bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programming Adaptive Laboratory Evolution of 4-Hydroxyisoleucine Production Driven by a Lysine Biosensor in Corynebacterium Glutamicum
Authors: Yu Xinping , Shi Feng , Liu Haiyan , Tan Shuyu , Li Yongfu 
Published: May 2021

Abstract
4-Hydroxyisoleucine (4-HIL) is a promising drug for treating diabetes. In our previous study, 4-HIL was synthesized from self-produced L-isoleucine (Ile) in Corynebacterium glutamicum by expressing an Ile dioxygenase gene. Although the 4-HIL production of recombinant strain SZ06 increased significantly, a by-product, L-lysine (Lys) was accumulated because of the share of the first several enzymes in Ile and Lys biosynthetic pathways. In this study, programming adaptive laboratory evolution (ALE) was designed and conducted in SZ06 to promote 4-HIL biosynthesis. At first, a programming evolutionary system pMK was constructed, which contains a Lys biosensor LysG-PlysE and an evolutionary actuator composed of a mutagenesis gene and a fluorescent protein gene. The evolutionary strain SZ06/pMK was then let to be evolved programmatically and spontaneously by sensing Lys concentration. After successive rounds of evolution, nine mutant strains K1 − K9 with significantly increased 4-HIL production and growth performance were obtained. The maximum 4-HIL titer was 152.19 ± 14.60 mM, 28.4% higher than that in SZ06. This titer was higher than those of all the metabolic engineered C. glutamicum strains ever constructed. The whole genome sequencing of the nine evolved strains revealed approximately 30 genetic mutations in each strain. Only one mutation was directly related to the Lys biosynthetic pathway. Therefore, programming ALE driven by Lys biosensor can be used as an effective strategy to increase 4-HIL production in C. glutamicum.
Tocilizumab Failed to Reduce Mortality in Severe COVID-19 Patients: Results From a ‎Randomized Controlled Clinical Trial
Authors: Talaschian Mona , Akhtari Maryam , Mahmoudi Mahdi , Mostafaei Shayan , Jafary Mohamadreza , Husseini Atiyeh Sadat , Sadeghi Kourosh , Moghadam Keivan Gohari , Tadi Hengameh Ansari , Jamshidi Ahmadreza 
Published: May 2021

Abstract
BackgroundSevere COVID-19 is associated with an increased level of blood IL-6. It is suggested that adjusting the IL-6 level or its effects may diminish the inflammation of the airway and alter the course of the disease. MethodsWe performed a controlled, randomized, double-blind clinical trial including severe hospitalized COVID-19 patients in Iran. The patients were randomly distributed by block randomization to take usual care plus IL-6 inhibitor (tocilizumab 8mg/kg, 1 or 2 dosages) or usual care alone (ratio 1:1). The endpoint was defined by the clinical improvement and discharge or death. Main and safety analysis was performed in the overall population. ResultsWe enrolled 40 eligible patients (20 patients in each group) from July 10, till October 10, 2020, in this study. After randomization, one patient in the usual care arm and three patients in the tocilizumab arm refused to participate in the study and were eliminated from the study and overall analysis. The mean age of participants was 59.62 ± 15.80 and 63.52 ± 12.83 years old in Tocilizumab (8 women and 9 men) and standard care (9 women and 10 men) groups respectively (P-value= 0.426). The number of recovered patients did not significantly differ between tocilizumab and usual care groups (70.6% (n=12) vs 78.9% (n=15) respectively) (P-value=0.563). Also, the survival time was not significantly varied between participants in the tocilizumab intervention and usual care group [Log rank test: P=0.973; Hazard ratio: 1.25; 95% C‎‎I: 0.‎249-4.209]. ConclusionThe study results recommended that tocilizumab could not be a beneficial agent for treating severe cases of COVID-19 patients and have not significantly affected patients' clinical improvement.Clinical trial registrationThis trial was registered in the Iranian Registry of Clinical Trials on 9 July 2020 (ID: IRCT20081027001411N4) (https://www.irct.ir/trial/48396).
Prognostic Role of Docetaxel-induced Suppression of Free Testosterone Serum Levels in Metastatic Prostate Cancer Patients
Authors: Kappler Paula , Brunotte Stefan , Ivanyi Philipp , Morgan Michael , Ganser Arnold , Reuter Christoph 
Published: May 2021

Abstract
To date, only few data concerning the biologically active, free form of testosterone (FT) are available in metastatic prostate cancer (mPC) and its impact on disease, therapy and outcome is largely unknown. We retrospectively studied the effect of docetaxel on FT and total testosterone (TT) serum levels in 67 mPC patients between April 2008 and November 2020. FT and TT levels were measured before and weekly during therapy. The primary endpoint was overall survival (OS). Secondary endpoints were prostate-specific antigen and radiographic response (PSAR, RR), progression-free survival (PFS), FT/TT levels and safety. Median FT and TT serum levels were completely suppressed below the detection limit during docetaxel treatment (FT: from 0.32 pg/mL to <0.18 pg/mL and TT: from 0.12 to <0.05 ng/mL, respectively). Multivariate Cox regression analyses identified requirement of non-narcotics, PSAR, complete FT suppression and FT nadir values <0.18 pg/mL as independent parameters for PFS. Prior androgen-receptor targeted therapy (ART), soft tissue metastasis and complete FT suppression were independent prognostic factors for OS. FT was not predictive for treatment outcome in mPC patients with a history of ART.
Synovial pH Is As Specific As Synovial Leukocyte Count But Less Sensitive For The Diagnosis of Chronic Prosthetic Joint Infection
Authors: Ackmann Thomas , Schwarze Jan , Goshger Georg , Schmidt-Braekling Tom , Klingebiel Sebastian , Moellenbeck Burkhard , Theil Christoph 
Published: May 2021

Abstract
Synovial fluid markers have been shown to be most accurate in diagnosing prosthetic joint infection (PJI). An inverse correlation for synovial leukocyte count and synovial pH is known assuming that leukocyte metabolism causes synovial fluid acidosis. This study analysis synovial pH as a potential marker for PJI. We prospectively included 92 patients who presented with painful total joint arthroplasty (TJA) of the hip (THA; n = 25) or knee (TKA, n = 67). Joints were diagnosed as infected (n = 30) or aseptic (n = 62) based on the Musculoskeletal Infection Society criteria of 2018. An ideal cut-off value for synovial pH and the sensitivity and specificity were calculated. Additionally, the sensitivity and specificity were calculated for synovial white blood cell (WBC) count (cut-off > 3000 leukocytes) and percentage of neutrophils (PMN%, cut-off > 80%). The median synovial pH level was significantly lower in the group with chronic PJI (7.09 vs. 7.27; p < 0.001) compared to implants with aseptic failure. The calculated optimal cut-off value was 7.11 (AUC 0.771) with a sensitivity of 53% and specificity of 89%. However, the sensitivity and specificity of synovial WBC count were 90% and 88% and for synovial PMN% 73% and 98%, respectively. Synovial pH may be a cost-effective parameter to diagnose chronic PJI.
Transcriptome Meta-Analysis Suggests the Existence of Two Molecular Subtypes in Alzheimer’s Disease
Authors: Nazari Anahita , Marashi Sayed-Amir , Montazeri Hesam 
Published: May 2021

Abstract
Alzheimer’s disease (AD) is the most common type of dementia that affects the lives of nearly 50 million people globally. No efficient treatment or cure has been found for AD yet. Different studies have been performed on heterogeneity in AD from various perspectives. Analyzing AD as a disease with several subtypes might assist us to identify effective personalized treatments for AD patients. Here, we investigated the heterogeneity in AD from a molecular perspective. In particular, we used gene expression profiles of 93 samples from the hippocampus of AD patients. To increase the sample size and enhance the robustness of the results, we applied meta-analysis on three different datasets. We first combined gene expression profiles from multiple relevant AD studies, and then, using a clustering analysis, we found two distinct molecular subtypes across AD samples. We validated the obtained results using various statistical and randomization approaches. Furthermore, we showed that the two transcriptomic subtypes are statistically independent of sex, age and Braak stage of the subjects. Notably, one of the identified subtypes indicates high similarity to control samples, which suggests that AD onset does not necessarily affect the hippocampal transcriptome. By performing differential gene expression and pathway enrichment analyses for various settings, we found 2371 differentially expressed genes that can be used for discriminating between the two AD subtypes. Finally, using a clustering approach, we introduced a novel molecular signature for the two subtypes based on14 differentially expressed genes.
Interventricular Septal Hematoma Detected by Transesophageal Echocardiography after Congenital Heart Surgery in an Infant: A Case Report
Authors: Jang Young-Eun , Kim Jin-Tae , Lee Ji-Hyun 
Published: May 2021

Abstract
BackgroundInterventricular septal hematoma is an extremely rare complication following congenital heart surgery. During cardiac surgery, interventricular septal hematomas can be detected only by intraoperative transesophageal echocardiography. Here, we report an interesting case of interventricular septal hematoma that was accidentally found in an infant following ventricular septal defect (VSD) closure.Case presentationTransesophageal echocardiography images were acquired from a 1-month-old boy after surgical repair of a large (6.5 mm) perimembranous outlet VSD with interventricular septal flattening. Surgical correction was performed with auto-pericardium and 7-0 Prolene sutures. The patient was successfully weaned from cardiopulmonary bypass, and transesophageal echocardiography showed no VSD leakage and good ventricular function. However, approximately 30 minutes later, two anechoic masses were found within the interventricular septum, which were suspected to be interventricular septal hematomas; the larger mass measured 1.51 x 1.48cm. The swollen interventricular septum showed decreased contractility and compressed both the right and left ventricles. However, there was no change in the size of hematomas or a significant hemodynamic instability for 30 minutes of observation. Therefore, expecting spontaneous resolution of the hematomas, the interventricular septum was not explored and the patient was removed from cardiopulmonary bypass. On postoperative day 4, follow-up transthoracic echocardiography revealed thrombi filling the hematomas. The patient was discharged on postoperative day 15 and followed-up with regular echocardiographic evaluations.ConclusionsWe describe a unique case of interventricular septal hematoma after VSD closure. Surgical manipulation of perimembranous VSD and injury of the septal perforating artery may contribute to development of an interventricular septal hematoma. In hemodynamically stable patients, conservative treatment and serial echocardiographic evaluation generally show gradual resolution of the hematoma. Pediatric cardiac anesthesiologists should be aware of this rare complication after VSD repair.
The correlation study on mandibular deviation and cervical vertebrae posture in patients with mandibular asymmetry
Authors: Guan Yuxin , Tian Pengfei , Li Bing , Wu Xiuping 
Published: May 2021

Abstract
Background: To explore the degree of skeletal mandibular deviation and the change of mandible position in patients with mandibular deformity and its correlation with cervical posture in patients with jaw deformity using CBCT and to provide the reference for clinical diagnosis and treatment planning. Methods: CBCT images from 30 adult patients with skeletal mandibular deviation and 30 adult individuals with facial symmetry were analyzed and imported in Invivo 5 to reconstruct a 3D hard-tissue surface model. A reference frame was set up and 20 measurements of the mandible and cervical vertebrae were performed to calculated. The difference between the three-dimensional position of the mandible and the posture of cervical spine were analyzed in patients with mandibular asymmetry and normal people. Results: Compared with the normal maxillofacial symmetry groups, there were significant differences in the degree of skeletal mandibular asymmetry and cervical deviation in the mandibular deviation groups(P ＜ 0.05). A strong positive, linear correlation was found in patients with mandibular deviation between the deviation of the mandible and cervical vertebrae posture. Conclusion: There is an inherent correlation between the occurrence of mandibular deviation and the deflection of cervical posture, and they interact on each other. The deformity of mandible affects the three-dimensional posture of the cervical vertebra and can cause different degrees of cervical deflection. The degree of mandible deviation and cervical vertebrae posture in patients with mandibular asymmetry are greater than those in individuals with facial symmetry. Compared with the patients with normal jaw, the deformity among the patients with skeletal mandibular asymmetry has a tendency to tilt forward and bend forward. The abnormal posture of the cervical spine will also affect the three-dimensional position of the mandible, causing the lower 1/3 of the face to appear facial asymmetry with the deflection of the head and neck posture.
Single-Molecule RNA Sequencing for Simultaneous Detection of m6A and 5mC
Authors: Ohshiro Takahito , Konno Masamitsu , Asai Ayumu , Komoto Yuki , Yamagata Akira , Doki Yuichiro , Eguchi Hidetoshi , Ofusa Ken , Taniguchi Masateru , Ishii Hideshi 
Published: May 2021

Abstract
Epitranscriptomics is the study of RNA base modifications involving functionally relevant changes to the transcriptome. In recent years, epitranscriptomics has been an active area of research. However, a major issue has been the development of sequencing methods to map transcriptome-wide RNA base modifications. We have proposed a single-molecule quantum sequencer for mapping RNA base modifications in microRNAs (miRNAs), such as N6-methyladenosine (m6A) or 5-methylcytidine (5mC), which are related to cancer cell propagation and suppression. Here, we investigated 5mC and m6A in hsa-miR-200c-5p extracted from colorectal cancer cells and determined their methylation rates; the rates were comparable to those determined by mass spectrometry. Furthermore, we evaluated the methylation ratio for each cytidine and adenosine site in the sequences and its relationship. These results suggest that the methylation ratio of cytidine and adenosine is facilitated by the presence of vicinal methylation. Our work provides a robust new tool for sequencing various types of RNA base modifications in their RNA context.
Surgical treatment of valve endocarditis in high-risk patients: predictors of long term outcome
Authors: Nasso Giuseppe , Santarpino Giuseppe , Moscarelli Marco , Bari Nicola Di , Dell'Aquila Angelo Maria , Peivandi Armin Darius , Gaudino Mario , Fiore Flavio , Mastroroberto Pasquale , Condello Ignazio , Speziale Giuseppe 
Published: May 2021

Abstract
Background
- Infective endocarditis represents a surgical challenge associated with perioperative mortality. The aim of this study is to identify risk factors that are associated with higher mortality and to determine if there are any patient subsets that should be defined as "inoperable".
Methods
- We retrospectively analyzed 123 patients operated on for infective endocardi-tis from January 2011 to December 2020. Of these, 18 patients had prosthetic valve endocarditis. We collected perioperative characteristics and performed an analysis for the identification of preoperative risk factors associated with postoperative mortality.
Results
- Preoperative renal failure, an elevation of all types of EuroSCORE (EuroSCORE I, II and logistic) and prior aortic valve re-replacement were found to be preoperative risk factors significantly associated with mortality. In-hospital mortality was 27% in patients who had previously undergone aortic valve replacement (n = 4 out of 15 operated, p = 0.01). Patients who were operated on during the active phase of infective endocarditis showed a higher mortality rate than those operated on after the acute phase (16% versus 0%; p = 0.02). The type of prosthesis used (biological or mechanical) was not associated with mortality, whereas cross-clamp time significantly correlated with mortality (mean cross-clamp time 135 ± 65 min in dead patients versus 76 ± 32 min in surviving patients; p = 0.0005).
Conclusions
- Our study demonstrates that an early and fast surgical approach may rep-resent a valuable treatment option for high-risk patients with infective endocarditis, also in case of prosthetic valve endocarditis. Although several risk factors are associated with higher mortal-ity, no patient subset is inoperable. These findings can be helpful to inform decision-making in heart team discussion.
Genomic analyses of fall armyworm (Spodoptera frugiperda) populations from Uganda using mitochondrial cytochrome oxidase subunit 1 and nuclear triose-phosphate isomerase (Tpi) genes
Authors: Omuut Geresemu , Mollel Happyness G. , Kanyesigye Dalton , Akohoue Félicien , Adumo Stella A. , Wagaba Henry , Otim Michael H. 
Published: May 2021

Abstract
The fall armyworm (FAW), Spodoptera frugiperda; J.E. Smith (Lepidoptera: Noctuidae), has become a newly established economically important pest that causes huge losses to maize productivity in sub-Saharan Africa. In 2017, a survey was conducted to collect S. frugiperda specimens across 11 agro-ecological zones in Uganda. Cytochrome oxidase subunits 1 (CO1A and CO1B) and triose-phosphate isomerase (Tpi) partial gene segments of FAW were sequenced and subjected to comparative genomic analyses, to elucidate genetic identity, diversity and determine the existence of corn sub-haplotypes, distribution, and likely origin of invading populations. Results revealed the presence of both rice and corn strains (haplotypes h4 and h1), with rice strain being more predominant. The analyses of both mitochondrial and nuclear Tpi marker sequences showed that the FAW host strain haplotypes from Uganda were identical to those found in Florida, three Asian nations (China, India, and Pakistan) and Australia. A wide distribution of both strains was observed across all agro-ecological zones in Uganda. Comparative genomic analyses showed strain identification concordant results between CO1A and CO1B partial gene markers. Upon comparison with Tpi marker result, discordances in discrimination of FAW strains were observed. The study findings imply that Florida, China, India and Pakistan are possible centers of origin of invasion and support a possibility of multiple introductions into Uganda and the region. There is therefore a need for in-depth characterization of FAW populations in the region and other African nations to better understand its genetics and mechanisms of invasion.
ENA-78/CXCL5 as a Predictive Factor for Baricitinib Effectiveness in Rheumatoid Arthritis
Authors: Isozaki Takeo , Gunji Ryutaro , Shimizu Kunika , Kawamori Kazutaka , Konishi Noriko , Fukuse Sayaka , Kasama Tsuyoshi 
Published: May 2021

Abstract
Objectives: To determine whether cytokines and chemokines are predictive factors for baricitinib effectiveness in rheumatoid arthritis (RA).Methods: Eleven patients were treated with baricitinib, and the levels of fractalkine/CX3CL1, CXCL16, ENA-78/CXCL5, IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 in serum were measured with enzyme-linked immunosorbent assays.Results: Nine of the 11 patients successfully completed the study at 12 weeks. Two patients were excluded due to noneffectiveness of baricitinib treatment. The simplified disease activity index (SDAI) at week 12 was significantly decreased in patients receiving baricitinib compared with the SDAI at week 0 (mean ± SEM; 5 ± 1 and 15 ± 3, respectively, p<0.05). One case of herpes zoster virus infection occurred at 12 weeks. The levels of MCP-1/CCL2, RANTES/CCL5, ENA-78/CXCL5, IL-8/CXCL8, CXCL16 and fractalkine/CX3CL1 in RA serum were not significantly different before and after baricitinib treatment. Finally, we found that the level of ENA-78/CXCL5 in patients with SDAI remission was significantly higher than that in patients without SDAI remission at 12 weeks (887 ±115 pg/ml and 461 ± 102 pg/ml, respectively).Conclusions: ENA-78/CXCL5 may be a predictor of the effectiveness of baricitinib in treating RA.
Design and Analysis of Various Solar Cell Technologies for Improvements in Efficiencies: A Review
Authors: Sharma Divya , Mehra Rajesh , Raj Balwinder 
Published: May 2021

Abstract
Solar energy is an inexhaustible source of energy existing on earth. Sun annually delivers approximately 10,000 times of energy that human race currently exploits. Being neat and clean, solar energy has steered path to redeem utilization of conventional resources of energy by birth of solar cells. Solar cells, modules and Photovoltaic systems have been industrialized substantially since race to conquer outer space started during 1960s. Further, oil crisis in 1970s forced the nations to embrace solar technologies as alternative means for conventional sources of energy. Developments in cost efficacy, compact constructions, consistency and lifetime enabled photovoltaics to be the first option for extensive range of uses in day to day life. Photovoltaics are widely used in telecommunications, remote power and cathodic protection. Objective of this paper is to review developments of solar cells since its origin, with comprehensive description of manufacturing processes, implementations and power conversion efficiencies of solar cells of various generations including their future trends and aspects.
Influence of Zno nanoparticle addition and Spark Peak Current on EDM Process of AISI 1045, AISI 4140, and AISI D3: MRR, Surface Roughness, and Surface Texture
Authors: Pour Masoud , Javadi S. Mohammad , K. Ehsan Layegh 
Published: May 2021

Abstract
In the recent studies, the effects of different metal oxide nanoparticles addition in different dielectrics of EDM process has been thoroughly investigated, showing that adding the nanoparticles improves the material removal rate and surface roughness. The results illustrate that the parameters such as density, particle size, particle concentration, and electrical and thermal conductivity of the nanoparticles can affect the process performance. Compared to the other metal oxides, ZnO has lower thermal and higher electrical resistance which makes it distinct from other nanoparticles used in EDM process in terms of physical properties. In this paper, the effects of the variation of peak current,and ZnO particle mass on MRR, surface roughness, and thermal conductivity of AISI1045، AISI4140, and AISID3 in EDM process are investigated. The results illustrate that 4 grams of the ZnO nanoparticle mass increase the MRR up to 10.71%, 50%, and 45.55%, for rough machining of AISI1045, AISI4140, and AISID3, respectively. In finish machining, they show that the surface roughness can be improved 16.66%, 29.41%, and 56.25%, respectively. It is observed that the amount of deposited particles on AISID3 is maximum followed by AISI 1045 and AISI4140. Therefore, in AISID3 both significant improvement of surface roughness and ZnO deposition can be achieved.