Miracle-dz/UniFAR-FTUs huggingface dataset:
Aggregation of Human Trophoblast Cells into Three-Dimensional Culture System Enhances Anti-Inflammatory Characteristics through Cytoskeleton Regulation

Background: Three-dimensional (3D) culture changes cell characteristics and function, suggesting that 3D culture provides a more physiologically relevant environment for cells compared with 2D culture. We investigated the differences in cell functions depending on the culture model in human trophoblast cells (Sw.71). Methods: Sw.71 cells were incubated in 2D monolayers or simple 3D spheroids. After incubation, cells were corrected to assess RNA-seq transcriptome or protein expression, and culture medium were corrected to detect cytokines. To clarify the role of actin cytoskeleton, spheroid Sw.71 cells were treated mycalolide B (inhibitor of actin polymerization) in a 3D culture. Results: RNA-seq transcriptome analysis, results revealed that 3D-cultured cells had a different transcriptional profile compared with 2D-cultured cells, especially regarding inflammation-related molecules. Although interleukin-6 (IL-6) mRNA level was higher in 3D-culured cells, its secretion levels were higher in 2D-cultured cells. In addition, the levels of mRNA and protein expression of regnase-1, regulatory RNase of inflammatory cytokine, significantly increased in 3D culture, suggesting post-translational modification of IL-6 mRNA via regnase-1. Treatment with mycalolide B reduced cell-to-cell contact to build 3D formation and increased expression of actin cytoskeleton, resulting in increased IL-6 secretin. Conclusion: Cell dimensionality plays an essential role in governing the spatiotemporal cellular outcomes, including inflammatory cytokine production and its negative regulation associated with regnase-1.
A Portrait of Pacing Profile of Cross-Country Skiers in the Vasaloppet 2004–2017

Abstract The aim of the study was to examine the effect of performance group by race time (10 groups;<3 h, 3–4 h, and so on up to>12 h) on pacing in women (n=19,465) and men (n=164,454) finishers in the ‘Vasaloppet’ cross-country (XC) skiing race from 2004 to 2017. The speed in the fastest and slowest split was analysed as a percentage of the mean race speed and pacing was defined as the difference (%) between the fastest and slowest split. Women had a larger pace range than men (44.0±10.6% versus 41.1±12.5%, respectively, p<0.001, d=0.25). An almost perfect relationship between performance group and pacing was observed in women (r=0.900, p<0.001) and men (r=0.908, p<0.001). A large main effect of performance on pacing was observed in women (p<0.001, η2=0.292), where the smaller range was in the<4 h group (22.8±3.3%) and the largest in the 10–11 h group (49.2±9.9%). In men, the corresponding values were 21.6±2.2% (<3 h group) and 51.6±11.2% (10–11 h group; p<0.001, η2=0.474). Based on these findings, it was concluded that fast XC skiers had relatively the most even pacing and pacing became less even with decreasing performance. This information is of practical value for coaches working with XC skiers to develop optimal sex- and performance-tailored pacing strategies.
Emergence of Nanoplatelet Light-Emitting Diodes

Since 2014, nanoplatelet light-emitting diodes (NPL-LEDs) have been emerged as a new kind of LEDs. At first, NPL-LEDs are mainly realized by CdSe based NPLs. Since 2016, hybrid organic-inorganic perovskite NPLs are found to be effective to develop NPL-LEDs. In 2017, all-inorganic perovskite NPLs are also demonstrated for NPL-LEDs. Therefore, the development of NPL-LEDs is flourishing. In this review, the fundamental concepts of NPL-LEDs are first introduced, then the main approaches to realize NPL-LEDs are summarized and the recent progress of representative NPL-LEDs is highlighted, finally the challenges and opportunities for NPL-LEDs are presented.
Sonic Hedgehog Medulloblastoma Cancer Stem Cells Mirnome and Transcriptome Highlight Novel Functional Networks

Molecular classification has improved the knowledge of medulloblastoma (MB), the most common malignant brain tumour in children, however current treatments cause severe side effects in patients. Cancer stem cells (CSCs) have been described in MB and represent a sub population characterised by self-renewal and the ability to generate tumour cells, thus representing the reservoir of the tumour. To investigate molecular pathways that characterise this sub population, we isolated CSCs from Sonic Hedgehog Medulloblastoma (SHH MB) arisen in Patched 1 (Ptch1) heterozygous mice, and performed miRNA- and mRNA-sequencing. Comparison of the miRNA-sequencing of SHH MB CSCs with that obtained from cerebellar Neural Stem Cells (NSCs), allowed us to obtain a SHH MB CSC miRNA differential signature. Pathway enrichment analysis in SHH MB CSCs mirnome and transcriptome was performed and revealed a series of enriched pathways. We focused on the putative targets of the SHH MB CSC miRNAs that were involved in the enriched pathways of interest, namely pathways in cancer, PI3k-Akt pathway and protein processing in endoplasmic reticulum pathway. In silico analysis was performed in SHH MB patients and identified several genes, whose expression was associated with worse overall survival of SHH MB patients. This study provides novel candidates whose functional role should be further investigated in SHH MB.
Combined Inhibition of PI3Kβ and mTOR Inhibits Growth of PTEN-null Tumors

Loss of the tumor suppressor PTEN confers a tumor cell dependency on the PI3Kβ isoform. Achieving maximal inhibition of tumor growth through PI3K pathway inhibition requires sustained inhibition of PI3K signaling; however, efficacy is often limited by suboptimal inhibition or reactivation of the pathway. To select combinations that deliver comprehensive suppression of PI3K signaling in PTEN-null tumors, the PI3Kβ inhibitor AZD8186 was combined with inhibitors of kinases implicated in pathway reactivation in an extended cell proliferation assay. Inhibiting PI3Kβ and mTOR gave the most effective antiproliferative effects across a panel of PTEN-null tumor cell lines. The combination of AZD8186 and the mTOR inhibitor vistusertib was also effective in vivo controlling growth of PTEN-null tumor models of TNBC, prostate, and renal cancers. In vitro, the combination resulted in increased suppression of pNDRG1, p4EBP1, as well as HMGCS1 with reduced pNDRG1 and p4EBP1 more closely associated with effective suppression of proliferation. In vivo biomarker analysis revealed that the monotherapy and combination treatment consistently reduced similar biomarkers, while combination increased nuclear translocation of the transcription factor FOXO3 and reduction in glucose uptake. These data suggest that combining the PI3Kβ inhibitor AZD8186 and vistusertib has potential to be an effective combination treatment for PTEN-null tumors. Mol Cancer Ther; 17(11); 2309–19. ©2018 AACR.
Epidemiology, prognostic factors, and outcome of trauma patients admitted in a Brazilian intensive care unit

Background Trauma is a major cause of hospital admissions and is associated with manifold complications and high mortality rates. However, data on intensive care unit (ICU) admissions are scarce in developing and low-income countries, where its incidence has been increasing. Objectives To analyze epidemiological and clinical factors and outcomes in adult trauma patients admitted to the ICU of a public teaching hospital in a developing country as well as to identify risk factors for complications in the ICU. Patients and methods Retrospective cohort of adult trauma patients admitted to the general ICU of a public teaching hospital in southern Brazil in the year 2012. Demographic, clinical, and outcome data from the ICU were analyzed. Results During the study period, 144 trauma patients were admitted (83% male, Acute Physiology and Chronic Health Evaluation Score II =18.6±7.2, age =33.3 years, 93% required mechanical ventilation). Of these, 60.4% suffered a traffic accident (52% motorcycle), and 31.2% were victims of violence (aggressions, gunshot wounds, or stabbing); 71% had brain trauma, 37% had chest trauma, and 21% had abdominal trauma. Patients with trauma presented a high incidence of complications, such as infections, acute renal failure, acute respiratory distress syndrome, and thrombocytopenia. The ICU mortality rate was 22.9%. Conclusion In a Brazilian public teaching ICU, there was a great variability of trauma etiologies (mainly traffic accidents with motorcycles and victims of violence); patients with trauma had a high incidence of complications and mortality in the ICU.
Iterative Carving for Self-supporting 3D Printed Cavities

Additive manufacturing technologies fabricate objects layer by layer, adding material on top of already solidified layers. A key challenge is to ensure that there is always material below, for otherwise added material simply falls under the effect of gravity. This is a critical issue with most technologies, and with fused filament in particular. In this work we investigate how to compute as large as possible empty cavities which boundaries are self-supporting. Our technique is based on an iterated carving algorithm, that is fast to compute and produces nested sets of inner walls. The walls have exactly the minimal printable thickness of the manufacturing process everywhere. Remarkably, our technique is out-of-core, sweeping through the model from the top down. Using our approach, we can print large objects using as little as a single filament thickness for the boundary, providing one order of magnitude reduction in print time and material use while guaranteeing printability.
Olive Mild Mosaic Virus Coat Protein and P6 Are Suppressors of RNA Silencing, and Their Silencing Confers Resistance against OMMV

RNA silencing is an important defense mechanism in plants, yet several plant viruses encode proteins that suppress it. Here the genome of Olive mild mosaic virus (OMMV) was screened for silencing suppressors using a green fluorescent based transient suppression assay. The full OMMV cDNA and 5 different OMMV open reading frames (ORFs) were cloned into Gateway binary destination vector pK7WG2, transformed into Agrobacterium tumefaciens C58C1 and agroinfiltrated into Nicotiana benthamiana 16C plants. Among all ORFs tested, CP and p6 showed suppressor activity, with CP showing a significant higher activity when compared to p6, yet lower than that of the full OMMV. This suggests that OMMV silencing suppression results from a complementary action of both CP and p6. Such discovery led to the use of those viral suppressors in the development of OMMV resistant plants through pathogen-derived resistance (PDR) based on RNA silencing. Two hairpin constructs targeting each suppressor were agroinfiltrated in N. benthamiana plants which were then inoculated with OMMV RNA. When silencing of both suppressors was achieved, a highly significant reduction in viral accumulation and symptom attenuation was observed as compared to that seen when each construct was used alone, and to the respective controls, thus showing clear effectiveness against OMMV infection. Data here obtained indicate that the use of both OMMV viral suppressors as transgenes is a very efficient and promising approach to obtain plants resistant to OMMV. Importance OMMV silencing suppressors were determined. Among all ORFs tested, CP and p6 showed suppressor activity, with CP showing a significant higher activity when compared to p6, yet lower than that of the full OMMV, suggesting a complementary action of both CP and p6 in silencing suppression. This is the first time that a silencing suppressor was found in a necrovirus and that two independent proteins act as silencing suppressors in a member of the Tombusviridae family. When silencing of both suppressors was achieved, a highly significant reduction in viral accumulation and symptom attenuation was observed as compared to that seen when each was used alone, thus showing clear effectiveness against OMMV infection. A high percentage of resistant plants was obtained (60%), indicating that the use of both OMMV viral suppressors as transgenes is a very efficient and promising approach to obtain plants resistant to OMMV.
The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene polymorphisms on dabigatran equilibrium peak concentration in patients after total knee arthroplasty

Background Non-vitamin K oral anticoagulants (NOACs) are commonly used for prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known safety and high potency of NOACs, potential interactions of NOACs with genetic polymorphisms are poorly understood. Dabigatran etexilate is one of the most commonly prescribed direct thrombin inhibitors for the prevention of VTE. The objectives of this study were to assess the effect of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in patients after total knee arthroplasty. Patients and methods A total of 60 patients, aged 37–81 years, who underwent surgery for knee replacement have been included in the study. VTE prophylaxis was conducted via administration of dabigatran etexilate 220 mg once daily. Genotyping for carrier state of polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene was carried out using real-time polymerase chain reaction (PCR). We also measured the peak and trough concentrations of plasma dabigatran by using high-performance liquid chromatography (HPLC). Results Our study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was associated with higher dabigatran equilibrium peak concentrations and the higher risk of bleeding than the presence of CC genotype (p<0.008). There was no statistically significant genotype-dependent difference in the trough concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of the CES1 gene. Conclusion Our findings indicate that the polymorphisms of ABCB1 rs1045642 may have a prominent contribution to the safety of dabigatran in patients after knee surgery. Moreover, TT genotype may be associated with the higher risk of hemorrhagic complications in this population. There were no influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran peak and through concentrations. Larger studies are needed to confirm our observations.
Optimizing Window Length for Turbulent Heat Flux Calculations from Airborne Eddy Covariance Measurements under Near Neutral to Unstable Atmospheric Stability Conditions

Airborne eddy covariance (EC) is one of the most effective ways to directly measure turbulent flux at a regional scale. This study aims to find the optimum spatial window length for turbulent heat fluxes calculation from airborne eddy covariance measurements under near neutral to unstable atmospheric stability conditions, to reduce the negative influences from mesoscale turbulence, and to estimate local meaningful turbulent heat fluxes accurately. The airborne flux measurements collected in 2008 in the Netherlands were used in this study. Firstly, the raw data was preprocessed, including de-spike, segmentation, and stationarity test. The atmospheric stability conditions were classified as near neutral, moderately unstable, or very unstable; the stable condition was excluded. Secondly, Ogive analysis for turbulent heat fluxes from all available segmentations of the airborne measurements was used to determine the possible window length range. After that, the optimum window length for turbulent heat flux calculations was defined based on the analysis of all possible window lengths and their uncertainties. The results show that the choice of the optimum window length strongly depends on the atmospheric stability conditions. Under near neutral conditions, local turbulence is mixed insufficiently and vulnerable to heterogeneous turbulence. A relatively short window length is needed to exclude the influence of mesoscale turbulence, and we found the optimum window length ranges from 2000 m to 2500 m. Under moderately unstable conditions, the typical scale of local turbulence is relative large, and the influence of mesoscale turbulence is relatively small. We found the optimum window length ranges from 3900 m to 5000 m. Under very unstable conditions, large convective eddies dominate the transmission of energy so that the window length needs to cover the large eddies with large energy transmission. We found the optimum window length ranges from 4500 m to 5000 m. This study gives a comprehensive methodology to determine the optimizing window length in order to compromise a balance between the accuracy and the surface representativeness of turbulent heat fluxes from airborne EC measurements.
Hematological parameters of the blood count in a healthy population of pregnant women in the Northwest of Morocco (Tetouan-M’diq-Fnideq provinces)

Introduction Numerous biological parameters are physiologically modified during normal pregnancy, in particular hematology. The knowledge of these modifications of the maternal body by biologists and clinicians allows the screening of possible anomalies. In Morocco, the reference values of the complete blood count test for pregnant woman are missing, as are those specific to different trimesters of pregnancy. The aim of this study is to look for the reference values for healthy pregnant women of the Northwest region of Morocco, to compare them to those of non-pregnant women (control) and to those of the literature. Methods Blood samples were taken voluntarily from 3898 healthy pregnant women from 18 to 46 years old who presented themselves at the center of health Kalaa and at the service of gynecology obstetrics of the Provincial Hospital Center of M'diq (Morocco), for prenatal care. To establish the reference intervals of the CBC for non-pregnant women, a control group was constituted by 7035 healthy women from 18 to 50 years old selected according to the Moroccan law of blood donation. The CBC was measured on a Sysmex KX21N® analyzer. For each sample a systematic blood smear was done to determine the leukocyte differential. Results A statistically significant difference between the pregnant women and control group was noted (p < 0.05) for all the hematological parameters: red blood cells, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, leukocytes, neutrophils, basophils, eosinophils, lymphocytes, monocytes, platelets and mean platelet volume. So, the comparison of the averages established between the first, second and third trimester of pregnancy showed the existence of a significant variation with regard to all the parameters of the CBC test looked for (p < 0.001). Conclusion The present study provides additional baseline data for basic hematological parameters in healthy pregnant Moroccan women and concluded that pregnancy in women has the tendency to alter some hematological indices. For these reasons, there is an interest to take these modifications into account for optimal maternal and fetal medical care.
The prognostic significance of lymph node size in node-positive colon cancer

Objectives To (i) show the outcome benefits of enlarged lymph nodes in node-positive colon cancer cases, as it was shown previously in negative node cases; (ii) disprove the stage migration theory and (iii) list the factors affecting lymph node size and yield. Methods A retrospective study including 234 node-positive colon cancer cases was scheduled and performed. All recovered lymph nodes (6969) from 234 cases were microscopically examined in regard to (a) lymph node size (b) presence of metastasis (c) extent of intra-nodal metastasis. On the basis of resulting data, a statistical analysis was performed. Results Metastases occurred in all size categories, though more often in larger lymph nodes. Fifty-one percent of all metastasised nodes were 2 to 6 mm in size. Approximately half of all nodes >10 mm were microscopically free of cancer. Cases with a small lymph node metastasis to lymph node size ratio (MSR) had a better prognosis than others: 85 months (95% CI: 72–97) vs. 67 months (95% CI: 47–88), p <0.001 (mean, overall survival). To differentiate between cases with the same ratio but different absolute lymph nodes sizes, we divided the cases into two groups that differed in their number of moderate to large lymph nodes. The group with more moderate to large lymph nodes showed a clear outcome benefit: 104 months (95% CI: 86–122) vs. 66 months (95% CI: 54–77), p = 0.014 (mean, overall survival). Conclusions Metastasised lymph nodes affect all size categories, and large lymph nodes are not always metastasised. The combination of enlarged lymph nodes and a small lymph node metastasis to lymph node size ratio (MSR) is associated with a better prognosis than others. When enlarged lymph nodes were considered as surrogate markers of an effective local immune response due to nodal hyperplasia, the immune system could be seen as the confounder affecting both lymph node size and prognosis. Our results are pointing in this direction and, along with other reasons, are challenging the stage migration theory.
Profiling undergraduate students from a Romanian medical university

Purpose Medical students’ personality traits, emotion regulation strategies, and empathic behavior are considered powerful predictors for their future achievements, professional adjustment, and mental strength. Coping strategies such as “self-blame,” “rumination,” “catastrophizing,” “blaming others,” lack of empathy, decreased emotion recognition abilities, and neuroticism are maladaptive and, thus, less desirable traits in medical professionals. The purpose of the study was to comparatively assess and find potential correlations between personality traits, empathy levels, emotion recognition abilities, and cognitive emotion regulation strategies of three medical student samples: general medicine (GM), dental medicine (DM), and general nursing (GN) students. Patients and methods This cross-sectional comparative study was conducted throughout the second semester of 2017, during Psychiatry class, on 306 medical undergraduates of the “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania. Personality was assessed by using Neuroticism–Extraversion–Openness to Experience Five-Factor Inventory (NEO-FFI). Cognitive emotion regulation strategies were identified using the Cognitive Emotion Regulation Questionnaire (CERQ). Empathy quotient (EQ) was used to measure empathy levels. Emotion recognition abilities were evaluated with the Reading the Mind in the Eyes test (RMET). Results GM students scored significantly higher than both DM and GN students in blaming others (CERQ) and significantly higher than GN students in “neuroticism” (NEO-FFI). GM and DM students obtained significantly lower scores than their GN colleagues in “agreeableness” (NEO-FFI) and empathy (EQ). Compared to DM students, GN students gave significantly more correct answers in RMET. Neuroticism was associated with less efficient coping mechanisms (self-blame, rumination, catastrophizing, blaming others) and lower empathy scores. Empathy correlated negatively with blaming others and was positively associated with agreeableness and emotion recognition abilities. Conclusion The differences found between the student samples can be consequences of several overlapping factors. Certain personality traits may predispose individuals to maladaptive coping responses, increased vulnerability to stress, and lower empathy levels. The results of this study can be viewed as baseline data for future, more comprehensive, longitudinal analyses.