bluuebunny/crossref_metadata_2025 huggingface dataset:
Is Crash Loading Acceptable in Carotid Artery Stenting?
Authors: Hajiyev Kamran , Henkes Hans , Hellstern Viktoria , Khanafer Ali , Wendl Christina , Bäzner Hansjörg , von Gottberg Philipp
Published: October 2022

Purpose

In elective carotid artery stenting (CAS), antiplatelet therapy (APT) is crucial. Several international societies have provided guidelines for loading time and dosage in endovascular treatment; however, no recommendations have been made for urgent, nonthrombectomy-associated CAS without adequate loading time. Here, we investigated the short-term outcomes for APT-naïve patients receiving “crash loading” (CL) on the day of intervention, compared with those for patients wi APT onset 3–5 days (semi-CL) or more than 5 days before CAS (EL).

Methods

Outcomes of patients 30 days after CAS were evaluated in terms of the rates of in-stent thrombus, re-stenosis, stroke, hemorrhagic and thrombotic events, other periprocedural occurrences, in-hospital death and CAS-associated death. Patients’ biological, pathological and hemostatic factors were recorded and compared.

Results

A total of 1158 patients who received CAS at the authors’ neuroradiology institution were analyzed: 275 EL, 846 semi-CL, and 37 CL. The patients receiving CL had the lowest rate of stroke, but the highest rates of CAS-associated and in-hospital deaths, although the deaths were not necessarily associated with APT. In-stent thrombosis was the highest in the semi-CL group. The rates and types of periprocedural occurrences favored the CL group.

Conclusion

With the medical regimen used in this study, urgent CAS with CL APT did not produce more ischemic, thrombotic and hemorrhagic complications than longer loading times. However, careful patient selection might be crucial and adequate loading times should remain the standard of care.
Stereotactic body radiotherapy for recurrent hemoptysis due to chronic pulmonary aspergillosis: a case report and systematic review of the literature
Authors: Koch Alexander , Schanne Daniel H. , Günther Gunar , Aebersold Daniel M. , Elicin Olgun
Published: October 2022

Purpose

Chronic pulmonary aspergillosis (CPA) can manifest as fungus balls in preexisting cavities of lung parenchyma and recurrent hemoptysis is among the most frequent complications. Radiotherapy can be considered for treatment-refractory aspergilloma and severe hemoptysis. To the best of our knowledge, we present the first application of stereotactic body radiotherapy (SBRT) for a pulmonary aspergilloma in a patient with limited functional lung capacity. The topic was further expanded on with a systematic review of the literature addressing the implementation of radiotherapy in CPA patients.

Case report

A 52-year-old man presented with recurring and treatment-refractory hemoptysis caused by chronic cavitary aspergillosis localized in the left lower lobe. We applied SBRT on two consecutive days with a total dose of 16 Gy. Hemoptysis frequency decreased to a clinically insignificant level.

Systematic review

We performed a systematic search of the literature in line with the PRISMA statement. The initial PubMed search resulted in 230 articles, of which 9 were included.

Results

The available literature contained 35 patients with CPA who received radiotherapy. Dose fractionation usually ranged from 2 to 4 Gy per fraction, applied almost exclusively in conventional two-dimensional (2D) techniques. There is no report of SBRT usage in such a scenario. Most cases report a positive treatment response after irradiation.

Conclusion

The presented case demonstrates long-term clinical stability after SBRT for recurrent hemoptysis due to pulmonary aspergilloma. The systematic literature search revealed that concept definition is still uncertain, and further work is necessary to establish radiotherapy in clinical practice.
Lateral para-olecranon approach: surgical guide and anatomical considerations to the anconeus branch: is there a nerve-free zone?
Authors: Plecko Michael , Schwarz Ulrike M. , Hohenberger Gloria M. , Hammer Niels , Schwarz Angelika M.
Published: October 2022

Purpose

In the last decades, total elbow arthroplasty, elbow osteosynthesis and revision surgery have been more popularized. The study aimed to assess the course of the anconeus branch of the radial nerve in relation to two variations of the lateral para-olecranon approach, considering iatrogenic nerve injuries.

Methods

The study consisted of 120 upper extremities from 60 Thiel-embalmed human specimens. Two randomized versions of the lateral para-olecranon approach (centrally orientated: P1 and laterally orientated: P2) were performed. The olecranon and the intersection points to the anconeus branch of the radial nerve were determined as anatomical landmarks. The measurements were assessed by two independent observers. Differences were analyzed using the Student’s t test; associations were computed with the Pearson correlation (r). An alpha of 0.05 (p) and a confidence interval of 95% were set.

Results

The intersection points averaged 12.3 cm (SD 1.8, range 8.2–16.8) for P1 versus 5.5 cm (SD 1.4, range 3.0–9.2) for P2 (p ≤ 0.001). Statistically significantly higher values for male and longer humeral specimens were revealed (all values: p < 0.05). Comparison of left and right sides yielded no difference. Excellent inter-rater agreements were found (ICC = 0.902, range 0.860–0.921). A correlation was evaluated between the humeral length and the distances in both approaches (P1: r = 0.550, p < 0.001, P2: r = 0.669, p < 0.001).

Conclusion

The data presented here allow preservation of the anconeus branch. The P1 forms a potential advantage by owing a broader safe zone. Using the centrally orientated approach seems to provide adequate nerve protection during surgery for one of the motor branches for extension of the elbow joint and might result in improved postoperative benefits.
The incidence of childhood-onset type 1 diabetes, time trends and association with the population composition in Sweden: a 40 year follow-up
Authors: Waernbaum Ingeborg , Lind Torbjörn , Möllsten Anna , Dahlquist Gisela
Published: October 2022

Aims/hypothesis

During the 1980s and 1990s, the incidence of childhood-onset type 1 diabetes more than doubled in Sweden, followed by a plateau. In the present 40 year follow-up, we investigated if the incidence remained stable and whether this could be explained by increased migration from countries reporting lower incidences.

Methods

We used 23,143 incident cases of childhood-onset type 1 diabetes reported between 1978 and 2019 to the nationwide, population-based Swedish Childhood Diabetes Registry and population data from Statistics Sweden. Generalised additive models and ANOVA were applied to analyse the effects of onset age, sex, time trends and parental country of birth and interaction effects between these factors.

Results

The flattening of the incidence increase seems to remain over the period 2005–2019. When comparing the incidence of type 1 diabetes for all children in Sweden with that for children with both parents born in Sweden, the trends were parallel but at a higher level for the latter. A comparison of the incidence trends between individuals with Swedish backgrounds (high diabetes trait) and Asian backgrounds (low diabetes trait) showed that the Asian subpopulation had a stable increase in incidence over time.

Conclusions/interpretation

In Sweden, the increase in incidence of childhood-onset type 1 diabetes in the late 20th century has been approaching a more stable albeit high level over the last two decades. Increased immigration from countries with lower incidences of childhood-onset type 1 diabetes does not provide a complete explanation for the observed levelling off.

Graphical abstract
Incidence and Impact of Non‐alcoholic Fatty Liver Disease (NAFLD) in Patients with Adenocarcinoma of the Esophagus Treated with Curative Intent
Authors: Reynolds John V. , Donlon Noel E. , Elliott Jessie A. , Moran Brendan , Temperley Hugo , Nugent Tim S. , Davern Maria , King Sinead , Conroy Melissa , Lysaght Joanne , Ravi Narayanasamy , Ryan Carmel , Finn Stephen , Norris Suzanne , Donohoe Clare L.
Published: October 2022

Background and Aims

Esophageal adenocarcinoma (EAC) is associated with visceral obesity (VO). Non‐alcoholic fatty liver disease (NAFLD) is common within this phenotype; however, its incidence and clinical significance in EAC have not been studied.

Study design

A total of 559 patients with hepatic stetatosis (HS) defined by unenhanced CT were enrolled. In a sub‐study, in 140 consecutive patients a liver biopsy was taken intraoperatively to study HS and non‐alcoholic steatohepatitis (NASH). Postoperative complications were defined as per the Esophageal Complications Consensus Group (ECCG). Liver biochemistry was measured peri‐operatively, with an ALT > 5 defined as acute liver injury (ALI). Mann–Whitney U test or Fisher's exact test was utilized and the Kaplan–Meier method for survival.

Results

42% (n = 234/559) of patients had CT‐defined HS. HS was associated with VO in 56% of cases, metabolic syndrome (Met S) in 37% and type 2 diabetes in 25%, compared with 44, 21, and 15% in non‐HS patients (p < 0.01). Pathologic HS was present in 32% (45/140) and graded as mild, moderate, and severe in 73, 24, and 3%, respectively, with NASH reported in 16% and indefinite/borderline NASH in 42% of HS cases. Postoperative ALI was similar (p = 0.88) in both HS (10%) and non‐HS cohorts (11%). Operative complication severity was similar in both cohorts. 5‐yr survival was 53% (HS) vs 50% (p = 0.890).

Conclusion

This study establishes for the first time the incidence and clinical impact of NAFLD in EAC patients undergoing surgery and highlights no major impact on oncologic outcomes, nor in the severity of complications.
Automatic segmentation of the thalamus using a massively trained 3D convolutional neural network: higher sensitivity for the detection of reduced thalamus volume by improved inter-scanner stability
Authors: Opfer Roland , Krüger Julia , Spies Lothar , Ostwaldt Ann-Christin , Kitzler Hagen H. , Schippling Sven , Buchert Ralph
Published: October 2022

Objectives

To develop an automatic method for accurate and robust thalamus segmentation in T1w-MRI for widespread clinical use without the need for strict harmonization of acquisition protocols and/or scanner-specific normal databases.

Methods

A three-dimensional convolutional neural network (3D-CNN) was trained on 1975 T1w volumes from 170 MRI scanners using thalamus masks generated with FSL-FIRST as ground truth. Accuracy was evaluated with 18 manually labeled expert masks. Intra- and inter-scanner test-retest stability were assessed with 477 T1w volumes of a single healthy subject scanned on 123 MRI scanners. The sensitivity of 3D-CNN-based volume estimates for the detection of thalamus atrophy was tested with 127 multiple sclerosis (MS) patients and a normal database comprising 4872 T1w volumes from 160 scanners. The 3D-CNN was compared with a publicly available 2D-CNN (FastSurfer) and FSL.

Results

The Dice similarity coefficient of the automatic thalamus segmentation with manual expert delineation was similar for all tested methods (3D-CNN and FastSurfer 0.86 ± 0.02, FSL 0.87 ± 0.02). The standard deviation of the single healthy subject’s thalamus volume estimates was lowest with 3D-CNN for repeat scans on the same MRI scanner (0.08 mL, FastSurfer 0.09 mL, FSL 0.15 mL) and for repeat scans on different scanners (0.28 mL, FastSurfer 0.62 mL, FSL 0.63 mL). The proportion of MS patients with significantly reduced thalamus volume was highest for 3D-CNN (24%, FastSurfer 16%, FSL 11%).

Conclusion

The novel 3D-CNN allows accurate thalamus segmentation, similar to state-of-the-art methods, with considerably improved robustness with respect to scanner-related variability of image characteristics. This might result in higher sensitivity for the detection of disease-related thalamus atrophy.

Key Points

• A three-dimensional convolutional neural network was trained for automatic segmentation of the thalamus with a heterogeneous sample of T1w-MRI from 1975 patients scanned on 170 different scanners.

• The network provided high accuracy for thalamus segmentation with manual segmentation by experts as ground truth.

• Inter-scanner variability of thalamus volume estimates across different MRI scanners was reduced by more than 50%, resulting in increased sensitivity for the detection of thalamus atrophy.
Planar Interferometric Tracking of droplets in evaporating conditions
Authors: Davies Hywel , Talibi Midhat , Ducci Andrea , Parsania Nishant , Balachandran Ramanarayanan
Published: October 2022

An effective Lagrangian Planar Interferometric Tracking (PIT) processor is proposed to track the size and path of multiple droplets, with spray droplet diameters (20–150 µm) and volumetric concentrations ($$\approx$$
≈
300 drops/cm$$^3$$

3

) consistent with industrial applications, produced by an ultrasonic atomiser in evaporating conditions. A test facility was developed where liquid droplets are exposed to a temperature gradient in a co-axial air flow, where the outer stream is preheated to the desired temperature (288–550 K). The PIT method builds on a TSI Global Sizing Velocimtery measurement technique and allows to detect, size and follow the path of droplets which were otherwise discarded or mis-analysed by the commercial software. The methodology was first tested under non-evaporating conditions, and multiple sources of errors, some common to most planar interferometric techniques, were identified and their order of magnitude and impact on final droplet measurement assessed. The main source of error is related to the out-of-plane motion of the droplets and the time they spend in the measurement volume. For non-evaporating conditions, measured data can be processed to filter out this source of error. In evaporating conditions, a novel method for assessing the impact of measurement error with respect to droplet evaporation and measurement timescales is defined. The PIT method allowed tracking of individual methanol droplets entrained within an airflow heated to 495 K and determining their size reduction under evaporating conditions. Measured droplet evaporation rates were then compared against those predicted by an iterative evaporation model, and a very good agreement was found between the modelled and measured estimates.

Graphical abstract
Rheumatologische Weiterbildungsstellen in Deutschland
Authors: Pfeil Alexander , Krusche Martin , Proft Fabian , Vossen Diana , Braun Jürgen , Baraliakos Xenofon , Berliner Michael N. , Keyßer Gernot , Krause Andreas , Lorenz Hanns-Martin , Manger Bernhard , Schuch Florian , Specker Christof , Wollenhaupt Jürgen , Voormann Anna , Fleck Martin
Published: October 2022

Hintergrund

In den nächsten Jahren gehen viele Haus- bzw. Fachärzt:innen in den Ruhestand. Wie in anderen Disziplinen stellt sich in der Rheumatologie die Frage, ob ausreichend Weiterbildungsstellen zur Verfügung stehen, um das Versorgungsangebot bedarfsgerecht aufrechterhalten bzw. ausweiten zu können. Daher hat die Deutsche Gesellschaft für Rheumatologie (DGRh) ihre Kommission Fort- und Weiterbildung beauftragt, die aktuell zur Verfügung stehenden Weiterbildungsmöglichkeiten in Deutschland zu überprüfen. Ziel dieser Arbeit ist die Erfassung der Weiterbildungskapazität zur Fachärztin bzw. zum Facharzt für Innere Medizin und Rheumatologie.

Methodik

Im Rahmen dieser Studie erfolgte die Erhebung der Weiterbildungsbefugten, deren Tätigkeitsort und die Dauer von deren Weiterbildungsbefugnis über die Homepages der 17 Landesärztekammern. Basierend auf diesen Daten erfolgte dann eine deutschlandweite Umfrage zu den Weiterbildungsstellen.

Ergebnisse

Die Weiterbildung zum/zur Facharzt/Fachärztin für Rheumatologie erfolgte in Deutschland im Jahr 2021 an 229 Weiterbildungsorten. Dabei standen von 187 Weiterbildungsorten nähere Daten für eine Analyse zur Verfügung (81,7 %). Die Weiterbildungsorte verteilten sich dabei auf Kliniken (52,4 %) und Niederlassungen (47,6 %), wobei der Großteil (81,8 %) der insgesamt 478,4 Weiterbildungsstellen (Klinik: 391,4 und Niederlassung: 87) im Krankenhausbereich lag. Insgesamt waren zum Erhebungszeitpunkt 17,2 % aller Weiterbildungsstellen (Klinik: 11,4 % und Niederlassung: 43,1 %) nicht besetzt.

Diskussion

Die Studie zeigt, dass die meisten Weiterbildungsstellen in klinischen Einrichtungen vorhanden sind. Demgegenüber gibt es im niedergelassenen Bereich vergleichsweise wenige Weiterbildungsstellen, die zudem zur Hälfte nicht besetzt sind. Für eine optimale Nutzung bereits bestehender Weiterbildungskapazitäten müssen sektorübergreifende Weiterbildungskonzepte entwickelt und v. a. muss auch eine eigenständige Vergütung des Weiterbildungsaufwandes etabliert werden. In diesem Kontext muss eine gute rheumatologische Versorgung in ganz Deutschland dauerhaft gewährleistet sein, um den betroffenen ca. 2 Mio. Patienten mit entzündlich rheumatischen Erkrankung gerecht werden zu können.
Pediatric spinal pilocytic astrocytomas form a distinct epigenetic subclass from pilocytic astrocytomas of other locations and diffuse leptomeningeal glioneuronal tumours
Authors: Métais Alice , Bouchoucha Yassine , Kergrohen Thomas , Dangouloff-Ros Volodia , Maynadier Xavier , Ajlil Yassine , Carton Matthieu , Yacoub Wael , Saffroy Raphael , Figarella-Branger Dominique , Uro-Coste Emmanuelle , Sevely Annick , Larrieu-Ciron Delphine , Faisant Maxime , Machet Marie-Christine , Wahler Ellen , Roux Alexandre , Benichi Sandro , Beccaria Kevin , Blauwblomme Thomas , Boddaert Nathalie , Chrétien Fabrice , Doz François , Dufour Christelle , Grill Jacques , Debily Marie Anne , Varlet Pascale , Tauziède-Espariat Arnault
Published: October 2022

Pediatric spinal low-grade glioma (LGG) and glioneuronal tumours are rare, accounting for less 2.8–5.2% of pediatric LGG. New tumour types frequently found in spinal location such as diffuse leptomeningeal glioneuronal tumours (DLGNT) have been added to the World Health Organization (WHO) classification of tumours of the central nervous system since 2016, but their distinction from others gliomas and particularly from pilocytic astrocytoma (PA) are poorly defined. Most large studies on this subject were published before the era of the molecular diagnosis and did not address the differential diagnosis between PAs and DLGNTs in this peculiar location. Our study retrospectively examined a cohort of 28 children with LGGs and glioneuronal intramedullary tumours using detailed radiological, clinico-pathological and molecular analysis. 25% of spinal PAs were reclassified as DLGNTs. PA and DLGNT are nearly indistinguishable in histopathology or neuroradiology. 83% of spinal DLGNTs presented first without leptomeningeal contrast enhancement. Unsupervised t-distributed stochastic neighbor embedding (t-SNE) analysis of DNA methylation profiles showed that spinal PAs formed a unique methylation cluster distinct from reference midline and posterior fossa PAs, whereas spinal DLGNTs clustered with reference DLGNT cohort. FGFR1 alterations were found in 36% of spinal tumours and were restricted to PAs. Spinal PAs affected significantly younger patients (median age 2 years old) than DLGNTs (median age 8.2 years old). Progression-free survival was similar among the two groups. In this location, histopathology and radiology are of limited interest, but molecular data (methyloma, 1p and FGFR1 status) represent important tools differentiating these two mitogen-activated protein kinase (MAPK) altered tumour types, PA and DLGNT. Thus, these molecular alterations should systematically be explored in this type of tumour in a spinal location.
A viscoelastic Mooney–Rivlin model for adhesive curing and first steps toward its calibration based on photoelasticity measurements
Authors: Lengger Michael , Possart Gunnar , Steinmann Paul
Published: October 2022

The transition of polymer adhesives from an initially liquid to a fully cured viscoelastic state is accompanied by three phenomenological effects, namely an increase in stiffness and viscosity in conjunction with a decrease in volume (curing shrinkage). Under consideration of these phenomena, some of us (Hossain et al. in Computational Mechanics 46:363-375, 2010) have devised a generic, viscoelastic finite strain framework for the simulation of the curing process of adhesives, which renders a thermodynamically consistent model regardless of the selected free energy density. In the present work, this generic curing framework is modified by means of more precise integration schemes and is applied to a hyperelastic Mooney–Rivlin material based on an additive volumetric-isochoric split of the strain energy density. The benefit of this decomposition is directly related to the distinct material responses of various polymers to volumetric and isochoric deformations [4]. The resulting Mooney–Rivlin curing model provides the foundation for implementing a user-defined material subroutine (UMAT) in Abaqus requiring the Cauchy stress and a non-standard formulation of the tangent operator. To this end, the corresponding transformations are presented. Additionally, a first attempt to determine the evolution of the curing-dependent material parameters through optimization with respect to a photoelasticity measurement is presented. A subset of the material properties, which reflect the emergence of shrinkage stresses inside a ceramic-epoxy composite after its fabrication, is determined via inverse parameter identification. However, due to a lack of experimental data and some rather strong assumptions made on the physics involved, this demonstration can currently be considered only as a proof-of-concept.
Risk of depression mediates the association between cardiorespiratory fitness and academic performance in adolescent boys and girls: DADOS study
Authors: Monzonís-Carda Irene , Adelantado-Renau Mireia , Beltran-Valls Maria Reyes , Moliner–Urdiales Diego
Published: October 2022

This study aims to analyze the mediating role of risk of depression in the association between cardiorespiratory fitness and academic performance in a sample of adolescents and to test the moderation effect of sex. A total of 263 adolescents (125 girls, 13.9 ± 0.3 years) from the DADOS (Deporte, ADOlescencia y Salud) study were included in the analysis. Cardiorespiratory fitness was assessed by the 20-m shuttle run test. Academic performance was assessed through the final academic grades and the test of educational abilities. Risk of depression was evaluated through the Behavior Assessment System for Children and Adolescents. Mediation analyses were performed to determine the direct and indirect associations between cardiorespiratory fitness, risk of depression, and academic performance. Indirect effects with confidence intervals not including zero were interpreted as statistically significant, and percentages of mediation were calculated in order to know how much of the association was explained by the mediation. Our findings indicated a significant mediating effect of risk of depression in the association between cardiorespiratory fitness with final grades in math, language, and grade point average (percentages of mediation: 26%, 53%, and 29%, respectively). These analyses were not moderated by sex (all confidence intervals included 0).

Conclusion: Risk of depression acts as a possible underlying mechanism in the association between cardiorespiratory fitness and academic grades in adolescents. Educational and health institutions could benefit from our findings since the promotion of higher cardiorespiratory fitness levels might reduce the risk of depression with potential benefits on adolescents’ academic performance.

What is Known:• Cardiorespiratory
fitness is positively associated with academic performance in adolescents.
Nevertheless, the psychological mechanisms underlying this association are
poorly understood.

What is New:• Risk of depression
mediates the association between cardiorespiratory fitness and academic
performance in adolescents, independently of sex.• Our findings may
improve the efficacy of mental health and educational programs by promoting the
enhancement of cardiorespiratory fitness levels, which may reduce risk of depression with potential benefits on academic performance.
Erwartungshorizonte und Möglichkeitsräume
Authors: Küchenhoff Joachim
Published: October 2022

Mit den im Titel genannten Begriffen Erwartungshorizont und Möglichkeitsraum werden einige grundlegende Merkmale der psychoanalytischen Kur benannt. Sie dienen als Ausgangspunkte, um Wirkungsweise und Ziel auch der psychoanalytischen Supervision zu umschreiben. Supervision arbeitet an und mit Möglichkeitsräumen und Erwartungshorizonten der Psychotherapie, stellt sie her oder erweitert sie. Der Begriff Supervision wird einer kritischen Revision unterzogen. Die psychodynamischen Faktoren, mit denen in der Supervision umgegangen werden muss, werden dargestellt, vor allem das Übertragungs- und Gegenübertragungsgeschehen in der Supervision selbst, aber auch andere Fallstricke, die Supervisionen gefährden können und auf die zu achten ist. Am Ende steht eine sehr alte chinesische Geschichte, die genutzt wird, um die Rolle der Supervision zu charakterisieren.
Emulation of the control cohort of a randomized controlled trial in pediatric kidney transplantation with Real-World Data from the CERTAIN Registry
Authors: Patry Christian , Sauer Lukas D. , Sander Anja , Krupka Kai , Fichtner Alexander , Brezinski Jolanda , Geissbühler Yvonne , Aubrun Elodie , Grinienko Anna , Strologo Luca Dello , Haffner Dieter , Oh Jun , Grenda Ryszard , Pape Lars , Topaloğlu Rezan , Weber Lutz T. , Bouts Antonia , Kim Jon Jin , Prytula Agnieszka , König Jens , Shenoy Mohan , Höcker Britta , Tönshoff Burkhard
Published: October 2022

Background

Randomized controlled trials in pediatric kidney transplantation are hampered by low incidence and prevalence of kidney failure in children. Real-World Data from patient registries could facilitate the conduct of clinical trials by substituting a control cohort. However, the emulation of a control cohort by registry data in pediatric kidney transplantation has not been investigated so far.

Methods

In this multicenter comparative analysis, we emulated the control cohort (n = 54) of an RCT in pediatric kidney transplant patients (CRADLE trial; ClinicalTrials.gov NCT01544491) with data derived from the Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry, using the same inclusion and exclusion criteria (CERTAIN cohort, n = 554).

Results

Most baseline patient and transplant characteristics were well comparable between both cohorts. At year 1 posttransplant, a composite efficacy failure end point comprising biopsy-proven acute rejection, graft loss or death (5.8% ± 3.3% vs. 7.5% ± 1.1%, P = 0.33), and kidney function (72.5 ± 24.9 vs. 77.3 ± 24.2 mL/min/1.73 m2P = 0.19) did not differ significantly between CRADLE and CERTAIN. Furthermore, the incidence and severity of BPAR (5.6% vs. 7.8%), the degree of proteinuria (20.2 ± 13.9 vs. 30.6 ± 58.4 g/mol, P = 0.15), and the key safety parameters such as occurrence of urinary tract infections (24.1% vs. 15.5%, P = 0.10) were well comparable.

Conclusions

In conclusion, usage of Real-World Data from patient registries such as CERTAIN to emulate the control cohort of an RCT is feasible and could facilitate the conduct of clinical trials in pediatric kidney transplantation.

Graphical abstract
Unraveling the role of dragon’s blood in the undisturbed growth of dragon trees
Authors: Jura-Morawiec Joanna , Marcinkiewicz Jan , Caujapé-Castells Juli
Published: October 2022

Key message

Dragon’s blood secretion is an integral part of the normal development of the leaves and of the tissue protecting the trunk of dragon trees.

Dragon’s blood is a common name of a red resin produced in response to wounding by tree-like monocot species of the genus Dracaena (Asparagaceae), known as dragon trees. This resin has important medicinal uses and economic value. However, its ecological significance and mechanism of secretion are understudied. We specifically addressed this knowledge gap through the investigation of leaf shedding, a natural processes in plant development, associated with self-wounding. We aimed to characterize the form of the resin of the Macaronesian (D. draco, D. tamaranae) and Socotran (D. cinnabari) dragon trees, and to explain its role in the development of leaves and of the tissue covering the leafless mature trunks. Based on the NADI test and the analysis of large-area longitudinal sections, we show for the first time that the resin occurs in parenchyma cells in the form of terpene-filled vesicles which tend to aggregate. The resin is an anatomical marker of the area where the leaf’s abscission zone will be formed. After leaf shedding, the resin containing leaf scars completely cover the trunk. This study highlights that dragon’s blood is secreted not only following wounding caused by external biotic and/or abiotic factors, but also in the undisturbed growth of dragon trees.
Direct prediction of genetic aberrations from pathology images in gastric cancer with swarm learning
Authors: Saldanha Oliver Lester , Muti Hannah Sophie , Grabsch Heike I. , Langer Rupert , Dislich Bastian , Kohlruss Meike , Keller Gisela , van Treeck Marko , Hewitt Katherine Jane , Kolbinger Fiona R. , Veldhuizen Gregory Patrick , Boor Peter , Foersch Sebastian , Truhn Daniel , Kather Jakob Nikolas
Published: October 2022

Background

Computational pathology uses deep learning (DL) to extract biomarkers from routine pathology slides. Large multicentric datasets improve performance, but such datasets are scarce for gastric cancer. This limitation could be overcome by Swarm Learning (SL).

Methods

Here, we report the results of a multicentric retrospective study of SL for prediction of molecular biomarkers in gastric cancer. We collected tissue samples with known microsatellite instability (MSI) and Epstein–Barr Virus (EBV) status from four patient cohorts from Switzerland, Germany, the UK and the USA, storing each dataset on a physically separate computer.

Results

On an external validation cohort, the SL-based classifier reached an area under the receiver operating curve (AUROC) of 0.8092 (± 0.0132) for MSI prediction and 0.8372 (± 0.0179) for EBV prediction. The centralized model, which was trained on all datasets on a single computer, reached a similar performance.

Conclusions

Our findings demonstrate the feasibility of SL-based molecular biomarkers in gastric cancer. In the future, SL could be used for collaborative training and, thus, improve the performance of these biomarkers. This may ultimately result in clinical-grade performance and generalizability.
First-line pembrolizumab ± chemotherapy for recurrent/metastatic head and neck cancer: Japanese subgroup of KEYNOTE-048
Authors: Takahashi Shunji , Oridate Nobuhiko , Tanaka Kaoru , Shimizu Yasushi , Fujimoto Yasushi , Matsumoto Koji , Yokota Tomoya , Yamazaki Tomoko , Takahashi Masanobu , Ueda Tsutomu , Hanai Nobuhiro , Yamaguchi Hironori , Hara Hiroki , Yoshizaki Tomokazu , Yasumatsu Ryuji , Nakayama Masahiro , Shiga Kiyoto , Fujii Takashi , Mitsugi Kenji , Takahashi Kenichi , Nohata Nijiro , Gumuscu Burak , Swaby Ramona F. , Tahara Makato
Published: October 2022

Background

Here, we report the results of the Japanese subgroup of the phase 3 KEYNOTE-048 study of pembrolizumab alone, pembrolizumab plus platinum and 5-fluorouracil (pembrolizumab–chemotherapy), or cetuximab plus platinum and 5-fluorouracil (EXTREME) in previously untreated recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

Methods

Primary end points were overall survival (OS) and progression-free survival (PFS). Efficacy was evaluated in patients with PD-L1 combined positive score (CPS) ≥ 20 and ≥ 1 and the total Japanese subgroup (n = 67).

Results

At data cutoff (25 February 2019), pembrolizumab led to longer OS versus EXTREME in the PD-L1 CPS ≥ 20 subgroup (median, 28.2 vs. 13.3 months; HR, 0.29 [95% CI 0.09–0.89]) and to similar OS in the total Japanese (23.4 vs. 13.6 months; HR, 0.51 [95% CI 0.25–1.05]) and CPS ≥ 1 subgroups (22.6 vs. 15.8 months; HR, 0.66 [95% CI 0.31–1.41]). Pembrolizumab–chemotherapy led to similar OS versus EXTREME in the PD-L1 CPS ≥ 20 (median, 18.1 vs. 15.8 months; HR, 0.72 [95% CI 0.23–2.19]), CPS ≥ 1 (12.6 vs. 15.8 months; HR, 1.19 [95% CI 0.55–2.58]), and total Japanese subgroups (12.6 vs. 13.3 months; unadjusted HR, 1.10 [95% CI 0.55–2.22]). Median PFS was similar for pembrolizumab and pembrolizumab–chemotherapy versus EXTREME in all subgroups. Grades 3–5 treatment-related adverse events occurred in 5 (22%), 19 (76%), and 17 (89%) patients receiving pembrolizumab, pembrolizumab–chemotherapy, and EXTREME, respectively. One patient receiving pembrolizumab–chemotherapy died because of treatment-related pneumonitis.

Conclusion

These results support the use of first-line pembrolizumab and pembrolizumab–chemotherapy for Japanese patients with R/M HNSCC.

Clinical trial registryClinicalTrials.gov, NCT02358031.
Status quo der unterschiedlichen Konjunkturbereinigungsverfahren der Länder
Authors: Kasseckert Markus
Published: October 2022

Seit dem Haushaltsjahr 2020 sind die Bundesländer verpflichtet, das Verschuldungsverbot nach Art. 109 (3) GG zu beachten. In diesem Zusammenhang konnten sie sich für ein Konjunkturbereinigungsverfahren entscheiden. Mit Ausnahme von Bayern wenden alle Bundesländer ein solches Verfahren zur Ermittlung der Konjunkturkomponente an. Aus den bisher durchgeführten Verfahren und ermittelten Konjunkturkomponenten lassen sich erste Schlussfolgerungen für mögliche und teilweise notwendige Weiterentwicklungen ziehen.
Gemeinschaftsdiagnose: Energiekrise, Inflation, Rezession und Wohlstandsverlust
Authors: Holtemöller Oliver , Kooths Stefan , Schmidt Torsten , Wollmershäuser Timo
Published: October 2022

Die deutsche Wirtschaft wird von der krisenhaften Zuspitzung auf den Gasmärkten schwer belastet. Die hochgeschnellten Gaspreise erhöhen die Energiekosten drastisch und gehen mit einem massiven gesamtwirtschaftlichen Kaufkraftentzug einher. Dies dämpft nicht nur die noch unvollständige Erholung von der Coronakrise, sondern drückt die deutsche Wirtschaft in die Rezession. Dabei kommen die Institute für den kommenden Winter zu dem Ergebnis, dass bei normalen Witterungsbedingungen keine Gasmangellage eintritt. Dennoch bleibt die Versorgungslage äußerst angespannt. Vor diesem Hintergrund dürfte die Wirtschaftsleistung im dritten Quartal bereits leicht gesunken sein. Im Winterhalbjahr ist aufgrund der steigenden Kosten für Energie, der nachlassenden Konsumnachfrage und der schwächelnden Weltwirtschaft mit einem deutlichen Rückgang zu rechnen.
Streit um Entlastungspaket: Steuersenkungen oder direkte Transfers?
Authors:   ZG Überblick
Published: October 2022

Durch die hohe Inflation profitiert der Staat auf verschiedene Weise, beispielsweise aufgrund der Ausgestaltung des progressiven Steuer- und Transfersystems in nominalen Größen. Einige Maßnahmen zur Entlastung sind bereits in Kraft getreten. Verschiedene weitere Maßnahmen sind angekündigt. Finanzminister Christian Lindner hat nun einen Vorschlag zu Steuerentlastungen gemacht, die einen Umfang von 10 Mrd. haben könnten. Dabei handelt es sich jedoch um eine einmalige ad-hoc-Maßnahme und nicht um eine grundlegende Reform. Ist eine Reform der Einkommensteuer nötig und ist die kalte Progression ein Problem, das beseitigt werden sollte? Oder sind andere Reformen derzeit dringlicher, damit sozial ausgeglichener entlastet werden kann? Wäre ein Pauschaltransfer — wie er im Koalitionsvertrag angelegt ist — effizienter und falls ja, woran scheitert dieser? Welche Einkommensgruppen sollten bei einer Reform besonders entlastet werden?
Entlasten! Aber wie? Wege im Dschungel der Möglichkeiten
Authors: Riedel Nadine , Peichl Andreas
Published: October 2022

Living costs in Germany have surged since Russia’s attack on Ukraine. In this article, we discuss pros and cons of different government policies to protect affected citizens. There is a vast domain of possible relief options, each coming with its own trade-offs and design pitfalls. Information gaps in German public administration render desirable options like income and energy-use-contingent transfers administratively infeasible. These frictions should be addressed — if not for the present, then for the next crisis. With regard to other options, governments must be mindful to design policies that are well-targeted to people in need and that do not distort incentives to reduce energy consumption. Possibilities for that do exist.
New Approach to Privacy-Preserving Clinical Decision Support Systems for HIV Treatment
Authors: Spini Gabriele , Mancini Emiliano , Attema Thomas , Abspoel Mark , de Gier Jan , Fehr Serge , Veugen Thijs , van Heesch Maran , Worm Daniël , De Luca Andrea , Cramer Ronald , Sloot Peter M.A.
Published: October 2022

Background

HIV treatment prescription is a complex process. Clinical decision support systems (CDSS) are a category of health information technologies that can assist clinicians to choose optimal treatments based on clinical trials and expert knowledge. The usability of some CDSSs for HIV treatment would be significantly improved by using the knowledge obtained by treating other patients. This knowledge, however, is mainly contained in patient records, whose usage is restricted due to privacy and confidentiality constraints.

Methods

A treatment effectiveness measure, containing valuable information for HIV treatment prescription, was defined and a method to extract this measure from patient records was developed. This method uses an advanced cryptographic technology, known as secure Multiparty Computation (henceforth referred to as MPC), to preserve the privacy of the patient records and the confidentiality of the clinicians’ decisions.

Findings

Our solution enables to compute an effectiveness measure of an HIV treatment, the average time-to-treatment-failure, while preserving privacy. Experimental results show that our solution, although at proof-of-concept stage, has good efficiency and provides a result to a query within 24 min for a dataset of realistic size.

Interpretation

This paper presents a novel and efficient approach HIV clinical decision support systems, that harnesses the potential and insights acquired from treatment data, while preserving the privacy of patient records and the confidentiality of clinician decisions.
Chelating Agents Assisted Rapid Synthesis of High Purity BiFeO3: Remarkable Optical, Electrical, and Magnetic Characteristics
Authors: Wahba Mohammed Ahmed , Yakout Saad Mabrouk , Youssef A. M. , Sharmoukh Walid , sayed A. M. El , Khalil M. Sh.
Published: October 2022

In this study, we presented two reliable methods, the sol–gel and autocombustion, to synthesis a high purity BiFeO3 single phase with low calcination time using glycine as chelating agent. The glycine-autocombustion method produced a high purity BiFeO3 phase using either low or high concentrations of the reactants (Bi(NO3)3 + Fe(NO3)3), while the glycine-sol–gel method delivered a high purity BiFeO3 phase using low concentrations of reactants. In the case of using tartaric acid and urea as chelating agents, mixtures of BiFeO3 and Bi25FeO40 phases were formed. The morphology, size, and porosity of the particles were obviously changed by varying the synthesis method and chelating agents. The high purity BiFeO3 samples exhibit a visible light band gap of 2.05 eV with long absorption tail extending to the infrared region, suggesting the suitability of the synthesized powders in the solar photocatalytic applications. A weak hysteresis ferromagnetic loop was observed for BiFeO3 (glycine method) and BiFeO3/Bi25FeO40 (urea method) with large contribution from the paramagnetic behavior. On contrast, robust ferromagnetic loops were found for BiFeO3/Bi25FeO40 sample synthesized by tartaric acid with saturation magnetization reaching to 2.5 emu/g. Remarkably, the pure single phase BiFeO3 powders synthesized by sol–gel and auto-combustion methods using glycine possess room temperature dielectric constant values of 622 and 845 respectively at a frequency of 42 Hz. In the case of BiFeO3 powders prepared by using tartaric acid, the dielectric constant exhibits values of 401 and 1118 for sol–gel and auto-combustion assisted samples, at the same frequency, respectively. At low frequency, the values of the real part of the complex permittivity tend to be zero which confirms a negligibly small contribution of the electrode effect.
Drawing lessons from PISA: Qatar’s use of PISA results
Authors: AlKaabi Nouf Abdullah , Al-Maadeed Najlaa , Romanowski Michael H. , Sellami Abdellatif
Published: October 2022

Worldwide, the Programme for International Student Assessment (PISA) has emerged as a valid and reliable benchmark for assessing students’ performance and for gaining significant influence over educational policy and decision-making. Since 2001, Qatar has engaged in massive educational reform, with high expectations for improving students’ achievement. Although significant growth has occurred in Qatar’s education system, students’ performance in PISA is still lagging. The purpose of this article is to examine PISA against the backdrop of Qatar’s education system. It addresses PISA’s objectives and limitations and identifies two common factors in high-achieving countries, teachers, and assessment. These factors are analyzed to determine how Qatar is developing in these areas, compared with other nations, raising issues that should be considered when using PISA to create policy. Finally, several recommendations are offered for policy makers.
Blood lead monitoring in a former mining area in Euskirchen, Germany: results of a representative random sample in 3- to 17-year-old children and minors
Authors: Bertram Jens , Ramolla Christian , Esser André , Schettgen Thomas , Fohn Nina , Steib Jasmina , Kraus Thomas
Published: October 2022

Heavy metal residues in former mining areas can pose a burden to the local environment and population even decades after closure of the mining sites. In the North Rhine-Westphalian (Germany) communities of Mechernich and Kall, both parts of the district of Euskirchen, lead residues are a source of health concerns for local residents. A statistically representative collective of both communities depending on sex, age, and area of residence was created, mirroring the local underage population. The blood lead levels (BLL) of 182 children and minors in the two adjacent communities were assessed via ICP-MSMS. The results were compared to German lead reference values, valid for the general underage population. In total, 32 (17.6%) of the subjects investigated exceeded the according reference values of 15 µg/L and 20 µg/L, respectively, depending on sex and age, thus pointing out an additional lead burden affecting children in the area. Potential lead sources contributing to the BLL were evaluated using a questionnaire. Factors that showed significant impact on the BLL were, other than age, sex, height, and weight, the factors occupancy, time spend in the garden, garden hand-to-mouth contact, consumption frequency of homegrown products, and lifestyle factors. The data presented enable both residents and the local authorities to further reduce lead exposure and to take appropriate personal and public action.
Abatement of the ecotoxicological risk of landfill leachate by heterogeneous Fenton-like oxidation
Authors: Hussain Sajid , Aneggi Eleonora , Comuzzi Clara , Baderna Diego , Zuccaccia Daniele , Trovarelli Alessandro , Goi Daniele
Published: October 2022

Landfill leachates are highly contaminated liquid waste, and their treatment and detoxification are a challenging task. The current system of ecotoxicological risk assessment is complex and time-consuming. It is of fundamental importance to develop simpler and faster tools for the evaluation of the treated liquid waste and for an easier preliminary screening of the most active catalytic formulation/reaction conditions of the Fenton-like process. Here, several analytical techniques have been used for the assessment of the reduction of toxicity of the landfill leachate after Fenton process over copper-zirconia catalyst (ZrCu). Ultraviolet–visible (UV–vis) spectroscopy and absorbable organic halogens (AOX) analysis have been coupled to achieve further insight into the degradation of contaminants. In addition, for the first time, the qualitative abatement of organic compounds is monitored through proton nuclear magnetic resonance (1H NMR) analysis, providing a new method for evaluating the effectiveness of the treatment. Spectroscopic techniques reveal that the Fenton process induces a significant abatement of the aromatic and halogen compounds (51%) in the landfill leachate with a reduction of the toxicity that has been confirmed by ecotoxicological test with algae. These results validate the investigated tool for a simple rapid preliminary evaluation of the detoxification efficacy.
Numerical Investigation of Burden Distribution in Hydrogen Blast Furnace
Authors: Li Jing , Kuang Shibo , Zou Ruiping , Yu Aibing
Published: October 2022

Hydrogen injection is a promising technology currently under development to reduce CO2 emissions in ironmaking blast furnaces (BFs). Therefore, hydrogen BF is studied by a recent process model based on computational fluid dynamics (CFD). It focuses on the effect of peripheral opening extent (POE), which represents the coke amount near the furnace wall. The simulations consider a 380 m3 BF operated with hydrogen injection through both shaft and hearth tuyeres. The overall performance of the BF is analyzed in terms of the inner states. It shows that increasing POE hinders the pre-reduction and pre-heating roles of shaft-injected hydrogen (SIH) but improves the CO indirect reduction rate. An optimum peripheral opening extent can be identified to achieve a maximum hot metal (HM) temperature, relatively low bed pressure, and good gas utilization. The interaction between SIH flow rate and burden distribution is also quantified. It shows that the increase in SIH flow rate slows down the CO indirect reduction rate but enhances the H2 indirect reduction rate. These opposite trends account for the less variation of HM temperature with POE as the SIH flow rate increases. This variation becomes trivial at relatively large SIH flow rates and small POEs. Overall, the POE affects the cohesive zones more than the SIH flow rate. However, under the conditions considered, both variables cannot significantly improve the penetration of the shaft injection, the effect of which is generally confined within the peripheral region.
Testing phaeophytinization as an index of ozone stress in trees
Authors: Agathokleous Evgenios , Kitao Mitsutoshi , Koike Takayoshi
Published: October 2022

Ground-level ozone pollution is a menace for vegetation in the northern hemisphere, limiting photosynthetic pigments and suppressing photosynthesis in trees and other types of plants. Phaeophytinization is the process of converting chlorophylls into phaeophytins, for example by acidification. Ozone is a highly oxidizing molecule and well known to degrade chlorophylls; however, the effect of ozone on phaeophytinization in leaves of higher plants is largely unknown. To reveal ozone effect on phaeophytinization and evaluate the potential of phaeophytinization as an index of ozone stress in trees, the absorbance at the optical density of 665 nm was measured before (OD665) and after (OD665a) acidification in three independent experiments with nearly 30 conditions of ozone exposure. Both current ambient and elevated ozone widely affected phaeophytinization, as indicated by decreases or increases in the phaeophytinization quotient OD665/OD665a. These effects were commonly moderate to large in magnitude and practically significant, and occurred even in ozone-asymptomatic leaves. It emerges that the ozone effect on phaeophytinization is bimodal, likely depending on the intensity of ozone stress. These results indicate a promising feature of OD665/OD665a as a thorough index of ozone stress in the future, but further studies are needed to reveal the underlying biochemical mechanisms of the bimodal effect on phaeophytinization.