bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-O1/non-O139 Vibrio cholerae bacteraemia in mainland China from 2005 to 2019: clinical, epidemiological and genetic characteristics
Authors: Li Xinyao , Wu Yuanyuan , Sun Xiaojun , Ma Jianping , Li Xiaofeng , Liu Cuiping , Xie Hongxiang 
Published: July 2020

Abstract
In mainland China, the clinical, epidemiological and genetic features of non-O1/non-O139 Vibrio cholerae (NOVC) bacteraemia have been scarcely investigated. Herein, we describe a patient with NOVC bacteraemia diagnosed in our hospital and present a retrospective analysis of literature reports of 32 other cases in China, detailing the clinical epidemiology, antibiotic resistance and molecular characteristics of isolates. Most patients were male (84.8%; median age, 53 years) and had predisposing factors, such as cirrhosis, malignant tumours, blood diseases and diabetes. In addition to fever, gastroenteritis was the most frequent presenting symptom. The mortality rate during hospitalisation was 12.1%. NOVC bacteraemia cases were more common in June–August, with the majority in coastal provinces and the Yangtze River basin. Only 42.4% of cases were attributed to consumption of marine (aquatic) products. Tetracycline, third-generation cephalosporins, and fluoroquinolones were the most effective antimicrobial agents, and the highest frequencies of resistance were recorded for ampicillin/sulbactam (37.5%), amoxicillin/clavulanic acid (33.3%), ampicillin (29.2%) and sulfamethoxazole (20%). Multi-drug resistant isolates were not detected. Limited data indicate that ctxAB and tcpA genes were absent in all NOVC isolates but other putative virulence genes (hlyA, toxR, hap and rtxA) were common. Ten multilocus sequence types were identified with marked genetic heterogeneity between different isolates. As clinical manifestations of NOVC bacteraemia may vary widely, and isolates exhibit genetic diversity, clinicians and public health experts should be alerted to the possibility of infection with this pathogen because of the high prevalence of liver disease in China.
A rare coincidence: the long QT syndrome and cardio-facio-cutaneous syndrome
Authors: Giray Dilek , Donmez Yasemin N. , Epcacan Serdar , Goktas Emine 
Published: July 2020

AbstractCardio-facio-cutaneous syndrome is a genetic anomaly characterised by craniofacial dysmorphia, developmental retardation, skin lesions, mental retardation/learning disability, and cardiac malformations. Cardio-facio-cutaneous syndrome rarely causes arrhythmias and has not been previously associated with long QT in the literature. With this report, it was aimed to draw attention to a different presentation of the long QT syndrome.
Memory Properties in Cloud‐Resolving Simulations of the Diurnal Cycle of Deep Convection
Authors: Daleu C. L. , Plant R. S. , Woolnough S. J. , Stirling A. J. , Harvey N. J. 
Published: July 2020

AbstractA series of high‐resolution three‐dimensional simulations of the diurnal cycle of deep convection over land are performed using the new Met Office NERC cloud‐resolving model. This study features scattered convection. A memory function is defined to identify the effects of previous convection in modifying current convection. It is based on the probability of finding rain at time t0 and at an earlier time t0−Δt compared to the expected probability given no memory. The memory is examined as a function of the lag time Δt. It is strongest at gray‐zone scales of 4–10 km, there is a change of behavior for spatial scales between 10 and 15 km, and it is reduced substantially for spatial scales larger than 25 km. At gray‐zone scales, there is a first phase of the memory function which represents the persistence of convection and it is maintained for about an hour. There is a second phase which represents the suppression of convection in regions which were raining 1 to 3 hr previously, and subsequently a third phase which represents a secondary enhancement of precipitation. The second and third phases of the memory function develop earlier for weaker forcing. When thermodynamic fluctuations resulting from the previous day are allowed to influence the development of convection on the next day, there are fewer rainfall events with relatively large sizes, which are more intense, and thus decay and recover more slowly, in comparison to the simulations where feedback from previous days is removed. Further sensitivity experiments reveal that convective memory attributed to these thermodynamic fluctuations resides in the lower troposphere.
Characterizing Tropical Cyclones in the Energy Exascale Earth System Model Version 1
Authors: Balaguru Karthik , Leung L. Ruby , Van Roekel Luke P. , Golaz Jean‐Christophe , Ullrich Paul A. , Caldwell Peter M. , Hagos Samson M. , Harrop Bryce E. , Mametjanov Azamat 
Published: July 2020

AbstractIn this study, we analyze the realism with which tropical cyclones (TCs) are simulated in the fully coupled low‐ and high‐resolution Energy Exascale Earth System Model (E3SM) version 1, with a focus on the latter. Compared to the low‐resolution (grid spacing of ∼1°), the representation of TCs improves considerably in the high‐resolution configuration (grid spacing of ∼0.25°). Significant improvements are found in the global TC frequency, TC lifetime maximum intensities, and the relative distribution of TCs among the different basins. However, at both resolutions, spurious TC activity is found in some basins, notably in the subtropical regions. Contrasting the simulated large‐scale TC environment with observations reveals that the model environment is unrealistically conducive for TC development in those regions. Further analysis indicates that these biases are likely related to those in thermodynamic potential intensity, caused by systematic SST biases, and vertical wind shear in the coupled model. TC‐ocean interaction is also examined in the high‐resolution configuration of the model. The salient features of the ocean's response to TC‐induced mixing and the ocean's impact on TC intensification are well‐reproduced. Finally, an evaluation of the influence of El Niño Southern Oscillation (ENSO) on TCs in the high‐resolution configuration of the model reveals that the ENSO‐TC relationship in the model has the right sign and is significant for the North Atlantic and Northwest Pacific, albeit weaker than in observations. In summary, the high‐resolution configuration of the E3SM model simulates TC activity reasonably and hence could be a useful tool for TC‐related research.
Latitudinal Variation in Plankton Traits and Ecosystem Function
Authors: Chakraborty Subhendu , Cadier Mathilde , Visser André W. , Bruggeman Jorn , Andersen Ken H. 
Published: July 2020

AbstractPlanktonic ecosystems are usually modeled in terms of autotrophic and heterotrophic compartments. However, the trophic strategy of unicellular organisms can take a range of mixotrophic strategies with both autotrophic and heterotrophic contributions. The dominant emerging strategy found in nature depends on the environment (both biotic and abiotic aspects) and the cell size and influences key ecosystem functions like trophic transfer and carbon export. Ecosystem models that faithfully represent this diversity of trophic strategies are lacking. Here we develop a trait‐based model of unicellular plankton with cell size as the master trait and three other traits that determine trophic strategies: investments in photosynthesis, nutrient uptake, and phagotrophy. This unicellular model spans the entire auto‐ mixo‐ hererotrophic strategy continuum and the entire size range of unicellular organisms. The model reproduces observed latitudinal patterns in biomass, primary productivity, vertical carbon export, and energy transfer efficiency; all increase with increasing latitude. The size range of mixotrophic cells is independent of the season at low latitudes. At high latitudes, the dominance of pure phototrophs during early spring restricts mixotrophic behavior to a narrower range of cell sizes and with the occurrence of relatively smaller mixotrophs during summer. The model's ability to adapt to different environmental conditions, combined with its simple conceptual structure and low number of parameters and state variables (10), makes it ideally suited for global simulation studies under changing environmental conditions.
Dynamic Amplification of Subtropical Extreme Precipitation in a Warming Climate
Authors: Norris Jesse , Chen Gang , Li Chao 
Published: July 2020

AbstractProjected precipitation changes in a warming climate vary considerably, spatially, and between intensities. The changes can be greater or less than the ∼7% K−1 Clausius‐Clapeyron (CC) prediction, owing to dynamic effects. Using two global‐climate‐model large ensembles, we quantify the dynamically induced changes to precipitation extremes from the present (1996–2005) to late‐21st‐century (2071–2080) climates, as a function of recurrence interval, focusing on the subtropics. We separate non‐CC changes into a term proportional to the present‐day vertical‐velocity spatial pattern (i.e., an amplification or damping thereof by a constant factor) and a residual. The amplitude term varies with recurrence interval, approximately canceling (doubling) CC for moderate (large) extremes, increasing precipitation variability. Contrastingly, the residual is quasi‐uniform across recurrence intervals but spatially heterogeneous, weakening extremes over dry zones. This residual may be related to Hadley cell expansion, although this explanation is insufficient to explain many features, and other possible mechanisms are discussed.
p190A RhoGAP induces CDH1 expression and cooperates with E-cadherin to activate LATS kinases and suppress tumor cell growth
Authors: Ouyang Hanyue , Luong Phi , Frödin Morten , Hansen Steen H. 
Published: July 2020

AbstractThe ARHGAP35 gene encoding p190A RhoGAP (p190A) is significantly altered by both mutation and allelic deletion in human cancer, but the functional implications of such alterations are not known. Here, we demonstrate for the first time that p190A is a tumor suppressor using a xenograft mouse model with carcinoma cells harboring defined ARHGAP35 alterations. In vitro, restoration of p190A expression in carcinoma cells promotes contact inhibition of proliferation (CIP) through activation of LATS kinases and phosphorylation of the proto-oncogenic transcriptional co-activator YAP. In contrast, p190A forms harboring recurrent cancer mutations exhibit loss of function in modulating the Hippo pathway, inducing CIP, as well as attenuated suppression of tumor growth in mice. We determine that p190A promotes mesenchymal to epithelial transition (MET) and elicits expression of a cassette of epithelial adherens junction-associated genes in a cell density-dependent manner. This cassette includes CDH1 encoding E-cadherin, which amplifies p190A-mediated LATS activation and is necessary for CIP. Oppositely, we establish that p190A is obligatory for E-cadherin to activate LATS kinases and induce CIP. Collectively, this work defines a novel mechanism by which p190A and E-cadherin cooperate in modulating Hippo signaling to suppress tumor cell growth.
Early treatment-related neutropenia predicts response to palbociclib
Authors: McAndrew Nicholas P. , Dickson Mark A. , Clark Amy S. , Troxel Andrea B. , O’Hara Mark H. , Colameco Christopher , Gallager Maryann , Gramlich Kristi , Zafman Kelly , Vaughn David , Schwartz Gary K. , O’Dwyer Peter J. , DeMichele Angela 
Published: July 2020

Abstract
Background
Palbociclib is highly active in oestrogen-receptor positive (ER+) metastatic breast cancer, but neutropenia is dose limiting. The goal of this study was to determine whether early neutropenia is associated with disease response to single-agent palbociclib.

Methods
Blood count and disease-response data were analysed from two Phase 2 clinical trials at different institutions using single-agent palbociclib: advanced solid tumours positive for retinoblastoma protein and advanced liposarcoma. The primary endpoint was PFS. The primary exposure variable was the nadir absolute neutrophil count (ANC) during the first two cycles of treatment.

Results
One hundred and ninety-six patients (61 breast, 135 non-breast) were evaluated between the two trials. Development of any grade neutropenia was significantly associated with longer median PFS in both the breast cancer (HR 0.29, 95% CI 0.11–0.74, p = 0.010) and non-breast cancer (HR 0.57, 95% CI 0.38–0.85, p = 0.006) cohorts. Grade 3–4 neutropenia was significantly associated with prolonged PFS in the non-breast cohort (HR 0.57, 95% CI 0.38–0.85, p = 0.006) but not in the breast cohort (HR 0.87, 95% CI 0.51–1.47, p = 0.596). Multivariate analysis yielded similar results.

Conclusions
Treatment-related neutropenia in the first two cycles was significantly and independently associated with prolonged PFS, suggesting that neutropenia may be a useful pharmacodynamic marker to guide individualised palbociclib dosing.

Clinical trials registration information
Basket Trial: NCT01037790; Sarcoma Trial: NCT01209598.
PIM2 promotes hepatocellular carcinoma tumorigenesis and progression through activating NF-κB signaling pathway
Authors: Tang Xuming , Cao Tingting , Zhu Yun , Zhang Liyi , Chen Jinna , Liu Tengfei , Ming Xiaoyan , Fang Shuo , Yuan Yun-fei , Jiang Lingxi , Huang Jian-Dong , Guan Xin-Yuan 
Published: July 2020

AbstractInflammatory factors and activation of oncogenes both played critical roles in the development and progression of human hepatocellular carcinoma (HCC). However, the interplay between these two has not been well studied. In this study, we found that regulated by TNFα, Pim-2 proto-oncogene, serine/threonine kinase (PIM2) was highly expressed in HCC and correlated with poor prognosis (P = 0.007) as well as tumor recurrence (P = 0.014). Functional studies showed that PIM2 could enhance abilities of cell proliferation, cell motility, angiogenesis, chemo-resistance, and in vivo tumorigenicity and HCC metastasis. Mechanistic studies revealed that PIM2 could activate NF-κB signaling pathway through upregulating phosphorylation level of RIPK2. Interestingly, TNFα treatment could induce the expression of PIM2, and overexpression of PIM2 could in turn upregulate the expression of TNFα in HCC cells. More importantly, we found the expression level of PIM2 increased with the progression of liver cirrhosis, and PIM kinase inhibitor AZD1208 treatment could effectively attenuate HCC cells’ tumorigenic ability both in vitro and in vivo. Collectively, our study revealed the interaction between an inflammatory factor and a proto-oncogene that contributed to tumorigenesis and progression of HCC, and PIM kinase inhibition may serve as a therapeutic target in the treatment of HCC.
Rab27a dependent exosome releasing participated in albumin handling as a coordinated approach to lysosome in kidney disease
Authors: Feng Ye , Zhong Xin , Tang Tao-Tao , Wang Cui , Wang Li-Ting , Li Zuo-Lin , Ni Hai-Feng , Wang Bin , Wu Min , Liu Dan , Liu Hong , Tang Ri-Ning , Liu Bi-Cheng , Lv Lin-Li 
Published: July 2020

AbstractExosomes are increasingly recognized as vehicles of intercellular communication. However, the role of exosome in maintaining cellular homeostasis under stress conditions remained unclear. Here we show that Rab27a expression was upregulated exclusively in tubular epithelial cells (TECs) during proteinuria nephropathy established by adriamycin (ADR) injection and 5/6 nephrectomy as well as in chronic kidney disease patients, leading to the increased secretion of exosomes carrying albumin. The active exosome production promoted tubule injury and inflammation in neighboring and the producing cells. Interferon regulatory factor 1 (IRF-1) was found as the transcription factor contributed to the upregulation of Rab27a. Albumin could be detected in exosome fraction and co-localized with exosome marker CD63 indicating the secretion of albumin into extracellular space by exosomes. Interestingly, inhibition of exosome release accelerated albumin degradation which reversed tubule injury with albumin overload, while lysosome suppression augmented exosome secretion and tubule inflammation. Our findings revealed that IRF-1/Rab27a mediated exosome secretion constituted a coordinated approach to lysosome degradation for albumin handling, which lead to the augment of albumin toxicity as a maladaptive response to maintain cell homeostasis. The findings may suggest a novel therapeutic strategy for proteinuric kidney disease by targeting exosome secretion.
BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?
Authors: Sharma Abhibhav , Kumar Sharma Saurabh , Shi Yufang , Bucci Enrico , Carafoli Ernesto , Melino Gerry , Bhattacherjee Arnab , Das Gobardhan 
Published: July 2020

AbstractCoronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome caused by Coronavirus 2 (SARS-CoV-2). In the light of its rapid global spreading, on 11 March 2020, the World Health Organization has declared it a pandemic. Interestingly, the global spreading of the disease is not uniform, but has so far left some countries relatively less affected. The reason(s) for this anomalous behavior are not fully understood, but distinct hypotheses have been proposed. Here we discuss the plausibility of two of them: the universal vaccination with Bacillus Calmette–Guerin (BCG) and the widespread use of the antimalarial drug chloroquine (CQ). Both have been amply discussed in the recent literature with positive and negative conclusions: we felt that a comprehensive presentation of the data available on them would be useful. The analysis of data for countries with over 1000 reported COVID-19 cases has shown that the incidence and mortality were higher in countries in which BCG vaccination is either absent or has been discontinued, as compared with the countries with universal vaccination. We have performed a similar analysis of the data available for CQ, a widely used drug in the African continent and in other countries in which malaria is endemic; we discuss it here because CQ has been used as the drug to treat COVID-19 patients. Several African countries no longer recommend it officially for the fight against malaria, due to the development of resistance to Plasmodium, but its use across the continent is still diffuse. Taken together, the data in the literature have led to the suggestion of a possible inverse correlation between BCG immunization and COVID-19 disease incidence and severity.
Is hydroxychloroquine beneficial for COVID-19 patients?
Authors: Li Xing , Wang Ying , Agostinis Patrizia , Rabson Arnold , Melino Gerry , Carafoli Ernesto , Shi Yufang , Sun Erwei 
Published: July 2020

AbstractThe outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world1–3, the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 20204. The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir5, to control the disease and halt the pandemic.
Autophagy as a modulator of cell death machinery
Authors: Noguchi Masayuki , Hirata Noriyuki , Tanaka Tsutomu , Suizu Futoshi , Nakajima Hiroshi , Chiorini John A. 
Published: July 2020

AbstractThe balance between cell death and survival is a critical parameter in the regulation of cells and the maintenance of homeostasis in vivo. Three major mechanisms for cell death have been identified in mammalian cells: apoptosis (type I), autophagic cell death (type II), and necrosis (type III). These three mechanisms have been suggested to engage in cross talk with each other. Among them, autophagy was originally characterized as a cell survival mechanism for amino acid recycling during starvation. Whether autophagy functions primarily in cell survival or cell death is a critical question yet to be answered. Here, we present a comprehensive review of the cell death-related events that take place during autophagy and their underlying mechanisms in cancer and autoimmune disease development.
Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice
Authors: Yang Lei , Ton Hoai , Zhao Ruohe , Geron Erez , Li Mengzhu , Dong Yuanlin , Zhang Yiying , Yu Buwei , Yang Guang , Xie Zhongcong 
Published: July 2020

AbstractSevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of sevoflurane. We found that sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.
Dextran-coated iron oxide nanoparticle-induced nanotoxicity in neuron cultures
Authors: Badman Ryan P. , Moore Shanna L. , Killian Jessica L. , Feng Tuancheng , Cleland Thomas A. , Hu Fenghua , Wang Michelle D. 
Published: July 2020

AbstractRecent technological advances have introduced diverse engineered nanoparticles (ENPs) into our air, water, medicine, cosmetics, clothing, and food. However, the health and environmental effects of these increasingly common ENPs are still not well understood. In particular, potential neurological effects are one of the most poorly understood areas of nanoparticle toxicology (nanotoxicology), in that low-to-moderate neurotoxicity can be subtle and difficult to measure. Culturing primary neuron explants on planar microelectrode arrays (MEAs) has emerged as one of the most promising in vitro techniques with which to study neuro-nanotoxicology, as MEAs enable the fluorescent tracking of nanoparticles together with neuronal electrical activity recording at the submillisecond time scale, enabling the resolution of individual action potentials. Here we examine the dose-dependent neurotoxicity of dextran-coated iron oxide nanoparticles (dIONPs), a common type of functionalized ENP used in biomedical applications, on cultured primary neurons harvested from postnatal day 0–1 mouse brains. A range of dIONP concentrations (5–40 µg/ml) were added to neuron cultures, and cells were plated either onto well plates for live cell, fluorescent reactive oxidative species (ROS) and viability observations, or onto planar microelectrode arrays (MEAs) for electrophysiological measurements. Below 10 µg/ml, there were no dose-dependent cellular ROS increases or effects in MEA bursting behavior at sub-lethal dosages. However, above 20 µg/ml, cell death was obvious and widespread. Our findings demonstrate a significant dIONP toxicity in cultured neurons at concentrations previously reported to be safe for stem cells and other non-neuronal cell types.