bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural flexibility as a promising biomarker for Alzheimer’s Disease
Authors: Varangis Eleanna , Liu Jun , Miao Yiqi , Zhu Xi , Stern Yaakov , Lee Seonjoo 
Published: January 2025

AbstractBackgroundNeural flexibility (NF) during tasks was associated with cognitive aging, while that during rest was not associated with aging and cognition in a healthy aging population. However, NF has not been studied in AD. We aim to evaluate whether AD is associated with alterations in NF and probe its predictive utility for AD conversion.MethodThe study included 862 older adults with valid resting‐state fMRI data: 461 who are cognitively normal (CN, 53.5%), 294 with Mild cognitive impairment (MCI, 34.1%), and 107 with Alzheimer’s Disease (AD, 12.4%) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The MRI images were processed using fMRIPrep, and the mean time series of each node was extracted according to the Power Atlas parcellation scheme. We performed dynamic community detection based on generalized Louvain methods. We defined the NF of a node as the number of times that a node changed its community assignment across the sliding windows, normalized by the total number of possible changes and computed global NF (GNF) and network‐level NF. We performed linear mixed models on NF to explore the effect of AD group indicators on NF controlling for the age at scan, gender, education level, and the random intercept of site. We then evaluated the dementia transition of neural flexibility using survival analysis. In the non‐demented participants at baseline, we performed Cox‐proportional hazard regression analysis with each NF.ResultsNF is significantly higher in AD group than the CN group on global, CON, MRN, SMN‐H, SMN‐M, VAN, and VIS networks (Figure 1); neural flexibility is significantly higher in the MCI group than the CN group in the VIS network (Figure 1). Among n = 670 non‐demented participants at baseline, n = 53 (8.6%) participants converted to dementia during the follow‐ups. Higher neural flexibility in VIS was positively associated with AD transition (HR = 1.323, 95%CI 1.002 to 1.747, p = 0.049, per 1 standard deviation in NF, Figure 2), controlling for age, gender, and education.ConclusionWe found that NF during resting was higher in AD patients and predicted dementia transition. Thus, NF can be a valuable biomarker of AD, and more validation and mechanistic studies need to be performed.
Amyloid Biomarker Discordance in Patients Evaluated for Anti‐Amyloid Therapy
Authors: Ramanan Vijay K. , Graff‐Radford Jonathan , Bornhorst Joshua A , Johnson Derek R. , Cogswell Petrice M , Burkett Brian J , Lowe Val J. , Stricker Nikki H. , Botha Hugo , Jones David T. , McCarter Stuart J , Neth Bryan J. , Jack Clifford R. , Knopman David S. , Petersen Ronald C. , Algeciras‐Schimnich Alicia 
Published: January 2025

AbstractBackgroundEvidence for abnormal amyloid‐β (Aβ) plaque accumulation is necessary prior to initiating anti‐amyloid therapy in early symptomatic Alzheimer’s disease (AD). While the clinical trials for lecanemab and related drugs utilized positron emission tomography (PET) to demonstrate brain amyloidosis, current appropriate use recommendations for clinical practice consider PET or cerebrospinal fluid (CSF) biomarkers as satisfactory for this purpose. Here, we present four clinical cases where CSF biomarker results were discordant from amyloid PET, with the potential to result in erroneous treatment targeting.MethodPatients were seen at a tertiary care subspecialty clinic in consideration for lecanemab therapy. All patients had office examination, neuropsychological assessment, structural magnetic resonance imaging (MRI), amyloid PET (with either 11C‐Pittsburgh compound B or 18F‐florbetapir), CSF AD biomarkers (Roche Elecsys p‐tau181/Aβ42 and Fujirebio Lumipulse Aβ42/Aβ40 ratios), and apolipoprotein E (APOE) allele testing. Amyloid PET interpretations were made by consensus visual review from experienced readers.ResultAll four patients had clinical diagnoses of mild cognitive impairment or mild dementia (Table 1). Two patients had positive CSF p‐tau181/Aβ42 and Aβ42/40 ratios with negative amyloid PET (indicating sparse to no neuritic plaques). Case 1 displayed aphasia (characterized by anomia and deep dysgraphia) and imaging findings possibly compatible with semantic dementia. Case 2 displayed a gait abnormality and imaging signs of abnormal CSF dynamics. Two other patients had negative CSF p‐tau181/Aβ42 measures with positive amyloid PET (indicating moderate to frequent neuritic plaques). In those instances, the clinical syndrome and imaging studies were strongly supportive of AD and the CSF Aβ42/40 ratio was “likely positive” (Table 1). For one patient (Case 4), tau PET and Lumipulse plasma p‐tau217 concentration were both positive.ConclusionClinicians prescribing anti‐amyloid therapies should be aware of the possibility for CSF biomarkers to be discordant from amyloid PET status in select scenarios. These cases highlight the value of considering PET imaging in the presence of clinically atypical features, concern for mixed etiology, or strong clinical suspicion for AD despite negative CSF biomarkers. Larger series are needed to identify broader patterns contributing to biomarker discordance by assay, modality (PET versus CSF/plasma measures), and medical/neurologic comorbidities.
Air pollution diesel particles decrease synaptosomal post‐synaptic but not pre‐synaptic proteins in mouse cortex
Authors: Godoy‐Lugo Jose A , Thorwald Max A , Sioutas Constantinos , Mack William J , Finch Caleb E 
Published: January 2025

AbstractBackgroundChronic air pollution exposure increases accelerates cognitive aging and AD risk. Synapse loss in AD correlates with decreased cognitive ability. In rodents, inhaled air pollutants decreased glutamatergic synapses, decreasing excitatory postsynaptic currents (EPSCs), while increasing total levels of AMPA and NMDA receptor protein. To further resolve air pollution effects in these synaptic components, we examined synaptosomal proteins from mice exposed to diesel exhaust particles (DEP).MethodC57BL/6 mice were exposed to re‐aerosolized DEP (n = 12, 100 µg/m3; NIST 2975) or filtered air (FA, n = 12) for 5 h/day for 8 weeks. Synaptosomes were isolated by centrifugation from cerebral cortex and proteins analyzed by immunoblots.ResultDEP exposure decreased synaptosomal PSD95 by ‐30% and Homer1, and SAP97 by ‐20%. Also decreasing NMDA receptor subunits GluN1 and GluN2A by ‐20%. In contrast, DEP did not alter pre‐synaptic vesicle proteins SNAP‐25, SYN1, SYT1, and SYP.ConclusionMechanisms behind early synapse disfunction after exposure to air pollution may relate to greater decreases in post‐synaptic than the pre‐synaptic proteins we assayed at the synapse. Future studies will evaluate the hippocampus, which has shown selective impact in CA1 neurons EPSCs, and the role of air pollution‐induced oxidative damage at synapse cites.
Altered Brain Effective Connectivity in MCI during Object‐Location Associations: an fMRI Study
Authors: Sun Boxin , Deng Jinxian , Scheel Norman , Bhaumik Arijit K , Ren Jian , Hampstead Benjamin M. , Li Tongtong 
Published: January 2025

AbstractBackgroundExisting work suggests that Alzheimer’s disease (AD) pathology can affect the direction and intensity of information signaling in functional brain regions. This study aims to explore how mild cognitive impairment (MCI) can affect the brain effective connectivity.MethodWe used an event‐related functional magnetic resonance imaging (fMRI) paradigm to compare patients with aMCI and healthy controls with normal cognition (NC) as they encoded 90 ecologically‐relevant object‐location associations (OLAs). Two additional OLAs, repeated a total of 45 times, served as control stimuli. Memory for these OLAs was assessed following a 1‐hour delay. The groups were well matched on demographics and brain volumetrics. A total of 44 right‐handed participants (19 NC, 25 aMCI, age mean: 71.5) completed this study.We evaluated the effective connectivity between all the possible functional brain region pairs using causalized convergent cross mapping (cCCM), which measures the intensity of directional information transfer between the brain regions.ResultThe region pairs where the effective connectivity (in terms of cCCM values) of NC and MCI exhibit the largest, statistically significant differences (p‐value < 0.05) are shown in Figure 1, and the result for the visuospatial network alone is shown in Figure 2. Our analysis shows that during the encoding of ecologically relevant object‐location associations, MCI demonstrated statistically significant reduction in effective connectivity (p‐value < 0.05) across some regions, but also showed increased effective connectivity across other regions.ConclusionThe increased effective connectivity of MCI in some regions indicates the presence of detours in information transfer due to the weakening of connectivity in other regions and may reflect the compensatory mechanism of the brain.
Reproducibility of Centiloid Values in Real‐World Amyloid PET Data: Comparison of the Imaging Dementia‐Evidence for Amyloid Scanning (IDEAS) to Four Large Research Datasets
Authors: Blazhenets Ganna , Zeltzer Ehud , Lagarde Julien , Landau Susan M. , Koeppe Robert A. , Carrillo Maria C. , Dickerson Bradford C. , Apostolova Liana G. , Jagust William J. , Rabinovici Gil D. , Joie Renaud La ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: January 2025

AbstractBackgroundThe Centiloid framework was developed to harmonize amyloid‐PET quantification across radiotracers and processing pipelines to facilitate data sharing and merging; it is now widely used across research and clinical trials. As we just completed the quantification of 10,361 amyloid‐PET scans from the largest “real‐world” study of amyloid‐PET (IDEAS) and are about to release the data, we aimed to compare the distribution of IDEAS Centiloid values with other available datasets.MethodIn IDEAS, amyloid scans were acquired across 343 facilities and centrally processed at UCSF using a PET‐only pipeline. We also had access to PET data from our own UCSF Alzheimer’s Disease Research Center and the LEADS study. Using the GAAIN platform, we identified two other cohorts with available Centiloids: ADNI and MCSA. For each cohort, we collected Centiloids, demographic, and basic clinical data. Gaussian mixture models (GMM) were fitted to Centiloid values for each cohort, and data‐driven Centiloid cutoffs were calculated as mean + 2SD of the first Gaussian. Finally, we compared Centiloids to PET visual reads (when available) and determined the Centiloid cutoff value maximizing correspondence between visual read and binarized Centiloids based on Cohen’s kappa.ResultThe 5 cohorts were heterogeneous in terms of sample characteristics and radiotracers (Table 1). In all cohorts, a two‐Gaussian model was considered the best fit for the data based on the integrated completed likelihood criteria (Figure 1). The first Gaussian peaks were close to zero, with mild variability across studies (from ‐5 in IDEAS to 10 CL in MSCA). The second peak was more heterogeneous across cohorts (from 67 to 102 CL) with a rightward shift in cohorts enriched with clinically impaired patients. Mean Centiloid values in visually negative and positive scans generally matched well with results derived from GMM (Figure 2). Across all cohorts, GMM‐based Centiloid cutoffs tended to be slightly lower (18‐26) compared to those based on visual inspection (25‐31).ConclusionThe availability of Centiloids across cohorts enables a direct comparison of amyloid‐PET results in otherwise different studies. Despite some variability across cohorts and analysis methods, Centiloid cutoffs align well with thresholds from the existing literature.
Metallaphotoredox Enabled Single Carbon Atom Insertion into Alkenes for Allene Synthesis
Authors: Liu Gang , Shi Zhaoxin , Guo Chuning , Gu Danyu , Wang Zhaobin 
Published: January 2025

AbstractEfficient methods for synthesizing allenes from readily available starting materials pose a persistent challenge in organic chemistry. In this work, we present a novel two‐stage protocol for allene synthesis involving the single‐atom insertion into alkenes, facilitated by synergistic photoredox and cobalt catalysis. Diverging from conventional methods such as the Doering‐LaFlamme reaction, this photochemical rearrangement approach operates efficiently under mild conditions in a radical‐based manner. The protocol exhibits a broad substrate scope and demonstrates applicability in the late‐stage diversification of alkene‐containing natural products and bioactive molecules. Preliminary mechanistic studies and density functional theory (DFT) calculations offer insights into the reaction pathway, indicating a radical mechanism involving fleeting cyclopropyl carbene intermediates followed by rapid ring opening to form allenes.
Mastering the Copolymerization Behavior of Ethyl Cyanoacrylate as Gel Polymer Electrolyte for Lithium‐metal Battery Application
Authors: Min Weixing , Li Lengwan , Wang Mingli , Ma Shuaijiang , Feng Hao , Wang Weirong , Ding Hang , Cheng Tianhui , Li Zhenxi , Saito Tomonori , Yang Huabin , Cao Peng‐Fei 
Published: January 2025

AbstractPolymers with strong electron‐withdrawing groups (e.g., cyano‐containing polymers) are attractive for a wide range of applications due to their high dielectric constant and outstanding electrochemical stability. However, the polymerization of such monomers is difficult to control with trace of water affording instant reactions, and copolymerization with other monomers without using strong acid is even more challenging. The present study demonstrates a facile approach enabling efficient and controllable copolymerization of ethyl cyanoacrylate (ECA) without adding undesired additives, achieving mechanically robust and high ion‐conduction gel polymer electrolyte (GPE) for safe and long cycle‐life lithium‐metal batteries (LMBs). The incorporated dual‐lithium salts, i.e., lithium difluoro(oxalato)borate (LiDFOB) and lithium bis(trifluoromethanesulphonyl)imide (LiTFSI) not only facilitate radical polymerization of ECA monomers by suppressing their anionic polymerization, but also promote the formation of high‐ionic conducting GPE. The incorporated methyl methacrylate (MMA) monomer accelerates the radical polymerization of ECA (confirmed by DFT calculations), achieving controlled copolymerization of ECA‐based copolymers. The mechanically robust polymer network made by the ECA copolymer enables LMBs with both LFP cathodes and high‐voltage LCO cathodes (4.5 V) operatable at different temperatures with ultra‐long cycle life at 1 C (capacity retention of 81.1 % and 83.8 %, respectively, over 1000 cycles).
Deciphering Polymer Interactions in Bioconjugates with Different Architectures by Structural Analysis via Time‐Resolved Limited Proteolysis Mass Spectrometry
Authors: Hamm Prisca , Driessen Marc D. , Hauptstein Niklas , Kehrein Josef , Worschech Rafael , Pouyan Paria , Haag Rainer , Schubert Ulrich S. , Müller Thomas D. , Meinel Lorenz , Lühmann Tessa 
Published: January 2025

AbstractTherapeutic proteins are commonly conjugated with polymers to modulate their pharmacokinetics but often lack a description of the polymer‐protein interaction. We deployed limited proteolysis mass spectrometry (LiP‐MS) to reveal the interaction of polyethylene glycol (PEG) and PEG alternative polymers with interferon‐α2a (IFN). Target conjugates were digested with the specific protease trypsin and a “heavy” 15N‐IFN wild type (IFN‐WT) for time‐resolved quantification of the cleavage dynamics. Interactions between IFN‐α2a and its high‐affinity receptor were detailed by LiP‐MS. Then, 10 kDa polymers of PEG, linear polyglycerol (LPG), and poly(2‐oxazoline) (POX) with two different cyclooctyne linkers (BCN/DBCO) were used for site‐specific bioconjugation to azide functionalized IFN‐α2a. Tryptic events at each cleavage site and in different structural environments (loops/helices) were compared. PEG and LPG were similar, and POX showed a reduced interaction profile with the IFN‐α2a surface. All‐atom molecular dynamics simulations of IFN‐DBCO‐polymer conjugates revealed distinct and transient (below 50 ns) protein‐interaction profiles for PEG, LPG, and POX. Cleavage dynamics of IFN‐polymer conjugates from the BCN handle were homogeneous, pointing to a more conserved IFN structure than DBCO‐polymer conjugates. In summary, time‐resolved LiP‐MS for quantification of cleavage events enhances the structural understanding of transient IFN‐polymer interactions, which may be extended to other bioconjugate types.
Delocalized Nonbonding Orbitals of Thioxanthone in Polycyclic Aromatic Hydrocarbons for Reduced Energy Gap and Narrowband Emission
Authors: Yang Zhihai , Liu Denghui , Cheng Xiangyi , Wang Tong , Li Zhizhi , Yang Guo‐Xi , Chen Zijian , Hu Juntao , Fu Yu , Nie Xuewei , Ren Yongxia , Zeng Yitong , Chen Yuling , Liu Kunkun , Li Mengke , Su Shi‐Jian 
Published: January 2025

AbstractChalcogen‐containing carbonyls, specifically thioxanthone (TX), hold great potential in organic light‐emitting diodes (OLEDs). While the development of narrowband OLEDs with chalcogen‐containing carbonyls remains challenging due to difficulties in achieving both high device efficiency and narrow emission spectra. Herein, via a strategic incorporation of the TX moiety, two orange‐red narrowband emitters, 2TXBN and BNTXBN, are designed and synthesized for the first time. Both 2TXBN and BNTXBN exhibit bright orange‐red emissions with peaks at 582 and 585 nm, respectively, along with narrow full widths at half maxima of 30 and 32 nm. Notably, 2TXBN demonstrates delocalization of the nonbonding orbital within the TX segment, which raises the first triplet energy level and reduces the singlet‐triplet energy gap. This electronic structural adjustment effectively shortens the delayed fluorescence lifetime, leading to enhanced device performance. Accordingly, OLED employing 2TXBN as the emitter achieves remarkable performance, with a maximum external quantum efficiency of 31.0 %, a current efficiency of 69.0 cd A−1, and a power efficiency of 76.0 lm W−1, highlighting the efficacy of the nonbonding orbital delocalization strategy in achieving bathochromic‐shifted narrowband OLED materials.
Synthesis of Phosphorus‐Nitrogen Synergistic Flame Retardant Containing Pyrimidine Ring/Vanillin for Improving Flame Retardancy, Smoke Suppressing, and Mechanical Properties of Epoxy Resin
Authors: Xiao Hongbo , Huang Xin , Huang Wanyu , Peng Yufei 
Published: January 2025

ABSTRACTIn order to improve the flame retardancy, smoke suppressing, and mechanical properties of epoxy resins (EP), while pursuing low toxicity, environmental protection, and sustainable development, a reactive biobased flame retardant (TVD) containing P/N was synthesized by the one‐pot method. The flame retardant, consisting of vanillin, 2,4,6‐triaminopyrimidine, and DOPO as reactants, contained reactive groups in its structure and was introduced as a co‐curing agent into the DDM‐cured EP system. EP/TVD10 (at a phosphorus content of 0.58 wt%) achieved a UL‐94 V‐0 rating with an increased limit oxygen index (LOI) value of 34.2% (26.5% for pure EP), and the cone calorimetric test (CCT) results showed a decrease in total heat release (THR) values of 33.8% and a decrease in total smoke production rate (TSP) of 21.1% compared to pure EP. In addition, the introduction of TVD improved the mechanical properties of the epoxy resin, with an increase in flexural strength and modulus of 8.7% and 6.5% and a slight increase in impact toughness for EP/TVD10. These results indicate that TVD is a multifunctional and efficient bio‐based flame retardant, which provides new ideas for the development of high‐performance modified epoxy resin materials.
Effects of Self‐Assembled β‐Crystal Nucleating Agents on Crystallization and Microcellular Foaming Behavior of Long‐Chain Branched Polypropylene
Authors: Liu Yaning , Liu Haiming , Wang Yaqiao , Sun Yibo , Chen Shihong , Wang Xiangdong 
Published: January 2025

ABSTRACTLong‐chain branched polypropylene (LCBPP) has become the material of choice for foaming due to its high melt strength and excellent strain hardening properties. In this work, different β‐crystal nucleating agents were melt‐blended with LCBPP. The morphology of the nucleating agents, melt strength, and melting crystallization behavior of the mixtures were characterized using POM, rotational rheometer, XRD, and DSC. After selecting the nucleating agent WBG‐II, high‐temperature self‐assembly was performed. The impact strength of the mixture containing 5 phr of the nucleating agent reached 5.36 kJ/m2, which is a 30% improvement compared to pure polypropylene samples. At a foaming temperature of 138°C, with scCO2 as the physical foaming agent, various microcellular LCBPP foams were prepared using the autoclave foaming method. When the content of the self‐assembled nucleating agent increased to 5 phr, the foam expansion ratio decreased from 25 times to about 2 times, the cell size was refined from 142 μm to about 7 μm, and the cell density increased from 2 × 107 to 3.8 × 109 cells/cm3. Simultaneously, the complex structure of the self‐assembled nucleating agent and the induced composite cells synergistically enhanced the compressive strength of the polymer foam.
Histopoly: A serious game for teaching histology to 1st year veterinary students
Authors: Marcos Ricardo , Gomes André , Santos Marta , Coelho António 
Published: January 2025

AbstractHistology is a preclinical subject transversal in medical, dental, and veterinary curricula. Classical teaching approaches in histology are often undermined by lower motivation and engagement of students, which may be addressed by innovative learning environments. Herein, we developed a serious game approach and compared it with a classical teaching style. The students' feedback was evaluated by questionnaires, and their performance on quizzes and exam's scores were assessed. The serious game (Histopoly) consisted of a game‐based web application for the teacher/game master, a digital gaming application used by the students as a controller, and a projected digital board game. The board featured rows for the four fundamental tissues (epithelial, connective, muscular, and nervous) paired with question tiles and additional tiles with more demanding activities (e.g., drawing, presenting slides, and making a syllabus). Participants included all veterinary students enrolled in the first year. Paired laboratory sessions were split with four sections (n = 94 students) playing Histopoly at the end of all sessions and two sections (n = 28 students) completing small evaluations every three weeks at the beginning of sessions. According to the questionnaires, students that played the serious game were more motivated, engaged, and more interconnected with classmates. The activity was considered fun, and students enjoyed the classes more. No differences in the final examination scores were found, but the percentage of correct answers provided throughout the serious game was significantly higher. Overall, these findings argue for the inclusion of serious games in modern histology teaching to promote student engagement in learning.
Distinguishing the Bimodal Interaction of a Squaraine Dye with a Protein by a Functional Group Photodeprotection Strategy
Authors: Anees Palapuravan , Saranya Giridharan , Sreejith Sivaramapanicker , Ajayaghosh Ayyappanpillai 
Published: January 2025

AbstractIn this study, we present a protecting group photocleavage method to investigate both covalent and noncovalent interactions between a squaraine dye (PSq) and Bovine Serum Albumin (BSA). This approach allows for the photoinduced activation and deactivation of PSq fluorescence, providing valuable insights into the dual‐mode interaction of the dye with the protein.