bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of endogenous Kv1.3 channel isoforms in T cells
Authors: Serna Julia , Peraza Diego A. , Moreno‐Estar Sara , Saez Juan J. , Gobelli Dino , Simarro Maria , Hivroz Claire , López‐López José R. , Cidad Pilar , de la Fuente Miguel A. , Pérez‐García M. Teresa 
Published: March 2023

AbstractVoltage‐dependent potassium channel Kv1.3 plays a key role on T‐cell activation; however, lack of reliable antibodies has prevented its accurate detection under endogenous circumstances. To overcome this limitation, we created a Jurkat T‐cell line with endogenous Kv1.3 channel tagged, to determine the expression, location, and changes upon activation of the native Kv1.3 channels. CRISPR‐Cas9 technique was used to insert a Flag‐Myc peptide at the C terminus of the KCNA3 gene. Basal or activated channel expression was studied using western blot analysis and imaging techniques. We identified two isoforms of Kv1.3 other than the canonical channel (54 KDa) differing on their N terminus: a longer isoform (70 KDa) and a truncated isoform (43 KDa). All three isoforms were upregulated after T‐cell activation. We focused on the functional characterization of the truncated isoform (short form, SF), because it has not been previously described and could be present in the available Kv1.3−/− mice models. Overexpression of SF in HEK cells elicited small amplitude Kv1.3‐like currents, which, contrary to canonical Kv1.3, did not induce HEK proliferation. To explore the role of endogenous SF isoform in a native system, we generated both a knockout Jurkat clone and a clone expressing only the SF isoform. Although the canonical isoform (long form) localizes mainly at the plasma membrane, SF remains intracellular, accumulating perinuclearly. Accordingly, SF Jurkat cells did not show Kv1.3 currents and exhibited depolarized resting membrane potential (VM), decreased Ca2+ influx, and a reduction in the [Ca2+]i increase upon stimulation. Functional characterization of these Kv1.3 channel isoforms showed their differential contribution to signaling pathways involved in formation of the immunological synapse. We conclude that alternative translation initiation generates at least three endogenous Kv1.3 channel isoforms in T cells that exhibit different functional roles. For some of these functions, Kv1.3 proteins do not need to form functional plasma membrane channels.
Population Pharmacokinetics of Monalizumab in Patients With Advanced Solid Tumors
Authors: Hwang Michael , Fan Chunling , Yue Mun Sang , Zhou Diansong , Paturel Carine , Andre Pascale , Cheng Lin‐Yang , Mitchell Patrick , Kourtesis Panagiotis , Ruscica Dario , Das Mayukh , Morsli Nassim , Ren Song , Gibbs Megan , Phipps Alex , Song Xuyang 
Published: March 2023

AbstractMonalizumab is a novel, first‐in‐class humanized immunoglobulin G4 monoclonal antibody immune checkpoint inhibitor that targets the inhibitory CD94/NKG2A receptors. The objectives of this analysis were to develop a population pharmacokinetic (PK) model of monalizumab, evaluate the impact of clinically relevant covariates on monalizumab PK, and provide dose justification for clinical trials. We developed a monalizumab population PK model to characterize the PK properties of monalizumab in patients with advanced solid tumors or head and neck squamous cell carcinoma. Data from clinical studies D419NC00001 (NCT02671435) and IPH2201‐203 (NCT02643550) were pooled for the analysis, resulting in a data set of 3066 PK samples derived from 507 subjects. The PK of monalizumab were reasonably described by a 2‐compartment model with first‐order elimination. Monalizumab generally exhibited linear PK over a dose range of 22.5‐750 mg or 10 mg/kg every 2 weeks. The estimate of clearance was ≈0.255 L/day, and apparent volume of distribution was 6.36 L for a typical individual, consistent with previous findings for endogenous immunoglobulin Gs and other therapeutic monoclonal antibodies. Baseline albumin and body weight were identified as significant covariates of clearance; body weight, sex, and smoking status had a significant impact on volume of distribution; and none of these covariates had impact on peripheral volume of distribution. Although these covariates were identified as statistically significant, they are considered to be not clinically meaningful, as changes in monalizumab exposure were <30%. Therefore, no dose adjustments of monalizumab based on patient or disease characteristics are recommended.
Transcriptome mapping of renal clear cell carcinoma revealed by machine learning algorithm based on enhanced computed tomography images
Authors: Yang Yu , Huang Hang , Liang Haote 
Published: March 2023

AbstractBackgroundA growing number of studies have shown that inflammation‐related components of the tumor microenvironment (TME) affect the clinical outcomes of cancer patients, and advances in radiomics may help predict survival and prognosis.MethodsWe performed a systematic analysis of inflammation‐related genes (IRGs) in clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus and mapped their interaction network to assess the specific relationship between these differentially expressed inflammation‐related genes (DEIRGs) and inflammation. The association between DEIRGs and prognosis was discussed and further validated using consensus cluster analysis. Next, we constructed IRGs‐related risk score from the collected information and validated the prognostic value of the model using Kaplan–Meier survival analysis and receiver operating characteristic analysis. Computed tomographic images corresponding to the TCGA‐ccRCC cohort were obtained from the Cancer Imaging Archive database for radiomics signature extraction.ResultsWe screened for prognostic IRGs and found that they were positively correlated with inflammatory cells in the tumor microenvironment associated with tumor progression and metastasis, such as activated CD8+ cells, myeloid‐derived suppressor cells and neutrophils. The impact of IRGs on the prognosis of ccRCC patients was also verified. Using these differentially expressed genes, we successfully constructed a risk signature and validated its good prognosis assessment for patients. Furthermore, radiomics‐based prognostic models performed better than those using risk signatures or clinical characteristics.ConclusionsIRG‐related risk scores play an important role in assessing the prognosis and improving the management of patients with ccRCC. Through this feature, the infiltration of immune cells in the TME can be predicted. Furthermore, non‐invasive radiomics signatures showed satisfactory performance in predicting ccRCC prognosis.
MAML1‐induced HPV E6 oncoprotein stability is required for cellular proliferation and migration of cervical tumor‐derived cells
Authors: Skelin Josipa , Đukić Anamaria , Filić Vedrana , Hufbauer Martin , Akgül Baki , Thomas Miranda , Banks Lawrence , Tomaić Vjekoslav 
Published: March 2023

AbstractWhile a small proportion of high‐risk (HR) alpha (α) human papillomaviruses (HPVs) is associated with numerous human malignancies, of which cervical cancer is the most prevalent, beta (β) HPVs predominantly act as co‐factors in skin carcinogenesis. A characteristic feature of both α‐ and β‐E6 oncoproteins is the presence of the LXXLL binding motif, which α‐E6s utilize to form a complex with E6AP and which enables β‐E6s to interact with MAML1. Here we show that multiple α‐E6 oncoproteins bind to MAML1 via the LXXLL binding motif and that this results in increased protein stability. Moreover, β‐E6 oncoprotein stability is also dependent on the interaction with MAML1. Additionally, in the absence of MAML1, endogenous HPV‐8 E6 and HPV‐18 E6 are rapidly degraded at the proteasome. Ablation of both E6AP and MAML1 leads to an even more profound downregulation of α‐E6 protein expression, whereas this is not observed with β‐E6. This highly suggests that there is one cellular pool for most of β‐E6 that interacts solely with MAML1, whereas there are two cellular pools of HR α‐E6, one forming a complex with MAML1 and the other interacting with E6AP. Furthermore, MAML1 induces HPV‐8 E6 shuttling from the nucleus to the cytosolic fraction, while MAML1 interaction with HR E6 induces a drastic nuclear and membrane upregulation of E6. Interestingly, the HR α‐E6/MAML1 complex does not affect targeting of some of the known HR E6 cellular substrates such as p53 and DLG1. However, MAML1 and E6AP joint co‐expression with HR α‐E6 leads to a significant increase in cellular proliferation, whereas silencing MAML1 decreases wound closure in HeLa cells. These results demonstrate that HR α‐E6 interaction with MAML1 results in a stable form of E6, which likely modulates MAML1's normal cellular activities, one consequence of which being an increased proliferative capacity of HPV‐transformed cancer cells. Thus, this study shows a novel function of the α‐E6 oncoprotein and how it's activity might affect HPV‐induced pathogenesis.
Urinary isoxanthopterin as a novel predictor following catheter ablation for atrial fibrillation
Authors: Koi Takahisa , Kataoka Naoya , Uchida Keisuke , Imamura Teruhiko , Kinugawa Koichiro 
Published: March 2023

AbstractBackgroundOxidative stress is associated with atrial fibrillation recurrence following catheter ablation. Urinary isoxanthopterin (U‐IXP) is one of the noninvasive markers which reflect the reactive oxygen species; however, its ability to predict atrial tachyarrhythmias (ATAs) occurrence following catheter ablation remains uncertain.MethodsAmong the patients who received scheduled catheter ablation for atrial fibrillation, baseline U‐IXP levels were measured just before the procedure. The prognostic impact of baseline U‐IXP upon postprocedural ATAs occurrence was investigated.ResultsAmong 107 patients (71 years old, 68% men), baseline U‐IXP level was 0.33 nmol/gCr on the median. During a mean of 603 days of follow‐up, 32 patients had ATAs. Baseline higher U‐IXP was independently associated with the occurrence of ATAs following catheter ablation with a hazard ratio of 4.69 (95% confidence interval: 1.82–12.37, p = .001) adjusted for the left atrial diameter, a persistent type, and hypertension which were potential confounders, with a cutoff of 0.46 nmol/gCr, which stratified cumulative incidence of ATAs occurrence ( p  < .001).ConclusionU‐IXP can be used as the noninvasive predictive biomarker for ATAs following catheter ablation for atrial fibrillation.
Assessing phosphorus efficiency and tolerance in maize genotypes with contrasting root systems at the early growth stage using the semi‐hydroponic phenotyping system
Authors: Liang Liyan , An Tingting , Liu Shuo , Gao Yamin , Yu Min , Xu Bingcheng , Zhang Suiqi , Deng Xiping , Bolan Nanthi , Siddique Kadambot H. M. , Chen Yinglong 
Published: March 2023

AbstractBackgroundDevelopment of an evaluation tool to determine genotypic variation in phosphorus (P) utilization efficiency is essential to ensure crop productivity and farmers’ income under low P environments.AimsThis study aimed to develop an evaluation tool to determine genotypic variation in low‐P tolerance and P use efficiency under low P environments.MethodsRoot response and P efficiency traits in 20 maize genotypes with contrasting root systems were assessed 32 days after transplanting into the semi‐hydroponic root phenotyping system under low P (10 µM) or optimal P (200 µM) supply.ResultsCompared to optimal P, low P supply increased root‐to‐shoot biomass ratio by 48.7% (shoot dry weight decreased by 20.0% and root dry weight increased by 20.6%). Low P supply increased total root length by 17.8% but decreased primary root depth, with no significant change in lateral root number across all genotypes. Low P stress enhanced P utilization efficiency. Based on genotypic variation and correlations among the 17 measured plant traits in response to low P stress, nine traits were converted to low‐P tolerance coefficients (LPTC), compressed by principal component analysis. The three principal component scores were extracted for hierarchical cluster analysis and classified the 20 genotypes into three groups with different P efficiency, including two P‐efficient genotypes and nine P‐inefficient genotypes.ConclusionsThe study demonstrated genotypic variation in response to low P stress. The P‐efficient genotypes with higher LPTC values better adapted to low P environments by adjusting root architecture and re‐distributing P and biomass in plant organs. The systematic cluster analysis using selected traits and their LPTC values can be used as an evaluation tool in assessing P efficiency among the genotypes.
Pupil size estimation model based on luminance and chromaticity spatial distribution
Authors: Huang Chenyu , Zhang Yuning , He Nailong , Weng Yishi 
Published: March 2023

AbstractAs an important index in studies on vision and display technology, pupil size controls the amount of the light entering human eye. Eye tracking systems are normally used to measure the pupil size while a pupil size estimation model can be applied when actual measurement is not available. The weighting functions of the reported pupil size estimation models show radial symmetry, which contradicted the radial asymmetric distribution of photoreceptors on the retina. Chromaticity spatial distribution has not been taken into consideration either. In this paper, the perceptual experiments are carried out with patterned and colored stimuli to evaluate the spatial and color varying effect of luminance to the pupil. A revised corneal flux density is proposed, which shows a high correlation with pupil diameters. Based on this, a pupil size estimation model is proposed. Pupil diameters can be calculated after inputting luminance and chromaticity spatial distribution matrixes. After verification, this model can be applied to indoor scenes with different lighting temperatures within the general illumination range. This model should be useful in scientific and practical applications where pupil diameter matters.
Severe drug eruption after antibiotic administration in patients receiving immune checkpoint inhibitors: A monocentric case series
Authors: Nishizawa Aya , Takeda Koichi , Urasaki Tetsuya , Ono Makiko , Mochizuki Toshiaki , Shiga Taro , Fujiwara Motohiro , Yuasa Takeshi , Murakami Atsushi , Koike Ryo , Yunokawa Mayu , Kanao Hiroyuki , Shimozaki Keitaro , Takahari Daisuke , Kogawa Takahiro , Takahashi Shunji , Kitano Shigehisa 
Published: March 2023

AbstractImmune checkpoint inhibitor (ICI) therapy is often associated with cutaneous immune‐related adverse events (irAEs). Drug eruptions stemming from concomitantly or consecutively administered medications are also frequent and tend to be severe. We herein present three cases of severe drug eruption in patients receiving antibiotics during ICI therapy in which hypotensive shock occurring during antibiotic administration was followed by generalized erythema and prolonged organ damage. Three patients received tazobactam/piperacillin (TAZ/PIPC) for an infection during ICI treatment. A high fever developed in all the patients after a switch was made to other antibiotics (Figures 2–4). Since no skin rash was observed at fever onset, a flare‐up of the infection was suspected, and TAZ/PIPC administration was resumed. Thereafter, the patients suddenly experienced hypotensive shock and respiratory failure requiring ICU management for generalized erythema and organ damage. Since anaphylaxis caused by TAZ/PIPC is rare, the patients’ clinical findings might be a manifestation of synergistic, complementary, immunomodulatory effects of ICI. In patients receiving ICI therapy, a fever occurring during antibiotic administration may indicate the onset of an immune hypersensitivity reaction to the drug. Resumption of antibiotic administration, especially TAZ/PIPC, during such a period may trigger an excessive inflammatory response, leading to an anaphylaxis‐like reaction and organ damage.
Complications associated with costal cartilage harvest in pediatric laryngotracheal reconstruction
Authors: Lava Christian X. , Martin Taylor S. , Leonard James A. , Blumenthal Daniel L. , Scriven‐Weiner Kelly , Chu Eugenia , Harley Earl H. 
Published: March 2023

AbstractObjectiveWe aimed to determine the rate of complications associated with autologous costal cartilage graft harvest for pediatric laryngotracheal reconstruction (LTR). Secondarily, we sought to identify risk factors associated with the harvest of autologous costal cartilage, as well as evaluate management strategies.Data SourcesAn electronic database search of Ovid MEDLINE, Ovid EMBASE, and PubMed was completed for articles pertaining to complications in autologous costal cartilage harvest for pediatric LTR.Review MethodsThis systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 guidelines. The study characteristics, operative information, and patient demographics were collected. The data concerning postoperative complications, risk factors, and management strategies were collected and analyzed for patterns.ResultsA total of 31 manuscripts representing 745 patients were included for analysis. The reported donor site complications included pneumothorax (n = 13, 1.74%), pleural tear (n = 5, 0.67%), infection (n = 8, 1.07%), and scar‐related problems (n = 2, 0.26%). There were no reported cases of seroma, persistent pain, or chest wall deformity. Only five studies discussed the management of donor site complications, with intervention in 11 (39.28%) patients including chest tube drainage and steroid injection.ConclusionThere is significant variability in the literature regarding complication rates in autologous costal cartilage harvest for pediatric LTR. The incidence of major postoperative complications is low and supports the use of autologous costal cartilage as graft material for pediatric LTR.Level of EvidenceNA.
Oxidized Dextran/Chitosan Hydrogel Engineered with Tetrasulfide‐Bridged Silica Nanoparticles for Postsurgical Treatment
Authors: Hu Lele , Song Chunli , Li Hongyi , Gao Yao , Zhang Jing , Gao Ting , Wei Youhua , Xu Zhuoran , Xue Weiming , Huang Saipeng , Wen Huiyun , Li Zigang , Wu Jun 
Published: March 2023

AbstractTumor recurrence and wound microbial infection after tumor excision are serious threats to patients. Thus, the strategy to supply a sufficient and sustained release of cancer drugs and simultaneously engineer antibacterial properties and satisfactory mechanical strength is highly desired for tumor postsurgical treatment. Herein, A novel double‐sensitive composite hydrogel embedded with tetrasulfide‐bridged mesoporous silica (4S‐MSNs) is developed. The incorporation of 4S‐MSNs into oxidized dextran/chitosan hydrogel network, not only enhances the mechanical properties of hydrogels, but also can increase the specificity of drug with dual pH/redox sensitivity, thereby allowing more efficient and safer therapy. Besides, 4S‐MSNs hydrogel preserves the favorable physicochemical properties of polysaccharide hydrogel, such as high hydrophilicity, satisfactory antibacterial activity, and excellent biocompatibility. Thus, the prepared 4S‐MSNs hydrogel can be served as an efficient strategy for postsurgical bacterial infection and inhibition of tumor recurrence.
Laccase Immobilization Using Polymeric Supports for Wastewater Treatment: A Critical Review
Authors: Iqhrammullah Muhammad , Fahrina Afrillia , Chiari Williams , Ahmad Khairunnas , Fitriani Fitriani , Suriaini Nanda , Safitri Eka , Puspita Kana 
Published: March 2023

AbstractGlobal threat from emerging contaminants to human health has pushed researchers to develop pollutant removal technologies including those based on biocatalytic degradation. Laccase, a multicopper enzyme, is reported for its applicability in treating wastewater and industrial effluent by catalyzing reduction of O2 to H2O in the presence of substrates (phenolic or non‐phenolic compounds). Scientific papers have discussed the ability of this enzyme to breakdown hazardous contaminants ranging from azo dyes, antibiotics, and up to hormones. Nonetheless, the cost production of this enzyme is high, hence the importance of the immobilization into solid supports. Polymers are considered suitable for the immobilization because they are easy for modification and have adjustable characteristics. This review discusses the immobilization of laccase into polymers via various techniques (adsorption, cross‐linking, covalent binding, encapsulation, and entrapment) and its implications on the pollutant removal performance. In addition, bibliometric analysis is performed and summarized the advantages and disadvantages of each immobilization technique.
The more the better? The negative effect of disseminators' donations in online donation
Authors: Zhu Guowei , Lu Jinfeng , Zhou Li , Luo Yingyu 
Published: March 2023

AbstractOnline donation platforms often present information regarding disseminators' donations to stimulate donations, but it is unclear how it affects potential donors' behavior. This paper examines how disseminators' donation amounts impact potential donors' donation likelihood. The findings of six studies show that potential donors are less (vs. more) likely to contribute to unfamiliar initiators when disseminators contribute large (vs. small) amounts. The following psychological response drives the effect: when potential donors observe disseminators contribute more, they infer that disseminators have assumed greater responsibility and thus reduce their perceived responsibility to the unfamiliar initiator. We also confirm the boundary conditions of tie strength and empathy. This effect is significant when donors have low levels of empathy or strong ties with the disseminator. In contrast, this effect is reversed when tie strength is high and attenuated when potential donors have high levels of empathy. Our research enriches the literature concerning the effects of others' donations and online donation and provides managerial guidance to enable the success of online donation projects.
What is it like to be idle versus busy for a service machine?
Authors: Söderlund Magnus 
Published: March 2023

AbstractCustomers have since long received service from various machines, and this development is expected to accelerate when AI‐powered synthetic agents—such as chatbots and embodied service robots—become more common. Existing research on customers' interactions with service machines is typically focused on perceptions of machine attributes when the machine is busy. However, many machines are idle for a considerable time (i.e., they are not used), and little is known about consumer perceptions of machine idleness—despite the fact that idle machine behavior can contribute to the user experience, too. In the present study, it is assumed that (a) idleness and busyness represent differently valenced states in a human‐to‐human context (i.e., idleness is more negatively charged than busyness for most humans). It is also assumed that (b) anthropomorphism can occur in relation to a service machine, and that (c) beliefs about idleness and busyness from a human‐to‐human context can carry over and inform views of machines' minds. Three experiments were conducted to explore these assumptions, and they show that an idle service machine is attributed less positively charged mind states than a busy service machine. The results also show that such attribution activities affect the overall evaluation of the service machine.