bluuebunny/crossref_metadata_2025 huggingface dataset:
Disposable Electrochemical Sensor Based on MXene/Graphene Nanoplatelets/Ionic Liquid for the Determination of Anticancer Drug Imiquimod
Authors: Kalambate Pramod K. , Primpray Vitsarut , Kamsong Wichayaporn , Karuwan Chanpen , Laiwattanapaisal Wanida
Published: November 2023

This study describes the development of a novel, ultrasensitive, and selective electrochemical sensor to determine imiquimod (IMQ) using a screen-printed carbon electrode (SPCE) modified with MXene (Ti3C2Tx), graphene nanoplatelets, and ionic liquid (Ti3C2Tx/GNPs/IL). This work reveals the synergistic effect of Ti3C2Tx, GNPs, and IL, where Ti3C2Tx and GNPs provide a large active electrode area and excellent electron transport, and IL exhibits remarkable electrocatalytic behavior. Benefiting from the excellent electrochemical properties of the composite, the developed sensing platform enabled superior electrochemical performance for IMQ in the broad linear range of 0.071–92.0 μM (R2 = 0.999) with a limit of detection (LOD) of 0.487 nM and a detection sensitivity of 7.558 μA μM−1 cm−2. Meanwhile, the sensor has shown good repeatability, reproducibility, stability, and anti-interference ability and has been subsequently used to detect IMQ in cream formulations with satisfactory recoveries (98.33%–99.34%) and lower relative standard deviations (<3%). The findings indicate that the newly developed sensor can contribute to the development of a portable, robust, and high-performance sensing strategy for multidisciplinary targets.
Acute high-dose MitoQ does not increase urinary kidney injury markers in healthy adults: a randomized crossover trial
Authors: Linder Braxton A. , Stute Nina L. , Hutchison Zach J. , Barnett Alex M. , Tharpe McKenna A. , Kavazis Andreas N. , Kirkman Danielle L. , Gutierrez Orlando M. , Robinson Austin T.
Published: November 2023

We found acute high-dose mitochondria-targeted antioxidant (MitoQ) supplementation was not nephrotoxic and had no effect on markers of acute kidney injury in healthy adults. These findings can help bolster further confidence in the safety of MitoQ, particularly for future investigations seeking to examine the role of mitochondrial oxidative stress, via acute MitoQ supplementation, on various physiological outcomes.
Effects of intermittent exercise during prolonged sitting on executive function, cerebrovascular, and psychological response: a randomized crossover trial
Authors: Horiuchi Masahiro , Pomeroy Alexander , Horiuchi Yukari , Stone Keeron , Stoner Lee
Published: November 2023

We assessed executive function, cardiovascular, and cerebrovascular responses during 3-h prolonged sitting, with or without an exercise interruption (1 min squats every 20 min). Compared to uninterrupted sitting, exercise interruption suppressed sitting-induced reductions in cerebral blood flow and impairments in executive function. These results demonstrated the efficacy of a half-squat intervention for individuals seeking to preserve cognition during prolonged sitting, which may be useful in environments with limited resources such as the workplace.
Adipose-Derived Mesenchymal Stem Cell Facilitate Hematopoietic Stem Cell Proliferation via the Jagged-1/Notch-1/Hes Signaling Pathway
Authors: Wang Hongbo , Bi Xiaojuan , Zhang Rongyao , Yuan Hailong , Xu Jianli , Zhang Kaile , Qi Songqing , Zhang Xue , Jiang Ming
Published: November 2023

Background. Poor graft function (PGF) is a life-threatening complication following hematopoietic stem cell transplantation (HSCT). Current therapies, such as CD34+ cell infusion, have shown limited effectiveness. Conversely, mesenchymal stem cells (MSCs) show potential in addressing PGF. Adipose-derived mesenchymal stem cells (ADSCs) effectively support long-term hematopoietic stem cell proliferation. Therefore, this study aimed to investigate the mechanisms underlying the long-term hematopoietic support provided by ADSCs. Methods. ADSCs were isolated from mice and subsequently identified. In vitro experiments involved coculturing ADSCs as feeders with Lin-Sca-1+c-kit+ (LSK) cells from mice for 2 and 5 weeks. The number of LSK cells was quantified after coculture. Scanning electron microscopy was utilized to observe the interaction between ADSCs and LSK cells. Hes-1 expression was assessed using western blot and real-time quantitative PCR. An γ-secretase inhibitor (GSI) was used to confirm the involvement of the Jagged-1/Notch-1/Hes-1 pathway in LSK cell expansion. Additionally, Jagged-1 was knocked down in ADSCs to demonstrate its significance in ADSC-mediated hematopoietic support. In vivo experiments were conducted to study the hematopoietic support provided by ADSCs through the infusion of LSK, LSK + fibroblasts, and LSK + ADSCs, respectively. Mouse survival, platelet count, leukocyte count, and hemoglobin levels were monitored. Results. ADSCs showed high-Jagged-1 expression and promoted LSK cell proliferation. There was a direct interaction between ADSCs and LSK cells. After coculture, Hes-1 expression increased in LSK cells. Moreover, GSI-reduced LSK cell proliferation and Hes-1 expression. Knockdown of Jagged-1 attenuated ADSCs-mediated promotion of LSK cell proliferation. Furthermore, ADSCs facilitated hematopoietic recovery and promoted the survival of NOD/SCID mice. Conclusion. The hematopoietic support provided by ADSCs both in vivo and in vitro may be mediated, at least in part, through the Jagged-1/Notch-1 signaling pathway. These findings provide valuable insights into the mechanisms underlying ADSCs-mediated hematopoietic support and may have implications for improving the treatment of PGF following HSCT.
Interrater Reliability of the Spanish (Colombia) Version of the Post-COVID-19 Functional Status Scale
Authors: Benavides-Córdoba Vicente , Ávila-Valencia Juan Carlos , Guerrero-Jaramillo Diana , Lorca Luz Alejandra , Palacios Mauricio , Torres-Castro Rodrigo , Betancourt-Peña Jhonatan
Published: November 2023

Background. COVID-19 has been one of the most critical public health challenges of recent decades. This disease develops severely in one in five patients, and approximately 5% require admission to a critical care unit. Due to the impact of the sequelae, the Post-COVID-19 Functional Status Scale (PCFS) was developed. This study is aimed at determining the interrater reliability of the Spanish (Colombia) version of the PCFS in adult patients with post-COVID-19 infection. Methods. This is an observational study performed with patients diagnosed with COVID-19. Two evaluators repeated the test-retest of the PCFS scale with knowledge and clinical experience in the care of patients with COVID-19 and had previously applied the test. The PCFS assesses functional limitations at discharge and can be used at 4 and 8 weeks to evaluate practical consequences and determine the degree of disability these patients may have. For interrater reliability, Cronbach’s alpha was applied with its respective confidence interval and the Bland-Altman method. A 95% confidence interval (CI) was taken as the basis for the interpretation of the Intraclass Correlation Coefficient (ICC). Results. A total of 112 adult patients participated in the study, aged

51.46
±
15.94

years. It was evidenced that the survival, constant care, and activities of daily living questions have an ICC of one (1.000) with an ICC (1.000-1.000), demonstrating excellent reliability, while those close to one were instrumental activities, role participation, symptoms, and final score with an ICC 0.918 to 0.984 and an ICC (0.881-0.989). Thus, a homogeneous distribution of the interrater data was evident. Conclusions. Excellent interobserver reliability of the Spanish (Colombia) version of the PCFS in patients with different degrees of functional status was reported.
Spatial–Temporal Characteristics of Semen Quality in Infertile Men in Wenzhou, China during 2010–2018
Authors: Dai Xuchao , Zhang Mengqi , Chen Gang , Pan Chengshuang , Zheng Jiujia , Fei Qianjin , Huang Hong , Wu Zhigang
Published: November 2023

Background. Declining semen quality has become one of the most serious public health problems worldwide; however, the spatial–temporal characteristics of semen quality of infertile men remain unknown. Objective. To explore spatial–temporal characteristics of semen quality of infertile men in Wenzhou from 2010 to 2018 and thereby provide a scientific basis for development of strategies to enhance male reproductive health. Methods. We obtained 22,978 semen sample data from 2010 to 2018 from the Reproductive Medicine Center and Urology of the First Affiliated Hospital of Wenzhou Medical University in Wenzhou, China. Linear regression analyses and spatial autocorrelation analyses were used to study spatial–temporal characteristics of semen quality parameters. Results. Overall, from 2010 to 2018, mean values for total sperm number and semen volume showed linear increasing trends, and mean values for total sperm motility showed linear decreasing trend (all

P
<
0.05

). Cold spot analyses of progressive sperm motility, total sperm motility, and normal sperm forms were also in main urban area of Wenzhou (Lucheng District, Ouhai District, Longwan District, and Dongtou District) and hot spot were also in nonmain urban area of Wenzhou (mainly including Taishun County, Pingyang County, and Wencheng County). However, hot spot analyses of total sperm number and semen volume were mainly in Dongtou District. Conclusions. The main urban area is the “harder-hit area” of semen quality, while for the islands area is the “high-withdrawal area.” Government departments need to pay more attention to improve male reproductive health in the main urban areas and actively control the potential influencing factors of male reproductive health, such as occupational exposure and life stress. Good environmental quality and plenty of seafood intake may be beneficial to semen quality.
An Experimental Analysis of Lean Binary Mixture Segregation in a Continuous Liquid Fluidized Bed
Authors: Narasimha Reddy S. , Venkata Ratnam M.
Published: November 2023

This study examined the phenomenon of particle segregation in lean-phase binary mixtures, with a specific focus on the effect of particle size variations while flowing over a continuous liquid fluidized bed (LFB). The experimental configuration included a cylindrical column with a 72 mm internal diameter and 3 m vertical height. The binary mixture considered for this investigation was made up of solid materials that were rich in flotsam and jetsam. The study encompassed various factors, including liquid velocity, solid feed rate, and feed composition, in order to examine the separations containing flotsam and jetsam. A segregation index was calculated for each of the various combinations. On the other hand, the fluidization of the blend consisting of two solid components displayed notable differences in its behavior when compared to the reported effects of particle separation in any of the mixtures. Empirical correlations have been employed to establish relationships between variables, particularly with respect to solid entrainment and top and bottom product purity levels.
Examining the Association between Abstinence from Smoking and Healthcare Costs among Patients with Cancer
Authors: Kypriotakis George , Kim Seokhun , Karam-Hage Maher , Robinson Jason D. , Minnix Jennifer A. , Blalock Janice A. , Cui Yong , Beneventi Diane , Kim Bumyang , Pan I.-Wen , Shih Ya-Chen Tina , Cinciripini Paul M.
Published: November 2023

Continuous tobacco use in patients with cancer is linked to substantial healthcare costs due to increased risks and complications, whereas quitting smoking leads to improved treatment outcomes and cost reductions. Addressing the need for empirical evidence on the economic impact of smoking cessation, this study examined the association between smoking cessation and healthcare cost utilization among a sample of 930 patients with cancer treated at The University of Texas MD Anderson Cancer Center's Tobacco Research and Treatment Program (TRTP). Applying conditional quantile regression and propensity scores to address confounding, our findings revealed that abstinence achieved through the TRTP significantly reduced the median cost during a 3-month period post-quitting by $1,095 [β = −$1,095, P = 0.007, 95% confidence interval (CI), = (−$1,886 to −$304)]. Sensitivity analysis corroborated these conclusions, showing a pronounced cost reduction when outlier data were excluded. The long-term accrued cost savings from smoking cessation could potentially offset the cost of participation in the TRTP program, underscoring its cost effectiveness. An important implication of this study is that by reducing smoking rates, healthcare systems can more efficiently allocate resources, enhance patient health outcomes, and lessen the overall cancer burden.

Prevention Relevance:

This study emphasizes the dual impact of smoking cessation programs in patients with cancer: quitting smoking and reducing healthcare costs. It highlights the importance of integrating cessation programs into cancer prevention strategies, ensuring both individual health benefits and broader, system-wide economic efficiencies.

See related Spotlight, p. 197
Table S5 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Supplementary Table 5 shows estimated pharmacodynamic parameters for MYC and MCL1 mRNA in blood following enitociclib treatment. ​
Table S4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Supplementary Table 4 shows the baseline characteristics of DH-DLBCL and other MYC+ NHL Patients (n=15) treated with 30 mg enitociclib i.v. QW from whom samples were collected for discovery of DEGs.
Table S3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Supplementary Table 3 contains the top DEGS from an unbiased analysis of RNAseq from MYC+ DLBCL cell lines treated with CDK9 inhibitors.
Table S1 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Supplementary Table 1 shows the enitociclib toxicity in a panel of lymphoma cell lines ranked by IC50
FIGURE 4 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Enitociclib treatment confers a robust shift in transcriptional activity in MYC+ DLBCL cell lines. A, Comparison of significant DEGs (Padj ≤ 0.05, fold change ≥2) after 4 hours pretreatment of DLBLC cell lines with three CDK9 inhibitors with unsupervised hierarchical clustering based on 250 nmol/L enitociclib treatment. Heat map showing gene intensity per sample relative to the average level across all samples. Individual genes are shown on the Y axis while samples are shown along the X axis. Red and blue cells correspond to higher and lower RNA-seq levels, respectively after 4 hours of treatment. B, List of top DEGs for each treatment ranked by Padj (cutoff 10–7) with overlapping DEGs as indicated by color coding. C, Significant DEGs were analyzed for enrichment of Reactome pathway membership using a hypergeometric test by mapping genes to genes (if appropriate) for each treatment condition and for KB-0742 treated cells, the Padj value cutoff for the pathway of 10–7 was selected for graphical representation because there were 182 significant pathways (30 shown). The three top pathways for enitociclib and atuveciclib are shown for KB-0742 but the Padj values do not meet the cutoff but are included for comparative purposes.
FIGURE 3 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Enitociclib treatment results in complete regression of MYC-overexpressing SU-DHL-10 lymphoma growth and mechanism of action confirmed in vivo. A, Growth curves where red arrows indicate dosing days and tumor volumes of SU-DHL-10 tumors treated with either vehicle [30 or 60% PEG400, 10% ethanol (EtOH), water for infusion] or enitociclib at 10 or 15 mg/kg (once weekly, i.v., n = 12/group) for 3 weeks. On days 16 and 20, the T/C ratios for 10 and 15 mg/kg enitociclib were 0.19 and 0.005, respectively. Unpaired t test were performed using comparison with the corresponding vehicle treatment: **, P = 0.011; ***, P < 0.001. B, Body weight changes were observed after application of enitociclib followed by recovery before the next application. C, Phosphorylated RNA polymerase II protein levels at residue Ser2 (p-Ser2) and Ser5 (p-Ser5) were quantified MYC and MCL1 mRNA levels (D) assessed by qPCR and Myc, Mcl-1, cPARP protein levels (E) were quantified from in vivo xenograft of SU-DHL-10 DLBCL cells at predose and indicated times postdose in vivo. Error bars denote SD.
FIGURE 2 from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Enitociclib depletes mRNA transcripts, MYC and MCL1; downregulates Myc and Mcl-1 protein levels and activates cell death in vitro MYC (A) and MCL1 (B) mRNA levels were determined using qPCR normalized to 18s rRNA from SU-DHL-10 and SU-DHL-4 DLBCL cells treated with indicated concentration of CDK9 inhibitor for 4 hours. The protein levels of Myc (C) and Mcl-1 (D) pretreatment and at indicated times after treatment washout were quantified relative to GAPDH in SU-DHL-10 and SU-DHL-4 cells. The inset shows Myc protein levels in SU-DHL-10 cells until 8 hours after treatment. E, The protein levels of cPARP is quantified from SU-DHL-10 DLBCL cells pretreatment and at indicated times after treatment.
Data from Enitociclib, a Selective CDK9 Inhibitor, Induces Complete Regression of MYC+ Lymphoma by Downregulation of RNA Polymerase II Mediated Transcription
Authors: Frigault Melanie M. , Mithal Arushi , Wong Harvey , Stelte-Ludwig Beatrix , Mandava Vinay , Huang Xin , Birkett Joseph , Johnson Amy J. , Izumi Raquel , Hamdy Ahmed
Published: November 2023

Abstract
Double-hit diffuse large B-cell lymphoma (DH-DLBCL) is an aggressive, and often refractory, type of B-cell non–Hodgkin lymphoma (NHL) characterized by rearrangements in MYC and BCL2. Cyclin-dependent kinase 9 (CDK9) regulates transcriptional elongation and activation of transcription factors, including MYC, making it a potential targeted approach for the treatment of MYC+ lymphomas. Enitociclib is a well-tolerated and clinically active CDK9 inhibitor leading to complete metabolic remissions in 2 of 7 patients with DH-DLBCL treated with once weekly 30 mg intravenous administration. Herein, we investigate the pharmacodynamic effect of CDK9 inhibition in preclinical models and in blood samples from patients [DH-DLBCL (n = 10) and MYC+ NHL (n = 5)] treated with 30 mg i.v. once weekly enitociclib. Enitociclib shows significant regulation of RNA polymerase II Ser2 phosphorylation in a MYC-amplified SU-DHL-4 cell line and depletion of MYC and antiapoptosis protein MCL1 in SU-DHL-4 and MYC-overexpressing SU-DHL-10 cell lines in vitro. Tumor growth inhibition reaching 0.5% of control treated SU-DHL-10 xenografts is achieved in vivo and MYC and MCL1 depletion as well as evidence of apoptosis activation after enitociclib treatment is demonstrated. An unbiased analysis of the genes affected by CDK9 inhibition in both cell lines demonstrates that RNA polymerase II and transcription pathways are primarily affected and novel enitociclib targets such as PHF23 and TP53RK are discovered. These findings are recapitulated in blood samples from enitociclib-treated patients; while MYC downregulation is most robust with enitociclib treatment, other CDK9-regulated targets may be MYC independent delivering a transcriptional downregulation via RNA polymerase II.
Significance:
MYC+ lymphomas are refractory to standard of care and novel treatments that downregulate MYC are needed. The utility of enitociclib, a selective CDK9 inhibitor in this patient population, is demonstrated in preclinical models and patients. Enitociclib inhibits RNA polymerase II function conferring a transcriptional shift and depletion of MYC and MCL1. Enitociclib intermittent dosing downregulates transcription factors including MYC, providing a therapeutic window for durable responses in patients with MYC+ lymphoma.
JAK Inhibitors in the Treatment of Lichen Planopilaris
Authors: Nasimi Maryam , Ansari Mahshid Sadat
Published: November 2023

Background: Lichen planopilaris (LPP) is an autoimmune disorder leading to lymphocytic cicatricial alopecia. Different agents such as hydroxychloroquine, methotrexate, cyclosporine, and mycophenolate mofetil have been tried to control hair loss with limited efficacy. JAK inhibitors are immune-modulating drugs which interfere with the JAK-STAT signaling pathway in lymphocytes and are used in treatment of inflammatory conditions such as rheumatoid arthritis and alopecia areata. Summary: Our aim was to determine effectiveness of JAK inhibitors in LPP and its clinical variant, frontal fibrosing alopecia. A literature search was conducted using PubMed, Google Scholar, and Cochrane databases. A total of 7 articles describing 35 patients were found. Although data on treatment are limited to retrospective studies and case reports, JAK inhibitors can be considered a new therapeutic option, especially in recalcitrant cases. Large prospective studies and randomized control trials are needed to provide further evidence supporting efficacy. Key Messages: Besides the fact that data on the treatment of LPP and FFA with JAK inhibitors are limited to retrospective studies and case reports, but JAK inhibitors can be considered as a new therapeutic option especially in recalcitrant cases.
lncRNA JPX-Enriched Chromatin Microenvironment Mediates Vascular Smooth Muscle Cell Senescence and Promotes Atherosclerosis
Authors: Gu Jiaming , Chen Jiajing , Yin Quanwen , Dong Mengdie , Zhang Yunjia , Chen Minghong , Chen Xiang , Min Jiao , He Xian , Tan Yongkang , Zheng Longbin , Jiang Hong , Wang Bingjian , Li Xuesong , Chen Hongshan
Published: November 2023

BACKGROUND:

Senescence is a series of degenerative changes in the structure and physiological function of an organism. Whether JPX (just proximal to XIST)—a newly identified age-related noncoding RNA by us—is associated with atherosclerosis is still unknown. Our study was to investigate the role of JPX and provide insights into potential therapies targeting atherosclerosis.

METHODS:

We analyzed clinical data from multiple tissues including meniscus tissue, leukemia cells, and peripheral blood monocytes to identify age-related noncoding RNAs in senescent vascular smooth muscle cells (VSMCs). The molecular mechanism of JPX was investigated by capture hybridization analysis of RNA targets and chromatin immunoprecipitation. IGVTools and real-time quantitative polymerase chain reaction were used to evaluate the JPX expression during phenotype regulation in age-related disease models. The therapeutic potential of JPX was evaluated after establishing an atherosclerosis model in smooth muscle–specific
Jpx
knockout mice.

RESULTS:

JPX expression was upregulated in activated
ras
allele (H-
ras
V12)-induced senescent VSMCs and atherosclerotic arteries. JPX knockdown substantially reduced the elevation of senescence-associated secretory phenotype (SASP) genes in senescent VSMCs. Cytoplasmic DNA leaked from mitochondria via mitochondrial permeability transition pore formed by VDAC1 (voltage-dependent anion channel 1) oligomer activates the STING (stimulator of interferon gene) pathway. JPX could act as an enhancer for the SASP genes and functions as a scaffold molecule through interacting with phosphorylated p65/RelA and BRD4 (bromodomain-containing protein 4) in chromatin remodeling complex, promoting the transcription of SASP genes via epigenetic regulation. Smooth muscle knockout of
Jpx
in
Apoe

KO

mice resulted in a decrease in plaque area, a reduction in SASP gene expression, and a decrease in senescence compared with controls.

CONCLUSIONS:

As an enhancer RNA, JPX can integrate p65 and BRD4 to form a chromatin remodeling complex, activating SASP gene transcription and promoting cellular senescence. These findings suggest that JPX is a potential therapeutic target for the treatment of age-related atherosclerosis.
Physical Contacts Between Mitochondria and WPBs Participate in WPB Maturation
Authors: Ma Jing , Hao Zhenhua , Zhang Yudong , Li Liuju , Huang Xiaoshuai , Wang Yu , Chen Liangyi , Yang Ge , Li Wei
Published: November 2023

BACKGROUND:

Weibel-Palade bodies (WPBs) are endothelial cell–specific cigar-shaped secretory organelles containing various biologically active molecules. WPBs play crucial roles in thrombosis, hemostasis, angiogenesis, and inflammation. The main content of WPBs is the procoagulant protein vWF (von Willebrand factor). Physical contacts and functional cross talk between mitochondria and other organelles have been demonstrated. Whether an interorganellar connection exists between mitochondria and WPBs is unknown.

METHODS:

We observed physical contacts between mitochondria and WPBs in human umbilical vein endothelial cells by electron microscopy and living cell confocal microscopy. We developed an artificial intelligence–assisted method to quantify the duration and length of organelle contact sites in live cells.

RESULTS:

We found there existed physical contacts between mitochondria and WPBs. Disruption of mitochondrial function affected the morphology of WPBs. Furthermore, we found that Rab3b, a small GTPase on the WPBs, was enriched at the mitochondrion-WPB contact sites. Rab3b deficiency reduced interaction between the two organelles and impaired the maturation of WPBs and vWF multimer secretion.

CONCLUSIONS:

Our results reveal that Rab3b plays a crucial role in mediating the mitochondrion-WPB contacts, and that mitochondrion-WPB coupling is critical for the maturation of WPBs in vascular endothelial cells.
HDAC9 Inhibition as a Novel Treatment for Stroke
Authors: Markus Hugh S.
Published: November 2023

The identification of a variant in the
HDAC9
gene as a risk factor for large-artery atherosclerotic stroke, and subsequently coronary artery disease, has opened novel treatment pathways for stroke and more widely atherosclerotic disease. This article describes the pathway from gene discovery to novel therapeutic approaches that are now entering man.
HDAC9
expression is elevated in human atherosclerotic plaque, while in animal and cellular models, reducing HDAC9 (histone deacetylase 9) protein is associated with reduced disease. Several mechanisms have been proposed to account for the association between HDAC9 and atherosclerosis including alterations in the inflammatory response and cholesterol efflux and endothelial-mesenchymal transition. The association raises the possibility that inhibiting HDAC9 may provide a novel treatment approach for atherosclerotic cardiovascular disease. This is supported by intervention studies demonstrating HDAC9 inhibition reduces atherosclerosis in animal and cellular models. Indirect data support such an approach in man. The antiseizure drug sodium valproate, which has nonspecific HDAC inhibitory properties, both inhibits atherosclerosis in animal models and is epidemiologically associated with reduced stroke and myocardial infarction risk in man. It is now being trailed in phase 2 studies in large-artery stroke, while more specific HDAC9 inhibitors are being developed.
Comparison of Parallel Genetic Algorithm and Particle Swarm Optimization for Parameter Calibration in Hydrological Simulation
Authors: Zhang Xinyu , Li Yang , Chu Genshen
Published: November 2023

Parameter calibration is an important part of hydrological simulation and affects the final simulation results. In this paper, we introduce heuristic optimization algorithms, genetic algorithm (GA) to cope with the complexity of the parameter calibration problem, and use particle swarm optimization algorithm (PSO) as a comparison. For large-scale hydrological simulations, we use a multilevel parallel parameter calibration framework to make full use of processor resources, and accelerate the process of solving high-dimensional parameter calibration. Further, we test and apply the experiments on domestic supercomputers. The results of parameter calibration with GA and PSO can basically reach the ideal value of 0.65 and above, with PSO achieving a speedup of 58.52 on TianHe-2 supercomputer. The experimental results indicate that using a parallel implementation on multicore CPUs makes high-dimensional parameter calibration in large-scale hydrological simulation possible. Moreover, our comparison of the two algorithms shows that the GA obtains better calibration results, and the PSO has a more pronounced acceleration effect.
Thermal biology of Lanthanotus borneensis (Lanthanotidae) in Sarawak, Borneo
Authors: Leah Veronica , Min Pui Yong , Das Indraneil
Published: November 2023

Lanthanotus borneensis, the Bornean earless monitor, is a monotypic member of the family Lanthanotidae, and restricted to the island of Borneo. Little has been published on its field ecology. This study investigated aspects of its thermal biology through an analysis of surface body temperatures of free ranging individuals against corresponding environmental temperatures, in order to explore aspects of microhabitat utilisation in relation to thermoregulation. A generalised linear mixed model shows significant effect of air and substrate temperatures, but not of water temperature. Further, the fixed effects of substrate temperature (coefficient estimate 0.396; ) versus ambient temperature (0.264; ), is suggestive of thigmothermy as the primary mode of thermoregulation. The species does not appear to utilise specific microhabitat structures to thermoregulate, the results of these observations suggesting that it is a thermoconformer.
Two new species of Leptobrachella Smith 1925 (Amphibia: Megophryidae) from Cao Bang Province, Vietnam
Authors: LUONG ANH MAI , HOANG CHUNG VAN , PHAM CUONG THE , ZIEGLER THOMAS , NGUYEN TRUONG QUANG
Published: November 2023

Two new species, Leptobrachella phiaoacensis sp. nov. and Leptobrachella phiadenensis sp. nov., are described from Phia Oac-Phia Den National Park, Cao Bang Province, Vietnam based on genetic divergence and morphological differences. Leptobrachella phiaoacensis sp. nov. is characterized by a combination of the following characters: size medium (27.8–33.3 mm in five adult males and 31.5–41.8 mm in five adult females); head longer than wide; tympanum distinct; dorsal skin shagreened with fine tubercles; toes webbing rudimentary, with narrow lateral fringes; supratympanic fold edged by a distinct black line; the presence of a dark brown triangle in interorbital region and a W-shaped marking in scapular region; belly from pinkish white to white with dark brown specking on belly periphery; iris bicolored copper in upper part, fading to silvery grey in lower part. Leptobrachella phiadenensis sp. nov. is distinguished from its congeners by a combination of the following morphological characters: size medium (27.6–28.6 mm in two adult females); head wider than long; tympanum distinct; skin on dorsal head and body rough with warts, tubercles and dermal ridges; toes webbing rudimentary, with narrow dermal fringes; supratympanic fold orange; dorsal surface of head and body with some large dark brown markings, a dark brown triangle in interorbital region, edged in white; flank light brown with some dark flecks; belly white with dark specking on outer margins; iris bicolored, copper in upper part, fading to silvery grey in lower part. In terms of genetic distance, the two new species differ from each other and other congeners for which comparable sequences are available by at least 3.7% (16S rRNA gene). Recognition of these new species brings the total number of known species in the genus Leptobrachella from Vietnam to 34.
Conservative Treatments of Adolescent Idiopathic Scoliosis: Physical Therapists’ Perspectives
Authors: Foley Davelaar Cassidy M. , Weber Goff Elizabeth , Granger Julie E. , Gill Danielle E. , Dela Cruz Nathalie Michelle Rosales , Sugimoto Dai
Published: November 2023

This study aimed to examine physical therapists’ perspectives in conservative treatments of pediatric patients with adolescent idiopathic scoliosis (AIS). A cross-sectional survey design was used. A validated questionnaire was distributed to physical therapists, and the responses were analyzed. Preferred treatment frequency was 60 minutes (53.8%), twice weekly (41.5%), over 3 to 5 months (44.6%). Top 3 clinical interventions were core and trunk stability enhancement (90.8%), abdominal strengthening (83.1%), and postural correction (80.0%). Top 3 therapeutic goal-setting parameters were activity-based (78.5%), quality-of-life measure-based (56.9%), and participation-based (50.8%). The most common quality-of-life survey used was Oswestry low back pain disability questionnaire (15.6%) followed by Scoliosis Research Society-22 instrument (12.5%). According to our data, physical therapists believe that pediatric patients with AIS can benefit with addressing core and trunk stability, a 60-minute per session, twice weekly, over 3 to 5 months based on activity-based goal-setting and quality-of-life measures using Oswestry questionnaire.
Investigating Heterogeneity in Response Strategies: A Mixture Multidimensional IRTree Approach
Authors: Alagöz Ö. Emre C. , Meiser Thorsten
Published: November 2023

To improve the validity of self-report measures, researchers should control for response style (RS) effects, which can be achieved with IRTree models. A traditional IRTree model considers a response as a combination of distinct decision-making processes, where the substantive trait affects the decision on response direction, while decisions about choosing the middle category or extreme categories are largely determined by midpoint RS (MRS) and extreme RS (ERS). One limitation of traditional IRTree models is the assumption that all respondents utilize the same set of RS in their response strategies, whereas it can be assumed that the nature and the strength of RS effects can differ between individuals. To address this limitation, we propose a mixture multidimensional IRTree (MM-IRTree) model that detects heterogeneity in response strategies. The MM-IRTree model comprises four latent classes of respondents, each associated with a different set of RS traits in addition to the substantive trait. More specifically, the class-specific response strategies involve (1) only ERS in the “ERS only” class, (2) only MRS in the “MRS only” class, (3) both ERS and MRS in the “2RS” class, and (4) neither ERS nor MRS in the “0RS” class. In a simulation study, we showed that the MM-IRTree model performed well in recovering model parameters and class memberships, whereas the traditional IRTree approach showed poor performance if the population includes a mixture of response strategies. In an application to empirical data, the MM-IRTree model revealed distinct classes with noticeable class sizes, suggesting that respondents indeed utilize different response strategies.
Asymmetric Exchange Rate Pass-through in India: A Non-linear ARDL Approach
Authors: Mendali Ganapati , Das Sanjukta
Published: November 2023

This study makes an attempt to examine the exchange rate pass-through (ERPT) to domestic prices in India from 1993M4 to 2021M3. In the empirical literature, the relationship between the exchange rate and the price was found to be linear. However, in emerging economies recently the asymmetric relationship between these variables is noticed: the effect of appreciation on price is found to be negligible while the effect of depreciation is found to be significant. To study this behaviour, we have used non-linear autoregressive distributed lag (NARDL) model by employing five variables (viz., exchange rate, consumer price, output gap, money supply and oil prices). The structural break techniques are used to examine the differential effects of the pass-through. It found that exchange rate shocks do not lead to significant changes in consumer prices in the long run. In terms of policy, this means that the ERPT has insignificant consequences for monetary policy, and depreciation might pose a little threat to price stability. It is also established that oil price shocks are not one of the major determinants of inflation in the country and they do not pose serious challenges to price stability. Economic growth and monetary expansion also do not seem to pose any risks to price stability in the long run.

JEL Classification: E31, E37, E52, F31
Neck Muscle Coactivation Response to Varied Levels of Mental Workload During Simulated Flight Tasks
Authors: Le Peter , Mills Emily H. L. , Weisenbach Charles A. , Davis Kermit G.
Published: November 2023

Objective

To evaluate neck muscle coactivation across different levels of mental workload during simulated flight tasks.

Background

Neck pain (NP) is highly prevalent among military aviators. Given the complex nature within the flight environment, mental workload may be a risk factor for NP. This may induce higher levels of neck muscle coactivity, which over time may accelerate fatigue, increase neck discomfort, and affect flight task performance.

Method

Three counterbalanced mental workload conditions represented by simulated flight tasks modulated by interstimulus frequency and complexity were investigated using the Modifiable Multitasking Environment (ModME). The primary measure was a neck coactivation index to describe the neuromuscular effort of the neck muscles as a system. Additional measures included perceived workload (NASA TLX), subjective discomfort, and task performance. Participants ( n = 60; 30M, 30F) performed three test conditions over 1 hr each while seated in a simulated seating environment.

Results

Neck coactivation indices (CoA) and subjective neck discomfort corresponded with increasing level of mental workload. Average CoAs for low, medium, and high workloads were: .0278(SD = .0232), .0286(SD = .0231), and .0295(SD = .0228), respectively. NASA TLX mental, temporal, effort, and overall scores also increased with the level of mental workload assigned. For ModME task performance, the overall performance score, monitoring accuracy, and resource management accuracy decreased while reaction times increased with the increasing level of mental workload. Communication accuracy was lowest with the low mental workload but had higher reaction times relative to increasing workload.

Conclusion

Mental workload affects neck muscle coactivation during combinations of simulated flight tasks within a simulated helicopter seating environment.

Application

The results of this study provide insights into the physical response to mental workload. With increasing multisensory modalities within the work environment, these insights may assist the consideration of physical effects from cognitive factors.
The US-China Semiconductor Power-Security Dilemma: Decoupling the Security and Power Struggles Through the Theory of Dr. Barry Buzan
Authors: Brundage Carter
Published: November 2023

Increasingly, both China and the US frame the secure domestic supply of semiconductors as a national security issue. Yet it is difficult to differentiate between the securitization of semiconductors as a national security vulnerability or as an arena for geopolitical competition. This article leverages Barry Buzan's theory of the power-security dilemma to provide a framework for deciphering and decoupling the two countries’ efforts to reduce their semiconductor supply-chain vulnerabilities and related power struggle. First, the US's and China's supply-chain vulnerabilities are explored as a security struggle, with special attention paid to their dependencies on Taiwan's semiconductor industry. Second, recent American efforts to restrict the flow of semiconductor technologies to China are explored as a power struggle. This article concludes by using Buzan's theory to draw conclusions about the origins and potential evolution of the US-China semiconductor power-security dilemma.
Fiscal conditions for multiparty elections in dictatorships
Authors: Mitchell Austin M
Published: November 2023

Multiparty elections can reduce the likelihood of conflict and help dictators secure their rule, but when does a dictator create electoral institutions? Existing research finds that one of the major reasons regimes introduce multiparty elections is to gain information about opposition demands. This article builds on that argument to explain that a regime’s finances determine whether or not it is able to benefit from creating electoral institutions. Dictators use the revenue of the regime to invest in different means of deterring opposition rebellion. A regime’s first priority is to build repressive capacity, after which it invests in public spending to buy the support of its winning coalition. Regimes only benefit from multiparty elections when they have sufficient revenue to fund repressive capacity but lack the finances to also buy regime security through massive public spending. Low-revenue regimes cannot benefit from elections and high-revenue regimes do not need elections to help secure their rule. I test the implications of the argument for regime spending and the creation of multiparty electoral institutions using a global sample of dictatorships between 1972 and 2014. The results of the hypothesis tests indicate that as revenue increases regimes decrease their shares of spending on repressive capacity but increase shares of spending on the public. The results also indicate the probability that a regime introduces elections rises as revenue increases from a low level, but the probability declines as revenue increases from a high level. The study builds upon the literature for how regime resources and state capacity influence authoritarian strategies of political survival. The findings for spending patterns are consistent with recent research on late modern regimes, and the results for the emergence of electoral institutions are consistent with research that finds dictators must have sufficient resources to survive holding elections.
Effectiveness of the SHARE Model in Improving the Knowledge of, Attitudes Toward, Intention to Provide, and Initiation of Hospice Care Among Caregivers of Terminally ill Patients With the Eight Major Non-Cancer Diseases
Authors: Pan Wen-Shiou , Lin Hung-Ru , Chen Miao-Yen
Published: November 2023

Objectives

To investigate the effects of a care intervention on the knowledge of, attitudes toward, intention to provide, and initiation of hospice care among caregivers of terminally ill patients with the eight major non-cancer diseases.

Methods

A two-group pre-post-test randomized intervention design was adopted. The intervention group received the SHARE model intervention. The SHARE intervention was implemented once a week for 6 weeks, with each session lasting 20–60 min.

Results

The intervention and control groups differed significantly in mean post-test scores for knowledge of hospice care ( t = −4.973, p = .00) and intentions to provide hospice care ( t = −2.424, p = .02). In the intervention group, pre- and post-test scores differed significantly for knowledge of hospice care ( t = −6.201, p = .000), attitudes toward hospice care ( t = −2.848, p = .008), and intentions to provide hospice care ( t = −2.781, p = .009).

Conclusions

The SHARE intervention improved knowledge of hospice care, intentions to provide, and initiation of hospice care among the caregivers of terminally ill patients with non-cancer diseases.
Body-worn cameras and unintended consequences: A case study of a British police force
Authors: L’Hoiry Xavier , Santorso Simone , Harrison Karen
Published: November 2023

This paper presents the results of a multi-method case study with a British police force carried out over a 2-year period examining the impacts of introducing body-worn cameras (BWCs). Our findings show that despite a broad enthusiasm for the potential of BWCs, police officers and staff in a British police force reported a series of unintended and undesirable consequences resulting from the introduction of BWCs. These impacts appear to have partly undermined some of the original intentions of introducing BWCs, such as improving policing standards, aiding prosecutorial processes thanks to improved evidential capture and reducing police officer workloads.
Language Teacher Educators’ Identity Construction through Teaching and Supporting Action Research: A Trioethnographic Study
Authors: Banegas Darío Luis , Beltrán-Palanques Vicent , Salas Araceli
Published: November 2023

Action research is a form of inquiry that allows language educators to understand and improve their own practice. The literature suggests that language teachers can employ it as a self-led and self-directed source of professional development and enhancement of their professional identity and agency. However, little is known about its impact on the development of identity of language teacher educators who teach and support action research. Against this backdrop, this article aims to explore the experience of three language teacher educators regarding the influence of action research on the construction of their professional identity. Drawing on verbal and visual data sets, findings show that when teacher educators teach and mentor action research in language teacher education programmes, they can become guiding knowers, reflective practitioners and agents of change. The roles that teacher educators enact may lead to a reflective process that enhances their professional development. These identities connected to agentic growth demonstrate the relevance of including action research in language teacher education programmes as it can help teacher educators nurture their professional identity, particularly concerning their professional knowledge. This study suggests that teaching and supporting action research can become a meaningful entry point for language teacher educators to reflect on their own practice and to carry out action research themselves in language teacher education programmes.