bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burstprop for Learning in Spiking Neuromorphic Hardware
Authors: Stuck Mike , Naud Richard 
Published: July 2023

AbstractThe need for energy-efficient solutions in Deep Neural Network (DNN) applications has led to a growing interest in Spiking Neural Networks (SNNs) implemented in neuromorphic hardware. The Burstprop algorithm enables online and local learning in hier-archical networks, and therefore can potentially be implemented in neuromorphic hardware. This work presents an adaptation of the algorithm for training hierarchical SNNs on MNIST. Our implementation requires an order of magnitude fewer neurons than the previous ones. While Burstprop outper-forms Spike-timing dependent plasticity (STDP), it falls short compared to training with backpropagation through time (BPTT). This work establishes a foundation for further improvements in the Burst-prop algorithm, developing such algorithms is essential for achieving energy-efficient machine learning in neuromorphic hardware.
Inhibition of skeletal muscle Lands cycle ameliorates weakness induced by physical inactivity
Authors: Shahtout Justin L. , Eshima Hiroaki , Ferrara Patrick J. , Maschek J. Alan , Cox James E. , Drummond Micah J. , Funai Katsuhiko 
Published: July 2023

ABSTRACTBackgroundLipid hydroperoxides (LOOH) have been implicated in skeletal muscle atrophy with age and disuse. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme of Lands cycle, conjugates a polyunsaturated fatty acyl chain to a lysophospholipid (PUFA-PL) molecule, providing substrates for LOOH propagation. Previous studies suggest that inhibition of Lands cycle is an effective strategy to suppress LOOH. Mice with skeletal muscle-specific tamoxifen-inducible knockout of LPCAT3 (LPCAT3-MKO) were utilized to determine if muscle-specific attenuation of LOOH may alleviate muscle atrophy and weakness with disuse.MethodsLPCAT3-MKO and control mice underwent 7 days of sham or hindlimb unloading (HU model) to study muscle mass and force-generating capacity. LOOH was assessed by quantifying 4-hydroxynonenal (4-HNE)-conjugated peptides. Quantitative PCR and lipid mass spectrometry were used to validate LPCAT3 deletion.Results7 days of HU was sufficient to induce muscle atrophy and weakness concomitant to an increase in 4-HNE. Deletion of LPCAT3 reversed HU-induced increase in muscle 4HNE. No difference was found in body mass, body composition, or caloric intake between genotypes. The soleus (SOL) and plantaris (PLANT) muscles of the LPCAT3-MKO mice were partially protected from atrophy compared to controls, concomitant to attenuated decrease in cross-sectional areas in type I and IIa fibers. Strikingly, SOL and extensor digitorum longus (EDL) were robustly protected from HU-induced reduction in force-generating capacity in the LPCAT3-MKO mice compared to controls.ConclusionOur findings demonstrate that attenuation of muscle LOOH is sufficient to restore skeletal muscle function, in particular a protection from reduction in muscle specific force. Thus, muscle LOOH contributes to atrophy and weakness induced by HU in mice.
Quantifying Myelin Water Fraction in a Guinea Pig Model of Spontaneous Intrauterine Growth Restriction
Authors: Sethi Simran , Friesen-Waldner Lanette J. , Regnault Timothy R.H. , McKenzie Charles A. 
Published: July 2023

ABSTRACTIntrauterine growth restriction (IUGR) is an obstetrical outcome where a fetus has not achieved its genetic potential. A consequence of IUGR is a decrease in brain myelin content. Myelin water imaging (MWI) has previously assessed fetal myelin water fraction (MWF) and can potentially assess myelination changes associated with IUGR. Thus, this study aims to quantify and compare the MWF of non-IUGR and IUGR fetal guinea pigs (GPs) in late gestation. Our sample consisted of 22 pregnant Dunkin-Hartley GPs with 71 fetuses (34 male) [mean ± standard deviation: 60 ± 1.2 days gestation]. Eight SPGR volumes [flip angles (α): 2° – 16°], and two sets of 8 bSSFP volumes (α: 8° – 64°), at 0° and 180° phase increments were acquired at 3.0 T. MWF maps were generated for each fetal GP brain using multicomponent driven equilibrium single pulse observation of T1/T2(mcDESPOT). Regions of interest (ROIs) were placed in the fetal corpus callosum (CC), fornix (FOR), and parasagittal white matter (PSW). Linear regression was performed between five fetal IUGR markers [body volume (BV), body-to-pregnancy volume ratio (BPrVR), brain-to-liver VR (BLVR), brain-to-placenta VR (BPlVR), and brain-to-BVR (BBVR)] and MWF for all regions (coefficient of determination, R2). A t-test with a linear mixed model compared the MWF of non-IUGR and IUGR fetal GPs for all three regions (α = 0.05). The MWF values are as follows: (mean ± standard deviation): 0.23 ± 0.02 (fetal CC), 0.19 ± 0.02 (fetal CC – IUGR), 0.31 ± 0.02 (fetal FOR), 0.27 ± 0.01 (fetal FOR – IUGR), 0.28 ± 0.02 (fetal PSW), and 0.24 ± 0.03 (fetal PSW – IUGR). Significant differences in MWF were found between the non-IUGR and IUGR fetuses in every region. In conclusion, the mean MWF of IUGR fetal GPs is significantly lower than non-IUGR fetal GPs.
Architectural asymmetry enables DNA transport through theHelicobacter pylori cagtype IV secretion system
Authors: Ryan Mackenzie E. , Damke Prashant P. , Bryant Caitlynn , Sheedlo Michael J. , Shaffer Carrie L. 
Published: July 2023

ABSTRACTStructural asymmetry within secretion system architecture is fundamentally important for apparatus diversification and biological function. However, the mechanism by which symmetry mismatch contributes to nanomachine assembly and interkingdom effector translocation are undefined. Here, we show that architectural asymmetry orchestrates dynamic substrate selection and enables trans-kingdom DNA conjugation through theHelicobacter pylori cagtype IV secretion system (cagT4SS). Structural analyses of asymmetric units within thecagT4SS periplasmic ring complex (PRC) revealed intermolecular π-π stacking interactions that coordinate DNA binding and license trans-kingdom conjugation without disrupting the translocation of protein and peptidoglycan effector molecules. Additionally, we identified a novel proximal translocation channel gating mechanism that regulates cargo loading and governs substrate transport across the outer membrane. We thus propose a model whereby the organization and geometry of architectural symmetry mismatch exposes π−π interfaces within the PRC to facilitate DNA transit through thecagT4SS translocation channel.
The management of blunt pancreatic injury in children in New South Wales
Authors: Chung Sally T W , Holland Andrew J A , Brown Julie , Adams Susan E 
Published: July 2023

AbstractBackgroundBlunt pancreatic injury is uncommon but associated with considerable morbidity. The optimal management strategy for children with this injury remains unclear, with laparotomy rates in North America of up to 55%. This has not been studied at a population level in Australia. This study aimed to examine the management of children with blunt pancreatic injury in New South Wales (NSW), Australia.MethodsUsing the NSW Admitted Patient Data Collection from 2001 to 2019, we identified patients <16 years old with blunt pancreatic injury. Cases were categorised as undergoing non-operative or operative management. Patient and injury characteristics and outcomes were compared between non-operative and operative groups. Independent predictors of operative management were identified using multivariable logistic regression.Results139 cases were identified: 37 (26.6%) underwent operative management, of whom 11 (29.7%) had a pancreas-specific operation. Two-thirds were managed at a paediatric trauma centre. Operation rates were highest in adult trauma centres, although treatment outside a paediatric trauma centre overall was not associated with operative management. Independent predictors of operative management were high-grade pancreatic injury, hollow viscus injury and transfusion. Morbidity and mortality were 30.2% and 1.4%, respectively.ConclusionBlunt pancreatic injury continues to carry substantial morbidity. Operation rates in NSW are lower than those reported in North America, with similar outcomes. Unlike other solid organ injuries, most children are managed at paediatric trauma centres. Future studies should investigate factors driving management decisions in the Australian context, with the aim of developing paediatric guidelines promoting non-operative management.HighlightsOperation rates for children with BPI were much lower than reported in international studies, with comparable morbidity and lower mortality.Operation rates were highest at ATCs, although, overall, children with BPI managed outside PTCs were not more likely to undergo an operation.Penetrating pancreatic injury is rare compared to the US, likely reflecting that firearm-related injury in Australia remains uncommon.
Positive Airway Pressure Therapy Predicts Lower Mortality and Major Adverse Cardiovascular Events Incidence in Medicare Beneficiaries with Obstructive Sleep Apnea
Authors: Mazzotti Diego R , Waitman Lemuel R. , Miller Jennifer , Sundar Krishna M. , Stewart Nancy H. , Gozal David , Song Xing ,   Greater Plains Collaborative
Published: July 2023

AbstractBackgroundObesity is associated with obstructive sleep apnea (OSA) and cardiovascular risk. Positive airway pressure (PAP) is the first line treatment for OSA, but evidence on its beneficial effect on major adverse cardiovascular events (MACE) prevention is limited. Using claims data, the effects of PAP on mortality and incidence of MACE among Medicare beneficiaries with OSA were examined.MethodsA cohort of Medicare beneficiaries with ≥2 distinct OSA claims was defined from multi-state, state-wide, multi-year (2011-2020) Medicare fee-for-service claims data. Evidence of PAP initiation and utilization was based on PAP claims after OSA diagnosis. MACE was defined as a composite of myocardial infarction, heart failure, stroke, or coronary revascularization. Doubly robust Cox proportional hazards models with inverse probability of treatment weights estimated treatment effects controlling for sociodemographic and clinical factors.ResultsAmong 888,835 beneficiaries with OSA (median age 73 years; 43.9% women; median follow-up 1,141 days), those with evidence of PAP initiation (32.6%) had significantly lower all-cause mortality (HR [95%CI]: 0.53 [0.52-0.54]) and MACE incidence risk (0.90 [0.89-0.91]). Higher quartiles of annual PAP claims were progressively associated with lower mortality (Q2: 0.84 [0.81-0.87], Q3: 0.76 [0.74-0.79], Q4: 0.74 [0.72-0.77]) and MACE incidence risk (Q2: 0.92 [0.89-0.95], Q3: 0.89 [0.86-0.91], Q4: 0.87 [0.85-0.90]).ConclusionPAP utilization was associated with lower all-cause mortality and MACE incidence among Medicare beneficiaries with OSA. Results might inform trials assessing the importance of OSA therapy towards minimizing cardiovascular risk and mortality in older adults.
Mid- and long-term risk of atrial fibrillation among breast cancer surgery survivors
Authors: Park Yong-Moon Mark , Jung Wonyoung , Yeo Yohwan , Park Sang Hyun , Fradley Michael G. , Malapati Sindhu J. , Tarun Tushar , Raj Vinay , Lee Hong Seok , Naqvi Tasneem Z. , Henry-Tillman Ronda S. , Mehta Jawahar L. , Schootman Mario , Amick Benjamin C. , Han Kyungdo , Shin Dong Wook 
Published: July 2023

AbstractBackgroundThe mid- and long-term risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. We aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment.MethodsUsing data from the Korean Health Insurance Service database between January 2010 and December 2017, 113,232 women newly diagnosed with breast cancer (aged ≥18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n=566,160). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities.ResultsDuring follow-up (mean [SD] follow-up, 5.1 [2.1] years), AF developed in 1,166 (1.0%) breast cancer surgery survivors at least 1 year after enrollment. Overall, breast cancer survivors had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00-1.13), but the association disappeared over time. Younger breast cancer survivors (age<40 years) had more than a 2-fold increase in AF risk (sHR 2.79; 95% CI 1.98-3.94), with the association remaining similar over 5 years of follow-up. The increased risk was not observed among older breast cancer survivors, especially those aged>65 years. Breast cancer survivors who received anthracyclines had an increased risk of AF compared to those without the exposure (sHR 1.57; 95% CI 1.28-1.92) over the entire course of follow-up. The association between anthracyclines and AF incidence was also more robust in younger breast cancer survivors (sHR 1.94; 95% CI 1.40-2.69 in those aged ≤50 years). Sensitivity analyses, including further adjustments for obesity and lifestyle factors, supported the results.ConclusionsOur findings suggest that younger breast cancer survivors had an elevated risk of incident AF, regardless of the length of follow-up. The use of anthracyclines may increase the mid-to-long-term AF risk among breast cancer surgery survivors.
Comparison of cardiovascular health profiles across population surveys from five high- to low-income countries
Authors: Ware Lisa , Vermeulen Bridget , Maposa Innocent , Flood David , Brant Luisa CC , Khandelwal Shweta , Singh Kavita , Soares Sara , Jessen Neusa , Perman Gastón , Riaz Baizid Khoorshid , Sachdev Harshpal Singh , Allen Norrina B , Labarthe Darwin R 
Published: July 2023

AbstractAimsWith the greatest burden of cardiovascular disease morbidity and mortality increasingly observed in lower-income countries least prepared for this epidemic, focus is widening from risk factor management alone to primordial prevention to maintain high levels of cardiovascular health (CVH) across the life course. To facilitate this, the American Heart Association (AHA) developed CVH scoring guidelines to evaluate and track CVH. We aimed to compare the prevalence and trajectories of high CVH across the life course using nationally representative adult CVH data from five diverse high- to low-income countries.MethodsSurveys with CVH variables (physical activity, cigarette smoking, body mass, blood pressure, blood glucose, and total cholesterol levels) were identified in Ethiopia, Bangladesh, Brazil, England, and the United States (US). Participants were included if they were 18-69y, not pregnant, and had data for these CVH metrics. Comparable data were harmonized and each of the CVH metrics was scored using AHA guidelines as high (2), moderate (1), or low (0) to create total CVH scores with higher scores representing better CVH. High CVH prevalence by age was compared creating country CVH trajectories.ResultsThe analysis included 28,092 adults (Ethiopia n=7686, 55.2% male; Bangladesh n=6731, 48.4% male; Brazil n=7241, 47.9 % male; England n=2691, 49.5% male, and the US n=3743, 50.3% male). As country income level increased, prevalence of high CVH decreased (>90% in Ethiopia, >68% in Bangladesh and under 65% in the remaining countries). This pattern remained using either five or all six CVH metrics and following exclusion of underweight participants. While a decline in CVH with age was observed for all countries, higher income countries showed lower prevalence of high CVH already by age 18y. Excess body weight appeared the main driver of poor CVH in higher income countries, while current smoking was highest in Bangladesh.ConclusionHarmonization of nationally representative survey data on CVH trajectories with age in 5 highly diverse countries supports our hypothesis that CVH decline with age may be universal. Interventions to promote and preserve high CVH throughout the life course are needed in all populations, tailored to country-specific time courses of the decline. In countries where CVH remains relatively high, protection of whole societies from risk factor epidemics may still be feasible.
Century-old chromatin architecture preserved with formaldehyde
Authors: Hahn Erin E. , Stiller Jiri , Alexander Marina , Grealy Alicia , Taylor Jennifer M. , Jackson Nicola , Frere Celine H. , Holleley Clare E. 
Published: July 2023

AbstractCo-ordinated regulation or dysregulation of chromatin architecture underpins fundamental biological processes, such as embryonic development, disease, cellular programming and response to environmental stress. The dynamic and plastic nature of chromatin accessibility is a major driver of phenotypic diversity, but we know shockingly little about the temporal dynamics of chromatin reorganisation and almost nothing prior to the existence of flash-frozen specimens. Linking two disparate fields by their common use and application of the preservative formaldehyde, we present an approach to characterise chromatin architecture in formaldehyde-preserved specimens up to 117 years old. We characterise how over-fixation modulates but does not eliminate genome-wide patterns of differential chromatin accessibility. Our novel analytical approach identifies promoter regions enriched for gene ontology terms matching the tissue of origin, resulting in sex-specific and environment-dependent genome-wide profiles. Contrary to prevailing dogma, we show that over-fixation is essential for the successful recovery of historical chromatin architecture. Our methodological and analytical advances open the door to the first detailed and comprehensive view of the epigenetic past and reveal a new role for museum collections in understanding chromatin architecture dynamics over the last century.
Sox3-null hypopituitarism depends on median eminence NG2-glia and is influenced by aspirin and gut microbiota
Authors: Galichet Christophe , Rizzoti Karine , Lovell-Badge Robin 
Published: July 2023

AbstractThe median eminence (ME), located at the base of the hypothalamus, is an essential centre of information exchange between the brain and the pituitary. We and others previously showed that mutations and duplications affecting the transcription factorSOX3/Sox3result in hypopituitarism, and this is likely of hypothalamic origin. We demonstrate here that the absence ofSox3predominantly affects the ME with phenotypes that first occur in juvenile animals, despite the embryonic onset of SOX3 expression. In the pituitary, reduction in hormone levels correlates with a lack of endocrine cell maturation. In parallel, ME NG2-glia renewal and oligodendrocytic differentiation potential are affected. We further show that low-dose aspirin treatment, which is known to affect NG2-glia, or changes in gut microbiota, rescue both proliferative defects and hypopituitarism inSox3mutants. Our study highlights a central role of NG2-glia for ME function during a transitional period of post-natal development, and indicates their sensitivity to environmental signals.
Single-cell gene expression prediction from DNA sequence at large contexts
Authors: Schwessinger Ron , Deasy Jacob , Woodruff Rob T. , Young Stephen , Branson Kim M. 
Published: July 2023

AbstractHuman genetic variants impacting traits such as disease susceptibility frequently act through modulation of gene expression in a highly cell-type-specific manner. Computational models capable of predicting gene expression directly from DNA sequence can assist in the interpretation of expression-modulating variants, and machine learning models now operate at the large sequence contexts required for capturing long-range human transcriptional regulation. However, existing predictors have focused on bulk transcriptional measurements where gene expression heterogeneity can be drowned out in broadly defined cell types. Here, we use a transfer learning framework, seq2cells, leveraging a pre-trained epigenome model for gene expression prediction from large sequence contexts at single-cell resolution. We show that seq2cells captures cell-specific gene expression beyond the resolution of pseudo-bulked data. Using seq2cells for variant effect prediction reveals heterogeneity within annotated cell types and enablesin silicotransfer of variant effects between cell populations. We demonstrate the challenges and value of gene expression and variant effect prediction at single-cell resolution, and offer a path to the interpretation of genomic variation at uncompromising resolution and scale.
The use of social information in vulture flight decisions
Authors: Yohan Sassi , Basile Nouzières , Martina Scacco , Yann Tremblay , Olivier Duriez , Benjamin Robira 
Published: July 2023

AbstractAnimals rely on a balance of personal and social information to decide when and where to move next in order to access a desired resource, such as food. The benefits from cueing on conspecifics to reduce uncertainty about resources availability can be rapidly overcome by the risks of within-group competition, often exacerbated toward low-ranked individuals. Being obligate soarers, relying on thermal updrafts to search for carcasses around which competition can be fierce, vultures represent ideal models to investigate the balance between personal and social information during foraging movements. Linking dominance hierarchy, social affinities and meteorological conditions to movement decisions of eight captive vultures,Gyps spp., released for free flights in natural-like soaring conditions, we found that they relied on social information (i.e. other vultures using/having used the thermals) to find the next thermal updraft, especially in unfavourable flight conditions. Low-ranked individuals were more likely to disregard social cues when deciding where to go next, possibly to minimise the competitive risk of social aggregation. These results exemplify the architecture of decision-making during flight in social birds. It suggests that the environmental context, the context of risk and the social system as a whole calibrate the balance between personal and social information use.
Noribogaine effects on wakefulness and sleep
Authors: Castro-Nin Juan Pedro , Serantes Diego , Rodriguez Paola , Gonzalez Bruno , Carrera Ignacio , Torterolo Pablo , González Joaquín 
Published: July 2023

AbstractIbogaine is a potent atypical psychedelic that has gained considerable attention due to its antiaddictive and antidepressant properties in preclinical and clinical studies. Previous research from our group showed that ibogaine suppresses sleep and produces an altered wakefulness state which resembles natural REM sleep. However, after systemic administration, ibogaine is rapidly metabolized to noribogaine, which also shows antiaddictive effects and a distinct pharmacological profile, making this drug a promising therapeutic candidate. Therefore, whether the sleep/wake alterations depend on ibogaine or its principal metabolite noribogaine remains unknown. To answer this question, we conducted polysomnographic recordings in rats following the administration of pure noribogaine. Our results show that noribogaine promotes wakefulness while reducing slow-wave sleep and blocking REM sleep. Thus, like ibogaine, noribogaine significantly alters the sleep-wake architecture, highlighting the possible role of serotonin reuptake inhibition as a likely candidate underlying the wake-promoting and REM sleep-suppressing effects.