bluuebunny/crossref_metadata_2025 huggingface dataset:
Rethinking the legal regulation of Internet platform monopoly in China
Authors: He Qing
Published: May 2022

The existing regulatory regime for single firm exclusionary activity is primarily to establish a dominant position for a finding of an abuse, but there are challenges coming out of relevant market definition, market power determination, and the efficiency or innovation justifications. This paper argues for an alternative solution: an effects‐based analysis methodology for regulating platforms which are not proven to be dominant. Based on case studies including the Alibaba decision, JD.com case, Meituan case, and Visa case, it follows that we should stay focused on foreclosure effects while specifying the type of conduct that calls for careful scrutiny. But it is controversial to apply the traditional leverage theory and essential facilities doctrine to digital markets, which are of great significance to the determination of foreclosure effects. This paper introduces a “related markets hypothesis” to illustrate the leverage of market power, and applies a modified “costs‐based test” to determine whether the data resources held by the platform constitute a bottleneck. This paper finally proposes a classification scheme different from the criteria on a basis of company size. The decisive factors for classification include: form of platform enterprises, behavioral pattern, nature of market, market structure, and the competitive environment in related markets.
Overview of Li‐ion battery energy storage system failures and risk management considerations
Authors: Stokes Roger
Published: May 2022

These articles explain the background of lithium‐ion battery systems, key issues concerning the types of failure, and some guidance on how to identify the cause(s) of the failures. It also provides an overview of the series and some further comments on risks, mitigations, escalation, and insurance aspects.
Laodelphax striatellus saliva mucin enables the formation of stylet sheathes to facilitate its feeding and rice stripe virus transmission
Authors: Huo Yan , Zhao Jing , Meng Xiangyi , Yang Jie , Zhang Ziyu , Liu Zhiwei , Fang Rongxiang , Zhang Lili
Published: May 2022

Background

Laodelphax striatellus transmits rice stripe virus (RSV) during sap feeding on the rice plant. The insect saliva proteins have direct and indirect roles in mediating RSV transmission; however, the function of most saliva proteins remains unclear.

Results

In this study, we sequenced L. striatellus saliva proteins using shotgun liquid chromatography–electrospray ionization–tandem mass spectrometry. We identified 41 secreted saliva proteins, among which a saliva mucin‐like protein, designated LssaMP, was the most abundant. In silico analysis revealed the sequence conservation among planthoppers. We revealed that the LssaMP gene is specifically expressed in the salivary glands and the protein is secreted as a component of gel saliva. Using LssaMP‐specific double‐stranded RNA (dsRNA) to silence gene expression, we revealed that LssaMP is required for formation of the salivary sheath, an important structure for sap feeding. Disrupting LssaMP expression resulted in inefficient formation of the feeding structure, thereby stopping insects from secreting watery saliva and acquiring sufficient nutrients from the phloem sap. We confirmed that RSV is mainly released via the watery saliva, which passes through the salivary sheathes into the plant phloem. An insufficient feeding structure results in decreased release of watery saliva, as well as the arboviruses.

Conclusion

This study clarified the function of an insect saliva protein in mediating insect feeding, as well as arbovirus transmission. © 2022 Society of Chemical Industry.
The pharmacological and pharmacokinetic properties of esculin: A comprehensive review
Authors: Li Chun‐xiao , Li Jing‐chun , Lai Jiang , Liu Ying
Published: May 2022

Cortex fraxini is a widely used traditional Chinese medicine. Esculin is one of the main active ingredients of Cortex fraxini and has attracted more and more attention from scholars. The purpose of the review is to systematically review relevant studies on the pharmacological effects and pharmacokinetic characteristics of esculin to support its further application as therapeutic agents. Pharmacological studies have shown that the anti‐inflammatory and anti‐oxidative stress effects of esculin are outstanding. This indicates that esculin is promising to be used to treat a variety of diseases closely related to inflammation and oxidative damage. Esculin has anti‐diabetic effect, which is closely related to improving pancreas damage, promoting insulin release, and enhancing glucose homeostasis. In addition, esculin has anti‐cancer, antibiosis, anti‐virus, neuroprotection, anti‐thrombosis and treating eye diseases properties. Pharmacokinetic studies show that esculin can be quickly and evenly distributed in the body. However, the first pass effect of esculin is serious. In short, esculin is promising to treat many diseases, but further high quality studies are needed to firmly establish the clinical efficacy of esculin.
Phytoestrogen arctigenin preserves the mucus barrier in inflammatory bowel diseases by inhibiting goblet cell apoptosis via the ERβ/TRIM21/PHB1 pathway
Authors: Tao Yu , Qiao Si‐miao , Lv Chang‐jun , Yun Xin‐ming , Yue Meng‐fan , Fang Yu‐lai , Wei Zhi‐feng , Dai Yue , Xia Yu‐feng
Published: May 2022

Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway‐mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor β (ERβ) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERβ knock down in the colons of mice with DSS‐induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERβ/TRIM21/PHB1 pathway.
TULP2 deletion mice exhibit abnormal outer dense fiber structure and male infertility
Authors: Oyama Yuki , Miyata Haruhiko , Shimada Keisuke , Larasati Tamara , Fujihara Yoshitaka , Ikawa Masahito
Published: May 2022

Purpose

Tulp2 (tubby‐like protein 2) is a member of the tubby protein family and expressed predominantly in mouse testis. Recently, it was reported that Tulp2 knockout (KO) mice exhibited disrupted sperm tail morphology; however, it remains to be determined how TULP2 deletion causes abnormal tail formation.

Methods

The authors analyzed male fertility, sperm morphology, and motility of two Tulp2 KO mouse lines that were generated using the conventional method that utilizes homologous recombination in embryonic stem (ES) cells as well as the clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9) system. Furthermore, the authors observed the spermatogenesis of Tulp2 KO mice in more detail using scanning and transmission electron microscopy (SEM and TEM).

Results

Both mouse lines of Tulp2 KO exhibited male infertility, abnormal tail morphology, and impaired sperm motility. No overt abnormalities were found in the formation of the mitochondrial sheath in Tulp2 KO mice using the freeze‐fracture method with SEM. In contrast, abnormal outer dense fiber (ODF) structure was observed in Tulp2 KO testis with TEM.

Conclusions

TULP2 may play roles in the correct formation and/or maintenance of ODF, which may lead to abnormal tail morphology, impaired sperm motility, and male infertility.
Blue catfish population characteristics and dispersal along a Great Plains river gradient
Authors: Dean Quintin J. , Werner Jacob P. , Pegg Mark A. , Hamel Martin J.
Published: May 2022

Understanding movement and dispersal dynamics of mobile, large‐river fishes is essential to adopting an ecologically relevant spatial scale for research and management. Movement and dispersal patterns of Blue CatfishIctalurus furcatus, a large‐river specialist, have been mostly investigated in large river systems within their native range, with little emphasis on tributaries and the influence of connectivity. Here, we examine longitudinal movement patterns, natal environments, and population demographics of Blue Catfish in a tributary system of a large Great Plains river. Blue Catfish tagged in the Kansas River were recaptured in five different rivers of varying size and order, and individual movement was highly variable (0–475 rkm). Adult fish (>400 mm) collected within segments (i.e., Segment 1 and 2) of the Kansas River with connectivity to the Missouri River displayed relatively equal natal contributions from the Kansas River (34–48%) and Missouri River (38–65%) while disconnected river segments contained a high percentage (64–87%) of individuals that originated from reservoirs located on tributaries to the Kansas River. The Kansas River segments (Segment 1 and 2) connected with the Missouri River had lower instantaneous mortality (Z = 0.19, SE = 0.05) and higher proportions of large fish (PSD‐M = 9 & 11, PSD‐T = 3 & 5, respectively) compared to disconnected reaches (Z = 0.27, SE = 0.08; PSD‐M = 3, PSD‐T = 0). Mean length of Blue Catfish collected in disconnected reaches were greater than those from connected reaches for individuals at age‐3 and age‐6, and relatively equal at age‐10. Our data provide additional resolution to movement and dispersal patterns of Blue Catfish within large‐river tributary systems, highlight the role of localized reservoir stock contributions, and illustrate species plasticity across varying levels of river network connectivity.
Fe/Mn‐Porphyrin Coordination Polymer Nanoparticles for Magnetic Resonance Imaging (MRI) Guided‐Combination Therapy between Photodynamic Therapy and Chemodynamic Therapy
Authors: Jin Lin , Miao Yuyang , Liu Dapeng , Song Fengling
Published: May 2022

Combination therapy is considered to be an effective strategy for enhanced tumor treatment. Here we fabricated amorphous dual metal (FeMn)‐porphyrin based coordination polymer nanoparticles FeMn‐TCPP NPs via a facile and mild protocol. The formed FeMn‐TCPP NPs possessed the combination therapy between photodynamic therapy attributed to TCPP ligand and chemodynamic therapy mainly ascribed to chemodynamic therapy agent Fe (II). Moreover, Mn (II) as a T1 contrast agent endowed the FeMn‐TCPP NPs with significant r1 relaxivity for MRI imaging. Notably, FeMn‐TCPP NPs not only integrated the functional agents into one nanoplatform but also exhibited synergetic effects for enhanced combination therapy. All the features allowed the FeMn‐TCPP NPs as an all‐in‐one nanoplatform toward precision cancer therapy.
Efficient Preparation of Rare Earth Oxides from Back Extraction Praseodymium Neodymium Chloride by Flash Pyrolysis
Authors: Lei Xiang , Wang Houqing , Fu Liwen , Wang Jinliang , Xu Shengming
Published: May 2022

Praseodymium‐neodymium‐oxide powder was prepared using a simple citric acid‐assisted ultrasonic spray pyrolysis. The rare‐earth oxide transformation process and temperature were clarified using the characterisation results. The results show that a sufficient mass ratio of citric acid can promote the decomposition of chlorine oxides produced during calcination. This favourable change is attributed to the unique composition and morphology of the precursors. Furthermore, the residual chlorine content and migration behaviour in the praseodymium‐neodymium‐oxide powder were studied and discussed. This study provides the necessary theoretical and experimental basis for the application of ultrasonic spray pyrolysis technology for rare‐earth oxide production.
Relational and individual stress pathways linking discrimination and ageing cardiometabolic health
Authors: Woods Sarah B. , Strenth Chance , Day Philip , Tsewang Tenzin , Aparicio Kimberly , Ross Kristin , Ventimiglia Joseph , Jetpuri Zaiba
Published: May 2022

Perceived discrimination is a significant risk factor for worse ageing health outcomes. Yet, the specific individual and relational stress pathways linking discrimination to disease are less understood, especially in the context of cardiometabolic health. We tested family stress and psychophysiological distress (negative affect and high‐risk lipid/fat metabolism) as mediators linking perceived discrimination to cardiometabolic morbidity and health appraisal over 20 years for midlife adults. Using data from participants who completed the Biomarker Project (2004–2009) of the Midlife in the U.S. project, and examining data over the study's three waves (1995–1996, 2004–2006, and 2013–2014), we used structural equation modelling to test pathways for participants who reported zero cardiometabolic conditions at baseline (n = 799). Greater Time 1 discrimination was associated with greater Time 2 family strain, which was in turn associated with worse negative affect; worse Time 2 negative affect was associated with worse Time 3 health appraisal; metabolic lipids risk did not serve as an indirect pathway to Time 3 cardiometabolic morbidity (χ2 = 147.74, p < 0.001; RMSEA = 0.056; CFI = 0.902; SRMR = 0.047). The inclusion of family in interventions to mitigate the impact of discrimination may be indicated for promoting cardiometabolic wellness.
The Impact of Prenitriding on the Microstructure and Mechanical Properties of the Carburized Surface Layer in a Martensitic Stainless Steel
Authors: Tian Yong , Song Chaowei , Wang Bin , Wang Zhaodong , Wang Guodong , Wang Haojie
Published: May 2022

Herein, it is proposed to obtain a favorable combination of microstructure and mechanical properties of martensitic stainless steel 14Cr14Co13Mo5 by prenitriding method before carburizing and appropriate heat treatment processes. The result indicates that the effective hardened layer depth is increased by 32% to 0.66 mm, and the hardness is significantly improved by prenitriding. The confocal laser scanning microscope and electron backscattered diffraction show that the prenitriding can effectively refine the martensite substructure of the carburized layer after quenching due to the refinement of prior austenite grain. In addition, plenty of second‐phase particles M2N with finer size appear at the same case layer depth instead of coarse M23C6 in the specimen prenitrided, which optimize the microstructure of the case layer.
Generation of eco‐friendly design for post‐tensioned axially symmetric reinforced concrete cylindrical walls by minimizing of CO2 emission
Authors: Bekdaş Gebrail , Yucel Melda , Nigdeli Sinan Melih
Published: May 2022

Structures should be designed in the direction of providing different vital requirements such as safety, durability, strength besides comfortable, and serviceability needs to be intended for usage purposes. Also, an effective structural design must carry on the other significant conditions consisting of being economic, even not destructive to the environment via various hazardous effects. Within the scope of this study, to realize all mentioned aims, an optimization process was carried out to generate an eco‐friendly and cost‐effective structural model for a post‐tensioned axial symmetric reinforced concrete cylindrical wall. While this process is realized, three different metaheuristic algorithms as harmony search (HS), teaching–learning based optimization (TLBO), and flower pollination algorithm (FPA) were benefited to observe optimal parameters and main objective conditions of different variations produced intended for the wall structure. These optimal conditions contain optimal section size as the thickness of the wall, value of post‐tensioning loads, and their coordinates applied along the wall, besides the main purpose is to minimize of emission amount of carbon dioxide (CO2) from the utilized structural materials namely, concrete, steel reinforcements, and post‐tensioning cables. As doing this, optimal levels for arising costs of materials can also be observed at the same time. With this study, all of these processes were provided with respect to many design combinations by utilizing various strength alternatives for concrete and even steel reinforcement grades together with different structural properties such as wall height, specific weight of liquid within the wall, and number of post‐tensioning loads. By this means, it was made possible to generate both nature‐friendly, cost‐effective together with reliable and sustainable structures. The investigation of the optimum design was done for three cases. The first case was done for limited variation of design constants, and the best effective algorithm was found as FPA after the evaluation of results for multiple cycles of the optimization process. The other cases were done for different values of design constants by using the best algorithm. For the evaluation of the optimum cost for different countries, the most expensive ones are for Germany and Canada. As the final finding, the increase in the number of post‐tensioning loads reduces the CO2 emission in the optimum design.
Tragopogon dubius: Multiple introductions to North America and the formation of the New World tetraploids
Authors: Soltis Douglas E. , Mavrodiev Evgeny V. , Gitzendanner Matthew A. , Alexeev Yuri E. , Godden Grant T. , Soltis Pamela S.
Published: May 2022

Tragopogon (Asteraceae) is an evolutionary model for the study of whole‐genome duplication, with two recently and repeatedly formed allopolyploids, T. mirus and T. miscellus, and many additional polyploid species. Tragopogon mirus and T. miscellus formed in western North America following the introduction of three diploids from Europe: T. dubius, T. porrifolius, and T. pratensis. Of these diploids, T. dubius is a shared parent of both tetraploids and is broadly defined and widely distributed in Eurasia. Because human‐mediated intercontinental introductions may lead to hybridization with local species, and associated polyploidization, the introduction history of T. dubius from Europe to North America provides further opportunity to investigate both the extent and consequences of plant introductions. Using ITS sequence data, we show that the morphologically diverse, broadly defined T. dubius comprises a complex of at least 10 different ITS types in its native range, six of which have been introduced from Europe into North America. Significantly, although the two allotetraploid species have each formed multiple times on geographical scales from local to regional, recurrent formation is the result of repeated hybridization involving only one of these ITS subtypes. These results reinforce earlier data suggesting that not all diploid genotypes can form allopolyploids. Several entities traditionally considered part of T. dubius s.l. are now recognized as distinct species (e.g., T. lainzii), and it is likely that other distinct ITS genotypes identified here may also mark unique lineages that ultimately merit recognition as separate species. However, more intensive phylogenetic analyses involving many more samples from across the geographic range of T. dubius are required, as are detailed assessments of taxonomy, morphology, and cytology.
A Nonlinear Filter with Constant‐Gains Using a Pseudo‐Formal Linearization Method Based on Chebyshev Expansion
Authors: Komatsu Kazuo , Takata Hitoshi
Published: May 2022

This paper deals with a design of a nonlinear filter using a pseudo‐formal linearization method based on Chebyshev expansion with constant filter gains. The given nonlinear dynamic and measurement equations are piecewisely linearized by a formal linearization method using Chebyshev expansion, therefore the steady‐state Kalman filter can be applied for each linearized system. Then the resulting filters are smoothly united into a single nonlinear filter by an automatic choosing function. We demonstrate the proposed method in nonlinear systems to verify the effectiveness. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Regulating Discoverability in Subscription Video-on-Demand Services
Authors: Lobato Ramon , Scarlata Alexa
Published: May 2022

In recent years, the growing popularity of services such as Netflix, Amazon Prime Video, and Disney+ has raised complex challenges for media policy. Established policy approaches in a range of areas including audio-visual licensing, classification, censorship, and local production support are now being disrupted as governments grapple with the “Netflix effect” and its implications for national markets and institutions. Meanwhile, consumption practices are also changing as the algorithmically curated interfaces of SVOD services invite audiences to discover content in new ways. In particular, the use of personalised recommendation and other algorithmic filtering techniques has prompted discussion of how SVODs manage the visibility of different kinds of content—and whether these discovery environments require a policy response. This chapter explores how discoverability has emerged as a topic of debate, specifically in relation to SVOD services, and how this is connected to other precedents in audio-visual law and policy such as prominence regulation. We reflect on the many tensions inherent in this area of policy—which exists at the interface of media and platform regulation—and consider some of the normative questions raised when governments intervene in audiences’ content choices.
The Broken Internet and Platform Regulation: Promises and Perils
Authors: Winseck Dwayne
Published: May 2022

A relatively small number of global Internet giants—Google, Apple, Facebook, Amazon, Microsoft, and Netflix—have come under intense and ongoing fire for precipitating a twin crisis of journalism and the media, destroying democracy, and centralizing control over the Internet. In response, a new wave of Internet regulation is now in the making in one country after another. This chapter agrees that a forceful response to the platforms is overdue but raises concerns that the case against GAFAM + has become orthodoxy, anchored in cherry-picked evidence and a tendency to see these firms as the cause of all perceived woes. I also argue that while attempts to regulate digital platforms by the standards of broadcasting regulation may be politically expedient, this approach rests on superficial analogies. It also ignores the fact that the media industries have developed in close proximity to the vastly larger telecoms, consumer electronics and banking firms since the mid-nineteenth century. The last sections of this chapter offer four principles of structural and behavioural regulation drawn from this history as guides for a new generation of internet regulation today: structural separation (break-ups), line of business restrictions (firewalls), public obligations and public alternatives.
Towards robust data-driven reduced-order modelling for turbulent flows: application to vortex-induced vibrations
Authors: Schubert Yannick , Sieber Moritz , Oberleithner Kilian , Martinuzzi Robert
Published: May 2022

This work presents a robust method that minimises the impact of user-selected parameter on the identification of generic models to study the coherent dynamics in turbulent flows. The objective is to gain insight into the flow dynamics from a data-driven reduced order model (ROM) that is developed from measurement data of the respective flow. For an efficient separation of the coherent dynamics, spectral proper orthogonal decomposition (SPOD) is used, projecting the flow field onto a low-dimensional subspace, so that the dominating dynamics can be represented with a minimal number of modes. A function library is defined using polynomial combinations of the temporal modal coefficients to describe the flow dynamics with a system of nonlinear ordinary differential equations. The most important library functions are identified in a two-stage cross-validation procedure (conservative and restrictive sparsification) and combined in the final model. In the first stage, the process uses a simple approximation of the derivative to match the model with the data. This stage delivers a reduced set of possible library function candidates for the model. In the second, more complex stage, the model of the entire flow is integrated over a short time and compared with the progression of the measured data. This restrictive stage allows a robust identification of nonlinearities and modal interactions in the data and their representation in the model. The method is demonstrated using data from particle image velocimetry (PIV) measurements of a circular cylinder undergoing vortex-induced vibration (VIV) at $$\mathrm{Re}=4000$$

Re
=
4000

. It delivers a reduced order model that reproduces the average dynamics of the flow and reveals the interaction of coexisting flow dynamics by the model structure.
In vitro–in silico-based prediction of inter-individual and inter-ethnic variations in the dose-dependent cardiotoxicity of R- and S-methadone in humans
Authors: Shi Miaoying , Dong Yumeng , Bouwmeester Hans , Rietjens Ivonne M. C. M. , Strikwold Marije
Published: May 2022

New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro–in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose–response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.
Satellite tagging and flipper tag recoveries reveal migration patterns and foraging distribution of loggerhead sea turtles (Caretta caretta) from eastern Australia
Authors: Perez Michelle A. , Limpus Colin J. , Hofmeister Kate , Shimada Takahiro , Strydom Aub , Webster Emily , Hamann Mark
Published: May 2022

Marine turtles encounter different threats during various life-history stages. Therefore, understanding their movements and spatial distribution is crucial for effectively managing these long-lived migratory organisms. This study combines satellite telemetry data with long-term capture-mark-recapture data derived from flipper tag studies to determine distribution patterns of endangered loggerhead turtles (Caretta caretta) during post-nesting migrations from different eastern Australian nesting sites. Individuals from the K’gari-Fraser Island and Great Barrier Reef island rookeries typically migrated northward, whereas individuals from mainland rookeries migrated equally northward and southward. Despite this difference in foraging distribution, loggerheads from the different rookeries did not differ substantially in their migration duration or distance travelled. The foraging distribution identified from successful satellite tag deployments represented 50% of the foraging distribution identified from a large long-term flipper tag recovery database. However, these satellite telemetry results have identified new migration and foraging habitats not previously recognised for loggerhead turtles nesting in eastern Australia. Additionally, they support the conclusion from a past study using flipper tag recovery data that the mainland nesting turtles migrate to different foraging grounds than the turtles nesting on Great Barrier Reef islands. Collectively, the two data sources provide valuable data on the migration route, habitat distribution and ecological range for a threatened genetic stock of loggerhead turtles.
Use of red, far-red, and near-infrared light in imaging of yeasts and filamentous fungi
Authors: Pócsi István , Szigeti Zsuzsa M. , Emri Tamás , Boczonádi Imre , Vereb György , Szöllősi János
Published: May 2022

While phototoxicity can be a useful therapeutic modality not only for eliminating malignant cells but also in treating fungal infections, mycologists aiming to observe morphological changes or molecular events in fungi, especially when long observation periods or high light fluxes are warranted, encounter problems owed to altered regulatory pathways or even cell death caused by various photosensing mechanisms. Consequently, the ever expanding repertoire of visible fluorescent protein toolboxes and high-resolution microscopy methods designed to investigate fungi in vitro and in vivo need to comply with an additional requirement: to decrease the unwanted side effects of illumination. In addition to optimizing exposure, an obvious solution is red-shifted illumination, which, however, does not come without compromises. This review summarizes the interactions of fungi with light and the various molecular biology and technology approaches developed for exploring their functions on the molecular, cellular, and in vivo microscopic levels, and outlines the progress towards reducing phototoxicity through applying far-red and near-infrared light.

Key points

• Fungal biological processes alter upon illumination, also under the microscope

• Red shifted fluorescent protein toolboxes decrease interference by illumination

• Innovations like two-photon, lightsheet, and near IR microscopy reduce phototoxicity
High DKK3 expression related to immunosuppression was associated with poor prognosis in glioblastoma: machine learning approach
Authors: Han Myung-Hoon , Min Kyueng-Whan , Noh Yung-Kyun , Kim Jae Min , Cheong Jin Hwan , Ryu Je Il , Won Yu Deok , Koh Seong-Ho , Myung Jae Kyung , Park Ji Young , Kwon Mi Jung
Published: May 2022

Background

Glioblastoma multiforme (GBM) is an aggressive malignant primary brain tumor. Wnt/β-catenin is known to be related to GBM stemness. Cancer stem cells induce immunosuppressive and treatment resistance in GBM. We hypothesized that Wnt/β-catenin-related genes with immunosuppression could be related to the prognosis in patients with GBM.

Methods

We obtained the clinicopathological data of 525 patients with GBM from the brain cancer gene database. The fraction of tumor-infiltrating immune cells was evaluated using in silico flow cytometry. Among gene sets of Wnt/β-catenin pathway, Dickkopf-3 (DKK3) gene related to the immunosuppressive response was found using machine learning. We performed gene set enrichment analysis (GSEA), network-based analysis, survival analysis and in vitro drug screening assays based on Dickkopf-3 (DKK3) expression.

Results

In analyses of 31 genes related to Wnt/β-catenin signaling, high DKK3 expression was negatively correlated with increased antitumoral immunity, especially CD8 + and CD4 + T cells, in patients with GBM. High DKK3 expression was correlated with poor survival and disease progression in patients with GBM. In pathway-based network analysis, DKK3 was directly linked to the THY1 gene, a tumor suppressor gene. Through in vitro drug screening, we identified navitoclax as an agent with potent activity against GBM cell lines with high DKK3 expression.

Conclusions

These results suggest that high DKK3 expression could be a therapeutic target in GBM. The results of the present study could contribute to the design of future experimental research and drug development programs for GBM.

Graphical abstract
Longitudinal effects of habitat quality, body condition, and parasites on colour patches of a multiornamented lizard
Authors: Megía-Palma Rodrigo , Merino Santiago , Barrientos Rafael
Published: May 2022

Ontogeny is expected to be a determinant factor affecting production of colour patches in lizards, while immune challenges or sudden weight loss may impair the maintenance of pigment-based coloration within a breeding season. We translocated males of the lizardPsammodromus algirusbetween two sampling plots that differed in distance to a road, vegetation structure, and predator abundance. We analysed variation in spectral reflectance of their colour patches the same and the following year. The change in the reflectance of the lizard colour patches within the first breeding season was explained by the interaction between plot and treatment, but not body condition. The maintenance of the breeding coloration was impaired only in those males translocated close to the road, probably reflecting that it is a poor-quality habitat forP. algirus. The following year, lizards that produced a more elaborate coloration were those that increased their body condition and controlled some parasitic infections, although suffered an increase of others. This study shows that colour patch production is plastic inP. algirus. Lizards increasing parasites or losing weight reduced pigmentation, although habitat quality can cushion these negative effects on pigmentation. However, not all parasites constrain the investment in coloration. In fact, some increased in those lizards that allocated more pigments to colour patches. In conclusion, longitudinal studies following experimental manipulation can contribute to understand pigment allocation rules in lizards.

Significance statement

Pigments involved in colour patches of animals are limiting resources that can be reallocated off the skin to other functions. However, longitudinal evidence of this phenomenon is scarce in reptiles. We designed a manipulative mark-recapture experiment to investigate effects of habitat and parasitic infections on colour patch maintenance (within-year variation) and production (between-year variation) in male free-ranging lizards that were reciprocally translocated between two patches of habitat that differed in quality. During the first year, lizards translocated to the habitat with more predators and worse vegetation impoverished their coloration, while lizards translocated to the more favourable habitat maintained it despite all translocated lizards loose body condition. The next year we detected different effects on the coloration of three different parasites investigated, suggesting that coloration can reflect the virulence of the infections.
On the choice of TLS versus OLS in climate signal detection regression
Authors: McKitrick Ross
Published: May 2022

Total least squares (TLS) or multivariate orthogonal regression is widely used as a remedy for attenuation bias in climate signal detection or “optimal fingerprinting” regression. But under some circumstances it overcorrects and imparts an upward bias, as well as generating extremely unstable and imprecise coefficient estimates. While there has been increasing attention paid recently to the validity of TLS-based confidence intervals, there has been no corresponding examination of coefficient bias problems. This note explains why they are pertinent and presents a Monte Carlo simulation to illustrate the hazards of using TLS in a signal detection application without testing whether the modeling context makes it a suitable choice. TLS is not automatically preferred over OLS even when explanatory variables are believed to contain random errors. Notably it can be sufficiently biased to cause false positives when explanatory signals are negatively correlated, and the bias gets worse as the signal-noise ratio on the explanatory variables rises. Additionally TLS should not be used on its own for climate signal detection inferences since if the no-signal null is true, TLS is generally inconsistent whereas OLS attenuation bias disappears.
Patients with multiple sclerosis: a burden and cost of illness study
Authors: Battaglia Mario Alberto , Bezzini Daiana , Cecchini Isabella , Cordioli Cinzia , Fiorentino Francesca , Manacorda Tommaso , Nica Mihaela , Ponzio Michela , Ritrovato Daniela , Vassallo Chiara , Patti Francesco
Published: May 2022

Background

Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease negatively impacting patients’ physical, psychological and social well-being with a significant economic burden.

Objectives

The study estimates MS burden and cost of illness in Italy from a societal perspective in 2019.

Methods

Information on the impact of the disease on daily activities, symptoms, employment, resource utilization and the role of caregivers was collected through questionnaires completed by 944 patients and caregivers. Results were stratified according to both disease severity and payer. Mean costs and overall costs were extrapolated from the sample to the Italian MS population considering published distribution of severity.

Results

The study showed a great impact of the disease on daily and work activities increasing with the disability. The overwhelming burden of fatigue emerged. Mean annual costs were estimated at €39,307/patient (€29,676, €43,464 and €53,454 in mild, moderate and severe cases, respectively). Direct healthcare costs were the major component (€21,069), followed by indirect costs (€15,004). The overall cost of the disease in Italy was €4.8 billion. The National Healthcare System (NHS) sustained most of the costs (80%), most notably direct healthcare costs, while patients paid almost all non-healthcare expenses.

Conclusions

This study confirmed that MS carries a substantial burden to patients and society, highlighting the need for awareness of this disease.
The role of re-resection in recurrent hepatocellular carcinoma
Authors: Bednarsch Jan , Czigany Zoltan , Heij Lara R. , Amygdalos Iakovos , Heise Daniel , Bruners Philip , Ulmer Tom F. , Neumann Ulf P. , Lang Sven A.
Published: May 2022

Purpose

While liver resection is a well-established treatment for primary HCC, surgical treatment for recurrent HCC (rHCC) remains the topic of an ongoing debate. Thus, we investigated perioperative and long-term outcome in patients undergoing re-resection for rHCC in comparative analysis to patients with primary HCC treated by resection.

Methods

A monocentric cohort of 212 patients undergoing curative-intent liver resection for HCC between 2010 and 2020 in a large German hepatobiliary center were eligible for analysis. Patients with primary HCC (n = 189) were compared to individuals with rHCC (n = 23) regarding perioperative results by statistical group comparisons and oncological outcome using Kaplan–Meier analysis.

Results

Comparative analysis showed no statistical difference between the resection and re-resection group in terms of age (p = 0.204), gender (p = 0.180), ASA category (p = 0.346) as well as main preoperative tumor characteristics, liver function parameters, operative variables, and postoperative complications (p = 0.851). The perioperative morbidity (Clavien-Dindo ≥ 3a) and mortality were 21.7% (5/23) and 8.7% (2/23) in rHCC, while 25.4% (48/189) and 5.8% (11/189) in primary HCC, respectively (p = 0.851). The median overall survival (OS) and recurrence-free survival (RFS) in the resection group were 40 months and 26 months, while median OS and RFS were 41 months and 29 months in the re-resection group, respectively (p = 0.933; p = 0.607; log rank).

Conclusion

Re-resection is technically feasible and safe in patients with rHCC. Further, comparative analysis displayed similar oncological outcome in patients with primary and rHCC treated by liver resection. Re-resection should therefore be considered in European patients diagnosed with rHCC.
Ethische Fragen im Gesundheitswesen als Gegenstand interprofessionellen Lernens: Überblick zur Situation in Deutschland und Projektbericht
Authors: Seidlein Anna-Henrikje , Salloch Sabine
Published: May 2022

Interprofessionelles Lernen von Auszubildenden der Pflegeberufe sowie Medizinstudierenden bietet vielfältige Chancen für die zukünftige Zusammenarbeit mit dem Ziel einer qualitativ hochwertigen Versorgung von Patient*innen. Expert*innengremien fordern daher eine frühzeitige Integration von interprofessionellen Lehr- und Lernformaten, um effektive und nachhaltige Verbesserungen in der Praxis erreichen zu können. In Deutschland wird interprofessionelle Lehre in der grundständigen Ausbildung der zwei Professionen in wachsendem Umfang in ausgewählten Fächern – obligat oder fakultativ – eingesetzt. Der Bereich der Ethik im Gesundheitswesen wird dabei bislang jedoch kaum berücksichtigt. Der Beitrag untersucht die Situation interprofessioneller Ethiklehre in Deutschland und beleuchtet deren Möglichkeiten und Grenzen vor dem Hintergrund eines Pilotprojektes.
Biomarker and compound-specific isotope records across the Toarcian CIE at the Dormettingen section in SW Germany
Authors: Ajuaba Stephen , Sachsenhofer Reinhard F. , Bechtel Achim , Galasso Francesca , Gross Doris , Misch David , Schneebeli-Hermann Elke
Published: May 2022

The Toarcian oceanic anoxic event (T-OAE) is associated with a prominent negative carbon isotope excursion (CIE; ~ 183 million years (Myr)). About 10-m-thick organic matter-rich sediments accumulated during the T-OAE in the Southwest German Basin (SWGB). Rock–Eval, maceral and biomarker analysis were used to determine variations of environmental conditions across the CIE interval. Carbon isotope records were determined for various n-alkanes, pristane and phytane to contribute to the reconstruction of the paleo-environment and to study the factors controlling molecular δ13C values. Geochemical redox indicators provide evidence for photic zone anoxia during the Toarcian CIE, which reached its maximum after deposition of the “Unterer Stein” marker horizon. The 2α-methylhopane index suggests enhanced activity of diazotrophic cyanobacteria, which is also supported by nitrogen isotope data. This distinguishes the SWGB from other basins with Toarcian black shale. Oxygen-depleted conditions, albeit with lower intensity continued after the CIE. All investigated compounds replicate the negative CIE, but the magnitudes vary considerably. The largest shift is observed for n-C27 (9‰) and reflects the combined effect of the global CIE and a major change in organic matter input (termination of terrigenous organic matter input). The shift for short-chain n-alkanes, pristane, and phytane, interpreted to reflect marine biomass, varies between 4.5 and 5.0‰. This is the highest value observed so far for any Toarcian section. δ13C values of pristane and phytane reach a minimum near the base of the CIE interval and increase upsection. Thus, the maximum negative isotope shift predates the strongest basin restriction by about 450 thousand years (kyr).
Compensatory biomechanics and spinal loading during dynamic maneuvers in patients with chronic low back pain
Authors: Nyayapati Priya , Booker Jacqueline , Wu Peter I-Kung , Theologis Alekos , Dziesinski Lucas , O’Neill Conor , Zheng Patricia , Lotz Jeffrey C. , Matthew Robert P. , Bailey Jeannie F.
Published: May 2022

Purpose

This study explores the biomechanics underlying the sit-to-stand (STS) functional maneuver in chronic LBP patients to understand how different spinal disorders and levels of pain severity relate to unique compensatory biomechanical behaviors. This work stands to further our understanding of the relationship between spinal loading and symptoms in LBP patients.

Methods

We collected in-clinic motion data from 44 non-specific LBP (NS-LBP) and 42 spinal deformity LBP (SD-LBP) patients during routine clinical visits. An RGB-depth camera tracked 3D joint positions from the frontal view during unassisted, repeated STS maneuvers. Patient-reported outcomes (PROs) for back pain (VAS) and low back disability (ODI) were collected during the same clinical visit.

Results

Between patient groups, SD-LBP patients had 14.3% greater dynamic sagittal vertical alignment (dSVA) and 10.1% greater peak spine torque compared to NS-LBP patients (p < 0.001). SD-LBP patients also had 11.8% greater hip torque (p < 0.001) and 86.7% greater knee torque (p = 0.04) compared to NS-LBP patients. There were no significant differences between patient groups in regard to anterior or vertical torso velocities, but anterior and vertical torso velocities correlated with both VAS (r = − 0.38, p < 0.001) and ODI (r = − 0.29, p = 0.01). PROs did not correlate with other variables.

Conclusion

Patients with LBP differ in movement biomechanics during an STS transfer as severity of symptoms may relate to different compensatory strategies that affect spinal loading. Further research aims to establish relationships between movement and PROs and to inform targeted rehabilitation approaches.
Zur Bedeutung der begleitenden Arbeit mit den Eltern in einer Kindertherapie. Eine Einzelfallstudie
Authors: Diem-Wille Gertraud
Published: May 2022

Die Bedeutung der begleitenden Arbeit mit Eltern bei einer Kindertherapie wird beschrieben. Die Eltern sind das zweite Patientensystem, mit dem ein Therapeut/eine Therapeutin eine stabile Kooperationsbeziehung etablieren muss, um die weitere Therapie des Kindes zu ermöglichen. Wir gehen von der Annahme aus, dass die innere Welt des Kindes mit Repräsentanzen erfüllt ist, die durch Introjektionen der äußeren und inneren Erlebniswelten gebildet werden. Das bedeutet, dass auch die Symptome und Probleme des Kindes in enger Verflochtenheit mit der inneren Welt der Mutter und des Vaters gedacht werden müssen. Es wird beschrieben, wie der Vater und die Mutter Zugang zu eigenen Möglichkeiten in sich fanden, ihr Kind in adäquate Weise zu fördern. Das wurde möglich, nachdem der Vater sich mit seinen ungelösten Konflikten („unresolved conflicts“ Fraiberg 2011) mit seinem Vater auseinandersetzen konnte, die er in seiner Beziehung zu Patrik wiederholte. Die Hypothese der emotionalen Verstrickung zwischen dem Vater und Patrik wird untersucht und der Prozess zu deren Auflösung wird beschrieben.
Theory as a source of software and system requirements
Authors: Chitchyan Ruzanna , Bird Caroline
Published: May 2022

Today, when undertaking requirements elicitation, engineers attend to the needs and wants of the user groups considered relevant for the software system. However, answers to some relevant questions (e.g., how to improve adoption of the intended system) cannot always be addressed through direct need and want elicitation. Using an example of energy demand-response systems, this paper demonstrates that use of grounded theory analysis can help address such questions. The theories emerging from such analysis produce a set of additional requirements which cannot be directly elicited from individuals/groups, and would otherwise be missed. Thus, we demonstrate that the theories generated through grounded theory analysis can serve as additional valuable sources of requirements for software and its wider system. This paper extends our previous work by demonstrating how several theories can be constructed and utilised for a single system analysis.