bluuebunny/crossref_metadata_2025 huggingface dataset:
Doing things with discourse in the mediated political arena
Authors: Fetzer Anita
Published: November 2022

This paper examines the contextual constraints and requirements of discursive action in question-answer-sequences
based discourse genres (interviews, Prime Minister’s Questions, People’s Prime Minister’s Questions) in mediated political
discourse. It considers the multilayeredness of participation and pluralism of discursive action on the one hand, and the
delimiting frame of the dialogic discourse genres on the other. It shows that both have a decisive impact on the participants’
meaning-making processes in context: the inherently unbounded participation framework contributes to pluralism of discursive
action, while genre- and media constraints narrow down the scope of production and interpretation. This does not only hold for the
stage at which a discursive action occurs in the discourse, but also for its degree of explicitness with regard to presuppositions
and felicity conditions.
Virtual dialogues in monologic political discourse
Authors: Cap Piotr
Published: November 2022

This paper describes ways in which political speakers define and legitimize future policies by construing different policy options in terms of ‘privileged’ and ‘oppositional’ futures. Privileged and oppositional futures are conceptual projections of alternative policy visions occurring in quasi-dialogic chunks of speech, revealing specific evidential, mood, and modality patterns. Privileged future involves the speaker’s preferred, or at least acknowledged vision and is articulated through absolute modality and evidential markers which derive from factual evidence, history, and reason. Oppositional future involves an antagonistic and plainly threatening vision, expressed by probabilistic modality and (usually) the interrogative mood. Following the principle of psychological consistency in belief, oppositional future is normally communicated first, allowing for a swift and strong response from the privileged future expressed in the speaker-preferred vision.
Transport properties of crystallized antiferromagnetic MnBi2Te4 thin films grown by magnetron sputtering
Authors: Lu Haoyu , Huang Yiya , Guo Qixun , Wang Kun , He Miaomiao , Yin Zhuo , Wang Dongwei , Liu Tao , Wang Jing , Yu Guanghua , Teng Jiao
Published: November 2022

The intrinsic magnetic topological insulator MnBi2Te4 has drawn great attention due to its novel quantum states, among which the most promising one is the quantum anomalous Hall effect. However, MnBi2Te4 is a metastable phase with a narrow temperature range for synthesis, which remains a challenge to grow uniform and high quality MnBi2Te4 sample. Large-area MnBi2Te4 thin films are mainly prepared by molecular beam epitaxy so far. Here, we report a highly versatile method for growing crystallized MnBi2Te4 films on amorphous SiO2/Si substrates by magnetron sputtering at room temperature and post-annealing. High-quality MnBi2Te4 films with a c-axis perpendicular to the substrate and low surface roughness are realized. MnBi2Te4 films have an antiferromagnetic Néel temperature of 21 K, with low carrier concentration (2.5 × 1019 cm−3) and decent mobility (34 cm2 V−1s−1). The films reveal ferromagnetic at ground state and a typical spin-flop transition at 2–3 T. This work provides a pathway toward the fabrication of sputtered-MnBi2Te4 devices for electronic and spintronic applications.
Spin–orbit coupling, orbitally entangled antiferromagnetic order, and collective spin–orbital excitations in

Sr2VO4
Authors: Mohapatra Shubhajyoti , Kumar Singh Dheeraj , Ray Rajyavardhan , Ghosh Sayandip , Singh Avinash
Published: November 2022

With electron filling n = 1 in the

Sr

2

VO

4

compound, the octahedrally coordinated

t

2

g

orbitals are strongly active when the tetragonal distortion induced crystal field is tuned by external agent such as pressure. Considering the full range of crystal field induced tetragonal splitting in a realistic three-orbital model, collective spin–orbital excitations are investigated using the generalized self-consistent plus fluctuation approach. At ambient pressure, an entangled orbital + antiferromagnetic order is found to be stabilized beyond a critical value (∼30 meV) of spin–orbit coupling which is in the realistic range for 3d ions. The behavior of the calculated energy scales of collective excitations with crystal field is consistent with that of the transition temperatures with pressure as obtained from susceptibility and resistivity anomalies in high-pressure studies.
Role of gas flow direction on monolayer MoS2 growth on patterned surfaces via CVD
Authors: Aras Fikret Gonca , Yeltik Aydan
Published: November 2022

The chemical vapor deposition (CVD) technique has been widely used to grow high quality single layer MoS2 crystals. However, there are still issues that need to be clarified in order to determine the appropriate conditions for the repeatable and scalable process. In this study, we experimentally investigated the effect of flow direction on the size distribution and optical signal of monolayer MoS2 flakes grown on microchannel arrayed surfaces. As an important parameter controlling the CVD process, the carrier gas flow was revealed to be highly sensitive to geometric orientation of the patterned surface. The flow direction parallel to the array yielded larger flakes with narrower size distribution, and enhanced photoluminescence (PL) peak intensities compared to the case with flow normal to the array while the Raman intensities for both the cases are almost the same. The size distributions were obtained as 6 ± 13 and 37 ± 4 µm for the perpendicular and parallel cases, respectively. It was also found that the PL peak intensity increased by approximately 1.5 times when switching to parallel configuration. This study presents an experimental approach to understand the influence of the precursor stream reshaped by the growth surface geometry on the structural and optical properties of monolayer MoS2, which has great potential for use in optoelectronic applications.
Graphene based Nano Gas Sensors: Mechanistic Study
Authors: Jaiswal Monica , Majumdar Neha , Kumar Robin , Mittal Jagjiwan , Jha Pika
Published: November 2022

Selective, sensitive and accurate gas monitoring system can help to control the air pollution, prevent an explosion and injury to industrial workers. Due to very high surface to volume ratio and unique properties, graphene is a highly suitable carbon material to detect toxic gases. As single layer, few layer or multi-layer, graphene either in pure form or after modifications has been studied for the application in gas sensors. Present paper serves as a compendium of research work carried out on graphene and its derivatives in gas sensing applications. Review is mainly concentrated on the sensing of three toxic gases namely nitrogen dioxide (NO2), carbon monoxide (CO) and ammonia (NH3). Special emphasis is done on describing the mechanisms for gas sensing by pristine graphene and after modifications.
Effects of pulse voltage on the droplet formation of glycol ethers solvent ink in a piezoelectric inkjet printing process for fabricating hydrophobic lines on paper substrate
Authors: Dinh Duc Minh Trinh , Le Ngan Nguyen , Lam Phuong Hong , Thi Le Anh Van , Thi Le Mai , Thi Dang Dung My , Thi Nguyen Hiep , Dang Chien Mau
Published: November 2022

Inkjet printing is a fabrication technique which can create designed patterns by ejecting many tiny ink droplets out of nozzles onto substrate. This technique has recently been applied into fabrication process of micro-electro-mechanical systems (MEMS). However, the exact understanding of the effect of pulse voltage on ink droplet is still the focus of many researchers today. Therefore, the goal of this work is to investigate the effect of voltage of phase 1 (V
1) and phase 2 (V
2) of drive waveform on an inkjet printing process to understand how the droplet and satellite droplet have been formed. Solvent ink was prepared from diethylene glycol monobutyl ether (DEGBE) and nonaethylene glycol monododecyl ether (C12E9). Ink droplets were observed by high speed camera which had been installed into our CeraPrinter X-Serie inkjet printer. Results showed that V
1 = −10 V and V
2 = 50 V are suitable for our inkjet printer to achieve stable jetting without the appearance of satellite drops. These optimum values of pulse voltage were confirmed through the printing of our solvent ink on paper substrate for fabricating hydrophobic lines.
The shape-controlled synthesis of alloyed CdSxSe1−x nanocrystals and their applications in LEDs
Authors: Le Na Vo Thi , Ngoc Pham Kim , Tuan Duong Anh , Huong Nguyen Viet , Hai Vu Ngoc , Huu Tuan Nguyen
Published: November 2022

Alloy nanocrystals (NCs) provide access and control of the parameters for nanoscale engineering because their physical and optical properties depend on size, shape, and composition. Here, alloy CdS
x
Se1−x
NCs with different shapes were synthesised via a one-pot method using cadmium acetate, sulfur, and selenium as precursors in trioctylphosphine solution. The luminescence and shapes of NCs were characterised by fluorescence spectroscopy and transmission electron microscopy, respectively. It was found that the modification of precursor concentration resulted in NC shape variation, including branched NCs, long and short nanorods. Consequently, a series of alloy CdS
x
Se1−x
NCs with different shape-based light emitting devices (LEDs) were fabricated and their operation characteristics were also compared. The obtained luminance and luminous efficiency showed that the control of NC shape is the key factor for the improvement of LED performance. We anticipate that this work will provide further insight into the design of CdSxSe1−x NCs-based LEDs with shape variation.
Three key areas in progressing delirium practice and knowledge: recognition and relief of distress, new directions in delirium epidemiology and developing better research assessments
Authors: MacLullich Alasdair M J , Hosie Annmarie , Tieges Zoë , Davis Daniel H J
Published: November 2022

Delirium presents formidable challenges: it affects one in four of older hospitalised adults, greatly elevates the risk of multiple short- and long-term complications including dementia and causes significant distress. Delirium care remains generally poor. Yet, there are clear grounds for optimism; the last decade has seen impactful policy advances and a tripling of research output. Here, we highlight three linked areas which have strong potential to transform delirium practice and knowledge in the near term.

Delirium-related distress is strikingly underrepresented in practice guidance and research. Proactive recognition combined with effective clinical responses based on good communication provides a critical and largely untapped opportunity to improve care.

Delirium epidemiology research is well positioned to produce novel insights through advanced prospective designs in populations such as emergency medical patients with detailed pre-, intra- and post-delirium assessments allied with fluid, imaging and other biomarkers.

Research-grade assessment of delirium currently involves a chaotic array of tools, methods and diagnostic algorithms. Areas for development: expand and analytically distinguish the range of features assessed (including distress), optimise feature assessment including use of validated neuropsychological tests where possible, produce standardised algorithms which articulate explicit pathways from features to diagnosis, and create new fine-grained approaches to the measurement of severity.

Delirium practice and knowledge show accelerating growth. This is encouraging but much of the necessary progress is still to come. Innovation in these three highlighted areas, as well as many others, will open up exciting possibilities in enhancing the care of patients with this common and often devastating condition.
Critical review of conformational B-cell epitope prediction methods
Authors: Cia Gabriel , Pucci Fabrizio , Rooman Marianne
Published: November 2022

Accurate in silico prediction of conformational B-cell epitopes would lead to major improvements in disease diagnostics, drug design and vaccine development. A variety of computational methods, mainly based on machine learning approaches, have been developed in the last decades to tackle this challenging problem. Here, we rigorously benchmarked nine state-of-the-art conformational B-cell epitope prediction webservers, including generic and antibody-specific methods, on a dataset of over 250 antibody-antigen structures. The results of our assessment and statistical analyses show that all the methods achieve very low performances, and some do not perform better than randomly generated patches of surface residues. In addition, we also found that commonly used consensus strategies that combine the results from multiple webservers are at best only marginally better than random. Finally, we applied all the predictors to the SARS-CoV-2 spike protein as an independent case study, and showed that they perform poorly in general, which largely recapitulates our benchmarking conclusions. We hope that these results will lead to greater caution when using these tools until the biases and issues that limit current methods have been addressed, promote the use of state-of-the-art evaluation methodologies in future publications and suggest new strategies to improve the performance of conformational B-cell epitope prediction methods.
varAmpliCNV: analyzing variance of amplicons to detect CNVs in targeted NGS data
Authors: Kumar Ajay Anand , Loeys Bart , Van De Beek Gerarda , Peeters Nils , Wuyts Wim , Van Laer Lut , Vandeweyer Geert , Alaerts Maaike
Published: November 2022

Motivation

Computational identification of copy number variants (CNVs) in sequencing data is a challenging task. Existing CNV-detection methods account for various sources of variation and perform different normalization strategies. However, their applicability and predictions are restricted to specific enrichment protocols. Here, we introduce a novel tool named varAmpliCNV, specifically designed for CNV-detection in amplicon-based targeted resequencing data (Haloplex™ enrichment protocol) in the absence of matched controls. VarAmpliCNV utilizes principal component analysis (PCA) and/or metric dimensional scaling (MDS) to control variances of amplicon associated read counts enabling effective detection of CNV signals.

Results

Performance of VarAmpliCNV was compared against three existing methods (ConVaDING, ONCOCNV and DECoN) on data of 167 samples run with an aortic aneurysm gene panel (n = 30), including 9 positive control samples. Additionally, we validated the performance on a large deafness gene panel (n = 145) run on 138 samples, containing 4 positive controls. VarAmpliCNV achieved higher sensitivity (100%) and specificity (99.78%) in comparison to competing methods. In addition, unsupervised clustering of CNV segments and visualization plots of amplicons spanning these regions are included as a downstream strategy to filter out false positives.

Availability and implementation

The tool is freely available through galaxy toolshed and at: https://hub.docker.com/r/cmgantwerpen/varamplicnv. Supplementary Data File S1: https://tinyurl.com/2yzswyhh; Supplementary Data File S2: https://tinyurl.com/ycyf2fb4.

Supplementary information

Supplementary data are available at Bioinformatics online.
Teleonomy as a problem of self-causation
Authors: Gontier Nathalie
Published: November 2022

A theoretical framework is provided to explore teleonomy as a problem of self-causation, distinct from upward, downward and reticulate causation. Causality theories in biology are often formulated within hierarchy theories, where causation is conceptualized as running up or down the rungs of a ladder-like hierarchy or, more recently, as moving between multiple hierarchies. Research on the genealogy of cosmologies demonstrates that in addition to hierarchy theories, causality theories also depend upon ideas of time. This paper explores the roots and impact of both time and hierarchy thinking on causal reasoning in the evolutionary sciences. Within evolutionary biology, the Neodarwinian synthesis adheres to a linear notion of time associated with linear hierarchies that portray upward causation. Eco-evo-devo schools recognize the importance of downward causation and consequently receive resistance from the standard view because downward causation is sometimes understood as backward causation, considered impossible by adherents of a linear time model. In contrast, downward causation works with a spatial or presential time notion. Hybridization, lateral gene transfer, infective heredity, symbiosis and symbiogenesis require recognition of reticulate causation occurring in both space and time, or spacetime, between distinct and interacting ontological hierarchies. Teleonomy is distinct from these types of causation because it invokes the problem of self-causation. By asking how the focal level in a hierarchy can persist through time, self-causation raises philosophical concerns on the nature of duration, identity and individuality.
Local brain environment changes associated with epileptogenesis
Authors: Ikoma Yoko , Sasaki Daichi , Matsui Ko
Published: November 2022

Plastic change of the neuronal system has traditionally been assumed to be governed primarily by the long-term potentiation/depression mechanisms of synaptic transmission. However, a rather simple shift in the ambient ion, transmitter and metabolite concentrations could have a pivotal role in generating plasticity upon the physiological process of learning and memory. Local brain environment and metabolic changes could also be the cause and consequences of the pathogenesis leading to epilepsy. Governing of the local brain environment is the primal function of astrocytes. The metabolic state of the entire brain is strongly linked to the activity of the lateral hypothalamus. In this study, plastic change of astrocyte reactions in the lateral hypothalamus was examined using epileptogenesis as an extreme form of plasticity. Fluorescent sensors for calcium or pH expressed in astrocytes were examined for up to one week by in vivo fibre photometry in freely moving transgenic male mice. Optical fluctuations on a timescale of seconds is difficult to assess because these signals are heavily influenced by local brain blood volume changes and pH changes. Using a newly devised method for the analysis of the optical signals, changes in Ca2+ and pH in astrocytes and changes in local brain blood volume associated with hippocampal-stimulated epileptic seizures were extracted. Following a transient alkaline shift in the astrocyte triggered by neuronal hyperactivity, a prominent acidic shift appeared in response to intensified seizure which developed with kindling. The acidic shift was unexpected as transient increase in local brain blood volume was observed in response to intensified seizures, which should lead to efficient extrusion of the acidic CO2. The acidic shift could be a result of glutamate transporter activity and/or due to the increased metabolic load of astrocytes leading to increased CO2 and lactate production. This acidic shift may trigger additional gliotransmitter release from astrocytes leading to the exacerbation of epilepsy. As all cellular enzymic reactions are influenced by Ca2+ and pH, changes in these parameters could also have an impact on the neuronal circuit activity. Thus, controlling the astrocyte pH and/or Ca2+ could be a new therapeutic target for treatment of epilepsy or prevention of undesired plasticity associated with epileptogenesis.
Cerebrospinal fluid biomarkers for assessing Huntington disease onset and severity
Authors: Caron Nicholas S , Haqqani Arsalan S , Sandhu Akshdeep , Aly Amirah E , Findlay Black Hailey , Bone Jeffrey N , McBride Jodi L , Abulrob Abedelnasser , Stanimirovic Danica , Leavitt Blair R , Hayden Michael R
Published: November 2022

The identification of molecular biomarkers in CSF from individuals affected by Huntington disease may help improve predictions of disease onset, better define disease progression and could facilitate the evaluation of potential therapies. The primary objective of our study was to investigate novel CSF protein candidates and replicate previously reported protein biomarker changes in CSF from Huntington disease mutation carriers and healthy controls. Our secondary objective was to compare the discriminatory potential of individual protein analytes and combinations of CSF protein markers for stratifying individuals based on the severity of Huntington disease. We conducted a hypothesis-driven analysis of 26 pre-specified protein analytes in CSF from 16 manifest Huntington disease subjects, eight premanifest Huntington disease mutation carriers and eight healthy control individuals using parallel-reaction monitoring mass spectrometry. In addition to reproducing reported changes in previously investigated CSF biomarkers (NEFL, PDYN, and PENK), we also identified novel exploratory CSF proteins (C1QB, CNR1, GNAL, IDO1, IGF2, and PPP1R1B) whose levels were altered in Huntington disease mutation carriers and/or across stages of disease. Moreover, we report strong associations of select CSF proteins with clinical measures of disease severity in manifest Huntington disease subjects (C1QB, CNR1, NEFL, PDYN, PPP1R1B, and TTR) and with years to predicted disease onset in premanifest Huntington disease mutation carriers (ALB, C4B, CTSD, IGHG1, and TTR). Using receiver operating characteristic curve analysis, we identified PENK as being the most discriminant CSF protein for stratifying Huntington disease mutation carriers from controls. We also identified exploratory multi-marker CSF protein panels that improved discrimination of premanifest Huntington disease mutation carriers from controls (PENK, ALB and NEFL), early/mid-stage Huntington disease from premanifest mutation carriers (PPP1R1B, TTR, CHI3L1, and CTSD), and late-stage from early/mid-stage Huntington disease (CNR1, PPP1R1B, BDNF, APOE, and IGHG1) compared with individual CSF proteins. In this study, we demonstrate that combinations of CSF proteins can outperform individual markers for stratifying individuals based on Huntington disease mutation status and disease severity. Moreover, we define exploratory multi-marker CSF protein panels that, if validated, may be used to improve the accuracy of disease-onset predictions, complement existing clinical and imaging biomarkers for monitoring the severity of Huntington disease, and potentially for assessing therapeutic response in clinical trials. Additional studies with CSF collected from larger cohorts of Huntington disease mutation carriers are needed to replicate these exploratory findings.
Ehm2 transcript variant 1 inhibits breast cancer progression and increases E-cadherin stability
Authors: Yin Xin , Li Gen , Fan Dongwei , Ge Zhicheng , Yang Tianshu , Shang Yaxin , Ma Tianyu , Yuan Baowen , Huang Wei , Teng Xu , Yu Hefen
Published: November 2022

Ehm2/1, an Ehm2 transcript variant, regulates the cytoskeleton by binding to plasma membrane proteins. However, the role of Ehm2/1 in breast cancer development remains poorly understood. This study shows that, the expression of Ehm2/1 was decreased in breast cancer and that patients with low Ehm2/1 expression had a significantly poorer prognosis than those with high expression of Ehm2/1. Overexpression of Ehm2/1 in MCF-7 breast cancer cells inhibited cell migration and invasion. Ehm2/1 markedly increased the stability and half-life of E-cadherin. Moreover, Ehm2/1 was collocated with E-cadherin in the plasma membrane of MCF-7 cells. Furthermore, downregulation of Ehm2/1 promoted ubiquitination of E-cadherin, whereas overexpression of Ehm2/1 inhibited ubiquitination of E-cadherin. These results suggest that Ehm2/1 could suppress the migration and invasion of breast cancer cells by increasing E-cadherin stability.
The comprehensive role of apoptosis inhibitor of macrophage (AIM) in pathological conditions
Authors: Yang Huiqing , Luo Yan , Lai Xiaofei
Published: November 2022

CD5L/AIM (apoptosis inhibitor of macrophage), as an important component in maintaining tissue homeostasis and inflammation, is mainly produced and secreted by macrophages but partially dissociated and released from blood AIM-IgM. AIM plays a regulatory role in intracellular physiological mechanisms, including lipid metabolism and apoptosis. AIM not only increases in autoimmune diseases, directly targets liver cells in liver cancer and promotes cell clearance in acute kidney injury, but also causes arteriosclerosis and cardiovascular events, and aggravates inflammatory reactions in lung diseases and sepsis. Obviously, AIM plays a pleiotropic role in the body. However, to date, studies have failed to decipher the mechanisms behind its different roles (beneficial or harmful) in inflammatory regulation. The inflammatory response is a “double-edged sword,” and maintaining balance is critical for effective host defense while minimizing the adverse side effects of acute inflammation. Enhancing the understanding of AIM function could provide the theoretical basis for new therapies in these pathological settings. In this review, we discuss recent studies on the roles of AIM in lipid metabolism, autoimmune diseases and organic tissues, such as liver cancer, myocardial infarction, and kidney disease.
Neurological soft signs in adolescents are associated with brain structure
Authors: Bonke Elena M , Bonfert Michaela V , Hillmann Stefan M , Seitz-Holland Johanna , Gaubert Malo , Wiegand Tim L T , De Luca Alberto , Cho Kang Ik K , Sandmo Stian B , Yhang Eukyung , Tripodis Yorghos , Seer Caroline , Kaufmann David , Kaufmann Elisabeth , Muehlmann Marc , Gooijers Jolien , Lin Alexander P , Leemans Alexander , Swinnen Stephan P , Bahr Roald , Shenton Martha E , Pasternak Ofer , Tacke Uta , Heinen Florian , Koerte Inga K
Published: November 2022

Neurological soft signs (NSS) are minor deviations in motor performance. During childhood and adolescence, NSS are examined for functional motor phenotyping to describe development, to screen for comorbidities, and to identify developmental vulnerabilities. Here, we investigate underlying brain structure alterations in association with NSS in physically trained adolescents. Male adolescent athletes (n = 136, 13–16 years) underwent a standardized neurological examination including 28 tests grouped into 6 functional clusters. Non-optimal performance in at least 1 cluster was rated as NSS (NSS+ group). Participants underwent T1- and diffusion-weighted magnetic resonance imaging. Cortical volume, thickness, and local gyrification were calculated using Freesurfer. Measures of white matter microstructure (Free-water (FW), FW-corrected fractional anisotropy (FAt), axial and radial diffusivity (ADt, RDt)) were calculated using tract-based spatial statistics. General linear models with age and handedness as covariates were applied to assess differences between NSS+ and NSS− group. We found higher gyrification in a large cluster spanning the left superior frontal and parietal areas, and widespread lower FAt and higher RDt compared with the NSS− group. This study shows that NSS in adolescents are associated with brain structure alterations. Underlying mechanisms may include alterations in synaptic pruning and axon myelination, which are hallmark processes of brain maturation.
Human motor sequence learning drives transient changes in network topology and hippocampal connectivity early during memory consolidation
Authors: Deleglise Alvaro , Donnelly-Kehoe Patricio Andres , Yeffal Abraham , Jacobacci Florencia , Jovicich Jorge , Amaro Jr Edson , Armony Jorge L , Doyon Julien , Della-Maggiore Valeria
Published: November 2022

In the last decade, the exclusive role of the hippocampus in human declarative learning has been challenged. Recently, we have shown that gains in performance observed in motor sequence learning (MSL) during the quiet rest periods interleaved with practice are associated with increased hippocampal activity, suggesting a role of this structure in motor memory reactivation. Yet, skill also develops offline as memory stabilizes after training and overnight. To examine whether the hippocampus contributes to motor sequence memory consolidation, here we used a network neuroscience strategy to track its functional connectivity offline 30 min and 24 h post learning using resting-state functional magnetic resonance imaging. Using a graph-analytical approach we found that MSL transiently increased network modularity, reflected in an increment in local information processing at 30 min that returned to baseline at 24 h. Within the same time window, MSL decreased the connectivity of a hippocampal-sensorimotor network, and increased the connectivity of a striatal-premotor network in an antagonistic manner. Finally, a supervised classification identified a low-dimensional pattern of hippocampal connectivity that discriminated between control and MSL data with high accuracy. The fact that changes in hippocampal connectivity were detected shortly after training supports a relevant role of the hippocampus in early stages of motor memory consolidation.
Linezolid Population Pharmacokinetics to Improve Dosing in Cardiosurgical Patients: Factoring a New Drug–Drug Interaction Pathway
Authors: Pai Manjunath P , Cojutti Pier Giorgio , Gerussi Valentina , Della Siega Paola , Tascini Carlo , Pea Federico
Published: November 2022

Background

Linezolid-induced myelosuppression limits optimal therapy in cardiosurgical patients with deep-seated infections at current doses.

Methods

Adult patients who received a cardiac surgery intervention and linezolid for a documented or presumed serious gram-positive infection were evaluated. Therapeutic monitoring data, dosing, concomitant medications, and other pertinent laboratory data were collected retrospectively. A population pharmacokinetic model was constructed to identify covariates and test potential drug–drug interactions that may account for interpatient variability. Simulations from the final model identified doses that achieve a target therapeutic trough concentration of 2–8 mg/L.

Results

This study included 150 patients (79.3% male) with sepsis and hospital-acquired pneumonia in 71.7% as the primary indication. The population had a median (minimum–maximum) age, body weight, and estimated glomerular filtration rate (eGFR) of 66 (30–85) years, 76 (45–130) kg, and 46.8 (4.9–153.7) mL/minute, respectively. The standard linezolid dosage regimen achieved the therapeutic range in only 54.7% of patients. Lower-than-standard doses were necessary in the majority of patients (77%). A 2-compartment Michaelis-Menten clearance model with weight, kidney function, and the number of interacting drugs identified as covariates that best fit the concentration-time data was used. Cyclosporine had the greatest effect on lowering the maximum elimination rate (Vmax) of linezolid. Empiric linezolid doses of 300–450 mg every 12 hours based on eGFR and the number of interacting medications are suggested by this analysis.

Conclusions

Lower empiric linezolid doses in cardiosurgical patients may avoid toxicities. Confirmatory studies are necessary to verify these potential drug interactions.
CaRPE: the Carbon Reduction Potential Evaluation tool for building climate mitigation scenarios on US agricultural lands
Authors: Manter Daniel K , Moore Jennifer M
Published: November 2022

The Carbon Reduction Potential Evaluation (CaRPE) tool is a web-based interactive tool that integrates two databases for the USA collected at county/multi-county scales to visualize and estimate the climate benefits of implementing a variety of conservation practices on croplands and grazing lands. The COMET-Planner tool provides county/multi-county carbon sequestration and greenhouse gas emission reduction coefficients associated with the adoption of climate-smart agricultural management practices. The CaRPE tool couples these coefficients, reported in tonnes of carbon dioxide equivalents (CO2e) per acre per year, with county-level cropland and grazing land acres extracted from the US Agricultural Census. The CaRPE graphical user interface allows users to quickly and easily build and export scenarios of new conservation practice adoption on desired acreages and locations at state, regional or national scales. Results are in tonnes CO2e per year, and each scenario can be exported in tabular and map formats at the selected scales. Existing county-level cropland acreage data provide the upper boundaries for acres of adoption and can be modified based on specific goals established by the user.The output may be used to develop potential targets of adoption and help inform decisions related to resource prioritization and planning efforts. In collaboration with local experts and farmer-led organizations, the results can provide a key starting block to prioritize practices and areas that contribute to climate benefits. As the underlying databases and models are updated and improved, CaRPE can be revised accordingly to increase accuracy and enhance applicability. The CaRPE tool and the user guide are available at:

Database URL: https://carpe.shinyapps.io/CarpeTool/
Prognostic impact of secondary prevention medical therapy following myocardial infarction with non-obstructive coronary arteries: a Bayesian and frequentist meta-analysis
Authors: Samaras Athanasios , Papazoglou Andreas S , Balomenakis Charalampos , Bekiaridou Alexandra , Moysidis Dimitrios V , Rampidis Georgios P , Kampaktsis Polydoros N , Apostolidou-Kiouti Fani , Haidich Anna-Bettina , Kassimis George , Kouskouras Konstantinos , Fragakis Nikolaos , Ziakas Antonios , Vassilikos Vassilios , Giannakoulas George
Published: November 2022

Aims

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a clinical entity with several causes and pathophysiologic mechanisms. Secondary prevention with medical therapy used in patients with obstructive coronary artery disease has unclear benefits in MINOCA patients.

Methods and results

A literature search was conducted until 8 March 2022. Random-effect frequentist and hierarchical Bayesian meta-analyses were performed to assess the clinical impact of medical therapy [renin–angiotensin–aldosterone system (RAAS) inhibitors, statins, dual antiplatelet therapy (DAPT), β-blockers] in MINOCA patients. Outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE). A total of 12 663 MINOCA patients among five observational studies were analysed. The mean follow-up ranged from 12 to 90 months across studies. In frequentist meta-analysis, statins and β-blockers were associated with a lower risk of all-cause mortality [pooled adjusted hazard ratios (aHRs) 0.53 and 0.81, with 95% confidence intervals (CIs) (0.37–0.76) and (0.67–0.97), respectively]. Only RAAS inhibitors were associated with a lower risk of MACE [pooled aHR: 0.69, with 95% CI (0.53–0.90)]. Bayesian meta-analysis based on informative prior assumptions offered strong evidence only for the benefit of statins on decreasing the risk of all-cause death [Bayes factor (BF): 33.2] and moderate evidence for the benefit of RAAS inhibitors on decreasing the risk of MACE (BF: 9); assigning less informative prior distributions did not affect the results, yet it downgraded the level of evidence to anecdotal.

Conclusion

In this meta-analysis, statins and RAAS inhibitors were consistently associated with a lower risk of all-cause mortality and MACE, respectively, in patients with MINOCA. Neutral prognostic evidence was demonstrated for β-blockers and DAPT.
Dietary metabolic signatures and cardiometabolic risk
Authors: Shah Ravi V , Steffen Lyn M , Nayor Matthew , Reis Jared P , Jacobs David R , Allen Norrina B , Lloyd-Jones Donald , Meyer Katie , Cole Joanne , Piaggi Paolo , Vasan Ramachandran S , Clish Clary B , Murthy Venkatesh L
Published: November 2022

Aims

Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood.

Methods and results

In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32–1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12–2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study.

Conclusion

Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD.
Global burden of disease attributable to high systolic blood pressure in older adults, 1990–2019: an analysis for the Global Burden of Disease Study 2019
Authors: Huang Yuxian , Meng Lingrui , Liu Canru , Liu Songyue , Tao Luqiu , Zhang Sijia , Gao Jiaying , Sun Lingmin , Qin Qiying , Zhao Yingchen , Wang Chang , Chen Zihan , Guo Xiaofan , Sun Yinxian , Li Guangxiao
Published: November 2022

Aims

High systolic blood pressure (HSBP), a significant public health challenge, has not been systematically studied in the elderly population in the context of global aging. Understanding the temporal trends of the disease burden associated with HSBP in the elderly population is essential to control and mitigate the harm caused by HSBP.

Methods and results

We used the estimated data derived from the Global Burden of Disease Study to analyse the disease burden of HSBP among the elderly population by region, sex, and temporal changes from 1990 to 2019. We found that the number of deaths due to HSBP increased to 7.86 (95% UI: 6.89–8.82) million, with an increase of 54.1%, and the number of disability-adjusted life years (DALYs) increased to 146 (95% UI: 130–162) million, with an increase of 52.4%. Conversely, the death and DALY rates of HSBP decreased by −27.0 and −27.8%, respectively. At the national and regional levels, Australasia and other high socio-demographic index regions have made significant improvements in the burden of HSBP, while it remains high in other regions of the world. Additionally, the burden of HSBP in older men is greater than that in older women.

Conclusion

Our findings indicate that the current prevention and control of HSBP in older adults is poor, with the total burden increasing significantly. There is an urgent need to implement feasible measures to resist HSBP and lessen the disparity of the global HSBP burden for older adults.
Aortic valve sclerosis and subclinical left ventricular dysfunction in the general population with normal left ventricular geometry
Authors: Yoshida Yuriko , Nakanishi Koki , Daimon Masao , Hirose Kazutoshi , Ishiwata Jumpei , Kaneko Hidehiro , Nakao Tomoko , Mizuno Yoshiko , Morita Hiroyuki , Di Tullio Marco R , Homma Shunichi , Komuro Issei
Published: November 2022

Aims

Aortic valve sclerosis (AVS) without haemodynamically significant obstruction is related to cardiovascular morbidity and mortality independent of left ventricular (LV) hypertrophy, although the underlying mechanisms remain unknown. This study investigated the prevalence of AVS and its association with subclinical LV systolic and diastolic dysfunction in individuals with normal LV geometry free of cardiovascular disease.

Methods and results

We examined 962 participants with normal LV geometry and free from significant AV stenosis who underwent standard and speckle-tracking echocardiography. AVS was categorized into four groups as follows: no AVS, AV thickening, calcification on one leaflet, and calcification on ≥2 leaflets. Among the 962 participants, 767 (79.7%) individuals were classified as no AVS, 74 (7.7%) as AV thickening, 87 (9.0%) as calcification on one leaflet, and 34 (3.5%) as calcification on ≥2 leaflets. The prevalence of subclinical LV diastolic dysfunction (E/e′ ratio ≥13) and systolic dysfunction [LV global longitudinal strain (GLS) > −17.0% for men and > −18.0% for women] were greater in AVS groups than those in no AVS group. Subclinical LV diastolic impairment was evident from AV thickening and systolic dysfunction was observed at AV calcification. Multivariable logistic regression analysis demonstrated that AV thickening as well as calcification were independently associated with subclinical LV diastolic impairment (all P < 0.05), while only AV calcification on ≥2 leaflets conferred significant increased risk of impaired LVGLS.

Conclusion

AVS was observed in approximately 20% individuals without cardiac disease and was associated with subclinical LV diastolic and systolic function even in the absence of LV morphological change.
Bernardin de Saint-Pierre’s ‘Explication de quelques termes de marine’ (1773)
Authors: Howells Robin
Published: November 2022

Bernardin de Saint-Pierre’s
Voyage à l’île de France
(1773), his first publication, contains near its end a curious segment which has received scant critical attention. This ‘Explication’ undertakes to elucidate maritime terms used in his travel narrative. Such short alphabetical glossaries, constituting in effect a subgenre of the nautical dictionary, appear in other voyage accounts of the period. But Bernardin begins by announcing that he has added to his explications of terms ‘des étymologies’, which are moreover ‘point sçavantes, mais conformes à l’esprit du peuple […] qui donne le nom aux choses’. This article argues that these allegedly popular etymologies, largely invented by Bernardin (who invokes Rabelais), are in the main to be read as ludic and satirical. Playing with ‘the body of the word’, employing fragmentation and punning, they mock both erudite and demotic derivations of terms. But the etymologies of the people also show that names contain their own meaning, establishing a comic Cratylism. The playful mode of this early piece allows Bernardin to adumbrate daring ideas while keeping them at an ironic distance. Taken seriously and attributed to Providence, the notion of an immanent signification in language, as in nature, exhibited to humankind, will be developed in later works.
ANKRD11 pathogenic variants and 16q24.3 microdeletions share an altered DNA methylation signature in patients with KBG syndrome
Authors: Awamleh Zain , Choufani Sanaa , Cytrynbaum Cheryl , Alkuraya Fowzan S , Scherer Stephen , Fernandes Sofia , Rosas Catarina , Louro Pedro , Dias Patricia , Neves Mariana Tomásio , Sousa Sérgio B , Weksberg Rosanna
Published: November 2022

Pathogenic variants in ANKRD11 or microdeletions at 16q24.3 are the cause of KBG syndrome (KBGS), a neurodevelopmental syndrome characterized by intellectual disability, dental and skeletal anomalies, and characteristic facies. The ANKRD11 gene encodes the ankyrin repeat-containing protein 11A transcriptional regulator, which is expressed in the brain and implicated in neural development. Syndromic conditions caused by pathogenic variants in epigenetic regulatory genes show unique patterns of DNA methylation (DNAm) in peripheral blood, termed DNAm signatures. Given ANKRD11’s role in chromatin modification, we tested whether pathogenic ANKRD11 variants underlying KBGS are associated with a DNAm signature. We profiled whole-blood DNAm in 21 individuals with ANKRD11 variants, 2 individuals with microdeletions at 16q24.3 and 28 typically developing individuals, using Illumina’s Infinium EPIC array. We identified 95 differentially methylated CpG sites that distinguished individuals with KBGS and pathogenic variants in ANKRD11 (n = 14) from typically developing controls (n = 28). This DNAm signature was then validated in an independent cohort of seven individuals with KBGS and pathogenic ANKRD11 variants. We generated a machine learning model from the KBGS DNAm signature and classified the DNAm profiles of four individuals with variants of uncertain significance (VUS) in ANKRD11. We identified an intermediate classification score for an inherited missense variant transmitted from a clinically unaffected mother to her affected child. In conclusion, we show that the DNAm profiles of two individuals with 16q24.3 microdeletions were indistinguishable from the DNAm profiles of individuals with pathogenic variants in ANKRD11, and we demonstrate the diagnostic utility of the new KBGS signature by classifying the DNAm profiles of individuals with VUS in ANKRD11.
BDDC Algorithms for Oseen problems with HDG Discretizations
Authors: Tu Xuemin , Zhang Jinjin
Published: November 2022

The balancing domain decomposition by constraints (BDDC) methods are applied to the linear system arising from the hybridizable discontinuous Galerkin (HDG) discretization of the Oseen equation of incompressible flow. The generalized minimal residual method (GMRES) is used to accelerate the convergence. The original system is first reduced to a subdomain interface problem that is asymmetric indefinite, but can be positive definite in a special subspace. Edge/face average constraints can ensure all BDDC-preconditioned GMRES iterates stay in this special subspace. The convergence of the algorithm is analyzed, and additional edge/face constraints are used to improve the convergence. If the subdomain size is small enough, the number of iterations is independent of the number of subdomains, and depends only slightly on the subdomain problem size when the viscosity is large. When the viscosity is small, the convergence deteriorates. However, the numerical examples can give satisfactory results for the linear HDG discretization even with a small viscosity.
Recognizing Everyday Youth Agency: Advocating for a Reflexive Practice in Everyday International Relations
Authors: Beattie Amanda , Bird Gemma
Published: November 2022

This article intervenes in the ongoing discussion of Everyday international relations (IR). It draws on the discourse of epistemic injustice to explore the discussions of emerging research on everyday childhood. The article draws on a series of research visits, between 2017 and 2019, along the so-called Balkan Route attending to the emerging influence of children in the Greek Reception and Identification Centre, on the island of Samos. The article references the emerging discourses of “field” research within the discipline of IR, noting the dynamic nature of such ventures and the role of a reflexive practice therein. Using open-ended interviews, research diaries, and author observations, the article provides a detailed description of the role that education nongovernmental organizations (NGOs) on the island play in supporting child refugees, while opening up spaces of education, solidarity, and community building. It argues for the inclusion of children, as agents, within the discussions of Everyday IR to redress the erasure of children’s lived experience within everyday IR. The potential role of adults in this process is acknowledged and the article puts forward an alternative understanding of the adult/child relationship paying attention to the dynamics of power, the need for reflexive and critical listening, to hear the stories and ideas of children and young people, on their own terms aware that the article itself falls prey to some of the articulated challenges. It hopes to ignite a conversation beyond the (potential) central role for children in Everyday IR imagining their role within knowledge production.