bluuebunny/crossref_metadata_2025_split huggingface dataset:
The reaction mechanism of the Ideonella sakaiensis PETase enzyme
Authors: Burgin Tucker , Pollard Benjamin C. , Knott Brandon C. , Mayes Heather B. , Crowley Michael F. , McGeehan John E. , Beckham Gregg T. , Woodcock H. Lee 
Published: March 2024

AbstractPolyethylene terephthalate (PET), the most abundantly produced polyester plastic, can be depolymerized by the Ideonella sakaiensis PETase enzyme. Based on multiple PETase crystal structures, the reaction has been proposed to proceed via a two-step serine hydrolase mechanism mediated by a serine-histidine-aspartate catalytic triad. To elucidate the multi-step PETase catalytic mechanism, we use transition path sampling and likelihood maximization to identify optimal reaction coordinates for the PETase enzyme. We predict that deacylation is likely rate-limiting, and the reaction coordinates for both steps include elements describing nucleophilic attack, ester bond cleavage, and the “moving-histidine” mechanism. We find that the flexibility of Trp185 promotes the reaction, providing an explanation for decreased activity observed in mutations that restrict Trp185 motion. Overall, this study uses unbiased computational approaches to reveal the detailed reaction mechanism necessary for further engineering of an important class of enzymes for plastics bioconversion.
Non-invasive measurements of blood glucose levels by time-gating mid-infrared optoacoustic signals
Authors: Uluç Nasire , Glasl Sarah , Gasparin Francesca , Yuan Tao , He Hailong , Jüstel Dominik , Pleitez Miguel A. , Ntziachristos Vasilis 
Published: March 2024

AbstractNon-invasive glucose monitoring (NIGM) represents an attractive alternative to finger pricking for blood glucose assessment and management of diabetes. Nevertheless, current NIGM techniques do not measure glucose concentrations in blood but rely on indirect bulk measurement of glucose in interstitial fluid, where glucose is diluted and glucose dynamics are different from those in the blood, which impairs NIGM accuracy. Here we introduce a new biosensor, termed depth-gated mid-infrared optoacoustic sensor (DIROS), which allows, for the first time, non-invasive glucose detection in blood-rich volumes in the skin. DIROS minimizes interference caused by the stratum corneum and other superficial skin layers by time-gating mid-infrared optoacoustic signals to enable depth-selective localization of glucose readings in skin. In measurements on the ears of (female) mice, DIROS displays improved accuracy over bulk-tissue glucose measurements. Our work demonstrates how signal localization can improve NIGM accuracy and positions DIROS as a holistic approach, with high translational potential, that addresses a key limitation of current NIGM methods.
Applications of Pulsed Field Gradient Nuclear Magnetic Resonance to Late-stage Pharmaceutical and Biopharmaceutical Development and Deployment
Authors: Mantle Michael D. 
Published: March 2024

Pulsed field gradient nuclear magnetic resonance (PFG-NMR) is a powerful methodology that encodes the microscopic molecular displacements of a substance. Subsequent analysis of the PFG-NMR data then recovers the substance’s molecular self-diffusivity, D, in units of m2 s−1. This chapter is primarily divided into two sections: the first section elucidates the background and theory behind the PFG-NMR experiment and describes mathematically how the molecular self-diffusion coefficient, D, is extracted from PFG-NMR datasets. The latter half of the first section demonstrates how numerical simulations of PFG-NMR data serve as valuable tools to illustrate the effects observed in real PFG-NMR datasets. These effects include multiple-component molecular diffusion, diffusive molecular exchange, and restricted diffusion. The second half of the chapter focuses on the diverse applications of PFG-NMR in late-stage pharmaceutical and biopharmaceutical development and deployment research. It emphasizes specific research aimed at enhancing our scientific comprehension of the principal challenges and questions faced by the pharmaceutical and biopharmaceutical industries.
Flow cytometry protocol for GLUT4-myc detection on cell surfaces
Authors: Zanni-Ruiz Emilia , Mayorga Luis Segundo , Pavarotti Martin Alejandro 
Published: March 2024

Abstract
Insulin and muscle contraction trigger GLUT4 translocation to the plasma membrane, which increases glucose uptake by muscle cells. Insulin resistance and Type 2 diabetes are the result of impaired GLUT4 translocation. Quantifying GLUT4 translocation is essential for comprehending the intricacies of both physiological and pathophysiological processes involved in glucose metabolism. The most commonly used methods for measuring GLUT4 translocation are the ELISA-type assay and the immunofluorescence assay. While some reports suggest that flow cytometry could be useful in quantifying GLUT4 translocation, this technique is not frequently used. Much of our current understanding of the regulation of GLUT4 has been based on experiments using the rat myoblast cell line (L6 cell) which expresses GLUT4 with a myc epitope on the exofacial loop. In the present study, we use the L6-GLUT4myc cell line to develop a flow cytometry-based approach to detect GLUT4 translocation. Flow cytometry offers the advantages of both immunofluorescence and ELISA-based assays. It allows easy identification of separate cell populations in the sample, similar to immunofluorescence, while providing results based on a population-level analysis of multiple individual cells, like an ELISA-based assay. Our results demonstrate a 0.6-fold increase with insulin stimulation compared with basal conditions. Finally, flow cytometry consistently yielded results across different experiments and exhibited sensitivity under the tested conditions.
Increasing Reciprocal Social Interactions Between Children Who Use Augmentative and Alternative Communication and Peers Using a Collaborative Learning Framework
Authors: Boster Jamie B. , Cordone Tori , Blosser Hailey 
Published: March 2024

Purpose:
Children with complex communication needs who rely on augmentative and alternative communication (AAC) strategies to express themselves face significant difficulties interaction with peers. This study sought to design, implement, and evaluate a collaborative photography intervention designed to increase reciprocal social interaction between children who use AAC and their same-age peers.

Method:
A single-subject, withdrawal design (ABAB) was used to explore the functional relationship between engagement in a collaborative photography intervention and the frequency of reciprocal social interactions between children who use AAC and their same-age peers. Partial-interval time sampling was used to code the number of reciprocal social interactions across four dyads.

Results:
Increased frequencies of reciprocal social interactions were observed in intervention phases across all four dyads. Very large levels of effect and 100% nonoverlapping data were noted for Dyads 1 and 4. Moderate levels of effect and 70% of nonoverlapping data were noted for Dyads 2 and 3.

Conclusions:
Collaborative learning frameworks may be used to increase reciprocal social interactions between children who use AAC and their peers. Speech-language pathologists should consider utilizing collaborative learning elements in activities with children who use AAC. Future research is needed to further explore collaborative learning frameworks for interventions for children who use AAC.

Supplemental Material:

https://doi.org/10.23641/asha.25464064
Evaluating Speaker–Listener Cognitive Effort in Speech Communication Through Brain-to-Brain Synchrony: A Pilot Functional Near-Infrared Spectroscopy Investigation
Authors: Green Geoff D. , Jacewicz Ewa , Santosa Hendrik , Arzbecker Lian J. , Fox Robert A. 
Published: March 2024

Purpose:
We explore a new approach to the study of cognitive effort involved in listening to speech by measuring the brain activity in a listener in relation to the brain activity in a speaker. We hypothesize that the strength of this brain-to-brain synchrony (coupling) reflects the magnitude of cognitive effort involved in verbal communication and includes both listening effort and speaking effort. We investigate whether interbrain synchrony is greater in native-to-native versus native-to-nonnative communication using functional near-infrared spectroscopy (fNIRS).

Method:
Two speakers participated, a native speaker of American English and a native speaker of Korean who spoke English as a second language. Each speaker was fitted with the fNIRS cap and told short stories. The native English speaker provided the English narratives, and the Korean speaker provided both the nonnative (accented) English and Korean narratives. In separate sessions, fNIRS data were obtained from seven English monolingual participants ages 20–24 years who listened to each speaker's stories. After listening to each story in native and nonnative English, they retold the content, and their transcripts and audio recordings were analyzed for comprehension and discourse fluency, measured in the number of hesitations and articulation rate. No story retellings were obtained for narratives in Korean (an incomprehensible language for English listeners). Utilizing fNIRS technique termed sequential scanning, we quantified the brain-to-brain synchronization in each speaker–listener dyad.

Results:
For native-to-native dyads, multiple brain regions associated with various linguistic and executive functions were activated. There was a weaker coupling for native-to-nonnative dyads, and only the brain regions associated with higher order cognitive processes and functions were synchronized. All listeners understood the content of all stories, but they hesitated significantly more when retelling stories told in accented English. The nonnative speaker hesitated significantly more often than the native speaker and had a significantly slower articulation rate. There was no brain-to-brain coupling during listening to Korean, indicating a break in communication when listeners failed to comprehend the speaker.

Conclusions:
We found that effortful speech processing decreased interbrain synchrony and delayed comprehension processes. The obtained brain-based and behavioral patterns are consistent with our proposal that cognitive effort in verbal communication pertains to both the listener and the speaker and that brain-to-brain synchrony can be an indicator of differences in their cumulative communicative effort.

Supplemental Material:

https://doi.org/10.23641/asha.25452142
In-depth analysis of solar models with high-metallicity abundances and updated opacity tables
Authors: Buldgen G. , Noels A. , Scuflaire R. , Amarsi A. M. , Grevesse N. , Eggenberger P. , Colgan J. , Fontes C. J. , Baturin V. A. , Oreshina A. V. , Ayukov S. V. , Hakel P. , Kilcrease D. P. 
Published: March 2024

Context. As a result of the high-quality constraints available for the Sun, we are able to carry out detailed combined analyses using neutrino, spectroscopic, and helioseismic observations. These studies lay the ground for future improvements of the key physical components of solar and stellar models because ingredients such as the equation of state, the radiative opacities, or the prescriptions for macroscopic transport processes of chemicals are then used to study other stars in the Universe.
Aims. We study the existing degeneracies in solar models using the recent high-metallicity spectroscopic abundances by comparing them to helioseismic and neutrino data and discuss the effect on their properties of changes in the micro and macro physical ingredients.
Methods. We carried out a detailed study of solar models computed with a high-metallicity composition from the literature based on averaged 3D models that were claimed to resolve the solar modelling problem. We compared these models to helioseismic and neutrino constraints.
Results. The properties of the solar models are significantly affected by the use of the recent OPLIB opacity tables and the inclusion of macroscopic transport. The properties of the standard solar models computed using the OPAL opacities are similar to those for which the OP opacities were used. We show that a modification of the temperature gradient just below the base of the convective zone is required to remove the discrepancies in solar models, particularly in the presence of macroscopic mixing. This can be simulated by a localised increase in the opacity of a few percent.
Conclusions. We conclude that the existing degeneracies and issues in solar modelling are not removed by using an increase in the solar metallicity, in contradiction to what has been suggested in the recent literature. Therefore, standard solar models cannot be used as an argument for a high-metallicity composition. While further work is required to improve solar models, we note that direct helioseismic inversions indicate a low metallicity in the convective envelope, in agreement with spectroscopic analyses based on full 3D models.
ALMA-ALPINE [CII] survey: The sub-kpc morphology of three main sequence galaxy systems at z ∼ 4.5 revealed by ALMA
Authors: Devereaux T. , Cassata P. , Ibar E. , Accard C. , Guillaume C. , Béthermin M. , Dessauges-Zavadsky M. , Faisst A. , Jones G. C. , Zanella A. , Bardelli S. , Boquien M. , D’Onghia E. , Giavalisco M. , Ginolfi M. , Gobat R. , Hayward C. C. , Koekemoer A. M. , Lemaux B. , Magdis G. , Mendez-Hernandez H. , Molina J. , Pozzi F. , Romano M. , Tasca L. , Vergani D. , Zamorani G. , Zucca E. 
Published: March 2024

Context. Going from a redshift of 6 down to nearly 4, galaxies grow rapidly from low-mass galaxies towards the more mature types of massive galaxies seen at cosmic noon. Growth via gas accretion and mergers undoubtedly shape this evolution, however, there is considerable uncertainty at present over the contribution of each of these processes to the overall evolution of galaxies. Furthermore, previous characterisations of the morphology of galaxies in the molecular gas phase have been limited by the coarse resolution of earlier observations.
Aims. In this work, we utilise new high-resolution ALMA [CII] observations to analyse three main sequence (MS) galaxy systems at a redshift of z ∼ 4.5 and at resolutions of up to 0.15″. This approach enables us to investigate the morphology and kinematics on a kpc scale and understand the processes at play as well as the classifications of galaxies at high resolution. Thanks to this unique window, we are able to gain insights into the molecular gas of MS galaxies undergoing mass assembly in the early Universe.
Methods. We used intensity and velocity maps, position-velocity diagrams, and radial profiles of [CII] in combination with dust continuum maps to analyse the morphology and kinematics of the three systems.
Results. In general, we find that the high-resolution ALMA data reveal more complex morpho-kinematic properties. For one galaxy in our sample, we identified interaction-induced clumps, demonstrating the profound effect that mergers have on the molecular gas in galaxies, which is consistent with what has been suggested by recent simulations. One galaxy that was previously classified as dispersion-dominated turned out to show two bright [CII] emission regions, which could either be classified as merging galaxies or massive star-forming regions within the galaxy itself. The high-resolution data for the other dispersion dominated object also revealed clumps of [CII] that had not been identified previously. Within the sample, we might also detect star-formation powered outflows (or outflows from active galactic nuclei) that appear to be fuelling diffuse gas regions and enriching the circumgalactic medium. The new high-resolution ALMA data we present in this paper reveal that the galaxies in our sample are much more complex than they previously appeared in the low-resolution ALPINE data. In particular, we find evidence of merger induced clumps in the galaxy DC8187, along with signs of merging components for the other two objects. This may be evidence that the number of mergers at high redshift are significantly underestimated at present.
Energetic particle acceleration and transport with the novel Icarus + PARADISE model
Authors: Husidic Edin , Wijsen Nicolas , Baratashvili Tinatin , Poedts Stefaan , Vainio Rami 
Published: March 2024

With the rise of satellites and mankind’s growing dependence on technology, there is an increasing awareness of space weather phenomena related to high-energy particles. Shock waves driven by coronal mass ejections (CMEs) and corotating interaction regions (CIRs) occasionally act as potent particle accelerators, generating hazardous solar energetic particles (SEPs) that pose risks to satellite electronics and astronauts. Numerical simulation tools capable of modelling and predicting large SEP events are thus highly demanded. We introduce the new Icarus + PARADISE model as an advancement of the previous EUHFORIA + PARADISE model. Icarus, based on the MPI-AMRVAC framework, is a three-dimensional magnetohydrodynamic code that models solar wind configurations from 0.1 au onwards, encompassing transient structures like CMEs or CIRs. Differing from EUHFORIA’s uniform-only grid, Icarus incorporates solution adaptive mesh refinement (AMR) and grid stretching. The particle transport code PARADISE propagates energetic particles as test particles through these solar wind configurations by solving the focused transport equation in a stochastic manner. We validate our new model by reproducing EUHFORIA + PARADISE results. This is done by modelling the acceleration and transport of energetic particles in a synthetic solar wind configuration containing an embedded CIR. Subsequently, we illustrate how the simulation results vary with grid resolution by employing different levels of AMR. The resulting intensity profiles illustrate increased particle acceleration with higher levels of AMR in the shock region, better capturing the effects of the shock.
Evidence-based Ultrasound Education? – A Systematic Literature Review
of Undergraduate Ultrasound Training Studies
Authors: Neubauer Ricarda , Bauer Claus Juergen , Dietrich Christoph F. , Strizek Brigitte , Schäfer Valentin Sebastian , Recker Florian 
Published: March 2024

AbstractDespite a large number of studies previously conducted on educational concepts of
ultrasound teaching in medical school, various controversial issues remain.
Currently, recommendations for ultrasound curricula that aim to standardize
ultrasound teaching are frequently based on expert panel advice instead of
relying on valid evidence-based literature. In December 2022, a systematic
literature review on the subject of undergraduate ultrasound education was
conducted. All ultrasound studies listed in the PubMed and Google Scholar
medical databases were filtered and analyzed with respect to various aspects of
their methodological conduct and curricular implementation. A total of 259
publications were considered in the data synthesis, including 145 teaching
studies in the field of undergraduate ultrasound education. The latter
encompassed 58 (40%) studies that did not compare their ultrasound training to a
control group. Furthermore, 84 (58%) of these studies did not assess knowledge
prior to the applied ultrasound training, neglecting this factor’s potential
influence on study outcomes. Despite a great interest in the development and
further implementation of ultrasound education during medical school, this
process is still compromised by significant deficiencies in studies that have
been conducted in the past. In order to provide a valid basis for curricular
decisions, teaching studies should fulfill essential methodological requirements
despite the multifactorial framework in which they are conducted. In the future,
a guide for the design of ultrasound studies could be a useful aid for
ultrasound enthusiasts and promote scientific knowledge gain.
Practices in the prescription of antiseizure medications: is it time to change?
Authors: Pinto Lécio Figueira , Silva Lucas Scárdua , João Rafael Batista , Boldrini Vinícius , Cendes Fernando , Yasuda Clarissa Lin 
Published: March 2024

AbstractThe treatment of epilepsy has advanced over the past 30 years through the development of new antiseizure medications (ASMs). Unfortunately, not all of them have been approved yet in Brazil, and many are still underused. When comparing new ASMs to older ones, they are generally not more effective in treating epilepsy. However, they offer better tolerability, with fewer interactions and long-term side effects, especially for patients with comorbidities or those requiring polytherapy. Enzyme induction caused by older ASMs is associated with increased cholesterol levels, drug interactions with decreased effects of statins and other cardiovascular medications, anticoagulants, chemotherapy, immunosuppressors, anti-infective agents (including HIV treatment), antidepressants, and contraceptives. Additionally, they can reduce levels of vitamin D and sex hormones, as well as decrease bone density. The increasing concern about these effects during life, especially after prolonged exposure, has led most developed countries to change prescription patterns in favor of new ASMs, particularly levetiracetam and lamotrigine. Both are also considered the safest options for women of childbearing age. Regrettably, the prescription trends in Brazil have remained largely unchanged over time. This can be partially attributed to the slower approval process of ASM and the reluctance of general physicians and neurologists to embrace these new concepts. In this concise review, we highlight the various advantages linked to the new ASM, aiming to promote a shift in the prescription pattern for ASM. The selection of ASM should be customized according to individual characteristics, and practical suggestions for choosing ASMs are provided in this paper.
Real-world Data on Treatment Patterns and Bleeding in Cancer-associated Thrombosis: Data from the TROLL Registry
Authors: Zaboras Zygimantas , Jørgensen Camilla Tøvik , Stensvold Andreas , Pettersen Heidi Hassel , Grdinic Aleksandra Galovic , Brækkan Sigrid Kufaas , Ghanima Waleed , Tavoly Mazdak 
Published: March 2024

Abstract
Background International guidelines are increasingly recommending direct oral anticoagulants (DOACs) as the first-line treatment for cancer-associated thrombosis (CAT). However, data regarding treatment patterns and adherence to guidelines in patients with CAT are scarce.
Objectives This study aimed to explore anticoagulant treatment patterns in patients with CAT and to calculate the incidence rates of bleeding events.
Methods Patients ≥18 years with active cancer and a first-time venous thromboembolism between 2005 and 2020 were identified through the Venous Thrombosis Registry in ØstfOLd HospitaL. Outcome measures were patterns of anticoagulant treatment during the study period and bleeding events. We calculated overall incidence rates per 100 person-years and 6- and 12-month cumulative incidence of major and clinically relevant nonmajor bleeding (CRNMB) during anticoagulant treatment.
Results Median age of 842 CAT patients at the time of thrombosis was 69 years (interquartile range 61–77), and 443 (52.6%) were men. In total, 526 patients (62.5%) had pulmonary embolism and 255 (30.3%) had deep vein thrombosis. Low molecular weight heparin (LMWH) was prescribed to 713 (85.8%) patients, whereas 64 (7.7%) received DOACs and 54 (6.5%) received vitamin K antagonists as the initial anticoagulant treatment. Prescription of DOACs as initial treatment increased from 3.0% in 2013/2014 to 18.0% in 2019/2020. The incidence rate of major bleeding was 6.9 (95% confidence interval [CI] 5.2–9.2) and 10.1 (95% CI 8.0–12.9) in CRNMB.
Conclusion Most patients were treated with LMWH. However, a gradual shift in treatment toward DOACs was observed. Overall, bleeding complications were rare and comparable to those reported in randomized trials.