bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clustering of prostate cancer healthcare pathways in the French National Healthcare database
Authors: Baulain Roméo , Jové Jérémy , Sakr Dunia , Gross‐Goupil Marine , Rouyer Magali , Puel Marius , Blin Patrick , Droz‐Perroteau Cécile , Lassalle Régis , Thurin Nicolas H. 
Published: January 2023

AbstractBackgroundHealthcare pathways of patients with prostate cancer are heterogeneous and complex to apprehend using traditional descriptive statistics. Clustering and visualization methods can enhance their characterization.MethodsPatients with prostate cancer in 2014 were identified in the French National Healthcare database (Système National des Données de Santé—SNDS) and their data were extracted with up to 5 years of history and 4 years of follow‐up. Fifty‐one‐specific encounters constitutive of prostate cancer management were synthesized into four macro‐variables using a clustering approach. Their values over patient follow‐ups constituted healthcare pathways. Optimal matching was applied to calculate distances between pathways. Partitioning around medoids was then used to define consistent groups across four exclusive cohorts of incident prostate cancer patients: Hormone‐sensitive (HSPC), metastatic hormone‐sensitive (mHSPC), castration‐resistant (CRPC), and metastatic castration‐resistant (mCRPC). Index plots were used to represent pathways clusters.ResultsThe repartition of macro‐variables values—surveillance, local treatment, androgenic deprivation, and advanced treatment—appeared to be consistent with prostate cancer status. Two to five clusters of healthcare pathways were observed in each of the different cohorts, corresponding for most of them to relevant clinical patterns, although some heterogeneity remained. For instance, clustering allowed to distinguish patients undergoing active surveillance, or treated according to cancer progression risk in HSPC, and patients receiving treatment for potentially curative or palliative purposes in mHSPC and mCRPC.ConclusionVisualization methods combined with a clustering approach enabled the identification of clinically relevant patterns of prostate cancer management. Characterization of these care pathways is an essential element for the comprehension and the robust assessment of healthcare technology effectiveness.
Integrated Lipidomics and Network Pharmacology Reveal Mechanism of Memory Impairment Improvement by Yuanzhi San
Authors: Zhao Fuxia , Li Pei , Deng Fanying , Wang Jiamin , Cheng Yangang , Pei Ke , Wang Yingli , Wang Yan 
Published: January 2023

AbstractMemory impairment (MI) is caused by a variety of causes, endangering human health. Yuanzhi San (YZS) is a common prescription used for the treatment of MI, but its mechanism of action needs further exploration. The purpose of this study was to investigate this mechanism through lipidomics and network pharmacology. Sprague Dawley (SD) rats were divided randomly into the normal, model, and YZS groups. The rats were gavaged with aluminum chloride (200 mg/kg) and intraperitoneally injected with D‐galactose (400 mg/kg) every day for 60 days, except for the normal group. From the 30th day, YZS (13.34 g/kg) was gavaged once a day to the rats in the YZS group. Post‐YZS treatment, ultra‐high‐performance liquid chromatography‐mass spectrometry (UHPLC/MS) analysis was implemented to conduct a lipidomics study in the hippocampus of rats with memory impairment induced by aluminum chloride and D‐galactose. Eight differential metabolites were identified between the normal group and the model group, whereas between the model group and the YZS group, 20 differential metabolites were established. Metabolic pathway analysis was performed on the aforementioned lipid metabolites, all of which were involved in sphingolipid and glycerophospholipid metabolism. Furthermore, serum pharmacochemistry analysis of YZS was carried out at the early stage of our research, which discovered 62 YZS prototype components. The results of the network pharmacology analysis showed that they were related to 1030 genes, and 451 disease genes were related to MI. There were 73 intersections between the YZS and MI targets. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these targets were closely related to the sphingolipid metabolic, calcium signaling, and other pathways. The integrated approach of lipidomics and network pharmacology was then focused on four major targets, including PHK2, GBA, SPTLC1, and AChE, as well as their essential metabolites (glucosylceramide, N‐acylsphingosine, phosphatidylserine, phosphatidylcholine, and phosphatidylcholine) and pathways (sphingolipid, glycerophospholipid, and arachidonic acid metabolism). The significant affinity of the primary target for YZS was confirmed by molecular docking. The obtained results revealed that the combination of lipidomics and network pharmacology could be used to determine the effect of YZS on the MI biological network and metabolic state, and evaluate the drug efficacy of YZS and its related mechanisms of action.
A Nucleophilic Activity‐Based Probe Enables Profiling of PLP‐Dependent Enzymes
Authors: Brody Scott I. , Buonomo Joseph A. , Orimoloye Moyosore O. , Jia Ziyi , Sharma Sachin , Brown Christopher D. , Baughn Anthony D. , Aldrich Courtney C. 
Published: January 2023

AbstractPLP‐dependent enzymes represent an important class of highly “druggable” enzymes that perform a wide array of critical reactions to support all organisms. Inhibition of individual members of this family of enzymes has been validated as a therapeutic target for pathologies ranging from infection with Mycobacterium tuberculosis to epilepsy. Given the broad nature of the activities within this family of enzymes, we envisioned a universally acting probe to characterize existing and putative members of the family that also includes the necessary chemical moieties to enable activity‐based protein profiling experiments. Hence, we developed a probe that contains an N‐hydroxyalanine warhead that acts as a covalent inhibitor of PLP‐dependent enzymes, a linear diazirine for UV crosslinking, and an alkyne moiety to enable enrichment of crosslinked proteins. Our molecule was used to study PLP‐dependent enzymes in vitro as well as look at whole‐cell lysates of M. tuberculosis and assess inhibitory activity. The probe was able to enrich and identify LysA, a PLP‐dependent enzyme crucial for lysine biosynthesis, through mass spectrometry. Overall, our study shows the utility of this trifunctional first‐generation probe. We anticipate further optimization of probes for PLP‐dependent enzymes will enable the characterization of rationally designed covalent inhibitors of PLP‐dependent enzymes, which will expedite the preclinical characterization of these important therapeutic targets.
Prolactin regulates RANKL expression via signal transducer and activator of transcription 5a signaling in mammary epithelial cells of dairy cows
Authors: Mao Yongjin , Yang Huilin , Ma Xiaocong , Wang Chunmei , Zhang Li , Cui Yingjun 
Published: January 2023

AbstractReceptor of activated nuclear factor kappa B ligand (RANKL) is regulated by prolactin in the mammary gland. However, the intrinsic molecular mechanism is not well understood. Herein, mammary epithelial cells (MECs) of dairy cows were isolated to characterize the molecular mechanism of prolactin in vitro. We demonstrated that prolactin stimulation increased the expression of RANKL in MECs. Moreover, the expression of RANKL induced by prolactin was inhibited by the prolactin receptor or signal transducer and activator of transcription 5A (STAT5a) knockdown. Furthermore, prolactin markedly increased RANKL‐Luciferase reporter activity in MECs. We identified a putative gamma‐interferon activated site (GAS) in the region between residues −883 to −239 bp of the RANKL promoter. Subsequently, we found that the mutated GAS sequence failed to respond to prolactin stimulation. In addition, STAT5a knockdown markedly decreased prolactin‐stimulated RANKL promoter activity. Western blot results revealed that RANKL overexpression markedly decreased the STAT5a phosphorylation level in MECs. These findings indicate that prolactin could regulate RANKL promoter activity via STAT5a, contributing to increased RANKL expression in MECs. RANKL may have a negative regulatory effect on STAT5a activity.
Visible‐Light Induced Fixation of SO2 into Organic Molecules with Polypyridine Chromium(III) Complexes
Authors: Sittel Steven , Sell Arne Christian , Hofmann Kamil , Wiedemann Christina , Nau Jan Philipp , Kerzig Christoph , Manolikakes Georg , Heinze Katja 
Published: January 2023

AbstractIncorporation of sulfur dioxide into organic compounds is achieved by a photocatalytic approach using sensitizers made from earth‐abundant chromium(III) ions and visible light leading to sulfones and sulfonamides. We employed three different chromium(III) sensitizers [Cr(ddpd)2]3+, [Cr(bpmp)2]3+ and [Cr(tpe)2]3+ with long excited state lifetimes and different ground and excited state redox potentials as well as varying stability under the reaction conditions (ddpd=N,N’‐dimethyl‐N,N’‐dipyridin‐2‐yl‐pyridine‐2,6‐diamine; bpmp=2,6‐bis(2‐pyridylmethyl)pyridine; tpe=1,1,1‐tris(pyrid‐2‐yl)ethane). Key reaction steps of the catalytic cycles are identified by electrochemical, luminescence quenching, photolysis, laser flash photolysis and catalytic experiments delivering a detailed picture of the challenges in these transformations. The reactivity of the reduced chromium complex was identified as a key property to explain the reaction outcomes. Initial cage escape yield determinations with [Cr(tpe)2]3+ revealed that desired photoreactions occur with unusually high quantum efficiencies, whereas side reactions are almost unproductive.
Configuration‐dependent stretchable all‐solid‐state supercapacitors and hybrid supercapacitors
Authors: Amiri Ahmad , Bruno Ashley , Polycarpou Andreas A. 
Published: January 2023

AbstractGiven the rise in the popularity of wearable electronics that are able to deform into desirable configurations while maintaining electrochemical functionality, stretchable and flexible (hybrid) supercapacitors (SCs) have become increasingly of interest as innovative energy storage devices. Their outstanding power density, long lifetime with low capacitance loss, and appropriate energy density, in particular in hybrid cases make them ideal candidates for flexible electronics. The aim of this review paper is to provide an in‐depth discussion of these stretchable and flexible SCs ranging from fabrication to electro‐mechanical properties. This review paper begins with a short overview of the fundamentals of charge storage mechanisms and different types of multivalent metal‐ion hybrid SCs. The research methods leading up to the current state of these stretchable and flexible SCs are then presented. This is followed by an in‐depth presentation of the challenges associated with the fabrication methods for different configurations. Proposed novel strategies to maximize the elastic and electrochemical properties of stretchable/flexible or quasi‐solid‐state SCs are classified and the pros and cons associated with each are shown. The advances in mechanical properties and the expected advancements for the future of these SCs are discussed in the last section.
Expanding the Horizon of Bio‐Inspired Catalyst Design with Tactical Incorporation of Drug Molecules
Authors: Afshan Gul , Ghorai Santanu , Rai Surabhi , Pandey Aman , Majumder Piyali , Patwari G. Naresh , Dutta Arnab 
Published: January 2023

AbstractThe development of potent H2 production catalysts is a key aspect in our journey toward the establishment of a sustainable carbon‐neutral power infrastructure. Hydrogenase enzymes provide the blueprint for designing efficient catalysts by the rational combination of central metal core and protein scaffold‐based outer coordination sphere (OCS). Traditionally, a biomimetic catalyst is crafted by including natural amino acids as OCS features around a synthetic metal motif to functionally imitate the metalloenzyme activity. Here, we have pursued an unconventional approach and implanted two distinct drug molecules (isoniazid and nicotine hydrazide) at the axial position of a cobalt core to create a new genre of synthetic catalysts. The resultant cobalt complexes are active for both electrocatalytic and photocatalytic H2 production in near‐neutral water, where they significantly enhance the catalytic performance of the unfunctionalized parent cobalt complex. The drug molecules showcased a dual effect as they influence the catalytic HER by improving the surrounding proton relay along and exerting subtle electronic effects. The isoniazid‐ligated catalyst C1 outperformed the nicotine hydrazide‐bound complex C2, as it produced H2 from water (pH 6.0) at a rate of 3960 s−1 while exhibiting Faradaic efficiency of about 90 %. This strategy opens up newer avenues of bio‐inspired catalyst design beyond amino acid‐based OCS features.
Distinct Reactivity of Trimethylytterbium toward AlMe3 and GaMe3: Synthesis of Donor‐Stabilized Dimethylytterbium
Authors: Mortis Alexandros , Maichle‐Mössmer Cäcilia , Anwander Reiner 
Published: January 2023

AbstractMe3TACN (1,4,7‐trimethyl‐1,4,7‐triazacyclononane)‐stabilized trimethylytterbium was obtained via a salt‐metathesis protocol employing [(Me3TACN)YbCl3] and methyllithium. Complex [(Me3TACN)YbMe3] seems not to engage in redox chemistry with potassium graphite and is thermally quite stable in the solid state. Treatment of trivalent [(Me3TACN)YbMe3] with 3 equiv. of AlMe3 afforded divalent tetramethylaluminate complex [(Me3TACN)Yb(AlMe4)2]. The reaction of [(Me3TACN)YbMe3] with GaMe3 in THF gave trivalent ion pair [(Me3TACN)YbMe2(thf)][GaMe4], which is susceptible to reduction with KC8. The thermally very labile divalent [(Me3TACN)YbMe(μ‐Me)]2 is the first discrete donor adduct of a divalent dimethyl rare‐earth‐metal complex.
A Non Expected Alternative Ni(0) Species in the Ni‐Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5‐Diaza‐3,7‐diphosphacyclooctane Ligand
Authors: Heitkämper Juliane , Posada‐Pérez Sergio , Escayola Sílvia , Solà Miquel , Kästner Johannes , Poater Albert 
Published: January 2023

AbstractFor decades there were many attempts to dispense with stoichiometric amounts of metal reagents for the synthesis of secondary alcohols. In 2021, the synthetic results of Newman and collaborators pioneered a synthesis still with metals, but not as reactants. Instead, they serverd as catalytic engines. Here we present a description by means of Density Functional Theory calculations of how this process can occur, and an attempt is made to shed light on the mechanism that facilitates the attainment of secondary alcohols, emphasizing the eternal cross‐coupling debate of whether the catalytically active species is Ni(0) or they are really taking shortcuts following the course of Ni(II). Effective Orbital analyses give a clear picture. Furthermore, this paper provides insight not only into the nature of the ligands of the metal catalyst but also the role of the base.
An investigation on worst‐case spectral reconstruction from RGB images via Radiance Mondrian World assumption
Authors: Lin Yi‐Tun , Finlayson Graham D. 
Published: January 2023

AbstractSpectral reconstruction (SR) algorithms recover hyperspectral measurements from RGB camera responses. Statistical models at different levels of complexity are used to solve the SR problem—from the simplest closed‐form regression, to sparse coding, to the complex deep neural networks (DNN). Recently, these methods were benchmarked based on the mean performance of the models and on a fixed set of real‐world scenes, suggesting that more complex (more non‐linear) models generally deliver better SR. In this paper, we investigate the relative performances of these models in terms of a real‐world worst‐case imaging condition called the Radiance Mondrian World (RMW) assumption. Under the RMW, testing hyperspectral images are composed of randomly‐arranged and overlapping rectangular patches, where each patch is filled with one random radiance spectrum uniformly sampled from the convex closure of all natural radiances (i.e., all spectra in the concerned hyperspectral image dataset). Surprisingly, we show that all compared algorithms—regardless of their model complexity—degrade to broadly the same level of performance on our RMW testing set. Further, by retraining all models with an RMW training set, we show that increasing model complexity also does not help learning better SR mappings from the RMW images. That is, using simple regression is as good as using a DNN. This similarity of performance is also shown to hold for images adhering to the conventional Mondrian World assumption (random reflectances lit by a single, per scene, randomly selected light source).
Quorum sensing centered bacterial horde algorithm for global optimization
Authors: Raviprabhakaran Vijay 
Published: January 2023

SummaryThis article proposes an intellectual quorum sensing‐centered bacterial horde optimization (QBHO) exert for assessing and authenticating the optimization problems. Quorum detection realizes the finest place of the bacteria by apprehending the most awful point within the hunt area. This mechanism is utilized in this study for problem‐solving. With this bacterial behavior and location perceptive, the superlative optimum result is obtained. In this anticipated QBHO algorithm, the competence of bacteria is enhanced to be beneficial so that results can be enhanced. The fundamental group‐built optimization procedures for instance, particle swarm, ant cluster, biogeography‐built algorithm, simulated bee constellation procedure and typical bacterial herd optimization through the distinctive considerations remain simulated and then associated through the intended practice for its ratification of results with QBHO. The projected QBHO practice is exploited to ensue with the seven‐typical benchmark with unimodal and multimodal trial functions intended to prove its practicability and ideality. The realized findings imply that the suggested QBHO approach surpasses the deemed optimization procedures for complex standard functions. Furthermore, the intended procedure might be appropriate to several engineering challenges, notably intended for intricate concurrent optimization problems.
C−H Activation by Iron‐Vanadium Bimetallic Oxide Cluster Anions FeV3O10− and FeV5O15−: A Comparison with Scandium‐Vanadium Oxide Clusters
Authors: Wei Gong‐Ping , Liu Qing‐Yu , Zhao Yan‐Xia , He Sheng‐Gui 
Published: January 2023

AbstractLate transition metal‐bonded atomic oxygen radicals (LTM−O⋅−) have been frequently proposed as important active sites to selectively activate and transform inert alkane molecules. However, it is extremely challenging to characterize the LTM−O⋅−‐mediated elementary reactions for clarifying the underlying mechanisms limited by the low activity of LTM−O⋅− radicals that is inaccessible by the traditional experimental methods. Herein, benefiting from our newly‐designed ship‐lock type reactor, the reactivity of iron‐vanadium bimetallic oxide cluster anions FeV3O10− and FeV5O15− featuring with Fe−O⋅− radicals to abstract a hydrogen atom from C2−C4 alkanes has been experimentally characterized at 298 K, and the rate constants are determined in the orders of magnitude of 10−14 to 10−16 cm3 molecule−1 s−1, which are four orders of magnitude slower than the values of counterpart ScV3O10− and ScV5O15− clusters bearing Sc−O⋅− radicals. Theoretical results reveal that the rearrangements of the electronic and geometric structures during the reaction process function to modulate the activity of Fe−O⋅−. This study not only quantitatively characterizes the elementary reactions of LTM−O⋅− radicals with alkanes, but also provides new insights into structure‐activity relationship of M−O⋅− radicals.
Digital economy development, corporate social responsibility and low‐carbon innovation
Authors: Chen Wen 
Published: January 2023

AbstractThe coordinated development of digitization and greening is the internal demand for the comprehensive transformation and upgrading of enterprises worldwide. Based on data of China's A‐share listed companies from 2012 to 2019, this article empirically confirms the stimulating effect of digital economy development on corporate low‐carbon innovation. The mechanism tests show that the above stimulating effect is due to both the reduction effects of financing constraints and environmental uncertainty brought by the rapid development of the digital economy. In addition, this article discusses the value of corporate social responsibility (CSR) and finds that the promotion of CSR can significantly improve the policy effect of digital economy development in enabling corporate low‐carbon innovation, especially for private listed enterprises in high‐pollution industries. The findings of this article deepen our understanding of how to promote corporate low‐carbon sustainable development in the digital era.
Flow cytometric assessment for minimal/measurable residual disease in B lymphoblastic leukemia/lymphoma in the era of immunotherapy
Authors: Chen Xueyan , Gao Qi , Roshal Mikhail , Cherian Sindhu 
Published: January 2023

AbstractMinimal/measurable residual disease (MRD) is the most important independent prognostic factor for patients with B‐lymphoblastic leukemia (B‐LL). MRD post therapy has been incorporated into risk stratification and clinical management, resulting in substantially improved outcomes in pediatric and adult patients. Currently, MRD in B‐ALL is most commonly assessed by multiparametric flow cytometry and molecular (polymerase chain reaction or high‐throughput sequencing based) methods. The detection of MRD by flow cytometry in B‐ALL often begins with B cell antigen‐based gating strategies. Over the past several years, targeted immunotherapy directed against B cell markers has been introduced in patients with relapsed or refractory B‐ALL and has demonstrated encouraging results. However, targeted therapies have significant impact on the immunophenotype of leukemic blasts, in particular, downregulation or loss of targeted antigens on blasts and normal B cell precursors, posing challenges for MRD detection using standard gating strategies. Novel flow cytometric approaches, using alternative strategies for population identification, sometimes including alternative gating reagents, have been developed and implemented to monitor MRD in the setting of post targeted therapy.
Functional traits and environment jointly determine the spatial scaling of population stability in North American birds
Authors: Hong Pubin , Li Zhouyuan , Yang Qi , Deng Wanlu , Xu Yanjie , Tobias Joseph A. , Wang Shaopeng 
Published: January 2023

AbstractUnderstanding the spatial scaling of population stability is critical for informing conservation strategies. A recently proposed metric for quantifying how population stability varies across scales is the invariability–area relationship (IAR), but the underlying drivers shaping IARs remain unclear. Using 15‐year records of 249 bird species in 1035 survey transects in North America, we derived the IAR for each species by calculating population temporal invariability at different spatial scales (i.e., number of routes) and investigated how species IARs were influenced by functional traits and environmental factors. We found that species with faster life history traits and reduced flight efficiency had higher IAR intercepts (i.e., locally more stable), whereas migratory species exhibited higher IAR slopes (i.e., a faster gain of stability with increasing spatial scale). In addition, spatial correlation in temperature and vegetation structure synchronized bird population dynamics over space and thus decreased IAR slopes. By demonstrating the joint influence of functional traits and environmental factors on bird population stability across scales, our results highlight the need for dynamic conservation strategies tailored to particular types of species in an era of global environmental changes.