bluuebunny/crossref_metadata_2025 huggingface dataset:
A computationally informed comparison between the strategies of rodents and humans in visual object recognition
Authors: Schnell Anna Elisabeth , Leemans Maarten , Vinken Kasper , de Beeck Hans Op
Published: October 2023

Many species are able to recognize objects, but it has been proven difficult to pinpoint and compare how different species solve this task. Recent research suggested to combine computational and animal modelling in order to obtain a more systematic understanding of task complexity and compare strategies between species. In the present study, we created a large multidimensional stimulus set and designed a visual discrimination task partially based upon modelling with a convolutional deep neural network (CNN). Experiments included rats (N = 11; 1115 daily sessions in total for all rats together) and humans (N = 45). Each species was able to master the task and generalize to a variety of new images. Nevertheless, rats and humans showed very little convergence in terms of which object pairs were associated with high and low performance, suggesting the use of different strategies. There was an interaction between species and whether stimulus pairs favoured early or late processing in a CNN. A direct comparison with CNN representations and visual feature analyses revealed that rat performance was best captured by late convolutional layers and partially by visual features such as brightness and pixel-level similarity, while human performance related more to the higher-up fully connected layers. These findings highlight the additional value of using a computational approach for the design of object recognition tasks. Overall, this computationally informed investigation of object recognition behaviour reveals a strong discrepancy in strategies between rodent and human vision.
A spatial threshold for astrocyte calcium surge
Authors: Lines Justin , Baraibar Andres , Nanclares Carmen , Martín Eduardo D. , Aguilar Juan , Kofuji Paulo , Navarrete Marta , Araque Alfonso
Published: October 2023

Astrocytes are active cells involved in brain function through the bidirectional communication with neurons, in which the astrocyte calcium signal plays a crucial role. Synaptically-evoked calcium increases can be localized to independent subcellular domains or expand to the entire cell, i.e., calcium surge. In turn, astrocytes may regulate individual synapses by calcium-dependent release of gliotransmitters. Because a single astrocyte may contact ∼100,000 synapses, the control of the intracellular calcium signal propagation may have relevant consequences on brain function by regulating the spatial range of astrocyte neuromodulation of synapses. Yet, the properties governing the spatial dynamics of the astrocyte calcium signal remains poorly defined. Imaging subcellular responses of cortical astrocytes to sensory stimulation in mice, we show that sensory-evoked astrocyte calcium responses originated and remained localized in domains of the astrocytic arborization, but eventually propagated to the entire cell if a spatial threshold of >23% of the arborization being activated was surpassed. Using transgenic
IP

3

R2

-/-

mice, we found that type-2 IP
3
receptors were necessary for the generation of the astrocyte calcium surge. We finally show using in situ electrophysiological recordings that the spatial threshold of the astrocyte calcium signal consequently determined the gliotransmitter release. Present results reveal a fundamental property of astrocyte calcium physiology, i.e., a spatial threshold for the astrocyte intracellular calcium signal propagation, which depends on astrocyte intrinsic properties and governs the astrocyte integration of local synaptic activity and the subsequent neuromodulation.There is a spatial threshold for the astrocyte intracellular calcium signal propagation that is determined by astrocyte intrinsic properties and controls gliotransmission.
Multi-omics characterization of partial chemical reprogramming reveals evidence of cell rejuvenation
Authors: Mitchell Wayne , Goeminne Ludger JE , Tyshkovskiy Alexander , Zhang Sirui , Chen Julie Y , Paulo Joao A , Pierce Kerry A , Choy Angelina H , Clish Clary B , Gygi Steven P , Gladyshev Vadim N
Published: October 2023

Partial reprogramming by cyclic short-term expression of Yamanaka factors holds promise for shifting cells to younger states and consequently delaying the onset of many diseases of aging. However, the delivery of transgenes and potential risk of teratoma formation present challenges for in vivo applications. Recent advances include the use of cocktails of compounds to reprogram somatic cells, but the characteristics and mechanisms of partial cellular reprogramming by chemicals remain unclear. Here, we report a multi-omics characterization of partial chemical reprogramming in fibroblasts from young and aged mice. We measured the effects of partial chemical reprogramming on the epigenome, transcriptome, proteome, phosphoproteome, and metabolome. At the transcriptome, proteome, and phosphoproteome levels, we saw widescale changes induced by this treatment, with the most notable signature being an upregulation of mitochondrial oxidative phosphorylation. Furthermore, at the metabolome level, we observed a reduction in the accumulation of aging-related metabolites. Using both transcriptomic and epigenetic clock-based analyses, we show that partial chemical reprogramming reduces the biological age of mouse fibroblasts. We demonstrate that these changes have functional impacts, as evidenced by changes in cellular respiration and mitochondrial membrane potential. Taken together, these results illuminate the potential for chemical reprogramming reagents to rejuvenate aged biological systems and warrant further investigation into adapting these approaches for in vivo age reversal.
Seasonally migratory songbirds have different historic population size characteristics than resident relatives
Authors: Winker Kevin , Delmore Kira
Published: October 2023

Modern genomic methods enable estimation of a lineage’s long-term effective population sizes back to its origins. This ability allows unprecedented opportunities to determine how adoption of a major life-history trait affects lineages’ populations relative to those without the trait. We used this novel approach to study the population effects of the life-history trait of seasonal migration in evolutionary time. Seasonal migration is a common life-history strategy, but its effects on long-term population sizes relative to lineages that don’t migrate are largely unknown. Using whole-genome data, we estimated effective population sizes over millions of years in closely related seasonally migratory and resident lineages in a group of songbirds. Our main predictions were borne out: Seasonal migration is associated with larger effective population sizes (

N
e

), greater long-term variation in

N
e

, and a greater degree of initial population growth than among resident lineages. Initial growth periods showed phylogenetic signal, and their length (0.75-4.3 Myr) parallels the expansion and adaptation phases of taxon cycles, a framework of lineage expansion and eventual contraction over time encompassing biogeography and evolutionary ecology. Heterogeneity among lineages is noteworthy, despite geographic proximity (including overlap) and close relatedness. Seasonal migration imbues these lineages with fundamentally different population size attributes through evolutionary time compared to closely related resident lineages.
Antigenic strain diversity predicts different biogeographic patterns of maintenance and decline of antimalarial drug resistance
Authors: He Qixin , Chaillet John K , Labbé Frédéric
Published: October 2023

The establishment and spread of antimalarial drug resistance vary drastically across different biogeographic regions. Though most infections occur in sub-Saharan Africa, resistant strains often emerge in low-transmission regions. Existing models on resistance evolution lack consensus on the relationship between transmission intensity and drug resistance, possibly due to overlooking the feedback between antigenic diversity, host immunity, and selection for resistance. To address this, we developed a novel compartmental model that tracks sensitive and resistant parasite strains, as well as the host dynamics of generalized and antigen-specific immunity. Our results show a negative correlation between parasite prevalence and resistance frequency, regardless of resistance cost or efficacy. Validation using chloroquine-resistant marker data supports this trend. Post discontinuation of drugs, resistance remains high in low-diversity, low-transmission regions, while it steadily decreases in high-diversity, high-transmission regions. Our study underscores the critical role of malaria strain diversity in the biogeographic patterns of resistance evolution.
Antigenic strain diversity predicts different biogeographic patterns of invasion and maintenance of anti-malarial drug resistance
Authors: He Qixin , Chaillet John K. , Labbé Frédéric
Published: October 2023

The establishment and spread of anti-malarial drug resistance vary drastically across different biogeographic regions. Though most infections occur in Sub-Saharan Africa, resistant strains often emerge in low-transmission regions. Existing models on resistance evolution lack consensus on the relationship between transmission intensity and drug resistance, possibly due to overlooking the feedback between antigenic diversity, host immunity, and selection for resistance. To address this, we developed a novel compartmental model that tracks sensitive and resistant parasite strains, as well as the host dynamics of generalized and antigen-specific immunity. Our results show a negative correlation between parasite prevalence and resistance frequency, regardless of resistance cost or efficacy. Validation using chloroquine-resistant marker data supports this trend. Post discontinuation of drugs, resistance remains high in low-diversity, low-transmission regions, while it steadily decreases in high-diversity, high-transmission regions. Our study underscores the critical role of malaria strain diversity in the biogeographic patterns of resistance evolution.
Acetylcholine modulates the precision of prediction error in the auditory cortex
Authors: Pérez-González David , Lao-Rodríguez Ana Belén , Aedo-Sánchez Cristian , Malmierca Manuel S
Published: October 2023

A fundamental property of sensory systems is their ability to detect novel stimuli in the ambient environment. The auditory brain contains neurons that decrease their response to repetitive sounds but increase their firing rate to novel or deviant stimuli; the difference between both responses is known as stimulus-specific adaptation or neuronal mismatch (nMM). Here, we tested the effect of microiontophoretic applications of ACh on the neuronal responses in the auditory cortex (AC) of anesthetized rats during an auditory oddball paradigm, including cascade controls. Results indicate that ACh modulates the nMM, affecting prediction error responses but not repetition suppression, and this effect is manifested predominantly in infragranular cortical layers. The differential effect of ACh on responses to standards, relative to deviants (in terms of averages and variances), was consistent with the representational sharpening that accompanies an increase in the precision of prediction errors. These findings suggest that ACh plays an important role in modulating prediction error signaling in the AC and gating the access of these signals to higher cognitive levels.
Sensitization of meningeal afferents to locomotion-related meningeal deformations in a migraine model
Authors: Blaeser Andrew S , Zhao Jun , Sugden Arthur U , Carneiro-Nascimento Simone , Andermann Mark L , Levy Dan
Published: October 2023

Migraine headache is hypothesized to involve the activation and sensitization of trigeminal sensory afferents that innervate the cranial meninges. To better understand migraine pathophysiology and improve clinical translation, we used two-photon calcium imaging via a closed cranial window in awake mice to investigate changes in the responses of meningeal afferent fibers using a preclinical model of migraine involving cortical spreading depolarization (CSD). A single CSD episode caused a seconds-long wave of calcium activation that propagated across afferents and along the length of individual afferents. Surprisingly, unlike previous studies in anesthetized animals with exposed meninges, only a very small afferent population was persistently activated in our awake mouse preparation, questioning the relevance of this neuronal response to the onset of migraine pain. In contrast, we identified a larger subset of meningeal afferents that developed augmented responses to acute three-dimensional meningeal deformations that occur in response to locomotion bouts. We observed increased responsiveness in a subset of afferents that were already somewhat sensitive to meningeal deformation before CSD. Furthermore, another subset of previously insensitive afferents also became sensitive to meningeal deformation following CSD. Our data provides new insights into the mechanisms underlying migraine, including the emergence of enhanced meningeal afferent responses to movement-related meningeal deformations as a potential neural substrate underlying the worsening of migraine headache during physical activity.
Tiktok’s effect on english vocabulary learning: an empirical study of English major curriculum
Authors: Tran Du Thanh
Published: October 2023

TikTok is a famous social networking site in Vietnam and throughout the world. Although several research on social media platforms has been undertaken for educational objectives, there are currently very few studies on TikTok. The purpose of this study is to determine the impact of TikTok on vocabulary learning of English Major students at Thu Dau Mot University, Vietnam as well as the attitudes of students and teachers about TikTok in learning vocabulary and developing other language abilities. The study involved 122 participants, and data were gathered using questionnaires, controlled experiments, tests (pre- and post-test), and organized interviews with students and teachers. The results suggest that survey participants thought TikTok was a good tool for learning English. It was also discovered that using videos on the TikTok platform as an English learning approach improved students' capacity to retain English vocabulary. This study aims to give insights into the possibilities of utilizing TikTok as a tool for learning English vocabulary as well as developing other language abilities.
Dashboard para apoio na tomada de decisão para investimento na aprendizagem profissional (Lei 10097) no Estado de Santa Catarina – Brasil
Authors: Fernandes Anita Maria da Rocha , Liebel Graziela , Da Silva Daniela Souza Moreira , Burigo Michel Goulart
Published: October 2023

O processo de gestão de toda organização passa pela tomada de decisão. Para tanto, indicadores claros são fundamentais. Mesmo as entidades sociais, para melhor performance, precisam tomar decisões baseadas em dados. Este trabalho apresenta o desenvolvimento de um dashboard que auxilie no processo de escolha dos municípios que mais precisam e tem potencial para programas de aprendizagem. O Dashboard de Aprendizagem Social funciona como uma ferramenta de visualização de indicadores com dados consolidados e combinados das oportunidades de vagas nos municípios mais promissores, Índice de Desenvolvimento Humano por Município, quantidade de população de adolescentes entre 15 e 24 anos, que são potenciais público-alvo dos projetos de aprendizagem, bem como a taxa de desocupação desta faixa etária, ou seja, adolescentes e jovens desempregados. Para o desenvolvimento do sistema foi utilizada a linguagem de programação JAVA para a o backend do sistema, a linguagem React para o frontend e a biblioteca javascript ApexCharts com aplicação no dashboard. Após a implementação foi realizado um processo de avaliação, com caderno de testes e através de formulário do Google Forms, com participação de quatro especialistas em programas sociais com juventude e especialista na área de design. O resultado das avaliações com especialistas validou o objetivo deste trabalho referendando a importância do sistema para os projetos de aprendizagem, bem como sua qualificação para apoio na tomada de decisão.
The impact of instruction on Web 2.0 tools on pre-service mathematics teachers' self-efficacy beliefs and their activity development experiences
Authors: Mersin Nazan , Danişman Şahin
Published: October 2023

The purpose of this study is to determine the impact the training has had on pre-service mathematics teachers' beliefs and opinions regarding Web 2.0 tools, and to determine their views about the use of Web 2.0 tools. The study employs the explanatory sequential design of mixed methods research with 37 sophomore pre-service mathematics teachers as participants. The data collected through the use of Web 2.0 Practical Content Development Self-Efficacy Belief Scale and semi-structured interviews were analyzed using content analysis. The quantitave findings of the study showed that the implementation in the experimental process had an impact on pre-service mathematics teachers’ self-efficacy beliefs for Web 2.0 content development and its subdimensions which are preparation, presentation and evaluation. The qualitative findings also revealed the views of pre-service mathematics teachers towards the benefits of use of Web 2.0 tools for students, teachers and in terms of functionality. Benefits for students include benefits for learning, and affective and aptitudinal contribution, while benefits for teacher consist of contribution for instruction and professional development. On the other hand, the study also revealed the negative features of Web 2.0 tools in addition to their positive contributions and advantages. The main findings of negative aspects include requiring internet, lack of language support, and having paid services for some extra features. Furthermore, Kahoot and Puzzle Maker were the most preferred tools by pre-service mathematics teachers.
Challenges Facing Teachers in the Implementation of Competence-Based Curriculum in Secondary Schools in Iringa Municipal, Tanzania
Authors: Nyoni Christopher
Published: October 2023

This study explores teachers' challenges in implementing a competence-based curriculum in secondary schools in Iringa Municipal, Tanzania. The Study employed a Qualitative approach and a case study design. Purposive sampling was used to obtain a sample of 47 respondents. Data collection instruments used were interviews, focus group discussions, and observation. Data from the field was analyzed through thematic analysis. The Study came up with the following findings: Shortage of time, Limited Knowledge, and Shortage of Teaching and Learning resources. The Study suggested to the government that the Ministry of Education, Science, and Technology should develop an implementable curriculum to ensure other education objectives are reached due to limited time. The Ministry of Education, Science, and Technology should go to developed countries to learn from them to overcome the challenges encountered in our education system, especially the implementation of a Competence-based Curriculum. There should be follow-up mechanisms by The Ministry of Education, Science and Technology and schools in particular for Competence-Based Curriculum teaching approaches offered by secondary school teachers in Tanzania.
Calprotectin as a Possible Biomarker in Various Lung Diseases
Authors: Abbas Maryam , Ijishakin Olumide , Gopal Shwetha , Saeed Iqra , Arcot Shilpa , Okezie Chidera Emmanuel , Agbo Gift Joanna , Ezeamii Victor Chiedozie , Ajayi Omobolaji Samuel , Amanze Ngozi , Alzaki Sadam , Isaac Tambi , Shahnoor Husna , Okunzuwa Efe , Alfy Amy
Published: October 2023

Calprotectin (CLP) comprises two calcium-binding proteins from the S-100 protein family, S100A8 and S100A9. CLP involves various cellular processes in lung health and disease, including anti-microbial functions, pro- and anti-tumor properties, angiogenesis, DNA damage response, and extracellular matrix remodeling. The systematic review explores the potential of calprotectin as a diagnostic and prognostic biomarker for various respiratory diseases. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and comprehensively searched electronic databases. Of 290 initially identified studies, 13 were included Olumide Ijishakin in the review, covering conditions such as cystic fibrosis (CF), lung cancer, COVID-19, asthma, and interstitial lung disease. For CF, fecal calprotectin showed promise as a non-invasive biomarker for diagnosing and monitoring pulmonary exacerbations. In lung cancer, calprotectin and other markers demonstrated potential for identifying high-risk individuals. In COVID-19, calprotectin levels were associated with disease severity and mortality risk. For asthma, calprotectin's role in neutrophil activation and neutrophilic asthma development was investigated. The review emphasizes the importance of robust biomarkers in improving disease management, reducing mortality rates, and enhancing patient care for respiratory conditions. Further research and validation studies are needed to establish the clinical utility of calprotectin as a biomarker for respiratory diseases.
Severity and Long-Term Mortality of COVID-19, Influenza, and Respiratory Syncytial Virus
Authors: Bajema Kristina L. , Bui David P. , Yan Lei , Li Yuli , Rajeevan Nallakkandi , Vergun Robert , Berry Kristin , Huang Yuan , Lin Hung-Mo , Aslan Mihaela , Ioannou George N.
Published: January 2025

Importance

SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) contribute to many hospitalizations and deaths each year. Understanding relative disease severity can help to inform vaccination guidance.

Objective

To compare disease severity of COVID-19, influenza, and RSV among US veterans.

Design, Setting, and Participants

This retrospective cohort study analyzed national US Veterans Health Administration electronic health record data of nonhospitalized veterans who underwent same-day testing for SARS-CoV-2, influenza, and RSV, and were diagnosed with a single infection between August 1, 2022, and March 31, 2023, or between August 1, 2023, and March 31, 2024.

Exposures

Infection with SARS-CoV-2, influenza, or RSV.

Main Outcomes and Measures

Following inverse probability weighting, the cumulative incidence and risk differences (RDs) were calculated for the primary outcomes of 30-day hospitalization, intensive care unit admission, and death, as well as the secondary outcome of long-term death extending through 180 days.

Results

Among 68 581 patients included in the 2022 to 2023 cohort (6239 [9.1%] with RSV, 16 947 [24.7%] with influenza, and 45 395 [66.2%] with COVID-19) and 72 939 in the 2023 to 2024 cohort (9748 [13.4%] with RSV, 19 242 [26.4%] with influenza, and 43 949 [60.3%] with COVID-19), the median (IQR) age was 66 (53-75) years, and 123 090 (87.0%) were male. During the 2023 to 2024 season, the 30-day risk of hospitalization was similar for COVID-19 (16.2%) and influenza (16.3%) but lower for RSV at 14.3% (RD for COVID-19 vs RSV, 1.9% [95% CI, 0.9%-2.9%]; RD for influenza vs RSV, 2.0% [95% CI, 0.8%-3.3%]). The 30-day risk of death during the 2022 to 2023 season was slightly higher for COVID-19 (1.0%) compared with influenza (0.7%) (RD, 0.4% [95% CI, 0.1%-0.6%]) or RSV (0.7%) (RD, 0.4% [95% CI, 0.1%-0.6%]) but similar during the 2023 to 2024 season. Mortality risk at 180 days was higher for COVID-19 during both seasons (2023-2024 RD for COVID-19 vs influenza, 0.8% [95% CI, 0.3%-1.2%]; RD for COVID-19 vs RSV, 0.6% [95% CI, 0.1%-1.1%]). Higher mortality in both seasons was observed for veterans without COVID-19 vaccination in the previous year compared to veterans without seasonal influenza vaccination. In contrast, among groups vaccinated against their respective infections, there were no mortality differences at any time point between COVID-19 and influenza.

Conclusions and Relevance

This cohort study showed that, during the 2022 to 2023 season, infection with SARS-CoV-2 was associated with more severe disease outcomes than influenza or RSV, whereas differences were less pronounced during the 2023 to 2024 season. During both seasons, RSV remained a milder illness, whereas COVID-19 was associated with higher long-term mortality. Vaccination attenuated differences in disease severity and long-term mortality.
The Future of US Sexual and Gender Minority Health Policy
Authors: Sandhu Sahil , Liu Michael , Keuroghlian Alex S.
Published: January 2025

This Viewpoint discusses potential changes to sexual and gender minority health care under the Trump-Vance administration.
Trends in Prostate Cancer Incidence and Mortality Rates
Authors: Van Blarigan Erin L. , McKinley Meg A. , Washington Samuel L. , Cooperberg Matthew R. , Kenfield Stacey A. , Cheng Iona , Gomez Scarlett L.
Published: January 2025

Importance

Incidence of distant stage prostate cancer is increasing in the United States. Research is needed to understand trends by social and geographic factors.

Objective

To examine trends in prostate cancer incidence and mortality rates in California by stage, age, race and ethnicity, and region.

Design, Setting, and Participants

This cohort study used mortality data from the California Cancer Registry and California Department of Public Health's Center for Health Statistics, and incidence data from the National Cancer Institute Surveillance, Epidemiology, and End Results program and the US Census. The dataset for these analyses was released in April 2024. Participants included males residing in California between 2004 and 2021. Analyses were conducted from April to October 2024.

Exposures

Stage at diagnosis, age, race and ethnicity, and region of California.

Main Outcomes and Measures

The delay-adjusted incidence rates and mortality rates were calculated and age-adjusted to the 2000 US standard population. Annual percentage changes (APC) were calculated using NCI’s Joinpoint Regression Program.

Results

Between 2004 and 2021, there were 387 636 prostate cancer cases (27 938 distant stage) and 58 754 prostate cancer deaths in California. In this study, 203 038 cases (52.4%) occurred among males aged 55 to 69 years, and 153 884 (39.7%) occurred among males 70 years or older. The distribution of race and ethnicity among cases was: 1031 American Indian or Alaska Native (0.3%); 31 366 Asian American, Native Hawaiian, and Pacific Islander (8.1%); 66 695 Hispanic or Latino (17.2%); 36 808 non-Hispanic Black (9.5%); 238 229 non-Hispanic White (61.5%); and 13 507 unknown or other races (3.5%). On average, the incidence of distant prostate cancer increased 6.7% (95% CI, 6.2% to 7.3%) per year between 2011 and 2021. By race and ethnicity, the APC ranged from 6.5% (95% CI, 4.2% to 13.4%) among Asian American, Native Hawaiian, and Pacific Islander males between 2011 and 2021 to 8.0% (95% CI, 6.9% to 9.5%) among Hispanic males between 2014 and 2021. In 9 of the 10 California regions, the incidence of distant prostate cancer increased by approximately 6% or more per year. Prostate cancer mortality rates declined 2.6% per year between 2004 and 2012 but plateaued between 2012 to 2021 (APC, 0.1%; 95% CI, −0.6% to 1.6%). The plateau in mortality occurred across ages, races and ethnicities, and regions.

Conclusions and relevance

In this cohort study among California residents, the incidence of distant stage prostate cancer increased throughout the state between 2011 and 2021. Mortality rates plateaued between 2012 and 2021, ending previous decades of decline. Implementation of more effective prostate cancer screening strategies are critically needed.
Apixaban to Prevent Covert Infarcts After Cryptogenic Stroke in Patients With Atrial Cardiopathy
Authors: Lansberg Maarten G. , Wintermark Max , Chen Hui , Howard George , Cassarly Christy , Pauls Qi , Kemp Stephanie , Harris Tashia L. , Krishnaiah Balaji , Stanton Robert J. , Lyerly Michael J. , Miller Benjamin R. , Smith Eric E. , Tirschwell David L. , Sheth Kevin N. , Kamel Hooman , Longstreth William T. , Elkind Mitchell S. V. , Broderick Joseph P. , Lazar Ronald M.
Published: January 2025

Importance

In the Atrial Cardiopathy and Antithrombotic Drugs in Prevention After Cryptogenic Stroke (ARCADIA) randomized clinical trial, anticoagulation did not prevent recurrent stroke among patients with a recent cryptogenic stroke and atrial cardiopathy. It is unknown whether anticoagulation prevents covert infarcts in this population.

Objective

To test the use of apixaban vs aspirin for prevention of nonlacunar covert infarcts after cryptogenic stroke in patients with atrial cardiopathy.

Design, Setting, and Participants

ARCADIA-MRI, an ancillary study to the ARCADIA trial with a median follow-up period of 27 months, enrolled participants from 75 sites in the US from November 14, 2019, until December 2, 2022. Participants in ARCADIA were invited to coenroll in ARCADIA-MRI if they had not permanently discontinued the study drug and had no contraindications on magnetic resonance imaging (MRI). A total of 310 (31%) of the 1015 ARCADIA participants enrolled in ARCADIA-MRI and of those 174 (56%) with adequate quality baseline and follow-up MRI were included in the present analyses.

Interventions

MRI performed at the time of the index stroke served as the baseline image unless it was unavailable or of insufficient quality, in which case a new research MRI was obtained. A follow-up research MRI was performed upon each participant’s completion of participation in the ARCADIA parent study.

Main Outcomes and Measures

The primary outcome was incident nonlacunar covert infarct on the follow-up MRI assessed by 2 independent raters who were masked to treatment assignment.

Results

Baseline characteristics were balanced between the apixaban (n = 79) and aspirin (n = 95) arms. The mean (SD) age was 66 (10.6) years, and the median (IQR) modified Rankin Scale (mRS) score 1 (0-2). Ninety-one participants (52.3%) were male. During the median (IQR) follow-up of 811 (487-1288) days, the risk of incident nonlacunar covert infarcts was lower in the apixaban group (5.1%) than the aspirin group (17.9%) (weighted relative risk, 0.29; 95% CI, 0.10-0.83).

Conclusions and Relevance

Apixaban compared to aspirin was associated with fewer incident nonlacunar covert infarcts among a subset of patients with a recent cryptogenic ischemic stroke and atrial cardiopathy who were enrolled in ARCADIA.

Trial Registration

ClinicalTrials.gov Identifier: NCT03192215
Predicting Individual Pain Sensitivity Using a Novel Cortical Biomarker Signature
Authors: Chowdhury Nahian S. , Bi Chuan , Furman Andrew J. , Chiang Alan K. I. , Skippen Patrick , Si Emily , Millard Samantha K. , Margerison Sarah M. , Spies Darrah , Keaser Michael L. , Da Silva Joyce T. , Chen Shuo , Schabrun Siobhan M. , Seminowicz David A.
Published: January 2025

Importance

Biomarkers would greatly assist decision-making in the diagnosis, prevention, and treatment of chronic pain.

Objective

To undertake analytical validation of a sensorimotor cortical biomarker signature for pain consisting of 2 measures: sensorimotor peak alpha frequency (PAF) and corticomotor excitability (CME).

Design, Setting, and Participants

This cohort study at a single center (Neuroscience Research Australia) recruited participants from November 2020 to October 2022 through notices placed online and at universities across Australia. Participants were healthy adults aged 18 to 44 years with no history of chronic pain or a neurological or psychiatric condition. Participants experienced a model of prolonged temporomandibular pain with outcomes collected over 30 days. Electroencephalography to assess PAF and transcranial magnetic stimulation (TMS) to assess CME were recorded on days 0, 2, and 5. Pain was assessed twice daily from days 1 through 30.

Exposure

Participants received an injection of nerve growth factor (NGF) to the right masseter muscle on days 0 and 2 to induce prolonged temporomandibular pain lasting up to 4 weeks.

Main Outcomes and Measures

The predictive accuracy of the PAF/CME biomarker signature was determined using a nested control-test scheme: machine learning models were run on a training set (n = 100), where PAF and CME were predictors and pain sensitivity was the outcome. The winning classifier was assessed on a test set (n = 50) comparing the predicted pain labels against the true labels.

Results

Among the final sample of 150 participants, 66 were female and 84 were male; the mean (SD) age was 25.1 (6.2) years. The winning classifier was logistic regression, with an outstanding area under the curve (AUC = 1.00). The locked model assessed on the test set had excellent performance (AUC = 0.88; 95% CI, 0.78-0.99). Results were reproduced across a range of methodological parameters. Moreover, inclusion of sex and pain catastrophizing as covariates did not improve model performance, suggesting the model including biomarkers only was more robust. PAF and CME biomarkers showed good to excellent test-retest reliability.

Conclusions and Relevance

This study provides evidence for a sensorimotor cortical biomarker signature for pain sensitivity. The combination of accuracy, reproducibility, and reliability suggests the PAF/CME biomarker signature has substantial potential for clinical translation, including predicting the transition from acute to chronic pain.
Molecular insights into the modulation of the 5HT2A receptor by serotonin, psilocin, and the G protein subunit Gqα
Authors: Viohl Niklas , Hakami Zanjani Ali Asghar , Khandelia Himanshu
Published: January 2025

5HT2AR is a G‐protein‐coupled receptor that drives many neuronal functions and is a target for psychedelic drugs. Understanding ligand interactions and conformational transitions is essential for developing effective pharmaceuticals, but mechanistic details of 5HT2AR activation remain poorly understood. We utilized all‐atom molecular dynamics simulations and free‐energy calculations to investigate 5HT2AR's conformational dynamics upon binding to serotonin and psilocin. We show that the active state of 5HT2AR collapses to a closed state in the absence of Gqα, underscoring the importance of G‐protein coupling. We discover an intermediate “partially‐open” receptor conformation. Both ligands have higher binding affinities for the orthosteric than the extended binding pocket. These findings enhance our understanding of 5HT2AR's activation and may aid in developing novel therapeutics.

Impact statement

This study sheds light on 5HT2AR activation, revealing intermediate conformations and ligand dynamics. These insights could enhance drug development for neurological and psychiatric disorders, benefiting researchers and clinicians in pharmacology and neuroscience.
Interaction between bacterial phytochromes Agp1 and Agp2 of Agrobacterium fabrum by fluorescence resonance energy transfer and docking studies
Authors: El Kurdi Afaf , Kaeser Gero , Scheerer Patrick , Hoffmann David , Akkus Ebru , Elstner Marcus , Krauß Norbert , Lamparter Tilman
Published: January 2025

Phytochromes are biliprotein photoreceptors found in bacteria, fungi, and plants. The soil bacterium Agrobacterium fabrum has two phytochromes, Agp1 and Agp2, which work together to control DNA transfer to plants and bacterial conjugation. Both phytochromes interact as homodimeric proteins. For fluorescence resonance energy transfer (FRET) measurements, various Agp1 mutants and wild‐type Agp2 were labeled with specific fluorophores to study their interaction. FRET efficiencies rose from position 122 to 545 of Agp1. The photosensory chromophore module (PCM) of Agp1 did not show a FRET signal, but the PCM of Agp2 did. Docking models suggest that Agp1 and Agp2 interact with their histidine kinase and PCM perpendicular to each, around 45 amino acids of Agp1 or Agp2 are involved.
CSF cytokine, chemokine and injury biomarker profile of glial fibrillary acidic protein (GFAP) autoimmunity
Authors: Segal Yahel , Mangioris Georgios , Lennon Vanda , Yang Binxia , Dubey Divyanshu , Flanagan Eoin P. , McKeon Andrew , Mills John R. , Toledano Michel , Vodopivec Ivana , Pittock Sean J. , Zekeridou Anastasia
Published: January 2025

Defining the CSF cytokine/chemokine and injury biomarker signature of glial fibrillary acidic protein (GFAP) autoimmunity can inform immunopathogenesis. CSF GFAP‐IgG‐positive samples (N = 98) were tested for 17 cytokines/chemokines, neurofilament light chain (NfL), and GFAP (ELLA, Bio‐Techne). Controls included non‐inflammatory (N = 42), AQP4‐IgG‐positive (N = 83), CNS infections (N = 13), and neurosarcoidosis (N = 32). IL5, IL6, IL10, IL8/CXCL8, CXCL9, CXCL10, CXCL13, BAFF, GM‐CSF, IFN‐gamma, and TNF‐alpha concentrations were higher compared to non‐inflammatory controls (P < 0.01). GFAP concentrations were similar to those of AQP4‐IgG‐positive patients; NfL was higher (P < 0.001) and correlated with MRI changes and outcomes. CSF cytokine/chemokine findings in GFAP autoimmunity correlate with histopathology; GFAP and NfL hold promise as disease biomarkers.
Priority Musculoskeletal Health Research Questions for People With Generalized Joint Hypermobility: An International Delphi Study
Authors: Habibian Sara , Pacey Verity , Chan Cliffton , Hakim Alan J. , Williams Cylie M.
Published: January 2025

Objective

This study aimed to identify the top 10 international research priorities for musculoskeletal health of people with generalized joint hypermobility.

Methods

A three‐round Delphi method using an online survey was implemented. Three participant stakeholder groups were eligible for inclusion: (1) people with lived experience of joint hypermobility or their carers, (2) health care professionals, and (3) researchers with experience working with individuals with hypermobility. Participants provided up to three priority research questions in round 1. In round 2, participants prioritized 10 research questions from the unique questions proposed in round 1. In round 3, participants were presented with the top 10 questions from the overall cohort and for their stakeholder group(s) and asked to rank these in order of importance.

Results

Round 1 commenced with 396 participants who provided 958 individual questions, which reduced to 210 unique questions following data cleaning. There were 257 participants (65% of 396) in round 2, and 249 participants (63% of 396, lived experience n = 230, health care professionals n = 73, and researchers n = 21) in round 3. The overall top‐ranked question was, “How can we prevent disability, pain, and poor quality of life associated with the musculoskeletal comorbidities of symptomatic generalized joint hypermobility?” Specific stakeholder group priority research questions varied. People with lived experience prioritized treatment questions, whereas health care professionals and researchers prioritized service‐impact and utilization research questions.

Conclusion

Priority research questions relating to musculoskeletal health of people with generalized joint hypermobility have been internationally identified. These questions provide a future focus for meaningful and necessary research in this field.

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Crystal Structural Editing: Novel Biaxial MgTe2O5 Crystal as Zero‐Order Waveplates
Authors: Dong Xiaofei , Guo Feifei , Chen Lijuan , Mu Wenxiang , Liu Lishan , Wang Shanpeng , Tao Xutang , Gao Zeliang
Published: January 2025

Waveplates are important optical components to control the polarization of light. Currently, they are often fabricated from uniaxial crystals, and there is no report about waveplates based on the biaxial crystals. In this work, a novel biaxial crystal MgTe2O5 with a structure constructed by 0D Te2O5 groups is designed and grown as waveplate materials for the first time. The exciting result is that the birefringence in the (001)‐plane is smaller than 0.0028 in the range from 0.4 to 5 µm, which is significantly smaller than that of the current waveplate materials. The polarization modulations of the MgTe2O5 devices working at 532 nm indicate that excellent zero‐order half and quarter waveplates have been successfully prepared. In addition, achromatic waveplates used in the visible, near‐infrared, and mid‐infrared ranges have also been calculated. The MgTe2O5 crystal not only exhibits a high laser damage threshold of up to 2.7 GW cm−2 but also shows a wide transmission range from 0.37 to 6.3 µm. These results provide an excellent waveplate crystal and explore the applications of biaxial crystals.
Prevalence of dementia in Singapore: Changes across a decade
Authors: Subramaniam Mythily , Abdin Edimansyah , Asharani PV , Roystonn Kumarasan , Devi Fiona , Peizhi Wang , Shafie Saleha , Sagayadevan Vathsala , Jeyagurunathan Anitha , Chua Boon Yiang , Tan Bernard , Vaingankar Janhavi Ajit , Yao Fengyuan , Magadi Harish , Ma Stefan , Chow Wai Leng , McCrone Paul , Heng Derrick , Mahendran Rathi , Prince Martin , Ng Li Ling , Chong Siow Ann
Published: January 2025

INTRODUCTION

The study aimed to assess changes in the prevalence of dementia in Singapore over the past decade.

METHODS

The Well‐being of the Singapore Elderly (WiSE) 2023 and the WiSE 2013 studies were comprehensive, single‐phase, cross‐sectional surveys conducted among older adults aged ≥60 years in Singapore. WiSE 2023 included 2010 older adults and 1798 informants, whereas WiSE 2013 comprised 2565 older adults and 2421 informants.

RESULTS

The weighted prevalence of dementia based on the 10/66 Diagnostic Research Group (DRG) criteria was 8.8% (95% confidence interval [CI]: 7.3–10.7) in the WiSE 2023 study compared to 10% in the WiSE 2013 study (95% CI: 8.7–11.5). The proportion of those with undiagnosed dementia decreased significantly from 70.6% in WiSE 2013 to 51.5% in WiSE 2023 (p‐value = 0.002).

DISCUSSION

A non‐significant 12% reduction (95% CI: 1.1–3.5) in dementia prevalence was observed in Singapore over a decade, based on the WiSE 2013 and WiSE 2023 studies.

Highlights

The prevalence of dementia decreased from 10% to 8.8% over a decade in Singapore.

The prevalence varied by age group, ethnicity, employment status, and health factors.

The prevalence of undiagnosed dementia decreased significantly from 70.6% to 51.5%.
An unsupervised learning approach for clustering joint trajectories of Alzheimer's disease biomarkers: An application to ADNI Data
Authors: Sönmez Teresa Filshtein , Harvey Danielle J. , Beckett Laurel A. ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: January 2025

INTRODUCTION

Current models of Alzheimer's disease (AD) progression assume a common pattern and pathology, oversimplifying the heterogeneity of clinical AD.

METHODS

We define a syndrome as a unique biomarker progression pattern and develop a lag measure to cluster pre‐dementia individuals, reflecting their pathology's multi‐dimensionality. The technique uses the time‐ordering of events to group individuals based on their position along the disease process and the relative positions of their markers.

RESULTS

An application using Alzheimer's Disease Neuroimaging Initiative (ADNI) data highlights the need for our novel approach to clustering individuals into syndrome groups.

DISCUSSION

Accurately characterizing biomarker curves associated with brain damage requires an initial step that groups individuals on a syndrome basis, accounting for the heterogeneity of underlying pathologies in clinical AD.

Highlights

Developed a novel distance measure and clustering approach for AD biomarker trajectories.

Identified distinct subgroups with different biomarker progression patterns in ADNI data.

Findings challenge the traditional amyloid cascade hypothesis and suggest AD heterogeneity.

Clustering approach accounts for shifts in time and emphasizes progression patterns.

Results have implications for AD diagnosis, targeted interventions, and clinical trials.
Investing in equitable healthy aging: Why Africa must reform social pension schemes to improve Alzheimer's disease and dementia outcomes
Authors: Mostert Cyprian M. , Mekkaoui Najat EL , Ali Shehzad , Trepel Dominic , Randcord Kirti , Udeh‐Momoh Chinedu , Nesic Olivera , Blackmon Karen , Karanja Mary , Thesen Thomas , Andai David , Ayadi Rym , Eyre Harris , Merali Zul
Published: January 2025

The eligibility criteria for social pension schemes in Africa hinder equitable and healthy aging. In 2019, women in 14 sub‐Saharan African countries had an average life expectancy of 67 years but a healthy life expectancy of only 57 years, leaving them 5 years in poor health before receiving a pension at age 62. Men had a similar situation—a life expectancy of 62 years and a healthy life expectancy of 53 years, spending 10 years in poor health before becoming eligible for pensions at age 63. Many men do not receive pensions due to early death. Delays and low pension payouts contribute to a 2.5% increase in the death rate from Alzheimer's disease and dementia.

Highlights

Eligibility criteria for social pension schemes in Africa hinder equitable and healthy aging.

Delays and low pension payouts are associated with worsening death rates from dementia.

Average health life expectancy for both genders should serve as a basis for initiating pension payouts.
Natural language processing‐based classification of early Alzheimer's disease from connected speech
Authors: Balabin Helena , Tamm Bastiaan , Spruyt Laure , Dusart Nathalie , Kabouche Ines , Eycken Ella , Statz Kevin , De Meyer Steffi , Van Hamme Hugo , Dupont Patrick , Moens Marie‐Francine , Vandenberghe Rik
Published: January 2025

INTRODUCTION

The automated analysis of connected speech using natural language processing (NLP) emerges as a possible biomarker for Alzheimer's disease (AD). However, it remains unclear which types of connected speech are most sensitive and specific for the detection of AD.

METHODS

We applied a language model to automatically transcribed connected speech from 114 Flemish‐speaking individuals to first distinguish early AD patients from amyloid negative cognitively unimpaired (CU) and then amyloid negative from amyloid positive CU individuals using five different types of connected speech.

RESULTS

The language model was able to distinguish between amyloid negative CU subjects and AD patients with up to 81.9% sensitivity and 81.8% specificity. Discrimination between amyloid positive and negative CU individuals was less accurate, with up to 82.7% sensitivity and 74.0% specificity. Moreover, autobiographical interviews consistently outperformed scene descriptions.

DISCUSSION

Our findings highlight the value of autobiographical interviews for the automated analysis of connecting speech.

Highlights

This study compared five types of connected speech for the detection of early Alzheimer's disease (AD).

Autobiographical interviews yielded a higher specificity than scene descriptions.

A preceding clinical AD classification task can refine the performance of amyloid status classification in cognitively healthy individuals.