bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Feasibility of Predicting Impending Malignant Ventricular Arrhythmias on the basis of Signal Complexity of Heartbeat Intervals
Authors: Chen Zheng , Kido Koshiro , Ono Naoaki , Altaf-Ul-Amin MD , Kanaya Shigehiko , Huang Ming 
Published: December 2019

AbstractMalignant ventricular arrhythmias (MAs), such as ventricular tachycardia (VT) that presages cardiac arrest, present the highest hurdle for the healthcare community to overcome. Given that MAs occur unpredictably and lead to emergencies, convenient tracking devices, e.g. photoplethysmogram (PPG), that could predict MAs would be irreplaceably valuable. Since the use of heartbeat intervals (HbI) to predict the occurrence of arrhythmias is becoming more feasible, a further attempt to establish a new convenient approach for predicting impending MAs with HbI is worth trying. Assuming that intrinsic characteristics of MAs (VT and ventricular fibrillation: VF) can be revealed by a suitable approach on the basis of signal complexity, we propose an approach that first expresses the physiological status of the heart by HbI; then delineates the patterns of HbI by a new complexity metric (refined composite multi-scale entropy: RCMsEn); and finally trains a nonlinear machine learning model (random forest: RF) to learn the specific patterns of MAs so as to differentiate them from the normal sinus heart rhythm(N) and other prevalent arrhythmias (atrial fibrillation: AF, and premature ventricular contraction: V).For calculating entropy values and predicting MAs as early as possible (which is the aim of this study), two specifications are of interest: the minimal length of HbI needed to delineate the MAs patterns sufficiently (lenmin), and the maximum time length at which our model can predict impending MAs (timemax). We compared the RF model with support vector machine (SVM) models based on linear and Gaussian kernels. Results show that the RF model performs the best, reaching a 99.24% recall and a 99.87% precision for a HbI of 500 heartbeats (thelenmin) 374 seconds (thetimemax) preceding the occurrence of MAs. The HbI samples in this study were extracted from an electrocardiograph (ECG). However, given the subtle difference (0.1 ms typically) between the R-R interval of ECG and the P-P interval of PPG, this approach could be extended to HbI acquired by the PPG sensor and thus should be of substantial theoretical and practical significance in cardiac arrest prevention.
Molecular Phylogenetic Analysis of16S rRNASequences Identified Two lineages ofH. pyloriStrains Detected from Different Regions in Sudan Suggestive of Differential Evolution
Authors: Idris Abeer Babiker , Hassan Hadeel Gassim , Salaheldin Ali Maryam Atif , Eltaher Sulafa Mohamed , Idris Leena Babiker , Altayb Hisham N. , Abass Amin Mohamed , Ahmed Ibrahim Mustafa Mohammed , Ibrahim El-Amin Mohamed , Hassan Mohamed A. 
Published: December 2019

AbstractBackgroundH. pyloriis ubiquitous among humans, and one of the best studied examples of an intimate association between bacteria and humans. Under several diverse socio-demographic factors in Sudan, a continuous increase in the prevalence rate ofH. pyloriinfection has been noticed which represents a major public health challenge. In this study, we analyzed the molecular evolution ofH. pyloriStrains detected from different ethnic and regions of Sudan using16S rRNAgene and phylogenetic approach.Materials and methodsA total of 75 gastric biopsies taken from patients who had been referred for endoscopy from different regions of Sudan. The DNA extraction was done by using the guanidine chloride method. Two sets of primers (universal and specific for H. pylori) were used to amplify the16S ribosomalgene. Sanger sequencing was performed; then Blast these sequences with those available in the NCBI nucleotide database. The evolutionary aspects were analyzed using a MEGA7 software.ResultMolecular detection ofH. pylorihas shown that 28 (37.33%) of patients were positive forH. pylori. Bivariate analysis has found no significant differences exhibited across sociodemographic, endoscopy series andH. pyloriinfection. Nucleotide variations were found at five nucleotide positions (positions 219, 305, 578, 741 and 763-764) and one insertion mutation (750_InsC_751) was present in sixty-seven percent (7/12) of our strains. The phylogenetic tree diverged into two lineages.ConclusionThe phylogenetic analysis of16S rRNAsequences identified two lineages ofH. pyloristrains detected from different regions in Sudan. Sex mutations were detected in regions of the16S rRNAnot closely associated with either tetracycline or tRNA binding sites. 66.67% of them were located in the central domain of16S rRNA. Studying the effect of these mutations on the functions of16S rRNAmolecules in protein synthesis and antibiotic resistance is of great importance.
Temporal interference stimulation targets deep brain regions by modulating neural oscillations
Authors: Esmaeilpour Zeinab , Kronberg Greg , Reato Davide , Parra Lucas C , Bikson Marom 
Published: December 2019

AbstractTemporal interference (TI) stimulation of the brain generates amplitude-modulated electric fields oscillating in the kHz range. A validated current-flow model of the human head estimates that amplitude-modulated electric fields are stronger in deep brain regions, while unmodulated electric fields are maximal at the cortical regions. The electric field threshold to modulate carbachol-induced gamma oscillations in rat hippocampal slices was determined for unmodulated 0.05-2 kHz sine waveforms, and 5 Hz amplitude-modulated waveforms with 0.1-2 kHz carrier frequencies. The neuronal effects are replicated with a computational network model to explore the underlying mechanisms. Experiment and model confirm the hypothesis that spatial selectivity of temporal interference stimulation depends on the phasic modulation of neural oscillations only in deep brain regions. This selectivity is governed by network adaption (e.g. GABAb) that is faster than the amplitude-modulation frequency. The applied current required depends on the neuronal membrane time-constant (e.g. axons) approaching the kHz carrier frequency of temporal interference stimulation.
ERK-mediated mechanochemical waves direct collective cell polarization
Authors: Hino Naoya , Rossetti Leone , Marín-Llauradó Ariadna , Aoki Kazuhiro , Trepat Xavier , Matsuda Michiyuki , Hirashima Tsuyoshi 
Published: December 2019

AbstractDuring collective migration of epithelial cells, the migration direction is aligned over a large, tissue-scale expanse. Although the collective cell migration is known to be directed by mechanical forces transmitted via cell-cell junctions, it remains elusive how the intercellular force transmission is coordinated with intracellular biochemical signaling to achieve collective movements. Here we show that intercellular coupling of extracellular signal-regulated kinase (ERK)-mediated mechanochemical feedback in individual cells yields long-distance transmission of guidance cues. Mechanical stretch activates ERK through epidermal growth factor receptor (EGFR) activation, and the ERK activation triggers cell contraction. In addition, the contraction of the activated cell pulls neighboring cells via cell-cell junctions, evoking another round of ERK activation and contraction in the neighbors. Furthermore, anisotropic contraction based on front-rear cell polarization guarantees unidirectional propagation of ERK activation waves, and in turn, the ERK activation waves direct multicellular alignment of the polarity, leading to long-range ordered migration. Our findings reveal that mechanical forces mediate intercellular signaling underlying sustained transmission of guidance cues for collective cell migration.
LegoBody: facile generation of bispecific and multi-specific antibodies
Authors: Lang Shanshan , Yang Su , Bidlingmaier Scott , Lee Nam-Kyung , Liu Bin 
Published: December 2019

AbstractBispecific and multi-specific antibodies are capable of recognizing multiple ligands simultaneously or synergistically, creating complex biological interactions not achievable by monoclonal antibodies, thus expanding opportunities for novel therapy development. With the large number of monoclonal antibodies either approved or under clinical development, there are numerous opportunities to combine their specificities to further improve therapeutic potential. Although simple in concept, clinical development of bi- and multi-specific antibodies face several challenges, chief of which is how to efficiently and reliably produce bispecific and multi-specific antibodies with expected specificity and desired biophysical properties. In this study, we developed a modular approach that uses temporary linkers to enforce proper chain pairing and proteases such as thrombin to remove those linkers from the final product. Combined with the ‘knob-into-hole’ design, we can generate IgG-like, bi- or multi-specific antibodies from any pre-existing monoclonal antibodies. The approach is highly versatile and applicable to any monoclonal antibody pair or panel, expediting evaluation and therapeutic development of bi- and multi-specific antibodies.
Mechanisms governing irritant-evoked activation and calcium modulation of TRPA1
Authors: Zhao Jianhua , Lin King John V. , Paulsen Candice E. , Cheng Yifan , Julius David 
Published: December 2019

AbstractThe TRPA1 ion channel is a chemosensory receptor that is critical for detecting noxious chemical agents that elicit or exacerbate pain or itch. Here we use structural and electrophysiological methods to elucidate how a broad class of reactive electrophilic irritants activate TRPA1 through a two-step cysteine modification mechanism that promotes local conformational changes leading to widening of the selectivity filter to enhance calcium permeability and opening of a cytoplasmic gate. We also identify a calcium binding pocket that is remarkably conserved across TRP channel subtypes and accounts for all aspects of calcium-dependent TRPA1 regulation, including potentiation, desensitization, and activation by metabotropic receptors. These findings provide a structural basis for understanding how endogenous or exogenous chemical agents activate a broad-spectrum irritant receptor directly or indirectly through a cytoplasmic second messenger.
A metal artifact reduction method for small field of view CT imaging
Authors: Choi Seungwon , Moon Seunghyuk , Baek Jongduk 
Published: December 2019

AbstractTo reduce metal artifacts, several sinogram inpainting-based metal artifact reduction (MAR) methods have been proposed where projection data within the metal trace region of the sinogram are treated as missing and subsequently estimated. However, these methods generally assume data truncation does not occur and all metal objects reside inside the field-of-view (FOV). For small FOV imaging, these assumptions are violated, and thus existing inpainting-based MAR methods would not be effective. In this paper, we propose a new MAR method to reduce metal artifacts effectively in the presence of data truncation. The main idea behind the proposed method is the synthesis of a sinogram, which is treated as the originally measured sinogram. First, an initial reconstruction step is performed to remove truncation artifacts. The next step consists of a forward projection of the small FOV image, replacing the original sinogram with the synthesized sinogram. The final step is the application of sinogram inpainting based MAR methods using the synthesized sinogram. Verification of the proposed method was performed for three situations: extended cardiac-torso (XCAT) simulation, clinical data, and experimental data. The proposed method was applied with linear MAR (LMAR) and normalized MAR (NMAR), and the performance of the proposed method was compared with that of the previous method. For quantitative evaluation, normalized mean squared error (NMSE) and structure similarity (SSIM) were used. The results show the effectiveness of the proposed method to reduce residual metal artifacts, which are present in the results obtained with the previous method. The evaluation results using NMSE and SSIM also indicate that the proposed method is more effective than the previous method.
Improving Probabilistic Infectious Disease Forecasting Through Coherence
Authors: Gibson Graham Casey , Moran Kelly R. , Reich Nicholas G. , Osthus Dave 
Published: December 2019

AbstractWith an estimated $10.4 billion in medical costs and 31.4 million outpatient visits each year, influenza poses a serious burden of disease in the United States. To provide insights and advance warning into the spread of influenza, the U.S. Centers for Disease Control and Prevention (CDC) runs a challenge for forecasting weighted influenza-like illness (wILI) at the national and regional level. Many models produce independent forecasts for each geographical unit, ignoring the constraint that the national wILI is a weighted sum of regional wILI, where the weights correspond to the population size of the region. We propose a novel algorithm that transforms a set of independent forecast distributions to obey this constraint, which we refer to as probabilistically coherent. Enforcing probabilistic coherence led to an increase in forecast skill for 90% of the models we tested over multiple flu seasons, highlighting the importance of respecting the forecasting system’s geographical hierarchy.Author SummarySeasonal influenza causes a significant public health burden nationwide. Accurate influenza forecasting may help public health officials allocate resources and plan responses to emerging outbreaks. The U.S. Centers for Disease Control and Prevention (CDC) reports influenza data at multiple geographical units, including regionally and nationally, where the national data are by construction a weighted sum of the regional data. In an effort to improve influenza forecast accuracy across all models submitted to the CDC’s annual flu forecasting challenge, we examined the effect of imposing this geographical constraint on the set of independent forecasts, made publicly available by the CDC. We developed a novel method to transform forecast densities to obey the geographical constraint that respects the correlation structure between geographical units. This method showed consistent improvement across 90% of models and that held when stratified by targets and test seasons. Our method can be applied to other forecasting systems both within and outside an infectious disease context that have a geographical hierarchy.
Proteomics of Extracellular Vesicles Produced byGranulicatellaSpecies that cause Infective Endocarditis
Authors: Alkandari Sarah A , Bhardwaj Radhika G , Ellepola Arjuna , Karched Maribasappa 
Published: December 2019

AbstractWhen oral bacteria accidentally enter the bloodstream due to transient tissue damage during dental procedures, they have the potential to attach to the endocardium or an equivalent surface of an indwelling prosthesis and cause infection. Many bacterial species produce extracellular vesicles (EVs) as part of normal physiology, but also use it as a virulence strategy. In this study, it was hypothesized thatGranulicatellaspecies produce EVs that possibly help them in virulence. Therefore, the objectives were to isolate and characterize EVs produced by these species and to investigate their immune-stimulatory effects. The reference strainsG. adiacensCCUG 27809 andG. elegansCCUG 38949 were cultured on chocolate blood agar for 2 days. From subsequent broth cultures, the EVs were isolated using differential centrifugation and filtration protocol and then observed using scanning electron microscopy. Proteins in the vesicle preparations were identified by nano LC-ESI-MS/MS. The EVs proteomes were analyzed and characterized using different bioinformatics tools. The immune-stimulatory effect of the EVs was studied via ELISA quantification of IL-8, IL-1β and CCL5, major proinflammatory cytokines, produced from stimulated human PBMCs. It was revealed that bothG. adiacensandG. elegansproduced EVs, ranging in diameter from 30 to 250 nm. Overall,G. adiacensEVs contained 160 proteins, andG. elegansEVs contained 107 proteins. Both proteomes consist of several ribosomal proteins, DNA associated proteins, binding proteins, and metabolic enzymes. It was also shown that these EVs carry putative virulence factors including moonlighting proteins. These EVs were able to induce the production of IL-8, IL-1β and CCL5 from human PBMCs. The diversity in EVs content indicates that these vesicles could have possible roles in bacterial survival, invasion, host immune modulation as well as infection. Further functional characterization of theGranulicatellaEVs may provide new insights into virulence mechanisms of these important but less studied oral bacterial species.
A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS
Authors: Golini E. , Rigamonti M. , Iannello F. , De Rosa C. , Scavizzi F. , Raspa M. , Mandillo S. 
Published: December 2019

AbstractAmyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects both central and peripheral nervous system, leading to the degeneration of motor neurons, which eventually results in muscle atrophy, paralysis and death. Sleep disturbances are common in patients with ALS, leading to even further deteriorated quality of life. Investigating methods to potentially assess sleep and rest disturbances in animal models of ALS is thus of crucial interest.We used an automated home cage monitoring system (DVC®) to capture activity patterns that can potentially be associated with sleep and rest disturbances and thus to the progression of ALS in the SOD1G93A mouse model. DVC®enables non-intrusive 24/7 long term animal activity monitoring, which we assessed together with body weight decline and neuromuscular function deterioration measured by grid hanging and grip strength tests in male and female mice from 7 until 24 weeks of age.We show that as the ALS progresses over time in SOD1G93A mice, activity patterns during day time start becoming irregular, with frequent activity bouts that are neither observed in control mice nor in SOD1G93A at a younger age. The increasing irregularities of activity patterns during day time are quantitatively captured by designing a novel digital biomarker, referred to as Rest Disturbance Index (RDI). We show that RDI is a robust measure capable of detecting rest/sleep-related disturbances during the disease progression earlier than conventional methods, such as the grid hanging test. Moreover RDI highly correlates with grid hanging and body weight decline, especially in males.The non-intrusive long-term continuous monitoring of animal activity enabled by DVC®has been instrumental in discovering activity patterns potentially correlated with sleep and rest disturbances in the SOD1G93A mouse model of the ALS disease.
XFlow: An algorithm for extracting ion chromatograms
Authors: Gutierrez Mathew , Smith Rob 
Published: December 2019

AbstractMass spectrometry is a fundamental tool for modern proteomics. The increasing availability of mass spectrometry data paired with the increasing sensitivity and fidelity of the instruments necessitates new and more potent analytical methods. To that end, we have created and present XFlow, a feature detection algorithm for extracting ion chromatograms from MS1 LC-MS data. XFlow is a parameter-free procedurally agnostic feature detection algorithm that utilizes the latent properties of ion chromatograms to resolve them from the surrounding noise present in MS1 data. XFlow is designed to function on either profile or centroided data across different resolutions and instruments. This broad applicability lends XFlow strong utility as a one-size-fits-all method for MS1 analysis or target acquisition for MS2. XFlow is written in Java and packaged with JS-MS, an open-source mass spectrometry analysis toolkit.
Abrogation of RAB27A expression transiently affects melanoma cell proliferation
Authors: Guo Dajiang , Beaumont Kimberley A. , Sharp Danae M. , Lui Goldie Y. L. , Weninger Wolfgang , Haass Nikolas K. , Tikoo Shweta 
Published: December 2019

AbstractThe role of the small GTPase RAB27A as an essential melanosome trafficking regulator in melanocytes is well-accepted. A decade ago, RAB27A was identified as a tumor dependency gene that promotes melanoma cell proliferation. RAB27A has since been linked to another propeller of cancer progression: exosome secretion. We have recently demonstrated that RAB27A is overexpressed in a subset of melanomas. High RAB27A gene and protein expression correlates with poor prognosis in melanoma patients. Mechanistic investigations revealed that the generation of pro-invasive exosomes was RAB27A-dependent and, therefore, silencing RAB27A reduced melanoma cell invasionin vitroandin vivo. However, previous studies have implicated RAB27A to be involved in both proliferation and invasion of melanoma cells. In this study, we demonstrate that the effects of abrogating RAB27A expression on proliferation are temporary, in contrast to the previously reported persistent effects on tumor invasion and metastasis. Therefore, we assist in the dissection of the short-term versus long-term effects of RAB27A knockdown on melanoma cell proliferation, invasion, and metastasis. We believe that our findings provide novel insights into the effects of RAB27A blockade.SignificanceRAB27A is known to serve as an essential regulator for melanosome trafficking. However, to date its role in melanoma biology has not been completely deciphered. While there are consistent independent reports on the pro-invasive effects of RAB27A, there are conflicting data on its impact on cell proliferation. Here we show that indeed abrogation of RAB27A does reduce cellular proliferation; however, this effect is only transient, while the impact on invasion as reported previously is persistent. This finding offers an explanation for the apparent contradiction in the literature and provides a deeper understanding of RAB27A function in melanoma cell biology.
Oxygen-generated spatial distribution of cell population links to p53 status
Authors: Taxak Shashank , Pati Uttam 
Published: December 2019

ABSTRACTLow oxygen induces wild type p53 inactivation and selects for mutant-like p53 phenotypes for aggressive tumor growth. Recently, we have shown wild type p53 as a cellular oxygen-sensor that operates in switch-like fashion to transform its characters of a tumor suppressor or promoter in a gradient of hypoxia. However, it is unclear how hypoxic tumors select for wild type p53 phenotypes for oxygen-sensitive responses. Here, we show that oxygen-generated spatial distribution of the cell population induces p53 phenotype-specific survival or death. We have found that a dynamic state of spatial scatters or clustering patterns of cell populations favor the survival of wild type more than the mutant phenotypes in a wide range of oxygen fluctuation by affecting p53 subcellular localization. Our results demonstrate how spatial distribution could function to establish wild type p53-mediated oxygen sensing and cell fate decisions in a cell population with heterogeneous p53 allele status. We anticipate that such behavior of cells in a gradient of oxygen can be utilized by the hypoxic tumors to maintain distinct p53 alleles and determine the release and metastasis of single or clustered circulating tumor cells (CTCs).Summary sentenceOxygen variation results in p53 phenotype-specific cell fate via the spatial distribution pattern of the cell population