bluuebunny/crossref_metadata_2025 huggingface dataset:
IDH1 mutation impairs antiviral response and potentiates oncolytic virotherapy in glioma
Authors: Chen Xueqin , Liu Jun , Li Yuqin , Zeng Yuequan , Wang Fang , Cheng Zexiong , Duan Hao , Pan Guopeng , Yang Shangqi , Chen Yuling , Li Qing , Shen Xi , Li Ying , Qin Zixi , Chen Jiahong , Huang Youwei , Wang Xiangyu , Lu Yuli , Shu Minfeng , Zhang Yubo , Wang Guocai , Li Kai , Lin Xi , Xing Fan , Zhang Haipeng
Published: October 2023

IDH1 mutations frequently occur early in human glioma. While IDH1 mutation has been shown to promote gliomagenesis via DNA and histone methylation, little is known regarding its regulation in antiviral immunity. Here, we discover that IDH1 mutation inhibits virus-induced interferon (IFN) antiviral responses in glioma cells. Mechanistically, D2HG produced by mutant IDH1 enhances the binding of DNMT1 to IRF3/7 promoters such that IRF3/7 are downregulated, leading to impaired type I IFN response in glioma cells, which enhances the susceptibility of gliomas to viral infection. Furthermore, we identify DNMT1 as a potential biomarker predicting which IDH1mut gliomas are most likely to respond to oncolytic virus. Finally, both D2HG and ectopic mutant IDH1 can potentiate the replication and oncolytic efficacy of VSVΔ51 in female mouse models. These findings reveal a pivotal role for IDH1 mutation in regulating antiviral response and demonstrate that IDH1 mutation confers sensitivity to oncolytic virotherapy.
Rapid sensing of hidden objects and defects using a single-pixel diffractive terahertz sensor
Authors: Li Jingxi , Li Xurong , Yardimci Nezih T. , Hu Jingtian , Li Yuhang , Chen Junjie , Hung Yi-Chun , Jarrahi Mona , Ozcan Aydogan
Published: October 2023

Terahertz waves offer advantages for nondestructive detection of hidden objects/defects in materials, as they can penetrate most optically-opaque materials. However, existing terahertz inspection systems face throughput and accuracy restrictions due to their limited imaging speed and resolution. Furthermore, machine-vision-based systems using large-pixel-count imaging encounter bottlenecks due to their data storage, transmission and processing requirements. Here, we report a diffractive sensor that rapidly detects hidden defects/objects within a 3D sample using a single-pixel terahertz detector, eliminating sample scanning or image formation/processing. Leveraging deep-learning-optimized diffractive layers, this diffractive sensor can all-optically probe the 3D structural information of samples by outputting a spectrum, directly indicating the presence/absence of hidden structures or defects. We experimentally validated this framework using a single-pixel terahertz time-domain spectroscopy set-up and 3D-printed diffractive layers, successfully detecting unknown hidden defects inside silicon samples. This technique is valuable for applications including security screening, biomedical sensing and industrial quality control.
Chromatin accessibility landscape of relapsed pediatric B-lineage acute lymphoblastic leukemia
Authors: Wang Han , Sun Huiying , Liang Bilin , Zhang Fang , Yang Fan , Cui Bowen , Ding Lixia , Wang Xiang , Wang Ronghua , Cai Jiaoyang , Tang Yanjing , Rao Jianan , Hu Wenting , Zhao Shuang , Wu Wenyan , Chen Xiaoxiao , Wu Kefei , Lai Junchen , Xie Yangyang , Li Benshang , Tang Jingyan , Shen Shuhong , Liu Yu
Published: October 2023

For around half of the pediatric B-lineage acute lymphoblastic leukemia (B-ALL) patients, the molecular mechanism of relapse remains unclear. To fill this gap in knowledge, here we characterize the chromatin accessibility landscape in pediatric relapsed B-ALL. We observe rewired accessible chromatin regions (ACRs) associated with transcription dysregulation in leukemia cells as compared with normal B-cell progenitors. We show that over a quarter of the ACRs in B-ALL are in quiescent regions with high heterogeneity among B-ALLs. We identify subtype-specific and allele-imbalanced chromatin accessibility by integrating multi-omics data. By characterizing the differential ACRs between diagnosis and relapse in B-ALL, we identify alterations in chromatin accessibility during drug treatment. Further analysis of ACRs associated with relapse free survival leads to the identification of a subgroup of B-ALL which show early relapse. These data provide an advanced and integrative portrait of the importance of chromatin accessibility alterations in tumorigenesis and drug responses.
Systematic review and integrated data analysis reveal diverse pangolin-associated microbes with infection potential
Authors: Ye Run-Ze , Wang Xiao-Yang , Li Yu-Yu , Wang Bao-Yu , Song Ke , Wang Yi-Fei , Liu Jing , Wang Bai-Hui , Wang Shan-Shan , Xu Qing , Li Ze-Hui , Du Yi-Di , Liu Jin-Yue , Zheng Jia-Jing , Du Li-Feng , Shi Wenqiang , Jia Na , Jiang Jia-Fu , Cui Xiao-Ming , Zhao Lin , Cao Wu-Chun
Published: October 2023

There has been increasing global concern about the spillover transmission of pangolin-associated microbes. To assess the risk of these microbes for emergence as human pathogens, we integrated data from multiple sources to describe the distribution and spectrum of microbes harbored by pangolins. Wild and trafficked pangolins have been mainly recorded in Asia and Africa, while captive pangolins have been reported in European and North American countries. A total of 128 microbes, including 92 viruses, 25 bacteria, eight protists, and three uncharacterized microbes, have been identified in five pangolin species. Out of 128 pangolin-associated microbes, 31 (including 13 viruses, 15 bacteria, and three protists) have been reported in humans, and 54 are animal-associated viruses. The phylogenetic analysis of human-associated viruses carried by pangolins reveals that they are genetically close to those naturally circulating among human populations in the world. Pangolins harbor diverse microbes, many of which have been previously reported in humans and animals. Abundant viruses initially detected in pangolins might exhibit risks for spillover transmission.
Imperceptive and reusable dermal surface EMG for lower extremity neuro-prosthetic control and clinical assessment
Authors: Park Jaeu , Jeong Jinwoong , Kang Minseok , Pritish Nagwade , Cho Youngjun , Ha Jeongdae , Yea Junwoo , Jang Kyung-In , Kim Hyojin , Hwang Jumin , Kim Byungchae , Min Sungjoon , Kim Hoijun , Kwon Soonchul , Pak ChangSik John , Suh HyunSuk Peter , Hong Joon Pio , Lee Sanghoon
Published: October 2023

Surface electromyography (sEMG) sensors play a critical role in diagnosing muscle conditions and enabling prosthetic device control, especially for lower extremity robotic legs. However, challenges arise when utilizing such sensors on residual limbs within a silicon liner worn by amputees, where dynamic pressure, narrow space, and perspiration can negatively affect sensor performance. Existing commercial sEMG sensors and newly developed sensors are unsuitable due to size and thickness, or susceptible to damage in this environment. In this paper, our sEMG sensors are tailored for amputees wearing sockets, prioritizing breathability, durability, and reliable recording performance. By employing porous PDMS and Silbione substrates, our design achieves exceptional permeability and adhesive properties. The serpentine electrode pattern and design are optimized to improve stretchability, durability, and effective contact area, resulting in a higher signal-to-noise ratio (SNR) than conventional electrodes. Notably, our proposed sensors wirelessly enable to control of a robotic leg for amputees, demonstrating its practical feasibility and expecting to drive forward neuro-prosthetic control in the clinical research field near future.
Structure and electromechanical coupling of a voltage-gated Na+/H+ exchanger
Authors: Yeo Hyunku , Mehta Ved , Gulati Ashutosh , Drew David
Published: October 2023

Voltage-sensing domains control the activation of voltage-gated ion channels, with a few exceptions1. One such exception is the sperm-specific Na+/H+ exchanger SLC9C1, which is the only known transporter to be regulated by voltage-sensing domains2–5. After hyperpolarization of sperm flagella, SLC9C1 becomes active, causing pH alkalinization and CatSper Ca2+ channel activation, which drives chemotaxis2,6. SLC9C1 activation is further regulated by cAMP2,7, which is produced by soluble adenyl cyclase (sAC). SLC9C1 is therefore an essential component of the pH–sAC–cAMP signalling pathway in metazoa8,9, required for sperm motility and fertilization4. Despite its importance, the molecular basis of SLC9C1 voltage activation is unclear. Here we report cryo-electron microscopy (cryo-EM) structures of sea urchin SLC9C1 in detergent and nanodiscs. We show that the voltage-sensing domains are positioned in an unusual configuration, sandwiching each side of the SLC9C1 homodimer. The S4 segment is very long, 90 Å in length, and connects the voltage-sensing domains to the cytoplasmic cyclic-nucleotide-binding domains. The S4 segment is in the up configuration—the inactive state of SLC9C1. Consistently, although a negatively charged cavity is accessible for Na+ to bind to the ion-transporting domains of SLC9C1, an intracellular helix connected to S4 restricts their movement. On the basis of the differences in the cryo-EM structure of SLC9C1 in the presence of cAMP, we propose that, upon hyperpolarization, the S4 segment moves down, removing this constriction and enabling Na+/H+ exchange.
Dopaminergic systems create reward seeking despite adverse consequences
Authors: Jovanoski Kristijan D. , Duquenoy Lucille , Mitchell Jessica , Kapoor Ishaan , Treiber Christoph D. , Croset Vincent , Dempsey Georgia , Parepalli Sai , Cognigni Paola , Otto Nils , Felsenberg Johannes , Waddell Scott
Published: October 2023

Resource-seeking behaviours are ordinarily constrained by physiological needs and threats of danger, and the loss of these controls is associated with pathological reward seeking1. Although dysfunction of the dopaminergic valuation system of the brain is known to contribute towards unconstrained reward seeking2,3, the underlying reasons for this behaviour are unclear. Here we describe dopaminergic neural mechanisms that produce reward seeking despite adverse consequences in Drosophila melanogaster. Odours paired with optogenetic activation of a defined subset of reward-encoding dopaminergic neurons become cues that starved flies seek while neglecting food and enduring electric shock punishment. Unconstrained seeking of reward is not observed after learning with sugar or synthetic engagement of other dopaminergic neuron populations. Antagonism between reward-encoding and punishment-encoding dopaminergic neurons accounts for the perseverance of reward seeking despite punishment, whereas synthetic engagement of the reward-encoding dopaminergic neurons also impairs the ordinary need-dependent dopaminergic valuation of available food. Connectome analyses reveal that the population of reward-encoding dopaminergic neurons receives highly heterogeneous input, consistent with parallel representation of diverse rewards, and recordings demonstrate state-specific gating and satiety-related signals. We propose that a similar dopaminergic valuation system dysfunction is likely to contribute to maladaptive seeking of rewards by mammals.
Multi-omics characteristics of tumor-associated macrophages in the tumor microenvironment of gastric cancer and their exploration of immunotherapy potential
Authors: Cao Feng , Liu Yanwei , Cheng Yunsheng , Wang Yong , He Yan , Xu Yanyan
Published: October 2023

The incidence and mortality rate of gastric cancer (GC) have remained high worldwide. Although some progress has been made in immunotargeted therapy, the treatment effect remains limited. With more attention has been paid to the immune potential of tumor-associated macrophages (TAMs), but the specific mechanisms of tumor immunity are still unclear. Thus, we screened marker genes in TAMs differentiation (MDMs) through single-cell RNA sequencing, and combined with GC transcriptome data from TCGA and GEO databases, the clinical and TME characteristics, prognostic differences, immune infiltration, and drug sensitivity among different subtypes of patients with GC in different data sets were analyzed. A prognostic model of GC was constructed to evaluate the prognosis and immunotherapy response of patients with GC. In this study, we extensively studied the mutations in MDMs such as CGN, S100A6, and C1QA, and found differences in the infiltration of immune cells and immune checkpoints including M2 TAMs, T cells, CD274, and CTLA4 in different GC subtypes. In the model, we constructed a predictive scoring system with high accuracy and screened out key MDMs-related genes associated with prognosis and M2 TAMs, among which VKORC1 may be involved in GC progression and iron death in tumor cells. Therefore, this study explores the therapeutic strategy of TAMs reprogramming in-depth, providing new ideas for the clinical diagnosis, treatment, and prognosis assessment of GC.
Touch, press and stroke: a soft capacitive sensor skin
Authors: Sarwar Mirza S. , Ishizaki Ryusuke , Morton Kieran , Preston Claire , Nguyen Tan , Fan Xu , Dupont Bertille , Hogarth Leanna , Yoshiike Takahide , Qiu Ruixin , Wu Yiting , Mirabbasi Shahriar , Madden John D. W.
Published: October 2023

Soft sensors that can discriminate shear and normal force could help provide machines the fine control desirable for safe and effective physical interactions with people. A capacitive sensor is made for this purpose, composed of patterned elastomer and containing both fixed and sliding pillars that allow the sensor to deform and buckle, much like skin itself. The sensor differentiates between simultaneously applied normal force and shear using summation and differences of signals from four deformable capacitors. Cross talk from shear to normal force is less than 2.5%, and between shear axes is less than 10%. Normal and shear stress sensitivity is 0.49 kPa and 0.31 kPa respectively, with a minimum displacement resolution of 40 μm. In addition, finger proximity is detectable at a range of up to 15 mm. The operation is demonstrated on a simple gripper holding a cup. The combination of features and the straightforward fabrication method make this sensor a candidate for implementation as a sensing skin for humanoid robotics applications.
The relationships between the plasma metabolome and orthostatic blood pressure responses
Authors: Zambach Christian , Pan Jingxue , Gerward Sofia , Fedorowski Artur , Smith J. Gustav , Engström Gunnar , Hamrefors Viktor
Published: October 2023

Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association between orthostatic blood pressure responses and 818 plasma metabolites in middle-aged subjects from the general population. We included 3803 out of 6251 subjects (mean age, 57 years; 52% women) from the Malmö sub-cohort of The Swedish CardioPulmonary bioImage Study with information on smoking habits, diabetes, antihypertensive drug treatment, anthropometrics, hemodynamic measurements and 818 plasma metabolites (mass-spectrometry). The associations between each metabolite and orthostatic systolic blood pressure responses were determined using multivariable linear regression analysis and p values were corrected using the Bonferroni method. Six amino acids, five vitamins, co-factors and carbohydrates, nine lipids and two xenobiotics were associated with orthostatic blood pressure after adjusting for age, gender and systolic blood pressure. After additional adjustments for BMI, diabetes, smoking and antihypertensive treatment, the association remained significant for six lipids, four amino acids and one xenobiotic. Twenty-two out of 818 plasma metabolites were associated with orthostatic blood pressure responses. Eleven metabolites, including lipids in the dihydrosphingomyelin and sphingosine pathways, were independently associated with orthostatic systolic blood pressure responses after additional adjustment for markers of cardio-metabolic disease.
Edoxaban in patients with non-valvular atrial fibrillation after percutaneous coronary intervention: ENCOURAGE-AF design
Authors: Baldus Stephan , Beyer-Westendorf Jan , Möllmann Helge , Rottbauer Wolfgang , Beyerlein Elisabeth , Goette Andreas
Published: October 2023

Approximately one fifth of patients diagnosed with atrial fibrillation (AF) undergo a percutaneous coronary intervention (PCI). Current guidelines recommend different combinations and durations of triple or dual antithrombotic therapy for these patients but data on the implementation of these recommendations in clinical routine are scarce. ENCOURAGE-AF is a prospective, non-interventional, non-comparative, multicentre study. Approximately 720 patients will be consecutively enrolled from 70 participating sites across Germany. Patients with non-valvular AF treated with edoxaban, who have undergone successful PCI, have no planned elective cardiac intervention during the study period, have capability, availability, and willingness for follow-up by telephone interview during the study, are aged ≥ 18 years with life expectancy ≥ 1 year, and provide written informed consent, will be included. Eligible patients will be enrolled between 4- and 72-h after completing a successful PCI. Duration of exposure to and dosing regimens of edoxaban, antiplatelet agents and other concomitant medications of interest will be monitored in line with the clinical practice. Physician- and patient-reported clinical events, adverse drug reactions, patient quality of life (EQ-5D-5L) and health resource utilisation (HRU) parameters will be evaluated at 30 days and 1-year post-PCI. The ENCOURAGE-AF non-interventional study will provide insights into the patterns of edoxaban usage in combination with antiplatelet treatment and other concomitant medications in AF patients with a successful PCI over a 1-year time period during routine clinical practice in Germany. The effectiveness and safety of edoxaban in this patient population, as well as patients’ quality of life and HRU will be evaluated.

Trial registration: Clinicaltrial.gov NCT04519944, registered on 20 August 2020.
Factors associated with COVID-19 vaccination among pregnant women in Rio De Janeiro City, Brazil
Authors: Borges Moara Alves Santa Bárbara , Florentino Pilar Tavares Veras , Cerqueira-Silva Thiago , de Carvalho Luciana Freire , de Araújo Oliveira Vinícius , Aguilar Gislani Mateus Oliveira , Prado Rodrigo de Sousa , Soranz Daniel , Werneck Guilherme Loureiro , Pescarini Julia M. , da Costa Paulo Sérgio Sucasas , Barreto Mauricio Lima , de Oliveira Garcia Márcio Henrique , Penna Gerson Oliveira , Barral-Netto Manoel , Paixão Enny S.
Published: October 2023

COVID-19 vaccination during pregnancy is safe and effective in reducing the risk of complications. However, the uptake is still below targets worldwide. This study aimed to explore the factors associated with COVID-19 vaccination uptake among pregnant women since data on this topic is scarce in low-to-middle-income countries. A retrospective cohort study included linked data on COVID-19 vaccination and pregnant women who delivered a singleton live birth from August 1, 2021, to July 31, 2022, in Rio de Janeiro City, Brazil. Multiple logistic regression was performed to identify factors associated with vaccination during pregnancy, applying a hierarchical model and describing odds ratio with 95% confidence intervals. Of 65,304 pregnant women included in the study, 53.0% (95% CI, 52–53%) received at least one dose of COVID-19 vaccine during pregnancy. Higher uptake was observed among women aged older than 34 (aOR 1.21, 95%CI 1.15–1.28), black (aOR 1.10, 1.04–1.16), or parda/brown skin colour (aOR 1.05, 1.01–1.09), with less than eight years of education (aOR 1.09, 1.02–1.17), living without a partner (aOR 2.24, 2.16–2.34), more than six antenatal care appointments (aOR 1.92, 1.75–2.09), and having a previous child loss (OR 1.06, 1.02–1.11). These results highlight the need for targeted educational campaigns, trustful communication, and accessibility strategies for specific populations to improve vaccination uptake during pregnancy.
Artificial intelligence models for methylene blue removal using functionalized carbon nanotubes
Authors: Mijwel Abd-Alkhaliq Salih , Ahmed Ali Najah , Afan Haitham Abdulmohsin , Alayan Haiyam Mohammed , Sherif Mohsen , Elshafie Ahmed
Published: October 2023

This study aims to assess the practicality of utilizing artificial intelligence (AI) to replicate the adsorption capability of functionalized carbon nanotubes (CNTs) in the context of methylene blue (MB) removal. The process of generating the carbon nanotubes involved the pyrolysis of acetylene under conditions that were determined to be optimal. These conditions included a reaction temperature of 550 °C, a reaction time of 37.3 min, and a gas ratio (H2/C2H2) of 1.0. The experimental data pertaining to MB adsorption on CNTs was found to be extremely well-suited to the Pseudo-second-order model, as evidenced by an R2 value of 0.998, an X2 value of 5.75, a qe value of 163.93 (mg/g), and a K2 value of 6.34 × 10–4 (g/mg min).The MB adsorption system exhibited the best agreement with the Langmuir model, yielding an R2 of 0.989, RL value of 0.031, qm value of 250.0 mg/g. The results of AI modelling demonstrated a remarkable performance using a recurrent neural network, achieving with the highest correlation coefficient of R2 = 0.9471. Additionally, the feed-forward neural network yielded a correlation coefficient of R2 = 0.9658. The modeling results hold promise for accurately predicting the adsorption capacity of CNTs, which can potentially enhance their efficiency in removing methylene blue from wastewater.
A GIS-based land suitability model for agricultural tractors in CALABARZON Region, Philippines
Authors: Amongo Rossana Marie , Saludes Ronaldo , Gallegos Ralph Kristoffer , Relativo Patrick Lemuel , Duminding Ria Salustia , Pantano Adrian Daniel , Cunan Julius John Paul , Lalap-Borja Gherlee Nelle
Published: October 2023

Agricultural machinery distribution programs are key components of the Philippine government to strengthen its economic productivity. However, concerns were reported that some of the distributed machines were under-utilized or unutilized in their respective farms. This study is focused on the development of a GIS-based model of determining suitable lowland rice areas for two-wheel and four-wheel tractors. A numerical rating system was designed that assigns a suitability score from three criteria, namely slope, road network proximity, and flood risk, based on established scales. Analytical Hierarchy Process was used as an approach to determine the relative influence in which results show that slope has the greatest weight (65%) followed by flood risk and road network proximity with 20% and 15%, respectively. The total suitability score (TSS) is then determined by getting the weighted average of the individual suitability scores. Land suitability mapping on the study area, the CALABARZON region, show that majority of the lowland rice areas are highly suitable for two-wheel and four-wheel tractors (81.39%) while some areas fall under marginal (15.03%) and moderate suitability (3.58%). Geotagged locations of the distributed agricultural tractors from 2015 to 2020 reveal that 78% of the distributed two-wheel tractors and 80% of four-wheel tractors in the region are situated in highly suitable areas. The GIS-based suitability model generated in this study can be utilized by the government to improve its machine distribution programs of two-wheel and four-wheel tractors in lowland rice farms.
Neutron reflectometry under high shear in narrow gap for tribology study
Authors: Yamashita Naoki , Hirayama Tomoko , Hino Masahiro , Yamada Norifumi L.
Published: October 2023

An operando analysis method has been established for evaluating the interfacial structure of an adsorbed layer formed by an additive on a metal surface under fluid lubricated conditions. A parallel-face narrow gap viscometer installed in an energy-resolved neutron reflectometer is used to evaluate the change in the interfacial structure under high shear. The viscometer was designed to operate at a high shear rate while maintaining a µm-order constant gap between two parallel surfaces. When an additive-free base oil was sandwiched in the gap, the neutron reflectivity profiles without and with upper surface rotation were the same. This demonstrates that the reflectivity profiles can be accurately measured regardless of whether the upper surface is rotated. When a base oil containing a polymethacrylate-based additive was sandwiched in the gap, both the thickness and density of the adsorbed additive layer in the rotation (shear field) condition were lower than those in the non-rotation (static) condition. This demonstrates that the proposed method can be used to analyse the structural changes in the adsorbed layer formed by an oil additive on a surface. This combination of a neutron reflectometer and narrow gap viscometer is a promising approach to near-future tribological studies.
MED19 encodes two unique protein isoforms that confer prostate cancer growth under low androgen through distinct gene expression programs
Authors: Ruoff Rachel , Weber Hannah , Wang Ying , Huang Hongying , Shapiro Ellen , Fenyö David , Garabedian Michael J.
Published: October 2023

MED19, a component of the mediator complex and a co-regulator of the androgen receptor (AR), is pivotal in prostate cancer cell proliferation. MED19 has two isoforms: a full-length “canonical” and a shorter “alternative” variant. Specific antibodies were developed to investigate these isoforms. Both exhibit similar expression in normal prostate development and adult prostate tissue, but the canonical isoform is elevated in prostate adenocarcinomas. Overexpression of canonical MED19 in LNCaP cells promotes growth under conditions of androgen deprivation in vitro and in vivo, mirroring earlier findings with alternative MED19-overexpressing LNCaP cells. Interestingly, alternative MED19 cells displayed strong colony formation in clonogenic assays under conditions of androgen deprivation, while canonical MED19 cells did not, suggesting distinct functional roles. These isoforms also modulated gene expression differently. Canonical MED19 triggered genes related to extracellular matrix remodeling while suppressing those involved in androgen-inactivating glucuronidation. In contrast, alternative MED19 elevated genes tied to cell movement and reduced those associated with cell adhesion and differentiation. The ratio of MED19 isoform expression in prostate cancers shifts with the disease stage. Early-stage cancers exhibit higher canonical MED19 expression than alternative MED19, consistent with canonical MED19’s ability to promote cell proliferation under androgen deprivation. Conversely, alternative MED19 levels were higher in later-stage metastatic prostate cancer than in canonical MED19, reflecting alternative MED19’s capability to enhance cell migration and autonomous cell growth. Our findings suggest that MED19 isoforms play unique roles in prostate cancer progression and highlights MED19 as a potential therapeutic target for both early and late-stage prostate cancer.
Electrical impedance myography for the early detection of muscle ischemia secondary to compartment syndrome: a study in a rat model
Authors: Lechtig Aron , Hanna Philip , Nagy Janice A. , Wixted John , Nazarian Ara , Rutkove Seward B.
Published: October 2023

Acute Compartment Syndrome (ACS) is one of the most devastating orthopedic conditions, affecting any of the body’s many compartments, which, if sufficiently severe, may result in disability and amputation. Currently, intra-compartmental pressure measurements serve as the gold standard for diagnosing ACS. Diagnosing limbs at risk for ACS before irreversible damage to muscle and nerve is critical. Standard approaches for diagnosing impending compartment syndrome include clinical evaluation of the limb, such as assessment for “tightness” of the overlying skin, reduced pulses distally, and degree of pain, none of which are specific or sensitive. We have proposed a novel method to detect ACS via electrical impedance myography (EIM), where a weak, high-frequency alternating current is passed between one pair of electrodes through a region of tissue, and the resulting surface voltages are measured via a second pair. We evaluated the ability of EIM to detect early muscle ischemia in an established murine model of compression-induced muscle injury, where we collected resistance, reactance, and their dimensionless product, defined as Relative Injury Index (RII) during the study. Our model generated reproducible hypoxia, confirmed by Hypoxyprobe™ staining of endothelial regions within the muscle. Under conditions of ischemia, we demonstrated a reproducible, stable, and significant escalation in resistance, reactance, and RII values, compared to uninjured control limbs. These data make a reasonable argument for additional investigations into using EIM for the early recognition of muscle hypoperfusion and ischemia. However, these findings must be considered preliminary steps, requiring further pre-clinical and clinical validation.
Deep proteome coverage advances knowledge of Treponema pallidum protein expression profiles during infection
Authors: Houston Simon , Gomez Alloysius , Geppert Andrew , Eshghi Azad , Smith Derek S. , Waugh Sean , Hardie Darryl B. , Goodlett David R. , Cameron Caroline E.
Published: October 2023

Comprehensive proteome-wide analysis of the syphilis spirochete, Treponema pallidum ssp. pallidum, is technically challenging due to high sample complexity, difficulties with obtaining sufficient quantities of bacteria for analysis, and the inherent fragility of the T. pallidum cell envelope which further complicates proteomic identification of rare T. pallidum outer membrane proteins (OMPs). The main aim of the present study was to gain a deeper understanding of the T. pallidum global proteome expression profile under infection conditions. This will corroborate and extend genome annotations, identify protein modifications that are unable to be predicted at the genomic or transcriptomic levels, and provide a foundational knowledge of the T. pallidum protein expression repertoire. Here we describe the optimization of a T. pallidum-specific sample preparation workflow and mass spectrometry-based proteomics pipeline which allowed for the detection of 77% of the T. pallidum protein repertoire under infection conditions. When combined with prior studies, this brings the overall coverage of the T. pallidum proteome to almost 90%. These investigations identified 27 known/predicted OMPs, including potential vaccine candidates, and detected expression of 11 potential OMPs under infection conditions for the first time. The optimized pipeline provides a robust and reproducible workflow for investigating T. pallidum protein expression during infection. Importantly, the combined results provide the deepest coverage of the T. pallidum proteome to date.
Heat transfer analysis of Maxwell tri-hybridized nanofluid through Riga wedge with fuzzy volume fraction
Authors: Zulqarnain Rana Muhammad , Nadeem Muhammad , Siddique Imran , Ahmad Hijaz , Askar Sameh , Samar Mahvish
Published: October 2023

This contribution aims to optimize nonlinear thermal flow for Darcy-Forchheimer Maxwell fuzzy $$\left( {{\text{Al}}_{{2}} {\text{O}}_{{3}} + {\text{Cu }} + {\text{TiO}}_{{2}} {\text{/EO}}} \right)$$

Al
2

O
3

+

Cu

+

TiO
2

/EO

tri-hybrid nanofluid flow across a Riga wedge in the context of boundary slip. Three types of nanomaterials, $${\text{Al}}_{{2}} {\text{O}}_{{3}} ,$$

Al
2

O
3

,

Cu and $${\text{TiO}}_{2}$$

TiO
2

have been mixed into the basic fluid known as engine oil. Thermal properties with the effects of porous surface and nonlinear convection have been established for the particular combination $$\left( {{\text{Al}}_{{2}} {\text{O}}_{{3}} + {\text{Cu}} + {\text{TiO}}_{{2}} {\text{/EO}}} \right){.}$$

Al
2

O
3

+
Cu
+

TiO
2

/EO

.

Applying a set of appropriate variables, the set of equations that evaluated the energy and flow equations was transferred to the dimensionless form. For numerical computing, the MATLAB software's bvp4c function is used. The graphical display is used to demonstrate the influence of several influential parameters. It has been observed that flow rate decay with expansion in porosity parameter and nanoparticles volumetric fractions. In contrast, it rises with wedge angle, Grashof numbers, Darcy-Forchheimer, nonlinear Grashof numbers, and Maxwell fluid parameter. Thermal profiles increase with progress in the heat source, nanoparticles volumetric fractions, viscous dissipation, and nonlinear thermal radiation. The percentage increases in drag force for ternary hybrid nanofluid are 13.2 and 8.44 when the Modified Hartmann number takes input in the range $$0.1 \le {\text{Mh}} \le 0.3$$

0.1
≤
Mh
≤
0.3

and wedge angle parameters $$0.1 \le m \le 0.3$$

0.1
≤
m
≤
0.3

. For fuzzy analysis, dimensionless ODEs transformed into fuzzy differential equations and employed symmetrical triangular fuzzy numbers (TFNs). The TFN makes a triangular membership function (M.F.) that describes the fuzziness and comparison. This study compared nanofluids, hybrid nanofluids, and ternary nanofluids through triangular M.F. The boundary layer flow caused by a wedge surface plays a crucial role in heat exchanger systems and geothermal.
Skimmianine attenuates liver ischemia/reperfusion injury by regulating PI3K–AKT signaling pathway-mediated inflammation, apoptosis and oxidative stress
Authors: Huo Cheng-long , Wang Bing , Zhang Xuewen , Sun Zhen-Gang
Published: October 2023

Liver ischemia/reperfusion (I/R) injury is a common injury after liver transplantation and hepatectomy. Skimmianine (Ski) has antibacterial, antiviral pharmacological effects. However, it is not clear whether Ski has a protective effect against liver I/R injury. In the present study, we established a mouse liver I/R model and an AML12 cell hypoxia-reoxygenation (H/R) model, both pretreated with different concentrations of Ski. Serum transaminase levels, necrotic liver area, cell viability, inflammatory factors, oxidative stress and apoptosis-related levels were measured to assess the protective effect of Ski against liver I/R injury. Western blotting was used to detect apoptosis-related proteins and PI3K–AKT pathway-related proteins. Mice and cells were also treated with PI3K inhibitor LY294002 to assess changes in indicators of liver injury. The results showed that Ski significantly reduced transaminase levels, liver necrosis area, oxidative stress, and apoptosis levels in mice with I/R. Ski also inhibited cell injury and apoptosis after H/R. Moreover, Ski activated phosphorylation of PI3K–AKT pathway-related proteins after liver I/R and cell H/R. Importantly, the PI3K inhibitor LY294002 effectively reversed the alleviation of I/R injury caused by Ski. These results confirm that Ski exerts a protective effect against liver I/R injury through activation of the PI3K–AKT pathway.
Numerical modeling of subduction and evaluation of Philippine Sea Plate tectonic history along the Nankai Trough
Authors: Moreno E. J. , Manea V. C. , Manea M. , Yoshioka S. , Suenaga N. , Bayona A.
Published: October 2023

The subduction of the Philippine Sea (PHS) plate along the Nankai Trough in in southwest Japan is a relatively recent process compared with subduction along the Japan Trench in northeast Japan. However, the tectonic evolution of the PHS plate along the Nankai Trough is still controversial and not fully understood. There are several competing hypotheses based on different estimates for the time variations of convergence rate and plate age. Our study employs numerical modelling of subduction in order to evaluate the slab evolution for the last 15 Myr and aims to evaluate each tectonic scenario against the present-day slab geometry along a profile passing through the Shikoku and Chugoku regions. The modelling strategy involves a parameter study where subduction initiation and various subduction parameters are analyzed in terms of subduction geometry evolution. Two-dimensional visco-elasto-plastic numerical simulations of spontaneous bending subduction predict that convergence rate and plate age variations play an important role in the evolution of subduction geometry. Modeling results after 15 Myr of evolution reveal that the tectonic model based on a high convergence rate between ~ 15 Ma and ~ 3 Ma produces a slab geometry that agrees well with the observed present-day slab shape specific for the Shikoku and Chugoku regions.
Performance of administrative databases for identifying individuals with multiple sclerosis
Authors: Ducatel Pauline , Debouverie Marc , Soudant Marc , Guillemin Francis , Mathey Guillaume , Epstein Jonathan
Published: October 2023

Administrative databases are an alternative to disease registries as a research tool to study multiple sclerosis. However, they are not initially designed to fulfill research purposes. Therefore, an evaluation of their performance is necessary. Our objective was to assess the performance of the French administrative database comprising hospital discharge records and national health insurance databases in identifying individuals with multiple sclerosis, in comparison with a registry that exhaustively compiles resident multiple sclerosis cases in Lorraine, northeastern France, as reference. We recorded all individuals residing in the Lorraine region who were identified by the administrative database or the registry as having multiple sclerosis from 2011 to 2016. We calculated the Matthews correlation coefficient and other concordance indicators. For identifying individuals with multiple sclerosis, the Matthews correlation coefficient by the administrative database was 0.79 (95% CI 0.78–0.80), reflecting moderate performance. The mean time to identification was 5.5 years earlier with the registry than the administrative database. Administrative databases, although useful to study multiple sclerosis, should be used with caution because results of studies based on them may be biased. Our study highlights the value of regional registries that allow for a more exhaustive and rapid identification of cases.
Variable-moment fluid closures with Hamiltonian structure
Authors: Burby J. W.
Published: October 2023

Based on ideas due to Scovel–Weinstein, I present a general framework for constructing fluid moment closures of the Vlasov–Poisson system that exactly preserve that system’s Hamiltonian structure. Notably, the technique applies in any space dimension and produces closures involving arbitrarily-large finite collections of moments. After selecting a desired collection of moments, the Poisson bracket for the closure is uniquely determined. Therefore data-driven fluid closures can be constructed by adjusting the closure Hamiltonian for compatibility with kinetic simulations.
Digital twin models of replicative ground stones: insight into simulating usage of Upper Paleolithic tools
Authors: Marulli Maria Rosaria , Sorrentino Giusi , Menna Fabio , Paggi Marco
Published: October 2023

This work presents the first attempt to create a physics-based digital twin model for predictive analysis of damage evolution during the use of ground stone tools (GSTs) in transformative tasks, encompassing the processing of raw resources for nutritional and non-alimentary purposes. The proposed methodology introduces a digital twin of the GSTs developed from 3D models generated using a photogrammetric technique based on Structure-from-Motion and Multi-View Stereo reconstruction. These models serve as the foundation for the development of the finite element (FE)-based digital twin model of the GSTs that exploits a contact formulation and the phase-field approach to simulate tool damage during pounding and grinding tasks. Defining the initial relative positions of the stones, their mechanical behaviour, and controlling the movement of the active stone in a way as close as possible to the real one, the digital twin model has been devised to evaluate how the surface damage is affected by perturbations in the loading conditions. The simulated damage is compared with the surface traces observed from experiments. The developed digital twin model aims at demonstrating its potentials for the GSTs investigations, as a supporting tool for experiments and for simulated tests on the archaeological records.
Abdominal organ segmentation via deep diffeomorphic mesh deformations
Authors: Bongratz Fabian , Rickmann Anne-Marie , Wachinger Christian
Published: October 2023

Abdominal organ segmentation from CT and MRI is an essential prerequisite for surgical planning and computer-aided navigation systems. It is challenging due to the high variability in the shape, size, and position of abdominal organs. Three-dimensional numeric representations of abdominal shapes with point-wise correspondence to a template are further important for quantitative and statistical analyses thereof. Recently, template-based surface extraction methods have shown promising advances for direct mesh reconstruction from volumetric scans. However, the generalization of these deep learning-based approaches to different organs and datasets, a crucial property for deployment in clinical environments, has not yet been assessed. We close this gap and employ template-based mesh reconstruction methods for joint liver, kidney, pancreas, and spleen segmentation. Our experiments on manually annotated CT and MRI data reveal limited generalization capabilities of previous methods to organs of different geometry and weak performance on small datasets. We alleviate these issues with a novel deep diffeomorphic mesh-deformation architecture and an improved training scheme. The resulting method, UNetFlow, generalizes well to all four organs and can be easily fine-tuned on new data. Moreover, we propose a simple registration-based post-processing that aligns voxel and mesh outputs to boost segmentation accuracy.
Predicting diagnosis and survival of bone metastasis in breast cancer using machine learning
Authors: Zhong Xugang , Lin Yanze , Zhang Wei , Bi Qing
Published: October 2023

This study aimed at establishing more accurate predictive models based on novel machine learning algorithms, with the overarching goal of providing clinicians with effective decision-making assistance. We retrospectively analyzed the breast cancer patients recorded in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016. Multivariable logistic regression analyses were used to identify risk factors for bone metastases in breast cancer, whereas Cox proportional hazards regression analyses were used to identify prognostic factors for breast cancer with bone metastasis (BCBM). Based on the identified risk and prognostic factors, we developed diagnostic and prognostic models that incorporate six machine learning classifiers. We then used the area under the receiver operating characteristic (ROC) curve (AUC), learning curve, precision curve, calibration plot, and decision curve analysis to evaluate performance of the machine learning models. Univariable and multivariable logistic regression analyses showed that bone metastases were significantly associated with age, race, sex, grade, T stage, N stage, surgery, radiotherapy, chemotherapy, tumor size, brain metastasis, liver metastasis, lung metastasis, breast subtype, and PR. Univariate and multivariate Cox regression analyses revealed that age, race, marital status, grade, surgery, radiotherapy, chemotherapy, brain metastasis, liver metastasis, lung metastasis, breast subtype, ER, and PR were closely associated with the prognosis of BCBM. Among the six machine learning models, the XGBoost algorithm predicted the most accurate results (Diagnostic model AUC = 0.98; Prognostic model AUC = 0.88). According to the Shapley additive explanations (SHAP), the most critical feature of the diagnostic model was surgery, followed by N stage. Interestingly, surgery was also the most critical feature of prognostic model, followed by liver metastasis. Based on the XGBoost algorithm, we could effectively predict the diagnosis and survival of bone metastasis in breast cancer and provide targeted references for the treatment of BCBM patients.
Comparative GC–MS based nutrients profiling of less explored legume seeds of Melilotus, Medicago, Trifolium, and Ononis analysed using chemometric tools
Authors: Fahmy Heba A. , El-Shamy Sherine , Farag Mohamed A.
Published: October 2023

Exploring novel sources of plant protein for nutrition of both humans and animals is motivated mainly by its growing demand worldwide, besides identifying healthy alternatives for animal protein. The present study evaluates metabolome diversity within 15 legume seed species. The examined samples comprised threeMelilotus, fourMedicago, fourTrifolium, and fourOnonisseed species. A holistic approach for metabolites profiling using gas chromatography-mass spectrometry (GC–MS) led to the annotation and quantification of 87 metabolites comprising alcohols, free amino acids, aromatics, fatty acids/esters, nitrogenous compounds, organic acids, sugar alcohols, sugars, terpenes, and steroids. Fatty acids represented the major metabolite class represented by palmitic, stearic, oleic, linoleic, and linolenic acids. Sucrose and pinitol were the major sugars and sugar alcohols among seeds.Ononisseeds (OR, OS and OA) were the most abundant in fatty acids, sugars, sugar alcohols, and free amino acids, whereasMelilotusspecies (MO and MS) were least enriched in these key nutrients posingOnonisas potential food source for humans and animals. The examined seeds were generally low in sulfur-containing free amino acids and lacking many of the essential free amino acids. Multivariate data analysis aided in the identification ofOnonismetabolite markers belonging to various classesi.e., (alcohol) glycerol, (sugar) allofuranose, and (sugar alcohol) pinitol, although the differentiation betweenMedicago,Melilotus, andTrifoliumgenera was not attained suggestive for other analytical platforms for its classification.