bluuebunny/crossref_metadata_2025 huggingface dataset:
Colluvial sediments originating from past land-use activities in the Erzgebirge Mountains, Central Europe: occurrence, properties, and historic environmental implications
Authors: Kaiser Knut , Tolksdorf Johann Friedrich , de Boer Anna Maartje , Herbig Christoph , Hieke Falk , Kasprzak Marek , Kočár Petr , Petr Libor , Schubert Matthias , Schröder Frank , Fülling Alexander , Hemker Christiane
Published: November 2021

Colluvial sediments originating from soil erosion on slopes have proven to constitute significant evidence for tracing past human impact on mountain landscapes. In the Central European Erzgebirge (Ore) Mountains, colluvial sediments are associated with specific landforms (footslopes, slope flattenings, dells) and cover a share of 11% (11,905 ha) of the regional soil landscape. Thirteen pedosedimentary sections with colluvial layers were investigated at five forested sites (520–730 m a.s.l.) within a context of mining archaeology, integrating data from pedology, archaeology, palaeobotany, and geochronology. The thickness of the gravel-bearing loamy, silty, and sandy colluvial layers is up to 70 cm, which are mostly located on top of the sections. The geochronological ages and archaeological data reveal a high to late medieval to post-medieval age of the colluvial sediments. Pollen data show a drastic decline of the mountain forests in the late twelfth to fifteenth centuries AD accompanied by an increase of pioneer trees and spruce at the expense of fir and beech. The primary cause of soil erosion and subsequent colluvial deposition at the sites investigated is medieval to post-medieval mining and other early industrial activities. A compilation of 395 radiocarbon and OSL ages, obtained from colluvial sediments at 197 upland sites in Central Europe, shows that anthropogenically initiated colluvial dynamics go as far back as the late Bronze Age to the early Iron Age. Most ages derive from the medieval to post-medieval period, corresponding to the general intensification of settlement and land-use activities including deforestation and widespread ore mining.
Habitability of the early Earth: liquid water under a faint young Sun facilitated by strong tidal heating due to a closer Moon
Authors: Heller René , Duda Jan-Peter , Winkler Max , Reitner Joachim , Gizon Laurent
Published: November 2021

Geological evidence suggests liquid water near the Earth’s surface as early as 4.4 gigayears ago when the faint young Sun only radiated about 70% of its modern power output. At this point, the Earth should have been a global snowball if it possessed atmospheric properties similar to those of the modern Earth. An extreme atmospheric greenhouse effect, an initially more massive Sun, release of heat acquired during the accretion process of protoplanetary material, and radioactivity of the early Earth material have been proposed as reservoirs or traps for heat. For now, the faint-young-Sun paradox persists as an important problem in our understanding of the origin of life on Earth. Here, we use the constant-phase-lag tidal theory to explore the possibility that the new-born Moon, which formed about 69 million years (Myr) after the ignition of the Sun, generated extreme tidal friction—and therefore, heat—in the Hadean and possibly the Archean Earth. We show that the Earth–Moon system has lost $${\sim }3~{\times }~10^{31}$$

∼
3

×

10
31

 J (99% of its initial mechanical energy budget) as tidal heat. Tidal heating of $${\sim }10\,\mathrm{W\,m}^{-2}$$

∼
10

W

m

-
2

through the surface on a time scale of 100 Myr could have accounted for a temperature increase of up to $$5\,^\circ $$

5

∘

C on the early Earth. This heating effect alone does not solve the faint-young-Sun paradox but it could have played a key role in combination with other effects. Future studies of the interplay of tidal heating, the evolution of the solar power output, and the atmospheric (greenhouse) effects on the early Earth could help in solving the faint-young-Sun paradox.
Darcy model with optimized permeability distribution (DMOPD) approach for simulating two-phase flow in karst reservoirs
Authors: Jamal Mohammad S. , Awotunde Abeeb A.
Published: November 2021

Darcy model fails to accurately model flow in karst reservoirs because the flow profiles in free-flow regions such as vugs, fractures and caves do not conform to Darcy’s law. Flows in karsts are often modelled using the Brinkman model. Recently, the DMOPD approach was introduced to reduce the complexity of modelling single-phase flow in Karst aquifers. Modelling two-phase flow using the Brinkman’s equation requires either a method of tracking the front or introducing the saturation component in the Brinkman’s equation. Both of these methods introduce further complexity to an already complex problem. We propose an alternative approach called the two-phase Darcy’s Model with optimized permeability distribution (TP-DMOPD) to model pressure and saturation distributions in karst reservoirs. The method is a modification to the DMOPD approach. Under the TP-DMOPD model, the caves are initially divided into zones and the permeability of each zone is estimated. During this stage of the TP-DMOPD model, the fluid inside the reservoir is assumed to be in a single-phase. Once the permeability distribution is obtained, the two-phase Darcy model is used to simulate flow in the reservoir. The example applications tested showed that the TP-DMOPD approach was able to model two-phase flow in karst reservoirs.
Comparative performance analysis of different swelling kinetic models for the evaluation of shale swelling
Authors: Lalji Shaine Mohammadali , Ali Syed Imran , Ahmed Rafiq , Hashmi Saud , Awan Zahoor Ul Hussain
Published: November 2021

Swelling of shale potentially occurs when it is exposed to water-based drilling fluid. The migration of hydrogen ions (H+) in the nano-interlayered platelets of the shale rock is utterly responsible for the swelling behavior in the shale. Conventionally, swelling behavior of any shale formation can be experimentally determined by linear dynamic swell meter. However, it is extremely important to validate these experimental results; hence, this research study aims in conducting a comparative performance analysis for different kinetic models, namely Peleg’s model, first-order exponential association equation and pseudo-second-order kinetic model, and a newly developed scaling swelling model in estimating the experimental results of three different shale samples, namely Talhar, Ranikot and Murree, obtained from different regions of Pakistan. It was found that the performance of the scaling swelling model was the most accurate in predicting the experimental swelling results with accuracy greater than 95% in all the three samples. Peleg’s model is found to be the most inaccurate with $$p \mathrm{values}< \alpha (0.05)$$

p
values
<
α
(
0.05
)

in all the three formations. The equilibrium state in all the three samples was unable to attain by the use of this model. This clearly shows that the transient states continue throughout the course of experimentation, thus demonstrating a higher water activity in the shale samples. Moreover, when comparison was made between the two remaining kinetic adsorption models, it was perceived that pseudo-second-order kinetic was far superior to first-order exponential association equation with $${\mathrm{mean}}_{\mathrm{model}}\simeq {\mathrm{mean}}_{\mathrm{experiment}}$$

mean
model

≃

mean
experiment

and less dispersion in the dataset. Nevertheless, the performance of this model also suffers with the increase in clay content. Furthermore, all these analyses were further validated by different statistical error analysis that includes MAE, APRE% and ANOVA.
Edukationsbedarfe von Kindern mit Brandverletzungen und deren Eltern – Ein Scoping Review
Authors: Meyer Julia , Buchmann Julia , Ritter-Herschbach Madeleine , Reinsperger Nicole , Zilezinski Max
Published: November 2021

Hintergrund

Brandverletzungen bei Kindern sind für die ganze Familie ein traumatisches Erlebnis und mit emotionalen und psychischen Auswirkungen sowie schmerzhaften medizinischen Eingriffen verbunden. Bei Kindern mit einer schwerwiegenden thermischen Verletzung beginnt die edukative Begleitung der Familien bereits bei der Aufnahme ins Krankenhaus und setzt das Wissen um die Bedarfe der Betroffenen voraus.

Ziel

Aufzeigen der Edukationsbedarfe von Kindern mit Brandverletzung und deren Eltern im stationären Setting.

Methode

Es wurde ein Scoping Review durchgeführt. Die Methodik orientiert sich an dem sechsstufigen Framework von Arksey und O’Malley. Eingeschlossen wurden Studien, die Kinder mit Brandverletzungen im Alter von 0 bis 18 Jahren sowie deren Eltern während des Krankenhausaufenthaltes berücksichtigen. Die Literaturrecherche wurde in MEDLINE via PubMed durchgeführt, und Referenzen wurden gesichtet.

Ergebnisse

Insgesamt konnten 3576 Studien identifiziert werden, von denen 21 Studien eingeschlossen wurden. Es ergaben sich 10 qualitative, 7 quantitative Studien sowie 4 Übersichtsarbeiten. In den meisten Studien berichten die betroffenen Kinder und deren Eltern von einem Informations- und Aufklärungsbedarf und dem Wunsch nach emotionaler und psychosozialer Entlastung. Der überwiegende Teil der Studien fokussiert die Erfahrungen von Eltern von Kindern mit Brandverletzungen.

Schlussfolgerung

Für Betroffene ergeben sich im Rahmen der stationären Versorgung unterschiedliche Bedarfe zu verschiedenen Zeitpunkten. Besondere Etappen (z. B. die Entlassung, Verbandwechsel) erfordern einen erhöhten Bedarf an emotionaler und psychosozialer Entlastung, Unterstützung und/oder Information und Aufklärung.
Incipient sliding of adhesive contacts
Authors: Pérez-Ràfols Francesc , Nicola Lucia
Published: November 2021

A model is proposed herein to investigate the incipient sliding of contacts in the presence of both friction and adhesion, where the interfacial response is modeled based on traction-separation laws. A Maugis-like parameter is defined to characterize the response in the tangential direction. Subsequently, the model is used to investigate the contact between a smooth cylinder and a flat body, where adhesion-friction interactions are strong. A range of behaviors are observed when a tangential displacement is imposed: When the parameter is low, the contact pressure exhibits a relatively constant profile; when it is high, a pressure spike is observed at the edge of the contact. This difference is caused by a significant interface compliance in the former case, which limits the amount of slip. The results for the mid-range values of the Maugis-like parameter can qualitatively replicate various experiments performed using polydimethylsiloxane (PDMS) balls.
Methane emissions from northern lakes under climate change: a review
Authors: Li Lingling , Xue Bin
Published: November 2021

Northern lakes are important sources of CH4 in the atmosphere under the background of permafrost thaw and winter warming. We synthesize studies on thermokarst lakes, including various carbon sources for CH4 emission and the influence of thermokarst drainage on carbon emission, to show the evasion potential of ancient carbon that stored in the permafrost and CH4 emission dynamics along with thermokarst lake evolution. Besides, we discuss the lake CH4 dynamics in seasonally ice-covered lakes, especially for under-ice CH4 accumulation and emission during spring ice melt and the possible influential factors for CH4 emission in ice-melt period. We summarize the latest findings and point out that further research should be conducted to investigate the possibility of abundant ancient carbon emission from thermokarst lakes under climate warming and quantify the contribution of ice-melt CH4 emission from northern lakes on a large scale.
The Rocky Road from Experience to Expression of Emotions—Women’s Anger About Sexism
Authors: Sasse Julia , van Breen Jolien A. , Spears Russell , Gordijn Ernestine H.
Published: November 2021

We investigated women’s anger expression in response to sexism. In three studies (Ns = 103, 317, and 241), we tested the predictions that women express less anger about sexism than they experience—the anger gap—and that the anger expressed by women is associated with instrumental concerns, specifically perceived costs and benefits of confronting sexism. To estimate the specificity of the proposed gap, we compared women’s anger reactions to men’s anger reactions as well as anger reactions to sadness reactions. Across studies, we found support for the anger gap, that is, lower anger expression than experience, and the gap was more pronounced for women than for men (Study 3). Surprisingly, a gap also occurred in sadness reactions. Regarding instrumental concerns, there was converging evidence that expressed anger was negatively associated with individual costs. We also investigated whether anger expression can be encouraged through women’s identification with feminists (Studies 1 and 2) and support by other women (Study 2); yet, we found no evidence. We conclude that, to understand women’s—and men’s—reactions to sexism, it is critical not to mistake their emotion expression for how they really feel, but instead to also consider strategic concerns.
Downregulation of EZH2 in Trophoblasts Induces Decidual M1 Macrophage Polarization: a Potential Cause of Recurrent Spontaneous Abortion
Authors: Shang Ye , Wu Shujuan , Li SaiJiao , Qin Xiaolin , Chen Jiao , Ding Jinli , Yang Jing
Published: November 2021

Macrophages are known to be pivotal for ensuring the establishment of the immune tolerance microenvironment at the maternal–fetal interface. In particular, trophoblasts stay in close contact with decidual macrophages (DMs), which have been reported to play an active role in the modulation of the polarization of DMs. Thus, any dysfunction of trophoblasts might be associated with certain pregnancy‐related complications, such as recurrent spontaneous abortion (RSA). Enhancer of zeste homolog 2 (EZH2) is an important epigenetic regulatory gene that has been previously shown to be related to immune regulation. The present study assessed the expression of EZH2 in villi tissue obtained from healthy controls and RSA patients. Trophoblasts conditioned medium was collected to incubate macrophages differentiated from the THP‐1 cell line. The expression and function of EZH2 in trophoblasts were knocked down either by the use of siRNA or GSK126 as an inhibitor. Our results show a significant decrease in the expression of EZH2 in villi tissue from RSA patients as compared to healthy controls. Further, the inhibition of expression or function of EZH2 in trophoblasts promoted M1 macrophage polarization, which might be involved in the pathogenesis of RSA. Moreover, the suppression of EZH2 was found to affect the secretion of immune and inflammatory cytokines in trophoblasts. Altogether, these results indicated the importance of EZH2 in the regulation of immune functions of trophoblasts and thus highlighted its potential to be explored as a therapeutic target to prevent and treat pregnancy loss.
Outcomes of Patients Diagnosed With Chronic Lymphocytic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: Results From a Tertiary Care Center
Authors: Linn Swe M. , Nampoothiri Ram V. , Chen Carol , Pasic Ivan , Al-Shaibani Zeyad , Lam Wilson , Law Arjun D. , Michelis Fotios V. , Kim Dennis D.H. , Gerbitz Armin , Lipton Jeffrey , Kumar Rajat , Mattsson Jonas , Viswabandya Auro
Published: November 2021

Background:

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is currently the only curative treatment for patients with chronic lymphocytic leukemia (CLL).

Methods:

We analyzed the outcomes of 93 patients (median age: 52 years) who underwent allo-HCT at our center between 1989 and 2019.

Results:

After a median follow-up of 35 months, relapse was observed in 15.1% (n = 14) patients. The estimated 2-year non-relapse mortality, relapse-free survival, and overall survival (OS) were 38.1%, 54.2%, and 58.7%, respectively. The ECOG performance status ≥ 2 (hazard ratio [HR]: 4.1; p = .001) and use of total body irradiation (in a myeloablative conditioning regimen; HR: 2.64; p = .005) were predictive of poor OS after multivariable analysis. The occurrence of sinusoidal obstruction syndrome/veno-occlusive disease post-transplant was associated with poor survival (p = .001).

Conclusion:

Although the use of kinase and bcl2 inhibitors may result in a decrease in the number and need of transplants, allo-HCT remains a viable option in selected patients with high-risk CLL and good performance status.
Ascending aortic pseudoaneurysm following Norwood Stage 1 surgery in an infant
Authors: Yilmaz Mustafa , Ecevit Ata Niyazi , Atalay Atakan
Published: November 2021

Pseudoaneurysms of the ascending aorta are rarely seen in paediatric patients. They may occur following complex cardiovascular surgery and are associated with a high risk of mortality due to their nature of spontaneous rupture. In this case report, we discuss a 1-year-old paediatric patient with an ascending aortic pseudoaneurysm following Norwood Stage 1 surgery with Sano modification for hypoplastic left heart syndrome and the patient’s successful recovery following aneurysmectomy with Norwood Stage 2 operation.
Impact of work resumption on air quality after subsiding of COVID-19: evidence from China
Authors: Zhang Guoguo , Zhu Jingci , Luo Weijie , Zhang Honghong
Published: November 2021

This paper explores the short-run impact of work resumption, extensively launched on February 10, 2020 in China, on air quality after the subsiding of COVID-19. Utilizing the data of 1012 air-quality monitoring sites in 233 cities derived from the Real-time Release Air Quality Platform and the difference-in-differences method, we find that alternative measures of air quality index in non-Hubei provinces increase significantly, compared with those in Hubei province which was temporarily not allowed work resumption due to the severity of epidemic. Specifically, our results reveal a rise in AQI of 11.28 per cent, in PM2.5 of 12.47 per cent, in PM10 of 10.49 per cent, and in NO2 of 23.64 per cent, relative to the baseline mean. Moreover, the deterioration of air quality is found to be caused by intracity rather than intercity migration.
Maternal carbohydrate intake during pregnancy is associated with child peripubertal markers of metabolic health but not adiposity
Authors: Mulcahy Molly C , Tellez-Rojo Martha Maria , Cantoral Alejandra , Solano-González Maritsa , Baylin Ana , Bridges Dave , Peterson Karen E , Perng Wei
Published: November 2021

Objective:

To examine the associations of trimester-specific maternal prenatal carbohydrate (CHO) intake with offspring adiposity and metabolic health during peripuberty.

Design:

Prospective cohort study in which maternal dietary intake was collected via validated FFQ during each trimester. Offspring adiposity and metabolic biomarkers were evaluated at age 8–14 years. We used multivariable linear regression to examine associations between total energy-adjusted maternal CHO intake and offspring BMI z-score, skinfold thickness and metabolic syndrome risk z-score calculated as the average of waist circumference, fasting glucose, fasting C-peptide, TAG:HDL and systolic blood pressure + diastolic blood pressure/2.

Setting:

Mexico City, Mexico

Participants:

237 mother–child pairs in the Early Life Exposure in Mexico to Environmental Toxicants cohort.

Results:

We found non-linear associations of maternal CHO intake during pregnancy with offspring metabolic health during peripuberty. After adjusting for maternal age, and child age, sex and pubertal status, children whose mothers were in the fourth v. first quartile of total CHO intake during the third trimester had 0·42 (95 % CI –0·01, 0·08) ng/ml lower C-peptide and 0·10 (95 % CI –0·02, 0·22) units lower C-peptide insulin resistance (CP-IR). We found similar magnitude and direction of association with respect to net CHO intake during the first trimester and offspring C-peptide and CP-IR. Maternal CHO intake during pregnancy was not associated with offspring adiposity.

Conclusions:

In this study of mother–child pairs in Mexico City, children born to women in the highest quartile of CHO intake during pregnancy had lowest C-peptide and CP-IR during peripuberty. Additional research is warranted to replicate and identify mechanisms.
Aufgabenteilung in der ambulanten Versorgung von Menschen mit Demenz
Authors: Drewelow Eva , Altiner Attila , Biedenweg Bianca , Buchhholz Maresa , Henning Esther , Hoffmann Wolfgang , Kohlmann Thomas , Lücker Petra , Michalowsky Bernhard , Oppermann Roman F. , Rädke Anika , Zorn Daniela , Wollny Anja
Published: November 2021

Zusammenfassung. Hintergrund: Menschen mit Demenz (MmD) zu versorgen, fordert Gesundheitssystem und pflegende Angehörige heraus und ist nur durch interprofessionelle medizinische und pflegerische Betreuung zu bewältigen. Fragestellung / Ziel: Die AHeaD-Studie untersuchte Einstellungen von Hausärzt_innen (HÄ) und Pflegefachpersonen (PFP) zur Übertragung bislang hausärztlich ausgeführter Tätigkeiten an PFP in der ambulanten Versorgung von MmD. Methoden: In vier Fokusgruppendiskussionen mit 10 HÄ und 13 PFP wurden Einstellungen zur Übertragung bestimmter Tätigkeiten inhaltsanalytisch untersucht sowie Chancen und Barrieren einer Einführung identifiziert. Ergebnisse: HÄ befürworteten die Übertragung bestimmter Tätigkeiten wie Blutentnahmen, Assessments, deren Monitoring oder Folgeverordnungen für Pflegehilfsmittel. „Klassische“ ärztliche Aufgaben (z. B. Diagnostik von Erkrankungen, Erstverordnung von Medikamenten) wurden weiter in hausärztlicher Hand gesehen. PFP forderten für die Beziehung zwischen PFP und HA mehr Wertschätzung und Anerkennung und bemängelten fehlendes Vertrauen sowie unzureichende Kommunikation. Beide Seiten verwiesen auf knappe Zeitbudgets, die sich kaum am reellen Bedarf der MmD orientierten. Schlussfolgerung: Die Umsetzung einer Aufgabenneuverteilung erfordert die Schaffung eines gesetzlichen und finanziellen Rahmens, zeitlicher Ressourcen, konkreter Aufgabenbeschreibungen sowie die stärkere Zusammenarbeit der involvierten Berufsgruppen. Innovative Konzepte könnten zum sinnvollen Einsatz der Ressourcen beider Berufsgruppen beitragen und die Versorgung von MmD stärken.
Palliative Radiotherapie – ein wichtiges Instrument bei schmerzhaften Knochenmetastasen
Authors: Guninski Ricarda Stella , Blum David , Guckenberger Matthias
Published: November 2021

Zusammenfassung. Viele Tumorpatientinnen und -patienten leiden im fortgeschrittenen Stadium unter Metastasen, besonders häufig an Knochenmetastasen, welche als dritthäufigste Metastasierungslokalisation oft bei Prostata-, Mamma- und Lungenkarzinomen auftreten und zu Schmerzen, pathologischen Frakturen und Myelonkompression mit Funktionsausfällen führen können. Häufig kommt es zu einer raschen Einschränkung der Lebensqualität der vulnerablen Patientinnen und Patienten. Die Behandlung erfolgt im interdisziplinären Setting mit Onkolog_innen, Palliativ- und Schmerzmediziner_innen, Radio-Onkolog_innen sowie Chirurg_innen. Eine lokale Radiotherapie erzielt eine rasche und nebenwirkungsarme Symptomkontrolle mit Verbesserung der Lebensqualität: basierend auf randomisierten Studien erreicht die analgetische Radiotherapie von Knochenmetastasen eine Ansprechrate von 60–80 %.
Compassionate Cities: Stärkung der sozialen Ressourcen in den Gemeinden für ein gemeinsam getragenes Lebensende
Authors: Michel Claudia , Felber Sibylle J. , Affolter Barbara , Greusing Marie-Hélène , Eychmüller Steffen
Published: November 2021

Zusammenfassung. Häufig haben Menschen am Lebensende den Wunsch, möglichst lange zuhause zu bleiben. Um dies vermehrt zu ermöglichen, benötigt es neben Gesundheitsfachpersonen, die Betroffene und ihre Angehörigen begleiten, auch Bildungsangebote zur Stärkung der Ressourcen im Umgang mit dem Lebensende. Im Rahmen des Projektes «Compassionate City Lab der Berner Bevölkerung» wurden Erfahrungen im Umgang mit dem Lebensende gesammelt und veröffentlicht sowie ein Kursangebot zur gesundheitlichen Vorausplanung für Menschen im dritten Lebensalter und betreuende Angehörige entwickelt. Das Projekt ist finanziert von Gesundheitsförderung Schweiz und getragen von einer Partnerschaft zwischen Berner Hochschulen und spezialisierten Institutionen der Palliative Care, der Grundversorgung, des Gemeinwesens sowie Ehrenamtlichen in der Stadt Bern und im Berner Oberland.
Telemedizin in der Palliative Care: Digitale Kommunikation in einem beziehungsbasierten Fachgebiet – ist das sinnvoll?
Authors: Ebneter Andreas Samuel , Fliedner Monica , Trapp Daniela , Ramseier Friederike , Sauter Thomas C. , Eychmüller Steffen
Published: November 2021

Zusammenfassung. Telemedizin in der Palliative Care ist insbesondere in Ländern mit grossen geografischen Distanzen etabliert. Am häufigsten werden digitale Kommunikationsformen verwendet (virtuelle Konsultationen), was von den Patientinnen und Patienten sowie den Angehörigen gut akzeptiert wird. Der Hauptnutzen liegt im erleichterten Kontakt zwischen Fachpersonen und Betroffenen im ambulanten Bereich. Das kann zu einer Stressreduktion bei Patientinnen und Patienten (weniger Reisestress, bessere Verfügbarkeit) sowie einer Reduktion der Betreuungslast bei Angehörigen führen. Ob gegenüber der Präsenzvisite ein zusätzlicher Nutzen bezüglich körperlicher Symptomkontrolle, Lebensqualität und Kosten besteht, ist unklar. Mögliche Risiken oder Bedenken können bezüglich der fehlenden physischen Interaktion und der Datensicherheit bestehen. Inwiefern Tele-Palliativversorgung in einem Gesundheitssystem hoher Dichte sinnvoll ist, ist schwierig vorauszusagen. Diese neuen Tools sollten also der Situation angepasst und wissenschaftlich begleitet angewendet werden.
Pädiatrische Palliative Care – wenn das Ende mit dem Anfang kommt
Authors: Streuli Jürg C. , von Mengershausen Ursula
Published: November 2021

Zusammenfassung. Palliative Care wird normalerweise nicht mit dem Kindes- und Jugendalter in Verbindung gebracht. Trotzdem leben allein im deutschsprachigen Europa mehr als 50 000 Kinder mit lebensverkürzenden Krankheiten und jährlich sterben etwa 5000 Kinder. Palliative Care für Kinder und Jugendliche (PPC) ist eine Haltung, die niemandem aufgezwungen werden darf, sondern gelebt werden muss; bei komplex-chronischen Krankheiten oftmals über viele Jahre. Eine erfolgreiche und nachhaltige Implementierung von PPC basiert deshalb auf einer wertschätzenden Zusammenarbeit zwischen verschiedenen Teams und den betroffenen Familien getreu der hier vorgestellten Quadriga einer umfassenden Symptomkontrolle mit Neugier, Geduld, Aktivität und persönliche Zurückhaltung. Notwendige Grundlagen wie der Betreuungsplan, der interprofessionelle Hausbesuch und der runde Tisch sowie die 24-Stunden-Erreichbarkeit werden ebenso vorgestellt wie eine Triage-Technik und Advanced Care Management.
Crustal Seismic Attenuation of the Central United States and Intermountain West
Authors: Levandowski Will , Boyd Oliver Salz , AbdelHameid Danya , McNamara Daniel Edward
Published: November 2021

Seismic attenuation is generally greater in the western United States (WUS) than the central and eastern United States (CEUS), but the nature of this transition or location of this boundary is poorly constrained. We conduct crustal seismic (Lg) attenuation tomography across a region that stretches from the CEUS across the Rocky Mountains to the Basin and Range using a total of 115,870 amplitude measurements from 106 earthquakes recorded on 544 stations across five frequency bands spanning 0.5–16 Hz. Similar to previous studies, we find higher attenuation in the WUS (Q0 ∼ 190) than the nominally CEUS (Q0 ∼ 250) and comparatively high attenuation on the Gulf Coast (Q0 ∼ 175). Our models defy simple east versus west regionalization, however. Heterogeneity within the Rocky Mountain region—low attenuation in the Colorado Plateau interior and Wyoming Craton (Q0 ∼ 230) compared to high attenuation in the southern Rockies (Q0 ∼ 110)—exceeds the gross differences between the CEUS and western United States. These province‐scale patterns are readily interpreted in terms of intrinsic attenuation. The boundary between the Colorado Plateau and Basin and Range hosts the highest attenuation imaged in the study area (Q0 ∼ 90), consistent with localized scattering across contrasting crustal structure. Focused high attenuation in the southern Rockies may represent the effects of represent in situ partial crustal melt. Within the CEUS, second‐order bands of comparatively high attenuation align with the Proterozoic Yavapai‐Mazatzal suture zone and Midcontinent Rift. This complex attenuation structure defies broad regionalization and suggests a need for path‐specific models near these boundaries and for critical infrastructure.
Determining the Source of the Explosive Sound Heard in Hokkaido, Japan, on 26 April 2021
Authors: Yamada Masumi
Published: November 2021

An explosive sound was heard over a wide area of Sapporo city, Hokkaido, Japan, on 26 April 2021. It was accompanied by minor shaking and was considered likely to be a sonic boom produced by a fireball. However, no luminous phenomenon was observed. We analyzed seismic data to identify the source of the sonic boom, and estimated the trajectory of the object from the associated signal arrival times. The source was located ∼100 km off the west coast of Hokkaido at an altitude of 50 km. The elevation angle was greater than 66° and the estimated velocity was higher than that of a fighter plane. Although the luminous phenomenon was not observed, the trajectory model suggested that the source of the sonic boom was not an aircraft and most likely a fireball. We compared trajectory models estimated from optical and seismic observations for past sonic boom events, and they were found to be in good agreement. Although our trajectory model is simplified and assumes that sound and the fireball have a constant speed, the model is highly accurate. The results show that seismic data can be used to estimate the trajectory of objects producing sonic booms, even when visual observations are unavailable.
Holocene Activity of the Xigeda Fault and Its Implications for the Crustal Deformation Pattern in the Southeastern Tibetan Plateau
Authors: Zhang Wei , Liu Yufa , Sun Haoyue , He Yulin , Ma Chao , Liu Shao , Yang Daibin
Published: November 2021

Intra‐block faults generally attract less attention because little slip occurs on them. However, some of them can host strong earthquakes and thus their faulting behaviors are also significant for assessing seismic risk and understanding crustal deformation patterns. The Xigeda fault is one of the intra‐block faults in the southeastern Tibetan Plateau and has generated twoM > 6 earthquakes in the past 70 years. Nevertheless, little is known about its faulting behavior, seismic hazard, and tectonic role. Focusing on this problem, we conducted field investigations, trench excavations, and shallow seismic exploration to characterize its fault activity. Our work reveals that the Xigeda fault slips left‐laterally at a rate of 0.8–1.6 mm/yr with a thrust component through high‐resolution landforms measuring and sample dating. The paleoseismic investigations determine the latest surface rupturing event along the Xigeda fault occurred between 1580 CE and 1970 CE, which is further determined as the 1732 earthquake with a reevaluated magnitude of 7.0–7.5. Therefore, the Xigeda fault is confirmed to be active in the Holocene and can generateM ≥ 7.0 earthquakes. Moreover, the Xigeda fault, along with the Yuanmou fault, makes up the shortage of slip rates between the Anninghe and Zemuhe faults and plays an important role in partitioning the slip along the Xianshuihe‐Xiaojiang fault system and accommodating the crustal deformation in the Sichuan‐Yunnan block. Additionally, our work suggests a crustal deformation pattern for the southeastern Tibetan Plateau that most of the crustal deformation within tectonic blocks is still expressed by slipping along significant intra‐block faults.
O-GlcNAcylation of Sox2 at threonine 258 regulates the self-renewal and early cell fate of embryonic stem cells
Authors: Kim Dong Keon , Lee Jang-Seok , Lee Eun Young , Jang Hansol , Han Suji , Kim Hee Yeon , Hwang In-Young , Choi Ji-Woong , Shin Hyun Mu , You Hye Jin , Youn Hong-Duk , Jang Hyonchol
Published: November 2021

Sox2 is a core transcription factor in embryonic stem cells (ESCs), and O-GlcNAcylation is a type of post-translational modification of nuclear-cytoplasmic proteins. Although both factors play important roles in the maintenance and differentiation of ESCs and the serine 248 (S248) and threonine 258 (T258) residues of Sox2 are modified by O-GlcNAcylation, the function of Sox2 O-GlcNAcylation is unclear. Here, we show that O-GlcNAcylation of Sox2 at T258 regulates mouse ESC self-renewal and early cell fate. ESCs in which wild-type Sox2 was replaced with the Sox2 T258A mutant exhibited reduced self-renewal, whereas ESCs with the Sox2 S248A point mutation did not. ESCs with the Sox2 T258A mutation heterologously introduced using the CRISPR/Cas9 system, designated E14-Sox2TA/WT, also exhibited reduced self-renewal. RNA sequencing analysis under self-renewal conditions showed that upregulated expression of early differentiation genes, rather than a downregulated expression of self-renewal genes, was responsible for the reduced self-renewal of E14-Sox2TA/WT cells. There was a significant decrease in ectodermal tissue and a marked increase in cartilage tissue in E14-Sox2TA/WT-derived teratomas compared with normal E14 ESC-derived teratomas. RNA sequencing of teratomas revealed that genes related to brain development had generally downregulated expression in the E14-Sox2TA/WT-derived teratomas. Our findings using the Sox2 T258A mutant suggest that Sox2 T258 O-GlcNAc has a positive effect on ESC self-renewal and plays an important role in the proper development of ectodermal lineage cells. Overall, our study directly links O-GlcNAcylation and early cell fate decisions.
Interactions between gastric microbiota and metabolites in gastric cancer
Authors: Dai Daofeng , Yang Yan , Yu Jieqing , Dang Tianfeng , Qin Wenjing , Teng Lisong , Ye Jing , Jiang Hongqun
Published: November 2021

The development and progression of gastric cancer (GC) is greatly influenced by gastric microbiota and their metabolites. Here, we characterized the gastric microbiome and metabolome profiles of 37 GC tumor tissues and matched non-tumor tissues using 16s rRNA gene sequencing and ultrahigh performance liquid chromatography tandem mass spectrometry, respectively. Microbial diversity and richness were higher in GC tumor tissues than in non-tumor tissues. The abundance of Helicobacter was increased in non-tumor tissues, while the abundance of Lactobacillus, Streptococcus, Bacteroides, Prevotella, and 6 additional genera was increased in the tumor tissues. The untargeted metabolome analysis revealed 150 discriminative metabolites, among which the relative abundance of the amino acids, carbohydrates and carbohydrate conjugates, glycerophospholipids, and nucleosides was higher in tumor tissues compared to non-tumor tissues. The targeted metabolome analysis further demonstrated that the combination of 1-methylnicotinamide and N-acetyl-D-glucosamine-6-phosphate could serve as a robust biomarker for distinction between GC tumors and non-tumor tissues. Correlation analysis revealed that Helicobacter and Lactobacillus were negatively and positively correlated with the majority of differential metabolites in the classes of amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids, respectively, suggesting that Helicobacter and Lactobacillus might play a role in degradation and synthesis of the majority of differential metabolites in these classes, respectively. Acinetobacter, Comamonas, Faecalibacterium, Sphingomonas, and Streptococcus were also significantly correlated with many differential amino acids, carbohydrates, nucleosides, nucleotides, and glycerophospholipids. In conclusion, the differences in metabolome profiles between GC tumor and matched non-tumor tissues may be partly due to the collective activities of Helicobacter, Lactobacillus, and other bacteria, which eventually affects GC carcinogenesis and progression.
Cas9-specific immune responses compromise local and systemic AAV CRISPR therapy in multiple dystrophic canine models
Authors: Hakim Chady H. , Kumar Sandeep R. P. , Pérez-López Dennis O. , Wasala Nalinda B. , Zhang Dong , Yue Yongping , Teixeira James , Pan Xiufang , Zhang Keqing , Million Emily D. , Nelson Christopher E. , Metzger Samantha , Han Jin , Louderman Jacqueline A. , Schmidt Florian , Feng Feng , Grimm Dirk , Smith Bruce F. , Yao Gang , Yang N. Nora , Gersbach Charles A. , Chen Shi-jie , Herzog Roland W. , Duan Dongsheng
Published: November 2021

Adeno-associated virus (AAV)-mediated CRISPR-Cas9 editing holds promise to treat many diseases. The immune response to bacterial-derived Cas9 has been speculated as a hurdle for AAV-CRISPR therapy. However, immunological consequences of AAV-mediated Cas9 expression have thus far not been thoroughly investigated in large mammals. We evaluate Cas9-specific immune responses in canine models of Duchenne muscular dystrophy (DMD) following intramuscular and intravenous AAV-CRISPR therapy. Treatment results initially in robust dystrophin restoration in affected dogs but also induces muscle inflammation, and Cas9-specific humoral and cytotoxic T-lymphocyte (CTL) responses that are not prevented by the muscle-specific promoter and transient prednisolone immune suppression. In normal dogs, AAV-mediated Cas9 expression induces similar, though milder, immune responses. In contrast, other therapeutic (micro-dystrophin and SERCA2a) and reporter (alkaline phosphatase, AP) vectors result in persistent expression without inducing muscle inflammation. Our results suggest Cas9 immunity may represent a critical barrier for AAV-CRISPR therapy in large mammals.
Mechanisms for destabilisation of RNA viruses at air-water and liquid-liquid interfaces
Authors: Brackley C. A. , Lips A. , Morozov A. , Poon W. C. K. , Marenduzzo D.
Published: November 2021

Understanding the interactions between viruses and surfaces or interfaces is important, as they provide the principles underpinning the cleaning and disinfection of contaminated surfaces. Yet, the physics of such interactions is currently poorly understood. For instance, there are longstanding experimental observations suggesting that the presence of air-water interfaces can generically inactivate and kill viruses, yet the mechanism underlying this phenomenon remains unknown. Here we use theory and simulations to show that electrostatics may provide one such mechanism, and that this is very general. Thus, we predict that the electrostatic free energy of an RNA virus should increase by several thousands of kBT as the virion breaches an air-water interface. We also show that the fate of a virus approaching a generic liquid-liquid interface depends strongly on the detailed balance between interfacial and electrostatic forces, which can be tuned, for instance, by choosing different media to contact a virus-laden respiratory droplet. Tunability arises because both the electrostatic and interfacial forces scale similarly with viral size. We propose that these results can be used to design effective strategies for surface disinfection.
ATR inhibition enables complete tumour regression in ALK-driven NB mouse models
Authors: Szydzik Joanna , Lind Dan E. , Arefin Badrul , Kurhe Yeshwant , Umapathy Ganesh , Siaw Joachim Tetteh , Claeys Arne , Gabre Jonatan L. , Van den Eynden Jimmy , Hallberg Bengt , Palmer Ruth H.
Published: November 2021

High-risk neuroblastoma (NB) often involvesMYCNamplification as well as mutations inALK. Currently, high-risk NB presents significant clinical challenges, and additional therapeutic options are needed. Oncogenes likeMYCNandALKresult in increased replication stress in cancer cells, offering therapeutically exploitable options. We have pursued phosphoproteomic analyses highlighting ATR activity in ALK-driven NB cells, identifying the BAY1895344 ATR inhibitor as a potent inhibitor of NB cell growth and proliferation. Using RNA-Seq, proteomics and phosphoproteomics we characterize NB cell and tumour responses to ATR inhibition, identifying key components of the DNA damage response as ATR targets in NB cells. ATR inhibition also produces robust responses in mouse models. Remarkably, a 2-week combined ATR/ALK inhibition protocol leads to complete tumor regression in two independent genetically modified mouse NB models. These results suggest that NB patients, particularly in high-risk groups with oncogene-induced replication stress, may benefit from ATR inhibition as therapeutic intervention.
Solution-processable and functionalizable ultra-high molecular weight polymers via topochemical synthesis
Authors: Anderson Christopher L. , Li He , Jones Christopher G. , Teat Simon J. , Settineri Nicholas S. , Dailing Eric A. , Liang Jiatao , Mao Haiyan , Yang Chongqing , Klivansky Liana M. , Li Xinle , Reimer Jeffrey A. , Nelson Hosea M. , Liu Yi
Published: November 2021

Topochemical polymerization reactions hold the promise of producing ultra-high molecular weight crystalline polymers. However, the totality of topochemical polymerization reactions has failed to produce ultra-high molecular weight polymers that are both soluble and display variable functionality, which are restrained by the crystal-packing and reactivity requirements on their respective monomers in the solid state. Herein, we demonstrate the topochemical polymerization reaction of a family of para-azaquinodimethane compounds that undergo facile visible light and thermally initiated polymerization in the solid state, allowing for the first determination of a topochemical polymer crystal structure resolved via the cryoelectron microscopy technique of microcrystal electron diffraction. The topochemical polymerization reaction also displays excellent functional group tolerance, accommodating both solubilizing side chains and reactive groups that allow for post-polymerization functionalization. The thus-produced soluble ultra-high molecular weight polymers display superior capacitive energy storage properties. This study overcomes several synthetic and characterization challenges amongst topochemical polymerization reactions, representing a critical step toward their broader application.
Synergistic insights into human health from aptamer- and antibody-based proteomic profiling
Authors: Pietzner Maik , Wheeler Eleanor , Carrasco-Zanini Julia , Kerrison Nicola D. , Oerton Erin , Koprulu Mine , Luan Jian’an , Hingorani Aroon D. , Williams Steve A. , Wareham Nicholas J. , Langenberg Claudia
Published: November 2021

Affinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques—the aptamer-based SomaScan® v4 assay and the antibody-based Olink assays—to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein targets across both platforms. We create a genetically anchored cross-platform proteome-phenome network comprising 547 protein–phenotype connections, 36.3% of which were only seen with one of the two platforms suggesting that both techniques capture distinct aspects of protein biology. We further highlight discordance of genetically predicted effect directions between assays, such as for PILRA and Alzheimer’s disease. Our results showcase the synergistic nature of these technologies to better understand and identify disease mechanisms and provide a benchmark for future cross-platform discoveries.
Evaluation of endogenous miRNA reference genes across different zebrafish strains, developmental stages and kidney disease models
Authors: Siegerist Florian , Lange Tim , Iervolino Anna , Koppe Thor Magnus , Zhou Weibin , Capasso Giovambattista , Endlich Karlhans , Endlich Nicole
Published: November 2021

The majority of kidney diseases arise from the loss of podocytes and from morphological changes of their highly complex foot process architecture, which inevitably leads to a reduced kidney filtration and total loss of kidney function. It could have been shown that microRNAs (miRs) play a pivotal role in the pathogenesis of podocyte-associated kidney diseases. Due to their fully functioning pronephric kidney, larval zebrafish have become a popular vertebrate model, to study kidney diseases in vivo. Unfortunately, there is no consensus about a proper normalization strategy of RT-qPCR-based miRNA expression data in zebrafish. In this study we analyzed 9 preselected candidates dre-miR-92a-3p, dre-miR-206-3p, dre-miR-99-1, dre-miR-92b-3p, dre-miR-363-3p, dre-let-7e, dre-miR-454a, dre-miR-30c-5p, dre-miR-126a-5p for their capability as endogenous reference genes in zebrafish experiments. Expression levels of potential candidates were measured in 3 different zebrafish strains, different developmental stages, and in different kidney disease models by RT-qPCR. Expression values were analyzed with NormFinder, BestKeeper, GeNorm, and DeltaCt and were tested for inter-group differences. All candidates show an abundant expression throughout all samples and relatively high stability. The most stable candidate without significant inter-group differences was dre-miR-92b-3p making it a suitable endogenous reference gene for RT-qPCR-based miR expression zebrafish studies.
Segmentation of infected region in CT images of COVID-19 patients based on QC-HC U-net
Authors: Zhang Qin , Ren Xiaoqiang , Wei Benzheng
Published: November 2021

Since the outbreak of COVID-19 in 2019, the rapid spread of the epidemic has brought huge challenges to medical institutions. If the pathological region in the COVID-19 CT image can be automatically segmented, it will help doctors quickly determine the patient’s infection, thereby speeding up the diagnosis process. To be able to automatically segment the infected area, we proposed a new network structure and named QC-HC U-Net. First, we combine residual connection and dense connection to form a new connection method and apply it to the encoder and the decoder. Second, we choose to add Hypercolumns in the decoder section. Compared with the benchmark 3D U-Net, the improved network can effectively avoid vanishing gradient while extracting more features. To improve the situation of insufficient data, resampling and data enhancement methods are selected in this paper to expand the datasets. We used 63 cases of MSD lung tumor data for training and testing, continuously verified to ensure the training effect of this model, and then selected 20 cases of public COVID-19 data for training and testing. Experimental results showed that in the segmentation of COVID-19, the specificity and sensitivity were 85.3% and 83.6%, respectively, and in the segmentation of MSD lung tumors, the specificity and sensitivity were 81.45% and 80.93%, respectively, without any fitting.