bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamma Music: A New Acoustic Stimulus for Gamma-frequency Auditory Steady-State Response
Authors: Yokota Yusuke , Tanaka Kenta , Ming Chang , Naruse Yasushi , Imamura Yasuhiko , Fujii Shinya
Published: August 2023

A frequency range exceeding approximately 30 Hz, denoted as the gamma frequency range, is associated with various cognitive functions, consciousness, sensory integration, short-term memory, working memory, encoding and maintenance of episodic memory, and retrieval processes. In this study, we proposed a new form of gamma stimulation, called gamma music, combining 40 Hz auditory stimuli and music. This gamma music consists of drums, bass, and keyboard sounds, each containing a 40 Hz frequency oscillation. Since 40 Hz stimuli are known to induce an auditory steady-state response (ASSR), we used the 40 Hz power and phase locking index (PLI) as indices of neural activity during sound stimulation. We also recorded subjective ratings of each sound through a questionnaire using a visual analog scale. The gamma music, gamma drums, gamma bass, and gamma keyboard sounds showed significantly higher values in 40 Hz power and PLI compared to the control music without a 40 Hz oscillation. Particularly, the gamma keyboard sound showed a potential to induce strong ASSR, showing high values in these indices. In the subjective ratings, the gamma music, especially the gamma keyboard sound, received more relaxed, comfortable, preferred, pleasant, and natural impressions compared to the control music with conventional gamma stimulation. These results indicate that our proposed gamma music has potential as a new method for inducing ASSR. Particularly, the gamma keyboard sound proved to be an effective acoustic source for inducing a strong ASSR while preserving the comfortable and pleasant sensation of listening to music.
Magnetic voluntary head-fixation in transgenic rats enables lifetime imaging of hippocampal neurons
Authors: Rich P. D. , Thiberge S. Y. , Scott B. B. , Guo C. , Tervo D. G. , Brody C. D. , Karpova A. Y. , Daw N. D. , Tank D. W.
Published: August 2023

The precise neural mechanisms within the brain that contribute to the remarkable lifetime persistence of memory remain unknown. Existing techniques to record neurons in animals are either unsuitable for longitudinal recording from the same cells or make it difficult for animals to express their full naturalistic behavioral repertoire. We present a magnetic voluntary head-fixation system that provides stable optical access to the brain during complex behavior. Compared to previous systems that used mechanical restraint, there are no moving parts and animals can engage and disengage entirely at will. This system is failsafe, easy for animals to use and reliable enough to allow long-term experiments to be routinely performed. Together with a novel two-photon fluorescence collection scheme that increases two-photon signal and a transgenic rat line that stably expresses the calcium sensor GCaMP6f in dorsal CA1, we are able to track and record activity from the same hippocampal neurons, during behavior, over a large fraction of animals’ lives.
The isoflavonoid brazilin inhibits viability and cell migration in breast cancer cells
Authors: Hernández-Moreno Alberto , Nava-Tapia Dania A. , Bello-Martínez Jorge , Olea-Flores Monserrat , Hernández-Moreno Tadeo , Zuñiga-Eulogio Miriam D. , Navarro-Tito Napoleón
Published: August 2023

Breast cancer is the most common neoplasm diagnosed in women and is the leading cause of cancer death worldwide. In recent years, compounds isolated from natural sources have been proposed as potential molecules in therapy for breast cancer. In this regard, brazilin has been evaluated in various biological sceneries and has shown pharmacological functions, including anticancer and anti-inflammatory activities. Brazilin was obtained fromHaematoxylum brasiletto. The chemical structure was confirmed by spectroscopic data (1H-NMR,13C-NMR). Concerning biological activity, by MTT assays, brazilin showed cytotoxic effects on MCF7 and MDA-MB-231 breast cancer cell lines. Interestingly, brazilin was not toxic in MCF10A non-tumorigenic breast epithelial cells. We also observed morphological changes to a rounded phenotype associated with apoptosis in breast cancer cell lines and decreased cell migration in a dose and time-dependent manner. Byin silicoanalysis, we found that brazilin interacts with JAK1, JAK2, and iNOS, essential molecules driven cell migration and metastasis in cancer. These data suggest that brazilin can potentially be used as an anti-cancer agent in the future.
Machine Learning Models to Interrogate Proteomewide Covalent Ligandabilities Directed at Cysteines
Authors: Liu Ruibin , Clayton Joseph , Shen Mingzhe , Bhatnagar Shubham , Shen Jana
Published: August 2023

Machine learning (ML) identification of covalently ligandable sites may accelerate targeted covalent inhibitor design and help expand the druggable proteome space. Here we report the rigorous development and validation of the tree-based models and convolutional neural networks (CNNs) trained on a newly curated database (LigCys3D) of over 1,000 liganded cysteines in nearly 800 proteins represented by over 10,000 three-dimensional structures in the protein data bank. The unseen tests yielded 94% and 93% AUCs (area under the receiver operating characteristic curve) for the tree models and CNNs, respectively. Based on the AlphaFold2 predicted structures, the ML models recapitulated the newly liganded cysteines in the PDB with over 90% recall values. To assist the community of covalent drug discoveries, we report the predicted ligandable cysteines in 392 human kinases and their locations in the sequence-aligned kinase structure including the PH and SH2 domains. Furthermore, we disseminate a searchable online database LigCys3D (https://ligcys.computchem.org/) and a web prediction server DeepCys (https://deepcys.computchem.org/), both of which will be continuously updated and improved by including newly published experimental data. The present work represents a first step towards the ML-led integration of big genome data and structure models to annotate the human proteome space for the next-generation covalent drug discoveries.
Dorsal raphe neurons signal integrated value during multi-attribute decision-making
Authors: Feng Yang-Yang , Bromberg-Martin Ethan S. , Monosov Ilya E.
Published: August 2023

The dorsal raphe nucleus (DRN) is implicated in psychiatric disorders that feature impaired sensitivity to reward amount, impulsivity when facing reward delays, and risk-seeking when grappling with reward uncertainty. However, whether and how DRN neurons signal reward amount, reward delay, and reward uncertainty during multi-attribute value-based decision-making, where subjects consider all these attributes to make a choice, is unclear. We recorded DRN neurons as monkeys chose between offers whose attributes, namely expected reward amount, reward delay, and reward uncertainty, varied independently. Many DRN neurons signaled offer attributes. Remarkably, these neurons commonly integrated offer attributes in a manner that reflected monkeys’ overall preferences for amount, delay, and uncertainty. After decision-making, in response to post-decision feedback, these same neurons signaled signed reward prediction errors, suggesting a broader role in tracking value across task epochs and behavioral contexts. Our data illustrate how DRN participates in integrated value computations, guiding theories of DRN in decision-making and psychiatric disease.
Habitat loss weakens the positive relationship between grassland plant richness and above-ground biomass
Authors: Yan Yongzhi , Jarvie Scott , Zhang Qing
Published: August 2023

Habitat loss and fragmentation per se have been shown to be a major threat to global biodiversity and ecosystem function. However, little is known about how habitat loss and fragmentation per se alters the relationship between biodiversity and ecosystem function (BEF relationship) in the natural landscape context. Based on 130 landscapes identified by a stratified random sampling in the agro-pastoral ecotone of northern China, we investigated the effects of landscape context (habitat loss and fragmentation per se) on plant richness, above-ground biomass, and the relationship between them in grassland communities using a structural equation model. We found that habitat loss directly decreased plant richness and hence decreased above-ground biomass, while fragmentation per se directly increased plant richness and hence increased above-ground biomass. Fragmentation per se also directly decreased soil water content and hence decreased above-ground biomass. Meanwhile, habitat loss decreased the magnitude of the positive relationship between plant richness and above-ground biomass by reducing the percentage of grassland specialists in the community, while fragmentation per se had no significant modulating effect on this relationship. These results demonstrate that habitat loss and fragmentation per se have inconsistent effects on biodiversity and ecosystem function, with the BEF relationship being modulated by landscape context. Our findings emphasise that habitat loss rather than fragmentation per se can weaken the positive BEF relationship by decreasing the degree of habitat specialisation of the community.

Highlights

BEF relationship is moderated by landscape context in fragmented landscapes.

Habitat loss and fragmentation per se have inconsistent effects.

Habitat loss can weaken the positive BEF relationship via reducing the percentage of grassland specialists in the community.
Timing dependent synergies between motor cortex and posterior spinal stimulation in humans
Authors: McIntosh James R. , Joiner Evan F. , Goldberg Jacob L. , Greenwald Phoebe , Murray Lynda M. , Thuet Earl , Modik Oleg , Shelkov Evgeny , Lombardi Joseph M. , Sardar Zeeshan M. , Lehman Ronald A. , Chan Andrew K. , Riew K. Daniel , Harel Noam Y. , Virk Michael S. , Mandigo Christopher , Carmel Jason B.
Published: August 2023

Volitional movement requires descending input from motor cortex and sensory feedback through the spinal cord. We previously developed a paired brain and spinal electrical stimulation approach in rats that relies on convergence of the descending motor and spinal sensory stimuli in the cervical cord. This approach strengthened sensorimotor circuits and improved volitional movement through associative plasticity. In humans it is not known whether dorsal epidural SCS targeted at the sensorimotor interface or anterior epidural SCS targeted within the motor system is effective at facilitating brain evoked responses. In 59 individuals undergoing elective cervical spine decompression surgery, the motor cortex was stimulated with scalp electrodes and the spinal cord with epidural electrodes while muscle responses were recorded in arm and leg muscles. Spinal electrodes were placed either posteriorly or anteriorly, and the interval between cortex and spinal cord stimulation was varied. Pairing stimulation between the motor cortex and spinal sensory (posterior) but not spinal motor (anterior) stimulation produced motor evoked potentials that were over five times larger than brain stimulation alone. This strong augmentation occurred only when descending motor and spinal afferent stimuli were timed to converge in the spinal cord. Paired stimulation also increased the selectivity of muscle responses relative to unpaired brain or spinal cord stimulation. Finally, paired stimulation effects were present regardless of the severity of myelopathy as measured by clinical signs or spinal cord imaging. The large effect size of this paired stimulation makes it a promising candidate for therapeutic neuromodulation.
Microsoft Bing outperforms five other generative artificial intelligence chatbots in the Antwerp University multiple choice medical license exam
Authors: Morreel Stefan , Verhoeven Veronique , Mathysen Danny
Published: August 2023

Recently developed chatbots based on large language models (further called bots) have promising features which could facilitate medical education. Several bots are freely available, but their proficiency has been insufficiently evaluated. In this study the authors have tested the current performance on the multiple-choice medical licensing exam of University of Antwerp (Belgium) of six widely used bots: ChatGPT (OpenAI), Bard (Google), New Bing (Microsoft), Claude instant (Anthropic), Claude+ (Anthropic) and GPT-4 (OpenAI). The primary outcome was the performance on the exam expressed as a proportion of correct answers. Secondary analyses were done for a variety of features in the exam questions: easy versus difficult questions, grammatically positive versus negative questions, and clinical vignettes versus theoretical questions. Reasoning errors and untruthful statements (hallucinations) in the bots’ answers were examined. All bots passed the exam; Bing and GPT-4 (both 76% correct answers) outperformed the other bots (62-67%, p= 0.03) and students (61%). Bots performed worse on difficult questions (62%, p= 0.06), but outperformed students (32%) on those questions even more (p<0.01). Hallucinations were found in 7% of Bing’s and GPT4’s answers, significantly lower than Bard (22%, p<0.01) and Claude Instant (19%, p=0.02). Although the creators of all bots try to some extent to avoid their bots being used as a medical doctor, none of the tested bots succeeded as none refused to answer all clinical case questions.

Bing was able to detect weak or ambiguous exam questions. Bots could be used as a time efficient tool to improve the quality of a multiple-choice exam.

Author Summary

Artificial chatbots such as ChatGPT have recently gained a lot of attention. They can pass exams for medical doctors, sometimes they even perform better than regular students. In this study, we have tested ChatGPT and five other (newer) chatbots in the multiple-choice exam that students in Antwerp (Belgium) must pass to obtain the degree of medical doctor. All bots passed the exam with results similar or better than the students. Microsoft Bing scored the best of all tested bots but still produces hallucinations (untruthful statements or reasoning errors) in seven percent of the answers. Bots performed worse on difficult questions but they outperformed students on those questions even more. Maybe they are most useful when humans don’t know the answer themselves? The creators of the bots try to some extent to avoid their bots being used as a medical doctor, none of the tested bots succeeded as none refused to answer all clinical case questions. Microsoft Bing also turns out to be useful to find weak questions and as such improve the exam.
A phase 2 open-label clinical trial to determine the effect of Famciclovir on Epstein-Barr virus activity as measured by EBV shedding in the saliva of patients with Multiple Sclerosis
Authors: Dobson Ruth , Holden David , Vickaryous Nicola , Bestwick Jonathan , George Katila , Sayali Tatiana , Bianchi Lucia , Wafa Mohammad , Gold Julian , Giovannoni Gavin
Published: August 2023

Background

There is increasing evidence that Epstein-Barr virus (EBV) plays a causal role in MS. No treatments have been shown to reduce EBV turnover. We studied the effect of famciclovir on salivary EBV shedding in people with MS (NCT05283551).

Methods

People with MS receiving natalizumab provided weekly saliva samples for 12 weeks before starting Famciclovir 500mg bd. 12 saliva samples were provided on treatment and 12 following treatment. A real-time quantitative PCR Taqman assay targeted to a non-repeated sequence of the EBV polymerase gene was used to detect EBV DNA in saliva. The proportion of saliva samples containing EBV DNA was compared using the Friedman test.

Results

30 patients were recruited (19F; mean age 41 years; median EDSS 3.5). 29 patients received famciclovir, 24 completed the 12-week course. 21 participants provided at least one usable saliva sample in all 3 epochs. 10/21 participants had shedding in at least one sample pre-drug; 7/21 when taking famciclovir (not significant). No difference in EBV DNA copy number was seen. There were no drug-related serious adverse events.

Conclusions

No significant effect of famciclovir on EBV shedding was seen. Salivary EBV shedding in this natalizumab-treated cohort was lower than in previous studies; this requires replication.
Lived experience co-design of self-harm interventions: A scoping review
Authors: Wright Lucy C. , Chemas Natalia , Cooper Claudia
Published: August 2023

Background

Self-harm prevalence is rising, yet service users encounter stigmatising attitudes and feel let down when they seek professional help. Co-design activities can potentially enable development of more acceptable and effective services.

Objectives

To map existing literature describing how people with lived experience of self-harm have engaged in co-designing self-harm interventions, understand barriers and facilitators to this engagement and how meaningfulness of co-design has been evaluated.

Inclusion criteria

Studies where individuals with lived experience of self-harm (first-hand or carer) have co-designed self-harm interventions.

Methods

In accordance with Joanna Briggs Institute (JBI) scoping review methodology we scoped PubMed, Embase, PsycINFO, Web of Science, Cochrane Library, PROSPERO,ClinicalTrials.govand relevant websites on 24.12.22. A protocol was published online (http://dx.doi.org/10.17605/OSF.IO/P52UD). Results were screened at title and abstract level, then full-text level by two researchers independently. Pre-specified data was extracted, charted, and sorted into themes.

Results

We included twenty co-designed interventions across mobile health, educational settings, prisons, and emergency departments. Involvement varied from designing content to multi-stage involvement in planning, delivery, and dissemination. Included papers described the contribution of 110 female and 26 male co-designers. Few contributors identified as from a minoritized ethnic or LGBTQ+ group. Six studies evaluated how meaningfully people with lived experience were engaged in co-design: by documenting the impact of contributions on intervention design, or through post-design reflections. Barriers included difficulties recruiting inclusively, making time for meaningful engagement in stretched services, and safeguarding concerns for co-designers. Explicit processes for ensuring safety and wellbeing, flexible schedules, and adequate funding facilitated co-design.

Conclusions

To realise the potential of co-design to improve self-harm interventions, people with lived experience must be representative of those who use services. This requires processes that reassure potential contributors and referrers that co-designers will be safeguarded, remunerated, and their contributions used and valued.

ARTICLE SUMMARY

Strengths and limitations of this study

Comprehensive search strategy with no restriction on publication date to capture breadth of evidence

All papers screened at title/abstract and full-text level by two researchers independently

Protocol uploaded to the Open Science Framework prior to conducting scoping review

Did not check all published self-harm intervention papers for evidence of co-design, so instances where co-design was not mentioned in the title or abstract could have been missed

Only the development paper for each intervention was included – follow up papers were excluded at full-text level which may have overlooked additional co-design details
Virtual transitional pain service delivered via telehealth is effective in preventing new and persistent opioid use amongst post-surgical spine patients
Authors: Hussain Maryam , Norgeot Beau , Zaafran Ahmed , Stark Jessica , Caridi John , Fenoy Albert , Pivalizza Evan
Published: August 2023

Opioid dependence is a national crisis, with 30 million patients annually at risk of becoming persistent opioid users after receiving opioids for post-surgical pain management. Translational Pain Services (TPS) demonstrate effectiveness for behavioral health improvements but its effectiveness in preventing persistent opioid use is less established, especially amongst opioid exposed patients. Prohibitive costs and accessibility challenges have hindered TPS program adoption. To address these limitations, we designed and implemented a remote telehealth TPS protocol focusing on preventing continued opioid use while improving behavioral health. Licensed therapists trained in the opioid-tapering CBT protocol delivered sessions reimbursed through standard payer reimbursement. Our prospective study evaluated the protocol’s effectiveness on preventing persistent opioid use and behavioral health outcomes amongst both opioid naïve and exposed patients. In an opioid-naive patient cohort (n=67), 100% completely tapered off opioids, while in an opioid-exposed cohort (n =19) 52% completely tapered off opioids, demonstrating promising results. In both cohorts, we observed significant improvements in behavioral health scores, including pain. This opioid-tapering digital TPS is effective, adoptable, and incurs no out-of-pocket cost for healthcare systems. We provide the opioid-tapering CBT protocol in the supplement to facilitate adoption.Trial RegistrationImpact of Daily, Digital and Behavioral Tele-health Tapering Program for Perioperative Surgical Patients Exposed to Opioids and Benzodiazepines registered at clinicaltrials.gov,NCT04787692.https://clinicaltrials.gov/ct2/show/NCT04787692?term=NCT04787692&draw=2&rank=1
Trends in Hallucinogen-associated Emergency Department Visits and Hospitalizations in California from 2016–2021
Authors: Tate Steven , Garel Nicolas , Nash Kristin , Lembke Anna
Published: August 2023

Objectives

Hallucinogens encompass a diverse range of compounds with increasing scientific and public interest. Risks associated with hallucinogen use are poorly understood. This study aims to evaluate the trends in hallucinogen-related emergency department visits and hospitalizations in California from 2016 to 2021, as compared to alcohol and cannabis visits and hospitalizations

Methods

We conducted a descriptive study on publicly available data on diagnosis codes associated with emergency department (ED) visits and hospitalizations from the California Department of Healthcare Access and Information (HCAI) to describe hallucinogen, alcohol, and cannabis associated encounters.

Results

Rates of hallucinogen associated ED visits increased by 69% between 2016 and 2021 compared to a 24% decrease and 1.9% decrease in rates of alcohol associated and cannabis associated ED visits respectively. Rates of hallucinogen associated hospitalizations increased by 74% compared to a 11% increase in alcohol associated hospitalizations and a 19% increase in cannabis associated hospitalizations.

Conclusions

The large relative, but small absolute, increase in hallucinogen associated ED visits and hospitalizations is concerning given changing public perception and increasing use of these substances. The categorization of a large number of compounds as hallucinogens limits our ability to understand trends in harms with ICD-10 codes. Improved systems for surveillance of potential harms of hallucinogen use are needed.
Cheese consumption and risk of diabetic retinopathies: A Mendelian Randomization study
Authors: Lin Zenan , Hu Di , Jiang Junhong ,   The μ-Biomedical Data Investigating Group (Mu-BioDig)
Published: August 2023

Objectives

Diabetic retinopathy (DR) is the leading cause of visual loss in working-age adults worldwide. Cheese is a widely consumed dairy product, and cheese intake has various health benefiting effects. This study aimed to use Mendelian randomization (MR) to investigate the impact of cheese consumption on DR.

Methods

The genome-wide association study (GWAS) summary statistic generated from 451486 European descent was introduced to identify the valid instrumental variables (IVs) for cheese intake. As the outcomes, the GWAS data of three outcome traits (DR, proliferative diabetic retinopathy or PDR, diabetic maculopathy or DMP) were obtained from the FinnGen research project. Multivariable MR (MVMR) analysis was also conducted to determine whether the causal associations were affected by the common risk factors of DR, such as Body Mass Index, systolic blood pressure (SBP), triglycerides (TG), HDL cholesterol and hemoglobin A1c (HbA1c) levels.

Results

The cheese consumption (per 1-SD increase) was found to be associated with a decreased risk of DR (OR=0.701,P=0.011), PDR (OR=0.671,P=0.020), and DMP (OR=0.357,P=0.001). The MVMR analyses demonstrated that the TG level did not affect the causal associations with the decreased risks of DR and PDR. The study on DMP proved that the causal relations were independent from the effect of SBP, TG, and HbA1c levels.

Conclusions

Genetic evidence suggested that cheese consumption was causally associated with the decreased risk of DR. Given widespread cheese consumption, this could have significant implications for global health burdens from DR.
Cardiorespiratory fitness and physical activity among children and adolescents with diabetes: A Systemic Review and Meta-analysis
Authors: Steinman De Visser Hannah , Fast Isaak , Brunton Nicole , Arevalo Edward , Askin Nicole , Rabbani Rasheda , Abou-Setta Ahmed M. , McGavock Jonathan
Published: August 2023

Background

It is unclear if cardiorespiratory fitness (CRF) and physical activity (PA) are lower among youth with type 1 (T1D) and type 2 diabetes (T2D) compared to youth without diabetes. The objective of this study was to describe the magnitude, precision and constancy of the differences in CRF and PA between youth with and without diabetes.

Methods

We searched MEDLINE, Embase, CINAHL, and SPORTDiscus from 2000 to May 2022 for cross sectional studies that included measures of CRF and PA in children and adolescents with and without T1D or T2D. The main outcomes were objectively measured CRF obtained from a graded maximal exercise test and subjective or objective measures of PA. Three reviewers independently screened studies for eligibility, extracted data, and assessed studies for bias. Random effects meta-analysis model was used to estimate differences in main outcomes. The pooled effect estimate was measured as standardized mean differences (SMD) with its 95% confidence intervals (95%CI). This study was registered with PROSPERO (CRD42022329303) and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Results

Of 7857 unique citations retrieved, we included 9 studies (n = 755 participants) with measures of CRF and 9 studies (n = 1233 participants) with measures of PA for youth with T2D, as well as 23 studies (n = 2082 participants) and 36 studies (n = 12,196 participants) for youth with T1D. Random effects models revealed that directly measured CRF was lower in youth with T2D [SMD = - 1.06; 95% CI: -1.57 to -0.56, I2=84%, n=9 studies; n=781 youth] and in youth with T1D compared to controls [SMD = -0.39; 95% CI: -0.70 to -0.09, I2=89%, n=22 studies; n=2082 youth]. Random effects models revealed that daily PA was marginally lower in youth with T1D [SMD= -0.29, 95% CI −0.46 to -0.11, I2=89%, n=32 studies; n = 12196 youth] but not different among youth with T2D compared to controls [SMD= -0.56, 95% CI −1.28 to +0.16, I2=91%, n=9 studies; n=1233 youth]. When analyses were restricted to studies with objective measures, PA was significantly lower in youth with T2D [SMD -0.71, 95% CI −1.36 to -0.05; I2=23%, n=3 studies; n=332 youth] and T1D [SMD -0.67, 95% CI –1.17 to -0.17; I2=93%; n=12 studies; n=1357 youth] compared to controls.

Conclusions

Children and adolescents living with T1D and T2D display lower CRF and objectively measured PA compared to controls without diabetes. Deficits in CRF, but not PA are larger and more consistent in youth with T2D, compared to youth with T1D. These data may contribute to the increased risk for cardiovascular disease-related morbidity observed in adolescents with diabetes, particularly those with T2D.

Funding

This study was funded by the Canadian Institutes of Health Research
Prognostic determinants of anterior large vessel occlusion in acute stroke in elderly patients
Authors: Mitsuhashi Takashi , Teranishi Kohsuke , Tokugawa Joji , Mitsuhashi Takumi , Hishii Makoto , Oishi Hidenori
Published: August 2023

Introduction

Mechanical thrombectomy(MT) has been shown to be safety and effectiveness for acute anterior circulation large vessel occlusion(LVO)of all ages, and together with intravenous thrombolysis has become an standard treatment for acute stroke. In an aging world, the effectiveness of MT for the elderly has not been fully demonstrated. We investigated factors associated with prognosis in elderly patients undergoing MT in Japanese practice, where the elderly are defined as those aged 80 years or older, in the context of an ageing population.

Method

MT was performed in 59 cases of LVO of the anterior circulation. Primary outcome evaluated functional outcome at three months. Parametric and/or non-parametric test and a binomial logistic regression model was performed to identify prognosis factors in elderly patients.

Results

Overall, Of the 59 patients, 47.5% (28/59) achieved an mRS ≤3 at 3 months. Mortality rate was 20.3% (12/59). Younger age(P=0.032), lower NIHSS on admission(P=0.00005), lower level of NT-proBNP on admission(P=0.041), lower level of D-dimer on admission(P=0.01), First Pass Effect (FPE) (P=0.024) and good recanalization(P=0.0025) were associated with favorable clinical outcome. In the binomial logistic regression model, only lower NIHSS on admission was significantly associated with good clinical outcome.

Conclusions

In the present study, not only were younger age, lower NIHSS on admission and FPE already reported as prognostic factors for MT for LVO in the elderly, but also, although not previously reported, lower levels of NT-proBNP on admission and lower level of D-dimer on admission were considered as possible prognostic factors.
Time To Navigate (TTN): A practical objective clinical measure for freezing of gait severity in people with Parkinson’s disease
Authors: Scully A.E. , Tan D. , de Oliveira B.I.R. , Hill K.D. , Clark R. , Pua Y.H.
Published: August 2023

Objectives

Existing objective assessments for freezing of gait (FOG) severity may be unwieldy for routine clinical practice. To provide an easy-to-use clinical measure, this cross-sectional study explored if time to complete the recently-validated FOG Severity Tool (or its components) could be used to reflect FOG severity.

Methods

People with Parkinson’s disease who could independently ambulate eight-metres, understand instructions, and without co-morbidities severely affecting gait were consecutively recruited from outpatient clinics. Participants were assessed with the FOG Severity Tool in a test-retest design, with time taken for each component recorded using a stopwatch during video-analysis. Validity of total FOG Severity Tool time, time taken to complete its turning and narrow-space components (i.e., Time To Navigate, TTN), and an adjusted-TTN were examined through correlations with the FOG Questionnaire, percentage of time spent with FOG, and FOG Severity Tool-Revised score. To facilitate clinical interpretation, TTN cutoff was determined using scatterplot smoothing (LOESS) regression whilst minimal important change (MIC) was calculated using predictive modelling.

Results

Thirty-five participants were included [82.9%(n=29)male; Median(IQR): age – 73.0(11.0)years; disease duration – 4.0(4.5)years]. The FOG Severity Tool time, TTN, and adjusted-TTN similarly demonstrated moderate correlations with the FOG Questionnaire and percentage-FOG, and very-high correlations with FOG Severity Tool-Revised. TTN was nonlinearly related to FOG severity such that a positive relationship was observed in the first 300-seconds, beyond which the association plateaued. MIC for TTN was 15.4-seconds reduction in timing (95%CI 3.2 to 28.7).

Conclusions

The TTN is a feasible, interpretable, and valid test of FOG severity, demonstrating strong convergent validity with the FOG Severity Tool-Revised. In busy clinical settings, TTN provides a viable alternative when use of existing objective FOG measures is (often) unfeasible.

Impact statement

Busy clinicians need easy-to-use measures. In under 300-seconds, TTN test offers this for FOG severity, with a 15.4-seconds decrease in TTN time considered minimal improvement.
Uncovering the links between physical activity and prosocial behaviour: A functional near-infrared spectroscopy hyperscanning study on brain connectivity and synchrony
Authors: Ishihara Toru , Hashimoto Shinnosuke , Tamba Natsuki , Hyodo Kazuki , Matsuda Tetsuya , Takagishi Haruto
Published: August 2023

The prevalence of sedentary lifestyles in modern society raises concerns about their potential association with poor brain health, particularly in the lateral prefrontal cortex (LPFC), which is crucial for human prosocial behaviour. Here, we show the relationship between physical activity and prosocial behaviour, focusing on potential neural markers, including intra-brain functional connectivity and inter-brain synchrony in the LPFC. Forty participants, each paired with a stranger, underwent evaluation of neural activity in the LPFC using functional near-infrared spectroscopy hyperscanning during eye-to-eye contact and an economic game. Results showed that individuals with exercise habits and more leisure-time physical activity demonstrated greater reciprocity, less trust, longer decision-making time, and stronger intra-brain connectivity in the dorsal LPFC and inter-brain synchrony in the ventral LPFC. Our findings suggest that a sedentary lifestyle may alter human prosocial behaviour by impairing adaptable prosocial decision-making in response to social factors through altered intra-brain functional connectivity and inter-brain synchrony.
New insights into the systematics of the AfrotropicalAmblyomma marmoreumcomplex (Acari, Ixodidae) and a novelRickettsia africaestrain using morphological and metagenomic approaches
Authors: Cotes-Perdomo Andrea P. , Sánchez-Vialas Alberto , Thomas Richard , Jenkins Andrew , Uribe Juan E.
Published: August 2023

TheAmblyomma marmoreumcomplex includes some Afrotropical species, such asAmblyomma sparsum, a three-host tick that parasitizes reptiles, birds, and mammals, and is a recognized vector ofEhrlichia ruminatum. However, the lack of morphological, genetic and ecological data onA. sparsumhas caused considerable confusion in its identification amongA. marmoreumcomplex members. In this study, we used microscopy and metagenomic approaches to analyzeA. sparsum ticks collected from a puff adder snake (Bitis arietans) in southwest Senegal (an endemic rickettsioses area) in order to supplement previous morphological descriptions, provide novel genomic data for theA. marmoreumcomplex, and search for some associated spotted fever agent. Based on stereoscope and scanning electron microscopy (SEM) morphological evaluations, we provided high-quality images and new insights about punctation and enameling in the male ofA. sparsumto facilitate identification for future studies. Additionally, the metagenomic approach allowed us assembly the complete mitochondrial genome ofA. sparsum, as well as the nearly entire chromosome and complete plasmid sequences of a novelRickettsia africaestrain. Phylogenomic analyses showed a close relationship betweenA. sparsumandA. nuttallifor the first time and confirmed the position ofA. sparsumwithin theA. marmoreumcomplex. Our results provide new insights into the systematic ofA. sparsumandA. marmoreumcomplex, as well as the genetic diversity ofR. africaein Afrotropical region. Future studies should consider the possibility thatA. sparsummay be a competent vector forR. africae.
Validation of the sleep EEG headband ZMax
Authors: Esfahani Mahdad Jafarzadeh , Weber Frederik D. , Boon Merel , Anthes Simone , Almazova Tatiana , Hal Maarten van , Keuren Yon , Heuvelmans Carmen , Simo Eni , Bovy Leonore , Adelhöfer Nico , Avest Milou M. ter , Perslev Mathias , Horst Rob ter , Harous Christiana , Sundelin Tina , Axelsson John , Dresler Martin
Published: August 2023

Polysomnography (PSG) is the gold standard for recording sleep. However, the standard PSG systems are bulky, expensive, and often confined to lab environments. These systems are also time-consuming in electrode placement and sleep scoring. Such limitations render standard PSG systems less suitable for large-scale or longitudinal studies of sleep. Recent advances in electronics and artificial intelligence enabled ‘wearable’ PSG systems. Here, we present a study aimed at validating the performance of ZMax, a widely-used wearable PSG that includes frontal electroencephalography (EEG) and actigraphy but no submental electromyography (EMG). We analyzed 135 nights with simultaneous ZMax and standard PSG recordings amounting to over 900 hours from four different datasets, and evaluated the performance of the headband’s proprietary automatic sleep scoring (ZLab) alongside our open-source algorithm (DreamentoScorer) in comparison with human sleep scoring. ZLab and DreamentoScorer compared to human scorers with moderate and substantial agreement and Cohen’s kappa scores of 59.61% and 72.18%, respectively. We further analyzed the competence of these algorithms in determining sleep assessment metrics, as well as shedding more lights on the bandpower computation, and morphological analysis of sleep microstructural features between ZMax and standard PSG. Relative bandpower computed by ZMax implied an error of 5.5% (delta), 4.5% (theta), 1.6% (alpha), 0.5% (sigma), 0.8% (beta), and 0.2% (gamma), compared to standard PSG. In addition, the microstructural features detected in ZMax did not represent exactly the same characteristics as in standard PSG. Besides similarities and discrepancies between ZMax and standard PSG, we measured and discussed the technology acceptance rate, feasibility of data collection with ZMax, and highlighted essential factors for utilizing ZMax as a reliable tool for both monitoring and modulating sleep.
Better long-term learning ability is predicted by higher surface folding of the human premotor cortex
Authors: Taubert Marco , Ziegler Gabriel , Lehmann Nico
Published: August 2023

The capacity to learn enabled the human species to adapt to various challenging environmental conditions and pass important achievements on to the next generation. A growing body of research suggests links between neocortical folding and numerous aspects of human behaviour, but their impact on enhanced human learning capacity remains unexplored. Here we leverage multiple training cohorts to demonstrate that higher levels of premotor cortical folding reliably predict individual long-term learning gains in a challenging new motor task, above and beyond initial performance differences. Individual folding-related predisposition to motor learning was found to be independent of cortical thickness and several intracortical microstructural parameters, but dependent on larger cortical surface area. We further show that learning-relevant features of cortical folding occurred in close spatial proximity to practice-induced structural plasticity and were primarily localized in hominoid-specific frontal tertiary sulci. Our results suggest a new link between neocortical surface folding and human behavioural adaptability.
Burst c-VEP Based BCI: Optimizing Stimulus Design for Enhanced Classification with Minimal Calibration Data and Improved User Experience
Authors: Castillos K. Cabrera , Ladouce S. , Darmet L. , Dehais F.
Published: August 2023

The Steady State Visual Evoked Potential (SSVEP) is a widely used technique in Brain-Computer Interface (BCI) research due to its high information transfer rate. However, this method has some limitations, including lengthy calibration time and visual fatigue. Recent studies have explored the use of code-modulated Visual Evoked Potentials (c-VEP) with aperiodic flickering visual stimuli as an alternative approach to address these issues. One advantage of c-VEP is that the training of the model is independent of the number and complexity of targets, which helps reduce calibration time. Nevertheless, the existing designs of c-VEP can be further improved to achieve a higher signal-to-noise ratio, and shorten the selection time and the calibration process. In this study, we propose a novel type of code-VEP called “Burst c-VEP” that consists of brief presentations of aperiodic visual flashes at approximately 3Hz. The rationale behind this design is to leverage the sensitivity of the primary visual cortex to transient changes in low-level stimuli features to reliably elicit distinctive series of visual evoked potentials. In comparison to other types of faster-paced codes,burstc-VEP exhibits favorable properties to achieve high decoding performance using convolutional neural networks (CNN). We also explore the attenuation of visual stimuli contrast and intensity to further reduce the perceptual saliency of c-VEP. The proposed solutions were tested through an offline 4-classes c-VEP protocol involving 12 participants. Following a factorial design, participants were asked to focus on c-VEP targets whose pattern (burst and maximum-length sequence) and amplitude (100% or 40% amplitude depth modulation) were manipulated across experimental conditions. Firstly, the full amplitudeburstc-VEP codes exhibited higher accuracy ranging from 90.5% (with 17.6sof calibration data) to 95.6% (with 52.8sof calibration data) than its m-sequence counterpart (71.4% to 85.0%). The mean selection time for the two types of codes (1.5s) compared favorably compared to existing studies. Secondly, our findings revealed that lowering the intensity of the stimuli barely decreased the accuracy of theburstto 94.2% accuracy while yielding a higher subjective visual user experience. Taken together, these results demonstrate the high potential of the proposedburstcodes to advance BCI beyond the confines of the lab. The collected datasets, along with the proposed CNN architecture implementation, are shared through open-access repositories.
Toxicokinetic Characterization of the Inter-Species Differences in 6PPD-Quinone Toxicity Across Seven Fish Species: Metabolite Identification and Semi-Quantification
Authors: Montgomery David , Ji Xiaowen , Cantin Jenna , Philibert Danielle , Foster Garrett , Selinger Summer , Jain Niteesh , Miller Justin , McIntyre Jenifer , de Jourdan Benjamin , Wiseman Steve , Hecker Markus , Brinkmann Markus
Published: August 2023

N-(1,3-Dimethylbutyl)-N’-Phenyl-P-Phenylenediamine-Quinone (6PPD-Q) is a recently identified contaminant that originates from the oxidation of the tire anti-degradant 6PPD. 6PPD-Q is acutely toxic to select salmonids at environmentally relevant concentrations, while other fish species display tolerance to concentrations surpassing those measured in the environment. The reasons for these marked differences in sensitivity are presently unknown. The objective of this research was to explore potential toxicokinetic drivers of species sensitivity by characterizing biliary metabolites of 6PPD-Q in sensitive and tolerant fishes. For the first time, we identified anO-glucuronide metabolite of 6PPD-Q using high-resolution mass spectrometry. The semi-quantified levels of this metabolite in tolerant species or life stages, including white sturgeon (Acipenser transmontanus), chinook salmon (Oncorhynchus tshawytscha), westslope cutthroat trout (Oncorhynchus clarkia lewisi) and non-fry life stages of Atlantic salmon (Salmo salar), were greater than those in sensitive species, including coho salmon (Oncorhynchus kisutch), brook trout (Salvelinus fontinalis), and rainbow trout (Oncorhynchus mykiss), suggesting that tolerant species might more effectively detoxify 6PPD-Q. Thus, we hypothesize that differences in species sensitivity are a result of differences in basal expression of biotransformation enzyme across various fish species. Moreover, the semi-quantification of 6PPD-Q metabolites in bile extracted from wild-caught fish might be a useful biomarker of exposure to 6PPD-Q, thereby being invaluable to environmental monitoring and risk assessment.
Cortical cell size regulates root metabolic cost
Authors: Sidhu Jagdeep Singh , Lynch Jonathan P.
Published: August 2023

It has been hypothesized that vacuolar occupancy in mature root cortical parenchyma cells regulates root metabolic cost and thereby plant fitness under conditions of drought, suboptimal nutrient availability, and soil mechanical impedance. However, the mechanistic role of vacuoles in reducing root metabolic cost was unproven. Here we provide evidence to support this hypothesis. We first show that root cortical cell size is determined by both cortical cell diameter (CCD) and cell length (CCL). Significant genotypic variation for both CCD (∼1.1 to 1.5- fold) and CCL (∼ 1.3 to 7-fold) was observed in maize and wheat. GWAS and QTL analyses indicate CCD and CCL are heritable and under independent genetic control. We identify candidate genes for both phenes. Empirical results from isophenic lines contrasting for CCD and CCL show that increased cell size, due to either CCD or CCL, is associated with reduced root respiration, root nitrogen content, and root phosphorus content.RootSlice, a functional-structural model of root anatomy, predicts that an increased ratio of vacuolar to cytoplasmic volume causes reduced root respiration and tissue nutrient content. Ultrastructural imaging of cortical parenchyma cells with varying CCD and CCL confirms thein-silicopredictions and shows that an increase in cell size is correlated with increased vacuolar volume and reduced cytoplasmic volume. Phylogenetic analysis of terrestrial plants reveals that CCD has not significantly changed throughout plant evolution. Vacuolar occupancy and its relationship with CCD/CCL merits further investigation as a phene for improving crop adaptation to edaphic stress.

Significance Statement

Cortical cell size is an important phene determining root metabolic cost, but the underlying physiological mechanism is unclear. Here, usingin silicoand empirical approaches, we provide evidence that supports the hypothesis that vacuolar occupancy in cortical parenchyma cells regulates root metabolic cost. We also show that vacuolar occupancy is associated with cortical cell diameter and cell length, phenes that are under distinct genetic control and hold the potential for improving crop yields under edaphic stress.
Progressive plasticity during colorectal cancer metastasis
Authors: Moorman AR , Cambuli F , Benitez EK , Jiang Q , Xie Y , Mahmoud A , Lumish M , Hartner S , Balkaran S , Bermeo J , Asawa S , Firat C , Saxena A , Luthra A , Sgambati V , Luckett K , Wu F , Li Y , Yi Z , Masilionis I , Soares K , Pappou E , Yaeger R , Kingham P , Jarnagin W , Paty P , Weiser MR , Mazutis L , D’Angelica M , Shia J , Garcia-Aguilar J , Nawy T , Hollmann TJ , Chaligné R , Sanchez-Vega F , Sharma R , Pe’er D , Ganesh K
Published: August 2023

Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5+intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.