bluuebunny/crossref_metadata_2025 huggingface dataset:
The Involvement of PPARγ In Anti-Inflammatory Activity of N-Stearoylethanolamide
Authors: Kosiakova Halyna , Berdyshev Andrii , Dosenko Victor , Drevytska Tetyana , Herasymenko Oleksandra , Hula Nadiya
Published: July 2021

N-stearoylethanolamide (NSE)– a cannabinoid-like compound with wide range of biological activity. Anti-inflammatory properties of NSE have been indicated on different animal models of pathological conditions. However, the molecular mechanisms of anti-inflammatory action of NSE remain unclear. In the current study, the involvement of PPARγ in the NF-kB -dependent anti-inflammatory action of NSE was evaluated using different methodological approach. First method - molecular modeling, evaluated the possibility of NSE to bind with PPAR. Then, in ex vivo experiment, using selective synthetic agonist of PPARα/γ LY-171883 and selective antagonist of PPARγ - GW9662, the role of PPARα /PPARγ in the NSE’s effect on nuclear NF-kB translocation was examined in LPS-activated rat peritoneal macrophages. Finally, the NSE action on the mRNA level of several PPARγ- dependent genes was studied in liver of insulin-resistant rats. The molecular docking results showed that NSE could bind to PPARγ and compete for the binding with antagonist GW9662 and agonist LY171883 in the active site of PPARγ. It also has been found that NSE prevented the LPS-induced NF-kB translocation into the nuclei of rat peritoneal macrophages during pre-treatment with NSE before LPS application. When NSE was added before GW9662 and LPS treatment, the level of NF-kB translocation and IL-1β content reduced to control cells’ levels. These data confirmed a competitive binding of NSE with GW9662 for the ligand-binding domen of PPARγ. In addition, NSE administration to insulin resistant rats changed the mRNA expression of several PPARγ target gens, including FATP1 and IL1-ra.
Repair of Damaged Parts Using Wire Arc Additive Manufacturing In Machine Tools Remanufacturing
Authors: Lee Jeong-Hak , Lee Choon Man , Kim Dong-Hyeon
Published: July 2021

Mechanical parts manufactured using additive manufacturing (AM) processes are used in various fields, such as the aerospace, automobile, and machine tool fields. Recently, many researchers have been actively researching AM processes, owing to their advantages in fabricating complex-shaped components that are difficult to process using conventional processes such as rolling, forging, and casting. One of the AM processes, wire arc additive manufacturing (WAAM), is widely used for manufacturing and repair. Mechanical parts usually suffer from severe damage, such as wear and cracks, during operation. Therefore, research on the damaged parts is often required for repairs. This study was performed to investigate the repair of damaged parts using WAAM in machine tool remanufacturing. In general, these parts are often damaged owing to falls of the workpieces and the inexperience of workers; the cross slide is one of the parts damaged most often in a lathe. Accordingly, this study used the cross slide as an example. First, the damaged area was partially cut flat. Second, it was filled with a metal wire using WAAM. Third, post-processing was performed to adjust the surface quality and shape accuracy. Then, the microstructure, chemical composition, and mechanical property of the repaired part were analyzed. Finally, the repaired cross slide was used to replace damaged parts. In general, this method can be applied to various mechanical parts such as impellers, turbine blades, and machine tools.
Novel Core-Shell Non-Sintered Lightweight Aggregate Concrete for Better Properties in Wallboard
Authors: PANG Chaoming , MENG Xinxin , ZHANG Chunpeng , PAN Jinlong
Published: July 2021

Shrinkage of foam concrete can easily cause cracking and thus makes it difficult for a manufacturer to maintain quality. The density of lightweight aggregate concrete is too high to meet specifications for lightweight and thermal insulation for wallboard. Two types of concrete with dry density in the range 1000–1200 kg/m3 for use in wallboard were designed and prepared using foam and lightweight aggregate. The properties of porous lightweight aggregate concrete with core-shell non-sintered lightweight aggregate were compared with sintered lightweight aggregate concrete along with several dimensions. The two aggregates were similar in particle size, density, and strength. The effects of each aggregate on the workability, compressive strength, dry shrinkage, and thermal conductivity of the lightweight concrete were analyzed and compared. Pore structures were determined by mercury intrusion porosimetry and X-ray computed tomography. Compressive strength ranged from 7.8 to 11.8 MPa, and thermal conductivity coefficients ranged from 0.193 to 0.219 W/m/K for both types of concrete. The results showed that the core-shell non-sintered lightweight aggregate bonded better with the paste matrix at the interface transition zone and had a better pore structure than the sintered lightweight aggregate concrete. Slump flow of the core-shell non-sintered lightweight aggregate concrete was about 20% greater than that of the sintered lightweight aggregate concrete, 28d compressive strength was about 10% greater, drying shrinkage was about 10% less, and thermal conductivity was less. Porous lightweight aggregate concrete using core-shell non-sintered lightweight aggregate performs well when used in wallboard because of its low density, high thermal insulation, and improved strength.
Myeloperoxidase as an Important Predictor of Cardiovascular Risk in Individuals with Rheumatoid Arthritis
Authors: Montes Elisangela Gueiber , Mansani Fabiana Postiglioni , Júnior Alceu de Oliveira Toledo , Schafranski Marcelo Derbli , Zardo Bruno Queiroz , Santos Fábio André dos , Grassiolli Sabrina , Calixto Lorena de Freitas , Costa Romulo Lopes da , Netto Felício de Freitas , Vellosa José Carlos Rebuglio
Published: July 2021

Background: Rheumatoid arthritis is an inflammatory disease with joint manifestations. In the presence of extra-articular manifestations, the morbidity and severity of the disease increases. Glucocorticoid is used as a treatment and may result in side effects related to cardiovascular risk. Methods: This was a cross-sectional study including 59 volunteers with rheumatoid arthritis receiving treatment at a Hospital of Campos Gerais, that aimed to establish the relation between cardiovascular risk, glucocorticoid treatment and myeloperoxidase in these patients. Subjects were divided into two groups: using (n = 39) and without glucocorticoids (n = 20). They underwent clinical evaluation, physical examination and blood samples were taken. Statistical analysis was performed using Student's t-test and Mann-Whitney test. Logistic regression was performed to assess cardiovascular risk. The significance level was 5% (α = 0.05). Calculations were performed using the Statistical Package for the Social Science version 21.0. Results: There has been a significant difference between groups in blood glucose values (p = 0.012), that can be explained by the different percentage of diabetic patients in the groups. When assessed cardiovascular risk using the predictors of glucocorticoid dose, time of glucocorticoid use, myeloperoxidase, and C-reactive protein together, these were responsible for significantly predicting cardiovascular risk (p = 0.015). Conclusions: A significant relation between the predictor myeloperoxidase alone was also demonstrated (p = 0.037), may it be an important predictor of cardiovascular risk among individuals with rheumatoid arthritis.
Airway Management for Penetrating Head and Neck Trauma, Experience of a Trauma Center from 2012 to 2020
Authors: Morvan Jean-Baptiste , Cungi Pierre-Julien , Cotte Jean , cassignol arnaud , Renard Aurélien , Bussone Claire-Marie , Maso Victorine , Pascaud Damien , Beucler Nathan , Vatin Loraine , Rivière Damien , Joubert Christophe , Cathelinaud Olivier , Bordes Julien
Published: July 2021

BackgroundFrom a series of penetrating head and neck trauma managed in a level-1 Trauma Center, the main aim of this study was to determine predictive factors for early definitive airway management, during pre-hospital time or in the emergency room. The secondary objective was to perform a descriptive epidemiological analysis of the series.MethodsA single-center retrospective study was conducted between January 1 2012 and June 30 2020. in a French Level 1 Trauma Center. The patients included were adults treated for penetrating head and neck trauma, regardless of the mechanism and the causal agent.Results 56 patients were included. Ballistic origin, Shock Index >0.9 and active bleeding in the emergency room were predictive criteria for definitive airway management during pre-hospital time or in the emergency room. 78.6% of patients were male. Median age was 54 years. The trauma followed a suicide attempt in 50% of cases, an accident in 26.7% and an assault in 23.2%, with use of a knife in 42.9% and firearm in 26.8%. Mortality was 10.7%. 16.1% of patients had undergone pre-hospital intubation and 19.1% intubation in the emergency room. CT scan was performed in 87.5% of cases, surgery in 96.4% and tracheotomy in 37.5%. A laryngotracheal lesion was seen in 14.2%. In 50% of patients, primary admission was to intensive care. Conclusions Ballistic origin, Shock Index >0.9 and active bleeding in the emergency room were predictive criteria for early definitive airway management. This study established the profile of patients suffering from penetrating head and neck trauma managed in a Trauma Center over a period of 9 years.
Integrated RNAi Screening Identifies The NEDDylation Pathway As A Synergistic Partner of Azacytidine In Acute Myeloid Leukemia
Authors: Klosner Justine , Agelopoulos Konstantin , Rohde Christian , Göllner Stefanie , Schliemann Christoph , Berdel Wolfgang E. , Müller-Tidow Carsten
Published: July 2021

Treatment of Acute Myeloid Leukemia (AML) remains challenging and novel targets and synergistic therapies still need to be discovered. We performed a high-throughput RNAi screen in three different AML cell lines and primary human leukemic blasts to identify genes that synergize with common antileukemic therapies. We used a pooled shRNA library that covered 5043 different genes and combined transfection with exposure to either azacytidine or cytarabine analog to the concept of synthetic lethality. Suppression of the chemokine CXCL12 ranked highly among the candidates of the cytarabine group. azacytidine in combination with suppression of genes within the neddylation pathway led to synergistic results. NEDD8 and RBX1 inhibition by the small molecule inhibitor pevonedistat inhibited leukemia cell growth. These findings establish an in vitro synergism between NEDD8 inhibition and azacytidine in AML. Azacytidine and NEDD8 inhibitors are currently undergoing clinical trials in combination with azacytidine. Taken together, neddylation constitutes a suitable target pathway for azacytidine combination strategies.
Increased Survival In Puppies Affected By Canine Parvovirus Type II Using An Immunomodulator As A Therapeutic Aid
Authors: Muñoz Adriana I , Vallejo-Castillo Luis , Fragozo Ana L , Vazquéz-Leyva Said , Pavón Lenin , Pérez-Sánchez Gilberto , Soria-Castro Rodolfo , Mellado-Sánchez Gabriela , Cobos-Marin Laura , Pérez-Tapia Sonia Mayra
Published: July 2021

Background: The canine parvoviral enteritis (CPE) promotes sepsis and systemic inflammatory response syndrome (SIRS). Mortality in this disease is usually registered within 48–72 h post-hospitalization, the critical period of the disease. It has been recently described that the use of an immunomodulator whose major component is monomeric ubiquitin (mUb) without the last two glycine residues (Ub∆GG) in pediatric patients with sepsis improves survival. It is known that CXCR4 is the cell receptor of extracellular ubiquitin in humans. The aim of this work was to explore the effect of one immunomodulator (hDLE) as a therapeutic auxiliary in CPE puppies with sepsis and SIRS.Results: We studied two groups of puppies with CPE confirmed by polymerase chain reaction. The first group received conventional treatment (CT) and vehicle (V), while the second group received CT plus an immunomodulator (I). In both groups, we assessed the survival, clinical condition, number of erythrocytes, neutrophils, and lymphocytes, and values of hematocrit, hemoglobin, plasma proteins, cortisol, and norepinephrine epinephrine, and serotonin, during hospitalization.Puppies treated with CT+I showed 81% survival and milder clinical signs and a significant decrease in circulating neutrophils and lymphocytes in the critical period of the treatment. In contrast, the CT+V group presented a survival of 42%, severe clinical status, and no improvement of the parameters evaluated in the critical period of the disease. We determined in silico that human Ub∆GG can stimulate dog CXCR4.Conclusions: The administration of an immunomodulator (5 mg/day x 5 days) to puppies with CPE under 6 months of age reduces the severity of clinical signs, increases survival, and modulates inflammatory cell parameters. Further studies are necessary to take full advantage of these clinical findings which might be mediated by the human Ub∆GG to canine CXCR4 interaction.
Impacts of Short-Term Water Restriction on Pelibuey Sheep: Physiological and Blood Parameters
Authors: Serrano Jorge Orlay , Villares-Garachana Asiel , Correa-Herrera Nelson , González-Morales Abel , Pérez-Bonachea Lisbet , Hernández Lázaro , Lorente Gustavo , Hajari Elliosha , Fonseca-Fuentes Norge , Martínez-Melo Jorge , Lorenzo José Carlos
Published: July 2021

One of the projected effects of climate change is a reduction in rainfall in certain regions of the world. Hence, the agricultural and livestock sectors will have to cope with increasing incidences of water shortage whilst still maintaining productivity levels to feed an ever increasing global population. This short communication reports on the effect of a two week water stress on Pelibuey sheep in Cuba. Three treatments were compared viz. supply of water ad libitum; water supplied once every 3 or 6 d. Following exposure to the water stress, the results showed no changes in sheep body weight or rectal temperature. However, respiration frequency was affected with water stress causing a reduction from 23.3 to 13.3 respirations per min in control and water deprived animals, respectively. Furthermore, there was evidence for hemoconcentration in response to water stress (levels of hemoglobin increased from 9.2 to 13.1 g L-1 and hematocrits from 27.6 to 39.3% in the control group and animals restricted to water once every 6 d. The imposed water stress was also evident in the reduction of lymphocytes (from ±63 to 43%), and in increase of neutrophils (from approximately 38 to 54%) and leukocytes (from 3133 to 4933 per mm3). The results indicated a decline in the levels of antioxidants, i.e. SOD (SOD from approximately 13 to 10 U mg-1 protein and CAT activity from 23 to 9 U mg-1 protein. To the best of our knowledge, this is the first report on the response of Pelibuey sheep to short-term water shortage stress under Cuban environmental conditions.
Development of A Modified Extended Model-Based Fault Detection And Diagnosis Approach
Authors: Alikhani Alireza , Sharifi Ghasem
Published: July 2021

A supervisory system for space missions is critical due to the high risk of missions, the costs, and the impossibility of adding redundancy. The model-based fault detection approaches are of interest due to their highly responsive speed, robustness against disturbances and uncertainties, and accuracy. Conventional model-based methods have some drawbacks such as feasibility and applicability. In this paper, a modified extended multiple models adaptive estimation (MEMMAE) method is developed which keep both the advantages of the previous model-based methods and take into account some limitations of that. This approach can be performed on various systems to detect and diagnose faults, with appropriate response speed and resistance to uncertainty and disturbances. By combining the recursive least-square algorithm with the extended multiple model adaptive estimation (EMMAE) method, the limitations of this method including simultaneous fault detection, diagnostics of failure cause, and high processing volume are eliminated. The method is implemented on a spacecraft as a case study using the MATLAB/SIMULINK software and demonstrates that the responsive speed and accuracy of the proposed method is significantly much more effective and accurate than the previous method.
Cluster-Based Ensemble Learning Model for Rapid Detection of Aortic Dissection
Authors: Gao Yan , Wang Min , Zhang Guogang , Zhou Lingjun , Luo Jingming , Liu Lijue
Published: July 2021

Background: Aortic dissection (AD) is a rare and high-risk cardiovascular disease with dangerous morbidity and high mortality, so it needs rapid diagnosis and timely treatment. However, due to its complex and changeable clinical manifestations and the lack of special symptoms and signs, it is easy to cause missed diagnosis and misdiagnosis.Methods: The data set used in this paper comes from 53213 patients, which collected from XiangYa Hospital in Hunan Province from 2008 to 2016. The data includes 802 patients with aortic dissection and 52411 patients with non-aortic dissection. In order to help clinicians predict AD, we designed an ensemble learning model based on clustering: Cluster Random Under-sampling Smote-Tomek-link Bagging (CRST-Bagging). This model combines the advantages of clustering-based compound resampling (CRST) method and Bagging ensemble classifier. It achieves good results on aortic dissection data sets.Results: The model validates the effectiveness of the CRST sampling method on the AD data set. We compared the CRST-Bagging model with the classical ensemble models RUSBoost and SMOTE-Bagging on the AD data set. The experimental results show that the CRST-Bagging model has the best performance in the detection of AD. Model’s accuracy and recall rate are 83.6% and 80.7% respectively. And the F1 value is 82.1%, which is 4.8% and 1.6% higher than that of RUSBoost and SMOTE-Bagging model.Conclusions: The model proposed in this paper can be used as an auxiliary diagnostic model of AD to provide reference for clinical medicine. The model can also help doctors to judge whether patients need further imaging examination. Thus help to reduce the rate of clinical misdiagnosis and missed diagnosis of AD.
The impact of decree laws on the performance of Turkish physiology academics: A repeated cross-sectional study
Authors: Gümüştekin Kenan , Aktürk Zekeriya
Published: July 2021

Objectives

This study aimed to describe the academic losses resulting from the Turkish purge and associated dismissals with the decree laws following the failed coup attempt in 2016 concerning physiology academics.
Methods

An observational study was conducted covering the time before 2008, 2009–2012, 2013–2016, and 2017–2020. All actively-working assistant, associate, and full professors of physiology in Turkey as of 15th July 2016 and recently hired academic staff after the coup attempt in 2016 were included in the study. Data collection was performed in December 2020. The primary outcome variable of the study was the total number of publications listed in Google Scholar.
Results

Data of 271 academics were analyzed. Of the participants, 209 (87.1%) continued on their positions, 31 (12.9%) were dismissed after the 2016 coup attempt, and 31 were hired after the purge. The number of publications of scholars hired before 2016 and dismissed were significantly higher before 2008, between 2009 and 2012, and between 2013 and 2016 compared to scholars hired before 2016 and not purged (p < 0.05). Also, the total number of citations, H-index, and i10-index values were significantly better in the purged individuals (p < 0.05). Although the purged academics had relatively higher performance indicators in the previous years, they experienced a 44.2% loss in the number of publications after 2016.
Conclusion

The mass dismissals after the coup attempt in 2016 harmed individual physiology academics as well as the general physiology academy. International academic and human rights organizations must be more sensitive to protect scholars who undergo similar persecutions.
Determining the Effect of Age on the Reproductive and Stress Physiology of Octopus Bimaculoides Using Dermal Hormones
Authors: Chancellor Stephanie , Grasse Bret , Sakmar Taylor , Scheel David , Brown Joel S. , Santymire Rachel M.
Published: July 2021

Our goal was to validate the use of dermal swabs to evaluate both reproductive and stress physiology in the California two-spot octopus, Octopus bimaculoides. Our objectives were to: 1. use a biological stressor to validate glucocorticoid analysis; 2. compare the concentration of reproductive hormones (estrogen and progesterone in females; testosterone in males) of reproductive (N = 4) and senescent (N = 8) individuals to determine the effect of age on hormonal patterns; and 3. determine the relationship between glucocorticoid and reproductive hormone production. For the stress test, individuals were first swabbed and then chased around the aquarium with a net for five minutes. Afterwards, individuals were swabbed for 2 hours at 15-minute intervals to compare to a pre-stress test swab. Reproductive individuals responded to the stressor with a 2-fold peak of cortisol at 15 and 90 minutes. Six of eight senescent individuals did not produce a 2-fold increase in cortisol. Reproductive females had significantly higher sex hormone concentrations (progesterone, estrogen, and testosterone) compared to senescent females. Reproductive males also had significantly higher levels of testosterone compared to their senescent counterparts. After the stressor, only reproductive males produced a 2-fold increase in testosterone concentrations, while sex hormones in females showed no change. Dermal swabs provide an effective and non-invasive means for evaluating octopus hormones, which can provide indicators of both reproductive state and perceptions of acute stressors.
Physical Processes of Summer Extreme Rainfall Interannual Variability in Eastern China. Part I: Observational Analysis
Authors: Tian Fangxing , Li Sihan , Dong Buwen , Klingaman Nicholas P , Freychet Nicolas , Sparrow Sarah
Published: July 2021

Extreme precipitation can have catastrophic effects in China by triggering floods, landslides, and other natural disasters. We measure extreme precipitation over eastern China by the seasonal maximum of total precipitation over 5 consecutive days (Rx5day) in June, July, and August (JJA), which contributes more than 20% of the climate mean of JJA regional total precipitation. Based on the empirical orthogonal teleconnection (EOT) method, this work identifies four dominant regions of observed Rx5day interannual variability in eastern China: north-eastern China (EOT1), the southern lower reaches of the Yangtze valley (EOT2), southern China (EOT3) and the northern lower reaches of the Yangtze valley (EOT4). EOT1 extreme precipitation is related to a strong East Asian Summer Monsoon (EASM), a weak monsoon front and a northward displaced upper-tropospheric westerly jet. EOT2 and EOT4 extreme precipitation are located to the south and north of the lower reaches of the Yangtze valley, respectively. They are related to an enhanced and stable monsoon front and a strong western North Pacific subtropical high (WNPSH). The WNPSH associated with EOT4 is stronger than that associated with EOT2, which pushes the monsoon front further north. EOT3 represents extreme precipitation in southern China, related to anomalous southerlies around the western ridge of the WNPSH. The southerlies transport warm and moist air to southern China and increase precipitation there. The four key regions and the related mechanisms are not sensitive to the EOT technique, as the EOT-based extreme precipitation patterns and circulation anomalies are confirmed using Self-Organising Maps (SOMs).
Cellulose Film with Air Barrier and Moisture-Conducting Character Fabricated by a Green Process
Authors: Peng Junwu , Li Yanan , Liu Xinglin , Ke Guizhen , Song Dengpeng , Wu Shuangquan , Xu Weilin , Zhu Kunkun
Published: July 2021

The use of nature polymer to prepare degradable films is a sustainable production concept that can improve resource utilization and reduce the environmental pollution caused by traditional packaging waste or another field. Here, a regenerated cellulose film was prepared through the N-methylmorpholine-N-oxide (NMMO) cellulose system. The most critical peculiarity is that films with air barrier and moisture conduction character, because the surface of film is dense and does not allow small molecules like oxygen to pass through, but water molecules can move freely in the film by means of hydrogen bonds. This shows that the cellulose film has in textiles, food preservation, medicine and other fields. Significantly, the film has good tensile strength (maximum strength reaches 149.5 MPa) and light transmittance (more than 80% at 600 nm). Moreover, the effect of coagulation bath concentration, temperature and the content of glycerin on film strength was discussed.
Gauss-Simpson Quadrature Algorithm for Calcaulting Additional Stress in Foundation Soils
Authors: WANG Shuai , WANG Chao , XING Chenliang
Published: July 2021

The additional pressure at the bottom of a building’s foundation produces an additional stress in the foundation soils under the building’s foundation. In order to overcome the limitations of traditional elastic theory methods and the finite element method when calculating the additional stress in foundation soils, we use the Gauss-Simpson formula to derive the Gauss-Simpson Quadrature Algorithm based on the elasticity theory. The Gauss-Simpson Quadrature Algorithm is a method designed to calculate the additional stress in foundation soils under an irregularly shaped foundation and an irregular load distribution. This new method is based on the fact that the Gaussian quadrature formula and the Simpson formula are independent of the specific type of integrand. The finite element method with n interpolation points can only achieve an algebraic accuracy of n. The interpolation points of the Gaussian quadrature formula are n zeros of orthogonal polynomials, which can achieve an algebraic accuracy of 2n + 1. Moreover, the weights of the nodes in the quadrature formula are all positive, and thus, it has a high numerical stability. In the proposed method, the Simpson formula is necessary. The Simpson formula is used to transform the implicit additional stress formula with the integral sign into an explicit cumulative integral, which can be considered similar to the rectangular domain case to obtain an explicit analytical algebraic formula for solving the additional stress approximation. In engineering applications, we only need to provide the field engineers with the locations of the interpolation points of the Gauss-Legendre formula, the interpolated weight coefficients, and the specific type of Simpson's formula, and then, the results of the additional stress can be calculated manually, which is nearly impossible using the traditional methods and finite element methods. From the point of view of academic rigor and theoretical completeness, it is possible to use the compound Gauss-Simpson Quadrature Algorithm in conjunction with the looping function in computer programs. Under standard conditions, the proposed Gauss-Simpson Quadrature Algorithm is in good agreement with the results of the traditional elasticity theory.
Investigation of Fluconazole Susceptibility to Candida Albicans by MALDI-TOF MS and Real-Time PCR for CDR1, CDR2, MDR1 and ERG11
Authors: Maenchantrarath Chanika , Khumdee Pradchama , Samosornsuk Seksun , Mungkornkaew Narissara , Samosornsuk Worada
Published: July 2021

Background C. albicans is the most important yeast that caused the infection in humans; the trend of resistance to fluconazole (FLC) was also increased, while the FLC susceptibility by conventional method takes time causing the treatment failure. To investigate FLC susceptibility to C. albicans using MALDI-TOF MS and Real-time PCR for CDR1, CDR2, MDR1 and ERG11, overall, 32 C. albicans strains included 4 reference strains (3 FLC susceptible (S) and 1 FLC resistant (R), 1 spontaneous mutant strain (FLC susceptible-dose dependent, SDD) and 27 clinical strains obtained from 2 Thai University Hospitals were performed FLC susceptibility testing by Sensititre YeastOne and broth microdilution method, FLC resistant expression mechanism by Real-time PCR and the major peak determination by MALDI-TOF MS.Results The change of CDR1 and CDR2 mRNA expression were only significantly observed in SDD and R strains. Using MALDI-TOF MS, the change of mass spectral intensity at range 3376-3382 m/z (major peak) was significantly related to FLC susceptibility as SDD (decreased at 4 µg/ml and increase at 8 µg/ml), S (all increased), and R (all slightly decreased or no change) after incubation for 6 h. All 27 clinical strains showed FLC MIC susceptible (MIC range 0.25-2 µg/ml), no change in CDR1 and CDR2 expression and S major peak type. The FLC resistance C. albicans with CDR1 and CDR2 expression may possibly effect the change of mass spectral intensity at range 3376-3382 m/z. Conclusions The MALDI-TOF MS may be used to simultaneously classify and predict FLC resistant C. albicans strains associated with CDR1 and CDR2 expression. Further studies are essential to clarify the methodology and improve the reliability of this assay for routine diagnosis.
Enhancing Esophageal Repair With Bioactive Bilayer Mesh Containing FGF
Authors: Cesur Ozkan , Tanir Tugba Endogan , Celepli Pinar , Ozarslan Fatma , Hucumenoglu Sema , Karaibrahimoglu Adnan , Hasirci Nesrin
Published: July 2021

We aimed to prepare a bioactive and biodegradable bilayer mesh formed by fibroblast growth factor (FGF) loaded gelatin film layer, and poly ε-caprolactone (PCL) film layer, and to investigate its treatment efficacy on esophageal anastomosis. It is envisaged that the bioactive mesh in in vivo model would improve tissue regeneration in rats. The full thickness semicircular defects of 0.5x0.5 cm2 were created in anterior walls of abdominal esophagus. The control group had abdominal esophagus isolated with distal esophageal blunt dissection, and sham group had primer anastomosis. In the test groups, the defects were covered with bilayer polymeric meshes containing FGF (5µg/2 cm²), or not. All rats were sacrificed for histopathology investigation after 7 or 28 days of operation. The groups are coded as FGF(-)-7th d, FGF(+)-7th d, and FGF(+)-28th d, based on their content and operation day. Highest burst pressures were obtained for FGF(+)-7th d, and FGF(+)-28th d groups (p < 0.005) and decreased inflammation grades were observed. Submucosal and muscular collagen deposition scores were markedly increased in these groups compared to sham and FGF(-)-7th d groups having no FGF (p = 0.002, p = 0.001, respectively). It was proved that FGF loaded bioactive bilayer mesh provided effective repair, reinforcement and tissue regeneration of esophageal defects.
The Microbiome of a Shell Mound: Ancient Anthropogenic Waste as a Source of Streptomyces Degrading Recalcitrant Polysaccharides
Authors: Huergo Luciano , Conzentino Marcelo , Gonçalves Maria V. , Gernet Marcos V. , Reis Rodrigo A. , Pedrosa Fábio O. , Baura Valter A. , Pires Araceli , Gerhardt Edileusa C. M , Tuleski Thalita R. , Balsanelli Eduardo , Guizelini Dieval , Souza Emanuel M. , Chandra Govind , Cruz Leonardo M.
Published: July 2021

Metagenome amplicon DNA sequencing and traditional cell culture techniques are helping to uncover the diversity and the biotechnological potential of prokaryotes in different habitats around the world. It has also had a profound impact on microbial taxonomy in the last decades. Here we used metagenome 16S rDNA amplicon sequencing to reveal the microbiome composition of different layers of an anthropogenic soil collected at a shell mound Sambaqui archeological site. The Samabaqui soil microbiome is mainly composed by phyla Acidobacteria, Rokubacteria, Proteobacteria and Thaumarchaeota. Using culture-dependent analysis we isolated few Streptomyces strains from the Sambaqui soil. One of the isolates, named Streptomyces sp. S3, was able to grow in minimal medium containing recalcitrant polysaccharides including chitin, xylan, carboxymethylcellulose or microcrystalline cellulose as sole carbon sources. The activities of enzymes degrading these compounds were confirmed in cell free supernatants. The genome sequence revealed not only an arsenal of genes related to polysaccharides degradation but also biosynthetic gene clusters which may be involved in the production of biotechnologically interesting secondary metabolites.
Human Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Attenuate Blood-Spinal Cord Barrier Disruption via the TIMP2/MMP Pathway after Acute Spinal Cord Injury
Authors: Xin Wang , Qiang Shi , Jianing Ding , Jiaming Liang , Fangqi Lin , Bin Cai , Yuanyuan Chen , Guowang Zhang , Jianguang Xu , Xiaofeng Lian
Published: July 2021

After spinal cord injury (SCI), destruction of the blood spinal cord barrier (BSCB) results in infiltration of blood cells, such as neutrophils and macrophages, leading to permanent neurological dysfunction. Previous studies have shown that human bone marrow mesenchymal stem cell (BMSC)-derived exosomes have a beneficial neuroprotective effect in SCI models. However, whether BMSC-Exos contribute to the integrity of the BSCB has not been clarified. The purpose of this study was to investigate the mechanism of BMSC-Exo-induced changes in the permeability of the BSCB after SCI. Here, we showed that BMSC-Exos can inhibit BSCB permeability damage and improve spontaneous repair in a SCI model. Importantly, tissue inhibitors of matrix metalloproteinases 2 (TIMP2) were shown to play an important role in the functions of BMSCS-Exos by inhibiting the matrix metalloproteinase (MMP) pathway, thereby mitigating the reduction in cell junction proteins. Moreover, the ability of BMSC-Exos was significantly attenuated when TIMP2 was inhibited by siRNA. This proof-of-principle study demonstrates that BMSC-Exos can preserve the integrity of the BSCB and improve functional recovery after SCI through the TIMP2/MMP signaling pathway.
AC010973.2 Promotes Cell Proliferation and Is One of Six Stemness-Related Genes That Predict Overall Survival of Renal Clear Cell Carcinoma
Authors: Liu Yingqing , Wei Yuang , Zhang Xu , Ren Xiaohan , Wang Jiawei , Li Lin , Qin Haibo , Ding Wei , Shen Xudong , Li Guangyao , Lu Zhongwen , Zhang Dong , Qin Chao , Tao Lingsong , Chen Xinglin
Published: July 2021

Background
Extensive research has revealed that tumor stemness plays a central role in promoting tumor progression. However, the underlying involvement of stemness-related genes in renal clear cell carcinoma (ccRCC) remains controversial.
Methods
The data used for bioinformatics analysis were downloaded from The Cancer Genome Atlas database. The R software, SPSS and GraphPad Prism 8 were used for mapping and statistical analysis.
Results
We first quantified the stemness index of each patient through a machine learning algorithm. Then, we identified the differentially expressed genes between high and low stemness index as stemness-related genes. Based on these genes, we finally established a stable and effective prognosis model to predict patients' overall survival using a random forest algorithm (Training cohort; 1-year AUC: 0.67; 3-year AUC: 0.79; 5-year AUC: 0.73; Validation cohort; 1-year AUC: 0.66; 3-year AUC: 0.71; 5-year AUC: 0.7). The model genes include AC010973.2, RNU6-125P, AP001209.2, Z98885.1, KDM5C-IT1 and AL021368.3. The gene AC010973.2 was selected for further research for its highest importance. In vitro experiments demonstrated that AC010973.2 is highly expressed in ccRCC tissue and cell lines. Meanwhile, knockdown of AC010973.2 could significantly hamper the proliferation of ccRCC cells according to the colony formation and CCK8 assays.
Conclusion
In summary, our finding indicated that the stemness-related gene AC01097.3 is closely associated with patients' survival and could remarkably facilitate cell proliferation in ccRCC, making it potential to be a novel therapeutic target.
Aggregation modeling of the influence of pH on the aggregation of variably charged nanoparticles
Authors: Xiong Yu , Xiong Hailing
Published: July 2021

The aggregation of variably charged nanoparticles is usually induced by the changes in internal and external conditions, such as solution temperature, pH, particle size, van der Waals force, and electrostatic repulsion among particles. In order to explore the effect of pH on the aggregation of variable charge nanoparticles, this paper proposed an extended model based on the 3D on-lattice Cluster-Cluster Aggregation (CCA) model. The extended model successfully established the relationship between pH and sticking probability, and used Smoluchowski theory to calculate the aggregation rate of nanoparticles. The simulation results showed that: (1) the change of the aggregation rate of the variable charge nanoparticles with pH conforms to the Gaussian distribution, (2) the initial particle concentration has a significant effect on the aggregation rate of the nanoparticles, and (3) pH can affect the competition between van der Waals force and electrostatic repulsion between particles, thereby affecting the degree of openness of clusters. The research demonstrated the extended CCA model is valuable in studying the aggregation of the variably charged nanoparticles via transforming the corresponding influence factors into the influence on the sticking probability.
Rate of breast biopsy referrals in BRCA mutation carriers: a retrospective comparative study and matched analysis
Authors: Pomerantz Adi , Tsoref Daliah , Grubstein Ahuva , Wadhawker Sonya , Rapson Yael , Gadiel Itay , Goldvaser Hadar , Hammerman Ariel , Shochat Tzipora , Sharon Eran , Yerushalmi Rinat
Published: July 2021

Purpose

To evaluate the total biopsy and positive biopsy rates in women at high risk of breast cancer compared to the general population.
Methods

The study group consisted of 330 BRCA mutation carriers attending the dedicated multidisciplinary breast cancer clinic of a tertiary medical center in Israel. Clinical, genetic, and biopsy data were retrieved from the central healthcare database and the medical files. Patients who were at age 50 years or older during follow-up were matched 1:10 to women in the general population referred for routine breast cancer screening at the same age, as recommended in the international guidelines. The groups were compared for rate of biopsy studies performed and percentage of positive biopsy results. Matched analysis was performed to correct for confounders.
Results

The matched analysis revealed that the total biopsy rate per 1000 follow-up-years was 61.7 in the study group and 22.7 in the control group (p < 0.001). The positive biopsy rates per 1000 follow-up-years were 26.4 and 2.0, correspondingly (p < 0.001), and the positive biopsy percentages were 42.9% and 8.7% correspondingly (p < 0.0001).
Conclusions

BRCA mutation carriers who attend a dedicated clinic, have a 2.7 times higher biopsy rate per 1000 follow-up-years, a 13.2 times higher positive biopsy rate per 1000 follow-up-years, and a 4.9 times higher positive biopsy percentage compared with women in the general population.
The Association Between Proton Pump Inhibitors and Incident Asthma in Patients with Coronary Artery Disease: A Population-Based Cohort Study
Authors: Lin Tsung-Kun , Huang Jing-Yang , Tsai Chin-Feng , Pan Lung-Fa , Jong Gwo-Ping
Published: July 2021

Observational studies have found a significant association between acid-suppressive drug use and incident asthma. However, the association between proton pump inhibitors (PPIs) and incident asthma in patients with coronary artery disease (CAD) is unclear. Thus, this study assessed the association between PPI use and incident asthma in patients with CAD. We conducted a retrospective cohort study using the National Health Insurance Research Database in Taiwan from 2004 to 2013. Each patient who took PPIs was assigned to the PPI group, whereas 1:1 sex-, age-, and drug index date-matched randomly selected patients without PPI prescription were assigned to the non-PPI group. We analyzed the risk of incident asthma using Cox proportional hazard regression models, including sex, age, urbanization, low income, and comorbidities. Sensitivity and subgroup analyses were also conducted. A total of 8499 cases were identified as PPI‐treated patients, and 8,499 subjects were included in the control group of PPI non‐users. After adjusting for sex, age, urbanization, low income, and comorbidities, PPI user was associated with a 1.18-fold (HR: 1.18; 95% CI: 1.05–1.34) increase for incident asthma in patients with CAD. We concluded that PPI use increased the risk of incident asthma in patients with CAD. The risk of incident asthma should be considered when weighing the benefits and risks of PPI and aspirin treatment in patients with CAD in clinical practice.
The Effect of Parathyroidectomy Compared to Non-Surgical Surveillance on Kidney Function in Primary Hyperparathyroidism: A Nationwide Historic Cohort Study
Authors: Matzen Josephine , Bislev Lise Sofie , Sikjær Tanja , Rolighed Lars , Hitz Mette Friberg , Eiken Pia , Hermann Anne Pernille , Jensen Jens-Erik Beck , Abrahamsen Bo , Rejnmark Lars
Published: July 2021

Background: Patients with primary hyperparathyroidism (pHPT) and impaired kidney function (estimated glomerular filtration rate (eGFR) <60 mL/min) are offered parathyroidectomy (PTX) to protect them from further complications. Surprisingly, two recent uncontrolled cohort studies have suggested a further decrease in kidney function following PTX. We aimed to examine the effects of PTX compared to non-surgical surveillance on kidney function in pHPT patients.Methods: Historic cohort study. From the Danish National Patient Registry (NPR) and major medical biochemistry laboratories in Denmark, we identified 3585 patients with biochemically confirmed pHPT among whom n=1977 (55%) were treated with PTX (PTX-group) whereas n=1608 (45%) were followed without surgery (non-PTX group). Baseline was defined as time of diagnosis and kidney function was re-assessed 9-15 months after PTX (PTX group) or 9-15 months after diagnosis (non-PTX group).Results: At follow-up, eGFR had decreased significantly in the PTX- compared to the non-PTX-group (median -4% vs. -1%, p<0.01). Stratification by baseline eGFR showed that the decrease was significant for those with a baseline eGFR value of 80-89 and >90 mL/min, but not for those with lower eGFR values. Findings did not differ between patients with mild compared to moderate/severe hypercalcemia. However, after mutual adjustments, we identified baseline levels of calcium, PTH, and eGFR as well as age and treatment (PTX vs. no-PTX) as independent predictors for changes in kidney function.Conclusion: Compared to non-surgical surveillance, PTX is associated with a small but significant decrease in kidney function in pHPT patients with an initial normal kidney function.
Contextual factors influencing physicians’ perception of antibiotic prescribing in primary care in Germany - A prospective observational study
Authors: Queder Annika , Arnold Christine , Wensing Michel , Poß-Doering Regina
Published: July 2021

BackgroundAntimicrobial resistance is a worldwide challenge for health services and systems alike. To reduce the overuse of antibiotics, multifaceted interventions are often used to achieve sustainable effects. It can be assumed that these effects are influenced by contextual factors. Embedded in the cluster randomized trial ARena (Sustainable reduction of antibiotic-induced antimicrobial resistance), the aim of this present study was to identify contextual factors associated with practitioners’ perceptions of antibiotic prescribing in German primary health care.MethodsIn a prospective observational study, data were generated in a three-wave survey study between January 2018 and July 2019. Analysis was performed using logistic regression models. The outcome of interest was the physician perceived impact of participating in the ARena project on decision-making regarding antibiotic prescribing, the independent variables of interest included individual characteristics, intervention arm allocation, primary care network (PCN) environment and characteristics of the medical practice.Results46.8% (n = 126) of participants indicated to have perceived an impact on their decision-making regarding antibiotic prescribing by participating in the ARena project. Bivariate logistic regression analyses indicated that work experience (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.006–1.103), PCN environment (OR 2.06, 95% CI 1.256–3.363), structural conditions (OR 1.66, 95% CI 1.161–2.371), environment of existing processes (OR 1.46, 95% CI 1.011–2.094), and externally defined general conditions (OR 1.57, 95% CI 1.035–2.378) were associated with physicians’ perceived impact of participating in the ARena project on decision-making regarding antibiotic prescribing. In the multivariate logistic regression analysis, only work experience OR 1.05 (95% CI 1.001–1.104) continuously showed a significant influence.ConclusionsThis study indicates that contextual factors at individual, practice, and system level influence physicians’ perceptions of antibiotic prescribing.Trial registrationISRCTN, ISRCTN58150046 (registered 13.09.2017).
Quantification of KRAS Gene Mutations in the Resection or Venous Margins of Pancreatic Ductal Adenocarcinomas Is Not Predictive of Disease Recurrence
Authors: Amintas Samuel , Fernandez Benjamin , Chauvet Alexandre , Chiche Laurence , Laurent Christophe , Belleannée Geneviève , Marty Marion , Buscail Etienne , dabernat sandrine
Published: July 2021

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) patients eligible for curative surgery undergo unpredictable disease relapse. Post-surgery tools’ prognostic value is insufficient. Even patients with good pathological response after neo-adjuvant treatment (NAT) remain susceptible to recurrent PDAC. Molecular analysis of R0 margins may identify patients with worse prognosis. Methods: Retrospective analysis of patients, either eligible for up-font surgery (UFS, n=17) or resected patients who underwent NAT with good pathological responses (n=18), collected progression-free and overall survivals 33 months ±17 months post-surgery and examined the molecular status of mutant KRAS by droplet digital PCR.Results: Expectedly, KRAS mutant allele frequencies (MAF) were higher in UFS than in NAT tumor tissues or remnants, and in the ypT1 than the ypT0 tumors in the NAT group. Mutant KRAS positivity or MAFs in margins did not identify patients with detectable pathological disease in the NAT group, nor was it predictive of shorter recurrence-free or overall survival within or between groups. KRAS-double positivity in both venous and tumor resection margins did not identify patients with worse prognosis, regardless of the groups.Conclusion: The cohorts ‘sizes were small due to limited numbers of patients meeting the inclusion criteria, but KRAS-positivity or MAFs in resection and venous margins did not carry prognostic value. Comparison of margins from good versus bad responders receiving NAT may carry a better clinical value.