bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of intensity-modulated radiotherapy alone versus intensity-modulated radiotherapy plus chemotherapy for treatment of intermediate-risk nasopharyngeal carcinoma
Authors: Aftab Omer , Liao Shufang , Zhang Rongjun , Tang Nan , Luo Meiqing , Zhang Bin , Shahi Sanjeev , Rai Raju , Ali Jazib , Jiang Wei 
Published: March 2020

Abstract
Background
This study directs to evaluate the efficacy and safety of intensity-modulated radiotherapy (IMRT) alone versus IMRT plus chemotherapy in intermediate-risk NPC (stage II and T3N0M0).

Methods
A total of 124 patients with stage II and T3N0M0 NPC were pair-matched (1:1 ratio) to form two groups: an IMRT-alone group and an IMRT/chemotherapy group. Survival outcomes (overall survival [OS], disease–free survival [DFS], locoregional relapse–free survival [LRRFS], distant metastasis–free survival [DMFS]) and treatment-related grade 3–4 acute toxicity events were compared between the groups.

Results
Survival outcomes for patients with stage II and T3N0M0 NPC were quiet comparable between patients treated with IMRT alone versus patients treated with IMRT/chemotherapy: 5-year OS was 91.9% vs. 90.3%, respectively (P = 0.727); DFS was 87.1% vs. 88.7%, respectively (P = 0.821); LRFFS was 96.8% vs. 95.2%, respectively (P = 0.646), and DMFS was 91.9% vs. 91.5%, respectively (P = 0.955). Grade 3 acute toxicities were significantly higher with IMRT/chemotherapy than with IMRT alone: mucositis, 15% vs. 5% (P = 0.004); leukopenia/neutropenia, 8% vs. 1% (P <  0.015); and nausea/vomiting, 22% vs. 3% (P <  0.001).

Conclusion
For intermediate-risk (stage II and T3N0M0) NPC patients, the addition of chemotherapy to IMRT does not appear to provide any survival benefit. Moreover, grade 3 acute toxicities are also more common in patients receiving IMRT plus chemotherapy.
Translating traditional herbal formulas into modern drugs: a network-based analysis of Xiaoyao decoction
Authors: Zhang Daiyan , Zhang Yun , Gao Yan , Chai Xingyun , Pi Rongbiao , Chan Ging , Hu Yuanjia 
Published: March 2020

AbstractBackgroundTraditional Chinese medicine (TCM) encompasses numerous herbal formulas which play critical therapeutic roles through “multi-components, multi-targets and multi-pathways” mechanisms. Exploring the interaction among these mechanisms can certainly help to depict the core therapeutic function of herbal formulas. Xiaoyao decoction (XYD) is one of the most well-known traditional Chinese medicine formulas which has been widely applied to treat various diseases. In this study, taking XYD as an example, we proposed a network pharmacology-based method to identify the main therapeutic targets of this herbal concoctions.MethodsChemical data of XYD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID) and Compound Reference Database (CRD) and screened oral bioavailability attributes from SwissADME using Veber’s filter. Targets of sample chemicals were identified using the online tool similarity ensemble approach (SEA), and pathways were enriched using STRING database. On the basis of targets–pathways interactions from the enrichment, a “targets–pathways–targets” (TPT) network was constructed. In the TPT network, the importance of each target was calculated by the declining value of network efficiency, which represents the influential strength of a specific set-off target on the whole network. Network-based predictive results were statistically validated with existing experimental evidence.ResultsThe TPT network was comprised of 279 nodes and 6549 edges. The declining value of network efficiency of the sample targets was significantly correlated with their involvement frequency in existing studies of XYD using Spearman’s test (p < 0.001). The top 10% of candidate targets, such as AKT1, PIK3R1, NFKB1 and RELA, etc., were chosen as XYD’s main therapeutic targets, which further show pharmacological functions synergistically through 11 main pathways. These pathways are responsible for endocrine, nutritional or metabolic diseases, neoplasms and diseases of the nervous system, etc.ConclusionsThe network pharmacology-based approach in the present study shows promising potential for identifying the main therapeutic targets from TCM formulas. This study provides valuable information for TCM researchers and clinicians for better understanding the main therapeutic targets and therapeutic roles of herbal decoctions in clinical settings.
Premature termination codon readthrough upregulates progranulin expression and improves lysosomal function in preclinical models of GRN deficiency
Authors: Frew Jonathan , Baradaran-Heravi Alireza , Balgi Aruna D. , Wu Xiujuan , Yan Tyler D. , Arns Steve , Shidmoossavee Fahimeh S. , Tan Jason , Jaquith James B. , Jansen-West Karen R. , Lynn Francis C. , Gao Fen-Biao , Petrucelli Leonard , Feldman Howard H. , Mackenzie Ian R. , Roberge Michel , Nygaard Haakon B. 
Published: March 2020

Abstract
Background
Frontotemporal lobar degeneration (FTLD) is a devastating and progressive disorder, and a common cause of early onset dementia. Progranulin (PGRN) haploinsufficiency due to autosomal dominant mutations in the progranulin gene (GRN) is an important cause of FTLD (FTLD-GRN), and nearly a quarter of these genetic cases are due to a nonsense mutation. Premature termination codons (PTC) can be therapeutically targeted by compounds allowing readthrough, and aminoglycoside antibiotics are known to be potent PTC readthrough drugs. Restoring endogenous PGRN through PTC readthrough has not previously been explored as a therapeutic intervention in FTLD.

Methods
We studied whether the aminoglycoside G418 could increase PGRN expression in HEK293 and human induced pluripotent stem cell (hiPSC)-derived neurons bearing the heterozygous S116X, R418X, and R493X pathogenic GRN nonsense mutations. We further tested a novel substituted phthalimide PTC readthrough enhancer in combination with G418 in our cellular models. We next generated a homozygous R493X knock-in hiPSC isogenic line (R493X−/− KI), assessing whether combination treatment in hiPSC-derived neurons and astrocytes could increase PGRN and ameliorate lysosomal dysfunction relevant to FTLD-GRN. To provide in vivo proof-of-concept of our approach, we measured brain PGRN after intracerebroventricular administration of G418 in mice expressing the V5-tagged GRN nonsense mutation R493X.

Results
The R418X and R493X mutant GRN cell lines responded to PTC readthrough with G418, and treatments increased PGRN levels in R493X−/− KI hiPSC-derived neurons and astrocytes. Combining G418 with a PTC readthrough enhancer increased PGRN levels over G418 treatment alone in vitro. PGRN deficiency has been shown to impair lysosomal function, and the mature form of the lysosomal protease cathepsin D is overexpressed in R493X−/− KI neurons. Increasing PGRN through G418-mediated PTC readthrough normalized this abnormal lysosomal phenotype in R493X−/− KI neuronal cultures. A single intracerebroventricular injection of G418 induced GRN PTC readthrough in 6-week-old AAV-GRN-R493X-V5 mice.

Conclusions
Taken together, our findings suggest that PTC readthrough may be a potential therapeutic strategy for FTLD caused by GRN nonsense mutations.
Sex difference in synaptic plasticity in the anterior cingulate cortex of adult mice
Authors: Liu Ren-Hao , Xue Man , Li Xu-Hui , Zhuo Min 
Published: March 2020

AbstractSex differences in certain types of pain sensitivity and emotional responses have been previously reported. Synaptic plasticity is a key cellular mechanism for pain perception and emotional regulation, including long-term potentiation (LTP) and long-term depression (LTD). However, it is unclear whether there is a sex difference at synaptic level. Recent studies indicate that excitatory transmission and plasticity in the anterior cingulate cortex (ACC) are critical in chronic pain and pain related emotional responses. In the present study, we used 64-channel multielectrode (MED64) system to record synaptic plasticity in the ACC of male and female adult mice. We found that there was no significant difference in theta-burst stimulation (TBS)-induced LTP between female and male mice. Furthermore, the recruitment of inactive channels was also not different. For LTD, we found that LTD was greater in slices of ACC in male mice than female mice. Our results demonstrate that LTP in the ACC does not show any sex-related difference.
BANDITS: Bayesian differential splicing accounting for sample-to-sample variability and mapping uncertainty
Authors: Tiberi Simone , Robinson Mark D. 
Published: March 2020

AbstractAlternative splicing is a biological process during gene expression that allows a single gene to code for multiple proteins. However, splicing patterns can be altered in some conditions or diseases. Here, we present BANDITS, a R/Bioconductor package to perform differential splicing, at both gene and transcript level, based on RNA-seq data. BANDITS uses a Bayesian hierarchical structure to explicitly model the variability between samples and treats the transcript allocation of reads as latent variables. We perform an extensive benchmark across both simulated and experimental RNA-seq datasets, where BANDITS has extremely favourable performance with respect to the competitors considered.
Calcineurin signaling pathway influences Aspergillus niger biofilm formation by affecting hydrophobicity and cell wall integrity
Authors: Liu Li , Yu Bin , Sun Wenjun , Liang Caice , Ying Hanjie , Zhou Shengmin , Niu Huanqing , Wang Yibing , Liu Dong , Chen Yong 
Published: March 2020

Abstract
Background
Biofilms, as a kind of fixed-cell community, can greatly improve industrial fermentation efficiency in immobilized fermentation, but the regulation process is still unclear, which restricts their application. Ca2+ was reported to be a key factor affecting biofilm formation. However, the effect of Ca2+ on biofilm structure and microbiology was yet only studied in bacteria. How Ca2+-mediated calcineurin signaling pathway (CSP) alters biofilm formation in bacteria and fungi has rarely been reported. On this basis, we investigated the regulation of CSP on the formation of biofilm in Aspergillus niger.

Results
Deletion of the key genes MidA, CchA, CrzA or CnaA in the CSP lowered the Ca2+ concentration in the mycelium to a different extent, inhibited the formation of A. niger biofilm, reduced the hydrophobicity and adhesion of spores, destroyed the cell wall integrity of hyphae, and reduced the flocculation ability of hyphae. qRT-PCR results showed that the expression of spore hydrophobic protein RodA, galactosaminogalactan (GAG) biosynthesis genes (uge3, uge5, agd3, gtb3), and α-1,3-glucan biosynthesis genes (ags1, ags3) in the ∆MidA, ∆CchA, ∆CrzA, ∆CnaA strains were significantly down-regulated compared with those of the wild type (WT). In addition, the transcription levels of the chitin synthesis gene (chsB, chsD) and β-1,3-glucan synthesis gene (FksA) were consistent with the change in chitin and β-1,3-glucan contents in mutant strains.

Conclusion
These results indicated that CSP affected the hydrophobicity and adhesion of spores, the integrity of mycelial cell walls and flocculation by affecting Ca2+ levels in mycelium, which in turn affected biofilm formation. This work provides a possible explanation for how CSP changes the formation of A. niger biofilm, and reveals a pathway for controlling biofilm formation in industrial immobilized fermentation.
Biodiesel and flavor compound production using a novel promiscuous cold-adapted SGNH-type lipase (HaSGNH1) from the psychrophilic bacterium Halocynthiibacter arcticus
Authors: Le Ly Thi Huong Luu , Yoo Wanki , Jeon Sangeun , Lee Changwoo , Kim Kyeong Kyu , Lee Jun Hyuck , Kim T. Doohun 
Published: March 2020

Abstract
Background
Biodiesel and flavor compound production using enzymatic transesterification by microbial lipases provides mild reaction conditions and low energy cost compared to the chemical process. SGNH-type lipases are very effective catalysts for enzymatic transesterification due to their high reaction rate, great stability, relatively small size for convenient genetic manipulations, and ease of immobilization. Hence, it is highly important to identify novel SGNH-type lipases with high catalytic efficiencies and good stabilities.

Results
A promiscuous cold-adapted SGNH-type lipase (HaSGNH1) from Halocynthiibacter arcticus was catalytically characterized and functionally explored. HaSGNH1 displayed broad substrate specificity that included tert-butyl acetate, glucose pentaacetate, and p-nitrophenyl esters with excellent stability and high efficiency. Important amino acids (N83, M86, R87, F131, and I173F) around the substrate-binding pocket were shown to be responsible for catalytic activity, substrate specificity, and reaction kinetics. Moreover, immobilized HaSGNH1 was used to produce high yields of butyl and oleic esters.

Conclusions
This work provides a molecular understanding of substrate specificities, catalytic regulation, immobilization, and industrial applications of a promiscuous cold-adapted SGNH-type lipase (HaSGNH1) from H. arcticus. This is the first analysis on biodiesel and flavor synthesis using a cold-adapted halophilic SGNH-type lipase from a Halocynthiibacter species.
Parasite associations predict infection risk: incorporating co-infections in predictive models for neglected tropical diseases
Authors: Clark Nicholas J. , Owada Kei , Ruberanziza Eugene , Ortu Giuseppina , Umulisa Irenee , Bayisenge Ursin , Mbonigaba Jean Bosco , Mucaca Jean Bosco , Lancaster Warren , Fenwick Alan , Soares Magalhães Ricardo J. , Mbituyumuremyi Aimable 
Published: March 2020

AbstractBackgroundSchistosomiasis and infection by soil-transmitted helminths are some of the world’s most prevalent neglected tropical diseases. Infection by more than one parasite (co-infection) is common and can contribute to clinical morbidity in children. Geostatistical analyses of parasite infection data are key for developing mass drug administration strategies, yet most methods ignore co-infections when estimating risk. Infection status for multiple parasites can act as a useful proxy for data-poor individual-level or environmental risk factors while avoiding regression dilution bias. Conditional random fields (CRF) is a multivariate graphical network method that opens new doors in parasite risk mapping by (i) predicting co-infections with high accuracy; (ii) isolating associations among parasites; and (iii) quantifying how these associations change across landscapes.MethodsWe built a spatial CRF to estimate infection risks forAscaris lumbricoides,Trichuris trichiura, hookworms (Ancylostoma duodenaleandNecator americanus) andSchistosoma mansoniusing data from a national survey of Rwandan schoolchildren. We used an ensemble learning approach to generate spatial predictions by simulating from the CRF’s posterior distribution with a multivariate boosted regression tree that captured non-linear relationships between predictors and covariance in infection risks. This CRF ensemble was compared against single parasite gradient boosted machines to assess each model’s performance and prediction uncertainty.ResultsParasite co-infections were common, with 19.57% of children infected with at least two parasites. The CRF ensemble achieved higher predictive power than single-parasite models by improving estimates of co-infection prevalence at the individual level and classifying schools into World Health Organization treatment categories with greater accuracy. The CRF uncovered important environmental and demographic predictors of parasite infection probabilities. Yet even after capturing demographic and environmental risk factors, the presences or absences of other parasites were strong predictors of individual-level infection risk. Spatial predictions delineated high-risk regions in need of anthelminthic treatment interventions, including areas with higher than expected co-infection prevalence.ConclusionsMonitoring studies routinely screen for multiple parasites, yet statistical models generally ignore this multivariate data when assessing risk factors and designing treatment guidelines. Multivariate approaches can be instrumental in the global effort to reduce and eventually eliminate neglected helminth infections in developing countries.
Culicoides species composition and molecular identification of host blood meals at two zoos in the UK
Authors: England Marion E. , Pearce-Kelly Paul , Brugman Victor A. , King Simon , Gubbins Simon , Sach Fiona , Sanders Christopher J. , Masters Nic J. , Denison Eric , Carpenter Simon 
Published: March 2020

AbstractBackgroundCulicoidesbiting midges are biological vectors of arboviruses including bluetongue virus (BTV), Schmallenberg virus (SBV) and African horse sickness virus (AHSV). Zoos are home to a wide range of ‘at risk’ exotic and native species of animals. These animals have a high value both in monetary terms, conservation significance and breeding potential. To understand the risk these viruses pose to zoo animals, it is necessary to characterise theCulicoidesfauna at zoos and determine which potential vector species are feeding on which hosts.MethodsLight-suction traps were used at two UK zoos: the Zoological Society of London (ZSL) London Zoo (LZ) and ZSL Whipsnade Zoo (WZ). Traps were run one night each week from June 2014 to June 2015.Culicoideswere morphologically identified to the species level and any blood-fedCulicoideswere processed for blood-meal analysis. DNA from blood meals was extracted and amplified using previously published primers. Sequencing was then carried out to determine the host species.ResultsA total of 11,648Culicoideswere trapped and identified (n = 5880 from ZSL WZ;n = 5768 from ZSL LZ), constituting 25 different species. The six putative vectors of BTV, SBV and AHSV in northern Europe were found at both zoos and made up the majority of the total catch (n = 10,701). A total of 31 host sequences were obtained from blood-fedCulicoides. Culicoides obsoletus/C. scoticus,Culicoides dewulfi,Culicoides parrotiandCulicoides punctatuswere found to be biting a wide range of mammals including Bactrian camels, Indian rhinoceros, Asian elephants and humans, withCulicoides obsoletus/C. scoticusalso biting Darwin’s rhea. The bird-biting species,Culicoides achrayi, was found to be feeding on blackbirds, blue tits, magpies and carrion crows.ConclusionsTo our knowledge, this is the first study to directly confirm blood-feeding ofCulicoideson exotic zoo animals in the UK and shows that they are able to utilise a wide range of exotic as well as native host species. Due to the susceptibility of some zoo animals toCulicoides-borne arboviruses, this study demonstrates that in the event of an outbreak of one of these viruses in the UK, preventative and mitigating measures would need to be taken.
The conserved DNMT1-dependent methylation regions in human cells are vulnerable to neurotoxicant rotenone exposure
Authors: Freeman Dana M. , Lou Dan , Li Yanqiang , Martos Suzanne N. , Wang Zhibin 
Published: March 2020

Abstract
Background
Allele-specific DNA methylation (ASM) describes genomic loci that maintain CpG methylation at only one inherited allele rather than having coordinated methylation across both alleles. The most prominent of these regions are germline ASMs (gASMs) that control the expression of imprinted genes in a parent of origin-dependent manner and are associated with disease. However, our recent report reveals numerous ASMs at non-imprinted genes. These non-germline ASMs are dependent on DNA methyltransferase 1 (DNMT1) and strikingly show the feature of random, switchable monoallelic methylation patterns in the mouse genome. The significance of these ASMs to human health has not been explored. Due to their shared allelicity with gASMs, herein, we propose that non-traditional ASMs are sensitive to exposures in association with human disease.

Results
We first explore their conservancy in the human genome. Our data show that our putative non-germline ASMs were in conserved regions of the human genome and located adjacent to genes vital for neuronal development and maturation. We next tested the hypothesized vulnerability of these regions by exposing human embryonic kidney cell HEK293 with the neurotoxicant rotenone for 24 h. Indeed,14 genes adjacent to our identified regions were differentially expressed from RNA-sequencing. We analyzed the base-resolution methylation patterns of the predicted non-germline ASMs at two neurological genes, HCN2 and NEFM, with potential to increase the risk of neurodegeneration. Both regions were significantly hypomethylated in response to rotenone.

Conclusions
Our data indicate that non-germline ASMs seem conserved between mouse and human genomes, overlap important regulatory factor binding motifs, and regulate the expression of genes vital to neuronal function. These results support the notion that ASMs are sensitive to environmental factors such as rotenone and may alter the risk of neurological disease later in life by disrupting neuronal development.
DNA looping by two 5-methylcytosine-binding proteins quantified using nanofluidic devices
Authors: Liu Ming , Movahed Saeid , Dangi Saroj , Pan Hai , Kaur Parminder , Bilinovich Stephanie M. , Faison Edgar M. , Leighton Gage O. , Wang Hong , Williams David C. , Riehn Robert 
Published: March 2020

Abstract
Background
MeCP2 and MBD2 are members of a family of proteins that possess a domain that selectively binds 5-methylcytosine in a CpG context. Members of the family interact with other proteins to modulate DNA packing. Stretching of DNA–protein complexes in nanofluidic channels with a cross-section of a few persistence lengths allows us to probe the degree of compaction by proteins.

Results
We demonstrate DNA compaction by MeCP2 while MBD2 does not affect DNA configuration. By using atomic force microscopy (AFM), we determined that the mechanism for compaction by MeCP2 is the formation of bridges between distant DNA stretches and the formation of loops.

Conclusions
Despite sharing a similar specific DNA-binding domain, the impact of full-length 5-methylcytosine-binding proteins can vary drastically between strong compaction of DNA and no discernable large-scale impact of protein binding. We demonstrate that ATTO 565-labeled MBD2 is a good candidate as a staining agent for epigenetic mapping.
The impact of peri-natal stress on psychosis risk: results from the Bo-FEP incidence study
Authors: De Matteis Tiziano , D’Andrea Giuseppe , Lal Jatin , Berardi Domenico , Tarricone Ilaria 
Published: March 2020

Abstract
Objective
According to the gene-environment interaction model the pathogenesis of psychosis relies on an adverse neuro-socio-developmental pathway. Perinatal stress represents an important risk factor for the development of psychosis because of the increasingly evident interference with socio-neuro-development in the earlier phases of life. We aim to investigate the correlation of perinatal risk factors with the onset of psychosis with a case–control–incidence study.

Results
Patients (and their mothers) were eligible if they presented with first-episode psychosis at the Bologna West Community Mental Health Centre (Bo-West CMHC) between 2002 and 2012. The Bo-West CMHC serves a catchment area of about 200,000 people. The controls were recruited in the same catchment area and study period. 42 patients, 26 controls and their mothers were included. We collected the history of peri-natal stress and calculated crude and adjusted Odds Ratios for onset of first-episode psychosis. Adjusted logistic regression showed that psychosis onset was significantly associated with stressful situations during pregnancy, lower level of maternal physical health before or during pregnancy, use of anti-inflammatory drugs during pregnancy, and low level of maternal education. The results of our study suggest that stress during perinatal period increases the risk of developing psychosis.