bluuebunny/crossref_metadata_2025 huggingface dataset:
ALARP demonstration in management of change using quantitative Bowtie analysis risk assessment tool for an offshore gas platform
Authors: Abdul Aziz Mohammad Afif , Md Said Mohamad Syazarudin
Published: September 2022

In this study, a framework for a quantitative Bowtie analysis based on the layer of protection analysis (LOPA) approach in the management of change (MOC) process flow was developed. The proposed tool can be used as a quantitative risk analysis method in supporting decisions when layers of protection or safeguards are unavailable. The proposed tool can quantify the frequency of the causes of a particular hazard via Fault Tree Analysis and identify the multiple consequences of the impact of the hazards with quantitative end events for risk analysis. The practicality of the proposed tool was demonstrated in a selected case study from the MOC database from Company A's offshore gas platform, where the consequences and impacts of the hazards to the people, environment, assets, and reputation were assessed. The LOPA quantification was introduced into the Bowtie diagram using a reliability database to determine the failure rates and probability of failure of the affected equipment. The risk tolerance level was subsequently determined. The outputs of risk analysis from the proposed quantitative Bowtie were then compared with the previous qualitative risk evaluation of the selected case study. Potential opportunities for further use of the proposed quantitative Bowtie tool were recommended.
Loureirin C ameliorates ischemia and reperfusion injury in rats by inhibiting the activation of the TLR4/NF‐κB pathway and promoting TLR4 degradation
Authors: Xu Jikai , Liu Jingyu , Li Qing , Mi Yan , Zhou Di , Wang Jian , Chen Gang , Liang Dong , Li Ning , Hou Yue
Published: September 2022

Ischemic stroke is a leading cause of death and disability worldwide. Post‐ischemia, microglia respond immediately to the alternations in neuronal activity and mediate inflammation. Toll‐like receptor 4 (TLR4) plays a key role in this phenomenon. To explore the effect of loureirin C, an effective compound from Chinese Dragon's blood, on ischemic stroke, Sprague–Dawley rats were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) with/without intragastric administration of loureirin C (7, 14, and 28 mg/kg). Loureirin C alleviated MCAO/R‐induced brain impairment evaluated by neurological scores (p < 0.001), brain water content (p < 0.001), and cerebral infarct volume (p = 0.001). The neuroprotective (p < 0.001) and inhibitory effects on microglial activation (p < 0.001) of loureirin C were revealed by immunofluorescence. Rescue studies with TLR4 overexpression in BV‐2 microglia showed that the antiinflammatory effect of loureirin C was attributable to the inhibition of TLR4 protein expression. Moreover, co‐immunoprecipitation assays showed that the binding of Triad3A, an E3 ubiquitin ligase of TLR4, was increased by loureirin C (p = 0.003). Our study demonstrates that loureirin C could be a promising therapeutic agent for the management of ischemic stroke by inhibiting microglial activation, potentially by Triad3A‐mediated promotion of TLR4 ubiquitination and degradation.
Imidazole Promoted Efficient Anomerization of β‐D‐Glucose Pentaacetate in Solid State and Reaction Mechanism
Authors: Wang Meifeng , Zhang Liyin , Li Yiqun , Gu Liuqun
Published: September 2022

Anomerization of glycosides was rarely performed under basic condition. Here, an imidazole promoted anomerization of β‐D‐glucose pentaacetate in solid state at room temperature was discovered. This unprecedent anomerization occurred after simple premixing and reaction proceeded continuously in solid state to full conversion without stirring or mechanomixing. Full conversion of all β‐forms in the mixture (α:β=2.2 : 1) into α‐forms only was demonstrated at 1 gram scale. A proposed mechanism involved with inter/intramolecular acyl transfer promoted by imidazoles in a concerted manner may promote the discovery of more new transformations in solid state.
Nature‐Inspired High Temperature Scale‐Resistant Slippery Lubricant‐Induced Porous Surfaces (HTS‐SLIPS)
Authors: Yao Xiaoxue , Lin Wenzhu , Wang Mingmei , Wang Steven
Published: September 2022

Scale formation is a longstanding and unresolved problem in a number of fields, including power production, petroleum exploration, thermal desalination, and construction. Herein, a high‐temperature scale‐resistant slippery lubricant‐induced surface (HTS‐SLIPS) is developed by one‐step electrodeposition and lubricant infusion. The fractal cauliflower‐like morphology with lubricant oil is conducive to forming an ultralow contact angle hysteresis of ≈1°. The 10‐d real‐world boiling trial indicates that by replacing the uncoated surface with HTS‐SLIPS, the reduction in scale mass is greater than 200% because of the low surface free energy (4.3 mJ m−2) and outstanding smoothness (Ra = 41 ± 8 nm) of HTS‐SLIPS. Thanks to the scale retardation, the bubble departure frequency of HTS‐SLIPS is eightfold higher than that of uncoated surfaces, signifying superior heat transfer efficiency. In these demonstrations, HTS‐SLIPS coated spiral tube exhibits better flowability and lower pressure drop than the uncoated one. In addition, favorable compatibility between HTS‐SLIPS and mechanical vibration is experimentally verified to strengthen the descaling of SLIPS synergistically. It is anticipated that the simple and scalable coating fabrication approach will be applicable in numerous industrial high‐temperature processes where scale formation is encountered.
Amplifying Dendritic Cell Activation by Bioinspired Nanometal Organic Frameworks for Synergistic Sonoimmunotherapy
Authors: Lu Zhixiang , Bai Shuang , Jiang Yonghe , Wu Shuaiying , Xu Dazhuang , Zhang Jianzhong , Peng Xuqi , Zhang Hongrui , Shi Yesi , Liu Gang
Published: September 2022

Despite recent advancements of sonodynamic therapy (SDT) in cancer immunotherapy, challenges have yet to be surmounted to further boost its immunotherapeutic efficacy due to the low‐level tumor antigens presentation of dendritic cells (DCs). Cell membrane camouflaged‐nanoparticles can integrate the neoantigens of the cancer cell membrane with the multifunctionalities of synthetic nanocores. Herein, sono‐responsive nanoparticles coated with DC‐targeted antibody chimeric cancer cell membrane are investigated for multimodal therapy. The nanometal organic frameworks (MOFs) that respond to ultrasound are loaded successfully inside the vesicles displaying an anti‐DEC205 antibody. The anti‐DEC205 chimeric vesicles can directly target and activate DCs, promote tumor antigens cross‐presentation, and then produce a cascade amplified T‐cell immune response. Upon deep tissue‐penetrating sonication, AMR‐MOF@AuPt generates large amounts of reactive oxygen species that directly kill cancer cells, further initiating an anti‐cancer T cell immune response. Such synergistic sono‐immunotherapies effectually inhibit tumor growth and induce strong systemic and long‐term immune memory against cancer recurrence and distant metastasis. The authors findings provide DCs and tumor cells of a dual active‐targeting cell membrane‐coated sono‐immunotherapeutic nanoplatform for cancer therapy.
Distinguishing Ultrafast Energy Transfer in Atomically Thin MoS2/WS2 Heterostructures
Authors: Zeng Yan , Dai Wei , Ma Rundong , Li Zhe , Ou Zhenwei , Wang Cheng , Yu Yiling , Zhu Tong , Liu Xiaoze , Wang Ti , Xu Hongxing
Published: September 2022

Van der Waals semiconducting heterostructures, known as stacks of atomically thin transition‐metal dichalcogenide (TMD) layers, have recently been reported as new quantum materials with fascinating optoelectronic properties and novel functionalities. These discoveries are significantly related to the interfacial carrier dynamics of the excited states. Carrier dynamics have been reported to be predominantly driven by the ultrafast charge transfer (CT) process; however, the energy transfer (ET) process remains elusive. Herein, the ET process in MoS2/WS2 heterostructures via transient absorption microscopy is reported. By analyzing the ultrafast dynamics using various MoS2/WS2 interfaces, an ET rate of ≈240 fs is obtain, which is not trivial to the CT process. This study elucidates the role of the ET process in interfacial carrier dynamics and provides guidance for engineering interfaces for optoelectronic and quantum applications of TMD heterostructures.
Organic Additive Engineering to Grow High‐Quality Inorganic CsPbX3 Perovskite Films for Efficient and Stable Solar Cells
Authors: Wang Guiqiang , Chang Jiarun , Bi Jiayu , Zhang Wei , Meng Fanning
Published: September 2022

Inorganic CsPbX3 (X: Br, I, or their mixture) perovskite solar cells have gained widespread attention due to their superior stability and the steadily increased conversion efficiency. Inorganic CsPbX3 perovskite for solar cell application are usually fabricated by the solution‐processing method. The nature of solution‐processing method and the rapid crystal growth of perovskite lead to the formation of a wide range of defects within CsPbX3 perovskite films, which deteriorate the performance and stability of CsPbX3 devices. Recently, organic additive engineering has been demonstrated to be an effective strategy for improving the perovskite quality. Herein, the recent progress of organic additive engineering to grow high‐quality inorganic CsPbX3 perovskite films for high‐performance solar cells is summarized. The role of organic additives in the formation of inorganic CsPbX3 perovskite films and their effect on the performance of corresponding perovskite solar cells are discussed. In addition, some issues of organic additive engineering that should be deeply understood are summarized, and the research trend on organic additive engineering for further improving the performance of CsPbX3 devices is suggested.
Long‐Term Reoxidation of Hot Briquetted Iron in Various Prepared Climatic Conditions
Authors: Daghagheleh Oday , Schenk Johannes , Zheng Heng , Taferner Bernd , Forstner Andreas , Rosenfellner Gerald
Published: September 2022

The application of hot briquetted iron (HBI) in the electric arc furnace (EAF) is a promising method to obtain high‐quality steel products with a guaranteed purity level. However, during the long‐term transportation and storage, the HBI will be partially reoxidized, resulting in a loss of metallization degree. Herein, long‐term reoxidation behaviors of commercial HBI under various prepared climatic conditions are investigated. The results show that HBI exposed to ambient air conditions develops nearly no reoxidation. However, interval and cyclic wetting and drying of HBI lead to the worst metallization loss problem, which must be avoided. Based on morphological analysis, the reoxidation is supposed to occur at the surface and then spread into the center area through cracks or pellet boundaries. The reoxidation gradually decreases the porosity of HBI by the closure of cracks and pores with rust but shows little influence on its physical strength.
Stimuli‐Responsive of Flexible Silver–Organic Framework Film with Molecular Rotors Based on Methylene Rotation
Authors: Zhu Ke , Cao Yang , Fan Ruiqing , Zhang Jian , Jia Wenwen , Jiang Xin , Ji Chengshan , Wu Jingkun , Yin Yuanyuan , Yang Yulin
Published: September 2022

Environmental stimuli‐responsive materials exhibit immense potential in various applications. Herein, three stable silver‐based organic frameworks (MOF‐Ag‐1, MOF‐Ag‐2, and MOF‐Ag‐3) are constructed connecting by the same [Ag2(CN4)2] secondary building blocks. The MOF‐Ag‐3 shows controllable molecular rotation driven by water vapor due to the flexible framework and methylene molecular rotor. Meanwhile, the soft materials (MOF‐Ag‐3@PVDF film, PVDF = polyvinylidene fluoride) that enable visible shape transformation have been prepared by integrating deformable MOF‐Ag‐3 crystals into polymer films. Moreover, the vertical distribution of MOF‐Ag‐3 crystals is adjusted by acid etching to prepare a double‐layer structure actuator, containing alternant moving layer and fixed layer. The smart actuator presents bending deformation in the water vapor (folding angle φ = 451°, RH = 80%), performing “pull‐ups” and “sit‐ups” stimuli‐responsive behaviors as the “arms” or “waist” part. In addition, the MOF‐Ag‐3@PVDF film not only produces distortion under a CH3SH vapor but also shows fluorescence quenching to the CH3SH/water mixture vapor (0.5% CH3SH) with a low detection limit of 0.48 μm. This work indicates the molecular‐level construction of stimuli‐responsive materials for pollutant monitoring.
‘The UK must ban farrowing crates’
Authors: McCulloch Steven
Published: September 2022

Steven McCulloch, head of research at the Conservative Animal Welfare Foundation, argues that the UK should ban the use of farrowing crates for pigs and the veterinary profession must provide its full support.
Waterbody status of upper Ganga basin and its major tributaries using enviro‐assessment techniques
Authors: Sharma Arvind Kumar , Malik Davendra Singh , Kamboj Vishal , Sharma Amit Kumar
Published: September 2022

In the past two decades, freshwater bodies and their water quality have deteriorated rapidly due to several natural and anthropogenic causes, as well as rapid urbanization and industrialization. Using environmental assessment tools, eight sampling stations were used to assess the water quality of the upper Ganga and its major headstreams between January 2019 and December 2021 and to assess the impact of human‐led activities on the environment and the suitability of the catchment basin to perpetuate aquatic ecological diversity. During the current study period, water quality indices such as the Water Quality Index (WQI), Nemerow Pollution Index (NPI), and the Overall index of pollution (OIP) were employed to assess water quality. Twelve physicochemical parameters were examined using appropriate techniques and then compared to international standards. A small increase was observed in some physicochemical parameters, such as pH, Turbidity, Dissolved Oxygen, and Biological Oxygen Demand, at sampling stations 7 and 8. In the upper Ganga basin, all three indices (WQI, NPI, and OIP) accurately recorded numerous natural and human events at the selected sample sites. The water quality demonstrated that aquatic species were abundant. The water quality at some sample stations was also negatively affected by human activities, such as riverbed mining. However, these types of activities must be monitored and assessed.
Einleitung
Authors: Kisch Tobias
Published: September 2022

Derzeitige Vergütungssysteme erlauben es kaum Sektorengrenzen aufzubrechen. Es existieren kaum Anreize zur Ambulantisierung und Ergebnisqualität. Der Reinerlös chirurgischer Einzelpraxen sinkt seit Jahren. Die Anzahl ambulanter Operationen nimmt dementsprechend ab. Ob die Besondere Versorgung in der Plastischen Chirurgie und Handchirurgie den Herausforderungen begegnen kann, soll in dieser Evaluation überprüft werden.
Ergebnisse der Projektrecherche und der empirischen Studie
Authors: Kisch Tobias
Published: September 2022

Die Ergebnisse der Recherche zur Besonderen Versorgung in den Fachgebieten, die verschiedenen Perspektiven, die Pretest-Ergebnisse, die Ergebnisse zu den aktuellen Projekten, der Struktur-, Prozess- und Ergebnisqualität sowie der Wirtschaftlichkeit werden präsentiert und diskutiert.
Schlussbetrachtung
Authors: Kisch Tobias
Published: September 2022

Es erfolgt eine Zusammenfassung der Evaluationsergebnisse mit kritischer Bewertung, Fazit und Ausblick.
Instructional Quality and Learning Design of Massive Open Online Courses
Authors: Stracke Christian M. , Burgos Daniel , Tlili Ahmed
Published: September 2022

This chapter analyzes the instructional quality and learning design of different categories of online courses and their history, with a special focus on massive open online courses (MOOCs). Online courses have a long tradition that has gained public attention, broad interest, and huge numbers of participants thanks to the introduction of free MOOCs accessible online for all interested learners worldwide. In this chapter, we first define MOOCs, their characteristics, and history. Afterward, theoretical frameworks and practical instruments and tools based on scientific research are presented. From the beginning, the quality of MOOCs (and of online courses in general) has been debated. That led to discussions about the learning design and outcomes of MOOCs, which we introduce in the next section. Key research findings and practical validated instruments for designing and evaluating MOOCs (and online courses in general) are presented. Then following, the key benefits of MOOCs and the main arguments and scenarios for their usage are summarized. Based on our analysis of the research results, practices, and standards, a framework for categories and types of (massive open) online courses is proposed, called the typologies of online courses (TOC) framework. As part of the global community for open educational resources (OER) and in combination with the UNESCO recommendation on OER, MOOCs can play a significant role in achieving the SDG4 of the United Nations: inclusive and equitable quality education for all. This is true in particular during times of public lockdowns, such as during the ongoing COVID-19 pandemic.
Proton and carbon ion beam treatment with active raster scanning method in 147 patients with skull base chordoma at the Heidelberg Ion Beam Therapy Center—a single-center experience
Authors: Mattke Matthias , Ohlinger Matteo , Bougatf Nina , Harrabi Semi , Wolf Robert , Seidensaal Katharina , Welzel Thomas , Röder Falk , Gerum Sabine , Ellerbrock Malte , Jäkel Oliver , Haberer Thomas , Herfarth Klaus , Uhl Matthias , Debus Jürgen
Published: September 2022

Background

This study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results.

Methods

A total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan–Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors.

Results

During the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8–53.8; reverse Kaplan–Meier median follow-up time 56.3 months, 95% CI: 51.9–60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1‑year, 3‑year, and 5‑year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation.

Conclusion

Outcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation.
Assessment of intrafractional prostate motion and its dosimetric impact in MRI-guided online adaptive radiotherapy with gating
Authors: Xiong Yuqing , Rabe Moritz , Nierer Lukas , Kawula Maria , Corradini Stefanie , Belka Claus , Riboldi Marco , Landry Guillaume , Kurz Christopher
Published: September 2022

Purpose

This study aimed to evaluate the intrafractional prostate motion captured during gated magnetic resonance imaging (MRI)-guided online adaptive radiotherapy for prostate cancer and analyze its impact on the delivered dose as well as the effect of gating.

Methods

Sagittal 2D cine-MRI scans were acquired at 4 Hz during treatment at a ViewRay MRIdian (ViewRay Inc., Oakwood Village, OH, USA) MR linac. Prostate shifts in anterior–posterior (AP) and superior–inferior (SI) directions were extracted separately. Using the static dose cloud approximation, the planned fractional dose was shifted according to the 2D gated motion (residual motion in gating window) to estimate the delivered dose by superimposing and averaging the shifted dose volumes. The dose of a hypothetical non-gated delivery was reconstructed similarly using the non-gated motion. For the clinical target volume (CTV), rectum, and bladder, dose–volume histogram parameters of the planned and reconstructed doses were compared.

Results

In total, 174 fractions (15.7 h of cine-MRI) from 10 patients were evaluated. The average (±1 σ) non-gated prostate motion was 0.6 ± 1.0 mm in the AP and 0.0 ± 0.6 mm in the SI direction with respect to the centroid position of the gating boundary. 95% of the shifts were within [−3.5, 2.7] mm in the AP and [−2.9, 3.2] mm in the SI direction. For the gated treatment and averaged over all fractions, CTV D98% decreased by less than 2% for all patients. The rectum and the bladder D2% increased by less than 3% and 0.5%, respectively. Doses reconstructed for gated and non-gated delivery were similar for most fractions.

Conclusion

A pipeline for extraction of prostate motion during gated MRI-guided radiotherapy based on 2D cine-MRI was implemented. The 2D motion data enabled an approximate estimation of the delivered dose. For the majority of fractions, the benefit of gating was negligible, and clinical dosimetric constraints were met, indicating safety of the currently adopted gated MRI-guided treatment workflow.
Datenstandards für Seltene Erkrankungen
Authors: Robinson Peter N. , Graessner Holm
Published: September 2022

Die Verwendung von einheitlichen Datenformaten (Datenstandards) im Gesundheitswesen dient vier Hauptzwecken: 1) dem Datenaustausch, 2) der Integration von Computersystemen und -instrumenten, 3) der Datenspeicherung und -archivierung und 4) der Unterstützung föderierter Datenbanken. Sie sind besonders wichtig für die Erforschung und die klinische Versorgung Seltener Erkrankungen (SE).

In dieser Übersicht stellen wir Standards im Gesundheitswesen vor und präsentieren eine Auswahl von Standards, die im Bereich der seltenen Krankheiten häufig verwendet werden. Die „Human Phenotype Ontology“ (HPO) ist der am häufigsten verwendete Standard zur Annotation phänotypischer Anomalien und zur Unterstützung der phänotypgesteuerten Analyse der diagnostischen Exom- und Genomsequenzierung. Es gibt zahlreiche Standards für Krankheiten, die unterschiedlichen Anforderungen entsprechen. Das „Online Mendelian Inheritance in Man“ (OMIM) und die „Orphanet Rare Disease Ontology“ (ORDO) sind die wichtigsten Standards, die speziell für seltene Krankheiten entwickelt wurden. Die „Mondo Disease Ontology“ (Mondo) ist eine neue Krankheitsontologie, die darauf abzielt, auf umfassende Weise Daten aus aktuellen Nosologien zu integrieren. Neue Standards und Schemata wie die „Medical Action Ontology“ (MAxO) und das „Phenopacket“ der Global Alliance for Genomics and Health (GA4GH) werden gegenwärtig eingeführt, um die Palette der verfügbaren Standards zur Unterstützung der Forschung an seltenen Krankheiten zu erweitern.

Um eine optimale Versorgung von Patienten mit SE in verschiedenen Bereichen des Gesundheitswesens zu ermöglichen, müssen die Standards für seltene Krankheiten besser in die elektronischen Ressourcen des Gesundheitswesens integriert werden, z. B. über den Standard „FHIR“ (Fast Healthcare Interoperability Resources).
Hierarchical Means Clustering
Authors: Vichi Maurizio , Cavicchia Carlo , Groenen Patrick J. F.
Published: September 2022

In the cluster analysis literature, there are several partitioning (non-hierarchical) methods for clustering multivariate objects based on model estimation. Distinct to these methods is the use of a system of n nested statistical models and the optimization of a loss function to best-fit a clustering model to observed data. Many hierarchical clustering methods are not model-based where hierarchy is obtained using a divisive or agglomerative greedy procedure. This paper aims to fill this gap by proposing a novel hierarchical cluster analysis methodology called Hierarchical Means Clustering. HMC produces a set of nested partitions with a centroid-based model estimated via least-squares by minimizing the total within-cluster deviance of the n partitions in the hierarchy. Hierarchical Means Clustering produces a hierarchy formed by n-1 nested partitions from 2 to n clusters with minimal total cluster deviance. Six real data examples are featured, and key links to k-means, Ward’s method, Bisecting k-means and model-based hierarchical agglomerative clustering methods are discussed.
Non-pharmacological interventions for vascular health and the role of the endothelium
Authors: Weaver Samuel R. C. , Rendeiro Catarina , Lucas Rebekah A. I. , Cable N. Timothy , Nightingale Tom E. , McGettrick Helen M. , Lucas Samuel J. E.
Published: September 2022

The most common non-pharmacological intervention for both peripheral and cerebral vascular health is regular physical activity (e.g., exercise training), which improves function across a range of exercise intensities and modalities. Numerous non-exercising approaches have also been suggested to improved vascular function, including repeated ischemic preconditioning (IPC); heat therapy such as hot water bathing and sauna; and pneumatic compression. Chronic adaptive responses have been observed across a number of these approaches, yet the precise mechanisms that underlie these effects in humans are not fully understood. Acute increases in blood flow and circulating signalling factors that induce responses in endothelial function are likely to be key moderators driving these adaptations. While the impact on circulating factors and environmental mechanisms for adaptation may vary between approaches, in essence, they all centre around acutely elevating blood flow throughout the circulation and stimulating improved endothelium-dependent vascular function and ultimately vascular health. Here, we review our current understanding of the mechanisms driving endothelial adaptation to repeated exposure to elevated blood flow, and the interplay between this response and changes in circulating factors. In addition, we will consider the limitations in our current knowledge base and how these may be best addressed through the selection of more physiologically relevant experimental models and research. Ultimately, improving our understanding of the unique impact that non-pharmacological interventions have on the vasculature will allow us to develop superior strategies to tackle declining vascular function across the lifespan, prevent avoidable vascular-related disease, and alleviate dependency on drug-based interventions.
Exploring the roles of FGF/MAPK and cVG1/GDF signalling on mesendoderm induction and convergent extension during chick primitive streak formation
Authors: Lee Hyung Chul , Oliveira Nidia M. M. , Stern Claudio D.
Published: September 2022

During primitive streak formation in the chick embryo, cells undergo mesendoderm specification and convergent extension at the same time and in the same cells. Previous work has implicated cVG1 (GDF3) as a key factor for induction of primitive streak identity and positioning the primitive streak, whereas FGF signalling was implicated in regulating cell intercalation via regulation of components of the WNT-planar cell polarity (PCP) pathway. FGF has also been reported to be able to induce a primitive streak (but lacking the most axial derivatives such as notochord/prechordal mesendoderm). These signals emanate from different cell populations in the embryo, so how do they interact to ensure that the same cells undergo both cell intercalation and acquire primitive streak identity? Here we begin to address this question by examining in more detail the ability of the two classes of signals in regulating the two developmental events. Using misexpression of inducers and/or exposure to inhibitors and in situ hybridisation, we study how these two signals regulate expression of Brachyury (TBXT) and PRICKLE1 as markers for the primitive streak and the PCP, respectively. We find that both signals can induce both properties, but while FGF seems to be required for induction of the streak by cVG1, it is not necessary for induction of PRICKLE1. The results are consistent with cVG1 being a common regulator for both primitive streak identity and the initiation of convergent extension that leads to streak elongation.
Metabolic changes during prostate cancer development and progression
Authors: Beier Alicia-Marie K. , Puhr Martin , Stope Matthias B. , Thomas Christian , Erb Holger H. H.
Published: September 2022

Metabolic reprogramming has been recognised as a hallmark in solid tumours. Malignant modification of the tumour’s bioenergetics provides energy for tumour growth and progression. Otto Warburg first reported these metabolic and biochemical changes in 1927. In prostate cancer (PCa) epithelial cells, the tumour metabolism also changes during development and progress. These alterations are partly driven by the androgen receptor, the key regulator in PCa development, progress, and survival. In contrast to other epithelial cells of different entities, glycolytic metabolism in prostate cells sustains physiological citrate secretion in the normal prostatic epithelium. In the early stages of PCa, citrate is utilised to power oxidative phosphorylation and fuel lipogenesis, enabling tumour growth and progression. In advanced and incurable castration-resistant PCa, a metabolic shift towards choline, amino acid, and glycolytic metabolism fueling tumour growth and progression has been described. Therefore, even if the metabolic changes are not fully understood, the altered metabolism during tumour progression may provide opportunities for novel therapeutic strategies, especially in advanced PCa stages. This review focuses on the main differences in PCa’s metabolism during tumourigenesis and progression highlighting glutamine’s role in PCa.
Learning to tango with four (or more): the molecular basis of adaptation to polyploid meiosis
Authors: Bomblies Kirsten
Published: September 2022

Polyploidy, which arises from genome duplication, has occurred throughout the history of eukaryotes, though it is especially common in plants. The resulting increased size, heterozygosity, and complexity of the genome can be an evolutionary opportunity, facilitating diversification, adaptation and the evolution of functional novelty. On the other hand, when they first arise, polyploids face a number of challenges, one of the biggest being the meiotic pairing, recombination and segregation of the suddenly more than two copies of each chromosome, which can limit their fertility. Both for developing polyploidy as a crop improvement tool (which holds great promise due to the high and lasting multi-stress resilience of polyploids), as well as for our basic understanding of meiosis and plant evolution, we need to know both the specific nature of the challenges polyploids face, as well as how they can be overcome in evolution. In recent years there has been a dramatic uptick in our understanding of the molecular basis of polyploid adaptations to meiotic challenges, and that is the focus of this review.
Skin cancer diagnosis based on deep transfer learning and sparrow search algorithm
Authors: Balaha Hossam Magdy , Hassan Asmaa El-Sayed
Published: September 2022

Skin cancer affects the lives of millions of people every year, as it is considered the most popular form of cancer. In the USA alone, approximately three and a half million people are diagnosed with skin cancer annually. The survival rate diminishes steeply as the skin cancer progresses. Despite this, it is an expensive and difficult procedure to discover this cancer type in the early stages. In this study, a threshold-based automatic approach for skin cancer detection, classification, and segmentation utilizing a meta-heuristic optimizer named sparrow search algorithm (SpaSA) is proposed. Five U-Net models (i.e., U-Net, U-Net++, Attention U-Net, V-net, and Swin U-Net) with different configurations are utilized to perform the segmentation process. Besides this, the meta-heuristic SpaSA optimizer is used to perform the optimization of the hyperparameters using eight pre-trained CNN models (i.e., VGG16, VGG19, MobileNet, MobileNetV2, MobileNetV3Large, MobileNetV3Small, NASNetMobile, and NASNetLarge). The dataset is gathered from five public sources in which two types of datasets are generated (i.e., 2-classes and 10-classes). For the segmentation, concerning the “skin cancer segmentation and classification” dataset, the best reported scores by U-Net++ with DenseNet201 as a backbone architecture are 0.104, $$94.16\%$$

94.16
%

, $$91.39\%$$

91.39
%

, $$99.03\%$$

99.03
%

, $$96.08\%$$

96.08
%

, $$96.41\%$$

96.41
%

, $$77.19\%$$

77.19
%

, $$75.47\%$$

75.47
%

in terms of loss, accuracy, F1-score, AUC, IoU, dice, hinge, and squared hinge, respectively, while for the “PH2” dataset, the best reported scores by the Attention U-Net with DenseNet201 as backbone architecture are 0.137, $$94.75\%$$

94.75
%

, $$92.65\%$$

92.65
%

, $$92.56\%$$

92.56
%

, $$92.74\%$$

92.74
%

, $$96.20\%$$

96.20
%

, $$86.30\%$$

86.30
%

, $$92.65\%$$

92.65
%

, $$69.28\%$$

69.28
%

, and $$68.04\%$$

68.04
%

in terms of loss, accuracy, F1-score, precision, sensitivity, specificity, IoU, dice, hinge, and squared hinge, respectively. For the “ISIC 2019 and 2020 Melanoma” dataset, the best reported overall accuracy from the applied CNN experiments is $$98.27\%$$

98.27
%

by the MobileNet pre-trained model. Similarly, for the “Melanoma Classification (HAM10K)” dataset, the best reported overall accuracy from the applied CNN experiments is $$98.83\%$$

98.83
%

by the MobileNet pre-trained model. For the “skin diseases image” dataset, the best reported overall accuracy from the applied CNN experiments is $$85.87\%$$

85.87
%

by the MobileNetV2 pre-trained model. After computing the results, the suggested approach is compared with 13 related studies.
Non-adjustable gravitational valves or adjustable valves in the treatment of hydrocephalus after aneurysmal subarachnoid hemorrhage patients?
Authors: Arts Sebastian , van Lieshout Jasper Hans , van Bilsen Martine , Karadag Cihat , Beez Thomas , van den Abbeele Leonie , Aquarius Rene , Vinke Saman , Bartels Ronald H. M. A. , van Lindert Erik J. , Hänggi Daniel , Boogaarts Hieronymus D.
Published: September 2022

Purpose

Hydrocephalus requiring permanent CSF shunting after aneurysmal subarachnoid hemorrhage (aSAH) is frequent. It is unknown which type of valve is optimal. This study evaluates if the revision rate of gravitational differential pressure valves (G-DPVs, GAV® system (B Braun)) (G-DPV) is comparable to adjustable pressure valves (Codman Medos Hakim) (APV) in the treatment of post-aSAH hydrocephalus.

Methods

The use of a gravitational differential pressure valve is placed in direct comparison with an adjustable pressure valve system. A retrospective chart review is performed to compare the revision rates for the two valve systems.

Results

Within the registry from Radboud University Medical Center, 641 patients with a SAH could be identified from 1 January 2013 until 1 January 2019, whereas at the Heinrich Heine University, 617 patients were identified, totaling 1258 patients who suffered from aSAH. At Radboud University Medical Center, a gravitational differential pressure valve is used, whereas at the Heinrich Heine University, an adjustable pressure valve system is used. One hundred sixty-six (13%) patients required permanent ventricular peritoneal or atrial shunting. Shunt dysfunction occurred in 36 patients: 13 patients of the 53 (25%) of the gravitational shunt cohort, and in 23 of the 113 (20%) patients with an adjustable shunt (p = 0.54). Revision was performed at a mean time of 3.2 months after implantation with the gravitational system and 8.2 months with the adjustable shunt system. Combined rates of over- and underdrainage leading to revision were 7.5% (4/53) for the gravitational and 3.5% (4/113) for the adjustable valve system (p = 0 .27).

Conclusion

The current study does not show a benefit of a gravitational pressure valve (GAV® system) over an adjustable pressure valve (CODMAN ® HAKIM®) in the treatment of post-aSAH hydrocephalus. The overall need for revision is high and warrants further improvements in care.
Early detection of COVID-19 cholangiopathy using cholangioscopy—a case report of two critically ill patients
Authors: Kroepfl Veronika , Treml Benedikt , Freund Martin Cornelius , Profanter Christoph
Published: September 2022

Background

The coronavirus disease 2019 (COVID-19) crisis caused by the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) rapidly led to a pandemic. While the majority of SARS-CoV-2-infected patients present with fever and respiratory symptoms, gastrointestinal symptoms may also occur. In addition, serious hepatic manifestations like cholangiopathy and liver failure have been described.

Patients and methods

We identified two critically ill patients suffering from SARS-CoV‑2 infection in our intensive care unit (ICU). In both patients, laboratory testing revealed elevated liver chemistries weeks after initial diagnosis with COVID-19.

Results

During repeated endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy, a severely destructed biliary mucosa with ischemia and epithelial roughness was seen in both patients. Due to the prolonged course of COVID-19 and chronic liver damage with ongoing sepsis, both patients succumbed to the disease.

Conclusion

In our opinion, a COVID-19 infection can lead to development of cholangiopathy in critically ill patients. Cholangioscopy performed early can confirm the diagnosis of COVID-19-associated cholangioscopy.
Morphometric Characterization of an Ex Vivo Porcine Model of Functional Tricuspid Regurgitation
Authors: Salurso Eleonora , Jaworek Michal , Perico Francesca , Frigelli Matteo , Romagnoni Claudia , Contino Monica , Gelpi Guido , Fiore Gianfranco Beniamino , Vismara Riccardo
Published: September 2022

Emerging treatments for tricuspid valve (TV) regurgitation require realistic TV pathological models for preclinical testing. The aim of this work was to investigate structural features of fresh and defrosted porcine right-heart samples as models of mild and severe functional tricuspid regurgitation (FTR) condition in ex-vivo pulsatile flow platform. Ten fresh hearts were tested ex-vivo under steady and pulsatile flow in typical right-heart loading conditions. Hemodynamics and 3D echocardiographic imaging of TV and right ventricle (RV) were acquired. Hearts were then kept frozen for 14 days, defrosted, and tested again with the same protocol. Morphometric parameters of TV and RV were derived from 3D reconstructions based on echo data. Fresh samples showed a slightly dilated TV morphology, with coaptation gaps among the leaflets. Sample freezing induced worsening of TV insufficiency, with significant (p < 0.05) increases in annulus size (annulus area and perimeter 7.7–3.1% respectively) and dilation of RV (9.5%), which led to an increase in tenting volume (123.7%). These morphologic alterations reflected into a significant increment of regurgitation fraction (27%). Together, such results suggest that fresh porcine heart samples may be a reliable ex-vivo model of mild FTR condition, which can be enhanced through freezing/thawing treatment to model a severe pathological condition.
The Use of Kinesthetic Empathy with Adults Living with Treatment Resistant Depression: A Survey Study
Authors: Christopher Neha , Tamplin Jeanette
Published: September 2022

Dance/movement therapy is an embodied healing practice which has been found to foster recovery from depression and boost quality of life. Although kinesthetic empathy holds great potential for addressing emotional dysregulation, it is an under-utilized dance/movement therapy intervention in health optimization, especially in adults living with treatment-resistant depression. The aim of this study was to collect data from dance/movement therapist on how they use kinesthetic empathy to foster self-regulation in adults living with treatment-resistant depression. A survey design was used to obtain this data. Eight dance/movement therapists (practicing in India, Philippines, Barbados, and the United States of America) were recruited. The participant demographics of the survey challenges the centrality of master’s level trained dance/movement therapists primarily practicing in Eurocentric cultures. The survey included open answer questions, and responses received were grouped into four categories: (i) dance/movement therapists’ rationale for using kinesthetic empathy (ii) therapist-described client responses to kinesthetic empathy, (iii) changes in self-regulation patterns of clients, and (iv) potential links between employing kinesthetic empathy as an intervention and witnessing emotional regulation in clients. Overall, kinesthetic empathy was described as a core part of the participants’ dance/movement therapy practice with this population. The identified client responses to kinesthetic empathy were categorized based on deWitte’s et al. (Frontiers in Psychology, 2021) therapeutic factors of change. ‘Observable client responses’, such as, use of metaphors, verbalization of body sensations and engaging in mirroring were categorized under specific therapeutic factors of dance/movement therapy. Alternatively, ‘emotionally felt client responses’ such as, increase in safety and trust within the therapeutic alliance were categorized under both ‘specific’ and ‘mixed-type’ factors based on the model. Finally, this article discusses movement interventions that may be incorporated by dance/movement therapists while working with this population. Further research is required to identify the long-term effect/s of kinesthetic empathy as an intentional intervention to foster self-regulation in adults living with treatment-resistant depression.
Sex, Sexuality, and Intimate Relationships Among Afghan Women and Men of Refugee Background Living in Melbourne, Australia: Experiences, Opportunities, and Transcultural Tensions
Authors: Russo Alana , Lewis Belinda , Ali Razia , Abed Atiq , Russell Grant , Luchters Stanley
Published: September 2022

Over the last two decades, Afghanistan has been a leading country of origin for asylum seekers and refugees arriving in Australia. It is widely recognized that humanitarian migrants experience poorer sexual and reproductive health than the broader population. In turn, a body of research has emerged exploring the sexual and reproductive health of the local Afghan community. However, this has predominantly focused on youth or perinatal experiences, and less attention has been given to the broader relational and social dimensions of sexuality. Accordingly, this research aimed to explore the perspectives and experiences of married Afghan women and men as they navigate and negotiate sex, sexuality, and intimate relationships following settlement in Melbourne, Australia. A total of 57 Afghan women and men participated in six focus group discussions and 20 semi-structured interviews. Male participants described the ways that having increased access to sex and sexually explicit materials in Australia is creating opportunities for them to establish more fulfilling sex lives. Many women also described a growing awareness of sexuality, although often expressed difficulty prioritizing and claiming more pleasurable sexual encounters for themselves. However, concerns about sexual freedom are also creating new challenges for the Afghan community living in Australia in relation to sex and relationships. For example, men expressed fears about women exercising sexual liberties outside of the home, and this appeared to place women’s everyday behavior under increased scrutiny. Women also voiced concerns about how easily men can access sex outside of marriage within Australia, and described how this amplified their sense of obligation to be sexually compliant and meet their husband’s desires. This study provides new insights into the ways that Afghan community members are moving between societies, and how their understandings of sexual participation, pleasure, desire, health, consent, and capacity for self-determination are being challenged, reshaped, and reconstructed throughout this process.
A close supermassive black hole binary in Centaurus A?
Authors: Cosandey David A.
Published: September 2022

The Event Horizon Telescope (EHT) project has recently published a high-resolution picture of the Centaurus A galaxy core, where a supermassive black hole (SMBH) is supposed to be located. This picture has been accompanied with interpretation difficulties. In particular, the expected central SMBH and its accretion disk are not detected, the conical forward plasma jet seems hollow and its bended shape is difficult to explain. We argue that this image could in fact reveal the existence of two SMBHs, instead of one. Within this alternative interpretation, the black holes and their disks become visible on the image, the curved jet shapes may more easily be explained and the jets display no dark spine. The putative SMBH binary system shows a projected separation distance of ∼0.4-0.7 milliparsec. This is 700 times narrower than the NGC 7674 SMBH binary, so far the visually-identified system with the shortest such distance (0.35 pc). The orbital period can be inferred to lie in the 101to 10−1yr magnitude range. The image suggests a double helical jet structure that, if real, would support the lower end of this estimation range. If confirmed by future observations, this close SMBH binary in Centaurus A will be of great interest as a testing ground for SMBH binary dynamics models and plasma jet studies.
An empirical evaluation of a novel domain-specific language – modelling vehicle routing problems with Athos
Authors: Hoffmann Benjamin , Urquhart Neil , Chalmers Kevin , Guckert Michael
Published: September 2022

Domain-specific languages (DSLs) are a popular approach among software engineers who demand for a tailored development interface. A DSL-based approach allows to encapsulate the intricacies of the target platform in transformations that turn DSL models into executable software code. Often, DSLs are even claimed to reduce development complexity to a level that allows them to be successfully applied by domain-experts with limited programming knowledge. Recent research has produced some scientifically backed insights on the benefits and limitations of DSLs. Further empirical studies are required to build a sufficient body of knowledge from which support for different claims related to DSLs can be derived. In this research study, we adopt current DSL evaluation approaches to investigate potential gains in terms of effectiveness and efficiency, through the application of our DSL Athos, a language developed for the domain of traffic and transportation simulation and optimisation. We compare Athos to the alternative of using an application library defined within a general-purpose language (GPL). We specified two sets of structurally identical tasks from the domain of vehicle routing problems and asked study groups with differing levels of programming knowledge to solve the tasks with the two approaches. The results show that inexperienced participants achieved considerable gains in effectiveness and efficiency with the usage of Athos DSL. Though hinting at Athos being the more efficient approach, the results were less distinct for more experienced programmers. The vast majority of participants stated to prefer working with Athos over the usage of the presented GPL’s API.