bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomarker Qualification for Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: Theory and Practice
Authors: Benatar Michael , Ostrow Lyle W. , Lewcock Joseph W , Bennett Frank , Shefner Jeremy , Bowser Robert , Larkin Paul , Bruijn Lucie , Wuu Joanne 
Published: December 2023

ObjectiveTo explore whether the utility of neurofilament light chain (NfL), as a biomarker to aid amyotrophic lateral sclerosis (ALS) therapy development, would be enhanced by obtaining formal qualification from the US Food and Drug Administration for a defined context‐of‐use.MethodsConsensus discussion among academic, industry, and patient advocacy group representatives.ResultsA wealth of scientific evidence supports the use of NfL as a prognostic, response, and potential safety biomarker in the broad ALS population, and as a risk/susceptibility biomarker among the subset of SOD1 pathogenic variant carriers. Although NfL has not yet been formally qualified for any of these contexts‐of‐use, the US Food and Drug Administration has provided accelerated approval for an SOD1‐lowering antisense oligonucleotide, based partially on the recognition that a reduction in NfL is reasonably likely to predict a clinical benefit.InterpretationThe increasing incorporation of NfL into ALS therapy development plans provides evidence that its utility—as a prognostic, response, risk/susceptibility, and/or safety biomarker—is already widely accepted by the community. The willingness of the US Food and Drug Administration to base regulatory decisions on rigorous peer‐reviewed data‐absent formal qualification, leads us to conclude that formal qualification, despite some benefits, is not essential for ongoing and future use of NfL as a tool to aid ALS therapy development. Although the balance of considerations for and against seeking NfL biomarker qualification will undoubtedly vary across different diseases and contexts‐of‐use, the robustness of the published data and careful deliberations of the ALS community may offer valuable insights for other disease communities grappling with the same issues. ANN NEUROL 2024;95:211–216
Engineered polymer‐based scaffold as an implantable therapeutic vaccine against melanoma
Authors: Unnikrishnan Anjana , Menon Meera , K. G. Gopika , Sam Reba Elsa , Koyakutty Manzoor , Ashokan Anusha 
Published: December 2023

AbstractAlthough tumor‐antigen‐based therapeutic cancer vaccines are a potential cancer immunotherapy strategy, recent clinical trials show low efficacy for multiple reasons. One method that has been recently investigated to improve the efficacy of therapeutic cancer vaccines is the development of implantable vaccines for sustained delivery of antigens and CD8 T cell activation. Here, we optimized the composition for an implantable vaccine scaffold composed of alginate, polyvinyl alcohol, and poly(methyl vinyl ether‐ alt‐maleic anhydride) loaded with tumor antigens. Considering the adjuvant property of aluminum compounds, aluminum ion was used to crosslink alginate in the scaffold. The scaffold showed an effective antigen incorporation efficiency of 90.34 ± 0.55% using ovalbumin as the model antigen and 89.67 ± 2.8% using B16‐F10 cell lysate. SEM analysis of the scaffold showed pore size ranging from 5 to 10 μm. Cell viability analysis using mouse RAW 264.7 macrophages proved the cytocompatibility of the scaffold. In vitro antigen release studies using ovalbumin showed 8.42% release for a period of 14 days. In vivo antitumor analysis carried out in subcutaneous mouse B16‐F10 melanoma model demonstrated that the scaffold vaccine reduced the rate of tumor growth and improved survival in tested animals. The median survival time increased from 29 days in untreated animals to 58 days in scaffold vaccine‐implanted animals.
Structured polymer dispersant for efficient phthalocyanine blue dispersion and color paste preparation
Authors: Yang Chongyang , Song Liyang , Sun Yumiao , Han Yuheng , Wang Ting , Zeng En 
Published: December 2023

AbstractTo overcome challenges in pigment dispersion, especially for difficult‐to‐disperse pigments like phthalocyanine blue, the structure of dispersants has been studied in recent years. Herein, we present the development and performance evaluation of a structured polymer dispersant for efficient dispersion of phthalocyanine blue and color paste preparation. The dispersant was synthesized using a two‐step free radical polymerization process, allowing precise control over its structure. The study investigates the impact of key factors on dispersion, including the molecular weight of the hydrophilic long‐chain poly(ethylene glycol) monomethyl ether (MPEG), the ratio of anchoring groups styrene (St) and dimethylaminoethyl methacrylate (DMAEMA), and the dispersant dosage. Optimal stability was achieved with MPEG‐400 as the hydrophilic long chain and a St:DMAEMA ratio of 1:1, along with a MPEG‐400AA:AA ratio of 0.5:1 at 2000 r min−1. At a dispersant dosage of 25%, the particle size of the color paste measured 340 nm, with viscosity reaching 600 mPa·s. The structured dispersant effectively synergized spatial potential resistance and electrostatic effects to achieve stable pigment dispersion. These findings offer promising prospects for advancing dispersant technologies, with implications for improving color‐based applications across various industries, such as paints, coatings, and inks.
Characterization and RNA interference‐mediated silencing of tryptophan 2,3‐dioxygenase gene inCarpophilus hemipterus(L.) (Coleoptera: Nitidulidae)
Authors: Bansal Raman , Zhao Chaoyang , Burks Charles S. , Walse Spencer S. , Hunter Wayne B. 
Published: December 2023

AbstractDried fruit beetle,Carpophilus hemipterus (Linnaeus, 1758) (Coleoptera: Nitidulidae), is a serious pest of ripened fresh fruit in the orchard and dried fruit in postprocessing storage. Despite the economic impact and widespread distribution ofC. hemipterus, there is a lack of functional genomics research seeking to elucidate features of molecular physiology for improved pest management. Here, we report the characterization of the gene namedVermilioninC. hemipterus(ChVer) that encodes for tryptophan 2,3‐dioxygenase. TheVermilionis frequently used as a visual marker for genomics approaches as tryptophan 2,3‐dioxygenase is involved in the biosynthesis of eye coloration pigments in insects. We identified 1628 bp long full‐length transcript ofChVerfrom transcriptomic database ofC. hemipterus. The expression analysis among adult body parts revealed peakChVerexpression in head compared to thorax and abdomen, which is consistent with its role. Among theC. hemipterusdevelopmental stages, peakChVerexpression was observed in first instar larva, second instar larva, and adult male stages, whereas the lowest levels of expression were seen in third instar larva, prepupa, and pupa. The nanoinjection ofChVerdouble‐stranded RNA in larvalC. hemipterusresulted in a significant reduction inChVertranscript levels as well as caused a loss of eye color, that is, the white‐eyed phenotype in adults. Characterization of visually traceable marker gene and robust RNA interference response seen in this study will enable genomics research is this important pest.
The anti‐breast cancer therapeutic potential of 1,2,3‐triazole‐containing hybrids
Authors: Song Juntao , Zhang Shuai , Zhang Bo , Ma Junwei 
Published: December 2023

AbstractBreast cancer, as one of the most common invasive malignancies and the leading cause of cancer‐related deaths in women globally, poses a significant challenge in the world health system. Substantial advances in diagnosis and treatment have significantly improved the survival rate of breast cancer patients, but the number of incidences and deaths of breast cancer are projected to increase by 40% and 50%, respectively, by 2040. Chemotherapy is one of the principal treatments for breast cancer therapy, but multidrug resistance and severe side effects remain the major obstacles to the success of treatment. Hence, there is a vital need to develop novel chemotherapeutic agents to combat this deadly disease. 1,2,3‐Triazole, which can be effectively constructed by click chemistry, not only can serve as a linker to connect different anti‐breast cancer pharmacophores but also is a valuable pharmacophore with anti‐breast cancer potential and favorable properties such as hydrogen bonding, moderate dipole moment, and enhanced water solubility. Particularly, 1,2,3‐triazole‐containing hybrids have demonstrated promising in vitro and in vivo anti‐breast cancer potential against both drug‐sensitive and drug‐resistant forms and possessed excellent selectivity by targeting different biological pathways associated with breast cancer, representing privileged scaffolds for the discovery of novel anti‐breast cancer candidates. This review concentrates on the latest advancements of 1,2,3‐triazole‐containing hybrids with anti‐breast cancer potential, including work published between 2020 and the present. The structure–activity relationships (SARs) and mechanisms of action are also reviewed to shed light on the development of more effective and multitargeted candidates.
Histone‐Specific CD4+ T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus
Authors: Ramirez Giuseppe A. , Tassi Elena , Noviello Maddalena , Mazzi Benedetta A. , Moroni Luca , Citterio Lorena , Zagato Laura , Tombetti Enrico , Doglio Matteo , Baldissera Elena M. , Bozzolo Enrica P. , Bonini Chiara , Dagna Lorenzo , Manfredi Angelo A. 
Published: December 2023

ObjectiveThe aim of this study was to assess whether circulating histone‐specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE).MethodsSeroprevalence of autoantibodies and HLA‐DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA–peptide autoepitope couples for ex vivo detection of antigen‐specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA‐DRB1*03:01 and/or HLA‐DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission.ResultsHistone‐specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti‐DNA antibodies, 77% had detectable histone‐specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone‐specific regulatory and effector T helper (Th) 1‐, Th2‐, and atypical Th1/Th17 (Th1*)‐polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1‐, Th2‐, and Th1*‐polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone‐specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone‐specific naive T (TN) and terminally differentiated T cells.ConclusionHistone‐specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.image
Anti‐Inflammatory Effect of High‐Density Lipoprotein Blunted by Delivery of Altered MicroRNA Cargo in Patients With Rheumatoid Arthritis
Authors: Wu Qiong , Sheng Quanhu , Michell Danielle , Ramirez‐Solano Marisol , Posey Olivia , Phothisane Anastasiia , Shaik Shahensha , Vickers Kasey C. , Ormseth Michelle J. 
Published: December 2023

ObjectiveHigh‐density lipoprotein (HDL) has well‐characterized anti‐atherogenic cholesterol efflux and antioxidant functions. Another function of HDL uncharacterized in rheumatoid arthritis (RA) is its ability to transport microRNAs (miRNAs) between cells and thus alter cellular function. The study's purpose was to determine if HDL‐miRNA cargo is altered and affects inflammation in RA.MethodsHDL‐microRNAs were characterized in 30 RA and 30 control participants by next generation sequencing and quantitative polymerase chain reaction. The most abundant differentially expressed miRNA was evaluated further. The function of miR‐1246 was assessed by miRNA mimics, antagomiRs, small interfering RNA knockdown, and luciferase assays. Monocyte‐derived macrophages were treated with miR‐1246‐loaded HDL and unmodified HDL from RA and control participants to measure delivery of miR‐1246 and its effect on interleukin‐6 (IL‐6).ResultsThe most abundant miRNA on HDL was miR‐1246; it was significantly enriched two‐fold on HDL from RA versus control participants. HDL‐mediated miR‐1246 delivery to macrophages significantly increased IL6 expression 43‐fold. miR‐1246 delivery significantly decreased DUSP3 1.5‐fold and DUSP3 small interfering RNA knockdown increased macrophage IL6 expression. Luciferase assay indicated DUSP3 is a direct target of miR‐1246. Unmodified HDL from RA delivered 1.6‐fold more miR‐1246 versus control participant HDL. Unmodified HDL from both RA and control participants attenuated activated macrophage IL6 expression, but this effect was significantly blunted in RA so that IL6 expression was 3.4‐fold higher after RA versus control HDL treatment.ConclusionHDL‐miR‐1246 was increased in RA versus control participants and delivery of miR‐1246 to macrophages increased IL‐6 expression by targeting DUSP3. The altered HDL‐miRNA cargo in RA blunted HDL's anti‐inflammatory effect.image
Command filter‐based adaptive fixed‐time fault‐tolerant control for stochastic nonlinear systems with actuator hysteresis
Authors: Xu Ke , Wang Huanqing , Liu Peter Xiaoping 
Published: December 2023

AbstractIn this paper, an adaptive fault‐tolerant fixed‐time control problem is considered via command‐filter technique for stochastic nonlinear systems with sensor fault and actuator hysteresis. With the application of command‐filtering technique, a novel command‐filter compensate mechanism is designed, which implies that the improved control scheme not only eliminates “the explosion of complexity” but also realizes the compensate signal is bounded within fixed‐time interval. The unavailability of state variables caused by sensor fault is solved by applying parameter separation and regrouping approach. Meanwhile, an adaptive auxiliary signal is designed to cope with the backlash‐like hysteresis phenomenon, which can avoid singularity, reduce chattering, and facilitate controller design. Combining backstepping technique and Lyapunov stability theorem, an adaptive fault‐tolerant control approach is developed, which can guarantee all closed‐loop signals remain semi‐globally practical fixed‐time stable (SGPFS) in probability. The validity of the proposed strategy is illustrated by simulation examples.
Bayesian change point prediction for downhole drilling pressures with hidden Markov models
Authors: Erivwo Ochuko , Makis Viliam , Kwon Roy 
Published: December 2023

AbstractIn the drilling of oil wells, the need to accurately detect downhole formation pressure transitions has long been established as critical for safety and economics. In this article, we examine the application of Hidden Markov Models (HMMs) to oilwell drilling processes with a focus on the real time evolution of downhole formation pressures in its partially observed state. The downhole drilling pressure system can be viewed as a nonlinear, non‐degrading stochastic process whose optimum performance is in a region in its warning state prior to random failure in time. The differential pressure system is modeled as a hidden 3 state continuous time Markov process. States 0 and 1 are not observable and represent the normally pressured (initiating ) and abnormally pressured or warning (reducing ) states respectively. State 2 is the observable failure state (from negative and loss of well control). The signal process of the evolution of differential pressure is identified in the changes in the observable rate of penetration (ROP) encoded in drilling performance data. The state and observation parameters of the HMM are estimated using the Expectation Maximization (EM) algorithm and we show, for a univariate system with a depth dependent time relationship, that the model parameter updates of the EM algorithm equation have explicit solutions. A Bayesian inference model, to determine the safety threshold of the system and early failure prediction at each sampling epoch, is thereafter proposed. The application of our stochastic model of the dynamic evolution of downhole pressures in operational time is illustrated with a hindcast case example. The analysis showed strong early indication of probable failure in real time and was validated in the field post drilling system failure that resulted in significant recovery costs. The potential to predict the differential pressure state transitions ahead of the bit represents a capability not currently available in the industry. This opens up significant opportunity for value creation from optimizing drilling operations to deliver substantial savings in well construction costs.
A geopolitics of knowledge analysis of higher education internationalisation in Kazakhstan
Authors: Hwami Munyaradzi 
Published: December 2023

AbstractThis critical interpretive paper deploys Walter Mignolo's geopolitics of knowledge concept to examine higher education internationalisation in Kazakhstan. Amidst growing concerns about economic and environmental sustainability, elitism and cognitive justice, among other critical issues, internationalisation remains a vital government policy. By tracing Kazakhstan's development since independence from the Soviet Union and focusing on key higher education development policy frameworks, the paper argues and illustrates that: (1) the internationalisation of higher education in Kazakhstan promotes a specific representation of the world that is considered universal and modern; (2) the internationalisation of higher education in Kazakhstan illustrates the existing hierarchical global higher education system that is dominated by the West as centres of knowledge and learning while allocating other countries peripheral roles; and (3) the geopolitics of knowledge concept enables the reading of higher education internationalisation beyond what is knowledge to who, why and where knowledge is produced. The data for this paper came from a qualitative study that involved 15 semi‐structured interviews with graduates who studied abroad at Western universities through the government‐sponsored Bolashak Scholarship. Three focus group sessions with 21 graduate students at Nazarbayev University complemented the interviews. The qualitative data suggest that Mignolo's geopolitics of knowledge offers a close‐to‐perfect description of the internationalisation of higher education in Kazakhstan. The conclusion drawn from this post‐Soviet study is the universalisation of Western knowledge as nations utilise it for meaningful development, despite decolonial and cognitive justice concerns.
Molecular mechanism of Xiaohuoluo wan for rheumatoid arthritis by integrating in vitro and in vivo chemomics and network pharmacology
Authors: Qin Wanli , Zhang Kai , Yu Ziyang , Liu Heyuan , Li Hangyu , Dong Ling , Han Dongran , Li Tiangang 
Published: December 2023

AbstractThe cause of rheumatoid arthritis (RA) is unclear. Xiaohuoluo wan (XHLW) is a classical Chinese medicine that is particularly effective in the treatment of RA. Given the chemical composition of XHLW at the overall level has been little studied and the molecular mechanism for the treatment of RA is not clear, we searched for the potential active compounds of XHLW and explored their anti‐inflammatory mechanism in the treatment of RA by flexibly integrating the high‐resolution ultra‐performance liquid chromatography–mass spectrometry (UPLC–MS)‐based in vitro and in vivo chemomics, network pharmacology, and other means. The results of the study identified that the active compounds of XHLW, such as alkaloids, nucleosides, and fatty acids, may play an anti‐inflammatory role by regulating key targets such as IL‐2, STAT1, JAK3, and MAPK8, inducing immune response through IL‐17 signaling pathway, T‐cell receptor, FoxO, tumor necrosis factor (TNF), and so forth, inhibiting the release of inflammatory factors and resisting oxidative stress and other pathways to treat RA. The results of this study provide referable data for the screening of active compounds and the exploration of molecular mechanisms of XHLW in the treatment of RA.
Impulsivity, decision‐making, and risk behavior in bipolar disorder and major depression from bipolar multiplex families
Authors: Ramírez‐Martín Almudena , Sirignano Lea , Streit Fabian , Foo Jerome C. , Forstner Andreas J. , Frank Josef , Nöthen Markus M. , Strohmaier Jana , Witt Stephanie H. , Mayoral‐Cleries Fermin , Moreno‐Küstner Berta , Rietschel Marcella , Guzmán‐Parra Jose 
Published: December 2023

AbstractObjectivesBipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision‐making, and risk‐taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision‐making, and risk‐taking behavior in BD and MDD patients from bipolar multiplex families.MethodsEighty‐two participants (BD type I, n = 25; MDD, n = 26; healthy relatives (HR), n = 17; and healthy controls (HC), n = 14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision‐making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains.ResultsParticipants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision‐making was associated with both mood disorders (BD and MDD). In risk‐taking behavior, no significant impairment was found in any group.LimitationsAs sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power.ConclusionsOur findings show that alterations of cognitive domains—while present in both disorders—are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders.