Miracle-dz/UniFAR-FTUs huggingface dataset:
ATVB IN FOCUS: Trained Immunity and Vascular Disease

Innate immune cells can develop exacerbated immunologic response and long-term inflammatory phenotype following brief exposure to endogenous or exogenous insults, which leads to an altered response towards a second challenge after the return to a nonactivated state. This phenomenon is known as trained immunity (TI). TI is not only important for host defense and vaccine response but also for chronic inflammations such as cardiovascular and metabolic diseases such as atherosclerosis. TI can occur in innate immune cells such as monocytes/macrophages, natural killer cells, endothelial cells (ECs), and nonimmune cells, such as fibroblast. In this brief review, we analyze the significance of TI in ECs, which are also considered as innate immune cells in addition to macrophages. TI can be induced by a variety of stimuli, including lipopolysaccharides, BCG (bacillus Calmette-Guerin), and oxLDL (oxidized low-density lipoprotein), which are defined as risk factors for cardiovascular and metabolic diseases. Furthermore, TI in ECs is functional for inflammation effectiveness and transition to chronic inflammation. Rewiring of cellular metabolism of the trained cells takes place during induction of TI, including increased glycolysis, glutaminolysis, increased accumulation of tricarboxylic acid cycle metabolites and acetyl-coenzyme A production, as well as increased mevalonate synthesis. Subsequently, this leads to epigenetic remodeling, resulting in important changes in chromatin architecture that enables increased gene transcription and enhanced proinflammatory immune response. However, TI pathways and inflammatory pathways are separated to ensure memory stays when inflammation undergoes resolution. Additionally, reactive oxygen species play context-dependent roles in TI. Therefore, TI plays significant roles in EC and macrophage pathology and chronic inflammation. However, further characterization of TI in ECs and macrophages would provide novel insights into cardiovascular disease pathogenesis and new therapeutic targets. GRAPHIC ABSTRACT: A graphic abstract is available for this article.
Estimation of fractional myocardial blood volume and water exchange using ferumoxytol‐enhanced magnetic resonance imaging

Fractional myocardial blood volume (fMBV) estimated using ferumoxytol‐enhanced magnetic resonance imaging (MRI) (FE‐MRI) has the potential to capture a hemodynamic response to myocardial hypoperfusion during contrast steady state without reliance on gadolinium chelates. Ferumoxytol has a long intravascular half‐life and its use for steady‐state MRI is off‐label. The aim of this prospective study was to optimize and evaluate a two‐compartment model for estimation of fMBV based on FE‐MRI. Nine healthy swine and one swine with artificially induced single‐vessel coronary stenosis underwent MRI on a 3.0 T clinical magnet. Myocardial longitudinal spin–lattice relaxation rate (R1) was measured using the 5(3)3(3)3 modified Look‐Locker inversion recovery (MOLLI) sequence before and at contrast steady state following seven ferumoxytol infusions (0.125–4.0 mg/kg). fMBV and water exchange were estimated using a two‐compartment model. Model‐fitted fMBV was compared to simple fast‐exchange fMBV approximation and percent change in pre‐ and postferumoxytol R1. Dose undersampling schemes were investigated to reduce acquisition duration. Variation in fMBV was assessed using one‐way analysis of variance. Fast‐exchange fMBV and ferumoxytol dose undersampling were evaluated using Bland–Altman analysis. Healthy normal swine showed a mean mid‐ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s−1. There was intersubject variation in fMBV (p < 0.05) without segmental variation (p = 0.387). fMBV derived from eight‐dose and four‐dose sampling schemes had no significant bias (mean difference = 0.07, p = 0.541, limits of agreement −1.04% [−1.45, −0.62%] to 1.18% [0.77, 1.59%]). Pixel‐wise fMBV in one swine model with coronary artery stenosis showed elevated fMBV in ischemic segments (apical anterior: 11.90 ± 4.00%, apical septum: 16.10 ± 5.71%) relative to remote segments (apical inferior: 9.59 ± 3.35%, apical lateral: 9.38 ± 2.35%). A two‐compartment model based on FE‐MRI using the MOLLI sequence may enable estimation of fMBV in studies of ischemic heart disease.
Biological and Histological Assessment of the Hepatoportoenterostomy Role in Biliary Atresia as a Stand-Alone Procedure or as a Bridge toward Liver Transplantation

Background and objectives: In patients with biliary atresia (BA), hepatoportoenterostomy (HPE) is still a valuable therapeutic tool for prolonged survival or a safer transition to liver transplantation. The main focus today is towards efficient screening programs, a faster diagnostic, and prompt treatment. However, the limited information on BA pathophysiology makes valuable any experience in disease management. This study aimed to analyze the evolution and survival of patients with BA referred for HPE (Kasai operation) in our department. Materials and Methods: A retrospective analysis was performed on fourteen patients with BA, diagnosed in the pediatric department and further referred for HPE in our surgical department between 2010 and 2016. After HPE, the need for transplantation was assessed according to patients cytomegalovirus (CMV) status, and histological and biochemical analysis. Follow-up results at 1–4 years and long term survival were assessed. Results: Mean age at surgery was 70 days. Surgery in patients younger than 60 days was correlated with survival. Jaundice’s clearance rate at three months was 36%. Total and direct bilirubin values had a significant variation between patients with liver transplants and native liver (p = 0.02). CMV was positive in eight patients, half with transplant need and half with native liver survival. Smooth muscle actin (SMA) positivity was proof of advanced fibrosis. The overall survival rate was 79%, with 75% for native liver patients and an 83% survival rate for those with liver transplantation. Transplantation was performed in six patients (43%), with a mean of 10 months between HPE and transplantation. Transplanted patients had better survival. Complications were diagnosed in 63% of patients. The mean follow-up period was six years. Conclusions: HPE, even performed in advanced cirrhosis, allows a significant survival, and ensures an essential time gain for patients requiring liver transplantation. A younger age at surgery is correlated with a better outcome, despite early CMV infection.
Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update

The scientific knowledge already attained regarding the way severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human cells and the clinical manifestations and consequences for Coronavirus Disease 2019 (COVID-19) patients, especially the most severe cases, brought gut microbiota into the discussion. It has been suggested that intestinal microflora composition plays a role in this disease because of the following: (i) its relevance to an efficient immune system response; (ii) the fact that 5–10% of the patients present gastrointestinal symptoms; and (iii) because it is modulated by intestinal angiotensin-converting enzyme 2 (ACE2) (which is the virus receptor). In addition, it is known that the most severely affected patients (those who stay longer in hospital, who require intensive care, and who eventually die) are older people with pre-existing cardiovascular, metabolic, renal, and pulmonary diseases, the same people in which the prevalence of gut microflora dysbiosis is higher. The COVID-19 patients presenting poor outcomes are also those in which the immune system’s hyperresponsiveness and a severe inflammatory condition (collectively referred as “cytokine storm”) are particularly evident, and have been associated with impaired microbiota phenotype. In this article, we present the evidence existing thus far that may suggest an association between intestinal microbiota composition and the susceptibility of some patients to progress to severe stages of the disease.
Attractiveness-related recognition bias captures the memory of the beholder.

Earlier electroencephalographic studies have compared attractive and unattractive faces and between faces with other objects, such as flowers, without revealing if a recognition memory bias toward faces and flowers exists or whether humans exhibit enhanced specific components toward all attractive objects or only toward attractive faces. For objects with similar degrees of attractiveness, we sought to determine if the N170, P1, and N250 reflect upon the attractiveness of faces and flowers and demonstrated by comparing event-related potentials of humans' different perceptual mechanisms recognizing high attractive faces and high attractive flowers. The repeated high attractive faces tended to elicit a larger N170. Simultaneously, the P1 was preferentially associated with the repeated high attractive flowers, but both indicated that the repetitive enhancement effect only occurred on repeated attractive faces. Thus, differences existed in the perceptual mechanisms for processing repeated high attractive faces and repeated high attractive flowers. However, there was no significant difference in N250 between repeated faces and repeated flowers or between high attractive faces and high attractive flowers. Consequently, high attractive faces and high attractive flowers capture the beholder's memory bias in different processing stages. The N170 and P1 components are affected by attractiveness, thereby demonstrating the differences between human perceptual mechanisms in recognizing high attractive faces and objects.
An Insight into the Role of Non-Porphyrinoid Photosensitizers for Skin Wound Healing

The concept behind photodynamic therapy (PDT) is being successfully applied in different biomedical contexts such as cancer diseases, inactivation of microorganisms and, more recently, to improve wound healing and tissue regeneration. The effectiveness of PDT in skin treatments is associated with the role of reactive oxygen species (ROS) produced by a photosensitizer (PS), which acts as a “double agent”. The release of ROS must be high enough to prevent microbial growth and, simultaneously, to accelerate the immune system response by recruiting important regenerative agents to the wound site. The growing interest in this subject is reflected by the increasing number of studies concerning the optimization of relevant experimental parameters for wound healing via PDT, namely, light features, the structure and concentration of the PS, and the wound type and location. Considering the importance of developing PSs with suitable features for this emergent topic concerning skin wound healing, in this review, a special focus on the achievements attained for each PS class, namely, of the non-porphyrinoid type, is given.
Plasticity of sentence processing networks: evidence from a patient with agrammatic variant of primary progressive aphasia (PPA)

ABSTRACT This study reports the results of a longitudinal study examining the effects of treatment for sentence processing deficits for a 70-year-old gentleman (DK) with the agrammatic variant of Primary Progressive Aphasia (PPA). On entry into the study, he presented with a 2-year history of impaired verb and sentence processing and concomitant neural atrophy in primarily subcortical regions. Spanning an 18-month period, treatment focused on improving comprehension and production of syntactically complex, passive and object cleft, structures, consecutively. Results, derived from extensive behavioral and neurocognitive testing, showed not only improved ability to comprehend and produce both trained and untrained, less complex, linguistically related structures in offline tasks, but also improved online sentence processing strategies as revealed by partially normalized eye movements in online comprehension (i.e., emergence of thematic prediction and thematic integration) and production (i.e., use of incremental processing) tasks. Changes in neural activation from pre- to post-treatment of both structures also were found, with upregulation of tissue in both the left and right hemispheres, overlapping with regions recruited by neurotypical adults performing the same task. These findings indicate that Treatment of Underlying Forms (TUF) is effective for treatment of patients with the agrammatic variant of PPA (as it is for those with stroke-induced agrammatism), and show that unaffected neural tissue in patients with PPA is malleable and may be recruited to support language, providing evidence of experience-based plasticity in neurodegenerative disease.
The global prevalence of apical periodontitis: a systematic review and meta-analysis.

BACKGROUND Apical periodontitis (AP) frequently presents as a chronic asymptomatic disease. To achieve its diagnosis, in addition to the clinical examination, it is mandatory to undertake radiographic examinations such as periapical or panoramic radiographs, or cone beam computed tomography (CBCT). Thus, the worldwide burden of AP is probably underestimated or unknown. Previous systematic reviews attempted to estimate the prevalence of AP, but none have investigated which factors may influence its prevalence worldwide. OBJECTIVES To assess: i) the prevalence of AP in the population worldwide, as well as the frequency of AP in all teeth, non-treated teeth and root filled teeth; ii) which factors can modify the prevalence of AP. METHODS A search was conducted in the PubMed-MEDLINE, EMBASE, Cochrane-CENTRAL, LILACS, Google scholar and OpenGrey databases, followed by hand searches, until September 2019. Cross-sectional, case-control and cohort studies reporting the prevalence of AP in humans, using panoramic or periapical radiograph or CBCT as image methods were included. No language restriction was applied. An adaptation of the Newcastle-Ottawa Scale was used to evaluate the quality of the studies. A meta-analysis was performed to determine the pooled prevalence of AP at the individual level. Secondary outcomes were the frequency of AP in all teeth, non-treated teeth and root filled teeth. Subgroup analyses using random-effect models were carried out to analyse the influence of explanatory covariables on the outcome. RESULTS The search strategy identified 6,670 articles, and 114 studies were included in the meta-analysis, providing data from 34,668 individuals and 639,357 teeth. The prevalence of AP was 52% at the individual level (95% CI, 42%-56%, I2 = 97.8%) and 5% at the tooth level (95% CI, 4%-6%; I2 = 99.5%). The frequency of AP in root filled teeth and non-treated teeth was 39% (95% CI, 36%-43%; I2 = 98.5%) and 3% (95% CI, 2%-3%; I2 = 99.3%), respectively. The prevalence of AP was higher in samples from dental care services (DCS) (57%; 95% CI, 52%-62%; I2 = 97.8%) and hospitals (51%; 95% CI, 40%- 63%; I2 =95.9%;) than in those from the general population (GP) (40%; 95% CI, 33%-46%; I2 = 96.5%); it was also higher in people with a systemic condition (63%; 95% CI, 56%-69%, I2 =89.7%) compared to healthy individuals (48%; 95%CI, 43%-53%; I2 = 98.3%). DISCUSSION The subgroup analyses identified explanatory factors related to the variability in the prevalence of AP. However, the high clinical heterogeneity and high risk of bias across the primary studies indicate that the findings must be interpreted with caution. CONCLUSIONS Half of the adult population worldwide have at least one tooth with apical periodontitis. The prevalence of AP is higher in samples from DCS, but it is also high among community representative samples from the general population. The present findings should bring the attention of health policymakers, medical and dental communities to the hidden burden of endodontic disease in the population worldwide.
Serrated neoplasia in the colorectum: gut microbiota and molecular pathways

ABSTRACT Colorectal cancer (CRC) is a heterogeneous disease with different gene expression patterns. There are two major colorectal carcinogenesis pathways: conventional adenoma-carcinoma pathway and alternative serrated neoplasia pathway. Apart from the conventional pathway that is typically initiated by characteristic APC mutation and chromosomal instability, the serrated neoplasia pathway is mainly characterized by mutations of BRAF or KRAS, microsatellite instability (MSI), and CpG island methylator phenotype (CIMP). Despite the malignant potential of serrated lesions, they can be easily overlooked during endoscopy screening and even in pathological assessment due to its anatomical location, morphology, and histological features. It has been shown that environmental factors especially the gut microbial composition play a key role in CRC pathogenesis. Thus, the preferential localization of serrated lesions in specific intestine areas suggest that niche-specific microbiota composition might intertwined with host genetic perturbations during the development of serrated lesions. Although serrated lesions and conventional adenomas are biologically different, most studies have focused on conventional adenomas, while the pathophysiology and role of microorganisms in the development of serrated lesions remain elusive. In this review, we discuss on the role of gut microbiota in the serrated neoplasia pathway of colorectal carcinogenesis and its specific clinical and molecular features, and summarize the potential mechanisms involved.
Alterations in Rat Accumbens Dopamine, Endocannabinoids and GABA Content During WIN55,212-2 Treatment: The Role of Ghrelin

The endocannabinoid/CB1R system as well as the central ghrelin signalling with its growth hormone secretagogoue receptors (GHS-R1A) are importantly involved in food intake and reward/reinforcement processing and show distinct overlaps in distribution within the relevant brain regions including the hypothalamus (food intake), the ventral tegmental area (VTA) and the nucleus accumbens (NAC) (reward/reinforcement). The significant mutual interaction between these systems in food intake has been documented; however, the possible role of ghrelin/GHS-R1A in the cannabinoid reinforcement effects and addiction remain unclear. Therefore, the principal aim of the present study was to investigate whether pretreatment with GHS-R1A antagonist/JMV2959 could reduce the CB1R agonist/WIN55,212-2–induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. The synthetic aminoalklylindol cannabinoid WIN55,212-2 administration into the posterior VTA induced significant accumbens dopamine release, which was significantly reduced by the 3 mg/kg i.p. JMV2959 pretreatment. Simultaneously, the cannabinoid-increased accumbens dopamine metabolic turnover was significantly augmented by the JMV2959 pretreament. The intracerebral WIN55,212-2 administration also increased the endocannabinoid arachidonoylethanolamide/anandamide and the 2-arachidonoylglycerol/2-AG extracellular levels in the NACSh, which was moderately but significantly attenuated by the JMV2959 pretreatment. Moreover, the cannabinoid-induced decrease in accumbens γ-aminobutyric acid/gamma-aminobutyric acid levels was reversed by the JMV2959 pretreatment. The behavioural study in the LABORAS cage showed that 3 mg/kg JMV2959 pretreatment also significantly reduced the systemic WIN55,212-2-induced behavioural stimulation. Our results demonstrate that the ghrelin/GHS-R1A system significantly participates in the rewarding/reinforcing effects of the cannabinoid/CB1 agonist that are involved in cannabinoid addiction processing.
Association of Cognitive Function and Retinal Neural and Vascular Structure in Type 1 Diabetes.

CONTEXT Cognitive dysfunction is a growing and understudied public health issue in the aging type 1 diabetic population and is difficult and time-consuming to diagnose. Studies in long duration type 1 diabetes have reported the presence of proliferative diabetic retinopathy (PDR) was associated with cognitive dysfunction. OBJECTIVE This study assessed whether structural and vascular abnormalities of the retina, representing an extension of the central nervous system, are associated with cognitive impairment and other complications of type 1 diabetes. DESIGN Observational cross-sectional study of individuals with ≥50 years of type 1 diabetes (Joslin Medalist Study). SETTING University hospital in United States. PARTICIPANTS 129 participants with complete cognitive testing. MAIN OUTCOME MEASURES Validated cognitive testing measures which include psychomotor speed, and immediate, and delayed memory. Optical coherence tomography (OCT) and OCT angiography (OCTA) were performed to obtain neural retinal layer thicknesses and vascular density (VD) for superficial (SCP) and deep retinal capillary plexus (DCP). Multivariable modeling adjusted for potential confounders associated with outcomes in unadjusted analyses. RESULTS Decreased vessel density of the SCP and DCP was associated with worse delayed memory (DCP: p=0.002) and dominant hand psychomotor speed (SCP: p=0.01). Thinning of retinal outer nuclear layer was associated with worse psychomotor speed in both non-dominant and dominant hands (p=0.01 and p=0.05, respectively). Outer plexiform layer thickness was associated with delayed memory (p=0.04). CONCLUSION These findings suggest that noninvasive retinal imaging using OCT and OCTA may assist in estimating the risks for cognitive dysfunction in people with type 1 diabetes.
Performance of a Point-of-Care Test for the Rapid Detection of SARS-CoV-2 Antigen

The rapid detection of infections caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary in the ongoing pandemic. Antigen-specific point-of-care tests (POCT) may be useful for this purpose. Here, such a POCT (SARS-CoV-2 NADAL® COVID-19 Ag) was compared to a laboratory-developed triplex real-time polymerase chain reaction (RT-PCR) designed for the detection of viral nucleoprotein gene and two control targets. This RT-PCR served as a reference to investigate POCT sensitivity by re-testing upper respiratory tract (URT) samples (n = 124) exhibiting different SARS-CoV-2 loads in terms of RT-PCR threshold cycle (Ct) values. The optical intensities of the antigen bands were compared to the Ct values of the RT-PCR. The infectivity of various virus loads was estimated by inoculating Vero cells with URT samples (n = 64, Ct 17-34). POCT sensitivity varied from 100% (Ct < 25) to 73.1% (Ct ≤ 30); higher SARS-CoV-2 loads correlated with higher band intensities. All samples with a Ct > 30 were negative; among SARS-CoV-2 free samples (n = 10) no false-positives were detected. A head-to-head comparison with another POCT (Abbott, Panbio™ COVID-19 Ag Rapid Test) yielded similar results. Isolation of SARS-CoV-2 in cell-culture was successful up to a Ct value of 29. The POCT reliably detects high SARS-CoV-2 loads and rapidly identifies infectious individuals.