bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving outcomes in intensified processing via optimization of the cell line development workflow
Authors: Balassi Vincent , Otto Mary , Kretzmer Corey , Petersen Amber , McLaurin Channing , Mahadevan Jana , Gustin Jason , Borgschulte Trissa , Razafsky David 
Published: February 2025

AbstractAs the industry continues to explore the benefits of continuous and intensified manufacturing, it is important to assure that the cell line development (CLD) workflows in practice today are well suited to generate clones that meet the unique challenges associated with these processes. Most cell lines used in intensified processes are currently developed using traditional fed‐batch CLD workflows followed by adaptation of these cell lines to perfusion processes. This method maybe suboptimal as fed‐batch CLD workflows select clones which produce high volumetric titers irrespective of cell growth rate and specific productivity (qP). Although sufficient for fed‐batch processes, performance of cells derived from this traditional CLD workflow may not be maintained in perfusion processes, where an intricate balance of performance parameters is needed. Until now, a thorough investigation into the effect of the CLD workflow on top clone performance in perfusion processes has not been conducted. Here, we show how the CLD workflow impacts cell performance in both fed‐batch and perfusion processes, emphasizing the advantages of adopting a perfusion‐specific CLD workflow which includes the use of medium specially designed for expansion and production in a perfusion setting, scale‐down models which more accurately simulate perfusion process, and the adoption of perfusion‐specific cell line selection criteria. Together, this results in the development of more efficient cell lines, fit for continuous and intensified processing.
A synthetic platform for developing recombinant adeno‐associated virus type 8 producer cell lines
Authors: Lin Yu‐Chieh , Kuo Han‐Jung , Lu Min , Mahl Thomas , Aslanidi George , Hu Wei‐Shou 
Published: February 2025

AbstractRecombinant adeno‐associated virus (rAAV) is one of the most widely used viral vectors for gene therapy. It is used in very high doses for the treatment of many diseases, making large‐scale production for clinical applications challenging. We have established a synthetic biology‐based platform to construct stable production cell lines, which can be induced to produce rAAV2. In this study, we extended our cell line construction pipelines for rAAV2 to rAAV8, a serotype whose tropism makes it attractive for gene delivery in multiple tissues. The Genome Module, encoding the rAAV2 genome, and Replication Modules, containing Rep68, DBP and E4orf6 coding sequences, originally used for rAAV2 were retained, but the Packaging Module was modified to replace the AAV2 intron‐less cap gene (VP123) with that of AAV8. These three genetic modules were integrated into HEK293 genome to generate four rAAV8 producer cell lines VH1‐4, which all produced rAAV8 upon induction. Their productivity was similar to the initial rAAV2 producer cell lines GX2/6 constructed using the same pipeline, but was much lower than conventional triple plasmid transfection. We identified Cap protein production and capsid formation as a potential limiting factor, just as we observed in GX2/6. By integrating more copies of AAV8 VP123 into VH3 clone, the encapsidated rAAV8 titer increased 20‐fold to a level comparable to triple transfection. By tuning induction conditions to modulate capsid production, the full particle content could be elevated. This study demonstrated that our rAAV producer cell line development platform is robust and applicable to different AAV serotypes.
Predictive Value of Neutrophil‐to‐Lymphocyte Ratio for Immune Checkpoint Inhibitor‐Related Myocarditis Among Patients Treated for Non‐Small‐Cell Lung Cancer
Authors: Xue Jian , Liu Chuanbin , Shao Jun , Wang Li , Han Yating , Wang Jing , Wang Jinda 
Published: February 2025

ABSTRACTBackgroundThe predictive value of the neutrophil‐to‐lymphocyte ratio (NLR) for immune checkpoint inhibitors (ICIs) in various tumors remains uncertain despite its use in forecasting the effectiveness of immunotherapy. The purpose of our research was to determine the prognostic significance of NLR for immune checkpoint inhibitor‐related myocarditis in non‐small‐cell lung cancer (NSCLC) patients.MethodsWe enrolled and monitored patients with NSCLC who received ICI therapy at the Fifth Medical Center of Chinese PLA General Hospital between January 1, 2018, and February 20, 2021. NLR was determined before and soon after each cycle of ICIs. All participants in this study were periodically examined for troponin and brain natriuretic peptide (BNP), and an electrocardiogram (ECG) and echocardiography were done. Cox's proportional hazards regression model and receiver operating characteristic (ROC) were used to assess the predictive value for ICI‐related myocarditis.ResultsA total of 146 patients received ICI treatment and completed a follow‐up. Of these, 17 patients (11.64%) developed ICI‐related myocarditis that met the diagnostic criteria. The initial cycle revealed that the NLR was a reliable predictor of potential myocarditis related to ICIs, with an area under the curve (AUC) of 0.833 and a 95% confidence interval (CI) of 0.721–0.945. Following the initial round of ICI treatment, an NLR elevation (NLR ≥ 3.25) appeared to be the most significant standalone indicator of ICI‐related myocarditis (HR: 11.094; 95% CI: 3.186–38.631; p < 0.001).ConclusionsOur study confirmed that NLR elevation in the early phase after ICI treatment of NSCLC is a reliable predictive factor of ICI‐related myocarditis. Regular and frequent cardiac monitoring may help to avoid the occurrence of severe and fatal cases.
Surgical Management of Thick Primary Cutaneous Melanoma in the US
Authors: Cowman Arthur W. , Lourdault Kristel , Hanes Douglas , Weiss Jessica , Nassoiy Sean , Goldfarb Melanie , Essner Richard 
Published: February 2025

ABSTRACTBackgroundThere remains significant variability in the surgical management of thick melanoma patients with clinically node‐negative disease. We evaluated factors influencing overall survival (OS) in these patients, focusing on the surgical management of the primary tumor and nodal basin.MethodsUsing the National Cancer Database, we identified 7647 patients diagnosed between 2012 and 2017 with thick melanoma (> 4 mm, T4) and clinically node‐negative disease. 4332 patients had complete data and met all inclusion criteria. These patients were stratified into three groups based on nodal assessment: sentinel lymph node biopsy (SLNB), elective lymphadenectomy (ELND), or no nodal evaluation (NNE). OS was compared using Kaplan–Meier analyses and multivariable Cox proportional hazard regression.ResultsIn the cohort, 2851 (65.8%) had a SLNB, 799 (18.4%) had an ELND, and 682 (15.7%) had NNE. OS significantly decreased for each millimeter of increasing Breslow thickness. Ulceration, lymphovascular invasion, and tumor‐positive SLN (+SLN) were associated with worse OS (all p < 0.001). The size of surgical margins was not significantly associated with OS. Five‐year OS of patients with SLNB was 67.1% ± 1.2% compared to 57.9% ± 2.3% with ELND and 46.8% ± 2.5% with NNE (p < 0.001). Among +SLN patients, a complete lymph node dissection (CLND) was performed in 400 (62.3%) but was not associated with improved OS (p = 0.67) when compared to the nodal observation group.ConclusionOur results suggest that increasing Breslow thickness and nodal assessment provide important prognostic information regarding OS for thick melanoma patients, which emphasizes the importance of SLNB for staging and confirm the lack of benefit of CLND after +SLN in thick melanoma. The size of surgical margins did not affect OS.
The Robot–Human Paradox: A Meta‐Analysis of Customer Service by Robots Versus Humans on Customer Experience
Authors: de Oliveira Santini Fernando , Lim Weng Marc , Sampaio Claudio Hoffmann , Rasul Tareq , Ladeira Wagner Junior , Thaichon Park , Choudhury Debdutta 
Published: February 2025

ABSTRACTThe integration of robots in customer service has attracted considerable interest from both academia and industry. While some studies highlight positive impacts on customer experience, others report neutral or negative outcomes. This meta‐analysis synthesises findings from 25 articles comprising 62 independent studies, 147 effect sizes, and a cumulative sample of 19,668 participants. The results indicate that robot‐provided services generally reduce customers' positive emotion and intention compared to human‐provided services. However, upon closer scrutiny, we found that robots outperform humans in contexts involving embarrassment (vs. non‐embarrassment) and in services with a utilitarian (vs. hedonic) orientation. Fur, robot use is more effective in low (vs. high) complexity service settings. Furthermore, humanoid robots with visual output capabilities are more effective than non‐humanoid or text‐based robots. Moreover, the negative effects of robots (vs. humans) on customers' satisfaction and intention are less pronounced in product‐oriented industries or sectors like electronics and retail than in service‐oriented ones like healthcare and hospitality. These findings underscore the conditions under which robots are suitable for customer service, thereby providing valuable insights for strategically optimizing their deployment to improve customer experience.
Non‐Ophthalmological Diagnosis of Posterior Dislocation of the Intraocular Lens
Authors: Carillio Guido , Arcuri Pier Paolo , Carillio Flora 
Published: February 2025

ABSTRACTIn case of sudden unilateral vision loss, a detailed search for symptoms and causes is mandatory. Dislocation of the intraocular lens can occur even in the absence of trauma and sometimes is not easily detectable, but must be carefully investigated and treated.
Assessing Career Decision‐Making Interventions: Effects of Career Courses and Group Counseling on High School Students
Authors: Zeng Hang , Ma Congfen 
Published: February 2025

ABSTRACTCareer decision‐making significantly impacts high school students' academic and career trajectories. Although career interventions are recognized as important, gaps persist, particularly in programs targeting Chinese high school students and the inconsistent findings on gender differences. This study evaluated the effects of career courses and group counseling on Chinese high school students. Study 1 assessed the impact of a career course on 308 first‐year high school students. The course increased self‐efficacy but did not reduce career decision‐making difficulties. Notably, gender differences were observed: male students reported increased difficulties, while female students showed a decreasing trend. Study 2 combined a career course with group counseling. The combined intervention significantly reduced career decision‐making difficulties, with no gender differences. These findings suggest that career courses boost self‐efficacy but adding group counseling helps address career decision‐making difficulties. Our study also highlights the need for gender‐responsive strategies.
Experimental investigation of spreading dynamics of glycerol droplets on a heated surface
Authors: Durubal Merve , Munck Martijn , Buist Kay , Kuipers J. A. M. (Hans) , Baltussen Maike 
Published: February 2025

AbstractThe dynamics of droplets impacting on solid surfaces are widely encountered in industrial applications. This paper presents an experimental study of the spreading dynamics of droplets of liquids with a temperature‐dependent viscosity on a heated horizontal sapphire surface. This surface can be heated between 40 and 90°C and allows for usual observation from different directions. The used liquids are glycerol water solutions with a volume percentage of 80%, 85.2%, and 92.8% glycerol, which feature a large dependency of the viscosity on the temperature. Using high‐speed imaging and infrared thermography, the shape of the droplet and the temperature of the droplet surface in contact with the surface are measured, respectively. Our experiments reveal that the spreading of the droplets increases with an increase in the surface temperature, which is also expected as the effective viscosity of the liquid will decrease with an increase in the droplet temperature. However, the heating of the droplets ensures that these effects only are apparent after sufficient time to heat the droplet. In addition, the amplitude of the oscillations in the spreading of the surface will increase when the temperature of the surface is increased, which is also related to the decreased viscosity. Finally, the effects on the local spreading cannot be directly correlated to the temperature of the droplet in contact with the surface, which indicates that the viscosity in the droplet is not homogeneous during the experiment and local gradients in the viscosity are important in the overall spreading behaviour of the droplet.
A General Approach for Fluoroalkylation of O‐Nucleophiles with Monofluoroalkylated Sulfonium Ylides†
Authors: Xiao Yisa , Shen Qilong 
Published: February 2025

Comprehensive SummaryThe development of a series of shelf‐stable monofluoroalkylated sulfonium ylide reagents and their reactions with a variety of O‐nucleophiles including phenols, sulfonic acids, carboxylic acids, 1‐hydroxy‐benzotrizoles, amino acids was described. In general, monofluoroakylated sulfonium ylides were synthesized in three steps from commercially available starting materials including thiophenols, alkyl halides and dimethyl 2‐diazomalonate. Reactions with the O‐nucleophiles occurred under mild conditions and afforded the corresponding monofluoroalkylated ethers, sulfonates, and esters in good to excellent yields, thus providing a robust approach for the preparation of these compounds. Further expansion of monofluoroalkylation of C‐terminus of peptides potentially provided modified drug‐like peptides.
The Scoring Model to Predict ICU Stay and Mortality After Emergency Admissions in Atrial Fibrillation: A Retrospective Study of 30 366 Patients
Authors: Hong Tao , Huang Jian , Deng Jiewen , Kuang Lirong , Sun Mengyan , Wang Qianqian , Luo Chao , Zhao Jikai , Liu Xiaozhu , Wang Huishan 
Published: February 2025

ABSTRACTBackgroundThe rapid assessment of the conditions is crucial for the prognosis of atrial fibrillation (AF) patients admitted to the emergency department (ED). We aim to derive and validate a more accurate and simplified scoring model to optimize the triage of AF patients in the ED.Materials and MethodsWe conducted a retrospective study using data from the Medical Information Mart for Intensive Care (MIMIC‐IV) database and developed scoring models employing the Random Forest algorithm. The area under the receiver operating characteristic (ROC) curve (AUC) was used to measure the performance of the prediction for intensive care unit (ICU) stay, and the death likelihood within 3, 7, and 30 days following the ED admission.ResultsThe study included 30 366 AF patients, randomly divided into training, validation, and testing cohorts at a 7:1:2 ratio. The training set consisted of 21 257 patients, the validation set included 3036 patients, and the remaining 6073 patients were classified as the validation set. Among the cohorts, 9594 patients (32%) required ICU transfers, with mortality rates of 1% at 3 days, 3% at 7 days, and 6% at 30 days. In the testing set, the scoring models demonstrated strong discriminative ability with AUCs of 0.724 for ICU stay, 0.782 for 3‐day mortality, 0.755 for 7‐day mortality, and 0.767 for 30‐day mortality.ConclusionWe derived and validated novel simplified scoring models with good discriminative performance to predict the likelihood of ICU stay, 3‐day, 7‐day, and 30‐day death in AF patients after ED admission.
Instigating Visible Light Inspired DNA Impairment by ROS Harvesting Ir(III)‐Cyclometallated Imidazophenanthroline Complexes Against MDA‐MB‐231 Cells
Authors: Ghosh Sreejani , Paira Priyankar 
Published: February 2025

AbstractDifficulties to abate the vehemence of deleterious triple‐negative breast cancer (TNBC) is an ardent issue in the current context of anticancer research due to the lack of a selective treatment modality. To address this issue, herein we have endeavored to establish the imidazophenanthroline‐based Ir(III)‐cyclometallated heteroleptic complexes, suited for the one‐photon photodynamic therapy (OP‐PDT) under irradiation of visible light (400–700 nm) possessing long‐lived excited triplet state and significant photostability. Among three synthesized complexes, [L1Ir], [L2Ir], [L3Ir], the complex [L2Ir] has been recognized as the most competent complex to exhibit selective phototoxicity (IC50=3.8 μM; PIc=78.94) in MDA‐MB‐231 triple‐negative breast cancer cells. The significant phototoxicity of the complexes has arisen due to the production of reactive singlet oxygen (1O2) following the type‐II pathway (Φs=0.26). Also, the complexes have shown the proficiency in oxidation of reduced nicotinamide adenine dinucleotide (NADH) (TOF=4.35 h−1) indicating the possibility of reactive oxygen species (O2⋅−, ⋅OH) generation through type‐I pathway upon visible light irradiation. Along with this, intracellular glutathione (GSH) depletion capabilities have endued the complexes to unarm the TNBC cells in front of the profuse amount of ROS instigating the programmed cell death (PCD) through substantial DNA damage.
Secretory Production of Heterologous Antimicrobial Peptides in Corynebacterium glutamicum
Authors: Long Wei , Apitius Lina , Lenz Patrick , Jakob Felix , Ruff Anna Joёlle , Schwaneberg Ulrich 
Published: February 2025

ABSTRACTAntimicrobial peptides (AMPs) are host defense peptides that act against a broad spectrum of microorganisms. AMPs are of high interest as medicinal products, antimicrobial coatings, and for controlling biofilm formation. Applications and research of many AMPs are still hampered by insufficient titers and lack of production platforms that can tolerate high titers of AMPs. Corynebacterium glutamicum is an excellent microbial host for protein secretion and has been barely explored as a host for AMP production. Here, we report the successful production and secretion of two AMPs (amounts of up to 130 mg/L for liquid chromatography peak I [LCI] and 54 mg/L for Psoriasin) by C. glutamicum with low amounts of secreted byproducts.
Performance Optimization of Double U‐Tube Borehole Heat Exchanger for Thermal Energy Storage
Authors: Kerme Esa Dube , Fung Alan S. , Saghir M. Ziad 
Published: February 2025

ABSTRACTThis paper presents an optimization study of the thermal performance of a double U‐tube borehole heat exchanger (BHE) with two independent circuits that can be used in borehole thermal energy storage. The study applies the Taguchi method and utility concept to obtain the optimum parameters for two objective functions: maximum heat transfer rate and thermal effectiveness of the BHE. A validated numerical heat transfer model with a fully implicit method is applied to compute the transient heat transfer in the BHE. The Taguchi optimization results revealed that the optimal factors (denoted with letters and numbers showing their levels) for achieving the maximum heat transfer rate and thermal effectiveness are A1B3C2D1E3F3G3H3 and A3B3C2D3E3F3G1H1, respectively. This resulted in an optimal heat transfer rate of 120 W/m and a thermal effectiveness of 69.3%. Using the utility concept method, a single set of optimal parameters (denoted by their levels as A3B3C3D2E3F3G2H3) is obtained to maximize the performance of the BHE. These parameters yielded an optimum heat transfer rate of 87.3 W/m and thermal effectiveness of 54.6%. Finally, analysis of variance (ANOVA) showed that ground thermal conductivity, the inlet temperature of the working fluid, and borehole depth are the most influential parameters affecting the performance of the BHE. The study provides crucial information for performance improvement, enhanced energy savings, reduced environmental impact, and optimization of a hybrid ground source heat pump system that can be integrated with borehole thermal energy storage.
Understanding the Demand‐Side of an Illegal Market: A Case Study of the Prohibition of Menthol Cigarettes
Authors: Kenkel Don , Mathios Alan , Phillips Grace , Suryanarayana Revathy , Wang Hua , Zeng Sen 
Published: February 2025

ABSTRACTEconomic research has long focused on illegal markets and the consequences of prohibitions. We provide a case study of the proposed prohibition of menthol cigarettes, which are smoked by almost 19 million people in the U.S. Illegal markets for menthol cigarettes could not only blunt the prohibition's intended consequence to reduce smoking but could also lead to unintended consequences. We use data from a discrete choice experiment. Our mixed logit model predicts a substantial potential consumer demand for illegal menthol cigarettes, especially if menthol e‐cigarettes are also illegal.
Convolutional Block Attention Module and Parallel Branch Architectures for Cervical Cell Classification
Authors: Cömert Zafer , Efil Ferat , Türkoğlu Muammer 
Published: February 2025

ABSTRACTCervical cancer persists as a significant global health concern, underscoring the vital importance of early detection for effective treatment and enhanced patient outcomes. While traditional Pap smear tests remain an invaluable diagnostic tool, they are inherently time‐consuming and susceptible to human error. This study introduces an innovative approach that employs convolutional neural networks (CNN) to enhance the accuracy and efficiency of cervical cell classification. The proposed model incorporates the Convolutional Block Attention Module (CBAM) and parallel branch architectures, which facilitate enhanced feature extraction by focusing on crucial spatial and channel information. The process of feature extraction entails the identification and utilization of the most pertinent elements within an image for the purpose of classification. The proposed model was meticulously assessed on the SIPaKMeD dataset, attaining an exceptional degree of accuracy (92.82%), which surpassed the performance of traditional CNN models. The incorporation of sophisticated attention mechanisms enables the model to not only accurately classify images but also facilitate interpretability by emphasizing crucial regions within the images. This study highlights the transformative potential of cutting‐edge deep learning techniques in medical image analysis, particularly for cervical cancer screening, providing a powerful tool to support pathologists in early detection and accurate diagnosis. Future work will explore additional attention mechanisms and extend the application of this architecture to other medical imaging tasks, further enhancing its clinical utility and impact on patient outcomes.