bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular insights into symbiosis—mapping sterols in a marine flatworm-algae-system using high spatial resolution MALDI-2-MS imaging with ion mobility separation
Authors: Bien Tanja , Hambleton Elizabeth A. , Dreisewerd Klaus , Soltwisch Jens 
Published: December 2020

AbstractWaminoa sp. acoel flatworms hosting Symbiodiniaceae and the related Amphidinium dinoflagellate algae are an interesting model system for symbiosis in marine environments. While the host provides a microhabitat and safety, the algae power the system by photosynthesis and supply the worm with nutrients. Among these nutrients are sterols, including cholesterol and numerous phytosterols. While it is widely accepted that these compounds are produced by the symbiotic dinoflagellates, their transfer to and fate within the sterol-auxotrophic Waminoa worm host as well as their role in its metabolism are unknown. Here we used matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging combined with laser-induced post-ionization and trapped ion mobility spectrometry (MALDI-2-TIMS-MSI) to map the spatial distribution of over 30 different sterol species in sections of the symbiotic system. The use of laser post-ionization crucially increased ion yields and allowed the recording of images with a pixel size of 5 μm. Trapped ion mobility spectrometry (TIMS) helped with the tentative assignment of over 30 sterol species. Correlation with anatomical features of the worm, revealed by host-derived phospholipid signals, and the location of the dinoflagellates, revealed by chlorophyll a signal, disclosed peculiar differences in the distribution of different sterol species (e.g. of cholesterol versus stigmasterol) within the receiving host. These findings point to sterol species-specific roles in the metabolism of Waminoa beyond a mere source of energy. They also underline the value of the MALDI-2-TIMS-MSI method to future research in the spatially resolved analysis of sterols.
Echinocandins: structural diversity, biosynthesis, and development of antimycotics
Authors: Hüttel Wolfgang 
Published: December 2020

Abstract
Echinocandins are a clinically important class of non-ribosomal antifungal lipopeptides produced by filamentous fungi. Due to their complex structure, which is characterized by numerous hydroxylated non-proteinogenic amino acids, echinocandin antifungal agents are manufactured semisynthetically. The development of optimized echinocandin structures is therefore closely connected to their biosynthesis. Enormous efforts in industrial research and development including fermentation, classical mutagenesis, isotope labeling, and chemical synthesis eventually led to the development of the active ingredients caspofungin, micafungin, and anidulafungin, which are now used as first-line treatments against invasive mycosis. In the last years, echinocandin biosynthetic gene clusters have been identified, which allowed for the elucidation but also engineering of echinocandin biosynthesis on the molecular level. After a short description of the history of echinocandin research, this review provides an overview of the current knowledge of echinocandin biosynthesis with a special focus of the diverse structural elements, their biosynthetic background, and structure−activity relationships.

Key points
• Complex and highly oxidized lipopeptides produced by fungi.
• Crucial in the design of drugs: side chain, solubility, and hydrolytic stability.
• Genetic methods for engineering biosynthesis have recently become available.
Intra-tumoural lipid composition and lymphovascular invasion in breast cancer via non-invasive magnetic resonance spectroscopy
Authors: Cheung Sai Man , Husain Ehab , Mallikourti Vasiliki , Masannat Yazan , Heys Steven , He Jiabao 
Published: December 2020

Abstract
Objectives
Despite improved survival due to new treatments, the 10-year survival rate in patients with breast cancer is approximately 75%. Lymphovascular invasion (LVI), a prognostic marker independent from histological grade and stage, can only be fully determined at final histological examination. Lipid composition is deregulated in tumour via de novo lipogenesis, with alteration in lipogenic genes in LVI. We hypothesise alteration in lipid composition derived from novel non-invasive spectroscopy method is associated with LVI positivity.

Methods
Thirty female patients (age 39–78) with invasive ductal carcinoma were enrolled, with 13 LVI negative and 17 LVI positive. Saturated, monounsaturated, polyunsaturated fatty acids and triglycerides (SFA, MUFA, PUFA and TRG) were quantified from ex vivo breast tumours freshly excised from patients on a 3 T clinical MRI scanner, and proliferative activity marker Ki-67 and serotonin derived histologically.

Results
There were significantly lower MUFA (p = 0.0189) in LVI positive (median: 0.37, interquartile range (IQR): 0.25–0.64) than negative (0.63, 0.49–0.96). There were significantly lower TRG (p = 0.0226) in LVI positive (1.32, 0.95–2.43) than negative (2.5, 1.92–4.15). There was no significant difference in SFA (p = 0.6009) or PUFA (p = 0.1641). There was no significant correlation between lipid composition against Ki-67 or serotonin, apart from a borderline negative correlation between PUFA and serotonin (r = - 0.3616, p = 0.0496).

Conclusion
Lipid composition might provide a biomarker to study lymphovascular invasion in breast cancer.

Key Points
• Monounsaturated fatty acids in lymphovascular invasion (LVI) positive invasive breast carcinoma were significantly lower than that in LVI negative.
• Triglycerides in LVI positive invasive breast carcinoma were significantly lower than that in LVI negative.
• Lipid composition from MR spectroscopy reflects the rate of de novo lipogenesis and provides a potential biomarker independent from histological grade and stage.
Adhärenz bei der Anti-VEGF-Therapie – Überlegungen und praktische Empfehlungen
Authors: Lommatzsch Albrecht , Eter Nicole , Ehlken Christoph , Lanzl Ines , Kaymak Hakan , Schuster Alexander K. , Ziemssen Focke 
Published: December 2020

Zusammenfassung
Hintergrund
Zahlreiche Studien haben eine mangelnde Therapieadhärenz als wichtigen Faktor identifiziert, der einer notwendigen Anzahl von Anti-VEGF-Behandlungen und somit einem besseren funktionellen Ergebnis entgegensteht.

Fragestellung
Der Beitrag diskutiert konkrete Maßnahmen, die das Risiko einer zu späten oder zu seltenen intravitrealen operativen Medikamenteneingabe (IVOM) im Sinne einer Unterbehandlung verringern.

Material und Methode
Im Rahmen einer Expertenrunde wurden relevante Parameter der Therapieadhärenz und Variablen identifiziert. Sinnvolle Abläufe strukturiert und organisatorischen Bereichen zugeordnet.

Ergebnisse
Die Zusammenstellung identifizierter Einflussfaktoren und sinnvoller Maßnahmen (Organisation, Transport, Kommunikation, Motivation) ermöglicht es Behandlern, die eigene Umsetzung der IVOM-Therapie in unterschiedlichen Bereichen zu optimieren. Regelmäßige Monitoring-Maßnahmen können den Umfang von Therapiepausen und -abbrüchen identifizieren. Für konkrete Kennzahlen (IVOM pro Zeitintervall, längstes Pausenintervall, Mindestabdeckung pro Zeit, Verzögerungen) wurde eine Auswirkung auf die Entwicklung der Sehfunktion nachgewiesen. Organisatorische Maßnahmen, die Schulung von Team und Zuweisern, die redundante und iterative Informationsweitergabe an Patienten haben sich in der Erfahrung von Experten bewährt. Die feste Integration dieser Prozesse in bestehende Strukturen wird durch die Arbeit mit Checklisten erleichtert.

Schlussfolgerungen
Eine Optimierung der Abläufe ist oft möglich, um die Adhärenz und somit die funktionellen Ergebnisse zu verbessern. Bisher fehlen jedoch noch interventionelle Studien, wie Adhärenz und Persistenz im deutschen Behandlungssetting erhöht werden.
The summer 2019 basaltic Vulcanian eruptions (paroxysms) of Stromboli
Authors: Giordano G. , De Astis G. 
Published: December 2020

AbstractStromboli is an active, open conduit mafic volcano, whose persistent mild Strombolian activity is occasionally punctuated by much stronger explosions, known as paroxysms. During summer 2019, the volcano unexpectedly produced one such paroxysm on July 3, followed by intense explosive and intermittent effusive activity culminating in a second paroxysm on August 28. Visual observations and the analysis of the fall deposits associated with the two paroxysms allowed us to reconstruct ballistic exit velocities of up to 160 m s−1. Plume heights of ~ 8.4 km and 6.4 km estimated for the two events correspond to mass eruption rates of 1.1 × 106 kg s−1 and 3.6 × 105 kg s−1, respectively. This is certainly an underestimate as directional pyroclastic flows into which mass was partitioned immediately formed, triggering small tsunamis at the sea entrance. The mass of ballistic spatters and blocks erupted during the July 3 event formed a continuous cover at the summit of the volcano, with a mass calculated at ~ 1.4 × 108 kg. The distribution of fall deposits of both the July 3 and August 28 events suggests that pyroclasts characterized by terminal fall velocities < 10–20 m s−1 remained fully suspended within the convective region of the plume and did not fall at distances closer than ca 1700 m to the vent. Based on the impulsive, blast-like phenomenology of paroxysms as well as the deposit distribution and type, paroxysms are classified as basaltic Vulcanian in style. The evolution of the summer 2019 eruptive events was not properly captured within the framework of the alert level system which is focused on tsunamigenic processes, and this is discussed so as to provide elements for the implementation of the reference scenarios and an upgrade of the system to take into account such events. In particular we find that, although still largely unpredictable, at least at operational time scales, and not necessarily tsunamigenic, Vulcanian eruptions and the subsequent evolution of the eruptive phenomena should be considered for the alert level system. This serves as a warning to the implementation of alert systems where the unexpected needs to be taken into account, even at systems that are believed to be relatively “predictable” as is the case at many persistently active, open vent mafic systems.
Perceptions on the management of varices and on the use of albumin in patients with cirrhosis among GI specialists in Austria
Authors: Pfisterer Nikolaus , Schmidbauer Caroline , Riedl Florian , Maieron Andreas , Stadlbauer Vanessa , Hennlich Barbara , Schwarzer Remy , Puespoek Andreas , Bucsics Theresa , Effenberger Maria , Bota Simona , Gschwantler Michael , Peck-Radosavljevic Markus , Mandorfer Mattias , Madl Christian , Trauner Michael , Reiberger Thomas 
Published: December 2020

Summary
Background
Portal hypertension (PH) causes severe complications in patients with liver cirrhosis, such as variceal bleeding and ascites; however, data on the knowledge and perceptions on guideline recommendations for the management of varices and the use of albumin is scarce.

Methods
We designed two structured surveys on (i) the management of varices and (ii) the use of albumin for Austrian physicians of specialized Gastro-Intestinal (GI) centers. The interviewed physicians were confronted spontaneously and provided ad hoc responses to the questionnaire.

Results
In total, 158 surveys were completed. Interestingly, many specialists (30%) would recommend a follow-up gastroscopy after 1 year in patients with compensated cirrhosis without varices (i.e., overtreatment). For small varices, 81.5% would use non-selective beta blockers (NSBB) for primary prophylaxis (PP). For PP in patients with large varices, endoscopic band ligation (EBL) plus NSBB was preferred by 51.4% (i.e., overtreatment). Knowledge on the indication criteria for early TIPS (transjugular intrahepatic portosystemic shunt) was reported by 54.3%, but only 20% could report these criteria correctly. The majority (87.1%) correctly indicated a preference to use NSBB and EBL for secondary prophylaxis (SP).
The majority of participating gastroenterologists reported no restrictions on the use of albumin (89.8%) in their hospitals. Of the interviewed specialists, 63.6% would use albumin in patients with SBP; however, only 11.4% would use the doses recommended by guidelines. The majority of specialists indicated using albumin at the recommended doses for hepatorenal syndrome (HRS-AKI, 86.4%) and for large volume paracentesis (LVP, 73.3%). The individual responses regarding albumin use for infections/sepsis, hyponatremia, renal impairment, and encephalopathy were heterogeneous.

Conclusion
The reported management of PH and varices is mostly adherent to guidelines, but endoscopic surveillance in patients without varices is too intense and EBL is overused in the setting of PP. Knowledge on the correct use of early TIPS must be improved among Austrian specialists. Albumin use is widely unrestricted in Austria; however, albumin is often underdosed in established indications.
Long-term (> 10 years) clinical outcomes of instrumented posterolateral fusion for spondylolisthesis
Authors: Lehr A. M. , Delawi D. , van Susante J. L. C. , Verschoor N. , Wolterbeek N. , Oner F. C. , Kruyt M. C. 
Published: December 2020

Abstract
Purpose
Despite the rapid increase in instrumented spinal fusions for a variety of indications, most studies focus on short-term fusion rates. Long-term clinical outcomes are still scarce and inconclusive. This study investigated clinical outcomes > 10 years after single-level instrumented posterolateral spinal fusion for lumbar degenerative or isthmic spondylolisthesis with neurological symptoms.

Methods
Cross-sectional long-term follow-up among the Dutch participants of an international multicenter randomized controlled trial comparing osteogenic protein-1 with autograft. Clinical outcomes were assessed using the Oswestry Disability Index (ODI), EQ-5D-3L and visual analogue scale (VAS) for leg and back pain, as well as questions on satisfaction with treatment and additional surgery.

Results
The follow-up rate was 73% (41 patients). At mean 11.8 (range 10.1–13.7) years after surgery, a non-significant deterioration of clinical outcomes compared to 1-year follow-up was observed. The mean ODI was 20 ± 19, mean EQ-5D-3L index score 0.784 ± 0.251 and mean VAS for leg and back pain, respectively, 34 ± 33 and 31 ± 28. Multiple regression showed that diagnosis (degenerative vs. isthmic spondylolisthesis), graft type (OP-1 vs. autograft) and 1-year fusion status (fusion vs. no fusion) were not predictive for the ODI at long-term follow-up (p = 0.389). Satisfaction with treatment was excellent and over 70% of the patients reported lasting improvement in back and/or leg pain. No revision surgeries for non-union were reported.

Conclusion
This study showed favourable clinical outcomes > 10 years after instrumented posterolateral spinal fusion and supports spondylolisthesis with neurological symptoms as indication for fusion surgery.
Differentiating influenza from COVID-19 in patients presenting with suspected sepsis
Authors: D’Onofrio Valentino , Van Steenkiste Eveline , Meersman Agnes , Waumans Luc , Cartuyvels Reinoud , Van Halem Karlijn , Messiaen Peter , Gyssens Inge C. 
Published: December 2020

AbstractThere is a need for a quick assessment of severely ill patients presenting to the hospital. The objectives of this study were to identify clinical, laboratory and imaging parameters that could differentiate between influenza and COVID-19 and to assess the frequency and impact of early bacterial co-infection. A prospective observational cohort study was performed between February 2019 and April 2020. A retrospective cohort was studied early in the COVID-19 pandemic. Patients suspected of sepsis with PCR-confirmed influenza or SARS-CoV-2 were included. A multivariable logistic regression model was built to differentiate COVID-19 from influenza. In total, 103 patients tested positive for influenza and 110 patients for SARS-CoV-2, respectively. Hypertension (OR 6.550), both unilateral (OR 4.764) and bilateral (OR 7.916), chest X-ray abnormalities, lower temperature (OR 0.535), lower absolute leukocyte count (OR 0.857), lower AST levels (OR 0.946), higher LDH (OR 1.008), higher ALT (OR 1.044) and higher ferritin (OR 1.001) were predictive of COVID-19. Early bacterial co-infection was more frequent in patients with influenza (10.7% vs. 2.7%). Empiric antibiotic usage was high (76.7% vs. 84.5%). Several factors determined at presentation to the hospital can differentiate between influenza and COVID-19. In the future, this could help in triage, diagnosis and early management. Clinicaltrial.gov Identifier: NCT03841162
Development of a data-driven model for spatial and temporal shallow landslide probability of occurrence at catchment scale
Authors: Bordoni M. , Vivaldi V. , Lucchelli L. , Ciabatta L. , Brocca L. , Galve J. P. , Meisina C. 
Published: December 2020

AbstractA combined method was developed to forecast the spatial and the temporal probability of occurrence of rainfall-induced shallow landslides over large areas. The method also allowed to estimate the dynamic change of this probability during a rainfall event. The model, developed through a data-driven approach basing on Multivariate Adaptive Regression Splines technique, was based on a joint probability between the spatial probability of occurrence (susceptibility) and the temporal one. The former was estimated on the basis of geological, geomorphological, and hydrological predictors. The latter was assessed considering short-term cumulative rainfall, antecedent rainfall, soil hydrological conditions, expressed as soil saturation degree, and bedrock geology. The predictive capability of the methodology was tested for past triggering events of shallow landslides occurred in representative catchments of Oltrepò Pavese, in northern Italian Apennines. The method provided excellently to outstanding performance for both the really unstable hillslopes (area under ROC curve until 0.92, true positives until 98.8%, true negatives higher than 80%) and the identification of the triggering time (area under ROC curve of 0.98, true positives of 96.2%, true negatives of 94.6%). The developed methodology allowed us to obtain feasible results using satellite-based rainfall products and data acquired by field rain gauges. Advantages and weak points of the method, in comparison also with traditional approaches for the forecast of shallow landslides, were also provided.
In vivo comparison of braided (Accero) and laser-cut intracranial stents (Acclino, Credo): evaluation of vessel responses at subacute and mid-term follow-up in a rabbit model
Authors: Mühl-Benninghaus Ruben , Tomori Toshiki , Krajewski Stefanie , Dietrich Philipp , Simgen Andreas , Yilmaz Umut , Brochhausen Christoph , Kießling Mara , Reith Wolfgang , Cattaneo Giorgio 
Published: December 2020

AbstractThis study aimed to investigate in vivo two stent technologies, with particular emphasis on thrombogenicity and inflammatory vessel remodeling processes. The micro-stents tested in this study were developed for intracranial aneurysm treatment. In our study twelve, New Zealand white rabbits were divided into two groups: 18 laser-cut stents (LCS) and 18 braided stents (BS) were impanated without admiration of antiplatelet medication. Three stents were implanted into each animal in the common carotid artery, subclavian artery, and abdominal aorta. Digital subtraction angiography was performed before and after stent implantation and at follow-up for the visualization of occurring In-stent thromboembolism or stenosis. The Stents were explanted for histopathological examination at two different timepoints, after 3 and 28 days. Angiographically neither in-stent thrombosis nor stenosis for both groups was seen. There was a progressive increase in the vessel diameter, which was more pronounced for BS than for LCS. We detected a higher number of thrombi adherent to the foreign material on day 3 for BS. On day 3, the neointima was absent, whereas the complete formation observed was on day 28. There was no significant difference between both groups regarding the thickness of the neointima. The in vivo model of our study enabled the evaluation of blood and vessel reactions for two different stent technologies. Differences in vessel dimension and tissue around the stents were observed on day 28. Histological analysis on day 3 enabled the assessment of thrombotic reactions, representing an important complementary result in long-term studies.
States in the decomposition of verbal predicates
Authors: Spathas Giorgos , Michelioudakis Dimitris 
Published: December 2020

AbstractThis paper proposes a new diagnostic for the detection of stative sub-events in the decomposition of verbal predicates. The diagnostic is based on a certain type of presupposition triggered by additive operators like Greekke‘also’, which we call Stative Presuppositions. It is argued that the generation of such Stative Presuppositions requires the existence of a syntactically accessible constituent that denotes a predicate of states that additive operators can take scope over. We investigate the distribution of Stative Presuppositions and observe that not all verbs that support inferences to a result state give rise to them. Based on this distribution we argue for a non-uniform analysis of result verbs; whereas some verbs require an event-decompositional analysis, others are better captured by scalar- and incrementality-based analyses. We cast our analysis in the framework of Distributed Morphology and propose to explain non-uniformity based on how different types of verbal roots interact with verbal functional material. Moreover, treating roots as the locus of encyclopedic information explains lexical variation in the generation of Stative Presuppositions within sub-classes of result verbs. We strengthen our conclusions by considering and rejecting alternative syntactic and semantic mechanisms for generating Stative Presuppositions. We conclude that the availability of Stative Presuppositions with additive operators is currently the most reliable diagnostic for the detection of syntactically accessible result states in verbal decomposition.
The Child’s Right to a Voice
Authors: Archard David , Uniacke Suzanne 
Published: December 2020

AbstractThis article provides a philosophical analysis of a putative right of the child to have their expressed views considered in matters that affect them. Article 12 of the United Nations Convention on the Rights of the Child 1989 is an influential and interesting statement of that right. The article shows that the child’s ‘right to a voice’ is complex. Its complexity lies in the problem of contrasting an adult’s normative power of choice with a child’s weighted views, in the various senses in which we might consider the child’s views, and in the questions of how to weight those views and how their weighting makes a practical difference in coming to a decision. In so doing we criticise other accounts that simply regard a child’s views as having consultative value. We also make better sense of how we might weight a child’s views. The philosophical issues addressed in the article carry implications for how we might understand Article 12 that are not satisfactorily identified and addressed in the voluminous literature on Article 12 within childhood studies. These issues also have implications for how we might understand the distinction between adults and children in respect of powers of personal choice. We conclude by emphasising the importance and value of the right that Article 12 seeks to formally identify.