bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal and Fetal Health Risks Among Female Military Aviation Officers
Authors: Stark Christopher M. , Sorensen Ian S. , Royall Matthew , Dorr Madeline , Brown Jill , Dobson Nicole , Salzman Sandra , Susi Apryl , Hisle-Gorman Elizabeth , Huggins Brian H. , Nylund Cade M.
Published: August 2024

INTRODUCTION: Military aviation poses unique occupational risks, including exposures to intermittent hypoxia, high gravitational force, and toxic materials, in addition to circadian disruption, cosmic radiation, and ergonomic stressors also present in commercial flight. We sought to investigate whether a military aviation officer’s career is associated with adverse maternal or fetal health outcomes.

METHODS: We conducted a retrospective cohort study of female aviation and nonaviation officers in the Military Health System from October 2002 to December 2019. Exposure was identified as assignment of an aviation occupation code. Maternal and fetal health outcomes were identified by International Classification of Diseases codes from medical records. Regression analysis was used to estimate adjusted relative risks (aRR).

RESULTS: Included in the study were 25,929 active-duty female officers, with 46,323 recorded pregnancies and 32,853 recorded deliveries; 2131 pregnancies were diagnosed in aviation officers. Pregnant aviation officers had a decreased risk of composite adverse pregnancy outcomes [aRR 0.82 (0.73–0.92)], including gestational diabetes [aRR 0.69 (0.57–0.85)] and gestational hypertension [aRR 0.84 (0.71–0.99)]. Pregnant aviation officers had a decreased risk of depression prior to delivery [aRR 0.43 (0.35–0.53)] and hyperemesis gravidarum [aRR 0.74 (0.57–0.96)], but an increased risk of placental complications [aRR 1.15 (1.02–1.30)] and fetal growth restriction [aRR 1.36 (1.16–1.60)].

DISCUSSION: Pregnant military aviation officers have an increased risk of placental complications and fetal growth restriction in spite of a lower risk of gestational diabetes and gestational hypertension. Further research is needed to determine how flight-related occupations impact pregnancy.

Stark CM, Sorensen IS, Royall M, Dorr M, Brown J, Dobson N, Salzman S, Susi A, Hisle-Gorman E, Huggins BH, Nylund CM. Maternal and fetal health risks among female military aviation officers. Aerosp Med Hum Perform. 2024; 95(9):675–682.
Upper- vs. Whole-Body Cooling During Exercise with Thermal Protective Clothing in the Heat
Authors: Mansouri Fatemeh , Nia Morteza Talebian , Villar Rodrigo , Cornish Stephen M. , Giesbrecht Gordon Grant
Published: August 2024

INTRODUCTION: Firefighters operating in hot environments face challenges from protective garments that restrict heat dissipation, resulting in increased core temperature, thermal discomfort, and performance decline. Cooling vests represent a viable solution. The study aim was to compare effectiveness of the same amount of cooling power to the upper body (UB) or whole body (WB) in alleviating thermoregulatory and physiological stress, enhancing cognitive function, and reducing ratings of thermal discomfort and exertion, during 60 min of exercise in a hot environment (40°C, 40% relative humidity) while wearing firefighter turnout gear.

METHODS: Eight healthy individuals (27.5 ± 3 y) participated in three conditions with either no cooling (Control) or active cooling with a liquid perfused shirt (UB cooling), or with a liquid perfused shirt and pants (WB cooling). In each trial, subjects performed three sets of 15 min of stepping (20 steps ⋅ min−1) and 5 min of rest.

RESULTS: Both cooling strategies were beneficial compared to having no cooling at all. Subjects could only complete two exercise bouts during Control, but they completed all three bouts with active cooling. WB cooling provided an advantage over UB cooling for core and skin temperature, and thermal comfort and sensation. The advantage in minimizing the increase in core temperature was only evident during the third exercise bout.

DISCUSSION: Active cooling is advantageous under these conditions. WB cooling provided some benefits vs UB cooling during heavy intensity exercise; however, it is uncertain whether these benefits would be observed during light-to-moderate exercise, which more likely reflects an actual firefighting scenario.

Mansouri F, Talebian Nia M, Villar R, Cornish SM, Giesbrecht GG. Upper- vs. whole-body cooling during exercise with thermal protective clothing in the heat. Aerosp Med Hum Perform. 2024; 95(9):659–666.
Human Evolution, Microgravity, and Challenges Colonizing Mars
Authors: Mermel Leonard
Published: August 2024

INTRODUCTION: Human colonization of Mars has captured the imagination of many. However, the challenges posed are immense. In microgravity, changes in human physiology, immune dysregulation, alterations of our microbiome, and enhanced virulence of various microbes are some of the barriers that stand in the way of a successful endeavor. Countermeasures can be brought to bear, but it remains unclear if success of such a mission in the foreseeable future is realistic or fanciful.

Mermel L. Human evolution, microgravity, and challenges colonizing Mars. Aerosp Med Hum Perform. 2024; 95(9):720–721.
The First Use of a Defibrillator on a U.S. Commercial Airline
Authors: McKenas David K.
Published: August 2024

Use of onboard commercial airline defibrillators began in 1997. At first, it was met with resistance but is now present on all planes. The first in-flight resuscitation of a passenger occurred in 1998 and is described here.
Implementation of Differentiated Learning Styles to Improve Analysis of Poetry Elements For Class X Students of SMA Negeri 22 Surabaya
Authors: Abdur Rahman Haidar  , Fransisca Dwi Harjanti  , Siti Umiati
Published: August 2024

The aim of this research is to observe the development of students' learning outcomes in dealing with poetry material by applying differentiated learning strategies and identifying students' learning styles and seeing how differential learning strategies, especially product differentiation, influence the mastery of students in class X.1 SMA Negeri 22 Surabaya to poetry material. The research was conducted using a qualitative descriptive approach. Data is collected through observation, document analysis, and assessment of students' work. The research results show that students display 3 types of learning styles: visual, auditory, and kinesthetic. The differential learning strategy applied is product differentiation, which allows students to express their understanding of poetry through different works. The implementation of this learning succeeded in achieving mastery above the minimum passing score (KKM) of 75, with a score range of 75-100. Assessment of student attitudes from the Pancasila Student Profile also provides scores in the same range. The implication of this research is that the use of differential learning strategies, especially product differentiation, can be an effective approach in teaching poetry material in high school. Identifying students' learning styles is also important in designing learning that suits their needs. In this way, teachers are able to pay more attention to the diversity of students in the learning process, increase their mastery of the material, and strengthen the expected attitude values, for example those reflected in the Pancasila profile.
Implementing Real Options Valuation under Macroeconomic Risk and Normally Distributed Cash Flows
Authors: Instefjord Norvald , Kenç Turalay
Published: August 2024

The paper highlights the encountered problems in implementing real options under
more realistic assumptions such as business cycle risk and normally distributed cash
flows. The problems considered include (i) estimating empirical distribution of cash
flows from real option investments; (ii) investment decisions across business cycles,
and (iii) calculating the probability of investing with the above stated rich features.
To this end, we estimate operating cash flows of US corporate firms using a Markov
chain model under both geometric and arithmetic Brownian motions assumptions for
cash flows and develop a valuation model of real option with normally distributed
cash flows. Associated investment valuation models incorporating these estimates
reveal that critical cash flow levels significantly differ across models and regimes.
Sala de Aula Invertida na Pós-Graduação Stricto Sensu: identificando elementos através da prática de ensino do professor
Authors: SANTOS DE CASTRO JUNIOR NADSON , Da Luz as Silva Nogueira Maria , Rosinira Bezerra Cavalcante Maria
Published: August 2024

A Sala de Aula Invertida (SAI) vem ganhando destaque no contexto da educação brasileira, por promover a inserção das tecnologias digitais no ensino, com aulas dinâmicas e interativas. Em razão disso, esta pesquisa visa investigar “quais os indicadores de presença da SAI na pratica de ensino do professor da disciplina de Introdução à Pesquisa em Ensino de Ciências e Matemática?”. Para responder tal pergunta, objetivou-se identificar os indiciadores de presença da SAI na prática de ensino do professor da disciplina de Introdução à Pesquisa em Ensino de Ciências e Matemática. Como fonte de dados, utilizou-se a observação participante na disciplina, além de questionários aplicados para o professor e os estudantes da turma. Os dados foram interpretados à luz de categorias emergentes, constituídas através do confronto entre a experiência investigada e a literatura da área. Os resultados revelaram que a prática do professor converge para a utilização da SAI, uma vez que os elementos essenciais, como: a criação e disponibilização de videoaulas; a possibilidade do contato prévio com os materiais bibliográficos; a discussão em sala de aula e a avaliação do processo, estiveram presentes ao longo dos encontros e são primordiais na aplicação da SAI
A Saúde Mental e Pandemia: percepções dos docentes IF Sudeste MG - Campus Juiz de Fora
Authors: De Castro Apolinário Pedro Henrique , Reder de Carvalho Adriano
Published: August 2024

Este artigo é um recorte de uma pesquisa que buscou analisar os efeitos das mudanças no mundo do trabalho vivenciados nos últimos dois anos pelos docentes do Instituto Federal do Sudeste de Minas Gerais. Mudanças essas, fruto da Pandemia da Covid-19, que provocou o isolamento social e a ressignificação dos ambientes de trabalho, migrando a sala de aula para a tela de um computador. O objetivo desta pesquisa foi compreender como o ensino remoto emergencial (ERE) afetou a saúde mental dos docentes dessa instituição. Como instrumento de pesquisa foi utilizado um questionário semiestruturado composto por 17 questões respondidas via Google Forms. A amostra que compôs este estudo foram 15 docentes da educação básica do Instituto Federal do Sudeste de Minas Gerais - Campus Juiz de Fora. A escolha desse público se deu devido às mudanças vivenciadas por aqueles profissionais nos últimos anos juntamente com os problemas relacionados à saúde mental e ao adoecimento dos mesmos. Os dados obtidos na aplicação do questionário foram submetidos à análise de conteúdo de Bardin (2011). Os resultados obtidos demonstram como foi desafiador o período do ERE e seus impactos na saúde mental dos professores.
As influências e tendências sobre/para a formação inicial de professores no Brasil
Authors: Vissotto Caroline , Cerignoni Benites Larissa
Published: August 2024

Este estudo de abordagem qualitativa apresenta os resultados de uma revisão bibliográfica que investigou as concepções e tendências que têm orientado as políticas de formação docente no Brasil e seus impactos, principalmente no que diz respeito à formação inicial. Foram analisados 17 artigos selecionados a partir da plataforma Portal CAPES e Scielo, considerando o período de 2001 a 2021. Os principais achados destacam: (1) que as concepções para a formação de professores se atrelam a uma concepção de mundo e sociedade; (2) as tendências para a formação têm matrizes variadas e muitas vezes reaparecem no decurso histórico, agregando ou alterando características decorrentes de reestruturações sociais e do mundo do trabalho; (3) a maioria das tendências presentes no Brasil advém de referenciais internacionais e se constituíram num contexto marcado pela mundialização econômica; (4) a constituição histórica do campo teórico-epistemológico da formação docente brasileira expressa disputas e evidencia também a presença de perspectivas progressistas, preocupadas em apreender diferentes determinações que perpassam o processo educativo. Como considerações, infere-se que esses achados ampliam as possibilidades de compreensão do contexto e da própria formação docente para além de sua aparência imediata.
Formação da identidade e conhecimento docente: o que revelam os clássicos?
Authors: Alves Godinho Patricia , Pasqualli Roberta
Published: August 2024

Essa revisão crítica de literatura tem como objetivo apresentar uma visão acerca da constituição e de quais saberes são fundantes para a atividade docente a partir de estudos como os de Nóvoa (2002; 2013), Saviani (1996), Tardif (2011), Shulman (2005), Gauthier et al. (2006), Pimenta e Anastasiou (2002), Freire (2019) entre outros. É uma pesquisa de natureza básica com abordagem qualitativa, classificada como exploratória e descritiva com procedimento técnico bibliográfico realizado através de pesquisa bibliográfica em livros e artigos. Traz à luz a discussão de que, na complexidade da prática docente, uma simples e didática definição não constitui uma receita na qual os elementos e conhecimentos essenciais para cada habilidade apresentada estão dados e basta ao professor aplicá-los na prática.
Unveiling the state of the art: a systematic review and meta-analysis of paper-based microfluidic devices
Authors: García-Azuma Rodrigo , Werner Karen , Revilla-Monsalve Cristina , Trinidad Oscar , Altamirano-Bustamante Nelly F. , Altamirano-Bustamante Myriam M.
Published: August 2024

Introduction

This systematic review and meta-analysis present a comprehensive evaluation of paper-based microfluidic devices, focusing on their applications in immunoassays. These devices are emerging as innovative solutions to democratize access to diagnostic technologies, especially in resource-limited settings. Our review consolidates findings from diverse studies to outline advancements in paper-based microfluidic technology, including design intricacies and operational efficacy. Key advantages such as low cost, portability, and ease of use are highlighted.

Materials and Methods

The review categorizes literature based on the design and operational nuances of these diagnostic tools, exploring various methodologies, fabrication techniques, detection methods, and applications, particularly in protein science. The meta-analysis extends to the diverse applications of these technologies, providing a framework for classifying and stratifying their uses in diagnostics.

Results and discussion

Notable findings include a critical analysis of performance metrics, such as sensitivity and specificity. The review addresses challenges, including the need for further validation and optimization for broader clinical applications. A critical discussion on the validation processes, including cross-validation and rigorous control testing, is provided to ensure the robustness of microfluidic devices. This study offers novel insights into the computational strategies underpinning these technologies and serves as a comprehensive roadmap for future research, potentially broadening the impact across the protein science universe.
Mucin adhesion of serial cystic fibrosis airways Pseudomonas aeruginosa isolates
Authors: Herrmann Christian , Lingner Meike , Herrmann Susanne , Brockhausen Inka , Tümmler Burkhard
Published: August 2024

The chronic airway infections with Pseudomonas aeruginosa are the major co-morbidity in people with cystic fibrosis (CF). Within CF lungs, P. aeruginosa persists in the conducting airways together with human mucins as the most abundant structural component of its microenvironment. We investigated the adhesion of 41 serial CF airway P. aeruginosa isolates to airway mucin preparations from CF sputa. Mucins and bacteria were retrieved from five modulator-naïve patients with advanced CF lung disease. The P. aeruginosa isolates from CF airways and non-CF reference strains showed a strain-specific signature in their adhesion to ovine, porcine and bovine submaxillary mucins and CF airway mucins ranging from no or low to moderate and strong binding. Serial CF clonal isolates and colony morphotypes from the same sputum sample were as heterogeneous in their affinity to mucin as representatives of other clones thus making ‘mucin binding’ one of the most variable intraclonal phenotypic traits of P. aeruginosa known to date. Most P. aeruginosa CF airway isolates did not adhere more strongly to CF airway mucins than to plastic surfaces. The strong binders, however, exhibited a strain-specific affinity gradient to O-glycans, CF airway and mammalian submaxillary mucins.
Association between apolipoprotein C-III levels and coronary calcification detected by intravascular ultrasound in patients who underwent percutaneous coronary intervention
Authors: Fukase Tatsuya , Dohi Tomotaka , Nishio Ryota , Takeuchi Mitsuhiro , Takahashi Norihito , Chikata Yuichi , Endo Hirohisa , Doi Shinichiro , Nishiyama Hiroki , Okai Iwao , Iwata Hiroshi , Koga Seiji , Okazaki Shinya , Miyauchi Katsumi , Daida Hiroyuki , Minamino Tohru
Published: August 2024

There are few reports on the association between apolipoprotein C-III (ApoC-III) and coronary calcification using intravascular modalities. This study aimed to investigate the impacts of ApoC-III levels on coronary calcification using grayscale intravascular ultrasound (IVUS). Consecutive 263 culprit lesions for 202 patients who underwent percutaneous coronary intervention using grayscale IVUS were included in this study and divided into four groups based on quartile ApoC-III values. This study assessed plaque characteristics, including severe calcification (>180° arc) at the minimum lumen area site and presence of calcified nodules within the culprit lesion using grayscale IVUS, and evaluated whether ApoC-III levels were associated with coronary calcified plaques. The highest ApoC-III quartile [Quartile 4 (Q4)] had a higher proportion of complex lesions, calcified plaques, severe calcification, calcified nodules, plaque burden, and total atheroma volume than the lowest ApoC-III quartile [Quartile 1 (Q1)]. Additionally, multivariable logistic regression analysis showed that Q4 was significantly associated with severe calcification and calcified nodules, with Q1 as the reference (odds ratio [OR]: 2.70, 95% confidence intervals [CIs]: 1.04–7.00, p = 0.042; and OR: 3.72, 95% CIs 1.26–11.0, p = 0.017, respectively). Furthermore, ApoC-III level (1-mg/dl increase) was a strong significant predictor of severe calcification (OR: 1.07, 95% CIs: 1.00–1.15, p = 0.040) and calcified nodules (OR: 1.09, 95% CIs: 1.01–1.19, p = 0.034) according to the multivariable logistic regression analysis. This study is the first to verify that elevated ApoC-III levels are associated with the development of severe calcification and progression to calcified nodules as detected by grayscale IVUS.
Efficient use of binned data for imputing univariate time series data
Authors: Darji Jay , Biswas Nupur , Padul Vijay , Gill Jaya , Kesari Santosh , Ashili Shashaanka
Published: August 2024

Time series data are recorded in various sectors, resulting in a large amount of data. However, the continuity of these data is often interrupted, resulting in periods of missing data. Several algorithms are used to impute the missing data, and the performance of these methods is widely varied. Apart from the choice of algorithm, the effective imputation depends on the nature of missing and available data. We conducted extensive studies using different types of time series data, specifically heart rate data and power consumption data. We generated the missing data for different time spans and imputed using different algorithms with binned data of different sizes. The performance was evaluated using the root mean square error (RMSE) metric. We observed a reduction in RMSE when using binned data compared to the entire dataset, particularly in the case of the expectation–maximization (EM) algorithm. We found that RMSE was reduced when using binned data for 1-, 5-, and 15-min missing data, with greater reduction observed for 15-min missing data. We also observed the effect of data fluctuation. We conclude that the usefulness of binned data depends precisely on the span of missing data, sampling frequency of the data, and fluctuation within data. Depending on the inherent characteristics, quality, and quantity of the missing and available data, binned data can impute a wide variety of data, including biological heart rate data derived from the Internet of Things (IoT) device smartwatch and non-biological data such as household power consumption data.
A preliminary examination of gut microbiota and emotion regulation in 2- to 6-year-old children
Authors: Faulkner Paul , Costabile Adele , Imakulata Florencia , Pandey Neeraj , Hepsomali Piril
Published: August 2024

Background

It is well known that having maladaptive emotion regulation skills during childhood may predict mental health issues later in life, therefore, establishing links with gut microbiome could help develop gut-derived interventions directed at improving maladaptive emotion regulation skills during this critical developmental period. While differences in gut microbiome diversity and composition have been associated with several mental health problems in adults and in infants, the current study is the first one to examine whether the gut microbiome diversity and composition are related to emotional regulation abilities during early childhood.

Method

In the current cross-sectional study, mothers of seventy-three children aged 2–6 years completed several questionnaires assessing their child's and their own emotion regulation skills and mental health, provided a stool sample from their child (via at-home gut microbiome testing kits), and reported on their child's dietary intake.

Results

Results revealed that compared to children in the low maladaptive emotion regulation group, alpha diversity, relative abundance of butyrate-producing genera (Butyricicoccus and Odoribacter), and vitamin synthesis scores (Vitamins B2, B3, B6, and B9) were significantly lower in the high maladaptive emotion regulation group.

Discussion

These findings suggest that maladaptive emotion regulation skills link to gut microbiome alterations in early childhood, a crucial time of both brain and gut-immune development, hence, may open the way to the development of early novel (dietary or pre/probiotic) interventions.
Exploring senescence as a modifier of β cell extracellular vesicles in type 1 diabetes
Authors: Motlagh Roozbeh Akbari , Pipella Jasmine , Thompson Peter J.
Published: August 2024

Type 1 Diabetes (T1D) is a chronic metabolic disease resulting from insulin deficiency due to autoimmune loss of pancreatic β cells. In addition to β cell destruction, it is now accepted that β cell stress and dysfunction, such as senescence, plays a crucial role in the development of the disease. Accumulation of senescent β cells occurs during development of T1D in humans and contributes to the progression of T1D in the nonobese diabetic (NOD) mouse model. Senescent β cells are thought to exacerbate the inflammatory response within the islets by production and secretion of senescence-associated secretory phenotype (SASP). Extracellular vesicles (EVs) from β cells have been shown to carry protein and microRNAs (miRNAs), influencing cellular signaling and may contribute to the development of T1D but it remains to be addressed how senescence impacts β cell EV cargo. In this minireview, we discuss emerging evidence that EV cargo proteins and miRNAs associated with senescence could contribute to the development of T1D and could suggest potential biomarkers and therapeutic targets for the regulation of SASP and elimination of senescent β cells in T1D. Future investigation exploring the intricate relationship between β cell senescence, EVs and miRNAs could pave the way for the development of novel diagnostic techniques and therapeutic interventions.
Gut redox and microbiome: charting the roadmap to T-cell regulation
Authors: Prasad Sujata , Singh Shilpi , Menge Samuel , Mohapatra Iteeshree , Kim Stefan , Helland Logan , Singh Gatikrushna , Singh Amar
Published: August 2024

The gastrointestinal (GI) tract redox environment, influenced by commensal microbiota and bacterial-derived metabolites, is crucial in shaping T-cell responses. Specifically, metabolites from gut microbiota (GM) exhibit robust anti-inflammatory effects, fostering the differentiation and regulation of CD8+ tissue-resident memory (TRM) cells, mucosal-associated invariant T (MAIT) cells, and stabilizing gut-resident Treg cells. Nitric oxide (NO), a pivotal redox mediator, emerges as a central regulator of T-cell functions and gut inflammation. NO impacts the composition of the gut microbiome, driving the differentiation of pro-inflammatory Th17 cells and exacerbating intestinal inflammation, and supports Treg expansion, showcasing its dual role in immune homeostasis. This review delves into the complex interplay between GI redox balance and GM metabolites, elucidating their profound impact on T-cell regulation. Additionally, it comprehensively emphasizes the critical role of GI redox, particularly reactive oxygen species (ROS) and NO, in shaping T-cell phenotype and functions. These insights offer valuable perspectives on disease mechanisms and potential therapeutic strategies for conditions associated with oxidative stress. Understanding the complex cross-talk between GI redox, GM metabolites, and T-cell responses provides valuable insights into potential therapeutic avenues for immune-mediated diseases, underscoring the significance of maintaining GI redox balance for optimal immune health.
Exploring cell-derived extracellular vesicles in peripheral blood and bone marrow of B-cell acute lymphoblastic leukemia pediatric patients: proof-of-concept study
Authors: Magalhães-Gama Fábio , Malheiros Araújo Silvestrini Marina , Neves Juliana Costa Ferreira , Araújo Nilberto Dias , Alves-Hanna Fabíola Silva , Kerr Marlon Wendell Athaydes , Carvalho Maria Perpétuo Socorro Sampaio , Tarragô Andréa Monteiro , Soares Pontes Gemilson , Martins-Filho Olindo Assis , Malheiro Adriana , Teixeira-Carvalho Andréa , Costa Allyson Guimarães
Published: August 2024

Extracellular vesicles (EVs) are heterogeneous, phospholipid membrane enclosed particles that are secreted by healthy and cancerous cells. EVs are present in diverse biological fluids and have been associated with the severity of diseases, which indicates their potential as biomarkers for diagnosis, prognosis and as therapeutic targets. This study investigated the phenotypic characteristics of EVs derived from peripheral blood (PB) and bone marrow (BM) in pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) during different treatment stages. PB and BM plasma were collected from 20 B-ALL patients at three time points during induction therapy, referred to as: diagnosis baseline (D0), day 15 of induction therapy (D15) and the end of the induction therapy (D35). In addition, PB samples were collected from 10 healthy children at a single time point. The EVs were measured using CytoFLEX S flow cytometer. Calibration beads were employed to ensure accurate size analysis. The following, fluorescent-labeled specific cellular markers were used to label the EVs: Annexin V (phosphatidylserine), CD235a (erythrocyte), CD41a (platelet), CD51 (endothelial cell), CD45 (leukocyte), CD66b (neutrophil), CD14 (monocyte), CD3 (T lymphocyte), CD19, CD34 and CD10 (B lymphoblast/leukemic blast). Our results demonstrate that B-ALL patients had a marked production of EV-CD51/61+, EV-CD10+, EV-CD19+ and EV-CD10+CD19+ (double-positive) with a decrease in EV-CD41a+ on D0. However, the kinetics and signature of production during induction therapy revealed a clear decline in EV-CD10+ and EV-CD19+, with an increase of EV-CD41a+ on D35. Furthermore, B-ALL patients showed a complex biological network, exhibiting distinct profiles on D0 and D35. Interestingly, fold change and ROC curve analysis demonstrated that EV-CD10+CD19+ were associated with B-ALL patients, exhibited excellent clinical performance and standing out as a potential diagnostic biomarker. In conclusion, our data indicate that EVs represent a promising field of investigation in B-ALL, offering the possibility of identifying potential biomarkers and therapeutic targets.
Antisense targeting of FOXP3+ Tregs to boost anti-tumor immunity
Authors: Akimova Tatiana , Wang Liqing , Bartosh Zhanna , Christensen Lanette M. , Eruslanov Evgeniy , Singhal Sunil , Aishwarya Veenu , Hancock Wayne W.
Published: August 2024

Our goal is to improve the outcomes of cancer immunotherapy by targeting FOXP3+ T-regulatory (Treg) cells with a next generation of antisense oligonucleotides (ASO), termed FOXP3 AUMsilence ASO. We performed in vitro experiments with human healthy donor PBMC and clinical samples from patients with lung cancer, mesothelioma and melanoma, and tested our approach in vivo using ASO FOXP3 in syngeneic murine cancer models and in humanized mice. ASO FOXP3 had no effects on cell viability or cell division, did not affect expression of other FOXP members, but decreased expression of FOXP3 mRNA in PBMC by 54.9% and in cancer samples by 64.7%, with corresponding 41.0% (PBMC) and 60.0% (cancer) decreases of Treg numbers (all p<0.0001). Hence, intratumoral Treg were more sensitive to the effects of ASO FOXP3 than peripheral blood Tregs. Isolated human Treg, incubated with ASO FOXP3 for 3.5 hours, had significantly impaired suppressive function (66.4%) versus Scramble control. In murine studies, we observed a significant inhibition of tumor growth, while 13.6% (MC38) to 22% (TC1) of tumors were completely resorbed, in conjunction with ~50% decrease of Foxp3 mRNA by qPCR and decreased numbers of intratumoral Tregs. In addition, there were no changes in FOXP3 mRNA expression or in the numbers of Tregs in draining lymph nodes and in spleens of tumor bearing mice, confirming that intratumoral Treg had enhanced sensitivity to ASO FOXP3 in vivo compared to other Treg populations. ASO FOXP3 Treg targeting in vivo and in vitro was accompanied by significant downregulation of multiple exhaustion markers, and by increased expression of perforin and granzyme-B by intratumoral T cells. To conclude, we report that targeting the key Treg transcription factor FOXP3, with ASO FOXP3, has a powerful anti-tumoral effect and enhances T cell response in vitro and in vivo.
Functional evaluation of rare variants in complement factor I using a minigene assay
Authors: Donelson Cobey J. H. , Ghiringhelli Borsa Nicolo , Taylor Amanda O. , Smith Richard J. H. , Zhang Yuzhou
Published: August 2024

The regulatory serine protease, complement factor I (FI), in conjunction with one of its cofactors (FH, C4BP, MCP, or CR1), plays an essential role in controlling complement activity through inactivation of C3b and C4b. The functional impact by missense variants in the CFI gene, particularly those with minor allele frequencies of 0.01% to 0.1%, is infrequently studied. As such, these variants are typically classified as variants of uncertain significance (VUS) when they are identified by clinical testing. Herein, we utilized a minigene splicing assay to assess the functional impact of 36 ultra-rare variants of CFI. These variants were selected based on their minor allele frequencies (MAF) and their association with low-normal FI levels. Four variants lead to aberrant splicing–one 5’ consensus splice site (NM_000204.5: c.1429G>C, p.Asp477His) and three exonic changes (c.355G>A, p.Gly119Arg; c.472G>A, p.Gly158Arg; and c.950G>A, p.Arg317Gln)–enabling their reclassification to likely pathogenic (LP) or pathogenic (P) based on ACMG guidelines. These findings underscore the value of functional assays, such as the minigene assay, in assessing the clinical relevance of rare variants in CFI.
Evaluation of efficacy and safety of Lacticaseibacillus rhamnosus LRa05 in the eradication of Helicobacter pylori: a randomized, double-blind, placebo-controlled trial
Authors: Niu Yue , Li Jing , Qian Hongwei , Liang Chunli , Shi Xinyi , Bu Shurui
Published: August 2024

Aim

This study aims to evaluate the efficacy of Lacticaseibacillus rhamnosus LRa05 supplementation in enhancing Helicobacter pylori (H. pylori) eradication rate and alleviating the gastrointestinal side effects associated with bismuth quadruple therapy.

Methods

H. pylori-positive patients were randomized to receive levofloxacin-based bismuth quadruple therapy combined either probiotic LRa05 or a placebo for two weeks, followed by LRa05 (1 × 1010 CFU) or maltodextrin for the next two weeks. H. pylori infection was detected by 13C breath test pre- and post-treatment. Blood and stool samples were collected at week 0 and week 4 for routine and biochemical analysis, and serum inflammatory markers. Gastrointestinal symptoms were evaluated using the gastrointestinal symptom rating scale (GSRS). Intestinal microbiota was analyzed using 16S rRNA sequencing. The research was listed under the Chinese Clinical Trial Registry (ChiCTR2300072220), and written informed consent was obtained from all participants.

Results

The LRa05 group exhibited a trend toward higher H. pylori eradication rates (86.11%) compared to the placebo group (82.86%), though the difference was not statistically significant. Significant reductions in neutrophil count, alanine aminotransferase, aspartate aminotransferase, pepsinogen I, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) (p < 0.05) suggest that LRa05 supplementation may mitigate inflammation, enhance liver function, and potential aid in early cancer prevention. GSRS symptom scores showed that LRa05 alleviated abdominal pain, acid reflux, bloating, and diarrhea, enhancing patient compliance. Furthermore, 16S rRNA sequencing showed that LRa05 countered the antibiotic-induced disruption of gut microbiota diversity, primarily by increasing beneficial bacteria.

Conclusion

Although LRa05 did not significantly improve the success rate of H. pylori eradication therapy, it has the potential to improve liver function and reduced levels of inflammatory markers such as IL-6 and TNF-α in the body, regulating the inflammatory response. In addition, it played a positive role in alleviating the adverse symptoms and gut microbiota disturbances caused by eradication therapy, providing a possible way to improve the overall health of patients and demonstrating promising clinical potential.

Clinical Trial Registration

http://www.chictr.org.cn, identifier ChiCTR2300072220.
The role of alternatives in the cognitive processing of German demonstratives: insights from online and offline processing
Authors: Çokal Derya , von Heusinger Klaus
Published: August 2024

This study, employing eye-tracking reading and sentence completion experiments, explores the impact of competing antecedents on the German demonstratives der and dieser. It challenges prior assumptions, revealing that in competitive alternative antecedent contexts, processing dieser initially posed challenges, indicating sensitivity to alternatives. Dieser exhibited less processing difficulties than der, potentially influenced by a register effect. Consistent with previous findings, in the offline task, references to the non-prominent entity were similar for both demonstratives, but our online experiment shows functional differences in cognitive processes between the two in reading. Our results suggest that Thematic Role accounts better explain antecedent preferences for der and dieser than Centering Theory.
Reversal of cadmium-induced toxicity in Meretrix meretrix as determined by alleviation of oxidative damage following short-term depuration
Authors: Zhou Jian , Cai Huiqi , Zhong Yuning , Zheng Yu , Wu Yinuo , Chang Alan Kueichieh , Ying Xueping
Published: August 2024

Cadmium (Cd) is a toxic heavy metal that, when present as a pollutant in the marine environment, is readily accumulated by marine bivalves, causing oxidative stress and tissue damage. This study explored whether short-term depuration could reverse Cd2+-induced toxicity in the ovary of the clam Meretrix meretrix. Clams exposed to 3 mg·L-1 Cd2+ for three days showed increased accumulated Cd2+ in their ovaries with obvious tissue damage as shown by loose structure and some apoptotic cells compared with non-exposed clams. Increased oxidative stress in the ovarian tissue was also obvious, as revealed by increased levels of oxidative indicators such as reactive oxygen species (ROS), malondialdehyde (MDA), DNA-protein crosslinking (DPC), and protein carbonylation (PCO) and increased expression levels of genes related to oxidative stress and apoptosis, which included the Bax, Bcl-2, caspase-3, HO-1, Hsp70, NQO1, Nrf2, and MT genes. When the clams were exposed to Cd2+ for three more days, the accumulated Cd2+ level in the ovary increased to more than 10-fold the level in the control clams, accompanied by more severe damage and cell death as well as oxidative stress. However, when the initial three-day Cd2+ exposure was followed by three days of depuration in Cd2+-free seawater, the Cd2+ level in the ovary was reduced by as much as 20%, accompanied by some recovery of tissue damage and reduced oxidative stress, suggesting that short-term depuration may mitigate Cd2+-induced toxicity in M. meretrix, allowing the clams to recover and potentially reducing the risk of Cd2+ exposure from consuming contaminated clams.
Effect of by-product fusel oil-diesel blends fuel on emissions of single-cylinder CI engine
Authors: Awad Omar Ibraheem , Kamil Mohammed , Abed Adnan Ajam , Jamal Omar , Mohammed Omar Khalaf , Mohammed M. N. , Alobaid Ahmed , Suwaed Mahmood Sh. , Yusri I. M. , Hasan Mohammed M.
Published: August 2024

Alcohol-based fuels have gained more interest due to their production process and availability and environmental point of view so based alcohol-based fuel like fusel oil has been studied as an alternative fuel for compression ignition engine engines. The objective of this experimental study was to investigate the performance of a compression ignition engine based on a performance and emissions of cylinder single-cylinder diesel engine. To maintain the original fuel system of the engine, a fixed blending ratio of 20% v/v was used. The research findings indicated a decrease in nitrogen oxide (NO) emissions when using fusel oil–diesel (F20) compared to diesel. Still, higher fuel consumption was observed due to the lower energy content of fusel oil. However, F20 led to increased carbon monoxide (CO) emissions and hydrocarbons (HC) compared to diesel. The most significant reduction in NOx emissions by up to 20% occurred at an engine speed of 1,500 rpm and an engine load of 75%, possibly attributed to the higher water content in fusel oil. It is crucial to evaluate the trade-offs between these parameters carefully. Insight into these trade-offs may facilitate the optimization of fusel oil use as a prospective fuel alternative for internal combustion engines.
A conceptual framework on determinants of the integrated tuberculosis control model implementation in China
Authors: Chen Xi , Zhou Jiani , Yuan Quan , Huang Chunji , Li Ying
Published: August 2024

Improving the provision of tuberculosis (TB) care is both urgent and imperative to achieve the goals outlined in the End TB Strategy. China has initiated the integrated TB control model to enhance the quality of TB care Since 2012. Despite these efforts, the integrated TB control health system encounters numerous challenges in delivering effective TB care. The factors influencing TB care provision are intricate, and a conceptual framework to comprehend these potential determinants is currently lacking. To bridge this gap, this article proposed a conceptual framework that was developed through insights from the fields of both public management and health services, adjustment of PRISM model and elements, reference to the blocks of health system and reference to the framework of outcome indicators in implementation research. This conceptual framework included 4 modules which can be coherently and logically deduced, offered a multi-perspective understanding of the determinants to TB care, and hypothesized that the TB control services provided by the integrated TB control model is a public service and must be “patient-centered”; determinants of the integrated TB control model implementation can be divided into seven domains; the evaluation of the integrated TB control model implementation covers implementation outcomes and service outcomes. This framework offers the potential to guide empirical investigations, aiding in the understanding and identification of determinants, including barriers and facilitators, associated with the implementation of the integrated TB control health model. Furthermore, it serves as a valuable tool for developing interventions that address system-level barriers, drawing insights from the realms of public management and health services.
Three feminizing Wolbachia strains in a single host species: comparative genomics paves the way for identifying sex reversal factors
Authors: Grève Pierre , Moumen Bouziane , Bouchon Didier
Published: August 2024

Introduction

Endosymbiotic bacteria in the genus Wolbachia have evolved numerous strategies for manipulating host reproduction in order to promote their own transmission. This includes the feminization of males into functional females, a well-studied phenotype in the isopod Armadillidium vulgare. Despite an early description of this phenotype in isopods and the development of an evolutionary model of host sex determination in the presence of Wolbachia, the underlying genetic mechanisms remain elusive.

Methods

Here we present the first complete genomes of the three feminizing Wolbachia (wVulC, wVulP, and wVulM) known to date in A. vulgare. These genomes, belonging to Wolbachia B supergroup, contain a large number of mobile elements such as WO prophages with eukaryotic association modules. Taking advantage of these data and those of another Wolbachia-derived feminizing factor integrated into the host genome (f element), we used a comparative genomics approach to identify putative feminizing factors.

Results

This strategy has enabled us to identify three prophage-associated genes secreted by the Type IV Secretion System: one ankyrin repeat domain-containing protein, one helix-turn-helix transcriptional regulator and one hypothetical protein. In addition, a latrotoxin-related protein, associated with phage relic genes, was shared by all three genomes and the f element.

Conclusion

These putative feminization-inducing proteins shared canonical interaction features with eukaryotic proteins. These results pave the way for further research into the underlying functional interactions.
Effect of Gegen Qinlian Decoction on the regulation of gut microbiota and metabolites in type II diabetic rats
Authors: Xu Jinyao , Zou Zhenkai , Li Xuanyi , Sun Xiangjun , Wang Xufeng , Qin Feng , Abulizi Abulikemu , Chen Qian , Pan Zhigang , Shen Hexiao , Lv Yongling , Yan Ruicheng
Published: August 2024

Gegen Qinlian Decoction (GGQLT) is a traditional Chinese herbal medicine that has been reported to have a significant therapeutic effect in the management of type II diabetes mellitus (T2DM). In this study, we constructed a T2DM rat model by feeding a high-fat diet and injecting streptozotocin (STZ) and tested the effects of feeding GGQLT and fecal transplantation on the physiological indices, microbiota, and metabolism of rats. The results showed that the administration of GGQLT can significantly improve the growth performance of rats and has a remarkable antihyperlipidemic effect. In addition, GGQLT altered the composition of gut microbiota by increasing beneficial bacteria such as Coprococcus, Bifidobacterium, Blautia, and Akkermansia. In addition, GGQLT elevated levels of specific bile acids by metabolomic analysis, potentially contributing to improvements in lipid metabolism. These findings suggest that GGQLT may have beneficial effects on T2DM by influencing lipid metabolism and gut microbiota. However, further studies are needed to elucidate its mechanisms and assess clinical applications.
A report card assessment of the prevalence of healthy eating among preschool-aged children: a cross-cultural study across Australia, Hong Kong, Singapore, and the US
Authors: Wan Alison Wing Lam , Chung Kevin Kien Hoa , Li Jian-Bin , Xu Shebe Siwei , Chan Derwin King Chung
Published: August 2024

Objective

This study aimed to initially adopt an International Healthy Eating Report Card for Preschool-Aged Children to assess the prevalence of healthy eating behaviours and favourable family home food environments (FHFEs) among preschool-aged children in Australia, Hong Kong, Singapore, and the US. We also examined which cultural contexts would exhibit significant differences in the report card scores among the four cultural contexts.

Methods

In this cross-cultural study, 2059 parent–child dyads, with approximately 500 dyads in each cultural context, were recruited. The parents were asked to complete the validated International Healthy Eating Report Card Scale to assess the dimensions of the Report Card [i.e., Indicator of Children’s Eating Behaviours: (1) Children’s Dietary Patterns and (2) Children’s Mealtime Behaviours, and Indicator of FHFEs: (3) Parental Food Choices and Preparation, (4) Home Healthier Food Availability and Accessibility and (5) Family Mealtime Environments]. Each indicator received a letter grade [i.e., A (≥80%) = excellent, B (60–79%) = good, C (40–59%) = fair, D (20–39%) = poor, F (<20%) = very poor and including the plus (+) and minus (−) signs] to represent the proportion of participants who could meet the predefined benchmarks. We also employed ANCOVA and Bonferroni’s post-hoc test to examine the differences in the report card scores between the four cultural contexts. A significance level was set at p < 0.05.

Results

The average overall report card grade across the four cultural contexts was “B−” (Good), ranging from “C+” (Singapore and the US) to “B−” (Australia and Hong Kong). The average grade for Children’s Eating Behaviours was classified as Fair (“C−”), while the average grade for FHFEs was classified as Good (“B+”) for all cultural contexts. A comparison of the overall report card scores revealed that Australia exhibited a significantly higher report card score than Singapore and the US, while Hong Kong achieved a significantly higher score than Singapore.

Conclusion

The International Healthy Eating Report Card provided an overview of the prevalence of healthy eating in different cultural contexts. We believe that the International Healthy Eating Report Card may offer new perspectives on interventions for fostering healthy eating in young children.