bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Alterations and Comprehensive Clinical Management of Oncocytic Thyroid Carcinoma
Authors: Bischoff Lindsay A. , Ganly Ian , Fugazzola Laura , Buczek Erin , Faquin William C. , Haugen Bryan R. , McIver Bryan , McMullen Caitlin P. , Newbold Kate , Rocke Daniel J. , Russell Marika D. , Ryder Mabel , Sadow Peter M. , Sherman Eric , Shindo Maisie , Shonka David C. , Singer Michael C. , Stack Brendan C. , Wirth Lori J. , Wong Richard J. , Randolph Gregory W.
Published: January 2024

Importance

Oncocytic (Hürthle cell) thyroid carcinoma is a follicular cell-derived neoplasm that accounts for approximately 5% of all thyroid cancers. Until recently, it was categorized as a follicular thyroid carcinoma, and its management was standardized with that of other differentiated thyroid carcinomas. In 2022, given an improved understanding of the unique molecular profile and clinical behavior of oncocytic thyroid carcinoma, the World Health Organization reclassified oncocytic thyroid carcinoma as distinct from follicular thyroid carcinoma. The International Thyroid Oncology Group and the American Head and Neck Society then collaborated to review the existing evidence on oncocytic thyroid carcinoma, from diagnosis through clinical management and follow-up surveillance.

Observations

Given that oncocytic thyroid carcinoma was previously classified as a subtype of follicular thyroid carcinoma, it was clinically studied in that context. However, due to its low prevalence and previous classification schema, there are few studies that have specifically evaluated oncocytic thyroid carcinoma. Recent data indicate that oncocytic thyroid carcinoma is a distinct class of malignant thyroid tumor with a group of distinct genetic alterations and clinicopathologic features. Oncocytic thyroid carcinoma displays higher rates of somatic gene variants and genomic chromosomal loss of heterozygosity than do other thyroid cancers, and it harbors unique mitochondrial DNA variations. Clinically, oncocytic thyroid carcinoma is more likely to have locoregional (lymph node) metastases than is follicular thyroid carcinoma—with which it was formerly classified—and it develops distant metastases more frequently than papillary thyroid carcinoma. In addition, oncocytic thyroid carcinoma rarely absorbs radioiodine.

Conclusions and Relevance

The findings of this review suggest that the distinct clinical presentation of oncocytic thyroid carcinoma, including its metastatic behavior and its reduced avidity to radioiodine therapy, warrants a tailored disease management approach. The reclassification of oncocytic thyroid carcinoma by the World Health Organization is an important milestone toward developing a specific and comprehensive clinical management for oncocytic thyroid carcinoma that considers its distinct characteristics.
Analysis of deep mining model for indentation data of biomaterials
Authors: Yuan Qingming
Published: January 2024

The traditional data mining model of indentation has low accuracy in analyzing the linear relationship between the relevant physical quantities of the indentation, so a deep mining model for indentation data of biomaterials is designed. Firstly, the constitutive relation of the material is set by the actual indentation, and the dimension data are collected by the independent free variable function. The characteristic Raman peak is obtained according to the properties of the biological nanomaterials. The stress data are preprocessed by selecting the direction of indentation, which is convenient to observe the dislocation nucleation and deformation twin phenomenon in the process of indenting. The synergistic effect of these dislocations leads to the fact that the load displacement curve shows obvious linear relationship, so as to complete the analysis of the deep mining model of the indentation data of biological nanomaterials. The experimental results show that in the linear relationship analysis of contact depth and indentation depth, the linear relationship discreteness of the designed model is 0.44 lower than that of the traditional model and in the linear relationship analysis of contact stiffness and indentation depth, the linear relationship discreteness of the designed model is 0.38 lower than that of the traditional model, which indicates that the accuracy of the designed model is higher than that of the traditional model in analyzing the linear relationship between the relevant physical quantities of the indentation. In addition, the average accuracy of the model for five different materials is 98.23%.
A DNA/Upconversion Nanoparticle Complex Enables Controlled Co‐Delivery of CRISPR‐Cas9 and Photodynamic Agents for Synergistic Cancer Therapy
Authors: Song Nachuan , Fan Xiaoting , Guo Xiaocui , Tang Jianpu , Li Hongjin , Tao Ruoyu , Li Fengqin , Li Junru , Yang Dayong , Yao Chi , Liu Peifeng
Published: January 2024

Photodynamic therapy (PDT) depends on the light‐irradiated exciting of photosensitizer (PS) to generate reactive oxygen species (ROS), which faces challenges and limitations in hypoxia and antioxidant response of cancer cells, and limited tissue‐penetration of light. Herein, a multifunctional DNA/upconversion nanoparticles (UCNPs) complex is developed which enables controlled co‐delivery of CRISPR‐Cas9, hemin, and protoporphyrin (PP) for synergistic PDT. An ultralong single‐stranded DNA (ssDNA) is prepared via rolling circle amplification (RCA), which contains recognition sequences of single guide RNA (sgRNA) for loading Cas9 ribonucleoprotein (RNP), G‐quadruplex sequences for loading hemin and PP, and linker sequences for combining UCNP. Cas9 RNP cleaves the antioxidant regulator nuclear factor E2‐related factor 2 (Nrf2), improving the sensitivity of cancer cells to ROS, and enhancing the synergistic PDT effect. The G‐quadruplex/hemin DNAzyme mimicks horseradish peroxidase (HRP) to catalyze the endogenous H2O2 to O2, overcoming hypoxia condition in tumors. The introduced UCNP converts NIR irradiation with deep tissue penetration to light with shorter wavelength, exciting PP to transform the abundant O2 to 1O2. The integration of gene editing and PDT allows substantial accumulation of 1O2 in cancer cells for enhanced cell apoptosis, and this synergistic PDT has shown remarkable therapeutic efficacy in a breast cancer mouse model.
Enhanced Photocatalytic and Photovoltaic Performance Arising from Unconventionally Low Donor–Y6 Ratios
Authors: Dolan Andrew , Pan Xun , Griffith Matthew J. , Sharma Anirudh , de la Perrelle Jessica M. , Baran Derya , Metha Gregory F. , Huang David M. , Kee Tak W. , Andersson Mats R.
Published: January 2024

Development of both organic photovoltaics (OPVs) and organic photocatalysts has focused on utilizing the bulk heterojunction (BHJ). The BHJ promotes charge separation and enhances the carrier lifetime, but may give rise to increased charge traps, hindering performance. Here, high photocatalytic and photovoltaic performance is displayed by electron donor–acceptor (D–A) nanoparticles (NPs) and films, using the nonfullerene acceptor Y6 and polymer donor PIDT‐T8BT. In contrast to conventional D–A systems, the charge generation in PIDT‐T8BT:Y6 NPs is mainly driven by Y6, allowing a high performance even at a low D:A mass ratio of 1:50. The high performance at the low mass ratio is attributed to the amorphous behavior of PIDT‐T8BT. Low ratios are generally thought to yield lower efficiency than the more conventional ≈1:1 ratio. However, the OPVs exhibit peak performance at a D:A ratio of 1:5. Similarly the NPs used for photocatalytic hydrogen evolution show peak performance at the 1:6.7 D:A ratio. Interestingly, for the PIDT‐T8BT:Y6 system, as the polymer proportion increases, a reduced photocatalytic and photovoltaic performance is observed. The unconventional D:A ratios provide lower recombination losses and increased charge‐carrier lifetime with undisrupted ambipolar charge transport in bulk Y6, enabling better performance than conventional ratios. This work reports novel light‐harvesting materials in which performance is reduced due to unfavorable morphology as D:A ratios move toward conventional ratios of 1:1.2–1:1.
High‐Quality NiFe Thin Films on Oxide/Non‐Oxide Platforms via Pulsed Laser Deposition at Room Temperature
Authors: Yan Hong , Omar Ganesh Ji , Zhang Zhaoting , Lim Zhi Shiuh , Ariando A.
Published: January 2024

Soft ferromagnetic permalloy (NiFe) thin films are promising for applications in spintronic devices because of their constituent electrical and magnetic properties. Electron beam evaporation and sputtering techniques have been used to deposit NiFe thin films. For in situ stacking of NiFe with functional complex oxides, the pulsed laser deposition (PLD) method is highly desirable. However, the growth of high‐quality NiFe (and non‐oxide thin films in general) by PLD remains a formidable task. Here, high‐quality NiFe thin films of various thicknesses on oxide/non‐oxide substrates with desirable magnetic properties by PLD at room temperature are reported. The magnetic properties are found to be strongly dependent on the laser fluence of the deposition process. The laser fluence of 4 J cm−2 produces the highest magnetization of ≈547 emu cc−1. The small coercivity (few Oersted) and sharp ferromagnetic switching behavior indicate uniaxial anisotropy with an easy axis along the in‐plane direction. In addition, thickness‐dependent magnetodynamics characterizations are studied via ferromagnetic resonance. These results offer significant insight into the PLD‐based development of thin metal magnetic films.
Stop Blaming Hopping Conduction in Nanocrystal Arrays, Use it for Active Photonics!
Authors: Ledos Nicolas , Dang Tung H. , Cavallo Mariarosa , Zhang Huichen , Bossavit Erwan , Khalili Adrien , Do Lam Nguyen , Gréboval Charlie , Ithurria Sandrine , Utterback James K. , Pierucci Debora , Vincent Gregory , Vasanelli Angela , Lhuillier Emmanuel
Published: January 2024

Nanocrystals (NCs) are now established building blocks for photonic applications. However, their integration for optoelectronics has not yet reached the same level of maturity, in part due to the perceived bottleneck that is the inherent limited mobility resulting from hopping conduction. Significant efforts are made to improve this mobility, notably by tuning the particle surface chemistry to enable larger interparticle electronic coupling, and values of mobility of ≈10 cm2 V−1 s−1 have been achieved. It is acknowledged that this value remains significantly lower than those obtained in 2D electron gases but is on par with the mobility reported for vertical transport in epitaxially grown heterostructures with similar confinement energies. Since there appears to be limited perspectives for further increasing mobility values, a suggestion is made that efforts should instead be directed toward exploring the potential benefits offered by hopping conduction. One of these benefits is the bias dependence of the diffusion length, which plays a key role in designing bias‐reconfigurable optical responses for NC‐based devices. Some recent achievements in building bias‐activated devices will be reviewed and the essential criteria for designing future structures will be discussed. Ultimately, hopping conduction is an opportunity to generate new functionalities that low‐disorder materials would be unable to provide.
Heterointerface Energetics Regulation Strategy Enabled Efficient Perovskite Solar Cells
Authors: Zhu Yunfei , Zhang Zuolin , Zhao Xuefan , Li Mengjia , Feng Yinsu , Zhang Shuliang , Gao Wenhuan , Chen Jiangzhao , Tang Jian‐Xin , Chen Cong
Published: January 2024

In the domain of perovskite photovoltaics, the heterointerfaces are subject to substantial trap‐assisted non‐radiative recombination, predominantly attributed to the energy offset, interface defects, and the roughness of the contact. This phenomenon at the heterointerfaces, where carrier non‐radiative recombination and energy dissipation occur due to defects and suboptimal energy level alignment, can be principally held accountable for the Voc losses. Herein, a heterointerface energetics regulation (HER) strategy is proposed by introducing potassium trifluoroacetate (KTFA) in the perovskite precursor solution to eliminate the trap defects and optimize surface potential and Fermi level. It is first demonstrated that non‐doping K+ but precipitating at the upper and buried perovskite will improve energy‐level alignment for charge extraction dynamics. In addition, the TFA− exhibits strong electrostatic force with undercoordinated Pb2+ in the buried contact of perovskite and Sn4+ in the SnO2 electron transporting layer. Based on the vacuum flash evaporation green treatment without anti‐solvent, the Rb0.02(Cs0.05FA0.95)0.98PbI0.91Br0.03Cl0.06 and Cs0.05FA0.95PbI3 based device can achieve maximum efficiency of 23.36% and 24.48%, respectively. Further, the modified devices exhibit 92% initial efficiency output after 1200 h of aging. HER strategy for addressing interface defects and bandgap alignment are poised to advance both the performance and stability of perovskite solar cells.
Oxygen‐18 Labeling Reveals a Mixed Fe−O Mechanism in the Last Step of Cytochrome P450 51 Sterol 14α‐Demethylation
Authors: McCarty Kevin D. , Tateishi Yasuhiro , Hargrove Tatiana Y. , Lepesheva Galina I. , Guengerich F. Peter
Published: January 2024

The 14α‐demethylation step is critical in eukaryotic sterol biosynthesis, catalyzed by cytochrome P450 (P450) Family 51 enzymes, for example, with lanosterol in mammals. This conserved three‐step reaction terminates in a C−C cleavage step that generates formic acid, the nature of which has been controversial. Proposed mechanisms involve roles of P450 Compound 0 (ferric peroxide anion, FeO2−) or Compound I (perferryl oxygen, FeO3+) reacting with either the aldehyde or its hydrate, respectively. Analysis of 18O incorporation into formic acid from 18O2 provides a means of distinguishing the two mechanisms. Human P450 51A1 incorporated 88 % 18O (one atom) into formic acid, consistent with a major but not exclusive FeO2− mechanism. Two P450 51 orthologs from amoeba and yeast showed similar results, while two orthologs from pathogenic trypanosomes showed roughly equal contributions of both mechanisms. An X‐ray crystal structure of the human enzyme showed the aldehyde oxygen atom 3.5 Å away from the heme iron atom. Experiments with human P450 51A1 and H218O yielded primarily one 18O atom but 14 % of the formic acid product with two 18O atoms, indicative of a minor contribution of a Compound I mechanism. LC–MS evidence for a Compound 0‐derived Baeyer–Villiger reaction product (a 14α‐formyl ester) was also found.
Iodinated Electron Acceptor with Significantly Extended Exciton Diffusion Length for Efficient Organic Photovoltaic Cells
Authors: Chen Zhihao , Zhang Shaoqing , Zhang Tao , Ren Junzhen , Dai Jiangbo , Li Huixue , Qiao Jiawei , Hao Xiaotao , Hou Jianhui
Published: January 2024

Iodination has unlocked new potentials in organic photovoltaics (OPVs). A newly designed and synthesized iodinated non‐fullerene acceptor, BO‐4I, showcases exceptional excitation delocalization property with the exciton diffusion length increased to 80 nm. The enhanced electron delocalization property is attributed to the larger atomic radius and electron orbit of the iodine atom, which facilitates the formation of intra‐moiety excitations in the acceptor phase. This effectively circumvents the charge transfer state‐related recombination mechanisms, leading to a substantial reduction in non‐radiative energy loss (ΔEnr). As a result, OPV cell based on PBDB‐TF : BO‐4I achieves an impressive efficiency of 18.9 % with a notable ΔEnr of 0.189 eV, markedly surpassing their fluorinated counterparts. This contribution highlights the pivotal role of iodination in reducing energy loss, thereby affirming its potential as a key strategy in the development of advanced next‐generation OPV cells.
Transition‐Metal‐Free Approach for Z‐Vinyl Fluorides by Hydrofluorination of Alkynes bearing SF4 and SF5 Groups
Authors: Murata Yusuke , Hada Kenshiro , Aggarwal Trapti , Escorihuela Jorge , Shibata Norio
Published: January 2024

The synthesis of vinyl fluorides plays a crucial role in various scientific disciplines, including pharmaceutical and materials sciences. Herein, we present a direct and stereoselective hydrofluorination method for the synthesis of Z isomers of vinyl fluorides from alkynes containing unexplored SF5 and SF4 groups. Our strategy employed tetrabutylammonium fluoride (TBAF) as a fluorine source. It demonstrates high compatibility with aryls, biaryls, heteroaryls, and tert‐alkyl groups, allowing facile incorporation of SF5 and SF4 groups across the triple bond without any transition‐metal catalysts. This approach avoids the potential decomposition of the SF5 or SF4 units via coordination with transition metals or acidic protic sources. Remarkably, this transformation proceeded at room temperature without any additional additives, providing the Z isomer of vinyl fluorides in excellent yield and high selectivity. The presence of a water molecule as a hydrate in TBAF is essential for efficient conversion. This methodology opens new avenues for the synthesis of enchanting SF5‐ and SF4‐containing fluorinated vinylic scaffolds, thereby providing advanced opportunities for novel drug discovery and fluorinated polymers.
Phase Behavior of Charged Star Block Copolymers at Fluids Interface
Authors: Chen Zhan , Ribbe Alexander E. , Steinmetz Christian , Coughlin E. Bryan , Hu Mingqiu , Gan Xuchen , Russell Thomas P.
Published: January 2024

The phase behavior of block copolymers (BCPs) at the water‐oil interface is influenced by the segmental interaction parameter (
) and chain architecture. We synthesized a series of star block copolymers (s‐BCPs) having polystyrene (PS) as core and poly(2‐vinylpyridine) (P2VP) as corona. The interaction parameters of block‐block (
PS‐P2VP) and block‐solvent (
P2VP‐solvent) were varied by adjusting the pH of the aqueous solution. Lowering pH increased the fraction of quaternized‐P2VP (Q‐P2VP) with enhanced hydrophilicity. By transferring the equilibrated interfacial assemblies, morphologies ranging from bicontinuous films at pH of 7 and 3.1 to nanoporous and nanotubular structure at pH of 0.65 were observed. The nanoporous films formed hexagonally packed pores in s‐BCP matrix, while nanotubes comprised Q‐P2VP as corona and PS as core. Control over pore size, d‐spacing between pores, and nanotube diameters was achieved by varying polymer concentration, molecular weight, volume fraction and arm number of s‐BCPs. Large‐scale nanoporous films were obtained by freeze‐drying emulsions. Remarkably, the morphologies of linear BCPs were inverted, forming hexagonal‐packed rigid spherical micelles with Q‐P2VP as core and PS as corona in multilayer. This work provides insights of phase behaviors of BCP at fluids interface and offer a facile approach to prepare nanoporous film with well‐controlled pore structure.
Valorization of kapok fiber by phosphorylation with a reactive phosphorus‐ and nitrogen‐containing flame retardant for enhanced fire safety
Authors: Zhang Jing‐Fang , Tang Ren‐Cheng
Published: January 2024

Kapok fiber (KF) with a naturally hollow structure has found an increasing application in filling and composite materials, most of which have a demand of flame retardancy. To realize this high‐value utilization, KF was phosphorylated by a reactive phosphorus‐ and nitrogen‐containing flame retardant for enhanced fire safety. The flame retardant was first synthesized by the reaction of urea and diethylene triamine pentakis (methyl phosphonic acid) (a commercially available scale inhibitor) with low cost, and then, applied in the phosphorylation of KF in the presence of dicyandiamide. In thermogravimetric analysis, phosphorylated KF showed 38.1% residue weight in nitrogen and 10.2% residue weight in air at 700°C, whereas the residue weight of KF was 8.4% in nitrogen and 1.5% in air. In microcalorimetric analysis, the heat release capacity and total heat release of phosphorylated KF displayed a reduction of 81% and 55%, respectively. In vertical combustion test, phosphorylated KF was difficult to ignite and had no afterburning or smoldering. The tests indicated that phosphorylated KF had excellent charring properties, low heat release, and good flame retardancy. This work suggests a promising strategy of enhancing the flame retardancy of KF and increasing its applicability in filling and composite materials.
Ultrafast Demagnetization Through Femtosecond Generation of Non‐Thermal Magnons
Authors: Weißenhofer Markus , Oppeneer Peter M.
Published: January 2024

Ultrafast laser excitation of ferromagnetic metals gives rise to correlated, highly non‐equilibrium dynamics of electrons, spins and lattice, which are, however, poorly described by the widely‐used three‐temperature model. Here, a fully ab initio parameterized out‐of‐equilibrium theory based on a quantum kinetic approach – termed (N+2) temperature model – is developed to describe magnon occupation dynamics due to electron‐magnon scattering. This model is applied to perform quantitative simulations on the ultrafast, laser‐induced generation of magnons in iron and demonstrates that on these timescales the magnon distribution is non‐thermal: predominantly high‐energy magnons are created, while the magnon occupation close to the center of the Brillouin zone even decreases, due to a repopulation toward higher energy states via a so‐far‐overlooked scattering term. It is demonstrated that the simple relation between magnetization and temperature computed at equilibrium does not hold in the ultrafast regime. The ensuing Gilbert damping, furthermore, becomes strongly magnon wavevector dependent and requires a description beyond the conventional Landau‐Lifshitz‐Gilbert spin dynamics. The ab initio parameterized calculations show that ultrafast generation of non‐thermal magnons provides a sizable demagnetization within 200 fs in excellent comparison with experimentally observed laser‐induced demagnetizations. This investigation thus emphasizes the importance of non‐thermal magnon excitations for the ultrafast demagnetization process.
Cluster Control for Construction of Bismuth‐Doped Glass Fiber with Broadband Optical Response
Authors: Zhang Ke , Dong Quan , Chen Jingfei , Wei Tianxia , Wang Dazhao , Li Hongwei , Hou Dianhao , Yan Jianfeng , Li Xueliang , Feng Xu , Zhou Shifeng
Published: January 2024

Bismuth(Bi)‐doped optical fibers are widely used in various aspects such as fiber lasers and amplifiers. Despite extensive research efforts to explore high‐gain Bi‐doped fibers, the pursuit of Bi‐doped fibers with emission over an extremely wide wavelength range remains unfulfilled. Here, the strategy of cluster control via regulating glass structure is proposed. It is applied to construct Bi‐doped photonic glass with ultra‐broadband near‐infrared (NIR) emission and a full width at half maximum (FWHM) of 343 nm. The strategy is further combined with the modified chemical vapor deposition (MCVD) technique with solution doping. The fiber exhibits ultra‐broadband amplified spontaneous emission (ASE) covering the entire fiber communication band (1260–1625 nm). Finally, the fiber exhibits higher optical gain and bandwidth compared with the fiber without cluster control. This device can be utilized to potentially enhance the capacity of telecommunication systems.
Chemical Methods to Identify Epigenetic Modifications in Cytosine Bases
Authors: N Madhumitha , Kumar Parvathy S. , Manna Debasish
Published: January 2024

Chemical modifications to Cytosine bases are among the most studied epigenetic markers and their detection in the human genome plays a crucial role in gaining more insights about gene regulation, prognosis of genetic disorders and unraveling genetic inheritance patterns. The Cytosine methylated at the 5th position and oxidized derivatives thereof generated in the demethylation pathways, perform separate and unique epigenetic functions in an organism. As the presence of various Cytosine modifications is associated with diverse diseases, including cancer, there has been a strong focus on developing methods, both chemical and alternative approaches, capable of detecting these modifications at a single‐base resolution across the entire genome. In this comprehensive review, we aim to consolidate the various chemical methods and understanding their chemistry that have been established to date for the detection of various Cytosine modifications.
Fair funding for pupils with special educational needs and disability in England?
Authors: Marsh Alan J. , Gray Peter , Norwich Brahm
Published: January 2024

School funding formulas have been applied across a number of countries for at least the last 50 years. A national funding formula (NFF) was introduced in England in 2018 and aims to provide a platform for fair funding across the country. This study explores the variations in the NFF's high needs block (HNB) funding and examines links with the use of specialist provision by English local authorities (LAs) for children with special educational needs and disability. The findings demonstrate significant and continuing differences in HNB funding between demographically similar LAs, notwithstanding a £3.5 billion (75%) HNB increase in real terms in the decade since 2013, which could have supported a shift towards a more equitable position. Published HNB funding for 2023–24 now varies by up to £49m in comparator LAs. Differences are largely the result of the persistent use of a historical factor in the formula and a ceiling on levels of income growth for lower funded LAs. The research also shows a significant link between HNB funding and the use of specialist provision. The discussion investigates how far the UK government's policy commitment to a more equitable system of HNB funding is matched by the reality, and the degree to which funding is based on need rather than demand or history.
The link between teacher buy‐in and intentions to continue working in their current school
Authors: Jerrim John
Published: January 2024

Previous research has found school working conditions—particularly school leadership—to be linked to teacher retention. At the same time, evidence from the management literature has suggested that obtaining ‘buy‐in’ from staff is critical to employee performance and instigating change. This paper brings these two literatures together, being the first study to explore the relationship between buy‐in and teachers' plans to continue working at their current school. The analysis illustrates how teachers who buy into the leadership team's strategy are much more likely to intend to continue working at the school, over and above their views on workload, pay and the quality of their relationships with their colleagues. We conclude by considering what school leaders might do to improve buy‐in amongst their staff, while also highlighting areas where further research is needed.
Control strategy for biopharmaceutical production by model predictive control
Authors: Eslami Touraj , Jungbauer Alois
Published: January 2024

The biopharmaceutical industry is rapidly advancing, driven by the need for cutting‐edge technologies to meet the growing demand for life‐saving treatments. In this context, Model Predictive Control (MPC) has emerged as a promising solution to address the complexity of modern biopharmaceutical production processes. Its ability to optimize operations and ensure consistent product yields has made it an attractive option for manufacturers in this sector. Furthermore, MPC's alignment with the Process Analytical Technology (PAT) initiative provides an additional layer of assurance, facilitating real‐time monitoring and enabling swift adjustments to maintain process integrity. This comprehensive review delves into the various applications of MPC, ranging from robust control to stochastic model predictive control, thereby equipping biotechnologists and process engineers with a powerful toolset. By harnessing the capabilities of MPC, as elucidated in this review, manufacturers can confidently navigate the intricate bioprocessing landscape and unlock this approach's full potential in their production processes.
Heterogeneity‐induced NGF‐NGFR communication inefficiency promotes mitotic spindle disorganization in exhausted T cells through PREX1 suppression to impair the anti‐tumor immunotherapy with PD‐1 mAb in hepatocellular carcinoma
Authors: Wang Xin , Yang Tongwang , Shi Shangheng , Xu Chuanshen , Wang Feng , Dai Deshu , Guan Ge , Zhang Yong , Wang Shuxian , Wang Jianhong , Zhang Bingliang , Liu Peng , Bai Xiaoshuai , Jin Yan , Li Xinqiang , Zhu Cunle , Chen Dexi , Xu Qingguo , Guo Yuan
Published: January 2024

Background

The mechanism of decreased T cells infiltrating tumor tissues in hepatocellular carcinoma is poorly understood.

Methods

Cells were separated from the single‐cell RNA‐sequence dataset of hepatocellular carcinoma patients (GSE149614) for cell‐cell communication. Flow cytometry, EDU staining, H3‐Ser28 staining, confocal immunofluorescence staining, western blotting and naked microsubcutaneous tumors were performed for the mechanism of NGF‐NGFR promoting proliferation.

Results

The present study has revealed that during the process of T‐cell infiltration from adjacent tissues to tumor tissues, an inefficiency in NGF‐NGFR communication occurs in the tumor tissues. Importantly, NGF secreted by tumor cells interacts with NGFR present on the membranes of the infiltrated T cells, thereby promoting the proliferation through the activation of mitotic spindle signals. Mechanistically, the mediation of mitotic spindle signal activation promoting proliferation is executed by HDAC1‐mediated inhibition of unclear trans‐localization of PREX1. Furthermore, PD‐1 mAb acts synergistically with the NGF‐NGFR communication to suppress tumor progression in both mouse models and HCC patients. Additionally, NGF‐NGFR communication was positively correlates with the PD‐1/PDL‐1 expression. However, expressions of NGF and NGFR are low in tumor tissues, which is responsible for the invasive clinicopathological features and the disappointing prognosis in HCC patients.

Conclusion

Inefficiency in NGF‐NGFR communication impairs PD‐1 mAb immunotherapy and could thus be utilized as a novel therapeutic target in the treatment of HCC patients in clinical practice.
Educational outcomes in siblings of childhood leukemia survivors: Factors associated with school difficulties and comparison with general population
Authors: Faust Cindy , Auquier Pascal , Gandemer Virginie , Bertrand Yves , Tabone Marie‐Dominique , Ansoborlo Sophie , Baruchel André , Bonneau Jacinthe , Dalle Jean‐Hugues , Chastagner Pascal , Kanold Justyna , Poirée Maryline , Theron Alexandre , Olivier Laura , Pellier Isabelle , Michel Gérard , Berbis Julie
Published: January 2024

Background

To investigate the educational outcomes of siblings of childhood leukemia survivors, explore determinants of school difficulties, and compare the rates of repeating grades between siblings and the general population.

Methods

A cross‐sectional study of childhood leukemia survivors' siblings recruited through the Leucémies de l'Enfant et de l'Adolescent cohort, a French long‐term follow‐up program, was conducted, and education‐related data were obtained via self‐report questionnaires. Adjusted logistic regression models were used to identify variables associated with school difficulties and time since diagnosis. Rates of repeating a grade in middle school were compared between siblings and the general population of the same generation.

Results

A total of 564 siblings with a mean time from diagnosis of 14.1 ± 6.4 years were included, among whom 139 (24.6%) repeated a grade, at an average of 6.4 ± 4.5 years after diagnosis. In multivariate analysis, the risk factors for repeating a grade were older siblings (odds ratio [OR] 2.3, p = 0.006), family financial difficulties (OR 2.8, p = 0.008), and history of repetition in survivors (OR, 2.5, p = 0.001). Sibling hematopoietic stem cell donors were at greater risk of repeating a grade long‐term after diagnosis (p = 0.018). Overall, siblings did not have a higher risk of educational delays at the end of middle school than the general population.

Conclusion

Although the results are reassuring, socioeconomic and cancer‐related factors may have an impact on siblings' schooling long after diagnosis. Paying attention to siblings contributes to identifying the most vulnerable families, allowing more attention and appropriate resources to avoid long‐term repercussions. Additionally, supportive and targeted interventions can be developed to improve the organization of education and the health care system.
An analysis of the relationship of triglyceride glucose index with gastric cancer prognosis: A retrospective study
Authors: Cai Chao , Chen Cheng , Lin Xiuli , Zhang Huihui , Shi Mingming , Chen Xiaolei , Chen Weisheng , Chen Didi
Published: January 2024

Aims/Introduction

Gastric cancer, one of the most common malignant tumors worldwide, is affected by insulin resistance. The triglyceride glucose (TYG) index is considered a surrogate indicator of insulin resistance; however, its prognostic value in patients with gastric cancer remains obscure. This study aimed to determine whether the TYG index could predict the long‐term prognosis of patients with gastric cancer after radical resection gastrectomy.

Materials and Methods

We retrospectively analyzed patients with gastric cancer who underwent radical resection gastrectomy. The preoperative TYG index was calculated using the patients' laboratory data. Patients were divided into two groups based on a high or low TYG index. We observed overall survival and evaluated the clinical application value of the index using Cox proportional hazards regression to calculate independent parameters. A prediction model was also established.

Results

In total, 822 patients with gastric cancer were included. The high and low TYG index groups comprised 353 and 469 patients, respectively. The overall survival time was significantly longer in the high‐index group than in the low‐index group. In the multivariate analysis, TYG index, preoperative age, surgical procedure, tumor node metastasis (TNM) stage, N stage, and postoperative complications (all p < 0.01) were considered independent prognostic predictors. Based on the multivariate analysis, the riglyceride glucose (TYG) index hazard ratio was 0.70 (95% confidence interval, 0.54–0.89, p = 0.004).

Conclusions

We established a model with a high clinical application value and clinical practice relevance to predict the prognosis of gastric cancer. In this model, TYG was an independent protective factor for gastric cancer prognosis.
Association of area‐level mortgage denial and guideline‐concordant non‐small‐cell lung cancer care and outcomes in the United States
Authors: Fan Qinjin , Hussaini S. M. Qasim , Barrow Lauren C. J. , Feliciano Josephine L. , Pollack Craig E. , Yabroff K. Robin , Nogueira Leticia
Published: January 2024

Background

Racial and socioeconomic disparities in receipt of care for non‐small‐cell lung cancer (NSCLC) are well described. However, no previous studies have evaluated the association between mortgage denial rates and receipt of timely and guideline‐concordant care for NSCLC and patient outcomes.

Methods

We identified individuals ≥18 years diagnosed with NSCLC between 2014 and 2019 from the National Cancer Database. Using the Home Mortgage Disclosure Act database, we calculated the proportion of denied home loans to total loans at the zip‐code level and categorized them into quintiles. Our outcomes included receipt of guideline‐concordant care based on clinical and pathologic stage at diagnosis and the National Comprehensive Cancer Network guidelines, time from surgery to chemotherapy initiation, and overall survival.

Results

Of the 629,288 individuals diagnosed with NSCLC (median age 69; IQR 61–76 years, 49.1% female), 47.8% did not receive guideline‐concordant care. Residing in areas with higher mortgage denial rates and lower income was associated with worse guideline‐concordant care overall (aRR = 1.28; 95% CI = 1.25–1.32) and for each cancer treatment modality, worse receipt of timely chemotherapy (aHR = 1.14; 95% CI = 1.11–1.17) and worse overall survival (aHR = 1.21; 95% CI = 1.19–1.22), compared with residing in areas with the lowest mortgage denial rate and highest income.

Conclusions

Area‐level mortgage denial rate was associated with worse receipt of timely and guideline‐concordant NSCLC care and survival. This highlights the critical need to understand and address systemic practices, such as mortgage denial, that limit access to resources and are associated with worse access to quality cancer care and outcomes.
Accessibility and affirmation in counselling: An exploration into neurodivergent clients' experiences
Authors: Jones Faith , Hamilton Jenny , Kargas Niko
Published: January 2024

Neurodivergence is having ‘a mind that functions in ways which diverge significantly from the dominant societal standards of “normal”’ (Walker, 2021, p. 33; Neuroqueer Heresies: Notes on the Neurodiversity Paradigm, Autistic Empowerment, and Postnormal Possibilities). The neurodiversity paradigm reframes the medical model of neurodivergence within the social context of disability (den Houting, 2018 [Autism, 23, 171]; Dwyer, 2022 [Human Development, 66, 73]). Research converges counselling and neurodiversity in a disorder‐specific context, for example, the wide range of barriers of access to counselling that autistic individuals face (Hallett & Kerr, 2020 [You need support, validation, good coping skills. You need and deserve acceptance]). More recent literature points towards the need for a flexible, clear approach to neurodivergence‐informed counselling (Bolton, 2023b [Three ideas in person‐centered, neurodivergent‐affirming therapy]; Chapman & Botha, 2022 [Developmental Medicine & Child Neurology, 65, 310]; Pantazakos, 2023 [Counselling and Psychotherapy Research]). This research aimed to explore whether lived experiences of neurodivergent individuals within counselling were accessible, validating and affirming, in particular, regarding reasonable adjustments, communication and environment. An inductive, qualitative approach was adopted. Five individuals participated in semi‐structured interviews, which were analysed following a six‐phase approach to thematic analysis. Six main themes were found: (1) Feelings of frustration and confusion at language used in counselling; (2) Feelings of clarity and validation in language; (3) Feelings of overwhelm due to uncertainty and masking; (4) Feeling understood, heard and able to self‐advocate; (5) The need for a safe, secure sensory environment and accommodations made; and (6) General accessibility and practicalities. Recommendations for practice include amending the counselling contracting process and sensitivity to the communication and sensory needs of each individual client. Further research may wish to explore specific details of the present, and other emergent, neurodiversity research in more detail.
DNAJA1 positively regulates amino acid‐stimulated milk protein and fat synthesis in bovine mammary epithelial cells
Authors: Li Zhuolin , Yuan Xiaohan , Wang Yuanhao , Sun Zheya , Ao Jinxia
Published: January 2024

Several cellular processes, including the recovery of misfolded proteins, the folding of polypeptide chains, transit of polypeptides across the membrane, construction and disassembly of protein complexes, and modulation of protein control, are carried out by DnaJ homolog subfamily A member 1 (DNAJA1), which belongs to the DnaJ heat‐shock protein family. It is unknown if DNAJA1 regulates the production of milk in bovine mammary epithelium cells (BMECs). Methionine and leucine increased DNAJA1 expression and nuclear location, as seen by us. In contrast to DNAJA1 knockdown, overexpression of DNAJA1 boosted the production of milk proteins and fats as well as mammalian target of rapamycin (mTOR) and sterol regulatory element binding protein‐1c (SREBP‐1c). As a result of amino acids, mTOR and SREBP‐1c gene expression are stimulated, and DNAJA1 is a positive regulator of BMECs' amino acid‐induced controlled milk protein and fat production.
Molybdenum‐Copper Antagonism In Metalloenzymes And Anti‐Copper Therapy
Authors: Maiti Biplab K. , Moura Isabel , Moura José J. G.
Published: January 2024

The connection between 3d (Cu) and 4d (Mo) via the “Mo−S−Cu” unit is called Mo−Cu antagonism. Biology offers case studies of such interactions in metalloproteins such as Mo/Cu−CO Dehydrogenases (Mo/Cu−CODH), and Mo/Cu Orange Protein (Mo/Cu−ORP). The CODH significantly maintains the CO level in the atmosphere below the toxic level by converting it to non–toxic CO2 for respiring organisms. Several models were synthesized to understand the structure–function relationship of these native enzymes. However, this interaction was first observed in ruminants, and they convert molybdate (MoO42−) into tetrathiomolybdate (MoS42−; TTM), reacting with cellular Cu to yield biological unavailable Mo/S/Cu cluster, then developing Cu‐deficiency diseases. These findings inspire the use of TTM as a Cu‐sequester drug, especially for treating Cu‐dependent human diseases such as Wilson diseases (WD) and cancer. It is well known that a balanced Cu homeostasis is essential for a wide range of biological processes, but negative consequence leads to cell toxicity. Therefore, this review aims to connect the Mo−Cu antagonism in metalloproteins and anti‐copper therapy.
DMSO‐Related Effects on Ligand‐Binding Properties of Lysine Methyltransferases G9a and SETD8
Authors: Feoli Alessandra , Sarno Giuliana , Castellano Sabrina , Sbardella Gianluca
Published: January 2024

Being the standard solvent for preparing stock solutions of compounds for drug discovery, DMSO is always present in assay buffers in concentrations ranging from 0.1 % to 5 % (v/v). Even at the lowest concentrations, DMSO‐containing solutions can have significant effects on individual proteins and possible pitfalls cannot be eliminated. Herein, we used two protein systems, the lysine methyltransferases G9a/KMT1 C and SETD8/KMT5 A, to study the effects of DMSO on protein stability and on the binding of the corresponding inhibitors, using different biophysical methods such as nano Differential Scanning Fluorimetry (nanoDSF), Differential Scanning Fluorimetry (DSF), microscale thermophoresis (MST), and surface plasmon resonance (SPR), all widely used in drug discovery screening campaigns. We demonstrated that the effects of DMSO are protein‐ and technique‐dependent and cannot be predicted or extrapolated on the basis of previous studies using different proteins and/or different assays. Moreover, we showed that the application of orthogonal biophysical methods can lead to different binding affinity data, thus confirming the importance of using at least two different orthogonal assays in screening campaigns. This variability should be taken into account in the selection and characterization of hit compounds, in order to avoid data misinterpretation.
The BALTO Registry: Long‐term results of percutaneous BALloon pericardioTomy in oncological patients
Authors: Rivero‐Santana Borja , Jimenez‐Valero Santiago , Jurado‐Roman Alfonso , Galeote Guillermo , Lopez‐Fernandez Teresa , Moreno Raul
Published: January 2024

Objectives

The aim of this study was to analyze the efficacy and safety of percutaneous balloon pericardiotomy (PBP) in oncological patients who present with a malignant pericardial effusion (MPE).

Background

The use of PBP as a treatment for MPE is not standardized due to the limited evidence. Furthermore, the performance of a second PBP for a recurrence after a first procedure is controversial.

Methods

The BALTO Registry (BALloon pericardioTomy in Oncological patients) is a prospective, single‐center, observational registry that includes consecutive PBP performed for MPE from October 2007 to February 2022. Clinical and procedural, characteristics, as well as clinical outcome were analyzed.

Results

Seventy‐six PBP were performed in 61 patients (65% female). Mean age was of 66.4 ± 11.2 years. In 15 cases, a second PBP procedure was performed due to recurrence despite the first PBP. The procedure could be performed effectively in all cases with only two serious complications. Ninety‐five percent of cases were discharged alive from the hospital. During a median follow‐up of 6.3 months (interquartile range [IQR], 0.9–10.8), MPE recurred in 24.5% cases although no recurrences were reported after the second procedure. No evidence of malignant pleural effusion developed on follow‐up. The median overall survival time was 5.8 months (IQR, 0.8–10.2) and the time to recurrence after the first PBP was 2.4 months (IQR, 0.7–4.5).

Conclusions

PBP is a safe and effective treatment for MPE. It could be considered an acceptable therapy in most MPE, even in those who recur after a first procedure.
Promising practices for online site supervision training for school counselors
Authors: Chae Nancy , Backer Adrienne
Published: January 2024

This qualitative case study examined a piloted online synchronous school counseling site supervision training program. The findings of the study included two key themes, Community of Learning and Opportunities for Reflection and Application, which revealed aspects of participant engagement and content delivery that enhanced school counseling site supervisors’ learning experiences.
Synthesis and Characterization of Bola‐Amphiphilic Porphyrin‐Perylenebisimide Architectures
Authors: Schulze Erik J. , Ritterhoff Christian L. , Franz Evanie , Tavlui Olha , Brummel Olaf , Meyer Bernd , Hirsch Andreas
Published: January 2024

We report on the synthesis and characterization of a family of three water‐soluble bola‐amphiphilic zinc‐porphyrin‐perylenebisimide triads containing oligo carboxylic‐acid capped Newkome dendrons in the periphery. Variations of the perylenebisimide (PBI) core geometry and dendron size (G1 and G2 dendrons with 3‐ and 9‐carboxylic acid groups respectively) allow for tuning the supramolecular aggregation behavior with respect to variation of the molecular architecture. The triads show good solubility in basic aqueous media and aggregation to supramolecular assemblies. Theoretical investigations at the DFT level of theory accompanied by electrochemical measurements unravel the geometric and electronic structure of the amphiphiles. UV/Vis and fluorescence titrations with varying amounts of THF demonstrate disaggregation.
Progress of Fluorescent Probes for Protein Phosphorylation and Glycosylation in Atherosclerosis
Authors: Li Jin , Xu Jiheng , Zhao Ruize , Zhang Wei , Li Ping , Zhang Wen , Wang Hui , Tang Bo
Published: January 2024

Exploring the post‐translational modification (PTM) of proteins in the course of atherosclerotic disease has important guiding significance for the early warning of atherosclerotic plaque, the development of targeted drugs and the treatment of disease. The advancement advanced detection and imaging methods for phosphorylated and glycosylated proteins is an important tool to further reveal the levels of protein phosphorylation and glycosylation during atherosclerotic plaque formation. We present research strategies for detecting protein phosphorylation and glycosylation from the perspective of fluorescent probes, and discuss the feasibility and future direction of the development of these methods for detecting and imaging phosphorylated and glycosylated proteins in atherosclerotic disease.