bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lactobionic acid-chitosan functionalised gold-coated poly(lactide-co-glycolide) nanoparticles for hepatocyte targeted gene delivery
Authors: Akinyelu Jude , Oladimeji Olakunle , Singh Moganavelli 
Published: January 2021

AbstractNanoscale non-viral gene delivery vectors are attractive systems for the efficient and safe delivery of therapeutic genes. This study explored the potential of surface tailored poly(lactide-co-glycolide) (PLGA) systems for targeted gene delivery to human hepatocellular carcinoma (HepG2) cells overexpressing the asialoglycoprotein receptor (ASGPR). Chitosan (CS) functionalised gold (G) PLGA nanoparticles (NPs) were synthesised with and without the targeting ligand, lactobionic acid (LA), and bound to pCMV-Luc-DNA (pDNA) to form nanocomplexes. NPs were physicochemically characterised, and pDNA binding and protection by the NPs were investigated using mobility shift, dye displacement and nuclease digestion assays. MTT and luciferase assays served to evaluate cytotoxicity and transgene expressionin vitro. Nanocomplexes of 20–40 nm in size effectively protected the DNA from nuclease digestion and exhibited low cytotoxicity (>90% cell viability). Targeted transgene expression was significantly greater than the untargeted expression, confirming ASPGR uptake. Our results highlight the potential of these hybrid CS-PLGA based nano-platforms for targeted gene therapy, warranting further development, especially for liver-directed gene therapy.
Urgent care for older people
Authors: Conroy Simon , Thomas Matt 
Published: January 2021

Abstract
Geriatric medicine is the clinical specialty that focuses upon the care of older people—especially those with frailty (a state of increased vulnerability). In hospital, older people living with frailty are at high risk of developing a range of unpleasant outcomes such as delirium, falls, fractures, pressure sores and death. Comprehensive geriatric assessment is a form of holistic care that incorporates a specific set of clinical competencies that are able to reduce these adverse outcomes. Over the years, geriatric medicine has moved from being more of a community-based service towards a more acute specialty—encroaching now upon emergency department care. The challenge now is to work out how best to deliver geriatric care across the whole hospital (older people with frailty are not just cared for in geriatric wards!). The themed collection published on the Age & Ageing journal website outlines key articles that are attempting to develop solutions to this challenging conundrum. We hope that you enjoy reading them.
Verifying Clinically Derived Reference Intervals for Daily Excretion Rates of Fractionated Metanephrines Using Modern Indirect Reference Interval Models
Authors: Doyle Kelly , Frank Elizabeth L 
Published: January 2021

AbstractObjectivesBiochemical testing of urinary metanephrines is useful in the diagnosis and monitoring of pheochromocytoma and paragangliomas. We investigated the feasibility of mixture decomposition (ie, indirect) methods in verifying clinically derived reference intervals for urinary deconjugated metanephrine metabolites.MethodsUrinary 24-hour metanephrine and normetanephrine excretion results were extracted from our data warehouse and intervals were estimated by the modern variant of the Hoffmann method, maximum likelihood estimation (MLE), and gamma mixture model using R software.ResultsHoffmann, MLE, and gamma mixture models provided metanephrine and normetanephrine intervals that closely matched those derived from clinical studies. However, three-component MLE and gamma models were required for normetanephrine in adult women because the Hoffmann method was not suitable. Some data transformations caused blending of the mixed distributions and subsequent widening of the reference interval estimation, emphasizing the importance of careful data transformation for Hoffmann and MLE analyses. Gamma mixture models gave overall good agreement without the need for data transformation.ConclusionsIndirect methods have utility in verifying reference intervals in 24-hour urine specimens collected by patients. We emphasize the benefits of applying multiple decomposition methods to corroborate findings and careful application of data transformation when using Gaussian-based models.
A proposed antioxidation mechanism of ergothioneine based on the chemically derived oxidation product hercynine and further decomposition products
Authors: Ando Chika , Morimitsu Yasujiro 
Published: January 2021

ABSTRACT
Ergothioneine (ERGO), a thiohistidine betaine, exists in various fungi, plants, and animals. Humans take in ERGO from their diet. ERGO is a strong biological antioxidant, but there are only a limited number of reports about its redox mechanism. The purpose of this study was to clarify the oxidation mechanism of ERGO. Reactions of ERGO with chemical oxidants were performed. The oxidation products of ERGO were analyzed by nuclear magnetic resonance and liquid chromatography-mass spectrometry (LC-MS). The major product of oxidation of ERGO by hydrogen peroxide in physiological conditions was identified as hercynine (histidine betaine). One molecule of ERGO was able to reduce 2 molecules of hydrogen peroxide. Hercynine was found to react with the more potent oxidant hypochlorite. One unstable decomposition product was detected by LC-MS. As a result, a mechanism of oxidation of ERGO, and hence its physiological antioxidant activity, was developed.
Multiple mutations in RNA polymerase β-subunit gene (rpoB) in Streptomyces incarnatus NRRL8089 enhance production of antiviral antibiotic sinefungin: modeling rif cluster region by density functional theory
Authors: Ogawa Saori , Shimidzu Hitomi , Fukuda Koji , Tsunekawa Naoki , Hirano Toshiyuki , Sato Fumitoshi , Yura Kei , Hasunuma Tomohisa , Ochi Kozo , Yamamoto Michio , Sakamoto Wataru , Hashimoto Kentaro , Ogata Hiroyuki , Kanao Tadayoshi , Nemoto Michiko , Inagaki Kenji , Tamura Takashi 
Published: January 2021

ABSTRACT
Streptomyces incarnatus NRRL8089 produces the antiviral, antifungal, antiprotozoal nucleoside antibiotic sinefungin. To enhance sinefungin production, multiple mutations were introduced to the rpoB gene encoding RNA polymerase (RNAP) β-subunit at the target residues, D447, S453, H457, and R460. Sparse regression analysis using elastic-net lasso-ridge penalties on previously reported H457X mutations identified a numeric parameter set, which suggested that H457R/Y/F may cause production enhancement. H457R/R460C mutation successfully enhanced the sinefungin production by 3-fold, while other groups of mutations, such as D447G/R460C or D447G/H457Y, made moderate or even negative effects. To identify why the rif cluster residues have diverse effects on sinefungin production, an RNAP/DNA/mRNA complex model was constructed by homology modeling and molecular dynamics simulation. The 4 residues were located near the mRNA strand. Density functional theory–based calculation suggested that D447, H457, and R460 are in direct contact with ribonucleotide, and partially positive charges are induced by negatively charged chain of mRNA.
Gastrodin attenuates lithium-pilocarpine-induced epilepsy by activating AMPK-mediated PPARα in a juvenile rat model
Authors: Yang Yanfei , Li Yabin , Han Jinli , Wang Yanfen 
Published: January 2021

ABSTRACTGastrodin has shown the potential as an anticonvulsant. Epilepsy is a neurological disease with significant effects in children. In the current study, the therapeutic potential of gastrodin in handling pediatric epilepsy was explored by focusing on the AMPK/PPARα pathway. Three-week-old Sprague–Dawley rats were subjected to lithium-pilocarpine method to induce epileptic symptoms and then administrated with gastrodin. The effects of gastrodin on rats were first assessed using electroencephalogram (EEG) recording, Racine classification, Morris water maze test, and histological staining. The levels of BDNF and NGF, and the activity of AMPK/PPARα were measured. Based on the results of EEG, behavior analyses, and histological staining, epileptic symptoms were significantly alleviated by gastrodin. Moreover, the administration of gastrodin also suppressed the levels of BDNF and NGF, and activated the AMPK/PPARα pathway. In conclusion, our results demonstrated that gastrodin contributed to the alleviation of pediatric epilepsy by activating AMPK/PPARα signaling transduction.
Metabolic analysis of unripe papaya (Carica papaya L.) to promote its utilization as a functional food
Authors: Hiraga Yasuhide , Ara Takeshi , Sato Nao , Akimoto Nayumi , Sugiyama Kenjiro , Suzuki Hideyuki , Kera Kota 
Published: January 2021

ABSTRACT
Papaya (Carica papaya L.) is widely cultivated in tropical and subtropical countries. While ripe fruit is a popular food item globally, the unripe fruit is only consumed in some Asian countries. To promote the utilization of unripe papaya based on the compositional changes of biological active metabolites, we performed liquid chromatography–Orbitrap–mass spectrometry-based analysis to reveal the comprehensive metabolite profile of the peel and pulp of unripe and ripe papaya fruits. The number of peaks annotated as phenolics and aminocarboxylic acids increased in the pulp and peel of ripe fruit, respectively. Putative carpaine derivatives, known alkaloids with cardiovascular effects, decreased, while carpamic acid derivatives increased in the peel of ripe fruit. Furthermore, the functionality of unripe fruit, the benzyl glucosinolate content, total polyphenol content, and proteolytic activity were detectable after heating and powder processing treatments, suggesting a potential utilization in powdered form as functional material.
Whole genome analysis of more than 10 000 SARS-CoV-2 virus unveils global genetic diversity and target region of NSP6
Authors: Saha Indrajit , Ghosh Nimisha , Pradhan Ayan , Sharma Nikhil , Maity Debasree , Mitra Kaushik 
Published: January 2021

Abstract
Whole genome analysis of SARS-CoV-2 is important to identify its genetic diversity. Moreover, accurate detection of SARS-CoV-2 is required for its correct diagnosis. To address these, first we have analysed publicly available 10 664 complete or near-complete SARS-CoV-2 genomes of 73 countries globally to find mutation points in the coding regions as substitution, deletion, insertion and single nucleotide polymorphism (SNP) globally and country wise. In this regard, multiple sequence alignment is performed in the presence of reference sequence from NCBI. Once the alignment is done, a consensus sequence is build to analyse each genomic sequence to identify the unique mutation points as substitutions, deletions, insertions and SNPs globally, thereby resulting in 7209, 11700, 119 and 53 such mutation points respectively. Second, in such categories, unique mutations for individual countries are determined with respect to other 72 countries. In case of India, unique 385, 867, 1 and 11 substitutions, deletions, insertions and SNPs are present in 566 SARS-CoV-2 genomes while 458, 1343, 8 and 52 mutation points in such categories are common with other countries. In majority (above 10%) of virus population, the most frequent and common mutation points between global excluding India and India are L37F, P323L, F506L, S507G, D614G and Q57H in NSP6, RdRp, Exon, Spike and ORF3a respectively. While for India, the other most frequent mutation points are T1198K, A97V, T315N and P13L in NSP3, RdRp, Spike and ORF8 respectively. These mutations are further visualised in protein structures and phylogenetic analysis has been done to show the diversity in virus genomes. Third, a web application is provided for searching mutation points globally and country wise. Finally, we have identified the potential conserved region as target that belongs to the coding region of ORF1ab, specifically to the NSP6 gene. Subsequently, we have provided the primers and probes using that conserved region so that it can be used for detecting SARS-CoV-2. Contact:indrajit@nitttrkol.ac.inSupplementary information: Supplementary data are available at http://www.nitttrkol.ac.in/indrajit/projects/COVID-Mutation-10K
ICN: extracting interconnected communities in gene co-expression networks
Authors: Wu Qiong , Ma Tianzhou , Liu Qingzhi , Milton Donald K , Zhang Yuan , Chen Shuo 
Published: January 2021

AbstractMotivationThe analysis of gene co-expression network (GCN) is critical in examining the gene-gene interactions and learning the underlying complex yet highly organized gene regulatory mechanisms. Numerous clustering methods have been developed to detect communities of co-expressed genes in the large network. The assumed independent community structure, however, can be oversimplified and may not adequately characterize the complex biological processes.ResultsWe develop a new computational package to extract interconnected communities from gene co-expression network. We consider a pair of communities be interconnected if a subset of genes from one community is correlated with a subset of genes from another community. The interconnected community structure is more flexible and provides a better fit to the empirical co-expression matrix. To overcome the computational challenges, we develop efficient algorithms by leveraging advanced graph norm shrinkage approach. We validate and show the advantage of our method by extensive simulation studies. We then apply our interconnected community detection method to an RNA-seq data from The Cancer Genome Atlas (TCGA) Acute Myeloid Leukemia (AML) study and identify essential interacting biological pathways related to the immune evasion mechanism of tumor cells.Availabilityand implementationThe software is available at Github: https://github.com/qwu1221/ICN and Figshare: https://figshare.com/articles/software/ICN-package/13229093.Supplementary informationSupplementary data are available at Bioinformatics online.
Phylogenetic relationships inBrachyotumand allies (Melastomataceae, Melastomateae): a reassessment of the limits of the genera
Authors: Meyer Fabrício Schmitz , Reginato Marcelo , Smidt Eric Camargo , De Santiago Gómez Jesús Ricardo , Michelangeli Fabián A , Goldenberg Renato 
Published: January 2021

AbstractIn the past decade, several phylogenetic studies based on molecular data have been generated and changed our view on the evolutionary history and classification of Melastomataceae. Nonetheless, given the size of the family, some groups are still under-sampled and poorly understood, such as the clade formed by Brachyotum and allies in Melastomateae, including three genera, Andesanthus, Brachyotum and Chaetogastra. The principal objective of this work was to further test the relationships in this clade by increasing taxon and locus sampling and by including morphological character reconstructions. In this study, we included nuclear (nrITS, nrETS and waxy) and plastid sequences (accD-psaI, psbK-psbL, trnS-trnG) from 129 species and 29 genera of Melastomataceae, corresponding to c. 46.5% of the species belonging to the clade, and that were used to build phylogenetic hypotheses. We also estimated the evolution of 23 morphological characters through ancestral state reconstruction and the elevational ranges of the species. Our results recovered two major clades: (1) Brachyotum, with species traditionally recognized in Brachyotum, but also including a few species traditionally recognized in Tibouchina; and (2) Chaetogastra, with most species traditionally recognized in Tibouchina, mainly from Tibouchina sections Pseudopterolepis, Diotanthera, Simplicicaules and Purpurella. Andesanthus was placed as sister to Brachyotum and allies in previous phylogenetic analyses; however, in this study it has been recovered as sister to the clades formed by Heterocentron and allies, Monochaetum and allies, and Brachyotum and allies. Four morphological characters can be useful to distinguish genera and clades among Brachyotum and allies: habit; flower position; the angle formed by the petals in relation to the hypanthium; and stamen arrangement. We also find that species in the Brachyotum clade occur at higher elevations (1500–4700 m) than Chaetogastra spp. (sea level to c. 3200 m, but more common at lower elevations, c. 600 to 1800 m). Based on all this evidence we propose the maintenance of Brachyotum as a genus segregated from the recently reinstated Chaetogastra. This work is a contribution to the systematics of Melastomateae, with an improvement in the resolution of the trees in relation to previous phylogenetic analyses, indicating that subclades have a strong relationship with geographical distribution.
Cerebrospinal fluid liquid biopsy for detecting somatic mosaicism in brain
Authors: Ye Zimeng , Chatterton Zac , Pflueger Jahnvi , Damiano John A , McQuillan Lara , Simon Harvey A , Malone Stephen , Do Hongdo , Maixner Wirginia , Schneider Amy , Nolan Bernadette , Wood Martin , Lee Wei Shern , Gillies Greta , Pope Kate , Wilson Michael , Lockhart Paul J , Dobrovic Alexander , Scheffer Ingrid E , Bahlo Melanie , Leventer Richard J , Lister Ryan , Berkovic Samuel F , Hildebrand Michael S 
Published: January 2021

Abstract
Brain somatic mutations are an increasingly recognized cause of epilepsy, brain malformations and autism spectrum disorders and may be a hidden cause of other neurodevelopmental and neurodegenerative disorders. At present, brain mosaicism can be detected only in the rare situations of autopsy or brain biopsy. Liquid biopsy using cell-free DNA derived from cerebrospinal fluid has detected somatic mutations in malignant brain tumours. Here, we asked if cerebrospinal fluid liquid biopsy can be used to detect somatic mosaicism in non-malignant brain diseases. First, we reliably quantified cerebrospinal fluid cell-free DNA in 28 patients with focal epilepsy and 28 controls using droplet digital PCR. Then, in three patients we identified somatic mutations in cerebrospinal fluid: in one patient with subcortical band heterotopia the LIS1 p. Lys64* variant at 9.4% frequency; in a second patient with focal cortical dysplasia the TSC1 p. Phe581His*6 variant at 7.8% frequency; and in a third patient with ganglioglioma the BRAF p. Val600Glu variant at 3.2% frequency. To determine if cerebrospinal fluid cell-free DNA was brain-derived, whole-genome bisulphite sequencing was performed and brain-specific DNA methylation patterns were found to be significantly enriched (P = 0.03). Our proof of principle study shows that cerebrospinal fluid liquid biopsy is valuable in investigating mosaic neurological disorders where brain tissue is unavailable.
The Leiden Convention coronary coding system: translation from the surgical to the universal view
Authors: Koppel Claire J , Vliegen Hubert W , Bökenkamp Regina , ten Harkel A Derk Jan , Kiès Philippine , Egorova Anastasia D , Jukema J Wouter , Hazekamp Mark G , Schalij Martin J , Gittenberger-de Groot Adriana C , Jongbloed Monique R M 
Published: January 2021

Abstract

Aims
The Leiden Convention coronary coding system structures the large variety of coronary anatomical patterns; isolated and in congenital heart disease. It is widely used by surgeons but not by cardiologists as the system uses a surgeons’ cranial view. Since thoracic surgeons and cardiologists work closely together, a coronary coding system practical for both disciplines is mandatory. To this purpose, the ‘surgical’ coronary coding system was adapted to an ‘imaging’ system, extending its applicability to different cardiac imaging techniques.

Methods and results
The physician takes place in the non-facing sinus of the aortic valve, oriented with the back towards the pulmonary valve, looking outward from the sinus. From this position, the right-hand sinus is sinus 1, and the left-hand sinus is sinus 2. Next, a clockwise rotation is adopted starting at sinus 1 and the encountered coronary branches described. Annotation of the normal anatomical pattern is 1R-2LCx, corresponding to the ‘surgical’ coding system. The ‘imaging’ coding system was made applicable for Computed Tomography (CT), Magnetic Resonance Imaging (MRI), echocardiography, and coronary angiography, thus facilitating interdisciplinary use. To assess applicability in daily clinical practice, images from different imaging modalities were annotated by cardiologists and cardiology residents and results scored. The average score upon evaluation was 87.5%, with the highest scores for CT and MRI images (average 90%).

Conclusion
The imaging Leiden Convention is a coronary coding system that unifies the annotation of coronary anatomy for thoracic surgeons, cardiologists, and radiologists. Validation of the coding system shows it can be easily and reliably applied in clinical practice.
Double-Counting of Investment*
Authors: Barro Robert J 
Published: January 2021

Abstract
The national-income accounts double-count investment, which enters once when it occurs and again in present value as rental income on added capital. The double-counting implies that GDP and national income overstate sustainable consumption. An alternative measure, ‘permanent income,’ equals consumption in the steady state but deviates from consumption outside of the steady state because expensing of gross investment applies to the long-run flow, not the current value. The permanent-income perspective substantially affects measured factor-income shares. When computed in relation to permanent income, the U.S. labor-income share has been reasonably stable, in contrast to the declining share based on GDP.
Stereotactic ablative radiotherapy versus surgery in older patients with stage I lung cancer
Authors: Park Samina , Kim Hak Jae , Park In Kyu , Kim Young Tae , Kang Chang Hyun 
Published: January 2021

Abstract

OBJECTIVES
Surgical resection is the best option for the treatment of early-stage lung cancer. However, older patients are less likely to receive curative treatment. Therefore, we compared long-term survival rates between surgical resection and stereotactic ablative radiotherapy (SABR) for the treatment of early-stage lung cancer in older patients.

METHODS
From 2013 to 2016, 272 patients aged ≥75 years with clinical stage I lung cancer underwent surgical resection (n = 191) or SABR (n = 81). A propensity score-matched analysis was performed. Overall survival, cumulative incidence of cancer-related death and recurrence were compared between the 2 groups.

RESULTS
In the matched cohort, 48 well-balanced pairs were extracted. An overall survival benefit was associated with surgery (surgery vs SABR = 65.9% vs 40.3%; P = 0.034); however, there was no significant difference in the cumulative incidence of cancer-related death (P = 0.089) or recurrence (P = 0.111) between the 2 groups. Systemic dissemination was the dominant pattern of progression in both groups. The 3-year cumulative incidence of regional recurrence was significantly higher in the SABR group compared to the surgery group (surgery vs SABR = 0% vs 11.4%, P = 0.046).

CONCLUSIONS
Surgical resection with mediastinal lymph node dissection provides better long-term survival compared to SABR in older patients with stage I lung cancer. Surgery should be considered for older patients aged ≥75 years who are appropriate candidates for surgery. SABR remains an alternative treatment with comparable cancer-related death and recurrence for patients unsuitable for surgery.