bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-WorldClinical Outcomes in Biological Subgroups of Breast Cancer in the Hospital District of Southwest Finland
Authors: Teerenhovi Heli , Tuominen Samuli , Nurmi-Rantala Susanna , Hemmilä Päivikki , Ellonen Antti
Published: May 2021

Background

Comparing breast cancer survival trends globally, Finland is among the top three countries in Europe. However, outcome data on breast cancer subgroups in the Finnish population are limited. This retrospective, registry-based study aimed to assess patient characteristics and clinical outcomes of different breast cancer subgroups in early (EBC) and metastatic breast cancer (MBC) in a real-life clinical setting.

Materials and Methods

The study consisted of 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005–2018. Patients were divided into four mutually exclusive groups: human epidermal growth factor receptor 2 positive (HER2+), triple negative, HER2−/hormone receptor positive (HR+), and HER2 and/or HR status unknown, and further into patients with EBC and MBC. Overall survival (OS) was assessed as a clinical outcome, as well as the following real-world (rw) clinical outcomes: disease-free survival (rwDFS), progression-free survival (rwPFS), and distant recurrence-free interval (rwDRFI).

Results

Within EBC, 5-year survival was the highest (88%) in HER2−/HR+, followed by 85% in HER2+, and 75% in triple negative. The rwDFS varied significantly in EBC (5-year rwDFS HER2 -/HR+, HER2+, triple negative: 87%, 80%, 71% respectively). In MBC, median survival was 2 years for both HER2−/HR+ and HER2+ and markedly shorter for triple negative (0.8 years). Independent predictors of mortality were age (hazard ratio [HR], 1.1), other subgroups than HER2−/HR+ (HR, 1.2–1.9), metastatic disease (HR, 9.8), and other malignancies (HR, 2.7).

Conclusion

This registry-based study demonstrates significant differences in breast cancer outcomes on the subgroup level, as well as poorer outcomes compared with clinical trials, giving complementary insight on clinical characteristics in an unselected patient population.

Implications for Practice

This retrospective, registry-based study assessed the clinical outcomes of different breast cancer subgroups in 6,977 adult, female patients with breast cancer diagnosed in Southwest Finland during 2005–2018. Results demonstrated significant variation in the survival between subgroups in both early breast cancer and metastatic breast cancer, as well as differences between unselected patients representing the standard of care and randomized clinical trials. Although, according to the global comparison of survival trends, the net survival of patients with breast cancer in Finland is generally high, there is great variation between subgroups. These real-life breast cancer data provide tools to further evaluate medical need in different breast cancer subgroups.
Theoretical characterization of the temperature‐dependent ultimate tensile strength of short‐fiber‐reinforced polymer composites
Authors: Yang Mengqing , Li Weiguo , Li Ying , Zhang Xuyao , Zhao Ziyuan , He Yi , Dong Pan , Zheng Shifeng , Xu Wenqi
Published: May 2021

Short fiber/polymer composites (SFPCs) are increasingly applied in the field of high‐temperature structures. Its reliability at high temperatures has always been the core issue concerned by researchers. Here, utilizing the Force–Heat Equivalence Energy Density Principle, we developed a physically based model of temperature‐dependent ultimate tensile strength (TDUTS) for SFPCs. This model quantitatively considers the evolution of residual thermal stress, interface, fiber, and matrix performance as temperature increases. Meanwhile, the influence of fiber agglomeration frequently observed in composites and fiber orientation and length distribution is taken into account in the proposed model. The model predictions over a wide temperature range are validated against the experimental data available from the literature, indicating its reasonability and accuracy. The comparison with Kelly–Tyson model and Li's model is also performed. Additionally, the quantitative effects of the fiber agglomeration and interfacial shear strength on the TDUTS are discussed in detail. The present research not only provides an accurate and feasible approach to estimate the TDUTS of SFPCs, but also offers some helpful insights for the fabrication and design of such composites.
Profiling of intact blood proteins by matrix‐assisted laser desorption/ionization mass spectrometry without the need for freezing – Dried serum spots as future clinical tools for patient screening
Authors: Okai Charles A. , Wölter Manja , Russ Manuela , Koy Cornelia , Petre Brindusa A. , Rath Werner , Pecks Ulrich , Glocker Michael O.
Published: May 2021

Rationale

To open up new ways for matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS)‐based patient screening, blood serum is the most preferred specimen because of its richness in patho‐physiological information and due to ease of collection. To overcome deleterious freeze/thaw cycles and to reduce high costs for shipping and storage, we sought to develop a procedure which enables MALDI‐MS protein profiling of blood serum proteins without the need for serum freezing.

Methods

Blood sera from patients/donors were divided into portions which after pre‐incubation were fast frozen. Thawed aliquots were deposited on filter paper discs and air‐dried at room temperature. Intact serum proteins were eluted with acid‐labile detergent‐containing solutions and were desalted by employing a reversed‐phase bead system. Purified protein solutions were screened by MALDI‐MS using standardized instrument settings.

Results

MALDI mass spectra from protein solutions which were eluted from filter paper discs and desalted showed on average 25 strong ion signals (mass range m/z 6000 to 10,000) from intact serum proteins (apolipoproteins, complement proteins, transthyretin and hemoglobin) and from proteolytic processing products. Semi‐quantitative analysis of three ion pairs: m/z 6433 and 6631, m/z 8205 and 8916, as well as m/z 9275 and 9422, indicated that the mass spectra from either pre‐incubated fast‐frozen serum or pre‐incubated dried serum spot eluted serum contained the same information on protein composition.

Conclusions

A workflow that avoids the conventional cold‐chain and yet enables the investigation of intact serum proteins and/or serum proteolysis products by MALDI‐MS profiling was developed. The presented protocol tremendously broadens the clinical application of MALDI‐MS and simultaneously allows a reduction in the costs for storage and shipping of serum samples. This will pave the way for clinical screening of patients also in areas with limited access to health care systems, and/or specialized laboratories.
3D Chiral Photonic Nanostructures Based on Blue‐Phase Liquid Crystals
Authors: Yang Yanzhao , Wang Ling , Yang Huai , Li Quan
Published: May 2021

3D photonic nanostructures with intrinsic chirality have recently entered the research limelight due to their fundamental importance and potential technological applications. Blue‐phase liquid crystals (BPLCs) with chiral cubic nanostructures are an inventive example of 3D chiral photonic nanostructures. The inherently self‐organized 3D chiral nanostructures give rise to a complete photonic bandgap, which results in the selective reflection of circularly polarized light in all three dimensions. Herein, a comprehensive review of the state‐of‐the‐art of BPLCs and their potential applications is presented. First, the history and fundamentals of BPLCs are introduced. Then, the recent endeavors in the design, synthesis, and properties of BPLCs such as lattice orientation control with different techniques, photonic bandgap tuning with external fields, and fabrication of free‐standing BPLC polymer films are summarized. Finally, a discussion of the future challenges and potential applications of BPLCs is provided. It is believed that this review would stimulate innovative ideas for the design and engineering of novel chiral nanostructured materials for advanced photonic systems with tailorable functionalities.
Statically driven generation of concurrent tests for thread‐safe classes
Authors: Terragni Valerio , Pezzè Mauro
Published: May 2021

Concurrency testing is an important activity to expose concurrency faults in thread‐safe classes. A concurrent test for a thread‐safe class is a set of method call sequences that exercise the public interface of the class from multiple threads. Automatically generating fault‐revealing concurrent tests within an affordable time budget is difficult due to the huge search space of possible concurrent tests. In this paper, we present DepCon+, a novel approach that reduces the search space of concurrent tests by leveraging statically computed dependencies among public methods. DepCon+ exploits the intuition that concurrent tests can expose thread‐safety violations that manifest exceptions or deadlocks, only if they exercise some specific method dependencies. DepCon+ provides an efficient way to identify such dependencies by statically analysing the code and relies on the computed dependencies to steer the test generation towards those concurrent tests that exhibit the computed dependencies. We developed a prototype DepCon+ implementation for Java and evaluated the approach on 19 known concurrency faults of thread‐safe classes that lead to thread‐safety violations of either exception or deadlock type. The results presented in this paper show that DepCon+ is more effective than state‐of‐the‐art approaches in exposing the concurrency faults. The search space pruning of DepCon+ dramatically reduces the search space of possible concurrent tests, without missing any thread‐safety violations.
Location and capacity determination of charging station based on electric vehicle charging behavior analysis
Authors: Cao Weitao , Wan Youhong , Wang Lu , Wu Yue
Published: May 2021

The infrastructure construction of charging facilities for electric vehicles (EVs) is one of the key factors influencing the development of electric vehicle industry. A reasonable location and capacity determination scheme is very crucial to this issue. In this study, a probability calculation model that fully analyses the charging behavior of the owners is proposed to predict the charging load of the planned land. Based on the results of electric vehicle load forecasting, a location model with the lowest users travel cost is established. The location of charging station is optimized by genetic algorithm to obtain the location and capacity library of charging station. Especially, the two‐way cost for both the owners and the operators is considered for the location and capacity decision, and the optimal scheme is selected from the location and capacity library as the final planning result. An example analysis shows that the proposed method is effective and feasible for the location and capacity determination of electric vehicles charging stations in cities. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Variation of the response to metal ions and nonsense‐mediated mRNA decay across different Saccharomyces cerevisiae genetic backgrounds
Authors: Wong Angelo , Lam Ernest Moses , Pai Cheryl , Gunderson Annika , Carter Tamar E. , Kebaara Bessie W.
Published: May 2021

Regulation of mRNA steady‐state levels is important in controlling gene expression particularly in response to environmental stimuli. This allows cells to rapidly respond to environment changes. The highly conserved nonsense‐mediated mRNA decay (NMD) pathway was initially identified as a pathway that degrades aberrant mRNAs. NMD is now recognized as a pathway with additional functions including precisely regulating the expression of select natural mRNAs. Majority of these natural mRNAs encode fully functional proteins. Regulation of natural mRNAs by NMD is activated by NMD targeting features and environmental cues. Here, we show that Saccharomyces cerevisiae strains from three genetic backgrounds respond differentially to NMD depending on the environmental stimuli. We found that wild type and NMD mutant W303a, BY4741, and RM11‐1a yeast strains respond similarly to copper in the environment but respond differentially to toxic cadmium. Furthermore, the PCA1 alleles encoding different mRNAs from W303a and RM11‐1a strains are regulated similarly by NMD in response to the bio‐metal copper but differentially in response to toxic cadmium.
Enrichment devices for green turtles (Chelonia mydas) reared in captivity programs
Authors: Kanghae Hirun , Thongprajukaew Karun , Inphrom Surasak , Malawa Saowalak , Sandos Patchawadee , Sotong Piyanan , Boonsuk Kullanat
Published: May 2021

Environmental enrichment supports the well‐being and welfare of captive animals. In the current study, the most suitable form of enrichment device for captive green turtles (Chelonia mydas) was investigated, to support head‐start programs rearing turtles for release into their natural habitat. Fifteen‐day‐old turtles (113–114 g initial weight, n = 75) were randomly distributed into 15 experimental plastic tanks, comprising 5 treatments across three pools of each condition. The turtles in the experimental groups were exposed to four forms of enrichment devices (RS, ring shape; HSQS, hollow square shape; SS, sphere shape; CS, cylinder shape), and their outcomes related to growth, feed utilization, behavior, reduction of injury from conspecifics, and several health parameters were compared to those of a control group. At the end of the 10‐week trial, the growth and feed utilization parameters did not differ across the five groups (p > .05). Of the turtles in the experimental treatments, those in the RS treatment spent more time interacting with the enrichment device, followed by the HSQS group. The percentage of wounds suffered through biting was significantly reduced in the groups exposed to enrichment devices, notably in the turtles exposed to the SS device, followed by the RS device. Significant differences between experimental groups in the specific activities of the major intestinal protein‐digesting enzymes (trypsin and chymotrypsin) were observed. There were no effects noted in the hematological parameters and the main carapace elemental profile as compared to the control treatment. These findings suggest that the RS device is most appropriate in enriching the environment of juvenile green turtles in captivity programs, as well as in zoos or aquaria.
Non-conform Evidence: The Impasse of 1990s Welfare Research
Authors: Kirchhelle Claas
Published: May 2021

This chapter traces the evolution of welfare science and the marketisation of farm animal welfare between 1980 and 2000. During this time, dedicated welfare publications soared, and welfare scientists obtained prestigious university posts. The field’s growth was aided by assurance schemes for animal welfare, which enabled mutually beneficial cooperation between researchers, industry, and NGOs like the RSPCA, whose Freedom Foods Label enjoyed great popularity from 1994 onwards. Assurance schemes shifted welfare politics to the marketplace and generated funds for research and NGOs. They also deescalated frontstage welfare politics by restricting access to corporate- and expert-led discussions about standards and enforcement. Ruth Harrison was sceptical of label claims and welfare’s transition from a moral into an economic value. Meanwhile, researchers continued to disagree on how to define welfare. While most researchers remained confident in their ability to produce meaningful results, animal welfare science entered a prolonged phase of epistemic navel-gazing.
Ruth the Ruthless: Activism, Welfare, and Generational Change
Authors: Kirchhelle Claas
Published: May 2021

This chapter studies the polarisation of 1970s’ British farm animal welfare politics and Ruth Harrison’s career as a full-time public campaigner on the RSPCA Council and as head of her own welfare Trust. Polarised conflicts triggered a professionalisation of RSPCA campaigning. The Society adopted new public pressure tactics, established expert committees, and started commissioning behavioural research. Internal tensions over elite “field sports” also led to the formation of the RSPCA Reform Group. Reform Group members oversaw a streamlining of RSPCA management and leadership. They also popularised animal rights thinking. Ruth Harrison supported opposition to “field sports” and helped trigger the internal crisis that led to the Reform Group’s formation. However, tensions over her role on FAWAC and her focus on gradualist reforms isolated Harrison. Forced to declare bankruptcy after a libel suit against another Council member, Harrison focused on developing her own Farm Animal Care Trust (FACT).
An ERA Acute Model Overview
Authors: Stephansen Cathrine , Bjørgesæter Anders , Brude Odd Willy , Brönner Ute , Rogstad Tonje Waterloo , Kjeilen-Eilertsen Grethe , Libre Jean-Marie , Collin-Hansen Christian
Published: May 2021

ERA Acute is a model for environmental risk assessment of acute discharges. The calculations follow a common framework for all environmental compartments, whilst maintaining the mechanistic integrity of each compartment and/or VEC group, by using compartment-specific inputs of oil exposure and VEC-specific geographical distribution, vulnerability and recovery-defining parameters/functions. The method allows for using three different levels of detailing in VEC in the exposure and impact calculations. For the highest level of detail, a second step calculates recovery times in three time-factors, as well as the ERA Acute-specific RDF which combines the extent of impact and recovery. The continuous functions of impact and recovery calculations are presented in this chapter, separately for all four compartments. All data are calculated in grid cells, facilitating the use of GIS for viewing inputs and results. The methodology adds up impacts from grid cells to populations, and calculates result statistics from single simulations to scenarios, to multi-scenario DSHAs and cases.
Handling Uncertainty and Sensitivity of ERA Acute Towards Input Parameters
Authors: Stephansen Cathrine , Bjørgesæter Anders , Brude Odd Willy , Brönner Ute , Rogstad Tonje Waterloo , Kjeilen-Eilertsen Grethe , Libre Jean-Marie , Collin-Hansen Christian
Published: May 2021

Uncertainty evaluation and sensitivity testing of the functions and parameters used in ERA Acute serve two functions. ERA Acute is a deterministic model which is sensitive to the range of values used for the parameters. Parameters have inherent uncertainties as to what their true values are, and functions may have varying strength of knowledge. The individual functions were tested with respect to their sensitivity towards variation of the parameter values using both deterministic and stochastic testing. Based on the testing, an uncertainty scoring system was used to identify and prioritize the most important parameters for reducing uncertainty. Recommendations for handling the uncertainty and securing comparability in spite of uncertainty were set up as a conclusion of the studies.
The coset construction for particles of arbitrary spin
Authors: Landry Michael J. , Sun Guanhao
Published: May 2021

Abstract

When a Poincaré-invariant system spontaneously breaks continuous internal symmetries, Goldstones’ theorem demands the existence of massless, spin-zero excitations in a one-to-one correspondence with the broken symmetry generators. When a system spontaneously breaks Poincaré symmetry, however, the kinds of excitations that satisfy Goldstone’s theorem can be quite unusual. In particular, they may have any spin and need not be particles or even quasiparticles. The standard coset construction used to formulate effective actions of Goldstones, however, is rather restrictive and is incapable of generating the full spectrum of possibilities allowed by Goldstone’s theorem. We propose a (partial) remedy to this problem by postulating a novel coset construction for systems that spontaneously break Poincaré symmetry. This new construction is capable of generating effective actions with a wide range of Goldstone excitations — including fermionic degrees of freedom — even when all symmetries are bosonic. To demonstrate its utility, we focus on constructing effective actions for point particles of various spins. We recover the known result that a particle of spin s requires an $$ \mathcal{N} $$
N
= 2s supersymmetric worldline reparameterization gauge symmetry, which we implement at the level of the coset construction. In the process, we discover that massless particles require a novel kind of inverse Higgs constraint that bears some resemblance to the dynamical inverse Higgs constraints that appear in certain fermi liquid effective field theories. We then consider particles that, in addition to quantum spin, have finite spatial extent and are free to rotate. We derive a novel action for such particles and find a ‘spin-orbital’ coupling between the intrinsic quantum spin and the physical-rotation degrees of freedom.
Multiple sclerosis is linked to MAPKERK overactivity in microglia
Authors: ten Bosch George J. A. , Bolk Jolande , ‘t Hart Bert A. , Laman Jon D.
Published: May 2021

Reassessment of published observations in patients with multiple sclerosis (MS) suggests a microglial malfunction due to inappropriate (over)activity of the mitogen-activated protein kinase pathway ERK (MAPKERK). These observations regard biochemistry as well as epigenetics, and all indicate involvement of this pathway. Recent preclinical research on neurodegeneration already pointed towards a role of MAPK pathways, in particular MAPKERK. This is important as microglia with overactive MAPK have been identified to disturb local oligodendrocytes which can lead to locoregional demyelination, hallmark of MS. This constitutes a new concept on pathophysiology of MS, besides the prevailing view, i.e., autoimmunity. Acknowledged risk factors for MS, such as EBV infection, hypovitaminosis D, and smoking, all downregulate MAPKERKnegative feedback phosphatases that normally regulate MAPKERKactivity. Consequently, these factors may contribute to inappropriate MAPKERKoveractivity, and thereby to neurodegeneration. Also, MAPKERKoveractivity in microglia, as a factor in the pathophysiology of MS, could explain ongoing neurodegeneration in MS patients despite optimized immunosuppressive or immunomodulatory treatment. Currently, for these patients with progressive disease, no effective treatment exists. In such refractory MS, targeting the cause of overactive MAPKERKin microglia merits further investigation as this phenomenon may imply a novel treatment approach.
The Burden of Disease and Pathology at a Rapidly Expanding Tertiary Paediatric Surgical Unit in South Africa
Authors: Zanini A. , Maistry N. , Brisighelli G. , Gabler T. , Harrison D. , Westgarth‐Taylor C. , Withers A. , Loveland J. , Patel N.
Published: May 2021

Background

The precise burden of paediatric surgical care in South Africa is unknown. In the absence of epidemiological data, hospital‐based study is a first step to gauge the burden and profile of paediatric surgical disease. We aim to describe the profile of pathology, pattern of referrals, and complications of paediatric surgical care at Chris Hani Baragwanath Academic Hospital (CHBAH).

Methods

A 1‐year retrospective record review for the period 3/1/2019 to 1/1/2020 was conducted by evaluation of the morbidity and mortality databases of the Department of Paediatric Surgery (DPS). Number of admissions, consultations, complications, and surgeries performed were analysed and classified.

Results

A total of 11,932 unique patient encounters occurred. Emergencies (79%, 1841/2329) accounted for the majority of admissions. Trauma accounted for 49% (896/1841) of emergency admissions. Elective surgery constituted 52% (1202/2316) and emergency surgery 48% (1114/2316) of all procedures performed. The emergency department (55%, 1271/2329), outpatients department (19%, 447/2329), and peripheral hospitals (16%, 378/2329) were the source of the majority of admissions. A complication rate of 9% (208/2316) was observed.

Conclusion

The high‐volume subspecialist environment at CHBAH presents the ideal environment for delivery of specialist paediatric surgical services and training. Injury prevention, optimal use of existing resources, and additional physical, human and financial resources are required to meet the existing and predicted future burden of paediatric surgical disease.
BRAF-V600E-Testung beim metastasierten kolorektalen Karzinom und neue, chemotherapiefreie Therapieoptionen
Authors: Hummel Michael , Hegewisch-Becker Susanna , Neumann Jens , Vogel Arndt
Published: May 2021

Die Therapie des metastasierten kolorektalen Karzinoms (mKRK) hat in den letzten 25 Jahren tief greifende Veränderungen erfahren. Auf die Zulassung neuerer Chemotherapeutika folgten ab 2005 die ersten zielgerichteten Therapien, die sich gegen den epidermalen Wachstumsfaktorrezeptor (EGFR) bzw. gegen Rezeptoren vaskulärer endothelialer Wachstumsfaktoren (VEGFR) richteten. Mit der fortschreitenden molekularen Charakterisierung des mKRK in den letzten 10 Jahren und der Einteilung der Erkrankung in 4 Konsensus-Subtypen zeichnet sich weiterer Wandel ab, unter anderem durch Einführung speziell entwickelter Proteinkinaseinhibitoren wie auch Immuncheckpoint-Inhibitoren in den Therapiealgorithmus.

Eine angepasste molekularpathologische Testung ist heute für eine leitliniengerechte Behandlung von mKRK-Patienten unabdingbar. Neben der RAS-Testung als Voraussetzung für die Therapieentscheidung bezüglich Cetuximab und Panitumumab ist die BRAF-Testung äußerst relevant, um – im Falle des Nachweises einer BRAF-V600E-Mutation – eine Therapieentscheidung zugunsten der neu zugelassenen, chemotherapiefreien Kombination aus dem BRAF-Inhibitor Encorafenib und Cetuximab treffen zu können. Eine erweiterte Diagnostik sollte auch die Genominstabilität (Mikrosatelliten-Instabilität) einbeziehen. Insgesamt müssen immer mehr molekulare Alterationen simultan untersucht werden, sodass sich zunehmend die Verwendung des fokussierten Next Generation Sequencing empfiehlt.

Diese Übersichtsarbeit beschreibt die prognostische Relevanz der BRAF-Testung im Rahmen der molekularpathologischen Diagnostik des mKRK, stellt neue Therapieoptionen zur Behandlung BRAF-mutierter mKRK-Patienten vor und erläutert, welche modernen DNA-analytischen und immunohistochemischen Verfahren zur BRAF-Diagnostik von mKRK-Patienten zur Verfügung stehen.
Die Mikroarchitektur des Pankreaskarzinoms aus Sicht des Pathologen und des Radiologen
Authors: Mayer Philipp , Gaida Matthias M.
Published: May 2021

Die diagnostische Radiologie ist gemeinsam mit der diagnostischen Pathologie eines der klinisch-morphologischen Fächer, welche in unterschiedlicher makroskopischer bzw. mikroskopischer Auflösung zur Detektion, Charakterisierung sowie zum Ausbreitungsmuster eines Tumors führen. Die klinischen Disziplinen sind oft voneinander getrennt, wenngleich es vor allem in klinischen Tumorboards immer stärkere Verzahnungen gibt. Am Beispiel des Pankreaskarzinoms sind die Korrelationen radiologischer und pathologischer Diagnostik dargestellt.
Correction to: Is debridement beneficial for focal cartilage defects of the knee: data from the German Cartilage Registry (KnorpelRegister DGOU)
Authors: Weißenberger Manuel , Heinz Tizian , Boelch Sebastian P. , Niemeyer Philipp , Rudert Maximilian , Barthel Thomas , Reppenhagen Stephan
Published: May 2021

A correction to this paper has been published: https://doi.org/10.1007/s00402-021-03905-0
David Hilbert and the foundations of the theory of plane area
Authors: Giovannini Eduardo N.
Published: May 2021

This paper provides a detailed study of David Hilbert’s axiomatization of the theory of plane area, in the classical monograph Foundation of Geometry (1899). On the one hand, we offer a precise contextualization of this theory by considering it against its nineteenth-century geometrical background. Specifically, we examine some crucial steps in the emergence of the modern theory of geometrical equivalence. On the other hand, we analyze from a more conceptual perspective the significance of Hilbert’s theory of area for the foundational program pursued in Foundations. We argue that this theory played a fundamental role in the general attempt to provide a new independent basis for Euclidean geometry. Furthermore, we contend that our examination proves relevant for understanding the requirement of “purity of the method” in the tradition of modern synthetic geometry.
ANN-aided incremental multiscale-remodelling-based finite strain poroelasticity
Authors: Dehghani Hamidreza , Zilian Andreas
Published: May 2021

Mechanical modelling of poroelastic media under finite strain is usually carried out via phenomenological models neglecting complex micro-macro scales interdependency. One reason is that the mathematical two-scale analysis is only straightforward assuming infinitesimal strain theory. Exploiting the potential of ANNs for fast and reliable upscaling and localisation procedures, we propose an incremental numerical approach that considers rearrangement of the cell properties based on its current deformation, which leads to the remodelling of the macroscopic model after each time increment. This computational framework is valid for finite strain and large deformation problems while it ensures infinitesimal strain increments within time steps. The full effects of the interdependency between the properties and response of macro and micro scales are considered for the first time providing more accurate predictive analysis of fluid-saturated porous media which is studied via a numerical consolidation example. Furthermore, the (nonlinear) deviation from Darcy’s law is captured in fluid filtration numerical analyses. Finally, the brain tissue mechanical response under uniaxial cyclic test is simulated and studied.
Notch regulates vascular collagen IV basement membrane through modulation of lysyl hydroxylase 3 trafficking
Authors: Gross Stephen J. , Webb Amelia M. , Peterlin Alek D. , Durrant Jessica R. , Judson Rachel J. , Raza Qanber , Kitajewski Jan K. , Kushner Erich J.
Published: May 2021

Collagen type IV (Col IV) is a basement membrane protein associated with early blood vessel morphogenesis and is essential for blood vessel stability. Defects in vascular Col IV deposition are the basis of heritable disorders, such as small vessel disease, marked by cerebral hemorrhage and drastically shorten lifespan. To date, little is known about how endothelial cells regulate the intracellular transport and selective secretion of Col IV in response to angiogenic cues, leaving a void in our understanding of this critical process. Our aim was to identify trafficking pathways that regulate Col IV deposition during angiogenic blood vessel development. We have identified the GTPase Rab10 as a major regulator of Col IV vesicular trafficking during vascular development using both in vitro imaging and biochemistry as well as in vivo models. Knockdown of Rab10 reduced de novo Col IV secretion in vivo and in vitro. Mechanistically, we determined that Rab10 is an indirect mediator of Col IV secretion, partnering with atypical Rab25 to deliver the enzyme lysyl hydroxylase 3 (LH3) to Col IV-containing vesicles staged for secretion. Loss of Rab10 or Rab25 results in depletion of LH3 from Col IV-containing vesicles and rapid lysosomal degradation of Col IV. Furthermore, we demonstrate that Rab10 is Notch responsive, indicating a novel connection between permissive Notch-based vessel maturation programs and vesicle trafficking. Our results illustrate both a new trafficking-based component in the regulated secretion of Col IV and how this vesicle trafficking program interfaces with Notch signaling to fine-tune basement membrane secretion during blood vessel development.
High endothelial venules (HEVs) in immunity, inflammation and cancer
Authors: Blanchard Lucas , Girard Jean-Philippe
Published: May 2021

High endothelial venules (HEVs) are specialized blood vessels mediating lymphocyte trafficking to lymph nodes (LNs) and other secondary lymphoid organs. By supporting high levels of lymphocyte extravasation from the blood, HEVs play an essential role in lymphocyte recirculation and immune surveillance for foreign invaders (bacterial and viral infections) and alterations in the body’s own cells (neoantigens in cancer). The HEV network expands during inflammation in immune-stimulated LNs and is profoundly remodeled in metastatic and tumor-draining LNs. HEV-like blood vessels expressing high levels of the HEV-specific sulfated MECA-79 antigens are induced in non-lymphoid tissues at sites of chronic inflammation in many human inflammatory and allergic diseases, including rheumatoid arthritis, Crohn’s disease, allergic rhinitis and asthma. Such vessels are believed to contribute to the amplification and maintenance of chronic inflammation. MECA-79+ tumor-associated HEVs (TA-HEVs) are frequently found in human tumors in CD3+ T cell-rich areas or CD20+ B-cell rich tertiary lymphoid structures (TLSs). TA-HEVs have been proposed to play important roles in lymphocyte entry into tumors, a process essential for successful antitumor immunity and lymphocyte-mediated cancer immunotherapy with immune checkpoint inhibitors, vaccines or adoptive T cell therapy. In this review, we highlight the phenotype and function of HEVs in homeostatic, inflamed and tumor-draining lymph nodes, and those of HEV-like blood vessels in chronic inflammatory diseases. Furthermore, we discuss the role and regulation of TA-HEVs in human cancer and mouse tumor models.
Effects of phosphorus enrichment on the spatial heterogeneity of stream periphyton under uneven light conditions
Authors: Iannino Alessandra , Vosshage Alexander Tim Ludwig , Weitere Markus , Fink Patrick
Published: May 2021

Spatial variations in light and nutrient availability usually lead to a heterogeneous distribution of periphyton biomass within streams, but the effects of nutrient enrichment on periphyton heterogeneity are still poorly understood. We tested phosphorus enrichment effects on the heterogeneity of periphyton quantity and nutritional quality in an environment with uneven light conditions. Natural periphyton was grown at either high or low P supply in circular running water flumes, each of which was half shaded and half in light. After 3 weeks, periphyton biomass was significantly more heterogeneous at high P than at low P supply, as algal production increased with light only in the P-enriched treatment. However, periphyton C:P ratio was equally homogeneous in both P treatments, despite the light differences within each experimental flume. Although this outcome seems to contrast with the light:nutrient hypothesis, it is likely that high-quantity periphyton patches acquired more P and depleted the available P for the low-quantity patches, leading to an even C:P ratio within each flume. Therefore, in an environment with heterogeneous light availability, nutrient enrichment has the potential to increase the heterogeneity of periphyton quantity without affecting the heterogeneity of periphyton quality, due to periphyton patches not being independent of one another.
The presence of fine sand in the muddy sediments affects habitat selection and accelerates the growth rate of Limnodrilus hoffmeisteri and Limnodrilus claparedianus (Oligochaeta)
Authors: Żbikowski Janusz , Żbikowska Elżbieta , Kobak Jarosław
Published: May 2021

Assessment of food conditions for animals is usually based on the quality and quantity of available food, whereas less attention is paid to other factors affecting the processing of ingested food. One of the commonly used mechanisms involving non-digestible objects from the environment is lithophagy (using swallowed stones or sand grains as gastroliths). Therefore, the aim of this laboratory study was to investigate the impact of sand present in muddy bottom sediments on ubiquitous freshwater oligochaetes: Limnodrilus hoffmeisteri and Limnodrilus claparedianus. They belong to the most common tubificid species and, as detritivores, play crucial role in the functioning of water ecosystems. We showed that the presence of sand in the environment has positive effects on oligochaete habitat preferences and growth. They selected the mixture of mud and 60–160 µm sand over pure mud and mud with larger sand fractions. Their growth rate was highest in the sediments with an admixture of this sand fraction, and simultaneously the largest number of sand grains of this size was found in their digestive tracts. In our opinion, the oligochaetes used the sand grains to grind the ingested food, which should accelerate digestion and nutrient assimilation, and stimulate their growth rate.
Contrasting Mind-Wandering, (Dark) Flow, and Affect During Multiline and Single-Line Slot Machine Play
Authors: Kruger Tyler B. , Dixon Mike J. , Graydon Candice , Larche Chanel J. , Stange Madison , Smith Stephen D. , Smilek Daniel
Published: May 2021

Slot machines are a very popular form of gambling in which a small proportion of gamblers experience gambling-related problems. These players refer to a trance-like state that researchers have labelled ‘dark flow’—a pleasurable, but maladaptive state where players become completely occupied by the game. We assessed 110 gamblers for mindfulness (using the Mindful Attention Awareness Scale), gambling problems (using the Problem Gambling Severity Index), depressive symptoms (using the Depression, Anxiety, and Stress Scale), and boredom proneness (using the Boredom Proneness Scale). Participants played both a multiline and single-line slot machine simulator and were occasionally interrupted with thought probes to assess whether they were thinking about the game or something else. After playing each game, we retrospectively assessed dark flow and affect during play. Our key results were that the number of “on-game” reports during the multiline game were significantly higher than the single-line game, and that we found significantly greater flow during the multiline game than the single-line game. We also found significantly lower negative affect during the multiline game than the single-line game. Using hierarchical multiple regression, we found that dark flow accounted for unique variance when predicting problem gambling severity (over and above depression, mindfulness, and boredom proneness). These assessments help bolster our previous assertions about escape gambling—if some players are prone to having their mind-wander to negative places, the frequent but unpredictable reinforcement of multiline slot machines may help rein in the wandering mind and prevent minds from unintentionally wandering to negative thoughts.
Saccadic Eye Movement in Mild Cognitive Impairment and Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Authors: Opwonya Julius , Doan Dieu Ni Thi , Kim Seul Gee , Kim Joong Il , Ku Boncho , Kim Soochan , Park Sunju , Kim Jaeuk U.
Published: May 2021

Alzheimer’s disease (AD) is the leading cause of dementia, and mild cognitive impairment (MCI) is considered the transitional state to AD dementia (ADD) and other types of dementia, whose symptoms are accompanied by altered eye movement. In this work, we reviewed the existing literature and conducted a meta-analysis to extract relevant eye movement parameters that are significantly altered owing to ADD and MCI. We conducted a systematic review of 35 eligible original publications in saccade paradigms and a meta-analysis of 27 articles with specified task conditions, which used mainly gap and overlap conditions in both prosaccade and antisaccade paradigms. The meta-analysis revealed that prosaccade and antisaccade latencies and frequency of antisaccade errors showed significant alterations for both MCI and ADD. First, both prosaccade and antisaccade paradigms differentiated patients with ADD and MCI from controls, however, antisaccade paradigms was more effective than prosaccade paradigms in distinguishing patients from controls. Second, during prosaccade in the gap and overlap conditions, patients with ADD had significantly longer latencies than patients with MCI, and the trend was similar during antisaccade in the gap condition as patients with ADD had significantly more errors than patients with MCI. The anti-effect magnitude was similar between controls and patients, and the magnitude of the latency of the gap effect varied among healthy controls and MCI and ADD subjects, but the effect size of the latency remained large in both patients. These findings suggest that, using gap effect, anti-effect, and specific choices of saccade paradigms and conditions, distinctions could be made between MCI and ADD patients as well as between patients and controls.
Detecting striations via the lateral photovoltage scanning method without screening effect
Authors: Kayser S. , Farrell P. , Rotundo N.
Published: May 2021

The lateral photovoltage scanning method (LPS) detects doping inhomogeneities in semiconductors such as Si, Ge and $${\hbox {Si}_{\hbox {x}}\hbox {Ge}_{1-\hbox {x}}}$$

Si
x

Ge

1
-
x

in a cheap, fast and nondestructive manner. LPS relies on the bulk photovoltaic effect and thus can detect any physical quantity affecting the band profiles of the sample. LPS finite volume simulation using commercial software suffer from long simulation times and convergence instabilities. We present here an open-source finite volume simulation for a 2D Si sample using the simulator. For low injection conditions we show that the LPS voltage is proportional to the doping gradient. For higher injection conditions, we directly show how the LPS voltage and the doping gradient differ and link the physical effect of lower local resolution to the screening effect. Previously, the loss of local resolution was assumed to be only connected to the enlargement of the excess charge carrier distribution.
The relationship between emotional intelligence and quality of life in schizophrenia and bipolar I disorder
Authors: Frajo-Apor Beatrice , Pardeller Silvia , Kemmler Georg , Mühlbacher Moritz , Welte Anna-Sophia , Hörtnagl Christine , Derntl Birgit , Hofer Alex
Published: May 2021

Purpose

Social cognitive skills, both psychosocial functioning and well-being of patients with schizophrenia (SZ) or bipolar disorder (BD), have consistently been shown to be interrelated. While previous research mainly focused on emotion perception, the present study investigates the impact of the other subdomains of emotion processing on a subjective Quality of Life (QoL) estimate and objective QoL indicators. We hypothesized that patients with better performance in the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) report better QoL; and assumed that SZ and BD patients report comparable subjective QoL, whereas BD patients show higher levels of objective QoL.

Methods

Patients diagnosed with either SZ (n = 63) or BD (n = 60), as well as 80 healthy controls, were included into a cross-sectional study. Emotional Intelligence (EI) and QoL were assessed using the MSCEIT and the German version of the Lancashire Quality of Life Profile.

Results

The two patient groups were comparable with regard to overall EI, as well as subjective and objective QoL, but indicated significantly lower levels of EI and QoL than healthy controls. Whereas EI was not associated with both patient groups’ subjective QoL, a significant correlation of EI with objective QoL was only observed in SZ. However, overall effect sizes were small.

Conclusion

Our findings point to a difference in the interrelation between EI and QoL in patients suffering from SZ and BD, and suggest that they may have different needs to achieve recovery. It will be critical to develop training programs targeting EI in SZ, and to examine their impact on objective QoL in these patients.
Role and activity of jasmonates in plants under in vitro conditions
Authors: Kamińska Monika
Published: May 2021

Jasmonates (JAs), such as jasmonic acid and its methyl ester, are lipid-derived compounds with signal functions in plant growth and development, as well as in responses to stress. JAs are widely distributed in plants as natural plant growth regulators. JAs do not work independently but work as a part of a complex signaling network with other phytohormones. They are deployed to induce response during wounding and are often used for elicitation and stimulation of secondary metabolites production in different in vitro culture systems. Application of JAs seems to be promising during different steps of the micropropagation system for different species. JAs stimulate proliferation rate of shoots, roots, callus and induce microtubers and bulblets formation. However, negative effects of JAs on the condition of plant tissues are also reported, e.g. leaf senescence, reduced growth and inhibited somatic embryogenesis. This review summarizes the current knowledge of the application and properties of jasmonates under in vitro conditions in terms of cell division, explant growth, proliferation ability, storage organ formation and stress response.
Concentration and ROC Curves, Revisited
Authors: Gasparini Mauro , Sacchetto Lidia
Published: May 2021

This work is aimed at illustrating the strict relationship between a general definition of concentration function appeared quite some time ago on this journal and a widely used measure of the diagnostic strength of a family of binary classifiers indexed by a threshold parameter, the so-called ROC curve. The ROC curve is a common work tool in Statistics, Machine Learning and Artificial Intelligence, appearing in many applications where a binary classification (diagnosis) procedure is of interest. Hence, it is worth remarking that diagnostic strength and concentration are two sides of the same coin: the higher the concentration of one probability measure with respect to another, the higher the diagnostic strength of the likelihood ratio classification rule.
Modelling and forecasting mortality improvement rates with random effects
Authors: Renshaw Arthur , Haberman Steven
Published: May 2021

A common feature in the modelling and extrapolation of the trends in mortality rates over time, based on fitted parametric structures, has tended to involve the treatment of a structured fitted main effects period component (with possibly a cohort component) as a random effects time series. In this paper, we follow the lead of Haberman and Renshaw (Insurance Math Econ 50:309–333, 2012) and other authors in modelling and forecasting mortality improvement rates over time, rather than mortality rates. In this context, we assume linear parametric structures for mortality improvement rates, and we examine the feasibility of modelling the main period effects (and possibly any cohort effects) as a random effect from the outset. We argue that this leads to a more unified approach to model fitting and extrapolation.