bluuebunny/crossref_metadata_2025_split huggingface dataset:
The RhoA dependent anti-metastatic function of RKIP in breast cancer
Authors: Kalpana Gardiyawasam , Figy Christopher , Feng Jingwei , Tipton Claire , De Castro Julius N. , Bach Vu N. , Borile Clariza , LaSalla Alexandria , Odeh Hussain N. , Yeung Miranda , Garcia-Mata Rafael , Yeung Kam C. 
Published: August 2021

AbstractRaf-1 kinase inhibitor protein was initially discovered as a physiological kinase inhibitor of the MAPK signaling pathway and was later shown to suppress cancer cell invasion and metastasis. Yet, the molecular mechanism through which RKIP executes its effects is not completely defined. RhoA has both a pro- and anti-metastatic cell-context dependent functions. Given that Rho GTPases primarily function on actin cytoskeleton dynamics and cell movement regulation, it is possible that one way RKIP hinders cancer cell invasion/metastasis is by targeting these proteins. Here we show that RKIP inhibits cancer cell invasion and metastasis by stimulating RhoA anti-tumorigenic functions. Mechanistically, RKIP activates RhoA in an Erk2 and GEF-H1 dependent manner to enhance E-cadherin membrane localization and inhibit CCL5 expression.
Risk-factors for re-admission and outcome of patients hospitalized with confirmed COVID-19
Authors: Green Hefziba , Yahav Dafna , Eliakim-Raz Noa , Karny-Epstein Nitzan , Kushnir Shiri , Shochat Tzippy , Tadmor Boaz , Grossman Alon 
Published: August 2021

AbstractBurden of COVID-19 on Hospitals across the globe is enormous and has clinical and economic implications. In this retrospective study including consecutive adult patients with confirmed SARS-CoV-2 who were admitted between 3/2020 and 30/9/20, we aimed to identify post-discharge outcomes and risk factors for re-admission among COVID-19 hospitalized patients. Mortality and re-admissions were documented for a median post discharge follow up of 59 days (interquartile range 28,161). Univariate and multivariate analyses of risk factors for re-admission were performed. Overall, 618 hospitalized COVID-19 patients were included. Of the 544 patient who were discharged, 10 patients (1.83%) died following discharge and 50 patients (9.2%) were re-admitted. Median time to re-admission was 7 days (interquartile range 3, 24). Oxygen saturation or treatment prior to discharge were not associated with re-admissions. Risk factors for re-admission in multivariate analysis included solid organ transplantation (hazard ratio [HR] 3.37, 95% confidence interval [CI] 2.73–7.5, p = 0.0028) and higher Charlson comorbidity index (HR 1.34, 95% CI 1.23–1.46, p < 0.0001). Mean age of post discharge mortality cases was 85.0 (SD 9.98), 80% of them had cognitive decline or needed help in ADL at baseline. In conclusion, re-admission rates of hospitalized COVID-19 are fairly moderate. Predictors of re-admission are non-modifiable, including baseline comorbidities, rather than COVID-19 severity or treatment.
Prior intracerebral hemorrhage and white matter hyperintensity burden on recurrent stroke risk
Authors: Park Jong-Ho , Kwon Sun U. , Kwon Hyuk Sung , Heo Sung Hyuk 
Published: August 2021

AbstractPrior intracerebral hemorrhage (ICH) is associated with increased risk of ischemic stroke. Since white matter hyperintensity (WMH) is associated with ischemic stroke and ICH, this study aimed to evaluate the relationship between ICH and the risk of recurrent stroke by WMH severity. From a prospective multicenter database comprising 1454 noncardioembolic stroke patients with cerebral small-vessel disease, patients were categorized by presence or absence of prior ICH and WMH severity: mild-moderate WMH (reference); advanced WMH; ICH with mild-moderate WMH; and ICH with advanced WMH. Among patients with ICH, the association with stroke outcomes by WMH burden was further assessed. The primary endpoint was ischemic stroke and hemorrhagic stroke. The secondary endpoint was major adverse cardiovascular events (MACE): stroke/coronary heart disease/vascular death. During the mean 1.9-year follow-up period, the ischemic stroke incidence rate per 100 person-years was 2.7, 4.0, 2.5, and 8.1 in increasing severity, and the rate of hemorrhagic stroke was 0.7, 1.3, 0.6, and 2.1, respectively. The risk of ischemic stroke was higher in ICH with advanced WMH (adjusted HR 2.62; 95% CI 1.22−5.60) than the reference group, while the risk of hemorrhagic stroke trended higher (3.75, 0.85–16.53). The risk of MACE showed a similar pattern in ICH with advanced WMH. Among ICH patients, compared with mild WMH, the risk of ischemic stroke trended to be higher in advanced WMH (HR 3.37; 95% CI 0.90‒12.61). Advanced WMH was independently associated with an increased risk of hemorrhagic stroke (HR 33.96; 95% CI 1.52−760.95). Given the fewer rate of hemorrhagic stroke, the risk of hemorrhagic stroke might not outweigh the benefits of antiplatelet therapy for secondary prevention.
Small RNA sequencing evaluation of renal microRNA biomarkers in dogs with X-linked hereditary nephropathy
Authors: Chu Candice P. , Liu Shiguang , Song Wenping , Xu Ethan Y. , Nabity Mary B. 
Published: August 2021

AbstractDogs with X-linked hereditary nephropathy (XLHN) are an animal model for Alport syndrome in humans and progressive chronic kidney disease (CKD). Using mRNA sequencing (mRNA-seq), we have characterized the gene expression profile affecting the progression of XLHN; however, the microRNA (miRNA, miR) expression remains unknown. With small RNA-seq and quantitative RT-PCR (qRT-PCR), we used 3 small RNA-seq analysis tools (QIAGEN OmicSoft Studio, miRDeep2, and CPSS 2.0) to profile differentially expressed renal miRNAs, top-ranked miRNA target genes, and enriched biological processes and pathways in CKD progression. Twenty-three kidney biopsies were collected from 5 dogs with XLHN and 4 age-matched, unaffected littermates at 3 clinical time points (T1: onset of proteinuria, T2: onset of azotemia, and T3: advanced azotemia). We identified up to 23 differentially expressed miRNAs at each clinical time point. Five miRNAs (miR-21, miR-146b, miR-802, miR-142, miR-147) were consistently upregulated in affected dogs. We identified miR-186 and miR-26b as effective reference miRNAs for qRT-PCR. This study applied small RNA-seq to identify differentially expressed miRNAs that might regulate critical pathways contributing to CKD progression in dogs with XLHN.
Relationship between arm-to-leg and limbs-to-trunk body composition ratio and cardiovascular disease risk factors
Authors: Jung Sunmi , Park Jihyun , Seo Young-Gyun 
Published: August 2021

AbstractWe aimed to analyze the relationship of the distribution of body fat mass (FM) and fat-free mass (FFM) in the limbs and trunk with the prevalence of cardiovascular disease risk factors (CVD-RF). In total, 13,032 adults were selected from the KNHANES (2008–2011). The prevalence of hypertension, diabetes mellitus (DM), dyslipidemia, and metabolic syndrome (MetS) according to the arm-to-leg ratio and limbs-to-trunk ratio for FM and FFM was compared, respectively. The higher the arm-to-leg FM ratio, the higher the prevalence of CVD-RF (DM-male-OR 7.04, 95% CI 4.22–11.74; DM-female-OR 10.57, 95% CI 5.80–19.26; MetS-male-OR 4.47, 95% CI 3.41- 5.86; MetS-female-OR 8.73, 95% CI 6.38–11.95). The higher the limbs-to-trunk FM ratio (DM-male-OR 0.12, 95% CI 0.07–0.21; DM-female-OR 0.12, 95% CI 0.06–0.23; MetS-male-OR 0.06, 95% CI 0.04–0.08; MetS-female-OR 0.02, 95% CI 0.01–0.04), the higher the limbs-to-trunk FFM ratio (DM-male-OR 0.19, 95% CI 0.11–0.31; DM-female-OR 0.46, 95% CI 0.30–0.70; MetS-male-OR 0.39, 95% CI 0.31–0.50; MetS-female-OR 0.62, 95% CI 0.50–0.78), and the higher the arm-to-leg FFM ratio (MetS-male-OR 0.75, 95% CI 0.59–0.94; MetS-female-OR 0.73, 95% CI 0.58–0.92), the lower the prevalence of CVD-RF. The higher the FM of the legs compared to the arms, FFM of the arms compared to the legs, and FM or FFM of the limbs compared to the trunk, the lower the prevalence of CVD-RF.
Nitrogen species specific phosphorus mineralization in temperate floodplain soils
Authors: Arenberg Mary R. , Arai Yuji 
Published: August 2021

AbstractAs an essential component of enzymes, higher N availability from agricultural runoff to forest soils may boost the activity of phosphatase, increasing the bioavailability of phosphate. The objective of this study was to evaluate P mineralization rates in temperate floodplain soils as a function of inorganic N species (i.e., ammonium and nitrate) and amendment rate (1.5–3.5 g N kg−1). Accordingly, the soil was amended with nitrate and ammonium, and P dynamics were monitored during a 40-day incubation. The addition of ammonium significantly boosted acid and alkaline phosphatase activity by 1.39 and 1.44 µmolp-nitrophenol P (pNP) g−1 h−1, respectively. The degree of increase was positively correlated with the amendment rate. Likewise, the P mineralization rate increased by 0.27 mg P kg−1in the 3.5 g N kg−1ammonium treatment.31P nuclear magnetic resonance spectroscopic analysis further supported the reduction in organic orthophosphate diesters on day 30. Meanwhile, the addition of nitrate promoted P mineralization to a lesser degree but did not increase phosphatase activity. While floodplain soils have great potential to sequester anthropogenic P, high availability of inorganic N, especially ammonium, could promote P mineralization, potentially increasing P fertility and/or reducing P the sequestration capacity of floodplain soils.
Cardiac troponin I and the risk of cardiovascular or non-cardiovascular death in patients visiting the emergency department
Authors: Park Jong Eun , Song Minseok , Kim Taerim , Lee Gun Tak , Hwang Sung Yeon , Yoon Hee , Cha Won Chul , Shin Tae Gun , Sim Min Sub , Jo Ik Joon , Lee Seung-Hwa , Park Hyung-Doo , Choi Jin-Ho 
Published: August 2021

AbstractThe prognostic implication of cardiac troponin I (cTnI) values for the determination of the magnitude or duration of cause-specific death risk is limited. We included consecutive patients with maximal cTnI values within 24 h of their emergency department visits. Multivariate analyses using variables selected by the Bayesian information criterion were performed to investigate the impact of cTnI on the event rate, time-dependent risk, and dose-dependent risk of cardiovascular or non-cardiovascular death within 360 days. There were 5472 (14.9%) all-cause deaths including 881 (2.4%) cardiovascular deaths and 4591 (12.5%) non-cardiovascular deaths. In patients with positive cTnI, defined as the ≥ 99th percentile of the upper normal limit, the cumulative risk of cardiac and non-cardiac death was 4.4- and 1.4-fold higher, respectively, than that of negative cTnI, respectively. In the competing risk analysis, positive cTnI was linked to 2.4- and 1.2-fold higher risks of cardiovascular and non-cardiovascular death, respectively. The cTnI value showed a positive relationship with the risk of both cardiovascular and non-cardiovascular deaths. In the time-dependent risk analysis, the excess risk of cardiovascular death was mostly evident in the first few weeks. Higher cTnI value was associated with an increased risk of both cardiovascular and non-cardiovascular death, especially which was in the early period.
Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo
Authors: Kimura Haruka , Nagoshi Tomohisa , Oi Yuhei , Yoshii Akira , Tanaka Yoshiro , Takahashi Hirotake , Kashiwagi Yusuke , Tanaka Toshikazu D. , Yoshimura Michihiro 
Published: August 2021

AbstractIncreasing evidence suggests natriuretic peptides (NPs) coordinate inter-organ metabolic crosstalk with adipose tissues and play a critical role in energy metabolism. We recently reported A-type NP (ANP) raises intracellular temperature in cultured adipocytes in a low-temperature-sensitive manner. We herein investigated whether exogenous ANP-treatment exerts a significant impact on adipose tissues in vivo. Mice fed a high-fat-diet (HFD) or normal-fat-diet (NFD) for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. ANP-treatment significantly ameliorated HFD-induced insulin resistance. HFD increased brown adipose tissue (BAT) cell size with the accumulation of lipid droplets (whitening), which was suppressed by ANP-treatment (re-browning). Furthermore, HFD induced enlarged lipid droplets in inguinal white adipose tissue (iWAT), crown-like structures in epididymal WAT, and hepatic steatosis, all of which were substantially attenuated by ANP-treatment. Likewise, ANP-treatment markedly increased UCP1 expression, a specific marker of BAT, in iWAT (browning). ANP also further increased UCP1 expression in BAT with NFD. Accordingly, cold tolerance test demonstrated ANP-treated mice were tolerant to cold exposure. In summary, exogenous ANP administration ameliorates HFD-induced insulin resistance by attenuating hepatic steatosis and by inducing adipose tissue browning (activation of the adipose tissue thermogenic program), leading to in vivo thermogenesis during cold exposure.
Frontal increase of beta modulation during the practice of a motor task is enhanced by visuomotor learning
Authors: Tatti E. , Ferraioli F. , Peter J. , Alalade T. , Nelson A. B. , Ricci S. , Quartarone A. , Ghilardi M. F. 
Published: August 2021

AbstractMovement is accompanied by beta power changes over frontal and sensorimotor regions: a decrease during movement (event-related desynchronization, ERD), followed by an increase (event-related synchronization, ERS) after the movement end. We previously found that enhancements of beta modulation (from ERD to ERS) during a reaching test (mov) occur over frontal and left sensorimotor regions after practice in a visuo-motor adaptation task (ROT) but not after visual learning practice. Thus, these enhancements may reflect local cumulative effects of motor learning. Here we verified whether they are triggered by the learning component inherent in ROT or simply by motor practice in a reaching task without such learning (MOT). We found that beta modulation during mov increased over frontal and left areas after three-hour practice of either ROT or MOT. However, the frontal increase was greater after ROT, while the increase over the left area was similar after the two tasks. These findings confirm that motor practice leaves local traces in beta power during a subsequent motor test. As they occur after motor tasks with and without learning, these traces likely express the cost of processes necessary for both usage and engagement of long-term potentiation mechanisms necessary for the learning required by ROT.
An integrated pore size distribution measurement method of small angle neutron scattering and mercury intrusion capillary pressure
Authors: Shen Rui , Zhang Xiaoyi , Ke Yubin , Xiong Wei , Guo Hekun , Liu Guanghao , Zhou Hongtao , Yang Hang 
Published: August 2021

AbstractSmall-angle neutron scattering and high-pressure mercury intrusion capillary pressure testing are integrated to analyze the pore size distribution of the broad sense shale oil reservoir samples of the Permian Lucaogou Formation in the Jimsar Sag, Junggar Basin, China. The results show that, compared with the measurement method integrating gas adsorption and mercury intrusion, combination of small-angle neutron scattering and mercury intrusion can more accurately characterize full-scale pore size distribution. The full-scale pore size distribution curve of the rock samples in the study area includes two types: the declining type and submicron pore-dominated type. The declining type is mainly found with silty mudstone and dolomitic mudstone, and most of its pores are smaller than 80 nm. Silt-fine sandstones and dolarenite are mostly of the submicron pores-dominated type, with most pores smaller than 500 nm. They also present large specific pore volumes and average pore diameters of macropores and are the favorable lithogenous facies for development of high-quality reservoirs.
Opportunities of combinatorial thin film materials design for the sustainable development of magnesium-based alloys
Authors: Hans Marcus , Keuter Philipp , Saksena Aparna , Sälker Janis A. , Momma Markus , Springer Hauke , Nowak Jakub , Zander Daniela , Primetzhofer Daniel , Schneider Jochen M. 
Published: August 2021

AbstractMagnesium-based lightweight structural materials exhibit potential for energy savings. However, the state-of-the-art quest for novel compositions with improved properties through conventional bulk metallurgy is time, energy, and material intensive. Here, the opportunities provided by combinatorial thin film materials design for the sustainable development of magnesium alloys are evaluated. To characterise the impurity level of (Mg,Ca) solid solution thin films within grains and grain boundaries, scanning transmission electron microscopy and atom probe tomography are correlatively employed. It is demonstrated that control of the microstructure enables impurity levels similar to bulk-processed alloys. In order to substantially reduce time, energy, and material requirements for the sustainable development of magnesium alloys, we propose a three-stage materials design strategy: (1) Efficient and systematic investigation of composition-dependent phase formation by combinatorial film growth. (2) Correlation of microstructural features and mechanical properties for selected composition ranges by rapid alloy prototyping. (3) Establishment of synthesis–microstructure–property relationships by conventional bulk metallurgy.
TRPA1 triggers hyperalgesia and inflammation after tooth bleaching
Authors: Chen Chang , Huang Xiansheng , Zhu Wenqiang , Ding Chen , Huang Piaopiao , Li Rong 
Published: August 2021

AbstractHyperalgesia has become a major problem restricting the clinical application of tooth bleaching. We hypothesized that transient receptor potential ankyrin 1 (TRPA1), a pain conduction tunnel, plays a role in tooth hyperalgesia and inflammation after bleaching. Dental pulp stem cells were seeded on the dentin side of the disc, which was cut from the premolar buccal tissue, with 15% (90 min) or 40% (3 × 15 min) bleaching gel applied on the enamel side, and treated with or without a TRPA1 inhibitor. The bleaching gel stimulated intracellular reactive oxygen species, Ca2+, ATP, and extracellular ATP in a dose-dependent manner, and increased the mRNA and protein levels of hyperalgesia (TRPA1 and PANX1) and inflammation (TNFα and IL6) factors. This increment was adversely affected by TRPA1 inhibitor. In animal study, the protein levels of TRPA1 (P = 0.0006), PANX1 (P < 0.0001), and proliferation factors [PCNA (P < 0.0001) and Caspase 3 (P = 0.0066)] increased significantly after treated rat incisors with 15% and 40% bleaching gels as detected by immunohistochemistry. These results show that TRPA1 plays a critical role in sensitivity and inflammation after tooth bleaching, providing a solid foundation for further research on reducing the complications of tooth bleaching.
Kallistatin limits abdominal aortic aneurysm by attenuating generation of reactive oxygen species and apoptosis
Authors: Krishna Smriti Murali , Li Jiaze , Wang Yutang , Moran Corey S. , Trollope Alexandra , Huynh Pacific , Jose Roby , Biros Erik , Ma Jianxing , Golledge Jonathan 
Published: August 2021

AbstractInflammation, vascular smooth muscle cell apoptosis and oxidative stress are believed to play important roles in abdominal aortic aneurysm (AAA) pathogenesis. Human kallistatin (KAL; gene SERPINA4) is a serine proteinase inhibitor previously shown to inhibit inflammation, apoptosis and oxidative stress. The aim of this study was to investigate the role of KAL in AAA through studies in experimental mouse models and patients. Serum KAL concentration was negatively associated with the diagnosis and growth of human AAA. Transgenic overexpression of the human KAL gene (KS-Tg) or administration of recombinant human KAL (rhKAL) inhibited AAA in the calcium phosphate (CaPO4) and subcutaneous angiotensin II (AngII) infusion mouse models. Upregulation of KAL in both models resulted in reduction in the severity of aortic elastin degradation, reduced markers of oxidative stress and less vascular smooth muscle apoptosis within the aorta. Administration of rhKAL to vascular smooth muscle cells incubated in the presence of AngII or in human AAA thrombus-conditioned media reduced apoptosis and downregulated markers of oxidative stress. These effects of KAL were associated with upregulation of Sirtuin 1 activity within the aortas of both KS-Tg mice and rodents receiving rhKAL. These results suggest KAL-Sirtuin 1 signalling limits aortic wall remodelling and aneurysm development through reductions in oxidative stress and vascular smooth muscle cell apoptosis. Upregulating KAL may be a novel therapeutic strategy for AAA.
Effect of endometrial preparation protocols on the risk of ectopic pregnancy for frozen embryo transfer
Authors: Jwa Seung Chik , Takamura Masashi , Kuwahara Akira , Kajihara Takeshi , Ishihara Osamu 
Published: August 2021

AbstractStudies have consistently reported a significantly reduced incidence of ectopic pregnancy (EP) for frozen-thawed embryo transfer (ET) cycles compared with fresh cycles. However, only a few studies reported an association between endometrial preparation protocols on EP and results were conflicting. A registry-based retrospective cohort study of 153,354 clinical pregnancies following frozen single ETs between 2014 and 2017 were conducted, of which 792 cases of EP (0.52%) were reported. Blastocyst embryo transfers accounted for 87% of the total sample and were significantly associated with a decreased risk for EP compared with early cleavage ET (0.90% vs. 0.46%, adjusted OR = 0.50, 95% CI, 0.41 to 0.60). Compared with natural cycles, hormone replacement cycles (HRC) demonstrated a similar risk for EP (0.53% vs. 0.47%, adjusted OR = 1.12, 95% CI, 0.89 to 1.42). Subgroup analysis with or without tubal factor infertility and early cleavage/blastocyst ETs demonstrated similar non-significant associations. Endometrial preparation protocols using clomiphene (CC) were associated with a significantly increased risk for EP (1.12%, adjusted OR = 2.34; 95% CI, 1.38 to 3.98). These findings suggest that HRC and natural cycles had a similar risk for EP. Endometrial preparation using CC was associated with an increased risk of EP in frozen embryo transfer cycles.
Hypergravity-induced malfunction was moderated by the regulation of NMDA receptors in the vestibular nucleus
Authors: Kim Gyutae , Kim Kyu-Sung 
Published: August 2021

AbstractGravity alteration is one of the critical environmental factors in the space, causing various abnormal behaviors related with the malfunctioned vestibular system. Due to the high plastic responses in the central vestibular system, the behavioral failures were resolved in a short period of time (in approx. 72 h). However, the plastic neurotransmission underlying the functional recovery is still elusive. To understand the neurotransmitter-induced plasticity under hypergravity, the extracellular single neuronal recording and the immunohistochemistry were conducted in the vestibular nucleus (VN). The animals were grouped as control, 24-h, 72-h, and 15-day exposing to 4G-hypergravity, and each group had two subgroups based on the origins of neuronal responses, such as canal and otolith. The averaged firing rates in VN showed no significant difference in the subgroups (canal-related: p > 0.105, otolith-related: p > 0.138). Meanwhile, the number of NMDAr was significantly changed by the exposing duration to hypergravity. The NMDAr decreased in 24 h (p = 1.048 × 10–9), and it was retrieved in 72 h and 15 days (p < 4.245 × 10–5). Apparently, the reduction and the retrieval in the number of NMDAr were synchronized with the generation and recovery of the abnormal behaviors. Thus, the plasticity to resolve the hypergravity-induced malfunctional behaviors was conducted by regulating the number of NMDAr.