bluuebunny/crossref_metadata_2025_split huggingface dataset:
A blood biomarker test for brain amyloid impacts the clinical evaluation of cognitive impairment
Authors: Monane Mark , Johnson Kim G. , Snider B. Joy , Turner Raymond S. , Drake Jonathan D. , Maraganore Demetrius M. , Bicksel James L. , Jacobs Daniel H. , Ortega Julia L. , Henderson Joni , Jiang Yan , Huang Shuguang , Coppinger Justine , Fogelman Ilana , West Tim , Braunstein Joel B. 
Published: August 2023

AbstractObjectiveThe objective of this study was to examine clinicians' patient selection and result interpretation of a clinically validated mass spectrometry test measuring amyloid beta and ApoE blood biomarkers combined with patient age (PrecivityAD® blood test) in symptomatic patients evaluated for Alzheimer's disease (AD) or other causes of cognitive decline.MethodsThe Quality Improvement and Clinical Utility PrecivityAD Clinician Survey (QUIP I, ClinicalTrials.gov Identifier: NCT05477056) was a prospective, single‐arm cohort study among 366 patients evaluated by neurologists and other cognitive specialists. Participants underwent blood biomarker testing and received an amyloid probability score (APS), indicating the likelihood of a positive result on an amyloid positron emission tomography (PET) scan. The primary study outcomes were appropriateness of patient selection as well as result interpretation associated with PrecivityAD blood testing.ResultsA 95% (347/366) concordance rate was noted between clinicians' patient selection and the test's intended use criteria. In the final analysis including these 347 patients (median age 75 years, 56% women), prespecified test result categories incorporated 133 (38%) low APS, 162 (47%) high APS, and 52 (15%) intermediate APS patients. Clinicians' pretest and posttest AD diagnosis probability changed from 58% to 23% in low APS patients and 71% to 89% in high APS patients (p < 0.0001). Anti‐AD drug therapy decreased by 46% in low APS patients (p < 0.0001) and increased by 57% in high APS patients (p < 0.0001).InterpretationThese findings demonstrate the clinical utility of the PrecivityAD blood test in clinical care and may have added relevance as new AD therapies are introduced.
Distinct Fluorescence Optical Imaging Patient Clusters Emerge for Seropositive and Seronegative Rheumatoid Arthritis
Authors: Kisten Yogan , Arnaud Laurent , Levitsky Adrian , Györi Noémi , Larsson Per , Hensvold Aase , Catrina Anca , af Klint Erik , Rezaei Hamed 
Published: August 2023

ObjectiveTo investigate whether digital activity fluorescence optical imaging (FOI) patterns of inflammation can identify distinct rheumatoid arthritis (RA) phenotypes.MethodsThe hands of newly diagnosed patients with RA were evaluated by clinical examination, musculoskeletal ultrasound, and FOI. Inflammation on FOI was defined when capillary leakage and/or fluorophore perfusion was present. The FOI composite image was quantified into a digital disease activity (DACT) score, using novel computerized algorithms. Unsupervised clustering on FOI inflammatory patterns was used to identify subgroups of patients relative to anticyclic citrullinated peptides (ACPA) and/or rheumatoid factor (RF).ResultsOf 1326 examined hand joints in 39 patients with RA (72% female; 56% ever‐smokers; 54% RF positive and 69% ACPA positive), 400 (30%) showed inflammation by FOI, and 95% (37 of 39) of patients had DACT‐FOI scores greater than 1. Unsupervised analysis on FOI patterns revealed two patient clusters, cluster 1 (n = 29) and cluster 2 (n = 10). The proportion of seropositive patients was significantly higher in cluster 1 versus cluster 2 (90%, 26 of 29 vs. 30%, 3 of 10; P < 0.01), whereas C‐reactive‐protein levels (minimum‐maximum) were significantly higher in cluster 2 (20 mg/l [1‐102]) versus cluster 1 (2 mg/l [0‐119]; P = 0.01). A wider variety and proportion of inflamed joints emerged for patients with RA in cluster 2 versus cluster 1, in which inflammation was more concentrated around the wrists and the right metacarpophalangeal 2 (MCP2), bilateral MCP3, and, to a lesser degree, left MCP2 and proximal interphalangeal joint and tendon regions. Cluster 1 displayed lower mean (±SD) DACT scores compared with cluster 2 (3.6 ± 2.1 vs. 5.4 ± 2.1; P = 0.03).ConclusionFOI‐based digital quantification of hand joint inflammation revealed two distinct RA subpopulations with and without ACPA and RF related autoantibodies.
Rational Ligand Design of Heteroleptic Iridium (III) Complexes toward Nearly Perfect Horizontal Dipole Orientation for Highly Efficient Red‐Emitting Phosphorescent Organic Light‐Emitting Diodes
Authors: Kim Sangdong , Kim Jae‐Min , Choi Jongwon , Sim Myungsun , Koishikawa Yasushi , Cho Yong‐Suk , Kim Sungjun , Kwak Seung‐Yeon , Jeon Aram , Kwon Ohyun , Lee Duck‐Hyung , Lee Jun Yeob , Choi Byungki 
Published: August 2023

AbstractThe horizontal orientation of the transition dipole moment of the phosphorescent emitters is understood to be an important factor to enhance the external quantum efficiency (EQE) of organic light‐emitting diodes by improving light out‐coupling in optical microcavity structures. Here, red‐emitting heteroleptic iridium (III) complexes exhibiting an extremely high horizontal ratio of emitting dipole orientation (EDO) and photoluminescence quantum yield (PLQY), as well as longer device operational lifetime, without scarifying any other photophysical properties are reported. The systematic molecular design of main and ancillary ligands in heteroleptic iridium complexes leads to the achievement of both a horizontal EDO of 92% and a PLQY of 98% in the red‐emitting phosphorescent devices along with a shorter exciton decay time of 0.71 µs. Accordingly, the red‐emitting devices show excellent performances of maximum EQE of 32% and low‐efficiency roll‐off with the 1931 Commission Internationale de L′Eclariage coordinates of (0.66, 0.34). Therefore, this approach opens the way for further development of new red‐emitting iridium complexes pushing the device efficiency toward the theoretical limits.
Calcite Twinning in Mollusk Shells and Carrara Marble
Authors: Castillo Alvarez Cristina , Grimsich John L. , Schmidt Connor A. , Lisabeth Harrison , Voigtländer Anne , Gilbert Pupa U. P. A. 
Published: August 2023

AbstractMollusk shells protect the animals that form and inhabit them. They are composites of minerals and organics, with diverse mesostructures, including nacre, prismatic calcite, crossed‐lamellar aragonite, and foliated calcite. Twins, that is, crystals mirror symmetric with respect to their coherent interface, occurring as formation or deformation twins, are observed in all mollusk shell mesostructures but never within calcite prisms. Here, nanotwins and microwins within single calcite prisms are observed in different shells. Using Polarization‐dependent Imaging Contrast (PIC) mapping with 20–60 nm resolution, twins are observed to be 0.2–3 µm thick layers of differently oriented and colored crystals with respect to the main prism crystal. Multiple twins are interspersed with the prism crystal, parallel to one another, and similarly oriented. When comparing images of calcite prisms and twins obtained by PIC mapping and by Electron Back‐Scattered Diffraction (EBSD), the images correspond precisely. All twins are e‐twin types, with 127° angular distance between c‐axes. E‐twins are the most common deformation twins in geologic calcite, as also observed here in Carrara marble. Location of all twins near the outer surface of all shells and e‐twin type both suggest that twins within calcite prisms in mollusk shells result from deformation twinning.
Concerted Intramolecular and Intermolecular Charge Transfer for High‐Efficiency Near‐Infrared Thermally Activated Delayed Fluorescent Materials Approaching 900 nm
Authors: Xu Jingyi , Dai Yu , Zhang Jinyuan , Jia Zhen , Meng Qingyu , Qiao Juan 
Published: August 2023

AbstractHindered by the energy gap law, the development of high‐efficiency near‐infrared (NIR) thermally activated delayed fluorescence (TADF) emitters with emission peaks over 800 nm remains challenging. The conventional strategy of enhancing intramolecular charge transfer for bathochromic shift commonly results in low radiative decay rates (kr) and emission efficiency. Herein, a superior strategy of concerted intramolecular CT (intra‐CT) and intermolecular CT (inter‐CT) for high‐efficiency NIR‐TADF materials is demonstrated. As a proof‐of‐concept, two novel emitters DTPZ and DtBuTPZ are developed based on a new acceptor phenazine‐2,3‐dicarbonitrile (PZ). High kr is achieved by large oscillator strength from appropriate intra‐CT property in monomers and effective electronic couplings between inter‐CT and intra‐CT states in aggregates. Suppressed nonradiative decay processes are realized through strong inter‐CT properties, abundant intermolecular attractive interactions, and negligible π∙∙∙π stacking. Consequently, organic light‐emitting diodes based on those emitters showed record‐high maximum external quantum efficiencies and radiances of 2.28%, 24.18 W Sr−1 m−2 at 817 nm, 0.57%, 14.38 W Sr−1 m−2 at 877 nm for DTPZ, and 2.34%, 23.55 W Sr−1 m−2 at 807 nm for DtBuTPZ, respectively.
Layer‐Specific BTX‐A Delivery to the Gastric Muscularis Achieves Effective Weight Control and Metabolic Improvement
Authors: Wang Siqi , Wang Yuqiong , Lin Long , Li Zongjie , Liu Fengyi , Zhu Long , Chen Jie , Zhang Nianrong , Cao Xinyu , Ran Sunman , Liu Genzheng , Gao Peng , Sun Weiliang , Peng Liang , Zhuang Jian , Meng Hua 
Published: August 2023

AbstractThe rising incidence of health‐endangering obesity constantly calls for more effective treatments. Gastric intramural injection of botulinum neurotoxin A (BTX‐A) as a new modality carries great promise yet inconsistent therapeutic efficacy. A layer‐specific delivery strategy enabled by dissolving microneedles is hence pioneered to investigate the working site of BTX‐A and the resulting therapeutic effects. The drug‐loaded tips of the layer‐specific gastric paralysis microneedles (LGP‐MN) rapidly release and achieve uniform distribution of BTX‐A within the designated gastric wall layers. In an obesity rat model, the LGP‐MNs not only prove safer than conventional injection, but also demonstrate consistently better therapeutic effects with muscular layer delivery, including 16.23% weight loss (3.06‐fold enhancement from conventional injection), 55.20% slower gastric emptying rate, improved liver steatosis, lowered blood lipids, and healthier gut microbiota. Further hormonal study reveals that the elevated production of stomach‐derived glucagon‐like peptide‐1 due to the muscularis‐targeting LGP‐MN treatment is an important contributor to its unique glucose tolerance‐improving effect. This study provides clear indication of the gastric muscularis as the most favorable working site of BTX‐A for weight loss and metabolic improvement purposes, and meanwhile suggests that the LGP‐MNs could serve as a novel clinical approach to treat obesity and metabolic syndromes.
Deubiquitinase OTUD5 as a Novel Protector against 4‐HNE‐Triggered Ferroptosis in Myocardial Ischemia/Reperfusion Injury
Authors: Liu Lulu , Pang Jiaojiao , Qin Dandan , Li Ruochuan , Zou Dan , Chi Kai , Wu Wenxiao , Rui Haiying , Yu Huaxiang , Zhu Wenyong , Liu Kai , Wu Xuting , Wang Jinxin , Xu Ping , Song Xiaoshuai , Cao Yihai , Wang Jiali , Xu Feng , Xue Li , Chen Yuguo 
Published: August 2023

AbstractDespite the development of advanced technologies for interventional coronary reperfusion after myocardial infarction, a substantial number of patients experience high mortality due to myocardial ischemia‐reperfusion (MI/R) injury. An in‐depth understanding of the mechanisms underlying MI/R injury can provide crucial strategies for mitigating myocardial damage and improving patient survival. Here, it is discovered that the 4‐hydroxy‐2‐nonenal (4‐HNE) accumulates during MI/R, accompanied by high rates of myocardial ferroptosis. The loss‐of‐function of aldehyde dehydrogenase 2 (ALDH2), which dissipates 4‐HNE, aggravates myocardial ferroptosis, whereas the activation of ALDH2 mitigates ferroptosis. Mechanistically, 4‐HNE targets glutathione peroxidase 4 (GPX4) for K48‐linked polyubiquitin‐related degradation, which 4‐HNE‐GPX4 axis commits to myocyte ferroptosis and forms a positive feedback circuit. 4‐HNE blocks the interaction between GPX4 and ovarian tumor (OTU) deubiquitinase 5 (OTUD5) by directly carbonylating their cysteine residues at C93 of GPX4 and C247 of OTUD5, identifying OTUD5 as the novel deubiquitinase for GPX4. Consequently, the elevation of OTUD5 deubiquitinates and stabilizes GPX4 to reverse 4‐HNE‐induced ferroptosis and alleviate MI/R injury. The data unravel the mechanism of 4‐HNE in GPX4‐dependent ferroptosis and identify OTUD5 as a novel therapeutic target for the treatment of MI/R injury.
The effect of CNTs/PEEK coating thickness on the friction and wear behavior of porous Ti‐30Ta alloys for biomaterial implants
Authors: Abd Halim Zulhelmi Alif , Mat Yajid M. A. , Hassan Ahmed. G. , Saud S. N. , Abu Bakar T. A. 
Published: August 2023

AbstractElectrophoretic deposition was used to deposit carbon nanotube/polyether ether ketone (CNTs/PEEK) composite coatings onto porous titanium‐tantalum (Ti‐30Ta) substrates at different PEEK concentrations (4.5, 6.0, and 7.5 mg/mL). Coatings were analyzed for thickness, porosity, surface roughness, microhardness and bonding strength, with higher PEEK concentrations producing thicker and more uniform coatings. However, optimal coating thickness showed highest bonding strength; lower and higher thickness led to decreased bonding strength. The tribological properties of the CNTs/PEEK coated Ti‐30Ta samples of different thicknesses (50, 70, and 100 μm) were evaluated using ball‐on‐flat linear reciprocating sliding tests under dry and wet conditions using simulated body fluid (SBF) as a lubricant. The CNTs/PEEK coatings provided excellent tribological protection under dry friction, with thicker coatings having lower friction and negligible wear. However, under wet sliding, the coating's wear rate increased significantly due to softening of the rubbing surface caused by SBF lubrication that increase transfer film onto the counter body surface. Coating with optimal thickness of 74 μm demonstrated the lowest friction and wear under SBF lubrication due to its highest hardness and bonding strength. This study highlights the importance of controlling coating thickness in determining the performance of the CNTs/PEEK coatings for orthopedic implants.
Chinaʼs diplomacy and diaspora perceptions: Evidence from the Pacific region
Authors: Zhang Denghua 
Published: August 2023

AbstractChinese diplomacy has been proactive under Xi Jinping and overseas Chinese are an important target. A better understanding of how overseas Chinese perceive Chinese diplomacy can increase our knowledge, but it is under‐studied in the literature. To fill part of this gap, this research focuses on the Pacific region where Chinaʼs activities have triggered growing geostrategic competition between traditional powers and China. Based on a survey of 182 ordinary overseas Chinese in Fiji and Tonga, this paper examines Chinese diasporaʼs perceptions of three aspects that are related to Chinaʼs diplomacy, including the Belt and Road Initiative, China‐Pacific bilateral relations, and old‐new Chinese issues. The survey reveals nuances in ordinary overseas Chinese views about Chinaʼs diplomacy, especially the concerns and apathy among some of them. It suggests that ordinary overseas Chinese support for Chinaʼs diplomacy is unlikely to grow substantially unless their views about this diplomacy become more positive.
The elusive search engine: How search engine use is reflected in survey reports
Authors: Andersson Cecilia , Sundin Olof 
Published: August 2023

AbstractThe overall aim of this article is to contribute to a research‐based understanding of the increasing invisibility of web search engines in society and to discussions about the potential impact of this invisibility. It examines how search engine use and online search activities are represented in national and regional reports on internet habits and experience published by public foundations and policy institutes. The elusiveness of search engines is understood through a theoretical perspective from infrastructure theory. National survey reports on internet habits and experience from the United States, UK, and Sweden from 2015 to 2021 are analyzed. The article shows how difficult it is to gain insights into how people search online and the role search engines play in everyday life. The nature of the survey report, which is often used to inform national policy, risks exacerbating the invisibility of search engines: what cannot be measured cannot be discussed at the policy level. This invisibility can lead to insufficient attention being paid to search engines, including their uses and effects, in legislation, in school education, and in the general formation of public knowledge about search engines in society.
DHT inhibits REDOX damage and neuroinflammation to reduce PND occurrence in aged mice via mmu_circ_0001442/miR‐125a‐3p/NUFIP2 axis
Authors: Liu Li , Liu Mei , Zhang Daying , Song Zhiping , Zhang Huaigen 
Published: August 2023

AbstractBackgroundPerioperative neurocognitive disorder (PND) is the main cause of poor postoperative recovery in elderly patients with age‐related reductions in androgen levels. However, the underlying mechanisms have not been completely elucidated.MethodsA mouse model of PND was constructed using abdominal surgery. Dihydrotestosterone (DHT), as the primary androgen, can improve the cognitive function of mice with PNDs by reducing REDOX damage. To clarify the role of circular RNA (circRNA) in DHT in improving cognitive function in mice with PND, circRNA sequencing was performed to analyze the expression of circRNA in the hippocampus of mice.ResultsWe confirmed that mmu_circ_0001442 is the primary circRNA responsive to DHT stimulation in mice with PND. The mmu_circ_0001442/miR‐125a‐3p/NUFIP2 axis was predicted and constructed according to the analysis of databases, including pita, miRanda, TargetScan, miRDB, micro‐CDS, PolymiRTS, and TarBase v.8. Subsequently, the axis was verified by qPCR and double‐luciferase reporter gene assays. In vitro, we found that DHT rarely had an effect on the growth of BV2 cells using the CCK‐8 assay, but it attenuated the cytotoxic effect of lipopolysaccharide (LPS) on BV2 cells. In addition, we found that LPS stimulation promoted the release of proinflammatory cytokines, including IL‐6 and TNF‐α, in BV2 cells, whereas mmu_circ_0001442 knockdown and NUFIP2 knockdown partially abrogated this effect.ConclusionsTaken together, DHT inhibited REDOX damage and neuroinflammation in the hippocampus to alleviate cognitive disorders in mice with PNDs via activation of the mmu_circ_0001442/miR‐125a‐3p/NUFIP2 axis. This study provides a novel rationale for developing DHT as a potential therapeutic agent for PND prevention.
β2‐adrenergic receptor expression in patients receiving bevacizumab therapy for metastatic melanoma
Authors: Schuster Cornelia , Akslen Lars A. , Straume Oddbjørn 
Published: August 2023

AbstractBackgroundVascular endothelial growth factor (VEGF) was initially known as vascular permeability factor and identified as a driver of tumour angiogenesis. Recently, its role in supporting an immunosuppressive tumour microenvironment was demonstrated, and anti‐VEGF treatment combined with immune checkpoint blockade is currently investigated. Further, beta‐adrenergic signalling as a modifier of cancer hallmarks like immune response, angiogenesis and metastasis gained increased attention during past years.MethodsFocusing on the aspect of immunosuppression in upregulated beta‐adrenergic signalling, we investigated predictive markers in patients with metastatic melanoma who received bevacizumab monotherapy, a specific VEGF‐A binding antibody. We explored the expression of beta‐2 adrenergic receptor (β2‐AR), interleukin 6‐receptor (IL6‐R), cyclooxygenase 2 (COX2) and VEGF‐A by immunohistochemistry in melanoma to assess the correlation between these proteins in melanoma cells and response to treatment.ResultsStrong β2‐AR expression in metastases was associated with clinical benefit of bevacizumab. Furthermore, expression of the latter was positively linked to expression of VEGF‐A and COX2. β2‐AR expression in melanoma metastasis appears to distinguish a subgroup of patients that might benefit from anti‐VEGF treatment.ConclusionOur results strengthen further exploration of anti‐VEGF therapy in combination with immune checkpoint blockade in clinical studies and the investigation of β2‐AR as predictive marker.
New Dibenzocyclooctadiene Lignans and Phenolics from Kadsura heteroclite with Anti‐Inflammatory Activity
Authors: Thuy Le Thi , Tram Le Huyen , Anh Dinh Thi Phuong , My Nguyen Thi Thuy , Thong Nguyen Van , Anh Nguyen Tuan , Toan Dao Huy , Ha Tran Thu , Thanh Bui Van , Mai Nguyen Thi Ngoc , Linh Nguyen Ngoc , Le Duc‐Dat , Huong Tran Thu , Bach Nguyen Van 
Published: August 2023

AbstractA chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes (1 and 2) together with 14 known compounds (3–16) by using multiple chromatographic techniques. New compounds (1 and 2) were obtained and identified by spectroscopic methods (HR‐ESI‐MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF‐α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)‐α production with IC50 value of 6.16±0.14 μM. Whereas, compounds (1, 3, and 6) showed the significant inhibition (IC50 values ranging from 9.41 to 14.54 μM), and compounds (2, 4, 9, 10, 13, 15, and 16) exhibited moderate inhibition (IC50 values ranging from 19.27 to 40.64 μM) toward TNF‐α production, respectively.
Activity‐Based Protein Profiling in Methicillin‐Resistant Staphylococcus aureus Reveals the Broad Reactivity of a Carmofur‐Derived Probe
Authors: Uddin Md Jalal , Overkleeft Hermen S. , Lentz Christian S. 
Published: August 2023

AbstractActivity‐based protein profiling is a powerful chemoproteomic technique to detect active enzymes and identify targets and off‐targets of drugs. Here, we report the use of carmofur‐ and activity‐based probes to identify biologically relevant enzymes in the bacterial pathogen Staphylococcus aureus. Carmofur is an anti‐neoplastic prodrug of 5‐fluorouracil and also has antimicrobial and anti‐biofilm activity. Carmofur probes were originally designed to target human acid ceramidase, a member of the NTN hydrolase family with an active‐site cysteine nucleophile. Here, we first profiled the targets of a fluorescent carmofur probe in live S. aureus under biofilm‐promoting conditions and in liquid culture, before proceeding to target identification by liquid chromatography/mass spectrometry. Treatment with a carmofur‐biotin probe led to enrichment of 20 enzymes from diverse families awaiting further characterization, including the NTN hydrolase‐related IMP cyclohydrolase PurH. However, the probe preferentially labeled serine hydrolases, thus displaying a reactivity profile similar to that of carbamates. Our results suggest that the electrophilic N‐carbamoyl‐5‐fluorouracil scaffold could potentially be optimized to achieve selectivity towards diverse enzyme families. The observed promiscuous reactivity profile suggests that the clinical use of carmofur presumably leads to inactivation of a number human and microbial enzymes, which could lead to side effects and/or contribute to therapeutic efficacy.