bluuebunny/crossref_metadata_2025_split huggingface dataset:
Delayed blood pressure recovery after exercise stress test is associated with autonomic dysfunction and pulse pressure in a middle-aged healthy group
Authors: Lee Hancheol , Kim Hyeongsoo , Oh Seungjin , Park Jong-Kwan , Jang Ji-Yong , Chun Kyeong-Hyeon , Yoon Se-Jung 
Published: May 2023

AbstractBackgroundDelayed heart rate (HR) and blood pressure recovery after exercise test is known as the reliable indexes of autonomic dysfunction. Here we tried to evaluate the serial changes in various indicators during exercise test and correlations among them in a normotensive healthy middle-aged group.MethodsA total of 122 patients without hypertension or diabetes was enrolled (mean age, 55.6 ± 11.0; male, 56.6 %; mean blood pressure, 124.8 ± 16.6 / 81.5 ± 9.6 mmHg). Treadmill test was performed for evaluation of chest pain. Patients with coronary artery disease, positive treadmill test result, left ventricular dysfunction or renal failure were excluded. Heart rate recovery was calculated by subtracting the HR in the first or second minute of recovery period from the HR of peak exercise (HRR1 or HRR2). Systolic blood pressure in the 4thminute of recovery stage (SBPR4) was used to show delayed blood pressure recovery.ResultsMetabolic equivalents (METs) and HR in stage 2 to 4 were significantly correlated with both HRR1 and HRR2. Multiple regression analysis of HRR revealed significant correlation of METs and SBPR4. SBPR4 was significantly correlated with both HRR1 and HRR2 (HRR1, r=-0.376, p<0.001; HRR2, r=-0.244, p=0.008). SBPR4 revealed significant correlation with SBP in the baseline to stage 3 and pulse pressure (r=0.406, p<0.001).ConclusionsDelayed BP recovery after peak exercise test revealed significant association with autonomic dysfunction and pulse pressure in normotensive middle-aged healthy group. It can be a simple and useful marker of autonomic dysfunction and arterial stiffness.
IL-10 constrains sphingolipid metabolism via fatty acid desaturation to limit inflammation
Authors: York Autumn G. , Skadow Mathias H. , Qu Rihao , Oh Joonseok , Mowel Walter K. , Brewer J. Richard , Kaffe Eleanna , Williams Kevin J. , Kluger Yuval , Crawford Jason M. , Smale Stephen T. , Bensinger Steven J. , Flavell Richard A. 
Published: May 2023

AbstractUnchecked chronic inflammation is the underlying cause of many diseases, ranging from inflammatory bowel disease to obesity and neurodegeneration. Given the deleterious nature of unregulated inflammation, it is not surprising that cells have acquired a diverse arsenal of tactics to limit inflammation. IL-10 is a key anti-inflammatory cytokine that can limit immune cell activation and cytokine production in innate immune cell types; however, the exact mechanism by which IL-10 signaling subdues inflammation remains unclear. Here, we find that IL-10 signaling constrains sphingolipid metabolism. Specifically, we find increased saturated very long chain (VLC) ceramides are critical for the heightened inflammatory gene expression that is a hallmark of IL-10-deficient macrophages. Genetic deletion of CerS2, the enzyme responsible for VLC ceramide production, limited exacerbated inflammatory gene expression associated with IL-10 deficiency bothin vitroandin vivo, indicating that “metabolic correction” is able to reduce inflammation in the absence of IL-10. Surprisingly, accumulation of saturated VLC ceramides was regulated by flux through thede novomono-unsaturated fatty acid (MUFA) synthesis pathway, where addition of exogenous MUFAs could limit both saturated VLC ceramide production and inflammatory gene expression in the absence of IL-10 signaling. Together, these studies mechanistically define how IL-10 signaling manipulates fatty acid metabolism as part of its molecular anti-inflammatory strategy and could lead to novel and inexpensive approaches to regulate aberrant inflammation.
Polygenic risk of obesity and BMI trajectories over 36 years: a longitudinal study of adult Finnish twins
Authors: Berntzen Bram J. , Palviainen Teemu , Silventoinen Karri , Pietiläinen Kirsi H. , Kaprio Jaakko 
Published: May 2023

AbstractObjectiveWe investigated 36-year body mass index (BMI) trajectories in twins whose BMI in young adulthood was below, within, or above their genetically expected BMI, with a focus on twin pairs with large intrapair BMI differences (within-pair ΔBMI ≥ 3 kg/m2).MethodsTogether, 3227 like-sexed twin pairs (34% monozygotic [MZ]) were examined at age ∼30 in 1975 and followed up in 1981, 1990, and 2011. In 1975, the observed BMI of an individual was considered either within (±2.0 kg/m2), below (<-2.0 kg/m2), or above (>+2.0 kg/m2) genetically expected BMI, measured by a polygenic risk score of 996,919 single nucleotide polymorphisms.ResultsIn MZ and DZ twin pairs with large intrapair BMI differences, the co-twin with a higher observed BMI in 1975 deviated above expected BMI more frequently (∼2/3rd) than the co-twin with a lower BMI deviated below expectation (∼1/3rd). Individuals below, within, and above expectation in 1975 reached, respectively, normal weight, overweight, and obesity by 2011, with a mean BMI increase of 4.5 (95% confidence interval 4.3 to 4.8) kg/m2.ConclusionCategorizing BMI as below, within, or above PRS-predicted BMI helps identifying individuals who have been resistant or susceptible to weight gain. This may provide new insights into determinants and consequences of obesity.
Assessing Contributing and Mediating Factors of Telemedicine on Burnout
Authors: Boksa Valerie , Pennathur Priyadarshini 
Published: May 2023

Scientific AbstractObjectiveThe prevalence of burnout among healthcare providers has been steadily increasing, with a call to action issued in 2019. Immediately following this call to action, the COVID-19 pandemic drastically changed demand. Use of telemedicine expanded in response to COVID-19 and changed the experience of care delivery for healthcare providers. The impact of telemedicine use during COVID-19 on the provider well-being is less well known. This study aims to assess the prevalence of burnout in providers who used telemedicine and to better understand how specific factors of telemedicine can impact workplace stress.MethodsProviders in urgent care clinics were invited to participate in a burnout assessment survey using the Maslach Burnout Inventory questionnaire. The prevalence of burnout, burnout profiles, and correlations were analyzed in the resulting data. Follow-up interviews provided further insight on contributing and mediating factors of telemedicine on provider burnout.ResultsThe findings from this study provide technology- and organizational-level recommendations to prevent increased risk of burnout among telemedicine providers. The classification of contributing and mediating factors also provides a framework for understanding the risks that this technology can pose to workplace stress. Future research recommendations to better quantify the relationship between burnout and telemedicine use and to effectively design intervention and implementation strategies are discussed.Public Interest SummaryConsidering the high rates of burnout in the healthcare industry prior to the pandemic, the severe demands the COVID-19 pandemic had on healthcare workers, and the drastic changes in workflow due to the widespread adoption of telemedicine, it is important to assess current levels of provider burnout and to collect information from frontline clinicians on how telemedicine impacts workplace stress. A survey was administered to assess burnout in healthcare workers who provided care via telemedicine. The interviews provided additional insight on how telemedicine affected workplace stress. Survey results showed that 25% of the respondents reported one or more manifestations of burnout; and there was a correlation between personal accomplishment scores and reported months of telemedicine use. Findings from the interviews and review of literature identified what design and use characteristics of telemedicine contributed to and/or alleviated burnout. Results address how organizations can best support their employees who administer care via telemedicine and guide researchers with direction for future studies.
Specific Modulation of CRISPR Transcriptional Activators through RNA-Sensing Guide RNAs in Mammalian Cells and Zebrafish Embryos
Authors: Pelea Oana , Mayes Sarah , Ferry Quentin RV. , Fulga Tudor A. , Sauka-Spengler Tatjana 
Published: May 2023

AbstractCellular transcripts encode important information regarding cell identity and disease status. The activation of CRISPR in response to RNA biomarkers holds the potential for controlling CRISPR activity with spatiotemporal precision. This would enable the restriction of CRISPR activity to specific cell types expressing RNA biomarkers of interest while preventing unwanted activity in other cells. Here, we present a simple and specific platform for modulating CRISPR activity in response to RNA detection through engineeringStreptococcus pyogenesCas9 single-guide RNAs (sgRNAs). sgRNAs are engineered to fold into complex secondary structures that, in the ground state, inhibit their activity. The engineered sgRNAs become activated upon recognising complementary RNAs, thus enabling Cas9 to perform its function. Our approach enables CRISPR activation in response to RNA detection in both HEK293T cells and zebrafish embryos. Iterative design optimisations allowed the development of computational tools for generating sgRNAs capable of detecting RNA sequences of choice. Mechanistic investigations reveal that engineered sgRNAs are cleaved during RNA detection, and we identify key positions that benefit from chemical modifications to improve the stability of engineered sgRNAsin vivo. Our sensors open up novel opportunities for developing new research and therapeutic applications using CRISPR activation in response to endogenous RNA biomarkers.
CD38 regulates ovarian function and fecundity via NAD+metabolism
Authors: Perrone Rosalba , Ashok Kumaar Prasanna Vadhana , Haky Lauren , Hahn Cosmo , Riley Rebeccah , Balough Julia , Zaza Giuliana , Soygur Bikem , Hung Kaitlyn , Prado Leandro , Kasler Herbert G. , Tiwari Ritesh , Matsui Hiroyuki , Hormazabal Genesis Vega , Duncan Francesca Elizabeth , Verdin Eric 
Published: May 2023

SummaryMammalian female reproductive lifespan is typically significantly shorter than life expectancy and is associated with a decrease in ovarian NAD+ levels. However, the mechanisms underlying this loss of ovarian NAD+ are unclear. Here, we show that CD38, a NAD+ consuming enzyme, is expressed in the ovarian extrafollicular space, primarily in immune cells, and its levels increase with reproductive age. Reproductively young mice lacking CD38 exhibit larger primordial follicle pools, elevated ovarian NAD+ levels, and increased fecundity relative to wild type controls. This larger ovarian reserve results from a prolonged window of follicle formation during early development. However, the beneficial effect of CD38 loss on reproductive function is not maintained at advanced age. Our results demonstrate a novel role of CD38 in regulating ovarian NAD+ metabolism and establishing the ovarian reserve, a critical process that dictates a female’s reproductive lifespan.
Prefrontal cortex proteomic alteration after social instability stress in adolescents rats
Authors: Santos Evelyn C. S. , Terceiro Ana Filipa , Vitorino Rui , Lopes Igor , Alves Renata L. , Relvas João B. , Summavielle Teresa , Magalhães Ana 
Published: May 2023

AbstractEarly life stress can have significant effects on the developing brain and lead to changes in the structure and function of brain regions involved in stress regulation, emotion and cognitive control. Here, we used the social instability stress (SIS) protocol to understand the impact of social stress during mild (PND30) and late (PND45) adolescence. Our results revealed that SIS can compromise the dominance-subordination coping strategy but does not affect social recognition and motivation in rats. Moreover, SIS can lead to subtle modifications at the molecular level that hamper normal development of the prefrontal cortex in a sex- and age-dependent manner. Understanding the impact of early life stress on brain organization is crucial for developing effective prevention and intervention strategies. By identifying those who are most vulnerable to the effects of stress and providing targeted support and resources, it may be possible to mitigate the negative consequences of early adversity and promote healthy brain development.
Genome-wide analysis of Respiratory burst oxidase homolog (Rboh) genes inAquilariaspecies and its association with agarwood formation
Authors: Begum Khaleda , Das Ankur , Ahmed Raja , Akhtar Suraiya , Kulkarni Ram , Banu Sofia 
Published: May 2023

AbstractRespiratory burst oxidase homolog (Rboh), generate reactive oxygen species (ROS) to maintain normal growth and pathogen induced defence responses in plants. InAquilariaplants, wounding and fungal invasion results in the biosynthesis of secondary metabolites as a defence response which with due course develop into agarwood. During pathogen invasion,Aquilariatree accumulate ROS species through the action of Rboh enzymes. Although in agarwood formation role of Rboh gene family has been implicated, an comprehensives study onRbohgene family and information of its role during agarwood formation in missing. In this study, sevenRbohgenes were identified from the genomes of twoAquilariaspecies viz.,Aquilaria agallochaandAquilaria sinensisand phylogenetically classified into five groups.Stress response, hormone regulation, and development related regulatory elements were identified in the promoter regions. The protein sequences comprised of four conserved domains, an EF-hand domain, and a transmembrane region which they probably utilise for MAPK signaling, plant-pathogen interaction and plant hormone signal transduction pathways. Expression analyses revealed that among the seven members,AaRbohAandAaRhobCwere involved in generation of ROS species, and also probably play role in agarwood formation. These findings provide valuable information regarding the Rboh members ofA. agallochawhich can be further used for functional analyses for in-depth understanding of ROS mediated signalling and regulation of agarwood formation.Graphical abstract
Application of a1H Brain MRS Benchmark Dataset to Deep Learning for Out-of-Voxel Artifacts
Authors: Gudmundson Aaron T. , Davies-Jenkins Christopher W. , Özdemir İpek , Murali-Manohar Saipavitra , Zöllner Helge J. , Song Yulu , Hupfeld Kathleen E. , Schnitzler Alfons , Oeltzschner Georg , Stark Craig E. L. , Edden Richard A. E. 
Published: May 2023

AbstractNeural networks are potentially valuable for many of the challenges associated with MRS data. The purpose of this manuscript is to describe the AGNOSTIC dataset, which contains 259,200 synthetic1H MRS examples for training and testing neural networks. AGNOSTIC was created using 270 basis sets that were simulated across 18 field strengths and 15 echo times. The synthetic examples were produced to resemblein vivobrain data with combinations of metabolite, macromolecule, residual water signals, and noise. To demonstrate the utility, we apply AGNOSTIC to train two Convolutional Neural Networks (CNNs) to address out-of-voxel (OOV) echoes. A Detection Network was trained to identify the point-wise presence of OOV echoes, providing proof of concept for real-time detection. A Prediction Network was trained to reconstruct OOV echoes, allowing subtraction during post-processing. Complex OOV signals were mixed into 85% of synthetic examples to train two separate CNNs for the detection and prediction of OOV signals. AGNOSTIC is available through Dryad and all Python 3 code is available through GitHub. The Detection network was shown to perform well, identifying 95% of OOV echoes. Traditional modeling of these detected OOV signals was evaluated and may prove to be an effective method during linear-combination modeling. The Prediction Network greatly reduces OOV echoes within FIDs and achieved a median log10normed-MSE of –1.79, an improvement of almost two orders of magnitude.
Connectome-wide structure-function coupling models implicate polysynaptic alterations in autism
Authors: Park Bo-yong , Benkarim Oualid , Weber Clara F. , Kebets Valeria , Fett Serena , Yoo Seulki , Martino Adriana Di , Milham Michael P. , Misic Bratislav , Hong Seok-Jun , Bernhardt Boris C. 
Published: May 2023

AbstractAutism spectrum disorder (ASD) is one of the most common neurodevelopmental diagnoses. Although incompletely understood, structural and functional network alterations are increasingly recognized to be at the core of the condition. We utilized multimodal imaging and connectivity modeling to study structure-function coupling in ASD, and probed mono- and polysynaptic mechanisms on structurally-governed network function. We examined multimodal magnetic resonance imaging data in 47 ASD and 37 neurotypical controls from the Autism Brain Imaging Data Exchange (ABIDE) II initiative. We predicted intrinsic functional connectivity from structural connectivity data in each participant using a Riemannian optimization procedure that varies the times that simulated signals can unfold along tractography-derived personalized connectomes. In both ASD and neurotypical controls, we observed improved structure-function prediction at longer diffusion time scales, indicating better modeling of brain function when polysynaptic mechanisms are accounted for. Prediction improvements were marked in transmodal association systems, such as the default mode network, in both controls and ASD. Improvements were, however, lower in ASD in a polysynaptic regime at higher simulated diffusion times. Regional differences followed a sensory-to-transmodal cortical hierarchy, with an increased gap between groups in transmodal compared to sensory/motor systems. Multivariate associative techniques revealed that structure-function differences reflected inter-individual differences in autistic symptoms and verbal as well as non-verbal intelligence. Our network modeling approach sheds light on atypical structure-function coupling in autism, and suggests that polysynaptic network mechanisms are implicated in the condition and can help explain its wide range of associated symptoms.
Patterned Metal Grids for Flexible and Transparent Neural Microelectrode Arrays
Authors: Trêpo Ivânia , Pinto Joana V. , Santa Ana , Pereira Maria E. , Calmeiro Tomás , Coelho Beatriz , Henriques Célia , Martins Rodrigo , Fortunato Elvira , Carey Megan R. , Marques Hugo G. , Barquinha Pedro , Neto Joana P. 
Published: May 2023

AbstractFlexible and transparent microelectrodes can provide large-scale neural recordings with temporal and spatial resolution when used alongside functional calcium imaging. Patterned metal grids defined by direct laser writing (DWL) are a promising approach for these electrodes, as they resort to standard microfabrication processes and materials, allowing the possibility of mass production. For these reasons, a study exploring transparent grid-based electrodes using DWL for measuring electrocorticography signal was performed. Patterned metal grids with 1 μm of linewidth and 22 μm of spacing between lines showed a sheet resistance of 6 Ω/sq and a transmittance of 81% at 550 nm. The grids were transferred to a 5 μm Parylene-C membrane using an optimized procedure that involves an oxygen plasma pre-treatment. This procedure ensures mechanical robustness and stability of the grids. Finally, a flexible and transparent prototype was fabricated with a microelectrode array composed by 16 electrodes with 500 μm of diameter. These microelectrodes shown an impedance of 10 kΩ at 1 kHz in saline solution and they are highly conformal facilitating in vivo implantation and the recording of neural activity in the mouse cerebellum surface. To conclude, patterned metal grids based-electrodes exhibit a promising performance compared to transparent conductive oxides or graphene. Moreover, the introduction of DLW enables easy and fast manipulation of grid shape and dimensions without the need of physical masks, while keeping large scale compatibility, which is important for tools used in neuroscience community.
Monomethylation of Lysine 27 at Histone 3 Confers Lifelong Susceptibility to Stress
Authors: Torres-Berrío Angélica , Estill Molly , Ramakrishnan Aarthi , Kronman Hope , Patel Vishwendra , Minier-Toribio Angélica , Issler Orna , Browne Caleb J. , Parise Eric M. , van der Zee Yentl , Walker Deena , Martínez-Rivera Freddyson J. , Lardner Casey K. , Durand-de Cuttoli Romain , Russo Scott J. , Shen Li , Sidoli Simone , Nestler Eric J. 
Published: May 2023

SUMMARYHistone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling, and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice exposed to early life stress (ELS) or to chronic social defeat stress (CSDS) in adulthood displayed increased enrichment of H3K27me1, and transient decreases in H3K27me2, in the nucleus accumbens (NAc), a key brain-reward region. Stress induction of H3K27me1 was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which is induced by chronic stress and controls H3K27 methylation patterns. Overexpression of the VEFS domain led to social, emotional, and cognitive abnormalities, and altered excitability of NAc D1 mediums spiny neurons. Together, we describe a novel function of H3K27me1 in brain and demonstrate its role as a “chromatin scar” that mediates lifelong stress susceptibility.
Optogenetic determination of dynamic and cell-type-specific chloride equilibrium potentials
Authors: Burman Richard J. , Diviney Tara , Călin Alexandru , Gothard Gemma , Jouhanneau Jean-Sébastien M. , Poulet James F.A. , Sen Arjune , Akerman Colin J. 
Published: May 2023

AbstractOptogenetics has revolutionized neurobiological research by providing tools for modulating neuronal activity. As these tools utilise light-activated ion fluxes, they afford new opportunities to examine the nature of transmembrane ion gradients. Traditional investigation into the equilibrium potential for chloride (ECl) has been limited to studying endogenous chloride-permeable receptors. Here we demonstrate the utility of using a light-activated chloride channel, stGtACR2, to probe somatic EClin rodent. This agonist-independent optogenetic strategy is validatedin vitroandin vivo, captures differences in ECldynamics following manipulations of endogenous chloride fluxes, and reveals distinct resting EClacross genetically-defined neuronal subpopulations. Using this approach to challenge chloride homeostasis, we uncover cell-specific ECldynamics that are supported by the differential expression of endogenous handling mechanisms. Our findings establish an optical method for investigating transmembrane chloride gradients and thereby expand the repertoire of optogenetics.