bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracing the Evolution: A Comprehensive Bibliometric Analysis of Drug Interaction Clinical Studies
Authors: Li Lanping , Zhou Yushi , Ye Lika , Xie Zhihong
Published: August 2024

This study aims to meticulously map the bibliometric landscape of drug‐drug interactions (DDIs) in clinical research. This represents the first use of bibliometric analysis to comprehensively highlight the evolutionary trends and core themes in this critical field of pharmacology. An exhaustive bibliometric search was performed within the Web of Science Core Collection, aiming to comprehensively gather literature on DDIs in clinical settings. A combination of sophisticated analytical tools including DIKW, VOSviewer, and Citespace was utilized for an in‐depth exploration of bibliometric patterns and trends. Of the 3421 initially identified articles, 2622 were considered relevant. The analysis revealed a marked escalation in DDIs publications, with a peak observed in 2020. Five principal thematic clusters emerged: Safety and Adverse Reactions, Drug Metabolism and Efficacy, Disease and Drug Treatment, Research Methods and Practices, and Special Populations and Combined Medication. Key insights included the escalating significance of drug metabolism in pharmacokinetics, heightened focus on cardiovascular and antiviral therapeutics, and the advancing frontier of personalized medicine. Additionally, the analysis underscored the necessity for strategic attention to vulnerable populations and innovative methodological approaches. This study calls for the global harmonization of research methods in DDIs clinical investigations, advocating for the integration of personalized medicine paradigms and the implementation of cutting‐edge computational analytics. It highlights the imperative for inclusive and collaborative research approaches to adeptly address the intricate challenges of contemporary pharmacotherapy.
Effect of Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of SHR4640, a Selective Human Urate Transporter 1 Inhibitor
Authors: Hu Xiaotong , Lin Hongda , Huang Yan , Xu Pingsheng , Xu Bin , Yu Haibin , Wang Meixia , Feng Sheng , Li Yijing , Shen Kai
Published: August 2024

This parallel‐group, open‐label Phase I study evaluated the effect of mild to moderate hepatic impairment on pharmacokinetics (PK), pharmacodynamics (PD), and safety of a single oral dose of SHR4640. Participants with mild or moderate hepatic impairment were enrolled, with each cohort consisting of eight individuals, alongside eight well‐matched controls with normal hepatic function. The participants were administered 10 mg SHR4640, and blood samples were collected for PK evaluation over 72 h. Additionally, serum uric acid (sUA) levels were measured to assess PD changes. Safety was evaluated through adverse events, laboratory tests, vital signs, and electrocardiograms. The Cmax of SHR4640 decreased by 15.0% in the mild hepatic impairment group (geometric least squares means of the ratios [GMR] = 0.850, 90% CI: 0.701‐1.03) and by 17.5% in the moderate hepatic impairment group (GMR = 0.825, 90% CI: 0.681‐1.00). These reductions were not statistically significant compared to the normal hepatic function group. AUC0‐t and AUC0‐inf were similar across all groups, indicating that overall exposure to the drug was not clinical significantly affected by hepatic impairment. Apparent clearance and volume of distribution of SHR4640 showed no association with the severity of hepatic impairment as measured by the Child–Pugh score. There were no significant differences in the changes in sUA levels from baseline across different levels of hepatic function. SHR4640 is well tolerated in participants with mild or moderate hepatic impairment. Mild and moderate hepatic impairment did not have a clinically relevant impact on PK, PD, and safety of SHR4640. SHR4640 can be used in patients with mild to moderate hepatic impairment without the need for dose adjustment.
Biopotency and surrogate assays to validate the immunomodulatory potency of extracellular vesicles derived from mesenchymal stem/stromal cells for the treatment of experimental autoimmune uveitis
Authors: Kaur Gagandeep , Bae Eun‐Hye , Zhang Yu , Ciacciofera Nicole , Jung Kyung Min , Barreda Heather , Paleti Carol , Oh Joo Youn , Lee Ryang Hwa
Published: August 2024

Extracellular vesicles (EVs) derived from mesenchymal stem/stromal cells (MSCs) have been recognized as promising cytotherapeutics due to their demonstrated immunomodulatory effects in various preclinical models. The immunomodulatory capabilities of EVs stem from the proteins and genetic materials they carry from parent cells, but the cargo contents of EVs are significantly influenced by MSC tissues and donors, cellular age and culture conditions, resulting in functional variations. However, there are no surrogate assays available to validate the immunomodulatory potency of MSC‐EVs before in vivo administration. In previous work, we discovered that microcarrier culture conditions enhance the immunomodulatory function of MSC‐EVs, as well as the levels of immunosuppressive molecules such as TGF‐β1 and let‐7b in MSC‐EVs. Building on these findings, we investigated whether TGF‐β1 levels in MSC‐EVs could serve as a surrogate biomarker for predicting their potency in vivo. Our studies revealed a strong correlation between TGF‐β1 and let‐7b levels in MSC‐EVs, as well as their capacity to suppress IFN‐γ secretion in stimulated splenocytes, establishing biopotency and surrogate assays for MSC‐EVs. Subsequently, we validated MSC‐EVs generated from monolayer cultures (ML‐EVs) or microcarrier cultures (MC‐EVs) using murine models of experimental autoimmune uveoretinitis (EAU) and additional in vitro assays reflecting the Mode of Action of MSC‐EVs in vivo. Our findings demonstrated that MC‐EVs carrying high levels of TGF‐β1 exhibited greater efficacy than ML‐EVs in halting disease progression in mice with EAU as well as inducing apoptosis and inhibiting the chemotaxis of retina‐reactive T cells. Additionally, MSC‐EVs suppressed the MAPK/ERK pathway in activated T cells, with treatment using TGF‐β1 or let‐7b showing similar effects on the MAPK/ERK pathway. Collectively, our data suggest that MSC‐EVs directly inhibit the infiltration of retina‐reactive T cells toward the eyes, thereby halting the disease progression in EAU mice, and their immunomodulatory potency in vivo can be predicted by their TGF‐β1 levels.
Comparison of EV characterization by commercial high‐sensitivity flow cytometers and a custom single‐molecule flow cytometer
Authors: Kim James , Xu Shihan , Jung Seung‐Ryoung , Nguyen Alya , Cheng Yuanhua , Zhao Mengxia , Fujimoto Bryant S. , Nelson Wyatt , Schiro Perry , Franklin Jeffrey L. , Higginbotham James N. , Coffey Robert J. , Shi Min , Vojtech Lucia N. , Hladik Florian , Tewari Muneesh , Tigges John , Ghiran Ionita , Jovanovic‐Talisman Tijana , Laurent Louise C. , Das Saumya , Gololobova Olesia , Witwer Kenneth W. , Xu Tuoye , Charest Al , Jensen Kendall Van Keuren , Raffai Robert L. , Jones Jennifer C. , Welsh Joshua A. , Nolan John P. , Chiu Daniel T.
Published: August 2024

High‐sensitivity flow cytometers have been developed for multi‐parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the characterization of identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high‐sensitivity flow cytometers, two commercial instruments, CytoFLEX/CellStream, and a custom single‐molecule flow cytometer (SMFC). DiFi EVs were stained with the membrane dye di‐8‐ANEPPS and with PE‐conjugated anti‐EGFR or anti‐tetraspanin (CD9/CD63/CD81) antibodies for estimation of EV size and surface protein copy numbers. The limits of detection (LODs) for immunofluorescence and vesicle size based on calibration using cross‐calibrated, hard‐dyed beads were ∼10 PE/∼80 nm EV diameter for CytoFLEX and ∼10 PEs/∼67 nm for CellStream. For the SMFC, the LOD for immunofluorescence was 1 PE and ≤ 35 nm for size. The population of EVs detected by each system (di‐8‐ANEPPS+/PE+ particles) differed widely depending on the LOD of the system; for example, CellStream/CytoFLEX detected only 5.7% and 1.5% of the tetraspanin‐labelled EVs detected by SMFC, respectively, and median EV diameter and antibody copy numbers were much larger for CellStream/CytoFLEX than for SMFC as measured and validated using super‐resolution/single‐molecule TIRF microscopy. To obtain a dataset representing a common EV population analysed by all three platforms, we filtered out SMFC and CellStream measurements for EVs below the CytoFLEX LODs as determined by bead calibration (10 PE/80 nm). The inter‐platform agreement using this filtered dataset was significantly better than for the unfiltered dataset, but even better concordance between results was obtained by applying higher cutoffs (21 PE/120 nm) determined by threshold analysis using the SMFC data. The results demonstrate the impact of specifying LODs to define the EV population analysed on inter‐instrument reproducibility in EV flow cytometry studies, and the utility of threshold analysis of SMFC data for providing semi‐quantitative LOD values for other flow cytometers.
Analysis of seasonal H3N2 influenza virus epidemic characteristics and whole genome features in Jining City from 2018 to 2023
Authors: Jiang Yajuan , Dou Huixin , Wang Xiaoyu , Song Tongyun , Jia Yongjian , Yue Ying , Li Libo , He Feifei , Kong Lingming , Wu Zengding , Huang Xiankun , Liang Yumin , Jiao Boyan , Jiao Baihai
Published: August 2024

Seasonal H3N2 influenza virus, known for its rapid evolution, poses a serious threat to human health. This study focuses on analyzing the influenza virus trends in Jining City (2018–2023) and understanding the evolving nature of H3N2 strains. Data on influenza‐like cases were gathered from Jining City's sentinel hospitals: Jining First People's Hospital and Rencheng Maternal and Child Health Hospital, using the Chinese Influenza Surveillance Information System. Over the period from 2018 to 2023, 7844 throat swab specimens were assessed using real‐time fluorescence quantitative PCR for influenza virus nucleic acid detection. For cases positive for seasonal H3N2 influenza virus, virus isolation was followed by whole genome sequencing. Evolutionary trees were built for the eight gene segments, and protein variation analysis was performed. From 2018 to 2023, influenza‐like cases in Jining City represented 6.99% (237 299/3 397 247) of outpatient visits, peaking in December and January. Influenza virus was detected in 15.67% (1229/7844) of cases, primarily from December to February. Notably, no cases were found in the 2020–2021 season. Full genome sequencing was conducted on 70 seasonal H3N2 strains, revealing distinct evolutionary branches across seasons. Significant antigenic site variations in the HA protein were noted. No resistance mutations to inhibitors were found, but some strains exhibited mutations in PA, NS1, PA‐X, and PB1‐F2. Influenza trends in Jining City saw significant shifts in the 2020–2021 and 2022–2023 seasons. Seasonal H3N2 exhibited rapid evolution. Sustained vigilance is imperative for vaccine updates and antiviral selection.
Microporous polysaccharide hemospheres for reducing pocket hematomas after cardiac device implantation in patients on antithrombotic therapy
Authors: Matsui Yuko , Higuchi Satoshi , Mori Fumiaki , Takehisa Kao , Kikuchi Kensuke , Kikuchi Haruka , Hirobe Kohei , Maeda Ryozo , Tsukamoto Kei , Saito Takashi , Shoda Morio , Yamaguchi Junichi
Published: August 2024

Background

Various surgical procedures have employed microporous polysaccharide hemosphere (MPH) hemostatic agents. However, data regarding their effectiveness in preventing pocket hematomas (PHs) during the implantation of cardiac implantable electronic devices (CIED) among the Asian population are limited. Therefore, this study aimed to investigate the potential benefits of using MPH hemostatic agents during CIED implantations as a preventive measure against post‐procedural PHs.

Methods

We conducted a retrospective, single‐center, observational study involving 255 consecutive Japanese patients who underwent CIED implantation between November 2017 and April 2021. We compared PH occurrences within 28 days after CIED implantation between patients who received MPH hemostatic agents (n = 145) and those who did not (n = 110).

Results

PH development was observed in nine (6.2%) patients who received MPH hemostatic agents and in 13 (11.8%) patients without MPH hemostatic (p = .111). Kaplan–Meier analysis of PH development revealed no significant difference between the two groups (log‐rank p = .102). However, utilizing MPH hemostatic agents among patients taking antithrombotic drugs, including antiplatelet medications, direct oral anticoagulants, and warfarin, significantly reduced PH incidence (log‐rank p = .03). The multivariate Cox proportional hazards model demonstrated that MPH hemostatic agent utilization independently correlated with a decreased PH risk (hazard ratio 0.22, 95% confidence interval 0.08–0.63, p = .004).

Conclusions

The findings of this study suggest that the incorporation of MPH hemostatic agents into standard practice may benefit to mitigate PH risk during CIED implantations in patients on antithrombotic therapy. This simple and practical measure may be valuable, especially in high‐risk patients, such as those taking antithrombotic medications.
Methotrexate and Rituximab Use in Highly Recurrent Idiopathic Subglottic Stenosis
Authors: Awadallah Andrew S. , Bowen Andrew J. , Ali Hawa M. , O'Byrne Thomas J. , Padilla Hannah M. , Khalil Yousuf H. , Aden Aisha A. , Edell Eric S. , Koster Matthew J. , Bayan Semirra L. , Ekbom Dale C.
Published: August 2024

Objective

To evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(−).

Methods

This was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated.

Results

A total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre‐drug interval: 338; mean post‐drug interval: 697 days) (p‐value = 0.25). Three patients did not recur following drug initiation with median follow‐up of 1265 days. All three treatment groups demonstrated a trend toward increased post‐drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post‐drug recurrence intervals (mean pre‐drug interval: 341 days, mean post‐drug interval 978 days) (p‐value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%).

Conclusion

MTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy.

Level of Evidence

3 Laryngoscope, 2024
Survival Outcomes of Transoral Microsurgery in T3/T4a Laryngeal Tumors: Systematic Review and Meta‐Analysis
Authors: Vasudevan Srivatsa Surya , Zulli Adam , Olinde Lindsay , Pang John , Nathan Cherie‐Ann O. , Asarkar Ameya A.
Published: August 2024

Objective

To critically evaluate oncological and functional outcomes following transoral laser microsurgery (TLM) in patients with T3/T4a glottic and supraglottic squamous cell carcinoma (SCC).

Data Sources

A comprehensive search of five major databases—PubMed, Embase, Scopus, ScienceDirect, and Web of Science—was conducted using a combination of relevant keywords and MeSH terms.

Review Methods

Systematic review and meta‐analysis of odds ratio (OR), hazards ratio (HR), and proportion, focusing on oncological and functional outcomes of TLM in advanced T3/T4a glottic and supraglottic tumors. A random‐effects meta‐analysis model was employed.

Results

The review incorporated 29 cohort studies, representing a total of 1,897 patients undergoing TLM for T3/T4a glottic and supraglottic SCC. The cumulative 5‐year disease‐free survival (DFS) rate for T3 glottic and supraglottic tumors was 44.4% (95% CI: 47–66%) and 62.8% (95% CI: 63–81%), while the 5‐year DFS for T4 glottic and supraglottic tumors was 41.1% (95% CI: 33.4–49.2%) and 32.9% (95% CI: 19.3–50.1%), respectively. T3 glottic tumors exhibited a 2.5‐fold significantly higher odds of local recurrence post‐TLM compared to their T3 supraglottic tumors (95% CI: 1.6–3.9, p < 0.0001). Laryngeal preservation rates for T3glottic and supraglottic tumors were 68.9% (95% CI: 48.7–83.8%) and 88.4% (95% CI: 79.4–93.8%), respectively. Both groups showed comparable rates of tracheostomy (p = 0.48) and gastrostomy performed (p = 0.17).

Conclusions

This meta‐analysis suggests that TLM is a viable larynx preservation approach in select patients with T3/T4a glottic and supraglottic tumors. However, glottic tumors may have less favorable outcomes after TLM compared to those with advanced supraglottic tumors.

Level of Evidence

N/A Laryngoscope, 2024 Laryngoscope, 2024
US public health surveillance, reimagined
Authors: Guralnik Elina
Published: August 2024

Introduction

This study presents two novel concepts for standardizing electronic health records (EHR)‐based public health surveillance through utilization of existing informatics methods and data platforms.

Methods

Drawing from the collective experience in applied epidemiology, health services research and health informatics, the author presents a vision for an alternative path to public health surveillance by repurposing existing tools and resources, such as (1) computable phenotypes which have already been created and validated for a variety of chronic diseases of interest to public health and (2) large data platforms/collaboratives, such as All of Us Research Program and National COVID Cohort Collaborative. Opportunities and challenges are discussed regarding EHR‐based chronic disease surveillance, as well as the concept of phenotype definitions and large data platforms reuse for public health needs.

Results/Framework

Reusing of computable phenotypes for EHR‐based public health surveillance would require secure data platforms and nationally representative data. Standardization metrics for reuse of previously developed and validated computable phenotypes are also necessary and are currently being developed by the author. This study presents a reimagined Learning Health System framework by incorporating Public Health and two novel concept sets of solutions into the healthcare ecosystem.

Conclusion/Next Steps

Alternative approaches to limited resources and current infrastructure of the US Public Health System, especially as applied to disease surveillance, are needed and may be possible when repurposing the resources and methodologies across the Learning Health System.
Study on corrosion resistance of arc sprayed Zn–xAl (x = 19, 27, and 37) pseudo alloy coatings in salt spray environment
Authors: Zhang Min , Wang Song , Li Qi , Liu Shifeng
Published: August 2024

To study the corrosion behavior of Zn–Al pseudo alloy coatings with different Al contents, Zn–xAl (x = 19, 27, and 37) pseudo alloy coatings were prepared by the wire arc spraying technique using Zn and Al wires with different diameters. This study investigated the microstructure, electrochemical corrosion behavior, and corrosion morphology and products of the as‐sprayed coatings after the salt spray test in 5 wt% NaCl solution. The results exhibited that the Zn–Al pseudo alloy coatings with higher Al content form denser corrosion products (Zn5(OH)8Cl2·H2O and Zn–Al layered double hydroxide) with stronger self‐shielding effect against corrosive media, thus provide better long‐term corrosion protection. Besides, electrochemical reactions are controlled by mass transfer until corrosion for 24 h, and then by a combination of mass transfer and diffusion for 96 h. Overall, it can be concluded that the Zn–37Al pseudo alloy coating in this study shows great potential to protect steel substrates from corrosion.
Narrowly Distributed Conjugated Polymers Synthesized Through Acid‐Catalyzed Aldol Polycondensations in Nanoreactors
Authors: Shi Huayu , Huang Xiaohua , Tian Donglai , Pan Huanghao , Hu Aiguo
Published: August 2024

Conjugated polymers are typically synthesized through transition metal‐mediated coupling reactions, which are often costly and have significant environmental impacts. Aldol condensation represents a more cost‐effective and sustainable synthetic technique for developing next‐generation organic functional materials. However, controlling the molecular weight and distribution of the resulting polymers remains challenging due to the uncontrollable step‐growth polymerization mechanism of aldol polycondensations. To this end, by selectively anchoring sulfonic acids inside the mesochannels of SBA‐15, the aldol polycondensation is exclusively confined within the pores. Experimental results demonstrate that this nanoreactor, by providing a spatially confined reaction environment, aids in controlling the progression of the polymerization and the growth of polymer chains, thereby achieving good control over polymer molecular weight and distribution, giving linear conjugated polymers and soluble conjugated polymeric nanoparticles with polymer dispersity down to 1.31.
Immunoglobulin class‐switch recombination: Mechanism, regulation, and related diseases
Authors: Liu Jia‐Chen , Zhang Ke , Zhang Xu , Guan Fei , Zeng Hu , Kubo Masato , Lee Pamela , Candotti Fabio , James Louisa Katherine , Camara Niels Olsen Saraiva , Benlagha Kamel , Lei Jia‐Hui , Forsman Huamei , Yang Lu , Xiao Wei , Liu Zheng , Liu Chao‐Hong
Published: August 2024

Maturation of the secondary antibody repertoire requires class‐switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high‐affinity antibodies. Following immune response or infection within the body, activation of T cell‐dependent and T cell‐independent antigens triggers the activation of activation‐induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper‐IgM syndrome, Waldenström macroglobulinemia, hyper‐IgD syndrome, selective IgA deficiency, hyper‐IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.
InspireGBs – Inspiratory muscle training in people with Guillain‐Barré syndrome: A feasibility study
Authors: Almeida Miguel P. , Winck João Carlos , Marques Alda
Published: August 2024

Background

Guillain‐Barré syndrome (GBS) is a rare immune‐mediated peripheral nerve disease often preceded by infections. Respiratory muscle weakness is a common complication in this population, leading to decreased vital capacity, weakened coughing ability, atelectasis, and pulmonary infections. Inspiratory muscle training (IMT) has been widely used to enhance inspiratory muscle strength and pulmonary function in various diseases; however, its application in GBS is unknown.

Objective

To assess the safety, feasibility, and preliminary effectiveness of an IMT protocol—InspireGBs—in people with GBS.

Methods

A pre/post feasibility study was conducted. Feasibility was determined by participant recruitment/retention, adherence, time spent in each session, and adverse events. Secondary outcome was inspiratory muscle strength. InspireGBs consisted of twice daily sessions 5 times/week, three sets of 10 breaths in each session, for 6 weeks. Initial resistance was set at 50% of participant's baseline maximal inspiratory pressure (MIP) and with a weekly increase of 10% calculated from the previous week's training intensity, if tolerated, otherwise the increase was 5%.

Results

Eleven patients (63% male; 63 ± 9 years) were recruited from inpatient rehabilitation and 10 completed the study. Recruitment and retention rates were high (79% and 91%, respectively). Excellent adherence rate (96%) was obtained with no reported adverse effects or safety issues. Sessions lasted from 4 to 6 minutes. The MIP improved (pretraining: 39 [26.5–50] cm H2O vs. posttraining: 61 [56.3–64.5] cm H2O, p = .005 and pretraining: 38 [30.5–53.8] % of predicted vs. posttraining: 60 [54.28–71.58] % of predicted, p = .009) with the InspireGBs.

Conclusion

InspireGBs is safe, feasible, and may be effective in improving inspiratory muscle strength in individuals with GBS. A randomized controlled trial is now needed to strengthen these findings.
Prescribed‐time consensus for multi‐agent systems using finite switching time‐varying gain
Authors: Li Yinsheng , Wang Bing , Chen Yuquan
Published: August 2024

In this paper, the prescribed‐time consensus problem of multi‐agent systems with finite control gain is investigated. A novel control Lyapunov function (CLF) framework for prescribed‐time stability is developed by using the time space deformation approach. For both leaderless and leader‐following prescribed‐time consensus, new switching time‐varying gain‐based protocols are proposed, in which, the infinite time‐varying control gain is turned off before the prescribed time and the global boundedness of control gain is thus guaranteed. It is mathematically proved that the agents equipped with the proposed protocols can achieve less conservative prescribed‐time consensus in both leaderless cases and leader‐following cases, on the basis of the developed CLF framework. The superiority of the proposed prescribed‐time protocols in terms of consensus accuracy, control energy consumption, and control peak value is demonstrated through comparison simulations using illustrative examples.
Super‐Resolution Imaging in Collagen‐Abundant Thick Tissues
Authors: Chuang Ya‐Han , Wu Yueh‐Feng , Lin Ya‐Hui , Chen Yin‐Hsu , Zhou Yu‐Xian , Hsu Shao‐Chun , Lee Hsin‐Mei , Chiang Ann‐Shyn , Chen Yunching , Chen Shiang‐Jiuun , Lin Sung‐Jan , Chu Li‐An
Published: August 2024

Expansion microscopy (ExM) has gained increasing popularity for 3D ultrastructural imaging of cultured cells and tissue slices at nanoscale resolution using conventional microscopes via physical expansion of biological tissues. However, its application to collagen‐abundant thick tissues is still challenging. Herein, a new method, collagen ExM (ColExM), optimized for expanding tissues containing more than 70% collagen, is demonstrated. ColExM succeeds in 4.5‐fold linear expansion with minimal structural distortion of corneal and skin tissues. It is compatible with immunostaining, allowing super‐resolution visualization of 3D neural structures innervating hair follicles, corneas, and pancreatic tumors with high stromal collagen content. The method succeeds in identifying individual mitochondria and previously unrecognized dendritic spinelike structures of corneal nerves. It also enables fine mapping of structural rearrangement of tight junctions and actin cytoskeletons. Therefore, ColExM can facilitate the exploration of 3D nanoscale structures in collagen‐rich tissues.
Research on the mechanical performance of circular concrete‐filled steel tube columns under bending‐torsional coupling
Authors: Ding Fa‐xing , Huang Xin‐yu , Gong Chen‐jie , Pi Zheng‐bo
Published: August 2024

Under the influence of wind and horizontal seismic forces, structures such as piers in curved beam bridges, main arches of steel tube concrete arch bridges, and frame columns may experience combined bending‐torsion stress states, affecting the safe usage of the structure. To investigate the mechanical performance of circular concrete‐filled steel tube(CFST) columns under bending‐torsional coupling, a three‐dimensional solid‐shell finite element model of circular concrete‐filled steel tube columns under various bending and torsion ratios (k) was established using ABAQUS software, and validated with existing experiments on such columns under bending‐torsional loading. Parametric analysis was conducted to explore the trends of interface slip and the restraining effect in circular concrete‐filled steel tube columns under different bending and torsion ratios, analyzing the impact of parameters such as the yield strength of steel, concrete strength, steel content in the cross‐section, and shear–span ratio on the combined bearing capacity. The results of the parametric analysis show that: (1) with the increase of k, the relative slip at the interface between the core concrete and the outer steel tube first increases and then decreases, with interface slip leading to a reduction in the load‐bearing capacity; (2) the relative slip at the interface between the core concrete and the outer steel tube first increases and then decreases, with interface slip leading to a reduction in the load‐bearing capacity; (3) with the increase of k, the circumferential and axial stresses in the steel tube surface of the circular concrete‐filled steel tube columns increase, while the shear stress decreases, leading to a transition in the failure mode of the columns from combined bending‐torsional failure to bending‐shear failure. Based on these findings, a practical calculation formula for the bending‐torsional combined bearing capacity of circular concrete‐filled steel tube columns is proposed, offering high calculation accuracy and serving as a reference for the design of such components.
Ductility‐oriented design of UHPC T‐beams: Mechanical model and design recommendations
Authors: Alsomiri Mujahed , Liu Zhao , Wang Tao , Meng Jie
Published: August 2024

Ultrahigh performance concrete (UHPC) has recently become a major focus garnering substantial attention due to its remarkable mechanical properties. UHPC has been increasingly employed across diverse projects in the construction industry. However, the structural ductility of UHPC members has yet to be fully established and is often compromised by the manifestation of the crack localization phenomenon. This paper presents the flexural test results of five T‐beams and introduces a model for predicting the flexural capacity and failure modes of UHPC T‐beams. The model employs the curvature ductility index as a measurement for evaluating and ensuring the member's ductility. The results show that the flexural behavior of UHPC T‐beams can be characterized by four key points representing cracking, reinforcement yielding, crack localization, and post‐localization capacity. The validity of the model is substantiated by experimental data from this study and complemented by test data collected from the literature. The proposed model is then employed to derive ductility‐oriented design limits, including minimum and maximum reinforcement ratios and minimum localization strain capacity. Finally, the paper summarizes the design recommendations and provides a classification of section conditions, reinforcement limits, localization strain limits, adequate ductility range, and the feasible ductile design range.
ABCD Team at SOMD 2024: Software Mention Detection in Scholarly Publications with Large Language Models
Authors: Nguyen Xuan Phi , Tran Minh Quang , Dang Van Thin
Published: August 2024

This paper outlines the ABCD team’s approach to employing LLMs for three subtasks at SOMD 2024, specifically focusing on Software Mention Detection in Scholarly Publications. The task revolves around scientific articles and information, comprising three subtasks: (1) extracting software entities from a given sentence, (2) extracting relevant entities related to software entities from the task I, and (3) determining the relationship between entities extracted from the previous two tasks. Our objective is to gain valuable insights into fine-tuning LLMs using LoRA. The experimental results showcase that our approach has demonstrated competitive performance across all three tasks, securing Top 1, Top 2, and Top 2 rankings for Subtask I, Subtask II, and Subtask III, respectively. We release our source code in this Github repository(https://github.com/Xphi310302/ABCD-team-NLSP.git).
The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis
Authors: Swart Maarten , Redpath Andia N. , Ogbechi Joy , Cardenas Ryan , Topping Louise , Compeer Ewoud B. , Goddard Michael , Chanalaris Anastasios , Williams Richard , Brewer Daniel S. , Smart Nicola , Monaco Claudia , Troeberg Linda
Published: August 2024

Heparan sulfate (HS) proteoglycans are important regulators of cellular responses to soluble mediators such as chemokines, cytokines and growth factors. We profiled changes in expression of genes encoding HS core proteins, biosynthesis enzymes and modifiers during macrophage polarisation, and found that the most highly regulated gene was Sulf2, an extracellular HS 6-O-sulfatase that was markedly downregulated in response to pro-inflammatory stimuli. We then generated Sulf2+/− bone marrow chimeric mice and examined inflammatory responses in antigen-induced arthritis, as a model of rheumatoid arthritis. Resolution of inflammation was impaired in myeloid Sulf2+/− chimeras, with elevated joint swelling and increased abundance of pro-arthritic Th17 cells in synovial tissue. Transcriptomic and in vitro analyses indicated that Sulf2 deficiency increased type I interferon signaling in bone marrow-derived macrophages, leading to elevated expression of the Th17-inducing cytokine IL6. This establishes that dynamic remodeling of HS by Sulf2 limits type I interferon signaling in macrophages, and so protects against Th17-driven pathology.
Heat Properties for Groups
Authors: Bédos Erik , Conti Roberto
Published: August 2024

We revisit Fourier’s approach to solve the heat equation on the circle in the context of (twisted) reduced group C*-algebras, convergence of Fourier series and semigroups associated to negative definite functions. We introduce some heat properties for countably infinite groups and investigate when they are satisfied. Kazhdan’s property (T) is an obstruction to the weakest property, and our findings leave open the possibility that this might be the only one. On the other hand, many groups with the Haagerup property satisfy the strongest version. We show that this heat property implies that the associated heat problem has a unique solution regardless of the choice of the initial datum.
A novel methodology for the selection of the optimal velocity profile for planned point-to-point trajectories in 1-DoF manipulators
Authors: Olier Camilo Andrés Gonzalez , Ramírez Heriberto Enrique Maury , Higuera Leidy Milena Mora
Published: August 2024

In this work, an approach based on velocity profile selection is developed and validated to decrease forces, acceleration, velocity, mechanical power, and energy consumption in 1 DOF Cartesian manipulators. Initially, a mathematical modeling of the kinematic and kinetic variables rising in linear, exponential, parabolic, sinusoidal, and s-curve ramp velocity profiles is proposed for different load conditions and saturation values of the velocity profiles, focusing on generic Cartesian manipulators moving a constant inertia load and not equipped with regenerative devices. Lastly, a summary table outlining the benefits and drawbacks of each velocity profile in relation to the relevant variables is given to the reader, along with a set of recommendations for selecting the best velocity profile in accordance with the load conditions and optimization goals. It was shown that, depending on the load conditions, the inappropriate choice of one type of speed profile can increase the required forces by up to 400%, the required maximum power by more than 88%, and the energy consumption by up to 77% with respect to the optimal speed profile.
Technical note: durable resolution of hydrocephalus after ultrasound-guided percutaneous fenestration of giant suprasellar arachnoid cyst in a neonate
Authors: Stuart Michael J. , Yoon Joseph , McEniery Jane , Jardim Amelia J. , Vonhoff Craig
Published: August 2024

Arachnoid cysts are relatively common, but rarely require intervention. While most arachnoid cysts in typical middle or posterior cranial fossa locations are seldom symptomatic, suprasellar cysts may become symptomatic due to the potential for ventricular outflow obstruction and hydrocephalus. Typical standard of care for the treatment of these lesions is endoscopic fenestration with third ventriculostomy, or the placement of ventriculoperitoneal or cystoperitoneal shunts. The surgical and anaesthetic risks of traditional interventions may be higher in the early neonatal period, including leak of cerebrospinal fluid, infection, and premature failure of ventriculostomy or shunts. This note describes a novel bedside ultrasound-guided technique to percutaneously fenestrate large suprasellar arachnoid cysts under local anaesthesia. The technique involves insertion of a 25-g spinal needle until contact with the membrane of the arachnoid cyst medially, followed by a lateral sweeping to widely incise/fenestrate the lesion into the ventricular space under continuous ultrasound visualisation. This note describes an example case which demonstrates durable radiological and clinical improvement after 2 years of follow-up. This may represent a management option to temporise, or perhaps definitively manage suprasellar arachnoid cysts in the neonatal period.
Current insights and assumptions on α-synuclein in Lewy body disease
Authors: Leak Rehana K. , Clark Rachel N. , Abbas Muslim , Xu Fei , Brodsky Jeffrey L. , Chen Jun , Hu Xiaoming , Luk Kelvin C.
Published: August 2024

Lewy body disorders are heterogeneous neurological conditions defined by intracellular inclusions composed of misshapen α-synuclein protein aggregates. Although α-synuclein aggregates are only one component of inclusions and not strictly coupled to neurodegeneration, evidence suggests they seed the propagation of Lewy pathology within and across cells. Genetic mutations, genomic multiplications, and sequence polymorphisms of the gene encoding α-synuclein are also causally linked to Lewy body disease. In nonfamilial cases of Lewy body disease, the disease trigger remains unidentified but may range from industrial/agricultural toxicants and natural sources of poisons to microbial pathogens. Perhaps due to these peripheral exposures, Lewy inclusions appear at early disease stages in brain regions connected with cranial nerves I and X, which interface with inhaled and ingested environmental elements in the nasal or gastrointestinal cavities. Irrespective of its identity, a stealthy disease trigger most likely shifts soluble α-synuclein (directly or indirectly) into insoluble, cross-β-sheet aggregates. Indeed, β-sheet-rich self-replicating α-synuclein multimers reside in patient plasma, cerebrospinal fluid, and other tissues, and can be subjected to α-synuclein seed amplification assays. Thus, clinicians should be able to capitalize on α-synuclein seed amplification assays to stratify patients into potential responders versus non-responders in future clinical trials of α-synuclein targeted therapies. Here, we briefly review the current understanding of α-synuclein in Lewy body disease and speculate on pathophysiological processes underlying the potential transmission of α-synucleinopathy across the neuraxis.
Comparison of barrier update strategies for interior point algorithms in single-crystal plasticity
Authors: Scheunemann Lisa , Steinmetz Felix , Nigro Paulo
Published: August 2024

This contribution discusses the influence of different barrier update strategies on the performance and robustness of an interior point algorithm for single-crystal plasticity at small strains. To this end, single-crystal plasticity is first briefly presented in the framework of a primal-dual interior point algorithm to outline the general algorithmic structure. The manner in which the barrier parameter is modified within the interior point method, steering the penalization of constraints, plays a crucial role for the robustness and efficiency of the overall algorithm. In this paper, we compare and analyze different strategies in the framework of crystal plasticity. In a thorough analysis of a numerical example covering a broad range of settings in monocrystals, we investigate robust hyperparameter ranges and identify the most efficient and robust barrier parameter update strategies.
Seroprevalence and associated risk factors for Neospora caninum infection in dairy cattle in South Africa
Authors: Tagwireyi Whatmore Munetsi , Thompson Peter N. , Garcia Gema Alvarez , Morar-Leather Darshana , Neves Luis
Published: August 2024

Bovine neosporosis is a widespread parasitic disease associated with significant economic losses. Its effects on the reproductive performance of cows have resulted in losses that run into the hundreds of millions of US dollars in dairy industries in various countries (Reichel et al., Int J Parasitol 43:133–142, 2013). Due to outdated and scant information on the occurrence of Neospora caninum infection in South Africa, the study aimed to determine the seroprevalence and risk factors associated with infection in dairy cattle in South Africa. A total of 1401 blood samples were randomly collected from cattle on 48 dairy farms in seven of the nine provinces in South Africa. A close-ended questionnaire was used in a cross-sectional study to obtain farm-level and animal-level data. Serological testing was done using a commercial IDvet Screen® Neospora caninum Indirect ELISA. An overall seroprevalence, adjusted for test sensitivity and specificity, of 2.3% (95% CI, 1.3–4.1) was detected and 48% (23/48) of sampled farms had at least one animal testing positive. The highest seroprevalence of N. caninum was in the KwaZulu-Natal province with 7.5% (95% CI, 3.8–14.3), and the lowest in Western Cape with 0.1% (95% CI, 0–1.2). The highest within-farm seroprevalence of 25% was detected on a farm in the North West Province. In a multivariable logistic regression model, the odds of N. caninum seropositivity were higher in Holstein–Friesian cattle when compared to other breeds. Good hygiene was identified as a protective factor. Cattle left out on pasture had increased odds of testing positive for N. caninum compared to those that were penned. The odds of testing seropositive for N. caninum was higher on farms that practised segregation of cattle into different age groups. The purchase of replacement animals was a significant risk factor, as open herds had increased odds of N. caninum seropositivity. Cattle on farms that did not have a specific calving location were more likely to be seropositive. This is the first such study in South Africa and shows that N. caninum is widely distributed in the country at a low seroprevalence, but it may be a cause of concern on certain farms.
Centrifugation is an effective and inexpensive way to determine Batrachochytrium dendrobatidis quantity in water samples with low turbidity
Authors: McMahon Taegan A. , Katz Tatum S. , Barnett Kate M. , Hilgendorff Bridget A.
Published: August 2024

Batrachochytrium dendrobatidis (Bd) is a pathogenic chytrid fungus that is particularly lethal for amphibians. Bd can extirpate amphibian populations within a few weeks and remain in water in the absence of amphibian hosts. Most efforts to determine Bd presence and quantity in the field have focused on sampling hosts, but these data do not give us a direct reflection of the amount of Bd in the water, which are useful for parameterizing disease models, and are not effective when hosts are absent or difficult to sample. Current methods for screening Bd presence and quantity in water are time, resource, and money intensive. Here, we developed a streamlined method for detecting Bd in water with low turbidity (e.g., water samples from laboratory experiments and relatively clear pond water from a natural lentic system). We centrifuged water samples with known amounts of Bd to form a pellet and extracted the DNA from that pellet. This method was highly effective and the resulting concentrations across all tested treatments presented a highly linear relationship with the expected values. While the experimentally derived values were lower than the inoculation doses, the values were highly correlated and a conversion factor allows us to extrapolate the actual Bd concentration. This centrifuge-based method is effective, repeatable, and would greatly expand the domain of tractable questions to be explored in the field of Bd ecology. Importantly, this method increases equity in the field, because it is time- and cost-efficient and requires few resources.
Democratizing biomedical simulation through automated model discovery and a universal material subroutine
Authors: Peirlinck Mathias , Linka Kevin , Hurtado Juan A. , Holzapfel Gerhard A. , Kuhl Ellen
Published: August 2024

Personalized computational simulations have emerged as a vital tool to understand the biomechanical factors of a disease, predict disease progression, and design personalized intervention. Material modeling is critical for realistic biomedical simulations, and poor model selection can have life-threatening consequences for the patient. However, selecting the best model requires a profound domain knowledge and is limited to a few highly specialized experts in the field. Here we explore the feasibility of eliminating user involvement and automate the process of material modeling in finite element analyses. We leverage recent developments in constitutive neural networks, machine learning, and artificial intelligence to discover the best constitutive model from thousands of possible combinations of a few functional building blocks. We integrate all discoverable models into the finite element workflow by creating a universal material subroutine that contains more than 60,000 models, made up of 16 individual terms. We prototype this workflow using biaxial extension tests from healthy human arteries as input and stress and stretch profiles across the human aortic arch as output. Our results suggest that constitutive neural networks can robustly discover various flavors of arterial models from data, feed these models directly into a finite element simulation, and predict stress and strain profiles that compare favorably to the classical Holzapfel model. Replacing dozens of individual material subroutines by a single universal material subroutine—populated directly via automated model discovery—will make finite element simulations more user-friendly, more robust, and less vulnerable to human error. Democratizing finite element simulation by automating model selection could induce a paradigm shift in physics-based modeling, broaden access to simulation technologies, and empower individuals with varying levels of expertise and diverse backgrounds to actively participate in scientific discovery and push the boundaries of biomedical simulation.