bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active particle feedback control with a single-shot detection convolutional neural network
Authors: Fränzl Martin , Cichos Frank 
Published: July 2020

AbstractThe real-time detection of objects in optical microscopy allows their direct manipulation, which has recently become a new tool for the control, e.g., of active particles. For larger heterogeneous ensembles of particles, detection techniques are required that can localize and classify different objects with strongly inhomogeneous optical contrast at video rate, which is often difficult to achieve with conventional algorithmic approaches. We present a convolutional neural network single-shot detector which is suitable for real-time applications in optical microscopy. The network is capable of localizing and classifying multiple microscopic objects at up to 100 frames per second in images as large as $$416 \times 416$$

416
×
416

pixels, even at very low signal-to-noise ratios. The detection scheme can be easily adapted and extended, e.g., to new particle classes and additional parameters as demonstrated for particle orientation. The developed framework is shown to control self-thermophoretic active particles in a heterogeneous ensemble selectively. Our approach will pave the way for new studies of collective behavior in active matter based on artificial interaction rules.
Hepatocytic transcriptional signatures predict comparative drug interaction potential of rifamycin antibiotics
Authors: Dyavar Shetty Ravi , Mykris Timothy M. , Winchester Lee C. , Scarsi Kimberly K. , Fletcher Courtney V. , Podany Anthony T. 
Published: July 2020

AbstractCurrent strategies to treat tuberculosis (TB) and co-morbidities involve multidrug combination therapies. Rifamycin antibiotics are a key component of TB therapy and a common source of drug–drug interactions (DDIs) due to induction of drug metabolizing enzymes (DMEs). Management of rifamycin DDIs are complex, particularly in patients with co-morbidities, and differences in DDI potential between rifamycin antibiotics are not well established. DME profiles induced in response to tuberculosis antibiotics (rifampin, rifabutin and rifapentine) were compared in primary human hepatocytes. We identified rifamycin induced DMEs, cytochrome P450 (CYP) 2C8/3A4/3A5, SULT2A, and UGT1A4/1A5 and predicted lower DDIs of rifapentine with 58 clinical drugs used to treat co-morbidities in TB patients. Transcriptional networks and upstream regulator analyses showed FOXA3, HNF4α, NR1I2, NR1I3, NR3C1 and RXRα as key transcriptional regulators of rifamycin induced DMEs. Our study findings are an important resource to design effective medication regimens to treat common co-conditions in TB patients.
Ehrlichia spp. and Anaplasma spp. in Xenarthra mammals from Brazil, with evidence of novel ‘Candidatus Anaplasma spp.’
Authors: Calchi Ana Cláudia , Vultão Juliana Gaboardi , Alves Mario Henrique , Yogui Débora Regina , Desbiez Arnaud Leonard Jean , De Santi Mariele , Santana Matheus de Souza , da Silva Thiago Merighi Vieira , Werther Karin , Teixeira Marta Maria Geraldes , Machado Rosangela Zacarias , André Marcos Rogério 
Published: July 2020

AbstractAnaplasmataceae agents are obligatory intracellular Gram-negative α-proteobacteria that are transmitted mostly by arthropod vectors. Although mammals of the Superorder Xenarthra (sloths, anteaters, and armadillos) have been implicated as reservoirs for several zoonotic agents, only few studies have sought to detect Anaplasmataceae agents in this group of mammals. This study aimed to investigate the occurrence and genetic diversity ofAnaplasmaspp. andEhrlichiaspp. in blood and spleen samples of free-living Xenarthra from four different states in Brazil (São Paulo, Mato Grosso do Sul, Rondônia, and Pará). Nested and conventional PCR screening assays were performed to detect therrsanddsbgenes ofAnaplasmaspp. andEhrlichiaspp., respectively. The assays were positive in 27.57% (91/330) of theAnaplasmaspp. and 24.54% (81/330) of theEhrlichiaspp. Of the 91 positiveAnaplasmaspp. samples, 56.04% were positive in a conventional PCR assay targeting the 23S–5S intergenic region. Phylogenetic and distance analyses based on therrsgene allocatedAnaplasmasequences from sloths captured in Rondônia and Pará states in a single clade, which was closely related to theA. marginale,A. ovis,andA. capraclades. The sequences detected in southern anteaters from São Paulo were allocated in a clade closely related to sequences ofAnaplasmaspp. detected inNasua nasua,Leopardus pardalis, andCerdocyon thousin Brazil. These sequences were positioned close toA. odocoileisequences. Genotype analysis corroborated previous findings and demonstrated the circulation of two distinctAnaplasmagenotypes in animals from north and southeast Brazil. The first genotype was new. The second was previously detected inN. nasuain Mato Grosso do Sul state. The intergenic region analyses also demonstrated two distinct genotypes ofAnaplasma. The sequences detected in Xenarthra from Pará and Rondônia states were closely related to those inA. marginale,A. ovis,andA. capra.Anaplasmaspp. sequences detected in Xenarthra from São Paulo and were allocated close to those inA. phagocytophilum. The analyses based on thedsbgene grouped theEhrlichiaspp. sequences with sequences ofE. canis(São Paulo, Mato Grosso do Sul, and Pará) andE. minasensis(Rondônia and Pará). The data indicate the occurrence ofE. canisandE. minasensisand two possible newCandidatusspecies ofAnaplasmaspp. in free-living mammals of the Superorder Xenarthra in Brazil.
Elevated troponin levels are associated with early neurological worsening in ischemic stroke with atrial fibrillation
Authors: Nam Ki-Woong , Kim Chi Kyung , Yu Sungwook , Chung Jong-Won , Bang Oh Young , Kim Gyeong-Moon , Jung Jin-Man , Song Tae-Jin , Kim Yong-Jae , Kim Bum Joon , Heo Sung Hyuk , Park Kwang-Yeol , Kim Jeong-Min , Park Jong-Ho , Choi Jay Chol , Park Man-Seok , Kim Joon-Tae , Choi Kang-Ho , Hwang Yang Ha , Seo Woo-Keun , Oh Kyungmi 
Published: July 2020

AbstractSerum cardiac troponin I (cTnI) is often elevated in patients with ischemic stroke, and is associated with their prognosis. Since cTnI is also closely related to atrial fibrillation (AF), cTnI may be a sensitive prognostic indicator in patients with AF-related stroke. This study aimed to evaluate the association between serum cTnI and early neurological deterioration (END) in patients with AF-related stroke. We included consecutive AF-related stroke patients between 2013 and 2015. END was defined as an increase ≥ 2 in the total NIHSS score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. A total of 1,133 patients with AF-related stroke were evaluated. In multivariable analysis, cTnI [adjusted odds ratio (aOR) = 1.16, 95% confidence interval (CI) 1.00–1.34; P = 0.047] remained significant after adjusting for confounders. Initial NIHSS score (aOR = 1.03, 95% CI 1.00–1.06; P = 0.043) was also positively associated with END; meanwhile, the use of anticoagulants was negatively associated in both vitamin K antagonists (aOR = 0.35, 95% CI 0.23–0.54; P < 0.001) and new oral anticoagulants (aOR = 0.41, 95% CI 0.19–0.89; P = 0.024). In conclusion, higher serum cTnI was associated with END in patients with AF-related stroke.
Structural analysis of 70S ribosomes by cross-linking/mass spectrometry reveals conformational plasticity
Authors: Tüting Christian , Iacobucci Claudio , Ihling Christian H. , Kastritis Panagiotis L. , Sinz Andrea 
Published: July 2020

AbstractThe ribosome is not only a highly complex molecular machine that translates the genetic information into proteins, but also an exceptional specimen for testing and optimizing cross-linking/mass spectrometry (XL-MS) workflows. Due to its high abundance, ribosomal proteins are frequently identified in proteome-wide XL-MS studies of cells or cell extracts. Here, we performed in-depth cross-linking of the E. coli ribosome using the amine-reactive cross-linker disuccinimidyl diacetic urea (DSAU). We analyzed 143 E. coli ribosomal structures, mapping a total of 10,771 intramolecular distances for 126 cross-link-pairs and 3,405 intermolecular distances for 97 protein pairs. Remarkably, 44% of intermolecular cross-links covered regions that have not been resolved in any high-resolution E. coli ribosome structure and point to a plasticity of cross-linked regions. We systematically characterized all cross-links and discovered flexible regions, conformational changes, and stoichiometric variations in bound ribosomal proteins, and ultimately remodeled 2,057 residues (15,794 atoms) in total. Our working model explains more than 95% of all cross-links, resulting in an optimized E. coli ribosome structure based on the cross-linking data obtained. Our study might serve as benchmark for conducting biochemical experiments on newly modeled protein regions, guided by XL-MS. Data are available via ProteomeXchange with identifier PXD018935.
Machine learning for predicting pathological complete response in patients with locally advanced rectal cancer after neoadjuvant chemoradiotherapy
Authors: Huang Chun-Ming , Huang Ming-Yii , Huang Ching-Wen , Tsai Hsiang-Lin , Su Wei-Chih , Chang Wei-Chiao , Wang Jaw-Yuan , Shi Hon-Yi 
Published: July 2020

AbstractFor patients with locally advanced rectal cancer (LARC), achieving a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) provides them with the optimal prognosis. However, no reliable prediction model is presently available. We evaluated the performance of an artificial neural network (ANN) model in pCR prediction in patients with LARC. Predictive accuracy was compared between the ANN, k-nearest neighbor (KNN), support vector machine (SVM), naïve Bayes classifier (NBC), and multiple logistic regression (MLR) models. Data from two hundred seventy patients with LARC were used to compare the efficacy of the forecasting models. We trained the model with an estimation data set and evaluated model performance with a validation data set. The ANN model significantly outperformed the KNN, SVM, NBC, and MLR models in pCR prediction. Our results revealed that the post-CRT carcinoembryonic antigen is the most influential pCR predictor, followed by intervals between CRT and surgery, chemotherapy regimens, clinical nodal stage, and clinical tumor stage. The ANN model was a more accurate pCR predictor than other conventional prediction models. The predictors of pCR can be used to identify which patients with LARC can benefit from watch-and-wait approaches.
Model-based optimization of combination protocols for irradiation-insensitive cancers
Authors: Hat Beata , Jaruszewicz-Błońska Joanna , Lipniacki Tomasz 
Published: July 2020

AbstractAlternations in the p53 regulatory network may render cancer cells resistant to the radiation-induced apoptosis. In this theoretical study we search for the best protocols combining targeted therapy with radiation to treat cancers with wild-type p53, but having downregulated expression of PTEN or overexpression of Wip1 resulting in resistance to radiation monotherapy. Instead of using the maximum tolerated dose paradigm, we exploit stochastic computational model of the p53 regulatory network to calculate apoptotic fractions for both normal and cancer cells. We consider combination protocols, with irradiations repeated every 12, 18, 24, or 36 h to find that timing between Mdm2 inhibitor delivery and irradiation significantly influences the apoptotic cell fractions. We assume that uptake of the inhibitor is higher by cancer than by normal cells and that cancer cells receive higher irradiation doses from intersecting beams. These two assumptions were found necessary for the existence of protocols inducing massive apoptosis in cancer cells without killing large fraction of normal cells neighboring tumor. The best found protocols have irradiations repeated every 24 or 36 h with two inhibitor doses per irradiation cycle, and allow to induce apoptosis in more than 95% of cancer cells, killing less than 10% of normal cells.
Cancer-associated fibroblasts stimulate primary tumor growth and metastatic spread in an orthotopic prostate cancer xenograft model
Authors: Linxweiler Johannes , Hajili Turkan , Körbel Christina , Berchem Carolina , Zeuschner Philip , Müller Andreas , Stöckle Michael , Menger Michael D. , Junker Kerstin , Saar Matthias 
Published: July 2020

AbstractThe unique microenvironment of the prostate plays a crucial role in the development and progression of prostate cancer (PCa). We examined the effects of cancer-associated fibroblasts (CAFs) on PCa progression using patient-derived fibroblast primary cultures in a representative orthotopic xenograft model. Primary cultures of CAFs, non-cancer-associated fibroblasts (NCAFs) and benign prostate hyperplasia-associated fibroblasts (BPHFs) were generated from patient-derived tissue specimens. These fibroblasts were coinjected together with cancer cells (LuCaP136 spheroids or LNCaP cells) in orthotopic PCa xenografts to investigate their effects on local and systemic tumor progression. Primary tumor growth as well as metastatic spread to lymph nodes and lungs were significantly stimulated by CAF coinjection in LuCaP136 xenografts. When NCAFs or BPHFs were coinjected, tumor progression was similar to injection of tumor cells alone. In LNCaP xenografts, all three fibroblast types significantly stimulated primary tumor progression compared to injection of LNCaP cells alone. CAF coinjection further increased the frequency of lymph node and lung metastases. This is the first study using an orthotopic spheroid culture xenograft model to demonstrate a stimulatory effect of patient-derived CAFs on PCa progression. The established experimental setup will provide a valuable tool to further unravel the interacting mechanisms between PCa cells and their microenvironment.
Rod function deficit in retained photoreceptors of patients with class B Rhodopsin mutations
Authors: Cideciyan Artur V. , Jacobson Samuel G. , Roman Alejandro J. , Sumaroka Alexander , Wu Vivian , Charng Jason , Lisi Brianna , Swider Malgorzata , Aguirre Gustavo D. , Beltran William A. 
Published: July 2020

AbstractA common inherited retinal disease is caused by mutations in RHO expressed in rod photoreceptors that provide vision in dim ambient light. Approximately half of all RHO mutations result in a Class B phenotype where mutant rods are retained in some retinal regions but show severe degeneration in other regions. We determined the natural history of dysfunction and degeneration of retained rods by serially evaluating patients. Even when followed for more than 20 years, rod function and structure at some retinal locations could remain unchanged. Other locations showed loss of both vision and photoreceptors but the rate of rod vision loss was greater than the rate of photoreceptor degeneration. This unexpected divergence in rates with disease progression implied the development of a rod function deficit beyond loss of cells. The divergence of progression rates was also detectable over a short interval of 2 years near the health-disease transition in the superior retina. A model of structure–function relationship supported the existence of a large rod function deficit which was also most prominent near regions of health-disease transition. Our studies support the realistic therapeutic goal of improved night vision for retinal regions specifically preselected for rod function deficit in patients.
Detection of femtosecond spin injection into a thin gold layer by time and spin resolved photoemission
Authors: Bühlmann K. , Saerens G. , Vaterlaus A. , Acremann Y. 
Published: July 2020

AbstractThe ultrafast demagnetization effect allows for the generation of femtosecond spin current pulses, which is expected to extend the fields of spin transport and spintronics to the femtosecond time domain. Thus far, directly observing the spin polarization induced by spin injection on the femtosecond time scale has not been possible. Herein, we present time- and spin-resolved photoemission results of spin injection from a laser-excited ferromagnet into a thin gold layer. The injected spin polarization is aligned along the magnetization direction of the underlying ferromagnet. Its decay time depends on the thickness of the gold layer, indicating that transport as well as storage of spins are relevant. This capacitive aspect of spin transport may limit the speed of future spintronic devices.
Lead sulphide colloidal quantum dots for room temperature NO2 gas sensors
Authors: Mitri Federica , De Iacovo Andrea , De Luca Massimiliano , Pecora Alessandro , Colace Lorenzo 
Published: July 2020

AbstractColloidal quantum dots (CQDs) have been recently investigated as promising building blocks for low-cost and high-performance gas sensors due to their large effective surface-to-volume ratio and their suitability for versatile functionalization through surface chemistry. In this work we report on lead sulphide CQDs based sensors for room temperature NO2 detection. The sensor response has been measured for different pollutant gases including NO2, CH4, CO and CO2 and for different concentrations in the 2.8–100 ppm range. For the first time, the influence of the QDs film thickness on the sensor response has been investigated and optimized. Upon 30 ppm NO2 release, the best room temperature gas response is about 14 Ω/Ω, with response and recovery time of 12 s and 26 min, respectively. A detection limit of about 0.15 ppb was estimated from the slope of the sensor response and its electric noise. The gas sensors exhibit high sensitivity to NO2, remarkable selectivity, repeatability and full recovery after exposure.
α-Hemolysin of uropathogenic E. coli regulates NLRP3 inflammasome activation and mitochondrial dysfunction in THP-1 macrophages
Authors: Verma Vivek , Kumar Parveen , Gupta Surbhi , Yadav Sonal , Dhanda Rakesh Singh , Thorlacius Henrik , Yadav Manisha 
Published: July 2020

AbstractHemolysin expressing UPEC strains have been associated with severe advanced kidney pathologies, such as cystitis and pyelonephritis, which are associated with an inflammatory response. Macrophages play an important role in regulating an inflammatory response during a urinary tract infection. We have studied the role of purified recombinant α-hemolysin in inducing inflammatory responses and cell death in macrophages. Acylation at lysine residues through HlyC is known to activate proHlyA into a fully functional pore-forming toxin, HlyA. It was observed that active α-hemolysin (HlyA) induced cleavage of caspase-1 leading to the maturation of IL-1β, while inactive α-hemolysin (proHlyA) failed to do so in THP-1 derived macrophages. HlyA also promotes deubiquitination, oligomerization, and activation of the NLRP3 inflammasome, which was found to be dependent on potassium efflux. We have also observed the co-localization of NLRP3 within mitochondria during HlyA stimulations. Moreover, blocking of potassium efflux improved the mitochondrial health in addition to a decreased inflammatory response. Our study demonstrates that HlyA stimulation caused perturbance in potassium homeostasis, which led to the mitochondrial dysfunction followed by an acute inflammatory response, resulting in cell death. However, the repletion of intracellular potassium stores could avoid HlyA induced macrophage cell death. The findings of this study will help to understand the mechanism of α-hemolysin induced inflammatory response and cell death.
Cell spheroid fusion: beyond liquid drops model
Authors: Kosheleva Nastasia V. , Efremov Yuri M. , Shavkuta Boris S. , Zurina Irina M. , Zhang Deying , Zhang Yuanyuan , Minaev Nikita V. , Gorkun Anastasiya A. , Wei Shicheng , Shpichka Anastasia I. , Saburina Irina N. , Timashev Peter S. 
Published: July 2020

AbstractBiological self-assembly is crucial in the processes of development, tissue regeneration, and maturation of bioprinted tissue-engineered constructions. The cell aggregates—spheroids—have become widely used model objects in the study of this phenomenon. Existing approaches describe the fusion of cell aggregates by analogy with the coalescence of liquid droplets and ignore the complex structural properties of spheroids. Here, we analyzed the fusion process in connection with structure and mechanical properties of the spheroids from human somatic cells of different phenotypes: mesenchymal stem cells from the limbal eye stroma and epithelial cells from retinal pigment epithelium. A nanoindentation protocol was applied for the mechanical measurements. We found a discrepancy with the liquid drop fusion model: the fusion was faster for spheroids from epithelial cells with lower apparent surface tension than for mesenchymal spheroids with higher surface tension. This discrepancy might be caused by biophysical processes such as extracellular matrix remodeling in the case of mesenchymal spheroids and different modes of cell migration. The obtained results will contribute to the development of more realistic models for spheroid fusion that would further provide a helpful tool for constructing cell aggregates with required properties both for fundamental studies and tissue reparation.
Characterization of skin surface and dermal microbiota in dogs with mast cell tumor
Authors: Zamarian Valentina , Catozzi Carlotta , Cuscó Anna , Stefanello Damiano , Ferrari Roberta , Ceciliani Fabrizio , Francino Olga , Sánchez Armand , Grieco Valeria , Zani Davide , Talenti Andrea , Crepaldi Paola , Lecchi Cristina 
Published: July 2020

AbstractThe skin microbiota interacts with the host immune response to maintain the homeostasis. Changes in the skin microbiota are linked to the onset and the progression of several diseases, including tumors. We characterized the skin surface and dermal microbiota of 11 dogs affected by spontaneous mast cell tumor (MCT), using skin contralateral sites as intra-animal healthy controls. The microbial profile differed between healthy and tumor skin surfaces and dermis, demonstrating that the change in microbiota composition is related to the presence of MCT. The number of observed taxa between MCT and healthy skin surfaces was detected, showing a decrease in number and heterogeneity of taxa over the skin surface of MCT, at both inter- and intra-individual level. Preliminary data on bacterial population of MCT dermis, obtained only on three dogs, demonstrated an intra-individual reduction of taxa number when compared to the skin surface. Taxonomy reveals an increase of Firmicutes phylum and Corynebacteriaceae family in MCT skin surface when compared to the healthy contralateral. In conclusion, we demonstrate that microbial population of skin surface and dermis is related to mast cell tumor. Our study provides the basis for future investigations aiming to better define the interaction between mast cell tumors, microbiota and host immune response.
Laparoscopic complete mesocolic excision with D3 lymph node dissection for right colon cancer in elderly patients
Authors: Hwang Duk Yeon , Lee Gyeo Ra , Kim Ji Hoon , Lee Yoon Suk 
Published: July 2020

AbstractComplete mesocolic excision (CME) with D3 lymph node dissection is considered an oncological surgery for right colon cancer. However, there is still controversy for extensive oncological surgery in elderly patients. The aim of this study is to evaluate the safety and oncological outcomes of laparoscopic CME with D3 lymph node dissection for right colon cancer in elderly patients. Patients who underwent laparoscopic right colectomy, from 2004 to 2014, were divided into Groups A (age ≥ 70 years, n = 80) or B (age < 70 years, n = 127). Short and long-term outcomes were analysed. Basic demographics and short-term surgical outcomes were similar between groups. Among pathological outcomes, the mean number of harvested lymph nodes was significantly less in Group A. Adjuvant chemotherapy refusal rate was significantly higher in Group A. Overall and recurrence-free survival were similar between groups. We found laparoscopic CME with D3 lymph node dissection is a safe and feasible surgical option for right colon cancer in elderly patients.