bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bias in nutrition-health associations is not eliminated by excluding extreme reporters in empirical or simulation studies
Authors: Yamamoto Nao , Ejima Keisuke , Zoh Roger S. , Brown Andrew W. 
Published: October 2022

AbstractSelf-reported nutrition intake (NI) data are prone to reporting bias that may induce bias in estimands in nutrition studies; however, they are used anyway due to high feasibility. We examined whether applying Goldberg cutoffs to remove “implausible” self-reported NI could reliably reduce bias compared to biomarkers for energy, sodium, potassium, and protein. Using IDATA data, significant bias in mean NI was removed with Goldberg cutoffs (120 among 303 participants excluded). Associations between NI and outcomes (weight, waist circumference, heart rate, systolic/diastolic blood pressure, and VO2 max) were estimated, but sample size was insufficient to evaluate bias reductions. We therefore simulated data based on IDATA. Significant bias in simulated associations using self-reported NI was reduced but not eliminated by Goldberg cutoffs in 14 of 24 nutrition-outcome pairs; bias was not reduced for remaining cases. 95% coverage probabilities were improved by applying Goldberg cutoffs in most cases but underperformed compared with biomarker data. Although Goldberg cutoffs may achieve bias elimination in estimating mean NI, bias in estimates of associations between NI and outcomes will not necessarily be reduced or eliminated after application of Goldberg cutoffs. Whether one uses Goldberg cutoffs should therefore be decided based on research purposes and not general rules.Impact StatementElimination of extreme reporters using Goldberg cutoffs does not always produce unbiased estimates of associations between nutrition intakes and health outcomes.
Bayesian multilevel hidden Markov models identify stable state dynamics in longitudinal recordings from macaque primary motor cortex
Authors: Kirchherr Sebastien , Moraga Sebastian Mildiner , Coudé Gino , Bimbi Marco , Ferrari Pier F , Aarts Emmeke , Bonaiuto James J 
Published: October 2022

AbstractNeural populations, rather than single neurons, may be the fundamental unit of cortical computation. Analyzing chronically recorded neural population activity is challenging not only because of the high dimensionality of activity in many neurons, but also because of changes in the recorded signal that may or may not be due to neural plasticity. Hidden Markov models (HMMs) are a promising technique for analyzing such data in terms of discrete, latent states, but previous approaches have either not considered the statistical properties of neural spiking data, have not been adaptable to longitudinal data, or have not modeled condition specific differences. We present a multilevel Bayesian HMM which addresses these shortcomings by incorporating multivariate Poisson log-normal emission probability distributions, multilevel parameter estimation, and trial-specific condition covariates. We applied this framework to multi-unit neural spiking data recorded using chronically implanted multi-electrode arrays from macaque primary motor cortex during a cued reaching, grasping, and placing task. We show that the model identifies latent neural population states which are tightly linked to behavioral events, despite the model being trained without any information about event timing. We show that these events represent specific spatiotemporal patterns of neural population activity and that their relationship to behavior is consistent over days of recording. The utility and stability of this approach is demonstrated using a previously learned task, but this multilevel Bayesian HMM framework would be especially suited for future studies of long-term plasticity in neural populations.
Using mechanistic models to highlight research priorities for tick-borne zoonotic diseases: Improving our understanding of the ecology and maintenance of Kyasanur Forest Disease in India
Authors: Hassall Richard , Burthe Sarah J. , Schäfer Stefanie M. , Hartemink Nienke , Purse Bethan V. 
Published: October 2022

AbstractThe risk of spillover of zoonotic diseases to humans is changing in response to multiple environmental and societal drivers, particularly in tropical regions where the burden of neglected zoonotic diseases is highest and land use change and forest conversion is occurring most rapidly. In these regions, neglected zoonotic diseases can have significant impacts on poor and marginalised populations in low-resource settings but ultimately receive less attention and funding for research and interventions. As such, effective control measures and interventions are often hindered by a limited ecological evidence base, which results in a limited understanding of epidemiologically relevant hosts or vectors and the processes that contribute to the maintenance of pathogens and spillover to humans. Here, we develop a generalisable next generation matrix modelling framework to better understand the transmission processes and hosts that have the greatest contribution to the maintenance of tick-borne diseases with the aim of improving the ecological evidence base and framing future research priorities for tick-borne diseases. Using this model we explore the relative contribution of different host groups and transmission routes to the maintenance of a neglected zoonotic tick-borne disease, Kyasanur Forest Disease Virus (KFD). The results highlight the potential importance of transovarial transmission and small mammals and birds in maintaining this disease. This contradicts previous hypotheses that primates play an important role influencing the distribution of infected ticks. There is also a suggestion that risk could vary across different habitat types. In light of these results we outline the key knowledge gaps for this system and future research priorities that would aid in informing effective interventions and control measures.
Adipocytes reprogram glucose metabolism in cancer cells promoting metastasis
Authors: Mukherjee Abir , Bezwada Divya , Zandbergen Malu , Greco Francesco , Chiang Chun-Yi , Tasdemir Medine , Fahrmann Johannes , Grapov Dmitry , La Frano Michael R. , Vu Hieu S , Newman John W. , McDonnell Liam A. , Nezi Luigi , Fiehn Oliver , DeBerardinis Ralph J. , Lengyel Ernst 
Published: October 2022

ABSTRACTIn the tumor microenvironment, adipocytes function as an alternate fuel source for cancer cells. However, whether adipocytes influence macromolecular biosynthesis in cancer cells is unknown. Here, we systematically characterized the bi-directional interaction between primary human adipocytes and ovarian cancer (OvCa) cells using multi-platform metabolomics, imaging mass spectrometry, [13C]-glucose isotope tracing, and gene expression analysis. We report that omental tumor explants and OvCa cells co-cultured with adipocytes divert part of the glucose from glycolysis and TCA cycle towards glycerol-3-phosphate (G3P) synthesis. Normoxic HIF1α protein, stabilized by adipokines, regulate this altered flow of glucose-derived carbons in cancer cells, resulting in increased synthesis of glycerophospholipids (GPL) and triacylglycerols. Blocking adipocyte-induced HIF1α expression increases lipid peroxidation levels in cancer cells and sensitizes them to ferroptosis-mediated cell death. Subsequently, the knockdown of HIF1α or G3P acyltransferase 3 (a regulatory enzyme of GPL synthesis) reduced metastasis in xenograft models of OvCa. In summary, we show that in an adipose-rich tumor microenvironment, cancer cells generate G3P as a precursor for critical membrane and signaling components, thereby promoting metastasis. Targeting biosynthetic processes specific to adipose-rich tumor microenvironments might be an effective strategy against metastasis.
Sniffing response to an odor through development in rats: modulatory role of repetition and association with an aversive event
Authors: Boulanger-Bertolus Julie , Courtiol Emmanuelle , Buonviso Nathalie , Mouly Anne-Marie 
Published: October 2022

AbstractSniffing has proven to be a useful behavioral readout for assessing olfactory performance in adult rats. However, little is known about how sniffing response changes through ontogeny. This study thus aimed at characterizing respiratory response to an odor through development in rats using paradigms applicable to both young pups and adults. We first analyzed the sniffing response to the arrival of a novel neutral odor. Then the value of the odor was changed through either its repeated presentation (odor habituation), or its association with a foot-shock resulting in odor fear. In the habituation task, we found that at the three ages, the first presentation of the novel odor induced a clear sniffing response but the peak respiratory frequency was higher in adults than in juveniles and infants. When the odor was presented repeatedly, the sniffing response gradually faded. This habituation of the response took more trials as the animal’s age increases. In the fear conditioning task, the odor induced an increase in respiratory rate that persisted until the end of the session in adults and infants, while it faded rapidly in juveniles. When the odor was explicitly unpaired with the foot-shock, at the three ages the respiratory response to the odor lasted less over the session than in the paired condition. Finally, we observed that shock delivery induced a similar respiratory response at the three ages in paired and unpaired condition. Collectively these data show that sniffing response constitutes a faithful index to assess rat’s olfactory abilities through ontogeny.
Overexpression of Interleukin-8 and Interleukin-13 as potent immune markers associated with survival and dietary habits in esophageal squamous cell carcinoma
Authors: Talukdar Jayasree , Malik Abdul , Kataki Kangkana , Choudhury Bikash Narayan , Baruah Munindra Narayan , Bhattacharyya Mallika , Alkholief Musaed , Alshamsan Aws , Sarma Manash Pratim , Bhattacharjee Minakshi , Basak Mrinmoy , Kashyap Manash Pratim , Bhattacharjee Sahana , Ali Eyashin , Keppen Chenole , Idris Mohammad Ghaznavi , Medhi Subhash 
Published: October 2022

AbstractBackgroundInterleukin-8 (IL8), Interleukin-12 (IL12) and Interleukin-13 (IL13) are cytokines that play regulatory role in cancer pathogenesis. We analysed their expression profile to evaluate as molecular biomarkers of esophageal squamous cell carcinoma (ESCC) and their association with different parameters.MethodsExpression analysis of IL8, IL12 and IL13 were performed by Real time qPCR in blood and tumor tissue of 120 ESCC patients. The expression profiles were associated with different clinicopathological and dietary factors. Survival and hazard analysis were also performed.ResultsWhen compared to normal controls, IL8 expression showed upregulation in 83% tissue samples (p=0.000) and 62% blood samples (p=0.388), IL12 expression showed upregulation in 62% tissue samples (p=0.435) and 57% blood samples (p=0.222) and IL13 expression showed upregulation in 83% tissue samples (p=0.001) and 68% blood samples (p=0.312). Significant positive correlation (p<0.05) was observed between tissue and blood level expression of IL8, IL12 and IL13. Different clinicopathological factors and dietary habits showed significant association (p<0.05) with IL8, IL12 and IL13 expression.. Statistically significant positive correlation were observed for IL8 and IL13 expression in tissue as well as IL13 and IL12 expression in both tissue and blood. Also significant negative correlation of IL8 and IL12 expression in blood and tissue were also observed. Tumor stage, node stage, metastasis, consumption of betel nut, tobacco, alcohol, hot food, smoked food, spices, IL8 expression in blood, IL13 expression in tissue and IL12 expression in blood and tissue showed significant association (p<0.05) with survival of ESCC patients.ConclusionsAltered expression of IL8, IL12 and IL13 may be associated with ESCC progression. Overexpression of IL8 and IL13 in tissue samples may be potential biomarkers for ECSS screening. Additionally, results from both survival and hazard analysis data indicate the effects of various parameters on the survival and mortality rate of ESCC patients.
A radiofrequency coil for infants and toddlers
Authors: Gilbert Kyle M. , Nichols Emily S. , Gati Joseph S. , Duerden Emma G. 
Published: October 2022

AbstractBackgroundInfants and toddlers are a challenging population on which to perform MRI of the brain, both in research and clinical settings. Due to the large range in head size during the early years of development, paediatric neuro-MRI requires a radiofrequency (RF) coil, or set of coils, that is tailored to head size to provide the highest image quality. Mitigating techniques must also be employed to reduce and correct for subject motion.ObjectiveTo develop an RF coil with a tailored mechanical-electrical design that can adapt to the head size of three-month-old infants to three-year-old toddlers.Materials and methodsAn RF coil was designed with tight-fitting coil elements to improve SNR in comparison to commercially available adult head coils, while simultaneously aiding in immobilization. The coil was designed without visual obstruction to facilitate an unimpeded view of the child’s face and the potential application of camera or motion-tracking systems.ResultsDespite the lack of elements over the face, the paediatric coil produced higher SNR over most of the brain compared to adult coils, including more than 2-fold in the periphery. Acceleration rates of 4-fold in each Cartesian direction could be achieved. Higher SNR allowed for shorter acquisition times through accelerated imaging protocols, reducing the probability of motion during a scan.ConclusionModification to the acquisition protocol, with immobilization of the head through the adjustable coil geometry, and subsequently combined with a motion tracking system provides a compelling platform for scanning paediatric populations without sedation and with improved image quality.
Local prediction-learning in high-dimensional spaces enables neural networks to plan
Authors: Stöckl Christoph , Yang Yukun , Maass Wolfgang 
Published: October 2022

Planning and problem solving are cornerstones of higher brain function. But we do not know how the brain does that. We show that learning of a suitable cognitive map of the problem space suffices. Furthermore, this can be reduced to learning to predict the next observation through local synaptic plasticity. Importantly, the resulting cognitive map encodes relations between actions and observations, and its emergent high-dimensional geometry provides a sense of direction for reaching distant goals. This quasi-Euclidean sense of direction provides a simple heuristic for online planning that works almost as well as the best offline planning algorithms from AI. If the problem space is a physical space, this method automatically extracts structural regularities from the sequence of observations that it receives so that it can generalize to unseen parts. This speeds up learning of navigation in 2D mazes and the locomotion with complex actuator systems, such as legged bodies. The cognitive map learner that we propose does not require a teacher, similar to self-attention networks (Transformers). But in contrast to Transformers, it does not require backpropagation of errors or very large datasets for learning. Hence it provides a blue-print for future energy-efficient neuromorphic hardware that acquires advanced cognitive capabilities through autonomous on-chip learning.One Sentence SummaryLocal synaptic plasticity is all you need for learning to solve problems
Identification of Aryl Hydrocarbon Receptor as a Barrier to HIV-1 Infection and Outgrowth in CD4+T-Cells
Authors: Chatterjee Debashree , Zhang Yuwei , Salinas Tomas Raul Wiche , Ngassaki-Yoka Christ-Dominique , Chen Huicheng , Smail Yasmine , Goulet Jean-Philippe , Bell Brendan , Routy Jean-Pierre , Ancuta Petronela 
Published: October 2022

ABSTRACTThe Aryl hydrocarbon receptor (AhR) identifies “non-pathogenic” Th17-polarized CD4+T-cells in autoimmune models. Thus, we explored whether AhR restricts HIV-1 in Th17-cells, consistent with its antiviral role in macrophages. AhR-specific CRISPR/Cas9-mediated knockout and pharmacological blockade decreased AhR target gene expression (CYP1A1/IL-22/IL-17A/IL-10/ ITGB7), while increasing HIV-1 replication in CD4+T-cells. Pharmacological AhR activation caused opposite effects. AhR agonism/antagonism modulated HIV-1 replication mainly in Th17/Th22-polarized CCR6+CD4+T-cells. Single-round VSV-G-pseudotyped HIV-1 infection demonstrated that AhR acts at post-entry levels, with AhR blockade increasing the efficacy of early/late reverse transcription steps and subsequently integration/translation. In viral outgrowth assay, the AhR blockade boosted the detection of replication-competent viral reservoirs in CD4+T-cells of people living with HIV-1 (PLWH) receiving antiretroviral therapy (ART). Finally, RNA-Sequencing revealed genes/pathways modulated by AhR blockade in CD4+T-cells of ART-treated PLWH, with known HIV-1 interactor activities (NCBI HIV Interactor Database) and AhR responsive elements in their promoters (ENCODE). Among them, HIC1, a repressor of Tat-mediated HIV-1 transcription and a tissue-residency inducer, represents a putative AhR mechanism of action. These results demonstrate that AhR governs an antiviral transcriptional program in CD4+T-cells and point to the use of AhR inhibitors to boost viral outgrowth in “shock and kill” HIV-1 remission/cure strategies.Model of AhR-mediated transcriptional reprogramming with implications for “silent” HIV-1 reservoir persistence and gut homing/residency.RNA-Sequencing revealed genes sets modulated by AhR blockade in CD4+T-cells of ART-treated PLWH, with known HIV-1 interactor activities (NCBI HIV Interactor Database) and AhR responsive elements in their promoters (ENCODE). Among them, HIC1, a repressor of Tat-mediated HIV-1 transcription and a tissue-residency regulator, represents a putative AhR mechanism of action. These results support a model in which AhR activation favors the gut homing and residencyviathe induction of ITGB7 and CXCR6 expression, respectively, and fuels the persistence of ‘silent” HIV-1 reservoirs in CD4+T-cells of ART-treated PLWH. At the opposite, pharmacological AhR blockade facilitates viral outgrowth, and by interfering with tissue residency, likely promotes the mobilization of « reactivated » reservoir cells from deep tissues into the circulations.BRIEF SUMMARYWe identified the aryl hydrocarbon receptor as a barrier to HIV-1 infection/outgrowth in Th17-polarized CD4+T-cells and a novel therapeutic target in HIV-1 cure/remission interventions.
Mu-Transcranial Alternating Current Stimulation Induces Phasic Entrainment and Plastic Facilitation of Corticospinal Excitability
Authors: Geffen Asher , Bland Nicholas , Sale Martin V 
Published: October 2022

AbstractTranscranial alternating current stimulation (tACS) has been proposed to modulate neural activity through two primary mechanisms: entrainment and neuroplasticity. The current study aimed to probe both of these mechanisms in the context of the sensorimotor µ-rhythm using transcranial magnetic stimulation (TMS) and electroencephalography (EEG) to assess entrainment of corticospinal excitability (CSE) during stimulation (i.e., online) and immediately following stimulation, as well as neuroplastic aftereffects on CSE and µ EEG power. Thirteen participants received 3 sessions of stimulation. Each session consisted of 90 trials of µ-tACS tailored to each participant’s individual µ frequency (IMF), with each trial consisting of 16 seconds of tACS followed by 8 seconds of rest (for a total of 24 minutes of tACS and 12 minutes of rest per session). Motor evoked potentials (MEPs) were acquired at the start and end of the session (n = 41) and additional MEPs were acquired across the different phases of tACS at 3 epochs within each tACS trial (n = 90 for each epoch): early online, late online, and offline echo. Resting EEG activity was recorded at the start, end, and throughout the tACS session. The data were then pooled across the three sessions for each participant to maximise the MEP sample size per participant. We present preliminary evidence of CSE entrainment persisting immediately beyond tACS and have also replicated the plastic CSE facilitation observed in previous µ-tACS studies, thus supporting both entrainment and neuroplasticity as mechanisms by which tACS can modulate neural activity.Graphical AbstractThirteen participants underwent 3 sessions of stimulation where they received 90 trials of mu-tACS (270 trials across the 3 sessions), with each trial consisting of 16 seconds of tACS (2mA at the participants individual mu frequency) followed by 8 seconds of rest. Motor evoked potentials (MEPs) were acquired at the start and end of the session (n = 41) and additional MEPs were acquired across the different phases of tACS at 3 epochs within each tACS trial (n = 90 for each epoch): early online, late online, and offline echo. We present preliminary evidence supporting entrainment of MEP amplitudes to tACS phase online to and immediately following stimulation and have also replicated the neuroplastic CSE facilitation observed in previous µ-tACS studies.
Ripple-locked coactivity of stimulus-specific neurons supports human associative memory
Authors: Kunz Lukas , Staresina Bernhard P. , Reinacher Peter C. , Brandt Armin , Guth Tim A. , Schulze-Bonhage Andreas , Jacobs Joshua 
Published: October 2022

AbstractAssociative memory is the ability to encode and retrieve relations between different stimuli. To better understand its neural basis, we investigated whether associative memory involves precisely timed spiking of neurons in the medial temporal lobes that exhibit stimulus-specific tuning. Using single-neuron recordings from epilepsy patients performing an associative object–location memory task, we identified the object- and place-specific neurons that encoded the separate elements of each memory. When patients encoded and retrieved particular memories, the relevant object- and place-specific neurons activated synchronously during hippocampal ripples. This ripple-locked coactivity of stimulus-specific neurons emerged over time as the patients’ associative learning progressed. Our results suggest a cellular account of associative memory, in which hippocampal ripples coordinate the activity of specialized cellular populations to facilitate links between stimuli.