bluuebunny/crossref_metadata_2025 huggingface dataset:
Strain‐Induced Decoupling Drives Gold‐Assisted Exfoliation of Large‐Area Monolayer 2D Crystals
Authors: Ziewer Jakob , Ghosh Abyay , Hanušová Michaela , Pirker Luka , Frank Otakar , Velický Matěj , Grüning Myrta , Huang Fumin
Published: February 2025

Gold‐assisted exfoliation (GAE) is a groundbreaking mechanical exfoliation technique that produces centimeter‐scale single‐crystal monolayers of 2D materials. Such large, high‐quality films offer unparalleled advantages over the micron‐sized flakes typically produced by conventional exfoliation techniques, significantly accelerating the research and technological advancements in the field of 2D materials. Despite its wide applications, the fundamental mechanism of GAE remains poorly understood. In this study, using MoS₂ on Au as a model system, ultra‐low frequency Raman spectroscopy is employed to elucidate how the interlayer interactions within MoS2 crystals are impacted by the gold substrate. The results reveal that the coupling at the first MoS2‐MoS2 interface between the adhered layer on the gold substrate and the adjacent layer is substantially weakened, with the binding force being reduced to nearly zero. This renders the first interface the weakest point in the system, thereby the crystal preferentially cleaves at this junction, generating large‐area monolayers with sizes comparable to the parent crystal. Biaxial strain in the adhered layer, induced by the gold substrate, is identified as the driving factor for the decoupling effect. The strain‐induced decoupling effect is established as the primary mechanism of GAE, which can also play a significant role in general mechanical exfoliations.
Toward High‐Performance, Flexible, Photo‐Assisted All‐Solid‐State Sodium‐Metal Batteries: Screening of Solid‐Polymer‐Based Electrolytes Coupled with Photoelectrochemical Storage Cathodes
Authors: Wang Rong‐Hao , Zhang Yu‐Zhen , Wang Weiyi , Ni Jia‐Hao , Hu Wei , Yue Liang , Zhang Wan‐Qun , Pei Gang , Yang Shangfeng , Chen Li‐Feng
Published: February 2025

The advancement of photo‐assisted rechargeable sodium‐metal batteries with high energy efficiency, lightweight structure, and simplified design is crucial for the growing demand in portable electronics. However, addressing the intrinsic safety concerns of liquid electrolytes and the sluggish reaction kinetics in existing photoelectrochemical storage cathodes (PSCs) remains a significant challenge. In this work, functionalized light‐driven composite solid electrolyte (CSE) fillers are systematically screened, and optimized PSC materials are employed to construct advanced photo‐assisted solid‐state sodium‐metal battery (PSSMB). To further enhance the mechanical properties and poly(ethylene oxide) compatibility of the CSE, natural lignocellulose is incorporated, enabling the fabrication of flexible PSSMBs. In situ tests and density functional theory calculations reveal that the light‐driven electric field facilitated sodium salt dissociation, reduced interfacial resistance, and improved ionic conductivity (0.1 mS cm−1). Meanwhile, energy‐level matching of the PSC maximized the utilization of photogenerated carriers, accelerating reaction kinetics and enhancing interface compatibility between the electrolyte and cathode. The resulting flexible pouch‐type PSSMB demonstrates a remarkable discharge capacity of 117 mAh g−1 and outstanding long‐term cycling stability, retaining 89.1% of its capacity and achieving an energy storage efficiency of 96.8% after 300 cycles at 1 C. This study highlights a versatile strategy for advancing safe, high‐performance solid‐state batteries.
T‐Cell‐Dependent Bispecific IgGs Protect Aged Mice From Lethal SARS‐CoV‐2 Infection
Authors: Fu Wenyan , Zhang Wei , You Zhongshuai , Li Guangyao , Wang Chuqi , Lei Changhai , Zhao Jian , Hou Jin , Hu Shi
Published: February 2025

T‐cell ageing may be a key factor in the disproportionate severity of coronavirus disease 2019 (COVID‐19) in older populations. For hospitalized COVID‐19 patients, treatment involving the use of monoclonal antibodies with the ability to neutralize SARS‐CoV‐2 usually involves the administration of high doses but has not been very effective at preventing complications or fatality, highlighting the need for additional research into anti‐SARS‐CoV‐2 therapies, particularly for older populations. In this study, it is discovered that older persons with a severe SARS‐CoV‐2 infection has weaker T‐cell responses. Therefore the development and characterization of spike‐targeting T‐cell‐dependent bispecific (TDB) full‐length human immunoglobulin Gs with enhanced efficacy in the treatment of COVID‐19 is described. Using S‐targeting TDBs, polyclonal T cells are guided to target and destroy S‐expressing cells, preventing the cell‐to‐cell transmission of SARS‐CoV‐2 and thereby eliminating the need for SARS‐CoV‐2‐specific immunity. Using animal models of COVID‐19, it is shown that the selective activation of T cells improves the efficiency of treatment in preinfected mice by attenuating disease‐induced weight loss and death. The significance of T‐cell‐based immunity during infection is highlighted by the findings. These results have implications for better clinical effectiveness of therapies for COVID‐19 and the development of T‐cell‐dependent medicines for the elderly population.
Syngas chemical looping process: Ni–Fe bimetallic oxygen carriers for maximizing blue hydrogen yield
Authors: Luan Chuanbao , Cheng Qifan , Zhu Ningjing , Tong Andrew , Zhang Yinan , Moatswi Usina Martha , Li Shiyu , Zeng Liang , Fan Liang‐Shih
Published: February 2025

The syngas chemical looping (SCL) process is an advanced thermochemical approach for hydrogen production with in situ carbon capture. This article proposes a novel Ni–Fe bimetallic oxide in a three‐reactor chemical looping system. In the moving bed reducer, a mixture of NiO and Fe3O4 is countercurrently reduced by syngas to Ni and Fe/FeO. In the oxidizer, the Fe/FeO mixture is oxidized back to Fe3O4 by steam, producing high‐purity H2, while Ni remains unchanged. In the combustor, Ni is oxidized to NiO by air to supply heat, while Fe3O4 is maintained without further oxidation to Fe2O3. The reducer's operating conditions are optimized using the operating line diagram method and the multistage equilibrium model. Process simulation results show that the Ni–Fe oxygen carrier can increase blue hydrogen production efficiency by more than 5% compared to the Fe‐based SCL process, while ensuring a carbon capture rate of over 99%.
Family closeness and bullying perpetration: The roles of associating with antisocial peers, bullying victimization, exposure to community violence, and gender differences among African American adolescents
Authors: Lawrence Timothy I. , Ettekal Idean , Buffington Carmen S. , Pinales Stephany , Hong Jun Sung , Voisin Dexter R.
Published: February 2025

Bullying victimization and perpetration negatively affect African American students' physical and mental health. Among the many risk factors associated with bullying behaviors, associating with antisocial peers, and exposure to community violence may function as important contextual risk factors, particularly among African American youth residing in underserved urban communities. However, few studies have explored the degree to which family closeness may mitigate these risk factors and serve as a potential promotive mechanism. The current study applies an ecological systems model to assess the nature of associations among adolescents' family, community, and peer contexts with bullying victimization and perpetration while assessing for gender differences (moderation). Results based on a sample of African American adolescents (n = 637, mean age = 15.83, SD = 1.39; 45.6% boys) indicated that for both boys and girls, indirect effects suggested that bullying victimization partially explained the association of associating with antisocial peers and community violence exposure on bullying perpetration. For boys, a significant indirect effect was found from family closeness to bullying perpetration via community violence exposure, and for girls, a direct effect was found from family closeness to bullying perpetration. These latter findings supported the potential promotive functioning of family closeness. Additional implications are discussed.
Design, Synthesis and Optical Properties of 2‐(1‐Azaazulenyl)pyrrole‐Boron Difluoride Complexes
Authors: Yang Fei , Ren Fangqin , Liu Xuanzheng , Zhao Mengna , Zhou Yifeng
Published: February 2025

Herein, 1‐azaazulene‐based BF2 complexes with pyrrole as the amido N‐donor were synthesized via Suzuki‐Miyaura cross coupling of 2‐bromo‐1‐azaazulene and 1‐Boc‐2‐pyrroleboronic acid. The structures, especially the unique N–B linkages, were discussed based on the single crystal analysis and DFT calculations. Compared to the parent BODIPY, the unsubstituted complex 3a exhibited similar absorption maximum and three times larger Stokes shift. The optical properties can be further tuned by introducing aryl substituents at the α‐position of pyrrole moiety.
Baeyer‐Villiger and epoxidation reactions of dihydrocarvone using hydrogen peroxide over Sn‐, Ti‐, Zr‐, and Hf‐beta zeolites: A DFT Study
Authors: Boekfa Bundet , Maihom Thana , Treesukol Piti , Kongpatpanich Kanokwan , Limtrakul Jumras
Published: February 2025

The Baeyer‐Villiger and epoxidation reactions of dihydrocarvone with hydrogen peroxide over zeolite catalysts is investigated using the M06‐L density functional theory. The Baeyer‐Villiger reaction over 38T quantum clusters of Sn‐, Ti‐, Zr‐, and Hf‐beta zeolites is thought to proceed via a two‐step mechanism with apparent activation energies of 5.3, 18.1, ‐1.3, and ‐0.9 kcal/mol and energy spans of 33.6, 40.1, 31.1, and 34.8 kcal/mol, respectively. The calculated activation energies of competitive epoxidation reactions over Sn‐, Ti‐, Zr‐, and Hf‐beta zeolites are 11.2, 16.2, 16.4, and 15.0 kcal/mol, respectively. The Sn‐beta zeolite selectively afforded the lactone product owing to the formation of thermodynamically favored adsorption and product complexes and the lower apparent activation energy of the Baeyer‐Villiger reaction. Zr‐Beta and Hf‐Beta zeolites are thought to be selective catalysts toward Baeyer‐Villiger oxidation. Reactions without zeolites are also studied over m‐chloroperbenzoic acid. The epoxidation is favored over the Baeyer‐Villiger reaction owing to its lower activation energy (16.6 kcal/mol vs. 39.4 kcal/mol). The catalytic activity and chemoselectivity are studied using various Lewis acid zeolite catalysts.
GABAergic modulation of beta power enhances motor adaptation in frontotemporal lobar degeneration
Authors: Hughes Laura E. , Adams Natalie E. , Rouse Matthew A. , Naessens Michelle , Shaw Alexander , Murley Alexander G. , Cope Thomas E. , Holland Negin , Nesbitt David , Street Duncan , Whiteside David J. , Rowe James B.
Published: February 2025

INTRODUCTION

We examined how abnormal prefrontal neurophysiology and changes in gamma‐aminobutyric acid‐ergic (GABAergic) neurotransmission contribute to behavioral impairments in disorders associated with frontotemporal lobar degeneration (FTLD).

METHODS

We recorded magnetoencephalography during an adaptive visuomotor task from 11 people with behavioral‐variant frontotemporal dementia, 11 with progressive supranuclear palsy, and 20 age‐matched controls. We used tiagabine, a gamma‐aminobutyric acid (GABA) re‐uptake inhibitor, as a pharmacological probe to assess the role of GABA during motor‐related beta power changes.

RESULTS

Task impairments were associated with diminished movement‐related beta power. Tiagabine facilitated partial recovery of behavioral impairments and neurophysiology, moderated by executive function, such that the greatest improvements were seen in those with higher cognitive scores. The right prefrontal cortex was revealed as a key site of drug interaction.

DISCUSSION

Behavioral and neurophysiological deficits can be mitigated by enhancement of GABAergic neurotransmission. Clinical trials are warranted to test for enduring clinical benefits from this restorative‐psychopharmacology strategy.

Highlights

Event‐related beta power changes during movement can be altered by the GABA reuptake inhibitor, tiagabine.

In people with behavioral‐variant frontotemporal dementia and progressive supranuclear palsy, tiagabine enhanced beta modulation and concurrently improved task performance, dependent on baseline cognition, and diagnosis.

The effects of the drug suggest a GABA‐dependent beta‐related mechanism that underlies adaptive motor control.

Restoring selective deficits in neurotransmission is a potential means to improve behavioral symptoms in patients with dementia.
Implementing a tridimensional diagnostic framework for personalized medicine in neurodegenerative diseases
Authors: Menendez‐Gonzalez Manuel
Published: February 2025

Neurodegenerative diseases (NDDs) pose a significant challenge in modern medicine due to their clinical heterogeneity, multifactorial etiologies, and frequent co‐pathologies. Traditional diagnostic systems, based on clinical symptoms and post mortem findings, are limited in capturing the complex interactions among genetic, molecular, and neuroanatomical factors. This manuscript introduces a novel tridimensional diagnostic framework that integrates these factors across three key axes: etiology (genetic and environmental influences), molecular markers (primary and secondary biomarkers), and neuroanatomoclinical correlations. Through case studies, we demonstrate the framework's ability to synthesize incomplete datasets, stratify patients, and guide precision medicine. By incorporating omics technologies, neuroimaging, and AI‐driven probabilistic modeling, the framework enhances diagnostic accuracy and clinical relevance. This approach may contribute to overcoming the limitations of traditional nosologies, offering a scalable and adaptable tool for both clinical practice and research and advancing the field of precision medicine in NDD management.

Highlights

Tridimensional diagnostic system: We propose a new framework that incorporates three axes – etiology, molecular markers, and neuroanatomical‐clinical correlations – to enhance diagnostic accuracy for NDDs.

Personalized medicine: The tridimensional system enables the integration of genetic, molecular, and clinical data, allowing for highly personalized treatment strategies tailored to individual patients.

Proteinopathies as key biomarkers: This diagnostic system emphasizes the use of primary proteinopathies (amyloid, tau, synuclein) and secondary biomarkers (eg, NfL, GFAP) to monitor disease progression and treatment efficacy.

Addressing clinical heterogeneity: The framework accommodates the complexity and heterogeneity of NDDs, offering an adaptable diagnostic approach for classical conditions like Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and ALS.

Case studies and real‐world application: Practical case studies illustrate how this system can be implemented in clinical practice, enabling the combination of DMTs with symptomatic treatments.
Spatial Chern‐Simons Interactions and Complex Magnetic Penetration Depth
Authors: Tao Yong
Published: February 2025

This paper examines the Landau‐Ginzburg theory in the presence of spatial Chern‐Simons interactions, which typically emerge in Weyl semimetals due to domain‐wall motion. It is demonstrated that the incorporation of a purely spatial Chern‐Simons term, which violates parity, into the Landau‐Ginzburg free energy leads to a complex magnetic penetration depth. This characteristic indicates that, aside from possessing an effective penetration depth, the magnetic field on the surface of the superconductor experiences periodic spatial oscillations, which significantly deviates from the conventional Meissner effect. In particular, it is observed that as the degree of parity breaking, quantified by the strength of the spatial Chern‐Simons term, increases, a vortex solution with magnetic field inversion may emerge. With the discovery of superconductivity in certain Weyl semimetals, the possibility of experimentally observing this phenomenon in these materials is anticipated.
Pallada‐electrocatalysis enables distal regioselective and atroposelective olefination reactions
Authors: Maiti Debabrata , Panja Subir , Pan Avishek , Biswas Swastik , Das Chandan , Guha Aritra , Nimje Roshan Y. , Dhar T. G. Murali , Gupta Anuradha , Mathur Arvind , Dutta Arnab , Roy Lisa
Published: February 2025

Regioselective and enantioselective C−H functionalization is a valuable method for synthesizing chiral and complex molecules. However, it often requires large amounts of toxic oxidants and high temperature, making it environmentally and economically adverse. Additionally, these traditional approaches generally suffer from regioselectivity and enantioselectivity issues. To overcome these limitations, a new mechanism is needed to control both of these simultaneously. Herein, we report the first Pd catalyzed regioselective distal and atroposelective olefination of simple arenes/biaryls via an electrooxidative reaction pathway. This unique electro‐oxidative strategy with Pd(II) catalysis demonstrates unprecedented access to ‘regio‐resolved’ reactions, furnishing chiral molecule synthesis under dynamic kinetic resolution without the conventional requirement of metal‐based oxidants and thermal energy. Both electroanalytical studies and DFT calculations suggest the involvement of a Pd(II)/Pd(IV) catalytic cycle via a crucial Pd(III) intermediate that initiates both the distal and atroposelective olefination reactions.
Robust Peptide‐Functionalized Gold Nanoparticles via Ethynyl Bonding for High‐Fidelity Bioanalytical Applications
Authors: Du Jinlian , Xu Haili , Zhu Xinyue , Long Keyu , Lang Jiaqi , Jiang Ling , Xiong Erhu , Yang Ronghua , Liu Juewen
Published: February 2025

While Au‐S bonds have been widely applied in preparing gold nanoparticle (AuNP) bioconjugates for biosensing, cell imaging, and biomedical research, biothiols in complex biological environments can seriously interfere with the stability of the conjugates due to ligand exchange. Herein, we communicate a robust and fast strategy for constructing peptide‐functionalized AuNP conjugates (PFCs) using the Au‐C≡C bond, which can be completed within two minutes. The resulting Au‐C≡C PFCs exhibited better stability and resistance to biothiols than the corresponding Au‐S PFCs, and also demonstrated excellent stability in high salt concentration, a wide range of pH values, and varying temperatures. The mechanism of Au‐C≡C conjugation was confirmed using molecular dynamics simulation and X‐ray photoelectron spectroscopy (XPS). The Au‐C≡C PFCs significantly improved the signal fidelity in an intracellular caspase imaging assay. Overall, the developed strategy provides a promising approach for constructing AuNP nanoprobes, allowing reliable detection and broadening the potential for diverse biological applications.
Fabrication Strategies of Mn2+‐based Scintillation Screens for X‐ray Detection and Imaging
Authors: Fan Jiali , Li Haibo , Liu Wei , Ouyang Gangfeng
Published: February 2025

Scintillators play a pivotal role in multiple ﬁelds such as medical imaging, radioactive contaminant detection, non‐destructive testing, high‐energy physics and homeland security. However, the traditional inorganic scintillators are faced with the shortcomings of high fabrication cost and low light yield. In recent years, organic‐inorganic hybrid metal halides have become the promising alternatives for their excellent luminescence properties, favorable air and irradiation stability, and low‐cost preparation. Among them, organic‐inorganic hybrid Mn(II) halides (OIMnHs) have attracted wide attention due to their particular flexible molecular structure design, easy synthesis and low toxicity. This minireview summarizes the latest progress in high performance Mn2+‐Based scintillation screens. Herein, the scintillation mechanism of OIMnHs scintillators is firstly discussed. Then, the different synthesis methods of OIMnHs scintillators are briefly described. After that, the recent strategies of OIMnHs for forming scintillation screens applying to X‐ray imaging are emphatically reviewed, in which recent fabrication progress and applications of OIMnHs‐based scintillation screens were introduced and the structure‐property relationship of these screens was discussed. Finally, the challenges of this new scintillator material are summarized, and the potential research directions for future exploration are proposed.
Improved High‐Temperature Energy Storage Performance of Mass Production‐Polypropylene Capacitive Films by Optimizing the Casting Temperatures
Authors: Liu Guoheng , Wang Tianqi , Zhang Tiandong , Yin Chao , Zhang Yue , Zhang Yongquan , Zhang Changhai , Chi Qingguo
Published: February 2025

Polypropylene (PP) are the most widely used dielectric materials for film capacitor due to the ultra‐low dielectric loss and high breakdown strength. However, PP films are not allowed to operate exceed 105°C due to the markedly increase in conduction loss at elevated temperature. This study proposes an efficient strategy to enhance the high‐temperature capacitive properties of PP films by regulating the casting temperatures during the melt‐extrusion‐casting process. The results show that the casting temperature has a deep influence on the surface morphology and crystal structures, which also affects the electrical performance especially the dielectric property at high temperature. The PP films prepared under an extrusion temperature of 210°C and the tape casting temperature of 140°C deliver the optimal energy storage property, a discharge energy density of 1.93 J cm−3 and an energy storage efficiency of 81% at 125°C, accompanying excellent cycle performance.
The role of Chalcogen Bonding in Organic Dichalcogenides of Biological Interest
Authors: Tripathi Abhishek , Calabrese Miriam , Pizzi Andrea , Dhaka Arun , Demitri Nicola , Turner David R. , Deacon Glen B. , Frontera Antonio , Resnati Giuseppe , Singh Harkesh B.
Published: February 2025

Dichalcogenides are important intermediates in the catalytic cycle of the Glutathione peroxidase (GPx), the enzyme regulating the level of reactive oxygen species (ROS). Due to their redox sensitivity, dichalcogenides are also employed in anticancer systems. The biological activity of these compounds can be related to the electrophilic behaviour of the chalcogen atoms, namely their ability to form Chalcogen Bonds (ChBs) with nucleophilic species. Herein we report the synthesis and the characterization of selenocystine hydrobromide and tellurocystine hydrochloride. X‐ray analysis confirm the ability of these dichalcogenides to act as ChB donors. A combination of surface molecular electrostatic potential (MEP) and Quantum Theory of Atom in Molecules (QTAIM) analysis proves the σ‐hole nature of the short contacts involving selenium and tellurium. ChBs involving tellurium are stronger, consistent with its major polarizability. The crystal structure of pyritinol, a synthetic analog of vitamin B6, is also reported, proving the different interactional landscape of disulfides compared to heavier dichalcogenides.
Pentafluorophenol‐Catalyzed Metal‐Free Fischer Indole Synthesis: A Novel Approach to Carbazole Derivatives and Desbromoarborescidine A*
Authors: Bansal Diksha , Sivaganesan Pooja , Elanchezhian Chibisree , Nataraj Gokulprasanth , Das Mrinal Kanti , Chaudhuri Saikat
Published: February 2025

Carbazoles represent significant heterocyclic compounds with a wide range of applications in organic synthesis. Conventional techniques, such as the Fischer indole synthesis, have been extensively utilized for the construction of these structures. In this study, we report the first use of pentafluorophenol (PFP) as a catalyst in a metal‐free approach for the synthesis of carbazoles. The strong electron‐withdrawing properties and low pKa of PFP facilitate the effective activation of electrophiles, leading to improved yields and selectivity. A comprehensive exploration of substrate diversity has been conducted, resulting in the synthesis and thorough characterization of various carbazole derivatives using 1H NMR, 13C NMR, DEPT‐135, IR, and mass spectrometry. A scale‐up synthesis was also executed to validate the method's scalability. Additionally, a natural carbazole alkaloid was synthesized, followed by post‐synthetic modifications to enhance the diversity of the compound library. This approach provides a valuable alternative to traditional acid‐catalysed methods, thereby broadening the synthetic avenues for carbazoles and their derivatives.
Quantification of Pectolinarin in Rat Plasma Using UPLC‐MS/MS and Its Pharmacokinetic Analysis
Authors: Shao Mengmeng , Wang Runrun , Wen Congcong , Wang Xianqin , Jin Yongxi , Chen Saiya
Published: February 2025

Pectolinarin is a flavonoid compound known for its wound‐healing properties, including anti‐inflammatory and antibacterial effects. In this study, we employed UPLC‐MS/MS to quantify pectolinarin in rat plasma and investigate its pharmacokinetics. Plasma samples were processed using an acetonitrile precipitation method. Chromatographic separation was performed on a UPLC BEH column with a gradient mobile phase of acetonitrile‐water (containing 0.1% formic acid). Detection was carried out using electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization, targeting transitions of m/z 623.3 → 315.3 for pectolinarin and m/z 370.5 → 125.0 for the IS. The results demonstrated that pectolinarin exhibited acceptable linearity in rat plasma within the concentration range of 1.2 to 2300 ng/mL (r > 0.995). The intraday and interday precision, expressed as relative standard deviation (RSD), was below 9.2%. Accuracy ranged from 97.3% to 108.3%, with average recovery exceeding 94.7%. The matrix effect was between 97.8% and 105.3%. The method was successfully applied to evaluate the pharmacokinetics of pectolinarin in rats following both oral and intravenous administration. The absolute bioavailability of pectolinarin in rats was determined to be 0.28%.
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

As 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

Recombinant 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

Background

The 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.

Methods

We 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.

Results

A 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).

Conclusions

Our 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

Background

There 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.

Methods

Using 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.

Results

In 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.

Conclusion

Our 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

The 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

In 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

Career 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.
Iron‐Catalyzed [2+2+2] Cycloadditions for the Construction of Aromatic and Heteroaromatic Rings
Authors: Lefèvre Guillaume , Ratovelomanana-Vidal Virginie , Parisot William , Phansavath Phannarath , Haddad Mansour
Published: February 2025

In this review, the state‐of‐the‐art of iron‐catalyzed [2+2+2] cycloadditions applied to the formation of benzene, pyridine, and phosphabenzene derivatives is described. For decades important efforts have been made to highlight the role of iron as a powerful tool in catalysis, and this work summarizes the scope of iron‐catalyzed systems for the development of new, eco‐friendly, inexpensive, and practical processes for the synthesis of (hetero)aromatic rings.
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

The 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 Summary

The 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

Background

The 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 Methods

We 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.

Results

The 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.

Conclusion

We 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.
Cobalt Bis(Pyridinethiolate N‐oxide) as a Precursor for HER Active Co Nanoparticles and Particle Size‐Dependent Electrocatalytic Properties
Authors: DenOtter Esmee , Larson Virginia , Lehnert Nicolai
Published: February 2025

The hydrogen evolution reaction (HER) produces (di)hydrogen (H2) as a clean energy carrier. Herein, a cobalt(pyridinethiolate N‐oxide)2 complex was synthesized and fully characterized, and tested for HER activity. While this complex did not show any reliable HER activity, we found that in acidic DMF, HER active nanoparticles were reductively deposited onto a glassy carbon electrode. The ellipsoidal Co nanoparticles were characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), SEM energy‐dispersive X‐ray spectroscopy (EDS), X‐ray photoelectron spectroscopy (XPS), and inductively coupled plasma mass spectrometry (ICP‐MS). The amount of deposited material, and the size and number of nanoparticles was shown to increase linearly with the number of deposition scans. Cyclic voltammetry scans showed that the onset potential for HER decreases and the catalytic current increases with the diameter of the nanoparticles. A drop‐cast Nafion thin film improved the durability of the nanoparticle‐covered electrodes, allowing for HER for at least 8 hrs. These electrodes have a Faradaic efficiency of 100 ± 3 %, and produce 14.1 mmol H2 per gram Co per second, at pH 1. Cobalt bis(mpo) is thus an ideal precursor complex for the controlled electrodeposition of metallic Co nanoparticles with a defined size and shape.
Decision‐Making Criteria and Methods for Initiating Late‐Stage Clinical Trials in Drug Development from a Multi‐Stakeholder Perspective: A Scoping Review
Authors: Jiang Ce , Beji Céline , Zebachi Sonia , Hayek Ghinwa Y. , Cetinyurek‐Yavuz Aysun , Fayyad Muhammad Bergas N. , Rodwell Laura , Roes Kit C. B. , Amzal Billy , Gerlinger Christoph , Porcher Raphaël , Tanniou Julien
Published: February 2025

The decision‐making process in drug development involves “go/no‐go” decisions, particularly at the transition from early to late‐stage trials. While the decisions are solely made by drug developers, they must take into account the perspectives of multiple stakeholders—such as regulatory agencies, HTA bodies, payers, patients, and ethics committees—to ensure well‐informed and robust decision‐making. These perspectives influence key considerations, including resource allocation, risk mitigation, regulatory compliance, etc. To support this process, quantitative methodologies, including Bayesian and hybrid frequentist‐Bayesian approaches, have been introduced to improve decision‐making. However, these methodologies often do not fully account for the diverse priorities and needs of all stakeholders. This scoping review examines criteria and methods used in decision‐making at the phase II to III transition, with a focus on broadening the probability of success (PoS) concept beyond efficacy alone. Our review explores PoS for different success definitions, such as regulatory approval, market access, financial viability, and competitive performance. Key themes include decision criteria selection, trial design optimization, utility‐based approaches, financial metrics, and multi‐stakeholder considerations in decision‐making. Our findings highlight both the limitations of current methodologies and potential paths forward, including the integration of real‐world data (RWD) and advanced analytics. This work complements a companion manuscript by Cetinyurek‐Yavuz et al. (2025) providing a detailed review of PoS methodologies focused solely on efficacy, specifically PoS for achieving statistical significance in phase III studies, including definitions, terminologies, and analytical approaches. Together, these studies provide a foundation for advancing late‐stage trial decisions toward a more balanced, data‐driven, and stakeholder‐aligned approach.
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

Difficulties 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.