bluuebunny/crossref_metadata_2025_split huggingface dataset:
The crosstalk between the caspase family and the cGAS‒STING signaling pathway
Authors: Xiong Yongai , Tang Yan-Dong , Zheng Chunfu 
Published: October 2021

AbstractEdited by Jiarui WuCytosolic nucleic acid sensors are critical for sensing nucleic acids and initiating innate immunity during microbial infections and/or cell death. Over the last decade, several key studies have characterized the conserved mechanism of cyclic guanosine monophosphate‒adenosine monophosphate synthase (cGAS) and the downstream signaling adaptor stimulator of interferon genes (STING) initiating the innate immune signaling pathways. Aside from its primary involvement in microbial infections and inflammatory diseases, there is growing interest in the alternate roles of cGAS‒STING-mediated signaling. Caspase family members are powerful functional proteins that respond to cellular stress, including cell death signals, inflammation, and innate immunity. Recent studies have uncovered how the caspase family cooperates with the cGAS‒STING signaling pathway. Most caspase family members negatively regulate the cGAS‒STING signaling pathway. In turn, some caspase family members can also be modulated by cGAS‒STING. This review gives a detailed account of the interplay between the caspase family and the cGAS‒STING signaling pathway, which will shed light on developing novel therapeutics targeting the caspase family and cGAS‒STING signaling in antiviral innate immunity, cancer, inflammatory, and autoimmunity.
Effects of dietary fats on the bioaccessibility and bioavailability of carotenoids: a systematic review and meta-analysis of in vitro studies and randomized controlled trials
Authors: Yao Yuanhang , Tan Peiyi , Kim Jung Eun 
Published: October 2021

Abstract

Context
Dietary fats are one of the well-known stimulators of carotenoid absorption, but the effects of the quantity and the type of dietary fats on carotenoid absorption have not yet been studied systematically.

Objective
This review aimed to analyze data from both in vitro studies and randomized controlled trials (RCTs) to examine the effects of dietary fats on the bioaccessibility and bioavailability of carotenoids.

Data Sources
A systematic search of 5 databases (Scopus, PubMed, Embase, CINAHL and the Cochrane Library) was conducted.

Study Selection
In vitro studies and RCTs were selected according to the PICOS criteria and were reviewed independently by 2 investigators.

Date Extraction
Key study characteristics from the eligible in vitro studies and RCTs were extracted independently by 2 investigators using a standardized table.

Results
A total of 27 in vitro studies and 12 RCTs were included. The meta-regression of in vitro studies showed that the bioaccessibility of carotenoids, except for lycopene, was positively associated with the concentration of dietary fats. The meta-analysis of RCTs showed that the bioavailability of carotenoids was enhanced when a higher quantity of dietary fats was co-consumed. Moreover, fats rich in unsaturated fatty acids resulted in greater improvement in carotenoid bioavailability (SMD 0.90; 95%CI, 0.69–1.11) as compared with fats rich in saturated fatty acids (SMD 0.27; 95%CI, 0.08–0.47).

Conclusions
Co-consuming dietary fats, particularly those rich in unsaturated fatty acids, with carotenoid-rich foods can improve the absorption of carotenoids.

Systematic Review Registration
PROSPERO registration number CRD42020188539.
Bioactives in bovine milk: chemistry, technology, and applications
Authors: Lin Tiantian , Meletharayil Gopinathan , Kapoor Rohit , Abbaspourrad Alireza 
Published: October 2021

Abstract
The significance of dairy in human health and nutrition is gaining significant momentum as consumers continue to desire wholesome, nutritious foods to fulfill their health and wellness needs. Bovine milk not only consists of all the essential nutrients required for growth and development, it also provides a broad range of bioactive components that play an important role in managing human homeostasis and immune function. In recent years, milk bioactives, including α-lactalbumin, lactoferrin, glycomacropeptide, milk fat globule membrane, and milk oligosaccharides, have been intensively studied because of their unique bioactivity and functionality. Challenges for the application of these bioactive components in food and pharmaceutical formulations are associated with their isolation and purification on an industrial scale and also with their physical and chemical instability during processing, storage, and digestion. These challenges can be overcome by advanced separation techniques and sophisticated nano- or micro-encapsulation technologies. Current knowledge about the chemistry, separation, and encapsulation technology of major bioactives derived from bovine milk and their application in the food industry is reviewed here.
Pre-Exposure to TiO2-NPs Aggravates Alcohol-Related Liver Injury by Inducing Intestinal Barrier Damage in Mice
Authors: Liu Shanji , Zhao Yu , Liu Yingxia , Tang Yizhou , Xu Xiaowei , Wang Mengqi , Tao Xueying , Xu Hengyi 
Published: October 2021

Abstract
The wide application of titanium dioxide nanoparticles (TiO2-NPs) and the increase in opportunities for its release into the environment undoubtedly compound the potential of these materials to harm people. Research on the effects of pre-exposure to TiO2-NPs on disease development is scarce. The purpose of this work was to assess whether pre-exposure to TiO2-NPs (20 and 200 mg/kg) for 28 days aggravates the development of alcohol-related liver injury in mice. Results showed that oral administration of 200 mg/kg TiO2-NPs induced only modest changes in liver function parameters, but could induce intestinal inflammation and destroy the integrity of intestinal barrier. After the subsequent alcohol intervention, pre-exposure to TiO2-NPs (200 mg/kg) was found to aggravate alcohol-related liver injury, including significantly increases in serum aspartate aminotransferase, alanine aminotransferase, total glycerol, and total cholesterol, as well as steatosis and inflammation in the liver. Further investigation revealed that alcohol could increase intestinal permeability and reduce the expression of tight junction proteins in mice pre-exposed high dosage of TiO2-NPs, thereby inducing the transfer of more lipopolysaccharides into the liver, ultimately triggering more severe liver inflammation. This study emphasizes that pre-exposed of TiO2-NPs (high doses of up to 200 mg/kg) can potentially promote the development of alcoholic liver diseases. Furthermore, this study provides new insights into evaluating the safety of NPs.
Epidemiological and clinical features of cutaneous leishmaniasis and its time trend model in a high-endemic focus of disease in the southwest of Iran from 2014 to 2019
Authors: Khosrotaj Mohammad Hossien , Rakhshani Tayebeh , Nazari Mahin , Gheibi Zahra , Soltani Aboozar 
Published: October 2021

Abstract

Background
Cutaneous leishmaniasis (CL) is a tropical infection with a relatively high incidence rate in Iran. The present study aimed to explore the time trend and associated factors of CL in Dezful, in southwest Iran.

Methods
This case series study was conducted on all CL patients registered from 2014 to 2019. The descriptive analysis of the data was done using SPSS 20 software and the time series model on the number of cases was run through Interactive Time Series Modeling software.

Results
A total of 5349 leishmaniasis cases were identified in the study area during 2014–2019. The highest incidence rate was 35 840 per 100 000 in 2014. The fitted time series model revealed a decreasing trend with an annual periodic pattern. The mean age of infection was 19.82 y (standard deviation 21.87). The infection was most frequent in the 1–10 y age group (41.7%). Also, females were more prone to leishmaniasis (54.7%). Most lesions were located on the hand (23.1%), face (19.7%), and forearm (17.75%) and 48.5% of patients had only one lesion.

Conclusions
The results revealed a decreasing trend of leishmaniasis in Dezful. It has been predicted that this infection will reach a minimum rate (300 per 100 000) in the winter of 2021.
Elevated admission C-reactive protein to albumin ratios are associated with disease severity and respiratory complications in adults with imported falciparum malaria
Authors: Hoffmeister Bodo , Aguilar Valdez Abner D 
Published: October 2021

Abstract

Background
In imported falciparum malaria, systemic inflammation with increased capillary permeability can cause life-threatening complications, such as acute pulmonary edema (APO) or adult respiratory distress syndrome (ARDS). This observational study assessed the association of the admission serum albumin level (ALB) and C-reactive protein to albumin ratio (CRP/ALB) with disease severity and these respiratory complications.

Methods
All adult cases hospitalized during 2001–2015 in the Charité University Hospital, Berlin, with ALB and CRP values measured upon admission, were retrospectively analysed.

Results
Seventy-six patients were enrolled (26 female, median age: 37 y), 60 with uncomplicated malaria and 16 with severe malaria (SM). SM was associated with lower ALB (p&lt;0.0001) and higher CRP/ALB (p&lt;0.0001) values; the areas under the receiver operator curves (AUROCs) were 0.85 (95% CI 0.74 to 0.96) for ALB and 0.88 (95% CI 0.80 to 0.97) for CRP/ALB. Radiologic changes consistent with APO/ARDS were detectable in 5 of 45 admission chest X-rays performed (11.1%); the AUROCs were 0.86 (95% CI 0.74 to 0.99) for ALB and 0.91 (95% CI 0.82 to 0.99) for CRP/ALB.

Conclusions
Diminished admission ALB levels and elevated CRP/ALB ratios are associated with disease severity and respiratory complications in imported falciparum malaria. These readily and ubiquitously available markers may facilitate early identification of at-risk patients.
Genotype-Phenotype Correlation of T Cell Subtypes Reveals Senescent and Cytotoxic Genes in Alzheimer’s Disease
Authors: Dressman Dallin , Buttrick Thomas , Cimpean Maria , Bennett David , Menon Vilas , Bradshaw Elizabeth M. , Vardarajan Badri , Elyaman Wassim 
Published: October 2021

AbstractRecent studies identifying expression quantitative trait loci (eQTL) in immune cells have uncovered important links between disease risk alleles and gene expression trends in monocytes, T cells, and other cell types. However, these studies are generally done with young, healthy subjects, limiting the utility of their findings for age-related conditions such as Alzheimer’s disease (AD). We have performed RNA sequencing on four T cell subsets in genome-wide genotyped and well-characterized AD subjects and age- and sex-matched healthy controls from the Religious Orders Study/Memory and Aging Project. Correlating gene expression data with AD neuropathological traits, and with single nucleotide polymorphisms (SNPs) to detect eQTLs, we identified several significant genes involved in T cell senescence and cytotoxicity, consistent with T cell RNA sequencing studies in aged/AD cohorts. We identified unexpected eQTLs previously associated with neuropsychiatric disease traits. Finally, we discovered that pathways related to axon guidance and synaptic function were enriched among trans-eQTLs in coding regions of the genome. Overall, our data sheds more light on the genetic basis behind phenotypic changes in T cells during aging and AD.
Antecedent Metabolic Health and Metformin (ANTHEM) Aging study: Rationale and study design for a randomized controlled trial
Authors: Kumari Santosh , Bubak Matthew , Schoenberg Hayden M. , Davidyan Arik , Elliehausen Christian J. , Kuhn Katrin G. , VanWagoner Timothy M. , Karaman Rowan , Scofield Robert Hal , Miller Benjamin F. , Konopka Adam R. 
Published: October 2021

AbstractThe antidiabetic medication metformin has been proposed to be the first drug tested to target aging and extend healthspan in humans. While there is extensive epidemiological support for the health benefits of metformin in patient populations, it is not clear if these protective effects apply to those free of age-related disease. Our previous data in older adults without diabetes suggest a dichotomous change in insulin sensitivity and skeletal muscle mitochondrial adaptations after metformin treatment when co-prescribed with exercise. Those who entered the study as insulin sensitive had no change to detrimental effects while those who were insulin resistant had positive changes. The objective of this clinical trial is to determine if 1) antecedent metabolic health and 2) skeletal muscle mitochondrial remodeling and function mediate the positive or detrimental effects of metformin monotherapy, independent of exercise, on the metabolism and biology of aging. In a randomized, double blind clinical trial, adults free of chronic disease (n=148, 40-75 years old) are stratified as either insulin sensitive or insulin resistant based on HOMA-IR (≤2.2 or ≥2.5) and take 1500 mg/day of metformin or placebo for 12 weeks. Hyperinsulinemic-euglycemic clamps and skeletal muscle biopsies are performed before and after 12 weeks to assess primary outcomes of peripheral insulin sensitivity and mitochondrial remodeling and function. Findings from this trial will identify clinical characteristics and cellular mechanisms involved in modulating the effectiveness of metformin treatment to target aging that could inform larger phase 3 clinical trials aimed at testing aging as an indication for metformin.
Feature representation under crowding in V1 and V4 neuronal populations
Authors: Henry Christopher A , Kohn Adam 
Published: October 2021

AbstractVisual perception depends strongly on spatial context. A profound example is visual crowding, whereby the presence of nearby stimuli impairs discriminability of object features. Despite extensive work on both perceptual crowding and the spatial integrative properties of visual cortical neurons, the link between these two aspects of visual processing remains unclear. To understand better the neural basis of crowding, we recorded simultaneously from neuronal populations in V1 and V4 of fixating macaque monkeys. We assessed the information about the orientation of a visual target available from the measured responses, both for targets presented in isolation and amid distractors. Both single neuron and population responses had less information about target orientation when distractors were present. Information loss was moderate in V1 and more substantial in V4. Information loss could be traced to systematic divisive and additive changes in neuronal tuning. Tuning changes were more severe in V4; in addition, tuning exhibited greater context-dependent distortions in V4, further restricting the ability of a fixed sensory readout strategy to extract accurate feature information across changing environments. Our results provide a direct test of crowding effects at different stages of the visual hierarchy, reveal how these effects alter the spiking activity of cortical populations by which sensory stimuli are encoded, and connect these changes to established mechanisms of neuronal spatial integration.
Structural Knowledge Transfer of Panoptic Kidney Segmentation to Other Stains, Organs, and Species
Authors: Ginley Brandon , Jen Kuang-Yu , Sarder Pinaki 
Published: October 2021

AbstractBackgroundPanoptic segmentation networks are a newer class of image segmentation algorithms that are constrained to understand the difference between instance-type objects (objects that are discrete countable entities, such as renal tubules) and group-type objects (uncountable, amorphous regions of texture such as renal interstitium). This class of deep networks has unique advantages for biological datasets, particularly in computational pathology.MethodsWe collected 126 periodic acid Schiff whole slide images of native diabetic nephropathy, lupus nephritis, and transplant surveillance kidney biopsies, and fully annotated them for the following micro-compartments: interstitium, glomeruli, globally sclerotic glomeruli, tubules, and arterial tree (arteries/arterioles). Using this data, we trained a panoptic feature pyramid network. We compared performance of the network against a renal pathologist’s annotations, and the method’s transferability to other computational pathology domain tasks was investigated.ResultsThe panoptic feature pyramid networks showed high performance as compared to renal pathologist for all of the annotated classes in a testing set of transplant kidney biopsies. The network was not only able to generalize its object understanding across different stains and species of kidney data, but also across several organ types.ConclusionsPanoptic networks have unique advantages for computational pathology; namely, these networks internally model structural morphology, which aids bootstrapping of annotations for new computational pathology tasks.
Real-Time Structure Search and Structure Classification for AlphaFold Protein Models
Authors: Aderinwale Tunde , Bharadwaj Vijay , Christoffer Charles , Terashi Genki , Zhang Zicong , Jahandideh Rashidedin , Kagaya Yuki , Kihara Daisuke 
Published: October 2021

AbstractAlphaFold2 showed a substantial improvement in the accuracy of protein structure prediction. Following the release of the software, whole-proteome protein structure predictions by AlphaFold2 for 21 organisms were made publicly available. Here, we developed the infrastructure, 3D-AF-Surfer, to enable real-time structure-based search for the AlphaFold2 models by combining molecular surface representation with 3D Zernike descriptors and deep neural networks.
Developing a Biomimetic Evaluation Method for Antiviral Coatings Using Artificial Saliva Droplets
Authors: Tanaka Naoki , Miyamae Nobuhiro 
Published: October 2021

AbstractRespiratory infections pose a serious threat worldwide, and many new antiviral agents and coatings have been developed to reduce the overall risk of viral infection. Here, we evaluate the methodology used to test these antiviral coatings and developed a novel system that is more similar to “real-world” conditions. Contact infection is largely mediated via contact with saliva containing the active virus released as droplets by coughing or sneezing, with these droplets adhering to objects and surfaces and subsequently entering the human body via indirect contact with the mucous membranes. Here, we evaluated the antiviral effect of a known antiviral coating agent using an artificial saliva based system, where artificial saliva containing phages were sprayed onto the antiviral coating under various conditions associated with viral replication and infectious spread. We used a commercially available antiviral coating in this evaluation, and M13 bacteriophages as model viruses. This method enables simple biomimetic evaluations of any product’s antiviral effects.
Evaluating test-retest reliability and sex/age-related effects on temporal clustering coefficient of dynamic functional brain networks
Authors: Long Yicheng , Yan Chaogan , Wu Zhipeng , Huang Xiaojun , Cao Hengyi , Liu Zhening , Palaniyappan Lena 
Published: October 2021

AbstractThe multilayer dynamic network model has been proposed as an effective method to understand how the brain functions dynamically. Specially, derived from the definition of clustering coefficient in static networks, the temporal clustering coefficient provides a direct measure of topological stability of dynamic brain networks and shows potential in predicting altered brain functions in both normal and pathological conditions. However, test–retest reliability and demographic-related effects on this measure remain to be evaluated. Using a publicly available dataset from the Human Connectome Project consisting of 337 young healthy adults (157 males/180 females; 22 to 37 years old), the present study investigated: (1) the test-retest reliability of temporal clustering coefficient across four repeated resting-state functional magnetic resonance imaging scans as measured by intraclass correlation coefficient (ICC); and (2) sex- and age-related effects on temporal clustering coefficient. The results showed that (1) the temporal clustering coefficient had overall moderate test-retest reliability (ICC > 0.40 over a wide range of densities) at both global and subnetwork levels; (2) female subjects showed significantly higher temporal clustering coefficient than males at both global and subnetwork levels, in particular within the default-mode and subcortical regions; (3) temporal clustering coefficient of the subcortical subnetwork was negatively correlated with age in young adults. Our findings suggest that temporal clustering coefficient is a reliable and reproducible approach for the identification of individual differences in brain function, and provide evidence for sex and age effects on human brain dynamic connectome.
Zika virus infection drives epigenetic modulation of immunity by the histone acetyltransferase CBP of Aedes aegypti
Authors: de Mendonça Amarante Anderson , de Abreu da Silva Isabel Caetano , Carneiro Vitor Coutinho , Revoredo Vicentino Amanda Roberta , de Amorim Pinto Marcia , Higa Luiza Mendonça , Moharana Kanhu Charan , Talyuli Octávio Augusto C. , Venancio Thiago Motta , de Oliveira Pedro Lagerblad , Fantappié Marcelo Rosado 
Published: October 2021

AbstractEpigenetic mechanisms are responsible for a wide range of biological phenomena in insects, controlling embryonic development, growth, aging and nutrition. Despite this, the role of epigenetics in shaping insect-pathogen interactions has received little attention. Gene expression in eukaryotes is regulated by histone acetylation/deacetylation, an epigenetic process mediated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). In this study, we explored the role of the Aedes aegypti histone acetyltransferase CBP (AaCBP) after infection with Zika virus (ZIKV), focusing on the two main immune tissues, the midgut and fat body. We showed that the expression and activity of AaCBP could be positively modulated by blood meal and ZIKV infection. Nevertheless, Zika-infected mosquitoes that were silenced for AaCBP revealed a significant reduction in the acetylation of H3K27 (CBP target marker), followed by downmodulation of the expression of immune genes, higher titers of ZIKV and lower survival rates. Importantly, in Zika-infected mosquitoes that were treated with sodium butyrate, a histone deacetylase inhibitor, their capacity to fight virus infection was rescued. Our data point to a direct correlation among histone hyperacetylation by AaCBP, upregulation of antimicrobial peptide genes and increased survival of Zika-infected-A. aegypti.Author summaryPathogens have coevolved with mosquitoes to optimize transmission to hosts. As natural vectors, mosquitoes are permissive to and allow systemic and persistent arbovirus infection, which intriguingly does not result in dramatic pathological sequelae that affect their lifespan. In this regard, mosquitoes have evolved mechanisms to tolerate persistent infection and develop efficient antiviral strategies to restrict viral replication to nonpathogenic levels. There is a great deal of evidence supporting the implication of epigenetics in the modulation of the biological interaction between hosts and pathogens. This study reveals that Zika virus infection positively modulates the expression and activity of A. aegypti histone acetyltransferase CBP (AaCBP). This study shows that AaCBP plays a role in the activation of immune-responsive genes to limit Zika virus replication. This first description that Zika virus infection has epigenomic consequences in the regulation of A. aegypti immunity opens a new avenue for research on mosquito factors that can drive vector competence.