bluuebunny/crossref_metadata_2025 huggingface dataset:
Los impresores bruselenses y su producción dirigida al mercado hispano, siglos XVI-XVII. El caso de la imprenta del Águila de Oro de Rutger Velpius, Hubert Anthoine-Velpius y la imprenta de los Mommaert.
Authors: Manrique Figueroa César
Published: April 2024

En contraste con los múltiples estudios sobre la tipografía amberina del siglo XVI y de sus relaciones con el mundo hispánico, poco se sabe de los impresores bruselenses de cuyas prensas salieron obras en español de gran difusión desde el último cuarto del siglo XVI y sobre todo durante el si­glo XVII. Por ejemplo, la primera edición del Quijote impresa fuera de la Península Ibérica, vio la luz en Bruselas en 1607 en la imprenta de Rutger Velpius apenas dos años después de la aparición de la primera edición. De ahí que el objetivo primordial de este trabajo sea proporcionar una visión detallada de la trayectoria de las familias Velpius, Anthoine-Velpius y Mommaert, quienes pusieron a Bruselas en el mapa de las ciudades europeas de cuyos talleres sa­lieron obras impresas en español de corte político, militar, literario, histórico y lexi­cográfico y cuyos libros aún se conservan en múltiples bibliotecas a lo largo y ancho de Europa y el continente americano.
La gestión del hambre. Discurso y praxis política de la falange en la huelva de la posguerra (1939-1945)
Authors: González Orta Juan Ignacio
Published: April 2024

El presente artículo pretende un acerca­miento, desde la provincia de Huelva, a los llamados “años del hambre” y sus diferen­tes manifestaciones, pero, sobre todo, in­tenta calibrar el papel que ocupó la Falange dentro de esa realidad. Así, trataremos de reflexionar sobre los puntos de desencuen­tro existentes entre el revolucionario men­saje de justicia social que pregonaba FET y de las JONS y los continuos casos de cor­rupción o acaparamiento que salpicaron a una buena parte de los jerarcas provinciales y locales; una realidad que contrastaba con la rotunda miseria de una muchedumbre hambrienta.
New stage of professional cooperation between ukrainian and german universities
Authors:   Lviv Polytechnic National University, Thevoho I. , ZADOROZHNYY V. ,   Lviv Polytechnic National University, SAVCHUK N ,   Lviv Polytechnic National University
Published: April 2024

The new steps of the longstanding cooperation between the Institute of Geodesy of Lviv Polytechnic and the Faculty of Landscape Architecture, Geomatics, and Geodesy of the University of Applied Sciences (Neubrandenburg, Germany) have been considered. In particular, the results of educational and scientific practice and the peculiarities of studying under the double degree program of Ukrainian students in Neubrandenburg in September 2023 are analyzed.
Transformation of certification requirements for surveyors and land managers
Authors:   Department of geodesy, Dnipro University of Technology, ave. Dmytro Yavornytskoho, RIABCHII V. , RIABCHII V. ,   Department of geodesy, Dnipro University of Technology, ave. Dmytro Yavornytskoho, YANKIN O. ,   Department of geodesy, Dnipro University of Technology, ave. Dmytro Yavornytskoho, HOICHUK A. ,   Department of geodesy, Dnipro University of Technology, ave. Dmytro Yavornytskoho
Published: April 2024

In this article, the authors highlight the latest changes in the requirements for the certification of surveying engineers and land surveying engineers, as well as in the upgrading of the qualifications of already certified surveying engineers and land surveying engineers, which took place in 2023, compared to the previous requirements for the certification and upgrading of the qualifications of engineers – surveyors and land surveying engineers who have been operating until now
Development of GNSS measurement models with the use of base stations and radio modules
Authors:   Latvia University of Life Sciences and Technologies, CELMS A. , TREVOHO I. ,   Lviv Polytechnic National University, KOLODIY P. ,   Lviv National Environmental University, RATKEVICS A. ,   Latvia University of Life Sciences and Technologies, LIDUMNIEKS T. ,   Latvia University of Life Sciences and Technologies, BRINKMANIS-BRIMANIS M. ,   Latvia University of Life Sciences and Technologies
Published: April 2024

Global navigation satellite systems (GNSS) historically been known as one of the newest technologies since the 1970s. GNSS originally developed for military purposes in the USA (GPS – Global Position System). There are several satellite systems in the world. Satelites, International Research Base Stations, regional/national and local base stations form a permanent geodetic frame. Research on the size and shape of the Earth-planet, climate, sea, urban planning. In geodesy, a network of global positioning base stations makes it possible to asses the movements of continents, land plates at international level. GNSS is an important technology in navigation, logistics, economics, land surveying and other “geo” sectors. GNSS equipment/receivers and their manufacturers are applying new designs and electronics. Initially GNSS instruments used with single frequency signal reception, later expanding the number of GNSS signal channels to two frequencies. Such technological improvements nowadays improve the certainty, reliability and accuracy – the overall quality – of GNSS measurements. The GNSS base station enables the surveyors, other user’s GNSS receiver to determine coordinates with an accuracy of two centimeters in real time (RTK) and with an accuracy of five millimetres using the accumulated post-processing data. Various types of factors hamper GNSS measurements. The GNSS signal (radio wave) travels in airspace, in urban environments and is a physical parameter. Any obstacle – tree, building walls, and atmospheric effect – makes GNSS measurements less accurate. The GNSS signal must be strong and free from attenuation and suppression effects. This study develops GNSS models that show the comparison, certainty and reliability of GNSS measurements using different types of GNSS techniques. Evaluation of Latvian Global Positioning Reference Station Network – LatPos system measurements against a corresponding RTK solution method using Latvian Global Positioning Network geodetic point (G2 class).
Nanozyme-based sensing of dopamine using cobalt-doped hydroxyapatite nanocomposite from waste bones
Authors: Nishan Umar , Jabeen Nighat , Badshah Amir , Muhammad Nawshad , Shah Mohibullah , Ullah Irfan , Afridi Saifullah , Iqbal Jibran , Asad Muhammad , Ullah Riaz , Ali Essam A. , Ahmed Sarfraz , Ojha Suvash Chandra
Published: April 2024

Dopamine is one of the most important neurotransmitters and plays a crucial role in various neurological, renal, and cardiovascular systems. However, the abnormal levels of dopamine mainly point to Parkinson’s, Alzheimer’s, cardiovascular diseases, etc. Hydroxyapatite (HAp), owing to its catalytic nature, nanoporous structure, easy synthesis, and biocompatibility, is a promising matrix material. These characteristics make HAp a material of choice for doping metals such as cobalt. The synthesized cobalt-doped hydroxyapatite (Co-HAp) was used as a colorimetric sensing platform for dopamine. The successful synthesis of the platform was confirmed by characterization with FTIR, SEM, EDX, XRD, TGA, etc. The platform demonstrated intrinsic peroxidase-like activity in the presence of H2O2, resulting in the oxidation of 3,3′,5,5′-tetramethylbenzidine (TMB). The proposed sensor detected dopamine in a linear range of 0.9–35 μM, a limit of detection of 0.51 µM, limit of quantification of 1.7 µM, and an R2 of 0.993. The optimization of the proposed sensor was done with different parameters, such as the amount of mimic enzyme, H2O2, pH, TMB concentration, and time. The proposed sensor showed the best response at 5 mg of the mimic enzyme, pH 5, 12 mM TMB, and 8 mM H2O2, with a short response time of only 2 min. The fabricated platform was successfully applied to detect dopamine in physiological solutions.
Design and application of a point-of-care testing system for triple detection of SARS-CoV-2, influenza A, and influenza B
Authors: Yang Huan , Zhang Xiaoming , Li Yating , Deng Jing , Liu Zhongming , Chen Qiyue , Zhang Haiyan
Published: April 2024

To mitigate the continued impact of SARS-CoV-2, influenza A, and influenza B viruses on human health, a smartphone-based point-of-care testing (POCT) system was designed to detect respiratory pathogens through a nucleic acid test. This compact, light-weight, highly automated, and universal system enables the differential diagnosis of SARS-CoV-2, influenza A, and influenza B in approximately 30 min in a single-tube reaction. Numerous hospitals and disease control and prevention center assessed the triple POCT system’s detection threshold, sensitivity, specificity, and stability, and have concluded that all the assessments were comparable to those of fluorescent quantitative polymerase chain reaction (PCR)-based testing. The triple POCT system is suitable as an onsite rapid-diagnosis device, as well as for pathogen screening at airports and customs.
Forskolin induces FXR expression and enhances maturation of iPSC-derived hepatocyte-like cells
Authors: Loerch Christiane , Szepanowski Leon-Phillip , Reiss Julian , Adjaye James , Graffmann Nina
Published: April 2024

The generation of iPSC-derived hepatocyte-like cells (HLCs) is a powerful tool for studying liver diseases, their therapy as well as drug development. iPSC-derived disease models benefit from their diverse origin of patients, enabling the study of disease-associated mutations and, when considering more than one iPSC line to reflect a more diverse genetic background compared to immortalized cell lines. Unfortunately, the use of iPSC-derived HLCs is limited due to their lack of maturity and a rather fetal phenotype. Commercial kits and complicated 3D-protocols are cost- and time-intensive and hardly useable for smaller working groups. In this study, we optimized our previously published protocol by fine-tuning the initial cell number, exchanging antibiotics and basal medium composition and introducing the small molecule forskolin during the HLC maturation step. We thereby contribute to the liver research field by providing a simple, cost- and time-effective 2D differentiation protocol. We generate functional HLCs with significantly increased HLC hallmark gene (ALB, HNF4α, and CYP3A4) and protein (ALB) expression, as well as significantly elevated inducible CYP3A4 activity.
The integrated microfluidic photocatalytic planar reactor under continuous operation
Authors: Ge Xue-hui , Wei Nanjie , Hu Xinyue , Xie Qinyin , Wang Xiaoda , Li Ling , Qiu Ting
Published: April 2024

An integrated microfluidic planar reactor is essential for achieving efficient and enhanced photocatalytic water treatment. Optimization of catalysts is an area of intense study owing to the need to enhance the performances of microreactors. A high-efficiency photocatalytic microreactor is presented here by combining a planar microreactor with a high-efficiency photocatalyst. TiO2 nanoparticles doped with Y and Yb were prepared to improve the photocatalytic reaction efficiency. First, better performance is achieved with the Y, Yb/TiO2 and TiO2 microreactors than conventional bulk reactors because of good photodegradation and a high reaction rate. Then, the Y, Yb/TiO2 film microreactor exhibits not only efficient catalytic activity with UV light but also higher photocatalytic activity under visible light irradiation than that achieved by a TiO2 film microreactor. The reaction rate constant of the Y, Yb/TiO2 film microreactor is approximately 0.530 s–1, which is twice that of the TiO2 film microreactor. Moreover, the performances under continuous and intermittent reactions are compared to evaluate the stability of the microreactor, thereby building the foundation for practical application of continuous water treatment in the microreactor.The planar microreactor provides a convenient platform for studying photodegradation under various conditions, such as different temperatures, flow rates, light irradiation (UV and Vis), and reaction modes (continuous and intermittent).
Development of rapid nucleic acid testing techniques for common respiratory infectious diseases in the Chinese population
Authors: Zhi Shenshen , Wu Wenyan , Ding Yan , Zhang Yuanyuan , Pan Liyan , Liu Guo , Li Wei
Published: April 2024

Background: Most respiratory viruses can cause serious lower respiratory diseases at any age. Therefore, timely and accurate identification of respiratory viruses has become even more important. This study focused on the development of rapid nucleic acid testing techniques for common respiratory infectious diseases in the Chinese population.

Methods: Multiplex fluorescent quantitative polymerase chain reaction (PCR) assays were developed and validated for the detection of respiratory pathogens including the novel coronavirus (SARS-CoV-2), influenza A virus (FluA), parainfluenza virus (PIV), and respiratory syncytial virus (RSV).

Results: The assays demonstrated high specificity and sensitivity, allowing for the simultaneous detection of multiple pathogens in a single reaction. These techniques offer a rapid and reliable method for screening, diagnosis, and monitoring of respiratory pathogens.

Conclusion: The implementation of these techniques might contribute to effective control and prevention measures, leading to improved patient care and public health outcomes in China. Further research and validation are needed to optimize and expand the application of these techniques to a wider range of respiratory pathogens and to enhance their utility in clinical and public health settings.
Effectiveness of climate information services: an evaluation of the accuracy and socio-economic benefits for smallholder farmers in Niger and Mali
Authors: Bizo Issiaka M. , Traore Bouba , Sidibé Amadou , Soulé Moussa
Published: April 2024

Climate information services are foundational means of building the farmer’s resilience. However, studies are scarce about the accuracy of climate information services in dryland regions such as the West Africa Sahel, like in Mali and Niger. Thus, this study examined the accuracy of climate forecasts and their socio-economic benefits in these two countries. For rainfall forecasts and alerts, we collected the 2022 data from the ‘SMS Sandji’ platform in Mali (Nara) and the national meteorological agency alert database in Niger (Zinder). The socio-economic benefits of climate information were determined using a sample of 900 individuals in Niger and 227 in Mali. The results indicate that both seasonal and daily climate forecasts have high to moderate accuracy from 0.7 to 0.58 for CSI and 0.11 to 0.43 for BS index in Niger, and 0.94 to 0.91 for CSI, and 0.06 to 0.25 for BS in Mali. The results of field survey show that, in general, 87 to 100% of the respondents in Niger and 100% in Mali received the seasonal forecasts. ANOVA also reveals with high significance (p value = 0.0001) that the utilization of climate information plays a crucial role in improving farmers’ average financial incomes with FCFA 24,943 per hectare at season onset to FCFA 15,355 per hectare during the cropping season, and FCFA 6204 per hectare at the end of the season, and time-saving of 36 h per hectare to 8 h per hectare, depending on the period when the information was used. Globally, this work underscores the importance of climate information services and highlights their positive socio-economic impacts to the livelihood of farmers.
Public perception of media social responsibility in developing countries: a case study of Albania
Authors: Skana Pranvera , Gjerazi Blerina
Published: April 2024

This study delves into public perceptions of media social responsibility within the contemporary Albanian media landscape. Through a comprehensive analysis of various factors, the study identifies the prevailing principles that the public deems crucial for the media’s social responsibility and how these principles can enhance the media’s contribution to society. A structured questionnaire was used to capture a wide range of public perceptions, with 1,321 questionnaires filled out. These questionnaires were distributed using a face-to-face method across five major urban centers in Albania, ensuring a comprehensive and representative sample of public viewpoints. The distribution method employed a stratified sampling approach to ensure diverse representation across different demographic groups. Additionally, employing a mixed-methods approach, the research includes qualitative interviews with 20 influential stakeholders, including media directors, professors, analysts, and media researchers. Purposive sampling was utilized to select stakeholders representing various sectors of the media landscape. Rigorous measures were taken to mitigate data pollution, including thorough interviewer training and constant monitoring of data quality. An overarching thematic analysis was conducted to identify common themes and patterns across the qualitative interviews, complementing the quantitative findings. To gain further insights, we purposefully selected and conducted a focus group with 28 journalists from various media platforms. The sampling method for the focus group involved purposive sampling to ensure representation from diverse media backgrounds and experiences. Data collected from the focus group underwent thematic analysis to identify common themes and patterns, contributing to an overarching qualitative analysis. This mixed-methods approach facilitated a comprehensive understanding of journalists’ perspectives on social responsibility and the challenges they encounter in fulfilling it. The empirical findings reveal that the media’s social responsibility in Albania does not fully adhere to the expected standards encompassing all relevant principles. Internal dynamics within media organizations and external forces from politics, economics, and society collectively influence this shortfall. The study highlights the importance of considering public perceptions and expectations in shaping media’s social responsibility, emphasizing the need for substantial improvements.
Multimodal input in the foreign language classroom: the use of hand gesture to teach morphology in L2 Spanish
Authors: Feijoo Sara , Anglada Mariona
Published: April 2024

Many studies describe the benefits of morphological awareness in reading comprehension in both first and second languages. In turn, several studies demonstrate the positive impact of multimodal input while learning. In this study, we looked for a relationship between multimodal input, gesture in particular, and the development of morphological awareness in L2 Spanish. An experiment was carried out with 38 students of L2 Spanish, aged between 14 and 16, from a secondary school in the UK. The experiment consisted of a pretest and a posttest of morphological awareness mediating three sessions of training. During the training sessions, the participants were divided into 4 groups with different input modalities: audiovisual, audiovisual with text enhancement, audiovisual-gestural and control. Participants worked on a series of words with a morphemic component through the visualization of videos. The experiment provided significant results in terms of learning from pre- to post-test in one of the groups, the audiovisual-gestural group. Hence, we conclude that, in the short term, this type of training might have a positive impact on the development of morphological awareness.
A new psychometrically validated questionnaire for assessing teacher agency in eight dimensions across pre-service and in-service teachers
Authors: Leijen Äli , Pedaste Margus , Baucal Aleksandar
Published: April 2024

Teacher agency is an increasingly important area of research across different learning and professional development settings. In our study, we followed the ecological model of teacher agency and developed a questionnaire that allows us to differentiate eight dimensions of teacher agency. Confirmatory factor analysis showed an acceptable fit of the eight-factor model in two different domains where teachers often make decisions: planning of teaching and learning activities and using information and communication technologies in teaching. Comparisons of configural, metric, and scalar models revealed good metric invariance across pre-service and in-service teachers in both agency domains. However, scalar invariance was not supported. Therefore, the new questionnaire seems suitable and sensitive for assessing teacher agency in these groups separately, but comparisons of the groups should not be made.
Factors associated with anxiety about handling contaminated patients during a nuclear disaster among disaster medical assistant teams in Japan: a cross-sectional study
Authors: Shibata Hisami , Yamaguchi Takumi , Yamada Yumiko , Shinkawa Tetsuko , Urata Hideko , Matsunari Yuko
Published: April 2024

Introduction

Japanese Disaster Medical Assistance Teams (DMATs) are pivotal in disaster response, especially during nuclear crises. The objective of this study was to identify factors associated with anxiety among Japanese DMAT personnel when handling contaminated patients during nuclear disasters.

Materials and methods

In this cross-sectional study, 609 Japanese DMAT members from Kyushu and Okinawa, Japan, were surveyed. Multivariate binomial logistic regression was used to determine anxiety predictors.

Results

Of the 276 respondents, 77.2% expressed anxiety about managing contaminated patients. Women and younger team members expressed the highest level of anxiety associated with handling contaminated patients during nuclear disasters.

Conclusion

This study revealed heightened anxiety among female and younger Japanese DMAT personnel regarding the handling of contaminated patients during nuclear disasters. Targeted training addressing these concerns is essential for effective disaster response.
An improved two-beat deadbeat synchronous predictive current control strategy for MMC based on Newton interpolation method
Authors: Cheng Yuan , Zhang Hui , Xing Jing , Xiao Zihan
Published: April 2024

Modular Multilevel Converter (MMC) is widely used in applications such as High Voltage Direct Current (HVDC) transmission, AC/DC power conversion centers, and large-scale power quality management in electrical grids due to its highly modular structure, strong redundancy and low harmonic content in AC output. The application of the traditional deadbeat predictive current control to MMC enhances the fast tracking ability of the output current, but it still has the problems of low output current accuracy and high dependence on bridge arm inductor. Based on this, this paper proposes an improved two-beat deadbeat synchronous predictive current control based on Newton interpolation method. By improving the two-beat deadbeat synchronous predictive current control strategy, the accuracy of the output current can be further improved and its fast tracking ability can be enhanced. Newton interpolation is introduced to improve the accuracy of the output current while reducing the dependence on the bridge arm inductor. The results show that the control strategy proposed in this paper reduces the output current THD by 2.88% compared with the two-beat deadbeat predictive current control, thus improving the accuracy; the bridge arm inductor value is reduced by 1.28%, thus reducing the dependence; and under the transient environment, the output current can be tracked to its predicted reference value 843 μs in advance, which enhances the fast tracking capability.
Identification of immune-related biomarkers for glaucoma using gene expression profiling
Authors: Wang Dangdang , Pu Yanyu , Tan Sisi , Wang Xiaochen , Zeng Lihong , Lei Junqin , Gao Xi , Li Hong
Published: April 2024

Introduction: Glaucoma, a principal cause of irreversible vision loss, is characterized by intricate optic neuropathy involving significant immune mechanisms. This study seeks to elucidate the molecular and immune complexities of glaucoma, aiming to improve our understanding of its pathogenesis.

Methods: Gene expression profiles from glaucoma patients were analyzed to identify immune-related differentially expressed genes (DEGs). Techniques used were weighted gene co-expression network analysis (WGCNA) for network building, machine learning algorithms for biomarker identification, establishment of subclusters related to immune reactions, and single-sample gene set enrichment analysis (ssGSEA) to explore hub genes’ relationships with immune cell infiltration and immune pathway activation. Validation was performed using an NMDA-induced excitotoxicity model and RT-qPCR for hub gene expression measurement.

Results: The study identified 409 DEGs differentiating healthy individuals from glaucoma patients, highlighting the immune response’s significance in disease progression. Immune cell infiltration analysis revealed elevated levels of activated dendritic cells, natural killer cells, monocytes, and immature dendritic cells in glaucoma samples. Three hub genes, CD40LG, TEK, and MDK, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the NMDA-induced excitotoxicity model.

Discussion: The findings propose the three identified immune-related genes (IRGs) as novel diagnostic markers for glaucoma, offering new insights into the disease's pathogenesis and potential therapeutic targets. The strong correlation between these IRGs and immune responses underscores the intricate role of immunity in glaucoma, suggesting a shift in the approach to its diagnosis and treatment.
Interventions to improve the quality of maternal care in Ethiopia: a scoping review
Authors: Birhane Binyam Minuye , Assefa Yibeltal , Belay Demeke Mesfin , Nibret Gedefaye , Munye Aytenew Tigabu , Liyeh Tewachew Muche , Gelaw Kelemu Abebe , Tiruneh Yenework Mulu
Published: April 2024

Introduction

Quality improvement interventions have been part of the national agenda aimed at reducing maternal and neonatal morbidities and mortality. Despite different interventions, neonatal mortality and morbidity rates remain steady. This review aimed to map and synthesize the evidence of maternal and newborn quality improvement interventions in Ethiopia.

Methods

A scoping review was reported based on the reporting items for systematic reviews and meta-analysis extensions for the scoping review checklist. Data extraction, collation, and organization were based on the Joanna Briggs Institute manual of the evidence synthesis framework for a scoping review. The maternal and neonatal care standards from the World Health Organization and the Donabedian quality of health framework were used to summarize the findings.

Results

Nineteen articles were included in this scoping review. The review found that the studies were conducted across various regions of Ethiopia, with the majority published after 2013. The reviewed studies mainly focused on three maternal care quality interventions: mobile and electronic health (eHealth), quality improvement standards, and human resource mobilization. Moreover, the reviewed studies explored various approaches to quality improvement, such as providing training to healthcare workers, health extension workers, traditional birth attendants, the community health development army, and mothers and supplying resources needed for maternal and newborn care.

Conclusion

In conclusion, quality improvement strategies encompass community involvement, health education, mHealth, data-driven approaches, and health system strengthening. Future research should focus on the impact of physical environment, culture, sustainability, cost-effectiveness, and long-term effects of interventions. Healthcare providers’ knowledge, skills, attitudes, satisfaction, and adherence to guidelines should also be considered.
Mathematical modeling of endogenous and exogenously administered T cell recirculation in mouse and its application to pharmacokinetic studies of cell therapies
Authors: Nikitich Antonina , Helmlinger Gabriel , Peskov Kirill , Bocharov Gennady
Published: April 2024

Introduction

In vivo T cell migration has been of interest to scientists for the past 60 years. T cell kinetics are important in the understanding of the immune response to infectious agents. More recently, adoptive T cell therapies have proven to be a most promising approach to treating a wide range of diseases, including autoimmune and cancer diseases, whereby the characterization of cellular kinetics represents an important step towards the prediction of therapeutic efficacy.

Methods

Here, we developed a physiologically-based pharmacokinetic (PBPK) model that describes endogenous T cell homeostasis and the kinetics of exogenously administered T cells in mouse. Parameter calibration was performed using a nonlinear fixed-effects modeling approach based on published data on T cell kinetics and steady-state levels in different tissues of mice. The Partial Rank Correlation Coefficient (PRCC) method was used to perform a global sensitivity assessment. To estimate the impact of kinetic parameters on exogenously administered T cell dynamics, a local sensitivity analysis was conducted.

Results

We simulated the model to analyze cellular kinetics following various T cell doses and frequencies of CCR7+ T cells in the population of infused lymphocytes. The model predicted the effects of T cell numbers and of population composition of infused T cells on the resultant concentration of T cells in various organs. For example, a higher percentage of CCR7+ T cells among exogenously administered T lymphocytes led to an augmented accumulation of T cells in the spleen. The model predicted a linear dependence of T cell dynamics on the dose of adoptively transferred T cells.

Discussion

The mathematical model of T cell migration presented here can be integrated into a multi-scale model of the immune system and be used in a preclinical setting for predicting the distribution of genetically modified T lymphocytes in various organs, following adoptive T cell therapies.
Efficacy and safety of different immunotherapies combined with chemotherapy as first-line therapy in patients with small cell lung cancer: a network meta-analysis
Authors: Gong Siyao , Li Qian , Yu Xin , Yang Sha
Published: April 2024

Background

The efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung cancer, limited-disease small-cell lung cancer and relapsed small-cell lung cancer) are still unknown, and there are no reports directly comparing the efficacy and safety of other immunotherapies.

Objective

This study aimed to compare the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with small-cell lung cancer.

Method

We searched Pubmed, Embase, Cochrane Library, CNKI, and Wanfang databases for relevant articles published from inception to November 11, 2020. The risk of bias of the included studies was conducted using the Cochrane risk-of-bias (RoB) tool. Multiple Bayesian network meta-analyses were performed. They conducted data analysis using R Studio and STATA version 15.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), stability of response (SOR), duration of response (DOR) and adverse events of grade 3 or higher (AE grade≥3). A 95% confidence interval (CI) was provided for each estimate.

Results

This meta-analysis included 16 RCT studies with 5898 patients. For OS, relative to chemotherapy (MD=-4.49; 95%CI [-7.97, -1.03]), durvalumab plus tremelimumab (MD=-4.62; 95%CI [-9.08, -0.11]), ipilimumab (MD=-4.26; 95%CI [-8.01, -0.3]) and nivolumab(MD=-5.66; 95%CI [-10.44, -1.11]) and nivolumab plus ipilimumab (MD=-4.56; 95%CI [-8.7, -0.1]), serplulimab can significantly increase the OS of SCLC patients. There was no significant difference between PFS, SOR and DOR. Analysis of AE showed that different immunotherapy combined chemotherapy regimens were similar to single chemotherapy regarding the overall incidence of AE grade≥3. However, after the cumulative ranking of the common symptoms of different adverse reactions, it was found that nivolumab ranked first in the occurrence probability of anemia (99.08%), fatigue (84.78%), and decreased appetite (89.66%). durvalumab was the most likely in nausea (75.4%). Pembrolizumab (76.24%) was most likely to cause pruritus. Chemotherapy combined with immunotherapy caused less diarrhea than chemotherapy alone (80.16%).

Conclusions

According to our analysis, serplulimab combined with chemotherapy is more likely to show better efficacy with a manageable safety profile for small-cell lung cancer. However, the evidence for this comparison shows some limitations due to the number of literature.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023486053.
Immunophenotypic variations in syphilis: insights from Mendelian randomization analysis
Authors: Xie Qinghui , Tang Yijie , Shen Lingyun , Yang Dandan , Zhang Jiaqin , Luo Qingqiong
Published: April 2024

Background

Infection with Treponema pallidum instigates complex immune responses. Prior research has suggested that persistent Treponema pallidum infection can manipulate host immune responses and circumvent host defenses. However, the precise role of immune cells in Treponema pallidum infection across different stages remains a contentious issue.

Methods

Utilizing summary data from genome-wide association studies, we employed a two-sample Mendelian randomization method to investigate the association between 731 immunophenotypes and syphilis. Syphilis was categorized into early and late stages in this study to establish a more robust correlation and minimize bias in database sources.

Results

Our findings revealed that 33, 36, and 27 immunophenotypes of peripheral blood were associated with syphilis (regardless of disease stage), early syphilis and late syphilis, respectively. Subsequent analysis demonstrated significant variations between early and late syphilis in terms of immunophenotypes. Specifically, early syphilis showcased activated, secreting, and resting regulatory T cells, whereas late syphilis was characterized by resting Treg cells. More B cells subtypes emerged in late syphilis. Monocytes in early syphilis exhibited an intermediate and non-classical phenotype, transitioning to classical in late syphilis. Early syphilis featured naive T cells, effector memory T cells, and terminally differentiated T cells, while late syphilis predominantly presented terminally differentiated T cells. Immature myeloid-derived suppressor cells were evident in early syphilis, whereas the dendritic cell immunophenotype was exclusive to late syphilis.

Conclusion

Multiple immunophenotypes demonstrated associations with syphilis, showcasing substantial disparities between the early and late stages of the disease. These findings hold promise for informing immunologically oriented treatment strategies, paving the way for more effective and efficient syphilis interventions.
A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance
Authors: Xu Meng-Yao , Xia Zhi-Yu , Sun Jian-Xuan , Liu Chen-Qian , An Ye , Xu Jin-Zhou , Zhang Si-Han , Zhong Xing-Yu , Zeng Na , Ma Si-Yang , He Hao-Dong , Wang Shao-Gang , Xia Qi-Dong
Published: April 2024

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.
Combating bone marrow failure with polymer materials
Authors: Koch Kayla C. , Jadon Nidhi , Thesmar Iris , Tew Gregory N. , Minter Lisa M.
Published: April 2024

Bone marrow failure (BMF) has become one of the most studied autoimmune disorders, particularly due to its prevalence both as an inherited disease, but also as a result of chemotherapies. BMF is associated with severe symptoms such as bleeding episodes and susceptibility to infections, and often has underlying characteristics, such as anemia, thrombocytopenia, and neutropenia. The current treatment landscape for BMF requires stem cell transplantation or chemotherapies to induce immune suppression. However, there is limited donor cell availability or dose related toxicity associated with these treatments. Optimizing these treatments has become a necessity. Polymer-based materials have become increasingly popular, as current research efforts are focused on synthesizing novel cell matrices for stem cell expansion to solve limited donor cell availability, as well as applying polymer delivery vehicles to intracellularly deliver cargo that can aid in immunosuppression. Here, we discuss the importance and impact of polymer materials to enhance therapeutics in the context of BMF.
Metrics to guide development of machine learning algorithms for malaria diagnosis
Authors: Delahunt Charles B. , Gachuhi Noni , Horning Matthew P.
Published: April 2024

Automated malaria diagnosis is a difficult but high-value target for machine learning (ML), and effective algorithms could save many thousands of children’s lives. However, current ML efforts largely neglect crucial use case constraints and are thus not clinically useful. Two factors in particular are crucial to developing algorithms translatable to clinical field settings: (i) clear understanding of the clinical needs that ML solutions must accommodate; and (ii) task-relevant metrics for guiding and evaluating ML models. Neglect of these factors has seriously hampered past ML work on malaria, because the resulting algorithms do not align with clinical needs. In this paper we address these two issues in the context of automated malaria diagnosis via microscopy on Giemsa-stained blood films. The intended audience are ML researchers as well as anyone evaluating the performance of ML models for malaria. First, we describe why domain expertise is crucial to effectively apply ML to malaria, and list technical documents and other resources that provide this domain knowledge. Second, we detail performance metrics tailored to the clinical requirements of malaria diagnosis, to guide development of ML models and evaluate model performance through the lens of clinical needs (versus a generic ML lens). We highlight the importance of a patient-level perspective, interpatient variability, false positive rates, limit of detection, and different types of error. We also discuss reasons why ROC curves, AUC, and F1, as commonly used in ML work, are poorly suited to this context. These findings also apply to other diseases involving parasite loads, including neglected tropical diseases (NTDs) such as schistosomiasis.
Numerical modelling of the interaction between flexible net panels and fluids using SPH method
Authors: Shi Qian , Zhao Depeng , Xue Dawen , Zhang Ning , Zhang Lifeng , Pan Yun
Published: April 2024

This study addresses the challenge of simulating fluid flow around flexible net panels, which are critical components in aquaculture systems. Traditional grid-based Eulerian methods struggle with the complex deformations and interactions of such panels. To fill this gap, a numerical approach leveraging the Smoothed Particle Hydrodynamics (SPH) method is introduced. The proposed approach employs a knot-spring model to represent the flexible net panels. The nets are idealized as a structure of physical net-knots linked by virtual elastic springs. The SPH method is used to simulate the fluid flow, capturing the movement of the knots and the resulting deformation of the nets. The model's parameters and numerical schemes are detailed, along with the implementation process. The accuracy of the model is validated through comparisons with existing experimental and simulation data. The results indicate that the SPH-based approach accurately simulates the flow past flexible net panels, providing a detailed velocity distribution and deformation analysis. The study's findings demonstrate the potential of the SPH method for aquaculture engineering applications. The proposed approach offers a promising alternative to traditional methods, particularly in scenarios involving significant net deformation or interaction with other objects. The implications for the design and operation of aquaculture facilities are discussed, along with suggestions for future research directions.
Paradoxical reaction to IL-17A inhibitor: a case report and literature review
Authors: Ren Jingyu , Deng Linjun , Guo Shuping , Liu Hongye
Published: April 2024

Objective

A case of pustular psoriasis after treatment with secukinumab in a patient with plaque psoriasis is reported, which is the first case in China. To summarize the clinical characteristics of patients who developed the rare paradoxical reaction and treatment options received IL-17A antagonist therapy, we conducted a further literature review.

Methods

Data were analyzed from a patient with plaque psoriasis who developed pustular psoriasis after treatment with secukinumab. A comprehensive review of relevant domestic and international literature was conducted, focusing on cases that met our inclusion criteria for analysis and synthesis.

Results

Anti IL-17A therapy may lead to type conversion, with reported cases more prevalent in women and varying in onset time, predominantly involving palmoplantar pustulosis.

Conclusion

Given the increasing use of IL-17A antagonists in psoriasis treatment, it is crucial to monitor for rare adverse reactions, including the paradoxical induction of pustular psoriasis.
Impact of the gut microbiome on skin fibrosis: a Mendelian randomization study
Authors: Zhao Zirui , Xu Zhongye , Lv Dongming , Rong Yanchao , Hu Zhicheng , Yin Rong , Dong Yunxian , Cao Xiaoling , Tang Bing
Published: April 2024

Objective

Skin fibrosis is a lesion in the dermis causing to itching, pain, and psychological stress. The gut microbiome plays as an essential role in skin diseases developments. We conducted a Mendelian randomization study to determine the causal association between the gut microbiome and skin fibrosis.

Methods

We retrieved valid instrumental variables from the genome-wide association study (GWAS) files of the gut microbiome (n = 18,340) conducted by the MiBioGen consortium. Skin fibrosis-associated data were downloaded from the GWAS Catalog. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to determine whether the gut microbiome was related to skin fibrosis. A reverse MR analysis was also performed on the bacterial traits which were causally associated with skin fibrosis in the forward MR analysis. In addition, we performed an MR-Pleiotropy Residual Sum and Outlier analysis to remove outliers and a sensitivity analysis to verify our results.

Results

According to the inverse variance-weighted estimation, we identified that ten bacterial traits (Class Actinobacteria, Class Bacteroidia, family Bifidobacteriaceae, family Rikenellaceae, genus Lachnospiraceae (UCG004 group), genus Ruminococcaceae (UCG013 group), order Bacteroidales, order Bifidobacteriales, genus Peptococcus and genus Victivallis) were negatively correlated with skin fibrosis while five bacterial traits (genus Olsenella, genus Oscillospira, genus Turicibacter, genus Lachnospiraceae (NK4A136group), and genus Sellimonas) were positively correlated. No results were obtained from reverse MR analysis. No significant heterogeneity or horizontal pleiotropy was observed in MR analysis.

Objective conclusion

There is a causal association between the gut microbiome and skin fibrosis, indicating the existence of a gut-skin axis. This provides a new breakthrough point for mechanistic and clinical studies of skin fibrosis.
The creation of an adaptable informed consent form for research purposes to overcome national and institutional bottlenecks in ethics review: experience from rare disease registries
Authors: Landi Annalisa , Mimouni Yanis , Giannuzzi Viviana , Schaefer Franz , Altavilla Annagrazia , Gibson Spencer , Julkowska Daria
Published: April 2024

Background

The lack of harmonization of evaluation criteria by Ethics Committees in the European Union (EU) has led to inconsistent ethics reviews received by research sites participating in multicenter non-interventional studies. The European General Data Protection Regulation (GDPR) appears to be implemented at national level with a substantial degree of variance in interpretation. The European Reference Networks (ERNs) were struggling in setting an Informed Consent Form (ICF) for registries, allowing reuse of data for research purposes. The aim of this work is to develop an adaptable ICF for research purposes to be used in ERN registries.

Methods

To work on this challenge, a team was established within the European Joint Programme on Rare Diseases (EJP RD) to develop a patients’ registry ICF template allowing easy adaptation to ERNs, country, and site-level specificities. ERN and patients’ representatives validated the choice of developing a GDPR-compliant template for research purposes. The feedback received from 34 Ethics Committees on the Clinical Patient Management System ICF, including the submission of patients’ data to the ERN registries and the EU consent regulatory framework were analyzed along with existing ontologies for data access and reuse. An adaptable ICF was developed following iterative cycles of consultation and review by clinicians, research experts, ethics and regulatory advisors, and patients’ representatives. The development of pediatric material for minor participants was also undertaken.

Results and Conclusion

Research oriented ICF templates for adults and for parents/legal representatives of patients were released in 26 national languages. This adaptable ICF aims to foster, according to patients’ preferences, the reuse of registries data for research purposes in compliance with the applicable laws and standards. Pediatric material is being finalized to collect minors’ assent. ICF machine-readability is also progressing to enhance data discovery and facilitate its access and reuse conditions.