bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ki-67 assessment in early breast cancer: SAKK28/12 validation study on the IBCSG VIII and IBCSG IX cohort
Authors: Varga Zsuzsanna , Li Qiyu , Jochum Wolfram , Perriard Ulrike , Rau Tilman , Tille Jean-Christoph , Hawle Hanne , Klingbiel Dirk , Thuerlimann Beat , Ruhstaller Thomas 
Published: September 2019

AbstractThe assessment of Ki-67 in early-stage breast cancer has become an important diagnostic tool in planning adjuvant therapy, particularly for the administration of additional chemotherapy to hormone-responsive patients. An accurate determination of the Ki-67 index is of the utmost importance; however, the reproducibility is currently unsatisfactory. In this study, we addressed the predictive/prognostic value of Ki-67 index assessed by using the most reproducible methods, which were identified in the pilot phase. Paraffin blocks obtained from patients with moderately differentiated, estrogen receptor (ER)-positive early-stage breast cancer in Switzerland, who were originally randomized to the treatment arms with and without chemotherapy in the IBCSG VIII-IX trials, were retrieved. Of these 344 randomized patients, we identified 158 patients (82 treated with and 76 treated without chemotherapy) for whom sufficient tumour tissue was available. The presence of Ki-67 was assessed visually by counting 2000 cells at the periphery (A) and estimating the number of positive cells in five different peripheral regions (C), which was determined to be the most reproducible method identified the pilot phase. The prognostic and predictive value was assessed by calculating the breast cancer-free interval (BCFI) and overall survival (OS) rate. Ki-67 was considered a numerical and categorical variable when different cut-off values were used (10%, 14%, 20% and 30%). An mRNA-based subtyping by using the MammaTyper kit with the application of a 20% Ki-67 immunohistochemistry (IHC) cut-off equivalent was also performed. 158 of 344 randomized patients could be included in the Ki-67 analysis. The mean Ki-67 values obtained by using the two methods differed (A: 21.32% and C: 16.07%). Ki-67 assessed by using method A with a cut-off of 10% was a predictive marker for OS, as the hazard ratio (>10% vs. <=10%) in patients with chemotherapy was 0.48 with a 95% confidence interval of [0.19–1.19]. Further, the HR of patients treated without chemotherapy was 3.72 with a 95% confidence interval of [1.16–11.96] (pinteraction=0.007). Higher Ki-67 index was not associated with outcome and using the 10% Ki-67 cut-off there was an opposite association for patients with and without chemotherapy. Ki-67 assessments with IHC significantly correlated with MammaTyper results (p=0.002). The exact counting method (A) performed via a light-microscope revealed the predictive value of Ki-67 assessment with a 10% cut-off value. Further analyses employing image analyses and/or mRNA-based-assessments in larger populations are warranted.
Process development for scale-up production of a therapeutic L-asparaginase by Streptomyces brollosae NEAE-115 from shake flasks to bioreactor
Authors: El-Naggar Noura El-Ahmady , Moawad Hassan , El-Shweihy Nancy M. , El-Ewasy Sara M. , Elsehemy Islam A. , Abdelwahed Nayera A. M. 
Published: September 2019

AbstractL-asparaginase is a promising enzyme that has a wide range of significant applications including cancer therapy and starchy food industries. The statistical design of Plackett–Burman and face centered central composite design were employed to optimize L-asparaginase production by Streptomyces brollosae NEAE-115. As a result, a medium of the following formula is the optimum for producing L-asparaginase in the culture filtrate of Streptomyces brollosae NEAE-115: Dextrose 2 g, starch 20 g, L-asparagine 10 g, KNO3 1 g, K2HPO4 1 g, MgSO4.7H2O 0.5 g, NaCl 0.1 g, pH 7, fermentation period 7 days, temperature 30 °C, inoculum size 4%, v/v, agitation speed 150 rpm and inoculum age 48 h. The kinetics of cell growth, carbohydrates consumption and L- asparaginase production were studied in 7-L stirred tank bioreactor under different cultivation conditions. A significant increase in both cell growth and carbohydrate consumption was observed as the stirring speed increased from 200 to 600 rpm under uncontrolled pH. The highest L- asparaginase activity of 108.46 U/mL was obtained after 96 h at 400 rpm. On the other hand, the specific enzyme production (Yp/x) under uncontrolled pH reached its maximal value of about 20.3 U/mg cells. Further improvement of enzyme production was attained by controlling pH at 7 using the selected stirring speed of 400 rpm. Enzyme production of 162.11 U/mL obtained from the controlled pH cultures exceeded this value gained from uncontrolled pH (108.46 U/mL) by about 50%.
Calcium chloride and 1-methylcyclopropene treatments delay postharvest and reduce decay of New Queen melon
Authors: Zhang Qiang , Dai Wenting , Jin Xinwen , Li Jixin 
Published: September 2019

AbstractIn this study, newly harvested New Queen melons were treated with calcium chloride (CaCl2) and 1-methylcyclopropene (1-MCP) alone or in combination before storage. The results showed that the respiration rate, ethylene release, the activity and gene expression of pectinases such as polygalacturonase (PG), pectin methylesterase (PME) and pectate lyase (PL) in New Queen melons were dramatically decreased by treatments with 0.18 mol/L CaCl2 and/or 1 μL/L 1-MCP. Meanwhile, the climacteric behavior and flesh hardness reduction were inhibited. We also found that softer melon flesh was more conducive to the growth and reproduction of decay-causing microorganisms according to their growth curves in melons that were different in flesh hardness, suggesting inhibiting fruit softening can slow down the growth of microorganisms in fruit flesh, and thus reduce fruit decay rate. The combined use of CaCl2 and 1-MCP was more effective in suppressing respiration rate, ethylene release and protopectin hydrolysis, which could greatly delay the softening, reduce the decay rate, and extend the shelf life of New Queen melons.
The interactome of 2-Cys peroxiredoxins in Plasmodium falciparum
Authors: Brandstaedter Christina , Delahunty Claire , Schipper Susanne , Rahlfs Stefan , Yates John R. , Becker Katja 
Published: September 2019

AbstractPeroxiredoxins (Prxs) are crucially involved in maintaining intracellular H2O2 homeostasis via their peroxidase activity. However, more recently, this class of proteins was found to also transmit oxidizing equivalents to selected downstream proteins, which suggests an important function of Prxs in the regulation of cellular protein redox relays. Using a pull-down assay based on mixed disulfide fishing, we characterized the thiol-dependent interactome of cytosolic Prx1a and mitochondrial Prx1m from the apicomplexan malaria parasite Plasmodium falciparum (Pf). Here, 127 cytosolic and 20 mitochondrial proteins that are components of essential cellular processes were found to interact with PfPrx1a and PfPrx1m, respectively. Notably, our data obtained with active-site mutants suggests that reducing equivalents might also be transferred from Prxs to target proteins. Initial functional analyses indicated that the interaction with Prx can strongly impact the activity of target proteins. The results provide initial insights into the interactome of Prxs at the level of a eukaryotic whole cell proteome. Furthermore, they contribute to our understanding of redox regulatory principles and thiol-dependent redox relays of Prxs in subcellular compartments.
Genome-wide analysis of Corsican population reveals a close affinity with Northern and Central Italy
Authors: Tamm Erika , Di Cristofaro Julie , Mazières Stéphane , Pennarun Erwan , Kushniarevich Alena , Raveane Alessandro , Semino Ornella , Chiaroni Jacques , Pereira Luisa , Metspalu Mait , Montinaro Francesco 
Published: September 2019

AbstractDespite being the fourth largest island in the Mediterranean basin, the genetic variation of Corsica has not been explored as exhaustively as Sardinia, which is situated only 11 km South. However, it is likely that the populations of the two islands shared, at least in part, similar demographic histories. Moreover, the relative small size of the Corsica may have caused genetic isolation, which, in turn, might be relevant under medical and translational perspectives. Here we analysed genome wide data of 16 Corsicans, and integrated with newly (33 individuals) and previously generated samples from West Eurasia and North Africa. Allele frequency, haplotype-based, and ancient genome analyses suggest that although Sardinia and Corsica may have witnessed similar isolation and migration events, the latter is genetically closer to populations from continental Europe, such as Northern and Central Italians.
Brain atrophy and patch-based grading in individuals from the CIMA-Q study: a progressive continuum from subjective cognitive decline to AD
Authors: Marcotte Christine , Potvin Olivier , Collins D. Louis , Rheault Sylvie , Duchesne Simon 
Published: September 2019

AbstractIt has been proposed that individuals developing Alzheimer’s disease (AD) first experience a phase expressing subjective complaints of cognitive decline (SCD) without objective cognitive impairment. Using magnetic resonance imaging (MRI), our objective was to verify whether SNIPE probability grading, a new MRI analysis technique, would distinguish between clinical dementia stage of AD: Cognitively healthy controls without complaint (CH), SCD, mild cognitive impairment, and AD. SNIPE score in the hippocampus and entorhinal cortex was applied to anatomical T1-weighted MRI of 143 participants from the Consortium pour l’identification précoce de la maladie Alzheimer - Québec (CIMA-Q) study and compared to standard atrophy measures (volumes and cortical thicknesses). Compared to standard atrophy measures, SNIPE score appeared more sensitive to differentiate clinical AD since differences between groups reached a higher level of significance and larger effect sizes. However, no significant difference was observed between SCD and CH groups. Combining both types of measures did not improve between-group differences. Further studies using a combination of biomarkers beyond anatomical MRI might be needed to identify individuals with SCD who are on the beginning of the clinical continuum of AD.
Interactions between Kuroshio Extension and Central Tropical Pacific lead to preferred decadal-timescale oscillations in Pacific climate
Authors: Joh Youngji , Di Lorenzo Emanuele 
Published: September 2019

AbstractThe Kuroshio Extension (KE) exhibits prominent decadal fluctuations that enhance the low-frequency variability of North Pacific climate. Using available observations, we show evidence that a preferred decadal timescale in the KE emerges from the interaction between KE and the central tropical Pacific via Meridional Modes. Specifically, we show that changes in the KE states apply a persistent downstream atmospheric response (e.g. wind stress curl, 0–12 months timescales) that projects on the atmospheric forcing of the Pacific Meridional Modes (PMM) over 9 months timescales. Subsequently, the PMM energizes the central tropical Pacific El Niño Southern Oscillation (CP-ENSO) and its atmospheric teleconnections back to the Northern Hemisphere (1–3 months timescale), which in turn excites oceanic Rossby waves in the central/eastern North Pacific that propagate westward changing the KE (~3 years timescales). Consistent with this hypothesis, the cross-correlation function between the KE and the PMM/CP-ENSO indices exhibits a significant sinusoidal shape corresponding to a preferred spectral power at decadal timescales (~10 years). This dynamics pathway (KE→PMM/CP-ENSO→KE) may provide a new mechanistic basis to explain the preferred decadal-timescale of the North Pacific and enhance decadal predictability of Pacific climate.
Elucidating the putative link between prefrontal neurotransmission, functional connectivity, and affective symptoms in irritable bowel syndrome
Authors: Icenhour Adriane , Tapper Sofie , Bednarska Olga , Witt Suzanne T. , Tisell Anders , Lundberg Peter , Elsenbruch Sigrid , Walter Susanna 
Published: September 2019

AbstractAltered neural mechanisms are well-acknowledged in irritable bowel syndrome (IBS), a disorder of brain-gut-communication highly comorbid with anxiety and depression. As a key hub in corticolimbic inhibition, medial prefrontal cortex (mPFC) may be involved in disturbed emotion regulation in IBS. However, aberrant mPFC excitatory and inhibitory neurotransmission potentially contributing to psychological symptoms in IBS remains unknown. Using quantitative magnetic resonance spectroscopy (qMRS), we compared mPFC glutamate + glutamine (Glx) and γ-aminobutyric acid (GABA+) concentrations in 64 women with IBS and 32 age-matched healthy women (HCs) and investigated their association with anxiety and depression in correlational and subgroup analyses. Applying functional magnetic resonance imaging (fMRI), we explored whether altered neurotransmission was paralleled by aberrant mPFC resting-state functional connectivity (FC). IBS patients did not differ from HCs with respect to mPFC GABA+ or Glx levels. Anxiety was positively associated with mPFC GABA+ concentrations in IBS, whereas Glx was unrelated to psychological or gastrointestinal symptoms. Subgroup comparisons of patients with high or low anxiety symptom severity and HCs revealed increased GABA+ in patients with high symptom severity, and lower mPFC FC with adjacent anterior cingulate cortex (ACC), a crucial region of emotion modulation. Our findings provide novel evidence that altered prefrontal inhibitory neurotransmission may be linked to anxiety in IBS.
Novel breast cancer screening: combined expression of miR-21 and MMP-1 in urinary exosomes detects 95% of breast cancer without metastasis
Authors: Ando Wataru , Kikuchi Kiyoshi , Uematsu Takayuki , Yokomori Hiroaki , Takaki Takashi , Sogabe Masaya , Kohgo Yutaka , Otori Katsuya , Ishikawa Shigemi , Okazaki Isao 
Published: September 2019

AbstractSerum and tissue miR-21 expression in patients with breast cancer (BC) is a useful biomarker for cancer diagnosis, progression, and treatment. Matrix metalloproteinase-1 (MMP-1) is also important in breast cancer carcinogenesis. However, miR-21 and MMP-1/CD63 in urine exosomes in these patients have not been examined. Urine samples were collected from patients with BC and 26 healthy females. Urinary exosomes were isolated and confirmed by western blotting with anti-CD63 antibody and electron microscopy observation. MiR-21 and MMP-1/CD63 expression was examined by quantitative RT-PCR and western blotting, respectively. Patients with very early stage breast cancer were evaluated. MiR-21 expression in the patients was 0.26 [95% CI: 0.20–0.78], which was significant lower than in the 26 controls (1.00 [95% CI: 1.01–3.37], p = 0.0947). MMP-1/CD63 expression in patients was significantly higher than in controls (1.74 [95% CI: 0.86–5.08] vs 0.535 [95% CI: −0.01–2.81], p = 0.0001). Sensitivity and specificity were 0.708 and 0.783 for miR-21 and 0.792 and 0.840 for MMP-1/CD63, respectively. Sensitivity and specificity of combined expression were 95% and 79%, respectively. The sensitivity of MMP-1/CD63 expression in urinary exosomes was better than that of miR-21 expression. Thus, miR-21 and MMP/CD63 may be useful markers for BC screening.
Quantum nanoconstrictions fabricated by cryo-etching in encapsulated graphene
Authors: Clericò V. , Delgado-Notario J. A. , Saiz-Bretín M. , Malyshev A. V. , Meziani Y. M. , Hidalgo P. , Méndez B. , Amado M. , Domínguez-Adame F. , Diez E. 
Published: September 2019

AbstractWe report on a novel implementation of the cryo-etching method, which enabled us to fabricate low-roughness hBN-encapsulated graphene nanoconstrictions with unprecedented control of the structure edges; the typical edge roughness is on the order of a few nanometers. We characterized the system by atomic force microscopy and used the measured parameters of the edge geometry in numerical simulations of the system conductance, which agree quantitatively with our low temperature transport measurements. The quality of our devices is confirmed by the observation of well defined quantized 2e2/h conductance steps at zero magnetic field. To the best of our knowledge, such an observation reports the clearest conductance quantization in physically etched graphene nanoconstrictions. The fabrication of such high quality systems and the scalability of the cryo-etching method opens a novel promising possibility of producing more complex truly-ballistic devices based on graphene.
Accuracy of matrix-assisted LASER desorption ionization–time of flight mass spectrometry for identification of Candida
Authors: Xie Tian-Ao , Liu Ye-Ling , Liang Chuan , Huang Yuan-Yuan , Li Jin-Wei , Li Zhong-Wei , Fan Shu-Jin , Chen Jin-Tao , Xia Yong , Li Xiao-Yan , Ouyang Shi , Ji Tian-Xing , Guo Xu-Guang 
Published: September 2019

Abstract
Background: Candida is a fungus that causes various types of candidemia, which is the fourth major infectious disease of the blood system. MALDI-TOF-MS is a simple and rapid detection instrument. The aim of the present study was to verify the accuracy of MALDI-TOF-MS in detecting Candida.
Method: A pooled analysis of articles on MALDI-TOF-MS for diagnosis of candidemia was performed. The quality of original research was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) guidelines. Stata 12.0 software was used to merge the correct identification rates of Candida and Candida subspecies and obtain pooled sensitivity and specificity of the diagnostic methods. Heterogeneity was found in the subgroup analysis of the included articles. Hence, we explored the factors causing the heterogeneity and its impact on the overall situation. Sensitivity analysis was used to examine the effect of Candida level on total response. Egger’s test was used to evaluate the publication bias of the included articles.
Results: A total of 16 articles in Pubmed, 79 articles in Embase, 1 article in Cochrane Library, 30 articles in Web of Science and 3 from other sources were identified, of which 10 articles were included based on the inclusion and exclusion criteria. The overall identification accuracy was 100%.
Conclusion: The accuracy of MALDI-TOF-MS for the identification of Candida was 100%. Further research is necessary to determine whether MALDI-TOF-MS can be used as a clinical diagnostic standard for the identification of Candida.
Evaluation of immune protection againstToxoplasma gondiiinfection in mice induced by a multi-antigenic DNA vaccine containing TgGRA24, TgGRA25 and TgMIC6
Authors: Xu Xiao-Pei , Liu Wen-Ge , Xu Qian-Ming , Zhu Xing-Quan , Chen Jia 
Published: September 2019

Toxoplasma gondiiinfection is prevalent in humans and animals worldwide. In this study, recombinant eukaryotic expression plasmids (pVAX-GRA24, pVAX-GRA25 and pVAX-MIC6) were constructed, and then injected into Kunming mice intramuscularly, as cocktailed plasmids or as single-gene plasmids. We evaluated immune protective responses by detecting the titer of antibodies and cytokine production of IFN-γ, IL-2, IL-4, IL-10, IL-12 and IL-23, the percentages of the subclasses of T lymphocytes, as well as the records of the survival time and cyst decrement in the brain of the mouse model after challenge with theT. gondiiRH and Pru strains, respectively. Compared with the control groups, antibody and cytokine production were significantly increased, while the survival times of mice in all immunized groups were also prolonged, and the number ofT. gondiicysts in their brains were decreased significantly (29.03% for pVAX-GRA24; 40.88% for pVAX-GRA25; 37.70% for pVAX-MIC6; 48.06% for pVAX-GRA24 + pVAX-GRA25; and 55.37% for pVAX-GRA24 + pVAX-GRA25 + pVAX-MIC6). The mouse group immunized with the three-gene cocktail (TgGRA24 + TgGRA25 + TgMIC6) had better performance in each detection index than the mouse groups immunized with the two-gene cocktail of TgGRA24 + TgGRA25, which was better than that in the group immunized with the single gene vaccine of TgGRA24, TgMIC6 or TgGRA25. In conclusion, TgGRA24 or TgGRA25 may be good vaccine candidates againstT. gondiiinfection, but the three-gene cocktail of TgGRA24, TgMIC6 and TgGRA25 may induce the strongest protective immunity. Further studies of multi-antigenic DNA vaccines or cocktailed vaccines againstT. gondiiinfection are necessary.
ESCOP 2019
Authors: Steinhoff Barbara , Wegener Tankred 
Published: September 2019

ZusammenfassungAnlässlich des 30. Geburtstages der ESCOP wird ein Blick auf deren anfängliche Pionierarbeit zur Harmonisierung der Bewertungskriterien zur Wirksamkeit und Unbedenklichkeit von Arzneipflanzen und die heute etablierte Online-Publikation wissenschaftlicher Monografien geworfen. Für die Mitglieder der Gesellschaft für Phytotherapie und die in der ESCOP zusammengeschlossenen weiteren nationalen Fachgesellschaften für Phytotherapie sind diese Monografien immer von großer Bedeutung gewesen; heute können die Mitglieder durch einen einfachen Zugang von den Arbeitsergebnissen profitieren. ESCOP trägt zur Harmonisierung wissenschaftlicher Informationen über den Nutzen und die Anwendung von Arzneipflanzen bei und stellt darüber hinaus auch eine Plattform für eine konstruktive Zusammenarbeit nationaler Fachgesellschaften für Phytotherapie dar.
Osteosynthesis or arthroplasty of fractures near the knee joint in geriatric patients – a clinical-economical comparison
Authors: Pasurka Mario , Krinner Sebastian , Gelse Kolja 
Published: September 2019

Abstract
Background The treatment of fractures of the tibial plateau or distal femur often represents a severe problem in geriatric patients. In particular, complex fracture types and concomitant severe osteoporosis are confronted with inferior results following internal fixation. Therefore, primary arthroplasty is increasingly propagated for such particular cases.
Patients, Materials and Methods In 16 patients suffering from fractures of the distal femur or tibial plateau were treated either by internal fixation (n = 8) or primary arthroplasty (n = 8). The outcome of each case was retrospectively analysed according to clinical and economic criteria.
Results In the investigated geriatric patients, primary arthroplasty was significantly superior to internal fixation regarding mobilisation and range of motion without being inferior in cost-effectiveness.
Conclusion Compared to internal fixation, primary arthroplasty represents an efficient and cost-effective therapeutical option for the treatment of complex fractures of the distal femur or tibial plateau of the elderly patient.
Der rheumatologische Patient auf der Intensivstation
Authors: Lehmann Petra , Ehrenstein Boris , Fleck Martin 
Published: September 2019

ZUSAMMENFASSUNGPatienten mit rheumatischer Systemerkrankung haben auf der Intensivstation trotz ihres allgemein jüngeren Altersdurchschnitts ein höheres Mortalitätsrisiko. Die Diagnose der Grunderkrankung, die Unterscheidung zwischen akutem Schub und infektiöser Komplikation sowie die Komplexität der spezifischen antirheumatischen Therapie können Probleme bereiten. Der folgende Artikel gibt eine Übersicht über die Besonderheiten bei der Diagnose und Behandlung von Patienten mit Autoimmunerkrankungen auf der Intensivstation.
Aphereseverfahren bei Autoimmunerkrankungen
Authors: Heibel Sebastian , de Groot Kirsten 
Published: September 2019

ZUSAMMENFASSUNGAphereseverfahren finden neben ihrem etablierten Einsatz in derTransplantations- und Transfusionsmedizin vor allem in der Therapie autoimmunologischer entzündlich-rheumatischer und neurologischer Erkrankungen zunehmende klinische Anwendung. Ihre grundsätzliche Funktionsweise liegt im Entzug pathophysiologisch wirksamer Blutbestandteile (v. a. IgG-Antikörper) und weiteren immunmodulatorischen Effekten. Mögliche Apheresemodalitäten sind die unselektive Plasmapherese mit nachfolgendem Ersatz des entzogenen Plasmas durch verschiedenartige Substituate sowie die selektivere Immunadsorption. Die Therapie ist logistisch aufwendig, jedoch für den Patienten nebenwirkungsarm.