bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory protein associations with brain MRI measures: Framingham Offspring Cohort
Authors: Chen Jiachen , Ragab Ahmed A. Y. , Doyle Margaret F. , Alosco Michael L. , Fang Yuan , Mez Jesse , Satizabal Claudia L. , Qiu Wei Qiao , Murabito Joanne M. , Lunetta Kathryn L. 
Published: September 2024

AbstractINTRODUCTIONBrain magnetic resonance imaging (MRI) and inflammatory biomarkers are crucial for investigating preclinical neurocognitive disorders. Current investigations focus on a few inflammatory markers. The study aims to investigate the associations between inflammatory biomarkers and MRI measures and to examine sex differences among the associations in the Framingham Heart Study.METHODSDementia and stroke‐free participants underwent OLINK Proteomics profiling and MRI measurements within 5 years. Pairwise cross‐sectional analysis assessed 68 biomarkers with 13 brain MRI volumes, adjusting for covariates and familial correlations.RESULTSElevated CDCP1, IL6, OPG, and 4E.BP1 were related to smaller total cerebral brain volume (TCBV), whereas higher HGF, IL8, and MMP10 were associated with smaller TCBV, total and frontal white matter volumes. Higher SCF and TWEAK were associated with larger TCBV. In sex‐stratified analyses, associations were observed exclusively among males.DISCUSSIONWe report several associations between inflammatory biomarkers and brain volumes, highlighting different associations within sex subgroups.Highlights
Higher CDCP1, IL6, OPG, and 4E.BP1 levels were associated with smaller TCBV.
Higher levels of HGF, IL8 and MMP10 were associated with smaller TCBV, CWV and FWV.
Higher levels of SCF and TWEAK, were associated with larger TCBV.
Significance diminished in models adjusting for CVD risk factors.
Associations were observed exclusively in males.
Effective Alkyl‐Alkyl Cross‐Coupling with an Iron‐Xantphos Catalyst: Mechanistic and Structural Insights
Authors: Gimeno Magali , Aguilera Maria Camila , Fleischauer Valerie E. , Brennessel William W. , Neidig Michael L. 
Published: September 2024

AbstractWhile iron‐catalyzed C(sp2)−C(sp3) cross‐couplings have been widely studied and developed in the last decade, alkyl‐alkyl cross‐coupling systems with iron remain underdeveloped despite the importance of C(sp3)−C(sp3) bonds in organic synthesis. A major challenge to the development of these reactions is the current lack of fundamental insight into ligand effects and organoiron intermediates that enable effective alkyl‐alkyl couplings. The current study addresses this longstanding limitation using a combination of 57Fe Mössbauer spectroscopy, SC‐XRD (single‐crystal X‐ray diffraction) and reactivity studies of alkyl‐alkyl coupling with iron‐Xantphos to define the in situ formed iron‐Xantphos intermediates in catalysis. Combined with detailed reactivity studies, the nature of the key mechanistic pathways in catalysis and ligands effects to achieve effective alkyl‐alkyl cross‐coupling over competing β‐H elimination pathways are probed. Overall, these foundational studies provide a platform for future bespoke ligand and pre‐catalyst design for alkyl‐alkyl cross‐coupling methods development with sustainable iron catalysis.
A Strongly Reducing sp2 Carbon‐Conjugated Covalent Organic Framework Formed by N‐Heterocyclic Carbene Dimerization
Authors: Pitt Tristan A. , Azbell Tyler J. , Kim Jaehwan , Shi Zixiao , Muller David A. , Addicoat Matthew A. , Milner Phillip J. 
Published: September 2024

AbstractCovalent organic frameworks linked by carbon‐carbon double bonds (C=C COFs) are an emerging class of crystalline, porous, and conjugated polymeric materials with potential applications in organic electronics, photocatalysis, and energy storage. Despite the rapidly growing interest in sp2 carbon‐conjugated COFs, only a small number of closely related condensation reactions have been successfully employed for their synthesis to date. Herein, we report the first example of a C=C COF, CORN‐COF‐1 (CORN=Cornell University), prepared by N‐heterocyclic carbene (NHC) dimerization. In‐depth characterization reveals that CORN‐COF‐1 possesses a two‐dimensional layered structure and hexagonal guest‐accessible pores decorated with a high density of strongly reducing tetraazafulvalene linkages. Exposure of CORN‐COF‐1 to tetracyanoethylene (TCNE, E1/2=0.13 V and −0.87 V vs. SCE) oxidizes the COF and encapsulates the radical anion TCNE⋅− and the dianion TCNE2− as guest molecules, as confirmed by spectroscopic and magnetic analysis. Notably, the reactive TCNE⋅− radical anion, which generally dimerizes in the solid state, is uniquely stabilized within the pores of CORN‐COF‐1. Overall, our findings broaden the toolbox of reactions available for the synthesis of redox‐active C=C COFs, paving the way for the design of novel materials.
A Modular Approach for Accessing 3D Heterocycles via 1,2‐Dicyanation of Planar N‐Heteroarenes
Authors: Pradhan Sukumar , Maiti Sudip , Dutta Suparna , Adam Russell C. , Tyagi Sameer , Maiti Debabrata 
Published: September 2024

AbstractThe rapid construction of three‐dimensional (3D) heterocyclic frameworks is a key challenge in contemporary medicinal chemistry. The molecules with three‐dimensional complexity hold a greater probability to improve clinical outcomes, solubility, selectivity for target proteins, and metabolic stability. However, the prevalence of flat molecules persists among new drug candidates, primarily owing to the multitude of chemical methods available for their synthesis. In principle, the dearomative functionalization of N‐heteroarene allows for the conversion of readily available planar molecules into partially or fully saturated nitrogen heterocycles, which are most significant structural motifs of pharmaceuticals and natural products. Unfortunately, these reactions are very rare because of the inherent challenge imposed by heteroarenes’ poor reactivity, rendering the process thermodynamically unfavorable. Herein, we report a modular approach for accessing 3D chemical space in translating planar heteroarenes into valuable 3D heterocycles via the installation of a highly versatile cyano group as a new vector. This approach is enabled by the in situ generation of reactive, non‐symmetric iodane by combining cyanide anion and bench‐stable PhI(OAc)2. This reaction represents a rare example of 1,2‐dicyanation of N‐heteroarenes that meets the numerous requirements for broad implementation in drug and agrochemical discovery. The transformation is highly selective and amenable to a wide range of N‐heteroarenes and late‐stage partial saturation of drugs and agrochemicals.
Conformation‐Confined Organic Butterfly‐Molecule with High Photoluminescence Efficiency, Deep‐Blue Amplified Spontaneous Emission, and Unique Piezochromic Luminescence
Authors: Dai Shuting , Li Xiao‐Ze , Liu Jiawen , Zhang Chenchen , Hu Jiasong , Liu Zhaoyang , Fang Hong‐Hua , Sun Hong‐Bo , Xu Bin , Tian Wenjing 
Published: September 2024

AbstractOrganic fluorophores with tunable π‐conjugated paths have attracted considerable attention owing to their diverse properties and promising applications. Herein, we present a tailored butterfly‐like molecule, 2,2’‐(2,5‐bis (2,2‐diphenylvinyl)‐1,4‐phenylene)dinaphthalene (BDVPN), which exhibits diverse photophysical features in its two polymorphs. The BP phase crystal, with its “aligned wings” conformation, possesses emissive characteristics that are nearly identical to those in dilute solutions. In contrast, the BN phase crystal, which adopts an “orthogonal wings” conformation, exhibits an unusual hypsochromic‐shifted emission compared to its dilute solution counterparts. This intriguing hypsochromic‐shifted emission originates from the reduction in the effective conjugated length of the molecular skeleton. Notably, BN phase crystals also exhibit exceptional optical performance, featuring high‐efficiency emission (76.6 %), low‐loss optical waveguides (0.571 dB mm−1), deep‐blue amplified spontaneous emission (ASE) with narrow full width at half maximum (FWHM: 6.4 nm), and a unique 200 nm bathochromic shift of piezochromic luminescence.
Sign Inversion of Circularly Polarized Luminescence in Cholesteric Liquid Crystals Induced by Mercury Ions through Binaphthyl Dopants′ Conjugation Control
Authors: Li Lulu , Jiang Peiting , Zhang Xueyan , Li Yang 
Published: September 2024

AbstractStimuli‐responsive circularly polarized luminescence (CPL) materials based on cholesteric liquid crystal (CLC) platforms show great promise for applications in information encryption and anticounterfeiting. In this study, we constructed a mercury ion‐responsive CPL system in CLCs by controlling the conjugation degree of axially chiral binaphthyl derivatives. Two chiral binaphthyl derivatives (R/S‐1 and R/S‐2) were initially used as chiral dopants to demonstrate that CPL inversion (glum values from 0.5/‐0.44 to −0.53/0.48) in CLCs could be achieved by modulating the conjugation degree of the chiral binaphthyls. Based on this concept, the thioacetal binaphthyl R‐2S was developed and used as a mercury‐responsive chiral dopant in CLCs. Under Hg ion treatment, the CPL sign inverted (glum value changed from 0.22 to −0.29) due to the transformation of the thioacetal into an aldehyde group. Additionally, the mercury ion‐responsive CPL material was applied in information encryption.
Tailor‐made production of mannosylerythritol lipids: From genetic modification to chemical synthesis
Authors: Saika Azusa , Fukuoka Tokuma 
Published: September 2024

AbstractMannosylerythritol lipids (MELs) are glycolipid biosurfactants produced by basidiomycetous yeasts. Mannosylerythritol lipids have received increasing attention because they not only have excellent interfacial activity but also have anti‐inflammatory and antimicrobial activity, and against cancer cell line, repair damaged skin, as carriers for drug delivery, and to interact with proteins. These properties are dependent on their structures; therefore, the tailored production of targeted MELs is required to obtain the desired properties. Over the past two decades, the genomes of MEL producers have been analyzed, revealing the MELs synthesis pathway and related genes. Using this information, it has become possible to tailor‐produce MELs by modifying the synthesis pathway. Furthermore, in recent years, novel chemical synthesis methods for MELs have been developed, enabling precise control over the fatty acid chain lengths of chemically synthesized MELs. This review compiles examples of the tailored production of MELs using methods ranging from the genetic modification of MELs producers to chemical synthesis methods.
Short‐Term Risk of Cardiovascular Events in People Newly Diagnosed With Gout
Authors: Cipolletta Edoardo , Nakafero Georgina , Richette Pascal , Avery Anthony J. , Mamas Mamas A. , Tata Laila J. , Abhishek Abhishek 
Published: September 2024

ObjectiveTo investigate the temporal association between the first diagnosis of gout and cardiovascular events in the short term.MethodsWe performed a self‐controlled case series analysis and a cohort study using data from linked primary care, hospitalization, and mortality records from the United Kingdom's Clinical Practice Research Database‐GOLD. We included individuals with a new diagnosis of gout either in the primary care or secondary care between January 1, 1997 and December 31, 2020. The first consultation at which gout was diagnosed was the exposure of interest. The main outcome consisted of cardiovascular events (ie, a composite of fatal and nonfatal myocardial infarction, ischemic or hemorrhagic stroke, and transient ischemic attack).ResultsThe 4,398 patients (66.9% male, mean age 74.6 years) had a cardiovascular event within at least two years of their first recorded diagnosis of gout. The incidence of cardiovascular events was significantly higher in the 30 days after the first diagnosis of gout compared to baseline (adjusted incidence rate ratio 1.55, 95% confidence interval [CI] 1.33–1.83). Among 76,440 patients (72.9% male, mean age 63.2 years) included in the cohort study, the incidence of cardiovascular events in the 30 days after the first gout diagnosis (31.2 events per 1,000 person‐years, 95% CI 27.1–35.9) was significantly higher than in days 31 to 730 after gout diagnosis (21.6 events per 1,000 person‐years, 95% CI 20.8–22.4) with a rate difference of −9.6 events per 1,000 person‐years (95% CI −14.0 to −5.1).ConclusionIndividuals had a short‐term increased risk of cardiovascular events in the 30 days following the first consultation at which gout was diagnosed.
IĸBζ as a Central Modulator of Inflammatory Arthritis Pathogenesis
Authors: Swarnkar Gaurav , Naaz Musarrat , Mims Dorothy , Gupta Prashant , Peterson Timothy , Christopher Matthew J. , Singamaneni Srikanth , Mbalaviele Gabriel , Abu‐Amer Yousef 
Published: September 2024

ObjectiveCurrent therapies targeting individual factors in inflammatory arthritis show variable efficacy, often requiring treatment with combinations of drugs, and are associated with undesirable side effects. NF‐ĸB is critical for the production and function of most inflammatory cytokines. However, given its essential role in physiologic processes, targeting NF‐ĸB is precarious. Hence, identifying pathways downstream of NF‐ĸB that selectively govern the expression of inflammatory cytokines in inflammatory arthritis would be advantageous. We have previously identified IĸBζ as a unique inflammatory signature of NF‐ĸB that controls the transcription of inflammatory cytokines only under pathologic conditions while sparing physiologic NF‐ĸB signals.MethodsWe generated mice harboring myeloid, lymphoid, and global deletion of Nfkbiz (the gene encoding IĸBζ). These models were subjected to serum transfer‐induced arthritis. Additionally, pharmacologic inhibitors of IĸBζ were injected intraperitonially. Joint swelling, microcomputed tomography, immunohistochemistry, flow cytometry, and cytokine measurements were conducted using synovial tissue samples.ResultsGlobal deletion of Nfkbiz or depletion of neutrophils (vastly IĸBζ+ cells) reduced inflammatory synovial cells and increased anti‐inflammatory and regenerative synovial cells, plummeted expression of inflammatory factors and ameliorated experimental mouse inflammatory arthritis. Further, expression of immune responsive gene‐1, the enzyme responsible for itaconate production, was increased in synovial cells. Accordingly, the itaconate derivative dimethyl itaconate (DI) inhibited IĸBζ‐mediated inflammatory factors. Further, in silico screen identified 8‐hydroxyquinoline (HQ) as a putative inhibitor of IĸBζ not affecting physiologic NF‐ĸB activity. Congruently, systemic administration of either DI or HQ inhibited joint swelling and damage.ConclusionOur study positions IĸBζ as an inflammation‐specific target for therapeutic consideration in rheumatoid arthritis because its inhibition spares the beneficial functions of NF‐ĸB.image
Special Educational Needs and Disability tribunals: Dyslexia, scientific validity and equity
Authors: Elliott Julian , Stanbridge Joanna , Branigan Kirsten 
Published: September 2024

AbstractThis paper examines the operation of the English Special Educational Needs and Disability tribunal system in relation to children who present with a dyslexia diagnosis. It identifies a number of significant weaknesses; in particular, the absence of clear diagnostic criteria capable of differentiating such children from large numbers of other struggling readers. It then explains why it is inappropriate to identify particular cognitive processes as indicating the presence of dyslexia, as distinct from a broader reading difficulty. The paper subsequently explores the erroneous nature of claims about specialised dyslexia teaching and resourcing that, while often asserted with confidence by some privately funded assessors, are not supported by the scientific literature. It is argued that the tribunal system is an inappropriate method for reconciling the competing needs of a diagnosed dyslexic subgroup in relation to the wider population of struggling readers, estimated to be 20% of the school population.
On the circular entrepreneurship across continents: An analysis of terms of business descriptors
Authors: Benita Francisco , Srinivasan Padmapriya 
Published: September 2024

AbstractThis study analyzes circular entrepreneurship trends across global regions using the 2014–2018 Global Entrepreneurship Monitor dataset. Content analysis of business descriptors from 79,663 unique entrepreneurs was used to position each startup within the 9R's framework. The results show that startups are mainly associated with “repurpose” and “recover”, which are less desirable for circularity. We further define circular entrepreneurs as those with the top 10% highest weighted score in circular strategies according to the type of business they run. The BERTopic approach is applied to identify specific business topics for these entrepreneurs. Similarities (North America and Latin America & the Caribbean) and differences (Europe) in popular topics are found across regions. Lastly, regression analysis reveals that entrepreneurial perception and the presence of role models are key factors driving circular entrepreneurship.
Assessment of membrane‐based downstream purification processes as a replacement to traditional resin bead for monoclonal antibody purification
Authors: Pasquier Victor , Botelho Ferreira Kevin , Lergenmuller Morgane , Tottoli Alexis , Perilleux Arnaud , Souquet Jonathan , Bielser Jean‐Marc 
Published: September 2024

AbstractMembrane chromatography devices are a viable alternative to packed‐bed resins and enable highly productive purification cascades for monoclonal antibodies and Fc‐fusion proteins. In this study, ion exchange and protein A membrane chromatography performances were assessed and compared with their resin counterparts. Protein A dynamic binding capacities were higher than 50 g/L for two of the tested membranes and with a residence time of 0.2 min. For polishing, it was observed that aggregate clearance was generally less performant with membrane separation when compared to resins with similar ligands. However, the comparable yield and increased productivity of membranes could be enough to consider their implementation. In addition, lifetime studies demonstrated that the performance of membranes remained robust over cycles. One hundred cycles were reached for most of the tested membranes with no impact on the process performance nor product quality. Finally, purification cascades were fully operated with membranes, from capture to polishing, reaching good levels of host cells proteins (less than 50 ppm) and aggregates (equal to or less than 1%). The outcome of this study demonstrated that resin chromatography could be fully replaced by membranes for monoclonal antibody and Fc‐fusion protein purification processes.
Chemical Characterization, Evaluation of Acute Oral Toxicity, and Anti‐Diabetic Activity of Aloe sabaea Flowers Extract on Alloxan‐Induced Diabetic Rats
Authors: Raweh Salwa M. , El‐Shaibany Amina , Al‐Mahbashi Hassan , Abdelkhalek Ahmed S. , Elkomy Nesreen M. I. M. , Elnagar Gehad M. , Elsayed Mohamed G. , Elaasser Mahmoud M. , Raslan Ali E. 
Published: September 2024

AbstractThe study aimed to conduct chemical profiling, acute in‐vivo toxicity evaluation, and the potential anti‐diabetic effect of standardized Aloe sabaea flowers ethanolic extracts (ASFEE) on alloxan‐induced diabetic rats. The chemical composition was analyzed using GC–MS and TLC techniques. The oral acute toxicity study was performed according to the WHO 2000 and the OECD 420 guidelines. Furthermore, anti‐diabetic activity was investigated using two doses of ASFEE (0.2 and 0.5 g/kg/day BW, p.o.) compared with glibenclamide (5 mg/kg/day, p.o.). A molecular docking investigation of the identified components with the PTPN9 enzyme was performed to figure out the proposed anti‐diabetic mechanism. GC–MS analysis displayed the existence of 18 compounds; most of the compounds were fatty acids and their esters, and phytosterols. Total phenolic and flavonoid contents were 42.00±1.26 mg GAE/g DW and 22.21±1.55 mg QE/g DW, respectively. The results of the in‐vivo toxicity study revealed the absence of noticeable signs of toxicity or mortality at various doses establishing the safety of the tested extract. The estimated LD50 value was higher than 10 g/kg. Antidiabetic action exhibited a noticeable decline in fasting blood glucose (FBG) levels comparable to glibenclamide with no inducing intense hypoglycemia and considerable excess weight.
Destroyed lung syndrome in patients with drug‐susceptible pulmonary tuberculosis
Authors: Gyabaah Solomon , Gyan Kwadwo Faka , Mensah Harris Osei , Darkwa Eric Amoako , Owiredu Michael Asiedu , Nyamuame Vera Selorm , Amponsah Gordon Manu , Amenuke Divine Aseye 
Published: September 2024

Key Clinical MessageDestroyed lung syndrome is a recognized devastating complication of pulmonary tuberculosis (TB) that affects the quality of life of patients. Clinicians in TB‐endemic countries should be aware of this complication aiming at prevention. TB control programs should intensify efforts at early detection and treatment and also provide interventions for post‐TB complications.
Research Progress of Catalysts with Atomic‐Scale Reactive Sites in Urea Electrosynthesis
Authors: Lu Lu , Zhan Peng , Chen Xuehan , Shi Wei , Si Zhihao , Qin Peiyong 
Published: September 2024

AbstractUrea (CO(NH2)2) is the main component of nitrogen‐based fertilizers and is widely used in various industries. Until now, urea production is conducted under high‐temperature and high‐pressure conditions, which involves a considerable carbon footprint. Urea electrosynthesis, which is powered by renewable energy‐derived electricity, has emerged as a sustainable single‐step process for urea production. The development of efficient and stable catalysts is the key to improving the efficiency of urea electrosynthesis. In this review, we summarized the research progress and applications of catalysts with atomic‐scale reactive sites in urea electrosynthesis. First, the catalytic mechanisms of urea electrosynthesis from CO2 and various nitrogenous molecules are discussed. Then, typical electrocatalysts such as single‐atom electrocatalysts, dual‐atom electrocatalysts, clusters, atomic dopants, vacancies, and so forth, are discussed. Furthermore, characterization methods for atomic‐scale reactive sites are summarized. Finally, challenges and suggestions for urea electrosynthesis are proposed. We hope this review can provide some inspiration toward the development of catalysts for efficient and sustainable urea electrosynthesis.