bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamical nonlinear memory capacitance in biomimetic membranes
Authors: Najem Joseph S. , Hasan Md Sakib , Williams R. Stanley , Weiss Ryan J. , Rose Garrett S. , Taylor Graham J. , Sarles Stephen A. , Collier C. Patrick 
Published: July 2019

AbstractTwo-terminal memory elements, or memelements, capable of co-locating signal processing and memory via history-dependent reconfigurability at the nanoscale are vital for next-generation computing materials striving to match the brain’s efficiency and flexible cognitive capabilities. While memory resistors, or memristors, have been widely reported, other types of memelements remain underexplored or undiscovered. Here we report the first example of a volatile, voltage-controlled memcapacitor in which capacitive memory arises from reversible and hysteretic geometrical changes in a lipid bilayer that mimics the composition and structure of biomembranes. We demonstrate that the nonlinear dynamics and memory are governed by two implicitly-coupled, voltage-dependent state variables—membrane radius and thickness. Further, our system is capable of tuneable signal processing and learning via synapse-like, short-term capacitive plasticity. These findings will accelerate the development of low-energy, biomolecular neuromorphic memelements, which, in turn, could also serve as models to study capacitive memory and signal processing in neuronal membranes.
Acute and short-term administrations of delta-9-tetrahydrocannabinol modulate major gut metabolomic regulatory pathways in C57BL/6 mice
Authors: Oza Megha , Becker William , Gummadidala Phani M. , Dias Travis , Omebeyinje Mayomi H. , Chen Li , Mitra Chandrani , Jesmin Rubaiya , Chakraborty Paramita , Sajish Mathew , Hofseth Lorne J. , Banerjee Koyeli , Wang Qian , Moeller Peter D. R. , Nagarkatti Mitzi , Nagarkatti Prakash , Chanda Anindya 
Published: July 2019

AbstractDelta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound in Cannabis, which is studied extensively for its medicinal value. A central gap in the science is the underlying mechanisms surrounding THC’s therapeutic effects and the role of gut metabolite profiles. Using a mass-spectrometry based metabolomics, we show here that intraperitoneal injection of THC in C57BL/6 mice modulates metabolic profiles that have previously been identified as integral to health. Specifically, we investigated the effects of acute (single THC injection denoted here as ‘1X’) and short -term (five THC injections on alternate days denoted as ‘5X’) THC administration on fecal and intestinal tissue metabolite profiles. Results are consistent with the hypothesis that THC administration alters host metabolism by targeting two prominent lipid metabolism pathways: glycerophospholipid metabolism and fatty acid biosynthesis.
A direct comparison of interphase FISH versus low-coverage single cell sequencing to detect aneuploidy reveals respective strengths and weaknesses
Authors: Andriani Grasiella A. , Maggi Elaine , Piqué Daniel , Zimmerman Samuel E. , Lee Moonsook , Quispe-Tintaya Wilber , Maslov Alexander , Campisi Judith , Vijg Jan , Mar Jessica C. , Montagna Cristina 
Published: July 2019

AbstractAneuploidy has been reported to occur at remarkably high levels in normal somatic tissues using Fluorescence In Situ Hybridization (FISH). Recently, these reports were contradicted by single-cell low-coverage whole genome sequencing (scL-WGS) analyses, which showed aneuploidy frequencies at least an order of magnitude lower. To explain these seemingly contradictory findings, we used both techniques to analyze artificially generated mock aneuploid cells and cells with natural random aneuploidy. Our data indicate that while FISH tended to over-report aneuploidies, a modified 2-probe approach can accurately detect low levels of aneuploidy. Further, scL-WGS tends to underestimate aneuploidy levels, especially in a polyploid background.
Accurate Detection of Dobutamine-induced Haemodynamic Changes by Kino-Cardiography: A Randomised Double-Blind Placebo-Controlled Validation Study
Authors: Hossein Amin , Mirica Daniela Corina , Rabineau Jérémy , Rio José Ignacio Del , Morra Sofia , Gorlier Damien , Nonclercq Antoine , van de Borne Philippe , Migeotte Pierre-François 
Published: July 2019

AbstractNon-invasive remote detection of cardiac and blood displacements is an important topic in cardiac telemedicine. Here we propose kino-cardiography (KCG), a non-invasive technique based on measurement of body vibrations produced by myocardial contraction and blood flow through the cardiac chambers and major vessels. KCG is based on ballistocardiography and measures 12 degrees-of-freedom (DOF) of body motion. We tested the hypothesis that KCG reliably assesses dobutamine-induced haemodynamic changes in healthy subjects. Using a randomized double-blinded placebo-controlled crossover study design, dobutamine and placebo were infused to 34 volunteers (25 ± 2 years, BMI 22 ± 2 kg/m², 18 females). Baseline recordings were followed by 3 sessions of increasing doses of dobutamine (5, 10, 20 μg/kg.min) or saline solution. During each session, stroke volume (SV) and cardiac output (CO) were determined by echocardiography and followed by a 90 s KCG recording. Measured linear accelerations and angular velocities were used to compute total Kinetic energy (iK) and power (Pmax). KCG sorted dobutamine infusion vs. placebo with 96.9% accuracy. Increases in SV and CO were correlated to iK (r = +0.71 and r = +0.8, respectively, p < 0.0001). Kino-cardiography, with 12-DOF, allows detecting dobutamine-induced haemodynamic changes with a high accuracy and present a major improvement over single axis ballistocardiography or seismocardiography.
Gains and losses of metabolic function inferred from a phylotranscriptomic analysis of algae
Authors: Goh Falicia Qi Yun , Jeyakani Justin , Tipthara Phornpimon , Cazenave-Gassiot Amaury , Ghosh Rajoshi , Bogard Nicholas , Yeo Zhenxuan , Wong Gane Ka-Shu , Melkonian Michael , Wenk Markus R. , Clarke Neil D. 
Published: July 2019

AbstractHidden Markov models representing 167 protein sequence families were used to infer the presence or absence of homologs within the transcriptomes of 183 algal species/strains. Statistical analyses of the distribution of HMM hits across major clades of algae, or at branch points on the phylogenetic tree of 98 chlorophytes, confirmed and extended known cases of metabolic loss and gain, most notably the loss of the mevalonate pathway for terpenoid synthesis in green algae but not, as we show here, in the streptophyte algae. Evidence for novel events was found as well, most remarkably in the recurrent and coordinated gain or loss of enzymes for the glyoxylate shunt. We find, as well, a curious pattern of retention (or re-gain) of HMG-CoA synthase in chlorophytes that have otherwise lost the mevalonate pathway, suggesting a novel, co-opted function for this enzyme in select lineages. Finally, we find striking, phylogenetically linked distributions of coding sequences for three pathways that synthesize the major membrane lipid phosphatidylcholine, and a complementary phylogenetic distribution pattern for the non-phospholipid DGTS (diacyl-glyceryl-trimethylhomoserine). Mass spectrometric analysis of lipids from 25 species was used to validate the inference of DGTS synthesis from sequence data.
Molecular basis of the scalp-ear-nipple syndrome unraveled by the characterization of disease-causing KCTD1 mutants
Authors: Smaldone Giovanni , Balasco Nicole , Pirone Luciano , Caruso Daniela , Di Gaetano Sonia , Pedone Emilia Maria , Vitagliano Luigi 
Published: July 2019

AbstractThe scalp-ear-nipple (SEN) syndrome is an autosomal-dominant disorder characterized by cutis aplasia of the scalp and malformations of breast, external ears, digits, and nails. Genetic analyses have shown that the disease is caused by missense mutations of the KCTD1 protein, although the functional/structural basis of SEN insurgence is hitherto unknown. With the aim of unravelling the molecular basis of the SEN syndrome associated with KCTD1 mutations we here expressed and characterized several disease causing mutants. A preliminary dissection of the protein provides insights into the role that individual domains play in KCTD1 stability. The characterization of SEN-causing mutants indicates that, although the mutation sites are located in distant regions of the BTB domain or of the pre-BTB region, all of them are unable to interact with the transcription factor AP-2α, a well-known KCTD1 biological partner. Notably, all mutations, including the one located in the pre-BTB region, produce a significant destabilization of the protein. The structural role of the pre-BTB region in KCTD1 and other proteins of the family is corroborated by its sequence conservation in orthologs and paralogs. Interestingly, SEN-causing mutations also favor the tendency of KCTD1 to adopt structural states that are characterized by the ability to bind the β-amyloid fluorescent dye thioflavin T. The formation of aggregation-prone species may have important implications for the disease etiology. Collectively, these findings provide an intriguing picture of the functional and structural alterations induced by KCTD1 mutations that ultimately lead to disease.
Machine Learning Approaches for Automated Lesion Detection in Microwave Breast Imaging Clinical Data
Authors: Rana Soumya Prakash , Dey Maitreyee , Tiberi Gianluigi , Sani Lorenzo , Vispa Alessandro , Raspa Giovanni , Duranti Michele , Ghavami Mohammad , Dudley Sandra 
Published: July 2019

AbstractBreast lesion detection employing state of the art microwave systems provide a safe, non-ionizing technique that can differentiate healthy and non-healthy tissues by exploiting their dielectric properties. In this paper, a microwave apparatus for breast lesion detection is used to accumulate clinical data from subjects undergoing breast examinations at the Department of Diagnostic Imaging, Perugia Hospital, Perugia, Italy. This paper presents the first ever clinical demonstration and comparison of a microwave ultra-wideband (UWB) device augmented by machine learning with subjects who are simultaneously undergoing conventional breast examinations. Non-ionizing microwave signals are transmitted through the breast tissue and the scattering parameters (S-parameter) are received via a dedicated moving transmitting and receiving antenna set-up. The output of a parallel radiologist study for the same subjects, performed using conventional techniques, is taken to pre-process microwave data and create suitable data for the machine intelligence system. These data are used to train and investigate several suitable supervised machine learning algorithms nearest neighbour (NN), multi-layer perceptron (MLP) neural network, and support vector machine (SVM) to create an intelligent classification system towards supporting clinicians to recognise breasts with lesions. The results are rigorously analysed, validated through statistical measurements, and found the quadratic kernel of SVM can classify the breast data with 98% accuracy.
Sex-, feeding-, and circadian time-dependency of P-glycoprotein expression and activity - implications for mechanistic pharmacokinetics modeling
Authors: Okyar Alper , Kumar Swati A. , Filipski Elisabeth , Piccolo Enza , Ozturk Narin , Xandri-Monje Helena , Pala Zeliha , Abraham Kristin , Gomes Ana Rita Gato de Jesus , Orman Mehmet N. , Li Xiao-Mei , Dallmann Robert , Lévi Francis , Ballesta Annabelle 
Published: July 2019

AbstractP-glycoprotein (P-gp) largely influences the pharmacokinetics (PK) and toxicities of xenobiotics in a patient-specific manner so that personalized drug scheduling may lead to significant patient’s benefit. This systems pharmacology study investigated P-gp activity in mice according to organ, sex, feeding status, and circadian time. Sex-specific circadian changes were found in P-gp ileum mRNA and protein levels, circadian amplitudes being larger in females as compared to males. Plasma, ileum and liver concentrations of talinolol, a pure P-gp substrate, significantly differed according to sex, feeding and circadian timing. A physiologically-based PK model was designed to recapitulate these datasets. Estimated mesors (rhythm-adjusted mean) of ileum and hepatic P-gp activity were higher in males as compared to females. Circadian amplitudes were consistently higher in females and circadian maxima varied by up to 10 h with respect to sex. Fasting increased P-gp activity mesor and dampened its rhythm. Ex-vivo bioluminescence recordings of ileum mucosae from transgenic mice revealed endogenous circadian rhythms of P-gp protein expression with a shorter period, larger amplitude, and phase delay in females as compared to males. Importantly, this study provided model structure and parameter estimates to refine PK models of any P-gp substrate to account for sex, feeding and circadian rhythms.
Compatibility of Maximum Inorganic and Organic Calcium and Phosphate Content in Neonatal Parenteral Solutions
Authors: Watrobska-Swietlikowska Dorota 
Published: July 2019

AbstractThe purpose of the study was to determine the maximum safe concentration of calcium and phosphate in neonatal parenteral nutrition (PN) solutions when various combinations of inorganic and organic salts are applied. Twelve PN solutions for neonatal use were aseptically prepared. Increasing concentrations of inorganic and organic calcium and phosphate were added to the standard formulas. Each admixture was separately tested according to the following conditions; after mixing, at 37 °C for 24 hr, and the maximum safe combination of calcium and phosphate were stored at 4 °C for 30 days and followed by 24 hr at 37 °C. Visual inspections and microscopic observation of undiluted PN solutions as well as the membrane filter after filtration of the PN solution, pH evaluation, and absorbance were examined. The safe maximum concentration of organic and inorganic calcium and phosphate were proposed individually for each composition of parenteral nutrition solutions. Surprisingly, organic calcium with organic phosphate showed precipitation but over the therapeutic range. The protective effect of amino acid was observed and higher concentrations of calcium and phosphate were free of precipitation. This work is valuable in daily practice as it allows an increase in the limits of calcium and phosphate in PN solutions for infants.
Analysis of serum adiponectin and leptin in patients with acute exacerbation of idiopathic pulmonary fibrosis
Authors: Enomoto Noriyuki , Oyama Yoshiyuki , Yasui Hideki , Karayama Masato , Hozumi Hironao , Suzuki Yuzo , Kono Masato , Furuhashi Kazuki , Fujisawa Tomoyuki , Inui Naoki , Nakamura Yutaro , Suda Takafumi 
Published: July 2019

AbstractWeight loss progresses with the progression of idiopathic pulmonary fibrosis (IPF), and acute exacerbation of IPF (AE-IPF) frequently occurs in its advanced stage. Adiponectin and leptin are adipokines produced from adipose tissue, and are related to thinness and obesity, respectively. Additionally, these adipokines are implicated in the regulation of inflammation and fibrosis centering on peroxisome proliferator-activated receptor γ (PPARγ). However, the relationship between adiponectin/leptin and AE-IPF remains poorly known. We conducted this study to evaluate levels of serum adiponectin/leptin, and to elucidate the clinical importance of adiponectin and leptin in patients with AE-IPF. Thirty-two patients (39 episodes) who were diagnosed with AE-IPF at our hospital from 1997 to 2016 were retrospectively studied. Serum adiponectin and leptin concentrations were measured with enzyme-linked immunosorbent assay. Patients with AE-IPF showed higher levels of serum adiponectin and leptin than those at initial diagnosis of IPF (p = 0.007 and p = 0.027, respectively). Serum adiponectin/leptin (A/L) ratio was negatively correlated with body mass index at AE-IPF (r = −0.456, p = 0.003) and PaO2 before AE-IPF (r = −0.498, p = 0.034), and positively correlated with C-reactive protein at AE-IPF (r = 0.316, p = 0.049). Patients with higher A/L ratios had worse survival than those with lower A/L ratios (log-rank, p = 0.026). Further, in multivariate analysis, serum A/L ratio was a significant prognostic factor in patients with AE-IPF (HR 2.60, p = 0.042). In conclusion, the higher adiponectin/leptin ratio may be associated with a poor prognosis in patients with AE-IPF.
Multistep Protein Unfolding Scenarios from the Rupture of a Complex Metal Cluster Cd3S9
Authors: Yuan Guodong , Ma Qun , Wu Tao , Wang Mengdi , Li Xi , Zuo Jinglin , Zheng Peng 
Published: July 2019

AbstractProtein (un)folding is a complex and essential process. With the rapid development of single-molecule techniques, we can detect multiple and transient proteins (un)folding pathways/intermediates. However, the observation of multiple multistep (>2) unfolding scenarios for a single protein domain remains limited. Here, we chose metalloprotein with relatively stable and multiple metal-ligand coordination bonds as a system for such a purpose. Using AFM-based single-molecule force spectroscopy (SMFS), we successfully demonstrated the complex and multistep protein unfolding scenarios of the β-domain of a human protein metallothionein-3 (MT). MT is a protein of ~60 amino acids (aa) in length with 20 cysteines for various metal binding, and the β-domain (βMT) is of ~30 aa with an M3S9 metal cluster. We detected four different types of three-step protein unfolding scenarios from the Cd-βMT, which can be possibly explained by the rupture of Cd-S bonds in the complex Cd3S9 metal cluster. In addition, complex unfolding scenarios with four rupture peaks were observed. The Cd-S bonds ruptured in both single bond and multiple bonds modes. Our results provide not only evidence for multistep protein unfolding phenomena but also reveal unique properties of metalloprotein system using single-molecule AFM.
Cimp-Positive Status is More Representative in Multiple Colorectal Cancers than in Unique Primary Colorectal Cancers
Authors: Tapial Sandra , Olmedillas-López Susana , Rueda Daniel , Arriba María , García Juan L. , Vivas Alfredo , Pérez Jessica , Pena-Couso Laura , Olivera Rocío , Rodríguez Yolanda , García-Arranz Mariano , García-Olmo Damián , González-Sarmiento Rogelio , Urioste Miguel , Goel Ajay , Perea José 
Published: July 2019

AbstractColorectal cancer (CRC) with CpG island methylator phenotype (CIMP) is recognized as a subgroup of CRC that shows association with particular genetic defects and patient outcomes. We analyzed CIMP status of 229 individuals with CRC using an eight-marker panel (CACNA1G, CDKN2A, CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1); CIMP-(+) tumors were defined as having ≥ 5 methylated markers. Patients were divided into individuals who developed a “unique” CRC, which were subclassified into early-onset CRC (EOCRC) and late-onset CRC (LOCRC), and patients with multiple primary CRCs subclassified into synchronous CRC (SCRC) and metachronous CRC (MCRC). We found 9 (15.2%) CIMP-(+) EOCRC patients related with the proximal colon (p = 0.008), and 19 (26.8%) CIMP-(+) LOCRC patients associated with tumor differentiation (p = 0.045), MSI status (p = 0.021) and BRAF mutation (p = 0.001). Thirty-five (64.8%) SCRC patients had at least one CIMP-(+) tumor and 20 (44.4%) MCRC patients presented their first tumor as CIMP-(+). Thirty-nine (72.2%) SCRC patients showed concordant CIMP status in their simultaneous tumors. The differences in CIMP-(+) frequency between groups may reflect the importance of taking into account several criteria for the development of multiple primary neoplasms. Additionally, the concordance between synchronous tumors suggests CIMP status is generally maintained in SCRC patients.
Severity of dental caries and risk of coronary heart disease in middle-aged men and women: a population-based cohort study of Korean adults, 2002–2013
Authors: Kim Kyuwoong , Choi Seulggie , Chang Jooyoung , Kim Sung Min , Kim Seon Jip , Kim Ryan Jin-Young , Cho Hyun-Jae , Park Sang Min 
Published: July 2019

AbstractWe aimed to evaluate the risk of coronary heart disease (CHD) according to dental caries status in middle-aged patients using a population-based cohort database containing medical/dental claims, health examination, and death records in the Republic of Korea. A total of 234,597 patients were identified in the database who were without history of cardiovascular disease, including 104,638 patients without dental caries, 41,696 with incipient/moderate stage dental caries, and 88,262 advanced/severe dental caries. We used Cox proportional hazards model adjusted for sociodemographic, lifestyle, and medical characteristics to compute hazard ratio (HR) and 95% confidence intervals (95% CI) for CHD according to severity of dental caries. During 1,491,190 person-years of follow-up, there were a total of 6,015 CHD events. After adjustment for potential confounders, patients in the highest quartile of outpatient visits for advanced/severe stage dental caries was associated with an increase in CHD risk (HR = 1.13; 95% CI: 1.04–1.22) as compared with patients without dental caries. When the analysis was restricted to the patients with advanced/severe dental caries, dose-response relationship between number of outpatient visits for dental caries and risk of CHD was observed (Ptrend: <0.001). Prevention and control of dental caries might be worth promoting in clinical practice to prevent CHD.
Transcriptomic analysis of mouse cochleae suffering from gentamicin damage reveals the signalling pathways involved in hair cell regeneration
Authors: Bai Huanju , Jiang Lingling , Wang Xi , Gao Xue , Bing Jie , Xi Chao , Wang Weiqian , Zhang Meiguang , Zhang Xinwen , Han Zhongming , Xu Jincao , Zeng Shaoju 
Published: July 2019

AbstractThere is a strong capacity for hair cell regeneration after damage in the inner ear of non-mammals. However, mammalian hair cells are substantially unable to regenerate. To obtain insights into the mechanism of this difference, we analyzed the transcriptomic changes in the mouse cochleae suffered from gentamicin damage and compared them with those in the chick cochleae suffered from the same damage. The results indicated that 2,230 genes had significantly differential expression between the gentamicin- and saline-treated mouse cochleae. Some of the differentially expressed genes were grouped into 265 signaling pathways, including the Notch, Wnt (Wingless and INT-1), Bmp (bone morphogenetic protein), FGF (fibroblast growth factor) and Shh (sonic hedgehog) pathways. Using pharmacological inhibitors or agonists of these pathways, the effects of these pathways on hair cell regeneration were further studied. The results indicated that Bmp alone and its coregulation with the Notch or Wnt signaling pathways increased the numbers of generated cells from transdifferentiation or proliferation in the mouse cochlea after damage, in addition to the reported coregulation of Notch and Wnt. Thus, this work indicates a new signaling pathway (Bmp) and its synergetic coregulation in mammalian hair cell regeneration, providing potential therapeutic targets to increase mammalian hair cell regeneration.