bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome‐Wide Associations of Cognitive Domains and their Correlation with Polygenic Risk Scores for Antidepressant Response in Late‐Life Depression
Authors: Elsheikh Samar , Marshe Victoria , Maciukiewicz Malgorzata , Islam Farhana , Men Xiaoyu , Gonçalves Vanessa SM , Felsky Daniel , Kennedy James L. , Mulsant Benoit H. , Reynolds Charles F. , Lenze Eric J. , Mueller Daniel
Published: January 2025

Background

Late‐life depression (LLD) often coincides with cognitive decline, impacting antidepressant treatment outcomes. Investigating the genetic profile of cognitive function and its association with antidepressant response in individuals with LLD is crucial.

Method

In the Incomplete Response in Late‐Life Depression: Getting to Remission (IRL‐GRey) study, 307 older adults with major depressive disorder underwent 12‐week venlafaxine treatment. A genome‐wide association study (GWAS) of five cognitive domains using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was conducted. Functional annotations were performed using FUMA. Polygenic risk scores (PRSs) for antidepressant non‐remission and symptom improvement were using PRSice v2. Associations between PRSs and cognitive domains were analyzed, adjusting for age, sex, and genomic principal components. Bonferroni correction and permutation tests were applied to address multiple testing issues.

Result

Out of the five cognitive domains, significant SNPs were identified for the attention domain (lead SNP rs67854110, beta = ‐9.91, CI = [‐13.12, ‐6.70], P = 4.4e−09). Top suggestive genes associated with language showed differential expression in the hypothalamus, cortex, and nucleus accumbens (Pbon = 0.001). The language gene set analysis exhibited significant enrichment with the GWAS Catalog set response to cognitive‐behavioral therapy in depression (P = 9.24e−11). Additionally, the top SNP associated with delayed memory (rs13087568, beta = ‐8.24, CI = [‐11.36, ‐5.11], P = 4.5e−07) was previously linked to depressive symptoms by other studies. Polygenic risk scores (PRS) for non‐remission negatively correlated with attention (PThreshold = 0.0001, NSNPS = 39, OR = 0.105 [0.016, 0.686], P = 0.019), immediate memory (PThreshold = 0.001, NSNPS = 320, OR = 0.074 [0.011, 0.490], P = 0.0072), and delayed memory (PThreshold = 0.01, NSNPS = 2449, OR = 0.107 [0.021, 0.540], P = 0.0074). PRS for symptom improvement showed a positive correlation with delayed memory (PThreshold = 0.001, NSNPS = 385, OR = 5.329 [1.056, 26.885], P = 0.044). However, none of the PRS associations survived the Bonferroni threshold.

Conclusion

These findings suggest a genetic link between cognitive domains and antidepressant response in LLD, reinforcing previous associations. Understanding genetic contributions to cognitive decline in older adults with depression could aid in early identification and interventions to prevent dementia.
Patterns of Tau deposition in Alzheimer’s Disease
Authors: Srinivasan Dhivya , Nasrallah Ilya M. , Yang Zhijian , Erus Guray , Davatzikos Christos
Published: January 2025

Background

Spread of tau tangles, one of the hallmarks of Alzheimer’s Disease (AD) is complex and heterogenous. While many studies focus on stereotypical patterns of tau, there are many individuals who deviates from Braak staging (ex.atypical tau). Understanding heterogeneity of tau spread and association with other factors has important implications in clinical trials. In this analysis, we derived four distinct patterns of tau using a data driven, deep learning‐based clustering method, Surreal‐GAN.

Method

We used data from 1445 (Amyloid+:792, Amyloid‐:653) subjects with 18F‐flortaucipir PET from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; N = 803), HABS; N = 195 and A4; N = 447. We used study‐defined cut‐offs for deriving amyloid status for each study separately. In this analysis, we utilized tau regional standardized uptake value ratios(SUVR) calculated for each of the aparc+aseg FreeSurfer labels. We then applied Surreal‐GAN on the regional tau SUVR for Amyloid + subjects with Amyloid ‐ as reference group to determine the Tau spatiotemporal subtypes. We tested the associations between r‐indices and cognitive scores.

Result

Participants had a mean age of 71.8 (±4.8); 73.5(±6.2); 73.8(±7.6) years for A4, HABS and ADNI respectively. Surreal‐GAN showed optimal agreement indices for four patterns. Pattern r1 (r.occipital) shows the involvement of cuneus, lingual gyrus; pattern r2 (r.frontotemporal) shows frontal and temporal; pattern r3 (r.parietal) shows precuneus and inferior parietal and pattern r4 (r.typical) shows typical AD regions. Pattern r.occiptal was associated with language area of cognitive function(MMSE language domain); We observed significant associations of r.typical with composite memory scores in ADNI.

Conclusion

Employing a data‐driven deep learning‐based approach, we derived more than one dissociable pattern of tau deposition. These findings could inform identification of subgroups of individuals who may or may not be responsive to particular clinical intervention.
Assessing perivascular spaces as a biomarker of Alzheimer’s disease in cognitively normal older adults
Authors: Houchin Lauren Abigail , Adams Jenna N. , Kim Soyun , Taylor Lisa M. , Sathishkumar Mithra , McMillan Liv , Harris Alyssa L. , Janssen Niels , Yassa Michael A.
Published: January 2025

Background

Perivascular spaces (PVS), the small spaces surrounding vasculature in the brain which are critical for glymphatic clearance, are an emerging marker of cerebrovascular dysfunction. Abnormal expansion of PVS has been associated with Alzheimer’s disease (AD), and, therefore, may provide a measure of disease risk. Here, we investigate the relationship between PVS burden, memory performance, neurodegeneration, and biomarkers of AD pathology in community‐dwelling older adults without cognitive impairment.

Method

We included 120 participants from the Biomarker Exploration in Aging, Cognition, and Neurodegeneration (BEACoN) study. PVS segmentation was conducted utilizing T1‐weighted MRI and an open‐source deep learning algorithm (the “SHIVA‐perivascular spaces (PVS)” software package), producing two global outcome measures: PVS volume and number of PVS clusters. PVS volumes were converted to a volume fraction using white matter and basal ganglia volumes for each participant. We then investigated the relationship between perivascular spaces and 1) delayed recall scores on the Rey Auditory Verbal Learning Test (RAVLT), 2) hippocampal volume, derived from Freesurfer segmentation of T1‐weighted images and corrected for intracranial volume, and 3) amyloid‐beta (Aβ) pathology, assessed using 18F‐florbetapir‐PET, and quantified continuously with global SUVR values and thresholded for amyloid‐positivity at >1.11. Associations with PVS were tested using correlations and t‐tests with age, sex, and education as covariates.

Result

Global PVS count and volume were not associated with RAVLT delayed recall scores. Additionally, while Aβ+ status was not significantly associated with PVS count or volume, a t‐test of mean SUVR using a median split of PVS count was trending toward significance (p = 0.07). Global PVS count was negatively correlated (r = ‐.228, p = 0.015) with hippocampal volume. When age, sex, and education were controlled for, the result was less robust but trending toward significance (p = 0.09).

Conclusion

Our results suggest that PVS may reflect early neurodegenerative changes and may be indicative of early AD pathological changes. Future efforts will examine longitudinal relationships and regional PVS values in regions associated with learning and memory, such as the medial temporal lobe.
Remote APOE counseling and genotyping via telehealth: Early findings from a new care delivery model in the United States
Authors: Rao Anitha , Anderson Leyla , Wilkes Travis , Verdooner Steven R
Published: January 2025

Introduction

APOE (apolipoprotein E) genotyping determines an individual’s risk of developing Alzheimer’s disease and unique pathological characteristics vital to treatment consideration. The presence of the ε4 allele is considered a dose‐dependent risk factor for late‐onset Alzheimer’s disease, with each additional copy of the allele adding to the risk. Genetic counseling and education are essential as disclosure can lead to psychosocial issues, employment issues, and family stress. Traditionally, genetic counseling for Alzheimer’s disease has occurred during face‐to‐face encounters, thereby marginalizing patients who live in rural and underserved areas with high social determinants of health. In this study, we evaluated the application of telehealth services for APOE‐specific genetic counseling with an emphasis on solutions‐based education promoting health literacy and equity.

Methods

Participants were enrolled into the program from an electronic referral process from a primary care or neurology outpatient practice. A HIPAA‐secure and encrypted electronic health system was used to conduct the telehealth visits. Consent was collected from all patients. A BrainHealth Educator (BHE), typically an RN, was trained on best practices and protocols on APOE testing from resources such as AGREEDementia.org. BHEs conducted pre‐ and post‐test education and counseling. In addition, BHEs coordinated logistics of at‐home buccal swab self‐collection and sample transportation to lab.

Results

A total of 29 patients enrolled in the genotyping program with 22 females and 7 males. Each patient had a 30‐minute pre‐test education that reviewed Mendelian inhertiance, APOE polymorphism combinations, and evidence based risk stratification for developing Alzheimer’s disease. All possible genotypes were represented amongst the study subjects (n = 29): E2/E2 (1), E2/E3 (3), E2/E4 (2), E3/E3 (12), E3/E4 (7), E4/E4 (1), pending (3).

Conclusions

Advancements in cognitive care are rapidly growing and there is a need for genetic risk assessment and stratification. Ordering genetic testing requires adequate pre‐test counseling to ensure appropriate timing and utilization. The interpretation and dissemination of genetic information requires structured support from a trained healthcare professional skilled with providing solutions‐based guidance. Under these circumstances, individuals can receive APOE‐specific genetic health information in a manner that enhances cognitive care planning, prevention, and treatment with targeted monoclonal antibody treatments.
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

Background

α‐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.

Method

We 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).

Result

As 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).

Conclusion

α‐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

Background

Cardiometabolic 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.

Methods

We 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.

Results

Our 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).

Conclusions

Administration 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

Background

Warfarin, 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 Presentation

A 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.

Conclusion

This 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

Copper‐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

A 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

Although 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.
Abstraction of Hydride from Alkanes and Dihydrogen by the Perfluorotrityl Cation
Authors: Leong Derek W. , Gogoi Achyut R. , Maity Tapas , Lee Chun-I , Bhuvanesh Nattamai , Gutierrez Osvaldo , Ozerov Oleg V.
Published: January 2025

Lewis acids play a central role in a large variety of chemical transformations. The reactivity of the strongest Lewis acids is typically studied in the context of affinity towards hard bases, such as fluoride or oxygenous species. Carbocations can be viewed as soft Lewis acids, possessing significant affinity for softer bases, such as hydride. This work presents the ambient‐temperature isolation of salts of the perfluorotrityl cation ((C6F5)3C+ or F15Tr+) in combination with halogenated carborane anions. The F15Tr+ cation exhibits remarkable hydride affinity, illustrated by the observation of hydride abstraction from dihydrogen, and of the rapid abstraction of hydride from ‐CH2‐ groups in alkanes. Theoretical studies support the favorability of hydride abstraction from dihydrogen, and indicate that the hydride abstraction from alkanes proceeds via a concerted hydride transfer process that is sensitive to steric effects.
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

For 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

This 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

Studying 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

Purpose

The 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).

Method

The 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.

Finding

These 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

Objective

Caregivers 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.

Methods

As 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.

Results

While 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.

Conclusion

Our 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

Background

Cancer‐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.

Objectives

To evaluate the risk factors and the clinical activity of edoxaban (EDO) for the prevention of ATE in patients with advanced lung cancer.

Methods

From 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.

Results

A 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).

Conclusions

The 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 Registration

This 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

Background

Expressive 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.

Methods

We 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).

Results

After 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).

Conclusions

This 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
Inclusion, characteristics and methodological limitations of systematic reviews in doctoral theses: A cross‐sectional study of all universities in Sweden
Authors: Ringsten M. , Färnqvist K. , Bruschettini M. , Johansson M.
Published: January 2025

Intro

A systematic review (SR) attempts to find, assess and summarize all the empirical evidence to answer a specific research question. We aim to explore to what extent reviews are included in doctoral theses from all universities with a medical faculty in Sweden, and to describe the type, topic and assess the methodological quality of the reviews.

Methods

Duplicate assessors independently searched local and national repositories for doctoral theses published in 2021 within all seven medical faculties in Sweden, and categorized identified reviews based on review type, topic, and methodological quality using AMSTAR‐2.

Results

5.4% (45/852) of all doctoral theses included a review, and 1.3% (45/3461) of all included studies were reviews. Of these, two thirds (31) were SRs and the rest (14) were broader ‘big picture’ reviews. The most common topics were interventions (42%) and exposure/etiology (32%), with no reviews of diagnostic tests. The majority of the SRs had very low (71%) or low (19%) quality, and few reached a high (7%) or moderate (3%) quality. The most common issues were limitations with protocols, limited search strategies, and failure to account for risk of bias in drawn conclusions.

Conclusions

Few doctoral students included SRs in their theses, and the few SRs included in doctoral theses generally had a low quality. There is no consensus on the appropriate proportion of doctoral thesis including a SR. We argue that conducting a SR within a doctoral thesis can reduce redundant, harmful and unethical research, identify knowledge gaps, and help the doctoral student obtain important skills to conduct and use research.
Improving Affinity while Reducing Kidney Uptake of CXCR4‐Targeting Radioligands Derived from the Endogenous Antagonist EPI‐X4
Authors: Gaonkar Raghuvir H. , Bailly Thibaud , Millul Jacopo , Mansi Rosalba , Harms Mirja , Münch Jan , Fani Melpomeni
Published: January 2025

The C−X‐C chemokine receptor 4 (CXCR4) is highly upregulated in most cancers, making it an ideal target for delivering radiation therapy to tumors. We previously demonstrated the feasibility of targeting CXCR4 in vivo using a radiolabeled derivative of EPI‐X4, an endogenous CXCR4 antagonist, named DOTA−K‐JM#173. However, this derivative showed undesirable accumulation in the kidneys, which would limit its clinical use. In this study, we identified that removing a positive charge from the peptide sequence significantly reduced renal uptake. We evaluated a series of optimized derivatives lacking this positive charge, in vitro and in vivo in a xenografted athymic nude mice model, after radiolabeling with 177Lu. The most promising derivatives were further assessed in vivo after 68Ga labeling. Among them, we identified DOTA‐JM#173 and D‐L1‐DOTA‐JM#173, where the D‐Ile1 was replaced by D‐Leu1, two optimized derivatives with a lysine residue removed. These two molecules represent the most advanced DOTA‐conjugated ligands derived from EPI‐X4 for CXCR4‐directed theranostic applications, offering enhanced potential for targeted cancer treatment.
Albumin Folding Changes Affect the Microfluidic Interfacial Broadening Revealed by Surface Plasmon Resonance
Authors: Calcagno Damiano , Perina Maria Luisa , Distefano Alessia , Parravano Mariacristina , Licciardello Antonino , Tuccitto Nunzio , Grasso Giuseppe
Published: January 2025

Understanding the conformation and diffusion behavior of proteins in biological fluids is crucial for advancements in conformational disease research. While several experimental techniques are available for probing protein conformations, they often come with limitations, such as the need for fluorophores or specific experimental conditions. Albumin, one of the most abundant proteins in the blood and used as a tear supplement in treating ocular surface disorders, plays a vital role as a transport protein, binding various ligands and facilitating their transport. However, the direct relationship between albumin conformation and diffusion coefficient (D) in water solutions remains unexplored. In this study, we describe a novel Surface Plasmon Resonance technique coupled with Stochastic Gillespie′s algorithm simulations to correlate albumin D values with its conformational states directly. Our findings demonstrate the feasibility of monitoring albumin conformational changes under different environmental conditions, as well as its degradation kinetics by trypsin, by analyzing its diffusion characteristics, presenting a promising avenue for advancing our understanding of conformational diseases.
Integrating AI Into Arbitration: Balancing Efficiency With Fairness and Legal Compliance
Authors: Alhasan Tariq K.
Published: January 2025

The integration of artificial intelligence (AI) into arbitration marks a significant transformation in alternative dispute resolution, aiming to enhance efficiency, objectivity, and accessibility. Advanced AI systems now extend beyond administrative tasks to analyze complex legal data, predict case outcomes, and even generate arbitral awards. This evolution addresses the growing volume and complexity of international disputes, particularly in commercial and investment arbitration. However, the adoption of AI introduces profound legal and ethical challenges. Key concerns include the absence of human judgment, potential biases embedded in AI algorithms, and the opacity of their decision‐making processes, accountability issues, and data privacy risks. Critically, current legal frameworks such as the New York Convention were not designed to accommodate AI‐generated awards, raising questions about their legitimacy, procedural fairness, and enforceability. This article explores these intersections, focusing on how AI impacts arbitration's efficiency and objectivity, the legal and ethical challenges arising from AI integration, and the extent to which existing legal frameworks accommodate AI‐generated awards. Employing a multidisciplinary approach that includes legal scholarship, case studies, and technological research, the analysis examines the practical implications of AI in arbitration and the specific enforcement challenges of AI‐generated awards. The article concludes with recommendations for regulatory reforms and the adoption of hybrid AI‐human models to balance technological benefits with the necessity for human oversight and ethical accountability.
Confining CoSe/MoSe2 Heterostructures in Interconnected Carbon Polyhedrons for Superior Potassium Storage
Authors: Ming Yu Zhi , Hui Jia Jian , Yong Wang Guo , Wen Zi , Cheng Yang Chun , Jiang Qing
Published: January 2025

Metal selenides hold promise as feasible anode materials for potassium‐ion batteries (PIBs), but still face problems such as poor potassium storage kinetics and dramatic volume expansion. Coupling heterostructure engineering with structural design could be an effective strategy for rapid and stable K+ storage. Herein, CoSe/MoSe2 heterojunction encapsulated in nitrogen‐doped carbon polyhedron and further interconnected by three‐dimensional nitrogen‐doped carbon nanofibers (CoMoSe@NCP/NCFs) is ingeniously constructed. The abundant CoSe/MoSe2 heterointerfaces equipped with built‐in electric fields and unique interconnected carbon polyhedrons (convenient electron/ion transfer pathway and robust mechanical buffer) promote the reaction kinetics and bolster the structural robustness. Accordingly, the CoMoSe@NCP/NCFs composite exhibits outstanding cycle life, with a capacity of 206 mAh g−1 preserved after 2500 cycles at 2 A g−1. Besides, CoMoSe@NCP/NCFs also achieves decent rate performance with 161 mAh g−1 at 10 A g−1. This research demonstrates a viable approach for constructing superior PIB anodes with both fast kinetics and high stability.
Carrion in Bomas: Multiple Observations of Cheetah (Acinonyx jubatus) Scavenging Events and Potential Causes in Managed Populations
Authors: Overton Elizabeth Kennedy , Davis Robert S. , Prugnolle Franck , Rougeron Virginie , Honiball Terry‐Lee , Sievert Olivia , Venter Jan A.
Published: January 2025

Facultative scavenging can be observed across a large range of carnivorous mammals but is an uncommon behavioural trait in cheetahs (Acinonyx jubatus). Very few incidents of cheetahs scavenging have been reported, with no explanation given as to why it may occur. In this paper, we provide three more observations of cheetahs scavenging between 2019 and 2023 in three different protected areas in South Africa and Malawi. We suggest a common factor between these observations, namely that all adult individuals involved were temporarily housed in holding enclosures (bomas) during relocation processes and were provisioned with carrion as supplemental feed. The observed scavenging events could also have been influenced by the easy access to food in a situation where food acquisition was potentially difficult (i.e. old age, loss of hunting partner, mother with cubs). We hypothesise that these contributing factors, combined with the prior exposure of the adult individuals to eating carrion, could be a potential explanation for our observations of cheetahs scavenging. These observations provide a basis for further research into cheetah scavenging behaviour and the potential impacts of translocations that require prolonged holding periods on wildlife behaviour post‐release. Understanding these behavioural shifts is crucial for cheetah conservation, as successful reintroduction efforts depend on the ability of cheetahs to adapt to new environments and food acquisition strategies.
Pawpaws prevent predictability: A locally dominant tree alters understory beta‐diversity and community assembly
Authors: Wassel Anna C. , Myers Jonathan A.
Published: January 2025

While dominant species are known to be important in ecosystem functioning and community assembly, biodiversity responses to the presence of dominant species can be highly variable. Dominant species can increase the importance of deterministic community assembly by competitively excluding species in a consistent way across local communities, resulting in low site‐to‐site variation in community composition (beta‐diversity) and nonrandom community structure. In contrast, dominant species could increase the importance of stochastic community assembly by reducing the total number of individuals in local communities (community size), resulting in high beta‐diversity and more random community structure. We tested these hypotheses in a large, temperate oak‐hickory forest plot containing a locally dominant tree species, pawpaw (Asimina triloba; Annonaceae), an understory tree species that occurs in dense, clonal patches in forests throughout the east‐central United States. We determined how the presence of pawpaw influences local species diversity, community size, and beta‐diversity by measuring the abundance of all vascular plant species in 1 × 1‐m plots both inside and outside pawpaw patches. To test whether the presence of pawpaw influences local assembly processes, we compared observed patterns of beta‐diversity inside and outside patches to a null model in which communities were assembled at random with respect to species identity. We found lower local species diversity, lower community size, and higher observed beta‐diversity inside pawpaw patches than outside pawpaw patches. Moreover, standardized effect sizes of beta‐diversity from the null model were lower inside pawpaw patches than outside pawpaw patches, indicating more random species composition inside pawpaw patches. Together these results suggest that pawpaw increases the importance of stochastic relative to deterministic community assembly at local scales, likely by decreasing overall numbers of individuals and increasing random local extinctions inside patches. Our findings provide insights into the ecological processes by which locally dominant tree species shape the assembly and diversity of understory plant communities at different spatial scales.