Miracle-dz/UniFAR-FTUs huggingface dataset:
No evidence of attenuation of placental insulin-stimulated Akt phosphorylation and amino acid transport in obesity and gestational diabetes mellitus.

Pregnancies complicated by obesity and/or gestational diabetes (GDM) are associated with peripheral insulin resistance, however the insulin responsiveness of the placenta in these pregnancy complications remains largely unknown. We tested the hypothesis that primary human trophoblast cells and placental villous explants will be insulin responsive characterized by amino acid transport, Akt and Erk activity with maternal obesity and/or GDM.We evaluated term placentas from women with normal body mass index (BMI) (NORMAL, n=15), obesity (OB, n=11), normal BMI with GDM (N-GDM, n=11) and obesity with GDM (OB-GDM, n=11). In a subgroup, primary human trophoblast cells (PHT) were isolated and in an independent subgroup placental villous explants were exposed to varying concentrations of insulin. Amino acid transport capacity and insulin signaling activity were determined. Insulin significantly increased amino acid transport activity to a similar degree in PHT cells isolated from NORMAL (+21%), N-GDM (+38%), OB (+37%) and OB-GDM (+35%) pregnancies. Insulin increased Akt and Erk phosphorylation in PHT cells (3-fold) and in villous explants (2-fold) in all groups to a similar degree.In contrast to the peripheral maternal insulin resistance commonly associated with obesity and/or GDM we found that the placenta is insulin sensitive in these pregnancy complications. We suggest that elevated maternal insulin levels in pregnancies complicated by obesity and/or GDM promote critical placental functions, including amino acid transport. Insulin-stimulated placental nutrient delivery may contribute to the increased risk of fetal overgrowth and adiposity in these pregnancies. Moreover, our findings may inform efforts to optimize insulin regimens for women with GDM.
Age‐ and Lesion‐Related Comorbidity Burden Among US Adults With Congenital Heart Disease: A Population‐Based Study

Background As patients with congenital heart disease (CHD) are living longer, understanding the comorbidities they develop as they age is increasingly important. However, there are no published population‐based estimates of the comorbidity burden among the US adult patients with CHD. Methods and Results Using the IBM MarketScan commercial claims database from 2010 to 2016, we identified adults aged ≥18 years with CHD and 2 full years of continuous enrollment. These were frequency matched with adults without CHD within categories jointly defined by age, sex, and dates of enrollment in the database. A total of 40 127 patients with CHD met the inclusion criteria (mean [SD] age, 36.8 [14.6] years; and 48.2% were women). Adults with CHD were nearly twice as likely to have any comorbidity than those without CHD (P<0.001). After adjusting for covariates, patients with CHD had a higher prevalence risk ratio for “previously recognized to be common in CHD” (risk ratio, 9.41; 95% CI, 7.99–11.1), “other cardiovascular” (risk ratio, 1.73; 95% CI, 1.66–1.80), and “noncardiovascular” (risk ratio, 1.47; 95% CI, 1.41–1.52) comorbidities. After adjusting for covariates and considering interaction with age, patients with severe CHD had higher risks of previously recognized to be common in CHD and lower risks of other cardiovascular comorbidities than age‐stratified patients with nonsevere CHD. For noncardiovascular comorbidities, the risk was higher among patients with severe than nonsevere CHD before, but not after, the age of 40 years. Conclusions Our data underscore the unique clinical needs of adults with CHD compared with their peers. Clinicians caring for CHD may want to use a multidisciplinary approach, including building close collaborations with internists and specialists, to help provide appropriate care for the highly prevalent noncardiovascular comorbidities.
Photodynamic Therapy Activity of New Porphyrin-Xylan-Coated Silica Nanoparticles in Human Colorectal Cancer

Photodynamic therapy (PDT) using porphyrins has been approved for treatment of several solid tumors due to the generation of cytotoxic reactive oxygen species (ROS). However, low physiological solubility and lack of selectivity towards tumor sites are the main limitations of their clinical use. Nanoparticles are able to spontaneously accumulate in solid tumors through an enhanced permeability and retention (EPR) effect due to leaky vasculature, poor lymphatic drainage, and increased vessel permeability. Herein, we proved the added value of nanoparticle vectorization on anticancer efficacy and tumor-targeting by 5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (TPPOH). Using 80 nm silica nanoparticles (SNPs) coated with xylan-TPPOH conjugate (TPPOH-X), we first showed very significant phototoxic effects of TPPOH-X SNPs mediated by post-PDT ROS generation and stronger cell uptake in human colorectal cancer cell lines compared to free TPPOH. Additionally, we demonstrated apoptotic cell death induced by TPPOH-X SNPs-PDT and the interest of autophagy inhibition to increase anticancer efficacy. Finally, we highlighted in vivo, without toxicity, elevated anticancer efficacy of TPPOH-X SNPs through improvement of tumor-targeting compared to a free TPPOH protocol. Our work demonstrated for the first time the strong anticancer efficacy of TPPOH in vitro and in vivo and the merit of SNPs vectorization.
Does Oxygen Stable Isotope Composition in Primates Vary as a Function of Vertical Stratification or Folivorous Behaviour?

Stable isotopes of oxygen often vary within a community of primates. For example, folivorous monkeys that forage in the upper reaches of the forest canopy tend to evince high δ18O values, whereas those that prefer the understory tend to have lower δ18O values. Given that leaves also have high δ18O values, particularly higher in the canopy, there is uncertainty as to which behavioural variable – vertical stratification or folivory – is the primary determinant of variation in δ18O values. Here, we explore further δ18O values from the Taï Forest monkeys (n = 7 species; n = 33 individuals) by examining the interaction between diet and vertical stratification, thereby allowing us to differentiate the effects of each covariate. We found that δ18O values varied as a function of mean canopy height, but not folivory, resolving uncertainty about the primary cause of δ18O variation. This outcome revolves largely, but not entirely, on the behaviours of Procolobus verus, a highly folivorous but understory forager. Relatively elevated values in Cercopithecus diana, a frugivorous but middle-to-high canopy forager, raises the possibility that plant reproductive tissues (e.g., fruits, flowers) may be increasingly sensitive to evaporative fractionation at higher forest canopy levels. Overall, our results further affirm the value of using δ18O values to estimate the vertical behaviour of primate species in a fossil assemblage.
Pancreas divisum inversus

Pancreatic duct variations are usually diagnosed incidentally, in particular when using magnetic resonance cholangiopancreatography (MRCP), the most accurate imaging modality for depicting the pancreatic ductal system. However, the frequency and the embryologic development of pancreatic variants have not been well investigated. The purpose of this prospective study was to investigate the frequency of pancreatic ductal variants, providing potential explanations of their embryologic basis. The pancreatic ductal anatomies of 202 patients with mean ± standard deviation (SD) age of 54 ± 27 years, 56% females, who underwent MRCP for different indications between April 2018 and March 2019, were prospectively collected. Normal pancreatic ductal variants were identified in 196 cases (97%), and variants of pancreas divisum in six cases (3%). In the type C variant of the normal pancreatic anatomy, found in 3% of the cases, the dorsal duct was joined to the ventral duct while the accessory duct did not communicate with the dorsal duct. Unlike the classic type C variant, in our cases, the accessory pancreatic duct (APD) was long (mean ± SD of 58 ± 8.5 mm) and originated in the lower portion of the pancreatic head, caudally to the duct of Wirsung. This was a new subtype of the type C variant or a new variant, which could be called “pancreas divisum inversus”; the APD could be called the isolated duct of Santorini. Reporting this new variant could increase knowledge regarding the pancreatic anatomy in order to avoid misdiagnosis and to help in better understanding pancreatic diseases and their relative treatment. Clin. Anat. , 33:646–652, 2020. © 2019 Wiley Periodicals, Inc.
Early Mortality Rates After Commencement of Maintenance Hemodialysis: A Systematic Review and Meta‐Analysis

Mortality rates are reported to be high soon after the commencement of maintenance HD for ESRD. Our aim was to estimate early mortality rates (deaths within 180 days of starting therapy), through a systematic review of literature, in this patient population. Medline and EMBASE were searched for publications between 1 January 1985 and 31 December 2017. Observational studies reporting deaths involving adults commencing HD were included. The Quality in Prognosis Studies tool was used to assess risk of bias in studies. Crude mortality rates (expressed in 100 person‐years) and age‐standardized mortality ratios (SMR) were calculated. Meta‐analyses of these rates were conducted for studies with lowest risk of bias (i.e. highest quality). In total, 32 studies were included (combined population: 1 083 264) representing 283 277 person‐years of observation; median follow‐up: 90 days. Mortality rates ranged between 12.8 and 55.6 per 100 person‐years. Cardiovascular causes accounted for the majority of early deaths. Meta‐analysis of high‐quality studies showed an overall crude mortality rate of 32.6 per 100 person‐years (95% CI 32.4–32.8). This equates to 16.3% mortality in first 180 days of starting HD. Six high‐quality studies contained sufficient data for calculation of SMR. Meta‐analysis of SMRs showed that patients starting HD therapy sustain 8.8 times higher mortality rates compared to the general population. We have combined the results of high‐quality studies to produce new estimates of early mortality rates after commencement of HD therapy. This information can help relay more reliable prognostic information to this patient population.
Importance of Zika Virus NS5 Protein for Viral Replication

Zika virus is the latest addition to an ever-growing list of arboviruses that are causing outbreaks with serious consequences. A few mild cases were recorded between 1960 and 1980 until the first major outbreak in 2007 on Yap Island. This was followed by more severe outbreaks in French Polynesia (2013) and Brazil (2015), which significantly increased both Guillain-Barre syndrome and microcephaly cases. No current vaccines or treatments are available, however, recent studies have taken interest in the NS5 protein which encodes both the viral methyltransferase and RNA-dependent RNA polymerase. This makes it important for viral replication alongside other important functions such as inhibiting the innate immune system thus ensuring virus survival and replication. Structural studies can help design inhibitors, while biochemical studies can help understand the various mechanisms utilized by NS5 thus counteracting them might inhibit or abolish the viral infection. Drug repurposing targeting the NS5 protein has also proven to be an effective tool since hundreds of thousands of compounds can be screened therefore saving time and resources, moreover information on these compounds might already be available especially if they are used to treat other ailments.
Role of Virtual Reality in Balance Training in Patients with Spinal Cord Injury: A Prospective Comparative Pre-Post Study

Study Design Prospective comparative pre–post study. Purpose To evaluate the effects of game-based virtual reality (VR) training program for trunk postural control and balance in patients with spinal cord injury (SCI) and to assess the results according to the motor completeness (severity) of lesions using the American Spinal Injury Association Impairment Scale (AIS). Overview of Literature Training with VR based gaming has a role to play in improving balance in patients with SCI. Methods Patients with SCI (traumatic and non-traumatic) for <6 months were included in this hospital-based study. Participants were divided into two groups: experimental group (EG) consisting 21 patients, and control group (CG) consisting 12. Both groups underwent the conventional rehabilitation program. An additional training with semi-immersive VR therapy was conducted 5 days a week for 3 weeks in the EG with the focus on balance rehabilitation using the “Rhetoric. ” The outcome measures were the Berg Balance Scale (BBS), balance section of the Tinetti Performance-Oriented Mobility Assessment (POMA-B), and Functional Reach Score (FRS). Results Both groups consisted of young participants (mean age, 28 and 30.5 years, respectively) and predominantly men (>80%). One-third of them had tetraplegia and two-third had paraplegia. Between-group analyses showed no statistically significant differences in the main effects between groups (p-value: BBS, 0.396; POMA-B, 0.238; FRS, 0.294), suggesting that the EG group did not show significant improvement in the trunk and posture at the end of training sessions than the CG group. Similarly, no significant difference was observed according to the severity (completeness) of SCI in the between-group analyses using the AIS (A/B vs. C/D). Conclusions VR is an adjunctive therapy for balance rehabilitation in patients with SCI.
N-cadherin-regulated FGFR ubiquitination and degradation control mammalian neocortical projection neuron migration

The functions of FGF receptors (FGFRs) in early development of the cerebral cortex are well established. Their functions in the migration of neocortical projection neurons, however, are unclear. We have found that FGFRs regulate multipolar neuron orientation and the morphological change into bipolar cells necessary to enter the cortical plate. Mechanistically, our results suggest that FGFRs are activated by N-Cadherin. N-Cadherin cell-autonomously binds FGFRs and inhibits FGFR K27- and K29-linked polyubiquitination and lysosomal degradation. Accordingly, FGFRs accumulate and stimulate prolonged Erk1/2 phosphorylation. Neurons inhibited for Erk1/2 are stalled in the multipolar zone. Moreover, Reelin, a secreted protein regulating neuronal positioning, prevents FGFR degradation through N-Cadherin, causing Erk1/2 phosphorylation. These findings reveal novel functions for FGFRs in cortical projection neuron migration, suggest a physiological role for FGFR and N-Cadherin interaction in vivo and identify Reelin as an extracellular upstream regulator and Erk1/2 as downstream effectors of FGFRs during neuron migration.
Effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood

Irinotecan is one of the most important anti‐tumour drugs against a broad spectrum of malignancies, but is known to be associated with possible oral complications. The aim of the present study was to evaluate the effect of irinotecan on the tongue mucosa of juvenile male albino rat at adulthood using different histological and immunohistochemical methods. Twenty juvenile male albino rats were divided equally into two groups: control and irinotecan‐treated group (single injection of 200 mg irinotecan/kg, then kept for four weeks without treatment). The tongue specimens were processed for light microscopy and scanning electron microscopy. The irinotecan‐treated group showed statistically significant shortening and thinning of the lingual papillae. There was loss of the normal appearance of the filiform papillae with focal cell loss alternating with areas of hyperkeratosis. Focal separation of the keratin layer, some nuclear changes and vacuolation of some epithelial cells were detected. Dilated congested blood vessels and mild mononuclear cellular infiltration were encountered. Atrophic fungiform papillae with ill‐defined taste bud cells were observed. A statistically significant decrease in the pattern of Ki67 immunohistochemical staining reaction was detected in comparision to the control group. Scanning electron microscopy revealed different signs of atrophy of the tongue papillae. Focal areas of desquamation of lingual papillae were observed revealing some filiform papillae with desquamated surface, bisected tips and evident thinning. Some extravasated red blood cells could be detected. Thus irinotecan caused significant morphological and morphometrical alterations of the tongue mucosa in particularly the filiform papillae.
The association between genetic polymorphism of glutathione peroxidase 1 (rs1050450) and keratoconus in a Turkish population.

PURPOSE To investigate the potential associations between keratoconus and catalase rs1001179, superoxide dismutase 2 rs4880, and glutathione peroxidase 1 rs1050450 gene polymorphisms in a Turkish population. METHODS The study group included 121 unrelated keratoconus patients and 94 unrelated healthy controls. Blood samples (200 ml) were collected from all patients and controls to isolate genomic DNA. Genotyping was performed to identify rs1001179, rs4880, and rs1050450 using real-time polymerase chain reaction (PCR). Genotype and allele frequencies were calculated; their associations with keratoconus risk were assayed, and the association with keratoconus risk and demographic factors was examined. RESULTS Glutathione peroxidase 1 rs1050450 polymorphism was present in 41% cases compared with 29% controls (OR=1.66; 95% CI=1.11-2.50; p=0.014). No association was observed between catalase rs1001179 and SOD2 rs4880 polymorphisms and keratoconus (for all, p>0.05). CONCLUSIONS This study evaluated possible relationships between rs1050450, rs1001179, and rs4880 polymorphisms and keratoconus susceptibility. We found a possible association between glutathione peroxidase 1 rs1050450 polymorphism and an increased risk of keratoconus. However, the genotype and allele frequencies were identical in the catalase rs1001179 and superoxide dismutase 2 rs4880 polymorphisms. Further studies are needed to analyze the effect of such variations in identifying keratoconus susceptibility.
Serum levels of infliximab in Brazilian patients with Crohn's disease: what are the reasons for differences from previous studies?

Dear Sir, It was with significant interest that we read the manuscript, entitled “Serum Levels of Infliximab and Anti-Infliximab Antibodies in Brazilian Patients with Crohn’s Disease”, recently published in this distinguished journal by Gomes et al. (). In this study, the authors measured the serum infliximab (IFX) levels of 40 patients with Crohn’s disease (CD) and correlated their findings with disease activity. There was no difference in the IFX level between patients with active disease and those with remission (p
Relevance of Antibody Validation for Flow Cytometry

Antibody reagents are the key components of multiparametric flow cytometry analysis. Their quality performance is an absolute requirement for reproducible flow cytometry experiments. While there is an enormous body of antibody reagents available, there is still a lack of consensus about which criteria should be evaluated to select antibody reagents with the proper performance, how to validate antibody reagents for flow cytometry, and how to interpret the validation results. The achievements of cytometry moved the field to a higher number of measured parameters, large data sets, and computational data analysis approaches. These advancements pose an increased demand for antibody reagent performance quality. This review summarizes the codevelopment of cytometry, antibody development, and validation strategies. It discusses the diverse issues of the specificity, cross‐reactivity, epitope, titration, and reproducibility features of antibody reagents, and this review discusses the validation principles and methods that are currently available and those that are emerging. We argue that significant efforts should be invested by antibody users, developers, manufacturers, and publishers to increase the quality and reproducibility of published studies. More validation data should be presented by all stakeholders; however, the data should be presented in sufficient experimental detail to foster reproducibility, and community effort shall lead to the public availability of large data sets that can serve as a benchmark for antibody performance. © 2019 International Society for Advancement of Cytometry
Production of Brucella melitensis Omp16 protein fused to the Human Interleukin 2 in Lactococcus lactis MG1363 toward developing Lactococcus-based vaccine against Brucellosis.

The use of food-grade bacterium Lactococcus lactis as a new cell factory is a promising alternative expression system for production of desired protein. The current study is conducted to clone, express and purify Omp16-IL2 fusion protein antigen. The Omp16-IL2 fusion gene was designed and cloned into pGH plasmid with appropriate restriction sites and sub cloned in pAMJ2008 expression vector (Bioneer A/S (Horsholm, Denmark) digested with the same enzymes. The purified recombinant constructed pAMJ2008-Omp-IL2 was introduced into L.lactis subsp. cremoris MG1363 by electro transformation. Finally the expression and purification of Omp16-IL2 fusion protein was investigated. This study reports the construction of recombinant Lactococcus lactis expressing Omp16-IL2 fusion protein as an oral Lactococcus-based vaccine compared to commonly used live attenuated vaccines for future studies against Brucellosis.
Blepharoptosis and Cholesterol-Lowering Medications: A Retrospective Study

Purpose: To investigate the prevalence and frequency of patients with blepharoptosis who take anticholesterol therapies. To our knowledge, this is the first large single-center series to evaluate this association. Methods: A retrospective chart review of adult patients presenting with ptosis on concomitant anticholesterol medications. Results: Two hundred ninety-three adult patients with ptosis taking anticholesterol therapy were identified from October 2011 to October 2016. Forty-seven patients (16.0%) reported muscle weakness. Laboratory markers including creatine kinase (CK) and myoglobin levels were obtained. Of the 47 patients, 13 patients (4.4%) were identified to have ptosis and laboratory confirmed anticholesterol therapy-induced myopathy. Two additional patients with statin-induced myositis and rhabdomyolysis were identified from the period 2008–2011. All patients had measurably elevated CK and/or myoglobin levels. All patients experienced improvement in ptosis or systemic symptoms after discontinuation or changing medications. Nine patients (60%) demonstrated statistically significant improvement in the ptosis. Conclusions: Many patients with involutional ptosis also have both cardiovascular disease and hyperlipidemia and thus take cholesterol-lowering medication. Our study demonstrates a World Health Organization-defined probable association between ptosis and anticholesterol-induced myopathy. The frequency of anticholesterol-induced myopathy in adult ptosis was 4.4%, which is substantially higher than previously predicted. Anticholesterol-induced myositis can cause a reversible ptosis, and thus, a thorough evaluation of adult patients presenting with involutional ptosis includes inquiry into the use of anticholesterol drugs and associated muscle weakness. Anticholesterol medication may induce or exacerbate myogenic ptosis in some individuals