bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary hypertension in patients with multiple myeloma: A comprehensive review
Authors: Maddipati Veeranna , Sankhyan Pratyaksha , Goswami Durga P. , Mahajan Akhilesh
Published: March 2023

Multiple myeloma (MM) is a common hematological malignancy resulting from clonal proliferation of plasma cells and is defined by criteria set forth by the international myeloma working group. Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20 mmHg measured during right heart catheterization. Echocardiography‐diagnosed PH is relatively common in patients with MM and has been associated with increased mortality, morbidity, and poor stem cell transplant outcomes. PH in patients with MM (PH‐MM) is usually multifactorial in origin. MM disease‐specific factors, host comorbidities, and treatment‐related adverse effects are the key factors for the development of PH‐MM. Pragmatically, patients with PH‐MM can be grouped into either (i) PH in patients with a new diagnosis of MM or (ii) PH that develops or worsens along the way of MM treatment. In the latter group, drug‐induced PH, venous thromboembolism, pulmonary veno occlusive disease, and cardiotoxicity should be considered as possible causes. PH‐MM should be evaluated and managed in a multidisciplinary setting. Select individuals with PH‐MM could be considered for pulmonary vasodilators at PH‐specialized centers.
Why does the upward surface turbulent heat flux resulting from sea ice loss over the Barents and Kara Seas last only for a few days?
Authors: Jiang Zhina , Feldstein Steven B. , Lee Sukyoung
Published: March 2023

This study explores the reason why strong upward anomalous surface turbulent heat fluxes (STHFs) over the Barents and Kara Seas (BKS) occur for a period of only a few days after wind‐driven sea ice loss, even though anomalously low sea ice persists for more than one month. Composite analysis with ERA5 reanalysis data reveals that the sea ice decline coincides with the poleward advection of warm, moist air on the eastern flank of a synoptic‐scale surface low. This results in the anomalous surface air temperature (SAT) exceeding the anomalous skin temperature (SKT) and a downward anomalous STHF. As the surface low propagates eastward, the wind direction changes, resulting in the advection of cold, dry air, the anomalous SKT exceeding the anomalous SAT and a brief period with a strong upward anomalous STHF. This period of strong upward anomalous STHF is cut short, as the surface low propagates southeastward out of the BKS. The eastward propagation of the surface low is crucial, as it allows for northward driving of sea ice to be followed by cold advection and a strong upward anomalous STHF. These results indicate that when wind‐driven sea ice motion exposes the ocean to the atmosphere, except for a brief episode, the reduction of sea ice does not coincide with an increase in a strong upward anomalous STHF.
Predictability of passive scalar dispersion in atmospheric surface layers with urban‐like roughness: A large‐eddy simulations study
Authors: Lu Yanle , Monache Luca Delle , Weil Jeffrey , Ngan Keith , Li Qi
Published: March 2023

The predictability of passive scalar dispersion is of both theoretical interest and practical importance, for example for high‐resolution numerical weather prediction and air quality modeling. However, the implications for the numerical modeling of urban areas remain relatively unexplored. Using obstacle‐resolving large‐eddy simulations (LES), we conducted twin experiments, with and without a velocity perturbation, to investigate how the presence of urban roughness affects error growth in streamwise velocity (u) and passive scalar (θ) fields, as well as the differences between error evolutions in u and θ fields. The predictability limit is characterized using the signal‐to‐noise ratio (SNR) as a continuous metric to indicate when error reaches saturation. The presence of urban roughness decreases of the passive scalar by around 20% compared to cases without them. The error statistics of θ indicate that urban roughness‐induced flow structures and different scalar source locations affect the scalar dispersion and relative fluctuations, which subsequently dictate the evolution of the SNR. Analysis of the passive scalar error energy (ϵθ2) budget indicates that the contributions from advective transport by the velocity and velocity error dominate. The error energy spectra of both u and θ exhibit a −5/3 slope in flat‐wall cases, but not in the presence of urban roughness, thereby highlighting the deviation from the assumption of locally isotropic turbulence. This study reveals that urban roughness can decrease the predictability of the passive scalar and destroy the similarity between the error statistics of the velocity and the passive scalar.
FMECA of CNC machine tool design stage based on CBWM and DEA
Authors: Yu Lijuan , Zhang Tianyu , Tian Hailong , Yang Zhaojun , Liu Ang , Zhang Fuyao
Published: March 2023

In view of the problems that FMECA in the design stage of CNC machine tools does not take into account the complexity of the designed functional structure, does not compare the weight of risk factors, and is not easy to distinguish the harm degree of failure mode, CBWM, and DEA are applied to the study of FMECA in the design stage of CNC machine tools. Based on the complexity of functional structure in machine tool design, score the factors of each potential failure mode, form a decision unit, re‐formulate the scoring table, and subdivide the severity into machine tool hazard (M), personal hazard (P), environmental hazard (E), and buyer satisfaction (B). The factors influencing risk factors were defined as the probability of failure mode (O), machine tool hazard (M), personal hazard (P), environmental hazard (E), and buyer satisfaction (B). On the basis of the scoring of each factor, the functional structure complexity (C) is taken as the input index, and the risk factor is taken as the output index. The CBWM method is applied to determine the weight of each risk factor, and DEA method is used to calculate the efficiency of each decision making unit. Finally, a new method for calculating risk priority number RPN is proposed by integrating the score value of factors, weight value of factors, and efficiency value of fault mode, and the hazard degree of fault mode is ranked according to the risk priority coefficient. Taking a machining center spindle system as an example, the proposed method is applied to analyze the fault mode and its influence, and the effectiveness of the proposed method is verified.
CRISPR/Cas9 Screen in Gastric Cancer Patient‐Derived Organoids Reveals KDM1A‐NDRG1 Axis as a Targetable Vulnerability
Authors: Mircetic Jovan , Camgöz Aylin , Abohawya Moustafa , Ding Li , Dietzel Julia , Tobar Sebastián García , Paszkowski‐Rogacz Maciej , Seidlitz Therese , Schmäche Tim , Mehnert Marie‐Christin , Sidorova Olga , Weitz Jürgen , Buchholz Frank , Stange Daniel E.
Published: March 2023

Viability CRISPR screens have proven indispensable in parsing genome function. However, their application in new, more physiologically relevant culturing systems like patient‐derived organoids (PDOs) has been much slower. To probe epigenetic contribution to gastric cancer (GC), the third leading cause of cancer‐related deaths worldwide, the first negative selection CRISPR screen in GC PDOs that faithfully preserve primary tumor characteristics is performed. Extensive quality control measurements showing feasibility of CRISPR screens in primary organoid culture are provided. The screen reveals the histone lysine demethylase‐1A (KDM1A) to constitute a GC vulnerability. Both genetic and pharmacological inhibition of KDM1A cause organoid growth retardation. Further, it is shown that most of KDM1A cancer‐supporting functions center on repression of N‐myc downstream regulates gene‐1 (NDRG1). De‐repression of NDRG1 by KDM1A inhibitors (KDM1Ai) causes inhibition of Wnt signaling and a strong G1 cell cycle arrest. Finally, by profiling 20 GC PDOs, it is shown that NDRG1 upregulation predicts KDM1Ai response with 100% sensitivity and 82% specificity in the tested cohort. Thus, this work pioneers the use of negative selection CRISPR screens in patient‐derived organoids, identifies a marker of KDM1Ai response, and accordingly a cohort of patients who may benefit from such therapy.
Long‐term treatment outcomes and risk factors for recurrence in feline corneal sequestrum: 72 cases (2009–2017)
Authors: Gómez Alberto Palella , Mazzucchelli Samuela , Smith Kinley , de Lacerda Rodrigo Pinheiro
Published: March 2023

Background

This study aimed to evaluate long‐term treatment outcomes in feline corneal sequestrum (FCS), compare the recurrence rates between different surgical techniques, identify possible recurrence risk factors and monitor the development of FCS in the contralateral eye.

Methods

The medical records of 72 cats (79 eyes) with FCS treated between 2009 and 2017 were retrospectively analysed.

Results

The most commonly affected breeds were Persian, domestic shorthaired and Burmesecats. The mean age was 6.9 years. Sixty‐five cats (90%) were affected unilaterally. Sixty‐six eyes (83%) underwent surgery: keratectomy in 34 eyes (52%) and keratectomy followed by a graft procedure in 32 eyes (48%). Recurrence occurred in 13 out of 66 eyes (19%) at a median of 245 days after surgery. Skull conformation, location of the FCS, type of surgical procedure and concurrent ocular surgery did not significantly affect the recurrence rate. Eighteen cats (27%) developed FCS in the contralateral eye at a median of 635 days after surgery.

Limitations

Limitations are related to the retrospective nature of the study, the use of telephone follow‐up for assessment of recurrence in some cats and the small number of cases.

Conclusions

Surgical excision had a successful outcome in most cases. The type of surgical procedure and skull conformation did not affect the recurrence rate. One‐quarter of the cats developed FCS in the contralateral eye.
OLFML3, as a potential predictor of prognosis and therapeutic target for glioma, is closely related to immune cell infiltration
Authors: Qu Shanqiang , Huang Chengying , Zhu Taichen , Wang Kaicheng , Zhang Huayang , Wang Luyao , Xu Rongyang , Zheng Haojie , Yuan Xi , Liu Guangjie , Zhu Rongzhang , Qu Jiayi , Yi Guozhong , Qi Songtao
Published: March 2023

The low response rate to immunosuppressant is mainly due to the lack of adequate knowledge about the tumor microenvironment (TME) and screening biomarkers for gliomas. We aimed to identify the promising immune biomarkers and new immune classification of glioma. In this study, multiple‐immune algorithms were used to calculate immune‐infiltration scores. Unsupervised and supervised machine learning methods were used to perform the classification. We observed that OLFML3 overexpression was indicated in gliomas and linked to poor prognosis. OLFML3 knockdown inhibited proliferation, invasion and increased the sensitivity of glioma cells to temozolomide. OLFML3 expression could also reflect the aberrant immune status. Based on the immune‐related signature, patients were divided into three immune subtypes via consensus clustering. Patients with C2 subtype presented poorer prognosis and shorter progression free survival than patients with other two subtypes. The TME patterns among subtypes were different. C2 and C3 subtypes are the immune‐inflamed and immune‐desert tumors, respectively. Additionally, compared with C3 subtype, patients with C1/C2 subtypes were more likely to respond to immunotherapy. The pRRophetic algorithm indicated patients with C1/C2 subtypes were more resistant to temozolomide, but sensitive to paclitaxel and cisplatin. To conclude, OLFML3 overexpression affects glioma cell proliferation, invasion, and TMZ sensitivity and has been proved to be an independent prognostic‐ and immune‐related biomarker. Additionally, the novel immune subtype's classification could provide the prognostic and predictive predictors for glioma patients and may guide physicians in selecting potential responders.
Influence of trans‐ferulic acid on the quality of ram semen upon cold preservation
Authors: Salimi Ali , Eslami Mohsen , Farrokhi‐Ardabili Farhad
Published: March 2023

Background

Due to lower antioxidant capacity and higher amounts of polyunsaturated fatty acids, ram spermatozoa are very susceptible during cooling process.

Objectives

The objective was to examine the effect of the trans‐ferulic acid (t‐FA) on the ram semen during liquid preservation.

Methods

Semen samples were collected from the Qezel rams, pooled, and extended with the Tris‐based diluent. Pooled samples enriched with different amounts of the t‐FA (0, 2.5, 5, 10, and 25 mM) and preserved at 4°C for 72 h. Spermatozoa's kinematics, membrane functionality, and viability were assessed by CASA system, hypoosmotic swelling test, and eosin‐nigrosin staining, respectively. Moreover, biochemical parameters were measured at 0, 24, 48, and 72 h.

Results

Results showed that 5 and 10 mM t‐FA improved forward progressive motility (FPM) and curvilinear velocity compared to the other groups at 72 h (p < 0.05). Samples treated with 25 mM t‐FA showed the lowest total motility, FPM, and viability at 24, 48, and 72 h of storage (p < 0.05). Higher total antioxidant activity levels were observed in the 10 mM t‐FA‐treated group compared to the negative control at 72 h (p < 0.05). Treatment with 25 mM t‐FA increased malondialdehyde amounts and decreased superoxide dismutase activity compared to other groups at the final time assessment (p < 0.05). Nitrate‐nitrite and lipid hydroperoxides values were not affected by treatment.

Conclusions

The current study indicates the positive and negative influences of different concentrations of t‐FA on the ram semen upon cold storage.
Molecular study of feline dermatophytosis and Toll‐like receptor 2 and 4 gene expression in their lesions
Authors: Kasmaei Anahita , Salimi Alireza , Helan Javad Ashrafi , Asl Seyed Ali Shabestari , Katiraee Farzad
Published: March 2023

Background

Pattern recognition receptors (PRRs) as the recognition of pathogenic fungal structures induce the secretion of cytokines by immune systems. Toll‐like receptors (TLRs) 2 and 4 are the main PRRs that recognize fungal components.

Aim

The present study aimed to assess the presence of dermatophyte species in symptomatic cats in a region of Iran and to investigate the expression of TLR‐2 and 4 in cat lesions with dermatophytosis.

Methods

A total of 105 cats suspected of dermatophytosis with skin lesions were examined. Samples were analysed by direct microscopy using potassium hydroxide (20%) and culture on Mycobiotic agar. Dermatophytes strains were confirmed by the polymerase chain reaction (PCR) amplification and then sequencing of the Internal Transcribed Spacer rDNA region. Also, for pathology and real‐time PCR studies, skin biopsies were taken by sterile single‐use biopsy punch from active ringworm lesions.

Results

Dermatophytes were found in 41 felines. Based on the sequencing of all strains, Microsporum canis (80.48%, p < 0.05), Microsporum gypseum (17.07%) and Trichophyton mentagrophytes (2.43%) were the dermatophytes isolated from cultures. Cats under 1 year (78.04%) revealed a statistically significantly higher prevalence of infection (p < 0.05). Gene expression by real‐time PCR revealed the increased TLR‐2 and 4 mRNA levels in skin biopsies of cats with dermatophytosis.

Conclusions

M. canis is the most prevalent dermatophyte species isolated from feline dermatophytosis lesions. Increased expression of TLR‐2 and TLR‐4 mRNAs in cat skin biopsies suggests that these receptors are involved in the immune response by recognizing dermatophytosis.
The adaptive evolution of cold‐activated TRPM8 in wildlife vertebrates
Authors: Lu Xiancui , Wu Jiayi , Shi Longyan , Zhou Yi , Su Yuqing , Wang Yunfei , Yang Shilong
Published: March 2023

Temperature influences all biological processes. In wild animals, the evolution of molecular thermosensors is crucial in ambient temperature adaption and habitat selection with species specificity. The transient receptor potential melastatin 8 (TRPM8, the most established cold receptor expressed in thermosensory nerve endings) is a cation permeable ion channel, which plays a critical role in thermal sensation and adaptation. The transition of TRPM8 from the closed to open state can be attributed to strong cold dependence. Comparative studies of TRPM8 orthologs have provided valuable insights into how thermosensation has evolved in wild vertebrates over time. Specifically, the appearance of the trpm8 gene in lungfishes provided a protogene structure without function. During the water‐to‐land transition, the trpm8 protogene accumulated mutations mainly in the MHR1‐3 domain that confer cold sensitivity to TRPM8 proteins of terrestrial vertebrates. Furthermore, trpm8 in terrestrial vertebrates acquired mutations at the pore domain that resulted in a change in cold activation efficacy at the molecular level. In marine mammals, TRPM8 orthologs are cold‐sensitive, based on the expectation that the MHR1‐3 domain and pore domain are consistent with those of terrestrial mammals. This review discusses the relationship between the biophysical properties of TRPM8 cold activation and ambient temperature adaptation in vertebrates.
Teacher Education of the Future: Trends and Possible Scenarios in the Nordic Context
Authors: Elstad Eyvind
Published: March 2023

This chapter uses current trends to outline possible scenarios in teacher education programmes in the Nordic countries. The starting point is that, aside from Finnish teacher education, teacher education programmes in Nordic countries have almost never been considered genuinely excellent. Therefore, teacher education has become a policy problem. As the developmental features of today’s teacher education in the Nordic region are deeply complex and partly characterized by inherent tensions between contradictory considerations, making predictions is a daunting task. There is considerable diversity among teacher education programmes in Nordic countries, and future developments might take several paths. Therefore, one cannot talk about a single current or future model for Nordic teacher education.

Several premises for discussing the future of teacher education are considered in this chapter, including the idea of a knowledge economy and an emphasis on equality values. Policy-making is often set within general critical discourse about teaching and teacher education. The question is how teacher education institutions will respond to the various challenges that exist. In this chapter, trends and possible scenarios for teacher education in the Nordic context are discussed on the basis of a complex theoretical framework.
The Evolution of the Extended Comprehensive School Model and the Modern Profession-Oriented Teacher Education After World War II
Authors: Elstad Eyvind
Published: March 2023

Despite the fact that the Nordic countries had very different experiences during World War II, cooperation intensified in the 1950s. The Nordic school model, with its emphasis on the child in focus, inclusion, equal opportunities for all, and an extended comprehensive and undifferentiated school system, emerged. The sorting of pupils into different tracks took place at age 15 or 16. The 1960s saw a significant expansion of the education systems, with the Swedish school model emerging as a paradigm for the other Nordic countries. With Finland’s success in the first comparative education studies, Finnish teacher education became the standard for teacher education in Iceland and Norway. Sweden follows more complex models for teacher education, while Danish teacher education is an outlier from a Nordic comparison perspective. While Finnish teacher education has shown stability, frequent changes in models of teacher education in the other Nordic countries are typical. In public discourse, crises in teacher education are a recurring theme. These crises concern criticism of the quality of applicants, what student teachers learn, and insufficient graduate production. The problems facing teacher education are varied, but where they occur, they are dire; there are no simple solutions to the challenges that currently exist.
Erzählstrategien
Authors: Stübe Raphael
Published: March 2023

So unterschiedlich die Diskurse über eine neue Romantik auch ausfallen, so lassen sich auf einer literarischen Ebene wiederkehrende Momente beobachten, mit denen Romantik um 1900 aufgegriffen und aktualisiert wird. Heinrich Mann, Hanns Heinz Ewers und Hermann Hesse repräsentieren drei unterschiedliche Spielarten einer Neoromantik, die mit jeweils verschiedenen Argumenten und in heterogenen Phasen betrieben wird. Dennoch zeigen die frühen Prosatexte dieser Autoren strukturelle Gemeinsamkeiten, sobald man auf ihre Remodellierung des Romantischen achtet. Die Perspektivenvielfalt zum Beispiel, mit der romantische Texte noch einen absoluten Fluchtpunkt umkreisen, weicht hier einer Tendenz zur Monoperspektivität, in der exotische Figuren einzelne Subbereiche des ‚Lebens‘ entschlüsseln. Mikroskopische Einzelgesetze dieser Art können mit den Blicken der Außenseiter durchdrungen werden, scheitern jedoch daran, in die Gesellschaft zurückübersetzt zu werden. Exkurse zur Idiosynkrasie der Routines, zum Lebensmonismus und zu den Autorinnen binden die Neoromantik an die aktuellen Forschungsdiskurse zurück.
Schedulability Analysis of Mixed-Criticality Data Under Fixed-Priority Scheduling
Authors: Jin Xi , Xia Changqing , Xu Chi , Li Dong
Published: March 2023

WirelessHART, as a robust and reliable wireless protocol, has been widely-used in industrial systems. Its real-time performance has been extensively studied, but limited to the single-criticality case. Many advanced applications have mixed-criticality communications, where different data flows come with different criticality levels. Hence, in this chapter, we study the real-time mixed-criticality communication based on WirelessHART networks, and present an end-to-end delay analysis method under fixed priority scheduling.
Identification of a key locus, qNL3.1, associated with seed germination under salt stress via a genome-wide association study in rice
Authors: Zhan Chengfang , Zhu Peiwen , Chen Yongji , Chen Xinyi , Liu Kexin , Chen Shanshan , Hu Jiaxiao , He Ying , Xie Ting , Luo Shasha , Yang Zeyuan , Chen Sunlu , Tang Haijuan , Zhang Hongsheng , Cheng Jinping
Published: March 2023

Key message

Two causal OsTTL and OsSAPK1genes of the key locus qNL3.1 significantly associated with seed germination under salt stress were identified via a genome-wide association study, which could improve rice seed germination under salt stress.

Rice is a salt-sensitive crop, and its seed germination determines subsequent seedling establishment and yields. In this study, 168 accessions were investigated for the genetic control of seed germination under salt stress based on the germination rate (GR), germination index (GI), time at which 50% germination was achieved (T50) and mean level (ML). Extensive natural variation in seed germination was observed among accessions under salt stress. Correlation analysis showed significantly positive correlations among GR, GI and ML and a negative correlation with T50 during seed germination under salt stress. Forty-nine loci significantly associated with seed germination under salt stress were identified, and seven of these were identified in both years. By comparison, 16 loci were colocated with the previous QTLs, and the remaining 33 loci might be novel. qNL3.1, colocated with qLTG-3, was simultaneously identified with the four indices in two years and might be a key locus for seed germination under salt stress. Analysis of candidate genes showed that two genes, the similar to transthyretin-like protein OsTTL and the serine/threonine protein kinase OsSAPK1, were the causal genes of qNL3.1. Germination tests indicated that both Osttl and Ossapk1 mutants significantly reduced seed germination under salt stress compared to the wild type. Haplotype analysis showed that Hap.1 of OsTTL and Hap.1 of OsSAPK1 genes were excellent alleles, and their combination resulted in high seed germination under salt stress. Eight accessions with elite performance of seed germination under salt stress were identified, which could improve rice seed germination under salt stress.
Neighbourhood cohesion, loneliness and perceived social isolation prior and during the COVID-19 pandemic. Longitudinal evidence from the German Ageing Survey
Authors: Hajek André , Kretzler Benedikt , Walther Carolin , Aarabi Ghazal , Zwar Larissa , König Hans-Helmut
Published: March 2023

Purpose

To investigate the longitudinal association between neighbourhood cohesion and loneliness as well as perceived social isolation prior and during the COVID-19 pandemic (stratified by sex).

Methods

Longitudinal data were taken from a nationally representative sample (German Ageing Survey) of inhabitants aged 40 years and over in Germany prior (wave 6: year 2017) and during the COVID-19 pandemic (wave 8: November 2020 until February 2021; n = 6688 observations, mean age was 67.4 years). The De Jong Gierveld tool was used to measure loneliness and the Bude and Lantermann tool was used to measure perceived social isolation. Neighbourhood cohesion was assessed based on different items.

Results

FE regressions showed that decreases in closeness of contact with neighbours were associated with increases in loneliness and perceived social isolation levels among men, but not women. In contrast, decreases in different indicators of involvement in neighbourhood activities were associated with increases in loneliness and perceived social isolation levels among women, but not men.

Conclusion

Changes in neighbourhood factors are differently associated with loneliness and perceived social isolation among middle-aged and older women and men. Gender-specific efforts to avoid loneliness and social isolation are, therefore, needed.
Adjustment of the geometries of the cutting front and the kerf by means of beam shaping to maximize the speed of laser cutting
Authors: Lind Jannik , Hagenlocher Christian , Weckenmann Niklas , Blazquez-Sanchez David , Weber Rudolf , Graf Thomas
Published: March 2023

The shape of the laser beam used for fusion cutting significantly influences the geometry of both the cutting front and the cutting kerf. The angle of the cutting front in turn impacts the local absorptivity, while the width of the kerf defines the amount of material, which has to be molten. The kerf’s geometry therefore determines the maximum possible cutting speed at which a successful cut is feasible with a given available laser power. The absorptivity, the width of the kerf, and the maximum possible cutting speed can be estimated from a simple model considering the conservation of energy and rough geometrical approximations. In order to verify the prediction of the model, the geometry of the cutting front and kerf resulting from different processing conditions was observed by means of online high-speed X-ray diagnostics. The geometry of the interaction zone was recorded with a framerate of 1000 Hz during fusion cutting of 10-mm-thick samples of stainless steel. Comparing the results obtained with different shapes of the laser beam, it was found that the absorptivity is increased when the beam’s longitudinal cross-section (parallel to the feed) is enlarged. Reducing the width of the beam in the transversal direction normal to the feed reduces the cross-sectional area of the cutting kerf. The findings show a good agreement with the geometric model which enabled the prediction of the absorptivity and the cross-sectional area of the cutting kerf and hence allows to reliably estimate the maximum cutting speed for different shapes of the laser beam, laser power, and sheet thicknesses.
Graphical characterizations of robust stability in biological interaction networks
Authors: Al-Radhawi M. Ali
Published: March 2023

Previous studies have inferred robust stability of reaction networks by utilizing linear programs or iterative algorithms. Such algorithms become tedious or computationally infeasible for large networks. In addition, they operate like black boxes without offering intuition for the structures that are necessary to maintain stability. In this work, we provide several graphical criteria for constructing robust stability certificates, checking robust non-degeneracy, verifying persistence, and establishing global stability. By characterizing a set of stability-preserving graph modifications that includes the enzymatic modification motif, we show that the stability of arbitrarily large nonlinear networks can be examined by simple visual inspection. We show applications of this technique to ubiquitous motifs in systems biology such as post-translational modification (PTM) cycles, the ribosome flow model (RFM),T-cell kinetic proofreading, and others. The results of this paper are dedicated in honor of Eduardo D. Sontag’s seventieth birthday and his pioneering work in nonlinear dynamical systems and mathematical systems biology.
Integrated transcriptomics and metabolomics analysis reveals the biomolecular mechanisms associated to the antitumoral potential of a novel silver-based core@shell nanosystem
Authors: Aragoneses-Cazorla Guillermo , Vallet-Regí María , Gómez-Gómez Ma. Milagros , González Blanca , Luque-Garcia Jose L.
Published: March 2023

A combination of omics techniques (transcriptomics and metabolomics) has been used to elucidate the mechanisms responsible for the antitumor action of a nanosystem based on a Ag core coated with mesoporous silica on which transferrin has been anchored as a targeting ligand against tumor cells (Ag@MSNs-Tf). Transcriptomics analysis has been carried out by gene microarrays and RT-qPCR, while high-resolution mass spectrometry has been used for metabolomics. This multi-omics strategy has enabled the discovery of the effect of this nanosystem on different key molecular pathways including the glycolysis, the pentose phosphate pathway, the oxidative phosphorylation and the synthesis of fatty acids, among others.

Graphical Abstract
Neue epilepsiechirurgische Techniken und intraoperatives Monitoring bei nichtläsioneller MRT-negativer Epilepsie
Authors: Rössler Karl , Dorfer Christian
Published: March 2023

Durch die Einführung moderner Techniken für die neurochirurgische Intervention bei nichtläsionellen (NL) MRT-negativen medikamentös therapierefraktären Epilepsien (temporal, aber v. a. auch extratemporal) zeigte sich im letzten Jahrzehnt sowohl bei Kindern und Adoleszenten als auch bei Erwachsenen eine deutliche Zunahme diese Eingriffe um etwa 10–15 % [1]. Für die prächirurgische Evaluation von NL-Epilepsien ist das invasive Monitoring zur Diagnostik einer fokalen Epilepsie bzw. zur Definition der potenziellen epileptogenen Zone für eine mögliche Resektion oder Ablation – insbesondere extratemporal – wünschenswert. Die Technik der invasiven Abklärung von NL-Epilepsien hat im letzten Jahrzehnt eine grundsätzliche Strategieänderung erfahren, weg von über eine Kraniotomie eingebrachten subduralen Elektroden, hin zum weniger invasiven Stereo-EEG (sEEG) mit Tiefenelektroden. Das minimal-invasive und weniger komplikationsbehaftete sEEG kann auch tief gelegene Anfallsgeneratoren und unter Einbeziehung von künstlicher Intelligenz (AI) auch sterische Ausdehnung der potenziellen epileptogenen Zone darstellen, was für eine mögliche Resektion bei nichtläsionellen Epilepsien Voraussetzung ist. In sprachrelevanten Kortexarealen bleiben allerdings das Monitoring und Mapping mit Subduralelektroden alternativlos. Gleichzeitig ermöglichen neue Techniken in der Neurochirurgie wie Neuronavigation, Neuromonitoring (IONM) und intraoperative MR-Bildgebung, Robotik und Laserablation (LITT) die Schonung von eloquenten Hirnarealen in der Nachbarschaft der epileptogenen Zone. Zusätzlich können neuerdings traditionelle Techniken (Elektrokortikographie (ECoG) und Neuromonitoring (IONM)) mit der Bildgebung direkt durch Dateneinspiegelung ins Operationsmikroskop in den operativen Situs zur Resektion miteinbezogen werden. Diese Entwicklungen haben dazu geführt, dass für immer mehr NL-fokale Epilepsien die Resektion möglich ist und dass sich das postoperative Epilepsie-Outcome von NL-Epilepsien deutlich verbessert hat.
Mink on the brink: comparing survey methods for detecting a critically endangered carnivore, the European mink Mustela lutreola
Authors: Croose Elizabeth , Hanniffy Ruth , Harrington Andrew , Põdra Madis , Gómez Asun , Bolton Polly L. , Lavin Jenna V. , Browett Samuel S. , Pinedo Javier , Lacanal David , Galdos Iñaki , Ugarte Jon , Torre Aitor , Wright Patrick , MacPherson Jenny , McDevitt Allan D. , Carter Stephen P. , Harrington Lauren A.
Published: March 2023

Monitoring rare and elusive species is critical in guiding appropriate conservation management measures. Mammalian carnivores are challenging to monitor directly, due to their generally nocturnal and solitary lifestyle, and relatively large home ranges. The European minkMustela lutreolais a critically endangered, small, semi-aquatic carnivore and is one of the most threatened mammal species in Europe. In northern Spain, the European mink population is monitored regionally using different methods and approaches, making assessment of national population status difficult. There is an urgent need to 1) assess the efficacy of survey methods and 2) identify a standard monitoring methodology that can be deployed rapidly and inexpensively over large areas of the mink’s range. We deployed four methods—camera trapping, hair tubes, live trapping, and environmental DNA (eDNA) from water samples—to compare the probability of detecting European mink when present at 25 sampling sites within five 10 × 10 km2, and the economic cost and time required for each method. All four methods successfully detected European mink but the probability of detection varied by method. Camera trapping and hair tubes had the highest probability of detection; however, eDNA and live trapping detected mink in one 10 × 10 km2where the latter two methods did not. For future European mink monitoring programs, we recommend a combination of at least two methods and suggest that camera traps or hair tubes are combined with live trapping or eDNA (depending on the scale and aims of the study), to gather critical information on distribution, occupancy and conservation status.
Anticancer effect of zanubrutinib in HER2-positive breast cancer cell lines
Authors: Dostálová Hana , Jorda Radek , Řezníčková Eva , Kryštof Vladimír
Published: March 2023

Small molecule Bruton’s tyrosine kinase (BTK) inhibitors have been developed for the treatment of various haemato-oncological diseases, and ibrutinib was approved as the first BTK inhibitor for anticancer therapy in 2013. Previous reports proved the receptor kinase human epidermal growth factor receptor 2 (HER2) to be a valid off-target kinase of ibrutinib and potentially other irreversible BTK inhibitors, as it possesses a druggable cysteine residue in the active site of the enzyme. These findings suggest ibrutinib as a candidate drug for repositioning in HER2-positive breast cancer (BCa). This subtype of breast cancer belongs to one of the most common classes of breast tumours, and its prognosis is characterized by a high rate of recurrence and tumour invasiveness. Based on their similar kinase selectivity profiles, we investigated the anticancer effect of zanubrutinib, evobrutinib, tirabrutinib and acalabrutinib in different BCa cell lines and sought to determine whether it is linked with targeting the epidermal growth factor receptor family (ERBB) pathway. We found that zanubrutinib is a potential inhibitor of the HER2 signalling pathway, displaying an antiproliferative effect in HER2-positive BCa cell lines. Zanubrutinib effectively inhibits the phosphorylation of proteins in the ERBB signalling cascade, including the downstream kinases Akt and ERK, which mediate key signals ensuring the survival and proliferation of cancer cells. We thus propose zanubrutinib as another suitable candidate for repurposing in HER2-amplified solid tumours.
Spatial and temporal patterns of stream nutrient limitation in an Arctic catchment
Authors: Hauptmann Demian , Myrstener Maria
Published: March 2023

Arctic stream biofilm responses to ongoing climate-related changes in physical and chemical conditions have major implications for stream food webs and biogeochemical cycles. Yet, such effects have rarely been studied outside summer months or at sub-catchment scales in the Arctic. We used deployments of nutrient diffusing substrates (NDS) to assess the spatial (20 deployments) and seasonal patterns (10 deployments) and physical and chemical drivers of nutrient limitation within an Arctic stream catchment. Results show that nutrient limitation of autotrophic processes was common during summer, but that light inhibited biomass accrual under the ice in winter. Alongside single N, P and C responses, co-limitation dominated the overall pattern of limitation over time and across the catchment. However, the primary limiting nutrient to autotrophs changed from N to P in parts of the catchment with higher N concentrations. As Arctic studies are often conducted at individual sites during summer, these may miss shifts in the drivers of stream productivity that arise from variable nutrient, temperature, and light regimes. Our results caution against focusing on one single most important limiting nutrient, as we found that this can shift seasonally and over small spatial scales in this Arctic catchment.
The green investment principles: from a nodal governance perspective
Authors: Cheng Wenting
Published: March 2023

China’s Belt and Road Initiative is now the world’s largest infrastructure initiative, with long-term climate change effects, and the Green Investment Principles (GIPs) for Belt and Road have been promoted as a key instrument to green the Belt and Road. This article focuses on the question: What role do the GIPs play in building a green Belt and Road and addressing relevant regulatory challenges? Based on the theory of nodal governance, it is argued that the GIPs’ two-layered networks facilitate China to influence investment decisions over many countries along the Belt and Road indirectly through fund providers as key nodes to transition toward green investment. China also avoided direct interference with the domestic policies of host countries through the GIP network. As a framework agreement, the GIPs also provide opportunities for signatories to contribute to the design and negotiation of specific implementation standards, enhanced capacity building, and the prospect of more stringent and prescriptive environmental standards in the future.
Aggregative Variational Inequalities
Authors: von Mouche Peter Hubert Mathieu , Szidarovszky Ferenc
Published: March 2023

We enrich the theory of variational inequalities in the case of an aggregative structure by implementing recent results obtained by using the Selten–Szidarovszky technique. We derive existence, semi-uniqueness and uniqueness results for solutions and provide a computational method. As an application we derive very powerful practical equilibrium results for Nash equilibria of sum-aggregative games and illustrate with Cournot oligopolies.
Comparative study of two mixture dyes based on PVA for industrial use as gamma radiation dosimeter
Authors: Khozemy Ehab E. , El-Kelany M. A. , Goda Heba , Awad Boshra
Published: March 2023

New film dosimeters PVA/(DCP/CR) and PVA/(DCP/BPR) have been prepared through the casting method. The colorimetric properties of both films changed from violet to pink and from green to yellow with exposures to gamma rays between 0–80 and 0–40 kGy, respectively. The color response was accelerated with chloral hydrate to half of the radiation dose between 0–40 and 0–20 kGy for both systems, respectively. The UV–visible spectrophotometer shows outstanding stability of the prepared dosimetric systems. Relative humidity was studied and the response indicated that both films possess very good stability during irradiation.

Graphical abstract
SETAR-Tree: a novel and accurate tree algorithm for global time series forecasting
Authors: Godahewa Rakshitha , Webb Geoffrey I. , Schmidt Daniel , Bergmeir Christoph
Published: March 2023

Threshold Autoregressive (TAR) models have been widely used by statisticians for non-linear time series forecasting during the past few decades, due to their simplicity and mathematical properties. On the other hand, in the forecasting community, general-purpose tree-based regression algorithms (forests, gradient-boosting) have become popular recently due to their ease of use and accuracy. In this paper, we explore the close connections between TAR models and regression trees. These enable us to use the rich methodology from the literature on TAR models to define a hierarchical TAR model as a regression tree that trains globally across series, which we call SETAR-Tree. In contrast to the general-purpose tree-based models that do not primarily focus on forecasting, and calculate averages at the leaf nodes, we introduce a new forecasting-specific tree algorithm that trains global Pooled Regression (PR) models in the leaves allowing the models to learn cross-series information and also uses some time-series-specific splitting and stopping procedures. The depth of the tree is controlled by conducting a statistical linearity test commonly employed in TAR models, as well as measuring the error reduction percentage at each node split. Thus, the proposed tree model requires minimal external hyperparameter tuning and provides competitive results under its default configuration. We also use this tree algorithm to develop a forest where the forecasts provided by a collection of diverse SETAR-Trees are combined during the forecasting process. In our evaluation on eight publicly available datasets, the proposed tree and forest models are able to achieve significantly higher accuracy than a set of state-of-the-art tree-based algorithms and forecasting benchmarks across four evaluation metrics.
Mixed Bacterial Growth in Prenatal Urine Cultures; An Investigation into Prevalence, Contributory Factors and the Impact of education-based Interventions
Authors: Kindinger Lindsay M , Linton Hannah , James Catherine P , Mallet Camille , Curtis Carmel , Macrae Bruce , David Anna L.
Published: March 2023

Purpose

Undiagnosed urinary tract infections (UTIs) in pregnancy are associated with adverse perinatal outcome. Urine microbiology cultures reported as ‘mixed bacterial growth’ (MBG) frequently present a diagnostic dilemma for healthcare providers. We investigated external factors contributing to elevated rates of (MBG) within a large tertiary maternity centre in London, UK, and assessed the efficacy of health service interventions to mitigate these.

Description

This prospective, observational study of asymptomatic pregnant women attending their first prenatal clinic appointment aimed to establish (i) the prevalence of MBG in routine prenatal urine microbiology cultures, (ii) the association between urine cultures and the duration to laboratory processing and (iii) ways in which MBG may be reduced in pregnancy. Specifically we assessed the impact of patient-clinician interaction and that of an education package on optimal urine sampling technique.

Assessment

Among 212 women observed over 6 weeks, the negative, positive and MBG urine culture rates were 66%, 10% and 2% respectively. Shorter duration from urine sample collection to laboratory arrival correlated with higher rates of negative cultures. Urine samples arriving in the laboratory within 3 hours of collection were most likely to be reported as culture negative (74%), and were least likely to be reported as MBG (21%) or culture positive (6%), compared to samples arriving > 6 hours (71%, 14% and 14% respectively; P < 0.001). A midwifery education package effectively reduced rates of MBG (37% pre-intervention vs 19% post-intervention, RR 0.70, 95% CI 0.55 to 0.89). Women who did not receive verbal instructions prior to providing their sample had 5-fold higher rates of MBG (P < 0.001).

Conclusion

As many as 24% of prenatal urine screening cultures are reported as MBG. Patient-midwife interaction before urine sample collection and rapid transfer of urine samples to the laboratory within 3 hours reduces the rate of MBG in prenatal urine cultures. Reinforcing this message through education may improve accuracy of test results.
Family Engagement at the Systems Level: A Framework for Action
Authors: Dworetzky Beth , Hoover Clarissa G. , Walker Deborah Klein
Published: March 2023

While family engagement at the individual level of health care, such as families partnering with providers in decision-making about health care for an individual child has been well studied, family engagement in systems-level activities (e.g., participation in advisory and other decision-making groups, or creation and revision of policies) that impact the health services families and children receive has not. This note from the field presents a framework that describes the information and supports that help families partner with professionals and contribute to systems-level activities. Without attention to these components of family engagement, family presence and participation may be only token. We engaged an expert Family/Professional Workgroup whose members represented key constituencies and diverse geography, race/ethnicity, and areas of expertise; conducted a review of peer-reviewed publications and grey literature; and conducted a series of key informant interviews to identify best practices for supporting meaningful family engagement at the systems level. Based on an analysis of the findings, the authors identified four action-oriented domains of family engagement and key criteria that support and strengthen meaningful family engagement in systems-level initiatives. Child- and family-serving serving organizations can use this Family Engagement in Systems framework to support meaningful family engagement in the design of policies, practices, services, supports, quality improvement projects, research, and other systems-level activities.
Assessment of the disassemblability of electric bicycle motors for remanufacturing
Authors: Erdmann Julian Grosse , Koller Jan , Brimaire Jil , Döpper Frank
Published: March 2023

In 2021, sales of electric bicycles in Germany increased compared to the previous year, leading to a 43% share of electric bicycles in the total German bicycle market. The German Bicycle Industry Association (ZIV) expects this growth to continue and that by 2025 every second bicycle sold in Germany will have an electric motor. Therefore, due to the increasing number of sales, both the built-in resources and the possible treatments after the use phase need to be considered regarding sustainable market development. In this context, remanufacturing is one promising end-of-life strategy that enables a new life cycle of products and components, thus reducing the consumption of natural resources and minimizing waste production. The used products are restored to their original conditions by disassembling, cleaning, sorting, reworking, and reassembling. Disassembly is a decisive process step as it creates the prerequisites for all further steps in the process chain and significantly determines the economic feasibility of a remanufacturing process. Therefore, this paper aims to evaluate the ease of disassembly of electric bicycle motors and thus determine their suitability for remanufacturing. To evaluate the disassemblability, the ease of Disassembly Metric (eDiM), a quantitative assessment method for evaluating disassembly effort, was adapted to the needs of the electric bicycle motors. The method was finally applied to five electric bicycle motors from established manufacturers and assessed their ease of disassembly. The results show that the electric bicycle motors can be disassembled without significant damage and classified as suitable for remanufacturing.