bluuebunny/crossref_metadata_2025_split huggingface dataset:
An extended analysis for a generalized Chaplygin gas model
Authors: Al Mamon Abdulla , Paliathanasis Andronikos , Saha Subhajit 
Published: March 2022

AbstractIn this work, we have extended the analysis on the generalized Chaplygin gas (GCG) model as the unification of dark energy and dark matter. Specifically, we have shown that the model of our consideration known as the new generalized Chaplygin gas (NGCG) model, admits a scalar field description, which means that there exist a minimally coupled scalar field for a given scalar field potential where the equation of state is that of the NGCG. With the use of the later property we can construct the slow-roll parameters and derive the corresponding values for the spectral indices for the tensor to scalar perturbation and for the density perturbations. We have also studied the growth rate of matter perturbations in the NGCG scenario. Finally, we have studied the viability of the generalized second law of thermodynamics by assuming that the dynamical apparent horizon in a NGCG universe is endowed with Hawking temperature and Bekenstein entropy.
Self-phoretic Brownian dynamics simulations
Authors: Roca-Bonet Sergi , Ripoll Marisol 
Published: March 2022

Abstract
A realistic and effective model to simulate phoretic Brownian dynamics swimmers based on the general form of the thermophoretic force is here presented. The collective behavior of self-phoretic dimers is investigated with this model and compared with two simpler versions, allowing the understanding of the subtle interplay of steric interactions, propulsion, and phoretic effects. The phoretic Brownian dynamics method has control parameters which can be tuned to closely map the properties of experiments or simulations with explicit solvent, in particular those performed with multiparticle collision dynamics. The combination of the phoretic Brownian method and multiparticle collision dynamics is a powerful tool to precisely identify the importance of hydrodynamic interactions in systems of self-phoretic swimmers.

Graphic Abstract
Gyrotactic cluster formation of bottom-heavy squirmers
Authors: Rühle Felix , Zantop Arne W. , Stark Holger 
Published: March 2022

AbstractSquirmers that are bottom-heavy experience a torque that aligns them along the vertical so that they swim upwards. In a suspension of many squirmers, they also interact hydrodynamically via flow fields that are initiated by their swimming motion and by gravity. Swimming under the combined action of flow field vorticity and gravitational torque is called gyrotaxis. Using the method of multi-particle collision dynamics, we perform hydrodynamic simulations of a many-squirmer system floating above the bottom surface. Due to gyrotaxis they exhibit pronounced cluster formation with increasing gravitational torque. The clusters are more volatile at low values but compactify to smaller clusters at larger torques. The mean distance between clusters is mainly controlled by the gravitational torque and not the global density. Furthermore, we observe that neutral squirmers form clusters more easily, whereas pullers require larger gravitational torques due to their additional force-dipole flow fields. We do not observe clustering for pusher squirmers. Adding a rotlet dipole to the squirmer flow field induces swirling clusters. At high gravitational strengths, the hydrodynamic interactions with the no-slip boundary create an additional vertical alignment for neutral squirmers, which also supports cluster formation.
Introducing the activity parameter for elementary cellular automata
Authors: Concha-Vega Pablo , Goles Eric , Montealegre Pedro , Ríos-Wilson Martín , Santivañez Julio 
Published: March 2022

Given an elementary cellular automaton (ECA) with local transition rule [Formula: see text], two different types of local transitions are identified: the ones in which a cell remains in its current state, called inactive transitions, and the ones in which the cell changes its current state, which are called active transitions. The number of active transitions of a rule is called its activity value. Based on latter identification, a rule [Formula: see text] is called a sub-rule of [Formula: see text] if the set of active transitions of [Formula: see text] is a subset of the active transitions of [Formula: see text]. In this paper, the notion of sub-rule for elementary cellular automata is introduced and explored: first, we consider a lattice that illustrates relations of nonequivalent elementary cellular automata according to nearby sub-rules. Then, we introduce statistical measures that allow us to compare rules and sub-rules. Finally, we explore the possible similarities in the dynamics of a rule with respect to its sub-rules, obtaining both empirical and theoretical results.
Comparative effects of tensioning and sliding neural mobilization on peripheral and autonomic nervous system function: A randomized controlled trial
Authors: Alharmoodi Budour Yousif , Arumugam Ashokan , Ahbouch Amal , Moustafa Ibrahim M. 
Published: March 2022

Background: Although different types of neural mobilization (NM) exercises induce different amounts of longitudinal nerve excursion and strain, the question whether the increased longitudinal stress and nerve excursion from sliding or tensioning intervention may subtly affect the neural functions has not been answered yet. Objective: To compare the effects of tensioning NM versus sliding NM of the median nerve on peripheral and autonomic nervous system function. Methods: In this randomized controlled trial, 90 participants were randomly assigned to tensioning NM, sliding NM, or sham NM. The neurophysiological outcome measures included peak-to-peak amplitude of the dermatomal somatosensory evoked potential (DSSEP) for dermatomes C6, C7, C8, and T1. Secondary outcome measures included amplitude and latency of skin sympathetic response. All outcome measures were assessed pretreatment, immediately after the two weeks of treatment and one week after the last session of the treatment. Results: A 2-way repeated measures ANOVA revealed significant differences between the three groups. The post hoc analysis indicated that tensioning NM significantly decreased the dermatomal amplitude for C6, C7, C8, and T1 ([Formula: see text]). Sympathetic skin responses in the gliding NM group showed lower amplitudes and prolonged latencies post-treatment when compared to tensioning NM group ([Formula: see text]). In contrast, no significant changes were observed in the DSSEPs and skin sympathetic responses for participants in the sham treatment group ([Formula: see text]). Conclusions: A tensioning NM on the median nerve had a possible adverse effect on the neurophysiology variables of the nerves involved in the neural mobilization. Thus, tensioning NM with the current parameters that place increased stress and strain on the peripheral nervous system should be avoided.
The Clinical Effects of Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients with Chronic Total Occlusion: A Meta-Analysis
Authors: Zhong Zhaoshuang , Zhao Long , Chen Kaiming , Xia Shuyue 
Published: March 2022

Background. The clinical effects of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with chronic total occlusion (CTO) lesions remain unclear. Methods. We identified all full-text published studies that compared the effects of IVUS-guided CTO-PCI with angiography-guided CTO-PCI by searching electric databases including PubMed, Embase, Cochrane Library, and ISI Web of Science from the establishment to Nov 2021. There was no language limitation. The endpoints included the incidence of major adverse cardiac events (MACE), cardiac death, all-cause death, myocardial infarction (MI), and target vessel revascularization (TVR). Results. Five studies involving a total of 2320 patients were included in this meta-analysis. Compared to the angiography-guided group, IVUS-guided PCI showed no significant reduction in the incidence of MACE (I2 = 27.4%,

P

= 0.239; RR 0.929, 95% CI 0.765 to 1.128,

P

= 0.457), cardiac death (I2 = 0.0%,

P

= 0.459; RR 0.574, 95% CI 0.299 to 1.103,

P

= 0.096), all-cause death (I2 = 0.0%,

P

= 0.964; RR 0.677, 95% CI 0.395 to 1.163,

P

= 0.158), MI (I2 = 46.7%,

P

= 0.131; RR0.836, 95% CI 0.508 to 1.377,

P

= 0.482), and TVR (I2 = 21.2%,

P

= 0.279; RR 0.929, 95% CI 0.679 to 1.272,

P

= 0.648). Conclusions. IVUS-guided PCI demonstrated no significant benefit on MACE, cardiac death, all-cause death, MI, and TVR in patients with CTO lesions. However, given the study’s limitations, additional high-quality RCTs are needed.
A Potential Prognostic Biomarker for Glioma: Aldo-Keto Reductase Family 1 Member B1
Authors: Zhao Hulin , Dong Xuetao , Huang Tianxiang , Li Xueji 
Published: March 2022

Aldo-keto reductase family 1 member B1 (AKR1B1) plays a vital role in tumor development and is involved in the tumor immune process. However, its role in glioma cell is poorly studied. This study’s aim was to assess the role of AKR1B1 in glioma through bioinformatics analysis. The AKR1B1 expression data and corresponding clinical data of glioma were collected from the Cancer Genome Atlas (TCGA) database. The R packages were used for data integration, extraction, analysis, and visualization. According to the median value of the risk score, all patients were divided into high-risk and low-risk groups to draw the Kaplan–Meier (KM) survival curves and to explore the level of immune infiltration. The expression of AKR1B1 was significantly elevated in glioma tissues compared to normal tissues (

P

< 0.001). The high expression of AKR1B1 was significantly associated with WHO grade (

P

< 0.001), IDH status (

P

< 0.001), 1p/19q codeletion (

P

< 0.001), primary therapy outcome (

P

= 0.004), and age (

P

< 0.05). Kaplan–Meier survival analysis found that OS (HR = 3.75,

P

< 0.001), DSS (HR = 3.85,

P

< 0.001), and PFI (HR = 2.76,

P

< 0.001) were lower in patients with glioma with high AKR1B1 expression than in the group with low AKR1B1 expression. Based on GESA, six pathways (including interferon gamma signaling, signaling by interleukins, cell cycle checkpoints, cytokine receptor interaction, cell adhesion molecules (CAMs), and cell surface interactions) at the vascular wall were identified as significantly different between the two groups. Moreover, highly expressed AKR1B1 was associated with immune cell infiltration. AKR1B1 plays a key role in glioma progression and prognosis and, therefore, serves as a potential biomarker for prediction of patients’ survival.
Oncogenic and Tumor-Suppressive Functions of the RNA Demethylase FTO
Authors: Zuidhof Hidde R. , Calkhoven Cornelis F. 
Published: March 2022

Abstract
The epitranscriptome represents the more than 140 types of chemically varying and reversable RNA modifications affecting RNA fate. Among these, the most relevant for this review are the mRNA modifications N6-methyladenosine and N6,2′-O-dimethyladenosine. Epitranscriptomic mRNA biology involves RNA methyltransferases (so-called “writers”), RNA demethylases (“erasers”), and RNA-binding proteins (“readers”) that interact with methylation sites to determine the functional outcome of the modification. In this review, we discuss the role of a specific RNA demethylase encoded by the fat mass and obesity–associated gene (FTO) in cancer. FTO initially became known as the strongest genetic link for human obesity. Only in 2010, 16 years after its discovery, was its enzymatic function as a demethylase clarified, and only recently has its role in the development of cancer been revealed. FTO functions are challenging to study and interpret because of its genome-wide effects on transcript turnover and translation. We review the discovery of FTO and its enzymatic function, the tumor-promoting and suppressive roles of FTO in selected cancer types, and its potential as a therapeutic target.
Aberrant Activation of Cell-Cycle–Related Kinases and the Potential Therapeutic Impact of PLK1 or CHEK1 Inhibition in Uterine Leiomyosarcoma
Authors: Yoshida Kosuke , Yokoi Akira , Yamamoto Tomofumi , Hayashi Yusuke , Nakayama Jun , Yokoi Tsuyoshi , Yoshida Hiroshi , Kato Tomoyasu , Kajiyama Hiroaki , Yamamoto Yusuke 
Published: March 2022

Abstract

Purpose:
Uterine leiomyosarcoma is among the most aggressive gynecological malignancies. No effective treatment strategies have been established. This study aimed to identify novel therapeutic targets for uterine leiomyosarcoma based on transcriptome analysis and assess the preclinical efficacy of novel drug candidates.

Experimental Design:
Transcriptome analysis was performed using fresh-frozen samples of six uterine leiomyosarcomas and three myomas. The Ingenuity Pathway Analysis (IPA) was used to identify potential therapeutic target genes for uterine leiomyosarcoma. Afterward, our results were validated using three independent datasets, including 40 uterine leiomyosarcomas. Then, the inhibitory effects of several selective inhibitors for the candidate genes were examined using SK-UT-1, SK-LMS-1, and SKN cell lines.

Results:
We identified 512 considerably dysregulated genes in uterine leiomyosarcoma compared with myoma. The IPA revealed that the function of several genes, including CHEK1 and PLK1, were predicted to be activated in uterine leiomyosarcoma. Through an in vitro drug screening, PLK1 or CHEK1 inhibitors (BI-2536 or prexasertib) were found to exert a superior anticancer effect against cell lines at low nanomolar concentrations and induce cell-cycle arrest. In SK-UT-1 tumor-bearing mice, BI-2536 monotherapy remarkably suppressed tumorigenicity. Moreover, the prexasertib and cisplatin combination therapy inhibited tumor proliferation and prolonged the time to tumor progression.

Conclusions:
We identified upregulated expressions of PLK1 and CHEK1; their kinase activity was activated in uterine leiomyosarcoma. BI-2536 and prexasertib demonstrated a significant anticancer effect. Therefore, cell-cycle–related kinases may present a promising therapeutic strategy for the treatment of uterine leiomyosarcoma.
Attenuating Adaptive VEGF-A and IL8 Signaling Restores Durable Tumor Control in AR Antagonist–Treated Prostate Cancers
Authors: Maxwell Pamela J. , McKechnie Melanie , Armstrong Christopher W. , Manley Judith M. , Ong Chee Wee , Worthington Jenny , Mills Ian G. , Longley Daniel B. , Quigley James P. , Zoubeidi Amina , de Bono Johann S. , Deryugina Elena , LaBonte Melissa J. , Waugh David J.J. 
Published: March 2022

Abstract

Inhibiting androgen signaling using androgen signaling inhibitors (ASI) remains the primary treatment for castrate-resistant prostate cancer. Acquired resistance to androgen receptor (AR)-targeted therapy represents a major impediment to durable clinical response. Understanding resistance mechanisms, including the role of AR expressed in other cell types within the tumor microenvironment, will extend the clinical benefit of AR-targeted therapy. Here, we show the ASI enzalutamide induces vascular catastrophe and promotes hypoxia and microenvironment adaptation. We characterize treatment-induced hypoxia, and subsequent induction of angiogenesis, as novel mechanisms of relapse to enzalutamide, highlighting the importance of two hypoxia-regulated cytokines in underpinning relapse. We confirmed AR expression in CD34+ vascular endothelium of biopsy tissue and human vascular endothelial cells (HVEC). Enzalutamide attenuated angiogenic tubule formation and induced cytotoxicity in HVECs in vitro, and rapidly induced sustained hypoxia in LNCaP xenografts. Subsequent reoxygenation, following prolonged enzalutamide treatment, was associated with increased tumor vessel density and accelerated tumor growth. Hypoxia increased AR expression and transcriptional activity in prostate cells in vitro. Coinhibition of IL8 and VEGF-A restored tumor response in the presence of enzalutamide, confirming the functional importance of their elevated expression in enzalutamide-resistant models. Moreover, coinhibition of IL8 and VEGF-A resulted in a durable, effective resolution of enzalutamide-sensitive prostate tumors. We conclude that concurrent inhibition of two hypoxia-induced factors, IL8 and VEGF-A, prolongs tumor sensitivity to enzalutamide in preclinical models and may delay the onset of enzalutamide resistance.

Implications:
Targeting hypoxia-induced signaling may extend the therapeutic benefit of enzalutamide, providing an improved treatment strategy for patients with resistant disease.
Intratumoral Electroporation of Plasmid Encoded IL12 and Membrane-Anchored Anti-CD3 Increases Systemic Tumor Immunity
Authors: Han Mia , Nguyen Bianca , Lee Jack Y. , Browning Erica , Zhang Jun , Mukhopadhyay Anandaroop , Gujar Ravindra , Salazar Jon , Hermiz Reneta , Svenson Lauren , Rolig Annah S. , Redmond William L. , Algazi Alain P. , Daud Adil I. , Canton David A. , Twitty Christopher G. 
Published: March 2022

AbstractIntratumoral delivery of plasmid IL12 via electroporation (IT-tavo-EP) induces localized expression of IL12 leading to regression of treated and distant tumors with durable responses and minimal toxicity. A key driver in amplifying this local therapy into a systemic response is the magnitude and composition of immune infiltrate in the treated tumor. While intratumoral IL12 typically increases the density of CD3+ tumor-infiltrating lymphocytes (TIL), this infiltrate is composed of a broad range of T-cell subsets, including activated tumor-specific T cells, less functional bystander T cells, as well as suppressive T regulatory cells. To encourage a more favorable on-treatment tumor microenvironment (TME), we explored combining this IL12 therapy with an intratumoral polyclonal T-cell stimulator membrane-anchored anti-CD3 to productively engage a diverse subset of lymphocytes including the nonreactive and suppressive T cells. This study highlighted that combined intratumoral electroporation of IL12 and membrane-anchored anti-CD3 plasmids can enhance cytokine production, T-cell cytotoxicity, and proliferation while limiting the suppressive capacity within the TME. These collective antitumor effects not only improve regression of treated tumors but drive systemic immunity with control of nontreated contralateral tumors in vivo. Moreover, combination of IL12 and anti-CD3 restored the function of TIL isolated from a patient with melanoma actively progressing on programmed cell death protein 1 (PD-1) checkpoint inhibitor therapy.Implications:This DNA-encodable polyclonal T-cell stimulator (membrane-anchored anti-CD3 plasmid) may represent a key addition to intratumoral IL12 therapies in the clinic.
Long‐Term Cardiovascular Risk and Management of Patients Recorded in Primary Care With Unattributed Chest Pain: An Electronic Health Record Study
Authors: Jordan Kelvin P. , Rathod‐Mistry Trishna , Bailey James , Chen Ying , Clarson Lorna , Denaxas Spiros , Hayward Richard A. , Hemingway Harry , van der Windt Danielle A. , Mamas Mamas A. 
Published: March 2022

Background
Most adults presenting with chest pain will not receive a diagnosis and be recorded with unattributed chest pain. The objective was to assess if they have increased risk of cardiovascular disease compared with those with noncoronary chest pain and determine whether investigations and interventions are targeted at those at highest risk.

Methods and Results
We used records from general practices in England linked to hospitalization and mortality information. The study population included patients aged 18 years or over with a new record of chest pain with a noncoronary cause or unattributed between 2002 and 2018, and no cardiovascular disease recorded up to 6 months (diagnostic window) afterward. We compared risk of a future cardiovascular event by type of chest pain, adjusting for cardiovascular risk factors and alternative explanations for chest pain. We determined prevalence of cardiac diagnostic investigations and preventative medication during the diagnostic window in patients with estimated cardiovascular risk ≥10%. There were 375 240 patients with unattributed chest pain (245 329 noncoronary chest pain). There was an increased risk of cardiovascular events for patients with unattributed chest pain, highest in the first year (hazard ratio, 1.25 [95% CI, 1.21–1.29]), persistent up to 10 years. Patients with unattributed chest pain had consistently increased risk of myocardial infarction over time but no increased risk of stroke. Thirty percent of patients at higher risk were prescribed lipid‐lowering medication.

Conclusions
Patients presenting to primary care with unattributed chest pain are at increased risk of cardiovascular events. Primary prevention to reduce cardiovascular events appears suboptimal in those at higher risk.
Use of Photovoice to Explore Pediatric Patients with Hypertrophic Cardiomyopathy and their Parents' Perceptions of a Heart‐Healthy Lifestyle
Authors: Sobierajski Frances , Storey Kate , Bird Melissa , Anthony Samantha , Pol Sarah , Pidborochynski Tara , Balmer‐Minnes Diana , Tharani Alliya Remtulla , Power Alyssa , Khoury Michael , Cunningham Chentel , Jeewa Aamir , Conway Jennifer 
Published: March 2022

Background
Heart‐healthy lifestyles promote lifelong cardiovascular health. However, patients with hypertrophic cardiomyopathy are often advised to avoid strenuous exercise because of the risk of sudden cardiac death. Given these restrictions, this study explored youth and parent perceptions of a heart‐healthy lifestyle and the barriers and facilitators to this lifestyle.

Methods and Results
Youth and parents were purposefully recruited at 2 Canadian hospitals for this photovoice project. Participants were given cameras and took pictures of everyday heart‐healthy or heart‐unhealthy choices. Photos were discussed during one‐on‐one qualitative interviews with youth and parents separately to understand the photos’ meaning and significance. Inductive descriptive thematic analysis was employed. A total of 16 youth (median age, 14.4 years [range, 10.5–17.7 years]; 63% boys) and 16 parents (100% women) participated. A total of 15 youth were activity restricted. Data analysis revealed 7 categories organized into perceptions of healthy living (health is holistic and individualized) and factors influencing engagement in healthy living (self‐awareness, ownership and autonomy, feeling restricted and peer pressure, support from parents, and support from the cardiologist). Participants had a complex understanding of health and discussed the importance of physical, mental, and social well‐being. Youth used self‐awareness and taking responsibility as facilitators of healthy living. Healthy living was shaped by peers, parent role‐modeling, and cardiologist recommendations.

Conclusions
This study depicts the realities for youth with hypertrophic cardiomyopathy and can be used to inform the development of responsive interventions. Holistic, patient‐specific interventions may be more successful, and strategies such as shared decision making may be important to promote self‐awareness and autonomy.