bluuebunny/crossref_metadata_2025 huggingface dataset:
Controversias frente al tratamiento farmacológico del TDAH entre padres y educadores de niños y adolescentes de Bogotá
Authors: Vargas Rodríguez Angela María
Published: May 2021

Se presentan resultados parciales de la investigación titulada “Narrativas de niños y niñas sobre el trastorno de hiperactividad” en relación con las experiencias subjetivas, así como saberes, creencias y prácticas alrededor del tratamiento farmacológico del TDAH en un grupo de padres y educadores de niños y niñas con dicho diagnóstico en la ciudad de Bogotá, Colombia. La información fue recolectada a través de entrevistas en profundidad y fue organizada y analizada a partir de seis categorías emergentes: actitud, conocimientos, efectividad, efectos secundarios, función y responsabilidad. Los resultados muestran que las ideas, creencias y prácticas alrededor del tratamiento farmacológico se organizan de acuerdo con el rol y el contexto del participante, respondiendo a procesos sociales de medicalización de la vida educativa.
Riesgos psicosociales: Análisis sociodemográfico y sociolaboral en una universidad privada ecuatoriana
Authors: Ramírez-Ocaña Ximena Alexandra , Zumárraga-Espinosa Marcos , Segovia-Marín Johanna Valeria , Lima-Acosta Edith Evelyn , Pillajo-Salcedo Guillermo Marcelo
Published: May 2021

Las condiciones actuales de trabajo demandan mayor énfasis en el estudio de los riesgos psicosociales laborales. La presente investigación evalúa dichos riesgos a partir de una muestra conformada por 559 docentes y administrativos de una universidad privada ecuatoriana, con el objetivo de indagar sobre las especificidades de los factores de riesgo psicosocial en relación con las variables sociodemográficas y sociolaborales, para proponer un perfil de riesgo psicosocial. El instrumento utilizado fue F-PSICO 3.1 y posteriormente a través de regresiones logísticas se analizó el efecto de dichas variables para identificar posibles factores de riesgo o de protección.  Los hallazgos evidencian que la exposición desfavorable a factores de riesgo psicosocial se incrementa en el personal que tiene ciertas características como: ser docente, con jornada de tiempo completo, ser menor de 35 años, contar con menos de 5 años de antigüedad en la institución y ser mujer. A modo de conclusión, al menos el 25% del personal percibe alguno de los factores psicosociales evaluados de una manera desfavorable.
Perfeccionismo y vida académica: un estudio correlacional en estudiantes de psicología
Authors: Aguilar Durán Leonardo Andrés
Published: May 2021

El objetivo de este estudio fue analizar la relación entre el perfeccionismo y algunas variables académicas (estrés, locus de control y rendimiento académico) en estudiantes universitarios. Se trató de una investigación cuantitativa con alcance descriptivo-correlacional y diseño transversal. Participaron 216 estudiantes de psicología de la Universidad Central de Venezuela, 126 mujeres (58.3 %) y 90 hombres (41.7 %), con edad promedio de 24.5 años (DE = 7.78). Los estudiantes completaron los siguientes instrumentos: el Inventario de Perfeccionismo Académico, el Cuestionario de Estrés Académico y el Inventario de Locus de Control Académico. Con el fin de conocer el rendimiento de los estudiantes, se consultó el historial académico de estos. El perfeccionismo académico y su dominio autorientado correlacionaron positivamente con el estrés ante las evaluaciones; el perfeccionismo socialmente orientado se asoció en forma positiva con el estrés académico y con sus facetas de estrés general, ante los exámenes y ante responsabilidades académicas. La única correlación significativa entre el perfeccionismo y el locus de control se dio entre los estándares perfeccionistas orientados a sí mismo y la atribución interna del éxito académico. El perfeccionismo y sus dimensiones hacia sí mismo y hacia los otros mostraron relaciones positivas con los promedios de notas simple y ponderado aprobado. Se concluye que, hasta cierto punto, el perfeccionismo pareciera estar involucrado en la consecución de una mejor actuación académica, lo que se discute en el marco de la visión negativa que sobre el perfeccionismo impera (como variable vinculada al malestar psicológico).
Deterioro cognitivo y recuperación espontánea en pacientes con diagnóstico de Consumo Perjudicial o Síndrome de Dependencia Alcohólico
Authors: Lage Manuel , Risso Alicia
Published: May 2021

El objetivo de este trabajo era conocer el alcance del deterioro de las funciones cognitivas debido al consumo abusivo de alcohol y su posible recuperación espontánea, así como observar la evolución temporal de esta recuperación, desde el inicio hasta los 24 meses de la abstinencia. Participaron voluntariamente 100 pacientes de ambos sexos, en tratamiento de deshabituación de consumo perjudicial o síndrome de dependencia alcohólico, agrupados en cohortes según tiempo de abstinencia. El grupo control estuvo formado por 20 personas sin antecedentes de alcoholismo, equiparadas con los pacientes en las variables edad, sexo y nivel de estudios. Los datos socio-demográficos y clínicos se recogieron con una anamnesis protocolizada, mientras que para evaluar el deterioro cognitivo se emplearon el Mini-Mental State Examination (MMSE) y el Montreal Cognitive Assessment (MOCA), en sus versiones al español. Para cada participante se obtuvieron 8 variables clínicas y socio-demográficas y 27 variables cognitivas. Se observaron diferencias significativas entre las medidas de las mismas variables cognitivas proporcionadas por ambos instrumentos, siendo más discriminativo el MOCA. Los resultados mostraron que el deterioro y la recuperación espontánea varían para las distintas funciones cognitivas y que los cambios más significativos se dan seis meses después de iniciada la deshabituación y entre los 18 y 24 meses. En base a la evidencia obtenida, atención, memoria y lenguaje se perfilan como las funciones más susceptibles de beneficiarse de un programa de rehabilitación cognitiva, que convendría implementar entre los 6 y 18 meses de abstinencia.
A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets
Authors: Wu Jin Patricia , Rousset Nassim , Hierlemann Andreas , Misun Patrick M.
Published: May 2021

Islet perifusion systems can be used to monitor the highly dynamic insulin release of pancreatic islets in glucose-stimulated insulin secretion (GSIS) assays. Here, we present a new generation of the microfluidic hanging-drop-based islet perifusion platform that was developed to study the alterations in insulin secretion dynamics from single pancreatic islet microtissues at high temporal resolution. The platform was completely redesigned to increase experimental throughput and to reduce operational complexity. The experimental throughput was increased fourfold by implementing a network of interconnected hanging drops, which allows for performing GSIS assays with four individual islet microtissues in parallel with a sampling interval of 30 s. We introduced a self-regulating drop-height mechanism that enables continuous flow and maintains a constant liquid volume in the chip, which enables simple and robust operation. Upon glucose stimulation, reproducible biphasic insulin release was simultaneously observed from all islets in the system. The measured insulin concentrations showed low sample-to-sample variation as a consequence of precise liquid handling with stable drop volumes, equal flow rates in the channels, and accurately controlled sampling volumes in all four drops. The presented device will be a valuable tool in islet and diabetes research for studying dynamic insulin secretion from individual pancreatic islets.
Understanding the Adult Mammalian Heart at Single-Cell RNA-Seq Resolution
Authors: Marín-Sedeño Ernesto , de Morentin Xabier Martínez , Pérez-Pomares Jose M. , Gómez-Cabrero David , Ruiz-Villalba Adrián
Published: May 2021

During the last decade, extensive efforts have been made to comprehend cardiac cell genetic and functional diversity. Such knowledge allows for the definition of the cardiac cellular interactome as a reasonable strategy to increase our understanding of the normal and pathologic heart. Previous experimental approaches including cell lineage tracing, flow cytometry, and bulk RNA-Seq have often tackled the analysis of cardiac cell diversity as based on the assumption that cell types can be identified by the expression of a single gene. More recently, however, the emergence of single-cell RNA-Seq technology has led us to explore the diversity of individual cells, enabling the cardiovascular research community to redefine cardiac cell subpopulations and identify relevant ones, and even novel cell types, through their cell-specific transcriptomic signatures in an unbiased manner. These findings are changing our understanding of cell composition and in consequence the identification of potential therapeutic targets for different cardiac diseases. In this review, we provide an overview of the continuously changing cardiac cellular landscape, traveling from the pre-single-cell RNA-Seq times to the single cell-RNA-Seq revolution, and discuss the utilities and limitations of this technology.
A Putative Lipid-Associating Motif in the West Nile Virus NS4A Protein Is Required for Efficient Virus Replication
Authors: Mikulasova Andrea , Gillespie Leah K. , Ambrose Rebecca L. , Aktepe Turgut E. , Trenerry Alice M. , Liebscher Susann , Mackenzie Jason M.
Published: May 2021

Flavivirus replication is intimately associated with re-organized cellular membranes. These virus-induced changes in membrane architecture form three distinct membranous “organelles” that have specific functions during the flavivirus life cycle. One of these structures is the replication complex in which the flaviviral RNA is replicated to produce progeny genomes. We have previously observed that this process is strictly dependent on cellular cholesterol. In this study we have identified a putative cholesterol recognition/interaction amino acid consensus (CRAC) motif within the West Nile virus strain Kunjin virus (WNVKUN) NS4A protein. Site-directed mutagenesis of this motif within a WNVKUN infectious clone severely attenuated virus replication and the capacity of the mutant viruses to form the replication complex. Replication of the mutant viruses also displayed reduced co-localization with cellular markers recruited to replication sites during wild-type virus replication. In addition, we observed that the mutant viruses were significantly impaired in their ability to remodel cytoplasmic membranes. However, after extensive analysis we are unable to conclusively reveal a role for the CRAC motif in direct cholesterol binding to NS4A, suggesting additional complex lipid-protein and protein-protein interactions. We believe this study highlights the crucial role for this region within NS4A protein in recruitment of cellular and viral proteins to specialized subdomains on membrane platforms to promote efficient virus replication.
Treatment of Heart Failure With Mid-Range Ejection Fraction: A Summary of Current Evidence
Authors: Ma Teng , Su Yang , Song Jing , Xu Dachun
Published: May 2021

Heart failure (HF) is a complex syndrome causing heavy burden in public health, and the modern objective assessment of it is based on the left ventricular ejection fraction (LVEF). In 2016, the European Society of Cardiology classified the “gray area” in HF with LVEF of 40–49% as a new HF phenotype (HFmrEF) in an attempt to uncover the specific characteristics and treatment of these patients, which might recover or worsen to HFpEF or HFrEF, respectively, or conversely from these two subtypes. Up to now, many studies have demonstrated that patients with HFmrEF would possibly gain more benefits from some targeted therapies with HFrEF than those with HFpEF. This review summarizes what is known about the findings in the treatment of HFmrEF and discusses what should be done to better define the peculiar HF phenotype in the future.
Aging Reduces Insulin Clearance in Mice
Authors: Marmentini Carine , Soares Gabriela M. , Bronczek Gabriela A. , Piovan Silvano , Mareze-Costa Cecília E. , Carneiro Everardo M. , Boschero Antonio C. , Kurauti Mirian A.
Published: May 2021

Hyperinsulinemia is frequently associated with aging and may cause insulin resistance in elderly. Since insulin secretion and clearance decline with age, hyperinsulinemia seems to be maintained, primarily, due to a decrease in the insulin clearance. To investigate these aging effects, 3- and 18-month-old male C57BL/6 mice were subjected to intraperitoneal glucose and insulin tolerance tests (ipGTT and ipITT) and, during the ipGTT, plasma c-peptide and insulin were measure to evaluate in vivo insulin clearance. Glucose-stimulated insulin secretion in isolated pancreatic islets was also assessed, and liver samples were collected for molecular analyses (western blot). Although insulin sensitivity was not altered in the old mice, glucose tolerance, paradoxically, seems to be increased, accompanied by higher plasma insulin, during ipGTT. While insulin secretion did not increase, insulin clearance was reduced in the old mice, as suggested by the lower c-peptide:insulin ratio, observed during ipGTT. Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) and insulin-degrading enzyme (IDE), as well as the activity of this enzyme, were reduced in the liver of old mice, justifying the decreased insulin clearance observed in these mice. Therefore, loss of hepatic CEACAM1 and IDE function may be directly related to the decline in insulin clearance during aging.
Data-Driven Machine Learning for Fault Detection and Diagnosis in Nuclear Power Plants: A Review
Authors: Hu Guang , Zhou Taotao , Liu Qianfeng
Published: May 2021

Data-driven machine learning (DDML) methods for the fault diagnosis and detection (FDD) in the nuclear power plant (NPP) are of emerging interest in the recent years. However, there still lacks research on comprehensive reviewing the state-of-the-art progress on the DDML for the FDD in the NPP. In this review, the classifications, principles, and characteristics of the DDML are firstly introduced, which include the supervised learning type, unsupervised learning type, and so on. Then, the latest applications of the DDML for the FDD, which consist of the reactor system, reactor component, and reactor condition monitoring are illustrated, which can better predict the NPP behaviors. Lastly, the future development of the DDML for the FDD in the NPP is concluded.
Association of CASR, CALCR, and ORAI1 Genes Polymorphisms With the Calcium Urolithiasis Development in Russian Population
Authors: Litvinova Maria M. , Khafizov Kamil , Korchagin Vitaly I. , Speranskaya Anna S. , Asanov Aliy Yu. , Matsvay Alina D. , Kiselev Daniil A. , Svetlichnaya Diana V. , Nuralieva Sevda Z. , Moskalev Alexey A. , Filippova Tamara V.
Published: May 2021

Kidney stone disease is an urgent medical and social problem. Genetic factors play an important role in the disease development. This study aims to establish an association between polymorphisms in genes coding for proteins involved in calcium metabolism and the development of calcium urolithiasis in Russian population. In this case-control study, we investigated 50 patients with calcium urolithiasis (experimental group) and 50 persons lacking signs of kidney stone disease (control group). For molecular genetic analysis we used a previously developed gene panel consisting of 33 polymorphisms in 15 genes involved in calcium metabolism: VDR, CASR, CALCR, OPN, MGP, PLAU, AQP1, DGKH, SLC34A1, CLDN14, TRPV6, KLOTHO, ORAI1, ALPL, and RGS14. High-throughput target sequencing was utilized to study the loci of interest. Odds ratios and 95% confidence intervals were used to estimate the association between each SNP and risk of urolithiasis development. Multifactor dimensionality reduction analysis was also carried out to analyze the gene-gene interaction. We found statistically significant (unadjusted p-value < 0.05) associations between calcium urolithiasis and the polymorphisms in the following genes: CASR rs1042636 (OR = 3.18 for allele A), CALCR rs1801197 (OR = 6.84 for allele A), and ORAI1 rs6486795 (OR = 2.25 for allele C). The maximum OR was shown for AA genotypes in loci rs1042636 (CASR) and rs1801197 (CALCR) (OR = 4.71, OR = 11.8, respectively). After adjustment by Benjamini-Hochberg FDR we found only CALCR (rs1801197) was significantly associated with the risk of calcium urolithiasis development. There was no relationship between recurrent course of the disease and family history of urolithiasis in investigated patients. Thus we found a statistically significant association of polymorphism rs1801197 (gene CALCR) with calcium urolithiasis in Russian population.
Identification of Potential Pathogenic Super-Enhancers-Driven Genes in Pulmonary Fibrosis
Authors: Li Hang , Zhao Caiping , Li Zeli , Yao Kainan , Zhang Jingjing , Si Wenwen , Liu Xiaohong , Jiang Yong , Zhu Meiling
Published: May 2021

Abnormal fibroblast differentiation into myofibroblast is a crucial pathological mechanism of pulmonary fibrosis (PF). Super-enhancers, a newly discovered cluster of regulatory elements, are regarded as the regulators of cell identity. We speculate that abnormal activation of super-enhancers must be involved in the pathological process of PF. This study aims to identify potential pathogenic super-enhancer-driven genes in PF. Differentially expressed genes (DEGs) in PF mouse lungs were identified from a GEO dataset (GDS1492). We collected super-enhancers and their associated genes in human lung fibroblasts and mouse embryonic fibroblasts from SEA version 3.0, a network database that provides comprehensive information on super-enhancers. We crosslinked upregulated DEGs and super-enhancer-associated genes in fibroblasts to predict potential super-enhancer-driven pathogenic genes in PF. A total of 25 genes formed an overlap, and the protein-protein interaction network of these genes was constructed by the STRING database. An interaction network of transcription factors (TFs), super-enhancers, and associated genes was constructed using the Cytoscape software. Gene enrichment analyses, including KEGG pathway and GO analysis, were performed for these genes. Latent transforming growth factor beta (TGF-β) binding protein 2 (LTBP2), one of the predicted super-enhancer-driven pathogenic genes, was used to verify the predicted network’s accuracy. LTBP2 was upregulated in the lungs of the bleomycin-induced PF mouse model and TGF-β1-stimulated mouse and human fibroblasts. Myc is one of the TFs binding to the LTBP2 super-enhancer. Knockout of super-enhancer sequences with a CRISPR/Cas9 plasmid or inhibition of Myc all decreased TGF-β1-induced LTBP2 expression in NIH/3 T3 cells. Identifying and interfering super-enhancers might be a new way to explore possible therapeutic methods for PF.
New Insights Into Structure and Function of TIFY Genes in Zea mays and Solanum lycopersicum: A Genome-Wide Comprehensive Analysis
Authors: Heidari Parviz , Faraji Sahar , Ahmadizadeh Mostafa , Ahmar Sunny , Mora-Poblete Freddy
Published: May 2021

TheTIFYgene family, a key plant-specific transcription factor (TF) family, is involved in diverse biological processes including plant defense and growth regulation. Despite TIFY proteins being reported in some plant species, a genome-wide comparative and comprehensive analysis ofTIFYgenes in plant species can reveal more details. In the current study, the members of theTIFYgene family were significantly increased by the identification of 18 and six new members using maize and tomato reference genomes, respectively. Thus, a genome-wide comparative analysis of theTIFYgene family between 48 tomato (Solanum lycopersicum, a dicot plant) genes and 26 maize (Zea mays, a monocot plant) genes was performed in terms of sequence structure, phylogenetics, expression, regulatory systems, and protein interaction. The identified TIFYs were clustered into four subfamilies, namely, TIFY-S, JAZ, ZML, and PPD. The PPD subfamily was only detected in tomato. Within the context of the biological process,TIFYfamily genes in both studied plant species are predicted to be involved in various important processes, such as reproduction, metabolic processes, responses to stresses, and cell signaling. The Ka/Ks ratios of the duplicated paralogous gene pairs indicate that all of the duplicated pairs in theTIFYgene family of tomato have been influenced by an intense purifying selection, whereas in the maize genome, there are three duplicated blocks containing Ka/Ks > 1, which are implicated in evolution with positive selection. The amino acid residues present in the active site pocket of TIFY proteins partially differ in each subfamily, although the Mg or Ca ions exist heterogeneously in the centers of the active sites of all the predicted TIFY protein models. Based on the expression profiles ofTIFYgenes in both plant species, JAZ subfamily proteins are more associated with the response to abiotic and biotic stresses than other subfamilies. In conclusion, globally scrutinizing and comparing the maize and tomatoTIFYgenes showed thatTIFYgenes play a critical role in cell reproduction, plant growth, and responses to stress conditions, and the conserved regulatory mechanisms may control their expression.
Nanoparticle Delivery of CRISPR/Cas9 for Genome Editing
Authors: Duan Li , Ouyang Kan , Xu Xiao , Xu Limei , Wen Caining , Zhou Xiaoying , Qin Zhuan , Xu Zhiyi , Sun Wei , Liang Yujie
Published: May 2021

The emerging clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated system (Cas) gene-editing system represents a promising tool for genome manipulation. However, its low intracellular delivery efficiency severely compromises its use and potency for clinical applications. Nanocarriers, such as liposomes, polymers, and inorganic nanoparticles, have shown great potential for gene delivery. The remarkable development of nanoparticles as non-viral carriers for the delivery of the CRISPR/Cas9 system has shown great promise for therapeutic applications. In this review, we briefly summarize the delivery components of the CRISPR/Cas9 system and report on the progress of nano-system development for CRISPR/Cas9 delivery. We also compare the advantages of various nano-delivery systems and their applications to deliver CRISPR/Cas9 for disease treatment. Nano-delivery systems can be modified to fulfill the tasks of targeting cells or tissues. We primarily emphasize the novel exosome-based CRISPR/Cas9 delivery system. Overall, we review the challenges, development trends, and application prospects of nanoparticle-based technology for CRISPR/Cas9 delivery.
Intra-Abdominal Lipopolysaccharide Clearance and Inactivation in Peritonitis: Key Roles for Lipoproteins and the Phospholipid Transfer Protein
Authors: Nguyen Maxime , Pallot Gaëtan , Jalil Antoine , Tavernier Annabelle , Dusuel Aloïs , Le Guern Naig , Lagrost Laurent , Pais de Barros Jean-Paul , Choubley Hélène , Bergas Victoria , Guinot Pierre-Grégoire , Masson David , Bouhemad Belaid , Gautier Thomas
Published: May 2021

Introduction

During peritonitis, lipopolysaccharides (LPS) cross the peritoneum and pass through the liver before reaching the central compartment. The aim of the present study was to investigate the role of lipoproteins and phospholipid transfer protein (PLTP) in the early stages of LPS detoxification.

Material and Methods

Peritonitis was induced by intra-peritoneal injection of LPS in mice. We analyzed peritoneal fluid, portal and central blood. Lipoprotein fractions were obtained by ultracentrifugation and fast protein liquid chromatography. LPS concentration and activity were measured by liquid chromatography coupled with mass spectrometry and limulus amoebocyte lysate. Wild-type mice were compared to mice knocked out for PLTP.

Results

In mice expressing PLTP, LPS was able to bind to HDL in the peritoneal compartment, and this was maintained in plasma from portal and central blood. A hepatic first-pass effect of HDL-bound LPS was observed in wild-type mice. LPS binding to HDL resulted in an early arrival of inactive LPS in the central blood of wild-type mice.

Conclusion

PLTP promotes LPS peritoneal clearance and neutralization in a model of peritonitis. This mechanism involves the early binding of LPS to lipoproteins inside the peritoneal cavity, which promotes LPS translocation through the peritoneum and its uptake by the liver.
Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function
Authors: Cai Zuchao , Lim David , Liu Guochao , Chen Chen , Jin Liya , Duan Wenhua , Ding Chenxia , Sun Qingjie , Peng Junxuan , Dong Chao , Zhang Fengmei , Feng Zhihui
Published: May 2021

Inadequate sustained immune activation and tumor recurrence are major limitations of radiotherapy (RT), sustained and targeted activation of the tumor microenvironment can overcome this obstacle. Here, by two models of a primary rat breast cancer and cell co-culture, we demonstrated that valproic acid (VPA) and its derivative (HPTA) are effective immune activators for RT to inhibit tumor growth by inducing myeloid-derived macrophages and polarizing them toward the M1 phenotype, thus elevate the expression of cytokines such as IL-12, IL-6, IFN-γ and TNF-α during the early stage of the combination treatment. Meanwhile, activated CD8+ T cells increased, angiogenesis of tumors is inhibited, and the vasculature becomes sparse. Furthermore, it was suggested that VPA/HPTA can enhance the effects of RT via macrophage-mediated and macrophage-CD8+ T cell-mediated anti-tumor immunity. The combination of VPA/HPTA and RT treatment slowed the growth of tumors and prolong the anti-tumor effect by continuously maintaining the activated immune response. These are promising findings for the development of new effective, low-cost concurrent cancer therapy.
Dysfunction of Decidual Macrophages Is a Potential Risk Factor in the Occurrence of Preeclampsia
Authors: Rong Miaomiao , Yan Xingyu , Zhang Hongya , Zhou Chan , Zhang Cong
Published: May 2021

Preeclampsia is a multi-factorial and multi-genetic disorder that affects more than eight million mother and baby pairs each year. Currently, most of the attention to the pathogenesis of preeclampsia has been focused on placenta, but recent progresses suggest that excellent decidualization lays foundation for placentation and growth. Moreover, preeclampsia is associated with an imbalance in immunoregulatory mechanisms, however, how the immune regulatory system in the decidua affects preeclampsia is still unclear. In our study, after intersecting the genes of differentially expressed between preeclampsia and the control gotten by conventional expression profile analysis and the genes contained in the ligand receptor network, we found eight differentially expressed genes in a ligand-receptor relationship, and the eight genes have a characteristic: most of them participate in the interaction between decidual macrophages and other decidual immune cells. The results of single-cell sequencing of decidual cells further demonstrated that decidual macrophages affect the functions of other immune cells through export. As a result, abnormal gene expression affects the export function of decidual macrophages, which in turn affects the interaction of decidual macrophages with other immune cells, thereby destroying the original immune regulation mechanism, and ultimately leading to the occurrence of preeclampsia.
Circulating Type I Interferon Levels and COVID-19 Severity: A Systematic Review and Meta-Analysis
Authors: da Silva Rafaela Pires , Gonçalves João Ismael Budelon , Zanin Rafael Fernandes , Schuch Felipe Barreto , de Souza Ana Paula Duarte
Published: May 2021

Introduction

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resulting in a range of clinical manifestations and outcomes. Laboratory and immunological alterations have been considered as potential markers of disease severity and clinical evolution. Type I interferons (IFN-I), mainly represented by IFN-α and β, are a group of cytokines with an important function in antiviral responses and have played a complex role in COVID-19. Some studies have demonstrated that IFN-I levels and interferon response is elevated in mild cases, while other studies have noted this in severe cases. The involvement of IFN-I on the pathogenesis and outcomes of SARS-CoV-2 infection remains unclear. In this study, we summarize the available evidence of the association of plasma protein levels of type I IFN with the severity of COVID-19.

Methods

The PRISMA checklist guided the reporting of the data. A systematic search of the MEDLINE (PubMed), EMBASE, and Web of Science databases was performed up to March of 2021, looking for articles that evaluated plasma protein levels of IFN-I in mild, severe, or critical COVID-19 patients. Comparative meta-analyses with random effects were performed to compare the standardized mean differences in plasma protein levels of IFN-I of mild versus severe and mild versus critical patients. Meta-regressions were performed to test the moderating role of age, sex, time that the IFN-I was measured, and limit of detection of the assay used in the difference between the means.

Results

There was no significant difference in plasma levels of IFN-α when comparing between mild and severe patients (SMD = -0.236, 95% CI -0.645 to 0.173, p = 0.258, I2 = 82.11), nor when comparing between patients mild and critical (SMD = 0.203, 95% CI -0.363 to 0.770, p = 0.481, I2 = 64.06). However, there was a significant difference between healthy individuals and patients with mild disease (SMD = 0.447, 95% CI 0.085 to 0.810, p = 0.016, I2 = 62.89).

Conclusions

Peripheral IFN-α cannot be used as a severity marker as it does not determine the clinical status presented by COVID-19 patients.
Citizen-Sourced Sightings and Underwater Photography Reveal Novel Insights About Green Sea Turtle Distribution and Ecology in Southern California
Authors: Hanna Megan E. , Chandler Erin M. , Semmens Brice X. , Eguchi Tomoharu , Lemons Garrett E. , Seminoff Jeffrey A.
Published: May 2021

East Pacific (EP) green turtles (Chelonia mydas) have undergone substantial population recovery over the last two decades owing to holistic protection at nesting beaches and foraging areas. At the northern end of their range in southern California United States, green turtles have been seen in more areas and in greater numbers since 2014 than before as a result. A resident population of green turtles has established near La Jolla Shores (LJS), a protected site with daily marine tourism (e.g., kayakers, snorkelers, divers). To study this local aggregation, innovative and non-invasive methods were required because the traditional capture-recapture methods were infeasible due to public relations sensitivities. Green turtle habituation to humans at this site has created a unique opportunity for citizen-based science using underwater photography to document turtles and their surroundings. We obtained 309 usable photographs of local green turtles from members of the dive/snorkel community in LJS. Photos were taken from April 2016 to June 2019. Images were processed in Hotspotter—a patterned species instance recognition software—to identify seven individuals, five of which were consistently photographed throughout that period. These images helped infer minimum residency duration (MRD), seasonal differences in algal coverage on the carapace, habitat association, behavioral patterns, and diet. Mean MRD was 424 days (SE = 131 days, calculated from entire population, n = 7), during which turtles were active in 82.8% of the photographs; the remainder of the photographs depicted foraging (14.9%) or resting behavior (2.3%). Green turtles were seen foraging in water temperatures as low as 15.8°C, the lowest recorded temperature for foraging green turtles documented in literature. Additional opportunistic observational platforms were used to look at trends of increasing green turtle abundance in southern California since 2015 that supported the arrival of a new aggregation of green turtles in LJS. Our use of citizen-sourced photographs confirms the presence of a resident aggregation of green turtles in LJS. Existence of green turtles and other protected species in highly populated areas provide excellent opportunities to educate beachgoers and seafarers about conservation of these species. This study also highlights the value of citizen-based science in areas where traditional research techniques are ill-suited.
Factors Determining the Susceptibility of Bacteria to Antibacterial Photodynamic Inactivation
Authors: Rapacka-Zdończyk Aleksandra , Woźniak Agata , Michalska Klaudia , Pierański Michał , Ogonowska Patrycja , Grinholc Mariusz , Nakonieczna Joanna
Published: May 2021

Photodynamic inactivation of microorganisms (aPDI) is an excellent method to destroy antibiotic-resistant microbial isolates. The use of an exogenous photosensitizer or irradiation of microbial cells already equipped with endogenous photosensitizers makes aPDI a convenient tool for treating the infections whenever technical light delivery is possible. Currently, aPDI research carried out on a vast repertoire of depending on the photosensitizer used, the target microorganism, and the light delivery system shows efficacy mostly on in vitro models. The search for mechanisms underlying different responses to photodynamic inactivation of microorganisms is an essential issue in aPDI because one niche (e.g., infection site in a human body) may have bacterial subpopulations that will exhibit different susceptibility. Rapidly growing bacteria are probably more susceptible to aPDI than persister cells. Some subpopulations can produce more antioxidant enzymes or have better performance due to efficient efflux pumps. The ultimate goal was and still is to identify and characterize molecular features that drive the efficacy of antimicrobial photodynamic inactivation. To this end, we examined several genetic and biochemical characteristics, including the presence of individual genetic elements, protein activity, cell membrane content and its physical properties, the localization of the photosensitizer, with the result that some of them are important and others do not appear to play a crucial role in the process of aPDI. In the review, we would like to provide an overview of the factors studied so far in our group and others that contributed to the aPDI process at the cellular level. We want to challenge the question, is there a general pattern of molecular characterization of aPDI effectiveness? Or is it more likely that a photosensitizer-specific pattern of molecular characteristics of aPDI efficacy will occur?
Clinical and Laboratory Findings of COVID-19 in High-Altitude Inhabitants of Saudi Arabia
Authors: Abdelsalam Mostafa , Althaqafi Raad M. M. , Assiri Sara A. , Althagafi Taghreed M. , Althagafi Saleh M. , Fouda Ahmed Y. , Ramadan Ahmed , Rabah Mohammed , Ahmed Reham M. , Ibrahim Zein S. , Nemenqani Dalal M. , Alghamdi Ahmed N. , Al Aboud Daifullah , Abdel-Moneim Ahmed S. , Alsulaimani Adnan A.
Published: May 2021

Background: SARS-CoV-2, the causative agent of COVID-19, continues to cause a worldwide pandemic, with more than 147 million being affected globally as of this writing. People's responses to COVID-19 range from asymptomatic to severe, and the disease is sometimes fatal. Its severity is affected by different factors and comorbidities of the infected patients. Living at a high altitude could be another factor that affects the severity of the disease in infected patients.

Methods: In the present study, we have analyzed the clinical, laboratory, and radiological findings of COVID-19-infected patients in Taif, a high-altitude region of Saudi Arabia. In addition, we compared matched diseased subjects to those living at sea level. We hypothesized that people living in high-altitude locations are prone to develop a more severe form of COVID-19 than those living at sea level.

Results: Age and a high Charlson comorbidity score were associated with increased numbers of intensive care unit (ICU) admissions and mortality among COVID-19 patients. These ICU admissions and fatalities were found mainly in patients with comorbidities. Rates of leukocytosis, neutrophilia, higher D-dimer, ferritin, and highly sensitive C-reactive protein (CRP) were significantly higher in ICU patients. CRP was the most independent of the laboratory biomarkers found to be potential predictors of death. COVID-19 patients who live at higher altitude developed a less severe form of the disease and had a lower mortality rate, in comparison to matched subjects living at sea level.

Conclusion: CRP and Charlson comorbidity scores can be considered predictive of disease severity. People living at higher altitudes developed less severe forms of COVID-19 disease than those living at sea level, due to a not-yet-known mechanism.
Bioethanol Production From H2/CO2 by Solventogenesis Using Anaerobic Granular Sludge: Effect of Process Parameters
Authors: He Yaxue , Cassarini Chiara , Lens Piet N. L.
Published: May 2021

Graphical Abstract

Bioethanol from H2/CO2 by solventogenesis using anaerobic granular sludges.
Altered Neurovascular Coupling in Subcortical Ischemic Vascular Disease
Authors: Liu Xiaoshuang , Cheng Runtian , Chen Li , Gong Junwei , Luo Tianyou , Lv Fajin
Published: May 2021

Patients with subcortical ischemic vascular disease (SIVD) exhibit a high risk of cognitive impairment that might be caused by neurologic deficits and vascular injuries. However, the mechanism remains unknown. In current study, 24 normal controls (NC) and 54 SIVD patients, including 26 SIVD patients with no cognitive impairment (SIVD-NCI) and 28 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the resting-state functional MRI (rs-fMRI) and neuropsychological assessments. We combined regional homogeneity (ReHo) and cerebral blood flow (CBF) by using the global ReHo-CBF correlations coefficient and the ReHo/CBF ratio to detect the inner link between neuronal activity and vascular responses. Correlations between the ReHo/CBF ratio and neuropsychological assessments were explored in patients with SIVD. As a result, we identified significantly decreased global ReHo-CBF coupling in the SIVD-NCI group and SIVD- MCI group with respect to the NC. The SIVD-MCI group showed more serious decoupling of the global ReHo-CBF correlation. We also found a significantly abnormal ReHo/CBF ratio predominantly located in cognitive-related brain regions, including the left insula, right middle temporal gyrus, right precuneus, left precentral gyrus, and left inferior parietal lobule but not the supramarginal and angular gyri. The SIVD-MCI group showed more severe disorders of neurovascular coupling than the other two groups. Moreover, the ReHo/CBF ratio in the left precentral gyrus of the SIVD-NCI group exhibited a positive correlation with the MMSE scores. These findings suggested that patients with SIVD show abnormal neurovascular coupling at the early stage of the disease and during disease development. It might be associated with disease severity and cognitive impairment. Neurovascular decoupling in brain may be a possible neuropathological mechanism of SIVD.
Fatigue After Aneurysmal Subarachnoid Hemorrhage: Clinical Characteristics and Associated Factors in Patients With Good Outcome
Authors: Western Elin , Nordenmark Tonje Haug , Sorteberg Wilhelm , Karic Tanja , Sorteberg Angelika
Published: May 2021

Fatigue after aneurysmal subarachnoid hemorrhage (post-aSAH fatigue) is a frequent, often long-lasting, but still poorly studied sequel. The aim of the present study was to characterize the nature of post-aSAH fatigue with an itemized analysis of the Fatigue Severity Scale (FSS) and Mental Fatigue Scale (MFS). We further wanted to assess the association of fatigue with other commonly observed problems after aSAH: mood disorders, cognitive problems, health-related quality of life (HRQoL), weight gain, and return to work (RTW). Ninety-six good outcome aSAH patients with fatigue completed questionnaires measuring fatigue, depression, anxiety, and HRQoL. All patients underwent a physical and neurological examination. Cognitive functioning was assessed with a neuropsychological test battery. We also registered prior history of fatigue and mood disorders as well as occupational status and RTW. The patients experienced fatigue as being among their three most disabling symptoms and when characterizing their fatigue they emphasized the questionnaire items “low motivation,” “mental fatigue,” and “sensitivity to stress.” Fatigue due to exercise was their least bothersome aspect of fatigue and weight gain was associated with depressive symptoms rather than the severity of fatigue. Although there was a strong association between fatigue and mood disorders, especially for depression, the overlap was incomplete. Post-aSAH fatigue related to reduced HRQoL. RTW was remarkably low with only 10.3% of patients returning to their previous workload. Fatigue was not related to cognitive functioning or neurological status. Although there was a strong association between fatigue and depression, the incomplete overlap supports the notion of these two being distinct constructs. Moreover, post-aSAH fatigue can exist without significant neurological or cognitive impairments, but is related to reduced HRQoL and contributes to the low rate of RTW.
Platelet Effects of Anti-diabetic Therapies: New Perspectives in the Management of Patients with Diabetes and Cardiovascular Disease
Authors: Nusca Annunziata , Tuccinardi Dario , Pieralice Silvia , Giannone Sara , Carpenito Myriam , Monte Lavinia , Watanabe Mikiko , Cavallari Ilaria , Maddaloni Ernesto , Ussia Gian Paolo , Manfrini Silvia , Grigioni Francesco
Published: May 2021

In type 2 diabetes, anti-thrombotic management is challenging, and current anti-platelet agents have demonstrated reduced efficacy. Old and new anti-diabetic drugs exhibited—besides lowering blood glucose levels—direct and indirect effects on platelet function and on thrombotic milieu, eventually conditioning cardiovascular outcomes. The present review summarizes existing evidence on the effects of glucose-lowering agents on platelet properties, addressing pre-clinical and clinical research, as well as drug–drug interactions with anti-platelet agents. We aimed at expanding clinicians’ understanding by highlighting new opportunities for an optimal management of patients with diabetes and cardiovascular disease. We suggest how an improvement of the thrombotic risk in this large population of patients may be achieved by a careful and tailored combination of anti-diabetic and anti-platelet therapies.
Neuroinflammation as a Therapeutic Target for Mitigating the Long-Term Consequences of Acute Organophosphate Intoxication
Authors: Andrew Peter M. , Lein Pamela J.
Published: May 2021

Acute intoxication with organophosphates (OPs) can cause a potentially fatal cholinergic crisis characterized by peripheral parasympathomimetic symptoms and seizures that rapidly progress to status epilepticus (SE). While current therapeutic countermeasures for acute OP intoxication significantly improve the chances of survival when administered promptly, they are insufficient for protecting individuals from chronic neurologic outcomes such as cognitive deficits, affective disorders, and acquired epilepsy. Neuroinflammation is posited to contribute to the pathogenesis of these long-term neurologic sequelae. In this review, we summarize what is currently known regarding the progression of neuroinflammatory responses after acute OP intoxication, drawing parallels to other models of SE. We also discuss studies in which neuroinflammation was targeted following OP-induced SE, and explain possible reasons why such therapeutic interventions have inconsistently and only partially improved long-term outcomes. Finally, we suggest future directions for the development of therapeutic strategies that target neuroinflammation to mitigate the neurologic sequelae of acute OP intoxication.
Diverse Functions of IAA-Leucine Resistant PpILR1 Provide a Genic Basis for Auxin-Ethylene Crosstalk During Peach Fruit Ripening
Authors: Wang Xiaobei , Meng Junren , Deng Li , Wang Yan , Liu Hui , Yao Jia-Long , Nieuwenhuizen Nicolaas Jacobus , Wang Zhiqiang , Zeng Wenfang
Published: May 2021

Auxin and ethylene play critical roles in the ripening of peach (Prunus persica) fruit; however, the interaction between these two phytohormones is complex and not fully understood. Here, we isolated a peachILRgene,PpILR1, which encodes an indole-3-acetic acid (IAA)-amino hydrolase. Functional analyses revealed that PpILR1 acts as a transcriptional activator of 1-amino cyclopropane-1-carboxylic acid synthase (PpACS1), and hydrolyzes auxin substrates to release free auxin. When Cys137 was changed to Ser137, PpILR1 failed to show hydrolase activity but continued to function as a transcriptional activator ofPpACS1in tobacco and peach transient expression assays. Furthermore, transgenic tomato plants overexpressingPpILR1exhibited ethylene- and strigolactone-related phenotypes, including premature pedicel abscission, leaf and petiole epinasty, and advanced fruit ripening, which are consistent with increased expression of genes involved in ethylene biosynthesis and fruit ripening, as well as suppression of branching and growth of internodes (related to strigolactone biosynthesis). Collectively, these results provide novel insights into the role of IAA-amino acid hydrolases in plants, and position the PpILR1 protein at the junction of auxin and ethylene pathways during peach fruit ripening. These results could have substantial implications on peach fruit cultivation and storage in the future.
“New” State Actors and Conflict-Affected States: Confronting Violence, Shifting Ambitions, and Adjusting Principles
Authors: Paczyńska Agnieszka
Published: May 2021

Over the past couple of decades, “new” state actors, such as Brazil, China, Russia, India, Turkey, and countries of the Arab Gulf, have been playing an increasingly prominent role in assistance provision to conflict-affected states. Skeptical of the liberal peace-building model, they have emphasized supporting economic development and avoided promoting political reforms, viewing them as too interventionist in domestic affairs of conflict-affected states. Rather, they have emphasized solidarity, cooperation, mutual support, and respect for state sovereignty; and they are committed to non-intervention norms. However, the foreign policies of “new” state actors have been far from static. This article argues that these norms mask more complex relationships between “new” state actors and conflict-affected states. Historically, the “new” actors have tended to adhere less to non-intervention norms in their immediate neighborhood. Now, as they become more deeply engaged with countries emerging out of violent conflict, have come to aspire playing more prominent global roles, and the competition among them has risen, their adherence to principles of non-interference is under strain and policies regarding issues of peace and security are shifting.