bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes
Authors: Sasaki Hironobu , Saisho Yoshifumi , Inaishi Jun , Watanabe Yuusuke , Tsuchiya Tami , Makio Masayoshi , Sato Midori , Nishikawa Masaru , Kitago Minoru , Yamada Taketo , Itoh Hiroshi
Published: May 2021

Aims/hypothesis

Type 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes.

Methods

Pancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell number was estimated from the product of fractional beta cell area and pancreas volume divided by beta cell size. The associations of beta cell size and number with islet morphology and metabolic status were examined.

Results

Both beta cell size (548.7 ± 58.5 vs 606.7 ± 65.0 μm3, p < 0.01) and number (5.10 × 108 ± 2.35 × 108 vs 8.16 × 108 ± 4.27 × 108, p < 0.01) were decreased in participants with type 2 diabetes compared with those without diabetes, with the relative reduction in beta cell number (37%) being greater than for beta cell size (10%). Beta cell number but not size was positively correlated with BCM in participants with and without type 2 diabetes (r = 0.97 and r = 0.98, both p < 0.01) and negatively correlated with HbA1c (r = −0.45, p < 0.01).

Conclusions/interpretation

Both beta cell size and number were reduced in participants with type 2 diabetes, with the relative reduction in beta cell number being greater. Decrease in beta cell number appears to be a major contributor to reduced BCM in type 2 diabetes.

Graphical abstract
Air pollution and trajectories of adolescent conduct problems: the roles of ethnicity and racism; evidence from the DASH longitudinal study
Authors: Karamanos A. , Mudway I. , Kelly F. , Beevers S. D. , Dajnak D. , Elia C. , Cruickshank J. K. , Lu Y. , Tandon S. , Enayat E. , Dazzan P. , Maynard M. , Harding S.
Published: April 2021

Purpose

No known UK empirical research has investigated prospective associations between ambient air pollutants and conduct problems in adolescence. Ethnic minority children are disproportionately exposed to structural factors that could moderate any observed relationships. This prospective study examined whether exposure to PM2.5 and NO2 concentrations is associated with conduct problems in adolescence, and whether racism or ethnicity moderate such associations.

Methods

Longitudinal associations between annual mean estimated PM2.5 and NO2 concentrations at the residential address and trajectories of conduct problems, and the potential influence of racism and ethnicity were examined school-based sample of 4775 participants (2002–2003 to 2005–2006) in London, using growth curve models.

Results

Overall, in the fully adjusted model, exposure to lower concentrations of PM2.5 and NO2 was associated with a decrease in conduct problems during adolescence, while exposure to higher concentrations was associated with a flattened trajectory of conduct symptoms. Racism amplified the effect of PM2.5 (β = 0.05 (95% CI 0.01 to 0.10, p < 0.01)) on adolescent trajectories of conduct problems over time. At higher concentrations of PM2.5, there was a divergence of trajectories of adolescent conduct problems between ethnic minority groups, with White British and Black Caribbean adolescents experiencing an increase in conduct problems over time.

Conclusion

These findings suggest that the intersections between air pollution, ethnicity, and racism are important influences on the development of conduct problems in adolescence.
Patientensicherheit in der endoprothetischen Weiterbildung
Authors: Rohe S. , Brodt S. , Windisch C. , Matziolis G. , Böhle S.
Published: April 2021

Hintergrund

Ziel der Studie war die Untersuchung, ob sich das perioperative Outcome und operationsspezifische Prozessgrößen bei Patienten mit Hüftgelenksersatz signifikant verschlechtern, wenn die Operation durch einen unerfahrenen Operateur, assistiert durch einen erfahrenen Operateur, im Kontext eines zertifizierten Endoprothesenzentrums durchgeführt wird.

Material und Methoden

Es wurden 1480 Patienten eingeschlossen, die zwischen 2013 und 2016 bei primärer Koxarthrose mit einer primären zementfreien Hüfttotalendoprothese (HTEP) versorgt wurden. Die relevanten Daten wurden retrospektiv aus dem Krankenhausinformationssystem, dem Entlassungsbrief und aus dem EndoCert-Bogen dokumentiert. Die Operateure wurden nach ihrer Qualifikation in erfahrene (Senior, > 50 HTEP pro Jahr) und unerfahrene Operateure (Junior, < 50 HTEP pro Jahr) unterteilt. Anschließend erfolgte der Vergleich der erhobenen Daten anhand dieser Unterteilung.

Resultate

Es zeigte sich bei unerfahrenen Operateuren eine signifikante Verlängerung der Operationsdauer um 20,7 min (Senior 62,6 ± 20,4 min; Junior 83,3 ± 19,5 min; p ≤ 0,001), der Krankenhausverweildauer um 0,25 Tage (Senior 8,8 ± 0,9 d; Junior 9,0 ± 0,9 d; p ≤ 0,001) und eine Erhöhung der Transfusionshäufigkeit von Erythrozytenkonzentraten (Senior 0,6 ± 1,1 Stk.; Junior 0,9 ± 1,4 Stk.; p ≤ 0,001). Dagegen zeigte sich kein Unterschied bei perioperativen Komplikationen (p = 0,682) und beim perioperativen Blutverlust (Senior 1,3 ± 0,5 l; Junior 1,3 ± 0,5 l; p = 0,097). Zwischen Operationsdauer und Blutverlust bestand allerdings eine positive Korrelation (Senior r = 0,183; Junior r = 0,214; jeweils p ≤ 0,01).

Schlussfolgerung

Die Ausbildung von unerfahrenen Operateuren an einem zertifizierten Endoprothesenzentrum führt bei Assistenz durch erfahrene Operateure nicht zur Reduktion der Patientensicherheit mit vermehrten Komplikationen. Aufgrund der Operationszeitverlängerung kommt es allerdings zu einer Mehrbelastung der Kliniken im Wettbewerb mit nichtausbildenden Kliniken, die nicht im DRG-System abgebildet ist.
Social robots and the risks to reciprocity
Authors: van Wynsberghe Aimee
Published: April 2021

A growing body of research can be found in which roboticists are designing for reciprocity as a key construct for successful human–robot interaction (HRI). Given the centrality of reciprocity as a component for our moral lives (for moral development and maintaining the just society), this paper confronts the possibility of what things would look like if the benchmark to achieve perceived reciprocity were accomplished. Through an analysis of the value of reciprocity from the care ethics tradition the richness of reciprocity as an inherent value is revealed: on the micro-level, as mutual care for immediate care givers, and on the macro-level, as foundational for a just society. Taking this understanding of reciprocity into consideration, it becomes clear that HRI cannot achieve this bidirectional value of reciprocity; a robot must deceive users into believing it is capable of reciprocating to humans or is deserving of reciprocation from humans. Moreover, on the macro-level, designing social robots for reciprocity threatens the ability and willingness to reciprocate to human care workers across society. Because of these concerns, I suggest re-thinking the goals of reciprocity in social robotics. Designing for reciprocity in social robotics should be dedicated to the design of robots to enhance the ability to mutually care for those that provide us with care, as opposed to designing for reciprocity between human and robot.
A multigrid preconditioner for tensor product spline smoothing
Authors: Siebenborn Martin , Wagner Julian
Published: April 2021

Penalized spline smoothing is a well-established, nonparametric regression method that is efficient for one and two covariates. Its extension to more than two covariates is straightforward but suffers from exponentially increasing memory demands and computational complexity, which brings the method to its numerical limit. Penalized spline smoothing with multiple covariates requires solving a large-scale, regularized least-squares problem where the occurring matrices do not fit into storage of common computer systems. To overcome this restriction, we introduce a matrix-free implementation of the conjugate gradient method. We further present a matrix-free implementation of a simple diagonal as well as more advanced geometric multigrid preconditioner to significantly speed up convergence of the conjugate gradient method. All algorithms require a negligible amount of memory and therefore allow for penalized spline smoothing with multiple covariates. Moreover, for arbitrary but fixed covariate dimension, we show grid independent convergence of the multigrid preconditioner which is fundamental to achieve algorithmic scalability.
Peptide array–based interactomics
Authors: Hernandez Daniel Perez , Dittmar Gunnar
Published: May 2021

The analysis of protein-protein interactions (PPIs) is essential for the understanding of cellular signaling. Besides probing PPIs with immunoprecipitation-based techniques, peptide pull-downs are an alternative tool specifically useful to study interactome changes induced by post-translational modifications. Peptides for pull-downs can be chemically synthesized and thus offer the possibility to include amino acid exchanges and post-translational modifications (PTMs) in the pull-down reaction. The combination of peptide pull-down and analysis of the binding partners with mass spectrometry offers the direct measurement of interactome changes induced by PTMs or by amino acid exchanges in the interaction site. The possibility of large-scale peptide synthesis on a membrane surface opened the possibility to systematically analyze interactome changes for mutations of many proteins at the same time. Short linear motifs (SLiMs) are amino acid patterns that can mediate protein binding. A significant number of SLiMs are located in regions of proteins, which are lacking a secondary structure, making the interaction motifs readily available for binding reactions. Peptides are particularly well suited to study protein interactions, which are based on SLiM-mediated binding. New technologies using arrayed peptides for interaction studies are able to identify SLIM-based interaction and identify the interaction motifs.

Graphical abstract
Correlation energy of a weakly interacting Fermi gas
Authors: Benedikter Niels , Nam Phan Thành , Porta Marcello , Schlein Benjamin , Seiringer Robert
Published: May 2021

We derive rigorously the leading order of the correlation energy of a Fermi gas in a scaling regime of high density and weak interaction. The result verifies the prediction of the random-phase approximation. Our proof refines the method of collective bosonization in three dimensions. We approximately diagonalize an effective Hamiltonian describing approximately bosonic collective excitations around the Hartree–Fock state, while showing that gapless and non-collective excitations have only a negligible effect on the ground state energy.
Cortical spectral matching and shape and volume analysis of the fetal brain pre- and post-fetal surgery for spina bifida: a retrospective study
Authors: Mufti Nada , Aertsen Michael , Ebner Michael , Fidon Lucas , Patel Premal , Rahman Muhamad Bin Abdul , Brackenier Yannick , Ekart Gregor , Fernandez Virginia , Vercauteren Tom , Ourselin Sebastien , Thomson Dominic , De Catte Luc , Demaerel Philippe , Deprest Jan , David Anna L. , Melbourne Andrew
Published: May 2021

Purpose

A retrospective study was performed to study the effect of fetal surgery on brain development measured by MRI in fetuses with myelomeningocele (MMC).

Methods

MRI scans of 12 MMC fetuses before and after surgery were compared to 24 age-matched controls without central nervous system abnormalities. An automated super-resolution reconstruction technique generated isotropic brain volumes to mitigate 2D MRI fetal motion artefact. Unmyelinated white matter, cerebellum and ventricles were automatically segmented, and cerebral volume, shape and cortical folding were thereafter quantified. Biometric measures were calculated for cerebellar herniation level (CHL), clivus-supraocciput angle (CSO), transverse cerebellar diameter (TCD) and ventricular width (VW). Shape index (SI), a mathematical marker of gyrification, was derived. We compared cerebral volume, surface area and SI before and after MMC fetal surgery versus controls. We additionally identified any relationship between these outcomes and biometric measurements.

Results

MMC ventricular volume/week (mm3/week) increased after fetal surgery (median: 3699, interquartile range (IQR): 1651–5395) compared to controls (median: 648, IQR: 371–896); P = 0.015. The MMC SI is higher pre-operatively in all cerebral lobes in comparison to that in controls. Change in SI/week in MMC fetuses was higher in the left temporal lobe (median: 0.039, IQR: 0.021–0.054), left parietal lobe (median: 0.032, IQR: 0.023–0.039) and right occipital lobe (median: 0.027, IQR: 0.019–0.040) versus controls (P = 0.002 to 0.005). Ventricular volume (mm3) and VW (mm) (r = 0.64), cerebellar volume and TCD (r = 0.56) were moderately correlated.

Conclusions

Following fetal myelomeningocele repair, brain volume, shape and SI were significantly different from normal in most cerebral layers. Morphological brain changes after fetal surgery are not limited to hindbrain herniation reversal. These findings may have neurocognitive outcome implications and require further evaluation.
NO donors and NO delivery methods for controlling biofilms in chronic lung infections
Authors: Cai Yu-Ming , Zhang Ying-Dan , Yang Liang
Published: May 2021

Nitric oxide (NO), the highly reactive radical gas, provides an attractive strategy in the control of microbial infections. NO not only exhibits bactericidal effect at high concentrations but also prevents bacterial attachment and disperses biofilms at low, nontoxic concentrations, rendering bacteria less tolerant to antibiotic treatment. The endogenously generated NO by airway epithelium in healthy populations significantly contributes to the eradication of invading pathogens. However, this pathway is often compromised in patients suffering from chronic lung infections where biofilms dominate. Thus, exogenous supplementation of NO is suggested to improve the therapeutic outcomes of these infectious diseases. Compared to previous reviews focusing on the mechanism of NO-mediated biofilm inhibition, this review explores the applications of NO for inhibiting biofilms in chronic lung infections. It discusses how abnormal levels of NO in the airways contribute to chronic infections in cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and primary ciliary dyskinesia (PCD) patients and why exogenous NO can be a promising antibiofilm strategy in clinical settings, as well as current and potentialin vivoNO delivery methods.

Key points

•The relationship between abnormal NO levels and biofilm development in lungs

•The antibiofilm property of NO and current applications in lungs

•Potential NO delivery methods and research directions in the future
Microbial methionine transporters and biotechnological applications
Authors: Mohany Nurul Amira Mohammad , Totti Alessandra , Naylor Keith R. , Janovjak Harald
Published: April 2021

Methionine (Met) is an essential amino acid with commercial value in animal feed, human nutrition, and as a chemical precursor. Microbial production of Met has seen intensive investigation towards a more sustainable alternative to the chemical synthesis that currently meets the global Met demand. Indeed, efficient Met biosynthesis has been achieved in genetically modified bacteria that harbor engineered enzymes and streamlined metabolic pathways. Very recently, the export of Met as the final step during its fermentative production has been studied and optimized, primarily through identification and expression of microbial Met efflux transporters. In this mini-review, we summarize the current knowledge on four families of Met export and import transporters that have been harnessed for the production of Met and other valuable biomolecules. These families are discussed with respect to their function, gene regulation, and biotechnological applications. We cover methods for identification and characterization of Met transporters as the basis for the further engineering of these proteins and for exploration of other solute carrier families. The available arsenal of Met transporters from different species and protein families provides blueprints not only for fermentative production but also synthetic biology systems, such as molecular sensors and cell-cell communication systems.

Key points

• Sustainable production of methionine (Met) using microbes is actively explored.

• Met transporters of four families increase production yield and specificity.

• Further applications include other biosynthetic pathways and synthetic biology.
Accurate Prediction of Prognosis After Radical Resection of Gastric Cancer by the Modified Systemic Inflammation Score; a Multicenter Dataset Analysis
Authors: Inagaki Kota , Kanda Mitsuro , Nakanishi Koki , Ito Seiji , Mochizuki Yoshinari , Teramoto Hitoshi , Ishigure Kiyoshi , Murai Toshifumi , Asada Takahiro , Ishiyama Akiharu , Matsushita Hidenobu , Tanaka Chie , Kobayashi Daisuke , Fujiwara Michitaka , Murotani Kenta , Kodera Yasuhiro
Published: May 2021

Background

The presence of chronic inflammation and nutritional status in cancer patients affects its prognosis. There is a clinical need for a prognostic predictor that is objective and accurate, and that can be easily evaluated by preoperative screening. We evaluated the importance and usefulness of the preoperative modified systemic inflammation score (mSIS) to predict the long‐term outcome of patients undergoing curative resection for gastric cancer (GC).

Methods

Of the 3571 patients who underwent curative resection for GC in nine institutions between January 2010 and December 2014, 1764 patients who met the inclusion criteria were included. The mSIS was formulated according to the serum albumin level (ALB) and lymphocyte‐to‐monocyte ratio (LMR) as follows: mSIS 0 (ALB ≥ 4.0 g/dL and LMR ≥ 3.4), mSIS 1 (ALB < 4.0 g/dL or LMR < 3.4), and mSIS 2 (ALB < 4.0 g/dL and LMR < 3.4).

Results

Patients were categorized into preoperative mSIS 0 (n = 955), mSIS 1 (n = 584), and mSIS 2 (n = 225) groups. The overall survival times and the disease‐free survival times of patients in preoperative mSIS 0,1 and 2 sequentially shortened (P < 0.0001), and mSIS 1 and 2 were identified as an independent prognostic factor (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.06–1.272, P = 0.0125 and HR 1.63, 95% CI 1.21–2.19, P = 0.0012). A stepwise increase in the prevalence of hematogenous recurrences was directly proportional to the mSIS. A forest plot revealed that mSIS 0,1 was associated with a greater risk of overall survival in most subgroups.

Conclusion

Preoperative mSIS can be easily calculated, and it is suggested that it is useful as a prognostic predictor of patients with different disease stages, for stratifying and evaluating clinical outcomes.
Structure-from-Motion on shallow reefs and beaches: potential and limitations of consumer-grade drones to reconstruct topography and bathymetry
Authors: David C. Gabriel , Kohl Nina , Casella Elisa , Rovere Alessio , Ballesteros Pablo , Schlurmann Torsten
Published: May 2021

Reconstructing the topography of shallow underwater environments using Structure-from-Motion—Multi View Stereo (SfM-MVS) techniques applied to aerial imagery from Unmanned Aerial Vehicles (UAVs) is challenging, as it involves nonlinear distortions caused by water refraction. This study presents an experiment with aerial photographs collected with a consumer-grade UAV on the shallow-water reef of Fuvahmulah, the Maldives. Under conditions of rising tide, we surveyed the same portion of the reef in ten successive flights. For each flight, we used SfM-MVS to reconstruct the Digital Elevation Model (DEM) of the reef and used the flight at low tide (where the reef is almost entirely dry) to compare the performance of DEM reconstruction under increasing water levels. Our results show that differences with the reference DEM increase with increasing depth, but are substantially larger if no underwater ground control points are taken into account in the processing. Correcting our imagery with algorithms that account for refraction did not improve the overall accuracy of reconstruction. We conclude that reconstructing shallow-water reefs (less than 1 m depth) with consumer-grade UAVs and SfM-MVS is possible, but its precision is limited and strongly correlated with water depth. In our case, the best results are achieved when ground control points were placed underwater and no refraction correction is used.
A note on weighted multi-glove games
Authors: Moretti Stefano , Norde Henk
Published: May 2021

In this note we consider the class of weighted multi-glove games. We will show that these games are totally balanced and we will characterize the weighted multi-glove games that are supermodular and pmas-admissible. Moreover, we will provide an explicit expression for the Shapley value of the supermodular and a large part of the pmas-admissible weighted multi-glove games.
Machbarkeit und Akzeptanz videobasierter Physiotherapie
Authors: Happe Lisa , Lau Sandra , Koschate Jessica , Diekmann Rebecca , Hein Andreas , Zieschang Tania
Published: May 2021

Hintergrund und Ziel

Einschränkungen des öffentlichen Lebens durch die COVID-19-Pandemie dienen insbesondere dazu, Risikogruppen vor einer Ansteckung zu schützen. Darunter fallen auch ältere, multimorbide Patienten, für die körperliche Inaktivität und Auslassen von Maßnahmen wie Physiotherapie jedoch negative Folgen haben können. Die vorliegende Studie untersucht die Machbarkeit und die subjektive Bewertung videobasierter Physiotherapie (VT).

Methoden

Von April bis Juni 2020 nahmen 4 Einrichtungen mit 9 Patienten (6 Frauen, 64 bis 82 Jahre) an der Studie teil, die mit Tablets ausgestattet wurden. Durch semistrukturierte Telefoninterviews wurden körperliche Aktivität, funktionelle Kompetenz und Partizipation vor und während den Einschränkungen bei 8 Patienten erfasst. Patienten und Therapeuten wurden zu ihren subjektiven Erfahrungen mit der VT befragt.

Ergebnisse

Es fanden insgesamt 92 VT-Einheiten statt. Die Umsetzung der Übungen wurde als gut bis sehr gut bewertet. Insgesamt zeigte sich eine hohe Akzeptanz der VT. Vier von 8 Patienten beschrieben eine subjektive Reduzierung ihrer körperlichen Aktivitäten aufgrund der Einschränkungen. Diese Veränderungen wurden über die verwendeten Fragebogen zur Partizipation und zur körperlichen Aktivität nicht abgebildet.

Diskussion

Bei älteren Patienten ist VT mit geringer technischer Unterstützung machbar. Sowohl in Pandemiesituationen als auch in anderen Kontexten stellt sich VT als eine realisierbare Ergänzung oder Alternative zur normalen Physiotherapie dar. Weitere Studien zur Identifikation von geeigneten Patientengruppen, Effektivität der VT und Weiterentwicklung inhaltlicher Aspekte sind dringend notwendig.
Ablation of lysozyme M-positive cells prevents aircraft noise-induced vascular damage without improving cerebral side effects
Authors: Frenis Katie , Helmstädter Johanna , Ruan Yue , Schramm Eva , Kalinovic Sanela , Kröller-Schön Swenja , Bayo Jimenez Maria Teresa , Hahad Omar , Oelze Matthias , Jiang Subao , Wenzel Philip , Sommer Clemens J. , Frauenknecht Katrin B. M. , Waisman Ari , Gericke Adrian , Daiber Andreas , Münzel Thomas , Steven Sebastian
Published: April 2021

Aircraft noise induces vascular and cerebral inflammation and oxidative stress causing hypertension and cardiovascular/cerebral dysfunction. With the present studies, we sought to determine the role of myeloid cells in the vascular vs. cerebral consequences of exposure to aircraft noise. Toxin-mediated ablation of lysozyme M+ (LysM+) myeloid cells was performed in LysMCreiDTR mice carrying a cre-inducible diphtheria toxin receptor. In the last 4d of toxin treatment, the animals were exposed to noise at maximum and mean sound pressure levels of 85 and 72 dB(A), respectively. Flow cytometry analysis revealed accumulation of CD45+, CD11b+, F4/80+, and Ly6G−Ly6C+ cells in the aortas of noise-exposed mice, which was prevented by LysM+ cell ablation in the periphery, whereas brain infiltrates were even exacerbated upon ablation. Aircraft noise-induced increases in blood pressure and endothelial dysfunction of the aorta and retinal/mesenteric arterioles were almost completely normalized by ablation. Correspondingly, reactive oxygen species in the aorta, heart, and retinal/mesenteric vessels were attenuated in ablated noise-exposed mice, while microglial activation and abundance in the brain was greatly increased. Expression of phagocytic NADPH oxidase (NOX-2) and vascular cell adhesion molecule-1 (VCAM-1) mRNA in the aorta was reduced, while NFκB signaling appeared to be activated in the brain upon ablation. In sum, we show dissociation of cerebral and peripheral inflammatory reactions in response to aircraft noise after LysM+ cell ablation, wherein peripheral myeloid inflammatory cells represent a dominant part of the pathomechanism for noise stress-induced cardiovascular effects and their central nervous counterparts, microglia, as key mediators in stress responses.
Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin
Authors: Förster Alisa , Brand Frank , Banan Rouzbeh , Hüneburg Robert , Weber Christine A. M. , Ewert Wiebke , Kronenberg Jessica , Previti Christopher , Elyan Natalie , Beyer Ulrike , Martens Helge , Hong Bujung , Bräsen Jan H. , Erbersdobler Andreas , Krauss Joachim K. , Stangel Martin , Samii Amir , Wolf Stephan , Preller Matthias , Aretz Stefan , Wiese Bettina , Hartmann Christian , Weber Ruthild G.
Published: April 2021

The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced β-catenin binding resulting in increased cytosolic and nuclear β-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/β-catenin signaling.
Heterogenous use of misoprostol for induction of labour: results of an online survey among midwives in German-speaking countries
Authors: Bossung Verena , Rath Werner , Rody Achim , Schwarz Christiane
Published: May 2021

Purpose

This online survey looked at the experiences and general perceptions of midwives concerning induction of labour and the specific use of misoprostol.

Methods

We published an online questionnaire with 24 questions in German on midwives’ experiences and perceptions of different methods of induction of labour.

Results

The online survey was answered by 412 midwives between February 2016 and February 2017. At least 20% of the 24 questions were answered in 333 questionnaires, which were included in this analysis. Oral misoprostol was the most common induction method for primipara and for women with a previous vaginal birth and an unfavourable cervix. Apart from alternative methods for induction of labour like castor oil and complementary/alternative methods, oral misoprostol was the preferred method of induction of labour by midwives. Midwives described a wide range of dosage schedules concerning application intervals, starting doses, and the maximum daily dose of misoprostol. Approximately 50% of the participants of this study described prescriptions of more than 200 µg misoprostol daily for induction of labour.

Conclusion

Misoprostol is widely used in Germany and was one of the three preferred methods of induction of labour among midwives in our study next to castor oil and complementary/alternative methods. The preparation and dosage of misoprostol vary significantly among hospitals and do not adhere to international guidelines. Midwives voiced their concerns about inconsistent indications and heterogenous use of different methods and dosages of induction. They wished for more patience with late-term pregnancies and individualized shared decision-making between pregnant women and obstetricians.
A bespoke health risk assessment methodology for the radiation protection of astronauts
Authors: Walsh Linda , Hafner Luana , Straube Ulrich , Ulanowski Alexander , Fogtman Anna , Durante Marco , Weerts Guillaume , Schneider Uwe
Published: April 2021

An alternative approach that is particularly suitable for the radiation health risk assessment (HRA) of astronauts is presented. The quantity, Radiation Attributed Decrease of Survival (RADS), representing the cumulative decrease in the unknown survival curve at a certain attained age, due to the radiation exposure at an earlier age, forms the basis for this alternative approach. Results are provided for all solid cancer plus leukemia incidence RADS from estimated doses from theoretical radiation exposures accumulated during long-term missions to the Moon or Mars. For example, it is shown that a 1000-day Mars exploration mission with a hypothetical mission effective dose of 1.07 Sv at typical astronaut ages around 40 years old, will result in the probability of surviving free of all types of solid cancer and leukemia until retirement age (65 years) being reduced by 4.2% (95% CI 3.2; 5.3) for males and 5.8% (95% CI 4.8; 7.0) for females. RADS dose–responses are given, for the outcomes for incidence of all solid cancer, leukemia, lung and female breast cancer. Results showing how RADS varies with age at exposure, attained age and other factors are also presented. The advantages of this alternative approach, over currently applied methodologies for the long-term radiation protection of astronauts after mission exposures, are presented with example calculations applicable to European astronaut occupational HRA. Some tentative suggestions for new types of occupational risk limits for space missions are given while acknowledging that the setting of astronaut radiation-related risk limits will ultimately be decided by the Space Agencies. Suggestions are provided for further work which builds on and extends this new HRA approach, e.g., by eventually including non-cancer effects and detailed space dosimetry.
A review of visualization techniques of post-mortem computed tomography data for forensic death investigations
Authors: Ebert Lars Christian , Franckenberg Sabine , Sieberth Till , Schweitzer Wolf , Thali Michael , Ford Jonathan , Decker Summer
Published: May 2021

Postmortem computed tomography (PMCT) is a standard image modality used in forensic death investigations. Case- and audience-specific visualizations are vital for identifying relevant findings and communicating them appropriately. Different data types and visualization methods exist in 2D and 3D, and all of these types have specific applications. 2D visualizations are more suited for the radiological assessment of PMCT data because they allow the depiction of subtle details. 3D visualizations are better suited for creating visualizations for medical laypersons, such as state attorneys, because they maintain the anatomical context. Visualizations can be refined by using additional techniques, such as annotation or layering. Specialized methods such as 3D printing and virtual and augmented reality often require data conversion. The resulting data can also be used to combine PMCT data with other 3D data such as crime scene laser scans to create crime scene reconstructions. Knowledge of these techniques is essential for the successful handling of PMCT data in a forensic setting. In this review, we present an overview of current visualization techniques for PMCT.
Mit Kontaktdaten gegen die Pandemie: Zur Ethik von Corona Warn-Apps
Authors: van Basshuysen Philippe , White Lucie
Published: April 2021

Zu Beginn der Pandemie im Frühjahr 2020, und nach einem weitreichenden Lockdown, ruhten große Erwartungen auf Corona-Warn-Apps, um einen erneuten Lockdown zu verhindern. Diese Erwartungen haben sich nicht erfüllt; stattdessen wurden in Deutschland als Reaktion auf erneute Wellen von COVID-19 weitere Kontaktbeschränkungen verordnet. Wie hätte die digitale Kontaktverfolgung wirksamer gestaltet werden können? Wir argumentieren, dass es ein Spannungsfeld zwischen der Datensparsamkeit und einer wirksamen Bekämpfung der Pandemie besteht. Im Gegensatz zur deutschen Corona-Warn-App wäre eine Variante der App, in der pseudonymisierte Kennungen zentral gespeichert werden, in der Lage gewesen, die Effektivität der Kontaktverfolgung entscheidend zu erhöhen. Schließlich argumentieren wir, dass das Spannungsfeld zwischen Datensparsamkeit und einer wirksamen Pandemiebekämpfung sich jedoch nicht in einen Wertekonflikt übersetzt, weil zentrale Systeme uns trotz ihrer erhöhten Wirksamkeit nicht vor deutlich gravierendere Probleme beim Datenschutz stellen als dezentrale Systeme. Zentrale Möglichkeiten der digitalen Kontaktverfolgung wären daher ethisch gerechtfertigt, um auf weitere Wellen von COVID-19 oder auf zukünftige Epidemien effektiv zu reagieren.
Perturbative Treatment of Three-Nucleon Force Contact Terms in Three-Nucleon Faddeev Equations
Authors: Witała H. , Golak J. , Skibiński R. , Topolnicki K.
Published: May 2021

We present a perturbative approach to solving the three-nucleon continuum Faddeev equation. This approach is particularly well suited to dealing with variable strengths of contact terms in a chiral three-nucleon force. We use examples of observables in the elastic nucleon-deuteron scattering as well as in the deuteron breakup reaction to demonstrate high precision of the proposed procedure and its capability to reproduce exact results. A significant reduction of computer time achieved by the perturbative approach in comparison to exact treatment makes this approach valuable for fine-tuning of the three-nucleon Hamiltonian parameters.
Pineal region tumours in the sitting position: how I do it
Authors: Sharma Priya , Abdul Mohd , Waraich Manprit , Samandouras George
Published: May 2021

Background

Pineal region tumours remain challenging neurosurgical pathologies.

Methods

Detailed anatomical knowledge of the posterior incisural space and its variations is critical. An opaque arachnoidal membrane seals the internal cerebral and basal veins, leading to thalamic, basal ganglia, mesencephalic/pontine infarctions if injured. Medium-size tumours can be removed en-bloc with all traction/manipulation applied on the tumour side, virtually without contact of ependymal surfaces of the pulvinars or third ventricle. Sacrifice of the cerebello-mesencephalic fissure vein may be required.

Conclusions

The sitting position offers superior anatomical orientation and remains safe with experienced teams. Meticulous microsurgical techniques and detailed anatomical knowledge are likely to secure safe outcomes.
The connections of Locus Coeruleus with hypothalamus: potential involvement in Alzheimer’s disease
Authors: Giorgi Filippo Sean , Galgani Alessandro , Puglisi-Allegra Stefano , Busceti Carla Letizia , Fornai Francesco
Published: May 2021

The hypothalamus and Locus Coeruleus (LC) share a variety of functions, as both of them take part in the regulation of the sleep/wake cycle and in the modulation of autonomic and homeostatic activities. Such a functional interplay takes place due to the dense and complex anatomical connections linking the two brain structures. In Alzheimer’s disease (AD), the occurrence of endocrine, autonomic and sleep disturbances have been associated with the disruption of the hypothalamic network; at the same time, in this disease, the occurrence of LC degeneration is receiving growing attention for the potential roles it may have both from a pathophysiological and pathogenetic point of view. In this review, we summarize the current knowledge on the anatomical and functional connections between the LC and hypothalamus, to better understand whether the impairment of the former may be responsible for the pathological involvement of the latter, and whether the disruption of their interplay may concur to the pathophysiology of AD. Although only a few papers specifically explored this topic, intriguingly, some pre-clinical and post-mortem human studies showed that aberrant protein spreading and neuroinflammation may cause hypothalamus degeneration and that these pathological features may be linked to LC impairment. Moreover, experimental studies in rodents showed that LC plays a relevant role in modulating the hypothalamic sleep/wake cycle regulation or neuroendocrine and systemic hormones; in line with this, the degeneration of LC itself may partly explain the occurrence of hypothalamic-related symptoms in AD.
One-year performance of posterior narrow diameter implants in hyperglycemic and normo-glycemic patients—a pilot study
Authors: Friedmann Anton , Winkler Marianna , Diehl Daniel , Yildiz Mehmet Selim , Bilhan Hakan
Published: May 2021

Objectives

The aim of the study was to compare the performance of narrow diameter implants in patients with uncontrolled diabetes mellitus type 2 (T2DM) and normo-glycemic individuals during the first 12 months after implant loading.

Material and methods

In 16 T2DM patients with HbA1C > 6.5% (test group) and 16 normo-glycemic patients (HbA1C < 6.0%; control group), one to two narrow diameter tissue level implants were placed in the posterior maxilla or mandible. After 3-month lasting integration period, implants were loaded by fixed dentures. The clinical parameters probing depth (PD), bleeding on probing (BOP), attachment loss (CAL), recession and papilla bleeding index (PBI) were assessed manually at loading and after 12 months of function. The paired digital periapical radiographs were analyzed with regard to the change in marginal bone level (MBL) from baseline to 12 months’ control. The mean values calculated for both patient groups were statistically analyzed. The technical complications were recorded.

Results

The T2DM group accounted 13 patients due to 3 dropouts. The overall implant survival rate after 12 months was 100%. The differences in means for the clinical parameters and the MBL were statistically non-significant between the T2DM and normo-glycemic patients for the short period of loaded function reported here. No technical complications were recorded.

Conclusions

The study demonstrated an encouraging clinical outcome with narrow diameter implants in patients with uncontrolled T2DM compared to non-diabetics after 12 months post loading. For the short observation period, no biological and technical complications were reported regardless the glycemic status.

Clinical relevance

Patients with HbA1C > 6.5% may benefit from the treatment with narrow diameter implants by avoiding complex surgical interventions with augmentation procedures.

Trial registration

Clinicaltrials.gov: NCT04630691
Effects of acute alcohol consumption on neuronal activity and cerebral vasomotor response
Authors: Balogh Eszter , Árokszállási Tamás , Körtefái Katalin , Nagy Veronika Éva , Csiba László , Oláh László
Published: April 2021

Introduction

In the majority of European countries, driving after drinking small-moderate amount of alcohol is legal. Motivated by our previous studies on cerebral hemodynamics, we aimed to study whether a small-moderate blood alcohol content (BAC), at which driving is legal in some countries (0.8 g/L), influences the neuronal activity, neurovascular coupling, and cerebral vasoreactivity.

Methods

Analyses of pattern-reversal visual evoked potential (VEP) and transcranial Doppler (TCD) examinations were performed in thirty young healthy adults before and 30 min after alcohol consumption. Cerebral vasoreactivity was evaluated by breath holding test in both middle cerebral arteries. By using a visual cortex stimulation paradigm, visually evoked flow velocity response during reading was measured in both posterior cerebral arteries (PCA).

Results

The BAC was 0.82 g/L and 0.94 g/L 30 and 60 min after drinking alcohol, respectively. Latency of the VEP P100 wave increased after alcohol consumption. Resting absolute flow velocity values increased, whereas pulsatility indices in the PCA decreased after alcohol ingestion, indicating vasodilation of cerebral microvessels. Breath holding index and the visually evoked maximum relative flow velocity increase in the PCA and steepness of rise of the flow velocity curve were smaller after than before alcohol consumption.

Conclusion

BAC close to a legal value at which driving is allowed in some European countries inhibited the neuronal activity and resulted in dilation of cerebral arterioles. Cerebral vasodilation may explain the decrease of cerebral vasoreactivity and might contribute to the disturbance of visually evoked flow response after alcohol consumption.
A meta-algorithm for finding large k-plexes
Authors: Conte Alessio , Firmani Donatella , Patrignani Maurizio , Torlone Riccardo
Published: May 2021

We focus on the automatic detection of communities in large networks, a challenging problem in many disciplines (such as sociology, biology, and computer science). Humans tend to associate to form families, villages, and nations. Similarly, the elements of real-world networks naturally tend to form highly connected groups. A popular model to represent such structures is the clique, that is, a set of fully interconnected nodes. However, it has been observed that cliques are too strict to represent communities in practice. The k-plex relaxes the notion of clique, by allowing each node to miss up to k connections. Although k-plexes are more flexible than cliques, finding them is more challenging as their number is greater. In addition, most of them are small and not significant. In this paper we tackle the problem of finding only large k-plexes (i.e., comparable in size to the largest clique) and design a meta-algorithm that can be used on top of known enumeration algorithms to return only significant k-plexes in a fraction of the time. Our approach relies on: (1) methods for strongly reducing the search space and (2) decomposition techniques based on the efficient computation of maximal cliques. We demonstrate experimentally that known enumeration algorithms equipped with our approach can run orders of magnitude faster than full enumeration.
Genetic variability in oilseed rape DH line population developed from F1 hybrids obtained by crossing black-and yellow-seeded DH lines. I. yield and yield components
Authors: Szała Laurencja , Kaczmarek Zygmunt , Wójtowicz Marek , Sosnowska Katarzyna , Cegielska-Taras Teresa
Published: May 2021

The aims of this study were to estimate the diversity of doubled haploid population of winter oilseed rape (Brassica napus L.) in terms of yield, yield structure and seed colour, to determine the correlation between the studied traits and their heritability, and to select the best yellow-seeded genotypes. We studied 44 doubled haploids, obtained from F1 hybrids of a cross between a black-seeded DH H2-26 line and a yellow-seeded DH Z-114 line, as well as the parental forms. The greatest variation in DH line populations was observed for seed colour, seed yield and the number of pods per plant, while the smallest variability was obtained for thousand seed weight. Seed yield was positively correlated with the number of pods per plant and the number of seeds per pod, but negatively correlated with yellow seed colour. The broad-sense heritability coefficient was highest for seed colour and number of seeds per pod, and lowest for the number of pods per plant. When divided into 4 homogeneous groups according to seed colour, the genotypes differed significantly with respect to all the studied traits. A group of DH lines with black seed colour was characterized by the highest seed yield as well as highest thousand seed weight. The lowest yielding DH line group, that with yellow–brown seeds, had on average the highest number of seeds per pod and the lowest thousand seed weight. The best yellow-seeded genotypes were selected. Four yellow-seeded lines gave significantly higher yields than the yellow-seeded parental line.
The Function of Mounts in Free-Ranging Barbary Macaques (Macaca sylvanus)
Authors: Anzá Simone , Majolo Bonaventura , Amici Federica
Published: May 2021

Generally, nonreproductive sex is thought to act as “social grease,” facilitating peaceful coexistence between subjects that lack close genetic ties. However, specifc nonreproductive sexual behaviors may fulfill different functions. With this study, we aimed to test whether nonreproductive mounts in Barbary macaques are used to 1) assert dominance, 2) reinforce social relationships, and/or 3) solve conflicts. We analyzed nonreproductive mounts (N= 236) and postmount behavior in both aggressive and nonaggressive contexts, in 118 individuals belonging to two semi-free-ranging groups at La Montagne des Singes (France). As predicted by the dominance assertion hypothesis, the probability to be the mounter increased with rank difference, especially in aggressive contexts (increasing from 0.066 to 0.797 in nonaggressive contexts, and from 0.011 to 0.969 in aggressive contexts, when the rank difference was minimal vs. maximal). The strength of the social bond did not significantly predict the proportion of mounts across dyads in nonaggressive contexts, providing no support for the relationship reinforcement hypothesis. Finally, in support of the conflict resolution hypothesis, when individuals engaged in postconflict mounts, 1) the probability of being involved in further aggression decreased from 0.825 to 0.517, while 2) the probability of being involved in grooming interactions with each other increased from 0.119 to 0.606. The strength of the social bond between former opponents had no significant effect on grooming occurrence and agonistic behavior after postconflict mounts. Overall, our findings suggest that nonreproductive mounts in Barbary macaques have different functions that are not affected by the strength of the social bond.