bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apathy and fatigue, but not depression, associated with inflammatory biomarkers in older adults
Authors: Harrison Fleur , Mortby Moyra E , Guastella Adam J , Trollor Julian N , Mather Karen A , Sachdev Perminder S. , Brodaty Henry 
Published: January 2025

AbstractBackgroundApathy (loss of motivation or goal‐directed behaviour) and depression each confer risk for dementia, cardiovascular disease and mortality in older adults. Mechanisms for this are not yet understood, and may involve systemic inflammation. However, this has received little attention, particularly in older adults where depression may present differently. Symptoms of apathy, fatigue, and physical symptoms are more common in late‐life depression. This research aims to investigate whether apathy, depression and fatigue are differentially associated with inflammatory biomarkers in older adults.Method1,037 community‐dwelling older adults without dementia (aged 70‐90, 55% women) completed self‐report assessments including measures of apathy and depression from the Geriatric Depression Scale, and fatigue from Assessment of Quality of Life‐6D. Inflammatory biomarkers from early morning fasting blood collection included C‐reactive protein (CRP) and interleukin‐6. Logistic regressions examined associations between levels of biomarkers and apathy, depression and fatigue separately. Analyses were initially unadjusted, then adjusted for baseline age, sex, education, global cognition (MMSE), health conditions, medications and BMI.ResultInterleukin‐6 was associated with apathy, depression and fatigue in unadjusted models (odds ratio [OR] per natural log unit increase in IL‐6: 1.73, 95% confidence interval [CI] 1.38‐2.22; OR 1.56, 95% CI 1.12‐2.15; OR 1.72, 95% CI 1.14‐2.59 respectively). The association with apathy remained significant after adjustment for other symptoms, socio‐demographics, cognition and health‐related covariates, but findings for depression and fatigue were attenuated. CRP was associated with apathy and fatigue (OR 1.10, 95% CI 1.00‐1.21; OR 1.34, 95% CI 1.11‐1.60 respectively) although the former was attenuated by adjustment for covariates. Previous associations between CRP and depression were not replicated.ConclusionIn older persons, apathy and fatigue were differentially linked with inflammatory biomarkers, whereas previous associations between inflammation and depression were not replicated. Findings confirm the importance of fatigue, and provide novel insight into apathy, as prevalent and impairing symptoms which map to peripheral inflammation in older adults. Inflammation may at least partially underly the complex associations between apathy, depression and poorer health outcomes including dementia.
The Nature of Episodic Memory Decline in Preclinical Alzheimer’s Disease
Authors: Sharma Anjali , Johnson Melanie L , Thomas Kelsey R. , Galasko Douglas R. , Bondi Mark W. , Gollan Tamar H. , Peavy Guerry M. , Jacobs Diane M. , Salmon David P. , Delis Dean C. 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) pathology (e.g., beta‐amyloid plaques, tau neurofibrillary tangles) accumulates before the emergence of cognitive deficits that lead to a diagnosis of mild cognitive impairment (MCI) or dementia. Early vulnerability of medial temporal lobe structures to AD suggests that subtle episodic memory decline should be among the first cognitive markers of the disease. Therefore, we examined the relationship between 2‐year change in episodic memory and baseline cerebrospinal fluid (CSF) biomarkers of AD in cognitively normal (CN) older adults.MethodsEpisodic memory was assessed with the California Verbal Learning Test, Second Edition (CVLT‐II), a sensitive 16‐item list learning test that measures multiple aspects of memory proficiency. We administered the CVLT‐II at baseline, 1‐year, and 2‐year evaluations to older adults who were CN and CSF AD biomarker‐negative (CN–; n = 94) or positive (CN+ or preclinical AD; n = 38; CSF tau/Aβ42 ratio>.609) at baseline. We compared groups on change over time on total recall on List A learning trials 1‐5, list B free recall, short‐ and long‐delay free and cued recall, intrusion errors, and recognition discriminability. We also examined target recognition (d’) in relation to distractor types that differed in degree of similarity to targets.ResultsGroup X time repeated measures ANCOVAs controlling for age and sex showed significantly greater 2‐year decline in CN+ than CN‐ on CVLT‐II measures of long‐delay free recall (interaction: F(2,256) = 4.39;p<.05) and recognition discriminability overall (interaction: F(2,256) = 3.08;p<.05) (Fig. 1) and against most distractor types (p’s<.05) (Fig. 2). Higher tau/Aβ42 ratio (i.e., more AD‐like) in CN older adults was associated with greater decline on long‐delay free recall (r(130) = –.205;p<.02) and recognition discriminability (r(130) = –.215;p<.02) (Fig. 3). However, magnitude of decline only marginally categorized individuals as CN‐ vs. CN+ in logistic regression analyses (95% specificity, but only 21% sensitivity).ConclusionSubtle decline in episodic memory is evident during the preclinical phase of AD, affecting both delayed recall and recognition consistent with medial temporal lobe dysfunction. In addition, greater preclinical memory decline is associated with higher levels of an AD biomarker in CSF. Further research will determine if these memory changes can serve as a cognitive marker of preclinical AD.
A delayed diagnosis of a case with multiple system atrophy
Authors: Elkasaby Mohamed , Hayden Elliott , Appleby Brian 
Published: January 2025

AbstractBackgroundA patient presented to movement disorder clinic with cognitive complaints, imbalance and prior diagnosis of NPH. The patient underwent ventriculoperitoneal shunt in the past with minimal improvement, a detailed history is suggestive of REM sleep behavioral disorder, autonomic dysfunction including orthostatic hypotension and urinary incontinence.MethodClinical evaluation was notable for bradykinesia, rigidity, truncal and cervical dystonia, shuffling steps, reduced arm swing bilaterally and pink, dusky skin of both hands.ResultDaTscan showed reduced uptake of dopamine transporter.ConclusionEvaluation at movement disorder clinic helps early diagnosis of neurodegenerative disorders with subtle findings which allows patients to benefit from available treatments and participation in appropriate clinical trials.
Konformationsplastizität und Steigerung der Bindungsaffinität durch Linker‐Derivatisierung in Makrozyklen
Authors: Buffa Vanessa , Walz Carlo , Meyners Christian , Zheng Min , Oki Sugiarto Wisely , Repity Maximilian , Achaq Hanaa , Brudy Christian , Spiske Moritz , Cica Matijas , Hausch Felix 
Published: January 2025

AbstractIn der Natur finden Makrozyklen häufig Anwendung, um die Zellpermeabilität von bioaktiven Molekülen zu ermöglichen. Synthetische, nicht‐peptidische Makrozyklen werden zunehmend als Modalitäten für Proteine in Betracht gezogen, die schwer zu binden sind. Strategien zur Makrozyklisierung sind jedoch noch unausgereift. Man geht davon aus, dass Makrozyklen die verfügbaren Konformationen einschränken, aber gleichzeitig eine Restflexibilität zulassen, wobei letzteres nur unzureichend verstanden ist. In dieser Arbeit zeigen wir, dass selbst mittelgroße Makrozyklen eine unerwartet hohe konformelle Plastizität aufweisen, auch wenn diese an ihr Zielprotein gebunden sind. Dabei können geringfügige Linkermodifikationen der Makrozyklen das Konformationsensemble in verschiedene konformelle Unterklassen verschieben, die jeweils unterschiedliche dreidimensionale Gerüste und somit weitere Optimierungsmöglichkeiten darstellen. Dies führte im hier vorgestellten Fall zu mehreren neuen Liganden mit verbesserter Affinität und vorteilhaften physikochemischen Parametern für das FK506‐bindende Protein 51, ein vielversprechender Ansatzpunkt für Depressionen, Fettleibigkeit und chronische Schmerzen. Von besonderer Bedeutung ist, dass keine der hier entdeckten vorteilhaften Modifikationen durch klassische medizinalchemische Ansätze hätte identifiziert werden können, da diese nur im makrozyklischen Kontext funktionieren. Unsere Ergebnisse zeigen auch, dass Makrozyklisierung mehr darstellt als die Zusammenfügung von „losen“ Enden. Vielmehr stellt es eine Plattform dar, um mehrere Serien von Makrozyklen mit unterschiedlichen Bindungsmodi zu generieren.
Efficient Alkaline‐Free Electrooxidation of 5‐Hydroxymethylfurfural to 2,5‐Furandicarboxylic Acid using Electrochemically‐Charged NixCo1‐x(OH)2 as a Redox Mediator
Authors: Zhang Jifang , Shen Yue , Wu Zenglong , Zhang Xinyuan , Kang Jian , Wu Yijin , Zhang Shengbo , Chen Shan , Wang Guozhong , Zhang Haimin , Yin Huajie , Zhao Huijun 
Published: January 2025

AbstractConverting biomass‐derived molecules like 5‐hydroxymethylfurfural (HMF) into value‐added products alongside hydrogen production using renewable energy offers significant opportunities for sustainable chemical and energy production. Yet, HMF electrooxidation requires strong alkaline conditions and membranes for efficient conversion. These harsh conditions destabilize HMF, leading to humin formation and reduced product purity, meanwhile membranes increase costs. Addressing these challenges, we introduce a two‐step, decoupling system that operates without strong alkaline conditions and eliminates the need of membranes. In this system, nickel‐cobalt hydroxides serve as effective redox mediators, driving HMF oxidation in pure water. The experimental results showed that Ni0.85Co0.15OOH effectively promotes the dehydrogenation of substrate and achieves a highly efficient oxidation of HMF in pure water, with the selectivity of product 2,5‐furandicarboxylic acid (FDCA) approaching 100 %. This system has been expanded to oxidize various substrates, achieving yields exceeding 92 % for the corresponding acids of functionalized compounds such as furfuryl alcohol, furfural, benzyl alcohol, and benzaldehyde. By replacing fixed electrodes with flow electrodes, the scalability of decoupling strategy was evaluated for the harvesting of pure solid FDCA, highlighting the broad prospects in practical applications.
Functionalization of Pyridines at the C4 Position via Metalation and Capture
Authors: Hsu Han‐Hsiang , Kang Seokmin , Chen Cheng‐Chun , Sk Md Raja , Thomas Andy A. 
Published: January 2025

AbstractThe functionalization of pyridines at positions remote to the N‐atom remains an outstanding problem in organic synthesis. The inherent challenges associated with overriding the influence of the embedded N‐atom within pyridines was overcome using n‐butylsodium, which provided an avenue to deprotonate and functionalize the C4‐position over traditionally observed addition products that are formed with organolithium bases. In this work, we show that freshly generated 4‐sodiopyrdines could undergo transition metal free alkylation reactions directly with a variety of primary alkyl halides bearing diverse functional groups. In addition, after transmetalation to zinc chloride a simple and efficient Negishi cross‐coupling protocol was formulated for a variety of aromatic and heteroaromatic halides. The robustness of this protocol was demonstrated through the late‐stage installation of 4‐pyridyl fragments into a variety of complex active pharmaceutical ingredients including loratadine and prochlorperazine. Furthermore, through rapid injection NMR investigations, we are able to directly observe the evolution of anionic intermediates and determined that two distinct mechanistic pathways lead to the observed site selectivity: (1) the C4‐H within 2,6‐disubstituted pyridines could be removed directly and (2) the C4 selectivity of unsubstituted pyridine originates from the intermolecular exchange of metalation sites via a thermodynamic pathway.
Low‐Temperature‐Assisted Interfacial Polymerization Toward Wrinkle‐Like Structured Thin‐Film Nanocomposite Nanofiltration Membranes
Authors: Gao Hongbao , Zhao Xiaojuan , Zhou WeiWei , Kang Xinwei , Xu Shuangcheng , Li Hanyun , Hou Junyan , Wu Daoji , Xu Jingtao , Lu Xiaozhen 
Published: January 2025

ABSTRACTConfining the diffusion rate of aqueous amine monomers during interfacial polymerization (IP) via incorporating nanoparticles/macromolecules with special functional groups and/or creating an interlayer owning suitable properties is an attractive alternative to construct a polyamide (PA) nanofilm featuring unique surface morphologies. However, the fabrication of high‐performance nanofiltration (NF) membranes with both special structural compositions and ultrathin PA separating layers is still a great challenge. Herein, a highly permeable, loose thin‐film nanocomposite (TFN) NF membrane with wrinkle‐like structures was fabricated by incorporating Ti3C2Tx nanosheets into the aqueous solution via a low‐temperature IP strategy. The Ti3C2Tx nanosheet hindered the diffusion rate of aqueous monomers toward the reaction zone, whereas the low temperature of the oil phase enabled the confined transfer rate of oil monomers. Thus, the double monomers restricting strategy (DMR) greatly changed the interfacial reaction environment, contributing to forming a sub‐15 nm PA film (TFC‐Mi) with a wrinkle‐structured surface. The TFC‐Mi membranes exhibited larger pore size and stronger Donnan exclusion, resulting in 98.6% of Na2SO4 rejection and high water permeance of 26.3 LMH/bar. The long‐term filtration test further evidenced its great performance stability. The DMR‐assisted IP owned great promise in tailoring high‐performance loose TFN NF membranes for environmental water applications.
Flammability Performance of Ceramifiable Polydimethylsiloxane (PDMS) Composites With Needle‐Like Wollastonite
Authors: Jiang Zhikun , Chen Zijian , An Yingying , Wang Siqi , Li Ting , Yang Wei , Lu Hongdian , Wei Chunxiang 
Published: January 2025

ABSTRACTCeramifiable flame retardant polydimethylsiloxane (PDMS) composites were successfully fabricated using solution blending and hot pressing, incorporating needle‐like wollastonite (WT), zinc borate (ZB), aluminum hydroxide (ATH), and glass powder (GP) as fillers. The thermal, mechanical, and flame retardant properties, along with the ceramization behavior of the composites, were thoroughly characterized. The findings demonstrate that WT is more effective than conventional lamellar mica in enhancing both tensile strength and flame retardancy, as well as promoting ceramization. The optimized PDMS/WT/ZB/ATH/GP system passed the UL‐94V‐0 rating and exhibited an increased limiting oxygen index (LOI) of 28.5%. Cone calorimetry results indicated that WT effectively reduced the peak heat release rate and delayed ignition of the composites. The flame retardant mechanism is mainly attributed to the WT with a high aspect ratio, which serves as a sintering aid, accelerates the eutectic reaction, and promotes the formation of a ceramic barrier at lower temperatures by reducing the resistance to liquid‐phase migration.
Study on Cut‐Resistance Properties of Composite Yarn Based Knitted UHMWPE Textiles: Influence of Reinforcement, Radiant Heat Exposure, Outdoor Environment, and Cutting Angles
Authors: Singh Shubham , Das Apurba , Kumar Nandan , Kumar Bipin 
Published: January 2025

ABSTRACTThe safety of workers in hazardous environments depends on personal protective clothing capable of withstanding various real‐world challenges, especially in automotive, glass, aerospace, mining, construction, and food industries where cut hazards are prevalent. Ultra‐high‐molecular‐weight‐polyethylene (UHMWPE) is widely utilized in cut‐protective textiles for its exceptional strength and durability. This study investigates the cut‐performance of stainless‐steel and glass fibers reinforced UHMWPE knitted fabrics under real‐world industrial conditions, focusing on the influence of varying cutting angles, outdoor environments, and thermal exposure on their cut‐protective efficacy. Reinforcement significantly improved cut‐performance, with stainless‐steel reinforced UHMWPE fabric (13SU) exhibited the highest tear strength (lengthwise‐313.1 N, widthwise‐405.8 N) and abrasion resistance (withstanding up to 800 rubbing cycles), providing best cut‐protection with cutting force of 32.43 N at 90° cutting angle. Differential scanning calorimetry (DSC) and scanning electron microscope (SEM) characterizations revealed UHMWPE's sensitivity to thermal effects, with a significant decrease in crystallinity after exposure to radiant heat flux of 20 kW/m2 at fabric surface, leading to diminished cut‐performance. Environmental durability assessments indicated a reduction in cut‐resistance properties due to changes in the chemical composition of UHMWPE polymer structure, such as the presence of ketone (CO) and hydroxy (OH) polar groups, as confirmed by Fourier‐transform infrared (FTIR) spectroscopy.
Comparative Assessment of the Antioxidant and Antibacterial Properties of Various Phenolic Acid‐Chitosan Grafted Polymers
Authors: Xia Zi‐Ang , Wang Long , Li Chaojie , Li Xue , Yang Jingxue , Xu Baoming , Zhang Heng 
Published: January 2025

ABSTRACTThe augmentation of chitosan's (CS) antioxidative and antibacterial properties via grafting with phenolic acids constitutes a significant method for expanding the utility of chitosan. In this investigation, four phenolic acids (gallic acid, GA; protocatechuic acid, PCA; hydroxybenzoic acid, HA; and salicylic acid, SA) were conjugated with CS utilizing carbodiimide (EDC)‐mediated grafting. The resultant phenolic acid‐CS graft copolymers underwent characterization employing infrared spectroscopy, x‐ray diffraction, and thermogravimetric analysis. Furthermore, ex vivo antioxidative and antibacterial assays were performed. Findings revealed that among the synthesized phenolic acid‐chitosan graft copolymers, gallic acid‐chitosan (GA‐CS) demonstrated the highest antioxidative and antibacterial efficacy, primarily attributed to its elevated grafting ratio and abundance of hydroxyl groups. The antioxidative and antibacterial performances of the remaining three graft copolymers followed this order: CS‐PCA > CS‐HA > CS‐SA, aligning with the trend in grafting ratios. This correlation arises from the higher grafting ratios of copolymers yielding more active OH groups, thereby exhibiting enhanced antioxidative and antibacterial properties. Phenolic acid‐chitosan graft polymers exhibit promising antioxidative and antibacterial attributes, making them suitable additives for application in the food preservation packaging industry.
Electrochemically Driven Site‐Selective N‐Hydroxymethylation of Indoles and Derivatives
Authors: Chomphunuch Thanathip , La‐ongthong Kannika , Katrun Praewpan , Sawektreeratana Natthapat , Keawkla Natchayatorn , Soorukram Darunee , Leowanawat Pawaret , Reutrakul Vichai , Surawatanawong Panida , Bunchuay Thanthapatra , Kuhakarn Chutima 
Published: January 2025

AbstractDescribed herein is a facile electrochemical strategy for the generation of formaldehyde from N,N‐dimethylacetamide (DMA) and water (H2O) toward a direct and site‐selective N‐hydroxymethylation of indoles and derivatives. Mechanistic studies suggested that N‐(hydroxymethyl)‐N‐methylacetamide generated in situ from DMA/H2O under electrochemical conditions serves as a formaldehyde surrogate. The developed methodology features mild, base‐ and metal catalyst‐free conditions. The reaction can accommodate a broad range of substrate scopes and offers an alternative route to access a series of N‐hydroxymethylated indole, bis‐indole, carbazole, and indazole derivatives. A gram‐scale synthesis was demonstrated to show the scaled‐up applicability of this transformation.
Combination of Hotspot Mutations With Methylation and Fragmentomic Profiles to Enhance Multi‐Cancer Early Detection
Authors: Nguyen Thi Hue Hanh , Vu Giang Hoang , Nguyen Tu Thi , Nguyen Tuan Anh , Tran Vu Uyen , Vu Luyen Thi , Nguyen Giang Thi Huong , Nguyen Nhat Duy , Tran Trung Hieu , Nguyen Van Thien Chi , Nguyen Thanh Dat , Nguyen Trong Hieu , Vo Dac Ho , Van Thi Tuong Vi , Do Thanh Thi , Le Minh Phong , Huynh Le Anh Khoa , Nguyen Duy Sinh , Tang Hung Sang , Nguyen Hoai‐Nghia , Phan Minh‐Duy , Giang Hoa , Tu Lan N. , Tran Le Son 
Published: January 2025

ABSTRACTBackgroundMulti‐cancer early detection (MCED) through a single blood test significantly advances cancer diagnosis. However, most MCED tests rely on a single type of biomarkers, leading to limited sensitivity, particularly for early‐stage cancers. We previously developed SPOT‐MAS, a multimodal ctDNA‐based assay analyzing methylation and fragmentomic profiles to detect five common cancers. Despite its potential, SPOT‐MAS exhibited moderate sensitivities for early‐stage cancers. This study investigated whether integrating hotspot mutations into SPOT‐MAS could enhance its detection rates.MethodA targeted amplicon sequencing approach was developed to profile 700 hotspot mutations in cell‐free DNA and integrated into the SPOT‐MAS assay, creating a single‐blood draw workflow. This workflow, namely SPOT‐MAS Plus was retrospectively validated in a cohort of 255 non‐metastatic cancer patients (breast, colorectal, gastric, liver, and lung) and 304 healthy individuals.ResultsHotspot mutations were detected in 131 of 255 (51.4%) cancer patients, with the highest rates in liver cancer (96.5%), followed by colorectal (59.3%) and lung cancer (53.7%). Lower detection rates were found for cancers with low tumor mutational burden, such as breast (31.3%) and gastric (41.9%) cancers. In contrast, SPOT‐MAS demonstrated higher sensitivities for these cancers (51.6% for breast and 62.9% for gastric). The combination of hotspot mutations with SPOT‐MAS predictions improved early‐stage cancer detection, achieving an overall sensitivity of 78.5% at a specificity of 97.7%. Enhanced sensitivities were observed for colorectal (81.36%) and lung cancer (82.9%).ConclusionThe integration of genetic and epigenetic alterations into a multimodal assay significantly enhances the early detection of various cancers. Further validation in larger cohorts is necessary to support broader clinical applications.