Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Olfactory Bulb Neural Stem Cells (Hu-OBNSCs) Can Be Loaded with Paclitaxel and Used to Inhibit Glioblastoma Cell Growth

Exploitation of the potential ability of human olfactory bulb (hOB) cells to carry, release, and deliver an effective, targeted anticancer therapy within the central nervous system (CNS) milieu remains elusive. Previous studies have demonstrated the marked ability of several types of stem cells (such as mesenchymal stem cells (MSCs) to carry and release different anti-cancer agents such as paclitaxel (PTX). Herein we investigate the ability of human olfactory bulb neural stem cells (Hu-OBNSCs) to carry and release paclitaxel, producing effective cytotoxic effects against cancer cells. We isolated Hu-OBNSCs from the hOB, uploaded them with PTX, and studied their potential cytotoxic effects against cancer cells in vitro. Interestingly, the Hu-OBNSCs displayed a five-fold increase in their resistance to the cytotoxicity of PTX, and the PTX-uploaded Hu-OBNSCs were able to inhibit proliferation and invasion, and to trigger marked cytotoxic effects on glioblastoma multiforme (GBM) cancer cells, and Human Caucasian fetal pancreatic adenocarcinoma 1 (CFPAC-1) in vitro. Despite their ability to resist the cytotoxic activity of PTX, the mechanism by which Hu-OBNSCs acquire resistance to PTX is not yet explained. Collectively our data indicate the ability of the Hu-OBNSCs to resist PTX, and to trigger effective cytotoxic effects against GBM cancer cells and CFPAC-1. This indicates their potential to be used as a carrier/vehicle for targeted anti-cancer therapy within the CNS.
Neutrons are forever! Historical perspectives

Abstract Purpose: Neutrons were an active field of radiobiology at the time of publication of the first issues of the International Journal of Radiation Biology in 1959. Three back-to-back papers published by Neary and his colleagues contain key elements of interest at the time. The present article aims to put these papers into context with the discovery of the neutron 27 years previously and then give a feel for how the field has progressed to the present day. It does not intend to provide a comprehensive review of this enormous field, but rather to provide selective summaries of main driving forces and developments. Conclusions: Neutron radiobiology has continued as a vigorous field of study throughout the past 84 years. Main driving forces have included concern for protection from the harmful effects of neutrons, exploitation and optimization for cancer therapy (fast beam therapy, brachytherapy and boron capture therapy), and scientific curiosity about the mechanisms of radiation action. Effort has fluctuated as the emphasis has shifted from time to time, but all three areas remain active today. Whatever the future holds for the various types of neutron therapy, the health protection aspects will remain with us permanently because of natural environmental exposure to neutrons as well as increased additional exposures from a variety of human activities.
Endoplasmic Reticulum (ER) Stress and Unfolded Protein Response (UPR) in Mammalian Oocyte Maturation and Preimplantation Embryo Development

Mammalian oocytes and early embryos derived from in vitro production are highly susceptible to a variety of cellular stresses. During oocyte maturation and preimplantation embryo development, functional proteins must be folded properly in the endoplasmic reticulum (ER) to maintain oocyte and embryo development. However, some adverse factors negatively impact ER functions and protein synthesis, resulting in the activation of ER stress and unfolded protein response (UPR) signaling pathways. ER stress and UPR signaling have been identified in mammalian oocytes and embryos produced in vitro, suggesting that modulation of ER stress and UPR signaling play very important roles in oocyte maturation and the development of preimplantation embryos. In this review, we briefly describe the current state of knowledge regarding ER stress, UPR signaling pathways, and their roles and mechanisms in mammalian (excluding human) oocyte maturation and preimplantation embryo development.
Gender Differences and Obesity Influence on Pulmonary Function Parameters

Objectives Overweight and obesity are known to cause various patterns of alteration to the pulmonary function test (PFT) parameters. We sought to investigate gender differences in PFT parameters and examine the relationship between body mass index (BMI) and PFT parameters. Methods We conducted a retrospective study of 126 patients referred for a PFT by various medical specialties between January and December 2015. PFT was measured using spirometry, and BMI was calculated using Quetelet’s index. Results Female patients exhibited lower mean values for all PFT parameters compared to male patients. The forced vital capacity (FVC)% predicted was less than 80% for all patients while the ratio of forced expiratory volume in 1 second (FEV1)/FVC was higher with increased BMI. BMI was positively correlated with peak expiratory flow in all patients, and with FEV1/FVC ratio in males but not in females. Conclusions In our studied population, males exhibited higher mean values of PFT parameters than females. Increased BMI may be associated with a restrictive pattern on spirometry.
Toxic Effect of Acute Cadmium and Lead Exposure in Rat Blood, Liver, and Kidney

Background: Cadmium and lead are widespread and non-biodegradable pollutants of great concern to human health. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and it is therefore of paramount importance to assess their toxicity. In this study, we investigated the toxicity of Cd and Pb alone and as a mixture in an animal model of acute exposure. Methods: Experimental groups received a single treatment of aqueous solution of Cd-chloride (15 and 30 mg/kg body weight (b.w.) and Pb-acetate (150 mg/kg b.w.), while the mixture group received 15 mg Cd/kg b.w. and 150 mg Pb/kg b.w. Toxic effects of individual metals and their mixture were investigated on hematological and biochemical parameters, and the redox status in the plasma, liver, and kidneys of treated Wistar rats. Results: Tissue-specific changes were recorded in various parameters of oxidative damage, while the accumulation of metals in tissues accompanied the disturbances of both hematological and biochemical parameters. It was observed that the level of toxic metals in tissues had a different distribution pattern after mixture and single exposure. Conclusions: Comprehensive observations suggest that exposure to Cd and Pb mixtures produces more pronounced effects compared to the response observed after exposure to single metal solutions. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic metals in the organisms.
Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns

DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an epigenetic mark that needs to be faithfully replicated during mitosis in order to maintain cell phenotype during successive cell divisions. This epigenetic mark is located on the 5′-carbon of the cytosine mainly within cytosine–phosphate–guanine (CpG) dinucleotides. DNA methylation is asymmetrically positioned on both DNA strands, temporarily generating a hemi-methylated state after DNA replication. Hemi-methylation is a particular status of DNA that is recognized by ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) through its SET- (Su(var)3-9, Enhancer-of-zeste and Trithorax) and RING-associated (SRA) domain. This interaction is considered to be involved in the recruitment of DNMT1 to chromatin in order to methylate the adequate cytosine on the newly synthetized DNA strand. The UHRF1/DNMT1 tandem plays a pivotal role in the inheritance of DNA methylation patterns, but the fine-tuning mechanism remains a mystery. Indeed, because DNMT1 experiences difficulties in finding the cytosine to be methylated, it requires the help of a guide, i.e., of UHRF1, which exhibits higher affinity for hemi-methylated DNA vs. non-methylated DNA. Two models of the UHRF1/DNMT1 dialogue were suggested to explain how DNMT1 is recruited to chromatin: (i) an indirect communication via histone H3 ubiquitination, and (ii) a direct interaction of UHRF1 with DNMT1. In the present review, these two models are discussed, and we try to show that they are compatible with each other.
Global distribution of malocclusion traits: A systematic review

Abstract Objective: Considering that the available studies on prevalence of malocclusions are local or national-based, this study aimed to pool data to determine the distribution of malocclusion traits worldwide in mixed and permanent dentitions. Methods: An electronic search was conducted using PubMed, Embase and Google Scholar search engines, to retrieve data on malocclusion prevalence for both mixed and permanent dentitions, up to December 2016. Results: Out of 2,977 retrieved studies, 53 were included. In permanent dentition, the global distributions of Class I, Class II, and Class III malocclusion were 74.7% [31 - 97%], 19.56% [2 - 63%] and 5.93% [1 - 20%], respectively. In mixed dentition, the distributions of these malocclusions were 73% [40 - 96%], 23% [2 - 58%] and 4% [0.7 - 13%]. Regarding vertical malocclusions, the observed deep overbite and open bite were 21.98% and 4.93%, respectively. Posterior crossbite affected 9.39% of the sample. Africans showed the highest prevalence of Class I and open bite in permanent dentition (89% and 8%, respectively), and in mixed dentition (93% and 10%, respectively), while Caucasians showed the highest prevalence of Class II in permanent dentition (23%) and mixed dentition (26%). Class III malocclusion in mixed dentition was highly prevalent among Mongoloids. Conclusion: Worldwide, in mixed and permanent dentitions, Angle Class I malocclusion is more prevalent than Class II, specifically among Africans; the least prevalent was Class III, although higher among Mongoloids in mixed dentition. In vertical dimension, open bite was highest among Mongoloids in mixed dentition. Posterior crossbite was more prevalent in permanent dentition in Europe.
PENGARUH CARA BELAJAR DAN PENGGUNAAN MEDIA PEMBELAJARAN TERHADAP PRESTASI BELAJAR AKUNTANSI SISWA KELAS XI IPS SMA NEGERI 2 BANTUL TAHUN AJARAN 2011/2012

Penelitian ini bertujuan untuk mengetahui: (1) Pengaruh Cara Belajar terhadapPrestasi Belajar Akuntansi Siswa Kelas XI IPS SMA Negeri 2 Bantul Tahun Ajaran2011/2012; (2) Pengaruh Penggunaan Media Pembelajaran terhadap Prestasi BelajarAkuntansi Siswa Kelas XI IPS SMA Negeri 2 Bantul Tahun Ajaran 2011/2012; (3) PengaruhCara Belajar dan Penggunaan Media Pembelajaran secara bersama-sama terhadap PrestasiBelajar Akuntansi Siswa Kelas XI IPS SMA Negeri 2 Bantul Tahun Ajaran 2011/2012.Penelitian ini merupakan penelitian kausal komparatif, populasi dalam penelitian iniberjumlah 118 siswa kelas XI IPS SMA Negeri 2 Bantul Tahun Ajaran 2011/2012, sampelyang digunakan sejumlah 90 siswa. Teknik pengumpulan data dengan angket dandokumentasi. Uji coba instrumen dilakukan kepada 28 responden. Uji validitas menggunakanrumus koefisien korelasi Product Moment, sedangkan uji reliabilitas menggunakan rumusAlpha. Uji prasyarat analisis meliputi uji normalitas, uji linieritas dan uji multikolinieritas.Teknik analisis data terdiri dari analisis regresi sederhana dan analisis regresi ganda. Tingkatsignifikansi hasil analisis ditentukan 5%. Berdasarkan hasil penelitian dapat diperoleh kesimpulan sebagai berikut: (1) CaraBelajar berpengaruh positif dan signifikan terhadap Prestasi Belajar Akuntansi Siswa KelasXI IPS SMA Negeri 2 Bantul Tahun Ajaran 2011/2012 dengan ditunjukkan harga rx1y sebesar0,587; r2x1y sebesar 0,345; thitung lebih besar dari ttabel pada taraf signifikansi 5% (6,806 >1,987) dan persamaan regresi sederhana Y = 0,508X1 + 48,107; (2) Penggunaan MediaPembelajaran berpengaruh positif dan signifikan terhadap Prestasi Belajar Akuntansi SiswaKelas XI IPS SMA Negeri 2 Bantul Tahun Ajaran 2011/2012 dengan ditunjukkan harga rx2ysebesar 0,500; r2x2y sebesar 0,250; thitung lebih besar dari ttabel pada taraf signifikansi 5% (5,420> 1,987) dan persamaan regresi sederhana Y = 0,404X2 + 55,393; (3) Cara Belajar danPenggunaan Media Pembelajaran secara bersama-sama berpengaruh positif dan signifikanterhadap Prestasi Belajar Akuntansi Siswa Kelas XI IPS SMA Negeri 2 Bantul Tahun Ajaran2011/2012 dengan ditunjukkan harga Ry(1,2) sebesar 0,635; R2y(1,2) sebesar 0,404; Fhitung lebihbesar dari Ftabel pada taraf signifikansi 5% (29,461 > 3,101) dan persamaan regresi ganda Y =0,398X1 + 0,225X2 + 42,190. Sumbangan Efektif (SE) sebesar 40,4% dimana sumbanganefektif dari Cara Belajar sebesar 25,97% dan Penggunaan Media Pembelajaran sebesar14,43%.
Impacto de un Plan de Acción Tutorial universitario: resultados académicos, implicación y satisfacción

Este trabajo se centra en el desarrollo del Plan de Accion Tutorial (PAT) de la Universidad de Burgos, Plan que inicia su experiencia en el curso academico 2009-2010. A partir del seguimiento de la implantacion del PAT en tres Grados, se pretende analizar la posible influencia del mismo en diferentes variables relacionadas con los alumnos de primer curso y con los profesores tutores: exito en los estudios, abandono, rendimiento, implicacion y satisfaccion con el Plan. La muestra la conforman 130 estudiantes y 49 profesores. Se han utilizado varias fuentes de informacion como registros de matricula del alumnado e informes de tutores y alumnos, que han permitido un analisis cuantitativo de los primeros y cualitativo de los segundos mediante una rubrica de evaluacion de tutorias elaborada ad hoc. Los resultados del estudio estadistico muestran una tendencia positiva entre el rendimiento y el exito del alumnado y la implicacion del tutor, para una de las titulaciones; en esta titulacion tambien parece existir una relacion positiva y relativamente alta, entre el abandono y la implicacion del tutor. Otros resultados, como la escasa participacion del alumnado y la baja implicacion de algunos tutores, nos llevan a sugerir algunas propuestas de mejora del Plan de Accion Tutorial. ABSTRACT Impact of a university Tutorial Action Plan: academic performance, involvement and satisfaction. This work focuses on the development of the Tutorial Action Plan (TAP) of University of Burgos, which begins its experience in the academic year 2009-2010. The objective of this work is the analysis, on three undergraduate Degrees, of the potential influence of the TAP on different variables related to first-year students and tutor-teachers: academic success, dropout, academic performance and involvement and satisfaction with the PAT. The sample is composed of 130 students and 49 teachers. We used several sources of information such as student enrollment records and reports of tutors and students about the TAP. Results from the statistical study show a positive trend for one of the analysed Degrees between performance and success of students and tutor involvement, and also a relatively high positive relationship between dropout and tutor involvement. Other outcomes, such as a general low student participation in the TAP and low involvement of some tutors, lead us to suggest some proposals in order to improve the TAP.
Efficacy and toxicity of proton with photon radiation for locally advanced nasopharyngeal carcinoma

Arnaud Beddok, Loïc Feuvret, Georges Noel, St ephanie Bolle, M elanie Deberne, Hamid Mammar, Adriel Chaze, Christophe Le Tourneau, Farid Goudjil, Sophia Zefkili, Philippe Herman, R emi Dendale and Valentin Calugaru Department of Radiation Therapy, Proton Therapy Center, Curie Institute, Orsay, France; Department of Radiation Therapy, Curie Institute, Paris, France; Department of Radiation Therapy, Piti e-Salpêtri ere Hospital, Paris, France; Department of Radiation Therapy, Paul Strauss Center, Strasbourg, France; Department of Radiation Therapy, Gustave Roussy Institute, Villejuif, France; Department of Radiation Therapy, Lyon Sud Hospital, Pierre-B enite, France; Statistician, Paris, France; Department of Medical Oncology, Curie Institute, Paris, France; Department of Otorhinolaryngology, Lariboisi ere Hospital, Paris, France
The association of a novel cognitive frailty index and physical functioning in older at-risk adults

Abstract Objectives: Cognitive frailty is a state at the lower end of the continuum of cognitive resilience in which one is at elevated risk for cognitive impairment and dementia. Metrics of a newly developed Cognitive Frailty Index (CFI) were examined for their association with objective functional limitations. Methods: We used baseline data from 607 participants from the Baltimore Experience Corps Trial with measures on the CFI, a computerized Stroop test, and Short Physical Performance Battery (SPPB) score ≤9. Multivariable log-binomial regression models were used to evaluate the associations of CFI metrics (mean reaction time (RT) for total, first-half and second-half trials per condition) with the SPPB. Latent growth models were used to create additional CFI metrics of initial level (intercept) and change (slope) in RT across accurate trials by easy (Color-X) and difficult (Color-Word) conditions. Models were adjusted for race, sex, age, income, major morbidities, depressive symptoms, self-reported health, and Stroop interference (for Color-Word condition only). Results: All CFI RT metrics were associated with SPPB <9, yet latent growth model approaches were most informative. Initial levels of performance on easy (Risk Ratio, [RR] = 1.24; 95% Confidence Interval, [CI]: 1.03, 1.49) and difficult conditions (RR = 1.22; 95% CI: 1.05, 1.41), not rates of learning (slope) (RR = 1.08, 95% CI: 0.81, 1.45 and RR = 1.11, 95% CI: 0.96, 1.27 respectively), were associated with worse physical functioning. Conclusions: The association between the CFI and physical functioning demonstrates the interplay of cognitive frailty and worse objective mobility within a sociodemographic at-risk sample.
Development and external evaluation of a population pharmacokinetic model for continuous and intermittent administration of vancomycin in neonates and infants using prospectively collected data

BACKGROUND Vancomycin is commonly used for nosocomial bacterial pathogens causing late-onset septicaemia in preterm infants. We prospectively collected pharmacokinetic data aiming to describe pharmacokinetics and determine covariates contributing to the variability in neonatal vancomycin pharmacokinetics. Further, we aimed to use the model to compare the ratio of AUC24 at steady-state to the MIC (AUC24,ss/MIC) of several intermittent and continuous dosing regimens. METHODS Newborns receiving vancomycin for suspected or confirmed late-onset sepsis were included. Peak and trough concentrations for intermittent vancomycin dosing and steady-state concentrations for continuous vancomycin dosing were measured. NONMEM 7.3 was used for population pharmacokinetic analysis. Monte Carlo simulations were performed to compare dosing schemes. RESULTS Data from 54 infants were used for model development and from 34 infants for the model evaluation {corrected gestational age [median (range)] = 29 (23.7-41.9) weeks and 28 (23.4-41.7) weeks, respectively}. The final model was a one-compartment model. Weight and postmenstrual age were included a priori, and then no additional covariate significantly improved the model fit. Final model parameter estimates [mean (SEM)]: CL = 5.7 (0.3) L/h/70 kg and V = 39.3 (3.7) L/70 kg. Visual predictive check of the evaluation dataset confirmed the model can predict external data. Simulations using MIC of 1 mg/L showed that for neonates with gestational age ≤25 weeks and postnatal age ≤2 weeks AUC24,ss/MIC was lower with the intermittent regimen (median 482 versus 663). CONCLUSIONS A population pharmacokinetic model for continuous and intermittent vancomycin administration in infants was developed. Continuous administration might be favourable for treating infections caused by resistant microorganisms in very young and immature infants.
The New Possibility of Lymphoscintigraphy to Guide a Clinical Treatment for Lymphedema in Patient With Breast Cancer

Objectives Lymphedema is a chronic disease that occurs frequently after breast cancer treatment. For the treatment of lymphedema, surgical approach such as vascularized lymph node transfer and super-microscopic lymphovenous anastomosis surgery is well established. Complex decongestive therapy (CDT) and sympathetic ganglion block (SGB) are two non-surgical therapeutic options. This study aimed to evaluate the effectiveness of lymphoscintigraphy in guiding the selection of the optimal non-surgical treatment in lymphedema. Methods A total of 81 lymphedema patients who underwent lymphoscintigraphy and were treated with CDT or SGB were retrospectively evaluated. The parameters for the lymphoscintigraphic findings included the extent of dermal backflow (small extent/large extent groups), the level of lymphatic flow (trunk flow pattern/upper arm-restricted pattern/forearm-restricted pattern groups), and the visualization of lymph nodes (visualized/non-visualized groups). The change in the circumferential difference between the two sides of the body at the upper arm and forearm was used as the clinical outcome variable. Paired comparison and group comparison analysis were conducted. Results Of 81 patients, 41 received CDT and 40 received SGB. There were no significant differences in demographic data between the CDT and SGB groups. Both CDT and SGB had a significant therapeutic effect. Upper arm edema was more significantly reduced after SGB than after CDT in the small extent group (P = 0.004), the forearm-restricted pattern group (P = 0.002), and the non-visualized group (P = 0.018). In the other groups, SGB and CDT showed comparable therapeutic effects without statistical differences. Conclusion SGB was found to have a better therapeutic effect in the lymphedema patients with specific lymphoscintigraphic findings compared with CDT. Lymphoscintigraphy may be helpful in selecting the appropriate approach to lymphedema treatment. Further well-designed prospective studies are warranted to validate the findings of this study.
Age-related alterations in the modulation of intracortical inhibition during stopping of actions

We investigated the effect of age on the ability to modulate GABAA-ergic and GABAB-ergic inhibitory activity during stopping of action (reactive inhibition) and preparation to stop (proactive inhibition). Twenty-five young and twenty-nine older adults performed an anticipated response version of the stop-signal task with varying levels of stop-signal probability. Paired-pulse transcranial magnetic stimulation was applied to left primary motor cortex to assess the modulation of GABAA-mediated short-interval intracortical inhibition (SICI) during stopping and GABAB-mediated long-interval intracortical inhibition (LICI) during the anticipation of a stop-signal. At the behavioral level, reactive inhibition was affected by aging as indicated by longer stop-signal reaction times in older compared to young adults. In contrast, proactive inhibition was preserved at older age as both groups slowed down their go response to a similar degree with increasing stop-signal probability. At the neural level, the amount of SICI was higher in successful stop relative to go trials in young but not in older adults. LICI at the start of the trial was modulated as a function of stop-signal probability in both young and older adults. Our results suggest that specifically the recruitment of GABAA-mediated intracortical inhibition during stopping of action is affected by aging.