bluuebunny/crossref_metadata_2025 huggingface dataset:
Observations on Portuguese natural history by Leonhard Thurneysser zum Thurn (1531–1596), including the dyes derived from Kermes vermilio and Dracaena draco
Authors: Jerosch Herold Bernardo , Paulo Cabral João
Published: June 2023

In 1555, Leonhard Thurneysser zum Thurn (1531–1596), a young apothecary, alchemist, astrologer and healer from Basle in Switzerland, travelled to Portugal and stayed in Lisbon with Damião de Góis (1502–1574), the Portuguese humanist and diplomat. The principal purpose of Thurneysser’s visit was the study of natural history and the observations and information that he collected then and during a second trip about 1562. These observations were recorded in a manuscript that remained unnoticed until the twenty first century. Thurneysser’s manuscript, now held in the Staatsbibliothek zu Berlin, contains descriptions of animals, plants and of two economically important dyestuffs, kermes and dragon’s blood, the first obtained from the scale insect, Kermes vermilio (associated with Quercus coccifera, kermes oak), and the second from Dracaena draco (dragon tree). Thurneysser’s contributions to knowledge of these two products and their associated plants were innovative and reveal an observer endowed with exceptional insight. His main sources of information, in addition to his personal fieldwork, observation of goods sold in Lisbon markets and conversations with vendors and merchants, were the classics of Antiquity and contemporary works including two of Damião de Góis’s works, Hispania (1542) and Urbis Olisiponis descriptio (1554).
The dispersal of Vivian Vaughan Davies Hewitt’s collection of great auk (Pinguinus impennis) eggs
Authors: Birkhead Tim R. , Clugston David L. , Fuller Errol
Published: June 2023

Private collectors and museums have coveted the eggs and skins of the great auk ( Pinguinus impennis) both before and after the species became extinct in 1844. Because of their monetary and scientific value, the provenance of most great auk eggs and skins is well documented. In the 1930s and 1940s one wealthy collector, Vivian Vaughan Davies Hewitt (1888–1965) amassed no fewer than thirteen great auk eggs (of a total of about 75 known) and four mounted skins (of 78 known). After he died in 1965, the skins and five of the eggs were sold through the dealer Spink & Son Ltd, but the remaining eight eggs remained unsold until 1992 when they were purchased by Dr John Alan (“Jack”) Gibson (1926–2013) of Kilbarchan, Renfrewshire, Scotland. Gibson informed several individuals that he intended to donate the eggs to the National Museum of Scotland. This did not happen, however, and the fate of these eggs has, until now, been unclear and undocumented. We present some details of how Gibson acquired and later disposed of the eight great auk eggs, and, where known, their current whereabouts.
Generation of Human Oligodendrocyte Progenitors for Treatment of Demyelinating Diseases and Spinal Cord Injury
Authors: Hazel Thomas , Hefferan Michael , Schwartz Kateryna , Yu Ningpu , Johe Karl , Levy Michael
Published: June 2023

Glial cells play a critical role in the development and function of the mammalian central nervous system (CNS). Among other roles, these cells provide the myelin sheath needed for the efficient propagation of impulses along nerve fibers, provide trophic support for neuronal cells, and remove toxins and excess neurotransmitters from the interstitial space. Transplantation of glial cells or glial progenitors into the diseased or injured CNS can provide therapeutic benefits. However, generation of therapeutically useful quantities of glia, in particular oligodendrocytes, is technically challenging. Furthermore, generation of glial precursors from sources such as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells poses potential safety risks due to the tumorigenic potential of undifferentiated cells. Here we report a method that enables the efficient generation and expansion of glial precursors from tissue-restricted neural stem cells (NSC). NSC-derived glial precursors can be expanded extensively in culture and retain the capacity to differentiate into oligodendrocytes and astrocytes in vitro and in vivo. Upon transplantation into different animal models of demyelination a substantial proportion of these cells become oligodendrocytes with the capacity to myelinate host axons. These results demonstrate that tissue-restricted human neural stem cells can serve as an efficient source for myelinating oligodendrocytes with therapeutic potential.
The Duration of Mechanical Ventilation is the Main Cause of Bacterial/Fungal Superinfection in Critically Ill Patients with COVID-19 at Altitude
Authors: Molano Franco Daniel , Masclans Joan R , Nuvials Xavier , Gomez Mario , Enciso Cesar , Villabon Mario , Beltran Edgar , Pérez Mauricio , Ramírez Gabriel , Gomez Andres , Escobar Luis , Villa Andres , Arias-Reyes Cristian , Soliz Jorge
Published: June 2023

Background. COVID-19 patients in intensive care units suffer from bacterial/fungal superinfections. However, the incidence and cause of such superinfections in high-altitude hospitals remain poorly investigated.

Objectives. The aim of this study was to evaluate the frequency of bacterial/fungal superinfection in patients with COVID-19 hospitalized in the intensive care unit (ICU) of the Hospital Universitario San José de Bogotá, Colombia, located at an altitude of 2,651 meters above sea level (high altitude). The impact of corticosteroids on the development of infection was also evaluated.

Methods. The cohort included 279 patients, of which 188 (67.4%) were male, 116 (42.3%) were treated with dexamethasone, and 48 (17.2%) were diagnosed with superinfection. A retrospective descriptive cohort study was performed to evaluate the association between bacterial/fungal superinfection frequency, corticosteroid treatment, mechanical ventilation, and mortality rate.

Results. Our results showed that bacteremia was the most frequent diagnosis (n=20; 41.6%) of patients with superinfection, followed by pulmonary superinfection (n=17; 35.4%). The most frequently identified causative agents of superinfection were K. pneumoniae (n=23; 26.1%), C. albicans (n=10; 11.4%) and P. aeruginosa (n=8; 9.1%). Moreover, our results showed no association between corticosteroid treatment (or the use of empiric antibiotic treatment) and mortality. However, we found a significant association between bacterial/fungal superinfection and the number of days on mechanical ventilation. However, bacterial/fungal superinfection showed no impact on the mortality rate.

Conclusions. We conclude that bacterial/fungal superinfection in ICU highland patients with SARS-CoV-2 treated at Hospital Universitario San José in Bogotá, Colombia, increases mainly in proportion to the time required for mechanical ventilation.
COVID-19: CHARACTERISTICS, THERAPY AND CURRENT ISSUES
Authors:   SE «Institute of Dermatology and Venereology of NAMS of Ukraine», Vitkovska M. O.
Published: June 2023

Based on a review of the scientific literature, the main data on the history of human coronavirus infections are given. Modern views on the etiology of COVID‑19, its epidemiology, pathogenesis, main clinical variants and their manifestations are described. The goal is to increase the awareness of patients, doctors and medical personnel about the epidemic of the new viral disease COVID‑19.
CASE OF GENERALIZED LOCAL SCLERODERMA
Authors:   SE «Institute of Dermatology and Venereology of NAMS of Ukraine», Oliinyk I. O. , Mashtakova I. O. ,   SE «Institute of Dermatology and Venereology of NAMS of Ukraine»
Published: June 2023

The case of generalized local scleroderma with the positive effect as a result of the therapy is described. The goal is to evaluate the therapeutic effectiveness of complex treatment using antifibrotic agents in a clinical case of generalized focal scleroderma.
Visão de Ciência Presente nas Diretrizes Curriculares Nacionais para os Cursos de Engenharia
Authors: Rosa Cleci Teresinha Werner da , Rosa Alvaro Becker da
Published: June 2023

A engenharia é entendida como conhecimento básico aplicado à busca por soluções de problemas que têm seu cerne na própria sociedade. Contudo, nem sempre olha exclusivamente para ela, voltando-se, por vezes, a buscar respostas à questão que é imposta por sua própria lógica interna. Partindo desse entendimento, o presente texto traz como objetivo analisar as Diretrizes Curriculares Nacionais para os Cursos de Graduação em Engenharia, investigando a visão de ciência e de construção do conhecimento cientí­fico subjacente ao documento. Como recorte do estudo, centra-se na análise dessas diretrizes pelo viés internalista e/ou externalista, que são duas formas de pensar a ciência. Em uma definição a priori, para os internalistas, seu fazer é possí­vel considerando apenas os elementos propriamente cientí­ficos, ao passo que, para os externalistas, o mais importante são as componentes sociais que interferem na produção cientí­fica. Para tanto, procede-se a uma pesquisa qualitativa, documental e bibliográfica na qual se realizam uma análise e discussão dos artigos que integram tais diretrizes. Como resultado, identifica-se uma forte presença do externalismo, sem deixar de lado o internalismo.
Lua: construção e representação interdisciplinar
Authors: Silva Josie Agatha Parrilha , Nardi Roberto
Published: June 2023

O artigo apresenta resultados referentes à pesquisa desenvolvida em um curso de extensão para formação interdisciplinar de professores da rede pública estadual das áreas de Ciência, Fí­sica, Geografia e Artes Visuais. O curso foi desenvolvido numa parceria entre o Programa de Pós-Graduação em Educação para a Ciência (UNESP-Bauru) e Secretaria de Estado da Educação - Diretoria de Ensino - Região Bauru (SEED-Bauru). O objetivo do curso foi propiciar uma vivência essencialmente interdisciplinar a partir do tema Lua, baseado na relação entre Arte e Ciência, que já existia de forma orgânica desde a publicação do Sidereus nuncius de Galileo Galilei. Um dos focos do curso foi a questão da observação e da representação da Lua. Em relação à Ciência (Fí­sica/Astronomia), foram apresentados conteúdos teórico-práticos sobre o tema como: lunação, morfologia e selenografia. Em relação à Arte (Artes Visuais), abordamos questões quanto à representação imagética a partir do desenho e de diferentes técnicas bi e tridimensionais. Inferimos que a observação e a representação imagética têm um caráter interdisciplinar uma vez que é fundamental para as áreas de Ciência e de Arte. Ao discutirmos sobre a imagem, um dos principais referenciais foi Panofsky (2007). Entre os resultados, destacamos a construção interdisciplinar realizada pelos professores nas representações da Lua.
Os Três Momentos Pedagógicos e a Abordagem Temática na Educação em Ciências: um olhar para as diferentes perspectivas
Authors: Schneider Tatiani Maria , Paniz Catiane Mazocco , Magoga Thiago Flores , Ferreira Marinês Verônica , Muenchen Cristiane
Published: June 2023

Este estudo tem com o objetivo identificar as perspectivas de Abordagens Temáticas presentes nos trabalhos que utilizam os Três Momentos Pedagógicos como dinâmica de sala de aula. Além disso, discutir os aspectos relacionados à escolha do tema, à interdisciplinaridade e o papel que o educando assume neste processo, em cada uma das perspectivas identificadas, assim como suas aproximações e distanciamentos. Destaca-se que as perspectivas de abordagem temática identificadas para o desenvolvimento dos Momentos Pedagógicos foram a Abordagem Temática Freireana, Situação de Estudo e Ciência Tecnologia e Sociedade (CTS). Sinaliza-se também a importância da construção de currí­culos a partir da dinâmica dos Momentos Pedagógicos como perspectiva curricular.
Utilização do programa MAXqda10 na investigação de subsunçores de estudantes de ní­vel médio a respeito do tema radioatividade e de sua relação com a ciência, tecnologia e sociedade (CTS)
Authors: Antiszko Thaiz Regina , Sauer Elenise
Published: June 2023

O presente artigo apresenta uma investigação a respeito dos subsunçores (ou concepções iniciais) que estudantes do Ensino Médio apresentam a respeito do conteúdo de radioatividade e suas relações com a ciência, tecnologia e sociedade (CTS) utilizando o programa MAXqda10. Aborda a teoria da aprendizagem significativa proposta por Ausubel, a qual estabelece a importância de se conhecer estes subsunçores para a transposição dos conteúdos de maneira a promover esta aprendizagem. A abordagem metodológica utilizada foi a qualitativa de natureza interpretativa, realizada com 18 estudantes, do segundo ano, do turno matutino, de um colégio da rede estadual de ensino da região Centro Sul do Paraná. A coleta de dados se deu por meio de questionário, e a análise do conteúdo nas respostas foi realizada no software MAXqda10, utilizado para a análise de dados qualitativos e métodos mistos de investigação, contribuiu na estratificação e registro das etapas de análise, dando transparência e agilidade ao processo, além dos recursos para apresentação e visualização dos resultados obtidos. O procedimento de análise consistiu em transcrever os questionários respondidos pelos estudantes, para arquivos Word codificados num sistema alfa numérico (AI1 a AIn). O critério de análise utilizou o conteúdo fornecido nas respostas para estratificação de categorias (C1 a Cn), e subcategorias (subC1 a subCn). Os resultados obtidos na presente investigação possibilitaram identificar os subsunçores que os estudantes possuem a respeito da radioatividade e de sua relação com a ciência, a tecnologia e a sociedade, que as informações que circulam pelos meios midiáticos interferem no modo como são estabelecidos, que apresentavam indí­cios conceituais de radioatividade e de suas aplicações, quanto à malefí­cio, benefí­cio e fatos históricos. Ofereceu ao professor subsí­dios para buscar estratégias adequadas para planejar uma sequência didática para realizar a transposição didática sobre o tema.
Edward Lear: considerações sobre a tradução de uma carta de Lear para Chichester Fortescue
Authors: Buch Bohrer Andréa Luciane
Published: June 2023

Resumo: O presente artigo apresenta a tradução de uma das cartas escritas por Edward Lear durante as viagens que fez ao longo se sua vida. Lear foi um dos precursores da literatura nonsense no século XIX, com a publicação do livro A Book of Nonsense. Durante esse trabalho, foram abordados alguns textos importantes do pensamento das teorias analisadas durante as aulas de História da Tradução. Há comentários acerca da tradução que realizei desta carta, assim como as decisões que foram sendo adotadas no decorrer dessa tradução.Palavras-chave: Edward Lear. Tradução. Teorias da Tradução. Cartas. Nonsense.
Minimally invasive treatment of pilonidal sinus disease (a systematic review and meta-analysis)
Authors: Kozyreva S. B. , Kostarev I. V. , Blagodarny L. A. , Polovinkin V. V. , Zakharyan A. V. , Titov A. Yu.
Published: June 2023

AIM: to estimate the effectiveness of minimally invasive methods for treatment of chronic inflammation in pilonidal sinus disease by systematic review.

PATIENTS AND METHODS: fifty-two clinical trials were selected from 2,576 papers in databases for systematic review. It included the following methods: the fibrin glue, the sinusectomy, the video-assisted pilonidal sinus treatment, the laser coagulation and the chemical destruction using crystallized phenol or its solution. Regarding the last two methods, a meta-analysis was carried out.

RESULTS: the meta-analysis demonstrated the high effectiveness of phenol and laser coagulation for pilonidal sinus disease. When comparing the results of phenol use and excisional techniques, there was a significant difference in higher frequency complications rate after excisional techniques (HR 0.42; 95% CI: 0.05–3.71), while the recurrence rate was the same (HR 0.98; 95% CI: 0.45–2.16). The probability of recurrence was significantly higher than after excision techniques in compare with SiLaC (HR 4.02; 95% CI: 1.13 14.3, p = 0.03). However, there was no significant differences in complication rate after SiLaC and excisional techniques (HR 0.63; 95% CI: 0.29–1.34).

CONCLUSION: the chemical destruction and laser coagulation are the most effective methods for pilonidal sinus treatment.
Neurogenic bladder dysfunction after total mesorectumectomy
Authors: Azimov E. G. , Aliyev S. A.
Published: June 2023

AIM:to estimate the rate, causes and features of neurogenic bladder dysfunction in patients with rectal cancer after total mesorectumectomy.

PATIENTS AND METHODS:the results of surgical treatment of 103 patients with rectal cancer were analyzed in the light of immediate and long-term outcomes, who underwent total mesorectumectomy using traditional (56-54.4%) and laparoscopic (47-45.6%) technologies. In 20 (19.4%) of 103 patients, the course of the immediate postoperative period was complicated by the development of neurogenic bladder dysfunction. In order to study the frequency of neurogenic bladder dysfunction depending on the technique of mesorectumectomy, the patients were divided into 2 groups. Group 1 included 9 patients who underwent laparoscopic total mesorectumectomy. Group 2 included 11patients who underwent traditional (open) mesorectumectomy.

RESULTS:the study of the functional state of the bladder according to the flowmetric indicators revealed that the frequency of development of postoperative bladder dysfunction has a gender dependence. The frequency of neurogenic bladder dysfunction was 25% in men and 10,7% in women. It is shown that during 1 week and 6 months after surgery, the average urination rate tends to increase in women and decrease in men, regardless of the technique of total mesorectumectomy. In both groups, there was not a statistically significant decrease in the maximum volumetric velocity in both men and women within 6 months after surgery. At the same time, during this period, there was a decrease in the average rate of urination only in men, regardless of the technique of total mesorectumectomy. And in women, this indicator remained unchanged or slightly increased.

CONCLUSION:it is shown that a complex system of therapeutic measures, including drug stimulation of the detrusor and urethral sphincter, repeated catheterization of the bladder, as well as epicystostomy performed according to indications, allows adequate correction of bladder dysfunction after total mesorectumectomy in patients with rectal cancer.
Clinical features and quality of life of patients with idiopathic megacolon
Authors: Aleshin D. V. , Achkasov S. I. , Sushkov O. I. , Shakhmatov D. G. , Surovegin E. S. , Fomenko O. Yu.
Published: June 2023

PATIENTS AND METHODS: the retrospective study of clinical features and diagnostic tests results included 81 patients with idiopathic megacolon/megarectum (2004–2022). The diagnosis of megacolon/megarectum was confirmed with a barium enema, Hirschsprung’s disease was excluded based on anorectal manometry and (if needed) rectal Swenson biopsy. The QoL was assessed by IBSQOL questionnaire; clinical symptoms were assessed with a point scale.

RESULTS: the quality of life in patients with idiopathic megacolon has most affected energy (emotional and physical) and physical role (work/main activity). In univariate analysis the significant correlation was revealed between QoL and age, sex, rate of defecation without assistance, rate of integral parameters “abdominal discomfort” and “defecation difficulties”, duration of anamnesis, Wexner constipation scale rate and gut transit time (p < 0,05). In the same time, the presence or absence of constipation or anal incontinence (leakage), colon and rectum sizes (based on barium enema), parameters of defecografy and rectal compliance test have not correlated with a QoL. No significant difference of QoL in patients added to conservative treatment and operated after. Due to multivariate analysis (multiple linear regression) the age and rate of “abdominal discomfort” and “defecation difficulties” were only independent factors affected quality of life.

CONCLUSION: in terms of quality of life, idiopathic megacolon has the greatest impact on general tone and ability to perform basic professional activities. Independent factors that statistically significantly affect the assessment of quality of life are the age of patients and the severity of symptoms of abdominal discomfort and defecation disorders.
Short-term prehabilitation of patients with colorectal cancer — protocol of a randomized trial
Authors: Zakharenko A. A. , Zavgorodniaia M. V. , Afanasiev A. A. , Potapchuk A. A.
Published: June 2023

AIM: to estimate effect of unimodal short preabilitation on functional reserves of patients, hospital stay, complication rate and quality of life.

PATIENTS AND METHODS: a single-centre, prospective, randomized study will include 128 patients undergoing colon resection for colorectal cancer. Patients will be divided into an intervention group that will receive 14 days of unimodal prehab (Group 1) and a control group that will not receive prehab (Group 2). Perioperative management of patients in both groups will be carried out in accordance with the guidelines for accelerated recovery after surgery (ERAS). The primary endpoint of the study will be the six-minute walk test (6MWT). Secondary endpoints will be: number of postoperative complications (by Clavien-Dindo), duration of the postoperative period, postoperative mortality, quality of life of patients and adherence of patients to the passage of the prehabilitation program.

DISCUSSION AND CONCLUSION: it is expected that short-term unimodal prehabilitation will improve the functional reserves of patients, reduce the duration of inpatient treatment and reduce the number and severity of postoperative complications, which can lead to a decrease in postoperative mortality and an improvement in the quality of life of patients. The adherence of the domestic cohort of patients to prehabilitation will be analyzed.
Bioprocess development for universal influenza vaccines based on inactivated split chimeric and mosaic hemagglutinin viruses
Authors: Puente-Massaguer Eduard , Beyer Annika , Loganathan Madhumathi , Sapse Iden , Carreño Juan Manuel , Bajic Goran , Sun Weina , Palese Peter , Krammer Florian
Published: June 2023

Seasonal influenza viruses account for 1 billion infections worldwide every year, including 3–5 million cases of severe illness and up to 650,000 deaths. The effectiveness of current influenza virus vaccines is variable and relies on the immunodominant hemagglutinin (HA) and to a lesser extent on the neuraminidase (NA), the viral surface glycoproteins. Efficient vaccines that refocus the immune response to conserved epitopes on the HA are needed to tackle infections by influenza virus variants. Sequential vaccination with chimeric HA (cHA) and mosaic HA (mHA) constructs has proven to induce immune responses to the HA stalk domain and conserved epitopes on the HA head. In this study, we developed a bioprocess to manufacture cHA and mHA inactivated split vaccines and a method to quantify HA with a prefusion stalk based on a sandwich enzyme-linked immunosorbent assay. Virus inactivation with beta-propiolactone (βPL) and splitting with Triton X-100 yielded the highest amount of prefusion HA and enzymatically active NA. In addition, the quantity of residual Triton X-100 and ovalbumin (OVA) was reduced to very low levels in the final vaccine preparations. The bioprocess shown here provides the basis to manufacture inactivated split cHA and mHA vaccines for pre-clinical research and future clinical trials in humans, and can also be applied to produce vaccines based on other influenza viruses.
Comprehensive analysis of REST corepressors (RCORs) in pan-cancer
Authors: Zheng Rong , Pan Yingying , Liu Xinhui , Liu Feiye , Li Aimin , Zheng Dayong , Luo Yue
Published: June 2023

REST corepressors (RCORs) are the core component of the LSD1/CoREST/HDACs transcriptional repressor complex, which have been revealed differently expressed in various cancers, but the therapeutic and prognostic mechanisms in cancer are still poorly understood. In this study, we analyzed expression, prognostic value, molecular subtypes, genetic alteration, immunotherapy response and drug sensitivity of RCORs in pan-cancer. Clinical correlation, stemness index, immune infiltration and regulatory networks of RCORs in hepatocellular carcinoma (HCC) were detected through TCGA and GSCA database. In-vitro experiments were conducted to explore the role of RCOR1 in HCC cells. The expression of RCORs varied among different cancers, and have prognostic values in several cancers. Cancer subtypes were categorized according to the expression of RCORs with clinical information. RCORs were significantly correlated with immunotherapy response, MSI, drug sensitivity and genetic alteration in pan-cancer. In HCC, RCORs were considered as potential predictor of stemness and also had association with immune infiltration. The ceRNA-TF-kinase regulatory networks of RCORs were constructed. Besides, RCOR1 acts as an oncogene in HCC and promotes the proliferation of HCC cells by inhibiting cell cycle arrest and cell apoptosis. Taken together, our study revealed the potential molecular mechanisms of RCORs in pan-cancer, offering a benchmark for disease-related research.
Leveraging electronic health record data for endometriosis research
Authors: Penrod Nadia , Okeh Chelsea , Velez Edwards Digna R. , Barnhart Kurt , Senapati Suneeta , Verma Shefali S.
Published: June 2023

Endometriosisis a chronic, complex disease for which there are vast disparities in diagnosis and treatment between sociodemographic groups. Clinical presentation of endometriosis can vary from asymptomatic disease—often identified during (in)fertility consultations—to dysmenorrhea and debilitating pelvic pain. Because of this complexity, delayed diagnosis (mean time to diagnosis is 1.7–3.6 years) and misdiagnosis is common. Early and accurate diagnosis of endometriosis remains a research priority for patient advocates and healthcare providers. Electronic health records (EHRs) have been widely adopted as a data source in biomedical research. However, they remain a largely untapped source of data for endometriosis research. EHRs capture diverse, real-world patient populations and care trajectories and can be used to learn patterns of underlying risk factors for endometriosis which, in turn, can be used to inform screening guidelines to help clinicians efficiently and effectively recognize and diagnose the disease in all patient populations reducing inequities in care. Here, we provide an overview of the advantages and limitations of using EHR data to study endometriosis. We describe the prevalence of endometriosis observed in diverse populations from multiple healthcare institutions, examples of variables that can be extracted from EHRs to enhance the accuracy of endometriosis prediction, and opportunities to leverage longitudinal EHR data to improve our understanding of long-term health consequences for all patients.
Time transfer and significance of vertical land motion in relativistic geodesy applications: a review paper
Authors: Bagherbandi Mohammad , Shirazian Masoud , Amin Hadi , Horemuz Milan
Published: June 2023

Determination of the Earth’s gravity field and geopotential value is one of the fundamental topics in physical geodesy. Traditional terrestrial gravity and precise leveling measurements can be used to determine the geopotential values at a local or regional scale. However, recent developments in optical atomic clocks have not only rapidly improved fundamental science but also contributed to applied research. The latest generation of optical clocks is approaching the accuracy level of 10−18 when facilitating atomic clock networks. These systems allow examining fundamental theories and many research applications, such as atomic clocks applications in relativistic geodesy, to precisely determine the Earth’s gravity field parameters (e.g., geopotential values). According to the theory of relativistic geodesy, the frequency difference measured by an optical clock network is related to the gravity potential anomaly, provided that the effects of disturbing signals (i.e., tidal and non-tidal contributions) are filtered out. The relativistic geodesy principle could be used for a practical realization of global geodetic infrastructure, most importantly, a vertical datum unification or realization of height systems. This paper aims to review the background of relativistic (clock-based) geodesy and study the variations of optical atomic clock measurements (e.g., due to hydrology loading and land motion).
Student teachers’ experience of participating in a research and development project in Norway
Authors: Blomsø Sindre Øyan , Jakhelln Rachel Elise , Postholm May Britt
Published: June 2023

This study investigates student teachers’ experience of participating in a research and development project named Learning, Assessment and Boundary-crossing in Teacher Education (LAB-TEd). LAB-TEd is a tripartite collaboration project between student teachers, practice teachers and university teachers from two universities in Norway. Framed by cultural-historical activity theory (CHAT), participatory data analysis workshops, known as Change Laboratories, have been used to ensure the relevance of the student teachers’ thesis work for professional development, and to uncover obstacles and barriers to change. Recent research highlights that teachers are typical participants in Change Laboratories implemented in teacher education and schools. There are few studies that highlight student teachers as participants in such interventions, and this may indicate that this is a field of research that is important to investigate. The purpose of the article is to provide insight about how student teachers’ experience participating in a research and development project grounded in CHAT. The data material consists of qualitative interviews with 34 student teachers. Findings from this study indicate that student teachers experienced a development journey by participating in the project. The following are the main findings from the study: The student teachers experienced that their own drive and motivation went from self-interest as the driving force for participation, to a more collective understanding. The student teachers first experienced tripartite collaboration as non-existent, later to become tripartite collaboration. The student teachers experienced how their role in the project’s tripartite collaboration developed from serving as a communication link between university and school, to becoming an actual participant. The student teachers also experienced how their role in Change Laboratories changed from being voiceless participants to becoming more equal partners in the project. The discussion elaborates on the development journey that the participants experienced.
The use of the ECHO model™ for education as an innovative approach to educator professional development
Authors: Dahl Ethan , Sturges Haley A. , Smith Olivia K. H. , Hardesty Canyon , Root-Elledge Sandra , Zlatkovic Sarah , Moody Eric J.
Published: June 2023

After entering the workforce, educators may face novel problems of practice that require additional training. Ongoing professional learning and development (PD) is meant to provide the additional training necessary to ensure educators are prepared to meet those challenges. PD offerings should meet the recommendations of Adult Learning Theory, the Model for Teacher Change, and recommended best practices for adult learning and PD. The ECHO Model for Education is an effective, high-quality model of educator PD that satisfies such recommendations. Practical issues are discussed, and recommendations are made for those interested in implementing this innovative model for PD.
Are relations between children’s hyperactive behavior, engagement, and social interactions in preschool transactional? A longitudinal study
Authors: Sjöman Madeleine
Published: June 2023

Based on bioecological systems theory, engagement is the mechanism for children’s learning and development. However, children with hyperactive behavior tend to be less engaged in early childhood education and care (ECEC), which might negatively influence their learning and development. On the other hand, social interaction might support children with hyperactive behavior staying engaged in these activities. The current study investigates whether the association between teacher responsiveness, positive peer-to-child interaction (i.e., the quality of peer interaction) and children’s hyperactive behavior and engagement levels are transactional. Two hundred and three children aged 1 to 5 in Swedish preschool settings were followed. Data was collected at three points in time between 2012 and 2014. This data was then analyzed to identify associations and how they changed over time. Transactional paths were found between children’s levels of core engagement, teacher responsiveness, and the quality of positive peer-to-child interaction. Children’s core engagement increases the probability of better quality positive peer-to-child interaction and teacher responsiveness, increasing core engagement over time. Teacher responsiveness and the quality of positive peer-to-child interaction are predictors of reduced hyperactive behavior over time. Meanwhile, children’s hyperactive behavior does not significantly influence these two types of social interaction, that is, decreased hyperactivity may not improve social interaction to the same extent as increased engagement. The findings are discussed in relation to how special support for children with hyperactive behavior can be designed, with a focus on increasing core engagement in preschool settings.
Birth size, growth trajectory and later cardio-metabolic risk
Authors: Cauzzo Chiara , Chiavaroli Valentina , Di Valerio Susanna , Chiarelli Francesco
Published: June 2023

There is increasing evidence of a strong association between intrauterine growth and subsequent development of chronic disease in adult life. Birth size and growth trajectory have been demonstrated to have an impact on cardio-metabolic health, both in childhood and adult life. Hence, careful observation of the children’s growth pattern, starting from the intrauterine period and the first years of life, should be emphasized to detect the possible onset of cardio-metabolic sequelae. This allows to intervene on them as soon as they are detected, first of all through lifestyle interventions, whose efficacy seems to be higher when they are started early. Recent papers suggest that prematurity may constitute an independent risk factor for the development of cardiovascular disease and metabolic syndrome, regardless of birth weight. The purpose of the present review is to examine and summarize the available knowledge about the dynamic association between intrauterine and postnatal growth and cardio-metabolic risk, from childhood to adulthood.
Multiphysics analysis of heat pipe cooled microreactor core with adjusted heat sink temperature for thermal stress reduction using OpenFOAM coupled with neutronics and heat pipe code
Authors: Jeong Myung Jin , Im Jaeuk , Lee San , Cho Hyoung Kyu
Published: June 2023

Heat-pipe-cooled microreactors (HPRs) have advantages such as a compact design, easy transportation, and improved system reliability and stability. The core of an HPR consists of fuel rods and heat pipes in a monolith, which is a solid block structure containing many holes for the fuel rods and heat pipes. When designing the core of an HPR, high thermal stress and reactivity feedback owing to thermal expansion are important considerations. Therefore, a high-fidelity multiphysics analysis tool is required for accurately analyzing an HPR core. When performing a multiphysics analysis, it is necessary to couple the heat pipe thermal analysis code, thermal-structural analysis code, and neutronics code. To develop a multiphysics analysis tool, OpenFOAM, an open source Computational Fluid Dynamics (CFD) tool, and ANLHTP, a heat pipe thermal analysis code, were coupled. In this process, the structural analysis solver of OpenFOAM was verified, and its limitations were improved. To confirm the proper working of the code, the mini-core problem was analyzed using the OpenFOAM-ANLHTP coupled code. Next, to consider the reactivity feedback, coupling with PRAGMA, a GPU-based continuous-energy-Monte Carlo neutronics code was performed, and the multiphysics analysis capability of the OpenFOAM-ANLHTP-PRAGMA coupled code was confirmed through an analysis of the MegaPower reactor core. To reduce the temperature distribution within the monolith, the temperature distribution of the heat pipe sink was adjusted, and the reduced thermal stress of an HPR core was observed.
Natural regeneration of wetlands under climate change
Authors: Zivec Peta , Sheldon Fran , Capon Samantha J.
Published: June 2023

Wetlands are increasingly valuable under climate change in terms of their ecological functions, ecosystem services, and biodiversity. Simultaneously, wetlands are hotspots for anthropogenic activity due to their high soil fertility and water supply, and have been subject to significant modification, degradation, and staggering losses. With climate change having increasing impacts on ecosystems globally, the need for wetland restoration is rapidly growing. Natural regeneration, whereby vegetation is allowed to regrow via propagules already present within the landscape, provides a cost-effective and large-scale approach to restoration for many, but not, all wetlands. This paper emphasises the importance of natural regeneration of wetland ecosystems as an effective restoration approach under climate change. We discuss drivers and barriers of natural regeneration of wetlands under climate change along with implications for management approaches. Drivers of wetland natural regeneration are depicted along with their interactions, displaying a range of abiotic and biotic factors that influence ecosystem change. Key adaption approaches to maintain and promote natural regeneration of wetlands under climate change include integrated land and water management, protecting and promoting key relevant biotic and abiotic processes within landscapes, and reconsidering current exotic species management strategies. Most importantly, however, natural regeneration should be recognised as an important and viable restoration approach under climate change in order to meet restoration demand and promote landscape resilience to changing conditions.
The rising death burden of atrial fibrillation and flutter in low-income regions and younger populations
Authors: Liu Ye-Mao , Wang Wenxin , Zhang Xingyuan , Lei Fang , Qin Juan-Juan , Huang Xuewei , Li Ruyan , Lin Lijin , Chen Mingming , Ji Yan-Xiao , Zhang Peng , Zhang Xiao-Jing , She Zhi-Gang , Cai Jingjing , Xu Chengsheng , Shen Zhengjun , Li Hongliang
Published: June 2023

Objective

The aim of the study was to depict the global death burden of atrial fibrillation and/or flutter (AFF) between 1990 and 2019 and predict this burden in the next decade.

Methods

We retrieved annual death data on cases and rates of AFF between 1990 and 2019 from the Global Burden of Disease (GBD) Study 2019 and projected the trends for 2020–2029 by developing the Bayesian age-period-cohort model.

Results

The global number of deaths from AFF increased from 117,038.00 in 1990 to 315,336.80 in 2019. This number is projected to reach 404,593.40 by 2029. The age-standardized mortality rates (ASMRs) of AFF have increased significantly in low- to middle-sociodemographic index (SDI) regions, which will surpass that in high SDI regions and reach above 4.60 per 100,000 by 2029. Globally, women have a higher ASMR than men, which is largely attributed to disproportionately higher mortality in women than men in lower SDI regions. Notably, AFF-related premature mortality continues to worsen worldwide. A pandemic of high systolic blood pressure and high body mass index (BMI) largely contributes to AFF-associated death. In particular, low- to middle-SDI regions and younger populations are increasingly affected by the rapidly growing current and future risk of high BMI.

Conclusion

The global death burden of AFF in low-income countries and younger generations have not been sufficiently controlled in the past and will continue growing in the future, which is largely attributed to metabolic risks, particularly for high BMI. There is an urgent need to implement effective measures to control AFF-related mortality.
Immunohistochemical scoring of LAG-3 in conjunction with CD8 in the tumor microenvironment predicts response to immunotherapy in hepatocellular carcinoma
Authors: Cheung Chun Chau Lawrence , Seah Yong Hock Justin , Fang Juntao , Orpilla Nicole Hyacinth Calpatura , Lau Mai Chan , Lim Chun Jye , Lim Xinru , Lee Justina Nadia Li Wen , Lim Jeffrey Chun Tatt , Lim Sherlly , Cheng Qing , Toh Han Chong , Choo Su Pin , Lee Suat Ying , Lee Joycelyn Jie Xin , Liu Jin , Lim Tony Kiat Hon , Tai David , Yeong Joe
Published: June 2023

Introduction

Immune checkpoint blockade (ICB) is a systemic therapeutic option for advanced hepatocellular carcinoma (HCC). However, low patient response rates necessitate the development of robust predictive biomarkers that identify individuals who will benefit from ICB. A 4-gene inflammatory signature, comprising CD8, PD-L1, LAG-3, and STAT1, was recently shown to be associated with a better overall response to ICB in various cancer types. Here, we examined whether tissue protein expression of CD8, PD-L1, LAG-3, and STAT1 predicts response to ICB in HCC.

Methods

HCC samples from 191 Asian patients, comprising resection specimens from 124 patients (ICB-naïve) and pre-treatment specimens from 67 advanced HCC patients treated with ICB (ICB-treated), were analyzed for CD8, PD-L1, LAG-3, and STAT1 tissue expression using multiplex immunohistochemistry followed by statistical and survival analyses.

Results

Immunohistochemical and survival analyses of ICB-naïve samples showed that high LAG-3 expression was associated with shorter median progression-free survival (mPFS) and overall survival (mOS). Analysis of ICB-treated samples revealed that high proportions of LAG-3+ and LAG-3+CD8+ cells pre-treatment were most closely associated with longer mPFS and mOS. Using a log-likelihood model, adding the total LAG-3+ cell proportion to the total CD8+ cell proportion significantly increased the predictive values for mPFS and mOS, compared with the total CD8+ cell proportion alone. Moreover, levels of CD8 and STAT1, but not PD-L1, were significantly correlated with better responses to ICB. After analyzing viral-related and non-viral HCC samples separately, only the LAG3+CD8+ cell proportion was significantly associated with responses to ICB regardless of viral status.

Conclusion

Immunohistochemical scoring of pre-treatment levels of LAG-3 and CD8 in the tumor microenvironment may help predict ICB benefits in HCC patients. Furthermore, immunohistochemistry-based techniques offer the advantage of being readily translatable in the clinical setting.
Free heme exacerbates colonic injury induced by anti-cancer therapy
Authors: Seika Philippa , Janikova Monika , Asokan Sahana , Janovicova Lubica , Csizmadia Eva , O’Connell Mckenzie , Robson Simon C. , Glickman Jonathan , Wegiel Barbara
Published: June 2023

Gastrointestinal inflammation and bleeding are commonly induced by cancer radiotherapy and chemotherapy but mechanisms are unclear. We demonstrated an increased number of infiltrating heme oxygenase-1 positive (HO-1+) macrophages (Mø, CD68+) and the levels of hemopexin (Hx) in human colonic biopsies from patients treated with radiation or chemoradiation versus non-irradiated controls or in the ischemic intestine compared to matched normal tissues. The presence of rectal bleeding in these patients was also correlated with higher HO-1+ cell infiltration. To functionally assess the role of free heme released in the gut, we employed myeloid-specific HO-1 knockout (LysM-Cre : Hmox1flfl), hemopexin knockout (Hx-/-) and control mice. Using LysM-Cre : Hmox1flfl conditional knockout (KO) mice, we showed that a deficiency of HO-1 in myeloid cells led to high levels of DNA damage and proliferation in colonic epithelial cells in response to phenylhydrazine (PHZ)-induced hemolysis. We found higher levels of free heme in plasma, epithelial DNA damage, inflammation, and low epithelial cell proliferation in Hx-/- mice after PHZ treatment compared to wild-type mice. Colonic damage was partially attenuated by recombinant Hx administration. Deficiency in Hx or Hmox1 did not alter the response to doxorubicin. Interestingly, the lack of Hx augmented abdominal radiation-mediated hemolysis and DNA damage in the colon. Mechanistically, we found an altered growth of human colonic epithelial cells (HCoEpiC) treated with heme, corresponding to an increase in Hmox1 mRNA levels and heme:G-quadruplex complexes-regulated genes such as c-MYC, CCNF, and HDAC6. Heme-treated HCoEpiC cells exhibited growth advantage in the absence or presence of doxorubicin, in contrast to poor survival of heme-stimulated RAW247.6 Mø. In summary, our data indicate that accumulation of heme in the colon following hemolysis and/or exposure to genotoxic stress amplifies DNA damage, abnormal proliferation of epithelial cells, and inflammation as a potential etiology for gastrointestinal syndrome (GIS).
Multiplexed bead-based assay for the simultaneous quantification of human serum IgG antibodies to tetanus, diphtheria, pertussis toxin, filamentous hemagglutinin, and pertactin
Authors: Rathod Vishal , Kadam Laxmikant , Gautam Manish , Gumma Prabhu Dasu , Marke Kevin , Asokanathan Cathy , Douglas-Bardsley Alex , Hassell Laura , Bhandare Sachin , Gupta Sumit , Parekh Sameer , Pujari Pramod , Rao Harish , Sharma Hitt , Shaligram Umesh , Gairola Sunil
Published: June 2023

Background

Luminex bead-based assays offer multiplexing to test antibodies against multiple antigens simultaneously; however, this requires validation using internationally certified reference standards. Therefore, there is an urgent need to characterize existing reference standards for the standardization of multiplex immunoassays (MIAs). Here, we report the development and validation of an MIA for the simultaneous estimation of levels of human serum immunoglobulin G (IgG) antibodies for pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), and tetanus toxoid (TT).

Methods

The MIA was assessed using a panel of human serum samples and WHO reference standards. The WHO reference standards were also studied for suitability in the MIA. Purified antigens (PT, FHA, PRN, DT, and TT) were coupled to the spectrally unique magnetic carboxylated microspheres. The method was validated in accordance with the United States Food and Drug Administration (US FDA), European Medicines Agency (EMA), and the International Committee of Harmonization Multidisciplinary (ICH M10) guidelines, and parameters such as precision, accuracy, dilutional linearity, assay range, robustness, and stability were assessed. Method agreements with commercially available IgG enzyme-linked immunosorbent assay (ELISA) assays were also evaluated. In addition, the study assessed the level of correlation between the IgG levels estimated by the MIA and the cell-based neutralizing antibody assays for PT and DT.

Results

We identified that an equimix of WHO international standards (i.e., 06/142, 10/262, and TE-3) afforded the best dynamic range for all the antigens in the MIA. For all five antigens, we observed that the back-fitted recoveries using the four-parameter logistic (4-PL) regression fits ranged between 80% and 120% for all calibration levels, and the percentage coefficient of variation (% CV) was < 20%. In addition, the difference in mean fluorescence intensity (MFI) between the monoplex and multiplex format was < 10% for each antigen, indicating no crosstalk among the beads. The MIA also showed good agreement with conventional and commercially available assays, and a positive correlation (> 0.75) with toxin neutralization assays for PT and DT was observed.

Conclusion

The MIA that was calibrated in accordance with WHO reference standards demonstrated increased sensitivity, reproducibility, and high throughput capabilities, allowing for the design of robust studies that evaluate both natural and vaccine-induced immunity.