bluuebunny/crossref_metadata_2025 huggingface dataset:
CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma
Authors: Giraud Julie , Seeneevassen Lornella , Rousseau Benoit , Bouriez Damien , Sifré Elodie , Giese Alban , Nguyen Tra Ly , Tiffon Camille , Lippi Yannick , Azzi-Martin Lamia , Pannequin Julie , Ménard Armelle , Bessède Emilie , Staedel Cathy , Mégraud Francis , Belleannée Geneviève , Lehours Philippe , Gronnier Caroline , Dubus Pierre , Varon Christine
Published: December 2022

Background

Cancer stem cells (CSCs) are at the origin of tumour initiation and progression in gastric adenocarcinoma (GC). However, markers of metastasis-initiating cells remain unidentified in GC. In this study, we characterized CD44 variants expressed in GC and evaluated the tumorigenic and metastatic properties of CD44v3+ cells and their clinical significance in GC patients.

Methods

Using GC cell lines and patient-derived xenografts, we evaluated CD44+ and CD44v3+ GC cells molecular signature and their tumorigenic, chemoresistance, invasive and metastatic properties, and expression in patients-derived tissues.

Results

CD44v3+ cells, which represented a subpopulation of CD44+ cells, were detected in advanced preneoplastic lesions and presented CSCs chemoresistance and tumorigenic properties in vitro and in vivo. Molecular and functional analyses revealed two subpopulations of gastric CSCs: CD44v3+ CSCs with an epithelial-mesenchymal transition (EMT)-like signature, and CD44+/v3– CSCs with an epithelial-like signature; both were tumorigenic but CD44v3+ cells showed higher invasive and metastatic properties in vivo. CD44v3+ cells detected in the primary tumours of GC patients were associated with a worse prognosis.

Conclusion

CD44v3 is a marker of a subpopulation of CSCs with metastatic properties in GC. The identification of metastasis-initiating cells in GC represents a major advance for further development of anti-metastatic therapeutic strategies.
The European carbon border adjustment mechanism: a small step in the right direction
Authors: Korpar Niko , Larch Mario , Stöllinger Roman
Published: December 2022

We estimate the effects of a European Carbon Border Adjustment (CBA) mechanism on exports, real GDP, welfare and emissions using the multi-region, multi-sector structural gravity model of Larch and Wanner (2017). Incorporating the main industries covered in the proposal of the European Commission from mid-2021, as well as its other design features, and assuming prevailing CO2 prices, we find only small effects of the European CBA mechanism. EU exports are estimated to decline by 0.04%, while CO2 emissions in EU countries increase by 0.24%. These negligible results mask larger adjustments at the sectoral level. The structural changes will shift the EU economy towards more emission-intensive industries, which will make achieving its climate goals harder. On the positive side, the European CBA mechanism will reduce global emissions by 0.08%. Given the minute economic costs in terms of GDP and welfare losses, the CBA mechanism seems an appropriate policy tool, though its proposed design will not be able to make a significant contribution to mitigating global climate change.
On Group Invariants Determined by Modular Group Algebras: Even Versus Odd Characteristic
Authors: García-Lucas Diego , del Río Ángel , Stanojkovski Mima
Published: December 2022

Let p be a an odd prime and let G be a finite p-group with cyclic commutator subgroup $G^{\prime }$

G

′

. We prove that the exponent and the abelianization of the centralizer of $G^{\prime }$

G

′

in G are determined by the group algebra of G over any field of characteristic p. If, additionally, G is 2-generated then almost all the numerical invariants determining G up to isomorphism are determined by the same group algebras; as a consequence the isomorphism type of the centralizer of $G^{\prime }$

G

′

is determined. These claims are known to be false for p = 2.
Developing a Workflow Management System Simulation for Capturing Internal IaaS Behavioural Knowledge
Authors: Al-Haboobi Ali , Kecskemeti Gabor
Published: December 2022

Scientific workflows are becoming increasingly important for complex scientific applications. Conducting real experiments for large-scale workflows is challenging because they are very expensive and time consuming. A simulation is an alternative approach to a real experiment that can help evaluating the performance of workflow management systems (WMS) and optimise workflow management techniques. Although there are several workflow simulators available today, they are often user-oriented and treat the cloud as a black box. Unfortunately, this behaviour prevents the evaluation of the infrastructure level impact of the various decisions made by the WMSs. To address these issues, we have developed a WMS simulator (called DISSECT-CF-WMS) on DISSECT-CF that exposes the internal details of cloud infrastructures. DISSECT-CF-WMS enables better energy awareness by allowing the study of schedulers for physical machines. It also enables dynamic provisioning to meet the resource needs of the workflow application while considering the provisioning delay of a VM in the cloud. We evaluated our simulation extension by running several workflow applications on a given infrastructure. The experimental results show that we can investigate different schedulers for physical machines on different numbers of virtual machines to reduce energy consumption. The experiments also show that DISSECT-CF-WMS is up to 295× faster than WorkflowSim and still provides equivalent results. The experimental results of auto-scaling show that it can optimise makespan, energy consumption and VM utilisation in contrast to static VM provisioning.
The Role of Guadua Bamboo in Land Management and Indigenous Perspectives on Bamboo Ecosystems in Southwestern Amazonia
Authors: Virtanen Pirjo Kristiina , Apurinã Francisco , Ruokolainen Kalle , Manchineri Lucas
Published: December 2022

We examine the Indigenous uses, oral histories, and knowledge of native Guadua bamboo species in southwestern Amazonia. Two Guadua species form dense stands in which individual plants die en masse at regular intervals of about 28 years. Scholars suggested that pre-colonial earth builders took advantage of these die-off events as a natural aid in removing the forest to construct geometric earthworks. Our results show that Guadua species have a significant position in Indigenous socio-cosmologies, land use, and as a protector of diverse resources. Indigenous ontological understandings cannot be separated from discussions of the abundance and geographical distribution of Guadua as a critical controlling factor in the vegetation structure and function of southwestern Amazonian rain forests. Furthermore, oral histories point to the connection between land management and bamboo, as well as bamboo and the use of fire, conforming to the suggestion of opening ceremonial spaces in bamboo patches in pre-colonial earthwork societies.
TRPA1/M8 agonists upregulate ciliary beating through the pannexin-1 channel in the human nasal mucosa
Authors: Nguyen Thi Nga , Koga Yuma , Wakasugi Tetsuro , Kitamura Takuro , Suzuki Hideaki
Published: December 2022

Background

Nasal breathing is important for maintaining physiological respiration. However, airflow in the nasal cavity has an inherent cooling effect and may suppress ciliary beating, an essential frontline defense in the airway. Nasal airflow is thought to be perceived by thermoreceptors for cool temperatures. We herein investigated the effect of the activation of thermosensitive transient receptor potentials (TRPs) for cool/cold temperatures on ciliary beating to search for a compensatory mechanism.

Methods

Inferior turbinates were collected from patients with chronic hypertrophic rhinitis. Ex vivo ciliary beat frequency (CBF) and ATP release were measured using a high-speed digital video camera and by luciferin-luciferase assay, respectively. Intracellular Ca2+ ([Ca2+]i) imaging of isolated ciliated cells was performed using Fluo-8. The nasal mucosae were also subjected to fluorescence immunohistochemistry and real-time RT-PCR for TRPA1/TRPM8.

Results

CBF was significantly increased by adding either cinnamaldehyde (TRPA1 agonist) or l-menthol (TRPM8 agonist). This increase was inhibited by pannexin-1 blockers, carbenoxolone and probenecid. Cinnamaldehyde and l-menthol also increased the ATP release from the nasal mucosa and [Ca2+]i of isolated ciliated cells. Immunohistochemistry detected TRPA1 and TRPM8 on the epithelial surface including the cilia and in the submucosal nasal glands. Existence of these receptors were confirmed at the transcriptional level by real-time RT-PCR.

Conclusions

These results indicate the stimulatory effect of the activation of TRPA1/TRPM8 on ciliary beating in the nasal mucosa, which would be advantageous to maintain airway mucosal defense against the fall of temperature under normal nasal breathing. This stimulatory effect is likely to be mediated by pannexin-1.
Deep learning-based system for automatic prediction of triple-negative breast cancer from ultrasound images
Authors: Boulenger Alexandre , Luo Yanwen , Zhang Chenhui , Zhao Chenyang , Gao Yuanjing , Xiao Mengsu , Zhu Qingli , Tang Jie
Published: December 2022

To develop a deep-learning system for the automatic identification of triple-negative breast cancer (TNBC) solely from ultrasound images. A total of 145 patients and 831 images were retrospectively enrolled at Peking Union College Hospital from April 2018 to March 2019. Ultrasound images and clinical information were collected accordingly. Molecular subtypes were determined from immunohistochemical (IHC) results. A CNN with VGG-based architecture was then used to predict TNBC. The model’s performance was evaluated using randomized k-fold stratified cross-validation. A t-SNE analysis and saliency maps were used for model visualization. TNBC was identified in 16 of 145 (11.03%) patients. One hundred fifteen (80%) patients, 15 (10%) patients, and 15 (10%) patients formed the train, validation, and test set respectively. The deep learning system exhibits good efficacy, with an AUC of 0.86 (95% CI: 0.64, 0.95), an accuracy of 85%, a sensitivity of 86%, a specificity of 86%, and an F1-score of 0.74. In addition, the internal representation features learned by the model showed clear differentiation across molecular subtype groups. Such a deep learning system can automatically predict triple-negative breast cancer preoperatively and accurately. It may help to get to more precise and comprehensive management.

Graphical Abstract
MicroRNA-149 Regulates Proliferation, Migration, and Invasion of Pituitary Adenoma Cells by Targeting ADAM12 and MMP14
Authors: Zhang Zhuo , Schäfer Agnes , Voellger Benjamin , Wang Jun-wen , Lei Ting , Nimsky Christopher , Bartsch Jörg W.
Published: December 2022

Objective

Pituitary adenomas (PAs) can adapt an aggressive phenotype by invading adjacent brain structures with rapid cellular proliferation. Previous studies demonstrated that excessive expression of metalloproteases ADAM12 and MMP-14 is instrumental for the active proliferation and invasiveness of PA cells in vitro and of tumors in vivo. However, the mechanisms regulating ADAM12 and MMP-14 expression in PAs remain unclear.

Methods

Target gene prediction and transcriptomic profiling of invasive vs. noninvasive human PA samples were performed to identify miRNA species potentially involved in the regulation of ADAM12 and MMP14. For cellular analyses of miRNA functions, two mouse PA cell lines (AtT20 and TtT/GF) were transfected with miR-149-3p and miR-149-5p, respectively. The effects of miR-149 (3p and 5p) on expression levels of ADAM12 and MMP14 were determined by Western blotting followed by an analysis of proliferation and colony formation assays, scratch migration assays, and invasion assays.

Results

A significant downregulation of miRNA-149 was observed in invasive vs. noninvasive PA (0.32 vs. 0.09, P<0.0001). In AtT-20 and TtT/GF mouse PAs cells, transfection of mimic miRNA-149 (3p and 5p) caused a significantly reduced cell proliferation and matrigel invasion, whilst the effect on cell migration was less pronounced. Both strands of miRNA-149 (3p and 5p) markedly reduced protein levels of ADAM12 and MMP-14 by at least 40% in both cell lines.

Conclusion

This study proved that the invasiveness of PA cells is, at least partly, regulated by miRNA-149-dependent expression of ADAM12 and MMP-14.
Competitive devaluations in the 1930s: myth or reality?
Authors: Ljungberg Jonas
Published: December 2022

This article is the first examination of competitive devaluation in the 1930s using data on exchange rates. It analyses the impact of currency changes on foreign trade flows of fourteen industrialized countries 1929–1939. It reviews the development of nominal and real effective exchange rates together with trade and economic growth and conducts a disaggregated analysis of trade and bilateral exchange rates with trade partners. Tests show that the beggar-thy-neighbour effects of exchange rate adjustments were few and temporary. Moreover, it is argued that currency depreciations were expansionary not only for countries that devalued but for the international economy as a whole. This argument draws on Ragnar Nurkse (Nurkse, International currency experience, Lessons of the Inter-War Period. League of Nations, 1944) who undeservingly has been associated with the notion of “competitive devaluation”. Nurkse showed that currency depreciations increased global monetary reserves, an observation that has gone remarkably overlooked in the literature.
Constraint relaxation for the discrete ordered median problem
Authors: Martínez-Merino Luisa I. , Ponce Diego , Puerto Justo
Published: December 2022

This paper compares different exact approaches to solve the Discrete Ordered Median Problem (DOMP). In recent years, DOMP has been formulated using set packing constraints giving rise to one of its most promising formulations. The use of this family of constraints, known as strong order constraints (SOC), has been validated in the literature by its theoretical properties and because their linear relaxation provides very good lower bounds. Furthermore, embedded in branch-and-cut or branch-price-and-cut procedures as valid inequalities, they allow one to improve computational aspects of solution methods such as CPU time and use of memory. In spite of that, the above mentioned formulations require to include another family of order constraints, e.g., the weak order constraints (WOC), which leads to coefficient matrices with elements other than {0,1}. In this work, we develop a new approach that does not consider extra families of order constraints and furthermore relaxes SOC -in a branch-and-cut procedure that does not start with a complete formulation- to add them iteratively using row generation techniques to certify feasibility and optimality. Exhaustive computational experiments show that it is advisable to use row generation techniques in order to only consider {0,1}-coefficient matrices modeling the DOMP. Moreover, we test how to exploit the problem structure. Implementing an efficient separation of SOC using callbacks improves the solution performance. This allows us to deal with bigger instances than using fixed cuts/constraints pools automatically added by the solver in the branch-and-cut for SOC, concerning both the formulation based on WOC and the row generation procedure.
Laser trimming for lithography-free fabrications of MoS2 devices
Authors: Xie Yong , Çakıroğlu Onur , Hu Wenshuai , He Kexin , Puebla Sergio , Pucher Thomas , Zhao Qinghua , Ma Xiaohua , Munuera Carmen , Castellanos-Gomez Andres
Published: December 2022

Single-layer MoS2 produced by mechanical exfoliation is usually connected to thicker and multilayer regions. We show a facile laser trimming method to insulate single-layer MoS2 regions from thicker ones. We demonstrate, through electrical characterization, that the laser trimming method can be used to pattern single-layer MoS2 channels with regular geometry and electrically disconnected from the thicker areas. Scanning photocurrent microscope further confirms that in the as-deposited flake (connected to a multilayer area) most of the photocurrent is being generated in the thicker flake region. After laser trimming, scanning photocurrent microscopy shows how only the single-layer MoS2 region contributes to the photocurrent generation. The presented method is a direct-write and lithography-free (no need of resist or wet chemicals) alternative to reactive ion etching process to pattern the flakes that can be easily adopted by many research groups fabricating devices with MoS2 and similar two-dimensional materials.
Implications of genetic variations, differential gene expression, and allele-specific expression on metformin response in drug-naïve type 2 diabetes
Authors: Vohra M. , Sharma A. R. , Mallya S. , Prabhu N. B. , Jayaram P. , Nagri S. K. , Umakanth S. , Rai P. S.
Published: December 2022

Purpose

Metformin is widely used to treat type 2 diabetes mellitus (T2DM) individuals. Clinically, inter-individual variability of metformin response is of significant concern and is under interrogation. In this study, a targeted exome and whole transcriptome analysis were performed to identify predictive biomarkers of metformin response in drug-naïve T2DM individuals.

Methods

The study followed a prospective study design. Drug-naïve T2DM individuals (n = 192) and controls (n = 223) were enrolled. T2DM individuals were administered with metformin monotherapy and defined as responders and non-responders based on their glycated haemoglobin change over three months. 146 T2DM individuals were used for the final analysis and remaining samples were lost during the follow-up. Target exome sequencing and RNA-seq was performed to analyze genetic and transcriptome profile. The selected SNPs were validated by genotyping and allele specific gene expression using the TaqMan assay. The gene prioritization, enrichment analysis, drug-gene interactions, disease-gene association, and correlation analysis were performed using various tools and databases.

Results

rs1050152 and rs272893 in SLC22A4 were associated with improved response to metformin. The copy number loss was observed in PPARGC1A in the non-responders. The expression analysis highlighted potential differentially expressed targets for predicting metformin response (n = 35) and T2DM (n = 14). The expression of GDF15, TWISTNB, and RPL36A genes showed a maximum correlation with the change in HbA1c levels. The disease-gene association analysis highlighted MAGI2 rs113805659 to be linked with T2DM.

Conclusion

The results provide evidence for the genetic variations, perturbed transcriptome, allele-specific gene expression, and pathways associated with metformin drug response in T2DM.
Increasing Use of Video Telehealth Among Veterans Experiencing Homelessness with Substance Use Disorder: Design of A Peer-Led Intervention
Authors: Garvin Lynn A. , Greenan Mary Alexis , Edelman E. Jennifer , Slightam Cindie , McInnes D. Keith , Zulman Donna M.
Published: December 2022

Telehealth offers promising opportunities, but also challenges, for veterans experiencing homelessness — during the COVID-19 pandemic and beyond. Recent research found low utilization of clinical video visits among homeless veterans receiving a VA tablet, and having a substance use disorder (SUD) further reduced visit likelihood. Hence, this study sought to identify unique barriers to telehealth use among veterans experiencing homelessness with a SUD and design an intervention to promote adoption. This qualitative study was guided by the Unified Theory of Acceptance and Use of Technology (UTAUT) model. The study’s three phases included veteran interviews (N = 28) to identify barriers and facilitators to video telehealth use and propose intervention candidates, a provider expert panel to obtain feedback on interventions, and a focus group with veterans to complete the intervention. Finally, a prototype was designed using the intervention mapping approach. Veteran interviews revealed that barriers to video telehealth included complex physical and mental health issues, lack of digital literacy, and insufficient technical support. Together, veterans and experts proposed five intervention candidates. In the end, a veteran focus group combined two candidates, peer-led digital training and motivational interviewing. Intervention mapping was used to design a “stepped care” intervention that trains and activates veterans at all skill levels. This study demonstrates how inclusion of expert and veteran views led to development of a novel intervention to support and sustain video telehealth use among veterans experiencing homeless with SUD.
Rolling bearing fault feature extraction method based on GWO-optimized adaptive stochastic resonance signal processing
Authors: Quan Zhenya , Zhang Xueliang
Published: December 2022

The failure of rolling bearings affects the function and precision of rotating machinery significantly, which has drawn lots of attention in this field. Dealing with the failure of rolling bearings, fault feature extraction is the first and most important problem. In this work, we convert the bearing fault signal into stochastic resonance dynamics equivalently. And, adaptive stochastic resonance is adopted to extract the fault signal feature. In addition, for industrial application of fault signal processing with large amplitude and noise intensity greater than 1, normalized scale transformation is introduced into adaptive stochastic resonance and then solved by fifth-order Runge–Kutta algorithm. Then, to further optimize the solving precision of stochastic resonance model, the scaling coefficient and step size of Runge–Kutta algorithm are chosen with the help of Grey Wolf Optimizer (GWO). Thus, we can obtain a fast convergence speed, high calculation accuracy and effective improvement of signal-to-noise ratio fault feature extraction method for rolling bearing fault signal processing. Finally, a comparation simulation was carried out to demonstrate the efficiency of the proposed method. Compared with Cuckoo Search Optimizer-based stochastic resonance signal processing method, the proposed method achieved a higher signal-to-noise ratio (SNR) to benefit the fault feature extraction. In summary, this work gives out a more practical and effective solution for rolling bearing fault feature extraction in rotating machinery fault diagnosis field.
Mapping gendered spaces and women’s rights in the modern egyptian public sphere
Authors: Abdelrazek-Alsiefy Amany
Published: December 2022

This paper draws on secularisation and feminist theories to analyse the intersection between political, religious and economic factors in defining the gendered borders and women’s rights in the modern Egyptian public sphere. However, this present study concludes that the struggle for power between Islamists and secular-oriented forces and the rise of interactive social media platforms in a patriarchal class society revived the heated debates on women's rights, gendered spaces and the role of religion in the public sphere. Discussions point to a wide range of Egyptians' responses to these issues and also suggest that a new feminist consciousness and behaviour are growing. This new feminist consciousness is more grounded in a socio-economic context than a religious one. Therefore, this study suggests a need for serious societal and legal discussions to re-actualise laws pertaining to women's rights and visibility in the public sphere. These laws and a pro-women discourse should cope with the current socio-economic context and individuals' needs and aspirations in their globalized societies.
Invariant family of leaf measures and the Ledrappier–Young property for hyperbolic equilibrium states
Authors: BEN OVADIA SNIR
Published: December 2022

The manifold M is a Riemannian, boundaryless, and compact manifold with
$\dim M\geq 2$
, and f is a
$C^{1+\beta }$
(
$\kern0.3pt\beta>0$
) diffeomorphism of M.
$\varphi $
is a Hölder continuous potential on M. We construct an invariant and absolutely continuous family of measures (with transformation relations defined by
$\varphi $
), which sit on local unstable leaves. We present two main applications. First, given an ergodic homoclinic class
$H_\chi (p)$
, we prove that
$\varphi $
admits a local equilibrium state on
$H_\chi (p)$
if and only if
$\varphi $
is ‘recurrent on
$H_\chi (p)$
’ (a condition tested by counting periodic points), and one of the leaf measures gives a positive measure to a set of positively recurrent hyperbolic points; and if an equilibrium measure exists, the said invariant and absolutely continuous family of measures constitute as its conditional measures. An immediate corollary is the local product structure of hyperbolic equilibrium states. Second, we prove a Ledrappier–Young property for hyperbolic equilibrium states: if
$\varphi $
admits a conformal family of leaf measures and a hyperbolic local equilibrium state, then the leaf measures of the invariant family (respective to
$\varphi $
) are equivalent to the conformal measures (on a full measure set). This extends the celebrated result by Ledrappier and Young for hyperbolic Sinai–Ruelle–Bowen measures, which states that a hyperbolic equilibrium state of the geometric potential (with pressure zero) has conditional measures on local unstable leaves which are absolutely continuous with respect to the Riemannian volume of these leaves.
Quantitative Heegaard Floer cohomology and the Calabi invariant
Authors: Cristofaro-Gardiner Daniel , Humilière Vincent , Mak Cheuk Yu , Seyfaddini Sobhan , Smith Ivan
Published: December 2022

We define a new family of spectral invariants associated to certain Lagrangian links in compact and connected surfaces of any genus. We show that our invariants recover the Calabi invariant of Hamiltonians in their limit. As applications, we resolve several open questions from topological surface dynamics and continuous symplectic topology: We show that the group of Hamiltonian homeomorphisms of any compact surface with (possibly empty) boundary is not simple; we extend the Calabi homomorphism to the group of hameomorphisms constructed by Oh and Müller, and we construct an infinite-dimensional family of quasi-morphisms on the group of area and orientation preserving homeomorphisms of the two-sphere.

Our invariants are inspired by recent work of Polterovich and Shelukhin defining and applying spectral invariants, via orbifold Floer homology, for links composed of parallel circles in the two-sphere. A particular feature of our work is that it avoids the orbifold setting and relies instead on ‘classical’ Floer homology. This not only substantially simplifies the technical background but seems essential for some aspects (such as the application to constructing quasi-morphisms).
Contra Teleology: Hegel on Subjective and Objective Purpose
Authors: Thompson Kevin
Published: December 2022

Hegel's system is not teleological. For a philosophy to be teleological, as I shall use the term, means that it takes the basic nature of the world itself or any foundational account of that world to be defined ultimately by final causality. Such a view has, of course, long stood as the dominant model for interpreting Hegel's system. This essay argues, to the contrary, that the accounts of Teleology and Life in the Science of Logic, and more precisely their analyses of what Hegel calls there subjective purpose and objective purpose, actually demonstrate this conception of teleology to be profoundly mistaken.

The conventional reading of these sections is that they argue for two related claims: (1) that the means-ends relationship of extrinsic purposiveness—subjective purpose—is made possible by the intrinsic self-organizing process of intrinsic purposiveness; and (2) that intrinsic purposiveness—objective purpose—takes the basic structure of an organism, a natural purpose (Naturzweck), as its model, a model defined by final causality. I show this to be a deeply flawed interpretation. Hegel certainly shows that extrinsic purposiveness entails intrinsic purposiveness, but he does not conceive of intrinsic purposiveness, objective purpose, in terms of the final causality inherent in the model of a natural purpose. Rather, the systematic account of logical life argues that the activity of life must be understood as genus and this as a process of self-differentiation where the immanent and necessary unfolding of determinate negation itself, and itself alone, engenders the development without possessing or relating itself to any antecedent content. Hence, this austere thesis, rather than any form of final causality, is, as Hegel puts it, the truth of teleology, the nature of the absolute idea, and, as a result, Hegel's system is shown, at its very core, not to be teleological.
Getting to zero: Impact of a device to reduce blood culture contamination and false-positive central-line–associated bloodstream infections
Authors: Tompkins Lucy S. , Tien Vivian , Madison Alexandra N.
Published: December 2022

Objective:

To assess the impact of initial specimen diversion device (ISDD) on inpatient and emergency department blood culture contamination (BCC), central-line–associated bloodstream infection (CLABSI) standardized infection ratios (SIRs), and antibiotic administration.

Design:

Single-center quasi-experimental prospective cohort study wherein phlebotomists used traditional venipuncture with or without the ISDD while registered nurses (RNs) used traditional venipuncture.

Method:

BCC events among phlebotomists and RNs were observed and compared from March 17, 2019, through January 21, 2020, defined by contaminant detection in 1 of 4 bottles for matched sets or 1 of 2 bottles in both subsets for coagulase negative staphylococci. CLABSIs throughout this period were recorded and SIRs were calculated. Enhanced oversight took place through July 21, 2019, with chart review assessing antibiotic use for patients with possible BCC.

Results:

Overall, 24% of blood cultures obtained were from patients in intensive care. Phlebotomists using traditional venipuncture (n = 4,759) had a 2.3% BCC rate; phlebotomists using the ISDD (n = 11,202) had a 0% BCC rate. RNs drew 7,411 BCs with a 0.8% BCC rate. The CLABSI SIR was decreased from 1.103 in 2017 and 0.658 in 2018 to 0.439 in 2019. The CLABSI incidence was 33%–64% of predicted value for each 2019 quarter. This range fell to 18%–37% after the exclusion of likely false-positive results. Among 42 patients with possible BCC under enhanced oversight, 2 patients were treated with prolonged antibiotic courses.

Conclusions:

ISDD use by phlebotomists was associated with BCC reduction and reduced false-positive CLABSI results. This patient-care quality improvement could constitute sustainable antibiotic stewardship expansion.
Morphological evolution during the last hurrah of the trilobites: morphometric analysis of the Devonian asteropyginid trilobites
Authors: Martin Rene P. , Carranza Natalia López , LaVine Rhiannon J. , Lieberman Bruce S.
Published: December 2022

The Asteropyginae Delo, 1935 is a group of phacopid trilobites in the family Acastidae Delo, 1935 that has served as the focus for several studies due to their distinctive morphologies and diversity. However, despite an interest in these characteristic morphologies, there have been no studies that have examined this group using morphometric techniques. Our investigation utilized both geometric morphometric and elliptical Fourier methods to quantify the morphology of cephalic sclerites of asteropyginid specimens representing wide taxonomic sampling of the clade. We constructed a phylomorphospace that shows temporal and spatial patterns of phenotypic evolution within the framework of a novel tip-dated phylogenetic tree generated using Bayesian inference. We recovered similar patterns in disparity regardless of the morphometric approach. Both analyses illustrated a marked expansion into morphospace throughout the temporal range of the clade, peaking in disparity in the Emsian and with European taxa exhibiting the highest disparity in glabellar morphospace. Additionally, glabellar shape showed low phylogenetic signal and no major patterns in phylomorphospace. This study highlights the utility of employing different methodologies to quantitatively explore the disparity of fossil taxa. It also illustrates some of the patterns of morphological change occurring during one of the final and major evolutionary radiations within Phacopida.
Target pollen isolation using automated infrared laser-mediated cell disruption
Authors: Kaneshiro Ikuma , Igarashi Masako , Higashiyama Tetsuya , Mizuta Yoko
Published: December 2022

Single-cell analysis is important to understand how individual cells work and respond at the cell population level. Experimental single-cell isolation techniques, including dilution, fluorescence-activated cell sorting, microfluidics, and micromanipulation, have been developed in recent decades. However, such applications typically require large cell populations and skilled professionals. Additionally, these methods are unsuitable for sequential analysis before and after cell isolation. In this study, we propose a method for target cell isolation using automated infrared laser-mediated disruption of pollen grains in pollen populations. Germination of the target pollen was observed at the same location as that before laser irradiation, and germinated pollen grains were enriched in the cell population. Pollination of laser-irradiated bulk pollen populations also showed that the target pollen preferentially germinated on the stigma. This method is expected to facilitate physiological analyses of target cells at the single-cell level and effectively produce seeds derived from target pollen.
Sphingolipids and acylcarnitines are altered in placentas from women with gestational diabetes mellitus
Authors: Pinto Gabriela D. A. , Murgia Antonio , Lai Carla , Ferreira Carolina S. , Goes Vanessa A. , Guimarães Deborah de A. B. , Ranquine Layla G. , Reis Desirée L. , Struchiner Claudio J. , Griffin Julian L. , Burton Graham J. , Torres Alexandre G. , El-Bacha Tatiana
Published: December 2022

Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy and a severe threat to pregnant people and offspring health. The molecular origins of GDM, and in particular the placental responses, are not fully known. The present study aimed to perform a comprehensive characterisation of the lipid species in placentas from pregnancies complicated with GDM using high-resolution MS lipidomics, with a particular focus on sphingolipids and acylcarnitines in a semi-targeted approach. The results indicated that despite no major disruption in lipid metabolism, placentas from GDM pregnancies showed significant alterations in sphingolipids, mostly lower abundance of total ceramides. Additionally, very long-chain ceramides and sphingomyelins with twenty-four carbons were lower, and glucosylceramides with sixteen carbons were higher in placentas from GDM pregnancies. Semi-targeted lipidomics revealed the strong impact of GDM on the placental acylcarnitine profile, particularly lower contents of medium and long-chain fatty-acyl carnitine species. The lower contents of sphingolipids may affect the secretory function of the placenta, and lower contents of long-chain fatty acylcarnitines is suggestive of mitochondrial dysfunction. These alterations in placental lipid metabolism may have consequences for fetal growth and development.
Petrogenesis and tectonic implications of the early Mesozoic granitoids in the northern Alxa region, Central Asian Orogenic Belt
Authors: Zhao Xiaochen , Liu Chiyang , Wang Jianqiang , Niu Yazhuo , Huang Lei , Zhang Shaohua , Du Fangpeng , Peng Heng , Chen Yingtao , Peng Tao , Mao Zhengzheng
Published: December 2022

The northern Alxa region is located in the central segment of the southern Central Asian Orogenic Belt. Many controversies and deficiencies still exist regarding the magma source characteristics, petrogenesis and tectonic regimes during the late Palaeozoic – early Mesozoic period within this region. This study presents whole-rock compositions and zircon U–Pb and Lu–Hf isotopic data for three early Mesozoic I- and A-type granitic plutons occurring in the northern Alxa region. The Haerchaoenji and Chahanhada I-type granitoids yielded zircon206Pb–238U ages of 245 ± 5 Ma and 245 ± 2 Ma, respectively. The variable positive zircon ϵHf(t) values between +1.8 and +11.8, with young TDMages of 425–837 Ma, indicate that these I-type granitoids were mainly derived from juvenile crustal materials. The Wulantaolegai pluton has a zircon206Pb–238U age of 237 ± 2 Ma and is classified as having high-K calc-alkaline A-type affinity. Furthermore, the positive zircon ϵHf(t) values of the Wulantaolegai granite range from +3.3 to +8.7 with young TDMages of 545–778 Ma, suggesting the involvement of a juvenile crustal source as well. Furthermore, the major-element compositions of the Chahanhada and Wulantaolegai granites suggest the input of metasedimentary components. Geochemically, the Haerchaoenji and Chahanhada I-type granitoids show an arc affinity, while the Wulantaolegai granite exhibits a post-collisional affinity. However, with regional data, we suggest that the Haerchaoenji and Chahanhada I-type granitoids were also emplaced in a post-collisional setting, and the arc affinity was probably inherited from recycled subduction-related materials. These lines of evidence obtained in this study enable us to argue that the Palaeo-Asian Ocean in the central segment of the Central Asian Orogenic Belt closed before Middle Triassic time.
Bayesian Seismic Source Inversion With a 3‐D Earth Model of the Japanese Islands
Authors: Simutė Saulė , Boehm Christian , Krischer Lion , Gokhberg Alexey , Vallée Martin , Fichtner Andreas
Published: December 2022

We present probabilistic centroid‐moment tensor solutions inferred from the combination of Hamiltonian Monte Carlo sampling and a 3‐D full‐waveform inversion Earth model of the Japanese islands. While the former provides complete posterior probability densities, the latter allows us to exploit waveform data with periods as low as 15 s. For the computation of Green's functions, we employ spectral‐element simulations through the radially anisotropic and visco‐elastic model, leading to substantial improvements of data fit compared to layered models. Focusing on 13 Mw 4.8–Mw 5.3 offshore earthquakes with a significant non‐double‐couple (non‐DC) component, we simultaneously infer the centroid location, time and moment tensor without any a priori constraints on the faulting mechanism. Furthermore, we perform the inversions across several period bands, varying the minimum period between 15 and 50 s. Accounting for 3‐D Earth structure at shorter periods can increase the double‐couple (DC) component of an event, compared to the GCMT solution, by tens of percent. This suggests that non‐DC events in the GCMT catalog may result from unmodeled Earth structure and the related limitation to longer‐period data. We also observe that significant changes in source parameters, and the DC component in particular, may be related to only small waveform changes, thereby accentuating the importance of a reliable Earth model. Posterior probability density distributions become increasingly multimodal for shorter‐period data that provide tighter constraints on source parameters. This implies, in our specific case, that stochastic approaches to the source inversion problem are required for periods below ∼20 s to avoid trapping in local minima.
Fault Gouge Dating in the Spanish Pyrenees: Fault Ages, Thrust Propagation Sequence, Wall‐Rock Provenance, and Thermal Constraints
Authors: Haines Samuel H. , van der Pluijm Ben A.
Published: December 2022

Dating brittle faults by the growth of authigenic illite in fault gouge allows for direct testing of kinematic models of orogenic evolution, such as in‐sequence versus out‐of‐sequence thrusting, and the presence of orogenic “pulses” of deformation on multiple thrusts simultaneously. We present illite gouge ages from five thrust faults along the Ter and Freser rivers in the south‐eastern Pyrenees fold‐and‐thrust belt dated by Ar‐Ar methods. The ages show in‐sequence thrusting for the south‐eastern Pyrenees fold‐thrust belt during the Eocene and early Oligocene, ranging from 49.5 + 4.4 Ma for the inboard Freser Antiformal Stack to 31.9 ± 3.9 Ma for the frontal L’Escala Thrust. Foreland progression of ages is preserved, although overlapping of ages of the frontal thrusts permits the interpretation of a period of more rapid fault displacement around 35 Ma. Shortening rates for the Ter‐Freser section range from 1.2–2.7 km/my, with strain rates ranging from 7.0 × 10−16 s−1 to 1.6 × 10−15 s−1 The latest Paleozoic ages of the cataclastically derived component inferred from the gouge dating methodology are shown to be pooled 2M1 illite/mica ages of wall rock sediments and have geological meaning. These inferred mica ages of the thrust wallrocks in the southeastern Pyrenees indicate Hercynian‐age micas were deposited in the Southern Pyrenean foreland basin as early as the late Cretaceous. Previous thermochronometer and Δ47 temperatures from syn‐faulting calcite veins constrain temperature of clay gouge formation in the Ter‐Freser section at 50–210°C, with most likely temperatures of 50–160°C, consistent with previous studies.
Biomolecular condensate phase diagrams with a combinatorial microdroplet platform
Authors: Arter William E. , Qi Runzhang , Erkamp Nadia A. , Krainer Georg , Didi Kieran , Welsh Timothy J. , Acker Julia , Nixon-Abell Jonathan , Qamar Seema , Guillén-Boixet Jordina , Franzmann Titus M. , Kuster David , Hyman Anthony A. , Borodavka Alexander , George-Hyslop Peter St , Alberti Simon , Knowles Tuomas P. J.
Published: December 2022

The assembly of biomolecules into condensates is a fundamental process underlying the organisation of the intracellular space and the regulation of many cellular functions. Mapping and characterising phase behaviour of biomolecules is essential to understand the mechanisms of condensate assembly, and to develop therapeutic strategies targeting biomolecular condensate systems. A central concept for characterising phase-separating systems is the phase diagram. Phase diagrams are typically built from numerous individual measurements sampling different parts of the parameter space. However, even when performed in microwell plate format, this process is slow, low throughput and requires significant sample consumption. To address this challenge, we present here a combinatorial droplet microfluidic platform, termed PhaseScan, for rapid and high-resolution acquisition of multidimensional biomolecular phase diagrams. Using this platform, we characterise the phase behaviour of a wide range of systems under a variety of conditions and demonstrate that this approach allows the quantitative characterisation of the effect of small molecules on biomolecular phase transitions.
A large-scale view of marine heatwaves revealed by archetype analysis
Authors: Chapman Christopher C. , Monselesan Didier P. , Risbey James S. , Feng Ming , Sloyan Bernadette M.
Published: December 2022

Marine heatwaves can have disastrous impacts on ecosystems and marine industries. Given their potential consequences, it is important to understand how broad-scale climate variability influences the probability of localised extreme events. Here, we employ an advanced data-mining methodology, archetype analysis, to identify large scale patterns and teleconnections that lead to marine extremes in certain regions. This methodology is applied to the Australasian region, where it identifies instances of anomalous sea-surface temperatures, frequently associated with marine heatwaves, as well as the broadscale oceanic and atmospheric conditions associated with those extreme events. Additionally, we use archetype analysis to assess the ability of a low-resolution climate model to accurately represent the teleconnection patterns associated with extreme climate variability, and discuss the implications for the predictability of these impactful events.
Caveolin-1 dolines form a distinct and rapid caveolae-independent mechanoadaptation system
Authors: Lolo Fidel-Nicolás , Walani Nikhil , Seemann Eric , Zalvidea Dobryna , Pavón Dácil María , Cojoc Gheorghe , Zamai Moreno , Viaris de Lesegno Christine , Martínez de Benito Fernando , Sánchez-Álvarez Miguel , Uriarte Juan José , Echarri Asier , Jiménez-Carretero Daniel , Escolano Joan-Carles , Sánchez Susana A. , Caiolfa Valeria R. , Navajas Daniel , Trepat Xavier , Guck Jochen , Lamaze Christophe , Roca-Cusachs Pere , Kessels Michael M. , Qualmann Britta , Arroyo Marino , del Pozo Miguel A.
Published: December 2022

In response to different types and intensities of mechanical force, cells modulate their physical properties and adapt their plasma membrane (PM). Caveolae are PM nano-invaginations that contribute to mechanoadaptation, buffering tension changes. However, whether core caveolar proteins contribute to PM tension accommodation independently from the caveolar assembly is unknown. Here we provide experimental and computational evidence supporting that caveolin-1 confers deformability and mechanoprotection independently from caveolae, through modulation of PM curvature. Freeze-fracture electron microscopy reveals that caveolin-1 stabilizes non-caveolar invaginations—dolines—capable of responding to low-medium mechanical forces, impacting downstream mechanotransduction and conferring mechanoprotection to cells devoid of caveolae. Upon cavin-1/PTRF binding, doline size is restricted and membrane buffering is limited to relatively high forces, capable of flattening caveolae. Thus, caveolae and dolines constitute two distinct albeit complementary components of a buffering system that allows cells to adapt efficiently to a broad range of mechanical stimuli.
Representation of nuclear magnetic moments via a Clifford algebra formulation of Bohm’s hidden variables
Authors: Santilli Ruggero Maria , Sobczyk Garret
Published: December 2022

In this paper, we outline the research conducted by the first named author and his associates on the axiom-preserving, thus isotopic completion of quantum mechanics into hadronic mechanics according to the historical legacy by A. Einstein, B. Podolsky and N. Rosen that quantum mechanics is not a complete theory and review the ensuing exact representation of the magnetic moment and spin of the Deuteron in its ground state thanks to the isotopic completion of Pauli’s matrices with an explicit and concrete content of D. Bohm’s hidden variable$$\lambda$$
λ
. We then outline the independent studies conducted by the second named author on the representation of the conventional Pauli’s matrices via geometric Clifford algebras. We finally show that the combination of the two studies allows a mathematically rigorous, numerically exact and time invariant geometric representation of the magnetic moment, spin and hidden variable of the Deuteron in its ground state.