bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantification for non-targeted LC/MS screening without standard substances
Authors: Liigand Jaanus , Wang Tingting , Kellogg Joshua , Smedsgaard Jørn , Cech Nadja , Kruve Anneli 
Published: April 2020

AbstractNon-targeted and suspect analyses with liquid chromatography/electrospray/high-resolution mass spectrometry (LC/ESI/HRMS) are gaining importance as they enable identification of hundreds or even thousands of compounds in a single sample. Here, we present an approach to address the challenge to quantify compounds identified from LC/HRMS data without authentic standards. The approach uses random forest regression to predict the response of the compounds in ESI/HRMS with a mean error of 2.2 and 2.0 times for ESI positive and negative mode, respectively. We observe that the predicted responses can be transferred between different instruments via a regression approach. Furthermore, we applied the predicted responses to estimate the concentration of the compounds without the standard substances. The approach was validated by quantifying pesticides and mycotoxins in six different cereal samples. For applicability, the accuracy of the concentration prediction needs to be compatible with the effect (e.g. toxicology) predictions. We achieved the average quantification error of 5.4 times, which is well compatible with the accuracy of the toxicology predictions.
Campylobacter gastroenteritis in children in north-eastern Israel comparison with other common pathogens
Authors: Sakran Waheeb , Hexner-Erlichman Zufit , Spiegel Ronen , Batheesh Hamed , Halevy Raphael , Koren Ariel 
Published: April 2020

AbstractGastroenteritis is common among children. Campylobacter jejuni is one of the main causative bacterial pathogens, together with Shigella, Salmonella and invasive Escherichia coli. Campylobacteriosis is a zoonotic, usually self-limited disease that does not always require antibiotic treatment. In cases of protracted diarrhoea in healthy children or immunocompromised patients, antibiotic treatment is recommended, and the drug of choice is still macrolides, with very low resistance rates in Campylobacter species. However, it is crucial to isolate the causative organism, because some cases, such as Shigella encephalitis, call for initiation of empiric antibiotic treatment. In this study, we compared the incidence, epidemiology, clinical findings and laboratory results of gastroenteritis with dysentery caused by these organisms in children in our area. C. jejuni was found to be the leading pathogen in children hospitalized with bacterial gastroenteritis, followed by Shigella and Salmonella. Macrolides were the drug of choice for Campylobacter, and ceftriaxone and ciprofloxacin were the best empiric treatments for Shigella and Salmonella, respectively.
Neuro-Musculoskeletal Mapping for Man-Machine Interfacing
Authors: Kapelner Tamas , Sartori Massimo , Negro Francesco , Farina Dario 
Published: April 2020

AbstractWe propose a myoelectric control method based on neural data regression and musculoskeletal modeling. This paradigm uses the timings of motor neuron discharges decoded by high-density surface electromyogram (HD-EMG) decomposition to estimate muscle excitations. The muscle excitations are then mapped into the kinematics of the wrist joint using forward dynamics. The offline tracking performance of the proposed method was superior to that of state-of-the-art myoelectric regression methods based on artificial neural networks in two amputees and in four out of six intact-bodied subjects. In addition to joint kinematics, the proposed data-driven model-based approach also estimated several biomechanical variables in a full feed-forward manner that could potentially be useful in supporting the rehabilitation and training process. These results indicate that using a full forward dynamics musculoskeletal model directly driven by motor neuron activity is a promising approach in rehabilitation and prosthetics to model the series of transformations from muscle excitation to resulting joint function.
Model of Carbon Footprint Assessment for the Life Cycle of the System of Wastewater Collection, Transport and Treatment
Authors: Zawartka Paweł , Burchart-Korol Dorota , Blaut Agata 
Published: April 2020

AbstractThis article presents a model of the environmental assessment of the system of wastewater collection, transport and treatment. The model was developed based on an original environmental assessment method of a system consisting of four elements: septic tanks, household wastewater treatment plants, a sewerage system and a central wastewater treatment plant. To conduct the environmental assessment, the Life Cycle Assessment technique was applied. The Intergovernmental Panel on Climate Change (IPCC) method was also applied, which enabled the determination of the carbon footprint of the analysed wastewater management system. This article presents the outline of an original method applied to create a model and an inventory of the data necessary for environmental assessment and the application of the model for the environmental assessment of a system of wastewater collection, transport and treatment in a city with over 50.000 inhabitants. Three feasible variants (from a functional, technical, organizational and financial point of view) of the system’s development were analysed. The variants were subjected to comparative analysis using the solution. The obtained results, together with the assessment method can be used as a practical tool to assess whether the European Commission’s guidelines are met, as well as the challenges facing wastewater management in the circular economy are overcome.
Crystallographic characterization of a tri-Asp metal-binding site at the three-fold symmetry axis of LarE
Authors: Fellner Matthias , Huizenga Kamren G. , Hausinger Robert P. , Hu Jian 
Published: April 2020

AbstractDetailed crystallographic characterization of a tri-aspartate metal-binding site previously identified on the three-fold symmetry axis of a hexameric enzyme, LarE from Lactobacillus plantarum, was conducted. By screening an array of monovalent, divalent, and trivalent metal ions, we demonstrated that this metal binding site stoichiometrically binds Ca2+, Mn2+, Fe2+/Fe3+, Co2+, Ni2+, Cu2+, Zn2+, and Cd2+, but not monovalent metal ions, Cr3+, Mg2+, Y3+, Sr2+ or Ba2+. Extensive database searches resulted in only 13 similar metal binding sites in other proteins, indicative of the rareness of tri-aspartate architectures, which allows for engineering such a selective multivalent metal ion binding site into target macromolecules for structural and biophysical characterization.
Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens
Authors: Larsson Peter , Engqvist Hanna , Biermann Jana , Werner Rönnerman Elisabeth , Forssell-Aronsson Eva , Kovács Anikó , Karlsson Per , Helou Khalil , Parris Toshima Z. 
Published: April 2020

AbstractCancer drug development has been riddled with high attrition rates, in part, due to poor reproducibility of preclinical models for drug discovery. Poor experimental design and lack of scientific transparency may cause experimental biases that in turn affect data quality, robustness and reproducibility. Here, we pinpoint sources of experimental variability in conventional 2D cell-based cancer drug screens to determine the effect of confounders on cell viability for MCF7 and HCC38 breast cancer cell lines treated with platinum agents (cisplatin and carboplatin) and a proteasome inhibitor (bortezomib). Variance component analysis demonstrated that variations in cell viability were primarily associated with the choice of pharmaceutical drug and cell line, and less likely to be due to the type of growth medium or assay incubation time. Furthermore, careful consideration should be given to different methods of storing diluted pharmaceutical drugs and use of DMSO controls due to the potential risk of evaporation and the subsequent effect on dose-response curves. Optimization of experimental parameters not only improved data quality substantially but also resulted in reproducible results for bortezomib- and cisplatin-treated HCC38, MCF7, MCF-10A, and MDA-MB-436 cells. Taken together, these findings indicate that replicability (the same analyst re-performs the same experiment multiple times) and reproducibility (different analysts perform the same experiment using different experimental conditions) for cell-based drug screens can be improved by identifying potential confounders and subsequent optimization of experimental parameters for each cell line.
Deep microbial proliferation at the basalt interface in 33.5–104 million-year-old oceanic crust
Authors: Suzuki Yohey , Yamashita Seiya , Kouduka Mariko , Ao Yutaro , Mukai Hiroki , Mitsunobu Satoshi , Kagi Hiroyuki , D’Hondt Steven , Inagaki Fumio , Morono Yuki , Hoshino Tatsuhiko , Tomioka Naotaka , Ito Motoo 
Published: April 2020

AbstractThe upper oceanic crust is mainly composed of basaltic lava that constitutes one of the largest habitable zones on Earth. However, the nature of deep microbial life in oceanic crust remains poorly understood, especially where old cold basaltic rock interacts with seawater beneath sediment. Here we show that microbial cells are densely concentrated in Fe-rich smectite on fracture surfaces and veins in 33.5- and 104-million-year-old (Ma) subseafloor basaltic rock. The Fe-rich smectite is locally enriched in organic carbon. Nanoscale solid characterizations reveal the organic carbon to be microbial cells within the Fe-rich smectite, with cell densities locally exceeding 1010 cells/cm3. Dominance of heterotrophic bacteria indicated by analyses of DNA sequences and lipids supports the importance of organic matter as carbon and energy sources in subseafloor basalt. Given the prominence of basaltic lava on Earth and Mars, microbial life could be habitable where subsurface basaltic rocks interact with liquid water.
Hydrostatic pressure promotes endothelial tube formation through aquaporin 1 and Ras-ERK signaling
Authors: Yoshino Daisuke , Funamoto Kenichi , Sato Kakeru , Kenry  , Sato Masaaki , Lim Chwee Teck 
Published: April 2020

AbstractVascular tubulogenesis is tightly linked with physiological and pathological events in the living body. Endothelial cells (ECs), which are constantly exposed to hemodynamic forces, play a key role in tubulogenesis. Hydrostatic pressure in particular has been shown to elicit biophysical and biochemical responses leading to EC-mediated tubulogenesis. However, the relationship between tubulogenesis and hydrostatic pressure remains to be elucidated. Here, we propose a specific mechanism through which hydrostatic pressure promotes tubulogenesis. We show that pressure exposure transiently activates the Ras/extracellular signal-regulated kinase (ERK) pathway in ECs, inducing endothelial tubulogenic responses. Water efflux through aquaporin 1 and activation of protein kinase C via specific G protein–coupled receptors are essential to the pressure-induced transient activation of the Ras/ERK pathway. Our approach could provide a basis for elucidating the mechanopathology of tubulogenesis-related diseases and the development of mechanotherapies for improving human health.
DNA copy number motifs are strong and independent predictors of survival in breast cancer
Authors: Pladsen Arne V. , Nilsen Gro , Rueda Oscar M. , Aure Miriam R. , Borgan Ørnulf , Liestøl Knut , Vitelli Valeria , Frigessi Arnoldo , Langerød Anita , Mathelier Anthony ,   OSBREAC, Bathen Tone F. , Borgen Elin , Børresen-Dale Anne-Lise , Engebråten Olav , Fritzman Britt , Garred Øystein , Geisler Jürgen , Geitvik Gry Aarum , Hofvind Solveig , Kristensen Vessela , Kåresen Rolf , Langerød Anita , Lingjærde Ole Christian , Mælandsmo Gunhild Mari , Naume Bjørn , Russnes Hege G. , Sahlberg Kristine Kleivi , Sauer Torill , Skjerven Helle Kristine , Schlichting Ellen , Sørlie Therese , Engebråten Olav , Kristensen Vessela , Wedge David C. , Van Loo Peter , Caldas Carlos , Børresen-Dale Anne-Lise , Russnes Hege G. , Lingjærde Ole Christian 
Published: April 2020

AbstractSomatic copy number alterations are a frequent sign of genome instability in cancer. A precise characterization of the genome architecture would reveal underlying instability mechanisms and provide an instrument for outcome prediction and treatment guidance. Here we show that the local spatial behavior of copy number profiles conveys important information about this architecture. Six filters were defined to characterize regional traits in copy number profiles, and the resulting Copy Aberration Regional Mapping Analysis (CARMA) algorithm was applied to tumors in four breast cancer cohorts (n = 2919). The derived motifs represent a layer of information that complements established molecular classifications of breast cancer. A score reflecting presence or absence of motifs provided a highly significant independent prognostic predictor. Results were consistent between cohorts. The nonsite-specific occurrence of the detected patterns suggests that CARMA captures underlying replication and repair defects and could have a future potential in treatment stratification.
Formation mechanism of insensitive tellurium hexanitride with armchair-like cyclo-N6 anions
Authors: Liu Zhao , Li Da , Zhuang Quan , Tian Fubo , Duan Defang , Li Fangfei , Cui Tian 
Published: April 2020

AbstractThe lower decomposition barriers of cyclo-N6 anions hinder their application as high-energy-density materials. Here, first-principles calculations and molecular dynamics simulations reveal that enhancing the covalent component of the interaction between cyclo-N6 anions and cations can effectively improve the stability of cyclo-N6 anions. Taking tellurium hexanitride as a representative, the exotic armchair-like N6 anions of tellurium hexanitride exhibit resistance towards electronic attack and gain extra stability through the formation of covalent bonds with the surrounding elemental tellurium under high pressures. These covalent bonds effectively improve the chemical barrier and insensitivity of tellurium hexanitride during blasting, which prevents the decomposition of solid cyclo-N6 salts into molecular nitrogen. Furthermore, the high-pressure induced covalent bonds between cyclo-N6 anions and tellurium enable the high bulk modulus, remarkable detonation performance, and high-temperature thermodynamic stability of tellurium hexanitride.
Estradiol and progesterone affect enzymes but not glucose consumption in a mink uterine cell line (GMMe)
Authors: Holmlund Hayden , Marín-Hernández Álvaro , Chase Jennifer R. 
Published: April 2020

Abstract
Cells lining the uterus are responsible for storage and secretion of carbohydrates to support early embryonic development. Histotrophic secretions contain glycogen and glycolytic products such as lactate and pyruvate. Insufficient carbohydrate storage as glycogen has been correlated with infertility in women. While it is clear that changes in estrogen (17-β-estradiol (E2)) and progesterone (P4) in vivo affect the distribution of glucose in the uterine cells and secretions, the biochemical mechanism(s) by which they affect this crucial allocation is not well understood. Furthermore, in cultured uterine cells, neither E2 nor P4 affect glycogen storage without insulin present. We hypothesized that P4 and E2 alone affect the activity of glycolytic enzymes, glucose and glycolytic flux to increase glycogen storage (E2) and catabolism (P4) and increase pyruvate and lactate levels in culture. We measured the rate of glucose uptake and glycolysis in a mink immortalized epithelial cell line (GMMe) after 24-h exposure to 10 μM P4 and 10 nM E2 (pharmacologic levels) at 5 mM glucose and determined the kinetic parameters (Vmax, Km) of all enzymes. While the activities of many glycolytic enzymes in GMMe cells were shown to be decreased by E2 treatment, in contrast, glucose uptake, glycolytic flux and metabolites levels were not affected by the treatments. The cellular rationale for P4- and E2-induced decreases in the activity of enzymes may be to prime the system for other regulators such as insulin. In vivo, E2 and P4 may be necessary but not sufficient signals for uterine cycle carbohydrate allocation.
Non-REM Parasomnie
Authors: Heidbreder Anna 
Published: April 2020

ZusammenfassungDie Non-REM-Parasomnien umfassen das Schlafwandeln, den Nachtschreck und das verwirrte Erwachen. Sie sind verbunden mit Verhaltensauffälligkeiten, die aus dem Tiefschlaf heraus auftreten. Das Verhalten variiert dabei zwischen einem kurzen plötzlichen Aufrichten bis hin zu komplexen Handlungen, z. B. Kochen, Autofahren. In EEG-Untersuchungen und bildgebenden Studien konnte gezeigt werden, dass es während solcher Episoden zu einer Dissoziation von Wach und Schlaf kommt. Meist treten NREM-Parasomnien in der Kindheit und frühen Jugend auf und verschwinden mit dem Erwachsenwerden. In bis zu 2 % bis 4 % spielen sie aber auch bei Erwachsenen eine Rolle und haben nicht selten relevante psychosoziale Konsequenzen für die Betroffenen. Für die Diagnostik ist in solchen Fällen auch zum Ausschluss von Differenzialdiagnosen eine Polysomnografie obligat, auch wenn diese durch die Diagnosekriterien bisher nicht gefordert wird. Meist ist eine Behandlung der NREM-Parasomnie nicht erforderlich, diese sollte jedoch eingesetzt werden, wenn psychosoziale Konsequenzen durch die nächtlichen Ereignisse bestehen. Da randomisierte Studien bisher fehlen, beruhen die Behandlungsempfehlungen auf Expertenmeinungen und Untersuchungen von Fallserien.
Metabolische Chirurgie bei Typ-2-Diabetes?
Authors: Blüher Matthias 
Published: April 2020

Was ist neu?
Indikationsstellung Unter metabolischer Chirurgie wird die nicht ausschließlich gewichtsabhängige chirurgische Therapie von Stoffwechselerkrankungen verstanden, deren Ziel unter anderem die Verbesserung der Hyperglykämie ist. Nach der seit 2018 gültigen S3-Leitlinie „Chirurgie der Adipositas und metabolischer Erkrankungen“ kann die Indikation zur metabolischen Chirurgie bei Menschen mit Typ-2-Diabetes und einem BMI ≥ 35 kg/m² gestellt werden, wenn diabetesspezifische individuelle Zielwerte nicht erreicht werden können. Ab einem BMI ≥ 40 kg/m² soll die metabolische Operation sogar als mögliche Therapieoption auch unabhängig von Parametern der glykämischen Kontrolle oder der medikamentösen Diabetestherapie empfohlen werden.
Nutzen der metabolischen Chirurgie In randomisierten kontrollierten Studien war die metabolische Chirurgie gegenüber der konservativen Diabetestherapie im Hinblick auf Verbesserungen der Blutzuckereinstellung und Gewichtsreduktion konsistent überlegen und konnte die Inzidenz an makro- und mikrovaskulären Diabeteskomplikationen senken.
Risiken der metabolischen Chirurgie Zu den Risiken der metabolischen Chirurgie zählen akute Komplikationen bis hin zu einer perioperativen Mortalität von 0,1–0,5 % und längerfristige Komplikationen wie defiziente Mikronährstoffversorgung, Suchtentwicklung oder erhöhtes Risiko für Suizidalität.
Fazit Für die meisten Menschen mit Typ-2-Diabetes wird die metabolische Chirurgie nicht die erste Wahl im eskalierenden Therapiekonzept sein. Dies begründet sich v. a. daraus, dass durch moderne Antidiabetika und modifizierte Insulintherapien eine sichere und langfristig wirksame Diabetestherapie bei guter Lebensqualität möglich ist. Gleichzeitig sollten aber Patienten mit Typ-2-Diabetes, die besonders von einer chirurgischen Therapie des Diabetes profitieren können, über diese Therapieoption aufgeklärt werden. Der Nutzen einer rechtzeitigen metabolischen Chirurgie sollte dabei immer gegenüber den Risiken abgewogen werden.
Barrett-Ösophagus – Update zu klinischem Management und Therapien
Authors: Quante Michael , Huspenina Julia Slotta , Abdelhafez Mohamed 
Published: April 2020

Was ist neu?
Pathogenese Adenokarzinome des Ösophagus sind denen des Magens sehr ähnlich und entstehen mit hoher Wahrscheinlichkeit im Bereich der Kardia im Magen, von wo aus proliferierende Zellen in den Ösophagus expandieren und dort zunächst benigne „Barrett-Schleimhautinseln“ bilden. Eine hinzukommende genomische Instabilität führt zur klonalen Evolution bestimmter Zellen, die zur Entwicklung eines Adenokarzinoms führen kann.
Risikofaktoren Eine klare Definition von Faktoren ist zur besseren Risikostratifizierung und Etablierung präventiver Strategien dringend notwendig. Aktuelle Prädiktionsmodelle, die unter anderem Übergewicht, Ernährungsweise oder Tabakkonsum erfassen, haben sich in der klinischen Anwendung noch nicht durchsetzen können.
Diagnostik und Überwachung Zur Diagnostik und Überwachung existieren aktuelle Leitlinien. Die Diagnose eines Barrett-Ösophagus erfolgt histopathologisch aus 4-Quadranten-Biopsien. Darüber hinaus sollten makroskopisch auffällige Areale der Barrett-Schleimhaut gezielt biopsiert werden. Die Detektion neoplastischer Areale kann durch Einsatz der Chromoendoskopie in Kombination mit Vergrößerungsendoskopie und Färbetechniken (Methylenblau oder Essigsäure) verbessert werden.
Therapie Die kurativ intendierte endoskopische Resektion ist die Standardtherapie der dysplastischen Barrett-Metaplasie, des mukosalen (T1a-m) und des oberflächlich submukosal (T1a-sm1) wachsenden Adenokarzinoms. Hier stellen die Kappen- und Ligatur-Resektion sowie zunehmend die endoskopische Submukosa-Dissektion die empfohlenen Resektionstechniken und in Kombination mit der Radiofrequenzablation die leitliniengerechte Therapie dar.
Konzept der sequenziellen natriuretischen Peptidmessungen im Behandlungsplan der Herzinsuffizienz
Authors: Becher Marc Ulrich 
Published: April 2020

Was ist neu?
NP-Grenzwert zur Diagnostik einer Herzinsuffizienz Von den klinisch verfügbaren Biomarkern sind die natriuretischen Peptide (NP) die robustesten Prädiktoren für die Diagnose und Prognose bei Herzinsuffizienz (HI). Der prognostische Wert ist insbesondere bei serieller Bestimmung der NP hoch, sodass der klinische Einsatz in internationalen HI-Leitlinien mit höchster Evidenz und Empfehlung weiter in den Vordergrund gerückt ist.
Strategie der sequenziellen NP-Messungen Das Konzept der sequenziellen NP-Messungen dient der Erfassung der Natrium- und Wasserüberladung zu klinisch definierten Zeitpunkten. Ziel eines NP-unterstützten Behandlungsplans ist, nicht nur die Dynamik des klinischen Therapieansprechens zu objektivieren, sondern den individuellen Therapieverlauf klinischen Szenarien zuzuordnen, die ihrerseits eine wesentliche Rolle für die Risikostratifizierung, Prognose und Notwendigkeiten von Therapieoptimierung in der stationären, aber auch ambulanten Versorgung spielen.
S3-Leitlinie Sepsis 2018: ausgewählte Empfehlungen
Authors: Brunkhorst Frank M. 
Published: April 2020

Was ist neu?
Definition der Sepsis Eine Sepsis ist eine akut lebensbedrohliche Organdysfunktion, hervorgerufen durch eine inadäquate Wirtsantwort auf eine Infektion. Für die Diagnose einer Sepsis-assoziierten Organdysfunktion ist eine Veränderung des Sequential Organ Failure Assessment (SOFA) Scores um ≥ 2 Punkte zu verwenden.
Therapie Zur hämodynamischen Stabilisierung von Patienten sollte eine intravenöse kristalloide Lösung innerhalb der ersten 3 Stunden verabreicht werden. 0,9 %ige Kochsalzlösung sollte NICHT verwendet werden. Eine schematische Mindestinfusionsmenge und ein allgemeiner Zielwert für den mittleren arteriellen Blutdruck werden nicht empfohlen. Intravenöse Antiinfektiva sollten so schnell wie möglich verabreicht werden – möglichst innerhalb 1 Stunde nach Diagnosestellung. Um alle wesentlichen Bakterien zu erfassen wird die Anwendung einer empirischen Breitspektrumtherapie mit einem oder mehreren Antibiotika empfohlen. Um die antimikrobielle Therapiedauer zu verkürzen, sollten Messungen des Procalcitonin-Werts vorgenommen werden.