bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of TP53 expression and MGMT methylation in glioblastoma patients treated with temozolomide combined with other chemotherapies
Authors: Kurdi Maher , Butt Nadeem Shafique , Baeesa Saleh , Alghamdi Badrah , Maghrabi Yazid , Bardeesi Anas , Saeedi Rothaina , Dallol Ashraf , Mohamed Fawaz , Bari Mohammed O. , Samkari Alaa , Lary Ahmed I. , Alkhayyat Shadi 
Published: March 2021

Abstract
Objective
To assess the recurrence interval and predictive significance of TP53 expression and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in glioblastomas treated with radiotherapy and combined chemotherapies, including temozolomide, lomustine, procarbazine and bevacizumab.

Method
We reviewed the clinical outcomes of 52 totally resected glioblastoma patients, who received conventional radiotherapy and temozolomide with other chemotherapeutic agents. Correlation of TP53 expression and MGMT promotor methylation with recurrence interval was analyzed using Kaplan Meier estimates.

Results
No significant association was found between MGMT promotor methylation and TP53 expression in glioblastomas (P-value = 0.158). Patients with non-methylated MGMT who received temozolomide chemotherapy with other chemotherapeutic agents showed significantly later recurrence (P-value = 0.007) compared with patients with non-methylated MGMT who received temozolomide alone. No significant difference was found in recurrence interval among glioblastoma patients with methylated MGMT who received temozolomide alone or with other chemotherapies (P-value = 0.667). Moreover, patients with non-TP53-expressing tumors who received temozolomide with other chemotherapies had significantly later recurrence (P-value = 0.04) compared with patients who received temozolomide alone.

Conclusion
Totally resected glioblastoma patients, with non-methylated MGMT or non-TP53-expressing tumors treated with radiotherapy and combined chemotherapies had a reduced chance of tumor recurrence and a more favorable outcome. Furthermore, both MGMT and TP53 are independent prognostic factors for glioblastoma.
Quality of information of websites dedicated to obesity: a systematic search to promote high level of information for Internet users and professionals
Authors: Perra Alessandra , Preti Antonio , De Lorenzo Valerio , Nardi Antonio Egidio , Carta Mauro G. 
Published: March 2021

Abstract
Background
The Internet is increasingly used as a source of information. This study investigates with a multidimensional methodology the quality of information of websites dedicated to obesity treatment and weight-loss interventions. We compared websites in English, a language that it is used for the international scientific divulgation, and in Italian, a popular local language.

Methods
Level of Evidence: Level I, systematic review search on four largely used search engines. Duplicated and unrelated websites were excluded. We checked: popularity with PageRank; technological quality with Nibbler; readability with the Flesch Reading Ease test or the Gulpease readability index; quality of information with the DISCERN scale, the JAMA benchmark criteria, and the adherence to the Health on the Net Code.

Results
63 Italian websites and 41 English websites were evaluated. English websites invested more in the technological quality especially for the marketing, experience of the user, and mobile accessibility. Both the Italian and English websites were of poor quality and readability.

Conclusions
These results can inform guidelines for the improvement of health information and help Internet users to achieve a higher level of information. Users must find benefits of treatment, support to the shared decision-making, the sources used, the medical editor's supervision, and the risk of postponing the treatment.
Linking bank clients using graph neural networks powered by rich transactional data
Authors: Shumovskaia Valentina , Fedyanin Kirill , Sukharev Ivan , Berestnev Dmitry , Panov Maxim 
Published: March 2021

AbstractFinancial institutions obtain enormous amounts of data about client transactions and money transfers, which can be considered as a large graph dynamically changing in time. In this work, we focus on the task of predicting new interactions in the network of bank clients and treat it as a link prediction problem. We propose a new graph neural network model, which uses not only the topological structure of the network but rich time-series data available for the graph nodes and edges. We evaluate the developed method using the data provided by a large European bank for several years. The proposed model outperforms the existing approaches, including other neural network models, with a significant gap in ROC AUC score on link prediction problem and also allows to improve the quality of credit scoring.
Housing Prices and Government Approval: The Impact of Housing Booms on Left- and Right-Wing Governments in 16 Advanced Industrialized Countries
Authors: Han Sung Min , Shin Mi Jeong 
Published: March 2021

AbstractIn this article, we argue that rising housing prices increase voter approval of incumbent governments because such a rise increases personal wealth, which leads to greater voter satisfaction. This effect is strongest under right-wing governments because those who benefit from rising prices—homeowners—are more likely to be right-leaning. Non-homeowners, who are more likely to vote for left-leaning parties, will view rising housing prices as a disadvantage and therefore feel the government does not serve them well, which will mitigate the advantage to left-wing governments. We find support for our arguments using both macro-level data (housing prices and government approval ratings in 16 industrialized countries between 1960 and 2017) and micro-level data (housing prices and individuals’ vote choices in the United Kingdom using the British Household Panel Survey). The findings imply that housing booms benefit incumbent governments generally and right-wing ones in particular.
“Hello. May I speak with someone, please? It's not about my physical pain.”: A retrospective study about the factors associated with phone calls to a Portuguese home-based palliative care team
Authors: Julião Miguel , Antunes Bárbara , Samorinha Catarina , Chochinov Harvey Max 
Published: March 2021

AbstractObjectiveTelephone availability is integrated into our home-based palliative care team (HPCT) with the aim of helping terminally ill patients and their caregivers alleviate their physical and psychosocial suffering, in addition to the team's home visits. We aimed to compare the differences between non-callers (patients with no phone calls during the team's follow-up period) vs. callers (≥1 phone call during the team's follow-up period) across sociodemographic, clinical, physical, and psychosocial variables.MethodRetrospective analysis of all patients with and without phone call entries registered in our anonymized database, from October 2018 to September 2020.ResultsWe analyzed 389 patients: 58% were male, and the average age was 71 years old; 84% had malignancies, with a mean palliative performance status of 45%. The majority of patients (n = 281, 72%) made at least one phone call to HPCT. On average, a mean of 2.5 calls (SD = 3.61; range: 0–26) per patient was registered. Callers compared with non-callers more frequently lived with someone (p = 0.030), preferred home as a place to die (p = 0.039), had more doctor (p = 0.010) and nurse home visits (p = 0.006), a prolonged HPCT follow-up time (p = 0.053), along with more frequent emergency room visits (p < 0.001) and hospitalizations (p = 0.043). Moreover, those who made at least one phone call to the HPCT had a higher frequency of conspiracy of silence (p = 0.046), anxiety (p = 0.044), and lower palliative performance status (p = 0.001). No statistically significant associations or differences were found for the other variables.Significance of resultsSeveral factors seem to correlate with an increased number of phone calls, and physical suffering does not play a relevant role in triggering contacts, in contrast with psychosocial and other clinical factors.
The translocator protein (TSPO) is prodromal to mitophagy loss in neurotoxicity
Authors: Frison Michele , Faccenda Danilo , Abeti Rosella , Rigon Manuel , Strobbe Daniela , England-Rendon Britannie S. , Cash Diana , Barnes Katy , Sadeghian Mona , Sajic Marija , Wells Lisa A. , Xia Dong , Giunti Paola , Smith Kenneth , Mortiboys Heather , Turkheimer Federico E. , Campanella Michelangelo 
Published: March 2021

AbstractDysfunctional mitochondria characterise Parkinson’s Disease (PD). Uncovering etiological molecules, which harm the homeostasis of mitochondria in response to pathological cues, is therefore pivotal to inform early diagnosis and therapy in the condition, especially in its idiopathic forms. This study proposes the 18 kDa Translocator Protein (TSPO) to be one of those. Both in vitro and in vivo data show that neurotoxins, which phenotypically mimic PD, increase TSPO to enhance cellular redox-stress, susceptibility to dopamine-induced cell death, and repression of ubiquitin-dependent mitophagy. TSPO amplifies the extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signalling, forming positive feedback, which represses the transcription factor EB (TFEB) and the controlled production of lysosomes. Finally, genetic variances in the transcriptome confirm that TSPO is required to alter the autophagy–lysosomal pathway during neurotoxicity.
Colocalization analysis of polycystic ovary syndrome to identify potential disease-mediating genes and proteins
Authors: Censin Jenny C. , Bovijn Jonas , Holmes Michael V. , Lindgren Cecilia M. 
Published: March 2021

AbstractPolycystic ovary syndrome (PCOS) is a common complex disease in women with a strong genetic component and downstream consequences for reproductive, metabolic and psychological health. There are currently 19 known PCOS risk loci, primarily identified in women of Han Chinese or European ancestry, and 14 of these risk loci were identified or replicated in a genome-wide association study of PCOS performed in up to 10,074 cases and 103,164 controls of European descent. However, for most of these loci the gene responsible for the association is unknown. We therefore use a Bayesian colocalization approach (Coloc) to highlight genes in PCOS-associated regions that may have a role in mediating the disease risk. We evaluated the posterior probabilities of evidence consistent with shared causal variants between 14 PCOS genetic risk loci and intermediate cellular phenotypes in one protein (N = 3301) and two expression quantitative trait locus datasets (N = 31,684 andN = 80–491). Through these analyses, we identified seven proteins or genes with evidence of a possibly shared causal variant for almost 30% of known PCOS signals, including follicle stimulating hormone andERBB3,IKZF4,RPS26,SUOX,ZFP36L2, andC8orf49. Several of these potential effector proteins and genes have been implicated in the hypothalamic–pituitary–gonadal signalling pathway and provide an avenue for functional follow-up in order to demonstrate a causal role in PCOS pathophysiology.
A cryptic splice-altering KCNQ1 variant in trans with R259L leading to Jervell and Lange-Nielsen syndrome
Authors: Torrado Mario , Fernández Germán , Ganoza Christian A. , Maneiro Emilia , García Diego , Sonicheva-Paterson Natalia , Rosa Isaac , Ochoa Juan Pablo , Santomé Luis , Vasichkina Elena , Monserrat Lorenzo 
Published: March 2021

AbstractHere we report an infant with clinical findings suggestive of Jervell and Lange-Nielsen syndrome (JLNS), including a prolonged QT interval (LQTS) and chronic bilateral sensorineural deafness. NGS analysis revealed one known heterozygous pathogenic missense variant, KCNQ1 p.R259L, previously associated with LQTS but insufficient to explain the cardioauditory disorder. In a screening of proximal intronic regions, we found a heterozygous variant, KCNQ1 c.1686−9 T > C, absent from controls and previously undescribed. Several splicing prediction tools returned low scores for this intronic variant. Driven by the proband’s phenotype rather than the neutral predictions, we have characterized this rare intronic variant. Family analysis has shown that the proband inherited the missense and the intronic variants from his mother and father, respectively. A minigene splicing assay revealed that the intronic variant induced an additional transcript, arising from skipping of exon 14, which was translated into a truncated protein in transfected cells. The splice-out of exon 14 creates a frameshift in exon 15 and a stop codon in exon 16, which is the last exon of KCNQ1. This mis-spliced transcript is expected to escape nonsense-mediated decay and predicted to encode a truncated loss-of-function protein, KCNQ1 p.L563Kfs*73. The analysis of endogenous KCNQ1 expression in the blood of the proband’s parents detected the aberrant transcript only in the patient’s father. Taken together, these analyses confirmed the proband’s diagnosis of JLNS1 and indicated that c.1686−9 T > C is a cryptic splice-altering variant, expanding the known genetic spectrum of biallelic KCNQ1 variant combinations leading to JLNS1.
Australia and New Zealand renal gene panel testing in routine clinical practice of 542 families
Authors: Tanudisastro Hope A. , Holman Katherine , Ho Gladys , Farnsworth Elizabeth , Fisk Katrina , Gayagay Thet , Hackett Emma , Jenkins Gemma , Krishnaraj Rahul , Lai Tiffany , Wong Karen , Patel Chirag , Mallawaarachchi Amali , Mallett Andrew J. , Bennetts Bruce , Alexander Stephen I. , McCarthy Hugh J. 
Published: March 2021

AbstractGenetic testing in nephrology clinical practice has moved rapidly from a rare specialized test to routine practice both in pediatric and adult nephrology. However, clear information pertaining to the likely outcome of testing is still missing. Here we describe the experience of the accredited Australia and New Zealand Renal Gene Panels clinical service, reporting on sequencing for 552 individuals from 542 families with suspected kidney disease in Australia and New Zealand. An increasing number of referrals have been processed since service inception with an overall diagnostic rate of 35%. The likelihood of identifying a causative variant varies according to both age at referral and gene panel. Although results from high throughput genetic testing have been primarily for diagnostic purposes, they will increasingly play an important role in directing treatment, genetic counseling, and family planning.
Colour vision deficiency and sputum colour charts in COPD patients: an exploratory mixed-method study
Authors: Channa Sunita , Gale Nicola , Lai Emma , Hall Lara , Quinn Mark , Turner Alice M. 
Published: March 2021

AbstractSputum colour may mark bacterial involvement in acute exacerbations of chronic obstructive pulmonary disease (COPD). However, whether colour vision deficiency (CVD) in COPD patients could impact the use of sputum colour charts as part of a guide to antibiotic use in exacerbations is unknown. This study used an exploratory mixed-method approach to establish the likelihood that COPD patients will be colour blind and whether this would result in the sputum colour chart being unusable in the context of the patients’ self-management of their condition. CVD is under-reported in primary care and comorbidities in COPD patients increase the risk of acquiring CVD. Participants diagnosed with CVD and risk of acquiring CVD were able to use the sputum colour charts. Colour charts are likely to be usable even in the context of undiagnosed CVD in COPD patients.
Archean continental crust formed by magma hybridization and voluminous partial melting
Authors: Hernández-Montenegro Juan David , Palin Richard M. , Zuluaga Carlos A. , Hernández-Uribe David 
Published: March 2021

AbstractArchean (4.0–2.5 Ga) tonalite–trondhjemite–granodiorite (TTG) terranes represent fragments of Earth’s first continents that formed via high-grade metamorphism and partial melting of hydrated basaltic crust. While a range of geodynamic regimes can explain the production of TTG magmas, the processes by which they separated from their source and acquired distinctive geochemical signatures remain uncertain. This limits our understanding of how the continental crust internally differentiates, which in turn controls its potential for long-term stabilization as cratonic nuclei. Here, we show via petrological modeling that hydrous Archean mafic crust metamorphosed in a non-plate tectonic regime produces individual pulses of magma with major-, minor-, and trace-element signatures resembling—but not always matching—natural Archean TTGs. Critically, magma hybridization due to co-mingling and accumulation of multiple melt fractions during ascent through the overlying crust eliminates geochemical discrepancies identified when assuming that TTGs formed via crystallization of discrete melt pulses. We posit that much Archean continental crust is made of hybrid magmas that represent up to ~ 40 vol% of partial melts produced along thermal gradients of 50–100 °C/kbar, characteristic of overthickened mafic Archean crust at the head of a mantle plume, crustal overturns, or lithospheric peels.
Detecting early myocardial ischemia in rat heart by MALDI imaging mass spectrometry
Authors: Aljakna Khan Aleksandra , Bararpour Nasim , Gorka Marie , Joye Timothée , Morel Sandrine , Montessuit Christophe A. , Grabherr Silke , Fracasso Tony , Augsburger Marc , Kwak Brenda R. , Thomas Aurélien , Sabatasso Sara 
Published: March 2021

AbstractDiagnostics of myocardial infarction in human post-mortem hearts can be achieved only if ischemia persisted for at least 6–12 h when certain morphological changes appear in myocardium. The initial 4 h of ischemia is difficult to diagnose due to lack of a standardized method. Developing a panel of molecular tissue markers is a promising approach and can be accelerated by characterization of molecular changes. This study is the first untargeted metabolomic profiling of ischemic myocardium during the initial 4 h directly from tissue section. Ischemic hearts from an ex-vivo Langendorff model were analysed using matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) at 15 min, 30 min, 1 h, 2 h, and 4 h. Region-specific molecular changes were identified even in absence of evident histological lesions and were segregated by unsupervised cluster analysis. Significantly differentially expressed features were detected by multivariate analysis starting at 15 min while their number increased with prolonged ischemia. The biggest significant increase at 15 min was observed for m/z 682.1294 (likely corresponding to S-NADHX—a damage product of nicotinamide adenine dinucleotide (NADH)). Based on the previously reported role of NAD+/NADH ratio in regulating localization of the sodium channel (Nav1.5) at the plasma membrane, Nav1.5 was evaluated by immunofluorescence. As expected, a fainter signal was observed at the plasma membrane in the predicted ischemic region starting 30 min of ischemia and the change became the most pronounced by 4 h. Metabolomic changes occur early during ischemia, can assist in identifying markers for post-mortem diagnostics and improve understanding of molecular mechanisms.
Comparative transcriptome and metabolome profiling reveal molecular mechanisms underlying OsDRAP1-mediated salt tolerance in rice
Authors: Wang Yinxiao , Huang Liyu , Du Fengping , Wang Juan , Zhao Xiuqin , Li Zhikang , Wang Wensheng , Xu Jianlong , Fu Binying 
Published: March 2021

AbstractIntegration of transcriptomics and metabolomics data can provide detailed information for better understanding the molecular mechanisms underlying salt tolerance in rice. In the present study, we report a comprehensive analysis of the transcriptome and metabolome of rice overexpressing theOsDRAP1gene, which encodes an ERF transcription factor and was previously identified to be conferring drought tolerance. Phenotypic analysis showed thatOsDRAP1overexpression (OE) improved salt tolerance by increasing the survival rate under salt stress.OsDRAP1affected the physiological indices such as superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) to enhance redox homeostasis and membrane stability in response to salt stress. Higher basal expression ofOsDRAP1resulted in differential expression of genes that potentially function in intrinsic salt tolerance. A core set of genes with distinct functions in transcriptional regulation, organelle gene expression and ion transport were substantially up-regulated in the OE line in response to salt stress, implying their important role inOsDRAP1-mediated salt tolerance. Correspondingly, metabolome profiling detected a number of differentially metabolites in the OE line relative to the wild type under salt stress. These metabolites, including amino acids (proline, valine), organic acids (glyceric acid, phosphoenolpyruvic acid and ascorbic acid) and many secondary metabolites, accumulated to higher levels in the OE line, demonstrating their role in salt tolerance. Integration of transcriptome and metabolome analysis highlights the crucial role of amino acids and carbohydrate metabolism pathways inOsDRAP1-mediated salt tolerance.
The discovery of a novel knockdown resistance (kdr) mutation A1007G on Aedes aegypti (Diptera: Culicidae) from Malaysia
Authors: Zuharah Wan Fatma , Sufian Maryam 
Published: March 2021

AbstractThe usage of insecticide rendered the successful vector control program with the high usage of the pyrethroid. However, the intensive and extensive use of pyrethroid, causing resistance in Aedesaegypti and hampered the control program. Knockdown resistance (kdr) resulting from the Voltage-Gated Sodium Channel (VGSC) is one of the mechanisms of resistance in pyrethroid group insecticide. Investigating the phenotypic status of Ae.aegypti mosquitoes is a lead in knowing the current resistance status and as an indicator of the genotypic resistance. In this study, we investigate the resistance in phenotypic and genotypic of Ae.aegypti with a new kdr mutation point A1007G was detected. Using the adult bioassay, we tested the phenotypic resistance from the Selangor state against 0.75% permethrin, 0.05% deltamethrin with and without the addition of PBO synergist. Permethrin-resistant and deltamethrin-resistant, including susceptible samples, were subjected to genotyping analysis on mutation point in domain II and domain III of Voltage-Gated Sodium Channel (VGSC). Adult bioassay revealed that the Ae.aegypti was highly resistance toward 0.75% permethrin and 0.05% deltamethrin. The bioassay with the presence of PBO synergist showed an increment of mortality rate, but Ae.aegypti status is still resistance towards both insecticides. Genotyping result showed that three common kdr mutations (S989P, V1016G, and F1534C) have existed in the Ae.aegypti population. A new novel mutation on A1007G was also detected in this population, which is the first time reported. This study has brought a piece of information on the current resistance status in Ae.aegypti in Malaysia. The detection of new mutation point of A1007G has added the knowledge on the resistance in mosquitoes. Thus, this study will aid with the decision making in the usage of insecticides in the vector control program; before this invaluable insecticide rendered ineffective in killing mosquitoes.