bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammation in children with cystic fibrosis: contribution of bacterial production of long-chain fatty acids
Authors: Felton Erin , Burrell Aszia , Chaney Hollis , Sami Iman , Koumbourlis Anastassios C. , Freishtat Robert J. , Crandall Keith A. , Hahn Andrea 
Published: March 2021

Abstract
Background
Cystic fibrosis (CF) affects >70,000 people worldwide, yet the microbiologic trigger for pulmonary exacerbations (PExs) remains unknown. The objective of this study was to identify changes in bacterial metabolic pathways associated with clinical status.

Methods
Respiratory samples were collected at hospital admission for PEx, end of intravenous (IV) antibiotic treatment, and follow-up from 27 hospitalized children with CF. Bacterial DNA was extracted and shotgun DNA sequencing was performed. MetaPhlAn2 and HUMAnN2 were used to evaluate bacterial taxonomic and pathway relative abundance, while DESeq2 was used to evaluate differential abundance based on clinical status.

Results
The mean age of study participants was 10 years; 85% received combination IV antibiotic therapy (beta-lactam plus a second agent). Long-chain fatty acid (LCFA) biosynthesis pathways were upregulated in follow-up samples compared to end of treatment: gondoate (p = 0.012), oleate (p = 0.048), palmitoleate (p = 0.043), and pathways of fatty acid elongation (p = 0.012). Achromobacter xylosoxidans and Escherichia sp. were also more prevalent in follow-up compared to PEx (p < 0.001).

Conclusions
LCFAs may be associated with persistent infection of opportunistic pathogens. Future studies should more closely investigate the role of LCFA production by lung bacteria in the transition from baseline wellness to PEx in persons with CF.

Impact

Increased levels of LCFAs are found after IV antibiotic treatment in persons with CF.

LCFAs have previously been associated with increased lung inflammation in asthma.

This is the first report of LCFAs in the airway of persons with CF.

This research provides support that bacterial production of LCFAs may be a contributor to inflammation in persons with CF.

Future studies should evaluate LCFAs as predictors of future PExs.
Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression
Authors: MahmoudianDehkordi Siamak , Ahmed Ahmed T. , Bhattacharyya Sudeepa , Han Xianlin , Baillie Rebecca A. , Arnold Matthias , Skime Michelle K. , John-Williams Lisa St. , Moseley M. Arthur , Thompson J. Will , Louie Gregory , Riva-Posse Patricio , Craighead W. Edward , McDonald William , Krishnan Ranga , Rush A. John , Frye Mark A. , Dunlop Boadie W. , Weinshilboum Richard M. , Kaddurah-Daouk Rima ,   The Mood Disorders Precision Medicine Consortium (MDPMC), Kaddurah-Daouk Rima , Rush John , Tenenbaum Jessica , Moseley Arthur , Thompson Will , Louie Gregory , Blach Colette , Mahmoudiandehkhordi Siamak , Baillie Rebecca , Han Xianlin , Bhattacharyya Sudeepa , Frye Mark , Weinshilboum Richard , Ahmed Ahmed , Neavin Drew , Liu Duan , Skime Michelle , Rinaldo Piero , Fiehn Oliver , Brydges Christopher , Mayberg Helen , Choi Ki Sueng , Cha Jungho , Kastenmüller Gabi , Arnold Matthias , Binder Elisabeth , Knauer-Arloth Janine , Nevado-Holgado Alejo , Shi Liu , Dunlop Boadie , Craighead Ed , McDonald William , Posse Patricio Riva , Penninx Brenda , Milaneschi Yuri , Jansen Rick , Krishnan Ranga 
Published: March 2021

AbstractSelective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment. After treatment, we saw increased levels of short-chain acylcarnitines and decreased levels of medium-chain and long-chain acylcarnitines, suggesting an SSRI effect on β-oxidation and mitochondrial function. Amines—including arginine, proline, and methionine sulfoxide—were upregulated while serotonin and sarcosine were downregulated, suggesting an SSRI effect on urea cycle, one-carbon metabolism, and serotonin uptake. Eighteen lipids within the phosphatidylcholine (PC aa and ae) classes were upregulated. Changes in several lipid and amine levels correlated with changes in 17-item Hamilton Rating Scale for Depression scores (HRSD17). Differences in metabolic profiles at baseline and post-treatment were noted between participants who remitted (HRSD17 ≤ 7) and those who gained no meaningful benefits (<30% reduction in HRSD17). Remitters exhibited (a) higher baseline levels of C3, C5, alpha-aminoadipic acid, sarcosine, and serotonin; and (b) higher week-8 levels of PC aa C34:1, PC aa C34:2, PC aa C36:2, and PC aa C36:4. These findings suggest that mitochondrial energetics—including acylcarnitine metabolism, transport, and its link to β-oxidation—and lipid membrane remodeling may play roles in SSRI treatment response.
Late-life depression and increased risk of dementia: a longitudinal cohort study
Authors: Ly M. , Karim H. T. , Becker J. T. , Lopez O. L. , Anderson S. J. , Aizenstein H. J. , Reynolds C. F. , Zmuda M. D. , Butters M. A. 
Published: March 2021

AbstractLate-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the community and whether stratification of LLD into early-onset depression (EOD) and late-onset depression (LOD) subtypes revealed differing rates and domain-specific expression of cognitive decline. We conducted a prospective, longitudinal study where 185 participants with LLD (remitted) and 114 NDC were followed for 5 years on average. EOD was defined as having first lifetime depressive episode at <60years and LOD at ≥60years. Every year, participants underwent comprehensive neuropsychological assessment. Composite scores for each cognitive domain were calculated through averaging standardized scores across tests. LLD compared to NDC demonstrated significant baseline impairment but did not decline more rapidly. EOD were significantly impaired in attention/processing speed and global cognitive function at baseline but did not experience more rapid decline as compared to NDC. Those with LOD compared to both NDC and EOD performed worse in all domains at baseline and experienced more rapid decline in verbal skills and delayed memory ability. Our findings suggest that baseline impairment may lower the threshold for those with LLD to develop dementia. EOD and LOD may represent distinct phenotypes of cognitive impairment with differing neural substrates. LOD may represent a distinct phenotype with a more rapid decline in verbal skills and delayed memory.
Structural brain network topology underpinning ADHD and response to methylphenidate treatment
Authors: Griffiths Kristi R. , Braund Taylor A. , Kohn Michael R. , Clarke Simon , Williams Leanne M. , Korgaonkar Mayuresh S. 
Published: March 2021

AbstractBehavioural disturbances in attention deficit hyperactivity disorder (ADHD) are thought to be due to dysfunction of spatially distributed, interconnected neural systems. While there is a fast-growing literature on functional dysconnectivity in ADHD, far less is known about the structural architecture underpinning these disturbances and how it may contribute to ADHD symptomology and treatment prognosis. We applied graph theoretical analyses on diffusion MRI tractography data to produce quantitative measures of global network organisation and local efficiency of network nodes. Support vector machines (SVMs) were used for comparison of multivariate graph measures of 37 children and adolescents with ADHD relative to 26 age and gender matched typically developing children (TDC). We also explored associations between graph measures and functionally-relevant outcomes such as symptom severity and prediction of methylphenidate (MPH) treatment response. We found that multivariate patterns of reduced local efficiency, predominantly in subcortical regions (SC), were able to distinguish between ADHD and TDC groups with 76% accuracy. For treatment prognosis, higher global efficiency, higher local efficiency of the right supramarginal gyrus and multivariate patterns of increased local efficiency across multiple networks at baseline also predicted greater symptom reduction after 6 weeks of MPH treatment. Our findings demonstrate that graph measures of structural topology provide valuable diagnostic and prognostic markers of ADHD, which may aid in mechanistic understanding of this complex disorder.
A novel art of continuous noninvasive blood pressure measurement
Authors: Fortin Jürgen , Rogge Dorothea E. , Fellner Christian , Flotzinger Doris , Grond Julian , Lerche Katja , Saugel Bernd 
Published: March 2021

AbstractWearable sensors to continuously measure blood pressure and derived cardiovascular variables have the potential to revolutionize patient monitoring. Current wearable methods analyzing time components (e.g., pulse transit time) still lack clinical accuracy, whereas existing technologies for direct blood pressure measurement are too bulky. Here we present an innovative art of continuous noninvasive hemodynamic monitoring (CNAP2GO). It directly measures blood pressure by using a volume control technique and could be used for small wearable sensors integrated in a finger-ring. As a software prototype, CNAP2GO showed excellent blood pressure measurement performance in comparison with invasive reference measurements in 46 patients having surgery. The resulting pulsatile blood pressure signal carries information to derive cardiac output and other hemodynamic variables. We show that CNAP2GO can self-calibrate and be miniaturized for wearable approaches. CNAP2GO potentially constitutes the breakthrough for wearable sensors for blood pressure and flow monitoring in both ambulatory and in-hospital clinical settings.
Observation of an electronic order along [110] direction in FeSe
Authors: Bu Kunliang , Zhang Wenhao , Fei Ying , Zheng Yuan , Ai Fangzhou , Wu Zongxiu , Wang Qisi , Wo Hongliang , Zhao Jun , Yin Yi 
Published: March 2021

AbstractMultiple ordered states have been observed in unconventional superconductors. Here, we apply scanning tunneling microscopy to probe the intrinsic ordered states in FeSe, the structurally simplest iron-based superconductor. Besides the well-known nematic order along [100] direction, we observe a checkerboard charge order in the iron lattice, which we name a [110] electronic order in FeSe. The [110] electronic order is robust at 77 K, accompanied with the rather weak [100] nematic order. At 4.5 K, The [100] nematic order is enhanced, while the [110] electronic order forms domains with reduced correlation length. In addition, the collective [110] order is gaped around [−40, 40] meV at 4.5 K. The observation of this exotic electronic order may shed new light on the origin of the ordered states in FeSe.
Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins
Authors: Chen Liwei , Park Jung Eun , Paa Peter , Rajakumar Priscilla D. , Prekop Hong-Ting , Chew Yi Ting , Manivannan Swathi N. , Chew Wei Leong 
Published: March 2021

AbstractMany genetic diseases are caused by single-nucleotide polymorphisms. Base editors can correct these mutations at single-nucleotide resolution, but until recently, only allowed for transition edits, addressing four out of twelve possible DNA base substitutions. Here, we develop a class of C:G to G:C Base Editors to create single-base genomic transversions in human cells. Our C:G to G:C Base Editors consist of a nickase-Cas9 fused to a cytidine deaminase and base excision repair proteins. Characterization of >30 base editor candidates reveal that they predominantly perform C:G to G:C editing (up to 90% purity), with rAPOBEC-nCas9-rXRCC1 being the most efficient (mean 15.4% and up to 37% without selection). C:G to G:C Base Editors target cytidine in WCW, ACC or GCT sequence contexts and within a precise three-nucleotide window of the target protospacer. We further target genes linked to dyslipidemia, hypertrophic cardiomyopathy, and deafness, showing the therapeutic potential of these base editors in interrogating and correcting human genetic diseases.
Structures of mouse and human GITR–GITRL complexes reveal unique TNF superfamily interactions
Authors: Wang Feng , Chau Bryant , West Sean M. , Kimberlin Christopher R. , Cao Fei , Schwarz Flavio , Aguilar Barbara , Han Minhua , Morishige Winse , Bee Christine , Dollinger Gavin , Rajpal Arvind , Strop Pavel 
Published: March 2021

AbstractGlucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) are members of the tumor necrosis superfamily that play a role in immune cell signaling, activation, and survival. GITR is a therapeutic target for directly activating effector CD4 and CD8 T cells, or depleting GITR-expressing regulatory T cells (Tregs), thereby promoting anti-tumor immune responses. GITR activation through its native ligand is important for understanding immune signaling, but GITR structure has not been reported. Here we present structures of human and mouse GITR receptors bound to their cognate ligands. Both species share a receptor–ligand interface and receptor–receptor interface; the unique C-terminal receptor–receptor enables higher order structures on the membrane. Human GITR–GITRL has potential to form a hexameric network of membrane complexes, while murine GITR–GITRL complex forms a linear chain due to dimeric interactions. Mutations at the receptor–receptor interface in human GITR reduce cell signaling with in vitro ligand binding assays and minimize higher order membrane structures when bound by fluorescently labeled ligand in cell imaging experiments.
General molten-salt route to three-dimensional porous transition metal nitrides as sensitive and stable Raman substrates
Authors: Guan Haomin , Li Wentao , Han Jing , Yi Wencai , Bai Hua , Kong Qinghong , Xi Guangcheng 
Published: March 2021

AbstractTransition metal nitrides have been widely studied due to their high electrical conductivity and excellent chemical stability. However, their preparation traditionally requires harsh conditions because of the ultrahigh activation energy barrier they need to cross in nucleation. Herein, we report three-dimensional porous VN, MoN, WN, and TiN with high surface area and porosity that are prepared by a general and mild molten-salt route. Trace water is found to be a key factor for the formation of these porous transition metal nitrides. The porous transition metal nitrides show hydrophobic surface and can adsorb a series of organic compounds with high capacity. Among them, the porous VN shows strong surface plasmon resonance, high conductivity, and a remarkable photothermal conversion efficiency. As a new type of corrosion- and radiation-resistant surface-enhanced Raman scattering substrate, the porous VN exhibits an ultrasensitive detection limit of 10−11 M for polychlorophenol.
Modeling of CO2-LPG WAG with asphaltene deposition to predict coupled enhanced oil recovery and storage performance
Authors: Cho Jinhyung , Min Baehyun , Jeong Moon Sik , Lee Young Woo , Lee Kun Sang 
Published: March 2021

AbstractCombined carbon capture and storage and CO2-enhanced oil recovery (CCS-EOR) can reconcile the demands of business with the need to mitigate the effects of climate change. To improve the performance of CCS-EOR, liquefied petroleum gas (LPG) can be co-injected with CO2, leading to a reduction in the minimum miscibility pressure. However, gas injection can cause asphaltene problems, which undermines EOR and CCS performances simultaneously. Here, we systematically examine the mechanisms of asphaltene deposition using compositional simulations during CO2-LPG–comprehensive water–alternating-gas (WAG) injection. The LPG accelerates asphaltene deposition, reducing gas mobility, and increases the performance of residual trapping by 9.2% compared with CO2 WAG. In contrast, solubility trapping performance declines by only 3.7% because of the greater reservoir pressure caused by the increased formation damage. Adding LPG enhances oil recovery by 11% and improves total CCS performance by 9.1% compared with CO2 WAG. Based on reservoir simulations performed with different LPG concentrations and WAG ratios, we confirmed that the performance improvement of CCS-EOR associated with increasing LPG and water injection reaches a plateau. An economic evaluation based on the price of LPG should be carried out to ensure practical success.
SSVEP phase synchronies and propagation during repetitive visual stimulation at high frequencies
Authors: Tsoneva Tsvetomira , Garcia-Molina Gary , Desain Peter 
Published: March 2021

AbstractSteady-state visual evoked potentials (SSVEPs), the brain response to visual flicker stimulation, have proven beneficial in both research and clinical applications. Despite the practical advantages of stimulation at high frequencies in terms of visual comfort and safety, high frequency-SSVEPs have not received enough attention and little is known about the mechanisms behind their generation and propagation in time and space. In this study, we investigated the origin and propagation of SSVEPs in the gamma frequency band (40–60 Hz) by studying the dynamic properties of EEG in 32 subjects. Using low-resolution brain electromagnetic tomography (sLORETA) we identified the cortical sources involved in SSVEP generation in that frequency range to be in the primary visual cortex, Brodmann areas 17, 18 and 19 with minor contribution from sources in central and frontal sites. We investigated the SSVEP propagation as measured on the scalp in the framework of the existing theories regarding the neurophysiological mechanism through which the SSVEP spreads through the cortex. We found a progressive phase shift from posterior parieto-occipital sites over the cortex with a phase velocity of approx. 8–14 m/s and wavelength of about 21 and 24 cm. The SSVEP spatial properties appear sensitive to input frequency with higher stimulation frequencies showing a faster propagation speed.
Fascia lata packing and tension suturing for symptomatic pseudomeningocele after recurrent cervical intradural tumour resection
Authors: Xu Huanbo , Huang Yangliang , Zhong Yi , Lu Guowang 
Published: March 2021

AbstractIn recurrent posterior cervical intradural tumour resections, serious complications can be developed. The dural can become affected by inflammatory factors or removed during tumor resection; if cerebrospinal fluid (CSF) leakage cannot be stopped by duraplasty, artificial meninges or fascia repair, large pseudomeningocele can develop posteriorly within the soft tissue of the neck. When the pressure of the CSF cannot be maintained steadily, persistent clinical symptoms can occur, such as postural headache or central fever. Moreover, the skin can also be penetrated in a few patients even after extension of the drainage duration, lumbar cistern drainage or skin suturing, leading to the induction of life-threatening intra-cranial infections. Is there a simple and effective surgical method to address this scenario? The aim of this study was, therefore, to investigate the effectiveness of fascia lata packing and tension suturing in the treatment of symptomatic pseudomeningocele after recurrent posterior cervical intradural tumour resection. In our study, nine consecutive spinal surgery patients were recruited from January 2008 to January 2018. All pseudomeningoceles were combined with postural headache, central neurological fever or wound non-union. There were 3 cases of melanocytoma, 3 cases of nasopharyngeal carcinoma metastasis, 2 cases of breast cancer metastasis, and 1 case of spinal canal lymphadenoma. Standard patient demographics, diagnosis, post-operative symptoms, wound healing time, and the largest pre- and last follow-up pseudomeningocele area on axial MRI sections were recorded. All cases were followed-up successfully, from 12 to 24 months, with an average of 15.3 months. Our observations indicate that all wounds healed successfully. The wound union time was 20.7 days on average. After wound union, these patients became symptom free. The largest cerebrospinal fluid area on axial MRI sections improved significantly from 42.9 ± 5.01 cm2 at p re-operation to 6.6 ± 1.89 cm2 at 1 year post-operation (P < 0.05); Our data indicate that .the proposed procedure is simple, safe and effective. And more importantly, it allows rapid closure of any cerebrospinal fluid leakage pools.
Workflow towards automated segmentation of agglomerated, non-spherical particles from electron microscopy images using artificial neural networks
Authors: Rühle Bastian , Krumrey Julian Frederic , Hodoroaba Vasile-Dan 
Published: March 2021

AbstractWe present a workflow for obtaining fully trained artificial neural networks that can perform automatic particle segmentations of agglomerated, non-spherical nanoparticles from scanning electron microscopy images “from scratch”, without the need for large training data sets of manually annotated images. The whole process only requires about 15 min of hands-on time by a user and can typically be finished within less than 12 h when training on a single graphics card (GPU). After training, SEM image analysis can be carried out by the artificial neural network within seconds. This is achieved by using unsupervised learning for most of the training dataset generation, making heavy use of generative adversarial networks and especially unpaired image-to-image translation via cycle-consistent adversarial networks. We compare the segmentation masks obtained with our suggested workflow qualitatively and quantitatively to state-of-the-art methods using various metrics. Finally, we used the segmentation masks for automatically extracting particle size distributions from the SEM images of TiO2 particles, which were in excellent agreement with particle size distributions obtained manually but could be obtained in a fraction of the time.
First evidence for the presence of amino acid sensing mechanisms in the fish gastrointestinal tract
Authors: Calo Jessica , Blanco Ayelén M. , Comesaña Sara , Conde-Sieira Marta , Morais Sofia , Soengas José L. 
Published: March 2021

AbstractThis study aimed to characterize amino acid sensing systems in the gastrointestinal tract (GIT) of the carnivorous fish model species rainbow trout. We observed that the trout GIT expresses mRNAs encoding some amino acid receptors described in mammals [calcium-sensing receptor (CaSR), G protein-coupled receptor family C group 6 member A (GPRC6A), and taste receptors type 1 members 1 and 2 (T1r1, T1r2)], while others [taste receptor type 1 member 3 (T1r3) and metabotropic glutamate receptors 1 and 4 (mGlur1, mGlur4)] could not be found. Then, we characterized the response of such receptors, as well as that of intracellular signaling mechanisms, to the intragastric administration of l-leucine, l-valine, l-proline or l-glutamate. Results demonstrated that casr, gprc6a, tas1r1 and tas1r2 mRNAs are modulated by amino acids in the stomach and proximal intestine, with important differences with respect to mammals. Likewise, gut amino acid receptors triggered signaling pathways likely mediated, at least partly, by phospholipase C β3 and β4. Finally, the luminal presence of amino acids led to important changes in ghrelin, cholecystokinin, peptide YY and proglucagon mRNAs and/or protein levels. Present results offer the first set of evidence in favor of the existence of amino acid sensing mechanisms within the fish GIT.