bluuebunny/crossref_metadata_2025_split huggingface dataset:
Place Coding in the Human Cochlea
Authors: Walia Amit , Ortmann Amanda J. , Lefler Shannon , Holden Timothy A. , Puram Sidharth V. , Herzog Jacques A. , Buchman Craig A. 
Published: April 2023

AbstractThe cochlea’s capacity to decode sound frequencies is enhanced by a unique structural arrangement along its longitudinal axis, a feature termed ‘tonotopy’ or place coding. Auditory hair cells at the cochlea’s base are activated by high-frequency sounds, while those at the apex respond to lower frequencies. Presently, our understanding of tonotopy primarily hinges on electrophysiological, mechanical, and anatomical studies conducted in animals or human cadavers. However, directin vivomeasurements of tonotopy in humans have been elusive due to the invasive nature of these procedures. This absence of live human data has posed an obstacle in establishing an accurate tonotopic map for patients, potentially limiting advancements in cochlear implant and hearing enhancement technologies. In this study, we conducted acoustically-evoked intracochlear recordings in 50 human subjects using a longitudinal multi-electrode array. These electrophysiological measures, combined with postoperative imaging to accurately locate the electrode contacts allow us to create the firstin vivotonotopic map of the human cochlea. Furthermore, we examined the influences of sound intensity, electrode array presence, and the creation of an artificial third window on the tonotopic map. Our findings reveal a significant disparity between the tonotopic map at daily speech conversational levels and the conventional (i.e., Greenwood) map derived at close-to-threshold levels. Our findings have implications for advancing cochlear implant and hearing augmentation technologies, but also offer novel insights into future investigations into auditory disorders, speech processing, language development, age-related hearing loss, and could potentially inform more effective educational and communication strategies for those with hearing impairments.Significance StatementThe ability to discriminate sound frequencies, or pitch, is vital for communication and facilitated by a unique arrangement of cells along the cochlear spiral (tonotopic place). While earlier studies have provided insight into frequency selectivity based on animal and human cadaver studies, our understanding of thein vivohuman cochlea remains limited. Our research offers, for the first time,in vivoelectrophysiological evidence from humans, detailing the tonotopic organization of the human cochlea. We demonstrate that the functional arrangement in humans significantly deviates from the conventional Greenwood function, with the operating point of thein vivotonotopic map showing a basal (or frequency downward) shift. This pivotal finding could have far-reaching implications for the study and treatment of auditory disorders.
Anaesthesia provision challenges in public hospitals of Pakistan’s Punjab province: a qualitative study of expert perspectives
Authors: Shahbaz Sumbal , Zakar Rubeena , Howard Natasha 
Published: April 2023

ABSTRACTBackgroundAnaesthesia delivery in Pakistan remains limited to conventional intraoperative procedures, with research showing ongoing challenges in quality and resourcing. We aimed to identify systemic challenges in the delivery of quality anaesthesia services for surgical support in Pakistan’s Punjab province.MethodsThis qualitative study included 22 semi-structured interviews with purposively selected anaesthesia system experts in Punjab province, including heads of teaching hospital anaesthesia departments, healthcare commission representatives, and health department officials. We analysed data thematically, using deductive and inductive coding.ResultsWe identified three themes of anaesthetist recruitment and retention, quality-of-care and in-service training, and discrepancies between specialities, describing major challenges experienced within the speciality. Findings indicated that workforce shortages and maldistribution, insufficient in-service training and standards, inadequate equipment maintenance, and lack of anaesthesia representation in decision-making compromised anaesthesia provision quality and safety.ConclusionsImproving anaesthesia provision in Punjab would require increasing physician and non-physician anaesthetist numbers and rotation to peripheral postings, strengthening training quality, and ensuring availability of minimum essential equipment and supplies. To achieve essential anaesthesia provision standards, policy interventions are needed to, for example, balance anaesthesiologist and surgeon numbers, require that anaesthesiology graduates work a few years in-country (e.g. scholarship bonds), ensure in-service training attendance for skills updates, and implement quality assurance standards for equipment and supplies.HIGHLIGHTSWhat is already known on this topic?Existing research on anaesthesia in lower-income economies focuses on provision discrepancies and capacity measurement of HIC-partnered interventions. However, managerial and frontline challenges that weaken quality anaesthesia provision in countries such as Pakistan, and thus affect global surgery indicators, are largely unexamined.What this study addsThis study is the first to highlight ongoing challenges within the anaesthesia delivery system in Punjab province as experienced by senior practitioners and health officials, thus contributing to the knowledge base on anaesthesia provision challenges in lower-income economies.How this study might affect research, practice, or policyFindings show the urgent need to increase recruitment, retention, and peripheral distribution of physician and non-physician anaesthetists along with developing clear national legislation and practice guidelines for standardised quality of anaesthesia care and raising the public profile of anaesthesia in Pakistan.
Public perceptions of Ebola vaccines and confidence in health services to treat Ebola, malaria, and tuberculosis: Findings from a cross-sectional household survey in Uganda, 2020
Authors: Koyuncu Aybüke , Carter Rosalind J. , Musaazi Joseph , Namageyo-Funa Apophia , Carter Victoria M. , Lamorde Mohammed , Prybylski Dimitri , Apondi Rose , Bakyaita Tabley , Boore Amy L. , Homsy Jaco , Brown Vance R. , Kigozi Joanita , Nabaggala Maria Sarah , Nakate Vivian , Nkurunziza Emmanuel , Stowell Daniel F. , Walwema Richard , Olowo Apollo , Jalloh Mohamed F. 
Published: April 2023

AbstractBackgroundUganda used Ebola vaccines as part of its preparedness and response during the 2018-2020 10thEbola virus disease (EVD) outbreak in neighboring Democratic Republic of the Congo (DRC). We evaluated the public’s perceptions of Ebola vaccines and compared their confidence in health services to treat Ebola versus malaria and tuberculosis as part of a survey on Ebola knowledge, attitudes, and practices (KAP) conducted in March 2020.MethodsA cross-sectional household survey was implemented in six districts in Uganda using multi-stage cluster sampling to randomly select participants. The districts were purposively selected from districts classified by the government as at high- or low-risk for an EVD outbreak. We describe perceptions of Ebola vaccines and confidence in health services to treat Ebola, tuberculosis, and malaria. Modified Poisson regression modeling was used to identify the demographic correlates of these outcomes.ResultsAmong 3,485 respondents, 18% were aware of Ebola vaccines. Of those, 92% agreed that the vaccines were needed to prevent Ebola. Participants aged 15-24 years were 4% more likely to perceive such need compared to those 60 years and older (adjusted prevalence ratio [aPR] 1.04, 95% confidence interval [CI] 1.0-1.08). The perceived need was 5% lower among participants with at least some secondary education compared to uneducated participants (aPR 0.95; 0.92-0.99). Overall, 81% of those aware of the vaccines believed that everyone or most people in their community would get vaccinated if offered, and 94% said they would likely get vaccinated if offered. Confidence in health services to treat Ebola was lower compared to treating malaria or tuberculosis (55% versus 93% and 77%, respectively). However, participants from the EVD high-risk districts were 22% more likely to be confident in health services to treat Ebola compared to those in low-risk districts (aPR: 1.22; 95% CI: 1.08, 1.38).ConclusionOur findings suggest that intent to take an Ebola vaccine during an outbreak was strong, but more work needs to be done to increase public awareness of these vaccines. The public’s high confidence in health services to treat other health threats, such as malaria and tuberculosis, offer building blocks for strengthening their confidence in health services to treat EVD in the event of an outbreak.
Life-course neighbourhood deprivation and brain structure in older adults: The Lothian Birth Cohort 1936
Authors: Baranyi Gergő , Buchanan Colin R. , Conole Eleanor L.S. , Backhouse Ellen V. , Maniega Susana Muñoz , Hernandez Maria Valdes , Bastin Mark E. , Wardlaw Joanna , Deary Ian J. , Cox Simon R. , Pearce Jamie 
Published: April 2023

ABSTRACTNeighbourhood disadvantage may be associated with brain health but the importance at different stages of the life course is poorly understood. Utilizing the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and regional neuroimaging measures at age 73. We found that residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (β=-0.06; SE=0.02;n=390) and grey matter volume (β=-0.11; SE=0.03;n=390), thinner cortex (β=-0.15; SE=0.06;n=379), and lower general white matter fractional anisotropy (β=-0.19; SE=0.06;n=388). Regional analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower occupational social classes, the brain-neighbourhood associations were stronger, with the impact of neighbourhood deprivation accumulating across the life course. Our findings suggest that living in deprived neighbourhoods is associated with adverse brain morphologies, with occupational social class adding to the vulnerability.
Complement-dependent mpox virus-neutralizing antibodies in infected and vaccinated individuals
Authors: Hubert Mathieu , Guivel-Benhassine Florence , Bruel Timothée , Porrot Françoise , Planas Delphine , Vanhomwegen Jessica , Wiedemann Aurélie , Burrel Sonia , Marot Stéphane , Palich Romain , Monsel Gentiane , Diombera Harouna , Gallien Sébastien , Lopez-Zaragoza Jose Luis , Vindrios William , Taieb Fabien , Fernandes-Pellerin Sandrine , Delhaye Maurine , Laude Hélène , Arowas Laurence , Ungeheuer Marie-Noelle , Hocqueloux Laurent , Pourcher Valérie , Prazuck Thierry , Marcelin Anne-Geneviève , Lelièvre Jean-Daniel , Batéjat Christophe , Lévy Yves , Manuguerra Jean-Claude , Schwartz Olivier 
Published: April 2023

ABSTRACTMpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. The Modified Vaccinia Ankara (MVA)-based vaccine was used as prophylaxis, but its effectiveness remains poorly characterized. Here, we developed two assays for quantification of neutralizing antibodies (NAbs), using MVA-GFP or a recently isolated MPXV. We measured NAb levels in 470 sera from control, MPXV-infected or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox or MVA vaccination. MPXV was barely sensitive to neutralization. Addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement-dependent and help uncover the mechanisms underlying vaccine effectiveness.SUMMARYIn 2022, mpox virus (MPXV) caused an unprecedented pandemic outbreak in non-endemic areas. The efficacy of currently available third generation MVA-based vaccines and the nature of the humoral response generated after MPXV infection remain poorly characterized. We established cell-based assays to measure neutralizing antibodies (NAbs) targeting MVA or MPXV. We analyzed 470 sera and detected robust levels of MVA NAbs after infection, historic smallpox vaccination or administration of MVA-based vaccines. Efficient MPXV neutralization required addition of complement. High NAb titers were measured in ancient smallpox-vaccinated MPXV-infected patients, suggesting a potential cross-protection mediated by hybrid immunity.
Multimodal imaging of microstructural cerebral changes and loss of synaptic density in Alzheimer’s disease
Authors: Moallemian Soodeh , Salmon Eric , Bahri Mohamed Ali , Beliy Nikita , Delhaye Emma , Balteau Evelyne , Phillips Christophe , Bastin Christine 
Published: April 2023

AbstractMultiple neuropathological changes are involved in Alzheimer’s disease (AD). The current study investigated the concurrence of neurodegeneration, increased iron content, atrophy, and demyelination in AD.Quantitative multiparameter MRI maps providing neuroimaging biomarkers for myelination and iron content along with synaptic density measurements using [18F] UCB-H PET were acquired in 24 AD and 19 Healthy controls (19 males).The whole brain voxel-wise group comparison revealed demyelination in the right hippocampus, while no significant iron content difference was detected. Bilateral atrophy and synaptic density loss was observed in the hippocampus and amygdala. The multivariate GLM (mGLM) analysis shows a bilateral difference in the hippocampus and amygdala, right pallidum, left fusiform and temporal lobe suggesting that these regions are the most affected despite the diverse changes in brain tissue properties in AD. Demyelination was identified as the most affecting factor in the observed differences.Here, the mGLM is introduced as an alternative for multiple comparisons between different modalities, reducing the risk of false positives while informing about the co-occurrence of neuropathological processes in AD.
Sleep Regularity and Mortality: A Prospective Analysis in the UK Biobank
Authors: Cribb Lachlan , Sha Ramon , Yiallourou Stephanie , Grima Natalie A , Cavuoto Marina , Baril Andree-Ann , Pase Matthew P. 
Published: April 2023

ABSTRACTBackgroundIrregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort.MethodsThe sleep regularity index (SRI) was calculated as the probability of an individual being in the same state (asleep or awake) at any two time points 24 hours apart, averaged over 7-days of accelerometry (range 0-100, with 100 being perfectly regular). The SRI was related to the risk of mortality in time-to-event models.FindingsThe mean sample age was 62 years (SD, 8), 56% were women, and the median SRI was 60 (SD, 10). There were 3010 deaths during a mean follow-up of 7.1 years. Following adjustments for demographic and clinical variables, we identified a non-linear relationship between the SRI and all-cause mortality hazard (p[global test of spline term] < 0·001). Hazard Ratios, relative to the median SRI, were 1·53 (95% confidence interval [CI]: 1·41, 1·66) for participants with SRI at the 5thpercentile (SRI = 41) and 0·90 (95% CI: 0·81, 1·00) for those with SRI at the 95thpercentile (SRI = 75), respectively. Findings for CVD mortality and cancer mortality followed a similar pattern.ConclusionsIrregular sleep-wake patterns are associated with higher mortality risk.FundingNational Health and Medical Research Council of Australia (GTN2009264; GTN1158384), National Institute on Aging (AG062531), Alzheimer’s Association (2018-AARG-591358), and the Banting Fellowship Program (#454104).
Impaired flexible reward learning is associated with blunted reinforcement sensitivity and attenuated learning and choice signals in ventral striatum and parietal cortex of ADHD patients
Authors: Aster Hans-Christoph , Waltmann Maria , Busch Anika , Romanos Marcel , Gamer Matthias , van Noort Betteke Maria , Beck Anne , Kappel Viola , Deserno Lorenz 
Published: April 2023

AbstractReward-based learning and decision-making are prime candidates to understand symptoms of attention deficit hyperactivity disorder (ADHD). However, only limited evidence is available regarding the neurocomputational underpinnings of the alterations seen in ADHD. This particularly concerns the flexible behavioral adaption in dynamically changing environments, which is challenging for individuals with ADHD. One previous study points to elevated choice switching in adolescent ADHD, which was accompanied by disrupted learning signals in medial prefrontal cortex.In the present study, we investigated young adults with ADHD (n=17, 18-32 years) and age and sex matched controls (n=17, 18-30 years) using a probabilistic reversal learning experiment during functional magnetic resonance imaging (fMRI). The task requires continuous learning to guide flexible behavioral adaptation to changing reward contingencies. To disentangle the neurocomputational underpinnings of the behavioral data, we used detailed reinforcement learning (RL) models, which informed the analysis of fMRI data.ADHD patients performed worse than controls particularly in trials before reversals, i.e., when reward contingencies were stable. This pattern resulted from ‘noisy’ choice switching regardless of previous feedback. RL modelling showed decreased reinforcement sensitivity and enhanced learning rates for negative feedback in ADHD patients. At the neural level, this was reflected in diminished representation of choice probability in the left posterior parietal cortex in ADHD. Moreover, modelling showed a marginal reduction of learning about the unchosen option, which was paralleled by an equally marginal reduction in learning signals incorporating the unchosen option in the left ventral striatum.Taken together, we show that flexible behavioral adaptation in the context of dynamically changing reward contingencies is impaired in ADHD. This is due to excessive choice switching (‘hyper-flexibility’), which can be detrimental or beneficial depending on the learning environment. Computationally, this results from blunted sensitivity to reinforcement. We detected neural correlates of this blunted sensitivity to reinforcement in the attention-control network, specifically in the parietal cortex. These neurocomputational findings are promising but remain preliminary due to the relatively small sample size.
Recognizing Activities of Daily Living using Multi-sensor Smart Glasses
Authors: Stankoski Simon , Sazdov Borjan , Broulidakis John , Kiprijanovska Ivana , Sofronievski Bojan , Cox Sophia , Gjoreski Martin , Archer James , Nduka Charles , Gjoreski Hristijan 
Published: April 2023

AbstractContinuous and automatic monitoring of an individual’s physical activity using wearable devices provides valuable insights into their daily habits and patterns. This information can be used to promote healthier lifestyles, prevent chronic diseases, and improve overall well-being. Smart glasses are an emerging technology that can be worn comfortably and continuously. Their wearable nature and hands-free operation make them well suited for long-term monitoring of physical activity and other real-world applications. To this end, we investigated the ability of the multi-sensor OCOsense™ smart glasses to recognize everyday activities. We evaluated three end-to-end deep learning architectures that showed promising results when working with IMU (accelerometer, gyroscope, and magnetometer) data in the past. The data used in the experiments was collected from 18 participants who performed pre-defined activities while wearing the glasses. The best architecture achieved an F1 score of 0.81, demonstrating its ability to effectively recognize activities, with the most problematic categories being standing vs. sitting.
Impaired Proactive Cognitive Control in Parkinson’s disease
Authors: Kricheldorff Julius , Ficke Julia , Debener Stefan , Witt Karsten 
Published: April 2023

AbstractAdaptive control has been studied in Parkinson’s disease (PD) mainly in the context of proactive control and with mixed results. We compared reactive- and proactive control in 30 participants with Parkinson’s disease (PD) to 30 age matched healthy control participants (HC). The electroencephalographic (EEG) activity of the participants was recorded over 128 channels while they performed a numerical Stroop task, in which we controlled for confounding stimulus-response learning. We assessed effects of reactive- and proactive control on reaction time-, accuracy- and EEG time-frequency data. Behavioral results show distinct impairments of proactive-reactive control in participants with PD, when tested on their usual medication. Participants with PD were unable to adapt cognitive control proactively and were less effective to resolve conflict using reactive control. Successful reactive and proactive control in the HC group was accompanied by a reduced conflict effect between congruent and incongruent items in midline-frontal theta power. Our findings provide evidence for a general impairment of proactive control in PD and suggest that the same may be the case for reactive control.
Thiamine alone rather than in combination with ascorbic acid is associated with improved survival in septic shock
Authors: Legouis David , Ourahmoune Aimad , Sgardello Sebastian , Sangla Frederic , Criton Gilles 
Published: April 2023

AbstractBackgroundSepsis and septic shock are common causes of ICU admission with devastating outcomes. Adjunctive therapies are urgently needed, and the use of high dose of vitamin B1 and C have recently gained interest. However, on the basis of a perceived possible synergic effect, most trials have never tested the combination of thiamine and ascorbic acid, with a separate assessment of the effect of each individual component. In this context, while the association of thiamine and ascorbic acid was not found to improve survival rates, potentially harmful effects were found when administering ascorbic acid alone. We have conducted a retrospective cohort study, comparing ICU mortality of septic shock patients receiving standard treatment, thiamine alone or a combination of thiamine and ascorbic acid.ResultsA total of 1800 patients were included, 1260 receiving standard care, 436 receiving only thiamine and 104 patients receiving a thiamine / ascorbic acid combination. Using doubly robust estimation of the treatment effect, combining propensity score weighting and variables adjustment, we found thiamine alone to be associated with a decrease in ICU mortality compared to the use of a thiamine / ascorbic acid combination (Hazar Ratio equal to 0.60, 95% Confidence Interval [0.36;0.99], p=0.048).ConclusionsIn septic shock patients, administration of thiamine is associated with improved ICU mortality when used alone rather than when associated with ascorbic acid. This result strengthens the evidence showing a lack of effectiveness of the ascorbic acid / thiamine combination reported in recent randomized controlled trials. Furthermore, it argues in favor of the need for further trials investigating the effect of thiamine in septic ICU patients as an adjunctive therapy.