Miracle-dz/UniFAR-FTUs huggingface dataset:
OxLDL/β2GPI/anti-β2GPI Ab complex induces inflammatory activation via the TLR4/NF-κB pathway in HUVECs

Patients with antiphospholipid syndrome have been identified to have higher incidence rates of atherosclerosis (AS) due to the elevated levels of anti-β2-glycoprotein I (β2GPI) antibody (Ab). Our previous studies revealed that the anti-β2GPI Ab formed a stable oxidized low-density lipoprotein (oxLDL)/β2GPI/anti-β2GPI Ab complex, which accelerated AS development by promoting the accumulation of lipids in macrophages and vascular smooth muscle cell. However, the effects of the complex on endothelial cells, which drive the initiation and development of AS, remain unknown. Thus, the present study aimed to determine the proinflammatory roles of the oxLDL/β2GPI/anti-β2GPI Ab complex in human umbilical vein endothelial cells (HUVECs) in an attempt to determine the underlying mechanism. Reverse transcription-quantitative PCR, enzymy-linked immunosorbent assay, western blotting and immunofluorescence staining were performed to detect the expressions of inflammation related factors and adhesion molecules. Monocyte-binding assay was used to investigate the effects of oxLDL/β2GPI/anti-β2GPI Ab complex on monocyte adhesion to endothelial cells. The results demonstrated that the oxLDL/β2GPI/anti-β2GPI Ab complex upregulated the expression of Toll-like receptor (TLR)4 and the levels of NF-κB phosphorylation in HUVECs, and subsequently enhanced the expression levels of inflammatory cytokines, including TNF-α, IL-1β and IL-6, as well as those of adhesion molecules, such as intercellular adhesion molecule 1 and vascular adhesion molecule 1. In addition, the complex facilitated the recruitment of monocytes by promoting the secretion of monocyte chemotactic protein 1 in HUVECs. Notably, the described effects of the oxLDL/β2GPI/anti-β2GPI Ab complex in HUVECs were abolished by either TLR4 or NF-κB blockade. In conclusion, these findings suggested that the oxLDL/β2GPI/anti-β2GPI Ab complex may induce a hyper-inflammatory state in endothelial cells by promoting the secretion of proinflammatory cytokines and monocyte recruitment, which was discovered to be largely dependent on the TLR4/NK-κB signaling pathway.
Comparison of cognitive functioning of elders with late-life depression and patients with and without a history of depressive episodes: a cross-sectional study

ABSTRACT Nowadays there are numerous studies on the occurrence of cognitive dysfunction in late-life depression (LLD). The role of executive dysfunctions in the psychopathology of depression is particularly emphasized and needs further examination. The aim was to assess cognitive functions and their relation to depressive symptoms in elders with LLD, previously depressed, and patients without the history of depressive episodes. The study consisted of 824 older adults who underwent a neuropsychological evaluation (97 currently depressed, 114 previously depressed and 613 patients without the history of depressive episodes). LLD patients performed poorer in ACE-III and AVLT and poorer in TMT-B than those previously depressed and never depressed. The LLD group also performed significantly poorer than the previously depressed on Digit Span Forward. Results of a multiple regression analysis indicated that performance on measures of executive functioning was associated with depression severity in LLD (β =.227, P =.024). The results of this study suggest that executive functions are the most impaired in the elderly with LLD. Furthermore, there is a relationship between executive dysfunction and the severity of depression in LLD. Executive dysfunction appears to be the core neurocognitive deficit in LLD.
miR-126 overexpression attenuates oxygen-glucose deprivation/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/Nrf2 signaling pathway in human umbilical vein endothelial cells

MicroRNA-126 (miR-126) has been reported to be implicated in the pathogenesis of cerebral ischemia/reperfusion (I/R) injury; however, its role is still unclear and requires further investigation. The objective of the present study was to determine the neuroprotective effect of miR-126 overexpression against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human umbilical vein endothelial cell (HUVEC) injury, an in vitro model of cerebral I/R injury, and to further explore the role of the NAD-dependent protein deacetylase sirtuin-1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in this process. The results of the present study revealed that miR-126 expression was markedly reduced in HUVECs subjected to OGD/R treatment. Functional experiments demonstrated that transfection with miR-126 mimics attenuated OGD/R-induced down-regulation of cell viability, and reversed OGD/R-induced up-regulation of lactate dehydrogenase release, apoptosis and caspase-3 activity in HUVECs. Notably, OGD/R reduced SIRT1 and heme oxygenase-1 expression, and induced the nuclear translocation of Nrf2, as demonstrated by the increase in cytoplasmic Nrf2 expression and the decrease in nuclear Nrf2 expression. Following transfection with miR-126 mimics, these effects of OGD/R were reversed, indicating that miR-126 overexpression promoted the SIRT1/Nrf2 signaling pathway. Additionally, miR-126 mimics attenuated OGD/R-induced cytotoxicity and apoptosis, which was blocked by inhibition of the SIRT1/Nrf2 signaling pathway followed by transfection with SIRT1-small interfering RNA (siRNA). Furthermore, miR-126 mimics decreased ROS generation and malondialdehyde content, and increased superoxide dismutase and glutathione peroxidase activity in HUVECs exposed to OGD/R, and these effects of miR-126 mimics were also blocked by SIRT1-siRNA. Additionally, the miR-126 mimics-induced the decreases in the levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and the miR-126 mimics-induced increase in anti-inflammatory cytokines, including IL-10, were reversed by SIRT1-siRNA. Overall, these results suggested that miR-126 overexpression attenuated OGD/R-induced neurotoxicity to HUVECs by alleviating oxidative stress and the inflammatory response via promotion of the SIRT1/Nrf2 signaling pathway.
Delayed diagnosis of multiple sclerosis in a low prevalence country

ABSTRACT Background: Early diagnosis and treatment of multiple sclerosis (MS) is crucial to avoid future disability. The factors that influence diagnostic delay in low prevalence settings have been poorly studied. Objectives: To evaluate the factors associated with a delayed diagnosis of MS after the symptomatic onset. Methods: Clinical records of confirmed MS patients were reviewed. Diagnostic delay was calculated by subtracting the date of onset from the date of diagnosis and categorized as early and delayed, when below and above than 1 year. Logistic regression was performed to evaluate the likelihood of a delayed diagnosis according to age at first symptom, gender, type of the first symptom, progressive vs relapsing onset, diagnostic criteria prevailing at the time of symptom onset, comorbidities, and family history of MS. Results: Data of 525 (95.6%) from a cohort of 549 patients were analyzed. About 69.1% were women. The mean age was 43.2 years. About 86.3% had relapsing-remitting MS. The mean overall diagnostic delay was 3.07 years. About 45.7% of the patients had a delayed diagnosis, and it was dependent on the symptom and the diagnostic criteria prevailing at the onset. Multivariate logistic regression showed onset during the Schumacher (OR = 10.03 [95%CI 1.30–77.1], p = 0.027) and Poser (OR = 4.26 [95%CI 1.25–15.15], p = 0.021) years were associated with delayed MS diagnosis. Conclusions: MS onset before the McDonald diagnostic criteria era is associated with delayed diagnosis.
Au nanoparticles on ultrathin MoS2 sheets for plasmonic organic solar cells

A novel hole transport layer (HTL) composed of ultrathin two-dimensional, molybdenum disulfide (MoS2) sheets decorated with 20 nm gold nanoparticles (NPs) (MoS2@Au) was developed to make use of plasmonics for organic solar cells (OSCs). Both experimental and theoretical simulations revealed that the device with the MoS2@Au composite as the HTL exhibited enhanced short-circuit photocurrent density (Jsc) and efficiency compared to that with MoS2 alone as the HTL.
Naturally Occurring Animal Coronaviruses as Models for Studying Highly Pathogenic Human Coronaviral Disease

Coronaviruses (CoVs) comprise a large group of positive stranded RNA viruses that infect a diverse host range including birds and mammals. Infection with CoVs typically presents as mild to severe respiratory or enteric disease, but CoVs have the potential to cause significant morbidity or mortality in highly susceptible age groups. CoVs have exhibited a penchant for jumping species barriers throughout history with devastating effects. The emergence of highly pathogenic or infectious CoVs in humans over the past 20 years, including severe acute respiratory syndrome CoV (SARS-CoV), Middle East respiratory syndrome CoV (MERS-CoV), and most recently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the significant threat that CoV spillovers pose to humans. Similar to the emergence of SARS-CoV-2, CoVs have been devastating to commercial animal production over the past century, including infectious bronchitis virus in poultry and bovine CoV, as well as the emergence and reemergence of multiple CoVs in swine including transmissible gastroenteritis virus, porcine epidemic diarrhea virus, and porcine deltacoronavirus. These naturally occurring animal CoV infections provide important examples for understanding CoV disease as many animal CoVs have complex pathogenesis similar to SARS-CoV-2 and can shed light on the ongoing SARS-CoV-2 outbreak. We provide an overview and update regarding selected existing animal CoVs and their primary host species, diseases caused by CoVs, how CoVs jump species, whether these CoVs pose an outbreak risk or risk to humans, and how we can mitigate these risks.
Recent Evidence in Epigenomics and Proteomics Biomarkers for Early and Minimally Invasive Diagnosis of Alzheimer’s and Parkinson’s Diseases

Background: Alzheimer’s (AD) and Parkinson’s diseases (PD) show deposits of improperly folded modified proteins. Protein expression mechanisms are involved since the early stages. Several studies evaluated epigenomics and proteomics profiles in these patients, with promising results. In general, they focused on early, specific, and minimally invasive biomarkers for the diagnosis and prognosis of AD and PD. Objectives This review aimed at summarizing results to find the most reliable evidence in the field. Results Among epigenomics studies, there is a focus on microRNAs (miRNAs) as candidate diagnostic biomarkers for AD or PD from blood samples like miR-342-3p, miR-107, miR-106a-5p, miR-106b-5p, miR-195, and miR-19b. In addition, DNA methylation has been tested in a few works, obtaining significant differences in some genes (NCAPH2/LMF2 COASY, SPINT1, BDNFTREM1, TREM2, NPAS2, PDE4D), which could be useful for evaluating the disease progression as well as potential risk factors. Regarding proteomics, most of the studies were untargeted and used plasma or serum samples. In general, they highlighted the importance of coagulation, inflammation pathways, and oxidative stress. Among targeted studies, some proteins (phosphorylated tau, C reactive protein (CRP), interleukins, necrosis factors, transferrin, glial fibrillary acidic protein (GFAP), and neurofilaments) showed different plasma levels in AD and PD patients in comparison with healthy participants. Finally, a few studies have identified specific-AD and PD epigenetic and proteomic biomarkers (ApoE and oxidized DJ-1) in comparison with other similar pathologies. Conclusion In general, there is a common lack of clinical validation of these potential biomarkers because of which its use in clinical practice is still limited.
Research Progress on Oviposition-Related Genes in Insects

Abstract Oviposition-related genes have remained a consistent focus of insect molecular biology. Previous research has gradually clarified our mechanistic understanding of oviposition-related genes, including those related to oviposition-gland-related genes, oogenesis-related genes, oviposition-site-selection-related genes, and genes related to ovulation and hatching. Moreover, some of this research has revealed how the expression of single oviposition-related genes affects the expression of related genes, and more importantly, how individual node genes function to link the expression of upstream and downstream genes. However, the research to date is not sufficient to completely explain the overall interactions among the genes of the insect oviposition system. Through a literature review of a large number of studies, this review provides references for future research on oviposition-related genes in insects and the use of RNAi or CRISPR/Cas9 technology to verify the functions of oviposition-related genes and to prevent and control harmful insects.
Atherosclerosis: cell biology and lipoproteins.

DOI:10.1097/MOL.0000000000000726 Atherosclerosis is currently treated with lipid-lowering drugs that promote the clearance of LDL from the circulation with the aim to hamper inflammation-promoting LDL accumulation in the aortic wall. Although lipid-lowering has revolutionized management of cardiovascular risk due to atherosclerosis, many are still at risk. To mitigate the residual risk, targeting the mediators and the cells that promote plaque inflammation directly has gained increasing interest. The feasibility of targeting inflammatory mediators was proven by the CANTOS study that showed that inhibition of the proinflammatory cytokine IL-1b with a monoclonal antibody could significantly lower the rate of recurrent cardiovascular events compared with placebo in a randomized double blind trial involving more than 10 000 individuals [1]. With the advent of single-cell RNA sequencing (scRNAseq) technologies, our understanding of the cellular composition of atherosclerotic plaques has taken a giant leap forward [2 && ]. The knowledge gained from these novel methods and technological advancements has been particularly helpful for the generation of new hypotheses and mechanisms to test and explore in animal models and human plaques. The role of smooth muscle cells (SMCs) in atherosclerosis has been refined and re-evaluated with the aid of recent technological advancements. Previously, lineage tracing experiments have indicated that many cells with a macrophage-like phenotype in plaques have a SMC origin [3]. Recently, Pan et al. [4 && ] has shown that SMCs can differentiate into multiple cell types in atherosclerotic plaques, including a multipotent intermediate cell state, fibrochondrocyte-like cells and several macrophage-like cells, and the transition of SMCs to the multipotent intermediate cell state was regulated by retinoic acid signalling. The existence of a human analogue to the SMC-derived intermediate cell state was shown by analysing scRNAseq data obtained from few human carotid artery plaques and public scRNAseq data from human atherosclerotic coronary arteries [4 && ]. Notably, a recent study by Alencar et al. [5 && ] reached very similar conclusions by using SMC-specific Klf4-knockout and Oct4-knockout mice and chromatin immunoprecipitation sequencing in addition to scRNAseq and lineage tracing. Alencar et al. [5 && ] define a major Lgals3-positive
Identification of microorganisms directly from blood culture bottles with polymicrobial growth: comparison of FilmArray and direct MALDI‐TOF MS

Bloodstream infections (BSIs) are related to high mortality and morbidity. Rapid administration of effective antimicrobial treatment is crucial for patient survival. Recently developed rapid methods to identify pathogens directly from blood culture bottles speed up diagnosis of BSIs. The present study compares the performance of two rapid identification methods, FilmArray and direct MALDI‐TOF MS, on identifying microorganisms directly from positive blood culture bottles with polymicrobial growth. FilmArray and direct MALDI‐TOF MS were performed directly on positive clinical and simulated polymicrobial blood culture bottles. Assay results were compared with standard culture methods. In total, 110 polymicrobial blood culture samples, of which 96 samples contained two microorganisms while 14 samples contained three microorganisms, were studied. FilmArray was able to identify 215/234 (92.0%) of isolates detected by the standard culture method and successfully identified all microorganisms in 88/110 (80.0%) of blood culture bottles. In contrast, direct MALDI‐TOF MS was only able to identify 65/234 (27.8%) of isolates and managed to identify all microoganisms in 2/110 (2.1%) of blood culture bottles. FilmArray is a rapid method for direct identification of polymicrobial blood culture samples that can complement the conventional identification methods. Direct MALDI‐TOF MS has low performance with polymicrobial samples.
A distinctive distribution of hypoxia‐inducible factor‐1α in cultured renal tubular cells with hypoperfusion simulated by coverslip placement

Chronic hypoxia in the renal tubulointerstitium plays a key role in the progression of chronic kidney disease (CKD). It is therefore important to investigate tubular hypoxia and the activity of hypoxia‐inducible factor (HIF)‐1α in response to hypoxia. Rarefaction of the peritubular capillary causes hypoperfusion in CKD; however, the effect of hypoperfusion on HIFs has rarely been investigated. We induced hypoperfusion caused by coverslip placement in human kidney‐2 cells, and observed an oxygen gradient under the coverslip. Immunocytochemistry of HIF‐1α showed a doughnut‐shaped formation on the edge of a pimonidazole‐positive area, which we named the “HIF‐ring”. The oxygen tension of the HIF‐ring was estimated to be between approximately 4 mmHg and 20 mmHg. This result was not compatible with those of past research showing HIF‐1α accumulation in the anoxic range with homogeneous oxygen tension. We further observed the presence of a pH gradient under a coverslip, as well as a shift of the HIF ring due to changes in the pH of the culture medium, suggesting that the HIF ring was formed by suppression of HIF‐1α related to low pH. This research demonstrated that HIF‐1α activation mimics the physiological state in cultured cells with hypoperfusion.
Bantu-speaker migration and admixture in southern Africa

Abstract The presence of Early and Middle Stone Age human remains and associated archeological artifacts from various sites scattered across southern Africa, suggests this geographic region to be one of the first abodes of anatomically modern humans. Although the presence of hunter-gatherer cultures in this region dates back to deep times, the peopling of southern Africa has largely been reshaped by three major sets of migrations over the last 2000 years. These migrations have led to a confluence of four distinct ancestries (San hunter-gatherer, East-African pastoralist, Bantu-speaker farmer and Eurasian) in populations from this region. In this review, we have summarized the recent insights into the refinement of timelines and routes of the migration of Bantu-speaking populations to southern Africa and their admixture with resident southern African Khoe-San populations. We highlight two recent studies providing evidence for the emergence of fine-scale population structure within some South-Eastern Bantu-speaker groups. We also accentuate whole genome sequencing studies (current and ancient) that have both enhanced our understanding of the peopling of southern Africa and demonstrated a huge potential for novel variant discovery in populations from this region. Finally, we identify some of the major gaps and inconsistencies in our understanding and emphasize the importance of more systematic studies of southern African populations from diverse ethnolinguistic groups and geographic locations.
Impact of a Systematic Pharmacist-Initiated Antibiotic Time-Out Intervention for Hospitalized Adults

Introduction: Antibiotic time-outs (ATO) are a recommended antimicrobial stewardship action, but data assessing their impact are lacking. This study investigated the impact of a systematic, pharmacist initiated ATO intervention. Methods: This pre-post study included inpatients on hospitalist and intensivist services receiving empiric antibiotics for ≥48 hours. The ATO was initiated by pharmacists after 48 hours of empiric therapy and the outcome was documented including antibiotic indication, plan, and duration. An electronic medical record (EMR) alert facilitated ATO completion and pharmacists and prescribers received education prior to implementation. The primary outcome was EMR documentation of an antibiotic plan by 72 hours. Secondary outcomes included antibiotic utilization and antibiotic therapy modifications by 2 hours. Results: 399 patients were included, 199 pre- and 200 post-intervention. The most common indications were pneumonia (32%), intra-abdominal infection (20%) and urinary tract infection (19%), with no between-group differences. EMR documentation of an antibiotic plan significantly improved in the post-intervention group (19% vs. 79%, p<0.0001) as did modifications to antibiotic therapy. The median duration of in-hospital antibiotic therapy was similar between groups (4.0 vs. 4.0 days, p = 0.2499). Approximately 45% of patients in each group received discharge antibiotics and median duration of discharge antibiotic therapy prescribed was reduced (7 vs. 5 days in the pre- and post-intervention groups, respectively; p = 0.0140). Discussion: Implementation of pharmacist initiated ATO was associated with improvements in supporting EMR documentation and antibiotic therapy modifications. These findings highlight an important role in which pharmacists can serve as part of a collaborative antibiotic stewardship team.
Detection of occluding targets in natural backgrounds

Detection of target objects in the surrounding environment is a common visual task. There is a vast psychophysical and modeling literature concerning the detection of targets in artificial and natural backgrounds. Most studies involve detection of additive targets or of some form of image distortion. Although much has been learned from these studies, the targets that most often occur under natural conditions are neither additive nor distorting; rather, they are opaque targets that occlude the backgrounds behind them. Here, we describe our efforts to measure and model detection of occluding targets in natural backgrounds. To systematically vary the properties of the backgrounds, we used the constrained sampling approach of Sebastian, Abrams, and Geisler (2017). Specifically, millions of calibrated gray-scale natural-image patches were sorted into a 3D histogram along the dimensions of luminance, contrast, and phase-invariant similarity to the target. Eccentricity psychometric functions (accuracy as a function of retinal eccentricity) were measured for four different occluding targets and 15 different combinations of background luminance, contrast, and similarity, with a different randomly sampled background on each trial. The complex pattern of results was consistent across the three subjects, and was largely explained by a principled model observer (with only a single efficiency parameter) that combines three image cues (pattern, silhouette, and edge) and four well-known properties of the human visual system (optical blur, blurring and downsampling by the ganglion cells, divisive normalization, intrinsic position uncertainty). The model also explains the thresholds for additive foveal targets in natural backgrounds reported in Sebastian et al. (2017).