bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic imaging of force chains in 3D granular media
Authors: Li Wei , Juanes Ruben
Published: March 2024

Granular media constitute the most abundant form of solid matter on Earth and beyond. When external forces are applied to a granular medium, the forces are transmitted through it via chains of contacts among grains—force chains. Understanding the spatial structure and temporal evolution of force chains constitutes a fundamental goal of granular mechanics. Here, we introduce an experimental technique, interference optical projection tomography, to study force chains in three-dimensional (3D) granular packs under triaxial shear loads and illustrate the technique with random assemblies of spheres and icosahedra. We find that, in response to an increasing vertical load, the pack of spheres forms intensifying vertical force chains, while the pack of icosahedra forms more interconnected force-chain networks. This provides microscopic insights into why particles with more angularity are more resistant to shear failure—the interconnected force-chain network is stronger (that is, more resilient to topological collapse) than the isolated force chains in round particles. The longer force chains with less branching in the pack of round particles are more likely to buckle, which leads to the macroscopic failure of the pack. This work paves the way for understanding the grain-scale underpinning of localized failure of 3D granular media, such as shear localization in landslides and stick–slip frictional motion in tectonic and induced earthquakes.
Highly efficient electrocatalytic CO
2
reduction by a Cr
III
quaterpyridine complex
Authors: Wang Jia-Wei , Luo Zhi-Mei , Yang Guangjun , Gil-Sepulcre Marcos , Kupfer Stephan , Rüdiger Olaf , Ouyang Gangfeng
Published: March 2024

Design tactics and mechanistic studies both remain as fundamental challenges during the exploitations of earth-abundant molecular electrocatalysts for CO
2
reduction, especially for the rarely studied Cr-based ones. Herein, a quaterpyridyl Cr
III
catalyst is found to be highly active for CO
2
electroreduction to CO with 99.8% Faradaic efficiency in DMF/phenol medium. A nearly one order of magnitude higher turnover frequency (86.6 s
−1
) over the documented Cr-based catalysts (<10 s
−1
) can be achieved at an applied overpotential of only 190 mV which is generally 300 mV lower than these precedents. Such a high performance at this low driving force originates from the metal–ligand cooperativity that stabilizes the low-valent intermediates and serves as an efficient electron reservoir. Moreover, a synergy of electrochemistry, spectroelectrochemistry, electron paramagnetic resonance, and quantum chemical calculations allows to characterize the key Cr
II
, Cr
I
, Cr
0
, and CO-bound Cr
0
intermediates as well as to verify the catalytic mechanism.
“The heart will stop beating”
Authors: Bartłomiejczyk Magdalena , Pöllabauer Sonja , Straczek-Helios Viktoria
Published: March 2024

This article highlights some ethical questions in activist interpreting in the context of transnational patient
mobility, with a specific focus on abortion travel from Poland to Austria. It presents a case study of Ciocia Wienia, a
Vienna-based activist collective which facilitates access to abortion mainly for Poles and provides support and interpreting
services in abortion clinics. Drawing primarily on the literature on activist interpreting and feminist interpreting and a corpus
of 13 in-depth qualitative interviews with members and associates of the collective, this study explores ethical dilemmas
experienced by the activist interpreters. We investigate the ways in which their translation choices are interwoven with the
feminist and pro-choice agenda that the collective embraces. Our data show that Ciocia Wienia has developed a feminist approach to
interpreting, one strongly informed by its political agenda. The activists adopt interventionist and sometimes highly visible
strategies of interpreting, including direct confrontation or negotiation with clinic staff, and have much leeway to use an array
of strategies of divergent rendition. While the priority of activist interpreters is to support and protect the women they assist,
they also risk impairing patient autonomy and service-providers’ control over interactions.
Lending a hand to speech
Authors: Cavicchio Federica , Grazia Busà Maria
Published: March 2024

This study examines the effect of gestures on second language (L2) pitch measures and fluency in storytelling tasks. It is well documented that L2 learners commonly use gestures in conversations and storytelling. Research has shown that gestures benefit L2 word learning and recall, but it is still unclear to what extent gestures affect speech fluency and pitch range. We compared a series of speech fluency and pitch measures across two storytelling tasks: task repetition and explicit instruction on the use of gestures. By analysing the use of gestures in these tasks, we provide insights on how gestures can help L2 fluency and intonation.
Tap/trill variation and change across generations of Spanish-Creole bilinguals in San Andrés, Colombia
Authors: Restrepo-Ramos Falcon
Published: March 2024

This work examines the behavior of vibrant (presenting linguo-alveolar contact) tap/trill variation across
generations of bilingual Afro-Caribbean speakers of Spanish and an English-Lexifier Creole, known here as Raizal Creole, in the
Archipelago of San Andrés, Colombia. In these islands, a bilingual Spanish variety, known here as Raizal Spanish, coexists with a
monolingual Spanish variety spoken by Colombian immigrants (Costeño Spanish). Data consists of over 3,300 tokens (867 trills and
2531 taps) compared across three generations of Raizal Spanish speakers with a sample of 528 segments (133 trills and 395 taps)
produced in Costeño Spanish. Results show that although the frequency of use of vibrant taps and trills in younger generations
increasingly resembles those presented in the monolingual variety, the behavior of rhotic variation is different in both Spanish
varieties. In addition, non-vibrant or approximant variants are increasingly prevalent in the first and second generation
informants with rates doubling those of the younger generation and monolingual Costeño Spanish. Results of the cross-variety
comparison show that Raizal Spanish displays a generational continuity where a restructuring of the constraint ordering starts in
the second generation and is completed with younger Raizales. On the contrary, Costeño Spanish behaves differently in terms of the
systematic linguistic conditionings. The evidence suggests that rhotic variation has changed internally within both varieties.
An approach to solving the effect of background in fluidized bed on electromagnetic tomography
Authors: Luan Xinyu , Wang Chao , Liang Xiao
Published: March 2024

As a non-invasive measurement technique, electromagnetic tomography (EMT) system based on tunneling magneto resistance (TMR) can detect the distribution of medium in the gas–liquid–solid fluidized bed by the difference of permeability. The distribution of medium in the three-phase fluidized bed is not uniform, and the solid clusters and bubble clusters are formed in the background of the gas–liquid–solid mixture. Since the effect of the background in the pipe of the fluidized bed on the boundary measurement data of the TMR-EMT system is much greater, it is difficult to detect solid clusters and bubble clusters when the image is reconstructed directly using the boundary measurement data. In order to improve the detection of clusters by the TMR-EMT system, a method to weaken the effect of the background is proposed. The equivalent magnetic circuit model is used to estimate the background permeability. Then the magnetic dipole theory and demagnetization effect theory are utilized to establish a simple background compensation model based on the estimated background permeability. Using the compensation model, the effect of the background is weakened from the boundary measurement data and the cluster distribution information is highlighted. Simulation and experimental results demonstrate the effectiveness of the proposed method.
Near-resonant light scattering by an atom in a state-dependent trap
Authors: Karanikolaou T D , Bettles R J , Chang D E
Published: March 2024

There are an increasing number of experimental scenarios where near-resonant light is applied to atoms tightly trapped in far off-resonant optical fields, such as for quantum optics applications or for atom imaging. Oftentimes, the electronic ground and excited states involved in the optical transition experience unequal trapping potentials. Here, we systematically analyze the effects of unequal trapping on near-resonant atom–light interactions. In particular, we identify regimes where such trapping can lead to significant excess heating compared to atoms in state-independent potentials, and a reduction of total and elastic scattering cross sections associated with a decreased atom–photon interaction efficiency. Understanding these effects can be valuable for achieving maximum efficiency in quantum optics experiments or atom imaging setups, where efficient atom–light interactions on resonance are desired, but achieving equal trapping is not feasible.
Sensitivity estimation of biosensor in a tapered cavity MOSHEMT
Authors: Dastidar Ananya , Patra Tapas Kumar , Mohapatra Sushanta Kumar , Pradhan K P , Alodhayb Abdullah N
Published: March 2024

The present research provides a comprehensive investigation of the structural modification at the cavity under the gate (CUG) on the metal oxide semiconductor high electron mobility transistor (MOSHEMT)-based biosensor by projecting its basic figures of merit (FOMs). The effect of a tapering dielectric on the sensitivity of the biosensor has not been extensively investigated in many research efforts. Therefore, to account for the larger binding surface, the current study considers a wide range of permittivity of the biomolecules from 1 to 10, using the dielectric modulation technique in the tapered cavity. Various cavities are analysed to enhance the sensitivity. The findings indicate that the presence of biomolecules causes a considerable fluctuation in the drain current, threshold voltage, on-current, off-current, channel potential, and oxide capacitance. It has also been estimated how various fill percentages and charged and neutral biomolecules affect the device’s sensitivity. The tapered dielectric MOSHEMT offered an on-current sensitivity and threshold voltage sensitivity of 1.25 and 0.889 for neutral biomolecule (k = 8) and 0.562 and 2.23 for positively charged biomolecule respectively. Thus, tapering of the oxide does offer better sensitivities that can be exploited for biosensing applications.
Dynamics in a light-sensitive neuron with two capacitive variables
Authors: Wang Binchi , Lv Mi , Zhang Xiaofeng , Ma Jun
Published: March 2024

Involvement of two capacitive variables into neuron models provides better description of the cell membrane property and then the diversity effect of electromagnetic field inner and outer of the cell membrane can be estimated in clear way. Specific electric components can be combined to build equivalent neural circuits for reproducing similar neural activities under some self-adaptive control schemes. A phototube converts external light into electric stimuli and the injected energy is encoded to excite the cell membranes for presenting suitable firing patterns. Two capacitors are connected via a linear resistor for mimicking the energy exchange and changes of membrane potentials. Combination of memristor into an additive branch circuit of the neural circuit can estimate the effect of electromagnetic induction and energy absorption. The energy function H for this light-sensitive and memristive neuron is calculated in theoretical way, and the average energy function 〈H〉 can predict the occurrence of stochastic resonance, which can be confirmed by estimating the distribution of signal to noise ratios. The firing mode is relative to the energy value of the neuron, and a control law is suggested to control the mode transition in neural activities in an adaptive way.
Navigating complexity of the medication management system within the home setting—a functional resonance analysis method (FRAM) analysis of people with dementia and their carers’ experiences
Authors: Lim Rosemary , Iflaifel Mais , Qamariat Zahra A L , Crowley Clare , Sharmeen Taniya
Published: March 2024

Background

There is a strong imperative to support people with dementia to live independently in their homes for as long as possible. A starting point is to understand how they manage medications on a daily basis.

Aim

To understand how people with dementia and their informal carers manage medications within the home setting to inform the identification of opportunities to improve medication management.

Methods

A qualitative study using the Functional Resonance Analysis Method (FRAM). Interview data with people with dementia and informal carers were analysed to (i) Identify and describe key functions, (ii) identify and describe variability in performing key functions, and its potential consequences and (iii) map performance variability to Resilient Healthcare capacities.

Results and discussion

A FRAM model was developed and consisted of 14 interdependent key functions. The interdependent nature of functions, and the different nature and sources of variability in how each key function was performed highlighted the level of complexity of the medication management system within the home setting. The medication system was managed almost entirely by the person with dementia and/or their informal carers. This shows the lack of system-level controls to support the safe functioning of the medication management system in the home setting.

Conclusion

Future work will develop a comprehensive FRAM model that includes the perspectives of health and social care professionals and those from the third sectors to underpin the development of a range of system recommendations to strengthen resilience in the medication management system within the home setting.
Parenteral nutrition at home/long-term parenteral nutrition
Authors: Kumpf Vanessa J , Gray Brenda , Monczka Jessica , Zeraschi Sarah , Klek Stanislaw
Published: March 2024

Purpose

Some diseases require that patients receive parenteral nutrition (PN) over a prolonged time period. Long-term administration of PN can further complicate an already complex therapy, posing additional risk of potential complications. This article is based on presentations and discussions held at the International Safety and Quality of PN Summit, providing insights into aspects of home PN (HPN) and examples of good HPN practice.

One critical step in the HPN process is when patients transition from a hospital to a home setting, and vice versa. Generally, electronic PN ordering is not feasible in an HPN setting, leading to potential difficulties in communication and coordination. HPN requires that patients (or their home caregivers) administer PN, and thus their education and competency are crucial. Likewise, the choice of PN formulation is of great importance. For example, using more modern intravenous lipid emulsions containing medium-chain triglycerides, olive oil, and/or fish oil can provide benefits in terms of liver function during long-term HPN. Internationally, there are wide variations in delivery of HPN, with compounded PN dominating in some countries while others make greater use of market-authorized multichamber bags (MCBs). Patient-related factors, institutional considerations, and the availability of different MCB formulations, are also contributing factors guiding formulation and delivery system preferences.

Conclusion

Education and communication remain key components of a successful HPN process. The information shared here may help to motivate efforts to improve HPN processes and to consider the often-differing perspectives of patients and their healthcare professionals.
Against the no-difference argument
Authors: Elga Adam
Published: March 2024

There are 1,000 of us and one victim. We each increase the level at which a ‘discomfort machine’ operates on the victim – leading to great discomfort. Suppose that consecutive levels of the machine are so similar that the victim cannot distinguish them. Have we acted permissibly? According to the ‘no-difference argument’ the answer is ‘yes’ because each of our actions was guaranteed to make the victim no worse off. This argument is of interest because, if it is sound, similar arguments threaten intuitive moral verdicts about many cases in which a large number of individual choices cumulatively make a great difference, while each choice seems to make no difference on its own. But the argument is not sound, as is shown by a simple objection based on a plausible dominance principle – an objection that avoids challenges that have been brought against previous criticisms of the no-difference argument.
Variations in wood anatomy in Afrotropical trees with a particular emphasis on radial and axial parenchyma
Authors: Plavcová Lenka , Jandová Veronika , Altman Jan , Liancourt Pierre , Korznikov Kirill , Doležal Jiří
Published: March 2024

Background and Aims

Understanding anatomical variations across plant phylogenies and environmental gradients is vital for comprehending plant evolution and adaptation. Previous studies on tropical woody plants have paid limited attention to quantitative differences in major xylem tissues, which serve specific roles in mechanical support (fibres), carbohydrate storage and radial conduction (radial parenchyma, rays), wood capacitance (axial parenchyma) and water transport (vessels). To address this gap, we investigate xylem fractions in 173 tropical tree species spanning 134 genera and 53 families along a 2200-m elevational gradient on Mount Cameroon, West Africa.

Methods

We determined how elevation, stem height and wood density affect interspecific differences in vessel, fibre, and specific axial (AP) and radial (RP) parenchyma fractions. We focus on quantifying distinct subcategories of homogeneous or heterogeneous rays and apotracheal, paratracheal and banded axial parenchyma.

Key Results

Elevation-related cooling correlated with reduced AP fractions and vessel diameters, while fibre fractions increased. Lower elevations exhibited elevated AP fractions due to abundant paratracheal and wide-banded parenchyma in tall trees from coastal and lowland forests. Vasicentric and aliform AP were predominantly associated with greater tree height and wider vessels, which might help cope with high evaporative demands via elastic wood capacitance. In contrast, montane trees featured a higher fibre proportion, scarce axial parenchyma, smaller vessel diameters and higher vessel densities. The lack of AP in montane trees was often compensated for by extended uniseriate ray sections with upright or squared ray cells or the presence of living fibres.

Conclusions

Elevation gradient influenced specific xylem fractions, with lower elevations showing elevated AP due to abundant paratracheal and wide-banded parenchyma, securing greater vessel-to-parenchyma connectivity and lower embolism risk. Montane trees featured a higher fibre proportion and smaller vessel diameters, which may aid survival under greater environmental seasonality and fire risk.
PyCoM: a python library for large-scale analysis of residue–residue coevolution data
Authors: Bibik Philipp , Alibai Sabriyeh , Pandini Alessandro , Dantu Sarath Chandra
Published: March 2024

Motivation

Computational methods to detect correlated amino acid positions in proteins have become a valuable tool to predict intra- and inter-residue protein contacts, protein structures, and effects of mutation on protein stability and function. While there are many tools and webservers to compute coevolution scoring matrices, there is no central repository of alignments and coevolution matrices for large-scale studies and pattern detection leveraging on biological and structural annotations already available in UniProt.

Results

We present a Python library, PyCoM, which enables users to query and analyze coevolution matrices and sequence alignments of 457 622 proteins, selected from UniProtKB/Swiss-Prot database (length ≤ 500 residues), from a precompiled coevolution matrix database (PyCoMdb). PyCoM facilitates the development of statistical analyses of residue coevolution patterns using filters on biological and structural annotations from UniProtKB/Swiss-Prot, with simple access to PyCoMdb for both novice and advanced users, supporting Jupyter Notebooks, Python scripts, and a web API access. The resource is open source and will help in generating data-driven computational models and methods to study and understand protein structures, stability, function, and design.

Availability and implementation

PyCoM code is freely available from https://github.com/scdantu/pycom and PyCoMdb and the Jupyter Notebook tutorials are freely available from https://pycom.brunel.ac.uk.
The spatial ecology of Mojave rattlesnakes (Crotalus scutulatus), prairie rattlesnakes (Crotalus viridis), and their hybrids in southwestern New Mexico
Authors: Maag Dylan W , Francioli Yannick Z , Castoe Todd A , Schuett Gordon W , Clark Rulon W
Published: March 2024

Hybridization between species provides unique opportunities to understand evolutionary processes that are linked to reproductive isolation and, ultimately, speciation. However, the extrinsic factors that limit hybridization are poorly understood for most animal systems. Although the spatial ecology of individuals in natural habitats is fundamental to shaping reproductive success and survival, analyses of the spatial ecology of hybrids and their parental groups are rarely reported. Here, we used radiotelemetry to monitor wild rattlesnakes across an interspecific hybrid zone (Crotalus scutulatus and Crotalus viridis) and measured movement parameters and space use (utilization distributions) of individuals to evaluate the hypothesis that hybridization resulted in transgressive or atypical movement patterns. Unexpectedly, of the spatial metrics we investigated, we found that hybrids were very similar to parental individuals. Nonetheless, hybrids did show increased patchiness of core utilization distributions, but this result is likely to be driven by increased habitat patchiness in the hybrid zone. Overall, we did not find evidence for overt extrinsic barriers to hybridization associated with spatial ecology; thus, we suggest that the close evolutionary history between the two parental species and their ecological and behavioural similarities are likely to increase the probability of hybridization events in this unique region of New Mexico.
Lesion network of oculogyric crises maps to brain dopaminergic transcriptomic signature
Authors: Al-Fatly Bassam , Neudorfer Clemens , Kaski Diego , Lang Anthony E , Kühn Andrea A , Fox Michael D , Horn Andreas , Ganos Christos
Published: March 2024

Oculogyric crises are acute episodes of sustained, typically upward, conjugate deviation of the eyes. Oculogyric crises usually occur as the result of acute D2-dopamine receptor blockade, but the brain areas causally involved in generating this symptom remain elusive. Here, we used data from 14 previously reported cases of lesion-induced oculogyric crises and employed lesion network mapping to identify their shared connections throughout the brain. This analysis yielded a common network that included basal ganglia, thalamic, and brainstem nuclei, as well as the cerebellum. Comparison of this network with gene expression profiles associated with the dopamine system revealed spatial overlap specifically with the gene coding for dopamine receptor type 2 (DRD2) as defined by a large-scale transcriptomic database of the human brain. Furthermore, spatial overlap with DRD2 and DRD3 gene expression was specific to brain lesions associated with oculogyric crises when contrasted to lesions that led to other movement disorders. Our findings identify a common neural network causally involved in the occurrence of oculogyric crises and provide a pathophysiological link between lesion locations causing this syndrome and its most common pharmacological cause, namely DRD2 blockade.
Messenger RNA-encoded antibody approach for targeting extracellular and intracellular tau
Authors: Wongsodirdjo Patricia , Caruso Alayna C , Yong Alicia K , Lester Madeleine A , Vella Laura J , Hung Ya Hui , Nisbet Rebecca M
Published: March 2024

Monoclonal antibodies have emerged as a leading therapeutic agent for the treatment of disease, including Alzheimer’s disease. In the last year, two anti-amyloid monoclonal antibodies, lecanemab and aducanumab, have been approved in the USA for the treatment of Alzheimer’s disease, whilst several tau-targeting monoclonal antibodies are currently in clinical trials. Such antibodies, however, are expensive and timely to produce and require frequent dosing regimens to ensure disease-modifying effects. Synthetic in vitro-transcribed messenger RNA encoding antibodies for endogenous protein expression holds the potential to overcome many of the limitations associated with protein antibody production. Here, we have generated synthetic in vitro-transcribed messenger RNA encoding a tau-specific antibody as a full-sized immunoglobulin and as a single-chain variable fragment. In vitro transfection of human neuroblastoma SH-SY5Y cells demonstrated the ability of the synthetic messenger RNA to be translated into a functional tau-specific antibody. Furthermore, we show that the translation of the tau-specific single-chain variable fragment as an intrabody results in the specific engagement of intracellular tau. This work highlights the utility of messenger RNA for the delivery of antibody therapeutics, including intrabodies, for the targeting of tau in Alzheimer’s disease and other tauopathies.
Maintained renin–angiotensin–aldosterone system inhibitor therapy with sodium zirconium cyclosilicate following a hyperkalaemia episode: a multicountry cohort study
Authors: Rastogi Anjay , Pollack Charles V , Sánchez Lázaro Ignacio José , Lesén Eva , Arnold Matthew , Franzén Stefan , Allum Alaster , Hernández Ignacio , Murohara Toyoaki , Kanda Eiichiro
Published: March 2024

Background

This observational cohort study compared the likelihood of maintained (stabilized/up-titrated) renin–angiotensin–aldosterone system inhibitor (RAASi) therapy at 6 months following hyperkalaemia in patients with chronic kidney disease (CKD) and/or heart failure (HF) from the USA, Japan and Spain who received sodium zirconium cyclosilicate (SZC) for at least 120 days, relative to those with no prescription for a potassium (K+) binder.

Methods

Using health registers and hospital medical records, patients with CKD and/or HF receiving RAASi therapy who experienced a hyperkalaemia episode were identified. Propensity score (PS) matching (1:4) was applied to balance the SZC cohort to the no K+ binder cohort on baseline characteristics. Logistic regression analysis was performed to compare the odds of maintained RAASi therapy at 6 months in the SZC versus no K+ binder cohorts.

Results

The PS-matched SZC cohort included 565 (USA), 776 (Japan) and 56 (Spain) patients; the no K+ binder cohort included 2068, 2629 and 203 patients, respectively. At 6 months, 68.9% (USA), 79.9% (Japan) and 69.6% (Spain) in the SZC cohorts versus 53.1% (USA), 56.0% (Japan) and 48.3% (Spain) in the no K+ binder cohorts had maintained RAASi therapy. Meta-analysed across countries, the odds ratio of maintained RAASi therapy in the SZC cohort versus no K+ binder cohort was 2.56 (95% confidence interval 1.92–3.41; P < .0001).

Conclusions

In routine clinical practice across three countries, patients treated with SZC were substantially more likely to maintain guideline-concordant RAASi therapy at 6 months following hyperkalaemia relative to patients with no K+ binder treatment.
High-resolution free-breathing automated quantitative myocardial perfusion by cardiovascular magnetic resonance for the detection of functionally significant coronary artery disease
Authors: Crawley R , Kunze K P , Milidonis X , Highton J , McElroy S , Frey S M , Hoefler D , Karamanli C , Wong N C K , Backhaus S J , Alskaf E , Neji R , Scannell C M , Plein S , Chiribiri A
Published: March 2024

Aims

Current assessment of myocardial ischaemia from stress perfusion cardiovascular magnetic resonance (SP-CMR) largely relies on visual interpretation. This study investigated the use of high-resolution free-breathing SP-CMR with automated quantitative mapping in the diagnosis of coronary artery disease (CAD). Diagnostic performance was evaluated against invasive coronary angiography (ICA) with fractional flow reserve (FFR) measurement.

Methods and results

Seven hundred and three patients were recruited for SP-CMR using the research sequence at 3 Tesla. Of those receiving ICA within 6 months, 80 patients had either FFR measurement or identification of a chronic total occlusion (CTO) with inducible perfusion defects seen on SP-CMR. Myocardial blood flow (MBF) maps were automatically generated in-line on the scanner following image acquisition at hyperaemic stress and rest, allowing myocardial perfusion reserve (MPR) calculation. Seventy-five coronary vessels assessed by FFR and 28 vessels with CTO were evaluated at both segmental and coronary territory level. Coronary territory stress MBF and MPR were reduced in FFR-positive (≤0.80) regions [median stress MBF: 1.74 (0.90–2.17) mL/min/g; MPR: 1.67 (1.10–1.89)] compared with FFR-negative regions [stress MBF: 2.50 (2.15–2.95) mL/min/g; MPR 2.35 (2.06–2.54) P < 0.001 for both]. Stress MBF ≤ 1.94 mL/min/g and MPR ≤ 1.97 accurately detected FFR-positive CAD on a per-vessel basis (area under the curve: 0.85 and 0.96, respectively; P < 0.001 for both).

Conclusion

A novel scanner-integrated high-resolution free-breathing SP-CMR sequence with automated in-line perfusion mapping is presented which accurately detects functionally significant CAD.
Mutation Rate and Effective Population Size of the Model Cooperative Bacterium Myxococcus xanthus
Authors: Wielgoss Sébastien , Van Dyken James David , Velicer Gregory J
Published: March 2024

Intrinsic rates of genetic mutation have diverged greatly across taxa and exhibit statistical associations with several other parameters and features. These include effective population size (Ne), genome size, and gametic multicellularity, with the latter being associated with both increased mutation rates and decreased effective population sizes. However, data sufficient to test for possible relationships between microbial multicellularity and mutation rate (µ) are lacking. Here, we report estimates of two key population-genetic parameters, Ne and µ, for Myxococcus xanthus, a bacterial model organism for the study of aggregative multicellular development, predation, and social swarming. To estimate µ, we conducted an ∼400-day mutation accumulation experiment with 46 lineages subjected to regular single colony bottlenecks prior to clonal regrowth. Upon conclusion, we sequenced one clonal-isolate genome per lineage. Given collective evolution for 85,323 generations across all lines, we calculate a per base-pair mutation rate of ∼5.5 × 10−10 per site per generation, one of the highest mutation rates among free-living eubacteria. Given our estimate of µ, we derived Ne at ∼107 from neutral diversity at four-fold degenerate sites across two dozen M. xanthus natural isolates. This estimate is below average for eubacteria and strengthens an already clear negative correlation between µ and Ne in prokaryotes. The higher and lower than average mutation rate and Ne for M. xanthus, respectively, amplify the question of whether any features of its multicellular life cycle—such as group-size reduction during fruiting-body development—or its highly structured spatial distribution have significantly influenced how these parameters have evolved.
Partisanship with Rightist and Leftist Parties in Central America: A Test of Four Hypotheses
Authors: Perelló Lucas , Navia Patricio
Published: March 2024

Although scholars have made substantial progress in the debate on party systems in Latin America, many questions about partisanship in the region remain unaddressed. This article explores how the determinants of partisanship identified in the literature navigate in Central America, a region commonly overlooked by scholars. We examine a decade of public opinion surveys by the Latin American Public Opinion Project (LAPOP) from 2008 to 2018 to explore the individual-level determinants of partisan attachments with sixty-six leftist and rightist parties in six Central American countries to test four hypotheses. While differences across countries exist, self-placement on the left-right ideological scale, engagement in societal organizations, and protest participation help portray partisan attachments.
Development of a Reversed-Phase UPLC Method for Assay of Fipronil Including Determination of Its Related Substances in Bulk Batches of Fipronil Drug Substance
Authors: Berger Shane N , Rustum Abu M
Published: March 2024

Background

Fipronil is a commonly used pesticide in the agricultural and animal health industries for the protection of crops and control of fleas, ticks, and chewing lice. It is difficult to obtain reproducible retention time and relative retention time (RRT) for a common hydrolytic degradation product of fipronil with the current European Pharmacopeia (EP) monograph for assay and estimation of related substances of fipronil. This situation causes misidentification, mislabeling, and/or false out-of-specification results for this hydrolytic degradation product of fipronil in bulk commercial batches during batch release and/or in the stability samples during the shelf life of a released batch.

Objective

This study aimed to develop a reversed-phase ultra performance liquid chromatography (UPLC) method for assay and identification of fipronil including identification and estimation of its related substances in bulk drug substance batches of fipronil and provide consistent retention time of the hydrolytic degradation product.

Methods

Fipronil and its related substances were separated by gradient elution on a Halo C18 column (50 mm × 2.1 mm id, 2.0 µm particle size) maintained at 40°C with 0.1% H3PO4 in H2O as mobile phase-A and acetonitrile–methanol (50 + 50, v/v) as mobile phase-B. Fipronil and its related substances were detected and quantified at 280 nm with a quantitation limit of 0.05% of the target (analytical) concentration.

Results

The UPLC method was able to separate all analytes of interest by gradient elution with a total run time of 7 min (approximately 40% faster than EP).

Conclusion

In this paper, we report the development and validation of a fast, stability-indicating reversed-phase UPLC method for assay and estimation of related substances of fipronil in stability samples and bulk batches of fipronil.

Highlights

The new UPLC method is approximately 40% faster than the current Ph. Eur. monograph for fipronil assay and the new method provides reproducible retention of a common hydrolytic degradation product of fipronil.
Building an ethical research culture: Scholars of refugee background researching refugee-related issues
Authors: Albtran Ahmad , Aksu Pinar , Al-Fakir Zuhair , Al-Hashimi Heidar , Baillot Helen , Izzeddin Azad , Yohannes Hyab Teklehaimanot , Kirkwood Steve , Mfaco Bulelani , Nicole Tandy , Ní Raghallaigh Muireann , Ogutu Gordon , O’Reilly Zoë , Younes Angham
Published: March 2024

Recent scholarship on the need to decolonize refugee research, and migration research more generally, points to the urgency of challenging ongoing colonial power structures inherent in such research. Increased involvement of scholars with lived experience is one way to challenge and remake unequal and colonial power relations. Through discussions with researchers of forced migration, we aimed to explore the challenges, barriers, and supports related to involvement in such research, and to identify how research practices and structures could be improved to increase and facilitate the involvement of scholars with refugee backgrounds. In this field reflection, we highlight key points and suggestions for better research practice that emerged from these discussions. In doing so, we are endeavouring to contribute to the important ongoing conversation about ethics and decolonizing research. We build on existing ethical guidelines by opening up some of the complexities of ethical practice and offering concrete actions that can be taken to work through these.
Identification of causal diffusion effects using placebo outcomes under structural stationarity
Authors: Egami Naoki
Published: March 2024

Social and biomedical scientists have long been interested in the process through which ideas and behaviours diffuse. In this article, we study an urgent social problem, the spatial diffusion of hate crimes against refugees in Germany, which has admitted more than 1 million asylum seekers since the 2015 refugee crisis. Despite its importance, identification of causal diffusion effects, also known as peer and contagion effects, remains challenging because the commonly used assumption of no omitted confounders is often untenable due to contextual confounding and homophily bias. To address this long-standing problem, we examine causal identification using placebo outcomes under a new assumption of structural stationarity, which formalizes the underlying diffusion process with a class of nonparametric structural equation models with recursive structure. We show under structural stationarity that a lagged dependent variable is a general, valid placebo outcome for detecting a wide range of biases, including the 2 types mentioned above. We then propose a difference-in-differences style estimator that can directly correct biases under an additional causal assumption. Analysing fine-grained geo-coded hate crime data from Germany, we show when and how the proposed methods can detect and correct unmeasured confounding in spatial causal diffusion analysis.
Comapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy
Authors: Tobe Yasutaka , Robertson Anne M , Ramezanpour Mehdi , Cebral Juan R , Watkins Simon C , Charbel Fady T , Amin-Hanjani Sepideh , Yu Alexander K , Cheng Boyle C , Woo Henry H
Published: March 2024

Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for acquiring and comapping local vascular wall biology data with local hemodynamic data. Here, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was developed to obtain three-dimensional (3D) datasets for smooth muscle actin, collagen, and elastin in intact vascular specimens. A cluster analysis was introduced to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC actin density. Finally, direct quantitative comparison of local flow and wall biology in 3D intact specimens was achieved by comapping both heterogeneous SMC data and wall thickness to patient-specific hemodynamic results.
Ocular Effects of MEK Inhibitor Therapy: Literature Review, Clinical Presentation, and Best Practices for Mitigation
Authors: Jeng-Miller Karen W , Miller Miles A , Heier Jeffrey S
Published: March 2024

MEK signaling pathway targeting has emerged as a valuable addition to the options available for the treatment of advanced cancers including melanoma and non-small cell lung cancer. Ophthalmologic monitoring of patients taking part in clinical trials of MEK inhibitors has shown that while ocular effects are common, generally emerging during the first days to weeks of treatment, the majority are either asymptomatic or have minimal visual impact and are benign, resolving without intervention or the need to reduce or stop MEK inhibitor therapy. However rare cases of serious, potentially vision-threatening ocular toxicities have been reported during MEK inhibitor therapy. There is currently no recommendation for routine ophthalmologic screening or monitoring of patients with advanced cancer who are initiating MEK inhibitor therapy. However, baseline ophthalmologic examination may be useful for all patients initiating MEK inhibitor therapy to allow the differentiation of preexisting pathology versus the development of MEK inhibitor-associated retinopathy in the event of the emergence of symptomatic ocular events. Regular ophthalmologic examination may be appropriate for patients at increased risk for ocular events, such as patients with a history of ocular inflammation, infection, or underlying macular/retinal disease. All patients reporting visual disturbance should be referred for prompt ophthalmologic review to determine the potential seriousness of any underlying abnormalities and whether there is a need for treatment modification or specific intervention. Understanding the potential consequences of ocular toxicities is of particular importance in the context of decision-making for the continuation of potentially life-prolonging medications such as MEK inhibitors.
The ideational robustness of liberal democracy in the wake of the pandemic: comparing the Danish and Swedish cases
Authors: Knaggård Åsa , Triantafillou Peter
Published: March 2024

The Covid-19 pandemic sparked unprecedented political responses dramatically affecting societies, markets, and the lives of individuals. Under great uncertainty and turbulent conditions, governments adopted far-reaching political interventions to curb the pandemic. These interventions might therefore be expected to challenge key ideas underpinning liberal democracy. We analyze and compare how the political interventions seeking to curb the spread of the coronavirus in Denmark and Sweden challenged and possibly adapted three key ideas underpinning liberal democracy, namely, constitutionality, parliamentarism, and public responsiveness. When ideas are adapted in ways that advance their ability to stay relevant when faced with turbulence, we understand them as robust. Our study found both similarities and differences between the two countries. The idea of constitutionality was challenged in Denmark but remained robust in Sweden. The idea of parliamentarism appeared robust in both countries, whereas the idea of public responsiveness was adapted in neither country but challenged further in Sweden than in Denmark. Paradoxically, Denmark saw fewer adaptations to the liberal democratic ideas than Sweden yet appeared better prepared to protect lives during turbulent times. Our study suggests that liberal democracies must very carefully balance trade-offs between individual liberties and the protection of public health to preserve the core public ideas of constitutionality, parliamentarism, and public responsiveness.
Genotoxicity and cytotoxicity of antineoplastic drugs at environmentally relevant concentrations after long-term exposure
Authors: da Cunha de Medeiros P , Nunes E A , Barcelos G R M , Perobelli J E
Published: March 2024

Introduction

5-fluorouracil (5-FU) and methotrexate (MTX) are the antineoplastic drugs most commonly used worldwide. Considered cytotoxic, these pharmaceuticals exhibit low specificity, causing damage not only to cancer cells but also to healthy cells in organisms. After being consumed and metabolized, these drugs are excreted through urine and feces, followed by wastewater treatment. However, conventional treatments do not have the capacity to completely remove these substances, risking their introduction into freshwater systems. This could pose a risk to human health even at low concentrations.

Aims

Thus, the present study aimed to investigate the genotoxicity, cytotoxicity, and mutagenicity of 5-FU and MTX at environmentally relevant concentrations after a long-term exposure, using adult male rats as an experimental model.

Methods

Male Wistar rats (70 days old) were distributed into 4 groups (n = 10/group): control, received only vehicle; MTX, received methotrexate at 10ngL−1; 5-FU received 5-fluorouracil at 10ngL−1; and MTX + 5-FU, received a combination of MTX and 5-FU at 10ngL−1 each. The period of exposure was from postnatal day (PND) 70 to PND 160, through drinking water. After that, the animals were euthanized and the samples (liver, testis, femoral bone marrow, and peripheral blood) were obtained.

Results

Increased DNA fragmentation was observed in the peripheral blood, liver, and testis, altering the parameters of the tail moment and tail intensity in the Comet assay. Besides, the change in the ratio between PCE and NCE indicates bone marrow suppression.

Conclusion

These findings warn the adverse effects for the general population worldwide chronically exposed to these drugs at trace concentration unintentionally.
Characterization of individual bile acids in vivo utilizing a novel low bile acid mouse model
Authors: Taylor Rulaiha , Yang Zhenning , Henry Zakiyah , Capece Gina , Meadows Vik , Otersen Katherine , Basaly Veronia , Bhattacharya Anisha , Mera Stephanie , Zhou Peihong , Joseph Laurie , Yang Ill , Brinker Anita , Buckley Brian , Kong Bo , Guo Grace L
Published: March 2024

Bile acids (BAs) are signaling molecules synthesized in the liver initially by CYP7A1 and CYP27A1 in the classical and alternative pathways, respectively. BAs are essential for cholesterol clearance, intestinal absorption of lipids, and endogenous modulators of farnesoid x receptor (FXR). FXR is critical in maintaining BA homeostasis and gut-liver crosstalk. Complex reactions in vivo and the lack of suitable animal models impede our understanding of the functions of individual BAs. In this study, we characterized the in vivo effects of three-day feeding of cholic acid (CA), deoxycholic acid (DCA), or ursodeoxycholic acid (UDCA) at physiological/non-hepatotoxic concentrations in a novel low-BA mouse model (Cyp7a1−/−/Cyp27a1−/−, DKO). Liver injury, BA levels and composition and BA signaling by the FXR-fibroblast growth factor 15 (FGF15) axis were determined. Overall, higher basal inflammation and altered lipid metabolism in DKO mice might be associated with low BAs. CA, DCA, and UDCA feeding activated FXR signals with tissue specificity. Dietary CA and DCA similarly altered tissue BA profiles to be less hydrophobic, while UDCA promoted a more hydrophobic tissue BA pool with the profiles shifted toward non-12α-OH BAs and secondary BAs. However, UDCA did not offer any overt protective effects as expected. These findings allow us to determine the precise effects of individual BAs in vivo on BA-FXR signaling and overall BA homeostasis in liver physiology and pathologies.