bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluaton Evaluation of Subdistrict Tasks in Implementation the Authority for Small-Scale Development in Kutai Kartanegara Regency
Authors: Subandi Muhammad , Raden Ince , Suprapto Heru
Published: January 2022

The implementation of sub-district tasks in managing small-scale development, which is the delegation of authority from the Regent of Kutai Kartanegara, has not been running optimally. This study aims to evaluate the authority of the sub-district in implementing small-scale development. The research method is descriptive qualitative by collecting data through semi-structured interviews conducted in 3 sub-districts and using a questionnaire for all locations in 15 sub-districts which are the source of the data. with the determination of informants by purposive sampling. From the results of the study, it has been concluded that the sub-district's authority in managing small-scale development cannot be fully implemented, this is due to the lack of clarity in the provisions regarding the criteria and specifications for an activity in the delegation of authority regulations, the weak coordination link between the sub-districts and the relevant local government agencies in the framework of the integrated planning system, lack of capacity sub-district officials in carrying out their duties, there is no measurable sub-district performance indicators and targets, it is recommended to the Kutai Kartanegara Regency Government to review to make improvements and development of policies regarding the delegation of the Regent's authority to the Camat, especially related to small-scale management policies and adjusting to the prevailing laws and regulations governing regional and sub-district governments.
Desarrollo de la lengua materna: Incidencia del género con una visión pragmática.
Authors: Gonzalez Valencia Heriberto , Cadena Tamayo Nathaly , Núñez Tobón Paula Andrea
Published: January 2022

La investigación analizó por medio de diferentes actividades los diversos componentes pragmáticos en el habla espontánea de un niño y una niña, teniendo en cuenta principalmente las variables del desarrollo del habla conversacional y los conceptos para su análisis. El objetivo principal se planteó en verificar si existe incidencia en el género en el desarrollo del lenguaje de un niño y una niña en la edad de los 3 años con un enfoque pragmático. Se realizó una investigación de tipo cualitativa descriptiva, utilizando un modelo de evaluación. Se describen las actividades propuestas y realizadas individualmente con un seguimiento estricto de los investigadores. El contexto está enmarcado en situaciones reales y de confianza para los participantes. Los resultados muestran que el contexto es uno de los factores influyentes en el argumento final, pero la incidencia del género no muestra una diferencia significativa. La participación del niño y la niña durante una actividad puede variar dependiendo del contexto y de la cercanía con los interlocutores. Se evidenció la influencia del contexto social; se deduce que no es el género el que incide en el desarrollo del componente pragmático en situaciones de habla espontánea.
INSTRUMENTOS DE EVALUACIÓN FISIOTERAPÉUTICA EN POBLACIÓN NEONATAL:
Authors: Martínez Santa Jaime , Del Pilar Martínez Andrea , Avendaño Vanegas Janneth Milena , Melo Cuervo Alejandra , Alfonso Mantilla Jose Ivan
Published: January 2022

RESUMEN
Introducción Los test y medidas utilizados en la evaluación específica de la población neonatal por el fisioterapeuta son diferentes a los usados en población pediátrica y adulta debido a que presentan un mayor costo fisiológico y una respuesta de estrés a la manipulación condicionando respuestas en el neonato. Por tal motivo, se hace de vital importancia profundizar e investigar en el conocimiento de los instrumentos de evaluación fisioterapéutica en el recién nacido de acuerdo a las categorías de la APTA con el fin de realizar procesos de evaluación específicos por categoría Método Revisión de la literatura por medio de la búsqueda de artículos científicos en bases de datos en el periodo 2000-2020 obteniendo 100 artículos Resultados El fisioterapeuta cuenta con instrumentos de evaluación en población neonatal para evaluar las siguientes categorías de la APTA: capacidad aeróbica y resistencia, características antropométricas, ventilación, respiración e intercambio gaseoso, circulación, funciones mentales, integridad de nervios craneales, desarrollo neuromotor, integridad refleja, rango de movimiento, desempeño muscular integridad integumentaria, dolor, tecnología de asistencia y factores ambientales Conclusiones El presente artículo evidencia que el fisioterapeuta tiene a disposición test y medidas con  adecuados niveles de validez y confiabilidad para lograr un acercamiento al estado funcional del neonato lo que permitirá realizar un diagnóstico y tratamiento basados en el razonamiento clínico y evidencia científica.
Un enfoque de redes neuronales para la alineación de prótesis transtibiales
Authors: Luengas-C. Lely A. , Wanumen Luis Felipe , Camargo Casallas Esperanza
Published: January 2022

Introducción: La presencia de enfermedades o alteraciones musculo-esqueléticas, así como trauma por accidentes tienen como posible consecuencia amputaciones, en Colombia se adiciona como causa el conflicto armado, ya que ha generado un grupo poblacional con discapacidad debido a los artefactos explosivos no identificados, donde amputaciones en extremidades inferiores son altamente frecuentes. La prótesis se emplea para que el amputado pueda adaptarse a su condición y reincorporarse en las actividades cotidianas, su uso se da luego de la alineación de la prótesis. La alineación tiende a ser un proceso subjetivo, donde el conocimiento y la práctica son esenciales en el momento de realizarla, no se tienen sistemas que reconozcan el impacto de este proceso sobre variables biomecánicas del sujeto con amputación. Por ello se propuso realizar una red neuronal que muestre la incidencia de la variación angular del socket de la prótesis en rangos articulares, la disposición de peso corporal y el centro de presión.

Método:  Se realizó un estudio descriptivo donde el socket de la prótesis de un amputado transtibial se colocó en siete posiciones angulares diferentes, en cada posición se midieron parámetros biomecánicos, con estos datos se programó una red neuronal de regresión generalizada (GRNN) para predecir datos biomecánicos a partir de la ubicación del socket y se generó una interfaz gráfica para visualizar los cambios de los parámetros.

Resultados: La red neuronal permitió predecir el comportamiento de los ángulos de cadera, rodilla y tobillo, la ubicación del centro de presión y el peso corporal soportado tanto en ipsilateral (amputado) como en contralateral (no amputado); y en la interfaz gráfica se pudo mostrar la afectación.

Conclusión: El uso de herramientas tecnológicas permite construir sistemas de apoyo al personal médico, en este caso al protesista, con el fin de hacer mejoras en el procedimiento de ajuste de la prótesis en los sujetos con amputación transtibial.
A Review of Monitoring Construction Equipment in Support of Construction Project Management
Authors: Nakanishi Yutaro , Kaneta Takashi , Nishino Sayaka
Published: January 2022

Progress monitoring is an important aspect of construction project control that is fundamental to proper project management and decision-making. Traditional monitoring methods are inaccurate, time-consuming, and labor-intensive because they rely on large-scale manual operations. The defect of the method has been identified as one of the major problems causing project delays and cost overruns. In recent years, a variety of emerging automated data collection, analysis, and visualization techniques have been used to establish methods for digitized, real-time progress monitoring, and there are several papers that address these methodologies and comprehensive reviews. Among them, the authors conducted a review of various studies focusing on how to apply the monitoring of construction equipment to project management. The authors selected the studies of interest using research databases such as Google Scholar and ScienceDirect. Then, the authors classified those studies by technology, purpose, and subject matter, and analyzed the details. Through a literature review, it was revealed that most of the studies were focused on digitalization and review of the lifted path for safety improvement, and few studies were conducted for progress management, such as collection and analysis of work results. In addition, the authors revealed that several studies use the combination of existing technologies with new modeling technologies such as BIM (Building Information Modeling). It was also clarified that the technology applied to the monitoring is not even one, but a combination of multiple technologies to achieve each objective. Furthermore, even in the case of monitoring construction equipment, the authors found that workers, construction materials, and even the activity itself are also monitored as well as construction equipment.
Heme in Cardiovascular Diseases: A Ubiquitous Dangerous Molecule Worthy of Vigilance
Authors: Guo Yuyang , Zhao Hengli , Lin Zhibin , Ye Taochun , Xu Dingli , Zeng Qingchun
Published: January 2022

Heme, the protoporphyrin IX iron complex is widely present in the human body and it is involved in oxygen storage, electron transfer, and enzymatic reactions. However, free heme can be toxic as it catalyzes the production of reactive oxygen species, oxidizes lipids and proteins, and causes DNA damage, thereby inducing a pro-inflammatory environment. The generation, metabolism, and degradation of heme in the human body are regulated by precise mechanisms to ensure that heme remains non-toxic. However, in several types of cardiovascular diseases, impaired metabolism and exposure to heme may occur in pathological processes, including neovascularization, internal hemorrhage, ischemia, and reperfusion. Based on years of research, in this review, we aimed to summarize the underlying mechanisms by which heme contributes to the development of cardiovascular diseases through oxidative stress, relative pathway gene expression regulation and phenotypic changes in cells. Excess heme plays a detrimental role in atherosclerosis, heart failure, myocardial ischemia-reperfusion injury, degenerative aortic valve stenosis, cardiac iron overload. Recent researches revealed that in some cases heme involved in cardiac damage though ferroptosis. Thus, heme concentrations beyond normal levels are dangerous. Further research on the role of heme in cardiovascular diseases is needed.
Enhancing Squalene Production in Saccharomyces cerevisiae by Metabolic Engineering and Random Mutagenesis
Authors: Xia Lu , Lv Yunbin , Liu Song , Yu Shiqin , Zeng Weizhu , Zhou Jingwen
Published: January 2022

Squalene is an important polyunsaturated triterpene with wide applications in the food, cosmetics, and pharmaceutical industries. Currently, the main method for squalene production is extraction from oil-producing plants, but the scale is limited. The microbial fermentation with Saccharomyces cerevisiae still needs improvement to be economically viable. This study aimed to improve squalene production by metabolic engineering and random mutagenesis. First, the mevalonate (MVA) pathway was enhanced, by integrating tHMG1 and IDI1 into multi-copy site Ty2. Subsequently, the ACL gene from Yarrowia lipolytica, encoding citrate lyase was introduced and the β-oxidation pathway was enhanced with multiple copies of key genes. In addition, a high throughput screening strategy based on Nile red staining was established for high squalene-producer screening. After treatment with ARTP mutagenesis, a higher-producing mutant was obtained, with squalene production enhanced by 18.4%. A two-stage fermentation of this mutant in a 5 L bioreactor produced 8.2 g/L of squalene. These findings may facilitate the development of industrial squalene production by fermentation and potentially, other terpenoids.
Towards Application of Electro-Fermentation for the Production of Value-Added Chemicals From Biomass Feedstocks
Authors: Yamada Shohei , Takamatsu Yuki , Ikeda Sota , Kouzuma Atsushi , Watanabe Kazuya
Published: January 2022

According to recent social demands for sustainable developments, the value of biomass as feedstocks for chemical industry is increasing. With the aid of metabolic engineering and genome editing, microbial fermentation has been developed for producing value-added chemicals from biomass feedstocks, while further improvements are desired for producing more diverse chemicals and increasing the production efficiency. The major intrinsic limitation in conventional fermentation technologies is associated with the need for balancing the net redox equivalents between substrates and products, resulting in limited repertories of fermentation products. One solution for this limitation would be “electro-fermentation (EF)” that utilizes bioelectrochemical systems for modifying the intracellular redox state of electrochemically active bacteria, thereby overcoming the redox constraint of fermentation. Recent studies have attempted the production of chemicals based on the concept of EF, while its utility has not been sufficiently demonstrated in terms of low production efficiencies. Here we discuss EF in terms of its concept, current status and future directions, which help us develop its practical applications to sustainable chemical industries.
New Imidazole-Based N-Phenylbenzamide Derivatives as Potential Anticancer Agents: Key Computational Insights
Authors: Malik M. Shaheer , Alsantali Reem I. , Jamal Qazi Mohammad Sajid , Seddigi Zaki S. , Morad Moataz , Alsharif Meshari A. , Hussein Essam M. , Jassas Rabab S. , Al-Rooqi Munirah M. , Abduljaleel Zainularifeen , Babalgith Ahmed O. , Altass Hatem M. , Moussa Ziad , Ahmed Saleh A.
Published: January 2022

An efficient atom-economical synthetic protocol to access new imidazole-based N-phenylbenzamide derivatives is described. A one-pot three-component reaction was utilized to provide a series of N-phenylbenzamide derivatives in a short reaction time (2–4 h) with an 80–85% yield. The cytotoxic evaluation revealed that derivatives 4e and 4f exhibited good activity, with IC50 values between 7.5 and 11.1 μM against the tested cancer cell lines. Computational studies revealed interesting insights: the docking of the active derivatives (4e and 4f) showed a higher affinity toward the target receptor protein than the control. Molecular dynamic simulations revealed that the active derivatives form stable complexes with the ABL1 kinase protein. Moreover, the ADME and drug-likeness of the derivatives reinforced the potential of the derivatives to be taken up for further development as anticancer agents.
Synergistic Interaction of Piperine and Thymol on Attenuation of the Biofilm Formation, Hyphal Morphogenesis and Phenotypic Switching in Candida albicans
Authors: Priya Arumugam , Nivetha Srinivasan , Pandian Shunmugiah Karutha
Published: January 2022

The incidence of fungal infections has significantly increased in recent years due to the emergence of antifungal resistance. Biofilm formation is considered to be a major contributor to both the infectious diseases and to antimicrobial resistance. Consequently, biofilm-associated infections are often problematic to treat with existing therapeutics. Adhesion of C. albicans to the host surface or implanted materials followed by hyphal invasion and biofilm formation enhances C. albicans pathogenicity and virulence. Thus, developing a therapeutic agent that inhibits candidal adherence, biofilm development and morphological switching could improve clinical management of infections. The present investigation studied two emerging and alternatives strategies, namely antibiofilm and combinatorial approach, to attenuate biofilm formation and the expression of Candida virulence factors. Piperine and thymol are major bioactive components of pepper and thyme, respectively. These phytochemicals are known to possess numerous biological activities, including recently reported antibiofilm effects against C. albicans. The minimum biofilm inhibitory concentration (MBIC) of both phytochemicals was determined to be 32 µg/ml. The phytochemical treatment of Candida biofilms using piperine and thymol revealed synergistic effects at four different combinations of concentrations, i.e. 8 and 8, 8 and 4, 8 and 2 and 4 and 8 µg/ml. These synergistic combinations resulted in the significant reduction in adherence of Candida, hyphal extension and morphological transformation. Moreover, limited exposure of synergistic combinations controlled the hyphal elongation. Results were validated through the gene expression analysis. Results from the present investigation suggest that piperine and thymol can be synergistically employed for the treatment of biofilm-associated C. albicans infection.
Serum IgG Responses to gp15 and gp40 Protein-Derived Synthetic Peptides From Cryptosporidium parvum
Authors: Urrea-Quezada Alejandro , Balmaceda-Baca Ruben , Garibay Adriana , Hernández Jesús , Valenzuela Olivia
Published: January 2022

Cryptosporidium spp. are responsible for moderate to severe diarrhea, mainly in children and immunocompromised patients. Using ELISA, the recognition of synthetic peptides generated from the sequences of the Cryptosporidium parvum gp40 and gp15 proteins by serum IgM and IgG antibodies from patients infected (cases) with Cryptosporidium hominis, C. parvum, and Cryptosporidium canis, and uninfected individuals (controls) was evaluated. A statistically significant difference (p = 0.0025) was found in terms of the recognition of peptides A133 and A32 between cases and controls. Additional studies are necessary to understand the potential of these peptides as vaccine candidates.
Tick Saliva and Salivary Glands: What Do We Know So Far on Their Role in Arthropod Blood Feeding and Pathogen Transmission
Authors: Neelakanta Girish , Sultana Hameeda
Published: January 2022

Ticks are blood-sucking arthropods that have developed myriad of strategies to get a blood meal from the vertebrate host. They first attach to the host skin, select a bite site for a blood meal, create a feeding niche at the bite site, secrete plethora of molecules in its saliva and then starts feeding. On the other side, host defenses will try to counter-attack and stop tick feeding at the bite site. In this constant battle between ticks and the host, arthropods successfully pacify the host and completes a blood meal and then replete after full engorgement. In this review, we discuss some of the known and emerging roles for arthropod components such as cement, salivary proteins, lipocalins, HSP70s, OATPs, and extracellular vesicles/exosomes in facilitating successful blood feeding from ticks. In addition, we discuss how tick-borne pathogens modulate(s) these components to infect the vertebrate host. Understanding the biology of arthropod blood feeding and molecular interactions at the tick-host interface during pathogen transmission is very important. This information would eventually lead us in the identification of candidates for the development of transmission-blocking vaccines to prevent diseases caused by medically important vector-borne pathogens.
Probiotic Lacticaseibacillus rhamnosus GG Increased Longevity and Resistance Against Foodborne Pathogens in Caenorhabditis elegans by Regulating MicroRNA miR-34
Authors: Yun Bohyun , Ryu Sangdon , Kang Minkyoung , Lee Juyeon , Yoo Jiseon , Kim Younghoon , Oh Sangnam
Published: January 2022

In this study, we investigated the relation of probiotic activity of Lacticaseibacillus rhamnosus strain GG (LGG) and expression of microRNA to immune response and longevity in Caenorhabditis elegans host model. First, we evaluated the survival rate of C. elegans due to LGG exposure and bacterial colonization in the intestine. Next, the expression of mRNA and miRNA was analyzed in C. elegans exposure to LGG for 24 h using microarray. After exposure to LGG to C. elegans, colonized LGG was observed in the intestines of C. elegans and induced to extend lifespan. Moreover, persistent LGG in the intestine significantly enhanced the resistance of C. elegans exposed to both pathogenic bacteria and prolonged the lifespan of C. elegans. Transcriptome analysis indicated that LGG affected the expression levels of genes related to the innate immune response and upregulated the abundance of genes in multiple pathways of C. elegans, including Wnt signaling, TGF-beta signaling and mitogen-activated protein kinase (MAPK) pathways. In addition, qRT-PCR analysis confirmed that the expression of antibacterial genes was increased by LGG. Moreover, as the expression of microRNA miR-34 and immune-related pathways increased by exposure to LGG, the lifespan of C. elegans increased. However, in the miR-34 mutant C. elegans, the lifespan by LGG did not increase, so it was determined that miR-34 indirectly affects immune-related pathways. There was no significant difference in the expression of PMK-1 for LGG exposure in miR-34 mutants, suggesting that miR-34 may regulate PMK-1. In conclusion, we suggest that exposure of LGG to C. elegans enhances lifespan and resistance to food-borne pathogen infection by stimulating miR-34 and indirectly promoting PMK-1 activity.
Self-Reported Mobile Health-Based Risk Factor and CHA2DS2-VASc-Score Assessment in Patients With Atrial Fibrillation: TeleCheck-AF Results
Authors: Hermans Astrid N. L. , Gawałko Monika , Hillmann Henrike A. K. , Sohaib Afzal , van der Velden Rachel M. J. , Betz Konstanze , Verhaert Dominique , Scherr Daniel , Meier Julia , Sultan Arian , Steven Daniel , Terentieva Elena , Pisters Ron , Hemels Martin , Voorhout Leonard , Lodziński Piotr , Krzowski Bartosz , Gupta Dhiraj , Kozhuharov Nikola , Gruwez Henri , Vernooy Kevin , Pluymaekers Nikki A. H. A. , Hendriks Jeroen M. , Manninger Martin , Duncker David , Linz Dominik
Published: January 2022

Introduction

The TeleCheck-AF approach is an on-demand mobile health (mHealth) infrastructure incorporating mobile app-based heart rate and rhythm monitoring through teleconsultation. We evaluated feasibility and accuracy of self-reported mHealth-based AF risk factors and CHA2DS2-VASc-score in atrial fibrillation (AF) patients managed within this approach.

Materials and Methods

Consecutive patients from eight international TeleCheck-AF centers were asked to complete an app-based 10-item questionnaire related to risk factors, associated conditions and CHA2DS2-VASc-score components. Patient's medical history was retrieved from electronic health records (EHR).

Results

Among 994 patients, 954 (96%) patients (38% female, median age 65 years) completed the questionnaire and were included in this analysis. The accuracy of self-reported assessment was highest for pacemaker and anticoagulation treatment and lowest for heart failure and arrhythmias. Patients who knew that AF increases the stroke risk, more often had a 100% or ≥80% correlation between EHR- and app-based results compared to those who did not know (27 vs. 14% or 84 vs. 77%, P = 0.001). Thromboembolic events were more often reported in app (vs. EHR) in all countries, whereas higher self-reported hypertension and anticoagulant treatment were observed in Germany and heart failure in the Netherlands. If the app-based questionnaire alone was used for clinical decision-making on anticoagulation initiation, 26% of patients would have been undertreated and 6.1%—overtreated.

Conclusion

Self-reported mHealth-based assessment of AF risk factors is feasible. It shows high accuracy of pacemaker and anticoagulation treatment, nevertheless, displays limited accuracy for some of the CHA2DS2-VASc-score components. Direct health care professional assessment of risk factors remains indispensable to ensure high quality clinical-decision making.
Farmers’ Perceptions of the Effects of Extreme Environmental Changes on Their Health: A Study in the Semiarid Region of Northeastern Brazil
Authors: Magalhães Henrique Fernandes , Feitosa Ivanilda Soares , Araújo Elcida de Lima , Albuquerque Ulysses Paulino
Published: January 2022

People living in areas vulnerable to diseases caused by extreme climate change events, such as semiarid regions, tend to recognize them quickly and, consequently, develop strategies to cope with their effects. Our study investigated the perception of diseases by farmers living in the semiarid region of Northeastern Brazil and the adaptive strategies locally developed and used. To this end, the effect of the incidence and severity of locally perceived diseases on the frequency of adaptive responses adopted by the farmers was tested. The research was conducted in rural communities in the Pernambuco State, Northeastern Region of Brazil. Semi-structured interviews with 143 farmers were conducted to collect information about major drought and rainfall events, the perceived diseases related to these events, and the adaptive strategies developed to mitigate them. The incidence and severity of diseases perceived by farmers were calculated using the Participatory Risk Mapping method and the frequency of adaptive strategies. Our findings demonstrated that few climate change-related diseases were frequently mentioned by farmers, indicating low incidence rates. Among them, direct transmission diseases were the most frequently mentioned. Adaptive strategies to deal with the mentioned diseases related to prophylactic behavior were less mentioned, except if already utilized. Our model demonstrated that incidence was the only explanatory variable with a significant impact on the adaptive strategies used to deal with the effects of these risks on health. Our findings suggest that the estimated incidence of diseases should be considered in the development of predictive climate change models for government policy measures for the public health security of populations in areas of greater socio-environmental vulnerability.
Interpretation of Convolutional Neural Networks for Acid Sulfate Soil Classification
Authors: Beucher Amélie , Rasmussen Christoffer B. , Moeslund Thomas B. , Greve Mogens H.
Published: January 2022

Convolutional neural networks (CNNs) have been originally used for computer vision tasks, such as image classification. While several digital soil mapping studies have been assessing these deep learning algorithms for the prediction of soil properties, their potential for soil classification has not been explored yet. Moreover, the use of deep learning and neural networks in general has often raised concerns because of their presumed low interpretability (i.e., the black box pitfall). However, a recent and fast-developing sub-field of Artificial Intelligence (AI) called explainable AI (XAI) aims to clarify complex models such as CNNs in a systematic and interpretable manner. For example, it is possible to apply model-agnostic interpretation methods to extract interpretations from any machine learning model. In particular, SHAP (SHapley Additive exPlanations) is a method to explain individual predictions: SHAP values represent the contribution of a covariate to the final model predictions. The present study aimed at, first, evaluating the use of CNNs for the classification of potential acid sulfate soils located in the wetland areas of Jutland, Denmark (c. 6,500 km2), and second and most importantly, applying a model-agnostic interpretation method on the resulting CNN model. About 5,900 soil observations and 14 environmental covariates, including a digital elevation model and derived terrain attributes, were utilized as input data. The selected CNN model yielded slightly higher prediction accuracy than the random forest models which were using original or scaled covariates. These results can be explained by the use of a common variable selection method, namely recursive feature elimination, which was based on random forest and thus optimized the selection for this method. Notably, the SHAP method results enabled to clarify the CNN model predictions, in particular through the spatial interpretation of the most important covariates, which constitutes a crucial development for digital soil mapping.
Stormwater Management Modeling in “Sponge City” Construction: Current State and Future Directions
Authors: Liu Qianhui , Cui Wenhui , Tian Zhan , Tang Yingdong , Tillotson Martin , Liu Junguo
Published: January 2022

In response to urban pluvial flooding and pollution, the Chinese government proposed a “sponge city” policy in 2013 that aims to improve urban stormwater management and promote sustainable urban development. However, at present, sponge city construction is still in its exploratory stage. It is still not clear which models are capable of simulating the six key processes (i.e., “retention,” “infiltration,” “storage,” “purification,” “discharge,” and “utilization”) of sponge city practices. Its various benefits (e.g., social, economic and environmental benefits) have not yet been systematically investigated in the context of the sponge city. In this study, we reviewed and compared 19 urban stormwater management models (including 13 hydrological models and 10 decision-support tools, as there are 4 overlap ones) and investigated their application in China. Firstly, we examined the mechanisms behind the hydrological models and compared the abilities of the models to simulate various processes. Secondly, we analyzed what kinds of benefits can be addressed by these decision support tools (DSTs). Finally, we discussed the applications and limitations of the models in various climate zones in China. The findings suggest that none of the models consider the impact of climate change on the sponge city practices (SCP) and none of DSTs can simulate the negative performance of SCP. Furthermore, the lack of sufficient databases in China limited the applications of many of the models. Additionally, we found that the hydrological processes corresponding to “storage” were given more attention in southern China, and “infiltration” of stormwater was of greater concern in northern China. In the context of sponge city construction, this paper provides suggestions for future model development of urban stormwater management in China, such as the development of a stormwater database and the incorporation of long-term climate change impacts into the model.
New Molecular and Organelle Alterations Linked to Down Syndrome Heart Disease
Authors: Venegas-Zamora Leslye , Bravo-Acuña Francisco , Sigcho Francisco , Gomez Wileidy , Bustamante-Salazar José , Pedrozo Zully , Parra Valentina
Published: January 2022

Down syndrome (DS) is a genetic disorder caused by a trisomy of the human chromosome 21 (Hsa21). Overexpression of Hsa21 genes that encode proteins and non-coding RNAs (ncRNAs) can disrupt several cellular functions and biological processes, especially in the heart. Congenital heart defects (CHDs) are present in 45–50% of individuals with DS. Here, we describe the genetic background of this condition (Hsa21 and non-Hsa21 genes), including the role of ncRNAs, and the relevance of these new players in the study of the pathophysiology of DS heart diseases. Additionally, we discuss several distinct pathways in cardiomyocytes which help maintain a functional heart, but that might trigger hypertrophy and oxidative stress when altered. Moreover, we highlight the importance of investigating how mitochondrial and lysosomal dysfunction could eventually contribute to understanding impaired heart function and development in subjects with the Hsa21 trisomy. Altogether, this review focuses on the newest insights about the gene expression, molecular pathways, and organelle alterations involved in the cardiac phenotype of DS.
Ferroptosis Activation Scoring Model Assists in Chemotherapeutic Agents’ Selection and Mediates Cross-Talk With Immunocytes in Malignant Glioblastoma
Authors: Wang Zeyu , Dai Ziyu , Zheng Lifu , Xu Binyuan , Zhang Hao , Fan Fan , Zhang Xun , Liang Xisong , Liu Zhixiong , Yang Kui , Cheng Quan
Published: January 2022

Gliomas are aggressive tumors in the central nervous system and glioblastoma is the most malignant type. Ferroptosis is a programmed cell death that can modulate tumor resistance to therapy and the components of tumor microenvironment. However, the relationship between ferroptosis, tumor immune landscape, and glioblastoma progression is still elusive. In this work, data from bulk RNA-seq analysis, single cell RNA-seq analysis, and our own data (the Xiangya cohort) are integrated to reveal their relationships. A scoring system is constructed according to ferroptosis related gene expression, and high scoring samples resistant to ferroptosis and show worse survival outcome than low scoring samples. Notably, most of the high scoring samples are aggressive glioblastoma subtype, mesenchymal, and classical, by calculating RNA velocity. Cross-talk between high scoring glioblastoma cells and immunocytes are explored by R package ‘celltalker’. Ligand–receptor pairs like the TRAIL or TWEAK signaling pathway are identified as novel bridges implying how ferroptosis modulate immunocytes’ function and shape tumor microenvironment. Critically, potential drugs target to high scoring samples are predicted, namely, SNX2112, AZ628, and bortezomib and five compounds from the CellMiner database. Taken together, ferroptosis associates with glioblastoma aggressiveness, cross-talk with immunocytes and offer novel chemotherapy strategy.
CD4+ T Cell Immune Specificity Changes After Vaccination in Healthy And COVID-19 Convalescent Subjects
Authors: Esparcia-Pinedo Laura , Martínez-Fleta Pedro , Ropero Noelia , Vera-Tomé Paula , Reyburn Hugh T. , Casasnovas José M. , Rodríguez Frade José M. , Valés-Gómez Mar , Vilches Carlos , Martín-Gayo Enrique , Muñoz-Calleja Cecilia , Sanchez-Madrid Francisco , Alfranca Arantzazu
Published: January 2022

The immune response promoted by SARS-CoV-2 vaccination is relevant to develop novel vaccines and optimized prevention strategies. We analyzed the adaptive immunity in healthy donors (HD) and convalescent individuals (CD), before and after administering BNT162b2 vaccine. Our results revealed specific changes in CD4+ T cell reactivity profile in vaccinated HD and CD, with an increase in S1 and S2 positive individuals, proportionally higher for S2. On the contrary, NCAP reactivity observed in HD and CD patients was no longer detectable after vaccination. Despite the substantial antibody response in CD, MPro-derived peptides did not elicit CD4+ lymphocyte activation in our assay in either condition. HD presented an increment in anti-S and anti-RBD IgG after first dose vaccination, which increased after the second vaccination. Conversely, anti-S and anti-RBD IgG and IgA titers increased in already positive CD after first dose administration, remaining stable after second dose inoculation. Interestingly, we found a strong significant correlation between S1-induced CD4+ response and anti-S IgA pre-vaccination, which was lost after vaccine administration.
Clinical Utility of Elecsys Anti-SARS-CoV-2 S Assay in COVID-19 Vaccination: An Exploratory Analysis of the mRNA-1273 Phase 1 Trial
Authors: Jochum Simon , Kirste Imke , Hortsch Sayuri , Grunert Veit Peter , Legault Holly , Eichenlaub Udo , Kashlan Basel , Pajon Rolando
Published: January 2022

Background

The ability to quantify an immune response after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential. This study assessed the clinical utility of the quantitative Roche Elecsys® Anti-SARS-CoV-2 S assay (ACOV2S) using samples from the 2019-nCoV vaccine (mRNA-1273) phase 1 trial (NCT04283461).

Methods

Samples from 30 healthy participants, aged 18–55 years, who received two injections with mRNA-1273 at a dose of 25 μg (n=15) or 100 μg (n=15), were collected at Days 1 (first vaccination), 15, 29 (second vaccination), 43 and 57. ACOV2S results (shown in U/mL – equivalent to BAU/mL per the first WHO international standard) were compared with results from ELISAs specific to antibodies against the Spike protein (S-2P) and the receptor binding domain (RBD) as well as neutralization tests including nanoluciferase (nLUC80), live-virus (PRNT80), and a pseudovirus neutralizing antibody assay (PsVNA50).

Results

RBD-specific antibodies were already detectable by ACOV2S at the first time point of assessment (d15 after first vaccination), with seroconversion before in all but two participants (25 μg dose group); all had seroconverted by Day 29. Across all post-baseline visits, geometric mean concentration of antibody levels was 3.27–7.48-fold higher in the 100 μg compared with the 25 μg dose group. ACOV2S measurements were highly correlated with those from RBD ELISA (Pearson’s r=0.938; p<0.0001) and S-2P ELISA (r=0.918; p<0.0001). For both ELISAs, heterogeneous baseline results and smaller increases in antibody levels following the second vs first vaccination compared with ACOV2S were observed. ACOV2S showed absence of any baseline noise indicating high specificity detecting vaccine-induced antibody response. Moderate–strong correlations were observed between ACOV2S and neutralization tests (nLUC80 r=0.933; PsVNA50, r=0.771; PRNT80, r=0.672; all p ≤ 0.0001).

Conclusion

The Elecsys Anti-SARS-CoV-2 S assay (ACOV2S) can be regarded as a highly valuable method to assess and quantify the presence of RBD-directed antibodies against SARS-CoV-2 following vaccination and may indicate the presence of neutralizing antibodies. As a fully automated and standardized method, ACOV2S could qualify as the method of choice for consistent quantification of vaccine-induced humoral response.
A Novel Polymeric Nanohybrid Antimicrobial Engineered by Antimicrobial Peptide MccJ25 and Chitosan Nanoparticles Exerts Strong Antibacterial and Anti-Inflammatory Activities
Authors: Haitao Yu , Yifan Chen , Mingchao Sun , Shuaijuan Han
Published: January 2022

Infection caused by antibiotic-resistant microorganisms (ARMs) has been declared a global threat to public health. Polymeric nanoparticles (PNPs) formed by antimicrobial peptides (AMPs) and synthetic PNPs against ARM infections are emerging. PNPs are also considered to be a promising natural biological preservative that prevents microbial spoilage through food processing and preservation. We engineered CNMs, a novel nanocomposite antibacterial agent based on chitosan nanoparticles and AMP microcin J25. In this study, we aimed to evaluate the comprehensive antimicrobial activity, potential antimicrobial mechanism, and anti-inflammatory activity of CNMs. We demonstrated that CNMs harbor excellent bactericidal activity against clinical foodborne pathogens and ARMs. CNMs caused fast mortality against different growth phases of tetracycline (Tet)-resistant enterotoxigenic E. coli (ETEC) and significantly killed Tet-resistant ETEC in food biological environments. Mechanistically, CNMs have the ability to bind lipopolysaccharides (LPS), neutralize endotoxin, and promote diaphragm permeability by damaging the cell membrane. CNMs did not cause mouse RAW264.7 cell cytotoxicity. Notably, CNMs significantly reduced the cytotoxicity of RAW264.7 macrophages induced by LPS. The LPS-induced inflammatory response was significantly ameliorated by CNMs by reducing the levels of nitric oxide and proinflammatory cytokines, including tumor necrosis factor α, interleukin (IL)-6, IL-8, IL-1β, Toll-like receptor 4, and nuclear factor κB (NF-κB), in LPS-challenged RAW264.7 macrophages. CNMs downregulated the NF-κB and mitogen-activated protein kinase signaling pathways, thereby inhibiting inflammatory responses upon LPS stimulation. Taken together, CNMs could be applied as effective antimicrobial/anti-inflammatory agents with lower cytotoxicity in food, medicine, and agriculture to prevent bacterial contamination and infection, respectively.
TLR7 Signaling Shapes and Maintains Antibody Diversity Upon Virus-Like Particle Immunization
Authors: Chang Xinyue , Krenger Pascal , Krueger Caroline C. , Zha Lisha , Han Jiami , Yermanos Alexander , Roongta Salony , Mohsen Mona O. , Oxenius Annette , Vogel Monique , Bachmann Martin F.
Published: January 2022

Virus-like particles (VLPs) are used in different marketed vaccines and are able to induce potent antibody responses. The innate pattern recognition receptors TLR7/8 recognize single stranded (ss) RNA naturally packaged into some VLPs and have been shown to enhance the production of IgG antibodies upon immunization. Here we demonstrate that, upon immunization with RNA-loaded bacteriophage-derived VLP Qβ, TLR7 signaling accelerates germinal center formation, promotes affinity/avidity maturation of VLP-specific IgG and isotype switching to IgG2b/2c. These findings extrapolated to antigens displayed on Qβ; as Fel d 1, the major cat allergen, chemically attached to Qβ also induced higher affinity/avidity IgG2b/2c antibodies in a TLR7-dependent fashion. Chimeric mice lacking TLR7-expression exclusively in B cells demonstrated that the enhanced IgG responses were driven by a B cell intrinsic mechanism. Importantly, deep sequencing of the BCR repertoire of antigen-specific B cells demonstrated higher diversity in mice with TLR7 signaling in B cells, suggesting that TLR7-signaling drives BCR repertoire development and diversity. Furthermore, the current data demonstrate that high levels of clonal diversity are reached early in the response and maintained by TLR7 signaling. In conclusion, TLR7 signaling enhances levels and quality of IgG antibodies, and this finding has major implications for vaccine design.
First-Line Treatments for Extensive-Stage Small-Cell Lung Cancer With Immune Checkpoint Inhibitors Plus Chemotherapy: A Network Meta-Analysis and Cost-Effectiveness Analysis
Authors: Kang Shuo , Wang Xinchen , Zhang Yue , Zhang Boyuan , Shang Fangjian , Guo Wei
Published: January 2022

Background

Immune checkpoint inhibitors (ICIs) plus chemotherapy were unlikely to be considered cost-effective compared with chemotherapy as the first-line treatment of patients with extensive-stage small-cell lung cancer (ES-SCLC) in China due to its high costs. However, the cost-effectiveness of the comparison between the regimens of ICIs plus chemotherapy were remained unclear yet. The aim of this study was to evaluate the efficacy and cost-effectiveness of ICIs plus chemotherapy as the first-line treatment for ES-SCLC from the perspective of the Chinese healthcare system.

Methods

A network meta-analysis (NMA) was conducted to indirect compare the clinical benefits between the ICIs plus chemotherapy regimens. A decision-analytic model was established to evaluate the cost-effectiveness from the Chinese healthcare system, the clinical efficacy and safety data were obtained from the clinical trials and the results of NMA. Cost and utility values were gathered from the local charges and previously studies. Key outputs of the NMA were overall survival (OS) and progression-free survival (PFS). Incremental cost-effectiveness ratios (ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed to explore the robustness of the model outcomes.

Results

Five clinical trials (IMpower133, CASPIAN, KEYNOTE-604, CA184-156, and EA5161) of 1,255 patients received first-line ICIs plus chemotherapy strategies were analyzed in the NMA. NMA showed that nivolumab plus chemotherapy was ranked higher than other strategies. The cost-effectiveness analysis showed that atezolizumab plus chemotherapy achieved relatively higher health benefits and lower costs. One-way sensitivity analyses revealed that the cost of ICIs had the substantial impact on model outcomes. The probabilistic sensitivity analyses suggested that the probability of atezolizumab plus chemotherapy could be considered cost-effective was more than 50% at the willingness-to-pay (WTP) threshold of $31,313/QALY in China. In scenario analyses, when the price of nivolumab reduced 80%, the probability of nivolumab plus chemotherapy being cost-effective was more than 50%.

Conclusions

The NMA and cost-effectiveness revealed that atezolizumab plus chemotherapy is the most favorable first-line treatment for previously untreated ES-SCLC patients compared other ICIs plus chemotherapy regimens in China. The price reduction of nivolumab would make nivolumab plus chemotherapy be the most cost-effective option in future possible context.
Prognostic Value and Correlation With Tumor Immune Infiltration of a Novel Metabolism-Related Gene Signature in Pancreatic Cancer
Authors: Chen Hui , Zu Fuqiang , Zeng Taofei , Chen Ziang , Wei Jinhong , Liu Peng , Li Zeyu , Zhou Lei , Wang Huaitao , Tan Hao , Tan Xiaodong
Published: January 2022

Background

Energy metabolism has been considered as one of the novel features of neoplasms. This study aimed to establish the prognostic signature for pancreatic cancer (PC) based on metabolism-related genes (MRGs).

Methods

We obtained MRGs from the Molecular Signatures Database (MSigDB) and gene sequence data in the Cancer Genome Atlas (TCGA) databases. Then, differentially expressed MRGs (DE-MRGs) were identified utilizing the R software. We built the prognostic model via multivariate Cox regression. Moreover, external validation of the prognostic signature was also performed. Nomogram was created to predict the overall survival (OS). Next, this study analyzed the prognostic value, clinical relationship, and metabolism-related signaling pathways of the prognostic signature. The role in tumor infiltration was further evaluated. Eventually, the expression level of the three MRGs along with the function of NT5E was validated.

Results

Twenty-two MRGs were chosen, eight of which were identified to be most significantly correlated with the prognosis of PC. Meanwhile, a 3-MRG prognostic signature was established, and we verified this prognostic model in two separate external cohorts. What is more, the nomogram was used to predict 1-/2-/3-year OS of PC patients. In addition, the immune cell infiltration and expression of immune checkpoint were significantly influenced by the risk score. Finally, three MRGs were highly expressed in PC cell lines, and NT5E was associated with the proliferation and migration ability of PC.

Conclusion

To sum up, the study established and validated a 3-MRG prognostic signature for PC, and the signature could be utilized to predict the prognosis and assist the individualized clinical management of patients with PC.
Sohlh2 Inhibits the Malignant Progression of Renal Cell Carcinoma by Upregulating Klotho via DNMT3a
Authors: Liu Yang , Cui Weiwei , Zhang Ruihong , Zhi Sujuan , Liu Lanlan , Liu Xuyue , Feng Xiaoning , Chen Yanru , Zhang Xiaoli , Hao Jing
Published: January 2022

Background

Renal cell carcinoma is the most common malignant tumor of the kidney. The 5-year survival of renal cell carcinoma with distant metastasis is very low. Sohlh2 is a newly discovered tumor suppressor gene playing inhibitory roles in a variety of tumors, but its role in renal cell carcinoma has not been reported.

Methods

To clarify the role of Sohlh2 in the occurrence and development of renal cell carcinoma, we constructed stably transfected human renal cell carcinoma cell lines with Sohlh2 overexpression and Sohlh2 knockdown, separately. First, we studied the effects of Sohlh2 on proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of renal cell carcinoma cells in vitro and in vivo. Then, we detected whether Sohlh2 functions through DNMT3a/Klotho using Western blotting, qPCR, and Cell Counting Kit-8 (CCK-8) assay. Finally, we collected 40 resected renal cell carcinoma samples to study the relevance between Sohlh2, DNMT3a, and Klotho by immunohistochemistry.

Results

Our results showed that Sohlh2 was downregulated in renal cell carcinoma, and its expression level was negatively correlated with tumor staging. Both in vitro and in vivo experiments confirmed that Sohlh2 overexpression inhibited the proliferation, migration, invasion, metastasis, and EMT of renal cell carcinoma. Sohlh2 functions through demethylation of Klotho by downregulating the expression of DNA methyltransferase of DNMT3a. In renal cell carcinoma, Sohlh2 was positively correlated with Klotho and negatively correlated with DNMT3a.

Conclusion

Sohlh2 functions as a tumor suppressor gene in renal cell carcinoma by demethylation of Klotho via DNMT3a. Sohlh2 correlated with Klotho positively and with DNMT3a negatively in renal cell carcinoma. Our study suggests that Sohlh2 and DNMT3a/Klotho can be used as potential targets for the clinical treatment of renal cell carcinoma.