bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Nutrition and Human Milk Nutrients
Authors: Kankaew Sukanya , Briere Carrie-Ellen
Published: October 2024

Purpose:

To explore the influence of maternal nutrition factors, including body mass index, nutritional supplementation, and dietary intake during the breastfeeding period, on macro and micronutrient composition in human milk.

Study Design and Methods:

We conducted a scoping review using the PRISMA-ScR checklist, initially identifying 5,984 original studies published in the English language from PubMed, Scopus, and Web of Science that presented findings on the association of maternal nutritional factors on human milk nutrient composition. After screening the title and abstract, we selected 69 studies for full review, including 3 studies found through checking reference lists. After full review, we included 23 studies in this scoping review.

Results:

Most studies found maternal body mass index and supplement consumption affected human milk macro and micronutrient composition, whereas inconsistent results were found on the relationship between maternal diet and human milk nutrients. Methodologies varied substantially across studies, especially for milk sample collection methods and maternal nutrition assessments.

Clinical implications:

Maternal nutrition factors may affect levels of human milk nutrients, requiring maternal nutrition monitoring during breastfeeding. However, given the considerable variability in the results between studies and methodological approaches, further studies should use standardized and validated procedures to strengthen the findings on this topic.
Physical Activity Levels, Cardiorespiratory Fitness, and Physical Literacy in Children With a Chronic Medical Condition
Authors: Noordstar Johannes J. , Sprong Maaike C.A. , Slieker Martijn G. , Takken Tim , van der Ent Cornelis K. , van Brussel Marco , Bartels Marije , Hulzebos Erik H.J.
Published: October 2024

Purpose:

This study investigated differences in cardiorespiratory fitness (CRF) and other physical literacy domains between children with a chronic medical condition (CMC) who adhered to with the physical activity guideline and those who did not.

Method:

Forty children with a CMC (7-12 years) wore an accelerometer for 7 days to measure moderate-to-vigorous physical activity. CRF and muscle power were assessed with a maximal cardiopulmonary exercise test, and motor performance was measured with an exercise course. Motivation, confidence, knowledge, and understanding were assessed with a questionnaire.

Results:

Children who adhered to the PA guideline (n = 13) scored significantly higher for CRF, muscle power, motivation and confidence than children who did not adhere to the PA guideline (n = 27). No significant differences were found for motor performance, knowledge and understanding.

Conclusion:

Future research should investigate the effect of paying specific attention to motivation and confidence in children with a CMC to stimulate their adherence to the PA guideline.
Intranasal Outer Cortex Splinting With a Kirschner Wire to Immobilize Reduced Buckle-out Segments in Nasal Fractures
Authors: Burm Jin Sik , Lee Jimin
Published: October 2024

High-velocity lateral impacts to the nose sometimes cause nasal buckle-out fractures with a trapdoor buckle-out segment displaced outwards. Prolonged immobilization of a reduced buckle-out segment at risk for outward redisplacement remains challenging. Here we introduce a novel method of intranasal outer cortex splinting with a Kirshner (K)-wire to reinforce the reduced state and prevent outward re-displacement of the buckle-out segment. Eighteen patients with nasal buckle-out fractures underwent outer cortex K-wire splinting to securely immobilize a reduced but unstable buckle-out segment after indirect open reduction through intercartilaginous incisions and inner cortex K-wire splinting. A thin K-wire (diameter 0.8 mm) was inserted at the vestibule, passed above the upper lateral cartilage and the outer cortex of the reduced buckle-out segment, and extended to the cephalic non-fractured bone. The wire served as a crossbeam, effectively supporting the reduced buckle-out segment. All K-wires for inner and outer cortex splinting were removed 10 to 14 days postoperatively. Immediate postoperative computed tomography scans showed successful immobilization of buckle-out segments in 17 patients (94.5%). Postoperative 6-month scans of 7 patients showed excellent maintenance and bony alignment of buckle-out segments in all cases. Sixteen patients (88.9%) were satisfied with the overall external nasal contour at the last follow-up. There were no complications directly related to outer cortex K-wire splinting. One patient complained of a focal lateral protrusion resulting from the under-correction of a buckle-out segment. This technique may be a valuable option for immobilizing and maintaining reduced nasal buckle-out segments until a stable bony union is established.
Influence of the Inferior Turbinate on the Accuracy of Superior Maxillary Repositioning
Authors: Yamamoto Daisuke , Tomomatsu Nobuyoshi , Nakamura Taishi , Takahara Namiaki , Kurasawa Yasuhiro , Yoda Tetsuya
Published: October 2024

Notably, many studies have focused on the bony interference in the maxillary segment when performing maxillary superior repositioning; however, few reports have described the interference with the inferior nasal turbinate. Therefore, the authors aimed to retrospectively analyze the soft tissue or bone tissue volume of the inferior nasal turbinate and the accuracy of maxillary superior repositioning in Le Fort I osteotomy (LF1). The authors included 83 patients with facial deformities who underwent conventional LF1 (maxillary molar elevation between 4.0 and 6.0 mm) with/without bilateral sagittal split ramus osteotomy. The ratio of the soft tissue of the inferior turbinate to that of the inferior nasal cavity was used to divide the participants into 2 subgroups (large and small ratio). Similarly, the bony tissue volume of the inferior turbinate was used to divide the participants into 2 subgroups (large and small bony tissues), and the planned or actual amount of superior repositioning was compared 3 dimensionally. In the soft tissue group, the subgroups showed no significant differences (P=0.934). However, the actual maxillary superior repositioning was significantly lower in the large bone group than in the planned maxillary elevation group (P<0.01). In cases where the maxillary molar needs to be elevated by >4 mm and the bone tissue of the inferior nasal turbinate is well developed, an adjunctive technique such as horseshoe osteotomy or partial inferior turbinate resection should be considered in addition to LF1 to avoid interference between the inferior nasal turbinate and the maxillary bone fragments.
Long-term Follow-up of Secondary Reconstruction of Facial Paralysis and Depressive Deformities After Subtotal Temporal Bone Resection
Authors: Umemoto Naoshi , Okazaki Mutsumi , Tanaka Kentaro , Miyamoto Shimpei , Iida Takuya
Published: October 2024

Subtotal temporal bone resection (STBR) frequently results in facial paralysis and depression, making reconstruction challenging due to significant tissue loss. This study aimed to evaluate the effectiveness of a procedure designed for simultaneous smile and soft tissue reconstruction after STBR. The authors included 3 patients who underwent latissimus dorsi (LD) neuromuscular flap combined with adipose flap transfer after STBR at the Tokyo Medical and Dental University Hospital between 2010 and 2016. Among these patients, 2 had facial vessels unsuitable for anastomosis due to prior neck dissection, and their masseteric nerves were unavailable for neurorrhaphy due to STBR. The thoracodorsal nerve was coaptated to the contralateral facial nerve in all patients and to the ipsilateral masseter nerve in one patient. Follow-up periods ranged from 7 to 13 years, with all patients achieving spontaneous smiles within 12 months post-surgery. Although depressive deformities improved, long-term follow-up revealed buccal muscle bulging due to unstable LD muscle fixation from a zygomatic arch defect caused by STBR. Revision surgeries, including muscle refixation with a tensor fasciae lata graft, muscle reduction, eyebrow lifting, blepharoplasty, and adipose tissue repositioning, were performed as needed. Ultimately, all patients achieved satisfactory facial contours and spontaneous smiles. This study demonstrates that free LD muscle with adipose flap transfer is effective for post-STBR reconstruction. However, detailed surgical planning and multistage reconstruction are often necessary due to the complexities involved.
An update on the role of focused ultrasound in neuro-oncology
Authors: Epstein Jordan E. , Pople Christopher B. , Meng Ying , Lipsman Nir
Published: October 2024

Purpose of review

Brain tumor treatment presents challenges for patients and clinicians, with prognosis for many of the most common brain tumors being poor. Focused ultrasound (FUS) can be deployed in several ways to circumvent these challenges, including the need to penetrate the blood–brain barrier and spare healthy brain tissue. This article reviews current FUS applications within neuro-oncology, emphasizing ongoing or recently completed clinical trials.

Recent findings

Most clinical interest in FUS for neuro-oncology remains focused on exploring BBB disruption to enhance the delivery of standard-of-care therapeutics. More recently, the application of FUS for radiosensitization, liquid biopsy, and sonodynamic therapy is garnering increased clinical attention to assist in tumor ablation, early detection, and phenotypic diagnosis. Preclinical studies show encouraging data for the immunomodulatory effects of FUS, but these findings have yet to be tested clinically.

FUS is a burgeoning area of neuro-oncology research. Data from several forthcoming large clinical trials should help clarify its role in neuro-oncology care.
Assessment of wearable robotics performance in patients with neurological conditions
Authors: Gerez Lucas , Micera Silvestro , Nuckols Richard , Proietti Tommaso
Published: October 2024

Purpose of review

While wearable robotics is expanding within clinical settings, particularly for neurological rehabilitation, there is still a lack of consensus on how to effectively assess the performance of these devices. This review focuses on the most common metrics, whose selection and design are crucial for optimizing treatment outcomes and potentially improve the standard care.

Recent findings

The literature reveals that while wearable robots are equipped with various embedded sensors, most studies still rely on traditional, nontechnological methods for assessment. Recent studies have shown that, although quantitative data from embedded sensors are available (e.g., kinematics), these are underutilized in favor of qualitative assessments. A trend toward integrating automatic assessments from the devices themselves is emerging, with a few notable studies pioneering this approach.

Our analysis suggests a critical need for developing standardized metrics that leverage the data from embedded sensors in wearable robots. This shift could enhance the accuracy of patient assessments and the effectiveness of rehabilitation strategies, ultimately leading to better patient outcomes in neurological rehabilitation.
Adherence to optimal delirium management practices in intensive care units in Brazil: a nationwide survey
Authors: Bispo Mateus Meneses , Souza Regina Claudia da Silva
Published: October 2024

Background:

Effective delirium management is crucial, considering its association with adverse outcomes. Adherence to best practices has the potential to reduce the incidence and prevalence of delirium and improve health outcomes.

Objectives:

The objectives of this project were to describe self-assessed adherence to best practices in delirium management by health care professionals in intensive care units (ICUs) in Brazil, assess the health care professionals’ perception of the importance of adequate delirium prevention and treatment in ICUs, and compare the compliance rates with best practices between public and private ICUs.

Method:

A cross-sectional study was conducted in Brazil using an online questionnaire consisting of three parts, namely, data about the health care professionals and the ICU in which they worked; statements about the 17 best practices; and questions related to perceptions of delirium prevention and management by ICU physicians and nurses. The survey was sent to email addresses registered with the Brazilian Association of Intensive Care Medicine.

Results:

The compliance rate exceeded 50% for only eight best practices. These included the identification and management of pressure sores and falls in delirium patients, with compliance rates of 77.8% and 74.1%, respectively.

Conclusion:

Among ICU professionals in Brazil, adherence to best practices in delirium management is low, particularly for practices involving patient education and involvement of their relatives in their care. These results emphasize the importance of enhancing delirium management in Brazilian health care institutions, regardless of hospital classification.

Spanish abstract:

http://links.lww.com/IJEBH/A274
Characterization of magnetically stabilized hinges for origami-inspired mechanisms
Authors: Pruett H. T. , Klocke P. , Howell L. , Magleby S.
Published: October 2024

Origami-inspired mechanisms provide opportunities for deployable systems, including reflectarray antennas. There is a need for approaches to deploy and stabilize such arrays. Magnetic mechanisms show promise for meeting those needs and how methods for modelling their behaviour would facilitate their design and analysis. We demonstrate the existence of bistability in select configurations of magnetically stabilized hinges and characterize their equilibrium positions as a function of parameters estimated from simulation data for these mechanisms. Other relevant information such as potential energy, axial force data, angular position of unstable equilibria and transition values from bistability to monostability are also modelled. The results are verified through experimental torque and stability data for selected configurations of the mechanisms.

This article is part of the theme issue ‘Origami/Kirigami-inspired structures: from fundamentals to applications’.
‘Golden Ratio Yoshimura’ for meta-stable and massively reconfigurable deployment
Authors: Deshpande Vishrut , Phalak Yogesh , Zhou Ziyang , Walker Ian , Li Suyi
Published: October 2024

Yoshimura origami is a classical folding pattern that has inspired many deployable structure designs. Its applications span from space exploration, kinetic architectures and soft robots to even everyday household items. However, despite its wide usage, Yoshimura has been fixated on a set of design constraints to ensure its flat foldability. Through extensive kinematic analysis and prototype tests, this study presents a new Yoshimura that intentionally defies these constraints. Remarkably, one can impart a unique meta-stability by using the Golden Ratio angle (

cot

−
1

⁡
1.618
≈

31.72
∘

) to define the triangular facets of a generalized Yoshimura (with

n

=

3

, where

n

is the number of rhombi shapes along its cylindrical circumference). As a result, when its facets are strategically popped out, a ‘Golden Ratio Yoshimura’ boom with

m

modules can be theoretically reconfigured into

8
m

geometrically unique and load-bearing shapes. This result not only challenges the existing design norms but also opens up a new avenue to create deployable and versatile structural systems.

This article is part of the theme issue ‘Origami/Kirigami-inspired structures: from fundamentals to applications’.
How periodic surfaces bend
Authors: Nassar Hussein
Published: October 2024

A periodic surface is one that is invariant by a two-dimensional lattice of translations. Deformation modes that stretch the lattice without stretching the surface are effective membrane modes. Deformation modes that bend the lattice without stretching the surface are effective bending modes. For periodic piecewise smooth simply connected surfaces, it is shown that the effective membrane modes are, in a sense, orthogonal to effective bending modes. This means that if a surface gains a membrane mode, it loses a bending mode, and conversely, in such a way that the total number of modes, membrane and bending combined, can never exceed 3. Various examples, inspired from curved-crease origami tessellations, illustrate the results.

This article is part of the theme issue ‘Origami/Kirigami-inspired structures: from fundamentals to applications’.
Optimization of a DNA extraction protocol for improving bacterial and fungal classification based on Nanopore sequencing
Authors: Soe Thu May , Sawaswong Vorthon , Chanchaem Prangwalai , Klomkliew Pavit , Campbell Barry J. , Hirankarn Nattiya , Fothergill Joanne L. , Payungporn Sunchai
Published: October 2024

Ribosomal RNA gene amplicon sequencing is commonly used to evaluate microbiome profiles in health and disease and document the impact of interventional treatments. Nanopore sequencing is attractive since it can provide greater classification at the species level. However, optimized protocols to target marker genes for bacterial and fungal profiling are needed. To achieve an increased taxonomic resolution, we developed extraction and full-length amplicon PCR-based approaches using Nanopore sequencing. Three lysis conditions were applied to a mock microbial community, including known bacterial and fungal species: ZymoBIOMICS lysis buffer (ML) alone, incorporating bead-beating (MLB) or bead-beating plus MetaPolyzyme enzymatic treatment (MLBE). In profiling of bacteria in comparison to reference data, MLB had more statistically different bacterial phyla and genera than the other two conditions. In fungal profiling, MLB had a significant increase of Ascomycota and a decline of Basidiomycota, subsequently failing to detect Malassezia and Cryptococcus. Also, a principal coordinates analysis plot by the Bray–Curtis metric showed a significant difference among groups for bacterial (P=0.033) and fungal (P=0.012) profiles, highlighting the importance of understanding the biases present in pretreatment. Overall, microbial profiling and diversity analysis revealed that ML and MLBE are more similar than MLB for both bacteria and fungi; therefore, using this specific pipeline, bead-beating is not recommended for whole gene amplicon sequencing. However, ML alone was suggested as an optimal approach considering DNA yield, taxonomic classification, reagent cost and hands-on time. This could be an initial proof-of-concept study for simultaneous human bacterial and fungal microbiome studies.
TSST-1 promotes colonization ofStaphylococcus aureuswithin the vaginal tract by activation of CD8+T cells
Authors: Dufresne Karine , Al Kait F. , Craig Heather C. , Coleman Charlotte E.M. , Kasper Katherine J. , Burton Jeremy P. , McCormick John K.
Published: October 2024

Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced byStaphylococcus aureusand is the determinant of menstrual toxic shock syndrome (mTSS); however, the impact of TSST-1 on the vaginal environment beyond mTSS is not understood. Herein, we assessed how TSST-1 affects vaginal colonization byS. aureus, host inflammatory responses, and changes in microbial communities within the murine vagina. We demonstrated that TSST-1 induced a CD8+T cell-dependent inflammatory response by 24 hours that correlated with an increased bacteria burden within the vaginal tract. This increase was due to superantigen-dependent T cell activation that triggered a change in microbial composition within the vaginal tract. Altogether, this study demonstrates that within the vaginal tract, TSST-1 modulates the vaginal microbiota to favor the survival ofS. aureusin the absence of mTSS.

Importance

Toxic shock syndrome toxin-1 (TSST-1) is a superantigen toxin produced fromStaphylococcus aureusthat causes the menstrual form of toxic shock syndrome. This research demonstrates that TSST-1 also has a wider function within the vaginal tract than previously expected. We show that TSST-1, by activating CD8+T cells, induces an inflammatory environment that modifies the vaginal microbiota to favor colonization byS. aureus. These are important findings asS. aureuscan colonize the human vaginal tract efficiently and subsequently trigger dysbiosis within the microbial communities leading to several adverse outcomes such as decreased fertility, increased risks for sexually transmitted diseases and issues related to pregnancy and birth.
High-dimensional Biomarker Identification for Scalable and Interpretable Disease Prediction via Machine Learning Models
Authors: Dai Yifan , Zou Fei , Zou Baiming
Published: October 2024

Omics data generated from high-throughput technologies and clinical features jointly impact many complex human diseases. Identifying key biomarkers and clinical risk factors is essential for understanding disease mechanisms and advancing early disease diagnosis and precision medicine. However, the high-dimensionality and intricate associations between disease outcomes and omics profiles present significant analytical challenges. To address these, we propose an ensemble data-driven biomarker identification tool, Hybrid Feature Screening (HFS), to construct a candidate feature set for downstream advanced machine learning models. The pre-screened candidate features from HFS are further refined using a computationally efficient permutation-based feature importance test, forming the comprehensive High-dimensional Feature Importance Test (HiFIT) framework. Through extensive numerical simulations and real-world applications, we demonstrate HiFIT’s superior performance in both outcome prediction and feature importance identification. An R package implementing HiFIT is available on GitHub (https://github.com/BZou-lab/HiFIT).
Single-cell resolution map of innate-like lymphocyte response toFrancisella tularensisinfection reveals MAIT cells’ role in protection from tularemia-like disease
Authors: Okoye G. Donald , Kumar Amrendra , Ghanbari Farshad , Chowdhury Nowrin U. , Wu Lan , Newcomb Dawn C. , Kaer Luc Van , Scott Algood Holly M. , Joyce Sebastian
Published: October 2024

Early immune dynamics during the initiation of fatal tularemia caused byFrancisella tularensisinfection remain unknown. Unto that end, we generated a transcriptomic map at single-cell resolution of the innate-like lymphocyte responses toF. tularensislive vaccine strain (LVS) infection of mice. We found that both interferon-γ-producing type 1 and interleukin-17-producing type 3 innate-like lymphocytes expanded in the infected lungs. Natural killer (NK) and NKT cells drove the type 1 response, whereas mucosal-associated invariant T (MAIT) and γδ T cells drove the type 3 response. Furthermore, tularemia-like disease-resistant NKT cell-deficient,Cd1d-/-mice accumulated more MAIT1 cells, MAIT17 cells, and cells with a hybrid phenotype between MAIT1 and MAIT17 cells than wild-type mice. Critically, adoptive transfer of LVS-activated MAIT cells fromCd1d-/-mice, which were enriched in MAIT17 cells, was sufficient to protect LVS-susceptible, immunodeficientRAG2-/-mice from severe LVS infection-inflicted pathology. Collectively, our findings position MAIT cells as potential mediators of interleukin-17-dependent protection from pulmonary tularemia-like disease.

HIGHLIGHTS

PulmonaryF. tularensisLVS infection induces type 1 & type 3 immune responses.

NK and NKT cells drive type 1, whilst MAIT and γδT cells drive type 3 responses.

Increased MAIT17 cell accumulation is associated with resistance to TID.

Adoptive transfer of MAIT17-enriched cells protect immunodeficient mice from TID.
Collective amoeboid dynamics drives colonization of drug-resistant ovarian cancer cells
Authors: Goutham Shyamili , Gopikrishnan Anchita , Harshavardhan BV , Venas Nivedhya , Sabarinathan Radhakrishnan , Jolly Mohit Kumar , Bhat Ramray
Published: October 2024

Epithelial ovarian cancer (EOC) is characterized by resistance to platinum-based therapy, resulting in rapid progression and poor survival. Here, we ask whether drug resistance and invasiveness coevolve to drive metastasis. Selection experiments involving pulsed carboplatin exposure established isogenic chemoresistant variants of lines, which typify high-grade serous ovarian carcinoma (HGSOC), the most aggressive type of EOC. Time-lapse imaging showed enhanced migration of resistant single cells and their collectives. Resistant cell spheroids spread faster on Collagen I substrata than sensitive controls. The resistant OVCAR-3 transcriptome was ontologically enriched for migration and showed overlap with previously reported markers of resistance in EOC patients and other evolved lines. Gene set enrichment predicted transition between epithelial, mesenchymal, and amoeboid states is higher in resistance compared to control lines. Lower matrix adhesion, weak focal adhesion, and highly deformable and translatory dynamics of cell collectives indicated that resistant cancer cells displayed a unique collective amoeboid-like migration. When injected intraperitoneally into immunodeficient mice, resistant cells colonized to a greater extent on parietal mucosae. Ex vivo, suspended resistant cells formed moruloids associated with quicker peritoneal adhesion, clearing human coelomic mesothelial monolayers with higher efficiency. Knockdown in resistant OVCAR-3 cells of two upregulated proteins, E-cadherin and LGALS3BP, had distinct consequences. E-cadherin knockdown partially restored sensitivity to carboplatin but did not affect invasion. In contrast, silencing LGALS3BP decreased invasion but not resistance. Our results suggest that drug resistance and invasiveness could coevolve through the upregulation of distinct trait drivers in EOC.
De novo design of α-helical peptide channels with designer stoichiometry
Authors: Niitsu Ai , Thomson Andrew R , Scott Alistair J , Sengel Jason T , Jung Jaewoon , Mahendran Kozhinjampara R , Sodeoka Mikiko , Bayley Hagan , Sugita Yuji , Woolfson Derek N , Wallace Mark I
Published: October 2024

Despite advances in peptide and protein design, the rational design of membrane-spanning peptides that form conducting channels remains challenging due to our imperfect understanding of the sequence-to-structure relationships that drive membrane insertion, assembly, and conductance. Here, we describe the design and computational and experimental characterization of a series of coiled coil-based peptides that form transmembrane α-helical barrels.

Through a combination of rational and computational design, we obtain barrels with 5 to 7 helices, as characterized in detergent micelles. In lipid bilayers, these peptide assemblies exhibit two conductance states with relative populations dependent on the applied potential: (i) a low-conductance states that correlate with variations in the modeled coiled-coil barrel geometries, indicating stable transmembrane α-helical barrels; and (ii) high-conductance states in which single pores change size in discrete steps. Notably, the high-conductance states are similar for all peptides in contrast to the low-conductance states. This indicates the formation of large, dynamic pores through the recruitment and expulsion of peptides, as observed in natural barrel-stave peptide pores. These findings establish rational routes to design and tune functional membrane-spanning peptide channels with specific conductance and geometry.
Inhibitors of dihydroorotate dehydrogenase synergize with the broad antiviral activity of 4′-fluorouridine
Authors: Schrell Leon , Fuchs Hannah L. , Dickmanns Antje , Scheibner David , Olejnik Judith , Hume Adam J. , Reineking Wencke , Störk Theresa , Müller Martin , Graaf-Rau Annika , Diederich Sandra , Finke Stefan , Baumgärtner Wolfgang , Mühlberger Elke , Balkema-Buschmann Anne , Dobbelstein Matthias
Published: October 2024

RNA viruses present a constant threat to human health, often with limited options for vaccination or therapy. Notable examples include influenza viruses and coronaviruses, which have pandemic potential. Filo- and henipaviruses cause more limited outbreaks, but with high case fatality rates. All RNA viruses rely on the activity of a virus-encoded RNA-dependent RNA polymerase (RdRp). An antiviral nucleoside analogue, 4′-Fluorouridine (4′-FlU), targets RdRp and diminishes the replication of several RNA viruses, including influenza A virus and SARS-CoV-2, through incorporation into nascent viral RNA and delayed chain termination. However, the effective concentration of 4′-FlU varied among different viruses, raising the need to fortify its efficacy. Here we show that inhibitors of dihydroorotate dehydrogenase (DHODH), an enzyme essential for pyrimidine biosynthesis, can synergistically enhance the antiviral effect of 4′-FlU against influenza A viruses, SARS-CoV-2, henipaviruses, and Ebola virus. Even 4′-FlU-resistant mutant influenza A virus was re-sensitized towards 4′-FlU by DHODH inhibition. The addition of uridine rescued influenza A virus replication, strongly suggesting uridine depletion as a mechanism of this synergy. 4′-FlU was also highly effective against SARS-CoV-2 in a hamster model of COVID. We propose that the impairment of endogenous uridine synthesis by DHODH inhibition enhances the incorporation of 4′-FlU into viral RNAs. This strategy may be broadly applicable to enhance the efficacy of pyrimidine nucleoside analogues for antiviral therapy.

Graphical Abstract

HIGHLIGHTS

Strong synergy of DHODH inhibitors with 4′-FlU

Activity of the combination against previously resistant influenza virus

Broadly active combination against a diverse set of RNA viruses

Successful targets include highly pathogenic Ebola and Nipah viruses
Single-Cell RNA-Seq Reveals Adventitial Fibroblast Alterations during Mouse Atherosclerosis
Authors: Fries Lauren E. , Chung Allen , Chang Hyun K. , Yuan Timothy L. , Bauer Robert C.
Published: October 2024

Background

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in the western world despite the success of lipid lowering therapies, highlighting the need for novel lipid-independent therapeutic strategies. Genome-wide association studies (GWAS) have identified numerous genes associated with ASCVD that function in the vessel wall, suggesting that vascular cells mediate ASCVD, and that the genes and pathways essential for this vascular cell function may be novel therapeutic targets for the treatment of ASCVD. Furthermore, some of these implicated genes appear to function in the adventitial layer of the vasculature, suggesting these cells are able to potentiate ASCVD.

Methods

To investigate the role of adventitial cells in atherosclerosis, we conducted single-cell RNA sequencing (scRNA-seq) of the aortic adventitia during atherogenesis in maleLdlr-/-mice via pools of three mice, two samples per condition. We cross-referenced the scRNA-seq data with human ASCVD GWAS to identify regulators of adventitial responses in ASCVD. These regulators were then validatedin vitroin human adventitial fibroblasts.

Results

We identified four adventitial fibroblast populations, all of which displayed shifts in population size and gene expression over the course of atherogenesis.SERPINH1, an ASCVD-linked GWAS gene, was differentially expressed in adventitial fibroblasts during atherogenesis. Knockdown ofSERPINH1 in vitroreduced fibroblast migration and altered subcluster marker gene expression.

Conclusions

These findings reveal dynamic changes in adventitial fibroblasts during atherosclerosis and suggest that reducedSERPINH1expression disrupts adventitial fibroblast function, contributing to ASCVD progression.
Computational Insights into the Allosteric Behavior of Mini Proinsulin Driven by C Peptide Mobility
Authors: Ayan Esra
Published: October 2024

Background/aim

The production of recombinant insulin remains challenging, particularly in enhancing refolding efficiency and bioactivity. Mini-proinsulin analogs, which involve reducing the length of the C-peptide, offer potential improvements in insulin production. This study aims to evaluate mini-proinsulin analogs’ design and receptor binding dynamics to optimize recombinant insulin production inE. coli.

Materials and methods

Mini-proinsulin analogs were engineered by replacing the 33-residue C-peptide with a pentapeptide sequence to improve refolding. The three-dimensional structure of mini-proinsulin was predicted using AlphaFold and performed docking analysis of mini-proinsulin analogs to the insulin receptor using AutoDock Tools, with comparisons made to previously available NMR-determined analog and the native insulin-insulin receptor complex. Normal Mode Analyses (GNM and ANM) were performed in detail to assess binding dynamics.

Results

In silicoanalyses revealed that mini-proinsulin analogs closely replicate the structural features of native insulin and display receptor binding dynamics similar to native insulin, though they follow distinct receptor interaction paths.

Conclusion

All analysis suggests that C-peptide mobility may contribute to the allosteric behavior observed in mini-proinsulin analogs during receptor interaction.
High aspect ratio graphene oxide: a highly efficient plasmid DNA deliverer for plant seed
Authors: Jiang Cheng , Pan Yue , Li Xinyu , Yang Zhongzhu
Published: October 2024

Plant genetic engineering plays a central role in crop improvement and the biosynthesis of natural products. However, the plant cell wall serves as a natural barrier that restricts the efficient delivery of exogenous biomolecules, particularly the direct transfer of plasmid DNA into plant seeds. Here, we introduce a novel form of graphene oxide characterized by a high aspect ratio, synthesized through low-voltage, low-current, and prolonged electrochemical oxidation in a 0.5 mol/L NaOH aqueous solution. The high aspect ratio graphene oxide (HARGO) can effectively deliver plasmid DNA toPoa crymophilaKeng seeds, achieving a 90% success rate. Furthermore, it is effective for both wheat and rice seeds. The underlying mechanism of this efficient delivery is that HARGO can physically absorb plasmid DNA and transport the adsorbed plasmid DNA into plant cells and deeper tissues through passive transport, eliminating the need for chemical modification of polyethylene glycol (PEG) and polyethyleneimine (PEI). These findings offer a dependable non-integrating plasmid DNA delivery tool for plant genetic engineering, which will significantly impact the advancement of plant biotechnology.
Extracellular vesicles from a novel chordoma cell line, ARF-8, promote tumorigenic microenvironmental changes when incubated with the parental cells and with human osteoblasts
Authors: Nguyen Khoa N , Graner Arin N , Fringuello Anthony R , Zizzo Zoe , Valenzuela Lorena , Anyanwu Kamara , Lillehei Kevin O , Youssef A Samy , Guzman Samuel , Coughlan Christina , Graner Michael W
Published: October 2024

Chordomas are rare, generally slow-growing spinal tumors that nonetheless exhibit progressive characteristics over time, leading to malignant phenotypes and high recurrence rates, despite maximal therapeutic interventions. The tumors are notoriously resistant to therapies and are often in locations that make gross total resections difficult. Here, we describe a new chordoma cell line (ARF-8) derived from an extensive clival chordoma that extended back to the cervical spine. From the cultured cell line we characterized the ARF-8 cellular and extracellular vesicle (EV) proteomes, as well as the impacts of ARF-8 EVs on proteomes and secretomes of recipient cells (both ARF-8 and human osteoblasts) in autocrine and paracrine settings. All the characteristics associated with chordomas as cancers – migration and invasion, therapeutic resistance, metastatic potential – can be driven by tumor EVs. Our proteomic analyses suggested roles for transforming growth factor beta (TGFB) and cell-matrix interactions involving the epithelial-to-mesenchymal transition (EMT), and cell/extracellular matrix interactions in cell migration, consistent with a metastatic tumor phenotype. Our results demonstrated that ARF-8 tumor cell migration was dependent on general (arginine-glycine-aspartic acid [RGD]-based) integrin activity, and ARF-8 EVs could promote such migration. ARF-8 EVs also prompted proteomic/secretomic changes in human osteoblast cells, again with indications that cell-cell and cell-extracellular matrix interactions would be activated. Overall, the EVs promoted predicted tumorigenic phenotypes in recipient cells.
Multiple context discrimination in adult rats: sex variability and dynamics of time-dependent generalization of an aversive memory
Authors: Lotz Fernanda Nogueira , Guerra Kétlyn Talise Knak , Crestani Ana Paula , Quillfeldt Jorge Alberto
Published: October 2024

Memory generalization can be defined as the transference of conditioned fear responses to novel contexts. It happens in systems consolidation, a time-dependent reduction of discrimination precision due to the rearrangement of brain regions supporting memory retrieval. To better understand the fine temporal structure of this process in different sexes, young adult female and male rats were trained in a contextual fear conditioning task and tested in the conditioning or in three novel contexts either 2, 28 or 45 days later. A set of neutral contexts was selected and graded levels of fear expression compared to the training context was obtained, albeit observed only in males, not females, in a recent memory test - the first of a number of sexual dimorphisms detected. This asymmetry, however, disappeared over time due to partial generalization, with fear converging to similar, higher values, grouped in two levels, in both sexes. In all experiments, females were better discriminators and displayed lower fear responses than males, apparently valuing different sensory modalities. This is the first study to compare fear responses between adult female and male rats retrieving recent or remote memories in multiple neutral contexts, allowing several dimorphic findings.
Separate timescales for spatial and anatomical information processing during action observation
Authors: Waltzing B.M. , McAteer S. , Moreno-Verdú M. , Van Caenegem E.E. , Du Yue , Hardwick R.M.
Published: October 2024

Introduction

Observing actions primes us to perform similar movements. Prior work indicates this effect is influenced by factors such as spatial congruence, perspective, and presenting biological/non-biological stimuli. We hypothesized that the influence of these factors would vary depending on the amount of time that participants had to process visual stimuli.

Method

Experiment 1 was a reaction time task (n=29) with stimuli varying in spatial congruence (congruent, incongruent, neutral), perspective (first- or third-person) and stimulus type (biological or non-biological). Experiment 2 (n=50) used the same stimuli in a “Forced Response” paradigm, which controlled the time participants had to prepare a response. This allowed us to assess responses as a function of preparation time.

Results

Experiment 1 showed effects of spatial congruence, with longer reaction times and more errors for spatially incongruent stimuli. This effect was greater for biological stimuli. Experiment 2 showed that spatial information was processed faster than anatomical information, inducing incorrect responses at short preparation times for spatially incongruent biological stimuli. There was little-to-no corresponding effect for non-biological stimuli. Both experiments also showed weak-to-no effects of perspective, which appear to have been driven by spatial congruence.

Discussion

Our results indicate that spatial information is processed faster than anatomical information during action observation. These data are consistent with the dual visual streams hypothesis, whereby spatial information would be processed rapidly via the dorsal stream, while anatomical processing would occur later via the ventral stream. These data also indicate differences in processing between biological and non-biological stimuli.

Public significance statements

This study provides novel insight into the time-course of information processing, showing that spatial information is processed faster than anatomical information during action observation. The results also challenge the established view that visual perspective is critical to action observation effects, demonstrating that this may instead result from lower-level effects of spatial congruence.
Switching of ferrotoroidal domains via an intermediate mixed state in the multiferroic Y-type hexaferrite
Ba0.5Sr1.5Mg2Fe12O22
Authors: Chen Jiahao , Chmiel Francis , Liu Jieyi , Prabhakaran Dharmalingam , Radaelli Paolo G. , Johnson Roger D.
Published: October 2024

We report a detailed study of the magnetic field switching of ferrotoroidal/multiferroic domains in the Y-type hexaferrite compound Ba0.5Sr1.5Mg2Fe12O22. By combining data from superconducting quantum interference device (SQUID) magnetometry, magnetocurrent measurements, and resonant x-ray scattering experiments, we arrive at a complete description of the deterministic switching, which involves the formation of a temperature-dependent mixed state in low magnetic fields. This mechanism is likely to be shared by other members of the hexaferrite family, and presents a challenge for the development of high-speed read-write memory devices based on these materials.

Published by the American Physical Society
2024
Quantum oscillation study of the large magnetoresistance in Mo substituted
WTe2
single crystals
Authors: Barua Sourabh , Lees M. R. , Balakrishnan G. , Goddard P. A.
Published: October 2024

The list of interesting electrical properties exhibited by transition metal dichalcogenides has grown with the discovery of extremely large magnetoresistance (MR) and type-II Weyl semimetal behavior in WTe2 and MoTe2. The extremely large MR in WTe2 is still not adequately understood. Here, we systematically study the effect of Mo substitution on the quantum oscillations in the MR in WTe2. The MR decreases with Mo substitution, however, the carrier concentrations extracted from the quantum oscillations show that the charge compensation improves. We believe that earlier interpretations based on the two-band theory, which attribute the decrease in MR to charge imbalance, could be incorrect due to overparametrization. We attribute the decrease in MR in the presence of charge compensation to a fall in transport mobility, which is evident from the residual resistivity ratio data. The quantum scattering time and the effective masses do not change within experimental errors upon substitution.

Published by the American Physical Society
2024
Flux qubit based detector of microwave photons
Authors: Ilinskaya O. A. , Ryzhov A. I. , Shevchenko S. N.
Published: October 2024

A theory of detection of microwave photons with a flux qubit based detector is presented. We consider a semiclassical approximation with the electromagnetic field being in a coherent state. The flux qubit is considered as a multilevel quantum system (qudit). By solving the Lindblad equation, we describe the time evolution of occupations of the qudit's levels for readout and reset stages of detection. When considering the reset stage, the time evolution is described by multiple avoided-level crossings, thus providing a multilevel Landau-Zener-Stückelberg-Majorana (LZSM) problem. In addition to numerical calculations, we present an approximate solution for the description of the reset stage dynamics based on the adiabatic-impulse approximation and rate equation approach. Our theory may be useful for the theoretical description of driven-dissipative dynamics of qudits, including applications such as single-photon detection.

Published by the American Physical Society
2024
Nuclear suppression of coherent
J/ψ
photoproduction in heavy-ion ultraperipheral collisions and leading twist nuclear shadowing
Authors: Guzey V. , Strikman M.
Published: October 2024

We determine the nuclear suppression factor SPb(x), where x=MJ/ψ2/Wγp2 with MJ/ψ the J/ψ mass and Wγp the photon-nucleon energy, for the cross section of coherent J/ψ photoproduction in heavy-ion ultraperipheral collisions at the Large Hadron Collider and Relativistic Heavy Ion Collider by performing the χ2 fit to all available data on the cross section dσAA→J/ψAA/dy as a function of the J/ψ rapidity y and the photoproduction cross section σγA→J/ψA(Wγp) as a function of Wγp. We find that while the dσAA→J/ψAA/dy data alone constrain SPb(x) for x≥10−3, the combined

d

σ

A

A

→

J

/

ψ

A

A

/

d

y

and σγA→J/ψA(Wγp) data allow us to determine SPb(x) in the wide interval 10−5<x<0.05. In particular, the data favor SPb(x), which decreases with a decrease of x in the 10−4<x<0.01 interval and can be both decreasing or constant for x<10−4. Identifying SPb(x) with the ratio of the gluon distributions in Pb and the proton Rg(x,Q02)=gA(x,Q02)/[Agp(x,Q02)], we demonstrate that the leading twist approximation for nuclear shadowing provides a good description of all the data on dσAA→J/ψAA/dy and σγA→J/ψA(Wγp) as well as on the experimental values for SPb(x) derived from σγA→J/ψA(Wγp). We also show that modern nuclear parton distributions reasonably reproduce SPb(x) as well.

Published by the American Physical Society
2024
Graph-based diffusion model for fast shower generation in calorimeters with irregular geometry
Authors: Kobylianskii Dmitrii , Soybelman Nathalie , Dreyer Etienne , Gross Eilam
Published: October 2024

Denoising diffusion models have gained prominence in various generative tasks, prompting their exploration for the generation of calorimeter responses. Given the computational challenges posed by detector simulations in high-energy physics experiments, the necessity to explore new machine-learning-based approaches is evident. This study introduces a novel graph-based diffusion model designed specifically for rapid calorimeter simulations. The methodology is particularly well-suited for low-granularity detectors featuring irregular geometries. We apply this model to the ATLAS dataset published in the context of the Fast Calorimeter Simulation Challenge 2022, marking the first application of a graph diffusion model in the field of particle physics.

Published by the American Physical Society
2024
Quasiparton distributions in massive QED2: Toward quantum computation
Authors: Grieninger Sebastian , Ikeda Kazuki , Zahed Ismail
Published: October 2024

We analyze the quasiparton distributions of the lightest η′ meson in massive two-dimensional quantum electrodynamics (QED2) by exact diagonalization. The Hamiltonian and boost operators are mapped onto spin qubits in a spatial lattice with open boundary conditions. The lowest excited state in the exact diagonalization is shown to interpolate continuously between an anomalous η′ state at strong coupling, and a nonanomalous heavy meson at weak coupling, with a cusp at the critical point. The boosted η′ state follows relativistic kinematics but with large deviations in the luminal limit. The spatial quasiparton distribution function and amplitude for the η′ state are computed numerically for increasing rapidity both at strong and weak coupling, and compared to the exact light front results. The numerical results from the boosted form of the spatial parton distributions, compare fairly with the inverse Fourier transformation of the luminal parton distributions, derived in the lowest Fock space approximation. Our analysis points out some of the limitations facing the current lattice program for the parton distributions.

Published by the American Physical Society
2024