bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vitro safety and off-target profile of the anti-parasitic arylmethylaminosteroid 1o
Authors: Blum Leonard , Gul Sheraz , Ulshöfer Thomas , Henke Marina , Krieg Reimar , Berneburg Isabell , Thomas Dominique , Trautmann Sandra , Kurz Jennifer , Geyer Joachim , Geisslinger Gerd , Becker Katja , Parnham Michael J. , Schiffmann Susanne 
Published: May 2020

AbstractParasite-mediated diseases like malaria and schistosomiasis are growing health problems worldwide and novel drug candidates are urgently needed. In this study, the in-vitro safety profile of steroid compound 1o (sc1o), effective against the parasites Plasmodium falciparum and Schistosoma mansoni with an IC50 value of 5 nM, was characterized. We assessed viability/proliferation, apoptosis and cell cycle tests to determine the cytotoxic profile of sc1o in cancer cells. The mutagenic potential was determined with the AMES test. To identify off-target effects we investigated whether sc1o interacts with safety-relevant molecules such as cytochrome P450 (CYP) enzymes, phosphodiesterases (PDE), histone deacteylases (HDAC) and human ether-a-go-go related gene (hERG). Furthermore, to predict the potential bioavailability of sc1o, its effect on Caco-2 cell barrier integrity, by measurement of the transepithelial electrical resistance (TEER), was determined. Sc1o at 25 µM reduced cell viability, probably through cell-cycle arrest, but did not induce apoptosis in cancer cells. No adverse off-target effects nor mutagenic potential of sc1o were observed. Furthermore, sc1o did not disturb the integrity of the cell barrier, but exhibited low membrane permeability, apparently due to cell adherence. In conclusion, sc1o up to 10 µM showed a good in-vitro safety profile.
Insight into the structural, elastic and electronic properties of a new orthorhombic 6O-SiC polytype
Authors: El Mendili Yassine , Orberger Beate , Chateigner Daniel , Bardeau Jean-François , Gascoin Stéphanie , Petit Sébastien , Perez Olivier , Khadraoui Fouzia 
Published: May 2020

AbstractDifferent polytypes of SiC are described and predicted in literature. Here, we report the first occurrence of an orthorhombic 6O-SiC polytype as rock-forming mineral in the nickel laterite mine of Tiebaghi (New Caledonia). This new class of SiC crystallizes in the space group Cmc21 with 12 atoms per unit cell [a = 3.0778(6) Å, b = 5.335(2) Å, c = 15.1219(6) Å, α = 90°, β = 90°, γ = 120°]. The density of 6O-SiC is about 3.22 g/cm3 and the calculated indirect bandgap at room temperature of 3.56 eV is identical to 6H-SiC. Our results suggest that 6O-SiC is the intermediate state in the wurtzite to rocksalt transformation of 6H-SiC.
Alterations in seminal plasma proteomic profile in men with primary and secondary infertility
Authors: Martins Ana D. , Panner Selvam Manesh Kumar , Agarwal Ashok , Alves Marco G. , Baskaran Saradha 
Published: May 2020

AbstractProteome of seminal plasma provides profound information related to the male reproductive health. This pilot study was conducted to characterize proteomic profile of seminal plasma from men with primary, or secondary infertility and compare it with proven fertile men. Study participants (n = 59) were recruited at the Cleveland Clinic and divided according to their fertility status: proven fertile (n = 39); primary infertility (n = 11) and secondary infertility (n = 9). Proteomic shotgun analysis revealed a total of 515 peptides common to primary infertility and control group; whereas 523 peptides were common to secondary infertility and control group. Bioinformatic analysis revealed dysregulation of biological processes such as cell secretion and vesicle mediated transport in primary infertility, whereas immune system response, regulation of proteolysis and iron homeostasis were dysregulated in secondary infertility. Western blot validation showed overexpression of ANXA2 and CDC42, and underexpression of SEMG2 proteins in primary infertility; and overexpression of ANXA2 and APP proteins in secondary infertility. This study elucidates the potential role of differentially expressed proteins in the seminal plasma as diagnostic biomarker for primary and secondary infertility. Furthermore, our results suggest maturation failure and immune reaction response as the main cause of infertility in men with primary and secondary infertility, respectively. Additional validation of the proteins involved in the above pathways is warranted.
Feasibility and accuracy of a robotic guidance system for navigated spine surgery in a hybrid operating room: a cadaver study
Authors: Burström Gustav , Balicki Marcin , Patriciu Alexandru , Kyne Sean , Popovic Aleksandra , Holthuizen Ronald , Homan Robert , Skulason Halldor , Persson Oscar , Edström Erik , Elmi-Terander Adrian 
Published: May 2020

AbstractThe combination of navigation and robotics in spine surgery has the potential to accurately identify and maintain bone entry position and planned trajectory. The goal of this study was to examine the feasibility, accuracy and efficacy of a new robot-guided system for semi-automated, minimally invasive, pedicle screw placement. A custom robotic arm was integrated into a hybrid operating room (OR) equipped with an augmented reality surgical navigation system (ARSN). The robot was mounted on the OR-table and used to assist in placing Jamshidi needles in 113 pedicles in four cadavers. The ARSN system was used for planning screw paths and directing the robot. The robot arm autonomously aligned with the planned screw trajectory, and the surgeon inserted the Jamshidi needle into the pedicle. Accuracy measurements were performed on verification cone beam computed tomographies with the planned paths superimposed. To provide a clinical grading according to the Gertzbein scale, pedicle screw diameters were simulated on the placed Jamshidi needles. A technical accuracy at bone entry point of 0.48 ± 0.44 mm and 0.68 ± 0.58 mm was achieved in the axial and sagittal views, respectively. The corresponding angular errors were 0.94 ± 0.83° and 0.87 ± 0.82°. The accuracy was statistically superior (p < 0.001) to ARSN without robotic assistance. Simulated pedicle screw grading resulted in a clinical accuracy of 100%. This study demonstrates that the use of a semi-automated surgical robot for pedicle screw placement provides an accuracy well above what is clinically acceptable.
Isolation of large dense-core vesicles from bovine adrenal medulla for functional studies
Authors: Birinci Yelda , Preobraschenski Julia , Ganzella Marcelo , Jahn Reinhard , Park Yongsoo 
Published: May 2020

AbstractLarge dense-core vesicles (LDCVs) contain a variety of neurotransmitters, proteins, and hormones such as biogenic amines and peptides, together with microRNAs (miRNAs). Isolation of LDCVs is essential for functional studies including vesicle fusion, vesicle acidification, monoamine transport, and the miRNAs stored in LDCVs. Although several methods were reported for purifying LDCVs, the final fractions are significantly contaminated by other organelles, compromising biochemical characterization. Here we isolated LDCVs (chromaffin granules) with high yield and purity from bovine adrenal medulla. The fractionation protocol combines differential and continuous sucrose gradient centrifugation, allowing for reducing major contaminants such as mitochondria. Purified LDCVs show robust acidification by the endogenous V-ATPase and undergo SNARE-mediated fusion with artificial membranes. Interestingly, LDCVs contain specific miRNAs such as miR-375 and miR-375 is stabilized by protein complex against RNase A. This protocol can be useful in research on the biological functions of LDCVs.
The polygenic architecture of left ventricular mass mirrors the clinical epidemiology
Authors: Mosley Jonathan D. , Levinson Rebecca T. , Farber-Eger Eric , Edwards Todd L. , Hellwege Jacklyn N. , Hung Adriana M. , Giri Ayush , Shuey Megan M. , Shaffer Christian M. , Shi Mingjian , Brittain Evan L. , Chung Wendy K. , Kullo Iftikhar J. , Arruda-Olson Adelaide M. , Jarvik Gail P. , Larson Eric B. , Crosslin David R. , Williams Marc S. , Borthwick Ken M. , Hakonarson Hakon , Denny Joshua C. , Wang Thomas J. , Stein Charles M. , Roden Dan M. , Wells Quinn S. 
Published: May 2020

AbstractLeft ventricular (LV) mass is a prognostic biomarker for incident heart disease and all-cause mortality. Large-scale genome-wide association studies have identified few SNPs associated with LV mass. We hypothesized that a polygenic discovery approach using LV mass measurements made in a clinical population would identify risk factors and diseases associated with adverse LV remodeling. We developed a polygenic single nucleotide polymorphism-based predictor of LV mass in 7,601 individuals with LV mass measurements made during routine clinical care. We tested for associations between this predictor and 894 clinical diagnoses measured in 58,838 unrelated genotyped individuals. There were 29 clinical phenotypes associated with the LV mass genetic predictor at FDR q < 0.05. Genetically predicted higher LV mass was associated with modifiable cardiac risk factors, diagnoses related to organ dysfunction and conditions associated with abnormal cardiac structure including heart failure and atrial fibrillation. Secondary analyses using polygenic predictors confirmed a significant association between higher LV mass and body mass index and, in men, associations with coronary atherosclerosis and systolic blood pressure. In summary, these analyses show that LV mass-associated genetic variability associates with diagnoses of cardiac diseases and with modifiable risk factors which contribute to these diseases.
Tetranectin, a potential novel diagnostic biomarker of heart failure, is expressed within the myocardium and associates with cardiac fibrosis
Authors: McDonald Kenneth , Glezeva Nadezhda , Collier Patrick , O’Reilly James , O’Connell Eoin , Tea Isaac , Russell-Hallinan Adam , Tonry Claire , Pennington Steve , Gallagher Joe , Ledwidge Mark , Baugh John , Watson Chris J. 
Published: May 2020

AbstractHeart failure (HF) screening strategies require biomarkers to predict disease manifestation to aid HF surveillance and management programmes. The aim of this study was to validate a previous proteomics discovery programme that identified Tetranectin as a potential HF biomarker candidate based on expression level changes in asymptomatic patients at future risk for HF development. The initial study consisted of 132 patients, comprising of HF (n = 40), no-HF controls (n = 60), and cardiac surgery patients (n = 32). Serum samples were quantified for circulating levels of Tetranectin and a panel of circulating fibro-inflammatory markers. Cardiac tissue served as a resource to investigate the relationship between cardiac Tetranectin levels and fibrosis and inflammation within the myocardium. An independent cohort of 224 patients with or without HF was used to validate serum Tetranectin levels. Results show that circulating Tetranectin levels are significantly reduced in HF patients (p < 0.0001), and are associated with HF more closely than B-type natriuretic peptide (AUC = 0.97 versus 0.84, p = 0.011). Serum Tetranectin negatively correlated with circulating fibrosis markers, whereas cardiac tissue Tetranectin correlated positively with fibrotic genes and protein within the myocardium. In conclusion, we report for the first time that Tetranectin is a promising HF biomarker candidate linked with fibrotic processes within the myocardium.
Prognostic Factors of Disease Recurrence in Breast Cancer Using Quantitative and Qualitative Magnetic Resonance Imaging (MRI) Parameters
Authors: Lee Jeongmin , Kim Sung Hun , Kang Bong Joo 
Published: May 2020

AbstractThe purpose of this study was to investigate prognostic factors predicting recurrence of breast cancer, focusing on imaging factors including morphologic features, quantitative MR parameters, and clinicopathologic factors. This retrospective study was approved by our institutional review board, and the requirement to obtain informed consent was waived. A total of 267 patients with breast cancer were enrolled in this study, who underwent dynamic contrast-enhanced magnetic resonance imaging (MRI) before surgery from February 2014 to June 2016. Imaging parameters of MRI, including morphologic features, perfusion parameters, and texture analysis, were retrospectively reviewed by two expert breast radiologists. Clinicopathologic information of enrolled patients was also reviewed using medical records. Univariable and multivariable Cox proportional hazards regression analyses were used to identify factors associated with cancer recurrence. C statistics was used to discriminate low and high risk patients for disease recurrence. Using Kaplan-Meier survival analysis, disease-free survival was compared between patients who experienced recurrence and those who did not. At a median follow up of 49 months, 32 patients (12%) showed disease: six cases of ipsilateral breast or axilla recurrence, one case of contralateral breast recurrence, 24 cases of distant metastasis, and one case of both ipsilateral breast recurrence and distant metastasis. Of multiple imaging features and parameters, increased ipsilateral vascularity and higher positive skewness of texture analysis showed significant association with disease recurrence in every multivariable model regardless of tumor subtype and pathologic stage. Pathologic stage, especially if higher than stage II, showed significant association with disease recurrence and its highest hazard ratio was 3.45 [95% confidence interval (CI): 1.37–8.67, p = 0.008]. Of the multivariable models, the model including clinico-pathologic factors and both qualitative and quantitative imaging parameters showed good discrimination with a high C index value of 0.825 (95% CI: 0.755–0.896). In addition, recurrence associated factors were associated with short interval time to disease recurrence by Kaplan-Meier survival analysis. Therefore, comprehensive analysis using both clinico-pathologic factors and qualitative and quantitative imaging parameters is more effective in predicting breast cancer recurrence. Among those factors, higher pathologic stage, increased ipsilateral vascularity and higher positive skewness of texture analysis could be good predictors of breast cancer recurrence. Moreover, when these three factors are applied comprehensively, they may also be the predictors for poor survival.
Correlation between total sperm count and sperm motility and pregnancy rate in couples undergoing intrauterine insemination
Authors: Findeklee Sebastian , Radosa Julia Caroline , Radosa Marc Philipp , Hammadeh Mohamad Eid 
Published: May 2020

AbstractThe frequency and significance of sterility is increasing due to different socio-demographic factors in the industrialized countries. At the same time, the patients’ demand for more natural and less invasive fertility treatments is increasing. The most common method used in subfertility is intrauterine insemination (IUI). Retrospectively, the data from the patients were analyzed, in which at least one insemination and a maximum of eight inseminations were performed in the last five years (observation period 01.01.2014–31.12.2018) at the Women’s University Hospital Homburg. The primary endpoint was the onset of a clinical pregnancy. Clinical pregnancy was correlated with the partner’s total sperm count (sperm density in millions), sperm concentration and motility during insemination. These three parameters were evaluated according the World Health Organization (WHO) 2010 guidelines. The results of the spermiograms were correlated with clinical pregnancy outcome. The data were examined for 138 women with sterility, in which a total of 345 inseminations were performed (median 2.5 per woman, range 8 inseminations). There was no correlation found between spermiogram parameters and pregnancy probability in any of the inseminations. After 5 inseminations no further pregnancy occurred. The present study showed no correlation between the conception probability of intrauterine insemination (IUI) and the total sperm count/concentration/motility. After the sixth IUI, we no longer found conceptions in our patient collective. Therefore, data from this study indicate that intrauterine inseminations can be performed at all severity levels of oligoasthenozoospermia. However, the treatment should be limited to five attempts.
Characterization of experimental diabetic neuropathy using multicontrast magnetic resonance neurography at ultra high field strength
Authors: Schwarz Daniel , Hidmark Asa S. , Sturm Volker , Fischer Manuel , Milford David , Hausser Ingrid , Sahm Felix , Breckwoldt Michael O. , Agarwal Nitin , Kuner Rohini , Bendszus Martin , Nawroth Peter P. , Heiland Sabine , Fleming Thomas 
Published: May 2020

AbstractIn light of the limited treatment options of diabetic polyneuropathy (DPN) available, suitable animal models are essential to investigate pathophysiological mechanisms and to identify potential therapeutic targets. In vivo evaluation with current techniques, however, often provides only restricted information about disease evolution. In the study of patients with DPN, magnetic resonance neurography (MRN) has been introduced as an innovative diagnostic tool detecting characteristic lesions within peripheral nerves. We developed a novel multicontrast ultra high field MRN strategy to examine major peripheral nerve segments in diabetic mice non-invasively. It was first validated in a cross-platform approach on human nerve tissue and then applied to the popular streptozotocin(STZ)-induced mouse model of DPN. In the absence of gross morphologic alterations, a distinct MR-signature within the sciatic nerve was observed mirroring subtle changes of the nerves’ fibre composition and ultrastructure, potentially indicating early re-arrangements of DPN. Interestingly, these signal alterations differed from previously reported typical nerve lesions of patients with DPN. The capacity of our approach to non-invasively assess sciatic nerve tissue structure and function within a given mouse model provides a powerful tool for direct translational comparison to human disease hallmarks not only in diabetes but also in other peripheral neuropathic conditions.
Prenatal diagnosis and pregnancy outcomes of 1492 fetuses with congenital heart disease: role of multidisciplinary-joint consultation in prenatal diagnosis
Authors: Qiu Xiuqing , Weng Zongjie , Liu Min , Chen Xiujuan , Wu Qiumei , Ling Wen , Ma Hong , Huang Hailong , Lin Yuan 
Published: May 2020

AbstractEarly diagnosis of congenital heart disease (CHD) can improve the prognosis of neonates with CHD. We retrospectively evaluated the value of prenatal diagnosis of CHD by comparing the pregnancy outcomes. Prenatal diagnosis of CHD was established by echocardiographic evaluation of fetal heart. Amniotic fluid and/or cord blood genetic examination, pathological anatomy, casting specimen, and/or multidisciplinary-joint consultation (MDJC) were performed. A total of 1492 fetuses with CHD were diagnosed by prenatal echocardiography from 67834 pregnant women. There were 445, 236, 583, and 228 cases in groups A (simple CHD), B (simple CHD plus extra-cardiac abnormality), C (complex CHD), and D (complex CHD plus extra-cardiac abnormality), respectively. The pregnancy continuation rate in the four groups was 98.67%, 85.71%, 67.65%, and 36.84%, respectively (P < 0.001). The pregnancy termination rate for fetal CHD with extra-cardiac abnormalities was significantly higher than that for fetuses with only CHD (81.24% vs. 53.6%, P < 0.05). Prenatal genetic test revealed chromosomal abnormalities in 20.43% of fetuses with CHD. MDJC significantly decreased the pregnancy termination rate. In 88 cases, the original decision to terminate the pregnancy was changed after consultation and the pregnancy was continued. Of these, 87 cases culminated in live births; 65 of these children had better prognosis. Nine-segment sequential segment analysis method for prenatal fetal echocardiography was compared with the results of pathological anatomy, cast specimen, postoperative diagnosis, and postnatal ultrasound. The accuracy of prenatal ultrasound for diagnosis of fetal complex CHD and fetal simple CHD was 90.5–91.66% and 98.6%, respectively. Prenatal ultrasound is still the most effective method for fetal CHD diagnosis.
Associations between pattern separation and hippocampal subfield structure and function vary along the lifespan: A 7 T imaging study
Authors: Riphagen Joost M. , Schmiedek Lisa , Gronenschild Ed H. B. M. , Yassa Michael A. , Priovoulos Nikos , Sack Alexander T. , Verhey Frans R. J. , Jacobs Heidi I. L. 
Published: May 2020

AbstractPattern separation (PS) describes the process by which the brain discriminates similar stimuli from previously encoded stimuli. This fundamental process requires the intact processing by specific subfields in the hippocampus and can be examined using mnemonic discrimination tasks. Previous studies reported different patterns for younger and older individuals between mnemonic discrimination performance and hippocampal subfield activation. Here, we investigated the relationship between the lure discrimination index (LDI) and hippocampal subfield volume and activity across the adult lifespan (20–70 years old). Using ultra-high field functional and structural magnetic resonance imaging at 7 T, we found that lower DG volume and higher CA3 activation was associated with worse LDI performance in individuals (>60 years), suggesting that this higher activation may be an indication of aberrant neurodegenerative-related processes. In fact, higher activation in the CA1 and DG was associated with lower volumes in these subfields. For individuals around 40–50 years old, we observed that greater left and right DG volume, and greater activity in the CA3 was associated with lower LDI performance. Taken together, these results suggest that the relationship between memory and hippocampal subfield structure or function varies nonlinearly and possibly reciprocally with age, with midlife being a critically vulnerable period in life.
A liver-targeting Cu(i) chelator relocates Cu in hepatocytes and promotes Cu excretion in a murine model of Wilson’s disease
Authors: Monestier Marie , Pujol Anaïs M , Lamboux Aline , Cuillel Martine , Pignot-Paintrand Isabelle , Cassio Doris , Charbonnier Peggy , Um Khémary , Harel Amélie , Bohic Sylvain , Gateau Christelle , Balter Vincent , Brun Virginie , Delangle Pascale , Mintz Elisabeth 
Published: May 2020

AbstractCopper chelation is the most commonly used therapeutic strategy nowadays to treat Wilson’s disease, a genetic disorder primarily inducing a pathological accumulation of Cu in the liver. The mechanism of action of Chel2, a liver-targeting Cu(i) chelator known to promote intracellular Cu chelation, was studied in hepatic cells that reconstitute polarized epithelia with functional bile canaliculi, reminiscent of the excretion pathway in the liver. The interplay between Chel2 and Cu localization in these cells was demonstrated through confocal microscopy using a fluorescent derivative and nano X-ray fluorescence. The Cu(i) bound chelator was found in vesicles potentially excreted in the canaliculi. Moreover, injection of Chel2 either intravenously or subcutaneously to a murine model of Wilson’s disease increased excretion of Cu in the faeces, confirming in vivo biliary excretion. Therefore, Chel2 turns out to be a possible means to collect and excrete hepatic Cu in the faeces, hence restoring the physiological pathway.