bluuebunny/crossref_metadata_2025_split huggingface dataset:
A combination of CMC and α-MSH inhibited ROS activated NLRP3 inflammasome in hyperosmolarity stressed HCECs and scopolamine-induced dry eye rats
Authors: Lv Ying , Chu Chenchen , Liu Ke , Ru Yusha , Zhang Yan , Lu Xiaoxiao , Gao Yichen , Zhang Caijie , Zhao Shaozhen 
Published: January 2021

AbstractAn important mechanism involved in dry eye (DE) is the association between tear hyperosmolarity and inflammation severity. Inflammation in DE might be mediated by the NLRP3 inflammasome, which activated by exposure to reactive oxygen species (ROS). A combination of carboxymethylcellulose (CMC) and α-melanocyte stimulating hormone (α-MSH) may influence DE through this mechanism, thus avoiding defects of signal drug. In this study, we assessed whether treatment comprising CMC combined with α-MSH could ameliorate ocular surface function; we found that it promoted tear secretion, reduced the density of fluorescein sodium staining, enhanced the number of conjunctival goblet cells, and reduced the number of corneal apoptotic cells. Investigation of the underlying mechanism suggested that the synergistic effect of combined treatment alleviated DE inflammation through reduction of ROS level and inhibition of the NLRP3 inflammasome in human corneal epithelial cells. These findings indicate that combined CMC + α-MSH treatment could ameliorate lesions and restore ocular surface function in patients with DE through reduction of ROS level and inhibition of NLRP3 signalling.
Effect of SSRI exposure on the proliferation rate and glucose uptake in breast and ovary cancer cell lines
Authors: Stapel Britta , Melzer Catharina , von der Ohe Juliane , Hillemanns Peter , Bleich Stefan , Kahl Kai G. , Hass Ralf 
Published: January 2021

AbstractBreast cancer is the most prevalent malignancy amongst women worldwide while ovarian cancer represents the leading cause of death among gynecological malignancies. Women suffering from these cancers displayed heightened rates of major depressive disorder, and antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) is frequently recommended. Recently, narrative reviews and meta-analyses showed increased recurrence risks and mortality rates in SSRI-treated women with breast and ovarian cancer. We therefore examined whether three commonly prescribed SSRIs, fluoxetine, sertraline and citalopram, affect proliferation or glucose uptake of human breast and ovarian cancer cell lines characterized by different malignancies and metastatic potential. SSRI treatment or serotonin stimulation with therapeutically relevant concentrations over various time periods revealed no consistent dose- or time-dependent effect on proliferation rates. A marginal, but significant increase in glucose uptake was observed in SK-OV-3 ovarian cancer cells upon fluoxetine or sertraline, but not citalopram treatment. In three breast cancer cell lines and in two additional ovarian cancer cell lines no significant effect of SSRIs on glucose uptake was observed. Our data suggest that the observed increase in recurrence- and mortality rates in SSRI-treated cancer patients is unlikely to be linked to antidepressant therapies.
Comparison of deep learning with traditional models to predict preventable acute care use and spending among heart failure patients
Authors: Lewis Maor , Elad Guy , Beladev Moran , Maor Gal , Radinsky Kira , Hermann Dor , Litani Yoav , Geller Tal , Pines Jesse M. , Shapiro Nathan l. , Figueroa Jose F. 
Published: January 2021

AbstractRecent health reforms have created incentives for cardiologists and accountable care organizations to participate in value-based care models for heart failure (HF). Accurate risk stratification of HF patients is critical to efficiently deploy interventions aimed at reducing preventable utilization. The goal of this paper was to compare deep learning approaches with traditional logistic regression (LR) to predict preventable utilization among HF patients. We conducted a prognostic study using data on 93,260 HF patients continuously enrolled for 2-years in a large U.S. commercial insurer to develop and validate prediction models for three outcomes of interest: preventable hospitalizations, preventable emergency department (ED) visits, and preventable costs. Patients were split into training, validation, and testing samples. Outcomes were modeled using traditional and enhanced LR and compared to gradient boosting model and deep learning models using sequential and non-sequential inputs. Evaluation metrics included precision (positive predictive value) at k, cost capture, and Area Under the Receiver operating characteristic (AUROC). Deep learning models consistently outperformed LR for all three outcomes with respect to the chosen evaluation metrics. Precision at 1% for preventable hospitalizations was 43% for deep learning compared to 30% for enhanced LR. Precision at 1% for preventable ED visits was 39% for deep learning compared to 33% for enhanced LR. For preventable cost, cost capture at 1% was 30% for sequential deep learning, compared to 18% for enhanced LR. The highest AUROCs for deep learning were 0.778, 0.681 and 0.727, respectively. These results offer a promising approach to identify patients for targeted interventions.
Comparing right- and left sided injection-drug related infective endocarditis
Authors: Clarelin Allan , Rasmussen Magnus , Olaison Lars , Ragnarsson Sigurdur 
Published: January 2021

AbstractThe aim of the study was to compare background characteristics, microbiology and outcome of patients with right-sided and left-sided intravenous drug use (IDU) associated infective endocarditis (IE). A nationwide retrospective study using the Swedish Registry on Infective Endocarditis between 2008 and 2019 was conducted. A total of 586 people with IDU-IE were identified and divided into left-sided (n = 204) and right-sided (n = 382) IE. Descriptive statistics, Cox-regression and Kaplan–Meier survival estimates were used. The mean age of patients in the left-sided group was 46 years compared to 35 years in the right-sided group, p < 0.001. Left-sided IE had a higher proportion of females. Staphylococcus aureus was the causative pathogen in 48% of cases in the left-sided group compared to 88% in the right-sided group. Unadjusted and adjusted long-term survival was better in right-sided IE compared to left-sided IE. Independent predictors of long-term mortality were increasing age, end-stage renal disease, nosocomial infection, brain emboli and left-sided IE. Left-sided IE was common in people with IDU but the proportion of females with left-sided IE was low. S. aureus was twice as common in right-sided IE compared to left-sided IE, and the long-term prognosis of right sided IDU-associated IE was better compared to left-sided IE despite the fact that few were operated.
Comprehensive analysis of metastatic gastric cancer tumour cells using single-cell RNA-seq
Authors: Wang Bin , Zhang Yingyi , Qing Tao , Xing Kaichen , Li Jie , Zhen Timing , Zhu Sibo , Zhan Xianbao 
Published: January 2021

AbstractGastric cancer (GC) is a leading cause of cancer-induced mortality, with poor prognosis with metastasis. The mechanism of gastric carcinoma lymph node metastasis remains unknown due to traditional bulk-leveled approaches masking the roles of subpopulations. To answer questions concerning metastasis from the gastric carcinoma intratumoural perspective, we performed single-cell level analysis on three gastric cancer patients with primary cancer and paired metastatic lymph node cancer tissues using single-cell RNA-seq (scRNA-seq). The results showed distinct carcinoma profiles from each patient, and diverse microenvironmental subsets were shared across different patients. Clustering data showed significant intratumoural heterogeneity. The results also revealed a subgroup of cells bridging the metastatic group and primary group, implying the transition state of cancer during the metastatic process. In the present study, we obtained a more comprehensive picture of gastric cancer lymph node metastasis, and we discovered some GC lymph node metastasis marker genes (ERBB2, CLDN11 and CDK12), as well as potential gastric cancer evolution-driving genes (FOS and JUN), which provide a basis for the treatment of GC.
Improved agreement and diagnostic accuracy of a cuffless 24-h blood pressure measurement device in clinical practice
Authors: Socrates Thenral , Krisai Philipp , Vischer Annina S. , Meienberg Andrea , Mayr Michael , Burkard Thilo 
Published: January 2021

AbstractA cuffless blood pressure (BP) device (TestBP) using pulse transit time is in clinical use, but leads to higher BP values compared to a cuff-based 24 h-BP reference device (RefBP). We evaluated the impact of a recent software update on BP results and TestBP’s ability to differentiate between normo- and hypertension. 71 individuals had TestBP (Somnotouch-NIBP) and RefBP measurements simultaneously performed on either arm. TestBP results with software version V1.5 were compared to V1.4 and RefBP. Mean 24 h (± SD) BP for the RefBP, TestBP-V1.4 and TestBP-V1.5 were systolic 134.0 (± 17.3), 140.8 (± 20) and 139.1 (± 20) mmHg, and diastolic 79.3 (± 11.7), 85.8 (± 14.1) and 83.5 (± 13.0) mmHg, respectively (p-values < 0.001). TestBP-V1.5 area under the curve (95% confidence interval) versus RefBP for hypertension detection was 0.92 (0.86; 0.99), 0.94 (0.88; 0.99) and 0.77 (0.66; 0.88) for systolic and 0.92 (0.86; 0.99), 0.92 (0.85; 0.99) and 0.84 (0.74; 0.94) for diastolic 24 h, awake and asleep BP respectively. TestBP-V1.5 detected elevated systolic/diastolic mean 24 h-BP with a 95%/90% sensitivity and 65%/70% specificity. Highest Youden’s Index was systolic 133 (sensitivity 95%/specificity 80%) and diastolic 87 mmHg (sensitivity 81%/specificity 98%). The update improved the agreement to RefBP. TestBP was excellent for detecting 24 h and awake hypertensive BP values but not for asleep BP values.
Vasohibin-1 rescues erectile function through up-regulation of angiogenic factors in the diabetic mice
Authors: Song Kang-Moon , Kim Woo Jean , Choi Min-Ji , Kwon Ki-Dong , Limanjaya Anita , Ghatak Kalyan , Ock Jiyeon , Yin Guo Nan , Sato Yasufumi , Hong Soon-Sun , Ryu Ji-Kan , Suh Jun-Kyu 
Published: January 2021

AbstractNeovascularization of the erectile tissue emerges as a beneficial curative approach to treat erectile dysfunction (ED). Here we for the first time report the unexpected role of vasohibin-1 (VASH1), mainly known as an anti-angiogenic factor, in restoring erectile function in diabetic mice. A diabetic patient has lower cavernous VASH1 expression than in the potent man. VASH1 was mainly expressed in endothelial cells. There were significant decreases in cavernous endothelial cell and pericyte contents in VASH1 knockout mice compared with those in wild-type mice, which resulted in impairments in erectile function. Intracavernous injection of VASH1 protein successfully restored erectile function in the diabetic mice (~ 90% of control values). VASH1 protein reinstated endothelial cells, pericytes, and endothelial cell–cell junction proteins and induced phosphorylation of eNOS (Ser1177) in the diabetic mice. The induction of angiogenic factors, such as angiopoietin-1 and vascular endothelial growth factor, is responsible for cavernous angiogenesis and the restoration of erectile function mediated by VASH1. Altogether, these findings suggest that VASH1 is proangiogenic in diabetic penis and is a new potential target for diabetic ED.
Non-disruptive uptake of anionic and cationic gold nanoparticles in neutral zwitterionic membranes
Authors: Canepa Ester , Salassi Sebastian , Simonelli Federica , Ferrando Riccardo , Rolandi Ranieri , Lambruschini Chiara , Canepa Fabio , Dante Silvia , Relini Annalisa , Rossi Giulia 
Published: January 2021

AbstractThe potential toxicity of ligand-protected nanoparticles (NPs) on biological targets is crucial for their clinical translation. A number of studies are aimed at investigating the molecular mechanisms shaping the interactions between synthetic NPs and neutral plasma membranes. The role played by the NP surface charge is still widely debated. We compare, via liposome leakage assays, the perturbation induced by the penetration of sub-6 nm anionic and cationic Au NPs into model neutral lipid membranes composed of the zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). Our charged Au NPs are functionalized by a mixture of the apolar 1-octanethiol and a ω-charged thiol which is either the anionic 11-mercapto-1-undecanesulfonate or the cationic (11-mercaptoundecyl)-N,N,N-trimethylammonium. In both cases, the NP uptake in the bilayer is confirmed by quartz crystal microbalance investigations. Our leakage assays show that both negatively and positively charged Au NPs do not induce significant membrane damage on POPC liposomes when penetrating into the bilayer. By means of molecular dynamics simulations, we show that the energy barrier for membrane penetration is the same for both NPs. These results suggest that the sign of the NP surface charge, per se, does not imply different physicochemical mechanisms of interaction with zwitterionic lipid membranes.
Personalized treatment options for chronic diseases using precision cohort analytics
Authors: Ng Kenney , Kartoun Uri , Stavropoulos Harry , Zambrano John A. , Tang Paul C. 
Published: January 2021

AbstractTo support point-of-care decision making by presenting outcomes of past treatment choices for cohorts of similar patients based on observational data from electronic health records (EHRs), a machine-learning precision cohort treatment option (PCTO) workflow consisting of (1) data extraction, (2) similarity model training, (3) precision cohort identification, and (4) treatment options analysis was developed. The similarity model is used to dynamically create a cohort of similar patients, to inform clinical decisions about an individual patient. The workflow was implemented using EHR data from a large health care provider for three different highly prevalent chronic diseases: hypertension (HTN), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HL). A retrospective analysis demonstrated that treatment options with better outcomes were available for a majority of cases (75%, 74%, 85% for HTN, T2DM, HL, respectively). The models for HTN and T2DM were deployed in a pilot study with primary care physicians using it during clinic visits. A novel data-analytic workflow was developed to create patient-similarity models that dynamically generate personalized treatment insights at the point-of-care. By leveraging both knowledge-driven treatment guidelines and data-driven EHR data, physicians can incorporate real-world evidence in their medical decision-making process when considering treatment options for individual patients.
Coastal wetlands can be saved from sea level rise by recreating past tidal regimes
Authors: Sadat-Noori Mahmood , Rankin Caleb , Rayner Duncan , Heimhuber Valentin , Gaston Troy , Drummond Christopher , Chalmers Anita , Khojasteh Danial , Glamore William 
Published: January 2021

AbstractClimate change driven Sea Level Rise (SLR) is creating a major global environmental crisis in coastal ecosystems, however, limited practical solutions are provided to prevent or mitigate the impacts. Here, we propose a novel eco-engineering solution to protect highly valued vegetated intertidal ecosystems. The new ‘Tidal Replicate Method’ involves the creation of a synthetic tidal regime that mimics the desired hydroperiod for intertidal wetlands. This synthetic tidal regime can then be applied via automated tidal control systems, “SmartGates”, at suitable locations. As a proof of concept study, this method was applied at an intertidal wetland with the aim of restabilising saltmarsh vegetation at a location representative of SLR. Results from aerial drone surveys and on-ground vegetation sampling indicated that the Tidal Replicate Method effectively established saltmarsh onsite over a 3-year period of post-restoration, showing the method is able to protect endangered intertidal ecosystems from submersion. If applied globally, this method can protect high value coastal wetlands with similar environmental settings, including over 1,184,000 ha of Ramsar coastal wetlands. This equates to a saving of US$230 billion in ecosystem services per year. This solution can play an important role in the global effort to conserve coastal wetlands under accelerating SLR.
Temporal division of labor in an aphid social system
Authors: Shibao Harunobu , Kutsukake Mayako , Fukatsu Takema 
Published: January 2021

AbstractTemporal division of labor, or age polyethism, in which altruistic caste individuals change their tasks with aging, is widely found in bees and ants (Hymenoptera) and also in other social insects. Here we report the discovery of elaborate age polyethism in a social aphid (Hemiptera). Tuberaphis styraci is a gall-forming aphid in which monomorphic first instar nymphs differentiate into normal nymphs and soldiers upon second instar molt. Soldiers neither grow nor reproduce but perform gall cleaning and colony defense. Using an artificial diet rearing system, we collected age-defined groups of soldiers and monitored their social behaviors. We observed that young soldiers tend to clean whereas old soldiers preferentially attack, thereby verifying age-dependent task switching from housekeeping to defense. Strategic sampling, age estimation and behavioral observation of soldiers from natural galls revealed that (1) young cleaning soldiers tend to inhabit upper gall regions with adult insects, (2) old attacking soldiers tend to be distributed in lower gall regions, particularly around the gall openings, and (3) the gall structure is linked to intra-nest movement, aging and task switching of soldiers in an adaptive manner. These results highlight an evolutionary parallelism comparable to the sophisticated temporal division of labor observed in honeybee colonies.
Delayed discharge is associated with higher complement C3 levels and a longer nucleic acid-negative conversion time in patients with COVID-19
Authors: Lin Peihuang , Chen Wenhuang , Huang Hongbo , Lin Yijian , Cai Maosheng , Lin Dongheng , Cai Hehui , Su Zhijun , Zhuang Xibin , Yu Xueping 
Published: January 2021

AbstractTo determine factors associated with delayed discharge of hospitalized patients with coronavirus disease (COVID-19). This retrospective cohort study included 47 patients with COVID-19 admitted to three hospitals in Quanzhou City, Fujian Province, China, between January 21, 2020 and March 6, 2020. Univariate and multivariate logistic regression analyses were conducted to identify factors associated with delayed discharge. The median length of hospital stay was 22 days. Patients in the delayed discharge group (length of hospital stay ≥ 21 days, n = 27) were more likely to have diarrhea, anorexia, decreased white blood cell counts, increased complement C3 and C-reactive protein levels, air bronchograms, undergo thymalfasin treatment, and take significantly longer to convert to a severe acute respiratory syndrome coronavirus (SARS-CoV-2) RNA-negative status than those in the control group (length of hospital stay, < 21 days; n = 20). In multivariate logistic regression analysis, the time to SARS-CoV-2 RNA-negative conversion (odds ratio [OR]: 1.48, 95% confidence interval [CI] 1.09–2.04, P = 0.01) and complement C3 levels (OR 1.14 95% CI 1.02–1.27, P = 0.03) were the only risk factors independently associated with delayed discharge from the hospital. Dynamic monitoring of complement C3 and SARS-CoV-2 RNA levels is useful for predicting delayed discharge of patients.
Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet
Authors: Swaminathan Anandini , Fokin Andrej , Venckūnas Tomas , Degens Hans 
Published: January 2021

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.
Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1
Authors: Gao Min , Yu Tianyi , Liu Dan , Shi Yan , Yang Peilang , Zhang Jie , Wang Jizhuang , Liu Yan , Zhang Xiong 
Published: January 2021

Abstract
Acute lung injury (ALI) is the leading cause of death in sepsis patients. Exosomes participate in the occurrence and development of ALI by regulating endothelial cell inflammatory response, oxidative stress and apoptosis, causing serious pulmonary vascular leakage and interstitial edema. The current study investigated the effect of exosomal miRNAs on endothelial cells during sepsis. We found a significant increase in miR-1-3p expression in cecal ligation and puncture (CLP) rats exosomes sequencing and sepsis patients’ exosomes, and lipopolysaccharide (LPS)-stimulated human umbilical vein endothelial cells (HUVECs) in vitro. However, the specific biological function of miR-1-3p in ALI remains unknown. Therefore, mimics or inhibitors of miR-1-3p were transfected to modulate its expression in HUVECs. Cell proliferation, apoptosis, contraction, permeability, and membrane injury were examined via cell counting kit-8 (CCK-8), flow cytometry, phalloidin staining, Transwell assay, lactate dehydrogenase (LDH) activity, and Western blotting. The miR-1-3p target gene was predicted with miRNA-related databases and validated by luciferase reporter. Target gene expression was blocked by siRNA to explore the underlying mechanisms. The results illustrated increased miR-1-3p and decreased stress-associated endoplasmic reticulum protein 1 (SERP1) expression both in vivo and in vitro. SERP1 was a direct target gene of miR-1-3p. Up-regulated miR-1-3p inhibits cell proliferation, promotes apoptosis and cytoskeleton contraction, increases monolayer endothelial cell permeability and membrane injury by targeting SERP1, which leads to dysfunction of endothelial cells and weakens vascular barrier function involved in the development of ALI. MiR-1-3p and SERP1 may be promising therapeutic candidates for sepsis-induced lung injury.