bluuebunny/crossref_metadata_2025_split huggingface dataset:
External validation of the European risk assessment tool for chronic cardio-metabolic disorders in a Middle Eastern population
Authors: Asgari Samaneh , Moosaie Fatemeh , Khalili Davood , Azizi Fereidoun , Hadaegh Farzad 
Published: July 2020

Abstract
Background
High burden of chronic cardio-metabolic disorders including type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD) have been reported in the Middle East and North Africa region. We aimed to externally validate a non-laboratory risk assessment tool for the prediction of the chronic cardio-metabolic disorders in the Iranian population.

Methods
The predictors included age, body mass index, waist circumference, use of antihypertensive medications, current smoking, and family history of cardiovascular disease and/or diabetes. For external validation of the model in the Tehran lipids and glucose study (TLGS), the Area under the curve (AUC) and the Hosmer–Lemeshow (HL) goodness of fit test were performed for discrimination and calibration, respectively.

Results
Among 1310 men and 1960 women aged 28–85 years, 29.5% and 47.4% experienced chronic cardio-metabolic disorders during the 6 and 9-year follow-up, respectively. The model showed acceptable discrimination, with an AUC of 0.72 (95% CI 0.69–0.75) for men and 0.73 (95% CI 0.71–0.76) for women. The calibration of the model was good for both genders (min HL P = 0.5). Considering separate outcomes, AUC was highest for CKD (0.76 (95% CI 0.72–0.79)) and lowest for T2DM (0.65 (95% CI 0.61–0.69)), in men. As for women, AUC was highest for CVD (0.82 (95% CI 0.78–0.86)) and lowest for T2DM (0.69 (95% CI 0.66–0.73)). The 9-year follow-up demonstrated almost similar performances compared to the 6-year follow-up. Using Cox regression in place of logistic multivariable analysis, model’s discrimination and calibration were reduced for prediction of chronic cardio-metabolic disorders; the issue which had more effect on the prediction of incident CKD among women. Moreover, adding data of educational levels and marital status did not improve, the discrimination and calibration in the enhanced model.

Conclusion
This model showed acceptable discrimination and good calibration for risk prediction of chronic cardio-metabolic disorders in short and long-term follow-up in the Iranian population.
Intensive care unit-acquired hyponatremia in critically ill medical patients
Authors: Sim Jae Kyeom , Ko Ryoung-Eun , Na Soo Jin , Suh Gee Young , Jeon Kyeongman 
Published: July 2020

Abstract
Background
Previous research has focused on intensive care unit (ICU)-acquired hypernatremia; however, ICU-acquired hyponatremia has frequently been overlooked and has rarely been studied in surgical or mixed ICUs. The aim of this study is to investigate the incidence of ICU-acquired hyponatremia, the risk factors associated with its development, and its impact on outcomes in critically ill medical patients.

Methods
We conducted a retrospective cohort study based on the prospective registry of all critically ill patients admitted to the medical ICU from January 2015 to December 2018. Baseline characteristics and management variables were compared between ICU-acquired hyponatremia and normonatremia patients.

Results
Of 1342 patients with initial normonatremia, ICU-acquired hyponatremia developed in 217 (16.2%) patients and ICU-acquired hypernatremia developed in 117 (8.7%) patients. The Sequential Organ Failure Assessment (8.0 vs 7.0, P = 0.009) and Simplified Acute Physiology Score 3 scores (55.0 vs 51.0, P = 0.005) were higher in ICU-acquired hyponatremia patients compared with normonatremia patients. Baseline sodium (137.0 mmol/L vs 139.0 mmol/L, P < 0.001), potassium (4.2 mmol/L vs 4.0 mmol/L, P = 0.001), and creatinine (0.98 mg/dL vs 0.88 mg/dL, P = 0.034) levels were different between the two groups. Net volume balance over first 3 days was higher in ICU-acquired hyponatremia patients (19.4 mL/kg vs 11.5 mL/kg, P = 0.004) and was associated with the development of ICU-acquired hyponatremia (adjusted odds ratio, 1.004; 95% confidence interval, 1.002–1.007; P = 0.001). ICU mortality was similar in both groups (15.2% vs. 14.4%, P = 0.751), but renal replacement therapy was more commonly required in ICU-acquired hyponatremia patients (13.4% vs 7.4%, P = 0.007).

Conclusions
ICU-acquired hyponatremia is not uncommon in critically ill medical patients. Increased volume balance is associated with its development. ICU-acquired hyponatremia is related to increased use of renal replacement therapy but not to mortality.
Effect of metabolically healthy obesity on the development of arterial stiffness: a prospective cohort study
Authors: Yuan Yue , Mu Jian-Jun , Chu Chao , Zheng Wen-Ling , Wang Yang , Hu Jia-Wen , Ma Qiong , Yan Yu , Liao Yue-Yuan , Chen Chen 
Published: July 2020

AbstractBackgroundMetabolically healthy obesity (MHO) has been reported to be associated with the development of vascular damage by the carotid intima-media thickness, but the relationship between metabolic health and obesity phenotypes and arterial stiffness is still unknown. Our hypothesized that different metabolic health and obesity phenotypes might be associated with the development of arterial stiffness, and that subjects in MHO phenotype might not have increased risks of arterial stiffness compared with those in metabolically healthy nonobesity phenotype (MHNO), while metabolic unhealthy individuals might have increased risks of arterial stiffness.MethodsA prospective cohort of 2076 participants (aged 36–48 years) who were enrolled in the Hanzhong Adolescent Hypertension Cohort Study in 2017 was analyzed in a cross-sectional analysis. A subgroup of 202 participants from 2005 to 2017 was selected by an isometric sampling method and was included in the final longitudinal analysis.ResultsWe identified four metabolic health and obesity phenotypes for both the cross-sectional and longitudinal analyses as follows: MHNO, metabolically unhealthy nonobesity (MUNO), MHO, and metabolically unhealthy obesity (MUO). In the cross-sectional analysis, individuals with the MHO phenotype had the lowest brachial-ankle pulse wave velocity (baPWV) levels of the four phenotypes (P < 0.001), and participants with the MHO phenotype had a similar risk of arterial stiffness after fully adjustment [odds ratio (OR) = 0.99 (0.61–1.60)] as the MUNO subjects. Subjects with metabolically unhealthy status had a significantly higher risk of arterial stiffness than the MHNO individuals, particularly females (P < 0.005). In the longitudinal analysis, subjects with the MUNO and MUO phenotypes had a significantly higher risk of arterial stiffness than the MHNO individuals after adjustment for age and sex [OR = 5.21 (2.26–12.02), OR = 3.32 (1.18–9.32), respectively].ConclusionsThe MHO phenotype did not significantly increase the progression of arterial stiffness. Metabolically unhealthy individuals (MUNO, MUO), regardless of obesity status, showed a worse effect for the development of arterial stiffness, particularly females.Trial registrationNCT02734472. Registered 12 April 2016 - Retrospectively registered, http:www.clinicaltrials.gov.
Relationship between the inflammation/immune indexes and deep venous thrombosis (DVT) incidence rate following tibial plateau fractures
Authors: Liu Dawei , Zhu Yanbin , Chen Wei , Li Junyong , Zhao Kuo , Zhang Junzhe , Meng Hongyu , Zhang Yingze 
Published: July 2020

Abstract
Objective
To determine the relationship between inflammation/immune-based indexes and deep venous thrombosis (DVT) incidence rate following tibial plateau fractures

Methods
Retrospective analysis of a prospectively collected data on patients undergoing surgeries of tibial plateau fractures between October 2014 and December 2018 was performed. Duplex ultrasonography (DUS) was routinely used to screen for preoperative DVT of bilateral lower extremities. Data on biomarkers (neutrophil, lymphocyte, monocyte, and platelet counts) at admission were collected, based on which neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte/lymphocyte (MLR), and systemic immune-inflammation index (SII, neutrophil* platelet/lymphocyte) were calculated. Receiver operating characteristic (ROC) was used to determine the optimal cutoff value for each variable. Multivariate logistic regression analysis was used to evaluate the independent relationship of each biomarker or index with DVT, after adjustment for demographics, co-morbidities, and injury-related variables.

Results
Among 1179 patients included, 16.3% (192/1179) of them had a preoperative DVT. Four factors were identified to be significantly associated with DVT, including open fracture, increased D-dimer level. Among the biomarkers and indexes, only platelet and neutrophil were identified to be independently associated with DVT, and the significance remained after exclusion of open fracture. The other independent variables were elevated D-dimer level (> 0.55 mg/L), male gender, and hypertension in the sensitivity analysis with open fractures excluded.

Conclusion
These identified factors are conducive to the initial screening for patients at risk of DVT, individualized risk assessment, risk stratification, and accordingly, development of targeted prevention programs.
Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice
Authors: He Jia , Yuan Renyikun , Cui Xiaolan , Cui Yushun , Han Shan , Wang Qin-Qin , Chen Yangling , Huang Liting , Yang Shilin , Xu Qiongming , Zhao Yonghui , Gao Hongwei 
Published: July 2020

AbstractBackgroundPneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient ofPulsatilla chinensis(Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses inKlebsiella pneumonia(KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model.MethodsThe network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP-induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (ribavirin or ceftriaxone sodium injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Proteins expression was quantified by western blotting.ResultsThe network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway.ConclusionOur findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.
The macrophage activation marker soluble CD163 is elevated and associated with liver disease phenotype in patients with Wilson’s disease
Authors: Glavind Emilie , Gotthardt Daniel N. , Pfeiffenberger Jan , Sandahl Thomas Damgaard , Bashlekova Teodora , Willemoe Gro Linno , Hasselby Jane Preuss , Weiss Karl Heinz , Møller Holger Jon , Vilstrup Hendrik , Lee William M. , Schilsky Michael L. , Ott Peter , Grønbæk Henning 
Published: July 2020

Abstract
Background
Macrophages play a significant role in liver disease development and progression. The macrophage activation marker soluble (s)CD163 is associated with severity and prognosis in a number of different acute and chronic liver diseases but has been only sparsely examined in Wilson’s disease (WD). We investigated sCD163 levels in patients with acute and chronic WD and hypothesized associations with liver disease phenotype and biochemical markers of liver injury.

Methods
We investigated sCD163 in two independent cohorts of WD patients: 28 patients with fulminant WD from the US Acute Liver Failure (ALF) Study Group registry and 147 patients with chronic disease from a German WD registry. We included a control group of 19 healthy individuals. Serum sCD163 levels were measured by ELISA. Liver CD163 expression was determined by immunohistochemistry.

Results
In the ALF cohort, median sCD163 was 10-fold higher than in healthy controls (14.6(2.5–30.9) vs. 1.5(1.0–2.7) mg/L, p < 0.001). In the chronic cohort, median sCD163 was 2.6(0.9–24.9) mg/L. There was no difference in sCD163 according to subgroups based on initial clinical presentation, i.e. asymptomatic, neurologic, hepatic, or mixed. Patients with cirrhosis at the time of diagnosis had higher sCD163 compared with those without cirrhosis (3.0(1.2–24.9) vs. 2.3(0.9–8.0) mg/L, p < 0.001); and both cohorts significantly lower than the ALF patients. Further, sCD163 correlated positively with ALT, AST, GGT and INR (rho = 0.27–0.53); and negatively with albumin (rho = − 0.37), (p ≤ 0.001, all). We observed immunohistochemical CD163 expression in liver tissue from ALF patients.

Conclusions
Although sCD163 is not specific for WD, it was elevated in WD patients, especially in those with ALF. Further, sCD163 was higher in patients with cirrhosis compared to patients without cirrhosis and associated with biochemical markers of liver injury and hepatocellular function. Thus, macrophage activation is evident in WD and associates with liver disease phenotype and biochemical parameters of liver disease. Our findings suggest that sCD163 may be used as a marker of liver disease severity in WD patients.
SM22α+ vascular mural cells are essential for vessel stability in tumors and undergo phenotype transition regulated by Notch signaling
Authors: Zhang Xinxin , Yan Xianchun , Cao Jing , Yang Ziyan , Cao Xiuli , Zhang Yufei , Liang Liang , Zheng Minhua , Liu Xiaowei , Zhang Jian , Han Hua 
Published: July 2020

Abstract
Background
Malformation of blood vessels represents a hallmark of cancers, but the role and regulation of vascular mural cells (vMCs), including vascular smooth muscle cells (vSMCs) and pericytes, in tumors has not been fully understood. SM22α has been identified as a marker of vSMCs. This study aims at elucidating the function and regulation of SM22α+ mural cells (SM22-MCs) in tumor stroma.

Methods
Gene-modified mice with a SM22α-CreERT2 transgene were employed to deplete SM22-MCs or activate/block Notch signaling in these cells. vSMCs from mouse dorsal aorta (vSMCs-DA) were cultured in vitro. RNA-seq was used to compare gene expression profiles. qRT-PCR and western blotting were used to determine gene expression level. Immunofluorescence was used to observe morphological alterations in tumors.

Results
SM22-MCs are essential for stabilizing tumor vasculature. Notch signaling was downregulated in tumor-derived SM22-MCs and vSMCs-DA treated with cancer cell-derived conditioned medium. Notch activation in SM22-MCs normalized tumor vasculature and repressed tumor growth. On the other hand, Notch disruption aggravated abnormal tumor vasculature and promoted growth and metastasis. Gene expression profiling of vSMCs-DA showed that Notch activation enhances their contractile phenotype and suppresses their secretory phenotype, further attenuating the invasion and proliferation of tumor cells. In contrast, Notch blockade in vSMCs-DA mitigated their contractile phenotype while strengthened the secretory phenotype.

Conclusion
SM22-MCs facilitate vessel stability in tumors, and they gain a secretory phenotype and promote tumor malignancy in the absence of Notch signaling.
Single dose versus 24 h antibiotic prophylaxis in reduction mammaplasty: study protocol for a randomized controlled trial
Authors: Veiga Daniela Francescato , da Silva Garcia Edgard , Moreira-Filho José Wilson , de Mattos Andrade Evelyne Borges , Juliano Yara , Veiga-Filho Joel , Ferreira Lydia Masako 
Published: July 2020

Abstract
Background
Reduction mammaplasty is among the most commonly performed procedures in plastic surgery. Antibiotics are widely prescribed, on an empirical basis, to prevent surgical site infections. However, there is a lack of evidence to support its use. This trial aims to compare the influence of the use of prophylatic antibiotics as a single dose or for 24 h on surgical site infection rates following reduction mammaplasty.

Methods
Randomized trial of non-inferiority, with two parallel groups. A total of 146 breast hypertrophy patients, with reduction mammaplasty already scheduled, will be enrolled. Patients will be randomly allocated to the placebo group that will receive antibiotics only at the anesthesia induction (n = 73) or to the antibiotics group that will receive antibiotics at the anesthesia induction and for 24 h (n = 73). None of the patients will receive antibiotics after hospital discharge. Patients will be followed-up weekly, for 30 days, regarding surgical site infection. The Centers for Disease Control and Prevention criteria will be applied. A statistical analysis of the data will be performed.

Discussion
Previous studies have demonstrated a decrease in infection rates after reduction mammaplasty when antibiotic prophylaxis was used, compared to the use of no antibiotics. However, the duration of antibiotic prophylaxis remains a point to be clarified. This study will test the hypothesis that maintaining the use of antibiotics for 24 h does not reduce infection rates compared to the use of a single preoperative dose.

Trial registration
Clinicaltrials.gov NCT04079686. Registered on September 6, 2019.
Using osmotic stress to stabilize mannitol production in Synechocystis sp. PCC6803
Authors: Wu Wenyang , Du Wei , Gallego Ruth Perez , Hellingwerf Klaas J. , van der Woude Aniek D. , Branco dos Santos Filipe 
Published: July 2020

Abstract
Background
Mannitol is a C(6) polyol that is used in the food and medical sector as a sweetener and antioxidant, respectively. The sustainable production of mannitol, especially via the direct conversion of CO2 by photosynthetic cyanobacteria, has become increasingly appealing. However, previous work aiming to achieve mannitol production in the marine Synechococcus sp. PCC7002 via heterologous expression of mannitol-1-phosphate-5-dehydrogenase (mtlD) and mannitol-1-phosphatase (m1p, in short: a ‘mannitol cassette’), proved to be genetically unstable. In this study, we aim to overcome this genetic instability by conceiving a strategy to stabilize mannitol production using Synechocystis sp. PCC6803 as a model cyanobacterium.

Results
Here, we explore the stabilizing effect that mannitol production may have on cells faced with osmotic stress, in the freshwater cyanobacterium Synechocystis sp. PCC6803. We first validated that mannitol can function as a compatible solute in Synechocystis sp. PCC6803, and in derivative strains in which the ability to produce one or both of the native compatible solutes was impaired. Wild-type Synechocystis, complemented with a mannitol cassette, indeed showed increased salt tolerance, which was even more evident in Synechocystis strains in which the ability to synthesize the endogenous compatible solutes was impaired. Next we tested the genetic stability of all these strains with respect to their mannitol productivity, with and without salt stress, during prolonged turbidostat cultivations. The obtained results show that mannitol production under salt stress conditions in the Synechocystis strain that cannot synthesize its endogenous compatible solutes is remarkably stable, while the control strain completely loses this ability in only 6 days. DNA sequencing results of the control groups that lost the ability to synthesize mannitol revealed that multiple types of mutation occurred in the mtlD gene that can explain the disruption of mannitol production.

Conclusions
Mannitol production in freshwater Synechocsytis sp. PCC6803 confers it with increased salt tolerance. Under this strategy, genetically instability which was the major challenge for mannitol production in cyanobacteria is tackled. This paper marks the first report of utilization of the response to salt stress as a factor that can increase the stability of mannitol production in a cyanobacterial cell factory.
Emergence of multidrug-resistant non-fermentative gram negative bacterial infection in hospitalized patients in a tertiary care center of Nepal
Authors: Yadav Santosh Kumar , Bhujel Rajshree , Mishra Shyam Kumar , Sharma Sangita , Sherchand Jeevan Bahadur 
Published: July 2020

AbstractObjectiveThis study was designed for the characterization and establishment of antibiotic susceptibility profiles of non-fermentative gram negative bacteria isolated from hospitalized patients in a tertiary care hospital of Nepal.ResultsA total of 402 non-fermentative gram negative bacteria was isolated in 1486 culture-positive cases from 6216 different clinical samples obtained from hospitalized patients. Among total non-fermentative gram negative bacterial isolates, the highest number was recovered from specimens collected from lower respiratory tract infections (n = 173, 43.0%) of hospitalized patients followed by pus/swab samples (n = 99, 24.6%) and urinary tract infections (n = 49, 12.2%). The most common non-fermentative gram negative bacteria identified wereAcinetobacter baumannii(n = 177, 44.0%),Pseudomonas aeruginosa(n = 161, 40.1%) andBurkholderia cepaciacomplex (n = 33, 8.2%). These bacterial isolates exhibited a higher rate of insusceptibility to beta-lactam antibiotics, fluoroquinolones, and aminoglycosides. On the other hand, all the isolates ofP. aeruginosaandA. baumanniiwere completely susceptible to colistin sulfate and polymyxin B. Among total isolates, 78.1% (n = 314) were multidrug-resistant with a high rate of multidrug-resistant amongA. baumannii(91.0%).