб ЗС РФ, ФСБ, представників російської політичної влади була утворена терористична організація «ДНР» з власними парамілітарними воєнізованими групами. Її мета полягала в провокуванні збройного конфлікту методом масового терору та провокацій. Ці дії супроводжували інші види інструментарію гібридної війни, серед яких важливе місце зайняла потужна інформаційна кампанія російських медіа ресурсів, контент якої еволюціонував в залежності від ситуації. З’ясовано, що успішне звільнення українськими військами тимчасово окупованих територій призвело до вторгнення регулярних російських військ, підписання Мінських домовленостей та переходу до збройного конфлікту в режим різного ступеня інтенсивності.
Legislative regulation of publishing in Ukraine
Authors: Ulitina Olha
Published: November 2021

Keywords: creative industries, publishing, book publishing, copyright, IP rights,copyright infringement, IP legislation

Publishing is animportant element for the development of many areas of human activity. The impactof publishing on culture, education and tourism in any country cannot be underestimated.Publishing is of great importance for the development of literature, both withinone country and in the world as a whole.Today, publishing faces many challenges, including piracy, the difficulty of distributingdigital copies of literary works and insufficient funding, along with a relativelylow interest in legal publications. However, publishing is defined in Ukraine as a creativeindustry and now the state's position on strengthening publishing as an industryin Ukraine is becoming more active. That is why the issues of legislative regulationof activities in this area, as well as its connection with intellectual propertyrights, are relevant. The creation of the list of economic activities that belong to the creative industries in Ukraine indicates the government's intention to graduallytransfer Ukraine's economy to a more modern model, where industries related to thecreative industries are of the greatest importance for the economy and the developmentof the state as a whole.The article is devoted to the issue of publishing legislative regulation in Ukraine.The author analyses the most important laws in this area, considering publishing primarilyas a creative industry. The state policy in this sphere is considered, which isdirected first on development of publishing and on support of publishing the Ukrainian-language editions.The author points out the existence of certain differences in the legislative regulationof book publishing and publishing of the periodicals in Ukraine.The article considers the data of the Ukrainian Book Institute on the current stateof publishing in Ukraine. According to these data, one of the biggest problems in thepublishing is the significant number of copyright infringements and IP rights infringementsin general.Given the high rate of copyright infringement and IP rights in general in the publishing,it is necessary to review the mechanism of influence on combating them, aswell as increase liability for such infringements.
MILLIMETER AND TERAHERTZ RADIATION DETECTOR
Authors:   Siberian State University of Geosystems and Technologies, Minin Igor V. , Minin Oleg V. ,   Siberian State University of Geosystems and Technologies
Published: November 2021

The aim of this work is an analytical review of terahertz and millimeter-wave radiation receivers. Classification of terahertz radiation receivers and their comparative characteristics are made. Various aspects of the application of terahertz radiation, as well as the main types and types of receivers of this radiation, are considered in this paper. Photon and thermal receivers, terahertz receivers based on Go-lay cells, and terahertz-to-infrared convectors are analyzed. As a result, a method for increasing the sensitivity of electromagnetic radiation receivers based on the application of the photon jet effect is proposed.
POSSIBILITIES OF GIS FOR STUDYING THE PROCESSES OF DISTRIBUTION OF THE USSURIYSK POLYGRAPH IN THE FIR FORESTS OF SIBERIA
Authors:   Institute of Monitoring of Climatic and Ecological Systems SB RAS, Kerchev Ivan A. , Volkova Elena S. ,   Institute of Monitoring of Climatic and Ecological Systems SB RAS, Melnik Mariya A. ,   Institute of Monitoring of Climatic and Ecological Systems SB RAS
Published: November 2021

In recent decades, the Siberian fir forests have been seriously damaged by the invasive bark beetle of Far Eastern origin, the Ussuri polygraph Polygraphus proximus Blandf. The damage from the impact of the pest is expressed in monetary value and in the loss of many ecological functions of forest ecosystems. Technologies for organizing ground monitoring of the spread of the pest are successfully tested by Siberian scientists, and with the involvement of GIS technologies, they can provide a spatio-temporal analysis of the scale of the negative processes occurring. The purpose of this article is to show the capabilities of GIS technologies in combination with remote sensing in studying the processes of invasion of the Ussuri polygraph using the example of forest areas in the Tomsk region. It is shown that the geoinformation approach to the study of the fir forests state in the centers of mass reproduction of the pest makes it possible to create a series of thematic maps reflecting large-scale spatial and temporal changes in plantations and to give a short-term forecast of the development of the centers. The high efficiency of this approach is shown in the local analysis of the centers’ development and to assess the dynamics of mass reproduction of the pest at the forestry level. Based on the built-in analytical information and cartographic display, it becomes possible to predict the emergence of new centers, monitor and control their development.
PollBasePro: Daily Estimates of Aggregate Voting Intention in Britain from 1955 to the Present Day
Authors: Bailey Jack , Pack Mark , Mansillo Luke
Published: November 2021

Political scientists often use public opinion polls to test their theories. Yet these data present some difficulties. First, they are noisy. Second, they occur at irregular intervals. Third, they measure both public preferences and pollsters’ survey design choices. We introduce a new dataset, PollBasePro, that accounts for these issues. It includes voting intention estimates for each of Britain’s three largest parties on each day between the 1955 general election and the present. As the dataset covers 24,106 days in total, it is perhaps more comprehensive than any other existing time series of British political opinion. We then use our estimates to test a question of pressing importance: how daily deaths attributable to COVID-19 have influenced support for the governing Conservative Party.
The Synthesis of Europium-Doped Calcium Carbonate by an Eco-Method as Free Radical Generator Under Low-Intensity Ultrasonic Irradiation for Body Sculpture
Authors: Kuan Che-Yung , Lin Yu-Ying , Yang I-Hsuan , Chen Ching-Yun , Chi Chih-Ying , Li Chi-Han , Chen Zhi-Yu , Lin Li-Ze , Yang Chun-Chen , Lin Feng-Huei
Published: November 2021

Body sculpture is a common method to remove excessive fat. The diet and exercise are the first suggestion to keep body shape; however, those are difficult to keep adherence. Ultrasound has been developed for fat ablation; however, it could only serve as the side treatment along with liposuction. In the study, a sonosensitizer of europium-doped calcium carbonate (CaCO3: Eu) would be synthesized by an eco-method and combined with low-intensity ultrasound for lipolysis. The crystal structure of CaCO3: Eu was identified by x-ray diffractometer (XRD). The morphology of CaCO3: Eu was analyzed by scanning electron microscope (SEM). The chemical composition of CaCO3: Eu was evaluated by energy-dispersed spectrophotometer (EDS) and inductively coupled plasma mass spectrometer (ICP-MS). The electronic diffraction pattern was to further check crystal structure of the synthesized individual grain by transmission electron microscope (TEM). The particle size was determined by Zeta-sizer. Water-soluble tetrazolium salt (WST-1) were used to evaluate the cell viability. Chloromethyl-2′,7′-dichlorofluorescein diacetate (CM-H2DCFDA) and live/dead stain were used to evaluate feasibility in vitro. SD-rat was used to evaluate the safety and efficacy in vivo. The results showed that CaCO3: Eu had good biocompatibility and could produce reactive oxygen species (ROS) after treated with low-intensity ultrasound. After 4-weeks, the CaCO3: Eu exposed to ultrasound irradiation on SD rats could significantly decrease body weight, waistline, and subcutaneous adipose tissue. We believe that ROS from sonoluminescence, CO2-bomb and locally increasing Ca2+ level would be three major mechanisms to remove away adipo-tissue and inhibit adipogenesis. We could say that the combination of the CaCO3: Eu and low-intensity ultrasound would be a non-invasive treatment for the body sculpture.
Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress
Authors: De Rosa Mariarosaria , Johnson Samuel A. , Opresko Patricia L.
Published: November 2021

Telomeres are protective nucleoprotein structures that cap linear chromosome ends and safeguard genome stability. Progressive telomere shortening at each somatic cell division eventually leads to critically short and dysfunctional telomeres, which can contribute to either cellular senescence and aging, or tumorigenesis. Human reproductive cells, some stem cells, and most cancer cells, express the enzyme telomerase to restore telomeric DNA. Numerous studies have shown that oxidative stress caused by excess reactive oxygen species is associated with accelerated telomere shortening and dysfunction. Telomeric repeat sequences are remarkably susceptible to oxidative damage and are preferred sites for the production of the mutagenic base lesion 8-oxoguanine, which can alter telomere length homeostasis and integrity. Therefore, knowledge of the repair pathways involved in the processing of 8-oxoguanine at telomeres is important for advancing understanding of the pathogenesis of degenerative diseases and cancer associated with telomere instability. The highly conserved guanine oxidation (GO) system involves three specialized enzymes that initiate distinct pathways to specifically mitigate the adverse effects of 8-oxoguanine. Here we introduce the GO system and review the studies focused on investigating how telomeric 8-oxoguanine processing affects telomere integrity and overall genome stability. We also discuss newly developed technologies that target oxidative damage selectively to telomeres to investigate roles for the GO system in telomere stability.
The Structural Effect of Electrode Mesh on Hydrogen Evolution Reaction Performance for Alkaline Water Electrolysis
Authors: Lee Hae In , Cho Hyun-Seok , Kim MinJoong , Lee Jae Hun , Lee ChangSoo , Lee Sechan , Kim Sang-Kyung , Kim Chang-Hee , Yi Kwang Bok , Cho Won-Chul
Published: November 2021

Alkaline water electrolysis (AWE) is a mature water electrolysis technology that can produce green hydrogen most economically. This is mainly attributed to the use of Ni-based materials that are easy to process and inexpensive. The nickel-based meshes with various structures such as woven mesh and expanded mesh are widely used as electrode in the AWE due to its common availability and easy fabrication. However, the morphological effect of meshes on hydrogen evolution reaction (HER) performance has not been studied. Here a new parameter to determine the structural effect of mesh on HER performance was first proposed. The key factors of the parameter were found to be the strand width, pore width and the strand surface area. The woven mesh with the ratio of pore width to strand width that converges to 1 showed the lowest the overpotential. The expanded mesh with the higher the structural surface area exhibited the lowest the overpotential. This study will help to choose an optimal structure for the mesh with the HER electrode.
Evaluation of Molecular Point-of-Care Testing for Respiratory Pathogens in Children With Respiratory Infections: A Retrospective Case-Control Study
Authors: Shen Nan , Zhou Yuanjie , Zhou Yajuan , Luo Lijuan , Chen Wenjuan , Wang Jing , Zhao Ruike , Xie Li , Cao Qing , Tao Yue , Mo Xi
Published: November 2021

Objectives

Overuse of antibiotics and antibiotic resistance are global healthcare problems. In pediatric patients with respiratory infections, viral and bacterial etiologies are challenging to distinguish, leading to irrational antibiotic use. Rapid and accurate molecular diagnostic testing methods for respiratory pathogens has been shown to facilitate effective clinical decision-making and guide antibiotic stewardship interventions in the developed regions, but its impacts on pediatric patient care in the developing countries remain unclear.

Methods

In this single-center, retrospective case-control study, we compared demographics, clinical characteristics, especially microbiological findings, and antibiotic usage between pediatric patients with respiratory infection receiving FilmArray Respiratory Panel (FilmArray RP) testing and a matched routine testing control group. Our primary outcome was the duration of intravenous antibiotics treatment (DOT) during hospitalization.

Results

Each group consisted of 346 children with a respiratory infection. In the FilmArray RP testing group, the DOT was shorter than that in the routine testing group (6.41 ± 3.67 days versus 7.23 ± 4.27 days; p = 0.006). More patients in the FilmArray RP testing group de-escalated antibiotic treatments within 72 hours of hospitalization (7.80%, 27/346 versus 2.60%, 9/346; p = 0.002). By contrast, fewer patients in the FilmArray RP testing group had escalated antibiotic treatments between 72 hours and seven days (7.80% versus 14.16%; p = 0.007). The cost of hospitalization was significantly lower in the FilmArray RP testing group ($ 1413.51 ± 1438.01 versus $ 1759.37 ± 1929.22; p = 0.008). Notably, the subgroup analyses revealed that the FilmArray RP test could shorten the DOT, improve early de-escalation of intravenous antibiotics within 72 hours of hospitalization, decline the escalation of intravenous antibiotics between 72 hours and seven days, and reduce the cost of hospitalization for both patient populations with or without underlying diseases.

Conclusions

Molecular point-of-care testing for respiratory pathogens could help to reduce intravenous antibiotic use and health care costs of pediatric patients with respiratory infections in developing countries.
The Old and the New: Can Physics-Informed Deep-Learning Replace Traditional Linear Solvers?
Authors: Markidis Stefano
Published: November 2021

Physics-Informed Neural Networks (PINN) are neural networks encoding the problem governing equations, such as Partial Differential Equations (PDE), as a part of the neural network. PINNs have emerged as a new essential tool to solve various challenging problems, including computing linear systems arising from PDEs, a task for which several traditional methods exist. In this work, we focus first on evaluating the potential of PINNs as linear solvers in the case of the Poisson equation, an omnipresent equation in scientific computing. We characterize PINN linear solvers in terms of accuracy and performance under different network configurations (depth, activation functions, input data set distribution). We highlight the critical role of transfer learning. Our results show that low-frequency components of the solution converge quickly as an effect of the F-principle. In contrast, an accurate solution of the high frequencies requires an exceedingly long time. To address this limitation, we propose integrating PINNs into traditional linear solvers. We show that this integration leads to the development of new solvers whose performance is on par with other high-performance solvers, such as PETSc conjugate gradient linear solvers, in terms of performance and accuracy. Overall, while the accuracy and computational performance are still a limiting factor for the direct use of PINN linear solvers, hybrid strategies combining old traditional linear solver approaches with new emerging deep-learning techniques are among the most promising methods for developing a new class of linear solvers.
Aging in the Digital Age: Using Technology to Increase the Reach of the Clinician Expert and Close the Gap Between Health Span and Life Span
Authors: Gomes-Osman Joyce , Solana-Sánchéz Javier , Rogers Emily , Cattaneo Gabriele , Souillard-Mandar William , Bates David , Gomez Enrique J. , Tormos-Muñoz Josep M. , Bartrés-Faz David , Pascual-Leone Álvaro
Published: November 2021

Age-related cognitive impairment (ARCI) has a profound impact on individuals, families, health care systems, and societies at large. Evidence suggests that ARCI is the consequence of underlying brain pathology. Therefore, efforts to minimize the impact of ARCI and thus closing the gap between health span and life span, which has widened in recent years, requires early detection and timely deployment of targeted, personalized interventions. Access to clinical experts is limited and technology screening and assessment methods are thus appealing. However, as traditionally implemented patients were deprived of the benefit of personalized connection with a clinician, which is particularly critical for the prescription and to ensure the adherence to and ultimate success of therapeutic interventions. We present the concept of Intelligent Technology Therapy Assistant (ITA) as a scalable solution that increases the reach of clinical experts while sustaining the personal connection between each patient and their clinician. We illustrate ITA with the “Guttman Neuro Personal Trainer”®, a tele-rehabilitation platform that provides neuropsychological evaluation and care, and the Barcelona Brain Health Initiative (BBHI) multimodal intervention coaching app, a mobile-based platform that provides lifestyle coaching support in domains related to brain health. In addition, we discuss the translation of these models to a large-scale enterprise with Linus Health. To this end, we conclude with a discussion of challenges and opportunities to move the field forward.
Alendronate Use and Risk of Type 2 Diabetes: A Nationwide Danish Nested Case-Control Study
Authors: Viggers Rikke , Al-Mashhadi Zheer , Starup-Linde Jakob , Vestergaard Peter
Published: November 2021

Objective

A link has been proposed between glucose homeostasis and bone metabolism. Bisphosphonates are first-line treatment of osteoporosis, and we aimed to investigate whether the risk of developing type 2 diabetes was associated with prior use of alendronate.

Research Design and Methods

We conducted a population-based nested case-control study through access to all discharge diagnoses (ICD-10 system) from the National Danish Patient Registry along with all redeemed drug prescriptions (ATC classification system) from the Health Service Prescription Registry. All cases with a diagnosis of type 2 diabetes between 2008 and 2018 were matched on sex and age with 3 randomly selected controls by incidence-density sampling. Exposure was defined as ever use of alendronate and further grouped as effective and compliant use. ORs were calculated by conditional logistic regression analysis with adjustment for several confounders and test for trend for dose-response relationship.

Results

We included 163,588 patients with type 2 diabetes and 490,764 matched control subjects with a mean age of 67 years and 55% male subjects. The odds of developing type 2 diabetes were lower among ever users of alendronate (multiple adjusted OR: 0.64 [95% CI 0.62-0.66]). A test for trend suggested a dose-response relationship between longer effective use of alendronate and lower risk of type 2 diabetes.

Conclusion

These results suggest a possible protective effect of alendronate in a dose-dependent manner against development of type 2 diabetes.
Linking Plant Functional Traits to Demography in a Fragmented Landscape
Authors: Portela Rita de Cássia Quitete , Colmenares-Trejos Sara Lucía , de Mattos Eduardo Arcoverde
Published: November 2021

Habitat loss in highly deforested landscapes such as the Brazilian Atlantic Forest has been severely affecting the diversity and survival of palm species. As some species are more sensitive than others, trait responses to the environment, as well as environmental effects on fecundity, growth, and mortality rates, may affect species demography. Considering this context, we studied functional and demographic responses of three palm species (Astrocaryum aculeatissimum, Euterpe edulis, and Geonoma schottiana) to habitat loss in the Atlantic Forest in southeastern Brazil by measuring morpho-physiological traits related to plant growth and light acquisition for photosynthesis. We also tested the response of population fitness to fragment size. Plant survival and growth was subsequently monitored in 2006 and 2007, and population dynamics were summarized in pool matrices for large and small forest fragments in the monitoring periods comprehending one full year between 2005–2006 and 2006–2007. The asymptotic growth rate of populations (defined here as population fitness, λ) in five forest fragments was then calculated. Diameter of individuals of the demography plots (from year 2005 to 2007) was used to calculate the relative diameter growth rate. Later, in 2015, we measured a set of morpho-physiological functional traits in palms in the same plots used in the demographic studies. While A. aculeatissimum populations were stable in both monitoring periods in small and large fragments, E. edulis populations were predicted to decline due to intense predation by monkeys in the large fragment, but were stable in the smaller fragments, and G. schottiana populations were stable in the large fragments in both monitoring periods, but populations in the smaller fragments were predicted to decline in the second period, i.e., with lower fitness in these fragments. In addition, the functional traits analyzed showed that G. schottiana is a forest interior species associated with the shade/understory environment response. E. edulis was also affected by the size of the fragment, but due to a disruptive interaction with a predator and showed intermediate functional traits values. On the other hand, A. aculeatissimum thrived in areas with higher and lower incidence of light and was not demographically affected by forest remnant size. This suggests that E. edulis and A. aculeatissimum are habitat generalists. We concluded that differences in the ecophysiological performance of palms due to distinct morpho-physiological functional traits related to leaf economic spectrum, such as LDMC or specific leaf area (SLA) and to photosynthetic responses to light environment as electron transport rate (ETR) and saturation irradiance (Ik) were linked to the demographic variation observed in forest remnants of different size.
Case Report: Identification of Germline Chimerism in Monochorionic Dizygotic Twins
Authors: Chen Juan , Xu Jian , Chen Zhi-Heng , Yin Min-Na , Guo Xin-Yu , Sun Ling
Published: November 2021

Monochorionic twins are generally considered to be monozygotic, as monochorionic dizygotic (MCDZ) twins are extremely rare in natural pregnancies. Several studies have reported this rare occurrence, and most of these pregnancies have been conceived by assisted reproductive technology (ART). These reports mostly focused on MCDZ twin pregnancies and the childhood development of the twins; a follow-up into adulthood and the effect on their reproduction has not been reported. In this case study, we report a case of chimerism in opposite-sex MCDZ twins who were naturally conceived and have reached reproductive maturity. We collected oral mucosal, endometrial, and germ cells from the twins and evaluated their chimerism using single-nucleotide polymorphism (SNP) array and droplet digital PCR (ddPCR). The SNP array showed that they had 4,049 non-allele shared loci, and they inherited nearly 50% informative SNP loci from each parent, confirming that they are dizygotic twins. We found that the female twin had a 46, XX (2)/46, XY (78) karyotype in her peripheral blood. The SNP array confirmed that the female twin and male twin had the same blood haplotype. The ddPCR result showed 92.84 (± 1.80%) chimerism in her blood. In case of chimerism in her germline, the female twin chose preimplantation genetic testing for aneuploidy for her blastocysts. Fortunately, the patient only had blood chimerism. A healthy boy was born at 39 weeks of gestation.
Case Report: A Synonymous Mutation in NF1 Located at the Non-canonical Splicing Site Leading to Exon 45 Skipping
Authors: Jin Pengzhen , Yan Kai , Ye Shaofen , Qian Yeqing , Wu Zaigui , Wang Miaomiao , Xu Yuqing , Xu Yanfei , Dong Minyue
Published: November 2021

Synonymous mutations are generally considered non-pathogenic because it did not alter the amino acids of the encoded protein. Publications of the associations between synonymous mutations and abnormal splicing have increased recently, however, not much observations available described the synonymous mutations at the non-canonical splicing sites leading to abnormal splicing. In this pedigree, the proband was diagnosed Neurofibromatosis type I due to the presence of typical cafe’ au lait macules and pectus carinatum. Whole-exome sequencing identified a synonymous mutation c.6795C > T (p.N2265N) of the NF1 gene which was located at the non-canonical splicing sites. Reverse transcription polymerase chain reaction followed by Sanger sequencing was carried out, and the skipping of exon 45 was observed. Therefore, the pathogenicity of the synonymous mutation c.6795C > T was confirmed. Our finding expanded the spectrum of pathogenic mutations in Neurofibromatosis type I and provided information for genetic counseling.
TMPRSS3 Gene Variants With Implications for Auditory Treatment and Counseling
Authors: Moon In Seok , Grant Andrew R. , Sagi Varun , Rehm Heidi L. , Stankovic Konstantina M.
Published: November 2021

Objective: To identify and report novel variants in the TMPRSS3 gene and their clinical manifestations related to hearing loss as well as intervention outcomes. This information will be helpful for genetic counseling and treatment planning for these patients.

Methods: Literature review of previously reported TMPRSS3 variants was conducted. Reported variants and associated clinical information was compiled. Additionally, cohort data from 18 patients, and their families, with a positive result for TMPRSS3-associated hearing loss were analyzed. Genetic testing included sequencing and copy number variation (CNV) analysis of TMPRSS3 and the Laboratory for Molecular Medicine’s OtoGenome-v1, -v2, or -v3 panels. Clinical data regarding patient hearing rehabilitation was interpreted along with their genetic testing results and in the context of previously reported cochlear implant outcomes in individuals with TMPRSS3 variants.

Results: There have been 87 previously reported TMPRSS3 variants associated with non-syndromic hearing loss in more than 20 ancestral groups worldwide. Here we report occurrences of known variants as well as one novel variant: deletion of Exons 1–5 and 13 identified from our cohort of 18 patients. The hearing impairment in many of these families was consistent with that of previously reported patients with TMPRSS3 variants (i.e., typical down-sloping audiogram). Four patients from our cohort underwent cochlear implantation.

Conclusion: Bi-allelic variants of TMPRSS3 are associated with down-sloping hearing loss regardless of ancestry. The outcome following cochlear implantation in patients with variants of TMPRSS3 is excellent. Therefore, cochlear implantation is strongly recommended for hearing rehabilitation in these patients.
Antibody or Anybody? Considering the Role of MRGPRX2 in Acute Drug-Induced Anaphylaxis and as a Therapeutic Target
Authors: Mackay Graham A. , Fernandopulle Nithya A. , Ding Jie , McComish Jeremy , Soeding Paul F.
Published: November 2021

Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromuscular blocking agents (NMBAs). However, the mast cell receptor MRGPRX2 has also been highlighted as a possible triggering mechanism in acute anaphylaxis to many clinically used drugs. Significantly, MRGPRX2 activation is not dependent upon the presence of drug-recognising antibody. Given the reasonable assumption that MRGPRX2 is expressed in all individuals, the corollary of this is that in theory, anybody could respond detrimentally to triggering drugs (recently suggested to be around 20% of a drug-like compound library). But this clearly is not the case, as the incidence of acute drug-induced anaphylaxis is very low. In this mini-review we consider antibody-dependent and -independent mechanisms of mast cell activation by small molecule drugs with a focus on the MRGPRX2 pathway. Moreover, as a juxtaposition to these adverse drug actions, we consider how increased understanding of the role of MRGPRX2 in anaphylaxis is important for future drug development and can complement exploration of this receptor as a drug target in broader clinical settings.
Transcriptomic Remodelling of Fetal Endothelial Cells During Establishment of Inflammatory Memory
Authors: Weiss Elisa , Vlahos Amanda , Kim Bowon , Wijegunasekara Sachintha , Shanmuganathan Dhanya , Aitken Thomas , Joo Ji-Hoon E. , Imran Samira , Shepherd Rebecca , Craig Jeffrey M. , Green Mark , Hiden Ursula , Novakovic Boris , Saffery Richard
Published: November 2021

Inflammatory memory involves the molecular and cellular ‘reprogramming’ of innate immune cells following exogenous stimuli, leading to non-specific protection against subsequent pathogen exposure. This phenomenon has now also been described in non-hematopoietic cells, such as human fetal and adult endothelial cells. In this study we mapped the cell-specific DNA methylation profile and the transcriptomic remodelling during the establishment of inflammatory memory in two distinct fetal endothelial cell types – a progenitor cell (ECFC) and a differentiated cell (HUVEC) population. We show that both cell types have a core transcriptional response to an initial exposure to a viral-like ligand, Poly(I:C), characterised by interferon responsive genes. There was also an ECFC specific response, marked by the transcription factor ELF1, suggesting a non-canonical viral response pathway in progenitor endothelial cells. Next, we show that both ECFCs and HUVECs establish memory in response to an initial viral exposure, resulting in an altered subsequent response to lipopolysaccharide. While the capacity to train or tolerize the induction of specific sets of genes was similar between the two cell types, the progenitor ECFCs show a higher capacity to establish memory. Among tolerized cellular pathways are those involved in endothelial barrier establishment and leukocyte migration, both important for regulating systemic immune-endothelial cell interactions. These findings suggest that the capacity for inflammatory memory may be a common trait across different endothelial cell types but also indicate that the specific downstream targets may vary by developmental stage.
Dynamic Process of Secondary Pulmonary Infection in Mice With Intracerebral Hemorrhage
Authors: Zhang Hanyu , Huang Yingying , Li Xiaojin , Han Xu , Hu Jing , Wang Bin , Zhang Lin , Zhuang Pengwei , Zhang Yanjun
Published: November 2021

Stroke is a common central nervous system disease in clinical practice. Stroke patients often have infectious complications, such as pneumonia and infections of the urinary tract and gastrointestinal tract. Although it has been shown that translocation of the host gut microbiota to the lungs and immune dysfunction plays a vital role in the development of infection after ischemic stroke, the occurrence and mechanism of pulmonary infection at different time points after hemorrhagic cerebral remain unclear. In this study, the changes in the immune system and intestinal barrier function in mice during disease development were investigated at 1 day (M 1 d), 3 days (M 3 d) and 7 days (M 7 d) following hemorrhagic stroke to clarify the mechanism of secondary pulmonary infection. The experimental results revealed that after hemorrhagic stroke, model mice showed increased brain damage from day 1 to 3, followed by a trend of brain recovery from day 3 to 7 . After hemorrhagic stroke, the immune system was disturbed in model mice. Significant immunosuppression of the peripheral immune system was observed in the M 3 d group but improved in the M 7 d group. Staining of lung tissues with hematoxylin and eosin (H&E) and for inflammatory factors revealed considerable disease and immune disorders in the M 7 d group. Stroke seriously impaired intestinal barrier function in mice and significantly changed the small intestine structure. From 1 to 7 d after stroke, intestinal permeability was increased, whereas the levels of markers for intestinal tight junctions, mucus and immunoglobulin A were decreased. Analysis based on 16S rRNA suggested that the microflora in the lung and ileum was significantly altered after stroke. The composition of microflora in lung and ileum tissue was similar in the M 7d group, suggesting that intestinal bacteria had migrated to lung tissue and caused lung infection at this time point after hemorrhagic stroke. In stroke mice, the aggravation of intestinal barrier dysfunction and immune disorders after intracerebral hemorrhage, promoted the migration of enteric bacteria, and increased the risk of pneumonia poststroke. Our findings reveal the dynamic process of infection after hemorrhagic stroke and provide clues for the optimal timing of intervention for secondary pulmonary infection in stroke patients.