bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of the Distortion of Vertical Wavenumber Spectra on Estimates of Turbulent Dissipation Using the Finescale Parameterization: Observations in the Antarctic Circumpolar Current
Authors: Takahashi Anne , Hibiya Toshiyuki 
Published: May 2021

AbstractFinescale parameterizations are powerful tools for estimating the global distribution of turbulent kinetic energy dissipation rates ɛ. However, they tend to overestimate ɛ in the Antarctic Circumpolar Current (ACC), where bottom‐reaching mesoscale eddies coexist with energetic internal waves such as wind‐induced near‐inertial waves and bottom‐generated internal lee waves. In this study, we explore the reason for such overestimations by analyzing simultaneous microstructure and finestructure measurements in the ACC. Finescale parameterizations overestimate ɛ where vertical wavenumber spectra of internal wave energy are distorted from the canonical Garrett‐Munk (GM) spectrum by a spectral hump at ∼0.01 cpm wavenumbers. Since shear and strain spectra are integrated over the noise‐free wavenumbers lower than the rolloff wavenumber, the spectral levels are overestimated for such spectra. These distorted shear spectra are mainly located in the upper ocean, while distorted strain spectra near the seafloor. Correlation analyses suggest that shear and strain spectral humps are caused by near‐inertial and lee wave packets superposed on a GM‐like internal wave field, and these wave packets are generated or amplified by geostrophic shear flows.
Restricted Oxygen‐Deficient Basins on the Northern European Epicontinental Shelf Across the Toarcian Carbon Isotope Excursion Interval
Authors: Wang Yunfeng , Ossa Frantz Ossa , Spangenberg Jorge E. , Wille Martin , Schoenberg Ronny 
Published: May 2021

AbstractThe worldwide recognition of the Toarcian carbon isotope excursion (T‐CIE) in organic‐rich sedimentary rocks has been linked to an oceanic anoxic event (OAE) which implies the world's deep oceans were anoxic ∼183 Ma. The majority of independent redox observations used to build this argument were mainly obtained from T‐CIE organic‐rich sediments deposited on northern European epicontinental shelf. However, increasing evidence has shown that this shelf had limited connection with the open ocean, making it unsuitable for reconstructing the T‐CIE ocean redox structure. To unveil such controversy, we present integrated δ15Nbulk and δ15Nker from Dotternhausen profile, Germany, combined with literature data from other T‐CIE profiles. Both δ15Nbulk and δ15Nker values are predominantly between +0.3 and +2.5‰. These positive near‐zero δ15N values imply enhanced N2 fixation by cyanobacteria using molybdenum (Mo)‐based nitrogenase to compensate bioavailable N loss following quantitative denitrification and/or anammox in a strongly redox‐stratified marine setting. Such N isotope composition contradicts the typical sedimentary δ15N values (>3‰) induced by partial water‐column denitrification and/or anammox in modern‐ocean oxygen minimum zones. We rather propose the existence of local oxygen‐deficient basins on northern European epicontinental shelf where dissolved N underwent extensive denitrification and/or anammox causing bioavailable N deficiency. Mo‐based diazotrophy thus played a critical role in discriminating N isotope compositions among multiple hydrographically restricted T‐CIE marginal basins. Restricted oxygen‐depleted environments on the northern European epicontinental shelf unlikely represent the open‐ocean redox landscape. The existence of the global OAE thus needs comprehensive redox investigations on Tethys and/or Panthalassa deep‐sea T‐CIE successions to validate.
Glutamate connectivity associations converge upon the salience network in schizophrenia and healthy controls
Authors: McCutcheon Robert A. , Pillinger Toby , Rogdaki Maria , Bustillo Juan , Howes Oliver D. 
Published: May 2021

AbstractAlterations in cortical inter-areal functional connectivity, and aberrant glutamatergic signalling are implicated in the pathophysiology of schizophrenia but the relationship between the two is unclear. We used multimodal imaging to identify areas of convergence between the two systems. Two separate cohorts were examined, comprising 195 participants in total. All participants received resting state functional MRI to characterise functional brain networks and proton magnetic resonance spectroscopy (1H-MRS) to measure glutamate concentrations in the frontal cortex. Study A investigated the relationship between frontal cortex glutamate concentrations and network connectivity in individuals with schizophrenia and healthy controls. Study B also used 1H-MRS, and scanned individuals with schizophrenia and healthy controls before and after a challenge with the glutamatergic modulator riluzole, to investigate the relationship between changes in glutamate concentrations and changes in network connectivity. In both studies the network based statistic was used to probe associations between glutamate and connectivity, and glutamate associated networks were then characterised in terms of their overlap with canonical functional networks. Study A involved 76 individuals with schizophrenia and 82 controls, and identified a functional network negatively associated with glutamate concentrations that was concentrated within the salience network (p < 0.05) and did not differ significantly between patients and controls (p > 0.85). Study B involved 19 individuals with schizophrenia and 17 controls and found that increases in glutamate concentrations induced by riluzole were linked to increases in connectivity localised to the salience network (p < 0.05), and the relationship did not differ between patients and controls (p > 0.4). Frontal cortex glutamate concentrations are associated with inter-areal functional connectivity of a network that localises to the salience network. Changes in network connectivity in response to glutamate modulation show an opposite effect compared to the relationship observed at baseline, which may complicate pharmacological attempts to simultaneously correct glutamatergic and connectivity aberrations.
Fatty acid β-oxidation promotes breast cancer stemness and metastasis via the miRNA-328-3p-CPT1A pathway
Authors: Zeng Feng , Yao Mingkang , Wang Yun , Zheng Wei , Liu Shengshan , Hou Zeyu , Cheng Xiaoming , Sun Suhong , Li Taolang , Zhao Hongyuan , Luo Yi , Li Jiang 
Published: May 2021

AbstractMicroRNAs (miRNA) have been shown to be associated with tumor diagnosis, prognosis, and therapeutic response. MiR-328-3p plays a significant role in breast cancer growth; however, its actual function and how it modulates specific biological functions is poorly understood. Here, miR-328-3p was significantly downregulated in breast cancer, especially in patients with metastasis. Mitochondrial carnitine palmitoyl transferase 1a (CPT1A) is a downstream target gene in the miR-328-3p-regulated pathway. Furthermore, the miR-328-3p/CPT1A/fatty acid β-oxidation/stemness axis was shown responsible for breast cancer metastasis. Collectively, this study revealed that miR-328-3p is a potential therapeutic target for the treatment of breast cancer patients with metastasis, and also a model for the miRNA-fatty acid β-oxidation-stemness axis, which may assist inunderstanding the cancer stem cell signaling functions of miRNA.
RETRACTED ARTICLE: Non-invasive vagus nerve stimulation improves clinical and molecular biomarkers of Parkinson’s disease in patients with freezing of gait
Authors: Mondal Banashree , Choudhury Supriyo , Banerjee Rebecca , Roy Akash , Chatterjee Koustav , Basu Purba , Singh Ravi , Halder Saptak , Shubham Shantanu , Baker Stuart N. , Baker Mark R. , Kumar Hrishikesh 
Published: May 2021

AbstractNon-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled crossover trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophin levels and markers of inflammation and oxidative stress in serum, before and after the experimental intervention. Thirty-three PD patients with associated freezing of gait were randomised to either nVNS or sham. After baseline assessments, patients were instructed to deliver 6 two-minute stimulations (total 12 min/day) of the nVNS/sham device (electroCore, Inc. USA) for one month at home. Patients were then re-assessed. After a washout period of one month, the same patients were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters were observed with nVNS, including walking speed, stance time and step length, compared to sham. Similarly, overall motor function (MDS-UPDRS III) also improved significantly following nVNS stimulation. Serum Tumor Necrosis Factor (TNF)-α and glutathione levels decreased and brain-derived neurotrophic factor (BDNF) levels increased significantly (p < 0.05) after treatment with nVNS. Here we present the first double-blind sham-controlled trial evidence of the efficacy and safety of nVNS in the treatment of gait and motor function in patients with PD.
Favourably regulating two-phase flow regime of flow boiling HFE-7100 in microchannels using silicon nanowires
Authors: Alam Tamanna , Li Wenming , Chang Wei , Yang Fanghao , Khan Jamil , Li Chen 
Published: May 2021

AbstractHigh performance miniaturized electronic devices require enhanced, compact and reliable thermal management system. As an efficient compact space cooling technique, flow boiling in microchannels has recently gained wide acceptance. However, weak buoyancy effects and microgravity in avionics and numerous space systems operations hinder the performance of flow boiling microchannel thermal management system due to poor bubble departure capacity and unfavorable development of flow regimes. Here we report the flow boiling silicon nanowires (SiNWs) microchannels which can favorably regulate two-phase flow regimes by enhancing explosive boiling, minimizing bubble departure diameter, and smoothing flow regime transition. Extensive experimental investigations along with high speed visualizations are performed. The experiments are performed with the dielectric fluid HFE-7100 in a forced convection loop for wide range of heat and mass fluxes. High speed flow visualizations have been employed at up to 70 k frames per second (fps) to understand the boiling mechanism in terms of bubble dynamics, flow patterns, and flow regime developments for SiNWs microchannels. These studies show that SiNWs reduce intermittent flow regimes (slug/churn), improve rewetting and maintain thin liquid film at wall. Therefore, flow boiling in SiNW microchannels is promising to thermal management owing to its high heat transfer rate with low pressure drop and negligible microgravity sensitivity.
Comparison of minimal residual disease detection in multiple myeloma between the DuraClone and EuroFlow methods
Authors: Yoroidaka Takeshi , Narita Kentaro , Takamatsu Hiroyuki , Fujisawa Momoko , Nakao Shinji , Matsue Kosei 
Published: May 2021

AbstractIn this study, the minimal residual disease (MRD) levels in patients with multiple myeloma (MM) were assessed by comparing the new 8-color single-tube multiparameter flow cytometry method (DuraClone), which reduces the cost of antibodies and labor burden of laboratories, with the EuroFlow next-generation flow (NGF) method. A total of 96 samples derived from 69 patients with MM were assessed to determine the total cell acquisition number (tCAN), percentages of total and normal plasma cells (PCs), and MRD levels using two methods. We found that the tCAN was significantly higher with EuroFlow-NGF than with DuraClone (median 8.6 × 106 vs. 5.7 × 106; p < 0.0001). In addition, a significant correlation in the MRD levels between the two methods was noted (r = 0.92, p < 0.0001). However, in the qualitative analysis, 5.2% (5/96) of the samples showed discrepancies in the MRD levels. In conclusion, the DuraClone is a good option to evaluate MRD in multiple myeloma but it should be used with caution.
DHHC21 deficiency attenuates renal dysfunction during septic injury
Authors: Yang Xiaoyuan , Zheng Ethan , Ma Yonggang , Chatterjee Victor , Villalba Nuria , Breslin Jerome W. , Liu Ruisheng , Wu Mack H. , Yuan Sarah Y. 
Published: May 2021

AbstractRenal dysfunction is one of the most common complications of septic injury. One critical contributor to septic injury-induced renal dysfunction is renal vascular dysfunction. Protein palmitoylation serves as a novel regulator of vascular function. Here, we examined whether palmitoyl acyltransferase (PAT)-DHHC21 contributes to septic injury-induced renal dysfunction through regulating renal hemodynamics. Multispectral optoacoustic imaging showed that cecal ligation and puncture (CLP)-induced septic injury caused impaired renal excretion, which was improved in DHHC21 functional deficient (Zdhhc21dep/dep) mice. DHHC21 deficiency attenuated CLP-induced renal pathology, characterized by tissue structural damage and circulating injury markers. Importantly, DHHC21 loss-of-function led to better-preserved renal perfusion and oxygen saturation after CLP. The CLP-caused reduction in renal blood flow was also ameliorated in Zdhhc21dep/dep mice. Next, CLP promoted the palmitoylation of vascular α1-adrenergic receptor (α1AR) and the activation of its downstream effector ERK, which were blunted in Zdhhc21dep/dep mice. Vasoreactivity analysis revealed that renal arteries from Zdhhc21dep/dep mice displayed reduced constriction response to α1AR agonist phenylephrine compared to those from wild-type mice. Consistently, inhibiting PATs with 2-bromopalmitate caused a blunted vasoconstriction response to phenylephrine in small arteries isolated from human kidneys. Therefore, DHHC21 contributes to impaired renal perfusion and function during septic injury via promoting α1AR palmitoylation-associated vasoconstriction.
A correlation study of beat-to-beat R-R intervals and pulse arrival time under natural state and cold stimulation
Authors: Peng Rong-Chao , Li Yi , Yan Wen-Rong 
Published: May 2021

AbstractBeat-to-beat R-R intervals (RRI) and pulse arrival time (PAT) provide pivotal information to evaluate cardiac autonomic functions for predicting arrhythmias and cardiovascular morbidity. However, their relationship has not been clearly understood. In this study, we simultaneously recorded electrocardiograms and photoplethysmograms on 34 subjects in the natural state, and on 55 subjects under the cold stimulation. The RRI and the PAT were calculated and then analyzed using Pearson correlation coefficient. The results showed that the RRI and the PAT were strongly correlated (r = 0.562) and the RRI series were 2.18 ± 0.40 beats advanced to the PAT series. After smoothing, the RRI and the PAT were more correlated in the low frequency than in the high frequency. Furthermore, when involving RRI with the phase effect, the proposed PAT based model showed better performance for blood pressure estimation. We think these results are helpful to understand the underlying regulatory mechanisms of the two cardiovascular factors, and would provide useful suggestions for non-invasive cuffless blood pressure estimation.
A high mutation load of m.14597A>G in MT-ND6 causes Leigh syndrome
Authors: Kishita Yoshihito , Ishikawa Kaori , Nakada Kazuto , Hayashi Jun-Ichi , Fushimi Takuya , Shimura Masaru , Kohda Masakazu , Ohtake Akira , Murayama Kei , Okazaki Yasushi 
Published: May 2021

AbstractLeigh syndrome (LS) is an early-onset progressive neurodegenerative disorder associated with mitochondrial deficiency. m.14597A>G (p.Ile26Thr) in the MT-ND6 gene was reported to cause Leberʼs hereditary optic neuropathy (LHON) or dementia/dysarthria. In previous reports, less than 90% heteroplasmy was shown to result in adult-onset disease. Here, by whole mitochondrial sequencing, we identified m.14597A>G mutation of a patient with LS. PCR–RFLP analysis on fibroblasts from the patient revealed a high mutation load (> 90% heteroplasmy). We performed functional assays using cybrid cell models generated by fusing mtDNA-less rho0 HeLa cells with enucleated cells from patient fibroblasts carrying the m.14597A>G variant. Cybrid cell lines bearing the m.14597A>G variant exhibited severe effects on mitochondrial complex I activity. Additionally, impairment of cell proliferation, decreased ATP production and reduced oxygen consumption rate were observed in the cybrid cell lines bearing the m.14597A>G variant when the cells were metabolically stressed in medium containing galactose, indicating mitochondrial respiratory chain defects. These results suggest that a high mutation load of m.14597A>G leads to LS via a mitochondrial complex I defect, rather than LHON or dementia/dysarthria.
Emulated retinal image capture (ERICA) to test, train and validate processing of retinal images
Authors: Young Laura K. , Smithson Hannah E. 
Published: May 2021

AbstractHigh resolution retinal imaging systems, such as adaptive optics scanning laser ophthalmoscopes (AOSLO), are increasingly being used for clinical research and fundamental studies in neuroscience. These systems offer unprecedented spatial and temporal resolution of retinal structures in vivo. However, a major challenge is the development of robust and automated methods for processing and analysing these images. We present ERICA (Emulated Retinal Image CApture), a simulation tool that generates realistic synthetic images of the human cone mosaic, mimicking images that would be captured by an AOSLO, with specified image quality and with corresponding ground-truth data. The simulation includes a self-organising mosaic of photoreceptors, the eye movements an observer might make during image capture, and data capture through a real system incorporating diffraction, residual optical aberrations and noise. The retinal photoreceptor mosaics generated by ERICA have a similar packing geometry to human retina, as determined by expert labelling of AOSLO images of real eyes. In the current implementation ERICA outputs convincingly realistic en face images of the cone photoreceptor mosaic but extensions to other imaging modalities and structures are also discussed. These images and associated ground-truth data can be used to develop, test and validate image processing and analysis algorithms or to train and validate machine learning approaches. The use of synthetic images has the advantage that neither access to an imaging system, nor to human participants is necessary for development.
Single tryptophan Y160W mutant of homooligomeric E. coli purine nucleoside phosphorylase implies that dimers forming the hexamer are functionally not equivalent
Authors: Narczyk Marta , Mioduszewski Łukasz , Oksiejuk Aleksandra , Winiewska-Szajewska Maria , Wielgus-Kutrowska Beata , Gojdź Adrian , Cieśla Joanna , Bzowska Agnieszka 
Published: May 2021

AbstractE. coli purine nucleoside phosphorylase is a homohexamer, which structure, in the apo form, can be described as a trimer of dimers. Earlier studies suggested that ligand binding and kinetic properties are well described by two binding constants and two sets of kinetic constants. However, most of the crystal structures of this enzyme complexes with ligands do not hold the three-fold symmetry, but only two-fold symmetry, as one of the three dimers is different (both active sites in the open conformation) from the other two (one active site in the open and one in the closed conformation). Our recent detailed studies conducted over broad ligand concentration range suggest that protein–ligand complex formation in solution actually deviates from the two-binding-site model. To reveal the details of interactions present in the hexameric molecule we have engineered a single tryptophan Y160W mutant, responding with substantial intrinsic fluorescence change upon ligand binding. By observing various physical properties of the protein and its various complexes with substrate and substrate analogues we have shown that indeed three-binding-site model is necessary to properly describe binding of ligands by both the wild type enzyme and the Y160W mutant. Thus we have pointed out that a symmetrical dimer with both active sites in the open conformation is not forced to adopt this conformation by interactions in the crystal, but most probably the dimers forming the hexamer in solution are not equivalent as well. This, in turn, implies that an allosteric cooperation occurs not only within a dimer, but also among all three dimers forming a hexameric molecule.
Effect of TNFα stimulation on expression of kidney risk inflammatory proteins in human umbilical vein endothelial cells cultured in hyperglycemia
Authors: Md Dom Zaipul I. , Pipino Caterina , Krolewski Bozena , O’Neil Kristina , Satake Eiichiro , Krolewski Andrzej S. 
Published: May 2021

AbstractWe recently identified a kidney risk inflammatory signature (KRIS), comprising 6 TNF receptors (including TNFR1 and TNFR2) and 11 inflammatory proteins. Elevated levels of these proteins in circulation were strongly associated with risk of the development of end-stage kidney disease (ESKD) during 10-year follow-up. It has been hypothesized that elevated levels of these proteins in circulation might reflect (be markers of) systemic exposure to TNFα. In this in vitro study, we examined intracellular and extracellular levels of these proteins in human umbilical vein endothelial cells (HUVECs) exposed to TNFα in the presence of hyperglycemia. KRIS proteins as well as 1300 other proteins were measured using the SOMAscan proteomics platform. Four KRIS proteins (including TNFR1) were down-regulated and only 1 protein (IL18R1) was up-regulated in the extracellular fraction of TNFα-stimulated HUVECs. In the intracellular fraction, one KRIS protein was down-regulated (CCL14) and 1 protein was up-regulated (IL18R1). The levels of other KRIS proteins were not affected by exposure to TNFα. HUVECs exposed to a hyperglycemic and inflammatory environment also showed significant up-regulation of a distinct set of 53 proteins (mainly in extracellular fraction). In our previous study, circulating levels of these proteins were not associated with progression to ESKD in diabetes.
Quantitative dual-energy CT for evaluating hepatocellular carcinoma after transarterial chemoembolization
Authors: Yue Xiaofei , Jiang Qiqi , Hu Xuehan , Cen Chunyuan , Song Songlin , Qian Kun , Lu Yuting , Yang Ming , Li Qian , Han Ping 
Published: May 2021

AbstractWe aimed to investigate the role of the quantitative parameters of dual-energy computed tomography (DECT) in evaluating patients with hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We retrospectively identified 80 HCC patients (mean age, 56 years; 61 men) treated by TACE who received contrast-enhanced DECT and were retreated by TACE within 7 days between November 2018 and December 2019. Taking digital subtraction angiography (DSA) and CT images as reference standard, two readers measured and calculated the values of normalized iodine concentration at arterial phase (NICAP), normalized iodine concentration at portal venous phase (NICPP), iodine concentration difference (ICD), arterial iodine fraction (AIF) and slope of the spectral Hounsfield unit curve (λHu) by placing matched regions of interests (ROIs) within the tumor active area (TAA), adjacent normal hepatic parenchyma (ANHP) and tumor necrotic area (TNA). Differences between the parameters were analyzed by the Kruskal–Wallis H test. Receiver operating characteristic analysis of the parameters performance in differentiating the three tissues types was performed. AIF exhibited a good performance in distinguishing TAA (0.93 ± 0.31) and ANHP (0.18 ± 0.14), the areas under the receiver operating characteristic curve (AUC) was 0.989, while the λHu exhibited an excellent performance in distinguishing TAA (3.32 ± 1.24) and TNA (0.29 ± 0.27), with an AUC of 1.000. In conclusion, quantitative DECT can be effectively used to evaluate the tumor viability in HCC patients treated by TACE.