bluuebunny/crossref_metadata_2025_split huggingface dataset:
The development of imatinib as a therapeutic agent for chronic myeloid leukemia
Authors: Deininger Michael , Buchdunger Elisabeth , Druker Brian J. 
Published: December 2004

AbstractImatinib has revolutionized drug therapy of chronic myeloid leukemia (CML). Preclinical studies were promising but the results of clinical trials by far exceeded expectations. Responses in chronic phase are unprecedented, with rates of complete cytogenetic response (CCR) of more than 40% in patients after failure of interferon-α (IFN) and more than 80% in newly diagnosed patients, a level of efficacy that led to regulatory approval in record time. While most of these responses are stable, resistance to treatment after an initial response is common in more advanced phases of the disease. Mutations in the kinase domain (KD) of BCR-ABL that impair imatinib binding have been identified as the leading cause of resistance. Patients with CCR who achieve a profound reduction of BCR-ABL mRNA have a very low risk of disease progression. However, residual disease usually remains detectable with reverse transcription–polymerase chain reaction (RT-PCR), indicating that disease eradication may pose a significant challenge. The mechanisms underlying the persistence of minimal residual disease are unknown. In this manuscript, we review the preclinical and clinical development of imatinib for the therapy of CML, resistance and strategies that may help to eliminate resistant or residual leukemia.
Differential effect of LFA703, pravastatin, and fluvastatin on production of IL-18 and expression of ICAM-1 and CD40 in human monocytes
Authors: Takahashi Hideo Kohka , Mori Shuji , Iwagaki Hiromi , Yoshino Tadashi , Tanaka Noriaki , Weitz-Schmidt Gabriele , Nishibori Masahiro 
Published: December 2004

AbstractA novel, proinflammatory cytokine, interleukin (IL)-18 production was detected in the medium of human monocytes treated with 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, pravastatin, and fluvastatin (0.1 and 1 μM) but not with the statin-derived lymphocyte function-associated antigen-1 (LFA-1) inhibitor LFA703, which did not inhibit HMG-CoA reductase. Pravastatin and fluvastatin also induced the production of IL-18, tumor necrosis factor α (TNF-α) and interferon-γ (IFN-γ) in human peripheral blood mononuclear cells (PBMC) in contrast to LFA703. IL-18 production by PBMC is located upstream of the cytokine cascade activated by these statins. The IL-18-induced cytokine production was demonstrated to be dependent on adhesion molecule expression on monocytes. In the absence and presence of lower concentrations (0.1 and 1 ng/ml) of IL-18, pravastatin and fluvastatin inhibited the expression of intercellular adhesion molecule (ICAM)-1 and induced the expression of CD40, whereas LFA703 had no effect. In the presence of higher concentrations (5, 10, and 100 ng/ml) of IL-18, pravastatin, fluvastatin, and LFA703 similarly inhibited the expression of ICAM-1 and CD40 as well as the production of IL-12, TNF-α, and IFN-γ in PBMC. The effects of pravastatin and fluvastatin but not LFA703 were abolished by the addition of mevalonate, indicating the involvement of HMG-CoA reductase in the action of pravastatin and fluvastatin. Thus, the effects of LFA703 were distinct from those of pravastatin and fluvastatin in the presence of lower concentrations of IL-18. It was concluded that LFA703 has the inhibitory effect on an IL-18-initiated immune response without any activation on monocytes.
Novel Association of Vav2 and Nek3 Modulates Signaling through the Human Prolactin Receptor
Authors: Miller Sommer L. , DeMaria Jamie E. , Freier David O. , Riegel Angela M. , Clevenger Charles V. 
Published: December 2004

AbstractProlactin (PRL) receptor activation contributes to the progression and motility of human breast cancer. This event activates multimeric signaling pathways, including the activation of the Vav family of guanine nucleotide exchange factors. To detect novel proteins interacting with Vav, yeast two-hybrid analysis was performed and demonstrated an interaction between the serine/threonine NIMA (never in mitosis A)-related family kinase p56Nek3 and Vav1. The PRL-dependent interaction of Nek3 with Vav1 and Vav2 was confirmed by coimmunoprecipitation analysis. PRL stimulation of T47D cells induced Nek3 kinase activity and the interaction of Vav2/Nek3 with the PRL receptor. Increased Nek3 levels up-regulated Vav2 serine and tyrosine phosphorylation, whereas knockdown of Nek3 resulted in a reduction of Vav2 phosphorylation. Activation of guanosine triphosphatase Rac-1 in Chinese hamster ovary transfectants required both Nek3 and Vav2 and was inhibited by the overexpression of a kinase inactivating Nek3 mutant. However, overexpression of either Nek3 or kinase-inactive Nek3 had no effect on Vav2-potentiated signal transducer and activator of transcription 5-mediated gene expression. Overexpression of kinase inactive Nek3 in T47D cells led to a 50% increase in apoptosis vs. controls. These data suggest that the PRL-mediated activation of Nek3 contributes differentially to Vav2 signaling pathways involving Rac1 and signal transducer and activator of transcription 5 and implicates Nek3 during PRL-mediated actions in breast cancer.
Visual Impairment and Real-World Home Physical Activity With Home Environment in an Older Population
Authors: Banerjee Seema , Mihailovic Aleksandra , Miller Rhonda , E Jian-Yu , Gitlin Laura N. , Xiong Yingzi , West Sheila , Friedman David S. , Ramulu Pradeep Y. 
Published: February 2024

ImportancePhysical activity levels are lower in visual impairment. However, additional factors, such as home environmental features, which can modify physical activity in this group, are unknown.ObjectiveTo investigate the association between home environment features and home physical activity in patients with visual impairment.Design, Setting, and ParticipantsThis cross-sectional study of clinical patients included participants with glaucoma suspect and primary glaucoma who were 60 years or older with varying degrees of visual field damage. Study participants were recruited from the Johns Hopkins Wilmer Eye Institute Glaucoma Clinic, Baltimore, Maryland, from September 2013 through March 2015. Data were analyzed from December 19, 2022, through December 25, 2022.Main Outcomes and MeasuresTotal in-home steps taken per day was the primary outcome measure; time in daily home physical activity and nonsedentary activity were secondary outcomes.ResultsA total of 153 participants were included in analyses with mean age of 71 (SD, 7.8) years and 71 were female (46%). Sixty percent had more than 1 comorbid illness, about one-third took 5 or more prescription drugs, and median daily home steps were 1137. Median integrated visual field sensitivity was 28 dB. Better-eye median visual acuity in logMAR was 0.05 (20/22 Snellen equivalent). For every 0.1-log unit increment in average measured home lighting, participants took 5% more daily steps (rate ratio [RR], 1.05; 95% CI, 1.00-1.10; P = .04) and had a 3% faster average daily peak cadence (RR, 1.03; 95% CI, 1.01-1.05; P = .01). The average number of nonsedentary activity minutes (RR, 1.04; 95% CI, 1.00-1.07; P = .06), average bout duration (β = 0.03; 95% CI, 0.00-.07; P = .06), and activity fragmentation (β = −0.06; 95% CI, −0.13 to 0.00; P = .06) showed associations with home lighting. The number of hazards was not associated with any activity metric (steps: RR, 1.14; 95% CI, 0.96-1.34; P = .13; peak cadence: RR, 1.00; 95% CI, 0.93-1.08; P = .98; and nonsedentary time: RR, 1.11; 95% CI, 0.98-1.26; P = .11), nor was the frequency of hazards.Conclusions and RelevanceIn this study, results demonstrated that home environment features, particularly lighting, may influence home activity metrics in older adults with visual impairment. Further prospective studies would be needed to confirm if home modifications can improve at-home activity.
Smoking, Drinking, and Dietary Risk Factors for Head and Neck Cancer in Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial Participants
Authors: Lander Daniel P. , Kallogjeri Dorina , Piccirillo Jay F. 
Published: February 2024

ImportanceThere is a paucity of large-scale prospective studies evaluating the risk of developing head and neck cancer (HNC) associated with smoking, drinking, and dietary habits.ObjectiveTo determine the association of smoking, drinking, and dietary habits with the risk of developing HNC.Design, Setting, and ParticipantsA nested cohort survival analysis of Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial participants was performed. Participants were between 55 and 74 years of age and recruited at 10 centers across the US from November 1993 to July 2001. Participants who developed HNC were matched with controls based on demographics and family history of HNC for analysis of smoking habits; for the analysis of drinking and dietary habits, matching was performed on smoking status and duration in addition to demographics and family history of HNC. Data analysis was performed from January to November 2023.ExposuresSmoking, drinking, and dietary habits.Main Outcome and MeasureDiagnosis of HNC.ResultsIn total, 139 926 participants (51% female; mean [SD] age, 62.6 [5.4] years) were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.1 (10.3-13.6) years, 571 of whom developed HNC. HNC risk associated with smoking increased the closer the proximity of the head and neck subsite to the lungs, with the greatest risk associated with smoking observed in laryngeal cancer (current smoker hazard ratio [HR], 9.36; 95% CI, 5.78-15.15 compared to a nonsmoker). For analysis of drinking and dietary habits, 94 466 participants were included in the analysis of smoking habits with a median (IQR) follow-up time of 12.2 (10.5-13.6) years, 264 of whom developed HNC. HNC risk increased with heavy drinking (HR, 1.85; 95% CI, 1.44-2.38) and decreased with consumption of whole grains (HR, 0.78; 95% CI, 0.64-0.94/oz per day), whole fruits (HR, 0.90; 95% CI, 0.82-0.98/cup per day), and overall healthy eating, as scored by Healthy Eating Index 2015 (HR, 0.87; 95% CI, 0.78-0.98/10 points).Conclusions and RelevanceIn this nested cohort study, the risk of HNC associated with smoking was higher for subsites that were closer to the lungs; heavy drinking was associated with greater HNC risk, while healthy eating was associated with a modest reduction in HNC risk.
Fluorogenic RNA Aptamer‐Based Amplification and Transcription Strategy for Label‐free Sensing of Methyltransferase Activity in Complex Matrixes
Authors: Gu Yu , Fan Cunxia , Yang Hongbin , Sun Huiping , Wang Xiaobao , Qiu Xingchen , Chen Bo , Li Chang‐Ming , Guo Chunxian 
Published: February 2024

AbstractDNA methyltransferase is significant in cellular activities and gene expression, and its aberrant expression is closely linked to various cancers during initiation and progression. Currently, there is a great demand for reliable and label‐free techniques for DNA methyltransferase evaluation in tumor diagnosis and cancer therapy. Herein, a low‐background fluorescent RNA aptamer‐based sensing approach for label‐free quantification of cytosine‐guanine (CpG) dinucleotides methyltransferase (M.SssI) is reported. The fluorogenic light‐up RNA aptamers‐based strategy exhibits high selectivity via restriction endonuclease, padlock‐based recognition, and RNA transcription. By combining rolling circle amplification (RCA), and RNA transcription with fluorescence response of RNA aptamers of Spinach‐dye compound, the proposed platform exhibited efficiently ultrahigh sensitivity toward M.SssI. Eventually, the detection can be achieved in a linear range of 0.02–100 U mL−1 with a detection limit of 1.6 × 10−3 U mL−1. Owing to these superior features, the method is further applied in serum samples spiked M.SssI, which delivers a recovery ranging from 92.0 to 107.0% and a relative standard deviation <7.0%, providing a promising and practical tool for determining M.SssI in complex biological matrices.
Organic Catalysis Promotor for Advanced Water Electrolysis
Authors: Lee Sechan , Lee Changsoo , Kim MinJoong , Doo Gisu , Seo Myeongmin , Park Hyeonjung , Lee Yeonsoo , Yun Young Hwa , Kim Ik‐Sun , Jung Hye Bin , Cho Hyun‐Seok 
Published: February 2024

AbstractAchieving carbon neutrality necessitates large‐scale water electrolyzers for green hydrogen production. Accordingly, it is emphasized to develop promising catalyst candidates, which can simultaneously achieve high catalysis efficiency, environmental friendliness, and sustainability. Recently, 3d‐transition‐metal–based catalysts are proposed to replace noble‐metal–based catalysts, which have limited reserves and emit CO2 during their production; however, the limited catalytic performance of 3d‐transition‐metal–based catalysts introduces a tradeoff. Therefore, in this work, the authors focus on suggesting a breakthrough that can intrinsically enhance the catalysis efficiency by adopting a new component in water electrolysis system. Here, a novel concept of organic catalysis promotor (OCP), dissolved in the electrolyte as an additive, which accelerates the sluggish oxygen evolution reaction in alkaline‐based water electrolysis, currently the most mature technology, is proposed. OCP acts as a liquid‐phase cocatalyst, decreasing the activation energy of oxygen evolution reaction by spontaneous chemical reduction to extract an electron from the reaction intermediates. This innovative approach of adopting the OCP of the 2,2,6,6‐tetramethylpiperidine‐1‐oxyl series significantly decreases the overpotential and shows successful general applicability, offering a new rudder in shifting the energy paradigm toward carbon neutrality.
UV‐Induced Synthesis of Graphene Supported Iridium Catalyst with Multiple Active Sites for Overall Water Splitting
Authors: Li Xu , Cao Jianyun , Chen Jiexin , Zhu Yanlei , Xia Huiqi , Xu Zifan , Gu Chengding , Xie Jiyang , Jones Mikey , Lyu Cheng , Corbin Jack , Li Xiaohong , Hu Wanbiao 
Published: February 2024

AbstractCatalysts that can promote the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) are in demand for efficient water splitting. Here, a general and practical UV‐induced synthesis of noble metal catalysts supported on reduced electrochemical graphene oxide (M‐rEGO, M = Ir, Pt or Pd) is proposed. The use of EGO with a low degree of oxidation and the generation of the highly reducing isopropanol radical from added isopropanol and acetone are crucial for this one‐step, one‐pot synthesis. Using Ir as a model material, the vacancies of rEGO allow the interaction of undercoordinated C with Ir, forming multiple active Ir species including single atoms (SAs), dual‐atom pairs (DAs) and nanoparticles. This Ir‐rEGO catalyst exhibits overpotentials of only 42.3 and 294 mV to reach 10 mA cm−2 in 0.5 м H2SO4 for HER and 1 м KOH for OER, respectively, at an extremely low Ir loading (2.1 wt%). The water‐splitting cells featuring Ir‐rEGO catalyst outperform those using commercial Pt/C (20 wt%) and RuO2 catalysts in both acidic and alkaline electrolytes. Density functional theory calculations confirm the stabilization of SAs and DAs at the vacancies of graphene lattice as well as the high activity of DAs in both HER and OER.
Self‐Powered Sweat‐Responsive Structural Color Display
Authors: Kim Taebin , Park Tae Hyun , Lee Jae Won , Lee Dongwook , Mun Seungsoo , Kim Gwangmook , Kim Yeonji , Kim Gwanho , Park Jong Woong , Lee Kyuho , Lee Seung Won , Jeon Seungbae , Ryu Du Yeol , Shim Wooyoung , Kim Jayoung , Park Cheolmin 
Published: February 2024

AbstractDespite the remarkable progress in the development of sweat sensors, self‐powered sweat‐responsive sensing displays that detect sweat in electric signals with simultaneous and direct visualization of the sweat is rarely demonstrated. Here, a self‐powered sweat‐responsive structural color (SC) display enabled by ionomer‐doped block copolymer (BCP) photonic crystals (PCs) is presented. The sweat‐responsive BCP PC is developed by employing a cross‐linking single‐mobile ionomer (SMI) with mobile anions anchored to immobile polycations to a 1‐D BCP PC. The hydrophobic SMI‐doped BCP PC is mechanically robust as well as water and temperature‐resistive, exhibiting ionomer concentration‐dependent full visible SCs. Moreover, the mobile anions periodically confined in the SMI‐doped BCP PC harvest triboelectric energy, giving rise to a high‐power density of ≈0.774 Mw cm−2. Cation‐sensitive SC variation is observed in the SMI‐doped BCP PC, allowing the visualization of sweat containing various cations. A skin‐patchable self‐powered sweat‐responsive display is demonstrated in which kirigami‐patterned SMI‐doped BCP PC incorporated in the display can withstand up to 50% strain during exercise. Sweat from the exercise is visualized via SC display and measured using both ionic resistance changes and triboelectric signals. In addition, the integration of sweat sensing membrane into SMI‐doped BCP PC enables the quantification of sweat.
Conversion of Host Cell Receptor into Virus Destructor by Immunodisc to Neutralize Diverse SARS‐CoV‐2 Variants
Authors: Hwang Jaehyeon , Kim Beom Kyu , Moon Seokoh , Park Wonbeom , Kim Kyeong Won , Yoon Jeong Hyeon , Oh Hyunseok , Jung Sangwon , Park Youngseo , Kim Suhyun , Kim Misoo , Kim Soomin , Jung Younghun , Park Myungseo , Kim Jun‐Ho , Jung Sang Taek , Kim Sang Jick , Kim Yong‐Sung , Chung Woo‐Jae , Song Min‐Suk , Kweon Dae‐Hyuk 
Published: February 2024

AbstractThe decreasing efficacy of antiviral drugs due to viral mutations highlights the challenge of developing a single agent targeting multiple strains. Using host cell viral receptors as competitive inhibitors is promising, but their low potency and membrane‐bound nature have limited this strategy. In this study, the authors show that angiotensin‐converting enzyme 2 (ACE2) in a planar membrane patch can effectively neutralize all tested severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants that emerged during the COVID‐19 pandemic. The ACE2‐incorporated membrane patch implemented using nanodiscs replicated the spike‐mediated membrane fusion process outside the host cell, resulting in virus lysis, extracellular RNA release, and potent antiviral activity. While neutralizing antibodies became ineffective as the SARS‐CoV‐2 evolved to better penetrate host cells the ACE2‐incorporated nanodiscs became more potent, highlighting the advantages of using receptor‐incorporated nanodiscs for antiviral purposes. ACE2‐incorporated immunodisc, an Fc fusion nanodisc developed in this study, completely protected humanized mice infected with SARS‐CoV‐2 after prolonged retention in the airways. This study demonstrates that the incorporation of viral receptors into immunodisc transforms the entry gate into a potent virucide for all current and future variants, a concept that can be extended to different viruses.
3D‐Printed Shape Memory Poly(alkylene terephthalate) Scaffolds as Cardiovascular Stents Revealing Enhanced Endothelialization
Authors: Van Daele Lenny , Chausse Victor , Parmentier Laurens , Brancart Joost , Pegueroles Marta , Van Vlierberghe Sandra , Dubruel Peter 
Published: February 2024

AbstractCardiovascular diseases are the leading cause of death and current treatments such as stents still suffer from disadvantages. Balloon expansion causes damage to the arterial wall and limited and delayed endothelialization gives rise to restenosis and thrombosis. New more performing materials that circumvent these disadvantages are required to improve the success rate of interventions. To this end, the use of a novel polymer, poly(hexamethylene terephthalate), is investigated for this application. The synthesis to obtain polymers with high molar masses up to 126.5 kg mol−1 is optimized and a thorough chemical and thermal analysis is performed. The polymers are 3D‐printed into personalized cardiovascular stents using the state‐of‐the‐art solvent‐cast direct‐writing technique, the potential of these stents to expand using their shape memory behavior is established, and it is shown that the stents are more resistant to compression than the poly(l‐lactide) benchmark. Furthermore, the polymer's hydrolytic stability is demonstrated in an accelerated degradation study of 6 months. Finally, the stents are subjected to an in vitro biological evaluation, revealing that the polymer is non‐hemolytic and supports significant endothelialization after only 7 days, demonstrating the enormous potential of these polymers to serve cardiovascular applications.
Granular Hydrogels Improve Myogenic Invasion and Repair after Volumetric Muscle Loss
Authors: Tanner Gabrielle I. , Schiltz Leia , Narra Niharika , Figueiredo Marxa L. , Qazi Taimoor H. 
Published: February 2024

AbstractSkeletal muscle injuries including volumetric muscle loss (VML) lead to excessive tissue scarring and permanent functional disability. Despite its high prevalence, there is currently no effective treatment for VML. Bioengineering interventions such as biomaterials that fill the VML defect to support cell and tissue growth are a promising therapeutic strategy. However, traditional biomaterials developed for this purpose lack the pore features needed to support cell infiltration. The present study investigates for the first time, the impact of granular hydrogels on muscle repair – hypothesizing that their flowability will permit conformable filling of the defect site and their inherent porosity will support the invasion of native myogenic cells, leading to effective muscle repair. Small and large microparticle fragments are prepared from photocurable hyaluronic acid polymer via extrusion fragmentation and facile size sorting. In assembled granular hydrogels, particle size and degree of packing significantly influence pore features, rheological behavior, and injectability. Using a mouse model of VML, it is demonstrated that, in contrast to bulk hydrogels, granular hydrogels support early‐stage (satellite cell invasion) and late‐stage (myofiber regeneration) muscle repair processes. Together, these results highlight the promising potential of injectable and porous granular hydrogels in supporting endogenous repair after severe muscle injury.
Surface Crystallization Modulation toward Highly‐Oriented and Phase‐Pure 2D Perovskite Solar Cells
Authors: Chen Bin , Meng Ke , Qiao Zhi , Zhai Yufeng , Yu Runze , Fang Zhu , Yan Pu , Xiao Mingyue , Pan Li , Zheng Liya , Cao Kecheng , Chen Gang 
Published: February 2024

Abstract2D perovskites have shown great potential toward stable and efficient photovoltaic devices. However, the crystal orientation and phase impurity issues of 2D perovskite films originating from the anisotropic crystal structure and specific growth mechanism have demoted their optoelectronic performances. Here, the surface crystallization modulation technique is introduced to fabricate the high‐quality 2D perovskite films with both vertical crystal orientation and high phase purity by regulating the crystallization dynamics. The solvent atmosphere condition is instituted during film processing, which promotes the formation of an oriented 2D perovskite layer in stoichiometric composition at the vapor–liquid interface and templates the subsequent film growth. The solar cells based on the optimized 2D perovskite films exhibit a power conversion efficiency of 15.04%, the record for 2D perovskites (with the perovskite slab thickness n ≤ 3 and high phase purity). The solar cells based on the highly‐oriented and phase‐pure 2D perovskite films also demonstrate excellent thermal and humidity stabilities.