bluuebunny/crossref_metadata_2025 huggingface dataset:
Subtropical Mode Water in a recent persisting Kuroshio large-meander period: part II—formation and temporal evolution in the Kuroshio recirculation gyre off Shikoku
Authors: Nishikawa Hatsumi , Oka Eitarou , Sugimoto Shusaku
Published: April 2023

Since August 2017, the large meander (LM) path of the Kuroshio south of Japan has continued to date for more than five years, with a local Kuroshio recirculation gyre off Shikoku (RGOS). The formation and temporal evolution of Subtropical Mode Water (STMW) in the isolated RGOS were examined by using Argo profiling float and shipboard observation data. Since the late winter of 2018, which was the first winter of the current LM event, multiple STMW layers with different densities overlapping with each other have been observed for more than three years inside the RGOS. The deeper STMW layer of 18.0 °C, which was formed in the late winter of 2017 before the current LM event began, has survived at least until September 2021 while its thickness and horizontal extent has decreased gradually. We may have succeeded in discovering the longest survived STMW ever observed due to a suitable environment for STMW conservation inside the RGOS. On the other hand, the shallower STMW layer(s) of 19.0–19.8 °C, which was originally formed over the deeper STMW layer in the late winter of 2018, has been repeatedly renewed or dissipated in the following years. The oxygen utilization rate at the core of the deeper STMW at a depth of 500 dbar was estimated to be 4.6 μmol kg−1 yr−1, which is believed to be explained solely by oxygen consumption due to remineralization.
The importance of monitoring cerebral oxygenation in non brain injured patients
Authors: Robba Chiara , Battaglini Denise , Rasulo Francesco , Lobo Francisco A. , Matta Basil
Published: April 2023

Over the past few years, the use of non-invasive neuromonitoring in non-brain injured patients has increased, as a result of the recognition that many of these patients are at risk of brain injury in a wide number of clinical scenarios and therefore may benefit from its application which allows interventions to prevent injury and improve outcome. Among these, are post cardiac arrest syndrome, sepsis, liver failure, acute respiratory failure, and the perioperative settings where in the absence of a primary brain injury, certain groups of patients have high risk of neurological complications. While there are many neuromonitoring modalities utilized in brain injured patients, the majority of those are either invasive such as intracranial pressure monitoring, require special skill such as transcranial Doppler ultrasonography, or intermittent such as pupillometry and therefore unable to provide continuous monitoring. Cerebral oximetry using Near infrared Spectroscopy, is a simple non invasive continuous measure of cerebral oxygenation that has been shown to be useful in preventing cerebral hypoxemia both within the intensive care unit and the perioperative settings. At present, current recommendations for standard monitoring during anesthesia or in the general intensive care concentrate mainly on hemodynamic and respiratory monitoring without specific indications regarding the brain, and in particular, brain oximetry. The aim of this manuscript is to provide an up-to-date overview of the pathophysiology and applications of cerebral oxygenation in non brain injured patients as part of non-invasive multimodal neuromonitoring in the early identification and treatment of neurological complications in this population.
The determinants of the mobility patterns of the elderly in Switzerland
Authors: Huggenberger Yashka , Wagner Joël , Wanzenried Gabrielle
Published: April 2023

Like most industrialized countries, Switzerland is characterized by an aging population. However, it differentiates itself from other countries because of its low home-ownership rate. Also, the lack of specialized housing for the elderly encourages them to stay in their current accommodation instead of moving to a smaller place thereby vacating space for family housing. Given this challenge, it is important for governments as well as other housing providers to understand better the needs of the elderly with respect to their housing situation and their patterns of mobility. Accordingly, our research aims to identify the key determinants that trigger the intention, on the part of the elderly in Switzerland, to move. For this purpose, we use secondary data obtained from the Swiss Household Panel, which is a longitudinal social sciences survey which annually interviews a random sample of private households in Switzerland using computer-assisted interviewing. We focus on respondents aged 60 and older over the period from 2013 to 2018, and our sample includes 13 313 observations. We investigate the role of intentions to move as a function of socio-demographic factors, health and life events, dwelling characteristics as well as satisfaction factors. By exploring the importance of these elements on the intention to move within a logistic regression model framework, we confirm the findings of recent studies including those that affirm that the willingness to move decreases with age, and that the elderly do not adapt the size of their home for a smaller dwelling. In addition, while we find no evidence for the impact of dwelling characteristics and health or life events, we provide empirical evidence for socio-demographic and satisfaction factors that influence the intention to move. From our results, we observe that not being satisfied with the accommodation, living in the German-speaking region of Switzerland, judging the accommodation to be too large, and being a tenant, all increase the intention to move. Our findings contribute to the welfare of the elderly in Switzerland by helping governments as well as private entities to plan housing adapted to their needs better.
Updated normative data for the EORTC QLQ-C30 in the general Dutch population by age and sex: a cross-sectional panel research study
Authors: de Ligt K. M. , Aaronson N. K. , Liegl G. , Nolte S. ,   the EORTC Quality of Life Group
Published: April 2023

Purpose

The European Organisation for Research and Treatment of Cancer (EORTC) quality of life core questionnaire (QLQ-C30) is a validated and widely-used Patient-Reported Outcome Measure for measuring the health-related quality of life (HRQoL) of cancer patients. To facilitate interpretation of results obtained in studies using the EORTC QLQ-C30, we generated normative data for the Dutch general population, stratified by age and sex.

Methods

Dutch participants were selected from a larger cross-sectional online panel research study collecting EORTC QLQ-C30 general population normative data across 15 countries. EORTC QLQ-C30 raw scores based on a 4-point response scale were transformed to linear scores ranging from 0 to 100. Transformed scores were weighted based on the United Nations population distribution statistics and presented by age and sex/age. Differences in scale scores of ≥ 10 points in HRQoL were applied to indicate clinical relevance.

Results

One thousand respondents completed the online survey. Stratified by age, clinically meaningful differences were observed, with worse physical functioning scores and better emotional functioning scores with increased age. Symptom scores remained stable across age groups, except for small age differences observed for fatigue, nausea/vomiting, diarrhoea, and financial difficulties. Stratified by sex/age, men generally scored better for both functioning and symptoms. However, these differences were not clinically meaningful.

Conclusions

These updated normative EORTC QLQ-C30 for the Dutch general population can be used to better interpret HRQoL data obtained from Dutch cancer patients. Being part of a larger international study, these data can further be used for inter-country comparisons in multi-national studies.
A traceable and revocable multi-authority attribute-based access control scheme for mineral industry data secure storage in blockchain
Authors: Zhang Xiaohong , Du Wenqi , Moshayedi Ata Jahangir
Published: April 2023

With the rapid advancements of the mineral industry, the data generated by this industry chain have increased dramatically. To reduce the growing pressure of data storage and security risks, we design a credible on-chain and off-chain collaborative dual storage system that integrates blockchain technology and Interplanetary file system (IPFS), also construct a traceable and revocable multi-authority ciphertext-policy attributed-based encryption (CP-ABE) algorithm to meet the demand of privacy protection and dynamic fine-grained access control. Furthermore, the multi-authority layered authorization with a central authority model distributes system overhead while enabling the platform can be regulated. More importantly, our scheme achieves accurate trace of the malicious users by white-box traceability and capable of implementing indirect immediate user and attribute revocation without requiring key or ciphertext updates. Finally, the proposed scheme is indistinguishably secure under chosen-plaintext attack (IND-CPA) in the standard model. And the performance analysis demonstrates that our scheme is feature-rich, practical and efficient.
Wear Reduction via CNT Coatings in Electrical Contacts Subjected to Fretting
Authors: Alderete Bruno , Mücklich Frank , Suarez Sebastian
Published: April 2023

Carbon nanotubes (CNT) are of great interest to the research community due to their outstanding mechanical, transport, and optical properties. These nanoparticles have also shown exceptional lubricating capabilities, which coupled with their electrical conductivity show promising results as solid lubricants in electrical contacts. In this study, three different CNT coatings were deposited over copper platelets via electrophoretic deposition and subsequently tribo-electrically characterized including electrical contact resistance evolution during fretting wear, wear protection, chemical analysis of fretting marks, as well as influence of CNT coating thickness, duration and normal load applied during fretting, and atmospheric humidity. Thicker CNT coatings show improved wear protection while retaining similar electrical behavior as uncoated copper, or even improving its electrical contact resistance. Moreover, the compaction of the porous CNT coating is crucial for optimal electrical performance at low humidity. For longer fretting tests (150,000 and 500,000 cycles), the coatings are displaced thus affecting the wear protection offered. However, the coatings stabilize and reduce ECR compared to uncoated samples. Furthermore, thicker CNT coatings can bear higher loads during fretting due to the increased lubricant reservoir, with carbonaceous tribofilm remaining at the contacting interface after 5,000 fretting cycles regardless of normal load.

Graphical Abstract
Monitoring of age- and gender-related alterations of endocannabinoid levels in selected brain regions with the use of SPME probes
Authors: Roszkowska Anna , Klejbor Ilona , Bogusiewicz Joanna , Plenis Alina , Bojko Barbara , Kowalik Katarzyna , Moryś Janusz , Bączek Tomasz
Published: April 2023

Introduction

The endocannabinoid system consists of different types of receptors, enzymes and endocannabinoids (ECs), which are involved in several physiological processes, but also play important role in the development and progression of central nervous system disorders.

Objectives

The purpose of this study was to apply precise and sensitive methodology for monitoring of four ECs, namely anandamide (AEA), 2-arachidonoyl glycerol (2-AG), N-arachidonoyl dopamine (NADA), 2-arachidonyl glyceryl ether (2-AGe) in selected brain regions of female and male rats at different stages of development (young, adult and old).

Methods

Biocompatible solid-phase microextraction (SPME) probes were introduced into the intact (non-homogenized) brain structures for isolation of four ECs, and the extracts were subjected to LC–MS/MS analysis. Two chemometric approaches, namely hierarchical cluster analysis (HCA) and Principal Component Analysis (PCA) were applied to provide more information about the levels of 2-AG and AEA in different brain structures.

Results

2-AG and AEA were extracted and could be quantified in each brain region; the level of 2-AG was significantly higher in comparison to the level of AEA. Two highly unstable ECs, NADA and 2-AGe, were captured by SPME probes from intact brain samples for the first time.

Conclusion

SPME probes were able to isolate highly unstable endogenous compounds from intact tissue, and provided new tools for precise analysis of the level and distribution of ECs in different brain regions. Monitoring of ECs in brain samples is important not only in physiological conditions, but also may contribute to better understanding of the functioning of the endocannabinoid system in various disorders.
Kant’s Formula of Autonomy: Continuity or Discontinuity?
Authors: Kleingeld Pauline
Published: April 2023

In two recent articles I have argued that Kant’s legal and political philosophy can shed new light on his much-contested account of moral autonomy and that important changes in his political theory help to explain why in his later work the Formula of Autonomy disappears. In the present essay, I respond to comments by Sorin Baiasu and Marie Newhouse, who argue that the changes in Kant’s political theory fail to explain the disappearance of the Formula of Autonomy, since in both phases Kant held that laws are given by the people’s representatives. I offer additional support for my original argument by developing a more detailed account of Kant’s conception of the relation between the legislating representatives and the people they are taken to represent. I argue that Kant’s conception of the proper representation relation changed, and that it changed so fundamentally that the analogy at the basis of the Formula of Autonomy was no longer apt, thus providing a plausible explanation for its disappearance. I also address several related comments and propose an explanation for why Kant dropped the very idea of autonomy as a property of the will.
Potato Ethics: What Rural Communities Can Teach Us about Healthcare
Authors: Fors Malin
Published: April 2023

In this paper I offer the term “potato ethics” to describe a particular professional rural health sensibility. I contrast this attitude with the sensibility behind urban professional ethics, which often focus on the narrow doctor–patient treatment relationship. The phrase appropriates a Swedish metaphor, the image of the potato as a humble side dish: plain, useful, versatile, and compatible with any main course. Potato ethics involves making oneself useful, being pragmatic, choosing to be like an invisible elf who prevents discontinuity rather than a more visible observer of formal rules and assigned tasks. It also includes actively taking part in everyday disaster-prevention and fully recognizing the rural context as a vulnerable space. This intersectional argument, which emphasizes the ongoing, holistic responsibility of those involved in rural communities, draws on work from the domains of care ethics, relational ethics, pragmatic psychology, feminist ethics of embodiment, social location theory, and reflections on geographical narcissism.
Proper biharmonic maps and $$(2,1)$$-harmonic morphisms from some wild geometries
Authors: Ghandour Elsa , Gudmundsson Sigmundur
Published: April 2023

In this work we construct a variety of new complex-valued proper biharmonic maps and (2, 1)-harmonic morphisms on Riemannian manifolds with non-trivial geometry. These are solutions to a non-linear system of partial differential equations depending on the geometric data of the manifolds involved.
Epoxy-Silicon Composite Materials from End-of-Life Photovoltaic Panels
Authors: Pavlopoulos C. , Christoula A. , Patsidis A. C. , Semitekolos D. , Papadopoulou K. , Psarras G. C. , Zoumpoulakis L. , Lyberatos G.
Published: April 2023

The prospect of using recovered solar cells from end-of-life (EoL) photovoltaic panels (PVPs) to produce composite materials with dielectric properties was studied. The main goal of this research was to reduce the waste originating from EoL PVPs by reusing the semiconductor, thus rendering solar energy an even greener energy source. Solar cells were recovered from EoL PVPs through thermal treatment to remove polymer sheets and screening to separate the solar cells from glass and electrodes. Composite materials were manufactured by reinforcing two different epoxy resins, Araldite LY556 and Resoltech 1050, with varying concentrations of ground solar cells (0–10% w/w). The mechanical and dielectric properties of the composite materials were examined with bending and shearing tests and Broadband Dielectric Spectroscopy (BDS), respectively. The responses from the two different resin matrices were compared. It was found that the produced composite material resulting from Resoltech resin reinforced with solar cells recovered from EoL PVPs had better mechanical and dielectric properties. BDS characterization of the composite materials indicated that the solar cells can be used to enhance the energy storage capacity of the polymeric matrix and thus may be potentially used in the manufacturing of capacitors.

Graphical Abstract
Seasonal shift in the diet of the notched-eared bat (Myotis emarginatus) in the Basque Country: from flies to spiders
Authors: Vallejo Nerea , Aihartza Joxerra , Olasagasti Lander , Aldasoro Miren , Goiti Urtzi , Garin Inazio
Published: April 2023

Myotis emarginatusseems fond of spiders and flies, a unique feeding style among European bats. The importance of each prey type varies among studies, so this paper aims to expand on the knowledge to unveil the trophic niche ofM. emarginatusby studying its diet changes throughout the maternity season. We sampled five maternity colonies in the Basque Country every 2 weeks for the whole duration of the maternity season and studied their diet using DNA metabarcoding methods. We observed significant changes in diet diversity and composition. At the beginning of the season,M. emarginatusconsumed a variety of prey orders, Diptera being the most abundant; but as the season progressed, the relative consumption of Araneae increased. By August, 80% of the weighted percentage of occurrences (wPOO) corresponded to the orb-web-building spiderAraneus diadematus. Orb-web-building spiders need habitats of high vertical complexity to grow in abundance. Therefore, conserving them is essential to preserve attractive hunting grounds for colonies ofM. emarginatus. Besides, diurnal flies, mainlyStomoxys calcitrans, were also considerably consumed in the colonies studied, which can become detrimental to the well-being of cattle, and can act as a vector of many diseases.
Parathyroid adenoma mimicking bethesda class III follicular thyroidal lesion: A case report
Authors: Peterson Caspar J. , Klasen Jennifer M. , Bubendorf Lukas , Freitag Martin , Delko Tarik , Lazaridis Ioannis I.
Published: April 2023

Abstract

Introduction and importance

Although the majority of thyroid lesions are benign, diagnostic workup including fine needle aspiration biopsy cytology is important to rule out cancerous lesions. However, cytological findings may pose challenges in interpretation because of similarities in cytomorphological features between certain thyroid nodules and parathyroid tissue. Similarly, parathyroid lesions may go unnoticed for a long period of time because they are misinterpreted as thyroid lesions and patients with parathyroid lesions are typically oligo- or asymptomatic for a long period of time.

Case presentation

We present the case of a 57-year-old female patient who was under observation for a hormone inactive mildly suspicious thyroid nodule for eight years before the suspected thyroid nodule was found to be a parathyroid adenoma. Repeated fine needle aspiration biopsies showed cytomorphological features of Bethesda Class III thyroid nodules and the patient was asymptomatic throughout all consultations. Finally, a pathological hip fracture and symptomatic kidney stone prompted further diagnostic work-up, confirming primary hyperparathyroidism and exposing the suspected thyroid lesion for a parathyroid adenoma. After focused parathyroidectomy the patient fully recovered.

Clinical discussion

Systematic blood sampling for Calcium and parathyroid hormone levels, which has to become part of the usual work up for suspicious thyroid nodules, may have exposed the diagnosis earlier preventing secondary complications.

Conclusion

This case highlights one of the major pitfalls in ultrasound interpretation and fine needle aspiration biopsy of the thyroid gland. Physicians need to be aware of these difficulties during the diagnostic work-up.

Highlights
Effects of dietary vitamins on obesity-related metabolic parameters
Authors: Lee Chooi Yeng
Published: April 2023

Type 2 diabetes mellitus (T2DM) is one of the leading causes of death worldwide. Genetic factors, some underlying medical conditions, and obesity are risk factors of T2DM. Unlike other risk factors which are non-modifiable, obesity is preventable and usually treatable, and is largely contributed by lifestyle factors. Management of these lifestyle factors may curb the development of T2DM and reduces T2DM prevalence. Dietary vitamins have been recommended as a lifestyle modification intervention to support obesity treatment. Vitamins correlate negatively with body weight, body mass index and body composition. Some of the vitamins may also have anti-adipogenic, anti-inflammatory and antioxidant effects. However, results from pre-clinical and clinical studies of the effects of vitamins on obesity are inconsistent. A clear understanding of the effects of vitamins on obesity will help determine dietary intervention that is truly effective in preventing and treating obesity as well as obesity-related complications including T2DM. This article reviews existing evidences of the effects of vitamin supplementation on obesity and obesity-related metabolic status.
Divine subjectivity and intersubjectivity
Authors: Zagzebski Linda
Published: April 2023

This article expands my previous work on omnisubjectivity, the divine property of having a complete and perfect grasp of the subjective states of all beings who have such states. By a subjective state I mean a conscious state as that state is experienced by the one who has it. I argue that only a being with subjectivity can be omnisubjective, and therefore, God has subjective states. The article explores the subjectivity of God as it applies to the Christian doctrines of the Trinity and the Incarnation, focusing on the important difference between a person and an instance of a nature. I propose that the uniqueness of persons is grounded in their unique subjective states, not their objective nature. Each person of the Trinity has a unique point of view and unique subjectivity even though they share an objective divine nature instantiated in a single divine being. The Son has a single set of subjective states before, during, and after the Incarnation. Each member of the Trinity is omnisubjective and fully grasps the unique subjective states of each other person of the Trinity. The perfect comprehension of each other while remaining unique persons is a model of perfect love within a community of persons.
Abortion and Directive Genetic Counseling
Authors: Kearney Matthew
Published: April 2023

This multi-method study uses statistical and comparative-historical investigations to find that abortion values shape genetic counseling practices across societies. Genetic counselors and genetically interested social scientists have long questioned, but never systematically demonstrated, whether this relationship exists. Genetic counseling data are drawn from cross-national surveys of genetic counselors (n= 2,906) from the mid-1990s, the key historical moment after this profession was globally established but before potentially confounding transnational professional effects. Data focus on Trisomy 21, severe open spina bifida, and Huntington’s chorea. Abortion data are drawn from a new comparative-historical investigation of abortion attitudes in 36 countries based on law, frequency of policy debate, incidence rates, and public opinion polling. The key overall finding is that the more controversial abortion is within a society, the less directive genetic counselors are willing to be, whereas the less controversial abortion is, the more directive the counseling. Polynomial regressions,t-tests, likelihood ratios, and Wald tests provide statistical evidence for the relationship observed through qualitative clustering.
Ice Shelf Basal Melt Sensitivity to Tide‐Induced Mixing Based on the Theory of Subglacial Plumes
Authors: Anselin J. , Reed B. C. , Jenkins A. , Green J. A. M.
Published: April 2023

Tidal currents are known to influence basal melting of Antarctic ice shelves through two types of mechanisms: local processes taking place within the boundary current adjacent to the ice shelf‐ocean interface and far‐field processes influencing the properties of water masses within the cavity. The separate effects of these processes are poorly understood, limiting our ability to parameterize tide‐driven ice shelf‐ocean interactions. Here we focus on the small‐scale processes within the boundary current. We apply a one‐dimensional plume model to a range of ice base geometries characteristic of Antarctic ice shelves to study the sensitivity of basal melt rates to different representations of tide‐driven turbulent mixing processes. Our simulations demonstrate that tides can either increase or decrease melt rates depending on the approach chosen to parameterize entrainment of ambient water into the turbulent plume layer, a process not yet well constrained by observations. A theoretical assessment based on an analogy with tidal bottom boundary layers suggests that tide‐driven shear at the ice shelf‐ocean interface enhances mixing through the pycnocline. Under this assumption our simulations predict a tide‐induced increase in melt and freeze rates along the base of the ice shelf, with the strongest plume path‐integrated effects for cold cavities (up to +400% in the realistic set up). An approximation is provided to account for this response in basal melt rate parameterizations that neglect the effect of tide‐induced turbulent mixing.
Investigation of Martian Regional Crustal Structure Near the Dichotomy Using S1222a Surface‐Wave Group Velocities
Authors: Xu Zongbo , Broquet Adrien , Fuji Nobuaki , Kawamura Taichi , Lognonné Philippe , Montagner Jean‐Paul , Pan Lu , Schimmel Martin , Stutzmann Eléonore , Banerdt William Bruce
Published: April 2023

Knowledge of Martian crust and uppermost mantle aid us studying the planet's evolution. NASA's InSight mission provides seismic data being used to reveal the interior structure. Most studies have focused on the crustal structure beneath InSight lander, but the seismic structure of other regions has remained poorly known. We use surface‐wave data to investigate the crustal structure of a large region along the Medusa Fossae Formation and the dichotomy. We adopt the largest‐magnitude marsquake (S1222a) that has been recorded, which provides both Rayleigh‐ and Love‐wave signals. We measure and jointly invert these surface‐wave fundamental‐mode group velocities from ∼15 to 40 s to estimate the average 1D isotropic velocity models. These models includes a high‐velocity layer at ∼7‐km depth, which could be due to a regional basaltic activity or regional stress. Our models also indicate that a common intra‐crustal structure (∼12–40 km depth) may exist in this region along the dichotomy.
Predictors of placebo response in three large clinical trials of the V1a receptor antagonist balovaptan in autism spectrum disorder
Authors: Tobe Russell , Zhu Yajing , Gleissl Teresa , Rossomanno Simona , Veenstra-VanderWeele Jeremy , Smith Janice , Hollander Eric
Published: April 2023

High rates of placebo response are increasingly implicated in failed autism spectrum disorder (ASD) clinical trials. Despite this, there are limited investigations of placebo response in ASD. We sought to identify baseline predictors of placebo response and quantify their influence on clinical scales of interest for three harmonized randomized clinical trials of balovaptan, a V1a receptor antagonist. We employed a two-step approach to identify predictors of placebo response on the Vineland-II two-domain composite (2DC) (primary outcome and a caregiver measure) and Clinical Global Impression (CGI) scale (secondary outcome and a clinician measure). The initial candidate predictor set of variables pertained to participant-level, site-specific, and protocol-related factors. Step 1 aimed to identify influential predictors of placebo response using Least Absolute Shrinkage and Selection Operator (LASSO) regression, while Step 2 quantified the influence of predictors via linear regression. Results were validated through statistical bootstrapping approaches with 500 replications of the analysis dataset. The pooled participant-level dataset included individuals with ASD aged 5 to 62 years (mean age 21 [SD 10]), among which 263 and 172 participants received placebo at Weeks 12 and 24, respectively. Although no influential predictors were identified for CGI, findings for Vineland-II 2DC are robust and informative. Decreased placebo response was predicted by higher baseline Vineland-II 2DC (i.e., more advanced adaptive function), longer trial duration, and European (vs United States) sites, while increased placebo response was predicted by commercial (vs academic) sites, attention deficit hyperactivity disorder and depression. Identification of these factors may be useful in anticipating and mitigating placebo response in drug development efforts in ASD and across developmental and psychiatric conditions.
Fatty acid desaturation by stearoyl-CoA desaturase-1 controls regulatory T cell differentiation and autoimmunity
Authors: Grajchen Elien , Loix Melanie , Baeten Paulien , Côrte-Real Beatriz F. , Hamad Ibrahim , Vanherle Sam , Haidar Mansour , Dehairs Jonas , Broos Jelle Y. , Ntambi James M. , Zimmermann Robert , Breinbauer Rolf , Stinissen Piet , Hellings Niels , Verberk Sanne G. S. , Kooij Gijs , Giera Martin , Swinnen Johannes V. , Broux Bieke , Kleinewietfeld Markus , Hendriks Jerome J. A. , Bogie Jeroen F. J.
Published: April 2023

The imbalance between pathogenic and protective T cell subsets is a cardinal feature of autoimmune disorders such as multiple sclerosis (MS). Emerging evidence indicates that endogenous and dietary-induced changes in fatty acid metabolism have a major impact on both T cell fate and autoimmunity. To date, however, the molecular mechanisms that underlie the impact of fatty acid metabolism on T cell physiology and autoimmunity remain poorly understood. Here, we report that stearoyl-CoA desaturase-1 (SCD1), an enzyme essential for the desaturation of fatty acids and highly regulated by dietary factors, acts as an endogenous brake on regulatory T-cell (Treg) differentiation and augments autoimmunity in an animal model of MS in a T cell-dependent manner. Guided by RNA sequencing and lipidomics analysis, we found that the absence of Scd1 in T cells promotes the hydrolysis of triglycerides and phosphatidylcholine through adipose triglyceride lipase (ATGL). ATGL-dependent release of docosahexaenoic acid enhanced Treg differentiation by activating the nuclear receptor peroxisome proliferator-activated receptor gamma. Our findings identify fatty acid desaturation by SCD1 as an essential determinant of Treg differentiation and autoimmunity, with potentially broad implications for the development of novel therapeutic strategies and dietary interventions for autoimmune disorders such as MS.
DAXX drives de novo lipogenesis and contributes to tumorigenesis
Authors: Mahmud Iqbal , Tian Guimei , Wang Jia , Hutchinson Tarun E. , Kim Brandon J. , Awasthee Nikee , Hale Seth , Meng Chengcheng , Moore Allison , Zhao Liming , Lewis Jessica E. , Waddell Aaron , Wu Shangtao , Steger Julia M. , Lydon McKenzie L. , Chait Aaron , Zhao Lisa Y. , Ding Haocheng , Li Jian-Liang , Purayil Hamsa Thayele , Huo Zhiguang , Daaka Yehia , Garrett Timothy J. , Liao Daiqing
Published: April 2023

Cancer cells exhibit elevated lipid synthesis. In breast and other cancer types, genes involved in lipid production are highly upregulated, but the mechanisms that control their expression remain poorly understood. Using integrated transcriptomic, lipidomic, and molecular studies, here we report that DAXX is a regulator of oncogenic lipogenesis. DAXX depletion attenuates, while its overexpression enhances, lipogenic gene expression, lipogenesis, and tumor growth. Mechanistically, DAXX interacts with SREBP1 and SREBP2 and activates SREBP-mediated transcription. DAXX associates with lipogenic gene promoters through SREBPs. Underscoring the critical roles for the DAXX-SREBP interaction for lipogenesis, SREBP2 knockdown attenuates tumor growth in cells with DAXX overexpression, and DAXX mutants unable to bind SREBP1/2 have weakened activity in promoting lipogenesis and tumor growth. Remarkably, a DAXX mutant deficient of SUMO-binding fails to activate SREBP1/2 and lipogenesis due to impaired SREBP binding and chromatin recruitment and is defective of stimulating tumorigenesis. Hence, DAXX’s SUMO-binding activity is critical to oncogenic lipogenesis. Notably, a peptide corresponding to DAXX’s C-terminal SUMO-interacting motif (SIM2) is cell-membrane permeable, disrupts the DAXX-SREBP1/2 interactions, and inhibits lipogenesis and tumor growth. These results establish DAXX as a regulator of lipogenesis and a potential therapeutic target for cancer therapy.
Inducible expression of interleukin-12 augments the efficacy of affinity-tuned chimeric antigen receptors in murine solid tumor models
Authors: Yang Yanping , Yang Huan , Alcaina Yago , Puc Janusz , Birt Alyssa , Vedvyas Yogindra , Gallagher Michael , Alla Srinija , Riascos Maria Cristina , McCloskey Jaclyn E. , Du Karrie , Gonzalez-Valdivieso Juan , Min Irene M. , de Stanchina Elisa , Britz Matt , von Hofe Eric , Jin Moonsoo M.
Published: April 2023

The limited number of targetable tumor-specific antigens and the immunosuppressive nature of the microenvironment within solid malignancies represent major barriers to the success of chimeric antigen receptor (CAR)-T cell therapies. Here, using epithelial cell adhesion molecule (EpCAM) as a model antigen, we used alanine scanning of the complementarity-determining region to fine-tune CAR affinity. This allowed us to identify CARs that could spare primary epithelial cells while still effectively targeting EpCAMhigh tumors. Although affinity-tuned CARs showed suboptimal antitumor activity in vivo, we found that inducible secretion of interleukin-12 (IL-12), under the control of the NFAT promoter, can restore CAR activity to levels close to that of the parental CAR. This strategy was further validated with another affinity-tuned CAR specific for intercellular adhesion molecule-1 (ICAM-1). Only in affinity-tuned CAR-T cells was NFAT activity stringently controlled and restricted to tumors expressing the antigen of interest at high levels. Our study demonstrates the feasibility of specifically gearing CAR-T cells towards recognition of solid tumors by combining inducible IL-12 expression and affinity-tuned CAR.
WHIM Syndrome-linked CXCR4 mutations drive osteoporosis
Authors: Anginot Adrienne , Nguyen Julie , Abou Nader Zeina , Rondeau Vincent , Bonaud Amélie , Kalogeraki Maria , Boutin Antoine , Lemos Julia P. , Bisio Valeria , Koenen Joyce , Hanna Doumit Sakr Lea , Picart Amandine , Coudert Amélie , Provot Sylvain , Dulphy Nicolas , Aurrand-Lions Michel , Mancini Stéphane J. C. , Lazennec Gwendal , McDermott David H. , Guidez Fabien , Blin-Wakkach Claudine , Murphy Philip M. , Cohen-Solal Martine , Espéli Marion , Rouleau Matthieu , Balabanian Karl
Published: April 2023

WHIM Syndrome is a rare immunodeficiency caused by gain-of-function CXCR4 mutations. Here we report a decrease in bone mineral density in 25% of WHIM patients and bone defects leading to osteoporosis in a WHIM mouse model. Imbalanced bone tissue is observed in mutant mice combining reduced osteoprogenitor cells and increased osteoclast numbers. Mechanistically, impaired CXCR4 desensitization disrupts cell cycle progression and osteogenic commitment of skeletal stromal/stem cells, while increasing their pro-osteoclastogenic capacities. Impaired osteogenic differentiation is evidenced in primary bone marrow stromal cells from WHIM patients. In mice, chronic treatment with the CXCR4 antagonist AMD3100 normalizes in vitro osteogenic fate of mutant skeletal stromal/stem cells and reverses in vivo the loss of skeletal cells, demonstrating that proper CXCR4 desensitization is required for the osteogenic specification of skeletal stromal/stem cells. Our study provides mechanistic insights into how CXCR4 signaling regulates the osteogenic fate of skeletal cells and the balance between bone formation and resorption.
Future strengthening of the Nordic Seas overturning circulation
Authors: Årthun Marius , Asbjørnsen Helene , Chafik Léon , Johnson Helen L. , Våge Kjetil
Published: April 2023

The overturning circulation in the Nordic Seas involves the transformation of warm Atlantic waters into cold, dense overflows. These overflow waters return to the North Atlantic and form the headwaters to the deep limb of the Atlantic meridional overturning circulation (AMOC). The Nordic Seas are thus a key component of the AMOC. However, little is known about the response of the overturning circulation in the Nordic Seas to future climate change. Here we show using global climate models that, in contrast to the North Atlantic, the simulated density-space overturning circulation in the Nordic Seas increases throughout most of the 21st century as a result of enhanced horizontal circulation and a strengthened zonal density gradient. The increased Nordic Seas overturning is furthermore manifested in the overturning circulation in the eastern subpolar North Atlantic. A strengthened Nordic Seas overturning circulation could therefore be a stabilizing factor in the future AMOC.
Assessing the impact of the global subsea telecommunications network on sedimentary organic carbon stocks
Authors: Clare M. A. , Lichtschlag A. , Paradis S. , Barlow N. L. M.
Published: April 2023

The sequestration of organic carbon in seafloor sediments plays a key role in regulating global climate; however, human activities can disturb previously-sequestered carbon stocks, potentially reducing the capacity of the ocean to store CO2. Recent studies revealed profound seafloor impacts and sedimentary carbon loss due to fishing and shipping, yet most other human activities in the ocean have been overlooked. Here, we present an assessment of organic carbon disturbance related to the globally-extensive subsea telecommunications cable network. Up to 2.82–11.26 Mt of organic carbon worldwide has been disturbed as a result of cable burial, in water depths of up to 2000 m. While orders of magnitude lower than that disturbed by bottom fishing, it is a non-trivial amount that is absent from global budgets. Future offshore developments that disturb the seafloor should consider the safeguarding of carbon stocks, across the full spectrum of Blue Economy industries.
The fragmentation-induced fluidisation of pyroclastic density currents
Authors: Breard Eric C. P. , Dufek Josef , Charbonnier Sylvain , Gueugneau Valentin , Giachetti Thomas , Walsh Braden
Published: April 2023

Pyroclastic density currents (PDCs) are the most lethal volcanic process on Earth. Forecasting their inundation area is essential to mitigate their risk, but existing models are limited by our poor understanding of their dynamics. Here, we explore the role of evolving grain-size distribution in controlling the runout of the most common PDCs, known as block-and-ash flows (BAFs). Through a combination of theory, analysis of deposits and experiments of natural mixtures, we show that rapid changes of the grain-size distribution transported in BAFs result in the reduction of pore volume (compaction) within the first kilometres of their runout. We then use a multiphase flow model to show how the compressibility of granular mixtures leads to fragmentation-induced fluidisation (FIF) and excess pore-fluid pressure in BAFs. This process dominates the first ~2 km of their runout, where the effective friction coefficient is progressively reduced. Beyond that distance, transport is modulated by diffusion of the excess pore pressure. Fragmentation-induced fluidisation provides a physical basis to explain the decades-long use of low effective friction coefficients used in depth-averaged simulations required to match observed flow inundation.
Unsteady natural convection flow of blood Casson nanofluid (Au) in a cylinder: nano-cryosurgery applications
Authors: Azmi Wan Faezah Wan , Mohamad Ahmad Qushairi , Jiann Lim Yeou , Shafie Sharidan
Published: April 2023

Nano-cryosurgery is one of the effective ways to treat cancerous cells with minimum harm to healthy adjacent cells. Clinical experimental research consumes time and cost. Thus, developing a mathematical simulation model is useful for time and cost-saving, especially in designing the experiment. Investigating the Casson nanofluid's unsteady flow in an artery with the convective effect is the goal of the current investigation. The nanofluid is considered to flow in the blood arteries. Therefore, the slip velocity effect is concerned. Blood is a base fluid with gold (Au) nanoparticles dispersed in the base fluid. The resultant governing equations are solved by utilising the Laplace transform regarding the time and the finite Hankel transform regarding the radial coordinate. The resulting analytical answers for velocity and temperature are then displayed and visually described. It is found that the temperature enhancement occurred by arising nanoparticles volume fraction and time parameter. The blood velocity increases as the slip velocity, time parameter, thermal Grashof number, and nanoparticles volume fraction increase. Whereas the velocity decreases with the Casson parameter. Thus, by adding Au nanoparticles, the tissue thermal conductivity enhanced which has the consequence of freezing the tissue in nano-cryosurgery treatment significantly.
A small fishing vessel recognition method using transfer learning based on laser sensors
Authors: Zheng Jianli , Cao Jianjun , Yuan Kun , Liu Yang
Published: April 2023

The management of small vessels has always been key to maritime administration. This paper presents a novel method for recognizing small fishing vessels based on laser sensors. Using four types of small fishing vessels as targets, a recognition method for small fishing vessels based on Markov transition field (MTF) time-series images and VGG-16 transfer learning is proposed. In contrast to conventional methods, this study uses polynomial fitting to obtain the contours of a fishing vessel and transforms one-dimensional vessel contours into two-dimensional time-series images using the MTF coding method. The VGG-16 model is used for the recognition process, and migration learning is applied to improve the results. The UCR time-series public dataset is used as a transfer learning dataset for the MTF time-series image encoding. The experiment demonstrates that the proposed method exhibits higher accuracy and performance than 1D-CNN and other general neural network models, and the highest accuracy rate is 98.92%.
Hierarchical data structures for flowchart
Authors: Zhang Peng , Dou Wenzhang , Liu Huaping
Published: April 2023

Flowcharts have broad applications in the fields of software development, engineering design, and scientific experimentation. Current flowchart data structure is mainly based on the adjacency list, cross-linked list, and adjacency matrix of the graph structure. Such design originated from the fact that any two nodes could have a connection relationship. But flowcharts have clear regularities, and their nodes have a certain inflow or outflow relationship. When graph structures such as an adjacency table or an adjacency matrix are used to store a flowchart, there is a large room for optimization in terms of traversal time and storage complexities, as well as usage convenience. In this paper we propose two hierarchical data structures for flowchart design. In the proposed structures, a flowchart is composed of levels, layers, and numbered nodes. The nodes between layers are connected according to a certain set of systematic design rules. Compared with the traditional graph data structures, the proposed schemes significantly reduce the storage space, improve the traversal efficiency, and resolve the problem of nesting between sub-charts. Experimental data based on flowchart examples used in this paper show that, compared with adjacency list, the hierarchical table data structure reduces the traversal time by 50% while their storage spaces are similar; compared with adjacency matrix, the hierarchical matrix data structure reduces the traversal time by nearly 70% and saves the storage space by about 50%. The proposed structures could have broad applications in flowchart-based software development, such as low-code engineering for smart industrial manufacturing.
Optimal dose of normal saline for confirming correct peripheral venous access with precordial Doppler ultrasonography in children
Authors: Omori Ayaka , Otaki Yuji , Tanaka Motoi , Miyazu Mitsunori , Ohde Sachiko , Kojima Taiki
Published: April 2023

Precordial Doppler ultrasound technology can be utilized to confirm correct peripheral intravenous vascular (PIV) access in children during surgery. This study aimed to determine the minimally required dose of normal saline (NS) for confirming correct PIV access. Healthy children were randomly allocated to receive a 0.1 mL/kg, 0.3 mL/kg, or 0.5 mL/kg dose of NS injected via PIV access. Two independent raters judged the change in the recorded precordial Doppler sound test (S-test) before and after NS injection. Typically, rapid injection of NS increased the pitch of the heartbeat as the injection volume increased. Changes in blood flow velocity test (V-test) results were evaluated using a cut-off value of 1 cm/s. Both in the S- and V-tests, the detection rate of correct PIV access was lower with 0.1 mL/kg NS than with 0.3 mL/kg or 0.5 mL/kg. Logistic regression analysis showed that the positive results in both the S- and V-tests were significantly decreased with a 0.1 mL/kg NS; no significant difference was observed with a 0.3 mL/kg NS (reference dose: 0.5 mL/kg). These results suggest 0.3 mL/kg is the minimally required dose of NS for confirming correct PIV access. This study is registered with the University Hospital Medical Information Network (UMIN000041330).
Hierarchical settlement behaviours of coral larvae to common coralline algae
Authors: Abdul Wahab M. A. , Ferguson S. , Snekkevik V. K. , McCutchan G. , Jeong S. , Severati A. , Randall C. J. , Negri A. P. , Diaz-Pulido G.
Published: April 2023

Natural regeneration of degraded reefs relies on the recruitment of larvae to restore populations. Intervention strategies are being developed to enhance this process through aquaculture production of coral larvae and their deployment as spat. Larval settlement relies on cues associated with crustose coralline algae (CCA) that are known to induce attachment and metamorphosis. To understand processes underpinning recruitment, we tested larval settlement responses of 15 coral species, to 15 species of CCA from the Great Barrier Reef (GBR). CCA in the family Lithophyllaceae were overall the best inducer across most coral species, with Titanoderma cf. tessellatum being the most effective species that induced at least 50% settlement in 14 of the coral species (mean 81%). Taxonomic level associations were found, with species of Porolithon inducing high settlement in the genus Acropora; while a previously understudied CCA, Sporolithon sp., was a strong inducer for the Lobophyllidae. Habitat-specific associations were detected, with CCA collected from similar light environment as the coral inducing higher levels of settlement. This study revealed the intimate relationships between coral larvae and CCA and provides optimal coral-algal species pairings that could be utilized to increase the success of larval settlement to generate healthy spat for reef restoration.