Miracle-dz/UniFAR-FTUs huggingface dataset:
Transportation assessment in artificial curved canals after instrumentation with Reciproc, Reciproc Blue, and XP-endo Shaper Systems.

AIM In the present study, we compared the transportation of three different instrumentation systems in different levels of standardized artificial curved canals. METHODS Sixty epoxy resin blocks containing simulated canals were divided into three groups (n = 20) according to the instrument used for canal preparation: Reciproc (REC), Reciproc Blue (REC Blue), and XP-endo Shaper (XPS). Pre- and post-instrumentation digital images of each specimen were superimposed by Photoshop software to evaluate the different amount of transportation. The Kruskal-Wallis and Wilcoxon were the non-parametric tests applied for the intergroup and intragroup analyses, respectively. The significance level was set at 5%. RESULTS The XPS showed significantly less canal transportation than REC Blue at five levels (P < 0.05) and significantly less canal transportation at seven evaluated levels when compared with the REC (P < 0.05). REC Blue showed significant less canal transportation than REC at four of the eight evaluated levels (P < 0.05). All evaluated instruments showed a significantly higher amount of resin removal toward the inner wall compared to the outer wall of the curvature (P < 0.001). CONCLUSION Although the XPS showed significantly less canal transportation than REC and REC Blue, all systems produced transportation from the original canal anatomy.
Age at Diagnosis of Type 2 Diabetes Mellitus and Associations With Cardiovascular and Mortality Risks: Findings From the Swedish National Diabetes Registry

Background: Risk of cardiovascular disease (CVD) and mortality for patients with versus without type 2 diabetes mellitus (T2DM) appears to vary by the age at T2DM diagnosis, but few population studies have analyzed mortality and CVD outcomes associations across the full age range. Methods: With use of the Swedish National Diabetes Registry, everyone with T2DM registered in the Registry between 1998 and 2012 was included. Controls were randomly selected from the general population matched for age, sex, and county. The analysis cohort comprised 318 083 patients with T2DM matched with just <1.6 million controls. Participants were followed from 1998 to 2013 for CVD outcomes and to 2014 for mortality. Outcomes of interest were total mortality, cardiovascular mortality, noncardiovascular mortality, coronary heart disease, acute myocardial infarction, stroke, heart failure, and atrial fibrillation. We also examined life expectancy by age at diagnosis. We conducted the primary analyses using Cox proportional hazards models in those with no previous CVD and repeated the work in the entire cohort. Results: Over a median follow-up period of 5.63 years, patients with T2DM diagnosed at ⩽40 years had the highest excess risk for most outcomes relative to controls with adjusted hazard ratio (95% CI) of 2.05 (1.81–2.33) for total mortality, 2.72 (2.13–3.48) for cardiovascular-related mortality, 1.95 (1.68–2.25) for noncardiovascular mortality, 4.77 (3.86–5.89) for heart failure, and 4.33 (3.82–4.91) for coronary heart disease. All risks attenuated progressively with each increasing decade at diagnostic age; by the time T2DM was diagnosed at >80 years, the adjusted hazard ratios for CVD and non-CVD mortality were <1, with excess risks for other CVD outcomes substantially attenuated. Moreover, survival in those diagnosed beyond 80 was the same as controls, whereas it was more than a decade less when T2DM was diagnosed in adolescence. Finally, hazard ratios for most outcomes were numerically greater in younger women with T2DM. Conclusions: Age at diagnosis of T2DM is prognostically important for survival and cardiovascular risks, with implications for determining the timing and intensity of risk factor interventions for clinical decision making and for guideline-directed care. These observations amplify support for preventing/delaying T2DM onset in younger individuals.
Poppy (Papaver somniferum L.) Intercropping with Spring Barley and with White Clover: Benefits and Competitive Effects

Poppy seed production is susceptible to abiotic and biotic stress and weed infestation, which introduces the risk of total crop failure. For the purpose of risk minimization, poppy was grown in additive intercropping systems with early and late sown white clover and spring barley sown at three different densities in a three year field trial to assess their roles in poppy cropping while adding ecological benefits to the crop rotation. Poppy yielded between 798.7 and 1293.1 kg ha−1, with no significant yield effects of intercropping with white clover, compared to poppy sole-cropping. Dry matter, height, leaf area index and C/N ratio of the poppy plants were not significantly impacted by the clover intercrop either, independent on its sowing date. Higher poppy yields (695.6–918.8 kg ha−1) and LERs (1.11–1.84) in the poppy–barley intercrop were achieved in 2018 and 2020 compared to 2019 (≤361.5 kg ha−1, LER ≤ 0.99), mainly due to differences in seeding dates, precipitation and nutrient availability. Therefore, previous seeding of poppy limits competition when intercropped with barley while white clover and poppy can be sown at the same time. The effect of barley seeding densities on the intercrop performance was small as was the influence of intercropping on weed cover, number and biomass. The weed regulating effect needs to be further examined, however, we conclude that intercropping of poppy is a promising strategy for its cultivation, in terms of minimizing the risk of total yield losses when precisely managed.
Frequency of ALK and GD2 Expression in Neuroblastoma

Abstract Background: The aim of this study was to elucidate the significance of immunohistochemical staining patterns of ALK and GD2 in peripheral neuroblastic tumors with different stages and favorable/unfavorable features. Materials and methods: 32 neuroblastomas, 7 ganglioneuroblastomas, and 1 ganglioneuroma cases were immunohistochemically stained with ALK and GD2, and the expressions were graded and correlated with differentiation, size, and favorable/unfavorable histology. Results: There was no statistically significant correlation between ALK immunopositivity and tumor differentiation or stage. Although there was no statistically significant correlation between GD2 immunopositivity and stage, the intensity and prevalence of GD2 immunostaining were statistically significantly higher in the well differentiated group and in tumors which were smaller than 10 cm. Conclusion: GD2 immunostaining levels correlated with tumor differentiation and size. ALK immunostaining was not related to tumor differentiation or stage.
In vivo transcriptomes of Streptococcus suis reveal genes required for niche-specific adaptation and pathogenesis

ABSTRACT Streptococcus suis is a Gram-positive bacterium and a zoonotic pathogen residing in the nasopharynx or the gastrointestinal tract of pigs with a potential of causing life-threatening invasive disease. It is endemic in the porcine production industry worldwide, and it is also an emerging human pathogen. After invasion, the pathogen adapts to cause bacteremia and disseminates to different organs including the brain. To gain insights in this process, we infected piglets with a highly virulent strain of S. suis, and bacterial transcriptomes were obtained from blood and different organs (brain, joints, and heart) when animals had severe clinical symptoms of infection. Microarrays were used to determine the genome-wide transcriptional profile at different infection sites and during growth in standard growth medium in vitro. We observed differential expression of around 30% of the Open Reading Frames (ORFs) and infection-site specific patterns of gene expression. Genes with major changes in expression were involved in transcriptional regulation, metabolism, nutrient acquisition, stress defenses, and virulence, amongst others, and results were confirmed for a subset of selected genes using RT-qPCR. Mutants were generated in two selected genes, and the encoded proteins, i.e., NADH oxidase and MetQ, were shown to be important virulence factors in coinfection experiments and in vitro assays. The knowledge derived from this study regarding S. suis gene expression in vivo and identification of virulence factors is important for the development of novel diagnostic and therapeutic strategies to control S. suis disease.
Optimization and characterization of pullulan production by a newly isolated high-yielding strain Aureobasidium melanogenum

Abstract Pullulan is an extracellular water-soluble polysaccharide with wide applications. In this study, we screened strains that could selectively produce high molecular weight pullulan for application in industrial pullulan production. A new fungus strain A4 was isolated from soil and identified as Aureobasidium melanogenum based on colony characteristics, morphology, and internally transcribed spacer analysis. Thin-layer chromatography, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance analysis suggested that the dominant exopolysaccharide produced by this strain, which presented a molecular weight of 1.384 × 106 Dalton in in-gel permeation chromatography, was pullulan. The culture conditions for A. melanogenum A4 were optimized at 30 °C and 180 rpm: carbon source, 50 g/L maltose; initial pH 7; and 8 g/L Tween 80. Subsequently, batch fermentation was performed under the optimized conditions in a 5-L stirred-tank fermentor with a working volume of 3 L. The fermentation broth contained 303 g/L maltose, which produced 122.34 g/L pullulan with an average productivity of 1.0195 g/L/h and 82.32 g/L dry biomass within 120 h. The conversion efficiency of maltose to pullulan (Y%) and specific production rate (g/h/g dry cells) (Qs) reached 40.3% and 0.0251 g/L/g dry cells, respectively. The results showed strain A4 could be a good candidate for industrial production.
Single- and multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual endothelin receptor antagonist aprocitentan in healthy adult and elderly subjects

Background Aprocitentan is an orally active, dual endothelin (ET) receptor antagonist developed for the treatment of hypertension in which, despite available treatments, a medical need exists for drugs with a new mechanism of action. Subjects and methods In this study, the single- and multiple-dose tolerability, safety, pharmacokinetics (PK), and pharmacodynamics of up to 600 mg (single doses) and 100 mg once a day (qd; multiple doses) of aprocitentan were investigated in healthy male and female subjects. The effect of age on the tolerability and PK parameters was investigated at a dose of 100 mg qd. Results Aprocitentan was well tolerated across all doses. No serious adverse events (AEs) occurred. The most frequently reported AE was headache. Small increases in body weight were recorded in subjects receiving 100 mg qd. Plasma concentration–time profiles of aprocitentan were similar after single- and multiple-dose administration, and support a qd dosing regimen based on a half-life of 44 hours. After multiple doses, PK was dose proportional. Accumulation at steady state, reached by Day 8, was 3-fold. Only minor differences in exposure between healthy females and males, healthy elderly and adult subjects, and fed and fasted conditions were observed. Plasma ET-1 concentrations, reflecting ETB receptor antagonism, significantly increased with doses ≥25 mg. Time-matched analysis of electrocardiogram (ECG) parameters did not suggest drug-induced ECG effects. Exposure–response analysis indicated no QTc prolongations at plasma levels up to 10 µg/mL. Conclusion Aprocitentan was well tolerated in healthy subjects with a PK profile favorable for qd dosing.
"I had no idea the university offered"…: The support needs of postgraduate taught students

This article was migrated. The article was marked as recommended. Introduction Medical schools have a duty to support students to ensure they fulfil their potential. Relatively little is known about the generic, or therapeutic, support needs of postgraduate taught (PGT) students. This is an important gap to address given the literature suggests that “one size does not fit all”. Thus, our aim was to explore and understand PGT support needs. Methods This was a qualitative research study using semi-structured focus groups, conducted in one UK university. We recruited medical and science undergraduates as well as PGT participants to get a sense of what was unique to the PGT student experience. Questions were drawn from the literature and local evaluation data. Discussions were audio-recorded and transcribed verbatim for inductive data coding and analysis. Results Six focus groups were conducted with 38 participants. Two main themes each with two sub-themes were identified: Communication (Practicalities; Fulfilled but not tailored) related to the transition into PGT, and Time and Contacts, related to managing the course. Discussion PGT students need to address non-academic, often practical, factors in a timely way to navigate university successfully. Knowing who to ask and informal supports are important. Poor and/or difficult-to-access institutional supports may leave PGT students vulnerable.
Transient blood–brain barrier disruption is induced by low pulsed electrical fields in vitro: an analysis of permeability and trans-endothelial electric resistivity

Abstract The blood–brain barrier (BBB) is limiting transcellular and paracellular movement of molecules and cells, controls molecular traffic, and keeps out toxins. However, this protective function is the major hurdle for treating brain diseases such as brain tumors, Parkinson’s disease, Alzheimer’s disease, etc. It was previously demonstrated that high pulsed electrical fields (PEFs) can disrupt the BBB by inducing electroporation (EP) which increases the permeability of the transcellular route. Our goal was to study the effects of low PEFs, well below the threshold of EP on the integrity and function of the BBB. Ten low voltage pulses (5–100 V) were applied to a human in vitro BBB model. Changes in permeability to small molecules (NaF) were studied as well as changes in impedance spectrum and trans-endothelial electric resistivity. Viability and EP were evaluated by Presto-Blue and endogenous Lactate dehydrogenase release assays. The effect on tight junction and adherent junction protein was also studied. The results of low voltage experiments were compared to high voltage experiments (200–1400 V). A significant increase in permeability was found at voltages as low as 10 V despite EP only occurring from 100 V. The changes in permeability as a function of applied voltage were fitted to an inverse-exponential function, suggesting a plateau effect. Staining of VE-cadherin showed specific changes in protein expression. The results indicate that low PEFs can transiently disrupt the BBB by affecting the paracellular route, although the mechanism remains unclear.
Suppression of c‐Myc using 10058‐F4 exerts caspase‐3‐dependent apoptosis and intensifies the antileukemic effect of vincristine in pre‐B acute lymphoblastic leukemia cells

Despite an old history behind the identification of the leading role of c‐Myc in leukemogenesis, the road to constructing a therapeutic perspective for this molecule in acute lymphoblastic leukemia (ALL) is yet mesmerizing. This study was designed to provide a better outlook for the anticancer property of 10058‐F4, an appealing inhibitor of c‐Myc, in pre‐B ALL cell lines either in the context of monotherapy or in combination with chemotherapeutic drugs. Our results declared that abrogation of c‐Myc decreased the proliferative capacity of pre‐B ALL‐derived cells through halting the transition of the cells from G1 phase, and reducing the replicative potential of both REH and Nalm‐6 cells, at least partly, through c‐Myc‐mediated suppression of human telomerase reverse transcriptase. Moreover, 10058‐F4 potently induced a caspase‐3‐dependent apoptosis in pre‐B ALL cells via shifting the balance between pro‐ and anti‐apoptotic target genes. Although the inhibition of PI3Kδ using Idelalisib upregulated the messenger RNA expression of autophagy‐related genes in 10058‐F4‐treated cells, treatment with autophagy inhibitor chloroquine decreased viability of the cells, either as a single agent or in combination with Idelalisib and/or 10058‐F4; suggesting that the activation of autophagy in pre‐B ALL cells could blunt apoptotic events and attenuate anticancer effect of both c‐Myc and PI3K inhibitors. Finally, the results of our synergistic experiments delineated that 10058‐F4 produced a synergistic effect with vincristine and provided an enhanced therapeutic efficacy in ALL cells, highlighting that c‐Myc oncoprotein could be a bona fide target for the treatment of ALL.
Overexpression of CKS2 is associated with a poor prognosis and promotes cell proliferation and invasion in breast cancer

Growing evidence indicates that cyclin dependent kinases regulatory subunit 2 (CKS2) serves an essential role in the regulation of multiple cellular processes in diverse human cancer types. The present study investigated the contribution of CKS2 to breast cancer (BC) progression. In the present study, CKS2 expression in BC was detected using Oncomine and The Cancer Genome Atlas database. The association between expression levels and clinical features was explored using Kaplan-Meier plotter and the Breast Cancer Gene-Expression Miner Version 4.0 (bc-GenExMiner) online database. In addition, the roles of CKS2 in BC progression were examined. It was identified that CKS2 expression was significantly increased in BC tissues at the mRNA and protein levels. Bc-GenExMiner demonstrated that high CKS2 expression was associated with a positive estrogen receptor status, progesterone receptor status, nodal status and basal-like status. High CKS2 expression was markedly associated with poor overall survival, relapse-free survival, and distant metastasis-free survival in patients with BC. Moreover, functional assays revealed that CKS2 inhibition suppressed cell proliferation and invasion ability in vitro and reduced tumor growth in vivo. Thus, the present findings suggested that CKS2 may act as a potential biomarker and therapeutic target for the treatment of BC.
Personalizing Content Presentation on Large 3D Head-Up Displays

Abstract Drivers' urge to access content on smartphones while driving causes a high number of fatal accidents every year. We explore 3D full-windshield size head-up displays as an opportunity to present such content in a safer manner. In particular, we look into how drivers would personalize such displays and whether it can be considered safe. Firstly, by means of an online survey we identify types of content users access on their smartphones while driving and whether users are interested in the same content on a head-up display. Secondly, we let drivers design personalized 3D layouts and assess how personalization impacts on driving safety. Thirdly, we compare personalized layouts to a one-fits-all layout concept in a 3D driving simulator study regarding safety. We found that drivers' content preferences diverge largely and that most of the personalized layouts do not respect safety sufficiently. The one-fits-all layout led to a better response performance but needs to be modified to consider the drivers' preferences. We discuss the implications of the presented research on road safety and future 3D information placement on head-up displays.
Efficiency drivers of insurers in GCC: an analysis incorporating company-specific and external environmental variables

Abstract The study aims to a comprehensive measure of listed insurance companies’ technical efficiency in GCC countries and benchmarking, peer count summary, and measuring productivity changes in the first stage. In the second stage, the technical efficiency, pure technical efficiency, and scale efficiency scores have been regressed with internal (company variables) and external environmental variables. This paper first examines financial freedom and reinsurance activities on 60 insurers’ efficiency from all GCC countries during 2016–2019. The results suggest a positive impact of economic freedom, solvency on technical efficiency components, and the negative effect of reinsurance ceding, market concentration on GCC insurers’ technical efficiency. In productivity changes, UAE companies are doing well as compared to other countries’ insurers. Overall, GCC insurers’ efficiency is improving with pure technical efficiency having a CAGR of 2.13% and scale efficiency a CAGR of 2.96%. Based on the peer count summary, only the UAE and Saudi Arabia’s companies can be benchmarked against another insurance company. Also, this research is one of the most comprehensive ones in the GCC region; this is the first study on an extensive data set to the best of our knowledge, including conventional insurers operating across GCC countries. This study is based on 60 insurers listed on the stock exchanges of six GCC countries. This will also be the first empirical evidence on the GCC insurers, which measures the impact of company-specific variables and unique environmental variables separately on the two components of technical efficiency using Tobit regression. The positive association of competition and financial freedom with technical efficiency may encourage regulators and policymakers to ensure less government intervention and give more support and freedom for a better competitive insurance industry.
A dosimetric comparison of Volumetric Modulated Arc Therapy (VMAT) and High Dose Rate brachytherapy (HDR) in localized cervical cancer radiotherapy.

BACKGROUND Cervical cancer radiotherapy is usually administrated through 3-Dimensional Conformal Radiation Therapy (3DCRT) followed by a brachytherapy (BT) boost. PURPOSE To investigate whether Volumetric Modulated Arc Therapy (VMAT) can replace High Dose Rate (HDR) intracavitary BT boost for patients undergoing cervical cancer radiotherapy. MATERIALS AND METHODS Computed Tomography (CT) images for ten patients with tandem and ovoids were included in this study. Target volumes, rectum, bladder, sigmoid, small bowel and both femoral heads were delineated. Two plans were carried out including (a) a BT plan optimized manually by modifying dwell time and Ir-192 source positions, (b) a VMAT plan generated using two partial arcs with 10 MV photon beam. The prescribed dose was 7 Gy. The relevant dose volume parameters (DVPs) of target volumes and OARs for the two plans were analyzed statistically using SPSS Wilcoxon Signed Rank test. RESULTS VMAT plan showed a significant reduction of 9.1%, 9.3%, 15.4%, 14.4% and 13.1% in rectum maximum dose, rectum D2cc, bladder maximum dose, bladder D2cc and sigmoid maximum dose (P < 0.05). VMAT and BT plans showed comparable D2cc of sigmoid and small bowel maximum doses (P = 0.333 and P = 0.646). On the other hand, VMAT showed significantly higher small bowel D2cc and maximum point dose on both femoral heads comparing to BT plan (P < 0.05). Last, VMAT plan yielded greater homogeneous target coverage compared to BT plan (P < 0.05). CONCLUSION The study demonstrated that VMAT plan achieves significant dose reduction of rectum, bladder and sigmoid, as well as superior homogeneous target coverage compared to BT plan. On the other hand, VMAT delivers more radiation exposures to small bowel and femoral heads.