bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modell unterrichtszentrierter Schulentwicklung in Richtung personalisierten Lernens (uSpL-Modell)
Authors: Galle Marco 
Published: September 2021

ZusammenfassungIn den letzten Jahrzehnten hat sich ein Verständnis von Schulentwicklung herausgebildet, dem zufolge verschiedene Akteurinnen und Akteure des Bildungssystems vermehrt kooperativ Entwicklungsprojekte zu initiieren haben und die Unterrichtsentwicklung sowie insbesondere das Lernen der Schülerinnen und Schüler als Ausgangs- und Zielpunkt von Entwicklungstätigkeiten aufgefasst werden (siehe Kapitel 2). Diese Merkmale eignen sich auch für die Beschreibung von Unterrichts- und Schulentwicklung in Richtung personalisierten Lernens: Schulteams passen Lernumgebungen an die personalen Voraussetzungen der Schülerinnen und Schüler an und erarbeiten Lernangebote für den Aufbau fachlicher und überfachlicher Kompetenzen, in deren Rahmen selbstgesteuertes und eigenverantwortliches Lernen möglich ist und Lehrpersonen wie auch die Lerngemeinschaft bildend wirken (siehe Kapitel 1). Vor diesem Hintergrund stellt sich die weiterführende Frage, in welchen Bereichen und wie Schulleitende und Lehrperson ihre Schule und ihren Unterricht weiterentwickeln, damit personalisiertes Lernen umgesetzt werden kann.
Tilings of the Infinite p-ary Tree and Cantor Homeomorphisms
Authors: Cobos Alberto , Navas Luis M. 
Published: September 2021

AbstractWe define a notion of tiling of the full infinite p-ary tree, establishing a series of equivalent criteria for a subtree to be a tile, each of a different nature; namely, geometric, algebraic, graph-theoretic, order-theoretic, and topological. We show how these results can be applied in a straightforward and constructive manner to define homeomorphisms between two given spaces of p-adic integers, $${\mathbb {Z}}_{p}$$

Z
p

and $${\mathbb {Z}}_{q}$$

Z
q

, endowed with their corresponding standard non-archimedean metric topologies.
Field Insights and Analysis of the 2018 Mw 7.5 Palu, Indonesia Earthquake, Tsunami and Landslides
Authors: Cilia Marcella G. , Mooney Walter D. , Nugroho Cahyo 
Published: September 2021

AbstractA devastating Mw 7.5 earthquake and tsunami struck northwestern Sulawesi, Indonesia on 28 September 2018, causing over 4000 fatalities and severe damage to several areas in and around Palu City. Severe earthquake-induced soil liquefaction and landslides claimed hundreds of lives in three villages within Palu. The mainshock occurred at 18:03 local time at a depth of 10 km on a left-lateral strike-slip fault. The hypocenter was located 70 km north of Palu City and the rupture propagated south, under Palu Bay, passing on land on the west side of Palu City. The surface rupture of the earthquake has been mapped onshore along a 30 km stretch of the Palu-Koro fault. We present results of field surveys on the effects of the earthquake, tsunami and liquefaction conducted between 1–3 and 12–19 of October 2018. Seismic intensities on the Modified Mercalli Intensity (MMI) scale are reported for 375 sites and reach a maximum value of 10. We consolidate published tsunami runup heights from several field studies and discuss three possible interrelated tsunami sources to explain the variation in observed tsunami runup heights. Due to limited instrumentation, PGA and PGV values were recorded at only one of our field sites. To compensate, we use our seismic intensities and Ground Motion to Intensity Conversion Equations (GMICEs) and Ground Motion Prediction Equations (GMPEs) developed for similar tectonic regions. Our results indicate that the maximum predicted PGAs for Palu range from 1.1 g for GMICEs to 0.6 g for GMPEs.
Dorsal Root Ganglion Morphometric Changes Under Oxaliplatin Treatment
Authors: Apostolidis Leonidas , Kowalscheck Lars , Weber Tim Frederik , Godel Tim , Bendszus Martin , Kauczor Hans-Ulrich , Jäger Dirk , Schlemmer Heinz-Peter , Bäumer Philipp 
Published: September 2021

Abstract
Purpose
Magnetic resonance neurography (MRN) can detect dorsal root ganglia (DRG) hypertrophy in patients with oxaliplatin-induced peripheral neuropathy (OXIPN) but is difficult to apply in clinical daily practice. Aims of this study were (i) to assess whether DRG volume is reliably measurable by routine computed tomography (CT) scans, (ii) to measure longitudinal changes in DRG during and after oxaliplatin administration and (iii) to assess correlation between DRG morphometry and individual oxaliplatin dose.

Methods
For comparison of MRN and CT measurements, CT scans of 18 patients from a previous MRN study were analyzed. For longitudinal assessment of DRG size under treatment, 96 patients treated with oxaliplatin between January and December 2014 were enrolled retrospectively. DRG volumetry was performed by analyzing routine CT scans, starting with the last scan before oxaliplatin exposure (t0) and up to four consecutive timepoints after initiation of oxaliplatin therapy (t1–t4) with the following median and ranges in months: 3.1 (0.4–4.9), 6.2 (5.3–7.8), 10.4 (8.2–11.9), and 18.4 (12.8–49.8).

Results
DRG volume measured in CT showed a moderately strong correlation with MRN (r = 0.51, p < 0.001) and a strong correlation between two consecutive CTs (r = 0.77, p < 0.001). DRG volume increased after oxaliplatin administration with a maximum at timepoint t2. Higher cumulative oxaliplatin exposure was associated with significantly higher absolute DRG volumes (p = 0.005). Treatment discontinuation was associated with a nonsignificant trend towards lower relative DRG volume changes (p = 0.08).

Conclusion
CT is a reliable method for continuous DRG morphometry; however, since no standardized assessment of OXIPN was performed in this retrospective study, correlations between DRG size, cumulative oxaliplatin dose and clinical symptoms in future prospective studies are needed to establish DRG size as a potential OXIPN biomarker.
Behandlung von Knochen- und Protheseninfektionen mit Bakteriophagen
Authors: Walter Nike , Deng Li , Brochhausen Christoph , Alt Volker , Rupp Markus 
Published: September 2021

Zusammenfassung
Hintergrund
Die Behandlung von Knochen- und Protheseninfektionen bleibt trotz moderner Behandlungskonzepte mit interdisziplinärem Therapieansatz schwierig und weitere Maßnahmen zur Verbesserung des Behandlungsergebnisses sind wünschenswert. Präklinischen Studien liefern ein vielversprechendes Bild der Wirksamkeit von Bakteriophagen zur Behandlung von Knochen- und Protheseninfektionen.

Ziel der Arbeit
Die vorliegende Arbeit gibt eine systematische Übersicht über die klinische Anwendung von Bakteriophagen zur Behandlung von Knochen- und Protheseninfektionen.

Material und Methoden
Eine systematische Suche wurde in PubMed zur Identifikation von primären klinischen Daten zur Anwendung der Phagentherapie bei Patienten mit Knochen- und Protheseninfektion durchgeführt.

Ergebnisse
Elf Studien wurden eingeschlossen, bestehend aus 8 Fallberichten und 3 Fallserien. Indikationen der Phagentherapie waren periprothetische Infektionen (n = 12, 52,2 %), frakturassoziierte Infektionen (n = 9, 39,1 %), Osteomyelitis (n = 1, 4,4 %) und eine Iliosakralgelenkinfektion nach Zementaugmentation einer Metastase (n = 1, 4,4 %). Die Interventionen waren heterogen, Phagen wurden intravenös verabreicht, intraoperativ ins Gelenk injiziert, intraoperativ lokal angewendet oder über Drainagen appliziert. In Kombination mit Antibiotikatherapie konnte eine vollständige Infekteradikation bei 18 Patienten (78,3 %) erreicht werden. Bei 91,3 % der Patienten wurden keine Nebenwirkungen berichtet.

Schlussfolgerung
Bakteriophagen sind eine vielversprechende Behandlungsmethode von Knochen- und Protheseninfektionen in Kombination mit einer Antibiotikatherapie. Zukünftige klinische Studien mit höherem Evidenzgrad werden benötigt, um eine erfolgreiche Translation der Bakteriophagentherapie in die klinische Praxis weiter zu etablieren.
Fiscal reaction functions for the advanced economies revisited
Authors: Iorio Francesca Di , Fachin Stefano 
Published: September 2021

AbstractWe revisit the relationship between the primary balances/GDP and debt/GDP ratios (fiscal reaction function, FRF), in the advanced economies, showing that using adequate tests and estimators leads to question the validity of the current consensus. Using data for 1961–2019, we find that long-run FRFs exist only in a small number of advanced economies (Belgium, Germany, Greece, Norway, Portugal and Sweden), with polynomial effects with fiscal fatigue only in Germany. These results warn against the widespread practice of estimating homogeneous polynomial panel FRFs. Limiting the sample to 1961–2007, thus excluding the 2008 crisis and its aftermath, FRFs hold also in Canada, Ireland, Italy (polynomial), Spain and USA, though not in Germany, and the coefficients are generally larger. Particularly, after 2008 European Union countries appear somehow to have been more likely to implement FRFs.
The Chow ring of hyperkähler varieties of $$K3^{[2]}$$-type via Lefschetz actions
Authors: Kretschmer Andreas 
Published: September 2021

AbstractWe propose an explicit conjectural lift of the Neron–Severi Lie algebra of a hyperkähler variety X of $$K3^{[2]}$$

K

3

[
2
]

-type to the Chow ring of correspondences $$\mathrm{CH}^*(X \times X)$$

CH

∗

(
X
×
X
)

in terms of a canonical lift of the Beauville–Bogomolov class obtained by Markman. We give evidence for this conjecture in the case of the Hilbert scheme of two points of a K3 surface and in the case of the Fano variety of lines of a very general cubic fourfold. Moreover, we show that the Fourier decomposition of the Chow ring of X of Shen and Vial agrees with the eigenspace decomposition of a canonical lift of the cohomological grading operator.
Guaranteed lower bounds on eigenvalues of elliptic operators with a hybrid high-order method
Authors: Carstensen Carsten , Ern Alexandre , Puttkammer Sophie 
Published: September 2021

AbstractThis paper introduces a novel hybrid high-order (HHO) method to approximate the eigenvalues of a symmetric compact differential operator. The HHO method combines two gradient reconstruction operators by means of a parameter $$0<\alpha <~1$$

0
<
α
<

1

and introduces a novel cell-based stabilization operator weighted by a parameter $$0<\beta <\infty $$

0
<
β
<
∞

. Sufficient conditions on the parameters $$\alpha $$
α
and $$\beta $$
β
are identified leading to a guaranteed lower bound property for the discrete eigenvalues. Moreover optimal convergence rates are established. Numerical studies for the Dirichlet eigenvalue problem of the Laplacian provide evidence for the superiority of the new lower eigenvalue bounds compared to previously available bounds.
Energizing effects of bupropion on effortful behaviors in mice under positive and negative test conditions: modulation of DARPP-32 phosphorylation patterns
Authors: Carratalá-Ros Carla , Olivares-García Régulo , Martínez-Verdú Andrea , Arias-Sandoval Edgar , Salamone John D. , Correa Mercè 
Published: September 2021

AbstractMotivational symptoms such as anergia, fatigue, and reduced exertion of effort are seen in depressed people. To model this, nucleus accumbens (Nacb) dopamine (DA) depletions are used to induce a low-effort bias in rodents tested on effort-based decision-making. We evaluated the effect of the catecholamine uptake blocker bupropion on its own, and after administration of tetrabenazine (TBZ), which blocks vesicular storage, depletes DA, and induces depressive symptoms in humans. Male CD1 mice were tested on a 3-choice-T-maze task that assessed preference between a reinforcer involving voluntary physical activity (running wheel, RW) vs. sedentary activities (sweet food pellet intake or a neutral non-social odor). Mice also were tested on the forced swim test (FST), two anxiety-related measures (dark–light box (DL), and elevated plus maze (EPM)). Expression of phosphorylated DARPP-32 (Thr34 and Thr75) was evaluated by immunohistochemistry as a marker of DA-related signal transduction. Bupropion increased selection of RW activity on the T-maze. TBZ reduced time running, but increased time-consuming sucrose, indicating an induction of a low-effort bias, but not an effect on primary sucrose motivation. In the FST, bupropion reduced immobility, increasing swimming and climbing, and TBZ produced the opposite effects. Bupropion reversed the effects of TBZ on the T-maze and the FST, and also on pDARPP32-Thr34 expression in Nacb core. None of these manipulations affected anxiety-related parameters. Thus, bupropion improved active behaviors, which were negatively motivated in the FST, and active behaviors that were positively motivated in the T-maze task, which has implications for using catecholamine uptake inhibitors for treating anergia and fatigue-like symptoms.
Signet ring cell cancer of stomach and gastro-esophageal junction: molecular alterations, stage-stratified treatment approaches, and future challenges
Authors: Kumar Naveena A. N. , Jose Anmi , Usman Nawaz , Rajan Keshava , Munisamy Murali , Shetty Preethi S. , Rao Mahadev 
Published: September 2021

Abstract
Purpose
There has been an increase in the incidence of signet ring cell cancer (SRCC) of the stomach and gastro-esophageal junction (GEJ). The multistage carcinogenesis involving genetic and epigenetic aberrations may have a major role in the increasing incidence of SRCC. Although there are numerous studies on the prognostic value of SRCC, they are markedly inconsistent in their results, making it impossible to draw any meaningful conclusions. We aimed to examine the available evidences on molecular alterations and stage-stratified treatment approaches in SRCC of the stomach and GEJ.

Methods
A systematic search was carried out in PubMed. Studies available in English related to SRCC of stomach and gastro-esophageal junction were identified and evaluated.

Results
This study reviewed the current evidence and provided an insight into the molecular alterations, stage-stratified treatment approaches, and future challenges in the management of SRCC of the stomach and GEJ. Specific therapeutic strategies and personalized multimodal treatment have been recommended based on the tumor characteristics of SRCC.

Conclusion
Multistage carcinogenesis involving genetic and epigenetic aberrations in SRCC is interlinked with stage-dependent prognosis. Specific therapeutic strategy and personalized multimodal treatment should be followed based on the tumor characteristics of SRCC. Endoscopic resection, radical surgery, and perioperative chemotherapy should be offered in carefully selected patients based on stage and prognostic stratification. Future studies in genetic and molecular analysis, histopathological classification, and options of multimodality treatment will improve the prognosis and oncological outcomes in SRCC of gastric and GEJ.
An analysis of 130 neuroendocrine tumors G3 regarding prevalence, origin, metastasis, and diagnostic features
Authors: Kasajima Atsuko , Konukiewitz Björn , Schlitter Anna Melissa , Weichert Wilko , Klöppel Günter 
Published: September 2021

AbstractLimited data exist on high-grade neuroendocrine tumors (NETs G3) which represent a new category among neuroendocrine neoplasms (NEN). We analyzed NETs G3 in a consultation series regarding prevalence, origin, metastasis, and diagnostic problems. Based on the WHO classification of digestive system tumors, 130 NETs G3 (9%) were identified in 1513 NENs. NET G3 samples were more often obtained from metastatic sites (69%) than NET G1/G2 samples (24%). NET G3 metastases presented most frequently in the liver (74%) and originated from the pancreas (38/90, 42%), followed by the lung (9%), ileum (7%), stomach (3%), rectum (1%), and rare sites (2%) such as the prostate and breast. The primaries remained unknown in 15%. NETs G3 had a median Ki67 of 30% that distinguished them from NECs (60%), though with great overlap. The expression of site-specific markers, p53, Rb1, and SST2 was similar in NETs G3 and NETs G1/G2, except for p53 and Rb1 which were abnormally expressed in 8% and 7% of liver metastases from NET G3 but not from NET G1/G2. NETs G3 were frequently referred as NECs (39%) but could be well distinguished from NECs by normal p53 (92% versus 21%) and Rb1 expression (93% versus 41%) expression. In conclusion, NETs G3 are frequently discovered as liver metastases from pancreatic or pulmonary primaries and are often misinterpreted as NEC. p53 and Rb1 are powerful markers in the distinction of NET G3 from NEC. Rarely, carcinomas from non-digestive, non-pulmonary organs with neuroendocrine features may present as NET G3.
GSTM1 and GSTT1 double null genotypes determining cell fate and proliferation as potential risk factors of relapse in children with hematological malignancies after hematopoietic stem cell transplantation
Authors: Jurkovic Mlakar Simona , Uppugunduri Satyanarayana Chakradhara Rao , Nava Tiago , Mlakar Vid , Golay Hadrien , Robin Shannon , Waespe Nicolas , Rezgui Mohamed Aziz , Chalandon Yves , Boelens Jaap Jan , Bredius Robert G. M. , Dalle Jean-Hugues , Peters Christina , Corbacioglu Selim , Bittencourt Henrique , Krajinovic Maja , Ansari Marc ,   the paediatric diseases working party of the European society for blood and marrow transplantation
Published: September 2021

Abstract
Purpose
This study aimed to retrospectively evaluate the genetic association of null variants of glutathione S-transferases GSTM1 and GSTT1 with relapse incidence in children with hematological malignancies (HMs) undergoing busulfan (BU)- containing allogeneic hematopoietic stem cell transplantation (HSCT) and to assess the impact of these variants on BU-induced cytotoxicity on the immortalized lymphoblastoid cell lines (LCLs) and tumor THP1 GST gene-edited cell models.

Methods
GSTM1- and GSTT1-null alleles were genotyped using germline DNA from whole blood prior to a conditioning BU-based regimen. Association of GSTM1- and GSTT1-null variants with relapse incidence was analyzed using multivariable competing risk analysis. BU-induced cell death studies were conducted in GSTs- null and non-null LCLs and CRISPR–Cas9 gene-edited THP1 leukemia cell lines.

Results
Carrying GSTM1/GSTT1 double null genotype was found to be an independent risk factor for post-HSCT relapse in 86 children (adjusted HR: 6.52 [95% Cl, 2.76–15.42; p = 1.9 × 10–5]). BU-induced cell death preferentially in THP1GSTM1(non−null) and LCLsGSTM1(non−null) as shown by decreased viability, increased necrosis and levels of the oxidized form of glutathione compared to null cells, while GSTT1 non-null cells showed increased baseline proliferation.

Conclusion
The clinical association suggests that GSTM1/GSTT1 double null genotype could serve as genetic stratification biomarker for the high risk of post-HSCT relapse. Functional studies have indicated that GSTM1 status modulates BU-induced cell death. On the other hand, GSTT1 is proposed to be involved in baseline cell proliferation.
p53 is functionally inhibited in clear cell renal cell carcinoma (ccRCC): a mechanistic and correlative investigation into genetic and molecular characteristics
Authors: Diesing Karoline , Ribback Silvia , Winter Stefan , Gellert Manuela , Oster Antonia M. , Stühler Viktoria , Gläser Eva , Adler Frank , Hartwig Christoph , Scharpf Markus , Bedke Jens , Burchardt Martin , Schwab Matthias , Lillig Christopher H. , Kroeger Nils 
Published: September 2021

Abstract
Purpose
Although p53 is rarely mutated in ccRCC, its overexpression has been linked to poor prognosis. The current study sought to elucidate the unique role of p53 in ccRCC with genomic, proteomic, and functional analyses.

Materials and methods
Data from the Cancer Genome Atlas (TCGA) were evaluated for genomic and proteomic characteristics of p53; a tissue micro array (TMA) study was carried out to evaluate the association of p53 and phosphorylated p53 (pp53) with clinical outcome. Mechanistic in vitro experiments were performed to confirm a pro-apoptotic loss of p53 in ccRCC and p53 isoforms as well as posttranslational modifications of p53 where assessed to provide possible reasons for a functional inhibition of p53 in ccRCC.

Results
A low somatic mutation rate of p53 could be confirmed. Although mRNA levels were correlated with poor prognosis and clinicopathological features, there was no monotonous association of mRNA levels with survival outcome. Higher p53 protein levels could be confirmed as poor prognostic features. In vitro, irradiation of ccRCC cell lines markedly induced levels of p53 and of activated (phosphorylated) p53. However, irradiated ccRCC cells demonstrated similar proliferation, migration, and p53 transcriptional activity like non-irradiated controls indicating a functional inhibition of p53. p53 isoforms and could not be correlated with clinical outcome of ccRCC patients.

Conclusions
p53 is rarely mutated but the wildtype p53 is functionally inhibited in ccRCC. To investigate mechanisms that underlie functional inhibition of p53 may provide attractive therapeutic targets in ccRCC.
Protective effects of Stevia rebaudiana extracts on beta cells in lipotoxic conditions
Authors: Bugliani Marco , Tavarini Silvia , Grano Francesca , Tondi Silvia , Lacerenza Serena , Giusti Laura , Ronci Maurizio , Maidecchi Anna , Marchetti Piero , Tesi Marta , Angelini Luciana G. 
Published: September 2021

Abstract
Aims
Stevia rebaudiana Bertoni leaf extracts have gained increasing attention for their potential protection against type 2 diabetes. In this study, we have evaluated the possible beneficial effects of Stevia rebaudiana leaf extracts on beta-cells exposed to lipotoxicity and explored some of the possible mechanisms involved.

Methods
Extracts, deriving from six different chemotypes (ST1 to ST6), were characterized in terms of steviol glycosides, total phenols, flavonoids, and antioxidant activity. INS-1E beta cells and human pancreatic islets were incubated 24 h with 0.5 mM palmitate with or without varying concentrations of extracts. Beta-cell/islet cell features were analyzed by MTT assay, activated caspase 3/7 measurement, and/or nucleosome quantification. In addition, the proteome of INS-1E cells was assessed by bi-dimensional electrophoresis (2-DE).

Results
The extracts differed in terms of antioxidant activity and stevioside content. As expected, 24 h exposure to palmitate resulted in a significant decrease of INS-1E cell metabolic activity, which was counteracted by all the Stevia extracts at 200 μg/ml. However, varying stevioside only concentrations were not able to protect palmitate-exposed cells. ST3 extract was also tested with human islets, showing an anti-apoptotic effect. Proteome analysis showed several changes in INS-1E beta-cells exposed to ST3, mainly at the endoplasmic reticulum and mitochondrial levels.

Conclusions
Stevia rebaudiana leaf extracts have beneficial effects on beta cells exposed to lipotoxicity; this effect does not seem to be mediated by stevioside alone (suggesting a major role of the leaf phytocomplex as a whole) and might be due to actions on the endoplasmic reticulum and the mitochondrion.