bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating experimental and distribution data to predict future species patterns
Authors: Kotta Jonne , Vanhatalo Jarno , Jänes Holger , Orav-Kotta Helen , Rugiu Luca , Jormalainen Veijo , Bobsien Ivo , Viitasalo Markku , Virtanen Elina , Sandman Antonia Nyström , Isaeus Martin , Leidenberger Sonja , Jonsson Per R. , Johannesson Kerstin 
Published: February 2019

AbstractPredictive species distribution models are mostly based on statistical dependence between environmental and distributional data and therefore may fail to account for physiological limits and biological interactions that are fundamental when modelling species distributions under future climate conditions. Here, we developed a state-of-the-art method integrating biological theory with survey and experimental data in a way that allows us to explicitly model both physical tolerance limits of species and inherent natural variability in regional conditions and thereby improve the reliability of species distribution predictions under future climate conditions. By using a macroalga-herbivore association (Fucus vesiculosus-Idotea balthica) as a case study, we illustrated how salinity reduction and temperature increase under future climate conditions may significantly reduce the occurrence and biomass of these important coastal species. Moreover, we showed that the reduction of herbivore occurrence is linked to reduction of their host macroalgae. Spatial predictive modelling and experimental biology have been traditionally seen as separate fields but stronger interlinkages between these disciplines can improve species distribution projections under climate change. Experiments enable qualitative prior knowledge to be defined and identify cause-effect relationships, and thereby better foresee alterations in ecosystem structure and functioning under future climate conditions that are not necessarily seen in projections based on non-causal statistical relationships alone.
Chromophore binding to two cysteines increases quantum yield of near-infrared fluorescent proteins
Authors: Buhrke David , Tavraz Neslihan N. , Shcherbakova Daria M. , Sauthof Luisa , Moldenhauer Marcus , Vélazquez Escobar Francisco , Verkhusha Vladislav V. , Hildebrandt Peter , Friedrich Thomas 
Published: February 2019

AbstractPhytochromes are red/far-red light sensing photoreceptors employing linear tetrapyrroles as chromophores, which are covalently bound to a cysteine (Cys) residue in the chromophore-binding domain (CBD, composed of a PAS and a GAF domain). Recently, near-infrared (NIR) fluorescent proteins (FPs) engineered from bacterial phytochromes binding biliverdin IXα (BV), such as the iRFP series, have become invaluable probes for multicolor fluorescence microscopy and in vivo imaging. However, all current NIR FPs suffer from relatively low brightness. Here, by combining biochemical, spectroscopic and resonance Raman (RR) assays, we purified and characterized an iRFP variant that contains a BV chromophore simultaneously bound to two cysteines. This protein with the unusual double-Cys attached BV showed the highest fluorescence quantum yield (FQY) of 16.6% reported for NIR FPs, whereas the initial iRFP appeared to be a mixture of species with a mean FQY of 11.1%. The purified protein was also characterized with 1.3-fold higher extinction coefficient that together with FQY resulted in almost two-fold brighter fluorescence than the original iRFP as isolated. This work shows that the high FQY of iRFPs with two cysteines is a direct consequence of the double attachment. The PAS-Cys, GAF-Cys and double-Cys attachment each entails distinct configurational constraints of the BV adduct, which can be identified by distinct RR spectroscopic features, i.e. the marker band including the C=C stretching coordinate of the ring A-B methine bridge, which was previously identified as being characteristic for rigid chromophore embedment and high FQY. Our findings can be used to rationally engineer iRFP variants with enhanced FQYs.
Cdh2 coordinates Myosin-II dependent internalisation of the zebrafish neural plate
Authors: Araya Claudio , Häkkinen Hanna-Maria , Carcamo Luis , Cerda Mauricio , Savy Thierry , Rookyard Christopher , Peyriéras Nadine , Clarke Jonathan D. W. 
Published: February 2019

AbstractTissue internalisation is a key morphogenetic mechanism by which embryonic tissues generate complex internal organs and a number of studies of epithelia have outlined a general view of tissue internalisation. Here we have used quantitative live imaging and mutant analysis to determine whether similar mechanisms are responsible for internalisation in a tissue that apparently does not have a typical epithelial organisation – the zebrafish neural plate. We found that although zebrafish embryos begin neurulation without a conventional epithelium, medially located neural plate cells adopt strategies typical of epithelia in order to constrict their dorsal surface membrane during cell internalisation. Furthermore, we show that Myosin-II activity is a significant driver of this transient cell remodeling which also depends on Cdh2 (N-cadherin). Abrogation of Cdh2 results in defective Myosin-II distribution, mislocalised internalisation events and defective neural plate morphogenesis. Our work suggests Cdh2 coordinates Myosin-II dependent internalisation of the zebrafish neural plate.
DeepSOFA: A Continuous Acuity Score for Critically Ill Patients using Clinically Interpretable Deep Learning
Authors: Shickel Benjamin , Loftus Tyler J. , Adhikari Lasith , Ozrazgat-Baslanti Tezcan , Bihorac Azra , Rashidi Parisa 
Published: February 2019

AbstractTraditional methods for assessing illness severity and predicting in-hospital mortality among critically ill patients require time-consuming, error-prone calculations using static variable thresholds. These methods do not capitalize on the emerging availability of streaming electronic health record data or capture time-sensitive individual physiological patterns, a critical task in the intensive care unit. We propose a novel acuity score framework (DeepSOFA) that leverages temporal measurements and interpretable deep learning models to assess illness severity at any point during an ICU stay. We compare DeepSOFA with SOFA (Sequential Organ Failure Assessment) baseline models using the same model inputs and find that at any point during an ICU admission, DeepSOFA yields significantly more accurate predictions of in-hospital mortality. A DeepSOFA model developed in a public database and validated in a single institutional cohort had a mean AUC for the entire ICU stay of 0.90 (95% CI 0.90–0.91) compared with baseline SOFA models with mean AUC 0.79 (95% CI 0.79–0.80) and 0.85 (95% CI 0.85–0.86). Deep models are well-suited to identify ICU patients in need of life-saving interventions prior to the occurrence of an unexpected adverse event and inform shared decision-making processes among patients, providers, and families regarding goals of care and optimal resource utilization.
Animal species identification in parchments by light
Authors: Alvarez Angel Martin Fernandez , Bouhy Julie , Dieu Marc , Charles Catherine , Deparis Olivier 
Published: February 2019

AbstractRecently, historical and conservation studies have attached an increasing importance to investigating the materials used in historic documents. In particular, the identification of the animal species from which parchments are made is of high importance and is currently performed by either genetic or proteomic methods. Here, we introduce an innovative, non-invasive optical method for identifying animal species based on light-parchment interaction. The method relies on conservation of light energy through reflection, transmission and absorption from the sample, as well as on statistical processing of the collected optical data. Measurements are performed from ultraviolet (UV) to near-infrared (NIR) spectral ranges by a standard spectrophotometer and data are processed by Principal Component Analysis (PCA). PCA data from modern parchments, made of sheep, calf and goat skins, are used as a database for PCA analysis of historical parchments. Using only the first two principal components (PCs), the method confirmed visual diagnostics about parchment appearance and aging, and was able to recognise the origin species of historical parchment of among database clusters. Furthermore, taking into account the whole set of PCs, species identification was achieved, with all results matching perfectly their proteomic counterparts used for method assessment. The validated method compares favourably with genetic and proteomic methods used for the same purpose. In addition to animals’ proteomic and genetic signatures, a unique “optical fingerprint” of the parchments’ origin species is revealed here. This new method is non-invasive, straightforward to implement, potentially cheap and accessible to scholars and conservators, with minimal training. In the context of cultural heritage, the method could help solving questions related to parchment production and, more generally, medieval writing production.
Ghrelin Receptor Influence on Cocaine Reward is Not Directly Dependent on Peripheral Acyl-Ghrelin
Authors: Wenthur Cody J. , Gautam Ritika , Zhou Bin , Vendruscolo Leandro F. , Leggio Lorenzo , Janda Kim D. 
Published: February 2019

AbstractThe peptide hormone acyl-ghrelin and its receptor, GHSR1a, represent intriguing therapeutic targets due to their actions in metabolic homeostasis and reward activity. However, this pleotropic activity makes it difficult to intervene in this system without inducing unwanted effects. Thus, it is desirable to identify passive and active regulatory mechanisms that allow differentiation between functional domains. Anatomical restriction by the blood brain barrier represents one major passive regulatory mechanism. However, it is likely that the ghrelin system is subject to additional passive mechanisms that promote independent regulation of orexigenic behavior and reward processing. By applying acyl-ghrelin sequestering antibodies, it was determined that peripheral sequestration of acyl-ghrelin is sufficient to blunt weight gain, but not cocaine rewarding effects. However, both weight gain and reward-associated behaviors were shown to be blocked by direct antagonism of GHSR1a. Overall, these data indicate that GHSR1aeffects on reward are independent from peripheral acyl-ghrelin binding, whereas centrally-mediated alteration of energy storage requires peripheral acyl-ghrelin binding. This demonstration of variable ligand-dependence amongst functionally-distinct GHSR1apopulations is used to generate a regulatory model for functional manipulation of specific effects when attempting to therapeutically target the ghrelin system.
The lipid head group is the key element for substrate recognition by the P4 ATPase ALA2: a phosphatidylserine flippase
Authors: Theorin Lisa , Faxén Kristina , Sørensen Danny Mollerup , Migotti Rebekka , Dittmar Gunnar , Schiller Jürgen , Daleke David L. , Palmgren Michael , López-Marqués Rosa Laura , Günther Pomorski Thomas 
Published: February 2019

Abstract
Type IV P-type ATPases (P4 ATPases) are lipid flippases that catalyze phospholipid transport from the exoplasmic to the cytoplasmic leaflet of cellular membranes, but the mechanism by which they recognize and transport phospholipids through the lipid bilayer remains unknown. In the present study, we succeeded in purifying recombinant aminophospholipid ATPase 2 (ALA2), a member of the P4 ATPase subfamily in Arabidopsis thaliana, in complex with the ALA-interacting subunit 5 (ALIS5). The ATP hydrolytic activity of the ALA2–ALIS5 complex was stimulated in a highly specific manner by phosphatidylserine. Small changes in the stereochemistry or the functional groups of the phosphatidylserine head group affected enzymatic activity, whereas alteration in the length and composition of the acyl chains only had minor effects. Likewise, the enzymatic activity of the ALA2–ALIS5 complex was stimulated by both mono- and di-acyl phosphatidylserines. Taken together, the results identify the lipid head group as the key structural element for substrate recognition by the P4 ATPase.
Spectral analysis of the barium central star of the planetary nebula Hen 2−39
Authors: Löbling L. , Boffin H. M. J. , Jones D. 
Published: February 2019

Context. Barium stars are peculiar red giants characterized by an overabundance of the elements synthesized in the slow neutron-capture nucleosynthesis (s-process elements) along with an enrichment in carbon. These stars are discovered in binaries with white dwarf companions. The more recently formed of these stars are still surrounded by a planetary nebula.
Aims. Precise abundance determinations of the various s-process elements, of further key elements that act as indicators for effectiveness of nucleosynthesis on the asymptotic giant branch and, especially, of the lightest, short-lived radionuclide technetium will establish constraints for the formation of s-process elements in asymptotic giant branch stars as well as mass transfer through, for example, stellar wind, Roche-lobe overflow, and common-envelope evolution.
Methods. We performed a detailed spectral analysis of the K-type subgiant central star of the planetary nebula Hen 2−39 based on high-resolution optical spectra obtained with the Ultraviolet and Visual Echelle Spectrograph at the Very Large Telescope using local thermodynamic equilibrium model atmospheres.
Results. We confirm the effective temperature of Teff = (4350 ± 150) K for the central star of the planetary nebula Hen 2−39. It has a photospheric carbon enrichment of [C∕H] = 0.36 ± 0.08 and a barium overabundance of [Ba∕Fe] = 1.8 ± 0.5. We find a deficiency for most of the iron-group elements (calcium to iron) and establish an upper abundance limit for technetium (log ɛTc < 2.5).
Conclusions. The quality of the available optical spectra is not sufficient to measure abundances of all s-process elements accurately. Despite large uncertainties on the abundances as well as on the model yields, the derived abundances are most consistent with a progenitor mass in the range 1.75–3.00 M⊙ and a metallicity of [Fe∕H] = −0.3 ± 1.0. This result leads to the conclusion that the formation of such systems requires a relatively large mass transfer that is most easily obtained via wind-Roche lobe overflow.
Risk factors for remaining liver injury in patients with virological elimination of chronic hepatitis C
Authors: Mauss Stefan , Buendgens Lukas , Christensen Stefan , Ingiliz Patrick , Berger Florian , Hüppe Dietrich , Simon Karl , Lutz Thomas , Schewe Knud , Boesecke Christoph , Tacke Frank 
Published: February 2019

Abstract
Background and aims Disease activity, but also demographics, lifestyle, and comorbidities, may influence alanine aminotransferase (ALT) levels in hepatitis C virus (HCV)-infected patients. Direct-acting antiviral agents (DAA) achieve virological cure in > 90 % of patients, regardless of HCV genotype and fibrosis stage. This allows assessing determinants for ALT levels before and after elimination of HCV.
Methods Our prospective cohort included HCV- and HIV/HCV-infected patients treated with DAA at 9 German centers (GECCO cohort). We analyzed all consecutive patients with sustained virological response (SVR) at week 12 (SVR12) and/or 24. Normal ALT was defined as ≤ 35 U/L, regardless of sex.
Results At baseline, 1477 out of 1774 patients (83 %) had ALT > 35 U/L, and 297 (17 %) had ALT ≤ 35 U/L. Baseline ALT > 35 U/L was independently associated with male sex, higher body mass index (BMI), liver cirrhosis, and not being on opioid substitution. After SVR, > 80 % of patients normalized ALT, and even patients with low baseline ALT further reduced ALT levels. However, ALT remained > 35 U/L in 15 % (221/1477) after SVR12. By multivariate analysis, ALT > 35 U/L at SVR12 was associated with male sex, higher BMI, liver cirrhosis, baseline ALT, HCV genotype 2, and younger age. Obesity, cirrhosis, and ALT were also independent factors associated with ALT > 15 U/L at SVR12 in patients with normal ALT at baseline.
Conclusions Male sex, advanced liver fibrosis, and obesity are main risk factors for the lack of ALT normalization and/or ALT decline after SVR, indicative of fatty liver disease as a relevant comorbidity in hepatitis C.
Interdisziplinarität in der akademischen Plastischen
Chirurgie – belanglos oder zukunftsorientiert?
Authors: Kemper Robert , Horch Raymund , Giunta Riccardo , Prantl Lukas 
Published: February 2019

Zusammenfassung
Hintergrund Die Plastische Chirurgie ist wie kein anderes Fach in der Lage
alle Körperregionen nicht nur formbewahrend/-gebend zu operieren, sondern auch
funktionell anatomische Einheiten zu rekonstruieren. Im Rahmen einer
interdisziplinären Behandlung komplexer traumatologischer, Tumor- und
infektionsbedingter Erkrankungen benötigen andere Fachbereiche diese spezielle
Expertise. Die Ärztliche Approbationsordnung (ÄApprO) sieht aber trotz der
vielzähligen interdisziplinären Aufgaben kein eigenständiges Lehrcurriculum für
die Plastische Chirurgie vor. Daher ist die Entwicklung der akademischen
Plastischen Chirurgie problematisch. In dieser Arbeit wird die akademische und
klinische Interdisziplinarität dieses Fachs beleuchtet.
Methoden Anhand eines Fragebogens werden die akademischen Aufgaben der
Plastischen Chirurgie sowie deren operativ interdisziplinäre Leistungsfähigkeit
erhoben und diskutiert.
Ergebnisse An 12 der 36 Universitätskliniken gibt es keine Plastische
Chirurgie. Es gibt 11 Kliniken, 5 Abteilung, 4 Sektionen und 4
Funktionsbereiche. Die 13 an der Evaluation teilnehmenden Einrichtungen haben
sich im medizinischen Lehrcurriculum über das Wahlfach hinaus etablieren können.
Die Diskrepanz in Bezug auf den Lehraufwand erscheint unabhängig von
Eigenständigkeit und Personalschlüssel. 10 der 13 Zentren wären bereit, mehr
akademischen Aufwand zu leisten. Alle teilnehmenden Zentren prüfen im
Staatsexamen. 2015 wurden durch die 13 teilnehmenden Zentren 1476 Fälle
interdisziplinär behandelt. In 1165 Fällen erfolgte keine Leistungsabrechnung
durch die Plastische Chirurgie.
Zusammenfassung Das interdisziplinäre Aufgabenfeld der Plastischen
Chirurgie ist in der Hochleistungsmedizin unabdingbar. An 12
Universitätskliniken gibt es bis heute keine akademische Plastische Chirurgie.
Dabei stellt gerade die Interdisziplinarität unseres Fachs eine hervorragende
Voraussetzung zur Integration im modularen Unterricht dar.Die teils komplexen rekonstruktiven Eingriffe komplettieren den Behandlungserfolg
anderer Fachrichtungen. Die redundante fehlende ökonomische Teilhabe an diesem
Erfolg lässt die Entwicklung des Fachs hinterherhinken. Eine einheitliche
Integration in das Lehrcurriculum wäre eine zukunftsgerichtete Aufwertung der
Plastischen Chirurgie.
Pityriasis rubra pilaris – eine seltene entzündliche Dermatose mit vielen Facetten
Authors: Kahlert K. , Hamm H. , Goebeler M. , Kerstan A. 
Published: February 2019

ZusammenfassungDie Pityriasis rubra pilaris (PRP) ist eine seltene entzündliche, papulosquamöse Dermatose, die in 6 verschiedenen Manifestationsformen (Subtypen) sowohl bei Kindern als auch bei Erwachsenen mit großer Variabilität auftreten kann. Bei allen Subtypen sind in den Anfangsstadien follikulär gebundene, keratotische Papeln zu beobachten, die nach variabler Latenz zu unterschiedlich großen, gut begrenzten Plaques mit krankheitstypischem, orange-rotem Farbton konfluieren. Dabei finden sich bei den ausgedehnteren Verlaufsformen charakteristischerweise innerhalb der Plaques Inseln gesunder Haut (nappes claires). Nicht selten entsteht eine palmare und plantare, wechselnd stark ausgeprägte Hyperkeratose. Die PRP bietet ein breites klinisches Spektrum, das von einem lokalisierten Befall der Extremitäten bis hin zu erythrodermatischen Formen reicht, die mitunter bereits im Säuglingsalter beginnen können.Die vorliegende Arbeit gibt eine Übersicht über den aktuellen Kenntnisstand dieser bislang wenig verstandenen Dermatose.
Pachyonychia congenita und Steatocystoma multiplex durch Mutation im Keratin-17-Gen
Authors: Herz C. , Wobser M. , Fischer J. , Hamm H. 
Published: February 2019

ZusammenfassungDie Pachyonychia congenita (PC) wird durch heterozygote Mutationen in den Keratin-Genen KRT6A, KRT6B, KRT6C, KRT16 oder KRT17 verursacht. Die Einteilung in PC Typ 1 und PC Typ 2 nach klinischen Kriterien wurde zugunsten einer molekulargenetischen Klassifikation auf Basis der 5 betroffenen Gene (PC-K6a, PC-K6b, PC-K6c, PC-K16, PC-K17) verlassen. Die Erkrankung wird autosomal-dominant vererbt, Spontanmutationen kommen in etwa 30 % der Fälle vor. Über 97 % der PC-Patienten weisen die 3 Hauptsymptome Verdickung der Fußnägel, Plantarkeratosen und Fußsohlenschmerzen auf. Lokalisierte Steatozystome, Vellushaarzysten oder das diffuse Steatocystoma multiplex zeichnen die PC durch Keratin-17-Mutationen aus. Konnatale oder perinatale Zähne und follikuläre Hyperkeratosen an Ellenbogen, Knien und Rumpf sind ebenfalls häufig mit einer Mutation in KRT17 vergesellschaftet. Wir berichten über eine 40-jährige Patientin mit Steatocystoma multiplex, Verdickung und distaler Dystrophie aller Nägel, schmerzhaften Plantarkeratosen und palmoplantarer Hyperhidrose. Molekulargenetisch konnte mittels Next-Generation-Sequencing eine Mutation im Exon 1 des KRT17-Gens als ursächlich nachgewiesen werden.
Implementierung der Ultraschallausbildung in das Kerncurriculum des Medizinstudiums – das Ulmer Modell
Authors: Pfahler Matthias , Baumann Sven , Schuhbaur Jasmin , Kratzer Wolfgang ,   für die Dozenten im Kerncurriculum Sonografie
Published: February 2019

ZusammenfassungDie Sonografie ist neben der konventionellen Röntgenaufnahme die am häufigsten verwendete diagnostische Methode im klinischen Alltag. Bei angehenden Ärzten besteht besonders im Umgang mit der Sonografie eine Lücke zwischen den gestiegenen Anforderungen im klinischen Alltag und den bisher erworbenen Fähigkeiten. In dieser Arbeit möchten wir den Aufbau unseres Sonografie-Kurses und die Implementierung in das Ulmer Kerncurriculum des Medizinstudiums vorstellen. Der Sonografie-Kurs basiert auf zwei Säulen. Das Sonografie-Seminar (Säule 1) hat Vorlesungscharakter und vermittelt regelmäßig fächerübergreifend die theoretischen Inhalte, Grundlagen und möglichen Anwendungsgebiete der Sonografie während 13 Terminen à 45 Minuten. Das Praktikum (Säule 2) besteht aus vier Terminen von je zwei Stunden. Die Gruppen mit vier Studierenden werden jeweils von einem studentischen Tutor betreut. Vermittelt werden neben den technischen Grundlagen und einer Einführung in die Gerätekunde die Organsysteme Leber, Gallenblase und Gallenwege, Nieren und Nebennieren, Milz, Pankreas sowie abdominelle Gefäße und Lymphknoten. Der Schwerpunkt dabei liegt auf den realitätsnahen Übungen mit High-end-Ultraschallgeräten in Kleingruppen mit einer abschließenden praktischen Prüfung. Der Kursaufbau und -ablauf wird von den Studierenden insgesamt als sehr positiv evaluiert.