bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Resolution Motor State Detection in Parkinson’s Disease Using Convolutional Neural Networks
Authors: Pfister Franz M. J. , Um Terry Taewoong , Pichler Daniel C. , Goschenhofer Jann , Abedinpour Kian , Lang Muriel , Endo Satoshi , Ceballos-Baumann Andres O. , Hirche Sandra , Bischl Bernd , Kulić Dana , Fietzek Urban M. 
Published: April 2020

AbstractPatients with advanced Parkinson’s disease regularly experience unstable motor states. Objective and reliable monitoring of these fluctuations is an unmet need. We used deep learning to classify motion data from a single wrist-worn IMU sensor recording in unscripted environments. For validation purposes, patients were accompanied by a movement disorder expert, and their motor state was passively evaluated every minute. We acquired a dataset of 8,661 minutes of IMU data from 30 patients, with annotations about the motor state (OFF,ON, DYSKINETIC) based on MDS-UPDRS global bradykinesia item and the AIMS upper limb dyskinesia item. Using a 1-minute window size as an input for a convolutional neural network trained on data from a subset of patients, we achieved a three-class balanced accuracy of 0.654 on data from previously unseen subjects. This corresponds to detecting the OFF, ON, or DYSKINETIC motor state at a sensitivity/specificity of 0.64/0.89, 0.67/0.67 and 0.64/0.89, respectively. On average, the model outputs were highly correlated with the annotation on a per subject scale (r = 0.83/0.84; p < 0.0001), and sustained so for the highly resolved time windows of 1 minute (r = 0.64/0.70; p < 0.0001). Thus, we demonstrate the feasibility of long-term motor-state detection in a free-living setting with deep learning using motion data from a single IMU.
Defining Individual-Level Genetic Diversity and Similarity Profiles
Authors: Ma Zhanshan , Li Lianwei , Zhang Ya-Ping 
Published: April 2020

AbstractClassic concepts of genetic (gene) diversity (heterozygosity) such as Nei & Li’s nucleotide diversity were defined within a population context. Although variations are often measured in population context, the basic carriers of variation are individuals. Hence, measuring variations such as SNP of an individual against a reference genome, which has been ignored previously, is certainly in its own right. Indeed, similar practice has been a tradition in community ecology, where the basic unit of diversity measure is individual community sample. We propose to use Renyi’s-entropy-based Hill numbers to define individual-level genetic diversity and similarity and demonstrate the definitions with the SNP (single nucleotide polymorphism) datasets from the 1000-Genomes Project. Hill numbers, derived from Renyi’s entropy (of which Shannon’s entropy is a special case), have found widely applications including measuring the quantum information entanglement and ecological diversity. The demonstrated individual-level SNP diversity not only complements the existing population-level genetic diversity concepts, but also offers building blocks for comparative genetic analysis at higher levels. The concept of individual covers, but is not limited to, individual chromosome, region of chromosome, gene cluster(s), or whole genome. Similarly, the SNP can be replaced by other structural variants or mutation types such as indels.
Pyrazine ring-based Na+/H+ exchanger (NHE) inhibitors potently inhibit cancer cell growth in 3D culture, independent of NHE1
Authors: Rolver Michala G. , Elingaard-Larsen Line O. , Andersen Anne P. , Counillon Laurent , Pedersen Stine F. 
Published: April 2020

AbstractThe Na+/H+ exchanger-1 (NHE1) supports tumour growth, making NHE1 inhibitors of interest in anticancer therapy, yet their molecular effects are incompletely characterized. Here, we demonstrate that widely used pyrazinoylguanidine-type NHE1 inhibitors potently inhibit growth and survival of cancer cell spheroids, in a manner unrelated to NHE1 inhibition. Cancer and non-cancer cells were grown as 3-dimensional (3D) spheroids and treated with pyrazinoylguanidine-type (amiloride, 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), 5-(N,N-dimethyl)-amiloride (DMA), and 5-(N,N-hexamethylene)-amiloride (HMA)) or benzoylguanidine-type (eniporide, cariporide) NHE1 inhibitors for 2–7 days, followed by analyses of viability, compound accumulation, and stress- and death-associated signalling. EIPA, DMA and HMA dose-dependently reduced breast cancer spheroid viability while cariporide and eniporide had no effect. Although both compound types inhibited NHE1, the toxic effects were NHE1-independent, as inhibitor-induced viability loss was unaffected by NHE1 CRISPR/Cas9 knockout. EIPA and HMA accumulated extensively in spheroids, and this was associated with marked vacuolization, apparent autophagic arrest, ER stress, mitochondrial- and DNA damage and poly-ADP-ribose-polymerase (PARP) cleavage, indicative of severe stress and paraptosis-like cell death. Pyrazinoylguanidine-induced cell death was partially additive to that induced by conventional anticancer therapies and strongly additive to extracellular-signal-regulated-kinase (ERK) pathway inhibition. Thus, in addition to inhibiting NHE1, pyrazinoylguanidines exert potent, NHE1-independent cancer cell death, pointing to a novel relevance for these compounds in anticancer therapy.
A Fragment of Collagen Type VI alpha-3 chain is Elevated in Serum from Patients with Gastrointestinal Disorders
Authors: Holm Nielsen Signe , Mortensen Joachim Høg , Willumsen Nicholas , Rasmussen Daniel Guldager Kring , Mogensen Ditte J. , Di Sabatino Antonio , Mazza Giuseppe , Jørgensen Lars Nannestad , Giuffrida Paolo , Pinzani Massimo , Klinge Lone , Kjeldsen Jens , Leeming Diana Julie , Karsdal Morten Asser , Genovese Federica 
Published: April 2020

AbstractExtracellular matrix (ECM) remodeling is a hallmark of the pathology of gastrointestinal disorders. Collagen type VI (COL6) is produced by fibroblasts, and the COL6 α3-chain has shown to be elevated in patients with ulcerative colitis (UC), Crohn’s disease (CD) and colorectal cancer (CRC). Measuring COL6α3 in serum may therefore have potential as a biomarker for gastrointestinal disorders. The aims of this study were to develop and validate a competitive ELISA targeting a specific neo-epitope of COL6α3 and evaluate its associations with the gastrointestinal disorders UC, CD and CRC, in comparison to healthy controls. A monoclonal antibody was raised against a matrix metalloproteinase-2 and -9 specific cleavage site of COL6α3 (C6Mα3) and employed in a competitive enzyme-linked immunosorbent assay (ELISA). The assay was developed and technically validated. Levels of C6Mα3 were measured in serum from patients with UC (n = 58), CD (n = 44) and CRC (n = 39) and compared to healthy controls (n = 32). The levels of C6Mα3 were elevated in patients with UC, CD and CRC patients compared to healthy controls (all p < 0.0001). The area under the receiver operating characteristics (AUROC) curve for separation of patients with UC from healthy controls was 0.972 (95% CI: 0.925–1.020, p < 0.0001), with CD from healthy controls was 0.947 (95% CI: 0.885–1.009, p < 0.0001) and with CRC from healthy controls was 0.890 (95% CI: 0.809–0.972, p < 0.0001). We developed a technically robust assay targeting a fragment of COL6, which was elevated in serum from patients with UC, CD and CRC.
ST2 and regulatory T cells in the colorectal adenoma/carcinoma microenvironment: implications for diseases progression and prognosis
Authors: Cui Guanglin , Yuan Aping , Li Zhenfeng , Goll Rasmus , Florholmen Jon 
Published: April 2020

AbstractST2 (also known as IL1RL1) is the critical functional receptor for interleukin (IL)-33 in stimulating regulatory T cell (Treg) expansion and function in physiological and pathological conditions. We examined the correlation between ST2 cell expression and FoxP3 positive Tregs in both colorectal adenoma and cancer (CRC) microenvironment by real-time PCR, immunohistochemistry (IHC) and double immunofluorescences. The clinicopathological and prognostic significance of cellular ST2-positive cells and FoxP3-positive Tregs in patients with adenoma and CRC were evaluated. Real-time PCR results revealed increased expression levels of ST2 and FoxP3 mRNAs in both adenoma and CRC tissues as compared with control tissues. IHC analysis confirmed increased densities of ST2-positive cells in both the adenoma/CRC epithelium and stroma, which show a close positive linear association with the densities of FoxP3-positive Tregs in respective compartments. Pathological feature analysis showed that densities of ST2-positive cells in the tumor stroma were notably associated with degree of dysplastic grading in patients with adenoma, and disease stages and lymph node metastasis in patients with CRC. Kaplan-Meier survival curves suggested that CRC patients with high densities of ST2-positive cells in the stroma tend to have a shorter overall survival. We therefore concluded that increased densities of ST2-postive cells relate to Treg accumulation within the adenoma/CRC microenvironment, suggesting the IL-33/ST2 pathway as a potential contributor for immunosuppressive milieu formation that impact disease stage and prognosis in patients with CRC.
Safety of Ligation of Aberrant Left Hepatic Artery Originating from Left Gastric Artery in Laparoscopic Gastrectomy for Gastric Cancer
Authors: Ang Rene Ronson G. , Lee Hyuk-Joon , Bae Jae Seok , Zhu Chun-Chao , Berlth Felix , Kim Tae Han , Park Shin-Hoo , Suh Yun-Suhk , Kong Seong-Ho , Kim Se Hyung , Yang Han-Kwang 
Published: April 2020

AbstractThere are still lot of controversies whether aberrant left hepatic artery (ALHA) originating from left gastric artery should be ligated or preserved during gastric cancer (GC) surgery. We aimed to investigate this issue. We reviewed ALHA cases who had laparoscopic gastrectomy for gastric cancer at Seoul National University Hospital (SNUH) from 2012 to 2016. Type of ALHA variants using Michel’s classification of hepatic arterial anatomy and diameter of each vessel were evaluated by 2 radiologists. Postoperative hepatic function and surgical outcome were collected until 6 months after surgery. Results showed that if the diameter of ALHA was larger than 1.5 mm, a transient elevation of SGOT and SGPT on postoperative day 2 was observed in the ligated cases. No differences were observed in operation time, amount of blood loss, overall complication rate, hospital stay, and number of lymph nodes retrieved between the ligated and preserved replaced left hepatic artery (RLHA) and accessory left hepatic artery (acLHA) group. In this study, we conclude that ligation of ALHA seems to be safe as none of the patients suffered adverse outcome. A transient rise in postoperative SGOT and SGPT levels were seen after ligating ALHA >1.5 mm in diameter regardless of subtype.
A multi-institutional real world data study from India of 3453 non-metastatic breast cancer patients undergoing upfront surgery
Authors: Doval Dinesh Chandra , Radhakrishna Selvi , Tripathi Rupal , Kashinath Renu Iyer , Talwar Vineet , Batra Ullas , Mullapudi Naga Amulya , Kumar Kapil , Dewan Ajay Kumar , Chaturvedi Harit , Tayal Juhi , Mehta Anurag , Gupta Sudeep , Nimmagadda Ramesh B. V. 
Published: April 2020

AbstractThe present analysis reports the clinical, pathological, treatment profile and overall survival (OS) and disease-free survival (DFS) outcomes of consecutive breast cancer patients from three Indian centres, who underwent curative surgery as their first treatment. Among the 3453 patients, stage I, II, and III cases were 11.75%, 66.79%, and 21.64%, respectively while hormone receptor positive/HER2 negative, triple negative (TNBC) and hormone receptor any/HER2 positive cases were 55.2%, 24.2% and 20.6%, respectively. The five-year OS in the entire cohort, node-negative and node-positive patients were 94.1% (93.25–94.98), 96.17% (95.2–97.15) and 91.83% (90.36–93.31), respectively, and the corresponding DFS were 88.1% (86.96–89.31), 92.0% (90.64–93.39) and 83.93% (82.03–85.89), respectively. The five-year OS in hormone receptor positive/HER2 negative, TNBC and HER2 subgroups were 96.11% (95.12–97.1), 92.74% (90.73–94.8) and 90.62% (88.17–93.15), respectively, and the corresponding DFS were 91.59% (90.19–93.02), 85.46% (82.79–88.22) and 81.29% (78.11–84.61), respectively. This is the largest dataset of early breast cancer patients from India with survival outcome analysis and can therefore serve as a benchmark for future studies.
A combined approach to establishing the timing and magnitude of anthropogenic nutrient alteration in a mediterranean coastal lake- watershed system
Authors: Fuentealba Magdalena , Latorre Claudio , Frugone-Álvarez Matías , Sarricolea Pablo , Giralt Santiago , Contreras-Lopez Manuel , Prego Ricardo , Bernárdez Patricia , Valero-Garcés Blas 
Published: April 2020

AbstractHuman activities have profoundly altered the global nutrient cycle through Land Use and Cover Changes (LUCCs) since the industrial revolution and especially during the Great Acceleration (1950 CE). Yet, the impact of such activities on terrestrial and aquatic ecosystems above their ecological baselines are not well known, especially when considering the response of these systems to the intensity of LUCCs on nutrient cycles. Here, we used a multiproxy approach (sedimentological, geochemical and isotopic analyses, historical records, climate data, and satellite images) to evaluate the role that LUCCs have on Nitrogen (N) cycling in a coastal mediterranean watershed system of central Chile over the last two centuries. Despite long-term anthropogenic use (agriculture, cattle grazing) in the Matanzas watershed– lake system, these LUCC appear to have had little impact on nutrient and organic matter transfer since the Spanish Colonial period. In contrast, the largest changes in N dynamics occurred in the mid-1970s, driven by the replacement of native forests and grasslands by government-subsidized tree plantations of introduced Monterey pine (Pinus radiata) and eucalyptus (Eucalyptus globulus). These LUCC had major impacts on the transfer of organic matter (which increased by 9.4%) and nutrients (as revealed by an increase in total N) to Laguna Matanzas. Our study shows that the presence of anthropogenic land use/cover changes do not necessarily alter nutrient supply and N availability per se but rather it is the magnitude and intensity of such changes that produce major impact on these processes in these mediterranean watersheds.
High variability of Blue Carbon storage in seagrass meadows at the estuary scale
Authors: Ricart Aurora M. , York Paul H. , Bryant Catherine V. , Rasheed Michael A. , Ierodiaconou Daniel , Macreadie Peter I. 
Published: April 2020

AbstractSeagrass meadows are considered important natural carbon sinks due to their capacity to store organic carbon (Corg) in sediments. However, the spatial heterogeneity of carbon storage in seagrass sediments needs to be better understood to improve accuracy of Blue Carbon assessments, particularly when strong gradients are present. We performed an intensive coring study within a sub-tropical estuary to assess the spatial variability in sedimentary Corgassociated with seagrasses, and to identify the key factors promoting this variability. We found a strong spatial pattern within the estuary, from 52.16 mg Corgcm−3in seagrass meadows in the upper parts, declining to 1.06 mg Corgcm−3in seagrass meadows at the estuary mouth, despite a general gradient of increasing seagrass cover and seagrass habitat extent in the opposite direction. The sedimentary Corgunderneath seagrass meadows came principally from allochthonous (non-seagrass) sources (~70–90 %), while the contribution of seagrasses was low (~10–30 %) throughout the entire estuary. Our results showed that Corgstored in sediments of seagrass meadows can be highly variable within an estuary, attributed largely to accumulation of fine sediments and inputs of allochthonous sources. Local features and the existence of spatial gradients must be considered in Blue Carbon estimates in coastal ecosystems.
The origin and fate of volatile elements on Earth revisited in light of noble gas data obtained from comet 67P/Churyumov-Gerasimenko
Authors: Bekaert David V. , Broadley Michael W. , Marty Bernard 
Published: April 2020

AbstractThe origin of terrestrial volatiles remains one of the most puzzling questions in planetary sciences. The timing and composition of chondritic and cometary deliveries to Earth has remained enigmatic due to the paucity of reliable measurements of cometary material. This work uses recently measured volatile elemental ratios and noble gas isotope data from comet 67P/Churyumov-Gerasimenko (67P/C-G), in combination with chondritic data from the literature, to reconstruct the composition of Earth’s ancient atmosphere. Comets are found to have contributed ~20% of atmospheric heavy noble gases (i.e., Kr and Xe) but limited amounts of other volatile elements (water, halogens and likely organic materials) to Earth. These cometary noble gases were likely mixed with chondritic - and not solar - sources to form the atmosphere. We show that an ancient atmosphere composed of chondritic and cometary volatiles is more enriched in Xe relative to the modern atmosphere, requiring that 8–12 times the present-day inventory of Xe was lost to space. This potentially resolves the long-standing mystery of Earth’s “missing xenon”, with regards to both Xe elemental depletion and isotopic fractionation in the atmosphere. The inferred Kr/H2O and Xe/H2O of the initial atmosphere suggest that Earth’s surface volatiles might not have been fully delivered by the late accretion of volatile-rich carbonaceous chondrites. Instead, “dry” materials akin to enstatite chondrites potentially constituted a significant source of chondritic volatiles now residing on the Earth’s surface. We outline the working hypotheses, implications and limitations of this model in the last section of this contribution.
High glucose induces phosphorylation and oxidation of mitochondrial proteins in renal tubular cells: A proteomics approach
Authors: Aluksanasuwan Siripat , Plumworasawat Sirikanya , Malaitad Thanyalak , Chaiyarit Sakdithep , Thongboonkerd Visith 
Published: April 2020

AbstractMitochondrial dysfunction has been thought to play roles in the pathogenesis of diabetic nephropathy (DN). However, precise mechanisms underlying mitochondrial dysfunction in DN remained unclear. Herein, mitochondria were isolated from renal tubular cells after exposure to normal glucose (5.5 mM glucose), high glucose (25 mM glucose), or osmotic control (5.5 mM glucose + 19.5 mM mannitol) for 96 h. Comparative proteomic analysis revealed six differentially expressed proteins among groups that were subsequently identified by tandem mass spectrometry (nanoLC-ESI-ETD MS/MS) and confirmed by Western blotting. Several various types of post-translational modifications (PTMs) were identified in all of these identified proteins. Interestingly, phosphorylation and oxidation were most abundant in mitochondrial proteins whose levels were exclusively increased in high glucose condition. The high glucose-induced increases in phosphorylation and oxidation of mitochondrial proteins were successfully confirmed by various assays including MS/MS analyses. Moreover, high glucose also increased levels of phosphorylated ezrin, intracellular ATP and ROS, all of which could be abolished by a p38 MAPK inhibitor (SB239063), implicating a role of p38 MAPK-mediated phosphorylation in high glucose-induced mitochondrial dysfunction. These data indicate that phosphorylation and oxidation of mitochondrial proteins are, at least in part, involved in mitochondrial dysfunction in renal tubular cells during DN.
Clinical significance of serum concentrations of neuregulin-4, in acute coronary syndrome
Authors: Rahimzadeh Mahsa , Farshidi Narges , Naderi Nadereh , Farshidi Hossein , Montazerghaem Hossein 
Published: April 2020

AbstractAcute coronary syndrome (ACS) is closely associated with an increased risk of death. Nrg4, a novel adipocytokine, has negative correlations with indicators of metabolic syndrome. Here, we investigated whether circulating Nrg4 associates with the prevalence of ACS. In this case-control study, a total of 257 subjects (144 patients with ACS and 56 patients diagnosed with stable angina pectoris (SAP)) compared to 57 healthy controls. Serum Nrg4 and hs-CRP concentrations were determined by ELISA. The associations of circulating Nrg4 with other clinical parameters were also analyzed. Serum levels of Nrg4 were lower in patients compared to the control subjects (0.7 ± 0.53 ng/mL versus 1.1 ± 0.9 ng/mL, P = 0.018). There was a significant association between higher Nrg4 level and lower risk of ACS (OR = 0.15; 95%CI = 0.02–0.9; P = 0.046), but not with SAP. This association was independent of potential confounders including traditional cardiovascular risk factors. The distribution of patients with no, 1, 2 and 3 vessel stenosis was significantly different in Nrg4 quartiles. Patients in the lower quartile of Nrg4 were more likely to experience 3 vessel diseases. Serum levels of Nrg4 correlated negatively with HDL-cholesterol in ACS patients. Decreased serum levels of Nrg4 might be an independent risk factor for ACS.
Compensating Atmospheric Channel Dispersion for Terahertz Wireless Communication
Authors: Strecker Karl , Ekin Sabit , O’Hara John F. 
Published: April 2020

AbstractWe report and demonstrate for the first time a method to compensate atmospheric group velocity dispersion of terahertz pulses. In ultra-wideband or impulse radio terahertz wireless communication, the atmosphere reshapes terahertz pulses via group velocity dispersion, a result of the frequency-dependent refractivity of air. Without correction, this can significantly degrade the achievable data transmission rate. We present a method for compensating the atmospheric dispersion of terahertz pulses using a cohort of stratified media reflectors. Using this method, we compensated group velocity dispersion in the 0.2-0.3 THz channel under common atmospheric conditions. Based on analytic and numerical simulations, the method can exhibit an in-band power efficiency of greater than 98% and dispersion compensation up to 99% of ideal. Simulations were validated by experimental measurements.
Classifying post-traumatic stress disorder using the magnetoencephalographic connectome and machine learning
Authors: Zhang Jing , Richardson J. Don , Dunkley Benjamin T. 
Published: April 2020

AbstractGiven the subjective nature of conventional diagnostic methods for post-traumatic stress disorder (PTSD), an objectively measurable biomarker is highly desirable; especially to clinicians and researchers. Macroscopic neural circuits measured using magnetoencephalography (MEG) has previously been shown to be indicative of the PTSD phenotype and severity. In the present study, we employed a machine learning-based classification framework using MEG neural synchrony to distinguish combat-related PTSD from trauma-exposed controls. Support vector machine (SVM) was used as the core classification algorithm. A recursive random forest feature selection step was directly incorporated in the nested SVM cross validation process (CV-SVM-rRF-FS) for identifying the most important features for PTSD classification. For the five frequency bands tested, the CV-SVM-rRF-FS analysis selected the minimum numbers of edges per frequency that could serve as a PTSD signature and be used as the basis for SVM modelling. Many of the selected edges have been reported previously to be core in PTSD pathophysiology, with frequency-specific patterns also observed. Furthermore, the independent partial least squares discriminant analysis suggested low bias in the machine learning process. The final SVM models built with selected features showed excellent PTSD classification performance (area-under-curve value up to 0.9). Testament to its robustness when distinguishing individuals from a heavily traumatised control group, these developments for a classification model for PTSD also provide a comprehensive machine learning-based computational framework for classifying other mental health challenges using MEG connectome profiles.