bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of α‐synuclein pathology in Alzheimer’s disease and normal aging
Authors: Winer Joseph R. , Plastini Melanie J. , Romero America , Wilson Edward N. , Young Christina B. , Trelle Alexandra N. , Henderson Victor W. , Wagner Anthony D. , Poston Kathleen L. , Mormino Elizabeth 
Published: January 2025

AbstractBackgroundα‐Synuclein is the hallmark pathology of Parkinson’s disease and dementia with Lewy bodies, described together as Lewy body disease (LBD). α‐Synuclein is also commonly observed in the context of Alzheimer’s disease (AD). Here we investigate the frequency of α‐synuclein positivity in an AD research cohort and clinically unimpaired individuals (CU), as well as associations with demographics and AD biomarkers.MethodWe assessed α‐synuclein status (αSyn±) in 69 clinically diagnosed AD (38 mild cognitive impairment and 31 dementia) and 277 CU using a cerebrospinal fluid α‐synuclein seeding aggregation assay. 91 LBD spectrum participants were included for comparison. Aβ status and tau levels were measured with cerebrospinal fluid Aβ42/40 and pTau181 using the Lumipulse G assay. Memory performance was examined in CU individuals enrolled in the Stanford Aging and Memory Study (SAMS, N = 164/277).ResultAs expected, αSyn+ was highest in LBD (81%). 16% of AD and 9% of CU were αSyn+. Among αSyn+ CU, 45% were Aβ+ compared to 31% in αSyn‐ CU. In a logistic regression that included only participants with AD, α‐synuclein positivity was associated with male sex, clinical impairment (dementia versus mild cognitive impairment), and higher pTau181 (Figure 1A). In CU, α‐synuclein positivity was associated with older age (Figure 1B). Among CU from SAMS, the αSyn+ group showed cross‐sectional memory reductions that were similar to the A+/T+ CU group (Figure 2).Conclusionα‐Synuclein status may be an important independent predictor of clinical impairment among individuals on the AD spectrum, as well as subtle memory changes in in aging.
Recovery of insulin/IGF‐1/GLP‐1 signaling protects the brain against cardiometabolic and neurodegenerative diseases
Authors: Duarte Ana Isabel 
Published: January 2025

AbstractBackgroundCardiometabolic diseases, such as type 2 diabetes, hypertension, dyslipidemia or obesity, constitute major causes of mortality and morbidity worldwide, especially among middle‐aged individuals. The increasing incidence and association with aging and lifestyle, render the cardiometabolic diseases a societal concern. This is further reinforced by their association with an increased risk of cognitive impairment and neurodegenerative diseases (namely dementia and Alzheimer’s disease (AD)).Given the poor knowledge on the precise crosslinking mechanisms between cardiometabolic and neurodegenerative diseases, we hypothesize that recovering insulin/IGF‐1/GLP‐1 signaling protects against brain and cognitive injury upon cardiometabolic diseases, ultimately preventing neurodegenerative diseases. We aimed to study the impact of recovering brain insulin/IGF‐1/GLP‐1 signaling on brain and cognitive function in animal models of cardiometabolic and neurodegenerative diseases.MethodsWe used rodent models of type 2 diabetes, high cardiovascular risk, AD and Huntington’s disease (HD), peripherally administered with commercially available GLP‐1 mimetics or anti‐dyslipidemia drugs, to analyze the features of cardiometabolic and neurodegenerative diseases, markers of oxidative stress, neuroinflammation, (mitochondrial) metabolism and autophagy/mitophagy, together with the motor and cognitive performance.ResultsOur studies suggest that recovering cerebral insulin/IGF‐1/GLP‐1, either by peripherally administered incretins or novel anti‐dyslipidemia drugs, may protect against oxidative stress, inflammation, dysregulated metabolic and autophagic mechanisms, ultimately counteracting motor and cognitive impairment and neurodegeneration/death in rodent models of cardiometabolic and neurodegenerative diseases (namely type 2 diabetes, AD, HD, high cardiovascular risk).ConclusionsAdministration of anti‐type 2 diabetes or anti‐dyslipidemia drugs that recover cerebral insulin/IGF‐1/GLP‐1 signaling may constitute a promising preventive/therapeutic strategy against persistent brain injury associated with cardiometabolic and neurodegenerative diseases. However, this issue deserves to be further clarified.Funded by: European Regional Development Fund, through the Centro2020 Operational Programme (Projects CENTRO‐01‐0145‐FEDER‐000012 (HealthyAging2020), POCI‐010145‐FEDER‐016577, POCI‐01‐0145‐FEDER‐029391 (Mito4ALS)); by COMPETE 2020 ‐ Operational Programme for Competitiveness and Internationalization; by Portuguese funds via FCT – Fundação para a Ciência e a Tecnologia, through the projects PTDC/SAU‐TOX/117481/2010, POCI‐01‐0145‐FEDER‐029391, PTDC/MED‐FAR/29391/2017, UIDB/04539/2020, UIDP/04539/2020, LA/P/0058/2020; by Santander‐Totta & Faculty of Medicine, University of Coimbra (PEPITA 2018); by the European Social Fund, though the contracts DOI: 10.54499/DL57/2016/CP1448/CT0006 and EU HORIZON‐WIDERA‐2022‐ACCESS‐04‐01 Excellence Hubs/CHAngeing/101087071/II0347.01 of AID.
Warfarin overdose successfully treated using prophylactic vitamin K infusion without severe coagulopathy: A case report
Authors: Omoto Ryosuke , Umemura Yutaka , Kokubu Yuki , Kiguchi Takeyuki , Fujimi Satoshi 
Published: January 2025

AbstractBackgroundWarfarin, a vitamin K antagonist, is widely used for preventing and treating thromboembolic diseases. While guidelines exist for managing elevated prothrombin time‐international normalized ratio (INR) in patients on warfarin, the treatment for warfarin overdose in these patients is yet to be standardized.Case PresentationA 41‐year‐old woman ingested 230 mg of warfarin with suicidal intent, along with other medications. Initially unconscious, her INR was 1.0, and laboratory results were normal. Prophylactic continuous menaquinone‐4, vitamin K2, injections were administered before the INR increased. After stopping vitamin K2 72 h later, her INR rose to 1.8, but she recovered without severe coagulopathy or bleeding, despite a high initial warfarin concentration.ConclusionThis is the first case of warfarin overdose managed with prophylactic vitamin K2 injections before INR elevation, successfully preventing severe complications. Prophylactic vitamin K infusion may be a practical approach for warfarin overdose treatment in non‐dependent patients.
Dynamically Stable Cu0Cuδ+ Pair Sites Based on In Situ‐Exsolved Cu Nanoclusters on CaCO3 for Efficient CO2 Electroreduction
Authors: Zhang Rongrong , Ma Haibin , Han Shuhe , Wu Zhitan , Zhou Xin , Chen Zhongxin , Liu Jia , Xiao Yukun , Chen Wei , Loh Kian Ping 
Published: January 2025

AbstractCopper‐based catalysts are the choice for producing multi‐carbon products (C2+) during CO2 electroreduction (CO2RR), where the Cu0Cuδ+ pair sites are proposed to be synergistic hotspots for C−C coupling. Maintaining their dynamic stability requires precise control over electron affinity and anion vacancy formation energy, posing significant challenges. Here, we present an in situ reconstruction strategy to create dynamically stable Cu0Cu0.18+OCa motifs at the interface of exsolved Cu nanoclusters and CaCO3 nanospheres (Cu/CaCO3). In situ XAFS analysis confirmed the low‐valency state of Cuδ+ during CO2RR. DFT calculations demonstrated that the nanocluster size arises from the balance between metal‐support interactions and Cu−Cu cohesive energy, while the dynamic stability of rich interfacial Cuδ+ sites is attributed to their low electron affinity and high CO32− vacancy formation energy, which collectively contribute to reduced reducibility. The transformed Cu/CaCO3 exhibits an impressive C2+ Faradaic efficiency of 83.7 % at a partial current density of 393 mA cm−2, facilitated by adsorption of *CO with varying electronegativity at heterogeneous copper sites that lowers the C−C coupling energy barrier. Our findings establish insoluble carbonate as an effective anion pairing for Cu0Cuδ+ sites, highlighting the effectiveness of the in situ reconstitution strategy in producing a high density of dynamically stable Cu0Cuδ+ pair sites.
Catalytic Asymmetric Total Synthesis of (+)‐Chamaecydin and (+)‐Isochamaecydin and their Stereoisomers
Authors: Zhang Yuan‐He , Deng Le‐Hua , Tan Dong‐Xing , Han Fu‐She 
Published: January 2025

AbstractA modular approach was developed for the first catalytic asymmetric total syntheses of naturally occurring C30 terpene quinone methides and their non‐natural stereoisomers, which feature the presence of an unprecedented spiro[4.4]nonane‐containing 6–6–6‐5–5–3 hexacyclic skeleton. Resting on a chiral phosphinamide‐catalyzed enantioselective reduction of 2,2‐disubstituted cyclohexane‐1,3‐dione, a concise route for the synthesis of enantioenriched 6–6 bicyclic fragment was developed. The 6–6 ring fragment and the five‐membered ring fragment were unified via a metal‐halogen exchange/intermolecular addition reaction. Subsequently, the central 6–5 bicyclic ring system was constructed through a Michael/aldol cascade. The successful establishment of these strategic transformations allowed for an efficient and rapid construction of spiroannulated 6–6–6–5–5 pentacarbocyclic core via a convergent manner. Finally, the total syntheses of naturally occurring (+)‐chamaecydin and (+)‐isochamaecydin and their corresponding 1’,5’‐stereoisomers have been achieved divergently by appropriately orchestrating the reaction sequence including isopropyl incorporation, oxidation state adjustment, and carbonyl group‐directed regio‐ and stereoselective cyclopropanation at a late stage.
Stereoselective Preparation and Palladium‐Catalyzed Suzuki–Miyaura Cross‐Coupling of Alkenyl Sulfoximines
Authors: Yasui Kosuke , Tomishima Yuichiro , Miura Tomoya , Yamazaki Ken , Hirano Koji 
Published: January 2025

AbstractAlthough numerous transition‐metal catalyzed cross‐coupling reactions of alkenyl electrophiles with a sulfur(VI) leaving group, mainly alkenyl sulfones, have been developed, most rely heavily on highly nucleophilic Grignard reagents, and the use of organoboron reagents remains challenging. We report herein facile preparation and the following Pd‐catalyzed Suzuki–Miyaura cross‐coupling reaction of alkenyl sulfoximine, a monoaza analog of sulfone. The condensation of alkyl sulfoximine with aldehydes, developed in this study, makes alkenyl sulfoximines more readily available. The resulting alkenes undergo an unprecedented oxidative addition of the C−S bond to the Pd center. This cross‐coupling proceeds with retention of its original stereochemistry and provided alkenes bearing three different functionalities in a stereoselective fashion. DFT calculations highlight the critical role of boronic acid and in situ‐generated boroxines in facilitating this transformation.
Photoinduced Shape Changes of Giant Vesicles Comprising Phospholipids and Azobenzene‐Containing Cationic Amphiphiles
Authors: Noguchi Yutaro , Sasaki Shoi , Liao Yifei , Matsuo Muneyuki , Asakura Kouichi , Banno Taisuke 
Published: January 2025

AbstractFor the development of new functional materials for various applications, such as drug or gene delivery and environmental remediation, the relationship between function and morphology has been considered an important aspect for controlling affinity to the targets. However, there are only a few reports on this relationship because the molecular strategy for the precise control of vesicle shape has been restricted. Herein, we report the photocontrol of vesicle shape using azobenzene‐containing amphiphilic switches. The addition of the photoswitches to vesicles composed of phospholipids yielded non‐spherical vesicles. They exhibited reversible deformation between a non‐spherical and spherical shape in response to ultraviolet and visible light illumination, respectively. From the results of the 1H NMR analyses, fluorescence spectra of the environmentally responsive probes, and Π‐A isotherm measurements, the reversible photoresponsivity can be attributed to the changes in the vesicular membrane structures caused by migration of the photoswitches between the aqueous phase and membrane through their photoisomerization.
Teachers as epistemic agents: A case study of interdisciplinary pedagogy
Authors: Resnick Vered , Kolikant Yifat Ben David 
Published: January 2025

AbstractThis qualitative case study explores teachers' epistemic agency during the implementation of interdisciplinary pedagogy in an Israeli high school. We examined science teachers collaborating on curriculum design through observations of weekly meetings. Micro‐analysis of a pivotal meeting uncovered conditions shaping teachers' epistemic agency. Our findings reveal two central themes: ‘fragile knowledge’ and ‘forward motion’, illustrating how teachers navigate uncertainty and construct new knowledge. We introduce a novel framework for understanding epistemic agency development, comprising four key elements: epistemic disruption, interaction, autonomy and epistemic stance. This framework provides a lens for analysing and fostering teachers' epistemic agency, with implications for teacher development in interdisciplinary contexts.
Shark Tooth Forensics: A Participatory Science Initiative to Unravel Ancient Shark Ecology
Authors: Gates Terry A. , Dunn Robert R. , Bourne Nathaniel W. , Boyd Raya I. , Argall Brittany , Shell Leonora , Alford Aaron , Zanno Lindsay E. 
Published: January 2025

AbstractStudying the ecology of ancient organisms requires a tremendous amount of data, as in the case of prehistoric sharks where our knowledge is based mostly on teeth. Shark Tooth Forensics is a participatory science project tackling the problem of deciphering the ecology of ancient sharks with assistance from public school students. Traditionally, paleontological data collection protocols use research staff or a cadre of trained volunteers to collect paleontological data, whereas participatory science provides a means to increase the number of people involved in paleontological research. Students contributing to our project search for fossil shark teeth in sediments from various geologic time periods, and measure and record the teeth they discover for accessioning in natural history museums. Statistical analyses reveal that middle school students provide measurements of shark teeth that are indistinguishable from those same measurements taken by research staff. However, it is necessary to collect data from large student populations, ~10–30 students, before obtaining a statistically reliable sample. In addition, we find students are able to recognize shark teeth from a variety of species, not just stereotypical triangular teeth of species like the Great White (Carcharodon carcharias). Teachers can utilize Shark Tooth Forensics curricular activities that use student data in curriculum as a way to gain more personal investment. We estimate over 2,000 students have already participated, and with the potential for this project to last for decades, many thousands more will have the opportunity to discover fossil sharks and reconstruct the lives of these ancient fish.
Neural Determinants of Sedentary Lifestyle in Older Adults: A Brain Network Analysis
Authors: Bahrami Mohsen , Burdette Jonathan H , Laurienti Paul J , Nicklas Barbara J , Rejeski W Jack , Fanning Jason 
Published: January 2025

ABSTRACTPurposeThe prevalence of sedentary lifestyles (SL), which includes both high volumes of extended sitting behavior and a low volume of steps accumulated across the day, among older adults continues to rise contributing to increases in associated comorbidities and the loss of independence. The social, personal, and economic burdens are enormous. In recognition of the health implications of SL, current public health physical activity guidelines now emphasize the complimentary goals of sitting less by moving more. We recently completed a 6‐month weight loss (WL) study followed by 12 months of reduced contact to examine weight regain in older adults with obesity. One of the treatment conditions involved WL + a day‐long movement intervention that explicitly targeted reducing sitting time and increasing steps across the day (SitLess).MethodThe goal of the current study, using baseline fMRI and accelerometry data from 36 participants and advanced machine learning tools, was to determine if we could identify complex brain circuits underlying variability associated with changes in sitting time and daily steps during the 6‐month intensive phase among participants randomized to the WL + SitLess treatment condition. Models generated from these analyses produced accuracy in predicting pre–post change in both measures that exceeded 92%, suggesting a critical role for the identified brain subnetworks in explaining variability in these outcomes in response to the intervention. The identified networks comprised regions, predominantly in the default mode and sensorimotor networks, that have been extensively linked to self‐regulation and decision‐making.FindingThese results provide insights into the theoretical basis of SL for older adults and in the design of future intervention research.
Patient and Caregiver Perceptions of Caregiving Contributions During Cancer Clinical Trials: A Mixed‐Methods Study
Authors: Cerutti Janine , Lent Maria C. , Holcombe Randall F. , Reblin Maija 
Published: January 2025

ABSTRACTObjectiveCaregivers play crucial roles in cancer treatment and outcomes. However, little is known regarding how caregivers support patients during cancer clinical trials. The aim of this study was to gain insight into the caregiver experience of rural and urban patients enrolled in cancer clinical trials.MethodsAs part of a quality improvement study, 21 patient–caregiver dyads were interviewed using closed and open‐ended interview questions. We analyzed quantitative and qualitative data on patient and caregiver perceptions of caregiver contributions and explored differences in the reported caregiving experience between rural and urban participants.ResultsWhile patient–caregiver dyads showed significant disagreement in the symptoms/medication management domain, with caregivers tending to acknowledge the contribution while patients did not (χ2 (1, 21) = 5.82, p = 0.016), both groups generally showed agreement in their perceptions of caregiver involvement and reported similar levels of involvement across the other six assessed domains. Qualitative analysis revealed three themes: patient independence, invisible support, and accepted forms of support. Despite patients valuing independence, patients benefited from caregivers' unseen support, and providing emotional support and attending appointments were widely accepted forms of support among patients. No meaningful differences in caregiver contributions were found between rural and urban patient–caregiver dyads.ConclusionOur study revealed that caregivers are assisting patients in often unseen and underestimated ways during cancer clinical trials, highlighting their multifaceted role. Cancer clinical trials should implement a family‐centered approach, especially for rural caregivers, to enhance patient retention and outcomes.
Arterial Thromboembolism in Patients With Advanced Lung Cancer: Secondary Analyses of the Rising‐VTE/NEJ037 Study
Authors: Furuya Naoki , Tsubata Yukari , Hotta Takamasa , Yokoyama Toshihide , Yamasaki Masahiro , Ishikawa Nobuhisa , Fujitaka Kazunori , Kubota Tetsuya , Kobayashi Kunihiko , Isobe Takeshi 
Published: January 2025

ABSTRACTBackgroundCancer‐associated thromboembolism has been thoroughly investigated in previous studies, and direct oral anticoagulants (DOACs) were established for the treatment and prevention of venous thromboembolism (VTE). However, the risks of cancer‐associated arterial thromboembolism (ATE) and the efficacy of DOACs remain unclear.ObjectivesTo evaluate the risk factors and the clinical activity of edoxaban (EDO) for the prevention of ATE in patients with advanced lung cancer.MethodsFrom the prospective Rising‐VTE/NEJ037 study which investigated VTE in newly diagnosed advanced lung cancer, we investigated the incidence rate and the risk factors of ATE as secondary endpoints.ResultsA total of 1008 patients were screened for VTE at study baseline and were followed up for 2 years. Excluding patients with a contraindication to DOACs, those with VTE were treated with EDO. ATE events were identified in 41 patients (4.1%). The most common location for ATE was cerebral infarction (N = 31, 75.6%), followed by myocardial infarction (N = 4, 9.8%). Multivariate analysis determined the incidence of VTE, D‐dimer, a comorbidity of atrial fibrillation, and four other factors as independent risk factors of ATE. For VTE (+) patients, the incidence rate of ATE was 15.9% for the EDO administration (+) patients, compared with 11.1% for the EDO administration (−) patients (p = 0.626).ConclusionsThe incidence rate of ATE was 4.1% over 2‐year follow‐up in advanced lung cancer patients. VTE was further identified as an independent risk factor for ATE, while intervention with DOACs was seen as less effective for the prevention of ATE in advanced lung cancer patients with VTE.Trial RegistrationThis trial was registered in the Japan Registry of Clinical Trials (jRCTs061180025)
The Effect of Expressive Writing on the Experiences of Head and Neck Cancer Patients Undergoing Radiotherapy: A Randomized Controlled Trial
Authors: Li Jiayuan , Gao Zhuoran , Li Siyu , Zhong Xia 
Published: January 2025

ABSTRACTBackgroundExpressive writing (EW) has emerged as an innovative strategy for improving mood and quality of life. Nevertheless, insufficient research has been conducted on the impact of offering EW to patients with HNC. Therefore, the purpose of this study was to investigate the effects of two forms of EW on anxiety, depression, nutrition, and sleep quality in HNC patients undergoing radiotherapy.MethodsWe conducted a single‐blind, pretest, posttest, three‐group randomized controlled trial. A total of 147 patients with HNC were randomly assigned to a benefit‐finding writing group, neutral writing group, or control group. The intervention group patients performed EW during radiotherapy, with each writing session lasting 20 min, once a week for 4 consecutive weeks. Patient anxiety, depression, nutritional status, and sleep quality were measured at baseline (T0) and at the end of radiotherapy (T1).ResultsAfter 4 weeks of intervention, patients in the BF and NW groups experienced improvements in anxiety, depression, and sleep (p < 0.05) compared with those in the CG group, but the intervention did not significantly affect patients' nutritional status (p > 0.05). Compared with those in the CG, anxiety in the BF and NW groups slowed down the trend of increasing anxiety, and repeated measures analysis revealed a significant group × time interaction (p = 0.017, F = 4.205, η2 = 0.059). Compared with those in the CG, the depression levels in the BF and NW groups were lower than those at baseline, and repeated measurement analysis revealed that the interaction effect between group × time was significant (p = 0.000, F = 16.262, η2 = 0.194). The sleep quality in the CG progressively worsened from T0 to T1 (p < 0.01), whereas in the BF, it progressively improved (p < 0.01).ConclusionsThis study provides preliminary evidence that two forms of EW are effective in alleviating anxiety and depression and improving sleep in patients with HNC but are not effective in improving their nutritional status.Trial Registration: ChiCTR2400084964