bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cloning of human ABCB11 gene in E. coli required the removal of an intragenic Pribnow-Schaller Box before it’s Insertion into genomic safe harbor AAVS1 site using CRISPR–Cas9
Authors: Vats Nisha , Sanal Madhusudana Girija , Venugopal Senthil Kumar , Taneja Pankaj , Sarin Shiv Kumar 
Published: December 2020

Background: Genomic safe harbors are sites in the genome which are safe for gene insertion such that the inserted gene will function properly, and the disruption of the genomic location doesn’t cause any foreseeable risk to the host. The AAVS1 site is the genetic location which is disrupted upon integration of adeno associated virus (AAV) and is considered a ‘safe-harbor’ in human genome because about one-third of humans are infected with AAV and so far there is no apodictic evidence that AAV is pathogenic or disruption of AAVS1 causes any disease in man. Therefore, we chose to target the AAVS1 site for the insertion of ABCB11, a bile acid transporter which is defective in progressive familial intra hepatic cholestasis type-2 (PFIC-2), a lethal disease of children where cytotoxic bile salts accumulate inside hepatocytes killing them and eventually the patient. Methods: We used the CRISPR Cas9 a genome editing system to insert the ABCB11 gene at AAVS1 site in human cell-lines. Results: We found that human ABCB11 sequence has a “Pribnow- Schaller Box” which allows its expression in bacteria and expression of ABCB11 protein which is toxic to E. coli; the removal of this was required for successful cloning. We inserted ABCB11 at AAVS1 site in HEK 293T using CRISPR-Cas9 tool. We also found that the ABCB11 protein has similarity with E. coli endotoxin (lipid A) transporter MsbA. Conclusions: We inserted ABCB11 at AAVS1 site using CRISPR-Cas9; however, the frequency of homologous recombination was very low for this approach to be successful in vivo.
Incidence and significance of findings on spinal MRIs in a paediatric population with spinal column complaints
Authors: Rathjen Karl , Dieckmann Rebecca J. , Thornberg David C. , Karam AnnMarie , Birch John G. 
Published: December 2020

Purpose We sought to identify correlations between working diagnosis, surgeon indication for obtaining spinal MRI and positive MRI findings in paediatric patients presenting with spinal disorders or complaints. Methods Surgeons recorded their primary indication for ordering a spinal MRI in 385 consecutive patients. We compared radiologist-reported positive MRI findings with surgeon response, indication, working diagnosis and patient demographics. Results The most common surgeon-stated indications were pain (70) and coronal curve characteristics (63). Radiologists reported 137 (36%) normal and 248 (64%) abnormal MRIs. In total, 58% of abnormal reports (145) did not elicit a therapeutic or investigative response, which we characterized as ‘clinically inconsequential’. In all, 42 of 268 (16%) presumed idiopathic scoliosis patients had intradural pathology noted on MRI. Younger age (10.3 years versus 12.0 years) was the only significant demographic difference between patients with or without intradural pathology. Surgeon indication ‘curve magnitude at presentation’ was associated with intradural abnormality identification. However, average Cobb angles between patients with or without an intradural abnormality was not significantly different (39° versus 37°, respectively). Back pain without neurological signs or symptoms was a negative predictor of intradural pathology. Conclusion Radiologists reported a high frequency of abnormalities on MRI (64%), but 58% of those were deemed clinically inconsequential. Patients with MRI abnormalities were two years’ younger than those with a normal or inconsequential MRI. ‘Curve magnitude at presentation’ in presumed idiopathic scoliosis patients was the only predictor of intrathecal pathology. ‘Pain’ was the only indication significantly associated with clinically inconsequential findings on MRI. Level of evidence III
The impact of comorbidities on post-operative complications following colorectal cancer surgery
Authors: Flynn David E. , Mao Derek , Yerkovich Stephanie T. , Franz Robert , Iswariah Harish , Hughes Andrew , Shaw Ian M. , Tam Diana P. L. , Chandrasegaram Manju D. 
Published: December 2020

Background
Colorectal cancer surgery is complex and can result in severe post-operative complications. Optimisation of surgical outcomes requires a thorough understanding of the background complexity and comorbid status of patients.

Aim
The aim of this study is to determine whether certain pre-existing comorbidities are associated with high grade post-operative complications following colorectal cancer surgery. The study also aims to define the prevalence of demographic, comorbid and surgical features in a population undergoing colorectal cancer resection.

Method
A colorectal cancer database at The Prince Charles Hospital was established to capture detailed information on patient background, comorbidities and clinicopathological features. A single-centre retrospective study was undertaken to assess the effect of comorbidities on post-operative outcomes following colorectal cancer resection. Five hundred and thirty-three patients were reviewed between 2010–2018 to assess if specific comorbidities were associated with higher grade post-operative complications. A Clavien-Dindo grade of three or higher was defined as a high grade complication.

Results
Fifty-eight percent of all patients had an ASA grade of ASA III or above. The average BMI of patients undergoing resection was 28 ± 6.0. Sixteen percent of all patients experienced a high grade complications. Patients with high grade complications had a higher mean average age compared to patients with low grade or no post-operative complications (74 years vs 70 years, p = 0.01). Univariate analysis revealed patients with atrial fibrillation, COPD, ischaemic heart disease and heart failure had an increased risk of high grade complications. Multivariate analysis revealed pre-existing atrial fibrillation (OR 2.70, 95% CI 1.53–4.89, p <0.01) and COPD (OR 2.02 1.07–3.80, p = 0.029) were independently associated with an increased risk of high grade complications.

Conclusion
Pre-existing atrial fibrillation and COPD are independent risk factors for high grade complications. Targeted perioperative management is necessary to optimise outcomes.
Deaths After Intravenous Misuse of Transdermal Fentanyl
Authors: Lilleng PK , Mehlum LI , Bachs L , Morild I 
Published: December 2020

Abstract
Fentanyl is a potent synthetic opioid used as a general anesthetic and analgetic. Fatal outcome from intravenous misuse of transdermal fentanyl is rare, and there are few such reports in literature. Here we report two cases of fatal intravenous injection of the content from fentanyl patches. Both were male drug addicts, found dead within a one week interval in the same apartment. Post-mortem femoral blood was screened for amphetamines, cannabinoids, cocaine, and opioids with immunological methods (EMIT II) and further with headspace gas chromatography for alcohol and with liquid chromatography mass spectrometry (LC-MS) for different drugs, including fentanyl. Confirmatory analysis of fentanyl and morphine was performed by gas chromatography-mass spectrometry (GC-MS). In the first case, the toxicological analysis revealed fentanyl (2.7 ng/mL), morphine (31.4 ng/mL), and ethanol (1.1 g/L) in postmortem blood and amphetamine, cannabinoids, morphine, and ethanol (1.4 g/L) in postmortem urine. In the second case, the analysis revealed fentanyl (13.8 ng/mL), 7-aminoclonazepam (57.1 ng/mL), and sertralin (91.9 ng/mL) in postmortem blood and a small amount of ethanol (0.1 g/L) in postmortem urine. Police investigation revealed that both the deceased had bought the patches from the same source. The present cases demonstrate the possibility of intravenous misuse of transdermal patches and the risk of fatal outcome.
Finding Distributed Needles in Neural Haystacks
Authors: Cox Christopher R. , Rogers Timothy T. 
Published: December 2020

The human cortex encodes information in complex networks that can be anatomically dispersed and variable in their microstructure across individuals. Using simulations with neural network models, we show that contemporary statistical methods for functional brain imaging—including univariate contrast, searchlight multivariate pattern classification, and whole-brain decoding with L1 or L2 regularization—each have critical and complementary blind spots under these conditions. We then introduce the sparse-overlapping-sets (SOS) LASSO—a whole-brain multivariate approach that exploits structured sparsity to find network-distributed information—and show in simulation that it captures the advantages of other approaches while avoiding their limitations. When applied to fMRI data to find neural responses that discriminate visually presented faces from other visual stimuli, each method yields a different result, but existing approaches all support the canonical view that face perception engages localized areas in posterior occipital and temporal regions. In contrast, SOS LASSO uncovers a network spanning all four lobes of the brain. The result cannot reflect spurious selection of out-of-system areas because decoding accuracy remains exceedingly high even when canonical face and place systems are removed from the dataset. When used to discriminate visual scenes from other stimuli, the same approach reveals a localized signal consistent with other methods—illustrating that SOS LASSO can detect both widely distributed and localized representational structure. Thus, structured sparsity can provide an unbiased method for testing claims of functional localization. For faces and possibly other domains, such decoding may reveal representations more widely distributed than previously suspected.SIGNIFICANCE STATEMENTBrain systems represent information as patterns of activation over neural populations connected in networks that can be widely distributed anatomically, variable across individuals, and intermingled with other networks. We show that four widespread statistical approaches to functional brain imaging have critical blind spots in this scenario and use simulations with neural network models to illustrate why. We then introduce a new approach designed specifically to find radically distributed representations in neural networks. In simulation and in fMRI data collected in the well studied domain of face perception, the new approach discovers extensive signal missed by the other methods—suggesting that prior functional imaging work may have significantly underestimated the degree to which neurocognitive representations are distributed and variable across individuals.
Each to Their Own: Visual Representations of Terry Pratchett’s Discworld in Time and Space
Authors: Sohár Anikó 
Published: December 2020

When a book is translated, publishers will often modify or completely change the cover design. This paper examines the similarities and differences that result in a sample of cover designs taken from Terry Pratchett’s Discworld series. The essay analyzes these images as a form of intersemiotic translation, which prioritizes the marketing apparatus of a novel over its narrative content.
Pyrite-Scale Removal Using Glutamic Diacetic Acid: A Theoretical and Experimental Investigation
Authors: Ahmed M. E. , Hussein I. A. , Onawole A. T. , Mahmoud M. , Saad M. A. 
Published: December 2020

SummaryIron sulfide scale causes major losses in both upstream and downstream sectors of the hydrocarbon industry. Pyrite is one of the most-difficult forms of iron sulfide scale from a removal point of view. Inorganic acids such as hydrochloric acid (HCl) are not recommended for removing pyrite scales because they have many drawbacks, including low pyrite solubility, high corrosivity to the tubular system, and generation of toxic hydrogen sulfide (H2S). In this work, pyrite-scale dissolution is studied using an ecofriendly formulation of glutamic diacetic acid [L-glutamic acid, N, N-diacetic acid (GLDA)] as an alternative to HCl. Although GLDA has shown potential for removing iron sulfide in general and pyrite scale in particular, still GLDA/pyrite kinetics have not been well-understood. Both experimental and theoretical techniques have been used. The reaction kinetics has been investigated in a rotating-disk apparatus (RDA) at typical reservoir conditions of 150°C and 1,000 psi (Conway et al. 1999). Characterization techniques, including X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM), have been used to study the surface chemistry before and after treatment with GLDA, and the results support pyrite removal. Furthermore, density-functional-theory (DFT) calculations have been performed to understand the ability of GLDA to dissolve iron sulfide scale at the atomistic level. From the laboratory results, the reaction rate using 20-wt% GLDA (pH of 3.8) was 5.378×10−8 mol/cm2·s. The measured rate outperformed other proposed formulations according to the tetrakis(hydroxymethyl)phosphonium sulfate (THPS) formulation by 15 times. In addition, GLDA surpassed the most recent results on diethylenetriamine penta-acetic acid (DTPA) by nearly an order of magnitude. Moreover, pyrite dissolution in GLDA increases as the disk rotational speed increased, which indicates mass-transfer control with a diffusion coefficient of 1.338×10−7 cm2/s. Furthermore, from molecular modeling using DFT, the binding energy between GLDA and Fe2+ is calculated as –105.97 kcal/mol. The negative value observed correlates with the stability constant and indicates the strong binding affinity to Fe2+. Finally, GLDA could be recommended for pyrite-scale removal because it is biodegradable, less corrosive, free of H2S, and achieved solubility that outperformed THPS- and DTPA-basedformulations.
Bayesian Multilevel Analysis of Determinants of Acute Respiratory Infection in Children under the Age of Five Years in Ethiopia
Authors: Merera Amanuel , Asena Tilahun , Senbeta Mebratu 
Published: December 2020

Abstract
Background: Acute respiratory tract infection (ARI) is a leading cause of morbidity and mortality in children under the age of five years in the world. ARIs, principally pneumonia, account for approximately 1.9 million (1.6 - 2.2 million) deaths globally in children under the age of five years in Ethiopia. Among these deaths majority occur in the developing world. The share for low and middle-income countries takes the highest indeed. In Ethiopia, the prevalence rate of ARI was 7% according to 2016 EDHS estimates. Method: Bayesian multilevel approach was employed to assess possible factors associated with the prevalence of acute respiratory infection (ARI) among under-five children in Ethiopia. The data was collected from 10,641 children under the age of five years out of which 9,918 children were considered in this study. Result: The ARI prevalence rate for children under five years was estimated as 8.4%, which was slightly higher than the estimated prevalence level of the country. The highest proportion of the prevalence of ARI was observed for children whose mothers had no education. The major health, environmental and nutritional related background characteristics of the proportion of children who had ARI varied from one region to another. The highest prevalence of ARI was observed in Tigray (15.31%) followed by Oromia (14.40%) as opposed to the low prevalence which was recorded in Benishangul Gumuz (2.58%). The utilization of vitamin A was analyzed and the results shows that about 43.10% who received vitamin A had the lowest proportion on the prevalence of ARI (7.75%) compared to not having vitamin A. About 11.13% of under-five children had Diarrhea with the highest prevalence of ARI (24.64%) and the highest prevalence of ARI was observed for the child whose source of drinking water were unprotected/unimproved (9.39%). Conclusion: The age of the child, household wealth index, mother educational level, and vitamin A supplement, history of diarrhea, maternal work, stunting and source of drinking water were found to be significantly affecting the prevalence of ARI among children under five years. Furthermore, the study revealed that there is a significant variation of incidence of ARI between and within the regions of Ethiopia. Attention should be given to those predictor variables while planning to increase the health status of children in Ethiopia.
Mixture Interactions at Mammalian Olfactory Receptors are Dependent on the Cellular Environment
Authors: Corey Elizabeth , Zolotukhin Sergei , Ache Barry , Ukhanov Kirill 
Published: December 2020

Abstract
Functional characterization of mammalian olfactory receptors (ORs) remains a major challenge to ultimately understanding the olfactory code. Here, we compare the responses of the mouse Olfr73 ectopically expressed in olfactory sensory neurons using AAV gene delivery in vivo and expressed in vitro in cell culture. The response dynamics and concentration-dependence of agonists for the ectopically expressed Olfr73 were similar to those reported for the endogenous Olfr73, but the receptor failed to mediate the antagonism between its cognate agonist and several antagonists reported for the OR expressed in vitro. Expressing the OR in vitro under the same conditions of stimulation retained the reported antagonism, but it was dependent on the duration of stimulation. Our findings suggest that both the cellular environment and the stimulus dynamics shape the functionality of Olfr73 and argue that characterizing ORs in ‘native’ conditions provides the most complete understanding of ligand-OR interactions.
Standardized Uptake Values&nbsp;of 99mTc-MDP in Normal Vertebrae Assessed Using&nbsp;Quantitative SPECT/CT for Differentiation Diagnosis of Benign and Malignant Bone Lesions
Authors: Qi Na , Meng Qingyuan , You Zhiwen , Chen Huiqian , Shou Yi , Zhao Jun 
Published: December 2020

Abstract
Background: Quantitative bone SPECT/CT is useful for disease follow up and inter-patient comparison. For bone metastatic malignant lesions, spine is the most commonly invaded site. However, Quantitative studies with large samples size investigating all the segments of normal cervical, thoracic and lumbar vertebrae are seldom reported. This study was to evaluate the quantitative tomography of normal vertebrae using 99mTc-MDP with SPECT/CT to investigate the feasibility of standardized uptake value (SUV) for differential diagnosis of benign and malignant bone lesions. Methods: A retrospective study was carried out involving 221 patients (116 males and 105 female) who underwent SPECT/CT scan using 99mTc-MDP. The maximum SUV (SUVmax), mean SUV (SUVmean) and CT values (Hounsfield Unit, HU) of 2416 normal vertebrae bodies, 157 benign bone lesions and 118 malignant bone metastasis foci were obtained. The correlations between SUVmax and CT values, age, height, weight of normal vertebrae were analyzed. Statistical analysis was performed with data of normal, benign and malignant groups corresponding to same sites and gender. Results: The SUVmax and SUVmean of vertebrae in males were markedly higher than those in females (P<0.0009). The SUVmax of each vertebral segment showed a strong negative correlation with CT values in both males and females (r=-0.89 and -0.92, respectively; P<0.0009). The SUVmax of vertebrae also showed significant correlation with weight and height in males (r=0.4, P<0.0009; r=0.28, P=0.005), and significant correlation with weight in females (r=0.32, P=0.009). The SUVmax of normal group, benign bone lesion group and malignant bone metastasis foci group showed statistical differences in both males and females. Conclusion: Our study evaluated SUVmax and SUVmean of normal vertebrae, benign bone lesion and malignant bone metastasis foci with a large sample population. Preliminary results proved the potential value of SUVmax in differentiation benign and malignant bone lesions. The results may provide a quantitative reference for clinical diagnosis and the evaluation of therapeutic response in vertebral lesions.
A comparison of FOLFIRI (Folinic Acid, Fluorouracil and Irinotecan) Plus Bevacizumab and FLOLFIRI Plus Aflibercept as Second-Line Treatment for Metastatic Colorectal Cancer
Authors: Lee Min-Sang , Lee Yong-Pyo , Kim Hongsik , Hong Jung Yong , Lee Jeeyun , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Kim Seung Tae 
Published: December 2020

Abstract
Background: To date, there are few clinical studies comparing the efficacy and safety of FOLFIRI (folinic acid, fluorouracil and irinotecan) plus bevacizumab or aflibercept in metastatic colorectal cancer patients (mCRC) pretreated with oxaliplatin-based chemotherapy. Methods: We analyzed the treatment outcomes of patients receiving FOLFIRI in combination with bevacizumab or aflibercept as second-line treatment for mCRC between October 2017 and March 2020. This analysis included 67 patients receiving FOLFIRI plus aflibercept and 83 receiving FOLFIRI plus bevacizumab. Results: The overall response rate (ORR) was 13.6% (95% CI: 4.85-22.34) in the FOLFIRI-aflibercept group and 14.7% (95% CI: 6.68-22.71) in the FOLFIRI-bevacizumab group. This difference in ORR was not statistically significant. The median progression free survival (PFS) was 8.6 months in the FOLFIRI-bevacizumab group and 8.5 months in the FOLFIRI-aflibercept group (P = 0.752) (Fig. 1). Patients in the FOLFIRI-bevacizumab group showed a median overall survival (OS) of 12.4 months, while patients in the FOLFIRI-aflibercept group had a median OS of 13.7 months (P = 0.276). There were no significant differences in survival between the two treatment groups. The adverse events were also largely similar between the two groups. However, hypertension of grade 3 or more was more frequent in the FOLFIRI-aflibercept group. Conclusion: FOLFIRI plus bevacizumab and FOLFIRI plus aflibercept had similar anti-tumor activities and toxicity profiles when used as second-line therapy in mCRC patients. Based on these data, both aflibercept and bevacizumab are suitable anti-angiogenic agents when used in combination with FOLFIRI for mCRC.
Archaea Are the Major Responsive Ammonia Oxidizers in a Paddy Soil Following Fertilization and Irrigation
Authors: Wang Limin , Huang Dongfeng 
Published: December 2020

Abstract
Because ammonia-oxidizing archaea (AOA) are ubiquitous and highly abundant in almost all terrestrial soils, they play an important role in soil nitrification. However, the changes in the structure and function of AOA communities and their specific environmental drivers in paddy soils under different fertilization and irrigation regimes remains unclear. In this study, we investigated archaeal abundance, activity and community composition in acid paddy soils by a 10-year field experiment. Results indicated that the highest potential ammonia oxidation (PAO) (0.011 µg NO2−-N g− 1 d.w.day− 1) was found in T2 (optimal irrigation and fertilization) - treated soils, whereas the lowest PAO (0.004 µg NO2−-N g− 1 d.w.day− 1) in T0 (traditional irrigation)- treated soils. Compared with the T0 - treated soil, the T2 treatment significantly (P < 0.05) increased AOA abundances. Furthermore, the abundance of AOA was significantly (P < 0.01) positively correlated with pH, soil organic carbon (SOC), and PAO. Meanwhile, pH and SOC content were significantly (P < 0.05) higher in the T2 - treated soil than those in the T1 (traditional irrigation and fertilization)- treated soil. In addition, these two edaphic factors further influenced the AOA community composition. The archaeal phylum Crenarchaeota and genus Candidatus Nitrosotalea were mainly found in the T2-treated soils. Phylogenetic analysis revealed that most of the identified OTUs of AOA were mainly affiliated with Crenarchaeota. Together, our findings confirmed that T2 might ameliorate soil chemical properties, regulate the AOA community structure, increase the AOA abundance, enhance PAO and consequently maintain optimum rice yields in a subtropical paddy field.