Miracle-dz/UniFAR-FTUs huggingface dataset:
Bidirectional ephrinB2-EphB4 signaling regulates the osteogenic differentiation of canine periodontal ligament stem cells

The aim of the present study was to evaluate the effect of ephrinB2 gene-transfected canine periodontal ligament stem cells (cPDLSCs) on the regulation of osteogenic differentiation. cPDLSCs were transfected with a transgenic null-control green fluorescent protein (GFP) vector (termed Vector-cPDLSCs) or with NFNB2 GFP-Blasticidin (termed EfnB2-cPDLSCs). Subsequently, the osteogenic differentiation of Vector-cPDLSCs and EfnB2-cPDLSCs was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), alkaline phosphatase (ALP) assay and Alizarin Red S staining. The migratory abilities of cPDLSCs, Vector-cPDLSCs and EfnB2-cPDLSCs were also assessed. Following osteogenic induction of Vector-cPDLSCs and EfnB2-cPDLSCs, the protein expression levels of collagen I, Runt-related transcription factor 2, osteocalcin, ephrin type-B receptor 4 (EphB4), phospho-EphB4, ephrinB2 and phosphoephrinB2 were analyzed by western blot assays. Following gene transfection, the RT-qPCR and western blotting results revealed that the mRNA and protein expression levels of ephrinB2, respectively, were significantly increased in EfnB2-cPDLSCs compared with that in Vector-cPDLSCs (P<0.05). ALP and Alizarin Red S staining assays revealed increased ALP activity and mineralization nodules, respectively, in EfnB2-cPDLSCs. Cell proliferation and migration assays revealed that EfnB2-cPDLSCs exhibited enhanced proliferation and migration compared with Vector-cPDLSCs (P<0.05). In conclusion, the findings of the current study indicated that ephrinB2 gene-modified cPDLSCs exhibited enhanced osteogenic differentiation, with the ephrinB2 reverse signaling and EphB4 forward signaling pathways serving a key role in this process. Furthermore, ephrinB2 gene modification was observed to promote the migration and proliferation of cPDLSCs.
Moderate prenatal ethanol exposure in the rat promotes kidney cell apoptosis, nephron deficits, and sex‐specific kidney dysfunction in adult offspring

Alcohol during pregnancy can impair fetal development and result in offspring with neurodevelopmental deficits. Less is known about how low to moderate alcohol exposure can affect other organs, such as the kidney. Here, the effects of moderate ethanol exposure throughout pregnancy on kidney development were examined using a rat model. Rats were fed a liquid diet containing 6% ethanol (vol/vol) or control (0% ethanol) throughout pregnancy. Kidneys were collected at embryonic day (E) 20 or postnatal day (PN) 30 and total glomerular (nephron) number determined using unbiased stereology. Kidney function was examined in offspring at 8 and 19 months. At E20, fetuses exposed to ethanol had fewer nephrons with increased apoptosis. Alcohol exposure caused kidney dysregulation of pro‐ (Bax) and anti‐ (Bcl‐2) apoptotic factors, and reduced expression of the cell proliferation marker, Ki67. Prenatal alcohol decreased expression of Gdnf and Tgfb1, important regulators of branching morphogenesis, in male fetuses. At PN30, kidney volume and nephron number were lower in offspring exposed to prenatal alcohol. Urine flow and osmolality were normal in offspring exposed to alcohol however sodium excretion tended to be lower in females prenatally exposed to alcohol. Findings suggest exposure to moderate levels of alcohol during pregnancy results in impaired kidney development and leads to a permanent nephron deficit. Although the impact on adult kidney function was relatively minor, these data highlight that even at moderate levels, alcohol consumption during pregnancy can have deleterious long‐term outcomes and should be avoided.
Unique microRNA Signals in Plasma Exosomes from Pregnancies Complicated by Preeclampsia

Supplemental Digital Content is available in the text. Although preeclampsia is a common and serious complication of pregnancy, insight into its pathobiology and diagnosis is lacking. Circulating plasma exosomes, which contain RNA and other molecules and have recently become accessible for diagnostics, may be informative in this regard. We tested the hypothesis that preeclampsia may affect the miRNA cargo within circulating maternal blood exosomes. We collected plasma from 60 pregnant women at term, including 20 women with pregnancy complicated by preeclampsia, and 20 women with fetal growth restriction and 20 with healthy pregnancy, serving as controls. We isolated exosomes from the maternal plasma by continuous density gradient ultracentrifugation. Our main outcome variable was exosomal miRNA cargo, analyzed by quantitative polymerase chain reaction-based TaqMan advanced miRNA assay in a card format and the expression of differentially expressed exosomal miRNA in whole plasma from the same participants. We found that 7 miRNA species were differentially expressed in exosomes from women with preeclampsia and those from controls. In contrast, there was no significant difference in exosomal miRNA expression between women with fetal growth restriction and controls. The results were not affected by fetal sex. Only one of the preeclampsia-related, differentially expressed exosomal miRNAs was significantly different in whole plasma miRNA analysis. We concluded that unlike whole plasma miRNA, exosomes extracted from the plasma of women with preeclampsia exhibit a unique miRNA profile, suggesting that plasma exosomal miRNA could provide insight into the pathophysiology of preeclampsia, and may play a role in disease diagnostics.
A Senior Management Perspective on the Policy Debate of Needle and Syringe Exchange Program Provision in Irish Prisons

This study examined from an Irish perspective the contentious policy debate about providing clean needles to injecting drug users within prison systems; specifically, it examined the views of six senior managers who were prison health staff and security management. Research participants were generally opposed to the introduction of prison-based needle and syringe exchange programs (PNSP) in Ireland. They argued that (1) PNSP were unnecessary since injecting drug use within Irish prisons has declined significantly, (2) PNSP, by making needles freely available to prisoners, would make prisons riskier since these needles might be used as weapons against prison staff or other prisoners, and (3) PNSP might be seen as condoning illicit drug use and sending the “wrong message. ” It is concluded that, for the moment at least, there is little likelihood of PNSP becoming a reality in the Irish Prison Service.
Angiogenic Marker Prognostic Models in Pregnant Women With Hypertension

Supplemental Digital Content is available in the text. Angiogenic markers such as PlGF (placental growth factor) and sFlt-1 (soluble Fms-like tyrosine kinase-1) have been shown to be useful for predicting adverse outcome in women suspected of having preeclampsia. The aim of the current study was to evaluate the prognostic value of angiogenic markers and maternal risk factors in pregnant women with hypertension. This was a prospective study of pregnancies complicated by preeclampsia, gestational hypertension, or chronic hypertension presenting to 1 of 2 tertiary referral hospitals between May 2013 and May 2018. Maternal characteristics along with blood samples for angiogenic marker analysis were obtained from participants. The primary outcome was delivery related to preeclampsia within 1 and 2 weeks. In total, 302 women with hypertension were included in the study cohort. The baseline model included maternal body mass index, mean arterial pressure, and clinical diagnosis at the time of assessment. The use of sFlt-1/PIGF ratio combined with the baseline model significantly improved the area under the curve values for predicting delivery within a week (0.83 versus 0.88; P=0.025) or in 2 weeks (0.86 versus 0.93; P=0.001) due to preeclampsia-related events in gestational ages <35 weeks. The magnitude of increase in accuracy was 7.9% (−0.5% to 16.4%, posterior probability of increase: 96.7%) for sFlt-1/PlGF ratio. Our results emphasize the additive value of angiogenic biomarkers and the superior performance of a continuous scale of sFlt-1/PlGF ratio in the model. The added utility of angiogenic markers diminishes after 35 weeks’ gestation.
Probing the mechanisms underpinning recovery in post‐surgical patients with cervical radiculopathy using Bayesian networks

Rehabilitation approaches should be based on an understanding of the mechanisms underpinning functional recovery. Yet, the mediators that drive an improvement in post‐surgical pain‐related disability in individuals with cervical radiculopathy (CR) are unknown. The aim of the present study is to use Bayesian networks (BN) to learn the probabilistic relationships between physical and psychological factors, and pain‐related disability in CR.
Expression of Stathmin and vascular endothelial growth factor C in esophageal cancer and their combined diagnostic value.

PURPOSE To investigate the expression of Stathmin and vascular endothelial growth factor C (VEGF-C) in the serum of patients with esophageal cancer (EC) and the diagnostic value of the combined two factors. METHODS 88 EC patients (the EC Group) treated in Shaanxi Provincial People's Hospital and 50 healthy people (the Control Group) were selected as subjects of this study. After detecting the levels of Stathmin mRNA and VEGF-C mRNA using real-time quantitative PCR (qRT-PCR) and the expression levels of Stathmin protein and VEGF-C protein using enzyme-linked immunosorbent assay (ELISA), analysis of the relationship between the expression levels of Stathmin mRNA and VEGF-C mRNA in the serum and the clinicopathological features of EC were analyzed. RESULTS The levels of Stathmin mRNA and VEGF-C mRNA, Stathmin protein and VEGF-C protein in the serum of the Control Group were lower than those in the EC group (p<0.001). The mRNA and protein expressions of Stathmin and VEGF-C in the serum of EC group were related to lymph node metastasis, clinical stage, grade of differentiation and degree of infiltration (p<0.05). Compared with the combined detection of mRNA, the sensitivity of separate detection of Stathmin mRNA and VEGF-C mRNA was lower, but the specificity of the separate detection of Stathmin mRNA was higher (p<0.05). Compared with the sensitivity of the combined detection of protein, the sensitivity of the separate test of Stathmin protein and VEGF-C protein was lower (p<0.05). CONCLUSION Stathmin and VEGF-C could be used as markers for early diagnosis of EC, and the combined detection of the two factors could improve the sensitivity of diagnosis since the expression levels of mRNAs and proteins of Stathmin and VEGFC in the serum of EC patients were proved to be higher than those of healthy volunteers.
Expression of Ki-67 and Βeta-Catenin in Pseudoepitheliomatous Hyperplasia and Squamous Cell Carcinoma in Oral Mucosal Biopsies : An Immunohistochemical Study

Objective: To examine the immunohistochemical expression of Ki-67 and beta-catenin in pseudoepitheliomatous hyperplasia and squamous cell carcinoma (SCC) in oral mucosal biopsies. Methods: In this comparative cross sectional study, 70 cases of each PEH and OSCC were taken from the patients of both genders and in all age groups. Study was conducted at Armed Forces Institute of Pathology (AFIP), Rawalpindi from Dec 2017 to March 2019. Statistical analysis was done with the help of SPSS Version 24.0. We used Chi-Squared test with p value of < 0.05 which was considered as statistically significant. Results: In the current study, 80 (57.1%) male and 60 (42.8%) female patients with the mean age of 51.69 ± 16.121 (mean ± SD) years were included. It was found that 6-25% Ki-67 labeling index was observed in all (70) PEH cases, which involved only basal layer of the epithelium. Whereas, Ki-67 labeling index was highly expressed in tumor of high grade malignancy than tumor of low grade malignancy. On the other hand, expression of membranous beta-catenin was higher in PEH and cytoplasmic beta-catenin expression was higher in OSCC. Conclusion : It is concluded that Ki-67 and beta-catenin showed significant expression in PEH and OSCC in oral mucosal biopsies especially those with intense inflammation or unoriented tissue, helping the clinicians to arrive at a final diagnosis before planning any surgical intervention.
Use of ixazomib, lenalidomide and dexamethasone in patients with relapsed amyloid light‐chain amyloidosis

With improving outcomes in amyloid light‐chain (AL) amyloidosis, there is a need to study novel agents in this setting. We report outcomes of 40 patients with relapsed AL amyloidosis treated with ixazomib + lenalidomide + dexamethasone (IRd). Haematological responses were assessed on an intention‐to‐treat basis at three months: complete response (CR) – 8 (20·5%), very good partial response (VGPR) – 8 (20·5%), partial response (PR) – 7 (17·9%) and no response (NR) – 16 (41·0%). One patient had missing data. Six patients subsequently improved response. Best responses were: CR – 10 (25·6%), VGPR – 8 (20·5%), PR – 7 (17·9%), NR – 14 (35·9%). Cardiac and renal organ responses occurred in 5·6% and 13·3% respectively. Median progession‐free survival (PFS) was 17·0 months (95% CI 7·3–20·7 months), improving to 28·8 months (95% CI 20·6–37·0 months) in those achieving CR/VGPR. Median overall survival was 29·1 months (95% CI 24–33 months). Serious adverse events were seen in 14 (35·0%) patients inclusive of 15 admissions due to: infection (6/15, 40·0%), fluid overload (5/15, 33·3%), cardiac arrhythmia (2/15, 13·3%), renal dysfunction (1/15, 6·6%) and anaemia (1/15, 6·6%). In summary, IRd is an oral treatment option with a manageable toxicity profile leading to deep responses in 47% of patients with relapsed AL amyloidosis.
Differential susceptibility of Xylella fastidiosa strains to synthetic bactericidal peptides.

The kinetics of cell inactivation and the susceptibility of Xylella fastidiosa subspecies fastidiosa, multiplex and pauca, to synthetic antimicrobial peptides from two libraries (CECMEL11 and CYCLO10), were studied. The bactericidal effect was dependent on the relative concentrations of peptide and bacterial cells, and was influenced by the diluent, either buffer or sap. The most bactericidal and lytic peptide was BP178, an enlarged derivative of the amphipathic cationic linear undecapeptide BP100. The maximum reduction in survivors after BP178 treatment occurred within the first 10-20 min of contact and at micromolar concentrations (<10 μM), resulting in pore formation in cell membranes, abundant production of outer membrane vesicles (OMV) and lysis. A threshold ratio of 109 molecules of peptide per bacterial cell was estimated to be necessary to initiate cell inactivation. There was a differential susceptibility to BP178 among strains, with DD1 being the most resistant and CFBP 8173 the most susceptible. Moreover, strains showed a proportion of cells under the viable but nonculturable state (VBNC), which was highly variable among strains. These findings may have implications for managing the diseases caused by X. fastidiosa.
Investigation of the effect of salt additives in Protein L affinity chromatography for the purification of tandem single-chain variable fragment bispecific antibodies

ABSTRACT Tandem single-chain variable fragment (scFv) bispecific antibodies (bsAb) are one of the most promising bsAb formats reported thus far. Yet, because of their increased aggregation propensity, high impurity content due to low expression level, smaller size and lack of the Fc region, it is challenging to isolate these products with high yield and purity within a limited number of purification steps in a scalable fashion. A robust purification process that is able to circumvent these issues is therefore of critical importance to allow effective isolation of this group of antibodies. We investigated the addition of sodium chloride (NaCl), calcium chloride (CaCl2), and L-arginine monohydrochloride (Arg·HCl) to the elution buffer of Protein L affinity chromatography, and propose here a novel mechanism for the modification of Protein L binding avidity that can lead to enhanced high molecular weight (HMW)-monomer separation, a preferential strengthening effect of the HMW-Protein L interaction compared to the monomer-Protein L interaction. In particular, we found Arg·HCl to be the most effective salt additive in terms of purity and recovery. The mechanism we propose is different from the widely reported chaotropic effect exerted by salt additives observed in Protein A chromatography. We also demonstrate here that a final eluate containing <1% HMW species and <100 ppm host cell proteins can be obtained within a two-step process with an overall yield of 65%, highlighting the promising suitability of Protein L affinity chromatography for the purification of kappa light chain-containing tandem scFv bsAb.
Autophagy promotion enhances the protective effect of Morroniside on human OA chondrocyte

ABSTRACT Morroniside plays a therapeutic role in knee osteoarthritis (OA) by protecting chondrocytes. PI3K/AKT signaling is involved in the regulation of chondrocytes by Morroniside. PI3K/AKT suppresses autophagy through downstream signaling. However, the regulation of chondrocyte autophagy by Morroniside and the significance of the above effect on protecting chondrocytes aren’t clear. The results showed that Morroniside inhibited the autophagiy of human OA chondrocytes. Besides, both PI3K inhibitors and mTOR inhibitors significantly reversed the autophagy reduced by Morroniside, but had no effect on the protective effect of Morroniside on chondrocytes. However, the enhanced autophagy caused by overexpression of autophagic genes enhanced the protective effect of Morroniside on chondrocytes. In conclusion, Morroniside represses the autophagy of human OA chondrocyte, which is related to PI3K/mTOR pathway. Moreover, the upregulation of autophagy further promoted the role of Morroniside in treating chondrocytes. Our data present a potential clue for the therapeutic strategies of Morroniside in treating OA. Graphical abstract The working model regarding the role of autophagy in Morroniside-regulated chondrocyte activity
A repeated cross-sectional study of sympathy for violent radicalization in Canadian college students.

The upsurge in violent radicalization is associated with a global increase in social inequalities and conflicts related to different markers of identity. To date, literature on the factors associated with legitimizing violence toward others is cross-sectional and does not provide information on the possible change of this phenomenon over time. Such information is necessary to design primary prevention programs that are adapted to and address a rapidly evolving social context. We use a repeated cross-sectional study design to explore the association between sociodemographic characteristics and scores on the Sympathy for Violent Radicalization Scale (SVR) in Quebec (Canada) college students at 2 times points. Results from an online survey completed by students of 6 colleges in 2015 (n = 854) and 2017 (n = 702) indicate that although overall scores on the SVR scale remained stable, there were changes in the association between age, identity, and the outcome at the two time points. Specifically, scores on the SVR were significantly higher among younger students in 2017 than in 2015. In addition, in 2017 we observed a relationship between collective identity and SVR that was not present in 2015. These results align with other recent studies in Canada and the U.S. documenting the emergence of new forms of youth politicized bullying associated with race, ethnicity, and religion. A close monitoring of the phenomenon is warranted to both better understand the impact of populist policies on the increase in hate incidents and crimes and develop programs to address these forms of violence from a public health perspective. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Genetic Risk of Coronary Artery Disease, Features of Atherosclerosis, and Coronary Plaque Burden

Background Polygenic risk scores (PRSs) based on risk variants from genome‐wide association studies predict coronary artery disease (CAD) risk. However, it is unknown whether the PRS is associated with specific CAD characteristics. Methods and Results We consecutively included 1645 patients with suspected stable CAD undergoing coronary computed tomography angiography. A multilocus PRS was calculated as the weighted sum of CAD risk variants. Plaques were evaluated using an 18‐segment model and characterized by stenosis severity and composition (soft [0%‐19% calcified], mixed‐soft [20%‐49% calcified], mixed‐calcified [50%‐79% calcified], or calcified [≥80% calcified]). Coronary artery calcium score and segment stenosis score were used to characterize plaque burden. For each standard deviation increase in the PRS, coronary artery calcium score increased by 78% (P=4.1e‐26) and segment stenosis score increased by 16% (P=2.4e‐29) in the fully adjusted model. The PRS was associated with a higher prevalence of obstructive plaques (odds ratio [OR ]: 1.78, P=5.6e‐16), calcified (OR: 1.69, P=6.5e‐17), mixed‐calcified (OR: 1.67, P=7.3e‐9), mixed‐soft (OR: 1.45, P=1.6e‐6), and soft plaques (OR: 1.49, P=2.5e‐6), and a higher prevalence of plaque in each coronary vessel (all P<1.0e‐4). However, when analyzing data on a plaque level (3007 segments with plaque in 849 patients) the PRS was not associated with stenosis severity, plaque composition, or localization (all P>0.05). Conclusions Our results suggest that polygenic risk based on large genome‐wide association studies increases CAD risk through an increased burden of coronary atherosclerosis rather than promoting specific plaque features. Clinical Trial Registration URL: https://www.clinicaltrials. gov. Unique identifier: NCT02264717.
Theoretical analysis of the kinetic isotope effect on carboxylation in RubisCO

Ribulose‐1,5‐bisphosphate carboxylase/oxygenase (RubisCO) fixes atmospheric carbon dioxide into bioavailable sugar molecules. It is also well known that a kinetic isotope effect (KIE; CO2 carbon atoms) accompanies the carboxylation process. To describe the reaction and the KIE α, two different types of molecular dynamics (MD) simulations (ab initio MD and classical MD) have been performed with an Own N‐layered Integrated molecular Orbitals and molecular Mechanics (ONIOM)‐hybrid model. A channel structure for CO2 transport has been observed during the MD simulation in RubisCO, and assuming the reaction path from the inlet to the product through the coordinate complex with Mg2+, simulations have been performed on several molecular configuration models fixing several distances between CO2 and ribulose‐1,5‐bisphosphate along the channel. Free energy analysis and diffusion coefficient analysis have been evaluated for different phases of the process. It is confirmed that the isotopic fractionation effect for CO2 containing either 13C or 12C would appear through the transiting path in the channel structure identified in RubisCO. The estimated isotope fractionation constant was quite close to the experimental value.
The Value of Twins for Health and Medical Research: A Third of a Century of Progress

Abstract In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide.