bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Association Between Radiographic Tumor Burden and Efficacy of Immune Checkpoint Inhibitors in Advanced Lung Cancer
Authors: Popat Vinita , Lu Rong , Ahmed Murtaza , Park Jason Y. , Xie Yang , Gerber David E. 
Published: March 2020

Abstract

Background
Historically, tumor burden has been considered an impediment to efficacy of immunotherapeutic agents, including vaccines, stem cell transplant, cytokine therapy, and intravesical bacillus Calmette-Guérin. This effect has been attributed to hypoxic zones in the tumor core contributing to poor T-cell infiltration, formation of immunosuppressive stromal cells, and development of therapy-resistant cell populations. However, the association between tumor burden and efficacy of immune checkpoint inhibitors is unknown. We sought to determine the association between radiographic tumor burden parameters and efficacy of immune checkpoint inhibitors in advanced lung cancer.

Materials and Methods
We performed a retrospective analysis of patients with advanced lung cancer treated with immune checkpoint inhibitors. Demographic, disease, and treatment data were collected. Serial tumor dimensions were recorded according to RECIST version 1.1. Associations between radiographic tumor burden (baseline sum of longest diameters, longest single diameter) and clinical outcomes (radiographic response, progression-free survival, and overall survival) were determined using log-rank tests, Cox proportional-hazard regression, and logistic regression.

Results
Among 105 patients, the median baseline sum of longest diameters (BSLD) was 6.4 cm; median longest single diameter was 3.6 cm. BSLD was not associated with best radiographic, progression-free survival, or overall survival. In univariate and multivariate analyses, no significant associations were observed for the other radiographic parameters and outcomes when considered as categorical or continuous variables.

Conclusion
Although tumor burden has been considered a mediator of efficacy of earlier immunotherapies, in advanced lung cancer it does not appear to affect outcomes from immune checkpoint inhibitors.

Implications for Practice
Historically, tumor burden has been considered an impediment to the efficacy of various immunotherapies, including vaccines, cytokines, allogeneic stem cell transplant, and intravesical bacillus Calmette-Guérin. However, in the present study, no association was found between tumor burden and efficacy (response rate, progression-free survival, overall survival) of immune checkpoint inhibitors in advanced lung cancer. These findings suggest that immune checkpoint inhibitors may provide benefit across a range of disease burden, including bulky tumors considered resistant to other categories of immunotherapy.
Being from a Bad Neighbourhood: Confronting Bad Decision Discourses in the Impoverished Inner City
Authors: Bisaillon Laura , Hassan Mehdia , Hassan Maryam 
Published: March 2020

This article confronts mainstream discourses about poverty and inner city poor neighbourhoods. It argues that the ways that poverty and poor inner city neighbourhoods are made publicly known in writing and through visual representations present problems such as overpowering structural causes of health and illness, reifying false dichotomy of us and them, and normalizing people living in poverty or working poor people as de facto vulnerable. This can happen when the social relations that govern poverty and sustain human suffering eschew the social relations that produce these experiences. Taking these relations as the objects of analysis, this article focuses sociologically on the Dundas/Sherbourne neighbourhood in Toronto, Canada, as the terrain of inquiry. The aim here is to contribute to analyses of the political, social, and economic determinants of health as well as to critiques of bad-neighbourhood and bad decision discourses. To do this, it bridges visual practice with critical social analysis: drawing together the authors’ individual practices as visual artists, marshaling their social positions as residents of the adjacent St. James Town neighbourhood, and sharing their experiences of the Dundas/Sherbourne area. They employ insights from sensory ethnography and street photography to offer an alternative source of knowledge about the poor inner city that contrasts and contests mainstream ways of knowing these same spaces.
El Precedente Administrativo en Colombia: Un Estudio a su Naturaleza Jurídica
Authors: Cabarcas-Mercado Cristian Enrique 
Published: March 2020

El presente artículo pretende dar a conocer la teoría del precedente administrativo en Colombia, pero de manera particular, demostrar que el precedente administrativo se encuentra inmerso y regulado en el ordenamiento jurídico Colombiano, dado que, que no solo la Corte Constitucional, a través de sus precedentes en los que acogió derechos fundamentales, como igualdad, seguridad jurídica; ha consolidado dicha teoría, sino que además, una serie de normatividades ha dado un plus a la consolidación de dicho precedente en Colombia, como lo fue en un inicio la ley de descongestión judicial (ley 1395 de 2010) y el actual código de procedimiento administrativo y de lo contencioso administrativo(ley 1437 de 2011).
Bayesian Estimates Based On Record Values Under Weighted LINEX Loss Function
Authors: Al-Duais Fuad , Alhagyan Mohammed 
Published: March 2020

In this paper, we developed linear exponential (LINEX) loss function by emerging weights to produce weighted linear exponential (WLINEX) loss function. Then we utilized WLINEX to derive scale parameter and reliability function of the Weibull distribution based on record values when the shape parameter is known. After, we estimated scale parameter and reliability function of Weibull distribution by using maximum likelihood (ML) estimation and by several Bayes estimations. The Bayes estimates were obtained with respect to symmetric loss function (squared error loss (SEL)), asymmetric loss function (LINEX) and asymmetric loss function (WLINEX). The ML and the different Bayes estimates are compared via a Monte Carlo simulation study. The result of simulation mentioned that the proposed WLINEX loss function is promising and can be used in real environment especially at the case of underestimate where it revealed better performance than LINEX loss function for estimating scale parameter.
The relationship between dyslipidemia and lupus nephritis in systemic lupus erythematosus patients attending a Saudi Rheumatic Center, Tabuk
Authors: Mirghani Hyder Osman , Abdul Khalig Alyoussef Abdullah , Mohammed Osama Salih 
Published: March 2020

Background: There is an increasing awareness of the role of dyslipidemia in lupus nephritis patients, no researchers have studied dyslipidemia in systemic lupus erythematosus (SLE) in Tabuk. In this study, we aimed to investigate the association between dyslipidemia and lupus nephritis in Tabuk, Saudi Arabia.
Methods: This cross-sectional comparative longitudinal hospital-based study was conducted at a rheumatic clinic in the North West Armed Force Hospital (NWAFH) during the period April 2014–June 2015. Seventy-three patients diagnosed with SLE were invited to participate in the study. All participants were required to sign a written informed consent, following which they were interviewed using a structured questionnaire. Data collected include demographic data, clinical characteristics, fasting lipid profile, renal function tests, urine analysis, antinuclear antibody, anti-double-stranded antibodies, complement levels, serum albumin, anticardiolipin, ant bodies, and antiphospholipid antibodies. Lupus nephritis was ascertained by renal biopsy. The research was approved by the ethical committees of both the University of Tabuk and the NWAFH and data were analyzed using the Statistical Package for Social Sciences (SPSS).
Results: Out of 73 patients with SLE, 86.3% were females with a mean age of 34 ± 6.4 years. Lupus nephritis was evident in 26% of the patients, proteinuria in 44.1%, high total cholesterol in 17.8%, high low-density lipoprotein in 15.1%, high triglycerides in 27.3%, and low high-density lipoproteins in 52.1%. Patients with lupus nephritis had high total cholesterol, high LDL, high TG, and low HDL than those without lupus nephritis P-value < 0.05.
Conclusion: Dyslipidemia was more common among patients with SLE nephritis, and an aggressive treatment is recommended to reduce this serious complication. The relatively small size of the study group and the fact that the study was conducted at a single tertiary center are the limitations of this study.
Keywords: dyslipidemia, lupus nephritis, Saudi Arabia
A Cross-sectional Study on Hepatitis B Immune Status among Vaccinated Healthcare Workers in Khartoum, Sudan
Authors: Elsheikh Mahgoub Abdullahi , Hamadalnil Yassir , Mohammed Osama , Nakhleh Rasha , Mohamed Khair Musa 
Published: March 2020

Background: Hepatitis B virus (HBV) infection can lead to chronic hepatitis, liver cirrhosis, and Hepatocellular Carcinoma (HCC). Vaccination against the virus plays an important role in its prevention. Health personnel at risk of infection are recommended to receive the vaccine and to check their immune status thereafterObjective: To determine Hepatitis B Immune status among vaccinated health personnel in Khartoum state, Sudan.A total of 106 health personnel from different hospitals and doctors’mess in Khartoum and from different jobs were surveyed and their HBV surface antibodies levels were determined by HBsAb (Quantitative) ELISA Kits.Methods: Of the 106 participants in this study, the majority were females 72.6%. The mean age of those involved was 27.69 years, and nurses made for more than 50% of those surveyed. About 56.6% (60) of the health personnel involved took three or more doses of HBV vaccine while the rest received one or two doses. The results of the participants who received three or more doses of the vaccine represented immunity by 70%. In general, about 47.2% (50) of the participants in this study did show excellent immune response (> 100 mIU/mL) and 18.9% (20) had weak protective levels (between 10 and 100 mIU/mL)So, we concluded that HBV post-vaccination immunity status of health personnel in Khartoum state is lower than post-vaccination HBV immunity in other parts of the world. There is an urgent need for a national protocol of HBV vaccination to improve the immunization status of health personnel with a regular checkup of HBV immunity and easy access to a good-quality vaccine.
Keywords: hepatitis B vaccines; healthcare workers; immune response
Identification of cholesterol-assimilating actinomycetes strain and application of statistical modeling approaches for improvement of cholesterol oxidase production by Streptomyces anulatus strain NEAE-94
Authors: El-Naggar Noura El-Ahmady , El-Shweihy Nancy M. 
Published: March 2020

Abstract

Background: Cholesterol oxidase biosensors have been used to determine the level of cholesterol in different serum and food samples. Due to a wide range of industrial and clinical applications of microbial cholesterol oxidase, isolation and identification of a new microbial source (s) of cholesterol oxidase are very important. Results: The local isolate Streptomyces sp. strain NEAE-94 is a promising source of cholesterol oxidase. It was identified based on cultural, morphological and physiological characteristics; in addition to the 16S rRNA sequence. The sequencing product had been deposited in the GenBank database under the accession number KC354803. Cholesterol oxidase production by Streptomyces anulatus strain NEAE-94 in shake flasks was optimized using surface response methodology. The different process parameters were first screened using a Plackett-Burman design and the parameters with significant effects on the production of cholesterol oxidase were identified. Out of the fifteen factors screened, agitation speed, cholesterol and yeast extract concentrations had the most significant positive effects on the production of cholesterol oxidase. The optimal levels of these variables and the effects of their mutual interactions on cholesterol oxidase production were determined using Box-Behnken design. Cholesterol oxidase production by Streptomyces anulatus strain NEAE-94 was 11.03, 27.31 U/mL after Plackett-Burman Design and Box-Behnken design; respectively, with a fold of increase of 6.06 times compared to the production before applying the Plackett-Burman design (4.51 U/mL). Conclusions: Maximum cholesterol oxidase activity is obtained at the following fermentation conditions: g/L (cholesterol 4, yeast extract 5, NaCl 0.5, K 2 HPO 4 1, FeSO 4 .7H 2 O 0.01, MgSO 4 .7H 2 O 0.5), pH 7, inoculum size 4 % (v/v), temperature 37°C, agitation speed 150 rpm, medium volume 50 mL and incubation time 5 days.
Pre-Hospital Low ALT Activity, a Marker of Sarcopenia and Frailty, is Associated with Increased Long-Term Mortality after COPD Exacerbations. Historic Prospective Cohort Study.
Authors: Lasman Nir , Shalom Matan , Turpashvili Natia , Goldhaber Gal , Lifshitz Yulia , Leibowitz Eyal , Berger Gideon , Zalzman-Shenhav Gilat , Brom Adi , Cohen Dor , Avaki Chen , Segal Gad 
Published: March 2020

Abstract
Background. COPD exacerbations have negative impact on patients' survival. Several risk factors for grave outcomes of such exacerbations have been descried. Muscle dysfunction and mass loss were shown to impact negatively on prognosis and survival. Low activity of the enzyme ALT (Alanine amino-transferase) in the blood is a known indicator for sarcopenia and frailty, however, no previous studies addressed the association of low ALT amongst patients hospitalized due to COPD exacerbation and long-term survival.
Methods. This is a historic prospective cohort study of patients hospitalized due to acute COPD exacerbation.
Results. Included were 232 consecutive COPD exacerbation patients. The median time of follow-up was 34.9 months (IQR 23.13 – 41.73 months). During this period 104 (44.8%) patients died. All patients were grouped to quartiles according to blood ALT levels (after exclusion of cases considered to have hepatitis (ALT > 40 IU)). The risk of long-term mortality increased, in a statistically significant manner, amongst patients with low ALT values: the median survival of patients with ALT < 11 IU was 18.5 months only while the median survival for the rest of the study group was not reached. For ALT < 11IU; 12-16IU; 17-20IU and >21IU the mortality rates were 69%; 40.9%; 36.3% and 25% respectively (p < 0.001 for comparison of lower quartile with upper three quartiles). The crude hazard ratio for mortality amongst patients with ALT levels lower than 11IU was 2.37 (95% CI; 1.6 – 3.5). This increased risk of mortality remained significant after adjustment for age, weight, creatinine, albumin concentration and cardiovascular diseases (HR = 1.83; 95% CI 1.08 – 3.1, p < 0.05).
Conclusions. Low ALT values, a biomarker of sarcopenia and frailty, are associated with poor long-term survival amongst patients hospitalized due to COPD exacerbation.
Metabolic engineering of Escherichia coli for efficient production of L-alanyl-L-glutamine
Authors: Zhu Jiangming , Yang Wei , Wang Bohua , Liu Qun , Zhong Xiaotong , Gao Quanxiu , Liu Jiezheng , Huang Jianzhong , Lin Baixue , Tao Yong 
Published: March 2020

Abstract
Background L-alanyl-L-glutamine (AQ) is a functional dipeptide with high water solubility, good thermal stability and high bioavailability. It is widely used in clinical medicine, post-operative rehabilitation, sports health care and other fields. AQ is mainly produced by chemical synthesis which is complicated, time-consuming, labor-consuming, low yield and accompany with by-products. It is highly desirable to develop an efficient biotechnological process for AQ production. Results A metabolic engineered E. coli strain for AQ production was developed by over-expressing L-amino acid-ligase (BacD) from Bacillus subtilis , peptidases including PepA, PepB, PepD, PepN and dipeptide transport system Dpp were inactivated. In order to use the more readily available substrate, glutamic acid, a glutamine synthetic module from glutamic acid to glutamine was constructed by introducing glutamine synthetase (GlnA), glsA-glsB catalyze the first step in glutamine metabolism and glnE-glnB involved in the ATP-dependent addition of AMP/UMP to a subunit of glutamine synthetase were blocked which resulted in increased glutamine supply. This glutamine synthetic module combined with AQ synthetic module to develope the engineered strain that using glutamic acid and alanine for AQ production. The expression of BacD and GlnA was further balanced to improve the AQ production. The engineered strain p15/AQ10 was used in the whole-cell biocatalysis and 65.6 mM AQ was produced with productivity of 7.29 mM/h and conversion rate of 65.6%. Conclusion Metabolic engineered strains were developed for AQ production. Strategies including inactivation of peptidases, screening of BacD, introducing glutamine synthetic module, and balancing the glutamine and AQ synthetic modules were applied to improve the yield of AQ. This work provides the biosynthetically industrial potential for efficient production of AQ by microbial cell factory.
Isolation and characterization of bacteriaophages against virulent Aeromonas hydrophila
Authors: Liu Jin , Gao Shanshan , Dong Yuhao , Lu Chengping , Liu Yongjie 
Published: March 2020

Abstract
Background: Aeromonas hydrophila is an important water-borne pathogen that leads to a great economic loss in aquaculture. Along with the abuse of antibiotics, drug-resistant strains rise rapidly. In addition, the biofilms formed by this bacterium limited the antibacterial effect of antibiotics. Bacteriophages have been attracting increasing attention as a potential alternative to antibiotics against bacterial infections. Results: Five phages against pathogenic A. hydrophila, named N21, W3, G65, Y71 and Y81, were isolated. Morphological analysis by transmission electron microscopy revealed that phages N21, W3 and G65 belong to the family Myoviridae, while Y71 and Y81 belong to the Podoviridae. These phages were found to have broad host spectra, short latent periods and normal burst sizes. They were sensitive to high temperature but had a wide adaptability to the pH. In addition, the phages G65 and Y81 showed considerable bacterial killing effect and potential in preventing formation of A. hydrophila biofilm; and the phages G65, W3 and N21 were able to scavenge mature biofilm effectively. Phage treatments applied to the pathogenic A. hydrophila in mice model resulted in a significantly decreased bacterial loads in tissues. Conclusions: Five A. hydrophila phages were isolated with broad host ranges, low latent periods, and wide pH and thermal tolerance. And the phages exhibited varying abilities in controlling A. hydrophila infection. This work presents promising data supporting the future use of phage therapy.
Neurotransmitter and tryptophan metabolite concentration changes in the Complete Freund’s adjuvant model of orofacial pain
Authors: Cseh Edina K , Veres Gábor , Körtési Tamás , Polyák Helga , Nánási Nikolett , Tajti János , Párdutz Árpád , Klivényi Péter , Vécsei László , Zádori Dénes 
Published: March 2020

Abstract
Background
The neurochemical background of the evolution of headache disorders, still remains partially undiscovered. Accordingly, our aim was to further explore the neurochemical profile of Complete Freund’s adjuvant (CFA)-induced orofacial pain, involving finding the shift point regarding small molecule neurotransmitter concentrations changes vs. that of the previously characterized headache-related neuropeptides. The investigated neurotransmitters consisted of glutamate, γ-aminobutyric acid, noradrenalin and serotonin. Furthermore, in light of its influence on glutamatergic neurotransmission, we measured the level of kynurenic acid (KYNA) and its precursors in the kynurenine (KYN) pathway (KP) of tryptophan metabolism.
Methods
The effect of CFA was evaluated in male Sprague Dawley rats. Animals were injected with CFA (1 mg/ml, 50 µl/animal) into the right whisker pad. We applied high-performance liquid chromatography to determine the concentrations of the above-mentioned compounds from the trigeminal nucleus caudalis (TNC) and somatosensory cortex (ssCX) of rats. Furthermore, we measured some of these metabolites from the cerebrospinal fluid and plasma as well. Afterwards, we carried out permutation t-tests as post hoc analysis for pairwise comparison.
Results
Our results demonstrated that 24 h after CFA treatment, the level of glutamate, KYNA and that of its precursor, KYN was still elevated in the TNC, all diminishing by 48 h. In the ssCX, significant concentration increases of KYNA and serotonin were found.
Conclusion
This is the first study assessing neurotransmitter changes in the TNC and ssCX following CFA treatment, confirming the dominant role of glutamate in early pain processing and a compensatory elevation of KYNA with anti-glutamatergic properties. Furthermore, the current findings draw attention to the limited time interval where medications can target the glutamatergic pathways.
Anterior Segment Optical Coherence Tomography Imaging in Peripheral Ulcerative Keratitis, a Corneal Structural Description
Authors: BONNET Clemence , Debillon Louis , Al-Hashimi Saba , Hoogewoud Florence , Monnet Dominique , Bourges Jean-Louis , Brézin Antoine 
Published: March 2020

Abstract
Background

Anterior-segment optical coherence tomography (AS OCT) is an important tool, helpful to diagnose and manage many corneal conditions, but has not been reported in cases of peripheral ulcerative keratitis (PUK). The aim of this study is to describe AS OCT findings in cases of PUK.

Methods

Retrospective observational case series of six eyes with a PUK with proven systemic vasculitis. Clinical course, slit lamp photographs, and AS OCT findings were the main outcomes.

Results

The AS OCT findings were found to correlate with the ocular disease’s level of activity. In the acute stage, an absence of corneal epithelium, a scrambled appearance of the anterior stroma and a heterogeneous stromal reflectivity were observed. During the reduction of disease level activity, an irregular hyporeflective epithelium, a smoother anterior stroma, and a homogenous hyperreflective stroma were seen. At the healed stage, a filling of the corneal defect by a hyporeflective thick epithelium, the persistence of the hyperreflective underlying stroma, and a demarcation line were observed. The mean total corneal thickness at last follow-up was significantly thicker (509 ± 147 µm) compared with the mean corneal thickness at onset (408 ± 131 µm; P = 0.03).

Conclusions

AS OCT provides an assessment of structural changes occurring in PUK, useful for its diagnosis and monitoring.