bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and electromechanical coupling of a voltage-gated Na+/H+ exchanger
Authors: Yeo Hyunku , Mehta Ved , Gulati Ashutosh , Drew David 
Published: October 2023

AbstractVoltage-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

AbstractResource-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

AbstractThe 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

AbstractSoft 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

AbstractWhereas 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

AbstractApproximately 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

AbstractCOVID-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

AbstractThis 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

AbstractAgricultural 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

AbstractAn 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

AbstractMED19, 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

AbstractAcute 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

AbstractComprehensive 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.