Miracle-dz/UniFAR-FTUs huggingface dataset:
Dyslipidemia in retinal metabolic disorders

The light‐sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid‐rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.
Identification of Patients With High Mortality Risk and Prediction of Outcomes in Delirium by Bispectral EEG.

BACKGROUND Delirium is common and dangerous, yet underdetected and undertreated. Current screening questionnaires are subjective and ineffectively implemented in busy hospital workflows. Electroencephalography (EEG) can objectively detect the diffuse slowing characteristic of delirium, but it is not suitable for high-throughput screening due to size, cost, and the expertise required for lead placement and interpretation. This study hypothesized that an efficient and reliable point-of-care EEG device for high-throughput screening could be developed. METHODS This prospective study, which measured bispectral EEG (BSEEG) from elderly inpatients to assess their outcomes, was conducted at the University of Iowa Hospitals and Clinics from January 2016 to October 2017. A BSEEG score was defined based on the distribution of 2,938 EEG recordings from the 428 subjects who were assessed for delirium; primary outcomes measured were hospital length of stay, discharge disposition, and mortality. RESULTS A total of 274 patients had BSEEG score data available for analysis. Delirium and BSEEG score had a significant association (P < .001). Higher BSEEG scores were significantly correlated with length of stay (P < .001 unadjusted, P = .001 adjusted for age, sex, and Charlson Comorbidity Index [CCI] score) as well as with discharge not to home (P < .01). Hazard ratio for survival controlling for age, sex, CCI score, and delirium status was 1.35 (95% CI,1.04 to 1.76; P = .025). CONCLUSIONS In BSEEG, an efficient and reliable device that provides an objective measurement of delirium status was developed. The BSEEG score is significantly associated with pertinent clinical outcomes of mortality, hospital length of stay, and discharge disposition. The BSEEG score better predicts mortality than does clinical delirium status. This study identified a previously unrecognized subpopulation of patients without clinical features of delirium who are at increased mortality risk.
Influence of the Accuracy of Intraoral Scanbodies on Implant Position: Differences in Manufacturing Tolerances.

PURPOSE To assess the manufacturing tolerances of three different intraoral scanbodies (ISBs) and their possible influence on the transfer of the intraoral implant position to the digital cast. MATERIALS AND METHODS Three different ISBs were measured using x-ray computed tomography. The length, diameter, angle, and target volume deviation were analyzed, and the data were subjected to a univariate analysis of variance. RESULTS There were significant differences between all three ISBs in length, diameter, and target volume deviations (P < .05). CONCLUSION Manufacturing tolerances of ISBs have the potential to decisively affect the transfer accuracy of the implant position from the recorded intraoral position to the digital cast, which needs to be considered.
A simplified 3D liver microsphere tissue culture model for hepatic cell signaling and drug-induced hepatotoxicity studies

Although a number of experimental models have been developed for liver research, each has its own advantages and disadvantages. The present study attempted to develop a simple and effective 3-dimensional mouse liver microsphere tissue culture (LMTC) model in vitro for the analysis of hepatic functions. Hepatic characteristics and potential applications of this model were compared with that of mouse model in vivo and mouse primary hepatocytes in vitro. Using freshly-perfused mouse liver tissue passed through 80-mesh sift strainer (sift80), it was demonstrated that under the optimal culture conditions, the sift80 microsphere tissue cultured in 2% bovine calf serum medium remained viable with marked proliferating cell nuclear antigen and anti-Myc proto-oncogene protein expression, exhibited normal hepatic functions including indocyanine green (ICG) uptake/release and periodic acid-Schiff staining, and expressed hepatocyte-specific genes for up to 2 weeks. The microsphere tissue was responsive to bone morphogenic protein 9 (BMP9) stimulation leading to upregulation of downstream targets of BMP9 signaling. Furthermore, 3 commonly-used liver-damaging drugs were indicated to effectively inhibit hepatic ICG uptake, and induce the expression of hepatotoxicity-associated genes. Therefore, this simplified LMTC model may be a useful in vitro tissue culture model to investigate drug-induced liver injury and metabolism, and hepatocyte-based cell singling.
Relationship between right heart echocardiographic parameters and invasive pulmonary artery pressures in canine models of chronic embolic pulmonary hypertension

Basic information related to the association between right heart echocardiographic parameters and invasive pulmonary artery pressure (PAP) in dogs with pulmonary hypetension (PH) is scarce. The aim of this study was to examine the association between conventional right heart echocardiographic parameters and invasive PAP by right heart catheterization (RHC) before and after PH. Five female beagle dogs regarded as clinically healthy were used. Echocardiography and RHC were conducted before and after creating chronic embolic pulmonary hypertension (CEPH) models. The acceleration time to ejection time ratio in pulmonary artery flow profile (AT/ET), the ratio of the pulmonary artery and aortic diameter in diastole (PA/Ao), the right pulmonary artery distensibility index by M-mode method (RPAD M-mode), the normalized right ventricular internal diameter in diastole (RVIDdn), and the normalized tricuspid annular plane systolic excursion (TAPSEn) were correlated with the invasive systolic PAP (sPAP), mean PAP (mPAP) and diastolic PAP (dPAP). Multiple linear regression analysis identified AT/ET and RVIDdn as independent predictors of sPAP, PA/Ao and RVIDdn as independent predictors of mPAP, and PA/Ao and RPAD M-mode as independent predictors of dPAP. AT/ET and PA/Ao had high sensitivity and specificity for predicting CEPH. In conclusion, AT/ET, PA/Ao, RPAD M-mode, RVIDdn and TAPSEn were significantly correlated with invasive PAP and alterations in PA/Ao or AT/ET might enable clinicians to predict PH, even if tricuspid regurgitation is not observed.
Effects of the microtubule nucleator Mto1 on chromosomal movement, DNA repair, and sister chromatid cohesion in fission yeast

Although the function of microtubules (MTs) in chromosomal segregation during mitosis is well characterized, much less is known about the role of MTs in chromosomal functions during interphase. In the fission yeast Schizosaccharomyces pombe, dynamic cytoplasmic MT bundles move chromosomes in an oscillatory manner during interphase via linkages through the nuclear envelope (NE) at the spindle pole body (SPB) and other sites. Mto1 is a cytoplasmic factor that mediates the nucleation and attachment of cytoplasmic MTs to the nucleus. Here, we test the function of these cytoplasmic MTs and Mto1 on DNA repair and recombination during interphase. We find that mto1Δ cells exhibit defects in DNA repair and homologous recombination (HR) and abnormal DNA repair factory dynamics. In these cells, sister chromatids are not properly paired, and binding of Rad21 cohesin subunit along chromosomal arms is reduced. Our findings suggest a model in which cytoplasmic MTs and Mto1 facilitate efficient DNA repair and HR by promoting dynamic chromosomal organization and cohesion in the nucleus.
LRRK2 N551K and R1398H variants are protective in Malays and Chinese in Malaysia: A case–control association study for Parkinson's disease

The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K‐R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population.
Evocalcet: A New Oral Calcimimetic for Dialysis Patients With Secondary Hyperparathyroidism

Patients with chronic kidney disease often develop secondary hyperparathyroidism (SHPT), marked by high levels of circulating parathyroid hormone (PTH) and increased risk of morbidity and mortality. Patients with SHPT are treated with a therapeutic combination that commonly includes calcimimetics, which have recently become popular in clinical settings, and other agents such as vitamin D preparations. Calcimimetics are a drug class that reduces PTH levels by targeting the calcium‐sensing receptor. Cinacalcet, a representative calcimimetic, is widely used; however, a high incidence of upper gastrointestinal (GI) tract‐related adverse events (AEs) can result in insufficient dosage and poor long‐term compliance. The newly approved evocalcet has equivalent efficacy to cinacalcet at a lower clinical dose, with improved bioavailability, fewer upper GI tract‐related AEs, and fewer safety concerns. This review gives an overview of calcimimetic agents, with a special focus on evocalcet, and describes the clinical advantages of evocalcet in the treatment of dialysis patients with SHPT.
MicroRNA-212 facilitates the motility and invasiveness of esophageal squamous carcinoma cells

As a tumor-associated microRNA (miR), miR-212 has dual functions; either as an oncogene or a tumor suppressor. A high expression level of miR-212 was reported to be associated with poor outcome in patients with esophageal squamous cell carcinoma (ESCC), however, its role in ESCC progression has not been explored. In the present study, an in vitro cell model of lentivirus-mediated gain-of-function demonstrated promotion of ESCC cell migration and invasion when miR-212 was overexpressed, and no effect on cell proliferation. miR-212 resulted in downregulation of the expression of E-cadherin, β-catenin, vimentin and Twist1. Moreover, it led to increased levels of extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinase-9 and urokinase-type plasminogen activator. Furthermore, berberine inhibited miR-212-induced ESCC cell migration, unlike the PI3K inhibitor LY294002, rapamycin (mTOR inhibitor), 5-(Tetradecyloxy)-2-furoic acid (TOFA; an acetyl-CoA carboxylase 1 inhibitor), metformin and propranolol. These data suggest that miR-212 activates multiple signaling cascades and facilitates ESCC cell motility and invasion by promoting the epithelial-mesenchymal transition and degrading the ECM. Berberine may be a potential therapeutic agent against metastasis in patients with ESCC, who express high levels of miR-212.
Germ Cell Lineage Homeostasis in Drosophila Requires the Vasa RNA Helicase

The conserved RNA helicase Vasa is required for germ cell development in many organisms. In Drosophila melanogaster loss of PIWI-interacting RNA pathway components, including Vasa, causes Chk2-dependent oogenesis arrest. However, whether the arrest is due to Chk2 signaling at a specific stage and whether continuous Chk2 signaling is required for the arrest is unknown. Here, we show that absence of Vasa during the germarial stages causes Chk2-dependent oogenesis arrest. Additionally, we report the age-dependent decline of the ovariole number both in flies lacking Vasa expression only in the germarium and in loss-of-function vasa mutant flies. We show that Chk2 activation exclusively in the germarium is sufficient to interrupt oogenesis and to reduce ovariole number in aging flies. Once induced in the germarium, Chk2-mediated arrest of germ cell development cannot be overcome by restoration of Vasa or by downregulation of Chk2 in the arrested egg chambers. These findings, together with the identity of Vasa-associated proteins identified in this study, demonstrate an essential role of the helicase in the germ cell lineage maintenance and indicate a function of Vasa in germline stem cell homeostasis.
RIM is essential for stimulated but not spontaneous somatodendritic dopamine release in the midbrain

Action potentials trigger neurotransmitter release at active zones, specialized release sites in axons. Many neurons also secrete neurotransmitters or neuromodulators from their somata and dendrites. However, it is unclear whether somatodendritic release employs specialized sites for release, and the molecular machinery for somatodendritic release is not understood. Here, we identify an essential role for the active zone protein RIM in stimulated somatodendritic dopamine release in the midbrain. In mice in which RIMs are selectively removed from dopamine neurons, action potentials failed to evoke significant somatodendritic release detected via D2 receptor-mediated currents. Compellingly, spontaneous dopamine release was normal upon RIM knockout. Dopamine neuron morphology, excitability, and dopamine release evoked by amphetamine, which reverses dopamine transporters, were also unaffected. We conclude that somatodendritic release employs molecular scaffolds to establish secretory sites for rapid dopamine signaling during firing. In contrast, basal release that is independent of action potential firing does not require RIM.
Homozygous NLRP1 gain-of-function mutation in siblings with a syndromic form of recurrent respiratory papillomatosis

Significance Recurrent respiratory papillomatosis is a disease caused by the human papillomavirus that leads to growth of warts in the throat. We report 2 brothers with a form of this disease that involves a mutation in the NLRP1 gene. This study provides a genetic explanation for our patients’ disease and suggests that other people may suffer from the same genetic disease. It also expands our understanding of diseases caused by mutations in NLRP1. Juvenile-onset recurrent respiratory papillomatosis (JRRP) is a rare and debilitating childhood disease that presents with recurrent growth of papillomas in the upper airway. Two common human papillomaviruses (HPVs), HPV-6 and -11, are implicated in most cases, but it is still not understood why only a small proportion of children develop JRRP following exposure to these common viruses. We report 2 siblings with a syndromic form of JRRP associated with mild dermatologic abnormalities. Whole-exome sequencing of the patients revealed a private homozygous mutation in NLRP1, encoding Nucleotide-Binding Domain Leucine-Rich Repeat Family Pyrin Domain-Containing 1. We find the NLRP1 mutant allele to be gain of function (GOF) for inflammasome activation, as demonstrated by the induction of inflammasome complex oligomerization and IL-1β secretion in an overexpression system. Moreover, patient-derived keratinocytes secrete elevated levels of IL-1β at baseline. Finally, both patients displayed elevated levels of inflammasome-induced cytokines in the serum. Six NLRP1 GOF mutations have previously been described to underlie 3 allelic Mendelian diseases with differing phenotypes and modes of inheritance. Our results demonstrate that an autosomal recessive, syndromic form of JRRP can be associated with an NLRP1 GOF mutation.
Severe Acne and Metabolic Syndrome: A Possible Correlation

Background/Purpose: Chronic inflammatory skin diseases have been shown to increase or predispose metabolic or vascular damage. However, little is known about systemic effects of the pro-inflammatory state of severe acne. We analyzed data of 85 patients at Lipid Outpatient Clinics (UNIFESP/EPM) who were treated for metabolic syndrome (MS). Medical history and physical examinations were performed in order to search characteristics of acne scars. Methods: Patients’ electronic records were accessed for one year. The ones presenting MS were evaluated by clinical examination in order to detect presence of acne scars. Clinical analysis comprised anamnesis, measurement of abdominal circumference, blood pressure, and body mass index (BMI). Laboratory tests included fasting glucose, CBC, serum levels of insulin, triglycerides, LDL, HDL, ALT, AST, urea, and creatinine. Statistical analysis consisted of prevalence (95% CI) of acne history/scars among patients treated at the Lipid Outpatient Clinics. The χ2 test, Pearson’s test, or Fisher’s exact test was used to evaluate the association of social and demographic data, clinical and lab exams with the presence of MS or acne scars. Statistical 5% significance level was adopted. Results: Fifty-two patients confirmed having a medical history of acne, and 33 denied. Acne scars were found in 61.17%. There was no statistical difference between the groups according to medium value of BMI, hypertension, abdominal circumference, and serum levels of hemoglobin, leucocytes, platelets, triglycerides, LDL, HDL, AST, ALT, glycemia, creatinine, and urea. Twenty-seven out of the 52 patients with acne history presented acne scars, which symbolizes a 31.76% prevalence. This equals a 51.92% prevalence among all patients with acne history. There was no statistical difference among groups according to mean (±SD) in data such as family history, weight, BMI, hypertension, abdominal circumference, serum levels of hemoglobin, leucocytes, platelets, LDL, HDL, AST, ALT, glycemia, creatinine, and urea. A statistical difference in the triglyceride level was present, being elevated in patients with acne scars. Discussion: Apart from the limitation (small sample size), a correlation between acne and MS could be suggested. The high prevalence of acne history/scars in patients treated for MS may indicate a possible correlation with any type of acne. This hypothesis may raise discussion about an association like the already proven risk of metabolic alterations in other inflammatory chronic dermatoses, such as psoriasis or rosacea, regardless of acne severity. We highlight the importance of early treatment and follow-up for patients with MS that could be observed in this study, as clinical and laboratory criteria were all within normal levels among patients from that specific outpatient clinic. Results can draw attention to evaluation of clinical and laboratory investigation related to risk of MS. It corroborates to early diagnosis and prevention of complications of MS. Further studies are needed to confirm our findings.
Differential responses of amphibian and reptile assemblages to size of riparian buffers within managed forests.

Streamside management zones (i.e., riparian buffers; SMZs) are commonly implemented within managed forests to protect water quality but may also provide habitat for riparian-associated wildlife. Yet, little research has rigorously addressed the value of SMZs for wildlife, particularly cryptic species such as amphibians and reptiles. Previous studies of herpetofauna within SMZs have focused on one or a few stream-associated species, and questions remain regarding variation among species or guilds and what role SMZs serve toward conservation of herpetofaunal diversity in managed forests. However, recent statistical advances have improved our ability to analyze large multi-species presence-absence datasets, accounting for low detection rates typical for some herpetofaunal species. Our study represents an extensive landscape-scale examination of herpetofaunal communities within SMZs using a multi-species occupancy approach. We conducted four replicate surveys at 102 headwater streams, spanning a gradient of SMZ widths and adjacent forest stand ages, within the Ouachita Mountains, Arkansas, USA. We used a hierarchical Bayesian community occupancy model to estimate species richness and species-specific occupancy responses to SMZ and overstory characteristics, accounting for variation in occupancy and detection attributable to site and sampling covariates. We documented high richness (37 species) within SMZs. Across the herpetofaunal community, occupancy and species richness were consistently positively associated with SMZ width, with maximum predicted richness of 30 species occurring at sites with buffers extending 51 m on either side of the stream. However, we documented considerable variation among groups and species within groups, underscoring the potential for different responses to forest management among taxa. Reptile predicted richness increased more rapidly up to SMZs of ~35 m, whereas maximum salamander predicted richness was not seen until a SMZ width of 55 m. Estimated salamander richness was highest within SMZs embedded in mature managed pine stands and was higher in SMZs comprised of a deciduous or mixed overstory versus a pine overstory. Compared to salamanders, more anuran species showed high mean estimated occupancy (>75%) at narrower SMZs (<30 m). Collectively, our results indicate that SMZs surrounding small first-order streams in intensively managed forests not only protect water quality, but also can support diverse amphibian and reptile communities. This article is protected by copyright. All rights reserved.
Discovery of natural naphthoquinones as sortase A inhibitors and potential anti‐infective solutions against Staphylococcus aureus

Three natural naphthoquinones were screened to find new anti‐virulence agents as inhibitors against sortase A from Staphylococcus aureus (SaSrtA) by quantifying the increase in fluorescence intensity upon substrate cleavage at various concentrations. The 5‐hydroxy‐1,4‐naphthalenedione derivatives, juglone and plumbagin, demonstrated a potent inhibitory effect, with IC50 values of 1.78 μM, respectively, 16.71 μM. The related 2‐hydroxy‐1,4‐naphthalenedione derivative, lawsone, demonstrated the selectivity of the chemical scaffold having no significant effect on SaSrtA. The experimental assay was reinforced by molecular docking experiments, antimicrobial, and toxicological studies. Molecular docking studies and the electrophilic character analysis suggest bonding to the enzyme active cysteine residue by a Michael addition reaction. None of the compounds had a significant effect on the concentration of total thiol proteins in the Daphnia magna toxicological assay after 24 hr exposure. Juglone and plumbagin moderately inhibited biofilm formation with no significant effect on bacterial growth of S. aureus, Enterococcus faecalis, and Staphylococcus epidermidis, indicating a selective anti‐virulence profile.