bluuebunny/crossref_metadata_2025 huggingface dataset:
Semantic Enrichment of 3D Models Based on Ontology Integration
Authors: Nzetchou Stéphane , Durupt Alexandre , Eynard Benoit , Remy Sébastien
Published: April 2021

The rise of new technologies has led to a growth in the number of 3D models. They can come from various source, hence they are heterogeneous and complex. The level of 3D data access is often a function of the user’s expertise since the 3D data are often registered to different file formats. Some file formats do not show the data tree, as IGES. For using information inside a 3D model, that does not show a data tree, each company adopts his own system that will allow him to access easily to 3D model in order to exploit the hidden knowledge within the models. In this article, we are going to speak about technologies that helps user to exploit and knowledge coming from different file formats. In addition, we are going to present a system named VAQUERO that uses ontology to access, store and share knowledge coming from 3D models.
Design for Manufacturing and Assembly: A Method for Rules Classification
Authors: Favi Claudio , Mandolini Marco , Campi Federico , Cicconi Paolo , Raffaeli Roberto , Germani Michele
Published: April 2021

The paper provides a method to acquire, process, and represent DfMA rules to help designers and engineers in the development of mechanical products compliant with manufacturing and assembly technology. This research work wants to define a general method able to link DfMA design guidelines (knowledge engineering) with geometrical product features that are available by the investigation of the 3D model. Numerical parameters of design features are related to design guidelines for the identification of manufacturing and assembly issues within the analysis of the 3D model.
Generation of Entrepreneurship Environments for New Product Development
Authors: Martin-Doñate Cristina , Lucena-Muñoz Fermín , García-Cabrera Lina Guadalupe , Mercado-Colmenero Jorge Manuel
Published: April 2021

The economic environment demands companies to be able of innovating and presenting new products and technologies. However, current industrial environments are composed of big established companies, small or medium family businesses and regional clusters. This business map does not comply with the dynamism required for detecting needs and proposals in form of new products that meet the current customer requirements. The creation of start-ups in the field of engineering is considered as a possibility to cover a growing market in designing high technological products. However, despite the importance and economic impact of the start-ups for less industrialized environments the courses in the engineering field do not include activities that contextualize theoretical knowledge and entrepreneurship. The paper presents the results of creating an entrepreneurial environment focused on the student as entrepreneurial unit. In this context, a series of new activities based on new design proposals have been developed on the basis of new technical solutions for industrial companies. The new designs have been presented as minimum viable products. The technical knowledge required for making the new designs has been complemented with entrepreneurial training. The results show an increase in students' willingness to create small companies based in new products as an employment option at the end of their studies.
Multicriteria Decision Making Methods in Engineering Design: An Application on Medical Devices
Authors: Renzi Cristina , Leali Francesco
Published: April 2021

The design of medical devices is challenging, due to strict geometry specifications and criteria belonging to several disciplines. The aim of this paper is to provide a design methodology which seems to lack in the literature of design of biomedical devices. In particular, the case study proposed in this paper concerns with the design of Bone-Biopsy (BB) needle devices. Following the design process of Pahl and Beitz, a functional analysis is carried out, to point out the interfaces between parts of existing BB needles. A morphology matrix is used to generate alternatives for the cannula holder, the core part of the product. Generated alternatives have been ranked and scored by means of the Pugh’s Controlled Convergence method according to the decision makers' opinions. In this work, the design peculiarities related to the BB needles which have been pointed out could be extended for guiding the design of other biomedical devices.
Smart Tightening Development for Aeronautical Bolted Assemblies in an Industry 4.0
Authors: Foissac Charly , Daidie Alain , Segonds Stephane , Chirol Clément
Published: April 2021

Smart tightening development is part of the Industry 4.0 transformation with the introduction of smart tools, and preload in bolted assemblies is of major interest in today’s aircraft manufacturing process. So far, it has been difficult to estimate the importance of each parameter for tightening process quality, mainly because of the large number of combinations and configurations that exist.

The present work aims at evaluating the effects and the interactions between different parameters that have to be taken in consideration in future torquing strategy. Many experimental tests have been conducted on an Automatica test bench using a Taguchi strategy and an analysis of the first main results is now presented, highlighting the complexity of the phenomena studied.

All these points will help us to better understand tightening, so as to improve performance during installation, maintenance and repair.
Cold Working Process on Hard Metal Stacked Assembly
Authors: Pichon Guillaume , Daidie Alain , Fau Adeline , Chirol Clément , Benaben Audrey
Published: April 2021

Designed for aeronautical and automotive applications, the split sleeve cold expansion process is used to improve the fatigue life of bolted metallic parts. Although its application has been well tested on aluminum assemblies, hard metal applications are still being studied. This paper presents experimental results of double bolt joint assemblies under double shear fatigue tests after stacked split sleeve cold expansion. The behaviors of two sizes of assemblies with different degrees of expansion are investigated. S-N curves are the main indicators of this study but thermal aspects are also investigated to observe fretting in the specimens as bolts are preloaded. Bolt tension is a major parameter in assembly regarding fatigue life. Interference between those two phenomena is at the heart of this paper. The first results show that stacked cold expansion has a negative effect on mechanical performances, as it deteriorates the fatigue life of the assembly. However, an examination of these results provides a coherent explanation for the loss of performance that occurs.
Numerical Simulation and Experimentation of Additive Manufacturing Processes with Polyurethane Foams
Authors: Paquet Elodie , Le Loch Sébastien , Furet Benoit , Bernard Alain , Garnier Sébastien
Published: April 2021

Foam Additive Manufacturing (FAM) is the additive manufacturing process allowing parts to be obtained by depositing layers of polyurethane foam using a high-pressure machine. This inexpensive technology allows large parts to be produced in a reduced time. However, the quality of the parts produced by the FAM technique is greatly affected by the various thermal phenomena present during manufacturing and by the geometrical deviations of the layers due to the expansion of the PU foam. Numerical simulation remains an effective analytical tool for studying these phenomena. The aim of this work is to build a geometric and thermal model predictive of the FAM process by the finite element method, the final objective of which is to provide temperature maps throughout the manufacturing process and also to choose the best 3D printing strategy to have a model with constant cords and the smallest possible form deviation. The proposed model and the various simulation techniques used are detailed in this article. This model is developed under the finite element code Rem3D, and validated by experimental tests carried out on a FAM machinery or a robot, an example of which is detailed in this article.
How Human Rights Cross-Pollinate and Take Root: Local Governments and Refugees in Turkey
Authors: Durmuş Elif
Published: April 2021

The human rights regime—as law, institutions and practice—has been facing criticism for decades regarding its effectiveness, particularly in terms of unsatisfactory overall implementation and the failure to protect the most vulnerable who do not enjoy the protection of their States: refugees. Turkey is the country hosting the largest refugee population, with around four million at the end of May 2020 (https://www.unhcr.org/tr/wp-content/uploads/sites/14/2020/06/UNHCR-Turkey-Operational-Update-May-2020.pdf). As an administratively centralised country, Turkey’s migration policy is implemented by central government agencies, but this has not proved sufficient to guarantee the human rights of refugees on the ground. Meanwhile, in connection with urbanisation, decentralisation and globalisation, local governments around the world are receiving increasing attention from migration studies, political science, law, sociology and anthropology. In human rights scholarship, the localisation of human rights and the potential role of local governments have been presented as ways to counter the shortcomings in the effectiveness of the human rights regime and discourse. While local governments may have much untapped potential, a thorough analysis of the inequalities between local governments in terms of access to resources and opportunities is essential. The Turkish local governments which form the basis of this research, operate in a context of legal ambiguity concerning their competences and obligations in the area of migration. They also have to deal with large differences when it comes to resources and workload. In practice, therefore, there is extreme divergence amongst municipalities in the extent to which they engage with refugee policies. This chapter seeks to answer the questionwhy and how certain local governments in Turkey come to proactively engage in policy-making that improves the realisation of refugees’ rights. Exploratory grounded field research among Turkish local governments reveals four main factors that enable and facilitate the engagement of local governments in refugee policies: (1) the capacity of and institutionalisation in local governments; (2) the dissemination of practices and norms surrounding good local migration and rights-based governance through networks; (3) the availability of cooperation and coordination with other actors in the field, and (4) political will. Collectively, these factors illustrate how a new norm—the norm that local governments can and ought to engage in policy-making improving the rights of refugees—is cross-pollinating and taking root among Turkish local governments. This understanding will provide valuable insights into how norms are developed, travel and are institutionalised within social and institutional networks, and how differences in access, capacity, political and cooperative opportunities may facilitate and obscure the path to policies improving human rights on the ground.
Human Rights Localisation and Individual Agency: From ‘Hobby of the Few’ to the Few Behind the Hobby
Authors: Sabchev Tihomir , Miellet Sara , Durmuş Elif
Published: April 2021

Human rights have been facing criticism on many fronts, including the challenges of the “enforcement gap” and the “citizenship gap”, laying bare the shortcomings with regard to the implementation of human rights law as well as regarding its protection of highly vulnerable groups such as refugees. Research on the effectiveness of human rights, the “localisation” of human rights through invocations and practices on the ground, the increased engagement of local authorities with human rights, are all responses to such challenges to some degree. Based on empirical research conducted within municipalities in four countries, this chapter focuses on a missing piece of the puzzle in terms of conceptual and empirical research: the role of “individual agency”. We adopt a socio-legal perspective on human rights and demonstrate that individual agency can make an important contribution to the effective implementation of human rights in the field of migration governance. Behind the black box of the state and local authorities, we find individuals who use human rights—as law, practice and discourse—in local policymaking, in circumstances where invoking human rights is not self-explanatory. Finally, we put forward the notion that reasons such as individual background, motivations, and interactions between individuals influence municipal officials’ engagement with human rights, and we reflect on the conceptual and practical implications that result from this.
G1-phase progression in pluripotent stem cells
Authors: ter Huurne Menno , Stunnenberg Hendrik G.
Published: April 2021

During early embryonic development both the rapid increase in cell number and the expression of genes that control developmental decisions are tightly regulated. Accumulating evidence has indicated that these two seemingly independent processes are mechanistically intertwined. The picture that emerges from studies on the cell cycle of embryonic stem cells is one in which proteins that promote cell cycle progression prevent differentiation and vice versa. Here, we review which transcription factors and signalling pathways play a role in both maintenance of pluripotency as well as cell cycle progression. We will not only describe the mechanism behind their function but also discuss the role of these regulators in different states of mouse pluripotency. Finally, we elaborate on how canonical cell cycle regulators impact on the molecular networks that control the maintenance of pluripotency and lineage specification.
Wie gut ist das Wissen über sexuell übertragbare Infektionen in Deutschland?
Authors: Matthiesen Silja , von Rüden Ursula , Dekker Arne , Briken Peer , Cerwenka Susanne , Fedorowicz Claudia , Wiessner Christian
Published: April 2021

Hintergrund

Sexuell übertragbare Infektionen (STI) sind ein relevanter Risikofaktor für die sexuelle Gesundheit des Einzelnen und der Bevölkerung. Für eine zielgruppenspezifische Präventionsarbeit ist der Wissensstand zu STI in verschiedenen Bevölkerungsgruppen daher von besonderem Interesse.

Ziel

Ziel der vorliegenden Arbeit ist es, den Wissensstand zu neun STI in der deutschen Bevölkerung zu analysieren. Dafür werden Zusammenhänge mit soziodemografischen Variablen, sexualitätsbezogenen Merkmalen sowie der subjektiven Zufriedenheit mit dem Informationsstand untersucht.

Methode

Die GeSiD-Studie „Gesundheit und Sexualität in Deutschland“ erhob von 4955 Personen per Face-to-Face-Interview repräsentative quantitative Daten zum Wissensstand zu STI. Als Auswahlverfahren wurde eine zweifache Zufallsstichprobe gezogen. Dafür wurden zunächst 200 Sample Points (Gemeinden) in ganz Deutschland regional proportional ausgewählt. Anschließend wurde eine Zufallsstichprobe von Adressen über die jeweiligen Einwohnermeldeämter gezogen. Die Teilnahmequote betrug 30,2 %; das Durchschnittsalter lag bei 46,3 Jahren.

Ergebnisse

Wissen über HIV/Aids war in allen Altersgruppen weit verbreitet. Andere STI waren deutlich weniger bekannt. Besonders wenig informiert zeigten sich Ältere und Befragte mit niedrigem Bildungsstand, regionaler sozialer Benachteiligung sowie mit Migrationshintergrund. Eine höhere Anzahl von SexualpartnerInnen hing mit einem besseren Wissensstand zusammen. Gut informiert zeigten sich Personen, die sich nicht als heterosexuell beschreiben, sowie Personen, die schon einmal an einer STI erkrankt waren.

Fazit

Heterosexuelle Erwachsene in Deutschland sind unzureichend über STI informiert. Zielgruppenspezifische Anstrengungen zur Verbesserung des Wissens über STI sind nötig, um sexuelles Risikoverhalten zu vermindern und die Inanspruchnahme von Präventionsangeboten zu verbessern.
The role of (dynamic) capabilities in the transformation of a multi-organizational setting
Authors: Paavola Lauri
Published: April 2021

This paper analyzes the role of dynamic capabilities in the transformation of a multi-organizational setting. I conduct an embedded multi-case study in which the cases represent critical transformational events in the history of a shopping center. The five critical transformational events, which have exerted substantial influence on the organizations operating in the context, are concerned with the construction of new premises, modernization of existing premises, and the introduction of new services. I analyze and classify related (dynamic) capabilities of individual organizations, resulting in aggregated outcomes that determine the evolution of the entity. Applying an abductive case research strategy, I then generate five distinct theoretical results on the effects and the interconnectedness of the multi-organizational context, the individual organizations, and their dynamic capabilities.
Characterizing growth instability: new evidence on unit roots and structural breaks in countries’ long run trajectories
Authors: Russo Emanuele , Foster-McGregor Neil
Published: April 2021

In this paper we investigate whether long run time series of income per capita are better described by a trend-stationary model with few structural changes or by unit root processes in which permanent stochastic shocks are responsible for the observed growth discontinuities. For a group of advanced and developing countries in the Maddison database, we employ a unit root test that allows for an unspecified number of breaks under the alternative hypothesis (up to some ex ante determined maximum). Monte Carlo simulations studying the finite sample properties of the test are reported and discussed. When compared with previous findings in the literature, our results show less evidence against the unit root hypothesis. We find even fewer rejections when relaxing the assumption of Gaussian shocks. Our results are broadly consistent with the implications of evolutionary macro models which posit frequent growth shifts and fat-tailed distribution of aggregate shocks.
Suspect screening and targeted analysis of acyl coenzyme A thioesters in bacterial cultures using a high-resolution tribrid mass spectrometer
Authors: Cakić Nevenka , Kopke Bernd , Rabus Ralf , Wilkes Heinz
Published: April 2021

Analysis of acyl coenzyme A thioesters (acyl-CoAs) is crucial in the investigation of a wide range of biochemical reactions and paves the way to fully understand the concerned metabolic pathways and their superimposed networks. We developed two methods for suspect screening of acyl-CoAs in bacterial cultures using a high-resolution Orbitrap Fusion tribrid mass spectrometer. The methods rely on specific fragmentation patterns of the target compounds, which originate from the coenzyme A moiety. They make use of the formation of the adenosine 3′,5′-diphosphate key fragment (m/z 428.0365) and the neutral loss of the adenosine 3′-phosphate-5′-diphosphate moiety (506.9952) as preselection criteria for the detection of acyl-CoAs. These characteristic ions are generated either by an optimised in-source fragmentation in a full scan Orbitrap measurement or by optimised HCD fragmentation. Additionally, five different filters are included in the design of method. Finally, data-dependent MS/MS experiments on specifically preselected precursor ions are performed. The utility of the methods is demonstrated by analysing cultures of the denitrifying betaproteobacterium “Aromatoleum” sp. strain HxN1 anaerobically grown with hexanoate. We detected 35 acyl-CoAs in total and identified 24 of them by comparison with reference standards, including all 9 acyl-CoA intermediates expected to occur in the degradation pathway of hexanoate. The identification of additional acyl-CoAs provides insight into further metabolic processes occurring in this bacterium. The sensitivity of the method described allows detecting acyl-CoAs present in biological samples in highly variable abundances.
Solution to the Quantum Symmetric Simple Exclusion Process: The Continuous Case
Authors: Bernard Denis , Jin Tony
Published: April 2021

The quantum symmetric simple exclusion process (Q-SSEP) is a model for quantum stochastic dynamics of fermions hopping along the edges of a graph with Brownian noisy amplitudes and driven out-of-equilibrium by injection-extraction processes at a few vertices. We present a solution for the invariant probability measure of the one dimensional Q-SSEP in the infinite size limit by constructing the steady correlation functions of the system density matrix and quantum expectation values. These correlation functions code for a rich structure of fluctuating quantum correlations and coherences. Although our construction does not rely on the standard techniques from the theory of integrable systems, it is based on a remarkable interplay between the permutation groups and polynomials. We incidentally point out a possible combinatorial interpretation of the Q-SSEP correlation functions via a surprising connexion with geometric combinatorics and the associahedron polytopes.
Prognostic value of myocardial perfusion scintigraphy in asymptomatic patients with diabetes mellitus at high cardiovascular risk: 5-year follow-up of the prospective multicenter BARDOT trial
Authors: Caobelli Federico , Haaf Philip , Haenny Gianluca , Pfisterer Matthias , Zellweger Michael J. ,   on behalf of the BARDOT Investigators
Published: April 2021

Background

The Basel Asymptomatic High-Risk Diabetics’ Outcome Trial (BARDOT) demonstrated that asymptomatic diabetic patients with an abnormal myocardial perfusion scintigraphy (MPS) were at increased risk of major adverse cardiovascular events (MACEs) at 2-year follow-up. It remains unclear whether this finding holds true even for a longer follow-up.

Methods

Four hundred patients with type 2 diabetes, neither history nor symptoms of coronary artery disease (CAD), were evaluated clinically and with MPS. Patients were followed up for 5 years. Major adverse cardiovascular events (MACEs) were defined as all-cause death, myocardial infarction, or late coronary revascularization.

Results

At baseline, an abnormal MPS (SSS ≥ 4 or SDS ≥ 2) was found in 87 of 400 patients (22%). MACE within 5 years occurred in 14 patients with abnormal MPS (16.1%) and in 22 with normal scan (1.7%), p = 0.009; 15 deaths were recorded. Patients with completely normal MPS (SSS and SDS = 0) had lower rates of MACEs than patients with abnormal scans (2.5% vs. 7.0%, p = 0.032). Patients with abnormal MPS who had undergone revascularization had a lower mortality rate and a better event-free survival from MI and revascularization than patients with abnormal MPS who had either undergone medical therapy only or could not be revascularized (p = 0.002).

Conclusions

MPS may have prognostic value in asymptomatic diabetic patients at high cardiovascular risk over a follow-up period of 5 years. Patients with completely normal MPS have a low event rate and may not need retesting within 5 years. Patients with an abnormal MPS have higher event rates and may benefit from a combined medical and revascularization approach.
The development and maintenance of sex differences in dietary breadth and complexity in Bornean orangutans
Authors: Schuppli Caroline , Atmoko S. Suci Utami , Vogel Erin R. , van Schaik Carel P. , van Noordwijk Maria A.
Published: April 2021

Orangutans show a pronounced sexual dimorphism, with flanged males (i.e., males with fully grown secondary sexual characteristics) reaching twice the size of adult females. Furthermore, adult orangutans show sex-specific dispersal and activity patterns. This study investigates sex differences in adult foraging behavior and sheds light on how these differences develop in immatures. We analyzed 11 years of feeding data on ten adult female, seven flanged male, and 14 immature Bornean orangutans (Pongo pygmaeus wurmbii) at Tuanan in Central Kalimantan, Indonesia. We found that the diets of the adult females were significantly broader and required more processing steps before ingestion than the diets of flanged males. We also found evidence for a similar difference in overall diet repertoire sizes. For the immatures, we found that whereas females reached 100% of their mothers’ diet spectrum size by the age of weaning, males reached only around 80%. From the age of 4 years on (i.e., years before being weaned) females had significantly broader daily diets than males. We found no difference in daily or overall diet processing intensity of immature males and females but found preliminary evidence that immature males included fewer items of their mother’s diet in their own diets that were processing-intensive. Overall, our results suggest that by eating a broader variety and more complex to process food items, female orangutans go to greater lengths to achieve a balanced diet than males do. These behavioral differences are not just apparent in adult foraging behavior but also reflected in immature development from an early age on.

Significance Statement

In many species, males and females have different nutritional needs and are thus expected to show sex-specific foraging behavior. Sex differences in several aspects of foraging behavior have been found in various species, but it remains largely unclear when and how those develop during ontogeny, which is especially relevant for long-lived altricial species that learn foraging skills over many years. In our study, we analyzed a cross-sectional and longitudinal data set containing more than 750,000 feeding events of adult and immature Bornean orangutans (Pongo pygmaeus wurmbii). We found that adult females had significantly broader and more complex diets than males. We also found that these differences started to develop during infancy, suggesting that immature orangutans prepare for their sex-specific foraging niches long before those become physiologically relevant while they are still in constant association with their mothers and before being frequently exposed to other role models.
Laparoscopic Versus Open Liver Resection for Hepatocellular Carcinoma: A Case Controlled Study with Propensity Score Matching
Authors: Uemoto Yusuke , Taura Kojiro , Nishio Takahiro , Kimura Yusuke , Nam Nguyen Hai , Yoshino Kenji , Yoh Tomoaki , Koyama Yukinori , Ogiso Satoshi , Fukumitsu Ken , Ishii Takamichi , Seo Satoru , Uemoto Shinji
Published: April 2021

Background

Several studies have suggested that laparoscopic liver resection (LLR) is associated with fewer postoperative complications than open liver resection (OLR) for hepatocellular carcinoma (HCC). However, this issue remains controversial since the data may have been attributable to an imbalance in patients’ background.

Methods

We retrospectively analyzed 290 hepatectomies for HCC undertaken between 2011 and 2019. Liver resection difficulty was based on the 3 levels of the Institut Mutualiste Montsouris classification. Resection ratio was calculated using computed tomography volumetry. Patient characteristics were compared between the LLR and OLR groups. Propensity score matching (PSM) was adopted to adjust the imbalance between the cohorts, and the incidence of postoperative complications was compared.

Results

The difficulty and resection ratio were significantly lower in LLR (n = 112) than in OLR (n = 178) (difficulty grade I/II/III: 84/10/18 vs. 43/39/96, p < 0.001; resection ratio: 11.4 ± 12.7 vs. 22.7 ± 17.2%, p < 0.001). The incidence of postoperative complications (Clavien–Dindo grade III or more) was lower in LLR (2.7% vs. 21.9%, p < 0.001), which was mainly attributable to fewer incidences of ascites and pleural effusion. PSM generated 68 well‐matched patients in each group. The lower incidence of postoperative complications in LLR was also maintained in the PSM cohort (2.9% vs. 16.2%, p = 0.017). On multivariate analysis, LLR was the independent predictor of postoperative complications (OR 0.184, 95% CI 0.051–0.672, p = 0.010).

Conclusion

The present study demonstrated that a laparoscopic approach reduces the incidence of postoperative complications in liver resection for HCC.
Correction to: Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis
Authors: Little M. W. , Gibson M. , Briggs J. , Speirs A. , Yoong P. , Ariyanayagam T. , Davies N. , Tayton E. , Tavares S. , MacGill S. , McLaren C. , Harrison R.
Published: April 2021

A correction to this paper has been published: https://doi.org/10.1007/s00270-021-02849-7
Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France — a cohort study using the French National Healthcare database (SNDS)
Authors: Touzeau Cyrille , Quignot Nadia , Meng Jie , Jiang Heng , Khachatryan Artak , Singh Moushmi , Taieb Vanessa , Chauny Jean-Vannak , Désaméricq Gaëlle
Published: April 2021

Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2–33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.
Cartilaginous bending spring for preventing tympanic membrane graft medialisation in anterior or subtotal tympanic membrane perforations—how I do it
Authors: Mantsopoulos Konstantinos , Iro Heinrich , Hornung Joachim
Published: April 2021

Background

The reconstruction of anterior or subtotal tympanic membrane perforations is critical due to the risk of anterior graft medialisation and retraction or recurrent perforation.

Method

After reconstruction of the tympanic membrane by means of grafting, a rectangular cartilage strut (length 6 mm, breadth 2 mm, thickness 0.1 mm) is prepared using a cartilage knife and scalpel. This strut graft is placed between the cartilage graft and the promontory in the anterior inferior part of the middle ear cavity.

Conclusion

Our experience shows that using a U-shaped cartilage strut to sustain the tympanic reconstruction effectively prevents the medialisation of the graft and recurrent perforations.
FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study
Authors: Bach Patrick , Weil Georg , Pompili Enrico , Hoffmann Sabine , Hermann Derik , Vollstädt-Klein Sabine , Kiefer Falk , Mann Karl , Sommer Wolfgang H.
Published: April 2021

Pharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.

We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial inN = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.

We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17–46.56,p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02–0.75,p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726,p = 0.454).

Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.
RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy
Authors: Tagliapietra Matteo , Cardellini Davide , Ferrarini Moreno , Testi Silvia , Ferrari Sergio , Monaco Salvatore , Cavallaro Tiziana , Fabrizi Gian Maria
Published: April 2021

Background

A biallelic intronic AAGGG repeat expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. “Chronic Idiopathic Axonal Polyneuropathy” (CIAP) is a common indolent axonal neuropathy of adulthood which remains without an identifiable cause despite thorough investigations.

Methods

We screened 234 probands diagnosed with CIAP for a pathogenic biallelic RFC1 AAGGG repeat expansion. Patients were selected from 594 consecutive patients with neuropathy referred to our tertiary-care center for a sural nerve biopsy over 10 years.

Results

The RFC1 AAGGG repeat expansion was common in patients with pure sensory neuropathy (21/40, 53%) and less frequent in cases with predominantly sensory (10/56, 18%, P < 0.001) or sensorimotor (3/138, 2%, P < 0.001) neuropathy. The mutation was associated with sensory ataxia (τb = 0.254, P < 0.001), autonomic disturbances (35% vs 8%, Prevalence Odds Ratio—POR 6.73 CI 95% 2.79–16.2, P < 0.001), retained deep tendon reflexes (score 18.0/24 vs 11.5/24, R = 0.275, P < 0.001). On pathology, we observed absent/scant regenerative changes (τb = − 0.362, P < 0.001), concomitant involvement of large (100% and 99%, n.s.), small myelinated (97% vs 81%, POR 7.74 CI 95% 1.03–58.4, P = 0.02) and unmyelinated nerve fibers (85% vs 41%, POR 8.52 CI 95% 3.17–22.9, P < 0.001). Cerebellar or vestibular involvement was similarly rare in the two groups.

Conclusions

This study highlights the frequent occurrence of the RFC1 AAGGG repeat expansion in patients diagnosed with CIAP and characterizes the clinical and pathological features of the related neuro(no)pathy.
Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer
Authors: Rachner Tilman D. , Kasimir-Bauer Sabine , Goebel Andy , Erdmann Kati , Hoffmann Oliver , Rauner Martina , Hofbauer Lorenz C. , Kimmig Rainer , Bittner Ann-Kathrin
Published: April 2021

Background

Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies.

Materials and methods

We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA.

Results

Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23–3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09–2.91).

Conclusion

Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.
Endoscopic cardial constriction with band ligation in the treatment of refractory gastroesophageal reflux disease: a preliminary feasibility study
Authors: Li Zhi-Tong , Ji Feng , Han Xin-Wei , Zhang Rui , Chen Li-Dong , Li Chun-Xia , Yuan Li-Li , Wang Zhong-Gao , Liu Kang-Dong
Published: April 2021

Background

Gastroesophageal reflux disease (GERD) is a common digestive disease, could cause extra-esophageal symptoms. Peroral endoscopic cardial constriction with band ligation (PECC-b) is a minimally invasive method for the treatment of GERD in recent years. The goals of this study were to evaluate the clinical efficacy of PECC-b to treat gastroesophageal reflux-related symptoms.

Methods

A retrospective study of patients undergoing PECC-b between January 2017 and December 2018 at a single institution was conducted. All patients confirmed GERD by endoscopy, esophageal PH-impedance monitoring, esophageal manometry and symptom questionnaires. The outcome measures included reflux-related scores, patients’ satisfaction and drug independence after 12 months following surgery.

Results

A total of 68 patients, with follow-up of 12 months post surgery, were included in the final analysis. The symptom scores were all significantly decreased as compared with preoperation (P < 0.05). The esophageal symptom scores showed a better improvement than extra-esophageal symptoms (P < 0.001). Fifty-three (77.9%) patients achieved complete drug therapy independence and 52 (76.5%) patients were completely or partially satisfied with the symptom relief following surgery.

Conclusions

The PECC-b is a safe, effective and recommended approach for the control of GERD-related symptoms. Further multicenter prospective studies are required to confirm these outcomes.
Oral health–related quality of life of patients with oral chronic graft-versus-host disease
Authors: Stolze Juliette , Boor Marlou , Hazenberg Mette D. , Brand Henk S. , Raber-Durlacher Judith E. , Laheij Alexa M. G. A.
Published: April 2021

Purpose

Symptoms of oral chronic graft-versus-host-disease (cGVHD) may significantly affect the oral health–related quality of life (OHRQoL). This study aimed to assess the OHRQoL in patients with oral cGVHD and to examine whether oral cGVHD symptoms, mucosal cGVHD, and salivary gland function correlated with OHRQoL.

Methods

Patients referred to the oral cGVHD outpatient clinic were included. Severity of oral mucosal cGVHD, oral cGVHD symptoms, and OHRQoL was assessed by the NIH OMS, NIH OSS, and OHIP-14, respectively. Unstimulated and stimulated whole salivary flow rates were determined and categorized into “hyposalivation,” “normal salivary flow,” and “hypersalivation.”

Results

Of 56 included patients, 80% had mild, moderate, or severe oral mucosal cGVHD. Mean total score of OHRQoL was 16.5 (±11.7), negatively affected by functional problems. Patients reported highest scores regarding oral sensitivity and xerostomia. Significant correlations were found between severity of oral pain and OHRQoL and between oral sensitivity and OHRQoL. No correlation was found between oral mucosal cGVHD and OHRQoL. Patients with hyposalivation, normal salivary flow, and hypersalivation reported equal levels of OHRQoL.

Conclusion

Results demonstrate that the OHRQoL was mostly negatively affected by complaints of oral pain and oral sensitivity and less by the severity of oral mucosal cGVHD assessed by the NIH OMS score. Special attention of (oral) health care professionals for patients with oral cGVHD is mandatory to alleviate their symptoms and improve OHRQoL.
Lights Out on graphs
Authors: Berman Abraham , Borer Franziska , Hungerbühler Norbert
Published: April 2021

We model the Lights Out game on general simple graphs in the framework of linear algebra over the field $$\mathbb{F}_{2}$$

F
2

. Based upon a version of the Fredholm alternative, we introduce a separating invariant of the game, i.e., an initial state can be transformed into a final state if and only if the values of the invariant of both states agree. We also investigate certain states with particularly interesting properties. Apart from the classical version of the game, we propose several variants, in particular a version with more than only two states (light on, light off), where the analysis relies on systems of linear equations over the ring $$\mathbb{Z}_{n}$$

Z
n

. Although it is easy to find a concrete solution of the Lights Out problem, we show that it is NP-hard to find a minimal solution. We also propose electric circuit diagrams to actually realize the Lights Out game.
One-step CZT electroplating from alkaline solution on flexible Mo foil for CZTS absorber
Authors: Marchi C. , Panzeri G. , Pedrazzetti L. , Khalil M. I. , Lucotti A. , Parravicini J. , Acciarri M. , Binetti S. , Magagnin L.
Published: April 2021

In this work, Cu-Zn-Sn (CZT) is co-electrodeposited onto a flexible Mo substrate exploiting an alkaline bath (pH 10). The plating solution is studied by cyclic voltammetry, highlighting the effects of potassium pyrophosphate (K4P2O7) and EDTA-Na2 on the electrochemical behavior and stability of the metallic ionic species. The optimized synthesis results in a homogeneous precursor layer, with composition Cu 44 ± 2 at. %, Zn 28 ± 1 at. %, and Sn 28 ± 2 at. %. Soft and reactive annealing are employed respectively to promote intermetallic phase formation and sulfurization of the precursor to obtain CZTS. Microstructural (XRD, Raman), morphological (SEM), and compositional (EDX, XRF) characterization is carried out on CZT and CZTS films, showing a minor presence of secondary phases. Finally, photo-assisted water splitting tests are performed considering a CZTS/CdS/Pt photoelectrode, showing a photocurrent density of 1.01 mA cm−2 at 0 V vs. RHE under 1 sun illumination.

Graphical abstract
Pyrrolizidine alkaloids cause cell cycle and DNA damage repair defects as analyzed by transcriptomics in cytochrome P450 3A4-overexpressing HepG2 clone 9 cells
Authors: Abdelfatah Sara , Naß Janine , Knorz Caroline , Klauck Sabine M. , Küpper Jan-Heiner , Efferth Thomas
Published: April 2021

Pyrrolizidine alkaloids (PAs) are a large group of highly toxic chemical compounds, which are found as cross-contaminants in numerous food products (e.g., honey), dietary supplements, herbal teas, and pharmaceutical herbal medicines. PA contaminations are responsible for serious hepatotoxicity and hepatocarcinogenesis. Health authorities have to set legal limit values to guarantee the safe consumption of plant-based nutritional and medical products without harmful health. Toxicological and chemical analytical methods are conventionally applied to determine legally permitted limit values for PAs. In the present investigation, we applied a highly sensitive transcriptomic approach to investigate the effect of low concentrations of five PAs (lasiocarpine, riddelliine, lycopsamine, echimidine, and monocrotaline) on human cytochrome P450 3A4-overexpressing HepG2 clone 9 hepatocytes. The transcriptomic profiling of deregulated gene expression indicated that the PAs disrupted important signaling pathways related to cell cycle regulation and DNA damage repair in the transfected hepatocytes, which may explain the carcinogenic PA effects. As PAs affected the expression of genes that involved in cell cycle regulation, we applied flow cytometric cell cycle analyses to verify the transcriptomic data. Interestingly, PA treatment led to an arrest in the S phase of the cell cycle, and this effect was more pronounced with more toxic PAs (i.e., lasiocarpine and riddelliine) than with the less toxic monocrotaline. Using immunofluorescence, high fractions of cells were detected with chromosome congression defects upon PA treatment, indicating mitotic failure. In conclusion, the tested PAs revealed threshold concentrations, above which crucial signaling pathways were deregulated resulting in cell damage and carcinogenesis. Cell cycle arrest and DNA damage repair point to the mutagenicity of PAs. The disturbance of chromosome congression is a novel mechanism of Pas, which may also contribute to PA-mediated carcinogenesis. Transcriptomic, cell cycle, and immunofluorescence analyses should supplement the standard techniques in toxicology to unravel the biological effects of PA exposure in liver cells as the primary target during metabolization of PAs.

Graphical abstract
Production Rate of SiO Gas from Industrial Quartz and Silicon
Authors: Sindland Caroline , Tangstad Merete
Published: April 2021

The production rate of SiO gas from industrial quartz and silicon has been investigated by isothermal heat treatment experiments. Mixtures of silicon and different quartz samples have been heated to temperatures ranging from 1650 °C to 1950 °C and held for 30 to 120 minutes before cooling. The weight loss of each sample has been correlated to degree of reaction and a model for the reaction rate of Si + SiO2 has been developed based on these values. Five different types of industrial quartz were used in the experiments. No significant difference was found in their reaction rate, even though there are large variations in impurity content, melting rate, decrepitation, and phase transformation rate of each sample. Further on, it is shown that the reaction rate of silicon mixed with various types of quartz can be described by an Arrhenius equation:

$${{\rm {d}}\alpha /{\rm {d}}t = k_0 \, A \, {\rm {exp}} (- Q / RT)}$$

d
α
/
d
t
=

k
0

A

exp

(
-
Q
/
R
T
)

. A reaction constant (k
0) equal to

$${6.25 \, 10^8 {\rm {g}}\, {\rm {s}}^{-1}\, {\rm{m^{-2}}}}$$

6.25

10
8

g

s

-
1

m

-
2

and an activation energy (Q) equal to

$${557\, {\rm {kJ \, mol^{-1}}}}$$

557

kJ

mol

-
1

were obtained by linear regression. The degree of reaction (

$${\alpha }$$

α

) is shown to be increasing with available reaction area, temperature, and time.
Pulmonary Hypertension Complicating Pregnancy
Authors: Krishnan Sheila , Fricke Erin M. , Cordoba Marcos , Chalifoux Laurie A. , Girgis Reda E.
Published: April 2021

Purpose of review

This study aims to describe the pathophysiology of pregnancy in pulmonary hypertension (PH) and review recent literature on maternal and fetal outcomes.

Recent findings

There is an increasing number of pregnant women with PH. Maternal mortality in pulmonary arterial hypertension (PAH) ranges from 9 to 25%, most commonly from heart failure and arrythmias. The highest risk of death is peri-partum and post-partum. Fetal/neonatal morbidity and mortality are also substantial. There are high rates of prematurity, intrauterine growth retardation, and preeclampsia. Women should be referred to expert centers for management. Combination PAH therapy with parenteral prostacyclin and a phosphodiesterase type V inhibitor is recommended. Induced vaginal delivery is preferred, except in cases of severe heart failure or obstetric indications for cesarean section.

Despite advances in management, pregnancy in PAH remains a high-risk condition and should be prevented.