bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of structural, biochemical, pharmacokinetic, and pharmacodynamic properties of the LSD1 inhibitor bomedemstat in preclinical models
Authors: Jasmine Sumer , Mandl Adel , Krueger Timothy E. G. , Dalrymple Susan L. , Antony Lizamma , Dias Jennifer , Celatka Cassandra A. , Tapper Amy E. , Kleppe Maria , Kanayama Mayuko , Jing Yuezhou , Speranzini Valentina , Wang Yuzhuo Z. , Luo Jun , Trock Bruce J. , Denmeade Samuel R. , Carducci Michael A. , Mattevi Andrea , Rienhoff Hugh Y. , Isaacs John T. , Brennen W. Nathaniel 
Published: April 2024

AbstractIntroductionLysine‐specific demethylase 1 (LSD1) is emerging as a critical mediator of tumor progression in metastatic castration‐resistant prostate cancer (mCRPC). Neuroendocrine prostate cancer (NEPC) is increasingly recognized as an adaptive mechanism of resistance in mCRPC patients failing androgen receptor axis‐targeted therapies. Safe and effective LSD1 inhibitors are necessary to determine antitumor response in prostate cancer models. For this reason, we characterize the LSD1 inhibitor bomedemstat to assess its clinical potential in NEPC as well as other mCRPC pathological subtypes.MethodsBomedemstat was characterized via crystallization, flavine adenine dinucleotide spectrophotometry, and enzyme kinetics. On‐target effects were assessed in relevant prostate cancer cell models by measuring proliferation and H3K4 methylation using western blot analysis. In vivo, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of bomedemstat are also described.ResultsStructural, biochemical, and PK/PD properties of bomedemstat, an irreversible, orally‐bioavailable inhibitor of LSD1 are reported. Our data demonstrate bomedemstat has >2500‐fold greater specificity for LSD1 over monoamine oxidase (MAO)‐A and ‐B. Bomedemstat also demonstrates activity against several models of advanced CRPC, including NEPC patient‐derived xenografts. Significant intra‐tumoral accumulation of orally‐administered bomedemstat is measured with micromolar levels achieved in vivo (1.2 ± 0.45 µM at the 7.5 mg/kg dose and 3.76 ± 0.43 µM at the 15 mg/kg dose). Daily oral dosing of bomedemstat at 40 mg/kg/day is well‐tolerated, with on‐target thrombocytopenia observed that is rapidly reversible following treatment cessation.ConclusionsBomedemstat provides enhanced specificity against LSD1, as revealed by structural and biochemical data. PK/PD data display an overall safety profile with manageable side effects resulting from LSD1 inhibition using bomedemstat in preclinical models. Altogether, our results support clinical testing of bomedemstat in the setting of mCRPC.
Neuroprotective and anti‐inflammatory effects of curcumin in Alzheimer's disease: Targeting neuroinflammation strategies
Authors: Azzini Elena , Peña‐Corona Sheila I. , Hernández‐Parra Héctor , Chandran Deepak , Saleena Lejaniya Abdul Kalam , Sawikr Yousef , Peluso Ilaria , Dhumal Sangram , Kumar Manoj , Leyva‐Gómez Gerardo , Martorell Miquel , Sharifi‐Rad Javad , Calina Daniela 
Published: April 2024

AbstractAlzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid‐beta plaques and neurofibrillary tangles, leading to neuronal loss. Curcumin, a polyphenolic compound derived from Curcuma longa, has shown potential neuroprotective effects due to its anti‐inflammatory and antioxidant properties. This review aims to synthesize current preclinical data on the anti‐neuroinflammatory mechanisms of curcumin in the context of AD, addressing its pharmacokinetics, bioavailability, and potential as a therapeutic adjunct. An exhaustive literature search was conducted, focusing on recent studies within the last 10 years related to curcumin's impact on neuroinflammation and its neuroprotective role in AD. The review methodology included sourcing articles from specialized databases using specific medical subject headings terms to ensure precision and relevance. Curcumin demonstrates significant neuroprotective properties by modulating neuroinflammatory pathways, scavenging reactive oxygen species, and inhibiting the production of pro‐inflammatory cytokines. Despite its potential, challenges remain regarding its limited bioavailability and the scarcity of comprehensive human clinical trials. Curcumin emerges as a promising therapeutic adjunct in AD due to its multimodal neuroprotective benefits. However, further research is required to overcome challenges related to bioavailability and to establish effective dosing regimens in human subjects. Developing novel delivery systems and formulations may enhance curcumin's therapeutic potential in AD treatment.
Elucidation of the Transport Properties of Calcium‐Doped High Entropy Rare Earth Aluminates for Solid Oxide Fuel Cell Applications
Authors: Kante Mohana V. , Nilayam Ajai R. Lakshmi , Hahn Horst , Bhattacharya Subramshu S. , Elm Matthias T. , Velasco Leonardo , Botros Miriam 
Published: April 2024

AbstractSolid oxide fuel cells (SOFCs) are paving the way to clean energy conversion, relying on efficient oxygen‐ion conductors with high ionic conductivity coupled with a negligible electronic contribution. Doped rare earth aluminates are promising candidates for SOFC electrolytes due to their high ionic conductivity. However, they often suffer from p‐type electronic conductivity at operating temperatures above 500 °C under oxidizing conditions caused by the incorporation of oxygen into the lattice. High entropy materials are a new class of materials conceptualized to be stable at higher temperatures due to their high configurational entropy. Introducing this concept to rare earth aluminates can be a promising approach to stabilize the lattice by shifting the stoichiometric point of the oxides to higher oxygen activities, and thereby, reducing the p‐type electronic conductivity in the relevant oxygen partial pressure range. In this study, the high entropy oxide (Gd,La,Nd,Pr,Sm)AlO3 is synthesized and doped with Ca. The Ca‐doped (Gd,La,Nd,Pr,Sm)AlO3 compounds exhibit a higher ionic conductivity than most of the corresponding Ca‐doped rare earth aluminates accompanied by a reduction of the p‐type electronic conductivity contribution typically observed under oxidizing conditions. In light of these findings, this study introduces high entropy aluminates as a promising candidate for SOFC electrolytes.
Engineering research‐practice partnerships for social justice
Authors: Tseng Vivian 
Published: April 2024

AbstractOur current systems for producing and using research are mired—as are all U.S. institutions—in a long history of racism, xenophobia, and a culture of paternalism. Fortunately, we are not beholden to maintaining those systems, and we can re‐imagine and re‐engineer the ways we approach research and what we seek to accomplish with it. Research–practice partnerships (RPPs) can play a unique and meaningful role in bringing research to bear on social justice for children and families, but the partnerships must be intentionally designed for those goals. In this essay, I discuss three design principles for RPPs: centering children marginalized by oppression, embracing historical perspectives, and contending with power asymmetries.
Phylogeny and re‐circumscription of Cheniella (Leguminosae: Cercidoideae) based on plastome data and morphology, with description of three new species
Authors: Gu Shi‐Ran , Zeng Qiu‐Biao , Clark Ruth , Jiang Kai‐Wen , Pérez‐Escobar Oscar Alejandro , Li Shi‐Jin , Tan Wei‐Ning , Xie Zhi , Mattapha Sawai , Shi Miao‐Miao , Wang Xiang‐Ping , Zhao Zhong‐Tao , Antonelli Alexandre , Tu Tie‐Yao , Wen Jun , Zhang Dian‐Xiang 
Published: April 2024

AbstractSubfamily Cercidoideae is an early‐diverging lineage of Leguminosae, within which the number and classification of genera have been controversial. Cheniella is a recently described genus in the Cercidoideae which requires revision and testing of its monophyly and circumscription. Here we infer the phylogenetic position and infrageneric relationships of Cheniella as well as the intergeneric relationships of Cercidoideae using 48 newly sequenced plastid genomes, including 34 individuals representing all species of Cheniella. Our phylogenetic analyses yield a well‐resolved tree of Cercidoideae with robust support at most nodes. We also present morphological studies through field work and herbarium studies to re‐assess the classification and circumscription of the genus. Based on the results of molecular analyses and morphological studies combined with distribution data, we broaden the circumscription of Cheniella to comprise a total of 15 species and 3 subspecies, including three new species (C. hechiensis, C. longistaminea, C. pubicarpa), one new combination (C. tianlinensis) and one new status and combination (C. longipes).
Voltammetry determination of Cd(II) and Pb(II) at TiO2/reduced graphene oxide modified electrodes
Authors: Luyen Nguyen Dinh , Toan Tran Thanh Tam , Thanh Nguyen Mau 
Published: April 2024

AbstractIn this article, a TiO2/reduced graphene oxide (rGO) composite was synthesized from rGO and soluble titanium hydroxide‐peroxide complexes. The obtained materials were characterized by X‐ray diffraction, scanning electron microscopy, nitrogen adsorption/desorption, Raman spectroscopy and energy dispersive X‐ray spectroscopy‐elementary mapping. The TiO2/rGO composite was used as an electrode modifier for developing an electrochemical sensor to simultaneous analysis of Cd(II) and Pb(II) by using differential pulse anodic stripping voltammetry (DP‐ASV). Under optimal conditions, the linear correlation between the stripping peak current and the metal ion concentration is good in the range of 5–100 ppb for both metals (R2 ≥ 0.998), and a low detection limit (3.17 ppb for Cd(II) and 2.42 ppb for Pb(II)) was obtained. The interference study revealed that some metal cations had little influence on the DP‐ASV signals of Cd(II) and Pb(II). In addition, the developed electrode exhibited satisfied reproducibility and repeatability. The TiO2/rGO‐modified electrode was tested toward the detection of Cd(II) and Pb(II) in river waters and the obtained exceptional recoveries and results were further associated with AAS results. This study indicates that the TiO2/rGO composite might be an alternative for practical applications in the electrochemical determination of heavy metal ions in aquatic solutions.
Binary color adsorption by zinc@magnetite nanocomposites: Robust parametric optimization using Taguchi method
Authors: Yadav Sangita , Chander Subhash , Luhach Neha , Kumari Sweta , Kashyap Ankur , Gupta Asha 
Published: April 2024

AbstractThe goal of the current study was to determine the optimal level (value) of adsorption process variables for the adsorption of color from binary aqueous solution. The impact of key adsorption factors, including adsorbent dose, initial color concentration, and contact time, on the color removal effectiveness of Zinc@magnetite nanocomposites (Zin@Fe3O4(ME) produced from bacterial extracts and Zin@Fe3O4(M) produced from bacterial cell mass), has been examined. Utilizing an L9 orthogonal array (OA), average values and the SN ratio for each variable at three diverse points are calculated. ANOVA has determined the most advantageous optimum conditions for raw and SN data. According to the study, the adsorbent dose is shown to be the most important parameter for color adsorption, while contact duration is determined to be the least important factor based on Pareto chart analysis. The percentage of color removal at optimal values for Zin@Fe3O4(M) and Zin@Fe3O4(ME) nanocomposites, respectively, was found to be 81% and 73%. The optimal parameters were found to be 12.5 mg of adsorbent, 125 mg/L initial dye concentration, and 90 min of contact time at pH 7, room temperature. The confirmatory experiments conducted under optimized conditions revealed a higher percentage of color eliminated than was optimized in each test run of the Taguchi design, proving the credibility of the process variables optimized within the designated experiments.
Sinus arrest during thoracic drain placement in a dog
Authors: Mulligan Annie , Nicholls Daniel 
Published: April 2024

AbstractA 5‐year‐old female neutered Podenco Canario dog presented with a moderate pleural effusion and subsequently underwent placement of bilateral thoracic drains. Pre‐medication consisted of intravenous medetomidine (2 µg/kg) and methadone (0.2 mg/kg), followed by induction with propofol (2.1 mg/kg, via intravenous administration). Anaesthesia was maintained with isoflurane in 100% oxygen. The modified Seldinger technique was used to place bilateral small‐bore, wire‐guided thoracic drains. During placement of the first chest drain, the dog developed sinus arrest. It is suspected that there was direct vagal nerve stimulation by the guide wire during placement, leading to severe bradycardia and subsequent sinus arrest that was responsive to atropine. It is important to note that the definitive cause of the transient cardiac arrest could not be ascertained. It is possible that this is a rare complication of thoracic drain placement, warranting further research in this area.
Faith, politics, and power: The evolution of secularism and authoritarianism in Bangladesh
Authors: Mostofa Shafi Md 
Published: April 2024

AbstractThis third article in the 2024 World Affairs special issue examines the intricate interplay between secularism, religious sentiment, and authoritarian politics in postindependence Bangladesh. Despite being founded on secular principles in 1971, the notion of Bangladesh as a strictly secular state is challenged. This article contends that while secularism was enshrined as a foundational state principle, its imposition occurred top‐down, diverging from prevailing societal ethos. The immediacy of the public backlash following its inclusion compelled ruling elites to adopt religion‐sensitive policies. I assert that the widespread religiosity among the populace steered subsequent political decisions. Notably, the shift from secularism to state‐sponsored Islam, the elevation of Islamic figures to cabinet roles, the recognition of Qawmi madrassa credentials, and the proliferation of Islamic rhetoric ensued. Analyzing a blend of archival data and field interviews, the article argues that the current authoritarian regime, emerging from an unconsolidated democratic framework, strategically exploits Islam as a political tool for legitimacy. By tapping into the prevailing Islamic sentiment, the regime aims to solidify its hold on power and navigate the complex political landscape of contemporary Bangladesh.
Curves that allow the motion of a regular polygon
Authors: Rochera David 
Published: April 2024

AbstractThis paper characterizes curves where a regular polygon of either a variable side length or a constant side length is allowed to rotate during k full revolutions while having its vertices on the curve during the motion. A constructive method to generate these curves is given based on the curve described by the polygon centers (centroids) during the motion and some examples are shown. Moreover, if the regular polygon divides the curve perimeter into parts of equal length, it is proved that the curve is either a rotational symmetric curve in the case of a variable side length or a circle otherwise. Finally, in the case of a regular polygon of constant side length rotating along a curve, a simple relation between the algebraic areas of such a curve and the curve of polygon centers is revisited.
The use of a low-cost, small-aperture array as an auxiliary tool to improve infrasound monitoring in the Azores region
Authors: do Céu Jesus Maria , Belli Giacomo , Gheri Duccio , Matos Sandro , Wallenstein Nicolau , Marchetti Emanuele 
Published: April 2024

AbstractThe 2022’s seismo-volcanic crisis on São Jorge Island of the Azores archipelago has provided an opportunity to deploy a portable infrasound array as a collaborative work between the Research Institute for Volcanology and Risk Assessment (IVAR) of the University of the Azores (UAc) and the University of Florence (UniFI). The four-element array, SJ1, became operational on 2 April 2022. Despite being deployed in a first stage to monitor the activities related to the volcanic unrest on São Jorge Island, SJ1 worked as a supporting tool to the existing IMS infrasound station IS42, located on Graciosa Island at ~ 40 km distance, leading to an enhancement of the infrasonic monitoring network in the region. This work emphasises the importance of low-cost portable infrasound arrays to improve the coverage of infrasound observations for local and regional monitoring purposes in the Azores region. Two events recorded by both arrays are briefly exemplified: a low-magnitude earthquake on São Jorge Island and a fireball which crossed the North Atlantic Ocean. Infrasound data from both arrays are combined to obtain a fast but still accurate source localization of the analysed events.
Impact of process parameters on the dynamic behavior of Inconel 718 fabricated via laser powder bed fusion
Authors: Abruzzo Michele , Macoretta Giuseppe , Monelli Bernardo Disma , Romoli Luca 
Published: April 2024

AbstractIn this research, we investigate the dynamic behavior of Inconel 718 fabricated through laser powder bed fusion (L-PBF), addressing a notable knowledge gap regarding the correlation between process parameters and dynamic properties. The process parameters adopted are deducted from an extension of the Rosenthal solution, formulated to increase the process productivity while avoiding the typical production process defects. The dynamic Young modulus and the structural damping of the material are estimated as a function of the process parameters through ping tests reproducing the flexural vibrations of the specimens in as-built, solutioned, and aged conditions. The microstructure and porosity are investigated through metallographic analyses. The results show a substantial influence of the L-PBF process parameters on the dynamic Young modulus, which markedly increases as the energy density is reduced (23%) and progressively becomes more similar to the conventionally produced material. This influence stands in stark contrast to the relatively modest impact of heat treatments, which underlines a negligible effect of the process-induced residual stress. The structural damping remained approximately constant across all test conditions. The elastic response of the material is found to be primarily influenced by the different microstructures produced as the L-PBF process parameters varied, particularly in terms of the dimensions and shape of the solidification structures. The unexpected relationship between the dynamic Young modulus, energy density, and microstructure unveils the potential to fine-tune the material’s dynamic behavior by manipulating the process parameters, thereby carrying substantial implications for all the applications of additively manufactured components susceptible to significant vibratory phenomena.
Incorporating IL7 receptor alpha signaling in the endodomain of B7H3-targeting chimeric antigen receptor T cells mediates antitumor activity in glioblastoma
Authors: Sakunrangsit Nithidol , Khuisangeam Nattarika , Inthanachai Thananya , Yodsurang Varalee , Taechawattananant Pasrawin , Suppipat Koramit , Tawinwung Supannikar 
Published: April 2024

AbstractCAR-T-cell therapy has shown promise in treating hematological malignancies but faces challenges in treating solid tumors due to impaired T-cell function in the tumor microenvironment. To provide optimal T-cell activation, we developed a B7 homolog 3 protein (B7H3)-targeting CAR construct consisting of three activation signals: CD3ζ (signal 1), 41BB (signal 2), and the interleukin 7 receptor alpha (IL7Rα) cytoplasmic domain (signal 3). We generated B7H3 CAR-T cells with different lengths of the IL7Rα cytoplasmic domain, including the full length (IL7R-L), intermediate length (IL7R-M), and short length (IL7R-S) domains, and evaluated their functionality in vitro and in vivo. All the B7H3-IL7Rα CAR-T cells exhibited a less differentiated phenotype and effectively eliminated B7H3-positive glioblastoma in vitro. Superiority was found in B7H3 CAR-T cells contained the short length of the IL7Rα cytoplasmic domain. Integration of the IL7R-S cytoplasmic domain maintained pSTAT5 activation and increased T-cell proliferation while reducing activation-induced cell death. Moreover, RNA-sequencing analysis of B7H3-IL7R-S CAR-T cells after coculture with a glioblastoma cell line revealed downregulation of proapoptotic genes and upregulation of genes associated with T-cell proliferation compared with those in 2nd generation B7H3 CAR-T cells. In animal models, compared with conventional CAR-T cells, B7H3-IL7R-S CAR-T cells suppressed tumor growth and prolonged overall survival. Our study demonstrated the therapeutic potential of IL7Rα-incorporating CAR-T cells for glioblastoma treatment, suggesting a promising strategy for augmenting the effectiveness of CAR-T cell therapy.
Frequency, characteristics and risk assessment of pulmonary arterial hypertension with a left heart disease phenotype
Authors: Toma Matteo , Savonitto Giulio , Lombardi Carlo Maria , Airò Edoardo , Driussi Mauro , Gentile Piero , Howard Luke , Moschella Martina , Di Poi Emma , Pagnesi Matteo , Monti Simonetta , Collini Valentino , D’Angelo Luciana , Vecchiato Veronica , Giannoni Alberto , Adamo Marianna , Barbisan Davide , Bauleo Carolina , Garascia Andrea , Metra Marco , Sinagra Gianfranco , Giudice Francesco Lo , Stolfo Davide , Ameri Pietro 
Published: April 2024

Abstract

Aim
To obtain real-world evidence about the features and risk stratification of pulmonary arterial hypertension (PAH) with a left heart disease (LHD) phenotype (PAH-LHD).

Methods and results
By reviewing the records of consecutive incident PAH patients at 7 tertiary centers from 2001 to 2021, we selected 286 subjects with all parameters needed to determine risk of death at baseline and at first follow-up with COMPERA and COMPERA 2.0 scores. Fifty seven (20%) had PAH-LHD according to the AMBITION definition. Compared with no-LHD ones, they were older, had higher BMI, more cardiovascular comorbidities, higher E/e’ ratio and left atrial area, but lower BNP concentrations and better right ventricular function and pulmonary hemodynamics. Survival was comparable between PAH-LHD and no-LHD patients, although the former were less commonly treated with dual PAH therapy. Both COMPERA and COMPERA 2.0 discriminated all-cause mortality risk of PAH-LHD at follow-up, but not at baseline. Risk profile significantly improved during follow-up only when assessed by COMPERA 2.0. At multivariable analysis with low-risk status as reference, intermediate-high and high-risk, but not LHD phenotype, were associated with higher hazard of all-cause mortality. Results were comparable in secondary analyses including patients in the last 10 years and atrial fibrillation and echocardiographic abnormalities as additional criteria for PAH-LHD.

Conclusions
In real life, PAH-LHD patients are frequent, have less severe disease and are less likely treated with PAH drug combinations than no-LHD. The COMPERA 2.0 model may be more appropriate to evaluate their mortality risk during follow-up and how it is modulated by therapy.