bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAB8, RAB10 and RILPL1 contribute to both LRRK2 kinase–mediated centrosomal cohesion and ciliogenesis deficits
Authors: Lara Ordónez Antonio Jesús , Fernández Belén , Fdez Elena , Romo-Lozano María , Madero-Pérez Jesús , Lobbestael Evy , Baekelandt Veerle , Aiastui Ana , López de Munaín Adolfo , Melrose Heather L , Civiero Laura , Hilfiker Sabine 
Published: August 2019

AbstractMutations in the LRRK2 kinase are the most common cause of familial Parkinson’s disease, and variants increase risk for the sporadic form of the disease. LRRK2 phosphorylates multiple RAB GTPases including RAB8A and RAB10. Phosphorylated RAB10 is recruited to centrosome-localized RILPL1, which may interfere with ciliogenesis in a disease-relevant context. Our previous studies indicate that the centrosomal accumulation of phosphorylated RAB8A causes centrosomal cohesion deficits in dividing cells, including in peripheral patient-derived cells. Here, we show that both RAB8 and RAB10 contribute to the centrosomal cohesion deficits. Pathogenic LRRK2 causes the centrosomal accumulation not only of phosho-RAB8 but also of phospho-RAB10, and the effects on centrosomal cohesion are dependent on RAB8, RAB10 and RILPL1. Conversely, the pathogenic LRRK2-mediated ciliogenesis defects correlate with the centrosomal accumulation of both phospho-RAB8 and phospho-RAB10. LRRK2-mediated centrosomal cohesion and ciliogenesis alterations are observed in patient-derived peripheral cells, as well as in primary astrocytes from mutant LRRK2 mice, and are reverted upon LRRK2 kinase inhibition. These data suggest that the LRRK2-mediated centrosomal cohesion and ciliogenesis defects are distinct cellular readouts of the same underlying phospho-RAB8/RAB10/RILPL1 nexus and highlight the possibility that either centrosomal cohesion and/or ciliogenesis alterations may serve as cellular biomarkers for LRRK2-related PD.
Differential north–south response of juvenile Chinook salmon (Oncorhynchus tshawytscha) marine growth to ecosystem change in the eastern Bering Sea, 1974–2010
Authors: Yasumiishi Ellen M , Farley Edward V , Maselko Jacek , Aydin Kerim Y , Kearney Kelly A , Hermann Albert J , Ruggerone Gregory T , Howard Katherine G , Strasburger Wesley W 
Published: August 2019

Abstract
Chinook salmon (Oncorhynchus tshawytscha, Salmonidae) returns to western Alaska were historically high and variable but recently reached record lows. Understanding the differential influence of climatic and oceanic conditions on the growth of juvenile Chinook salmon in the north and south eastern Bering Sea is key to understanding mechanisms and factors affecting the production dynamics of Chinook salmon from western Alaska and the Arctic. Summer growth was lower and more variable among years for Chinook salmon in the south than the north eastern Bering Sea. Summer growth decreased with a rise in sea temperatures in the north and south and increased with more sea ice coverage and a later time of ice retreat in the south but not in the north. Capelin (Mallotus villosus), an important prey for juvenile Chinook salmon in the north and during cold years may link increased growth to cooler sea temperatures. Reduced and more variable summer growth of juvenile Chinook salmon from the eastern Bering Sea with warming may have implications on overwintering survival.
Controllability criteria of fractional differential dynamical systems with non-instantaneous impulses
Authors: Vadivoo B Sundara , Raja R , Cao Jinde , Rajchakit G , Seadawy Aly R 
Published: August 2019

AbstractThis manuscript prospects the controllability criteria of non-instantaneous impulsive Volterra type fractional differential systems. By enroling an appropriate Gramian matrix that is often defined by the Mittag-Leffler function and with the assistance of Laplace transform, the necessary and sufficiency conditions for the controllability of non-instantaneous impulsive Volterra-type fractional differential equations are derived by using algebraic approach and Cayley–Hamilton theorem. An important feature present in our paper is that we have taken non-instantaneous impulses into the fractional order dynamical system and studied the controllability analysis, since this do not exist in the available source of literature. Inclusively, we have provided two illustrative examples with the existence of non-instantaneous impulse into the fractional dynamical system. So this demonstrates the validity and efficacy of our obtained criteria of the main section.
On Analytic Todd Classes of Singular Varieties
Authors: Bei Francesco , Piazza Paolo 
Published: August 2019

AbstractLet $(X,h)$ be a compact and irreducible Hermitian complex space. This paper is devoted to various questions concerning the analytic K-homology of $(X,h)$. In the 1st part, assuming either $\dim (\operatorname{sing}(X))=0$ or $\dim (X)=2$, we show that the rolled-up operator of the minimal $L^2$-$\overline{\partial }$ complex, denoted here $\overline{\eth }_{\textrm{rel}}$, induces a class in $K_0 (X)\equiv KK_0(C(X),\mathbb{C})$. A similar result, assuming $\dim (\operatorname{sing}(X))=0$, is proved also for $\overline{\eth }_{\textrm{abs}}$, the rolled-up operator of the maximal $L^2$-$\overline{\partial }$ complex. We then show that when $\dim (\operatorname{sing}(X))=0$ we have $[\overline{\eth }_{\textrm{rel}}]=\pi _*[\overline{\eth }_M]$ with $\pi :M\rightarrow X$ an arbitrary resolution and with $[\overline{\eth }_M]\in K_0 (M)$ the analytic K-homology class induced by $\overline{\partial }+\overline{\partial }^t$ on $M$. In the 2nd part of the paper we focus on complex projective varieties $(V,h)$ endowed with the Fubini–Study metric. First, assuming $\dim (V)\leq 2$, we compare the Baum–Fulton–MacPherson K-homology class of $V$ with the class defined analytically through the rolled-up operator of any $L^2$-$\overline{\partial }$ complex. We show that there is no $L^2$-$\overline{\partial }$ complex on $(\operatorname{reg}(V),h)$ whose rolled-up operator induces a K-homology class that equals the Baum–Fulton–MacPherson class. Finally in the last part of the paper we prove that under suitable assumptions on $V$ the push-forward of $[\overline{\eth }_{\textrm{rel}}]$ in the K-homology of the classifying space of the fundamental group of $V$ is a birational invariant.
Notch1 Signaling Pathway Promotes Proliferation and Mediates Differentiation Direction in Hippocampus of Streptococcus pneumonia Meningitis Rats
Authors: Zhang Zhijie , Xu Danfeng , Zhao Shengnan , Lian Di , Wu Jing , He Dake , Li Ling 
Published: August 2019

Abstract

Background
Streptococcus pneumonia meningitis (PM) is a major cause of childhood neurological deficits. Although the Notch1 signaling pathway regulates neurogenesis and neuroinflammation, we know little about its expression or influence on hippocampal neurogenesis and gliogenesis during PM.

Methods
We used immunofluorescence and Western blots to detect Notch1 signaling expression during experimental PM. Through double-labeling immunofluorescence, we investigated proliferation and differentiation in the dentate gyrus (DG) in PM before and after treatment with exogenous Notch1 activator (Jagged1) and inhibitor (IMR-1).

Results
Our results showed that Notch1 was activated after 24 hours in PM. Compared with the phosphate-buffered saline (PBS) control, Jagged1 increased the proliferation of neural stem cells and progenitor cells (NS/PCs) in DG. After 14 and 28 days of meningitis, astrocyte differentiation increased compared with control. Astrocyte differentiation was higher in the Jagged1 versus the PBS group. In contrast, IMR-1 increased neuronal differentiation but decreased astrocyte differentiation compared with dimethyl sulfoxide treatment.

Conclusions
Under PM, Notch1 signaling promotes NS/PC proliferation and astrocyte differentiation in DG, while decreasing neuronal differentiation. Transient activation of the Notch1 signaling pathway explains the reactive gliogenesis and limited neuronal differentiation observed in PM.
qRT-PCR versus IFA-based Quantification of Male and Female Gametocytes in Low-Density Plasmodium falciparum Infections and Their Relevance for Transmission
Authors: Gruenberg Maria , Hofmann Natalie E , Nate Elma , Karl Stephan , Robinson Leanne J , Lanke Kjerstin , Smith Thomas A , Bousema Teun , Felger Ingrid 
Published: August 2019

Abstract

Background
Accurate quantification of female and male gametocytes and sex ratios in asymptomatic low-density malaria infections are important for assessing their transmission potential. Gametocytes often escape detection even by molecular methods, therefore ultralow gametocyte densities were quantified in large blood volumes.

Methods
Female and male gametocytes were quantified in 161 PCR-positive Plasmodium falciparum infections from a cross-sectional survey in Papua New Guinea. Ten-fold concentrated RNA from 800 µL blood was analyzed using female-specific pfs25 and male-specific pfmget or mssp qRT-PCR. Gametocyte sex ratios from qRT-PCR were compared with those from immunofluorescence assays (IFA).

Results
Gametocytes were identified in 58% (93/161) P. falciparum-positive individuals. Mean gametocyte densities were frequently below 1 female and 1 male gametocyte/µL by qRT-PCR. The mean proportion of males was 0.39 (95% confidence interval, 0.33–0.44) by pfs25/pfmget qRT-PCR; this correlated well with IFA results (Pearsons r2 = 0.91; P &lt; .001). A Poisson model fitted to our data predicted 16% P. falciparum-positive individuals that are likely to transmit, assuming at least 1 female and 1 male gametocyte per 2.5 µL mosquito bloodmeal.

Conclusions
Based on model estimates of female and male gametocytes per 2.5 µL blood, P. falciparum-positive individuals detected exclusively by ultrasensitive diagnostics are negligible for human-to-mosquito transmission.
Estimating the transmission potential of ultralow-density malaria infections informs interventions. Almost all infections with ≥1 female and male gametocyte per 2.5 µL mosquito bloodmeal, and thus with highest likelihood of contributing to human-to-mosquito transmission, were detectable by standard molecular diagnostics.
Plasma Levels of C-Type Lectin REG3α and Gut Damage in People With Human Immunodeficiency Virus
Authors: Isnard Stéphane , Ramendra Rayoun , Dupuy Franck P , Lin John , Fombuena Brandon , Kokinov Nikola , Kema Ido , Jenabian Mohammad-Ali , Lebouché Bertrand , Costiniuk Cecilia T , Ancuta Petronela , Bernard Nicole F , Silverman Michael S , Lakatos Peter L , Durand Madeleine , Tremblay Cécile , Routy Jean-Pierre ,   Montreal Primary HIV Infection Study, the Canadian Cohort of HIV+ Slow Progressors, and the Canadian HIV and Aging Cohort Groups, Milne C , Lavoie S , Friedman J , Duchastel M , Villielm F , Asselin F , Boissonnault M , Maziade P J , Lavoie S , Milne M , Miaki N Z , Thériault M E , Lessard B , Charron M A , Dufresne S , Turgeon M E , Vézina S , Huchet E , Kerba J P , Poliquin M , Poulin S , Rochette P , Junod P , Longpré D , Pilarski R , Sasseville E , Charest L , Hamel A , Cloutier-Blais A , Massoud S , Chano F , Trottier B , Labrecque L , Fortin C , Hal-Gagne V , Munoz M , Deligne B , Martel-Laferrière V , Trottier B , Goyer M E , Teltscher M , de Pokomandy A , Cox J , Beauchamp E , Klein M , Haraoui L P 
Published: August 2019

AbstractBackgroundRegenerating islet-derived protein 3α (REG3α) is an antimicrobial peptide secreted by intestinal Paneth cells. Circulating REG3α has been identified as a gut damage marker in inflammatory bowel diseases. People living with human immunodeficiency virus (PWH) on antiretroviral therapy (ART) present with an abnormal intestinal landscape leading to microbial translocation, persistent inflammation, and development of non-AIDS comorbidities. Herein, we assessed REG3α as a marker of gut damage in PWH.MethodsPlasma from 169 adult PWH, including 30 elite controllers (ECs), and 30 human immunodeficiency virus (HIV)–uninfected controls were assessed. REG3α plasma levels were compared with HIV disease progression, epithelial gut damage, microbial translocation, and immune activation markers.ResultsCross-sectionally, REG3α levels were elevated in untreated and ART-treated PWH compared with controls. ECs also had elevated REG3α levels compared to controls. Longitudinally, REG3α levels increased in PWH without ART and decreased in those who initiated ART. REG3α levels were inversely associated with CD4 T-cell count and CD4:CD8 ratio, while positively correlated with HIV viral load in untreated participants, and with fungal product translocation and inflammatory markers in all PWH.ConclusionsPlasma REG3α levels were elevated in PWH, including ECs. The gut inflammatory marker REG3α may be used to evaluate therapeutic interventions and predict non-AIDS comorbidity risks in PWH.
In vitro synergy of β-lactam combinations against KPC-producing Klebsiella pneumoniae strains
Authors: Lawandi Alexander , Leite Gleice , Cheng Matthew P , Lefebvre Brigitte , Longtin Jean , Lee Todd C 
Published: August 2019

AbstractBackgroundDouble carbapenem therapy has been promoted as an alternative treatment for infections due to carbapenemase-producing Enterobacteriaceae where carbapenemase inhibitors are unavailable or when other agents have demonstrated toxicity with equally limited evidence. The capacity of other β-lactams and β-lactamase inhibitors to provide synergistic activity with carbapenems is unclear.ObjectivesThis study sought to investigate the in vitro synergistic potential of other β-lactam/β-lactamase combinations with meropenem against KPC producers.MethodsTime–kill assays were performed on 24 unique strains of KPC-producing Klebsiella pneumoniae. Combinations evaluated included meropenem or imipenem with one of the following: ertapenem, piperacillin/tazobactam or ceftolozane/tazobactam. Concentrations used for each drug were those considered physiologically attainable in patients with a time above the concentration exceeding 40%–50% of the dose interval. Combinations were considered to be synergistic when they reduced bacterial cfu/mL by ≥2 log10 at 24 h as compared with the single most active agent.ResultsThe combination of piperacillin/tazobactam with meropenem was found to be synergistic against 70.8% of the isolates, followed by ertapenem with meropenem (58.3%) and ceftolozane/tazobactam with meropenem (41.7%). The piperacillin/tazobactam combination was found to be more bactericidal than the other combinations, with 58.3% of isolates demonstrating a ≥4 log10 cfu/mL reduction at 24 h, as compared with 37.5% for ertapenem and 20.8% for ceftolozane/tazobactam combinations.ConclusionsThe combination of piperacillin/tazobactam with meropenem may be a potential therapy against KPC-producing K. pneumoniae when other therapies are unavailable or prohibitively toxic.
Extracting entities with attributes in clinical text via joint deep learning
Authors: Shi Xue , Yi Yingping , Xiong Ying , Tang Buzhou , Chen Qingcai , Wang Xiaolong , Ji Zongcheng , Zhang Yaoyun , Xu Hua 
Published: August 2019

Abstract

Objective
Extracting clinical entities and their attributes is a fundamental task of natural language processing (NLP) in the medical domain. This task is typically recognized as 2 sequential subtasks in a pipeline, clinical entity or attribute recognition followed by entity-attribute relation extraction. One problem of pipeline methods is that errors from entity recognition are unavoidably passed to relation extraction. We propose a novel joint deep learning method to recognize clinical entities or attributes and extract entity-attribute relations simultaneously.

Materials and Methods
The proposed method integrates 2 state-of-the-art methods for named entity recognition and relation extraction, namely bidirectional long short-term memory with conditional random field and bidirectional long short-term memory, into a unified framework. In this method, relation constraints between clinical entities and attributes and weights of the 2 subtasks are also considered simultaneously. We compare the method with other related methods (ie, pipeline methods and other joint deep learning methods) on an existing English corpus from SemEval-2015 and a newly developed Chinese corpus.

Results
Our proposed method achieves the best F1 of 74.46% on entity recognition and the best F1 of 50.21% on relation extraction on the English corpus, and 89.32% and 88.13% on the Chinese corpora, respectively, which outperform the other methods on both tasks.

Conclusions
The joint deep learning–based method could improve both entity recognition and relation extraction from clinical text in both English and Chinese, indicating that the approach is promising.
Ensuring electronic medical record simulation through better training, modeling, and evaluation
Authors: Zhang Ziqi , Yan Chao , Mesa Diego A , Sun Jimeng , Malin Bradley A 
Published: August 2019

Abstract

Objective
Electronic medical records (EMRs) can support medical research and discovery, but privacy risks limit the sharing of such data on a wide scale. Various approaches have been developed to mitigate risk, including record simulation via generative adversarial networks (GANs). While showing promise in certain application domains, GANs lack a principled approach for EMR data that induces subpar simulation. In this article, we improve EMR simulation through a novel pipeline that (1) enhances the learning model, (2) incorporates evaluation criteria for data utility that informs learning, and (3) refines the training process.

Materials and Methods
We propose a new electronic health record generator using a GAN with a Wasserstein divergence and layer normalization techniques. We designed 2 utility measures to characterize similarity in the structural properties of real and simulated EMRs in the original and latent space, respectively. We applied a filtering strategy to enhance GAN training for low-prevalence clinical concepts. We evaluated the new and existing GANs with utility and privacy measures (membership and disclosure attacks) using billing codes from over 1 million EMRs at Vanderbilt University Medical Center.

Results
The proposed model outperformed the state-of-the-art approaches with significant improvement in retaining the nature of real records, including prediction performance and structural properties, without sacrificing privacy. Additionally, the filtering strategy achieved higher utility when the EMR training dataset was small.

Conclusions
These findings illustrate that EMR simulation through GANs can be substantially improved through more appropriate training, modeling, and evaluation criteria.
Excess dietary leucine in diets for growing pigs reduces growth performance, biological value of protein, protein retention, and serotonin synthesis1
Authors: Kwon Woong B , Touchette Kevin J , Simongiovanni Aude , Syriopoulos Kostas , Wessels Anna , Stein Hans H 
Published: August 2019

Abstract
An experiment was conducted to test the hypothesis that excess dietary Leu affects metabolism of branched-chain amino acids (BCAA) in growing pigs. Forty barrows (initial body weight [BW]: 30.0 ± 2.7 kg) were housed individually in metabolism crates and allotted to 5 dietary treatments (8 replicates per treatment) in a randomized complete block design. The 5 diets were based on identical quantities of corn, soybean meal, wheat, and barley and designed to contain 100%, 150%, 200%, 250%, or 300% of the requirement for standardized ileal digestible Leu. Initial and final (day 15) BW of pigs were recorded. Daily feed consumption was also recorded. Urine and fecal samples were collected for 5 d following 7 d of adaptation to the diets. At the end of the experiment, blood and tissue samples were collected to analyze plasma urea N (PUN), plasma and hypothalamic serotonin, tissue BCAA, serum and tissue branched-chain α-keto acids, and messenger ribonucleic acid abundance of genes involved in BCAA metabolism. Results indicated that acid detergent fiber, average daily feed intake, and gain-to-feed ratio decreased (linear, P < 0.05) as dietary Leu increased. A trend (linear, P = 0.082) for decreased N retention and decreased (linear, P < 0.05) biological value of dietary protein was also observed, and PUN increased (linear, P < 0.05) as dietary Leu increased. A quadratic reduction (P < 0.05) in plasma serotonin and a linear reduction (P < 0.05) in hypothalamic serotonin were observed with increasing dietary Leu. Concentrations of BCAA in liver increased (linear, P < 0.001), whereas concentrations of BCAA in skeletal muscle decreased (linear, P < 0.05) as dietary Leu increased. Concentration of α-ketoisovalerate was reduced (linear and quadratic, P < 0.001) in liver, skeletal muscle, and serum, and α-keto-β-methylvalerate was reduced (linear, P < 0.001; quadratic, P < 0.001) in skeletal muscle and serum. In contrast, α-keto isocaproate increased (linear, P < 0.05) in liver and skeletal muscle and also in serum (linear and quadratic, P < 0.001) with increasing dietary Leu. Expression of mitochondrial BCAA transaminase and of the E1α subunit of branched-chain α-keto acid dehydrogenase increased (linear, P < 0.05) in skeletal muscle as dietary Leu increased. In conclusion, excess dietary Leu impaired growth performance and nitrogen retention, which is likely a result of increased catabolism of Ile and Val, which in turn reduces availability of these amino acids resulting in reduced protein retention, and excess dietary Leu also reduced hypothalamic serotonin synthesis.
Xylanase, and the role of digestibility and hindgut fermentation in pigs on energetic differences among high and low energy corn samples1
Authors: Petry Amy L , Masey O’Neill Helen V , Patience John F 
Published: August 2019

AbstractThe experimental objective was to evaluate the digestibility and fermentation differences between high and low energy corn samples and their response to xylanase supplementation. Four corn samples, 2 with higher DE content (HE-1 and HE-2; 3.74 and 3.75 Mcal DE/kg DM, respectively) and 2 with a lower DE content (LE-1 and LE-2; 3.63 and 3.56 Mcal DE/kg DM, respectively) were selected based upon a previous digestibility trial. Sixteen individually housed barrows (PIC 359 × C29; initial BW = 34.8 ± 0.23kg) were surgically fitted with an ileal T-cannula and randomly allotted to treatments in an 8 × 4 Youden square design. Dietary treatments were arranged in a 4 × 2 factorial: HE-1, HE-2, LE-1, and LE-2, with and without xylanase supplementation. Diets were formulated using one of the 4 corn samples, casein, vitamins, minerals, and 0.4% chromic oxide as an indigestible marker. Feed intake was established at approximately 3 times the estimated energy required for maintenance (NRC 2012) based upon the average initial BW of the pigs at the start of each collection period, which consisted of 9 d adaptation, 2 d of fecal, and 3 d of ileal collections. Diets, ileal, and fecal samples were analyzed for DM, GE, and total dietary fiber (TDF), to determine apparent total tract (ATTD), hindgut fermentation (HF), apparent ileal digestibility (AID) coefficients. A diet × enzyme interaction was not observed for any of the measured variables (P > 0.10). The HE-1 and HE-2 diets had greater ATTD of GE, and HE-2 diet had greater ATTD of DM (P < 0.001 and P = 0.007, respectively). Xylanase, independent of diet, improved the ATTD of GE and DM (84.8 vs. 83.6% for GE with and without enzyme, respectively, P = 0.008; and 84.2 and 83.0% with and without enzyme, respectively, P = 0.007). The energetic differences among these corn samples appeared to be driven by fermentability in the hindgut. Supplementing xylanase improves digestibility irrespective of the digestibility energy content of corn.