bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydroxamic acid derivatives as HDAC1, HDAC6 and HDAC8 inhibitors with antiproliferative activity in cancer cell lines
Authors: Sixto-López Yudibeth , Gómez-Vidal José Antonio , de Pedro Nuria , Bello Martiniano , Rosales-Hernández Martha Cecilia , Correa-Basurto José 
Published: June 2020

AbstractHistone deacetylases (HDACs) belong to a family of enzymes that remove acetyl groups from the ɛ-amino of histone and nonhistone proteins. Additionally, HDACs participate in the genesis and development of cancer diseases as promising therapeutic targets to treat cancer. Therefore, in this work, we designed and evaluated a set of hydroxamic acid derivatives that contain a hydrophobic moiety as antiproliferative HDAC inhibitors. For the chemical structure design, in silico tools (molecular docking, molecular dynamic (MD) simulations, ADME/Tox properties were used to target Zn2+ atoms and HDAC hydrophobic cavities. The most promising compounds were assayed in different cancer cell lines, including hepatocellular carcinoma (HepG2), pancreatic cancer (MIA PaCa-2), breast cancer (MCF-7 and HCC1954), renal cancer (RCC4-VHL and RCC4-VA) and neuroblastoma (SH-SY5Y). Molecular docking and MD simulations coupled to the MMGBSA approach showed that the target compounds have affinity for HDAC1, HDAC6 and HDAC8. Of all the compounds evaluated, YSL-109 showed the best activity against hepatocellular carcinoma (HepG2 cell line, IC50 = 3.39 µM), breast cancer (MCF-7 cell line, IC50 = 3.41 µM; HCC1954 cell line, IC50 = 3.41 µM) and neuroblastoma (SH-SY5Y cell line, IC50 = 6.42 µM). In vitro inhibition assays of compound YSL-109 against the HDACs showed IC50 values of 259.439 µM for HDAC1, 0.537 nM for HDAC6 and 2.24 µM for HDAC8.
Prevalence of cervical anterior and posterior spondylolisthesis and its association with degenerative cervical myelopathy in a general population
Authors: Murakami Kimihide , Nagata Keiji , Hashizume Hiroshi , Oka Hiroyuki , Muraki Shigeyuki , Ishimoto Yuyu , Yoshida Munehito , Tanaka Sakae , Minamide Akihito , Nakagawa Yukihiro , Yoshimura Noriko , Yamada Hiroshi 
Published: June 2020

AbstractThe purpose of this study was to examine the prevalence of cervical spondylolisthesis according to age and vertebral level and its association with degenerative cervical myelopathy (DCM). This study included 959 participants (319 men and 640 women; mean age, 66.4 years) in the Wakayama Spine Study from 2008 to 2010. The outcome measures were cervical spinal canal (CSC) diameter at C5 level on plain radiographs, the degree of cervical spondylosis using the Kellgren-Lawrence (KL) grade, cervical cord compression on sagittal T2-weighted magnetic resonance imaging, and physical signs related to DCM. The prevalence of cervical anterior and posterior spondylolisthesis was investigated in men and women by age. In addition, logistic regression analysis determined the association between CSC diameter, posterior spondylolisthesis, and clinical DCM after overall adjustment for age, sex, and body mass index. The prevalence of anterior spondylolisthesis was 6.0% in men and 6.3% in women, and that of posterior spondylolisthesis was 13.2% and 8.9%, respectively. In addition, posterior spondylolisthesis prevalence increased with age in both sexes. Logistic regression analysis revealed that developmental canal stenosis (≤13 mm) and cervical posterior spondylolisthesis are independent significant predictive factors for DCM. The prevalence of degenerative cervical posterior spondylolisthesis was increasing with age and more frequent in men than in women. Narrow canal and degenerative cervical posterior spondylolisthesis on X-ray may be useful in predicting or diagnosing DCM.
Development of Label-Free Impedimetric Immunosensors for IKZF1 and IKZF3 Femtomolar Detection for Monitoring Multiple Myeloma Patients Treated with Lenalidomide
Authors: Abdulkarim Haya , Zourob Mohammed , Siaj Mohamed 
Published: June 2020

AbstractLenalidomide is an immunomodulatory drug (IMiD) used to treat multiple myeloma (MM) patients. Lenalidomide destroys MM cells by inducing ubiquitination and the consequent degradation of Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3). High expression of IKZF1 and IKZF3 in MM results in less sensitivity to lenalidomide treatment and possible cytotoxic effect. Therefore, detecting the expression of IKZF1 and IKZF3 proteins is of utmost importance in the treatment of MM. Here, we report the fabrication of a novel label-free electrochemical immunosensor for the rapid detection and quantification of IKZF1 and IKZF3 using electrochemical impedance spectroscopy (EIS). Gold electrodes were used to fabricate the immunosensors by immobilizing IKZF1 and IKZF3 specific antibodies using cysteamine and PDITC crosslinkers. The immunosensors were able to detect IKZF1 and IKZF3 protein levels with respective low detection limits of 0.68 and 0.97 pg/ml (11.8 and 16.7 fM). Furthermore, the immunosensors’ successful application in human serum and their high selectivity and sensitivity enables their possible application in other biofluids as simple point-of-care devices for monitoring multiple myeloma patients treated with lenalidomide, to prevent the drug’s cytotoxicity and minimize its side effects.
Immobilization of FGF on Poly(xylitol dodecanedioic Acid) Polymer for Tissue Regeneration
Authors: Firoozi Negar , Kang Yunqing 
Published: June 2020

AbstractFibroblast growth factor (FGF) plays a vital role in the repair and regeneration of most tissues. However, its low stability, short half-life, and rapid inactivation by enzymes in physiological conditions affect their clinical applications. Therefore, to increase the effectiveness of growth factors and to improve tissue regeneration, we developed an elastic polymeric material poly(xylitol dodecanedioic acid) (PXDDA) and loaded FGF on the PXDDA for sustained drug delivery. In this study, we used a simple dopamine coating method to load FGF on the surface of PXDDA polymeric films. The polydopamine-coated FGF-loaded PXDDA samples were then characterized using FTIR and XRD. The in vitro drug release profile of FGF from PXDDA film and cell growth behavior were measured. Results showed that the polydopamine layer coated on the surface of the PXDDA film enhanced the immobilization of FGF and controlled its sustained release. Human fibroblast cells attachment and proliferation on FGF-immobilized PXDDA films were much higher than the other groups without coatings or FGF loading. Based on our results, the surface modification procedure with immobilizing growth factors shows excellent application potential in tissue regeneration.
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) determination of cantharidin in biological specimens and application to postmortem interval estimation in cantharidin poisoning
Authors: Zhang Youyou , Liu Liang , Ren Liang 
Published: June 2020

AbstractA rapid, sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination and quantification of cantharidin in rats liver and kidney. After grinding with methanol, the supernatant was determined by LC-MS/MS using an Thermo Accucore C18 column (100 mm×2.1 mm, 2.6 μm) with a gradient elution of 0.1% formic acid and 0.1% acetonitrile, and in the subsequent analysis using selected reaction monitoring mode, three ion transitions were monitored for analyte. The limit of detection (LOD) was 0.741 ng/ml and the limit of quantitation (LOQ) was 2.471 ng/ml. Good linearity (R2 = 0.9998) was observed for the analyte over the linear range (5–400 ng/ml). The LC-MS/MS method was applied to the analysis of rats liver and kidney in different postmortem intervals (6 h, 12 h, 24 h, 48 h, 72 h and 168 h after death) after a single dose (4 mg/kg) of cantharidin administration by gavage. At 72 h after death, the cantharidin concentration in livers and kidneys were significantly higher than that in other postmortem intervals. Linear regression equations between postmortem interval and lg postmortem cantharidin concentration in rats liver and kidney were Y = 0.007455*X + 1.332(R2 = 0.863) and Y = 0.002689*X + 1.433 (R2 = 0.115) respectively. The animal experiment demonstrated LC-MS/MS method can be used to determine the postmortem cantharidin concentration in rats liver and kidney and the determination of cantharidin in the rats liver after death has potential value for postmortem interval estimation in cantharidin poisoning.
Clay minerals as a source of cadmium to estuaries
Authors: Hao Weiduo , Kashiwabara Teruhiko , Jin Rong , Takahashi Yoshio , Gingras Murray , Alessi Daniel S. , Konhauser Kurt O. 
Published: June 2020

AbstractGiven the high surface reactivity of clay minerals, it is assumed that flocculation will lead to metal accumulation in marginal marine settings. However, the degree of metal sorption to clays is impacted by solution pH and ionic strength, and it remains unknown whether riverine clays indeed serve as a metal sink once they encounter seawater where pH and ionic strength markedly increase. Here, we conducted cadmium (Cd) adsorption experiments to three types of common clay minerals – kaolinite, illite and montmorillonite. We found that 20–30% of Cd from illite and montmorillonite surfaces were desorbed when transitioning from freshwater to seawater pH and ionic strength conditions, while kaolinite showed no discernible differences. Synchrotron X-ray adsorption spectroscopy confirmed that Cd release corresponded to a change in bonding from outer- to inner-sphere complexes when clays encountered seawater pH and ionic strength conditions. If other trace nutrients (such as Cu, Zn, Co) adsorbed onto riverine clay minerals behave in a similar manner to Cd, we speculate that their desorption in marginal marine settings should exert a significant impact on the productivity of the biosphere.
Abscisic acid enriched fig extract promotes insulin sensitivity by decreasing systemic inflammation and activating LANCL2 in skeletal muscle
Authors: Leber Andrew , Hontecillas Raquel , Tubau-Juni Nuria , Zoccoli-Rodriguez Victoria , Goodpaster Bret , Bassaganya-Riera Josep 
Published: June 2020

AbstractAbscisic acid is a phytohormone found in fruits and vegetables and is endogenously produced in mammals. In humans and mice, lanthionine synthetase C-like 2 (LANCL2) has been characterized as the natural receptor for ABA. Herein, we characterize the efficacy of a fig fruit extract of ABA in promoting glycemic control. This ABA-enriched extract, at 0.125 µg ABA/kg body weight, improves glucose tolerance, insulin sensitivity and fasting blood glucose in diet-induced obesity (DIO) and db/db mouse models. In addition to decreasing systemic inflammation and providing glycemic control without increasing insulin, ABA extract modulates the metabolic activity of muscle. ABA increases expression of important glycogen synthase, glucose, fatty acid and mitochondrial metabolism genes and increases direct measures of fatty acid oxidation, glucose oxidation and metabolic flexibility in soleus muscle cells from ABA-treated mice with DIO. Glycolytic and mitochondrial ATP production were increased in ABA-treated human myotubes. Further, ABA synergized with insulin to dramatically increase the rate of glycogen synthesis. The loss of LANCL2 in skeletal muscle abrogated the effect of ABA extract in the DIO model and increased fasting blood glucose levels. This data further supports the clinical development of ABA in the treatment of pre-diabetes, type 2 diabetes and metabolic syndrome.
Effect of nitrogen (N) deposition on soil-N processes: a holistic approach
Authors: Verma Preeti , Sagar R. 
Published: June 2020

AbstractNitrogen (N) deposition is a serious environmental issue for soil fertility and human wellbeing. Studies on various terrestrial ecosystems yielded fragmented information on soil-N status (microbial biomass- and mineral-N) and dynamics (N-mineralization and -leaching) whereas the holistic view on this issue is relatively unknown. A complete understanding of soil-N status and dynamics in response to N deposition is essential for sustainable management of ecosystem structure and function as needed for human wellbeing. Therefore, we conducted an experiment in the N-limited tropical grassland to explore the question whether N-deposition weakens the soil-N status and dynamics; if yes, then what could be the optimum amount of deposited N and the related controlling mechanism? We undertook a 3-year (2013–2016) experimental N fertilization (control, 30, 60, 90, 120, and 150 kg N ha−1 year−1) study (using urea as a source of N deposition). The data from a total of 72, 1 × 1 m plots (six treatments with 12 replicates) were collected and properly analysed with statistical software. N deposition caused significant differences in the parameters of soil-N status and dynamics. The responses of microbial biomass-N, N-mineralization, and mineral-N to the N deposition were quadratic (maximum values were in N90) whereas N-leaching showed a linear response. Compared to control, N deposition (30–150 kg N) consistently enhanced (29–96%) leaching of N. As a mechanism, acidification induced aluminium toxicity, carbon to nitrogen ratio and litter decomposition governed the soil-N status and dynamics. N deposition over and above 90 kg ha−1 year−1 resulted in a negative feedback to soil N transformation and availability. Hence, N deposition below 90 kg ha−1 year−1 could be a limit for the sustainable functioning of the tropical or similar grasslands.
Validation of bifurcation DEFINITION criteria and comparison of stenting strategies in true left main bifurcation lesions
Authors: Wang Juan , Guan Changdong , Chen Jue , Dou Kefei , Tang Yida , Yang Weixian , Shi Yanpu , Hu Fenghuan , Song Lei , Yuan Jiansong , Cui Jingang , Zhang Min , Hou Shuang , Wu Yongjian , Yang Yuejin , Qiao Shubin , Xu Bo 
Published: June 2020

AbstractThere are controversies on optimal stenting strategy regarding true left main (LM) bifurcation lesions. The present study compared 1- and 2-stenting strategy for patients with true LM bifurcation lesions as differentiated by DEFINITION criteria. 928 patients with true LM bifurcation lesions (Medina 1,1,1 or 0,1,1) treated with DES were enrolled consecutively. 297 (32.0%) patients were identified as complex LM bifurcation, and 631 (68.0%) patients into simple LM bifurcation group according to DEFINTION criteria. Patients in complex vs. simple LM bifurcation group had significantly higher major adverse cardiac event (MACE, including cardiac death, myocardial infarction [MI] and ischemia-driven target vessel revascularization) rate at 30 days (7.8% vs. 4.0%, p = 0.01), 1 year (10.3% vs. 6.4%, p = 0.04), and numerically at 3 years (14.2% vs. 10.1%, p = 0.07), which was mainly driven by increased MI. Moreover, patients in the 2-stent strategy group had strong trend towards lower incidence of cardiac death in both complex LM bifurcation group (2.0% vs. 5.9%, p = 0.08) and simple LM bifurcation group (1.9% vs. 4.5%, p = 0.07). In conclusion, the complex bifurcation lesion criteria established in DEFINITION study was able to risk-stratify LM bifurcation patients. Two-stent technique yielded numerically lower 3-year cardiac mortality regardless of LM bifurcation complexity.
Machine learning analysis identifies genes differentiating triple negative breast cancers
Authors: Kothari Charu , Osseni Mazid Abiodoun , Agbo Lynda , Ouellette Geneviève , Déraspe Maxime , Laviolette François , Corbeil Jacques , Lambert Jean-Philippe , Diorio Caroline , Durocher Francine 
Published: June 2020

AbstractTriple negative breast cancer (TNBC) is one of the most aggressive form of breast cancer (BC) with the highest mortality due to high rate of relapse, resistance, and lack of an effective treatment. Various molecular approaches have been used to target TNBC but with little success. Here, using machine learning algorithms, we analyzed the available BC data from the Cancer Genome Atlas Network (TCGA) and have identified two potential genes, TBC1D9 (TBC1 domain family member 9) and MFGE8 (Milk Fat Globule-EGF Factor 8 Protein), that could successfully differentiate TNBC from non-TNBC, irrespective of their heterogeneity. TBC1D9 is under-expressed in TNBC as compared to non-TNBC patients, while MFGE8 is over-expressed. Overexpression of TBC1D9 has a better prognosis whereas overexpression of MFGE8 correlates with a poor prognosis. Protein–protein interaction analysis by affinity purification mass spectrometry (AP-MS) and proximity biotinylation (BioID) experiments identified a role for TBC1D9 in maintaining cellular integrity, whereas MFGE8 would be involved in various tumor survival processes. These promising genes could serve as biomarkers for TNBC and deserve further investigation as they have the potential to be developed as therapeutic targets for TNBC.
Isolieren wir Keime oder Patienten? Isolationsmaßnahmen unter der Lupe
Authors: Haeberle Helene A. 
Published: June 2020

ZusammenfassungIsolationsmaßnahmen zur Prävention der Übertragung multiresistenter Erreger (MRE) gehören in Anbetracht der steigenden Resistenzentwicklung auf Intensivstationen mittlerweile zur Routine. Noch wichtiger sind allerdings Basishygiene und der verantwortungsvolle Umgang mit antiinfektiven Therapien. Dieser Beitrag widmet sich den verschiedenen Präventionsmaßnahmen, die nur in Kombination effektiv und zielführend sind.
Der onkologische Patient: relevante Aspekte für die Anästhesie
Authors: Ohnesorge Johanna , Weigand Markus A. 
Published: June 2020

ZusammenfassungOnkologische Operationen stellen einen Großteil der chirurgischen Eingriffe dar. Daher ist es für die anästhesiologische Tätigkeit unabdingbar, Kenntnisse über Nebenwirkungen und spezielle Risiken onkologischer Therapiekonzepte zu erwerben. Dieser Artikel bietet eine praxisnahe Grundlage für Anästhesisten in der Betreuung onkologischer Patienten und stellt Chemo- und Immuntherapeutika und deren anästhesierelevante Nebenwirkungen vor.
Zirkulierende und disseminierte Tumorzellen beim Mammakarzinom
Authors: Banys-Paluchowski Malgorzata , Fehm Tanja , Janni Wolfgang , Solomayer Erich-Franz , Hartkopf Andreas 
Published: June 2020

ZusammenfassungDie hämatogene Dissemination vereinzelter Tumorzellen aus dem Primärtumor ist ein weitverbreitetes Phänomen bei den meisten soliden Malignomen. Beim Mammakarzinom weisen zirkulierende Tumorzellen (ZTZ) im peripheren Blut und disseminierte Tumorzellen (DTZ) im Knochenmark auf eine schlechte klinische Prognose hin, sowohl im Frühstadium als auch bei der metastasierten Erkrankung. Darüber hinaus ist der Nachweis von ZTZ/DTZ auch mit kürzeren rezidivfreien Intervallen assoziiert. Zahlreiche Studien haben gezeigt, dass sich diese Zellen hinsichtlich ihres Hormon- und HER2-Rezeptor-Status von den Tumorzellen des Primärtumors unterscheiden, und es wurde die Hypothese aufgestellt, dass einige von ihnen in Wirklichkeit Tumorstammzellen sein könnten. Vor Kurzem wurde anlässlich des 2018 San Antonio Breast Cancer-Symposiums die erste positive Studie über ZTZ-basierende Therapien vorgestellt, die zeigte, dass der Nachweis von ZTZ die Wahl der Behandlungsmethode beim metastasierten HR-positiven HER2-negativen Mammakarzinom beeinflussen kann. In diesem Übersichtsartikel stellen wir den aktuellen Stand zum Nachweis der Tumorzelldissemination vor und diskutieren die Implikationen für künftige Studien.
Monitoring Matches and Small-sided Games in Elite Young Soccer Players
Authors: Darbellay Jonas , Meylan César Marius Philippe , Malatesta Davide 
Published: June 2020

AbstractThe aim of this study was to compare the distances at various intensity in matches and small-sided games in elite-young soccer players using the metabolic power approach and running speed methods through fixed and individual speed zones. The second aim was to investigate the difference in high intensity external workload (% of total distances covered > 16 km/h or > 20 W/kg) between matches and small-sided games. Global positioning system data from 14 elite-youth players were analyzed during 13 matches and two types of small sided-games. Five intensity zones were used to compare the running distances between the metabolic power approach and the classic performance analysis. Metabolic power recorded more distances covered at high intensity than the running speed methods for every playing situations, except for the zone 5 of fixed speed (> 19 km/h) in matches (P<0.05). Smaller differences of external workload at high intensity were found when using the metabolic power approach compared to the traditional performance analysis. Our results highlight that the traditional analysis underestimates the athlete’s high intensity efforts. The metabolic power approach seems more relevant to monitor matches and training situations but also to compare matches to small-sided games in elite-young soccer players.
Wie sinnvoll ist der Einsatz von oralen Antidiabetika bei älteren Patienten?
Authors: Friedl Alexander 
Published: June 2020

ZUSAMMENFASSUNGDie Möglichkeiten einer medikamentösen Diabetestherapie sind heutzutage größer denn je. Eine breite Auswahl oraler Antidiabetika mit jeweils unterschiedlichen Eigenschaften steht zur Verfügung. Zudem stehen verschiedene Insuline und GLP-1-Analoga zur Injektion bereit. Entsprechend dieser Vielfalt gibt es oft sehr verschiedene Argumente für oder gegen ein bestimmtes Therapieprinzip. Dies trifft insbesondere auch auf ältere Menschen mit Diabetes mellitus zu, da bei diesen die jeweiligen Umstände oft sehr unterschiedlich sind. Die Auswahl einer Diabetestherapie sollte möglichst auf der Grundlage rationaler Argumente erfolgen. Im Zentrum steht dabei immer der jeweilige Mensch mit seinen individuellen Gegebenheiten. Dazu ist es wichtig, die Charakteristika der Behandlungsoptionen gut zu kennen, um so im Einzelfall die am besten geeignete Möglichkeit auswählen zu können.
Ethik in einer technisierten Medizin
Authors: Gleditsch Jochen 
Published: June 2020

SummaryDie technischen Entwicklungen in der Medizin haben die diagnostischen und therapeutischen Optionen auf vielfältige Weise erweitert und bereichert. Sie bergen allerdings die Gefahr einer Entfremdung zwischen Arzt und Patient. Dem empathischen Kontakt zwischen Arzt und Patient, am besten „hands-on“, kommt nach wie vor eine enorme Bedeutung zu. Dies zeigt sich besonders offensichtlich als Herausforderung für den Arzt im Angesicht des Todes. Ein empathischer Kontakt kann nur entstehen, wenn der Patient nicht nur rational-analytisch, sondern auch intuitiv-ganzheitlich wahrgenommen wird: mit der Öffnung für eine transzendenzoffene Sicht des Lebens im Sinne eines integralen Bewusstseins.