bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Single‐Cell Transcriptome and Surface Protein Expression in Ankylosing Spondylitis Identifies OX40‐Positive and Glucocorticoid‐Induced Tumor Necrosis Factor Receptor–Positive Pathogenic Th17 Cells
Authors: Yi Kijong , Jo Sungsin , Song Woogil , Lee Hae‐In , Kim Hui‐Ju , Kang Ji‐Hyoun , Kim Seon Uk , Lee Seung Hoon , Park Jinsung , Kim Tae‐Hwan , Lee Jeong Seok , Lee Eun Young , Kim Tae‐Jong 
Published: February 2023

ObjectiveTo demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single‐cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells.MethodsThis study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single‐cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid‐induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan‐injected SKG mice in which anti‐GITR ligand and/or anti‐OX40 ligand were used.ResultsWe identified pathogenic Th17 cells as polyfunctional interleukin‐17A (IL‐17A)– and interferon‐γ (IFNγ)–producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan‐injected SKG mouse model.ConclusionOur results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.image
A 24‐Week, Phase IIa, Randomized, Double‐Blind, Placebo‐Controlled Study of Ziritaxestat in Early Diffuse Cutaneous Systemic Sclerosis
Authors: Khanna Dinesh , Denton Christopher P. , Furst Daniel E. , Mayes Maureen D. , Matucci‐Cerinic Marco , Smith Vanessa , de Vries Dick , Ford Paul , Bauer Yasmina , Randall Matthew J. , Ebrahimpoor Mitra , Kupcsik Laszlo , Stiers Pieter‐Jan , Deberdt Liesbeth , Prasad Niyati , Lim Sharlene , Pujuguet Philippe , Ahmed Sohail 
Published: February 2023

ObjectiveWe undertook this study to explore the efficacy, safety, and tolerability of ziritaxestat, a selective autotaxin inhibitor, in patients with early diffuse cutaneous systemic sclerosis (dcSSc).MethodsNOVESA was a 24‐week, multicenter, phase IIa, double‐blind, placebo‐controlled study. Adults with dcSSc were randomized to oral ziritaxestat 600 mg once daily or matching placebo. The primary efficacy end point was change from baseline in modified Rodnan skin score (MRSS) at week 24. Secondary end points assessed safety and tolerability; other end points included assessment of skin and blood biomarkers. Patients in NOVESA could enter a 104‐week open‐label extension (OLE).ResultsPatients were randomized to ziritaxestat (n = 21) or placebo (n = 12). Reduction in MRSS was significantly greater in the ziritaxestat group versus the placebo group (–8.9 versus –6.0 units, respectively; P = 0.0411). Placebo patients switching to ziritaxestat in the OLE showed similar reductions in MRSS to those observed for ziritaxestat patients in the parent study. Ziritaxestat was well tolerated; the most frequent treatment‐related treatment‐emergent adverse events were headache and diarrhea. Circulating lysophosphatidic acid (LPA) C18:2 was significantly reduced, demonstrating ziritaxestat target engagement, and levels of fibrosis biomarkers were reduced in the blood. No differentially expressed genes were identified in skin biopsies. Significant changes in 109 genes were identified in blood samples.ConclusionZiritaxestat resulted in significantly greater reduction in MRSS at week 24 than placebo; no new safety signals emerged. Biomarker analysis suggests ziritaxestat may reduce fibrosis. Modulation of the autotaxin/LPA pathway could improve skin involvement in patients with dcSSc. A plain language summary is provided in the Supplementary Material, available on the Arthritis & Rheumatology website at https://onlinelibrary.wiley.com/doi/10.1002/art.42477.image
Electrode Materials of Cobaltous Fluoride for Supercapacitor and Electrocatalysis Applications
Authors: He Zheng‐Hua , Gao Jian‐Fei , Kong Ling‐Bin 
Published: February 2023

AbstractHerein, CoF2 was synthesized by a solvothermal method. The characterization results of the phase and morphology of the sample show that it was successfully synthesized and its morphology is composed of micron particles with uneven size and shape. The electrochemical test results of SCs in different electrolytes show that CoF2 has electrochemical activity only in alkaline electrolytes. Notably, the electrochemical behavior of CoF2 in LiOH solution is different from that in other alkaline solutions in that charge‐discharge curve has a quasi‐isosceles triangle shape and the CV curve has no obvious redox peak. That is, it has pseudocapacitance behavior in LiOH. Furthermore, CoF2 as catalyst for HER requires an overpotential of only 168 mV to obtain current density of 10 mA cm−2 and a Tafel slope of 116 mV dec−1 in 1 M KOH solution. This research provides a novel way to explore excellent performance electrode materials for SC and HER.
Carboxylate Ligand‐supported Agn (n=21 and 24) Alkynyl Clusters Induced by Single/Double Carbonate Ions
Authors: Li Li , Liu Na , Zhou Kun , Liang Guang‐Min , Tan Yi‐Fan , Ji Jiu‐Yu , Chen Bao‐Kuan , Bi Yan‐Feng 
Published: February 2023

AbstractStructural transformation is important for the study of silver cluster compounds, in which controlled synthesis of their shapes and sizes via anion template‐driven is one key scientific question. In this work, the CO32− anion templates were captured by the [tBuC≡CAg]n system under the stimulation induced by carboxylate ligand CF3COO−/PhCOO−, and two silver alkynyl clusters [(CO32−)@Ag21(tBuC≡C)16(CF3COO)3(H2O)]⋅DMF⋅2CH2Cl2 (1) and [(CO32−)2@Ag24(tBuC≡C)16(PhCOO)4]⋅CH3OH⋅4DMF (2) have been successfully isolated and charactered. With the increase of the number of CO32− templates from single to double, the outer silver atoms from twenty‐one to twenty‐four, accompanied by the growth of the cluster skeleton from 9.8 Å ×6.9 Å of the (CO32−)@Ag21 unit to 10.5 Å ×7.3 Å of the (CO32−)2@Ag24 unit. In addition, the syntheses, structures, photocurrent responses, cyclic voltammetry characteristics, luminescence, and photodegradation of compounds 1 and 2 have been studied.
Sodium valproate exposure influences the expression of pparg in the zebrafish model
Authors: Merola Carmine , Caioni Giulia , Cimini Annamaria , Perugini Monia , Benedetti Elisabetta 
Published: February 2023

AbstractValproic acid (VPA) is an anti‐epileptic drug used alone or in combination with other medications to treat seizures, mania, and bipolar disorder. VPA recognized as a teratogenic chemical can cause severe birth defects mainly affecting the brain and spinal cord when administered during pregnancy. However, the potential mechanisms of developmental toxicity are still less studied, and in the present study, the influence of VPA exposure was evaluated on zebrafish early‐life stages. Zebrafish were exposed to two sublethal concentrations of sodium valproate (SV) (0.06 mM and 0.15 mM) from 24 hours post‐fertilization (hpf) to 96 hpf and the SV teratogenic potential was investigated through morphometric analysis of zebrafish larvae combined with the evaluation of cartilage profile. Moreover, the effect of SV on the transcription level of pparg was also performed. The results of the study showed the teratogenic potential of SV, which disrupts the morphometric signature of the head and body. The marked distortion of cartilage structures was paralleled to a malformation of telencephalon and optic tectum in both concentrations suggesting a high teratogen effect of SV on the brain. These data were further confirmed by the increased expression of pparg in the zebrafish head. Overall, the present study confirms the teratogenic activity of SV in the zebrafish model and, for the first time, points out the potential protective role of pparg in the SV dose‐dependent toxicity.
Garcinia gummi‐gutta: Phytochemicals and pharmacological applications
Authors: Anilkumar Amrita Thandayamparambil , Manoharan Suryaa , Balasubramanian Satheeswaran , Perumal Ekambaram 
Published: February 2023

AbstractGarcinia gummi‐gutta, also known as Garcinia cambogia, is a member of the Guttiferae family. Garcinia is a polygamous genus consisting 200 species of trees and shrubs. It is found in different zones of the planet including Asia's tropical regions. In India alone, around 30 species have been discovered. They are widely used as a flavoring agent to garnish fish curry in southern India, particularly in Kerala and Karnataka. The fruit rind of G. gummi‐gutta has traditionally been used to treat gastrointestinal problems, diarrhea, and ulcers. South Indian people have been utilizing it traditionally as evidenced by its ethnobotanical properties. In vivo and in vitro effects of the crude fruit extract showed anti‐inflammatory, anti‐cancer, anthelmintic, anti‐microbial, and antioxidant activities. G. gummi‐gutta fruit rind is medicinally significant and is frequently used in ayurvedic and traditional medicine for many diseases. Various secondary metabolites such as organic acids—hydroxycitric acid (HCA), flavonoids, terpenes, polysaccharides and polyisoprenylated benzophenones—garcinol, xanthochymol, guttiferone, benzophenone, xanthone, biflavonoids, alkaloids, tannins, phenols, and saponins isolated from the G. gummi‐gutta have diverse pharmacological activities. This review provides a summary of G. gummi‐gutta, including its biological activities, phytochemistry, and ethnobotanical applications.
Periodic step polarization accelerates electron recovery by electroactive biofilms (EABs)
Authors: Gao Yaohuan , Xia Longfei , Yao Peiru , Lee Hyung‐Sool 
Published: February 2023

AbstractRelatively low rate of electron recovery is one of the factors that limit the advancement of bioelectrochemical systems. Here, new periodic polarizations were investigated with electroactive biofilms (EABs) enriched from activated sludge and Geobacter sulfurreducens biofilms. When representative anode potentials (Ea) were applied, redox centers with midpoint potentials (Emid) higher than Ea were identified by localized cyclic voltammetry. The electrons held by these redox centers were accessible when Ea was raised to 0.4 V (vs. Ag/AgCl). New periodic polarizations that discharge at 0.4 V recovered electrons faster than normal periodic and fixed‐potential polarizations. The best‐performing periodic step polarization accelerated electron recovery by 23%−24% and 12%−76% with EABs and G. sulfurreducens biofilms, respectively, compared to the fixed‐potential polarization. Quantitative reverse transcription polymerase chain reaction showed an increased abundance of omcZ mRNA transcripts from G. sulfurreducens after periodic step polarization. Therefore, both the rate of energy recovery by EABs and the performance of bioelectrochemical systems can be enhanced by improving the polarization schemes.
Psychometric properties of the full‐form and short‐form versions of the Integration of Stressful Life Experiences Scale (ISLES) among Iranian university students
Authors: Azadfar Zahra , Bijari Azam Farah , Khosravi Zohreh , Abdollahi Abbas 
Published: February 2023

AbstractBackgroundMaking adaptive meaning of stressful life experiences has been identified as an important determinant of adjustment. The Integration of Stressful Life Experiences Scale (ISLES) was developed to assess the outcome of meaning‐making processes in the face of negative events.AimsThe psychometric properties of this scale have not been measured in Iranian populations. The purpose of the present study was to examine the psychometric properties of the 16‐item and 6‐item versions of ISLES with a sample of 502 university students who had experienced relationship dissolution.ResultsFindings support a two‐factor structure with acceptable validity and reliability. Positive correlations between the scores of ISLES with Centrality of Event Scale and PTSD symptoms provided evidence of concurrent validity.ConclusionThe results of measurement invariance indicated that both the 16‐item and 6‐item versions of ISLES are gender invariant and can be used to assess meaning‐made in both men and women.
Teaching agile hardware development with an open‐source engineering simulator: An evaluation with industry participants
Authors: Omidvarkarjan Daniel , Hofelich Manfred , Conrad Jonas , Klahn Christoph , Meboldt Mirko 
Published: February 2023

AbstractEducational games are increasingly used to teach Agile development approaches to practitioners. Most of these training modules simplify the development environment, for example, by using LEGO bricks or playing cards. This oversimplification has been shown to result in limited transferability of learning to industrial practice. Furthermore, there is a lack of teaching modules that specifically address the challenges of applying Agile to physical products. In this paper, we present an open‐source educational game that realistically simulates a hardware development project to teach Agile principles. Over 2 days, participants design, manufacture, and test modifications for a physical wire bending machine within an authentic engineering and production setting. The training mimics the typical roles, processes, and tools of industrial engineering teams to reflect the challenges of Agile hardware development. The module was evaluated with 44 industry professionals regarding perceived learning and user reaction. A combination of quantitative and qualitative methods was used for the experimental evaluation. The results showed a positive learning effect as the participants' average agreement with Agile principles increased through the training. Concerning user reaction, respondents reported a high degree of relevance, interaction, and confidence, indicating that the realistic simulation of the hardware development appropriately balanced the degree of realism with simplicity. The study showcases the opportunities of properly aligning game components to provoke learning situations targeted by the instructors. It contributes to the extant literature by providing a design framework (product, process, setting, and instruction) and open‐source access to the tools used for implementation.
Exploring the Effects of Mutagenesis on FusionRed by Using Excited‐State QM/MM Dynamics and Classical Force Field Simulations**
Authors: Murphy Ashlyn R. , Hix Mark A. , Walker Alice R. 
Published: February 2023

AbstractFluorescent proteins (FPs) are a powerful tool for examining tissues, cells, and subcellular components in vivo and in vitro. FusionRed is a particular FP variant mutated from mKate2 that, in addition to lower cytotoxicity and aggregation rates, has shown potential for acting as a tunable photoswitch. This was posited to stem partially from the presence of a bulky side chain at position 158 and a further stabilizing residue at position 157. In this work, we apply computational techniques including classical molecular dynamics (MD) and combined quantum mechanics/molecular mechanics simulations (QM/MM) to explore the effect of mutagenesis at these locations in FusionRed on the chromophore structure, the excited‐state surface, and relative positional stability of the chromophore in the protein pocket. We find specific connections between the statistical sampling of the underlying protein structure and the nonradiative decay mechanisms from excited‐state dynamics. A single mutation (C158I) that restricts the motion of the chromophore through a favorable hydrophobic interaction corresponds to an increase in fluorescence quantum yield (FQY), while a second rescue mutation (C158I‐A157N) partially restores the flexibility of the chromophore and photoswitchability with favorable water interactions on the surface of the protein that counteracts the original interaction. We suggest that applying this understanding of structural features that inhibit or favor rotation on the excited state can be applied for rational design of new, tunable and red photoswitches.
Peptide‐Based Nanoarchitectonics for the Treatment of Liver Fibrosis
Authors: Li Bowen , Huang Yan , Zou Qianli 
Published: February 2023

AbstractLiver fibrosis is a process of excessive accumulation of extracellular matrix caused by liver injury. Liver fibrosis can progress to cirrhosis or even liver cancer without proper intervention. Until now, no effective therapeutic drugs have been clinically approved for treating liver fibrosis. Hence, the development of safe and effective antifibrotic drugs is particularly important. As a representative biomaterial, peptides have been investigated as key components for constructing antifibrotic nanomaterials given their advantages of biological origination, synthetic availability, and good biocompatibility. Peptides serve as multifunctional motifs in antifibrotic nanomaterials, such as liver‐targeting molecules, antifibrotic molecules, and self‐assembling building blocks for the formation of the nanomaterials. In this review, we focus on peptide‐based nanoarchitectonics for treating liver fibrosis, including nanomaterials modified with liver‐targeting peptides, nanomaterials for the efficient delivery of antifibrotic peptides, and self‐assembled peptide nanomaterials for the delivery of antifibrotic drugs. The design rules of these peptide‐based nanomaterials are described. The antifibrotic mechanisms and effects of these peptide‐based nanomaterials in treating liver fibrosis and related diseases are highlighted. The challenges and future perspectives of using peptide‐based nanoarchitectonics for the treatment of liver fibrosis are discussed. These results are expected to accelerate the rational design and clinical translation of antifibrotic nanomaterials.
Clinical outcomes after unprotected left main coronary artery occlusion: A retrospective multicentre cohort analysis
Authors: Dürig Marco , Arroyo Diego , Bedossa Marc , Commeau Philippe , Fournier Stephane , Müller Olivier , Barragan Paul , Le Breton Hervé , Puricel Serban , Cook Stéphane 
Published: February 2023

AbstractAimsUnprotected left main coronary artery (ULMCA) occlusion is a rare and disastrous condition with scarce data on presentation and outcomes. Herein, we report data on patients presenting with acute coronary syndrome due to ULMCA occlusion at four different institutions.MethodsThis is an international multicentre observational study. Baseline characteristics were retro‐ and prospectively collected. Clinical follow‐up was prospective. The primary outcome was in‐hospital death. Patients surviving the index hospitalization were compared with nonsurvivors to find predictors of survival.ResultsThe study population consisted of 55 patients. Eight patients (15%) died in the cath lab, and 23 (42%) died in hospital. Three (6%) deaths were noncardiac and due to major bleeding. Thirty‐two (58%) patients survived the index hospitalization and were discharged. These patients were followed for a median of 17.5 months during which three cardiac deaths occurred. Repeat revascularization was performed in 25% (n = 8). Overall mortality at maximum follow‐up was 47% (n = 26). The only significant predictor for hospital survival was left ventricular ejection fraction (odds ratio [OR]: 1.10 (per 1 point increase); 95% confidence interval [CI]: 1.02–1.19; p = 0.02).ConclusionULMCA occlusion carries a high short‐term mortality. Patients who survive index hospitalization have similar mortality rates as compared with other st elevation myocardial infarction patients.
Intraplaque wiring enables drug‐coated balloons to be utilized for percutaneous recanalization of chronically occluded coronary arteries
Authors: Terashita Kazunori , Shimada Yoshihisa , Yamanaka Yuki , Motohashi Yoshikazu , Tonomura Daisuke , Yoshitani Kazuyasu , Yoshida Masataka , Tsuchida Takao , Fukumoto Hitoshi 
Published: February 2023

AbstractObjectivesThis study aimed to determine whether drug‐coated balloon (DCB) angioplasty following intraplaque wiring and the use of modified balloons is safe and effective in the percutaneous treatment of coronary chronic total occlusions (CTOs).BackgroundDCB is an alternative therapeutic option without the limitations of permanent vascular implants. However, its efficacy in CTOs has yet to be confirmed. The combination of modified balloons and DCB can be effectively applied when the intraplaque passage of the guidewire is achieved in CTOs.MethodsData from 124 consecutive CTO lesions (105 patients) treated at our hospital between February 2016 and December 2020 were screened for inclusion and retrospectively analyzed. Among the 118 lesions successfully recanalized, intraplaque wiring was achieved in 108, and 85 were treated by the DCB‐only approach following cutting/scoring balloon dilatation.ResultsFollow‐up data were available for 82 lesions (71 patients). The median occlusion length was 18.5 mm, and the J‐CTO score was 1.7 ± 0.9. No in‐hospital major adverse cardiac events occurred, including abrupt vessel closure. During the median 29‐month follow‐up period, target lesion revascularization was performed for 10 lesions. Follow‐up coronary angiography (8.7 ± 3.9 months after the index procedure) was performed for 64 lesions, demonstrating late lumen loss of −0.15 mm (interquartile range −0.4 to 0.23 mm), binary restenosis (diameter stenosis ≥50%) in 12 lesions (18.8%), and late lumen enlargement in 37 (57.8%).ConclusionThe DCB‐only approach following the use of modified balloons is a promising strategy for coronary CTOs when intraplaque wiring is achieved.
Pro‐aromaticity Enabled Dealkenylative Functionalizations via Photo‐Excitation and Oxidation
Authors: Chen Si‐Cong , Zhu Qi , Chen Han , Chen Zijing , Luo Tuoping 
Published: February 2023

AbstractA general and practical approach for diverse dealkenylative functionalization of olefin‐containing substrates has been developed through the one‐pot formation and utilization of pro‐aromatic 1,4‐dihydropyridazines using tetrazine as the key cycloaddition reagent. Triggered by either excitation or oxidation, the targeted C−C bonds in the 1,4‐dihydropyridazine intermediates could be readily cleaved to generate alkyl radicals for subsequent transformations. Diverse carbon‐carbon and carbon‐hetero bond forming protocols, including Giese‐type addition, hydrazination, borylation, Minisci‐type alkylation, copper‐catalyzed NH alkylation, acylation, alkynylation, cyanation, and azidation, are achieved in a highly modular fashion.