bluuebunny/crossref_metadata_2025_split huggingface dataset:
The prognostic relevance of urokinase-type plasminogen activator (uPA) in the blood of patients with metastatic breast cancer
Authors: Banys-Paluchowski Malgorzata , Witzel Isabell , Aktas Bahriye , Fasching Peter A. , Hartkopf Andreas , Janni Wolfgang , Kasimir-Bauer Sabine , Pantel Klaus , Schön Gerhard , Rack Brigitte , Riethdorf Sabine , Solomayer Erich-Franz , Fehm Tanja , Müller Volkmar 
Published: February 2019

AbstractIn breast cancer (BC), elevated levels of urokinase-type plasminogen activator (uPA) in tumor tissue have been confirmed as a strong prognostic factor in level-of-evidence-1 studies. The aim of the present study was to evaluate the clinical relevance of uPA levels in serum of metastatic BC patients and to compare uPA with other blood-based biomarkers. 252 patients were enrolled in this prospective, multicentre study. Blood samples were collected before begin of first-line or later-line systemic treatment. Serum uPA was quantified by a commercially available ELISA. Circulating tumor cells (CTCs) were detected using CellSearch; other biomarkers (EGFR, VEGF, HER2, RAS p21, TIMP1, CAIX) by ELISA. Using the ROC analysis, the optimal cut-off value (determined by the Youden index) of serum uPA was 2.52 ng/ml. Using this value, 26% of patients had elevated uPA levels. Patients with visceral metastasis and more than one metastatic site were significantly more likely to present with elevated uPA levels. CTC status, serum HER2, RAS p21, CAIX, TIMP1 and VEGF correlated significantly with uPA levels. Elevated uPA levels predicted shorter overall and progression-free survival in univariate analysis (median OS: 7.5 months [95%-CI 4.5–10.5 months] vs. not reached, p < 0.001; PFS: 4.8 [95%-CI: 3.1–6.5] vs. 9.1 [7.4–10.8] months, p < 0.001). In multivariate analysis, elevated uPA, presence of ≥5 CTCs, elevated RAS p21, higher grading and higher line of therapy were independent predictors of shorter OS, while elevated CTC counts, higher line of therapy and negative estrogen receptor status were independent predictors of shorter PFS. In conclusion, elevated uPA levels independently predict reduced overall survival and improved prognostication in patients with known CTC status. Whether high serum uPA might identify patients most likely to benefit from therapies targeting uPA, remains to be evaluated in future trials.
Protective effects of fermented goat milk on genomic stability, oxidative stress and inflammatory signalling in testis during anaemia recovery
Authors: Moreno-Fernandez Jorge , Alférez María J. M. , López-Aliaga Inmaculada , Diaz-Castro Javier 
Published: February 2019

AbstractOxidative stress is a harmful factor for male reproductive function, and a major cause of infertility. On the other hand, fermented goat milk has positive effects on anemia recovery and mineral metabolism. This study evaluated the effect of feeding rats with fermented milks during anaemia recovery on molecular mechanisms linked to oxidative stress and inflammatory signalling in rats reproductive system. Forty male Wistar rats were placed on a pre-experimental period of 40 days (control group, receiving normal-Fe diet and Fe-deficient group, receiving low-Fe diet). Lately, rats were fed with fermented goat or cow milk-based diets during 30 days. After feeding the fermented milks, Total antioxidant status (TAS) and non-esterified fatty acids (NEFA) increased and 8-hydroxy-2’-deoxyguanosine (8-OHdG), 15-F2t-isoprostanes and thiobarbituric acid reactive substances (TBARS) decreased in testis. DNA oxidative damage in testis germ cells was lower with fermented goat milk. Fermented goat milk reduced IL-6 and TNF-α in control animals, increasing INF-γ in control and anaemic rats. NRF2 and PGC-1α protein levels increased in testis after fermented goat milk consumption in control and anaemic rats. Fermented goat milk also increased TAS and decreased oxidative damage, protecting the main testis cell bioconstituents (lipids, proteins, DNA, prostaglandins) from oxidative damage and reduced inflammatory activity, preventing injuries to testis germinal epithelium. Fermented goat milk enhanced lipolysis, fatty acids degradation and immune response, attenuating inflammatory signalling, representing a positive growth advantage for testicular cells.
Influence of rewetting on microbial communities involved in nitrification and denitrification in a grassland soil after a prolonged drought period
Authors: Hammerl Verena , Kastl Eva-Maria , Schloter Michael , Kublik Susanne , Schmidt Holger , Welzl Gerhard , Jentsch Anke , Beierkuhnlein Carl , Gschwendtner Silvia 
Published: February 2019

AbstractThe frequency of extreme drought and heavy rain events during the vegetation period will increase in Central Europe according to future climate change scenarios, which will affect the functioning of terrestrial ecosystems in multiple ways. In this study, we simulated an extreme drought event (40 days) at two different vegetation periods (spring and summer) to investigate season-related effects of drought and subsequent rewetting on nitrifiers and denitrifiers in a grassland soil. Abundance of the microbial groups of interest was assessed by quantification of functional genes (amoA, nirS/nirK and nosZ) via quantitative real-time PCR. Additionally, the diversity of ammonia-oxidizing archaea was determined based on fingerprinting of the archaeal amoA gene. Overall, the different time points of simulated drought and rewetting strongly influenced the obtained response pattern of microbial communities involved in N turnover as well as soil ammonium and nitrate dynamics. In spring, gene abundance of nirS was irreversible reduced after drought whereas nirK and nosZ remained unaffected. Furthermore, community composition of ammonia-oxidizing archaea was altered by subsequent rewetting although amoA gene abundance remained constant. In contrast, no drought/rewetting effects on functional gene abundance or diversity pattern of nitrifying archaea were observed in summer. Our results showed (I) high seasonal dependency of microbial community responses to extreme events, indicating a strong influence of plant-derived factors like vegetation stage and plant community composition and consequently close plant-microbe interactions and (II) remarkable resistance and/or resilience of functional microbial groups involved in nitrogen cycling to extreme weather events what might indicate that microbes in a silty soil are better adapted to stress situations as expected.
Metabolomics reveals citric acid secretion in mechanically–stimulated osteocytes is inhibited by high glucose
Authors: Villaseñor Alma , Aedo-Martín Daniel , Obeso David , Erjavec Igor , Rodríguez-Coira Juan , Buendía Irene , Ardura Juan Antonio , Barbas Coral , Gortazar Arancha R. 
Published: February 2019

AbstractOsteocytes are the main cells of bone tissue and play a crucial role in bone formation and resorption. Recent studies have indicated that Diabetes Mellitus (DM) affects bone mass and potentially causes higher bone fracture risk. Previous work on osteocyte cell cultures has demonstrated that mechanotransduction is impaired after culture under diabetic pre-conditioning with high glucose (HG), specifically osteoclast recruitment and differentiation. The aim of this study was to analyze the extracellular metabolic changes of osteocytes regarding two conditions: pre-conditioning to either basal levels of glucose (B), mannitol (M) or HG cell media, and mechanical stimulation by fluid flow (FF) in contrast to static condition (SC). Secretomes were analyzed using Liquid Chromatography and Capillary Electrophoresis both coupled to Mass Spectrometry (LC-MS and CE-MS, respectively). Results showed the osteocyte profile was very similar under SC, regardless of their pre-conditioning treatment, while, after FF stimulation, secretomes followed different metabolic signatures depending on the pre-conditioning treatment. An important increment of citrate pointed out that osteocytes release citrate outside of the cell to induce osteoblast activation, while HG environment impaired FF effect. This study demonstrates for the first time that osteocytes increase citrate excretion under mechanical stimulation, and that HG environment impaired this effect.
Hyperosmotic stress induces cell-dependent aggregation of α-synuclein
Authors: Fragniere Alexandra M. C. , Stott Simon R. W. , Fazal Shaline V. , Andreasen Maria , Scott Kirsten , Barker Roger A. 
Published: February 2019

AbstractThe aggregation of alpha-synuclein (α-syn) is a pathological feature of a number of neurodegenerative conditions, including Parkinson’s disease. Genetic mutations, abnormal protein synthesis, environmental stress, and aging have all been implicated as causative factors in this process. The importance of water in the polymerisation of monomers, however, has largely been overlooked. In the present study, we highlight the role of hyperosmotic stress in inducing human α-syn to aggregate in cells in vitro, through rapid treatment of the cells with three different osmolytes: sugar, salt and alcohol. This effect is cell-dependent and not due to direct protein-osmolyte interaction, and is specific for α-syn when compared to other neurodegeneration-related proteins, such as Tau or Huntingtin. This new property of α-syn not only highlights a unique aspect of its behaviour which may have some relevance for disease states, but may also be useful as a screening test for compounds to inhibit the aggregation of α-syn in vitro.
Radiation Pneumonitis after Intensity-Modulated Radiotherapy for Esophageal Cancer: Institutional Data and a Systematic Review
Authors: Tonison J. J. , Fischer S. G. , Viehrig M. , Welz S. , Boeke S. , Zwirner K. , Klumpp B. , Braun L. H. , Zips D. , Gani C. 
Published: February 2019

AbstractRadiation pneumonitis (RP) is a serious complication that can occur after thoracic radiotherapy. The goal of this study is to investigate the incidence of RP after radiochemotherapy with intensity modulated radiotherapy (IMRT) in patients with esophageal cancer and correlate this with dose volume histogram (DVH) related parameters. For this purpose, the clinical course of 73 patients was evaluated and irradiation doses to the lungs were extracted from radiotherapy treatment plans. Furthermore, a systematic review on this topic was conducted across PubMed. In our institutional cohort, Common Terminology Criteria for Adverse Events (CTCAE) grade II or higher RP occurred in four patients (5.5%). The systematic review identified 493 titles of which 19 studies reporting 874 patients qualified for the final analysis. No grade IV or V RP after radiochemotherapy with IMRT for esophageal cancer was reported in the screened literature. Grade II or higher RP is reported in 6.6% of the patients. A higher incidence can be seen with increasing values for lung V20. In conclusion, our institutional data and the literature consistently show a low incidence of symptomatic RP after radiochemotherapy in patients with esophageal cancer treated with IMRT. However, efforts should be made to keep the lung V20 below 23% and specific caution is warranted in patients with pre-existing lung conditions.
To jump or not to jump - The Bereitschaftspotential required to jump into 192-meter abyss
Authors: Nann M. , Cohen L. G. , Deecke L. , Soekadar S. R. 
Published: February 2019

AbstractSelf-initiated voluntary acts, such as pressing a button, are preceded by a surface-negative electrical brain potential, the Bereitschaftspotential (BP), that can be recorded over the human scalp using electroencephalography (EEG). While the BP’s early component (BP1, generated in the supplementary and cingulate motor area) was linked to motivational, intentional and timing properties, the BP’s late component (BP2, generated in the primary motor cortex) was found to be linked to motor execution and performance. Up to now, the BP required to initiate voluntary acts has only been recorded under well-controlled laboratory conditions, and it was unknown whether possible life-threatening decision making, e.g. required to jump into a 192-meter abyss, would impact this form of brain activity. Here we document for the first time pre-movement brain activity preceding 192-meter bungee jumping. We found that the BP’s spatiotemporal dynamics reflected by BP1 and BP2 are comparable before 192-meter bungee jumping and jumping from 1-meter. These results, possible through recent advancements in wireless and portable EEG technology, suggest that possible life-threatening decision-making has no impact on the BP’s spatiotemporal dynamics.
RETRACTED ARTICLE: Optical rectification and absorption coefficients studied by a short-range topless exponential potential well with inverse square root
Authors: Yu Qiucheng , Guo Kangxian , Hu Meilin 
Published: February 2019

AbstractA topless potential energy with inverse square root is introduced to solve the energy spectrum equations and the bound state wave functions of the static Schrödinger equation by coordinate variation and combining the extraordinary coefficients of the confluent hypergeometric functions. Furthermore, the model of optical rectification (OR) and absorption coefficients (AC) with this special potential energy V(x) will appear regular changes. In this work, we explore the specific characteristics of the OR and AC with the inverse square root potential through multiple factors such as energy intervals and matrix elements.
Identification of MRP2 as a targetable factor limiting oxaliplatin accumulation and response in gastrointestinal cancer
Authors: Myint Khine , Biswas Riya , Li Yan , Jong Nancy , Jamieson Stephen , Liu Johnson , Han Catherine , Squire Christopher , Merien Fabrice , Lu Jun , Nakanishi Takeo , Tamai Ikumi , McKeage Mark 
Published: February 2019

AbstractOxaliplatin is important for the clinical treatment of colorectal cancer and other gastrointestinal malignancies, but tumour resistance is limiting. Several oxaliplatin transporters were previously identified but their relative contributions to determining oxaliplatin tumour responses and gastrointestinal tumour cell sensitivity to oxaliplatin remains unclear. We studied clinical associations between tumour expression of oxaliplatin transporter candidate genes and patient response to oxaliplatin, then experimentally verified associations found with MRP2 in models of human gastrointestinal cancer. Among 18 oxaliplatin transporter candidate genes, MRP2 was the only one to be differentially expressed in the tumours of colorectal cancer patients who did or did not respond to FOLFOX chemotherapy. Over-expression of MRP2 (endogenously in HepG2 and PANC-1 cells, or induced by stable transfection of HEK293 cells) decreased oxaliplatin accumulation and cytotoxicity but those deficits were reversed by inhibition of MRP2 with myricetin or siRNA knockdown. Mice bearing subcutaneous HepG2 tumour xenografts were sensitised to oxaliplatin antitumour activity by concurrent myricetin treatment with little or no increase in toxicity. In conclusion, MRP2 limits oxaliplatin accumulation and response in human gastrointestinal cancer. Screening tumour MRP2 expression levels, to select patients for treatment with oxaliplatin-based chemotherapy alone or in combination with a MRP2 inhibitor, could improve treatment outcomes.
Langmuir films at the oil/water interface revisited
Authors: Mottola Milagro , Caruso Benjamín , Perillo Maria A. 
Published: February 2019

AbstractWe studied monomolecular layers at the oil/water interface (O/Wint) in a Langmuir interfacial trough using egg-yolk phosphatidylcholine (EPC) (the model phospholipid) and Vaseline (VAS) as oil phase. The temporal dynamics in the surface pressure (π) evolution depended on the method (spreading/adsorption) used for monolayers preparation and reflected the different distribution of EPC between all the system compartments (bulk phases and interfaces). We distinguished between EPC located either stable at the interface or hopping between the interface and bulk phases. The size order of the apparent mean molecular area, at constant π, of EPC at different interfaces (EPCO/W > EPC/VAS0.02;A/W > EPCA/W), suggested that VAS molecules intercalated between the hydrocarbon chains of EPCO/W, at a molar fraction xVAS > 0.02. However, EPC/VAS0.02;A/W showed the highest compressional free energy. This leaded us to study the EPC/VAS0.02 mixture at A/W by Brewster Angle Microscopy (BAM), finding that upon compression VAS segregated over the monolayer, forming non-coalescent lenses (as predicted by the spreading coefficient S = −13 mN/m) that remained after decompression and whose height changed (increase/decrease) accompanied the compression/decompression cycle. At the O/Wint, while some VAS molecules remained at the interface up to the collapse, others squeezed out towards the VAS bulk phase with an energy requirement lower than towards the air.
Rho-kinase inhibitor coupled to peptide-modified albumin carrier reduces portal pressure and increases renal perfusion in cirrhotic rats
Authors: Klein Sabine , Frohn Franziska , Magdaleno Fernando , Reker-Smit Catharina , Schierwagen Robert , Schierwagen Irela , Uschner Frank Erhard , van Dijk Fransien , Fürst Dieter O. , Djudjaj Sonja , Boor Peter , Poelstra Klaas , Beljaars Leonie , Trebicka Jonel 
Published: February 2019

AbstractRho-kinase (ROCK) activation in hepatic stellate cells (HSC) is a key mechanism promoting liver fibrosis and portal hypertension (PTH). Specific delivery of ROCK-inhibitor Y-27632 (Y27) to HSC targeting mannose-6-phosphate-receptors reduces portal pressure and fibrogenesis. In decompensated cirrhosis, presence of ascites is associated with reduced renal perfusion. Since in cirrhosis, platelet-derived growth factor receptor beta (PDGFRβ) is upregulated in the liver as well as the kidney, this study coupled Y27 to human serum albumin (HSA) substituted with PDGFRβ-recognizing peptides (pPB), and investigated its effect on PTH in cirrhotic rats. In vitro collagen contraction assays tested biological activity on LX2 cells. Hemodynamics were analyzed in BDL and CCl4 cirrhotic rats 3 h, 6 h and 24 h after i.v. administration of Y27pPBHSA (0.5/1 mg/kg b.w). Phosphorylation of moesin and myosin light chain (MLC) assessed ROCK activity in liver, femoral muscle, mesenteric artery, kidney and heart. Three Y27 molecules were coupled to pPBHSA as confirmed by HPLC/MS, which was sufficient to relax LX2 cells. In vivo, Y27pPBHSA-treated rats exhibited lower portal pressure, hepatic vascular resistance without effect on systemic vascular resistance, but a tendency towards lower cardiac output compared to non-treated cirrhotic rats. Y27pPBHSA reduced intrahepatic resistance by reduction of phosphorylation of moesin and MLC in Y27pPBHSA-treated cirrhotic rats. Y27pPBHSA was found in the liver of rats up to 6 hours after its injection, in the HSC demonstrated by double-immunostainings. Interestingly, Y27pPBHSA increased renal arterial flow over time combined with an antifibrotic effect as shown by decreased renal acta2 and col1a1 mRNA expression. Therefore, targeting the ROCK inhibitor Y27 to PDGFRβ decreases portal pressure with potential beneficial effects in the kidney. This unique approach should be tested in human cirrhosis.
Both cold and sub-zero acclimation induce cell wall modification and changes in the extracellular proteome in Arabidopsis thaliana
Authors: Takahashi Daisuke , Gorka Michal , Erban Alexander , Graf Alexander , Kopka Joachim , Zuther Ellen , Hincha Dirk K. 
Published: February 2019

AbstractCold acclimation (CA) leads to increased plant freezing tolerance during exposure to low, non-freezing temperatures as a result of many physiological, biochemical and molecular changes that have been extensively investigated. In addition, many plant species, such asArabidopsis thaliana, respond to a subsequent exposure to mild, non-damaging freezing temperatures with an additional increase in freezing tolerance referred to as sub-zero acclimation (SZA). There is comparatively little information available about the molecular basis of SZA. However, previous transcriptomic studies indicated that cell wall modification may play an important role during SZA. Here we show that CA and SZA are accompanied by extensive changes in cell wall amount, composition and structure. While CA leads to a significant increase in cell wall amount, the relative proportions of pectin, hemicellulose and cellulose remained unaltered during both CA and SZA. However, both treatments resulted in more subtle changes in structure as determined by infrared spectroscopy and monosaccharide composition as determined by gas chromatography-mass spectrometry. These differences could be related through a proteomic approach to the accumulation of cell wall modifying enzymes such as pectin methylesterases, pectin methylesterase inhibitors and xyloglucan endotransglucosylases/hydrolases in the extracellular matrix.
Aplysinopsin-type and Bromotyrosine-derived Alkaloids from the South China Sea Sponge Fascaplysinopsis reticulata
Authors: Wang Qi , Tang Xu-Li , Luo Xiang-Chao , de Voog Nicole J. , Li Ping-Lin , Li Guo-Qiang 
Published: February 2019

AbstractSeven pairs of new oxygenated aplysinopsin-type enantiomers, (+)- and (−)-oxoaplysinopsins A‒G (1‒7), two new bromotyrosine-derived alkaloids, subereamollines C and D (18 and 19), together with ten known compounds (8‒17) were isolated from the Xisha Islands sponge Fascaplysinopsis reticulata. The planar structures were determined by extensive NMR and MS spectroscopic data. Each of the optically pure enantiomers was achieved by chiral HPLC separation. The absolute configurations were assigned by the quantum chemical calculation methods. Compound 19 showed cytotoxicity against Jurkat cell lines with IC50 value of 0.88 μM. Compounds 2, 16 and 17 showed tyrosine phosphatase 1B (PTP1B) inhibition activity with IC50 value ranging from 7.67 to 26.5 μM, stronger than the positive control of acarbose and 1-deoxynojirimycin. A structural activity relationship for the aplysinopsin-type enantiomers were observed in PTP1B inhibition activity of 2 and cytotoxicity of 3 that the dextrorotary (+)-2 and (+)-3 showed stronger activity than the levorotary (−)-2 and (−)-3.
Compressing the lumbar nerve root changes the frequency-associated cerebral amplitude of fluctuations in patients with low back/leg pain
Authors: Zhou Fuqing , Zhao Yanlin , Zhu Li , Jiang Jian , Huang Muhua , Zhang Yong , Zhuang Ying , Gong Honghan 
Published: February 2019

AbstractUnderstanding the central mechanisms responsible for lumbar nerve root compression may facilitate the development of new therapeutic strategies. In this study, our aim was to investigate the amplitude of fluctuations (AF) in five specific frequency bands and the full-frequency band realm to provide novel insight into the rhythm of the neuronal activity of low back/leg pain (LBLP) patients (n = 25). Compared with healthy controls, LBLP patients exhibited a significantly altered AF in multiple brain regions, including the right or left middle and inferior temporal gyri, bilateral precuneus, right anterior insula/frontal operculum, right or left inferior parietal lobule/postcentral gyrus, and other locations at five specific frequencies (P < 0.01, with Gaussian random field theory correction). Trends of an increase and a decrease in the AF in pain- and sensory-related regions, respectively, were also observed from low to high frequencies (Bonferroni-corrected α level of P < 0.05/84). In addition, in the bilateral rectal gyrus, a significant association was identified between the AF in the five specific frequency bands and disease status (P < 0.05). These findings suggest that in LBLP patients, intrinsic functional plasticity related to low back pain, leg pain and numbness affects the AF of the pain matrix and sensory-processing regions in both low- and high-frequency bands.