Miracle-dz/UniFAR-FTUs huggingface dataset:
In vitro effects of hydrogen peroxide on rat uterine contraction before and during pregnancy

Aim To assess the in vitro effect of hydrogen peroxide (H2O2) on uterine contractions in pregnant and non-pregnant rats. Methods The study was performed at the Department of Physiology, College of Medicine, King Saud University from December 2016 to October 2017. Intact uterine samples were obtained from non-pregnant (n = 7-8) and term-pregnant (n = 6-7) rats. Small longitudinal uterine strips were dissected and mounted in an organ bath. Isometric force measurements were used to assess the effect of 400, 800, and 1000 μM H2O2 on spontaneous uterine contractions and contractions induced by oxytocin (5 nM), high calcium (Ca+2) solution (6 mmol/L), and high potassium chloride (KCl) solution (60 mmol/L). Results In both term-pregnant and non-pregnant uterine strips, H2O2 elicited a biphasic response, consisting of a transient contraction followed by a persistent decrease in spontaneously generated contractions, contractions induced by oxytocin, and contractions induced by high Ca+2 (all P < 0.01, compared with controls) in a concentration-dependent manner. The effect of H2O2 was more pronounced in non-pregnant than in pregnant rats (P < 0.05). In both groups, H2O2 failed to relax uterine strips pre-contracted with high-KCl solution (P > 0.05 compared with controls). Conclusion H2O2 was shown to be a potent uterine relaxant in pregnant and non-pregnant states. The pregnant uterus better withstood the inhibitory effect of H2O2 than non-pregnant uterus.
The effector of Hippo signaling, Taz, is required for formation of the micropyle and fertilization in zebrafish

The mechanisms that ensure fertilization of eggs by a single sperm are not fully understood. In all teleosts, a channel called the ‘micropyle’ is the only route of entry for sperm to enter and fertilize the egg. The micropyle forms by penetration of the developing vitelline envelope by a single specialized follicle cell, the micropylar cell, which subsequently degenerates. The mechanisms underlying micropylar cell specification and micropyle formation are poorly understood. Here, we show that an effector of the Hippo signaling pathway, the Transcriptional co-activator with a PDZ-binding domain (Taz), plays crucial roles in micropyle formation and fertilization in zebrafish. Genome editing mutants affecting taz can grow to adults, however, eggs from homozygous taz females are not fertilized even though oocytes in mutant females are histologically normal with intact animal-vegetal polarity, complete meiosis and proper ovulation. However, taz mutant eggs have no micropyle. We show that Taz protein is specifically enriched from mid-oogenesis onwards in two follicle cells located at the animal pole of the oocyte, and co-localizes with the actin and tubulin cytoskeleton. Taz protein and micropylar cell are not detected in taz mutant ovaries. Our work identifies a novel role for the Hippo/Taz pathway in micropylar cell specification in zebrafish, and uncovers the molecular basis of micropyle formation in teleosts.
Position of a panel of international lung cancer experts on the approval decision for use of durvalumab in stage III non-small-cell lung cancer (NSCLC) by the Committee for Medicinal Products for Human Use (CHMP).

Peters, Solange ; Dafni, Urania ; Boyer, Michael ; De Ruysscher, Dirk ; Faivre-Finn, Corinne ; Felip, Enriqueta ; Garrido, Pilar ; Girard, Nicolas ; Guckenberger, Matthias ; Haanen, John ; Le Pechoux, Cecile ; Mornex, Francoise ; Ozsahin, Mahmut ; Paz-Ares, Luis ; Planchard, David ; Raben, David ; Ramalingam, Suresh ; Reck, Martin ; Smit, Egbert ; Stahel, Rolf ; Stenzinger, Albrecht ; Swanton, Charlie ; Vallone, Stefania ; Garassino, Marina C
Um estudo empírico de um sistema de reconhecimento facial utilizando o classificador KNN

Neste artigo, apresenta-se um estudo empirico de otimizacao das taxas de acuracias resultantes de um sistema de reconhecimento facial baseado nas tecnicas Eigenfaces e K-Nearest Neighbors. Foram investigadas as seguintes variaveis: imagens com tres dimensoes distintas, numero de caracteristicas (Eigenfaces), valores de k da tecnica K-Nearest Neighbors e tres medidas de distância (euclidiana, Manhattan e euclidiana normalizada). Os estudos foram importantes para entender empiricamente quais parâmetros sao os mais relevantes para as tecnicas analisadas e que resultam em melhores taxas de acuracias de reconhecimento facial. Os resultados dos experimentos comprovaram que as imagens com dimensoes 12x9 pixels produzem as melhores taxas de acuracias de reconhecimento facial, combinando com a medida de distância euclidiana normalizada e um numero de Eigenfaces igual a vinte.
Psychometric Properties of the Spanish Version of the Caregiver Burden Inventory

Although the Caregiver Burden Inventory (CBI) is the most widely used multidimensional burden instrument for assessing perceived burden of caregivers, there is no data on its psychometric properties in Spanish, nor on caregivers of dependent persons with various diseases. The objective of this study was to translate the CBI into Spanish and validate it in caregivers of dependent persons with various diseases. Trained evaluators administered the CBI and assessed emotional distress and probable mental disorder in 201 caregivers (87.1% women, mean age 56.2 years). The internal consistency of the CBI was 0.89 (0.74–0.83 among the subscales). There was a significant correlation of emotional distress with both the total burden and each subscale (p < 0.001 in all cases). A total score of 39 and scores of 16, 9, 8, 4, and 2 in burden per time dedicated to care, personal life burden, physical burden, social burden, and emotional burden were suitable cut-off points to discriminate caregivers with probable mental disorder (sensitivity = 63.0%–75.6%, specificity = 63.4%–74.4%). To achieve a greater goodness of fit, the model was re-specified, resulting in a shortened (15-item) instrument. The internal consistency reliability coefficients of the 15-item CBI were satisfactory (Cronbach α = 0.83; 0.77–0.86 among the subscales). Within the 15-item CBI, emotional distress was significantly correlated with the total burden, personal life burden, physical burden, social burden (p < 0.001 in all those cases), and emotional burden (p = 0.001). A total score of 25 and scores of 12, 5, 5, 3, and 1, respectively, in the subscales were identified as cut-off points to discriminate caregivers with probable mental disorder (sensitivity = 46.2%–70.6%, specificity = 43.9%–79.3%). Therefore, the 15-item CBI validly measured caregiver burden with better fit and more parsimoniously than the original CBI.
Environmental Change-Dependent Inherited Epigenetic Response

Epigenetic modifications are a mechanism conveying environmental information to subsequent generations via parental germ lines. Research on epigenetic responses to environmental changes in wild mammals has been widely neglected, as well as studies that compare responses to changes in different environmental factors. Here, we focused on the transmission of DNA methylation changes to naive male offspring after paternal exposure to either diet (~40% less protein) or temperature increase (10 °C increased temperature). Because both experiments focused on the liver as the main metabolic and thermoregulation organ, we were able to decipher if epigenetic changes differed in response to different environmental changes. Reduced representation bisulfite sequencing (RRBS) revealed differentially methylated regions (DMRs) in annotated genomic regions in sons sired before (control) and after the fathers' treatments. We detected both a highly specific epigenetic response dependent on the environmental factor that had changed that was reflected in genes involved in specific metabolic pathways, and a more general response to changes in outer stimuli reflected by epigenetic modifications in a small subset of genes shared between both responses. Our results indicated that fathers prepared their offspring for specific environmental changes by paternally inherited epigenetic modifications, suggesting a strong paternal contribution to adaptive processes.
Targeted arsenite-loaded magnetic multifunctional nanoparticles for treatment of hepatocellular carcinoma

Arsenic trioxide (ATO), an FDA-approved drug for acute promyelocytic leukemia, also has great potential for treatment of solid tumors. Drug delivery powered by recent advances in nanotechnology has boosted the efficacy of many drugs, which is enlightening for applications of ATO in treating solid tumors. Herein, we reported arsenite-loaded multifunctional nanoparticles that are capable of pH-responsive ATO release for treating hepatocellular carcinoma (HCC) and real-time monitoring via magnetic resonance imaging. We fabricated these nanoparticles (designated as magnetic large-pore mesoporous silica nanoparticle (M-LPMSN)-NiAsOx) by loading nanoparticulate ATO prodrugs (NiAsOx) into the pores of large-pore mesoporous silica nanoparticles (LPMSNs) that contain magnetic iron oxide nanoparticles in the center. The surface of these nanodrugs was modified with a targeting ligand folic acid (FA) to further enhance the drug efficacy. Releasing profiles manifest the responsive discharging of arsenite in acidic environment. In vitro experiments with SMMC-7721 cells reveal that M-LPMSN-NiAsOx-FA nanodrugs have significantly higher cytotoxicity than traditional free ATO and induce more cell apoptosis. In vivo experiments with mice bearing H22 tumors further confirm the superior antitumor efficacy of M-LPMSN-NiAsOx-FA over traditional free ATO and demonstrate the outstanding imaging ability of M-LPMSN-NiAsOx-FA for real-time tumor monitoring. These targeted arsenite-loaded magnetic mesoporous silica nanoparticles integrating imaging and therapy hold great promise for treatment of HCC, indicating the auspicious potential of LPMSN-based nanoplatforms.
HepaCAM inhibits cell proliferation and invasion in prostate cancer by suppressing nuclear translocation of the androgen receptor via its cytoplasmic domain

Hepatocyte cell adhesion molecule (HepaCAM) is a tumour suppressor. However, the mechanism of HepaCAM function in prostate cancer (PCa) remains unknown. In the present study, HepaCAM, androgen receptor (AR) and Ran were analysed in 46 PCa tissue samples using immunohistochemistry. Subsequently, the influence of HepaCAM and its cytoplasmic domain on cell proliferation, migration, and invasion, and associated proteins was examined using MTT, wound healing, Transwell and western blotting assays, respectively. Furthermore, nuclear translocation of AR and Ran was analysed using immunofluorescence and Western blot assays. The results demonstrated that HepaCAM expression was reduced in PCa, and there was an association between downregulation of HepaCAM and changes in the distribution of AR and Ran. Furthermore, HepaCAM, specifically the cytoplasmic domain, was involved in cell proliferation, migration and invasion. Nuclear translocation of AR was dependent on HepaCAM and its cytoplasmic domain. Additionally, HepaCAM suppression of the nuclear translocation of AR occurred via Ran. The results suggest that HepaCAM and its cytoplasmic domain suppress the nuclear translocation of AR via Ran in PCa. The cytoplasmic domain of HepaCAM may serve as a novel target for therapy in PCa.
Adding double carbapenem therapy to the armamentarium against carbapenem-resistant Enterobacteriaceae bloodstream infections

Abstract Background: Carbapenem-resistant Enterobacteriaceae (CRE) constitute a threat, since they cause infections with high mortality rates. Historically, polymyxin-based therapies have been the regimens of choice for CRE bloodstream infection (BSI). Recent studies have shown improved outcomes with β-lactam-based therapies, including double carbapenem regimens for CRE BSIs compared to polymyxin-based regimens. The purpose of this report was to review the data supporting double carbapenem therapy for CRE BSI and provide recommendations regarding their use. Methods: A systematic literature search through 31 January 2018 was performed. Results: Multiple in vitro studies have described synergistic activity with ertapenem-based double carbapenem regimens for KPC-producing Enterobacteriaceae. Additionally, efficacy has been observed with double carbapenem regimens in multiple case reports and case series. A prospective multi-centre observational study of double carbapenem therapies in patients with CRE BSIs showed lower mortality compared to standard therapy. Conclusions: Clinicians should consider double carbapenem therapy as an option for treating CRE infections.
Magnetometer Calibration and Field Mapping through Thin Plate Splines

While the undisturbed Earth’s magnetic field represents a fundamental information source for orientation purposes, magnetic distortions have been mostly considered as a source of error. However, when distortions are temporally stable and spatially distinctive, they could provide a unique magnetic landscape that can be used in different applications, from indoor localization to sensor fusion algorithms for attitude estimation. The main purpose of this work, therefore, is to present a method to characterize the 3D magnetic vector in every point of the measurement volume. The possibility of describing the 3D magnetic field map through Thin Plate Splines (TPS) interpolation is investigated and demonstrated. An algorithm for the simultaneous estimation of the parameters related to magnetometer calibration and those describing the magnetic map, is proposed and tested on both simulated and real data. Results demonstrate that an accurate description of the local magnetic field using TPS interpolation is possible. The proposed procedure leads to errors in the estimation of the local magnetic direction with a standard deviation lower than 1 degree. Magnetometer calibration and magnetic field mapping could be integrated into different algorithms, for example to improve attitude estimation in highly distorted environments or as an aid to indoor localization.
Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor

Isoprenyl cysteine carboxyl methyltransferase (ICMT) plays a key role in post-translational regulation of prenylated proteins. On the basis of previous results, we hypothesized that the p53 pathway and ICMT expression may be linked in cancer cells. Here, we studied whether WT p53 and cancer-associated p53 point mutants regulate ICMT levels and whether ICMT overexpression affects tumor progression. Studying the effect of p53 variants on ICMT mRNA and protein levels in cancer cells, we found that WT p53 and p53 mutants differentially affect ICMT expression, indicating that p53 status influences ICMT levels in tumors. To investigate the underlying mechanisms, we constructed ICMT–luciferase reporters and found that WT p53 represses ICMT transcription. In contrast, p53 mutants showed a positive effect on ICMT expression. Promoter truncation analyses pinpointed the repressive effect of WT p53 to the −209 and −14 region on the ICMT promoter, and ChIP assays indicated that WT p53 is recruited to this region. Instead, a different promoter region was identified as responsible for the mutant p53 effect. Studying the effect of ICMT overexpression on tumor-associated phenotypes in vitro and in vivo, and analyzing breast and lung cancer databases, we identified a correlation between p53 status and ICMT expression in breast and lung cancers. Moreover, we observed that ICMT overexpression is correlated with negative clinical outcomes. Our work unveils a link between postprenylation protein processing and the p53 pathway, indicating that the functional interplay between WT and mutant p53 alters ICMT levels, thereby affecting tumor aggressiveness.
The potential of biobanked liquid based cytology samples for cervical cancer screening using Raman spectroscopy

Patient samples are unique and often irreplaceable. This allows biobanks to be a valuable source of material. The aim of this study was to assess the ability of Raman spectroscopy to screen for histologically confirmed cases of Cervical Intraepithelial neoplasia (CIN) using biobanked liquid based cytology (LBC) samples. Two temperatures for long term storage were assessed; 80°C and −25°C. The utility of Raman spectroscopy for the detection of CIN was compared for fresh LBC samples and biobanked LBC samples. Two groups of samples were used for the study with one group associated with disease (CIN 3) and the other associated with no disease (cytology negative). The data indicates that samples stored at −80°C are not suitable for assessment by Raman spectroscopy due to a lack of cellular material and the presence of cellular debris. However, the technology can be applied to fresh LBC samples and those stored at −25°C and is, moreover, effective in the discrimination of negative samples from those where CIN 3 has been confirmed. Pooled fresh and biobanked samples are also amenable to the technology and achieve a similar sensitivity and specificity for CIN 3. This study demonstrates that cervical cytology samples stored within biobanks at temperatures that preclude cell lysis can act as a useful resource for Raman spectroscopy and will facilitate research and translational studies in this area.
Enhancement of Aqueous Solubility and Dissolution of Celecoxib through Phosphatidylcholine-Based Dispersion Systems Solidified with Adsorbent Carriers

This study aimed to design phosphatidylcholine (PC)-based solid dispersion (SD) systems for enhancing the apparent aqueous solubility and dissolution of celecoxib (CLC), a selective cyclooxygenase-2 inhibitor with a highly hydrophobic property. Although PC-based dispersion formulations considerably increased solubilities of CLC, the lipidic texture of PC was not appropriate as a solid dosage form for oral administration of CLC. To mask the lipidic texture of PC-based matrices, Neusilin® US2, an adsorbent material with a porous structure and large surface area widely used in the pharmaceutical industry, was employed and thereby fully powderized PC-based dispersion formulations could be fabricated. However, PC matrices containing CLC strongly adsorbed to the pores of Neusilin® US2 was not able to be rapidly released. To address this problem, different hydrophilic materials were examined to promote the release of the CLC-dispersed PC matrices from Neusilin® US2. Among tested hydrophilic materials, croscarmellose sodium was the most suitable to facilitate fast drug dissolution from Neusilin® US2 particles, showing significantly enhanced apparent aqueous solubility and dissolution behavior of CLC. Through differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR) analysis, a considerably reduced crystallinity of CLC dispersed in the PC-based dispersion formulations was demonstrated. The PC-based SD formulations developed in this study would be useful for improving the oral bioavailability of poorly soluble drugs such as CLC.
ASPECTS OF CANCER REHABILITATION: AN AUSTRIAN PERSPECTIVE Resistance exercise and breast cancer related lymphedema – a systematic review update

Background: Purpose of this systematic review update was analyzing resistance exercise (RE) intervention trials in breast cancer survivors (BCS) regarding their effect on breast cancer-related lymphedema (BCRL) status. Articles published until 31 September 2017 were included. Methods: A systematic literature search was conducted utilizing PubMed, MEDLINE, and EMBASE databases. Included articles were analyzed regarding their level of evidence and their methodological quality using the Cochrane risk of bias tool. Results: Altogether, 23 articles could be included of which 16 were independent RE intervention studies and seven additional articles. Lymphedema assessment was so heterogeneous that conduction of a thorough meta-analysis regarding lymphedema status was still impossible. In all but one study, which reported a small but methodologically weak increase in arm volume, no negative effects of RE on BCRL was recorded. Conclusions: RE seems to be a safe exercise intervention for BCS and not to be harmful concerning the risk of lymphedema. Lymphedema assessment methods that allow for a qualitative analysis of arm tissue composition should be favored. IMPLICATIONS FOR REHABILITATION Breast cancer-related lymphedema affects a considerable proportion of breast cancer patients and is debilitating on the physical, functional, social, and psychological domain. At the current time breast cancer related lymphedema is incurable but well manageable by a number of physical therapy modalities, especially complete decongestive therapy (CDT). One of the encouraging treatment methods is resistance exercise. ARTICLE HISTORY Received 13 December 2017 Revised 28 May 2018 Accepted 22 June 2018
Editorial "D'un rythme à l'autre"

Les performances interessant l’ethnopoetique – rituels de la Grece ancienne, ahwash berberes, semah alevis, ou battles de hip hop anglo-saxon – sont traversees par des changements de rythme – que celui-ci soit verbal, musical ou danse. Ces variations rythmiques animent les performances et assurent leur efficacite. Mais qu’arrive-t-il lorsque le rythme change ? Quand le fait-il et pourquoi ? C’est moins le rythme en lui-meme que ses basculements qui sont interroges dans ce numero ; c’est-a-dire les moments ou « quelque chose se passe » (During, 1994) et advient, qui va tout changer, donnant a ces pratiques le statut d’evenements a proprement parler.
Giving room to subjectivity in understanding and assessing problem gambling: A patient-centered approach focused on quality of life

Background and aims Problem gambling is characterized by high stigma and self-stigma, making relevant measurement of the burden of the disorder complex. The aim of our qualitative study was to describe health-related quality of life (HRQOL) impacted by problem gambling from the patients’ perspective. Methods We conducted 6 focus groups with 25 current or lifetime at-risk problem gamblers to identify key domains of quality of life impacted by problem gambling. A content analysis from the focus groups data was conducted using Alceste© software, using descendant hierarchical classification analysis, to obtain stable classes and the significant presences of reduced forms. The class of interest, detailing the core of impacted quality of life, was described using a cluster analysis. Results Thematic content analysis identified three stable classes. Class 1 contained the interviewers’ speech. Class 3 was composed of the vocabulary related to gambling practice, games and gambling venues (casino, horse betting, etc.). Class 2 described the core of impact of gambling on quality of life and corresponded to 43% of the analyzed elementary context units. This analysis revealed seven key domains of impact of problem gambling: loneliness, financial pressure, relationships deterioration, feeling of incomprehension, preoccupation with gambling, negative emotions, and avoidance of helping relationships. Conclusions We identified, beyond objective damage, the subjective distress felt by problem gamblers over the course of the disorder and in the helping process, marked in particular by stigma and self-stigma. Four impacted HRQOL areas were new and gambling-specific: loneliness, feeling of incomprehension, avoidance of helping relationships, and preoccupation with gambling. These results support the relevance of developing, in a next step, a specific HRQOL scale in the context of gambling.