bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy
Authors: Yousefi Meysam , Rajaie Sara , Keyvani Vahideh , Bolandi Somayeh , Hasanzadeh Malihe , Pasdar Alireza
Published: May 2021

Circulating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).
Simulation study on the mining conditions of dissolution of low grade solid potash ore in Qarhan Salt Lake
Authors: Li Ruiqin , Liu Chenglin , Jiao Pengcheng , Hu Yufei , Liu Wanping , Wang Shijun
Published: May 2021

The output and grade of liquid potash minerals in Qarhan Salt Lake are decreasing year by year, which has become the main problem restricting the sustainable production of potassium fertilizer. The exploitation and utilization of low-grade solid potash ore, which is in the strata of the Qarhan Salt Lake, represents the fundamental framework for the sustainable development of Qarhan Salt Lake’s potash fertilizer. PHREEQC is a simulation software for hydrogeochemistry. In this paper, PHREEQC was applied to simulate temperature, pH value and solvent chemical characteristics which affect the dissolution process of low-grade solid potash minerals. The simulation results indicate that the optimum temperature for ore dissolution is around 25 °C, because, around this temperature, the dissolving ability of solvents to low-grade solid potash minerals is enhanced, while the dissolving ability to halite remains basically unchanged, which is conducive to selective dissolution of low-grade solid potash. It is recommended the temperature is between 20 and 30 ℃. The simulation results show that, when the pH value of solvents is more than 9, although it is advantageous to selective dissolution of low-grade solid potash minerals, the solvent becomes strong alkali solution, which will cause environmental pollution and seriously corrode materials and equipment in actual production, so it is recommended the pH value of the solvent is adjusted between 6 and 8. The simulation results show that, when the values of K+, Na+, Mg2+, Ca2+, Cl− and SO42− in the solvent are 0.1%, 2.9%, 3.77%, 0.05%, 15.72% and 0.13% respectively, the solubility of low-grade solid potash ores is stronger, which is more conducive to selective ore dissolution. It is suggested that in actual production, the chemical composition of solvents prepared with old brine and fresh water should be as close as possible to the above chemical composition characteristics.
Predicting anemia using NIR spectrum of spent dialysis fluid in hemodialysis patients
Authors: Matović Valentina , Jeftić Branislava , Trbojević-Stanković Jasna , Matija Lidija
Published: May 2021

Anemia is commonly present in hemodialysis (HD) patients and significantly affects their survival and quality of life. NIR spectroscopy and machine learning were used as a method to detect anemia in hemodialysis patients. The aim of this investigation has been to evaluate the near-infrared spectroscopy (NIRS) as a method for non-invasive on-line detection of anemia parameters from HD effluent by assessing the correlation between the spectrum of spent dialysate in the wavelength range of 700–1700 nm and the levels of hemoglobin (Hb), red blood cells (RBC), hematocrit (Hct), iron (Fe), total iron binding capacity (TIBC), ferritin (FER), mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC) in patient blood. The obtained correlation coefficient (R) for RBC was 0.93, for Hb 0.92, for Fe 0.94, for TIBC 0.96, for FER 0.91, for Hct 0.94, for MCV 0.92, for MCHC 0.92 and for MCH 0.93. The observed high correlations between the NIR spectrum of the dialysate fluid and the levels of the studied variables support the use of NIRS as a promising method for on-line monitoring of anemia and iron saturation parameters in HD patients.
Early bradycardia detection and therapeutic interventions in preterm infant monitoring
Authors: Doyen Matthieu , Hernández Alfredo I. , Flamant Cyril , Defontaine Antoine , Favrais Géraldine , Altuve Miguel , Laviolle Bruno , Beuchée Alain , Carrault Guy , Pladys Patrick
Published: May 2021

In very preterm infants, cardio-respiratory events and associated hypoxemia occurring during early postnatal life have been associated with risks of retinopathy, growth alteration and neurodevelopment impairment. These events are commonly detected by continuous cardio-respiratory monitoring in neonatal intensive care units (NICU), through the associated bradycardia. NICU nurse interventions are mainly triggered by these alarms. In this work, we acquired data from 52 preterm infants during NICU monitoring, in order to propose an early bradycardia detector which is based on a decentralized fusion of three detectors. The main objective is to improve automatic detection under real-life conditions without altering performance with respect to that of a monitor commonly used in NICU. We used heart rate lower than 80 bpm during at least 10 sec to define bradycardia. With this definition we observed a high rate of false alarms (64%) in real-life and that 29% of the relevant alarms were not followed by manual interventions. Concerning the proposed detection method, when compared to current monitors, it provided a significant decrease of the detection delay of 2.9 seconds, without alteration of the sensitivity (97.6% vs 95.2%) and false alarm rate (63.7% vs 64.1%). We expect that such an early detection will improve the response of the newborn to the intervention and allow for the development of new automatic therapeutic strategies which could complement manual intervention and decrease the sepsis risk.
Exploring the effect of alcohol on disease activity and outcomes in rheumatoid arthritis through systematic review and meta-analysis
Authors: Turk Jaime N. , Zahavi Erin R. , Gorman Aine E. , Murray Kieran , Turk Matthew A. , Veale Douglas J.
Published: May 2021

To evaluate the effects of alcohol consumption on disease activity in rheumatoid arthritis. EMBASE, Pubmed, the Cochrane Library, and Web of Science were searched until July 29, 2020. English language studies that reported disease activity outcomes in rheumatoid arthritis were included. Studies were excluded if they were reviews, case reports, had fewer than 20 patients, or reported on prevalence but not disease activity in RA. Forest plots were used to determine pooled mean difference and were generated on RevMan5.3. Linear regression was used to determine correlations between alcohol and antibody status, gender, and smoking status. The search identified 4126 citations of which 14 were included. The pooled mean difference in DAS28 (95% CI) was 0.34 (0.24, 0.44) (p < 10−5) between drinkers and non-drinkers with lower DAS28 in non-drinkers, 0.33 (0.05, 0.62) (p = 0.02) between heavy drinkers and non-drinkers with lower DAS28 in heavy drinkers, and 0.00 (− 0.30, 0.30) (p = 0.98) between low- and high-risk drinkers.
The mean difference of HAQ assessments was significantly different between those who drink alcohol compared to those who do not, with drinkers reporting lower HAQ scores (0.3 (0.18, 0.41), p < 10−5). There was no significant correlation between drinking and gender, smoking status, or antibody positivity. Alcohol consumption is associated with lower disease activity and self-reported health assessment in rheumatoid arthritis. However, drinking has no correlation with smoking, gender, or antibody status.
Factors affecting in-stent restenosis after angioplasty with the Enterprise stent for intracranial atherosclerotic diseases
Authors: Zhang Kun , Li Tian-Xiao , Wang Zi-Liang , Gao Bu-Lang , Gu Jian-Jun , Gao Hui-Li , Wang Yong-Feng , Xia Jin-Chao
Published: May 2021

This study investigated factors affecting the safety and in-stent restenosis after intracranial stent angioplasty using the Enterprise stent for symptomatic intracranial atherosclerotic stenosis. Between January 2017 and March 2019, patients with intracranial atherosclerotic stenosis treated with Enterprise stent angioplasty were enrolled, including 400 patients in the modeling group and 89 patients in the validation group. The clinical factors affecting in-stent restenosis after Enterprise stent angioplasty in the modeling group were analyzed, and a logistic regression model of these factors was established and validated in the validation group. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were analyzed. In the modeling group with 400 patients, there were 410 lesions, including 360 stenotic lesions and 50 occluded lesions, with 176 (42.9%) lesions in the anterior circulation and 234 (57.1%) in the posterior circulation. Successful stenting was performed in 398 patients (99.5%). Stenosis was significantly (P < 0.05) improved after stenting compared with before stenting (27.7% ± 2.9% vs. 77.9% ± 8.0%). Periprocedural complications included ischemic stroke (3.25%), hemorrhagic stroke (0.75%), and death (0.50%), with a total periprocedural complication rate of 4.0%. The first follow-up angiography was performed in 348 (87.0%) patients with 359 lesions 3.5–14 months (mean 5.7 months) after stenting. In-stent restenosis occurred in 62 (17.3%) lesions, while the other 295 (82.7%) had no restenosis. Lesion location, calcification degree, balloon expansion pressure, residual stenosis, intraprocedural dissection, and cerebral blood flow TICI grade were significant (P < 0.05) risk factors for in-stent restenosis. The in-stent restenosis prediction model was established as follows: P = 1/[1 + e−(−6.070–1.391 location + 2.745 calcification + 4.117 balloon inflation pressure + 2.195 intraprocedural dissection + 1.163 residual stenosis + 1.174 flow TC grade)]. In the validation group, the AUC in the ROC curve analysis was 0.902 (95% CI: 0.836–0.969), and when the cutoff value was 0.50, the sensitivity and specificity of this model were shown to be 76.92% and 80.26%, respectively, in predicting in-stent restenosis at angiographic follow-up, with a total coincidence rate of 79.78%. In conclusion, in-stent restenosis after intracranial Enterprise stenting is affected by stenosis location, calcification, balloon inflation pressure, intraprocedural arterial dissection, residual stenosis, and cerebral flow grade, and establishment of a logistic model with these factors can effectively predict in-stent restenosis.
A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure
Authors: Langley Raymond J. , Migaud Marie E. , Flores Lori , Thompson J. Will , Kean Elizabeth A. , Mostellar Murphy M. , Mowry Matthew , Luckett Patrick , Purcell Lina D. , Lovato James , Gandotra Sheetal , Benton Ryan , Files D. Clark , Harrod Kevin S. , Gillespie Mark N. , Morris Peter E.
Published: May 2021

Acute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition.
Hepatic parenchyma and vascular blood flow changes after TIPS with spectral CT iodine density in HBV-related liver cirrhosis
Authors: Wang Lei , Wang Rengui , Zhang Chunyan , Yue Zhendong , Zhao Hongwei , Fan Zhenhua , Wu Yifan , Zhang Yu , Liu Fuquan , Dong Jian
Published: May 2021

To compare changes in spectral CT iodine densities of hepatic parenchyma and vessels before and after transjugular intrahepatic portosystemic shunt (TIPS) in hepatitis B virus (HBV)-related liver cirrhosis. Twenty-five patients with HBV-related liver cirrhosis who received TIPS for gastroesophageal varices bleeding were recruited. Each patient underwent three phases contrast CT before and after TIPS within 4 weeks, with the raw data reconstructed at 1.25-mm-thick slices. Iodine density (in milligrams per milliliter) was measured on iodine-based material decomposition image. Multiple regions of interest (ROIs) in liver parenchyma, aorta and portal vein were selected from three slices of images. Portal vein trunk was set as the central one, and mean liver parenchymal iodine densities from arterial phase (AP), venous phase (VP) and equilibrium phase (EP) were recorded. Quantitative indices of iodine density (ID), including normalized ID in liver parenchyma for arterial phase (NIDLAP), ID of liver parenchyma for venous phase (IDLVP), ID of portal vein in venous phase (IDPVP) and liver arterial iodine density fraction (AIF), were measured and compared before and after TIPS. Based on Child–Pugh stage, 4, 12 and 9 patients were classified as grade A, B, and C, respectively. Liver volume was comparable before and after TIPS (1110.5 ± 287.4 vs. 1092.0 ± 276.3, P = 0.28). After TIPS, ID was decreased in aorta (146.0 ± 34.5 vs. 120.9 ± 30.7, P < 0.01) whereas increased in liver parenchyma at arterial phase, as demonstrated by IDAP (9.3 ± 3.1 vs. 13.4 ± 4.4 mg/mL) and AIF (0.40 ± 0.11 vs. 0.58 ± 0.11, P < 0.01). For venous or equilibrium phase, quantitative indices remained stable (23.1 ± 4.5 vs. 23.0 ± 5.3, 19.8 ± 4.1 vs. 19.4 ± 4.6) mg/mL (Ps > 0.05). For portal vein, ID and NID were increased after TIPS (23.1 ± 11.7 vs. 36.5 ± 13.0, 16.4 ± 8.5 vs. 31.8 ± 12.8) (P < 0.01). No positive correlation between iodine density and preoperative Child–Pugh score was observed. Based on iodine density measurement, spectral CT as a noninvasive imaging modality may assess hepatic parenchyma and vascular blood flow changes before and after TIPS in HBV-related liver cirrhosis.

Clinical registration number: ChiCTR- DDC-16009986.
A PROSS-designed extensively mutated estrogen receptor α variant displays enhanced thermal stability while retaining native allosteric regulation and structure
Authors: Kriegel Mark , Wiederanders Hanna J. , Alkhashrom Sewar , Eichler Jutta , Muller Yves A.
Published: May 2021

Protein stability limitations often hamper the exploration of proteins as drug targets. Here, we show that the application of PROSS server algorithms to the ligand-binding domain of human estrogen receptor alpha (hERα) enabled the development of variant ERPRS* that comprises 24 amino acid substitutions and exhibits multiple improved characteristics. The protein displays enhanced production rates in E. coli, crystallizes readily and its thermal stability is increased significantly by 23 °C. hERα is a nuclear receptor (NR) family member. In NRs, protein function is allosterically regulated by its interplay with small molecule effectors and the interaction with coregulatory proteins. The in-depth characterization of ERPRS* shows that these cooperative effects are fully preserved despite that 10% of all residues were substituted. Crystal structures reveal several salient features, i.e. the introduction of a tyrosine corner in a helix-loop-helix segment and the formation of a novel surface salt bridge network possibly explaining the enhanced thermal stability. ERPRS* shows that prior successes in computational approaches for stabilizing proteins can be extended to proteins with complex allosteric regulatory behaviors as present in NRs. Since NRs including hERα are implicated in multiple diseases, our ERPRS* variant shows significant promise for facilitating the development of novel hERα modulators.
The role of phase I, phase II, and DNA-repair gene polymorphisms in the damage induced by formaldehyde in pathologists
Authors: Ghelli Federica , Cocchi Enrico , Buglisi Martina , Squillacioti Giulia , Bellisario Valeria , Bono Roberto , Santovito Alfredo
Published: May 2021

Formaldehyde (FA) is a human carcinogen used as formalin in hospital laboratories. We evaluated its association with human chromosomal aberrations (CAs) and the risk/protective role played by several genetic polymorphisms in this relationship, on a cohort of 57 exposed pathologists vs 48 controls. All subjects were assessed for CAs on peripheral blood lymphocytes and genotyped for the most common cancer-associated gene polymorphisms which could be related with the genotoxic outcome: CYP1A1 exon 7 (A>G), CYP1A1*2A (T>C), CYP2C19*2 (G>A), GSTT1 (Positive/Null), GSTM1 (Positive/null), GSTP1 (A>G), XRCC1 (G399A), XRCC1 (C194T), XRCC1 (A280G), XPD (A751C), XPC exon 15 (A939C), XPC exon 9 (C499T), TNFα − 308 (G>A), IL10 − 1082 (G>A), IL10 − 819 (C>T) and IL6 − 174 (G>C). Air-FA concentration was assessed through personal samplers. The comparison between pathologists and controls showed a significantly higher CAs frequency in pathologists. Significant positive correlations were found between CAs frequency and air-FA concentration while significant associations were found between variation in CAs frequency and the mutated allele for CYP1A1 exon 7 (A>G), CYP2C19*2 (G>A), GSTT1-positive, GSTM1-positive and XRCC1 (G399A). Our study confirms the role of FA as genotoxicity inductor, even in workers chronically exposed to low air-FA levels and reveals the role played by some genetic polymorphisms in this association, highlighting the importance of individual susceptibility biomarkers assessment in occupational health studies.
Serological surveys to inform SARS-CoV-2 epidemic curve: a cross-sectional study from Odisha, India
Authors: Kshatri Jaya Singh , Bhattacharya Debdutta , Kanungo Srikanta , Giri Sidhartha , Palo Subrata Kumar , Parai Debaprasad , Turuk Jyotirmayee , Mansingh Asit , Choudhary Hari Ram , Pattnaik Matrujyoti , Dash Girish Chandra , Mohanty Prasantajyoti , Mishra Niranjan , Satapathy Durga Madhab , Sahoo Sanjaya Kumar , Pati Sanghamitra ,   ICMR-RMRC [OdiSHA-COVID-19] Serosurvey Team, Mohanta Amiya Ranjan , Bishoyee Anjan Kumar , Sadangi Ashish Kumar , Mahakuda Ashok Kumar , Mishra Biswakalyan , Padhan Dinabandhu , Sethi Gopinath , Jain Hitesh kumar , Biswal Janaki , Mohanta Jeevan Kumar , Pritam Jitendriya Amrit , Pradhan Jwell Kiran , sahoo Kanhu Charan , Dalai Keshab Chandra , Bhoi Manas kumar , Sahoo Nirupama , Dwibedi Nutan , Sahoo Pradyuspita , Khan Sadruddin , Pradhan Sagarkanta , Rout Satyabrata , Barik Shakti Ranjan , Patro Sithun Kumar , Samal Smitanjali , Soni Soni , Bhanjadeo Spandan Kumar , Patra Srikant Kumar , Dwivedy Subhralaxmi , Nayak Subrat kumar , Bhoi Trilochan
Published: May 2021

This was a population based cross-sectional study carried out to estimate and compare the seroprevalence, hidden prevalence and determine the demographic risk factors associated with SARS-CoV-2 infection among adults in the three largest cities of Odisha, India, and ascertain the association with the progression of the epidemic. The survey carried out in August 2020 in the three largest cities of the state of Odisha, India. Blood samples were collected from the residents using random sampling methods and tested for anti- SARS CoV-2 antibodies using an automated CLIA platform. A total of 4146 participants from the 3 cities of Bhubaneswar (BBS), Berhampur (BAM) and Rourkela (RKL) participated. The female to male participation ratio was 5.9:10 across the three cities. The gender weighted seroprevalence across the three cities was 20.78% (95% CI 19.56–22.05%). While females reported a higher seroprevalence (22.8%) as compared to males (18.8%), there was no significant difference in seroprevalence across age groups. A majority of the seropositive participants were asymptomatic (90.49%). The case to infection ratio on the date of serosurvey was 1:6.6 in BBS, 1:61 in BAM and 1:29.8 in RKL. The study found a high seroprevalence against COVID-19 in urban Odisha as well as high numbers of asymptomatic infections. The epidemic curves had a correlation with the seroprevalence.
Karyotypic and molecular evidence supports the endemic Tibetan hamsters as a separate divergent lineage of Cricetinae
Authors: Romanenko Svetlana A. , Lebedev Vladimir S. , Bannikova Anna A. , Pavlova Svetlana V. , Serdyukova Natalia A. , Feoktistova Natalia Yu. , Jiapeng Qu , Yuehua Sun , Surov Alexey V. , Graphodatsky Alexander S.
Published: May 2021

The genus status of Urocricetus was defined recently based on morphological and molecular data. Even though the amount of evidence for a separate phylogenetic position of this genus among Cricetinae continues to increase, there is still no consensus on its relationship to other groups. Here we give the first comprehensive description of the U. kamensis karyotype (2n = 30, NFa = 50) including results of comparative cytogenetic analysis and detailed examination of its phylogenetic position by means of numerous molecular markers. The molecular data strongly indicated that Urocricetus is a distant sister group to Phodopus. Comparative cytogenetic data showed significant reorganization of the U. kamensis karyotype compared to karyotypes of all other hamsters investigated earlier. The totality of findings undoubtedly means that Urocricetus belongs to a separate divergent lineage of Cricetinae.
Blood gas phenotyping and tracheal intubation timing in adult in-hospital cardiac arrest: a retrospective cohort study
Authors: Wang Chih-Hung , Wu Meng-Che , Wu Cheng-Yi , Huang Chien-Hua , Tsai Min-Shan , Lu Tsung-Chien , Chou Eric , Wu Yen-Wen , Chang Wei-Tien , Chen Wen-Jone
Published: May 2021

To investigate whether the optimal time to tracheal intubation (TTI) during cardiopulmonary resuscitation would differ by different blood gas phenotypes. Adult patients experiencing in-hospital cardiac arrest (IHCA) from 2006 to 2015 were retrospectively screened. Early intra-arrest blood gas analysis, performed within 10 min of resuscitation, was used to define different phenotypes. In total, 567 patients were included. Non-severe acidosis (pH≧7.15) was associated with favourable neurological outcome (odds ratio [OR]: 4.60, 95% confidence interval [CI] 1.63–12.95; p value = 0.004) and survival (OR: 3.25, 95% CI 1.72–6.15; p value < 0.001) in the multivariable logistic regression analyses. In the interaction analysis, normal blood gas phenotype (pH: 7.35–7.45, PCO2: 35–45 mm Hg, HCO3− level: 22–26 mmol/L) × TTI ≦ 6.3 min (OR: 20.40, 95% CI 2.53–164.75; p value = 0.005) and non-severe acidosis × TTI ≦ 6.3 min (OR: 3.35, 95% CI 1.00–11.23; p value = 0.05) were associated with neurological recovery while metabolic acidosis × TTI ≦ 5.7 min (OR: 3.63, 95% CI 1.36–9.67; p value = 0.01) and hypercapnic acidosis × TTI ≦ 10.4 min (OR: 2.27, 95% CI 1.20–4.28; p value = 0.01) were associated with survival. Intra-arrest blood gas analysis may help guide TTI during for patients with IHCA.
Egg-trading worms start reciprocation with caution, respond with confidence and care about partners’ quality
Authors: Lorenzi Maria Cristina , Schleicherová Dáša , Robles-Guerrero Franco G. , Dumas Michela , Araguas Alice
Published: May 2021

Conditional reciprocity (help someone who helped you before) explains the evolution of cooperation among unrelated individuals who take turns helping each other. Reciprocity is vulnerable to exploitations, and players are expected to identify uncooperative partners who do not return the help they received. We tested this prediction in the simultaneously hermaphroditic worm, Ophryotrocha diadema, which engages in mutual egg donations by alternating sexual roles (one worm releases’ eggs and the other fertilizes them). We set up dyads with different cooperativeness expectations; partners were either the same or a different body size (body size predicts clutch size). Large worms offered larger clutches and did so sooner when paired with large rather than small partners. They also released smaller egg clutches when they started egg donations than when they responded to a partners’ donation, fulfilling the prediction that a players’ first move will be prudent. Finally, behavioral bodily interactions were more frequent between more size-dissimilar worms, suggesting that worms engaged in low-cost behavioral exchanges before investing in such costly moves as egg donations. These results support the hypothesis that simultaneously hermaphroditic worms follow a conditional reciprocity paradigm and solve the conflict over sexual roles by sharing the costs of reproduction via the male and the female functions.
G protein-coupled receptor kinase 5 deletion suppresses synovial inflammation in a murine model of collagen antibody-induced arthritis
Authors: Toya Masakazu , Akasaki Yukio , Sueishi Takuya , Kurakazu Ichiro , Kuwahara Masanari , Uchida Taisuke , Tsutsui Tomoaki , Tsushima Hidetoshi , Yamada Hisakata , Lotz Martin K. , Nakashima Yasuharu
Published: May 2021

G protein-coupled receptor kinase 5 (GRK5) regulates inflammatory responses via the nuclear factor-kappa B (NF-κB) pathway. This study investigated the functional involvement of GRK5 in the pathogenesis of inflammatory arthritis. Immunohistochemically, rheumatoid arthritis (RA) synovium had a significantly higher proportion of GRK5-positive cells in the synovial lining layer than healthy control synovium. Gene expression and NF-κB activation in lipopolysaccharide-stimulated human SW982 synovial cells were significantly suppressed by silencing of the GRK5 gene. Similarly, GRK5 kinase activity inhibition in human primary RA synovial cells attenuated gene expressions of inflammatory factors. In a murine model of collagen antibody-induced arthritis, arthritis scores and serum IL6 production of GRK5 knockout (GRK5-/-) mice were significantly lower than those of wild-type mice. Histologically, the degree of synovitis and cartilage degeneration in GRK5-/- mice was significantly lower than in wild-type mice. In in vitro analyses using activated murine macrophages and fibroblast-like synoviocytes, gene expression of inflammatory factors and p65 nuclear translocation were significantly lower in GRK5-/- mice compared to wild-type mice. In conclusion, our results suggested that GRK5 is deeply involved in the pathogenesis of inflammatory arthritis, therefore, GRK5 inhibition could be a potential therapeutic target for types of inflammatory arthritis such as RA.
High-grade extracellular vesicles preparation by combined size-exclusion and affinity chromatography
Authors: Bellotti Cristina , Lang Kristina , Kuplennik Nataliya , Sosnik Alejandro , Steinfeld Robert
Published: May 2021

Extracellular vesicles (EVs) have recently gained growing interest for their diagnostic and therapeutic potential. Despite this, few protocols have been reported for the isolation of EVs with preserved biological function. Most EV purification methods include a precipitation step that results in aggregation of vesicles and most available techniques do not efficiently separate the various types of EVs such as exosomes and ectosomes, which are involved in distinct biological processes. For this reason, we developed a new two-step fast performance liquid chromatography (FPLC) protocol for purification of large numbers of EVs. The method comprises size exclusion chromatography followed by immobilized metal affinity chromatography, which is enabled by expression of poly-histidine tagged folate receptor α in the parental cells. Characterisation and comparison of the EVs obtained by this method to EVs purified by differential centrifugation, currently the most common method to isolate EVs, demonstrated higher purity and more selective enrichment of exosomes in EV preparations using our FPLC method, as assessed by comparison of marker proteins and density distribution. Our studies reveal new possibilities for the isolation of defined subpopulations of EVs with preserved biological function that can easily be upscaled for production of larger amounts of EVs.
Relation between preoperative benzodiazepines and opioids on outcomes after total joint arthroplasty
Authors: Doan Lisa V. , Padjen Kristoffer , Ok Deborah , Gover Adam , Rashid Jawad , Osmani Bijan , Avraham Shirley , Wang Jing , Kendale Samir
Published: May 2021

To examine the association of preoperative opioids and/or benzodiazepines on postoperative outcomes in total knee and hip arthroplasty, we retrospectively compared postoperative outcomes in those prescribed preoperative opioids and/or benzodiazepines versus those who were not who underwent elective total knee and hip arthroplasty at a single urban academic institution. Multivariable logistic regression was performed for readmission rate, respiratory failure, infection, and adverse cardiac events. Multivariable zero-truncated negative binomial regression was used for length of stay. After exclusions, there were 4307 adult patients in the study population, 2009 of whom underwent total knee arthroplasty and 2298 of whom underwent total hip arthroplasty. After adjusting for potential confounders, preoperative benzodiazepine use was associated with increased odds of readmission (p < 0.01). Preoperative benzodiazepines were not associated with increased odds of respiratory failure nor increased length of stay. Preoperative opioids were not associated with increased odds of the examined outcomes. There were insufficient numbers of infection and cardiac events for analysis. In this study population, preoperative benzodiazepines were associated with increased odds of readmission. Preoperative opioids were not associated with increased odds of the examined outcomes. Studies are needed to further examine risks associated with preoperative benzodiazepine use.
Evaluation of the Idylla ctEGFR mutation assay to detect EGFR mutations in plasma from patients with non-small cell lung cancers
Authors: Gilson Pauline , Saurel Chloé , Salleron Julia , Husson Marie , Demange Jessica , Merlin Jean-Louis , Harlé Alexandre
Published: May 2021

The assessment of EGFR mutations is recommended for the management of patients with non-small cell lung cancer (NSCLC). Presence of EGFR mutation is associated with response or resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI). Liquid biopsy is nowadays widely used for the detection of resistance to EGFR-TKI. We evaluated here the performance of the Idylla ctEGFR mutation assay for the detection of EGFR mutations in circulating tumour DNA (ctDNA) in plasma from patients with NSCLC. Previously characterized plasma samples from 38 patients with NSCLC were analysed using 2 different analytical conditions (C1 and C2). The limit of detection (LOD) was evaluated using 2 mL of healthy donor plasma spiked with commercial DNA controls. Overall agreement, sensitivity and specificity were 92.1%, 86.7% and 95.7% for C1 condition respectively and 94.7%, 86.7% and 100% for C2 condition respectively. The T790M secondary resistance mutation was detected in two samples out of 3. The Idylla system was able to detect the exon 19 deletion from 6 copies/mL and up to 91 copies/mL for the G719S mutation. These results support that the Idylla ctEGFR mutation assay is a rapid option for the detection of EGFR hotspots mutations in plasma samples, however a particular attention is needed for its interpretation.
Fabrication, functionalization and advanced applications of magnetic hollow materials in confined catalysis and environmental remediation
Authors: Arora Gunjan , Yadav Manavi , Gaur Rashmi , Gupta Radhika , Yadav Priya , Dixit Ranjana , Sharma Rakesh Kumar
Published: May 2021

A comprehensive overview of the magnetic hollow core and nano-rattle architectures with focus on emerging trends in synthetic protocols, functionalization approaches and applications in the field of confined catalysis and environmental remediation.
Water/gas separation based on the selective bubble-passage effect of underwater superaerophobic and superaerophilic meshes processed by a femtosecond laser
Authors: Yong Jiale , Zhuang Jian , Bai Xue , Huo Jinglan , Yang Qing , Hou Xun , Chen Feng
Published: May 2021

This paper proposes a method to separate bubbles from water by integrating underwater superaerophobic and superaerophilic porous membranes, including bubble removal and collection methods.
Controllable DNA strand displacement by independent metal–ligand complexation
Authors: Wang Liang-Liang , Zhang Qiu-Long , Wang Yang , Liu Yan , Lin Jiao , Xie Fan , Xu Liang
Published: May 2021

This metal-mediated artificial base pair can function as an independent toehold based on metal–ligand coordination and exhibit flexible and reversible controllability to manipulate the dynamics of strand displacement.
A crystalline/amorphous CoP@CoB hierarchical core–shell nanorod array for enhanced hydrogen evolution
Authors: Shi Peidong , Zhang Yu , Zhang Guanglu , Zhu Xiaojuan , Wang Shaohua , Wang An-Liang
Published: May 2021

A hierarchical nanoarray comprising an inner crystalline CoP nanorod and an outer amorphous CoB nanosheet exhibits excellent performance toward hydrogen evolution.
High glucose–induced Smad3 linker phosphorylation and CCN2 expression are inhibited by dapagliflozin in a diabetic tubule epithelial cell model
Authors: Pan Xinlu , Phanish Mysore K. , Baines Deborah L. , Dockrell Mark E.C.
Published: May 2021

Background: In the kidney glucose is freely filtered by the glomerulus and, mainly, reabsorbed by sodium glucose cotransporter 2 (SGLT2) expressed in the early proximal tubule. Human proximal tubule epithelial cells (PTECs) undergo pathological and fibrotic changes seen in diabetic kidney disease (DKD) in response to elevated glucose. We developed a specific in vitro model of DKD using primary human PTECs with exposure to high D-glucose and TGF-β1 and propose a role for SGLT2 inhibition in regulating fibrosis. Methods: Western blotting was performed to detect cellular and secreted proteins as well as phosphorylated intracellular signalling proteins. qPCR was used to detect CCN2 RNA. Gamma glutamyl transferase (GT) activity staining was performed to confirm PTEC phenotype. SGLT2 and ERK inhibition on high D-glucose, 25 mM, and TGF-β1, 0.75 ng/ml, treated cells was explored using dapagliflozin and U0126, respectively. Results: Only the combination of high D-glucose and TGF-β1 treatment significantly up-regulated CCN2 RNA and protein expression. This increase was significantly ameliorated by dapagliflozin. High D-glucose treatment raised phospho ERK which was also inhibited by dapagliflozin. TGF-β1 increased cellular phospho SSXS Smad3 serine 423 and 425, with and without high D-glucose. Glucose alone had no effect. Smad3 serine 204 phosphorylation was significantly raised by a combination of high D-glucose+TGF-β1; this rise was significantly reduced by both SGLT2 and MEK inhibition. Conclusions: We show that high D-glucose and TGF-β1 are both required for CCN2 expression. This treatment also caused Smad3 linker region phosphorylation. Both outcomes were inhibited by dapagliflozin. We have identified a novel SGLT2 -ERK mediated promotion of TGF-β1/Smad3 signalling inducing a pro-fibrotic growth factor secretion. Our data evince support for substantial renoprotective benefits of SGLT2 inhibition in the diabetic kidney.
Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver–α-cell axis
Authors: Liu Qiaofeng , Lin Guangyao , Chen Yan , Feng Wenbo , Xu Yingna , Lyu Jianjun , Yang Dehua , Wang Ming-Wei
Published: May 2021

Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver–α-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance. They also exhibited hyperglucagonemia, pancreas enlargement and α-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acid metabolism. It was found that GcgrV369M+/+ mice displayed increased plasma amino acid levels in general, but significant accumulation of the ketogenic/glucogenic amino acids was observed in animals fed with a high-fat diet (HFD), resulting in deleterious metabolic consequence characteristic of α-cell proliferation and hyperglucagonemia.
Mode‐dependent switching control of bilateral teleoperation against random denial‐of‐service attacks
Authors: Hu Lingyan , Wang Kun , Hu Dongxia , Wang Yiming
Published: May 2021

As communication networks are implemented for information exchange between the master and slave sides of bilateral teleoperation systems, they are exposed to cyber‐attack threats. This paper aims to analyse the performance of bilateral teleoperation systems in the presence of random denial‐of‐service (DoS) attacks and constant transmission delays and propose a mode‐dependent switching controller to mitigate the influence of DoS attacks. The characteristics of DoS attacks and networks are thoroughly incorporated in the design; also considered is the case of both communication directions behaving independently. Specifically, the model of a teleoperation system under a DoS attack is integrated as a stochastic jump system. A mode‐dependent control approach is proposed for a teleoperation system to mitigate the influence of random DoS attacks. In case studies, vulnerability analysis and time‐domain simulation results show that teleoperation system performance can be degraded under continuous random DoS attacks. When the proposed mode‐based switching controllers are installed, the trajectory tracking performance and authenticity of interaction force feedback are significantly improved during the attacking period.
Polarimetric HRRP recognition based on feature‐guided Transformer model
Authors: Zhang Liang , Han Chang , Wang Yanhua , Li Yang , Long Teng
Published: May 2021

Polarimetric high‐resolution range profile (HRRP) holds great potential for radar automatic target recognition (RATR) owing to its capability of providing both polarimetric and spatial scattering information. In recent years, deep learning (DL) has obtained state‐of‐the‐art results in many classification tasks and has drawn great attention in the RATR field. However, as one of the most challenging tasks in RATR, small training sample case will restrict the application of DL because its superior performance generally depends on a large number of training samples. A feature‐guided deep model based on Transformer framework is proposed for polarimetric HRRP recognition with limited training samples. In the proposed model, artificial features are introduced to the attention module to guide the model focus on the range cells of HRRP with more target scattering information so as to reduce the dependence of the model on the number of training samples. Several different approaches are also studied to measure the similarity between artificial features and HRRP data to further improve the learning capacity of the model. Experimental results demonstrate that the proposed feature‐guided Transformer model modifying by Cosine similarity measure is able to achieve a better performance for polarimetric HRRP recognition with limited training samples.
Temperature‐dependent partial discharge characteristics of high temperature materials at DC voltage for hybrid propulsion systems
Authors: Shahsavarian Tohid , Wu Xin , Lents Charles , Zhang Di , Li Chuanyang , Cao Yang
Published: May 2021

The safe and reliable operation of insulation material used in key high voltage components under extreme environmental conditions represents the major concerns for manufacturers and operators of More Electric Aircrafts (MEA). Surface discharge occurring in high current carrying components in DC power system diminishes the insulation material’s performance and life, especially at high‐temperature conditions. Here, the surface discharge behaviour of two commonly used high‐temperature insulation materials, ethylene‐tetrafluoroethylene (ETFE) and polyetheretherketone (PEEK) is studied at different temperatures under ramp and DC voltages. Extracted partial discharge (PD) features are presented and the impact of voltage polarity on surface discharge propagation is discussed. Our studies reveal that, while both materials exhibit non‐linear PD behaviour with respect to their electrical conductivity, ETFE generally shows PDs with higher intensity at high temperature above 100°C with a higher possibility of surface discharge due to its lower permittivity. Overall, the PD mechanism in high‐temperature, DC voltage applications is explored, and a basis for the selection of high‐temperature PD suppressing materials is developed.
A two‐stage multi microgrids p2p energy trading with motivational game‐theory: A case study in malaysia
Authors: Yap Yu‐Hang , Tan Wen‐Shan , Wong Jinnie , Ahmad Noor Azlinda , Wooi Chin‐Leong , Wu Yuan‐Kang , Ariffin Aznan Ezraie
Published: May 2021

Peer‐to‐peer (P2P) energy trading is expected to be emerged as a new energy management paradigm that allows the transaction of energy from one prosumer to another prosumer without any dependency on a central controller. In Malaysia, first pilot test of P2P trading has been conducted recently, which exclusively participated by industrial prosumers and commercial consumers only. In order to investigate the impact of P2P energy trading to Malaysia market, this paper proposes an auction‐based two‐stage P2P trading market‐clearing strategy, for multi‐cities and intra‐city in Malaysia. A motivational game theory‐based price scheme is presented to ensure an unbiased market operation, to maximize the saving and payoff for each prosumer, at the same time benefits the power utility company. The proposed two‐stage market clearing model is solved by Linear Programming optimization approach. A realistic representation of P2P trading in Malaysia is constructed and tested out under multi‐cities and intra‐city energy trading test cases. Comparison between the proposed P2P energy trading with existing solar generation net metering scheme is also presented. The numerical results indicate the viability and potential of motivational game theory based P2P trading in future Malaysia transactive energy market.
ISS estimates in the spatial sup-norm for nonlinear 1-D parabolic PDEs
Authors: Karafyllis Iasson , Krstic Miroslav
Published: May 2021

This paper provides novel Input-to-State Stability (ISS)-style maximum principle estimates for classical solutions of nonlinear 1-D parabolic Partial Differential Equations (PDEs). The derivation of the ISS-style maximum principle estimates is performed in two ways: by using an ISS Lyapunov Functional for the sup norm and by exploiting well-known maximum principles. The estimates provide fading memory ISS estimates in the sup norm of the state with respect to distributed and boundary inputs. The obtained results can handle parabolic PDEs with nonlinear and non-local in-domain terms/boundary conditions. Three illustrative examples show the efficiency of the proposed methodology for the derivation of ISS estimates in the sup norm of the state.
Dépistage néonatal de la mucoviscidose
Authors: Munck Anne , Cheillan David , Audrezet Marie-Pierre , Guenet David , Huet Frédéric
Published: May 2021

Le dépistage néonatal (DNN) de la mucoviscidose a permis une prise en charge multidisciplinaire très précoce des nourrissons et a amélioré le pronostic de cette maladie. Il a connu, en une vingtaine d’années, un développement international spectaculaire. Les performances du DNN national français, réalisé depuis 2002, répondent aux exigences des standards européens en termes de valeur prédictive positive et de sensibilité. Nous pouvons noter, en particulier, un nombre très faible de cas en attente de conclusion, un pourcentage très élevé de tests de la sueur réalisés et d’identification des mutations du gène cystic fibrosis transmembrane conductance regulator (CFTR), un ratio important de cas de mucoviscidose par rapport aux cas de diagnostics non conclus, ainsi qu’une stratégie efficace pour repérer les faux-négatifs. Une nouvelle organisation du DNN français a été mise en place. Il est donc capital de maintenir l’efficacité du processus ainsi mis en place, du nouveau-né en maternité jusqu’au diagnostic dans des centres de ressources et de compétences de la mucoviscidose, avec le recueil exhaustif des données et leur validation.
Dépistage néonatal de la drépanocytose en France
Authors: Brousse Valentine , Allaf Bichr , Benkerrou Malika
Published: May 2021

Le dépistage néonatal de la drépanocytose, la plus fréquente des maladies rares en France, a permis, entre 1984 et 2019, l’identification de 9 260 nouveau-nés atteints de drépanocytose (dont 586 en 2019) et de 180 687 hétérozygotes AS. Ce dépistage a permis la mise en œuvre précoce de mesures prophylactiques chez ces enfants, grâce à un tissu sanitaire et social structuré. Depuis que ce dépistage est organisé, on a pu observer, dès l’âge pédiatrique, une diminution majeure de la mortalité et de la morbidité de la drépanocytose, qui concerne notamment les complications infectieuses invasives, anémiques et neuro-vasculaires. En métropole, ce dépistage garde la particularité d’être ciblé vers les nouveau-nés dont les parents sont originaires de régions à risque. La fréquence croissante de la drépanocytose (1/1 303 nouveau-nés identifiés en 2019 contre 1/2 089 en 2009) et l’augmentation de la fréquence des hétérozygotes plaident aujourd’hui pour un dépistage systématique étendu à tous les nouveau-nés et pour une meilleure information sur cette maladie, devenue un enjeu majeur de santé publique.