bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of CT Perfusion Software Packages for Thrombectomy Eligibility
Authors: Pisani Leonardo , Haussen Diogo C. , Mohammaden Mahmoud , Perry da Camara Catarina , Jillella Dinesh V. , Rodrigues Gabriel M. , Bouslama Mehdi , Al‐Bayati Alhamza , Prater Adam , Liberato Bernardo , Frankel Michael R. , Nogueira Raul G. 
Published: July 2023

IntroductionComputed tomography perfusion (CTP) has played an important role in patient selection for mechanical thrombectomy (MT) in acute ischemic stroke. We aimed to investigate the agreement between perfusion parametric maps of 3 software packages – RAPID (RapidAI‐IschemaView), Viz CTP(Viz.ai), and e‐CTP(Brainomix) – in estimating baseline ischemic core volumes of near completely/completely reperfused patients.MethodsWe retrospectively reviewed a prospectively maintained MT database to identify patients with anterior circulation large vessel occlusion strokes (LVOS) involving the internal carotid artery or middle cerebral artery M1‐segment and interpretable CTP maps treated during September 2018 to November 2019. A subset of patients with near‐complete/complete reperfusion (expanded thrombolysis in cerebral infarction [eTICI] 2c–3) was used to compare the pre‐procedural prediction of final infarct volumes.ResultsIn this analysis of 242 patients with LVOS, RAPID and Viz CTP relative cerebral blood flow (rCBF) < 30% values had substantial agreement (ρ = 0.767 [95% confidence interval [CI] = 0.71–0.81]) as well as for RAPID and e‐CTP (ρ = 0.668 [95% CI = 0.61–0.71]). Excellent agreement was seen for time to maximum of the residue function (Tmax) > 6 seconds between RAPID and Viz CTP (ρ = 0.811 [95% CI = 0.76–0.84]) and substantial for RAPID and e‐CTP (ρ = 0.749 [95% CI = 0.69–0.79]). Final infarct volume (FIV) prediction (n = 136) was substantial in all 3 packages (RAPID ρ = 0.744; Viz CTP ρ = 0.711; and e‐CTP ρ = 0.600).ConclusionPerfusion parametric maps of the RAPID, Viz CTP, and e‐CTP software have substantial agreement in predicting final infarct volume in near‐completely/completely reperfused patients. ANN NEUROL 2023;94:848–855
Anakinra‐Associated Systemic Amyloidosis
Authors: Alehashemi Sara , Dasari Surendra , Metpally Anvitha , Uss Kat , Castelo‐Soccio Leslie A. , Heller Theo , Kellman Peter , Chen Marcus Y. , Ahlman Mark , Kim Jeff , Wargo Susannah , Kuhns Douglas B. , Fink Danielle , de Jesus Adriana , Martin Paul S. , Chang Richard , Bolanos Jonathan , Lee Chyi‐Chia Richard , Nasr Samih H. , Goldbach‐Mansky Raphaela , McPhail Ellen 
Published: July 2023

ObjectiveTo describe a 41‐year‐old woman with a history of neonatal onset multisystem inflammatory disease, on treatment with daily subcutaneous injections of 600 mg of recombinant interleukin‐1 receptor antagonist (IL‐1Ra) protein, anakinra, since the age of 28, who presented with golf‐ball size nodules at the anakinra injection sites, early satiety, new onset nephrotic syndrome in the context of normal markers of systemic inflammation.MethodsClinical history and histologic evaluation of biopsies of skin, gastric mucosa, and kidney with Congo‐red staining and proteomic evaluation of microdissected Congo red–positive amyloid deposits by liquid chromatography‐tandem mass spectrometry.ResultsThe skin, stomach, and kidney biopsies all showed the presence of Congo red–positive amyloid deposits. Mass spectrometry‐based proteomics demonstrated that the amyloid deposits in all sites were of AIL1RAP (IL‐1Ra protein)‐type. These were characterized by high spectral counts of the amyloid signature proteins (apolipoprotein AIV, apolipoprotein E, and serum amyloid P‐component) and the amyloidogenic IL‐1Ra protein, which were present in Congo red–positive areas and absent in Congo red–negative areas. The amino acid sequence identified by mass spectrometry confirmed that the amyloid precursor protein was recombinant IL‐1Ra (anakinra) and not endogenous wild‐type IL‐1Ra.ConclusionThis is the first report of iatrogenic systemic amyloidosis due to an injectable protein drug, which was caused by recombinant IL1Ra (anakinra).
Tau, microtubule dynamics, and axonal transport: New paradigms for neurodegenerative disease
Authors: Cario Alisa , Berger Christopher L. 
Published: July 2023

AbstractThe etiology of Tauopathies, a diverse class of neurodegenerative diseases associated with the Microtubule Associated Protein (MAP) Tau, is usually described by a common mechanism in which Tau dysfunction results in the loss of axonal microtubule stability. Here, we reexamine and build upon the canonical disease model to encompass other Tau functions. In addition to regulating microtubule dynamics, Tau acts as a modulator of motor proteins, a signaling hub, and a scaffolding protein. This diverse array of functions is related to the dynamic nature of Tau isoform expression, post‐translational modification (PTM), and conformational flexibility. Thus, there is no single mechanism that can describe Tau dysfunction. The effects of specific pathogenic mutations or aberrant PTMs need to be examined on all of the various functions of Tau in order to understand the unique etiology of each disease state.
Improving phytase production in Pichia pastoris fermentations through de‐repression and methanol induction optimization
Authors: Luna‐Flores Carlos H. , Weng Yilun , Wang Alexander , Chen Xiaojing , Peng Bingyin , Zhao Chun‐Xia , Navone Laura , von Hellens Juhani , Speight Robert E. 
Published: July 2023

AbstractPichia pastoris (Komagataella phaffii) is a fast‐growing methylotrophic yeast with the ability to assimilate several carbon sources such as methanol, glucose, or glycerol. It has been shown to have outstanding secretion capability with a variety of heterologous proteins. In previous studies, we engineered P. pastoris to co‐express Escherichia coli AppA phytase and the HAC1 transcriptional activator using a bidirectional promoter. Phytase production was characterized in shake flasks and did not reflect industrial conditions. In the present study, phytase expression was explored and optimized using instrumented fermenters in continuous and fed‐batch modes. First, the production of phytase was investigated under glucose de‐repression in continuous culture at three dilution factors, 0.5 d−1, 1 d−1, and 1.5 d−1. The fermenter parameters of these cultures were used to inform a kinetic model in batch and fed‐batch modes for growth and phytase production. The kinetic model developed aided to design the glucose‐feeding profile of a fed‐batch culture. Kinetic model simulations under glucose de‐repression and fed‐batch conditions identified optimal phytase productivity at the specific growth rate of 0.041 h−1. Validation of the model simulation with experimental data confirmed the feasibility of the model to predict phytase production in our newly engineered strain. Methanol was used only to induce the expression of phytase at high cell densities. Our results showed that high phytase production required two stages, the first stage used glucose under de‐repression conditions to generate biomass while expressing phytase, and stage two used methanol to induce phytase expression. The production of phytase was improved 3.5‐fold by methanol induction compared to the expression with glucose alone under de‐repression conditions to a final phytase activity of 12.65 MU/L. This final volumetric phytase production represented an approximate 36‐fold change compared to the flask fermentations. Finally, the phytase protein produced was assayed to confirm its molecular weight, and pH and temperature profiles. This study highlights the importance of optimizing protein production in P. pastoris when using novel promoters and presents a general approach to performing bioprocess optimization in this important production host.
Sodium chloride impacts glycosylation and N‐ and O‐glycan site occupancy of an Fc‐fusion protein
Authors: Bohl Susanne , Le Mignon Maxime , Kilian Thomas , Zimmer Aline 
Published: July 2023

AbstractFc‐fusion proteins are highly complex molecules, difficult to manufacture at scale. In this work, undesired proteoforms were detected during the manufacture of a therapeutic fusion protein produced in CHO cells. These species were characterized using gel electrophoresis, size exclusion chromatography and liquid chromatography‐mass spectrometry leading to the identification of low molecular weight proteoforms presenting low N‐ and O‐glycan site occupancy, as well as a low sialylation content. Upstream process parameters were investigated, and fusion protein quality was shown to be linked to the sodium chloride content of the medium. A mitigation strategy was developed to avoid formation of unwanted glyco‐variants, resulting in an increased yield of highly glycosylated Fc‐fusion protein. The effect of sodium chloride was shown to be independent of the osmolality increase and was hypothesized to be linked to a modulation of Golgi acidity, which is required for the correct localization and function of glycosyltransferases. Altogether, this study highlights the importance of the salt balance in cell culture media used to produce highly sialylated and occupied glycoproteins, helping to maximize the yield and increase robustness of processes aiming at producing biopharmaceutical complex therapeutic molecules.
Brands are calling your AVATAR in Metaverse–A study to explore XR‐based gamification marketing activities & consumer‐based brand equity in virtual world
Authors: Arya Vikas , Sambyal Rachita , Sharma Anshuman , Dwivedi Yogesh K 
Published: July 2023

AbstractBrands are moving towards the Metaverse (3D immersive virtual spaces), where the growth of intangible products and nonfungible tokens (NFTs) are evolving into a new type of hybrid experience for the users. This paper aims to establish the role of a “gamification of marketing activities” and its influence on consumer‐based brand equity for intangible products (NFTs) in the Metaverse and examine the mediating role of consumers' brand engagement and brand love. To evaluate the conceptual model based on the cross‐cultural data from two emerging countries in Asia and Africa, the study followed a two‐stage, hybrid mechanism using PLS‐SEM and neural network modeling. This study provides insights into the Metaverse–a new taxonomy of technology, in the context of embodiment, presence of AVATAR, and interactivity in the virtual world, supported by the social exchange theory. This study also suggests practitioners focus on brand authenticity while projecting their brand in the Metaverse.
Caulobacter segnis Dioxygenase CsO2: A Practical Biocatalyst for Stilbenoid Ozonolysis
Authors: De Vitis Valerio , Cannazza Pietro , Mattio Luce , Romano Diego , Pinto Andrea , Molinari Francesco , Laurenzi Tommaso , Eberini Ivano , Contente Martina L. 
Published: July 2023

AbstractOzonolysis is a useful as well as dangerous reaction for performing alkene cleavage. On the other hand, enzymes are considered a more sustainable and safer alternative. Among them, Caulobacter segnis dioxygenase (CsO2) known so far for its ability to catalyze the coenzyme‐free oxidation of vinylguaiacol into vanillin, was selected and its substrate scope evaluated towards diverse natural and synthetic stilbenoids. Under optimized conditions, CsO2 catalyzed the oxidative cleavage of the C=C double bonds of various trans‐stilbenes, providing that a hydroxyl moiety was necessary in para‐position of the phenyl group (e. g., resveratrol and its derivatives) for the reaction to take place, which was confirmed by modelling studies. The reactions occurred rapidly (0.5–3 h) with high conversions (95–99 %) and without formation of by‐products. The resveratrol biotransformation was carried out on 50–mL scale thus confirming the feasibility of the biocatalytic system as a preparative method.
Base‐Stabilized Phosphinidene Oxide, Imide and Sulfide
Authors: Baradzenka Aliona G. , Vyboishchikov Sergei F. , Pilkington Melanie , Nikonov Georgii I. 
Published: July 2023

AbstractOxidation of a base‐stabilized phosphinidene (κ2‐NNP)P (12, NNP=phosphinoamidinate) with N2O afforded a labile phosphinidene oxide (κ2‐NNP)P=O (16) which was characterized by NMR spectroscopy. Further oxidation of 16 by N2O or reaction of 12 with two equivalents of pyridine oxide afforded the isolable dioxide (κ2‐NNP)PO2 which was characterized by NMR and SC XRD. Trapping of 16 with tolyl isocyanate resulted in P=O/N=C metathesis, eventually affording a urea‐ligated phosphine (κ1‐NNP)P(NTol)2C=O (17) The mechanism of this reaction was elucidated by DFT calculations. Reactions of phosphinidene 12 with azides generated transient imines (NNP)P=NR, which in the case of R=Tol underwent cycloaddition with tolyl Isocyanate to afford the urea product 17, and in the case of R=SiMe3 reacts with N3SiMe3 via the addition of N−Si across the P=N bond affording, after the extrusion of dinitrogen, a P,N‐heterocyclic compound. Both products of the reactions with azides have been fully characterized, both in solution and the solid‐state. Finally, reaction of phosphinidene 12 with one equivalent of sulfur resulted in the isolation of the base‐stabilized phosphinidene sulfide (κ2‐NNP)P=S that has also been fully characterized.
Strain‐Driven, Non‐Catalysed Ring Expansion of Silicon Heterocycles
Authors: Müller Maximilian P. , Hinz Alexander 
Published: July 2023

AbstractSilacycles are ubiquitous building blocks. Small silacycles can typically be expanded catalytically. A silirane, silirene and phosphasilirene as well as a siletane and a silolene were prepared starting from the base‐free bromosilylene [(dtbpCbz)SiBr] (dtbpCbz=1,8‐bis(3,5‐ditertbutylphenyl)‐3,6‐ditertbutylcarbazolyl). As these heterocycles were derived from a dicoordinated silylene, they are susceptible to reactions with an external base. The three‐membered silacycles readily undergo non‐catalysed ring expansion reactions with isonitriles yielding the related four‐membered silacycles. Surprisingly, the ring‐expanded derivatives of the silirane undergo up to two further isomerisation reactions, first by enamine formation and then by another ring expansion. DFT computations were utilised to gauge the scope of this reactivity pattern. Three‐membered silacycles should essentially universally undergo a ring expansion with isonitriles, while for four‐membered silacycles, only very few instances are predicted to accommodate more challenging kinetic requirements of this ring expansion. Larger silacycles lack the ring strain energy required for this ring expansion reaction and are not expected to be expanded.
Low‐Energy Driven Ring‐Opening Behavior of Benzocyclobutene Derivatives
Authors: Yuan Ziwei , Sun Quan , Xiao Jinchong , Zhang Pingxia , Levchenko Konstantin S. , Demin Dmitry Y. , Fu Wenxin 
Published: July 2023

Comprehensive SummaryIt's urgent to develop benzocyclobutene (BCB)‐based polymers with low curing temperature for temperature‐sensitive applications such as liquid crystal displays (LCDs) and flexible electronics. Herein, the effect of substituents on the ring‐opening behavior of BCB derivatives was investigated. The ring‐opening activation energy barriers (ΔGA) of BCB derivatives with one or two substituents on the four‐membered alkyl ring were systematically calculated using the B3LYP function. Both mono‐ and di‐substituted BCBs adopted the conrotatory ring‐opening process, obeying the Woodward‐Hoffmann's Rules upon heating. The mono‐/di‐substituted BCBs exhibited 8.2%—69% lower ΔGA compared with BCB, attributed to the electronic effects of the substituents. Disubstituted BCBs with both electron‐donating and electron‐withdrawing groups, e.g., 1‐NH2‐8‐NO2‐BCB, demonstrated the lowest ΔGA. In addition, BCB derivatives with amide/ester/acyloxy group modified on C1 position were synthesized as model molecules, and their ring‐opening temperature can be decreased by 20 °C compared to the unsubstituted one, also consistent with our calculation results. This work combined theoretical calculation methods with experimental results to provide valuable insights into the design and synthesis of BCB derivatives and next‐generation BCB functional packaging materials with low ring‐opening temperature.
Engaging Black sexual minority women in breast cancer research: Lessons in community partnerships
Authors: Geffen Sophia R. , Poteat Tonia , Dean Lorraine T. , Malone Jowanna , Greene Naomi , Adams Mary Anne 
Published: July 2023

AbstractBackgroundBlack sexual minority women (BSMW) face significant breast cancer health inequities and are underrepresented in health research because of historical and present‐day exclusion. However, there exists no peer‐reviewed literature on best practices for the inclusion of BSMW in cancer research. “Our Breast Health: The Access Project” was a national primary data collection study in June 2018 through October 2019 that aimed to identify facilitators and barriers to breast cancer care among BSMW, and that successfully recruited the highest number of BSMW for any national breast cancer screening study at the time of its publication.MethodsThe present analysis highlights best practices for reaching BSMW by examining by how effective various recruitment sources were at recruiting BSMW. Recruitment partners were grouped into several categories: (1) cancer focused, (2) Black women or sexual minority women focused, (3) BSMW focused, (4) social media, and (5) other. Then logistic regression was used to estimate the odds that a particular recruitment source category could recruit BSMW compared with other categories.ResultsPartnerships with community‐based organizations led by and intended for BSMW were the most successful at recruiting BSMW, demonstrating the importance of an intersectional approach to recruitment. Community‐based organizations focused on BSMW specifically were 26 times more successful in recruiting BSMW to the study compared with recruiting Black women who were not sexual minorities (odds ratio, 26.43 [95% CI, 7.50–93.10]).ConclusionsSuccessful recruitment enables breast cancer research grounded in the perspectives of BSMW, which can generate key findings that have the potential to remedy longstanding health inequities for this population.
A portable C++ library for memory and compute abstraction on multi‐core CPUs and GPUs
Authors: Incardona Pietro , Gupta Aryaman , Yaskovets Serhii , Sbalzarini Ivo F. 
Published: July 2023

AbstractWe present a C++ library for transparent memory and compute abstraction across CPU and GPU architectures. Our library combines generic data structures like vectors, multi‐dimensional arrays, maps, graphs, and sparse grids with basic generic algorithms like arbitrary‐dimensional convolutions, copying, merging, sorting, prefix sum, reductions, neighbor search, and filtering. The memory layout of the data structures is adapted at compile time using C++ tuples with optional memory double‐mapping between host and device and the capability of using memory managed by external libraries with no data copying. We combine this transparent memory layout with generic thread‐parallel algorithms under two alternative common interfaces: a CUDA‐like kernel interface and a lambda‐function interface. We quantify the memory and compute performance and portability of our implementation using micro‐benchmarks, showing that the abstractions introduce negligible performance overhead, and we compare performance against the current state of the art in a real‐world scientific application from computational fluid mechanics.
Integrated single‐cell and spatial transcriptomic profiling reveals higher intratumour heterogeneity and epithelial–fibroblast interactions in recurrent bladder cancer
Authors: Shi Zhen‐Duo , Sun Zhuo , Zhu Zuo‐Bin , Liu Xing , Chen Jun‐Zhi , Hao Lin , Zhu Jie‐Fei , Pang Kun , Wu Di , Dong Yang , Liu Yu‐Fei , Chen Wei‐Hua , Liang Qing , Zhuo Shi‐Chao , Han Cong‐Hui 
Published: July 2023

AbstractBackgroundRecurrent bladder cancer is the most common type of urinary tract malignancy; nevertheless, the mechanistic basis for its recurrence is uncertain. Innovative technologies such as single‐cell transcriptomics and spatial transcriptomics (ST) offer new avenues for studying recurrent tumour progression at the single‐cell level while preserving spatial data.MethodThis study integrated single‐cell RNA (scRNA) sequencing and ST profiling to examine the tumour microenvironment (TME) of six bladder cancer tissues (three from primary tumours and three from recurrent tumours).FindingsscRNA data‐based ST deconvolution analysis revealed a much higher tumour heterogeneity along with TME in recurrent tumours than in primary tumours. High‐resolution ST analysis further identified that while the overall natural killer/T cell and malignant cell count or the ratio of total cells was similar or even lower in the recurrent tumours, a higher interaction between epithelial and immune cells was detected. Moreover, the analysis of spatial communication reveals a marked increase in activity between cancer‐associated fibroblasts (CAFs) and malignant cells, as well as other immune cells in recurrent tumours.InterpretationWe observed an enhanced interplay between CAFs and malignant cells in bladder recurrent tumours. These findings were first observed at the spatial level.
Multifunctional cytokine production marks influenza A virus‐specific CD4 T cells with high expression of survival molecules
Authors: Westerhof Lotus M. , Noonan Jonathan , Hargrave Kerrie E. , Chimbayo Elizabeth T. , Cheng Zhiling , Purnell Thomas , Jackson Mark R. , Borcherding Nicholas , MacLeod Megan K. L. 
Published: July 2023

AbstractCytokine production by memory T cells is a key mechanism of T cell mediated protection. However, we have limited understanding of the persistence of cytokine producing T cells during memory cell maintenance and secondary responses. We interrogated antigen‐specific CD4 T cells using a mouse influenza A virus infection model. Although CD4 T cells detected using MHCII tetramers declined in lymphoid and non‐lymphoid organs, we found similar numbers of cytokine+ CD4 T cells at days 9 and 30 in the lymphoid organs. CD4 T cells with the capacity to produce cytokines expressed higher levels of pro‐survival molecules, CD127 and Bcl2, than non‐cytokine+ cells. Transcriptomic analysis revealed a heterogeneous population of memory CD4 T cells with three clusters of cytokine+ cells. These clusters match flow cytometry data and reveal an enhanced survival signature in cells capable of producing multiple cytokines. Following re‐infection, multifunctional T cells expressed low levels of the proliferation marker, Ki67, whereas cells that only produce the anti‐viral cytokine, interferon‐γ, were more likely to be Ki67+. Despite this, multifunctional memory T cells formed a substantial fraction of the secondary memory pool. Together these data indicate that survival rather than proliferation may dictate which populations persist within the memory pool.
Highly sensitive glucose electrochemical sensor using sugar‐lectin interactions
Authors: Sugiyama Kyoko , Sato Fumiya , Komatsu Sachiko , Kamijo Toshio , Yoshida Kentaro , Kawabe Yusuke , Nishikawa Hiromi , Fujimura Tsutomu , Takahashi Yasufumi , Sato Katsuhiko 
Published: July 2023

AbstractIn this study, glucose oxidase (GOx) was immobilized on the electrode surface by layer‐by‐layer and gel membrane technique and characterized the GOx immobilized film morphology, H2O2 permeability, and glucose response. Concanavalin A (Con A)‐GOx multilayer electrodes showed higher glucose‐related current response than GOx‐bovine serum albumin gel membrane‐coated electrode, a common modification method. The thin thickness of the Con A/GOx multilayer film efficiently catalyzed the enzymatic reaction, and H2O2 was produced near the electrode surface, resulting in an immediate electrode response.