bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of an early survival prognostic gene signature for localized osteosarcoma patients
Authors: Patel Tajhal D. , Grimm Sandra L. , Kanchi Rupa S. , Gandhi Tanmay , Koirala Amrit , Yustein Jason T. , Coarfa Cristian
Published: March 2024

Osteosarcoma is the most prevalent bone tumor in pediatric patients. Neoadjuvant chemotherapy has improved osteosarcoma patient survival, however the 5-year survival rate for localized osteosarcoma is 75% with a 30–50% recurrence rate. We, therefore, sought to identify a prognostic gene signature which could predict poor prognosis in localized osteosarcoma patients. Using the TARGET osteosarcoma transcriptomic dataset, we identified a 13-hub gene signature associated with overall survival and time to death of localized osteosarcoma patients, with the high-risk group showing a 22% and the low-risk group showing 100% overall survival. Furthermore, network analysis identified five modules of co-expressed genes that significantly correlated with survival, and identified 65 pathways enriched across 3 modules, including Hedgehog signaling, which includes 2 of the 13 genes, IHH and GLI1. Subsequently, we demonstrated that GLI antagonists inhibited growth of a recurrent localized PDX-derived cell line with elevated IHH and GLI1 expression, but not a non-relapsed cell line with low pathway activation. Finally, we show that our signature outperforms previously reported signatures in predicting poor prognosis and death within 3 years in patients with localized osteosarcoma.
A novel multi-variate immunological approach, reveals immune variation associated with environmental conditions, and co-infection in the koala (Phascolarctos cinereus)
Authors: Fernandez Cristina M. , Krockenberger Mark B. , Valentina  , Mella S. A. , Wright Belinda R. , Crowther Mathew S. , Higgins Damien P.
Published: March 2024

External signs of disease are frequently used as indicators of disease susceptibility. However, immune profiling can be a more effective indicator to understand how host responses to infection may be shaped by host, pathogen and environmental factors. To better inform wildlife health assessment and research directions, we investigated the utility of a novel multivariate immunophenotyping approach examining innate and adaptive immune responses in differing climatic, pathogen co-infection and demographic contexts across two koala (Phascolarctos cinereus) populations in New South Wales: the Liverpool Plains (LP), and Southern Highlands to South-west Sydney (SHSWS). Relative to the comparatively healthy SHSWS, the LP had greater and more variable innate immune gene expression (IL-1β, IL-6), and KoRV transcription. During extreme heat and drought, koalas from the LP displayed upregulation of a stress pathway gene and reduced adaptive immune genes expression, haematocrit and plasma protein, suggesting the possibility of environmental impacts through multiple pathways. In those koalas, KoRV transcription status, Chlamydia pecorum infection loads, and visible urogenital inflammation were not associated with immune variation, suggesting that immune markers were more sensitive indicators of real-time impacts than observed disease outcomes.
Biosynthesis and assessment of antibacterial and antioxidant activities of silver nanoparticles utilizing Cassia occidentalis L. seed
Authors: Arya Arvind , Tyagi Pankaj Kumar , Bhatnagar Sachin , Bachheti Rakesh Kumar , Bachheti Archana , Ghorbanpour Mansour
Published: March 2024

This research explores the eco-friendly synthesis of silver nanoparticles (AgNPs) using Cassia occidentalis L. seed extract. Various analytical techniques, including UV–visible spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscopy (EDX), were employed for comprehensive characterization. The UV–visible spectra revealed a distinct peak at 425 nm, while the seed extract exhibited peaks at 220 and 248 nm, indicating the presence of polyphenols and phytochemicals. High-resolution TEM unveiled spherical and oval-shaped AgNPs with diameters ranging from 6.44 to 28.50 nm. The SEM exhibiting a spherical shape and a polydisperse nature, thus providing insights into the morphology of the AgNPs. EDX analysis confirmed the presence of silver atoms at 10.01% in the sample. XRD results unequivocally confirm the crystalline nature of the AgNPs suspension, thereby providing valuable insights into their structural characteristics and purity. The antioxidant properties of AgNPs, C. occidentalis seed extract, and butylated hydroxytoluene (BHT) were assessed, revealing IC50 values of 345, 500, and 434 μg/mL, respectively. Antibacterial evaluation against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli demonstrated heightened sensitivity of bacteria to AgNPs compared to AgNO3. Standard antibiotics, tetracycline, and ciprofloxacin, acting as positive controls, exhibited substantial antibacterial efficacy. The green-synthesized AgNPs displayed potent antibacterial activity, suggesting their potential as a viable alternative to conventional antibiotics for combating pathogenic bacterial infections. Furthermore, potential biomedical applications of AgNPs were thoroughly discussed.
Clinical outcomes of interstitial lung abnormalities: a systematic review and meta-analysis
Authors: Seok Jinwoo , Park Shinhee , Yoon Eun Chong , Yoon Hee-Young
Published: March 2024

Interstitial lung abnormalities (ILA), incidental findings on computed tomography scans, have raised concerns due to their association with worse clinical outcomes. Our meta-analysis, which included studies up to April 2023 from PubMed/MEDLINE, Embase, and Cochrane Library, aimed to clarify the impact of ILA on mortality, lung cancer development, and complications from lung cancer treatments. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for outcomes. Analyzing 10 studies on ILA prognosis and 9 on cancer treatment complications, we found that ILA significantly increases the risk of overall mortality (RR 2.62, 95% CI 1.94–3.54; I2 = 90%) and lung cancer development (RR 3.85, 95% CI 2.64–5.62; I2 = 22%). Additionally, cancer patients with ILA had higher risks of grade 2 radiation pneumonitis (RR 2.28, 95% CI 1.71–3.03; I2 = 0%) and immune checkpoint inhibitor-related interstitial lung disease (RR 3.05, 95% CI 1.37–6.77; I2 = 83%) compared with those without ILA. In conclusion, ILA significantly associates with increased mortality, lung cancer risk, and cancer treatment-related complications, highlighting the necessity for vigilant patient management and monitoring.
Exploring the relationship across autonomous motivation, affects, and anxiety among gym practitioners during the second COVID-19 lockdown
Authors: Antunes Raúl , Rodrigues Filipe , Jacinto Miguel , Amaro Nuno , Matos Rui , Monteiro Diogo
Published: March 2024

The present study explores the association of autonomous motivation and the relationship of positive and negative affect on anxiety levels among individuals engaged in gym practitioners during the second COVID-19 lockdown. A total of 196 exercisers (29.17 ± 10.77) were enrolled in the present study, of which 112 (57.1%) were women and 84 (42.9%) were men. The survey included sociodemographic data, as well as validated instruments measuring autonomous motivation, positive and negative affect, and anxiety states related to the COVID-19 pandemic. The results revealed a positive association between autonomous motivation and positive affect (β = 0.36, CI 0.12, 0.37; p < 0.001), and a negative association between autonomous motivation and negative affect (β = − 0.17, CI − 0.31, − 0.01; p = 0.03). Moreover positive, and negative affect are negatively (β = − 0.33, CI − 0.43, − 0.24; p < 0.001) and positively (β = 0.72, CI 0.57, 0.82; p < 0.001) associated to anxiety, respectively. Thus, this study appears to emphasize the association of autonomous motivation on affect as a potential buffer against anxiety levels, particularly in a context where practitioners found themselves restricted in their usual gym practices.
Obesity differentially effects the somatosensory cortex and striatum of TgF344-AD rats
Authors: Ahmed Minhal , Lai Aaron Y. , Hill Mary E. , Ribeiro Jessica A. , Amiraslani Ashley , McLaurin JoAnne
Published: March 2024

Lifestyle choices leading to obesity, hypertension and diabetes in mid-life contribute directly to the risk of late-life Alzheimer’s disease (AD). However, in late-life or in late-stage AD conditions, obesity reduces the risk of AD and disease progression. To examine the mechanisms underlying this paradox, TgF344-AD rats were fed a varied high-carbohydrate, high-fat (HCHF) diet to induce obesity from nine months of age representing early stages of AD to twelve months of age in which rats exhibit the full spectrum of AD symptomology. We hypothesized regions primarily composed of gray matter, such as the somatosensory cortex (SSC), would be differentially affected compared to regions primarily composed of white matter, such as the striatum. We found increased myelin and oligodendrocytes in the somatosensory cortex of rats fed the HCHF diet with an absence of neuronal loss. We observed decreased inflammation in the somatosensory cortex despite increased AD pathology. Compared to the somatosensory cortex, the striatum had fewer changes. Overall, our results suggest that the interaction between diet and AD progression affects myelination in a brain region specific manner such that regions with a lower density of white matter are preferentially affected. Our results offer a possible mechanistic explanation for the obesity paradox.
Employing deep learning and transfer learning for accurate brain tumor detection
Authors: Mathivanan Sandeep Kumar , Sonaimuthu Sridevi , Murugesan Sankar , Rajadurai Hariharan , Shivahare Basu Dev , Shah Mohd Asif
Published: March 2024

Artificial intelligence-powered deep learning methods are being used to diagnose brain tumors with high accuracy, owing to their ability to process large amounts of data. Magnetic resonance imaging stands as the gold standard for brain tumor diagnosis using machine vision, surpassing computed tomography, ultrasound, and X-ray imaging in its effectiveness. Despite this, brain tumor diagnosis remains a challenging endeavour due to the intricate structure of the brain. This study delves into the potential of deep transfer learning architectures to elevate the accuracy of brain tumor diagnosis. Transfer learning is a machine learning technique that allows us to repurpose pre-trained models on new tasks. This can be particularly useful for medical imaging tasks, where labelled data is often scarce. Four distinct transfer learning architectures were assessed in this study: ResNet152, VGG19, DenseNet169, and MobileNetv3. The models were trained and validated on a dataset from benchmark database: Kaggle. Five-fold cross validation was adopted for training and testing. To enhance the balance of the dataset and improve the performance of the models, image enhancement techniques were applied to the data for the four categories: pituitary, normal, meningioma, and glioma. MobileNetv3 achieved the highest accuracy of 99.75%, significantly outperforming other existing methods. This demonstrates the potential of deep transfer learning architectures to revolutionize the field of brain tumor diagnosis.
Impact of 24 h shifts on urinary catecholamine in emergency physicians: a cross-over randomized trial
Authors: Dutheil Frédéric , Fournier Alicia , Perrier Christophe , Richard Damien , Trousselard Marion , Mnatzaganian George , Baker Julien S. , Bagheri Reza , Mermillod Martial , Clinchamps Maelys , Schmidt Jeannot , Bouillon-Minois Jean-Baptiste
Published: March 2024

24-h shift (24 hS) exposed emergency physicians to a higher stress level than 14-h night shift (14 hS), with an impact spreading on several days. Catecholamines are supposed to be chronic stress biomarker. However, no study has used catecholamines to assess short-term residual stress or measured them over multiple shifts. A shift-randomized trial was conducted to study urinary catecholamines levels of 17 emergency physicians during a control day (clerical work on return from leave) and two working day (14 hS and 24 hS). The Wilcoxon matched-pairs test was utilized to compare the mean catecholamine levels. Additionally, a multivariable generalized estimating equations model was employed to further analyze the independent relationships between key factors such as shifts (compared to control day), perceived stress, and age with catecholamine levels. Dopamine levels were lower during 24 hS than 14 hS and the control day. Norepinephrine levels increased two-fold during both night shifts. Epinephrine levels were higher during the day period of both shifts than on the control day. Despite having a rest day, the dopamine levels did not return to their normal values by the end of the third day after the 24 hS. The generalized estimating equations model confirmed relationships of catecholamines with workload and fatigue. To conclude, urinary catecholamine biomarkers are a convenient and non-invasive strong measure of stress during night shifts, both acutely and over time. Dopamine levels are the strongest biomarker with a prolonged alteration of its circadian rhythm. Due to the relation between increased catecholamine levels and both adverse psychological effects and cardiovascular disease, we suggest that emergency physicians restrict their exposure to 24 hS to mitigate these risks.
Validation of reference gene stability for normalization of RT-qPCR in Phytophthora capsici Leonian during its interaction with Piper nigrum L.
Authors: Vijayakumar Saranya , Sakuntala Manjula
Published: March 2024

The selection of stable reference genes for the normalization of reverse transcription quantitative real-time PCR (RT-qPCR) is generally overlooked despite being the crucial element in determining the accuracy of the relative expression of genes. In the present study, the stability of seven candidate reference genes: actin (act), α-tubulin (atub), β-tubulin (btub), translation elongation factor 1-α (ef1), elongation factor 2 (ef2), ubiquitin-conjugating enzyme (ubc) and 40S ribosomal protein S3A (ws21) inPhytophthora capsicihas been validated. The validation was performed at six infection time points during its interaction with its susceptible hostPiper nigrum, two developmental stages, and for the combined dataset. Four algorithms: geNorm, NormFinder, BestKeeper, and the ΔCt method were compared, and a comprehensive ranking order was produced using RefFinder. The overall analysis revealed thatef1,ws21, andubcwere identified as the three most stable genes in the combined dataset,ef1,ws21, andactwere the most stable at the infection stages, and,ef1,btub, andubcwere most stable during the developmental stages. These findings were further corroborated by validating theP. capsicipathogenesis geneNPP1expression. The findings are significant as this is the first study addressing the stability of reference genes forP. capsici–P. nigruminteraction studies.
Wetting and evaporation behavior of dilute sodium dodecyl sulfate droplets on soft substrates under a direct current electric field
Authors: Jiang Biao , Xu Shuai , Lu Yingfa , Yu Yingsong
Published: March 2024

Wetting and evaporation behavior of dilute sodium dodecyl sulfate (SDS) droplets on planar polydimethylsiloxane (PDMS) surfaces under a direct current (DC) electric field were experimentally investigated. Two characteristic voltages—actuation voltage and saturation voltage were observed in the electrowetting of dilute SDS droplets on PDMS surfaces. It was found that for dilute SDS droplets with a fixed SDS concentration substrate elasticity has an obvious influence on actuation voltage, and saturation voltage increased with the increase of mass ratio of PDMS surfaces. SDS concentration was also found to obviously influence actuation voltage and saturation voltage when SDS concentration was in a certain range. For the case of evaporation of sessile dilute SDS droplets on PDMS surfaces with the application of a DC electric field, substrate elasticity, SDS concentration and the magnitude of applied voltage were all found to have an influence on the duration of CCR stage. Moreover, contact angle hysteresis for dilute SDS droplets on a planar PDMS 10:1 surface under different applied voltage was measured and it was found that the magnitude of applied voltage greatly influenced contact angle hysteresis, which also depends on SDS concentration and KCl concentration.
Artificial intelligence-based assessment of PD-L1 expression in diffuse large B cell lymphoma
Authors: Yan Fang , Da Qian , Yi Hongmei , Deng Shijie , Zhu Lifeng , Zhou Mu , Liu Yingting , Feng Ming , Wang Jing , Wang Xuan , Zhang Yuxiu , Zhang Wenjing , Zhang Xiaofan , Lin Jingsheng , Zhang Shaoting , Wang Chaofu
Published: March 2024

Diffuse large B cell lymphoma (DLBCL) is an aggressive blood cancer known for its rapid progression and high incidence. The growing use of immunohistochemistry (IHC) has significantly contributed to the detailed cell characterization, thereby playing a crucial role in guiding treatment strategies for DLBCL. In this study, we developed an AI-based image analysis approach for assessing PD-L1 expression in DLBCL patients. PD-L1 expression represents as a major biomarker for screening patients who can benefit from targeted immunotherapy interventions. In particular, we performed large-scale cell annotations in IHC slides, encompassing over 5101 tissue regions and 146,439 live cells. Extensive experiments in primary and validation cohorts demonstrated the defined quantitative rule helped overcome the difficulty of identifying specific cell types. In assessing data obtained from fine needle biopsies, experiments revealed that there was a higher level of agreement in the quantitative results between Artificial Intelligence (AI) algorithms and pathologists, as well as among pathologists themselves, in comparison to the data obtained from surgical specimens. We highlight that the AI-enabled analytics enhance the objectivity and interpretability of PD-L1 quantification to improve the targeted immunotherapy development in DLBCL patients.
Graphene oxide-based membranes for water desalination and purification
Authors: Tiwary Saurabh Kr , Singh Maninderjeet , Chavan Shubham Vasant , Karim Alamgir
Published: March 2024

Millions of people across the globe are severely afflicted because of water potability issues, and to proffer a solution to this crisis, efficient and cost-effective desalination techniques are necessitated. Membranes, in particular Graphene-derived membranes, have emerged as a potential answer to this grave problem because of their tunable ionic and molecular sieving capability, thin structure, and customizable microstructure. Among graphene-derived membranes, Graphene Oxide membranes have been the most promising, given the replete presence of oxygen-containing functional groups on its surface. However, the prospects of commercial applicability of these membranes are currently plagued by uneven stacking, crossflow delamination, flawed pores, screening and pH effects, and horizontal defects in the membrane. In addition, due to the selectivity–permeability trade-off that commonly exists in all membranes, the separation efficiency is negatively influenced. This review, while studying these challenges, aims to outline the most recent ground-breaking developments in graphene-based membrane technology, encompassing their separation mechanism, selectivity, adjustable mechanical characteristics, and uses. Additionally, we have covered in detail how several process variables such as temperature, total oxygen concentration, and functional groups affect the effectiveness of membrane separation with the focal point tilted toward studying the currently used intercalation techniques and effective nanomaterial graphene oxide membranes for water desalination
Enhancing dielectric passivation on monolayer WS2 via a sacrificial graphene oxide seeding layer
Authors: Wyndaele P.-J. , de Marneffe J.-F. , Sergeant S. , de la Rosa C. J. L. , Brems S. , Caro A. M. , De Gendt S.
Published: March 2024

The full utilization of two-dimensional transition metal dichalcogenides (2D TMDCs) faces several challenges, among which is realizing uniform material deposition on the 2D surface. Typical strategies to enable material growth lead to a poor interface quality, degrading the 2D TMDC’s properties. In this work, a sacrificial, graphene oxide-based seeding layer is used (1) as passivation layer, protecting the underlying 2D TMDC and (2) as nucleation layer, enabling uniform material growth. Graphene is transferred on monolayer WS2, establishing a high-quality van der Waals interface. After transfer, the polymeric residues on graphene are cleaned via a combination of wet- and dry treatments and functionalized via dry UV/O3 oxidation. The rate of graphene oxidation is shown to be substrate dependent, which is explained by UV light-induced ultrafast charge transfer between the graphene and WS2 monolayer. The carbon-oxygen functionalities serve as nucleation sites in a subsequent HfO2 ALD process, achieving more uniform dielectric growth and faster layer closure compared to direct deposition. The graphene-based nucleation- / passivation approach offers adaptability, allowing for tailored surface chemistry to enable any alternative material growth, while maintaining a prefect van der Waals interface.
TRPM5 activation depends on a synergistic effect of calcium and PKC phosphorylation
Authors: Nmarneh Alaa , Priel Avi
Published: March 2024

Transient receptor potential melastatin 5 (TRPM5) is a calcium-activated monovalent-specific ion channel involved in insulin secretion and taste transduction, making it an attractive target for drug development in various pathologies. While TRPM5 activation involves ligand binding to Gq/G-protein coupled receptors (GPCR) and subsequent elevation of intracellular calcium levels, recent reports suggest the need for additional molecular determinants. Hence, the mechanism of TRPM5 activation remains to be elucidated. Here, we show that PKC phosphorylation and the elevation of intracellular Ca2+ levels are required for TRPM5 activation, with PKC phosphorylation being crucial for channel-evoked currents, primarily at physiological membrane potentials. In contrast, physiological relevant calcium levels alone only induce TRPM5 activation at positive voltages. Our findings highlight the necessity of coordinated intracellular calcium release and PKC phosphorylation for TRPM5 activation. Thus, our results suggest that regulation of PKC activity could be a promising therapeutic target for diseases associated with TRPM5 modulation.
The reaction mechanism of the Ideonella sakaiensis PETase enzyme
Authors: Burgin Tucker , Pollard Benjamin C. , Knott Brandon C. , Mayes Heather B. , Crowley Michael F. , McGeehan John E. , Beckham Gregg T. , Woodcock H. Lee
Published: March 2024

Polyethylene terephthalate (PET), the most abundantly produced polyester plastic, can be depolymerized by the Ideonella sakaiensis PETase enzyme. Based on multiple PETase crystal structures, the reaction has been proposed to proceed via a two-step serine hydrolase mechanism mediated by a serine-histidine-aspartate catalytic triad. To elucidate the multi-step PETase catalytic mechanism, we use transition path sampling and likelihood maximization to identify optimal reaction coordinates for the PETase enzyme. We predict that deacylation is likely rate-limiting, and the reaction coordinates for both steps include elements describing nucleophilic attack, ester bond cleavage, and the “moving-histidine” mechanism. We find that the flexibility of Trp185 promotes the reaction, providing an explanation for decreased activity observed in mutations that restrict Trp185 motion. Overall, this study uses unbiased computational approaches to reveal the detailed reaction mechanism necessary for further engineering of an important class of enzymes for plastics bioconversion.
Non-invasive measurements of blood glucose levels by time-gating mid-infrared optoacoustic signals
Authors: Uluç Nasire , Glasl Sarah , Gasparin Francesca , Yuan Tao , He Hailong , Jüstel Dominik , Pleitez Miguel A. , Ntziachristos Vasilis
Published: March 2024

Non-invasive glucose monitoring (NIGM) represents an attractive alternative to finger pricking for blood glucose assessment and management of diabetes. Nevertheless, current NIGM techniques do not measure glucose concentrations in blood but rely on indirect bulk measurement of glucose in interstitial fluid, where glucose is diluted and glucose dynamics are different from those in the blood, which impairs NIGM accuracy. Here we introduce a new biosensor, termed depth-gated mid-infrared optoacoustic sensor (DIROS), which allows, for the first time, non-invasive glucose detection in blood-rich volumes in the skin. DIROS minimizes interference caused by the stratum corneum and other superficial skin layers by time-gating mid-infrared optoacoustic signals to enable depth-selective localization of glucose readings in skin. In measurements on the ears of (female) mice, DIROS displays improved accuracy over bulk-tissue glucose measurements. Our work demonstrates how signal localization can improve NIGM accuracy and positions DIROS as a holistic approach, with high translational potential, that addresses a key limitation of current NIGM methods.
NMR Crystallography in Pharmaceutical Development
Authors: Hughes Leslie P. , Szell Patrick M. J. , Blade Helen , Brown Steven P.
Published: March 2024

NMR crystallography is the combined use of experimental solid-state nuclear magnetic resonance (NMR) with density-functional theory (DFT) calculation of NMR parameters for a structure, as obtained, for example, by complementary diffraction or crystal structure prediction (CSP) approaches. We give an overview of how NMR crystallography can be applied to active pharmaceutical ingredients (APIs) and their formulations, including considering polymorphism, solvates and hydrates, salt and co-crystal formation, and amorphous dispersions. Specifically, the use of the gauge-including projector augmented wave (GIPAW) method, as implemented, for instance, in CASTEP or Quantum Espresso, is widely employed to calculate NMR chemical shifts for nuclei such as 1H, 13C, 14/15N, 19F, and 35Cl, as well as quadrupolar parameters for spin I ≥ 1 nuclei such as 14N and 35Cl, complementing experimental data obtained using magic-angle spinning (MAS). We describe the application of key MAS NMR experiments such as cross-polarisation (CP) MAS, notably for polymorph fingerprinting and determination of the number of distinct molecules in the asymmetric unit cell (Z′), and 1H-based two-dimensional experiments including heteronuclear correlation and double-quantum (DQ) MAS. Experiments probing internuclear dipolar couplings provide structural insight via identifying specific atomic proximities and determining specific distances and characterise dynamic processes via quantitative measurement of dipolar couplings.
Using Water Proton NMR to Characterize Aluminum-adjuvanted Vaccines
Authors: Briggs K. T. , Taraban M. B. , YU Y. B.
Published: March 2024

wNMR, which stands for water proton nuclear magnetic resonance, is an emerging noninvasive analytical technology for pharmaceutical manufacturing and product inspection. In wNMR, the NMR signal from water protons is used to assess the physicochemical status of the solutes dissolved or suspended in water. The primary experimental outputs in wNMR are the longitudinal and transverse relaxation rates of water protons, R1(1H2O) and R2(1H2O). Aluminum-adjuvanted vaccines include some of the most commonly used vaccines and contain micron-sized aluminum salt particles, with antigens adsorbed to the particles, and are formulated as whitish aqueous suspensions. This type of suspension vaccine presents a unique challenge for analytical characterization because the sample is very heterogeneous and opaque. Most analytical techniques require significant sample preparations, such as dilution and antigen desorption, which may significantly perturb the sample being analyzed. wNMR offers a simple but effective analytical tool to characterize aluminum-adjuvanted vaccines. In this chapter, the basic principles of wNMR are discussed and specific examples are given of using wNMR to characterize two aluminum adjuvants (ALHYDROGEL® and ADJU-PHOS®) and three marketed aluminum-adjuvanted vaccines (DAPTACEL®, ENGERIX-B®, and VAQTA®). wNMR was used to detect vaccine freeze/thaw and vial-to-vial variability and to monitor vaccine sedimentation kinetics. Analysis is performed on sealed and labelled vials and does not involve any sample preparation. wNMR paves the way for quantitatively inspecting every vial of a finished drug product at the point of release and the point of care.
Applications of Pulsed Field Gradient Nuclear Magnetic Resonance to Late-stage Pharmaceutical and Biopharmaceutical Development and Deployment
Authors: Mantle Michael D.
Published: March 2024

Pulsed field gradient nuclear magnetic resonance (PFG-NMR) is a powerful methodology that encodes the microscopic molecular displacements of a substance. Subsequent analysis of the PFG-NMR data then recovers the substance’s molecular self-diffusivity, D, in units of m2 s−1. This chapter is primarily divided into two sections: the first section elucidates the background and theory behind the PFG-NMR experiment and describes mathematically how the molecular self-diffusion coefficient, D, is extracted from PFG-NMR datasets. The latter half of the first section demonstrates how numerical simulations of PFG-NMR data serve as valuable tools to illustrate the effects observed in real PFG-NMR datasets. These effects include multiple-component molecular diffusion, diffusive molecular exchange, and restricted diffusion. The second half of the chapter focuses on the diverse applications of PFG-NMR in late-stage pharmaceutical and biopharmaceutical development and deployment research. It emphasizes specific research aimed at enhancing our scientific comprehension of the principal challenges and questions faced by the pharmaceutical and biopharmaceutical industries.
Short-T2 Imaging Applications in Pharmaceutical Research
Authors: Newling B.
Published: March 2024

This chapter describes magnetic resonance imaging (MRI) techniques designed specifically for the imaging of short-lifetime (broad-line) materials and their application in pharmaceutical research. Ultrashort echo time, zero echo time, and constant time imaging methods are compared, and selected instances from the literature are described. Short-lifetime MRI methods are not widely employed in the pharmaceutical literature but have provided complementary information and sometimes unique mechanistic insight where applied. There is certainly scope for fruitful applications and continued methods development in this area of materials MRI.
Chemisorption of silicon tetrachloride on silicon nitride: a density functional theory study
Authors: Chowdhury Tanzia , Khumaini Khabib , Hidayat Romel , Kim Hye-Lee , Lee Won-Jun
Published: March 2024

For the chemisorption of SiCl4 on silicon nitride, three sequential reactions forming NH3+Cl− were simulated using an NH2/NH-terminated slab model.
Tuning the magnetic properties of double transition-metal carbide CoMC (M = Ti, V, Cr, Mn, Fe, Ni) monolayers
Authors: Zhang Honghai , Lou Yaya , Wu Dongni , Liao Yangfang , Xie Jing
Published: March 2024

Hole doping and biaxial strain were applied to the double transition metal carbide CoMC to control its magnetic properties.
Physical insight of random fluctuation in metal/IGZO Schottky barriers for low-variation contact optimal design
Authors: Xu Lijun , Luo Kun , Zhan Guohui , Liu Jiangtao , Wu Zhenhua
Published: March 2024

The study aimed to investigate the impact of random fluctuations in Schottky barrier formation at polar interfaces between InGaZnO4 (IGZO) and different metals, particularly in the context of device miniaturization.
Superconductivity in Ca-intercalated bilayer graphene: C2CaC2
Authors: Tan Jin-Han , Wang Hao , Chen Ying-Jie , Jiao Na , Zheng Meng-Meng , Lu Hong-Yan , Zhang Ping
Published: March 2024

C2CaC2 has a higher intercalation metal concentration, it is a superconductor with Tc of 18.9 K. By further applying −4% biaxial compressive strain, the Tc can be boosted to 26.6 K, which is the highest Tc in bilayer graphenes.
Radical reactions enabled by polyfluoroaryl fragments: photocatalysis and beyond
Authors: Zubkov Mikhail O. , Dilman Alexander D.
Published: March 2024

The review summarizes advances in the radical chemistry of polyfluorinated arenes under photocatalytic conditions. The fluoroaryl fragment serves as enabling motif for the reaction design and efficient generation of reactive intermediates.
Extended similarity methods for efficient data mining in imaging mass spectrometry
Authors: Ellin Nicholas R. , Guo Yingchan , Miranda-Quintana Ramón Alain , Prentice Boone M.
Published: March 2024

Extended similarity indices facilitate processing complex IMS data and quickly finding correlations between multiple compounds and tissue regions.
Investigation of emission plane control in GaInN/GaN multiple-quantum shells for efficient nanowire-based LEDs
Authors: Inaba Soma , Lu Weifang , Shima Ayaka , Ii Shiori , Takahashi Mizuki , Yamanaka Yuki , Hattori Yuta , Kubota Kosei , Huang Kai , Iwaya Motoaki , Takeuchi Tetsuya , Kamiyama Satoshi
Published: March 2024

To improve the emission properties of multiple-quantum-shells nanowire-based LEDs, we assessed the effect of GaInN/GaN superlattices grown at varying growth temperatures, as well as the control of emission plane via p-GaN shell and emission sizes.
Evaluating the consistency of rice and paddy quality using four-dimensional fingerprint analysis
Authors: Ren Yu , Li Gang , Yang Ting , Sun Guoxiang
Published: March 2024

The aim of this paper is to evaluate the quality of 13 batches of rice and 17 batches of paddy.
Telomerase: a nexus between cancer nanotherapy and circadian rhythm
Authors: Ghosh Pramit Kumar , Rao Maddila Jagapathi , Putta Chandra Lekha , Ray Sandipan , Rengan Aravind Kumar
Published: March 2024

The use of nanoparticles for identifying and suppressing telomerase presents promising opportunities for anticancer strategies, particularly in relation to circadian regulation.
Bioinspired ginsenoside Rg3 PLGA nanoparticles coated with tumor-derived microvesicles to improve chemotherapy efficacy and alleviate toxicity
Authors: Zhang Shulei , Zheng Bo , Wei Yiqi , Liu Yuhao , Yang Lan , Qiu Yujiao , Su Jing , Qiu Mingfeng
Published: March 2024

Breast cancer, a pervasive malignancy affecting women, demands a diverse treatment approach including chemotherapy, radiotherapy, and surgical interventions.
Nanopore sensitization based on a double loop hybridization chain reaction and G-quadruplex
Authors: Li Yanru , Yu Chunmiao , Wang Yesheng , Yu Jin , Wang Huaning , Li Bingling
Published: March 2024

In this study, we’ve developed a nucleic acid amplifier to enhance the sensitivity of solid-state nanopores, utilizing a G-rich sequence and hybridization chain reaction.
Exploring the full range of N⋯I⋯X halogen-bonding interactions within a single compound using pressure
Authors: Jones Richard H. , Bull Craig L. , Funnell Nicholas P. , Knight Kevin S. , Marshall William G.
Published: March 2024

The response of the trimethylammonium–iodinechloride and diiodide (TMA–ICl/I2) crystal structures have been examined under high pressure using neutron powder diffraction.
Iodine-mediated oxidative triple functionalization of indolines with azoles and diazonium salts
Authors: Liu Yifeng , Gu Xiaoting , Zhang Xiaoxiang , Xu Meilan , Zhang Zhuan , Liang Taoyuan
Published: March 2024

A tandem oxidative multi-functionalization strategy for the synthesis of the C2,3,5-trifunctional indoles from indolines, aryldiazonium salts and azoles was developed.
Naphthalene-based donor–acceptor covalent organic frameworks as an electron distribution regulator for boosting photocatalysis
Authors: Wang Zeming , Song Qiang , He Cheng , Feng Pengyu , Zhao Liang , Duan Chunying
Published: March 2024

The introduction of naphthalene as an electron donor resulted in the formation of a D–A COF, which boosted green-light-driven photocatalysis.
Engineering mechanical compliance in polymers and composites for the design of smart flexible sensors
Authors: Sahu Shivank , Tripathy Kamalesh , Bhattacharjee Mitradip , Chopra Deepak
Published: March 2024

The importance of organic polymers and their role in the development of sensors with tunable mechanical/electrical properties has been discussed. The translation of such technologies to the healthcare and energy sector is of importance in the future.
Halloysite-derived mesoporous silica with high ionic conductivity improves Li–S battery performance
Authors: Ao Ranxiao , Zhu Ziqi , Zhang Shilin , Zhang Qiang , Yan Chenyu , Tu Feiyue , Li Tianbao , Li Mitch Guijun , Fu Liangjie , Tang Aidong , Yang Huaming
Published: March 2024

Ordered mesoporous channels of Fe–HSBA-15 as a sulfur carrier improve the transport rate of lithium-ions.
Zn1−xMgxTe and P:Zn1−xMgxTe (x = 0.06–0.25) bulk crystals grown by travelling Te solution method
Authors: Song Yuchen , Zhang Tingting , Lv Jiahui , Zhang Guorong , Liu Changyou , Wang Tao , Zha Gangqiang , Jie Wanqi
Published: March 2024

Zn1−xMgxTe and P:Zn1−xMgxTe (x = 0.06–0.25) bulk crystals were successfully grown by travelling Te solution method. The segregation of Mg with the growth of crystal is weaken and the as-grown crystal has high homogeneity.
A new Cd(ii)-based coordination polymer as a luminescent sensor and adsorbent for dichromate ions
Authors: Xia Ying-Gui , Lan Xue , Wang Jun , Liu Xiao-Hong , Muddassir Mohd. , Srivastava Devyani , Kushwaha Aparna , Kumar Abhinav
Published: March 2024

A new 3,5-bis(1-imidazol)pyridine-appended Cd(ii) coordination polymer was synthesized and used as a luminescent sensor and adsorbent for dichromate ions.
Harnessing halogen bond donors for enhanced nitrogen reduction: a case study on metal-free boron nitride single-atom catalysts
Authors: Choutipalli Venkata Surya Kumar , Subramanian Venkatesan
Published: March 2024

Catalyst design for NH3 synthesis is vital yet challenging. This study highlights the role of halogen bond donors as catalytic promoters, aiding activation of N2. This study offers insights for robust metal-free catalysts and promoters in NRR research.
A multi-FLP approach for CO2 capture: investigating nitrogen, boron, phosphorus and aluminium doped nanographenes and the influence of a sodium cation
Authors: Ferrer Maxime , Alkorta Ibon , Elguero José , Oliva-Enrich Josep M.
Published: March 2024

The reaction of nitrogen, boron, phosphorus and aluminium doped nanographenes (NGs) with CO2 in the absence/presence of Na+ is studied. The Al3P3-NG system is the most suitable one for the activation/sequestration of up to three CO2 molecules.
Photocatalytic α-aminoalkyl radical addition of amines mediated by benzophenone under visible light
Authors: Chen Jinke , Lian Qi , Jiang Xinru , Zhang Juan , Luo Xiang , Fang Jiansong , Wei Wentao
Published: March 2024

The photocatalytic α-aminoalkyl radical addition of amines faciliated by benzophenone is disclosed. This is an example of a photocatalytic alkylation method that uses low-toxicity solvents and mild reaction conditions.
A sulfur-doped alga-like g-C3N4 photocatalyst for enhanced photocatalytic and antimicrobial properties
Authors: Li Le , Chao Min , Zhang Bei , Song Chengjun , Luo Chunjia , Yan Luke
Published: March 2024

Graphitic carbon nitride (g-C3N4) is a non-metallic semiconductor photocatalyst which is widely used in water treatment.
Expression of concern: Naturally derived sugar-based ionic liquids: an emerging tool for sustainable organic synthesis and chiral recognition
Authors: Muthukuru Priyanka , P. Krishnaraj , Rayadurgam Jayachandra , Rajasekhara Reddy Sabbasani
Published: March 2024

Expression of concern for ‘Naturally derived sugar-based ionic liquids: an emerging tool for sustainable organic synthesis and chiral recognition’ by Priyanka Muthukuru et al., New J. Chem., 2021, 45, 20075–20090, https://doi.org/10.1039/D1NJ03914H.
Iron-catalyzed selective construction of indole derivatives via oxidative C(sp3)–H functionalization of indolin-2-ones
Authors: Chen Wei , Wen Lang-Qi , Lu Xiao-Bing , Zhou Hui
Published: March 2024

We have developed a clean and efficient iron-catalyzed C(sp3)–H functionalization of indolin-2-ones for the chemodivergent synthesis of value-added indole derivatives, including isatins, and symmetrical and non-symmetrical isoindigos.
Exploring the self-assembly dynamics of novel steroid–coumarin conjugates: a comprehensive spectroscopic and solid-state investigation
Authors: Ramírez-Lozano Claudia M. , Ochoa Ma. Eugenia , Labra-Vázquez Pablo , Jiménez-Sánchez Arturo , Farfán Norberto , Santillan Rosa
Published: March 2024

The design, synthesis, and characterization of seven novel steroid–coumarin conjugates with diverse steroidal nuclei as lipophilic fluorescent materials for bioimaging applications are presented.
Synthesis, characterization, and biomedical evaluation of ethylene-bridged tetra-NHC Pd(ii), Pt(ii) and Au(iii) complexes, with apoptosis-inducing properties in cisplatin-resistant neuroblastoma cells
Authors: Büchele Wolfgang R. E. , Schlachta Tim P. , Gebendorfer Andreas L. , Pamperin Jenny , Richter Leon F. , Sauer Michael J. , Prokop Aram , Kühn Fritz E.
Published: March 2024

New ethylene-bridged N-heterocyclic carbene ligand systems and their respective transition metal complexes are characterized and the electronic properties are discussed.
Pinning–depinning transition of droplets on inclined substrates with a three-dimensional topographical defect
Authors: Mhatre Ninad V. , Kumar Satish
Published: March 2024

The influence of defect geometry on the critical inclination angle required for droplet depinning on inclined substrates is studied.
Ultrafast sintering of boron nitride nanosheet assembled microspheres with strong processability for high-performance thermal management materials
Authors: Ding Siyuan , Zhen Fangzheng , Du Yu , Zhan Ke , Wu Yinghui , Zhu Jiuyi , Zheng Qijun , Ding Baofu , Yu Aibing , Cheng Hui-Ming , Liu Minsu , Qiu Ling
Published: March 2024

A novel strategy produces BNNS microspheres for isotropic thermal conductivity, utilizing high-temperature ultrafast sintering and surface engineering to enhance processability for producing thermal management materials.
Self-assembly of peptides in living cells for disease theranostics
Authors: Mo Xiaowei , Zhang Zeyu , Song Jinyan , Wang Yushi , Yu Zhilin
Published: March 2024

In situ self-assembly of peptides in living cells regulated by biocompatible stimuli allows for precise creation of well-defined nanostructures and thus offering a versatile strategy for formulation of biomedical agents at pathological lesions.
Activin E is a transforming growth factor β ligand that signals specifically through activin receptor-like kinase 7
Authors: Vestal Kylie A. , Kattamuri Chandramohan , Koyiloth Muhasin , Ongaro Luisina , Howard James A. , Deaton Aimee M. , Ticau Simina , Dubey Aditi , Bernard Daniel J. , Thompson Thomas B.
Published: March 2024

Activins are one of the three distinct subclasses within the greater Transforming growth factor β (TGFβ) superfamily. First discovered for their critical roles in reproductive biology, activins have since been shown to alter cellular differentiation and proliferation. At present, members of the activin subclass include activin A (ActA), ActB, ActC, ActE, and the more distant members myostatin and GDF11. While the biological roles and signaling mechanisms of most activins class members have been well-studied, the signaling potential of ActE has remained largely unknown. Here, we characterized the signaling capacity of homodimeric ActE. Molecular modeling of the ligand:receptor complexes showed that ActC and ActE shared high similarity in both the type I and type II receptor binding epitopes. ActE signaled specifically through ALK7, utilized the canonical activin type II receptors, ActRIIA and ActRIIB, and was resistant to the extracellular antagonists follistatin and WFIKKN. In mature murine adipocytes, ActE invoked a SMAD2/3 response via ALK7, like ActC. Collectively, our results establish ActE as a specific signaling ligand which activates the type I receptor, ALK7.
Flow cytometry protocol for GLUT4-myc detection on cell surfaces
Authors: Zanni-Ruiz Emilia , Mayorga Luis Segundo , Pavarotti Martin Alejandro
Published: March 2024

Insulin and muscle contraction trigger GLUT4 translocation to the plasma membrane, which increases glucose uptake by muscle cells. Insulin resistance and Type 2 diabetes are the result of impaired GLUT4 translocation. Quantifying GLUT4 translocation is essential for comprehending the intricacies of both physiological and pathophysiological processes involved in glucose metabolism. The most commonly used methods for measuring GLUT4 translocation are the ELISA-type assay and the immunofluorescence assay. While some reports suggest that flow cytometry could be useful in quantifying GLUT4 translocation, this technique is not frequently used. Much of our current understanding of the regulation of GLUT4 has been based on experiments using the rat myoblast cell line (L6 cell) which expresses GLUT4 with a myc epitope on the exofacial loop. In the present study, we use the L6-GLUT4myc cell line to develop a flow cytometry-based approach to detect GLUT4 translocation. Flow cytometry offers the advantages of both immunofluorescence and ELISA-based assays. It allows easy identification of separate cell populations in the sample, similar to immunofluorescence, while providing results based on a population-level analysis of multiple individual cells, like an ELISA-based assay. Our results demonstrate a 0.6-fold increase with insulin stimulation compared with basal conditions. Finally, flow cytometry consistently yielded results across different experiments and exhibited sensitivity under the tested conditions.
The role of calcium in neuronal membrane tension and synaptic plasticity
Authors: Lin Guanyu , Rennie Madison , Adeeko Ayobami , Scarlata Suzanne
Published: March 2024

Calcium is a primary second messenger that plays a role in cellular functions including growth, movement and responses to drugs. The role that calcium plays in mediating communication between neurons by synaptic vesicle release is well established. This review focuses on the dependence of the physical properties of neuronal plasma membranes on calcium levels. After describing the key features of synaptic plasticity, we summarize the general role of calcium in cell function and the signaling pathways responsible for intracellular increase in calcium levels. We then present findings showing that increases in intracellular calcium levels cause neurites to contract and break synaptic connections by changes in membrane tension.