bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood functional assay for rapid clinical interpretation of germline TP53 variants
Authors: Raad Sabine , Rolain Marion , Coutant Sophie , Derambure Céline , Lanos Raphael , Charbonnier Françoise , Bou Jacqueline , Bouvignies Emilie , Lienard Gwendoline , Vasseur Stéphanie , Farrell Michael , Ingster Olivier , Baert Desurmont Stéphanie , Kasper Edwige , Bougeard Gaëlle , Frébourg Thierry , Tournier Isabelle 
Published: October 2020

BackgroundThe interpretation of germline TP53 variants is critical to ensure appropriate medical management of patients with cancer and follow-up of variant carriers. This interpretation remains complex and is becoming a growing challenge considering the exponential increase in TP53 tests. We developed a functional assay directly performed on patients’ blood.MethodsPeripheral blood mononuclear cells were cultured, activated, exposed to doxorubicin and the p53-mediated transcriptional response was quantified using reverse transcription–multiplex ligation probe amplification and RT-QMPSF assays, including 10 p53 targets selected from transcriptome analysis, and two amplicons to measure p53 mRNA levels. We applied this blood functional assay to 77 patients addressed for TP53 analysis.ResultsIn 51 wild-type TP53 individuals, the mean p53 functionality score was 12.7 (range 7.5–22.8). Among eight individuals harbouring likely pathogenic or pathogenic variants, the scores were reduced (mean 4.8, range 3.1–7.1), and p53 mRNA levels were reduced in patients harbouring truncating variants. We tested 14 rare unclassified variants (p.(Pro72His), p.(Gly105Asp), p.(Arg110His), p.(Phe134Leu), p.(Arg158Cys), p.(Pro191Arg), p.(Pro278Arg), p.(Arg283Cys), p.(Leu348Ser), p.(Asp352Tyr), p.(Gly108_Phe109delinsVal), p.(Asn131del), p.(Leu265del), c.-117G>T) and 12 yielded functionally abnormal scores. Remarkably, the assay revealed that the c.*1175A>C polymorphic variant within TP53 poly-adenylation site can impact p53 function with the same magnitude as a null variant, when present on both alleles, and may act as a modifying factor in pathogenic variant carriers.ConclusionThis blood p53 assay should therefore be a useful tool for the rapid clinical classification of germline TP53 variants and detection of non-coding functional variants.
Association between ARID2 and RAS-MAPK pathway in intellectual disability and short stature
Authors: Kang Eungu , Kang Minji , Ju Younghee , Lee Sang-Joon , Lee Yong-Seok , Woo Dong-Cheol , Sung Young Hoon , Baek In-Jeoung , Shim Woo Hyun , Son Woo-Chan , Choi In Hee , Seo Eul-Ju , Yoo Han-Wook , Han Yong-Mahn , Lee Beom Hee 
Published: October 2020

BackgroundARID2 belongs to the Switch/sucrose non-fermenting complex, in which the genetic defects have been found in patients with dysmorphism, short stature and intellectual disability (ID). As the phenotypes of patients with ARID2 mutations partially overlap with those of RASopathy, this study evaluated the biochemical association between ARID2 and RAS-MAPK pathway.MethodsThe phenotypes of 22 patients with either an ARID2 heterozygous mutation or haploinsufficiency were reviewed. Comprehensive molecular analyses were performed using somatic and induced pluripotent stem cells (iPSCs) of a patient with ARID2 haploinsufficiency as well as using the mouse model of Arid2 haploinsufficiency by CRISPR/Cas9 gene editing.ResultsThe phenotypic characteristics of ARID2 deficiency include RASopathy, Coffin-Lowy syndrome or Coffin-Siris syndrome or undefined syndromic ID. Transient ARID2 knockout HeLa cells using an shRNA increased ERK1 and ERK2 phosphorylation. Impaired neuronal differentiation with enhanced RAS-MAPK activity was observed in patient-iPSCs. In addition, Arid2 haploinsufficient mice exhibited reduced body size and learning/memory deficit. ARID2 haploinsufficiency was associated with reduced IFITM1 expression, which interacts with caveolin-1 (CAV-1) and inhibits ERK activation.DiscussionARID2 haploinsufficiency is associated with enhanced RAS-MAPK activity, leading to reduced IFITM1 and CAV-1 expression, thereby increasing ERK activity. This altered interaction might lead to abnormal neuronal development and a short stature.
Can myocardial work indices contribute to the exploration of patients with cardiac amyloidosis?
Authors: Roger-Rollé Aénora , Cariou Eve , Rguez Khailène , Fournier Pauline , Lavie-Badie Yoan , Blanchard Virginie , Roncalli Jérôme , Galinier Michel , Carrié Didier , Lairez Olivier 
Published: October 2020

BackgroundCardiac amyloidosis (CA) is a life-threatening restrictive cardiomyopathy. Identifying patients with a poor prognosis is essential to ensure appropriate care. The aim of this study was to compare myocardial work (MW) indices with standard echocardiographic parameters in predicting mortality among patients with CA.MethodsClinical, biological and transthoracic echocardiographic parameters were retrospectively compared among 118 patients with CA. Global work index (GWI) was calculated as the area of left ventricular pressure–strain loop. Global work efficiency (GWE) was defined as percentage ratio of constructive work to sum of constructive and wasted works. Sixty-one (52%) patients performed a cardiopulmonary exercise.ResultsGWI, GWE, global longitudinal strain (GLS), left ventricular ejection fraction (LVEF) and myocardial contraction fraction (MCF) were correlated with N-terminal prohormone brain natriuretic peptide (R=−0.518, R=−0.383, R=−0.553, R=−0.382 and R=−0.336, respectively; p<0.001). GWI and GLS were correlated with peak oxygen consumption (R=0.359 and R=0.313, respectively; p<0.05). Twenty-eight (24%) patients died during a median follow-up of 11 (4–19) months. The best cut-off values to predict all-cause mortality for GWI, GWE, GLS, LVEF and MCF were 937 mm Hg/%, 89%, 10%, 52% and 15%, respectively. The area under the receiver operator characteristic curve of GWE, GLS, GWI, LVEF and MCF were 0.689, 0.631, 0.626, 0.511 and 0.504, respectively.ConclusionIn CA population, MW indices are well correlated with known prognosis markers and are better than LVEF and MCF in predicting mortality. However, MW does not perform better than GLS.
Bicuspid aortic valve: different clinical profiles for subjects with versus without repaired aortic coarctation
Authors: Lim Michelle S , Bannon Paul G , Celermajer David S 
Published: October 2020

ObjectivesA small proportion of patients undergoing bicuspid aortic valve (BAV) intervention have had prior repair of aortic coarctation (CoA). We aimed to describe phenotypic differences between BAV patients, comparing those with versus those without previous coarctation repair.Methods556 adults with BAV who had undergone aortic valve and/or ascending aortic surgery were identified, and relevant clinical and operative details were retrospectively analysed.ResultsOf the total cohort, 532 patients (95.7%) had isolated BAV (‘BAV-only’), and 24 (4.3%) had had a previous successful CoA repair (‘BAV-CoA’). The median age at surgery was significantly lower in BAV-CoA patients compared with BAV-only (median, IQR: 40 years, 26–57 vs 62 years, 51–69, p<0.001). Indications for surgery also differed, with BAV-CoA patients much more likely to undergo surgery for aortic regurgitation (BAV-CoA 38% vs BAV-only 13%, p<0.001); patients with isolated BAV were more likely to require surgery for aortic stenosis (BAV-only 75% vs BAV-CoA 50%, p<0.001). Two different BAV morphotypes were commoner in the BAV-CoA group; type 0 valves (24% vs 8%, p<0.05) and type 2 valves (12% vs 3%, p<0.05). The proportion of patients undergoing concomitant aortic surgery at the time of valve surgery were similar (BAV-only 38% vs BAV-CoA 42%, p=0.8).ConclusionIn adult patients undergoing aortic valve surgery for BAV disease, those with a prior history of repaired CoA underwent surgery at a very much younger age, and a higher proportion required intervention for aortic regurgitation.
News coverage of the E-cigarette, or Vaping, product use Associated Lung Injury (EVALI) outbreak and internet searches for vaping cessation
Authors: Leas Eric C , Nobles Alicia L , Caputi Theodore L , Dredze Mark , Zhu Shu-Hong , Cohen Joanna E , Ayers John W 
Published: October 2020

BackgroundIn the latter half of 2019, an outbreak of pulmonary disease in the USA resulted in 2807 hospitalisations and 68 deaths, as of 18 February 2020. Given the severity of the outbreak, we assessed whether articles during the outbreak era more frequently warned about the dangers of vaping and whether internet searches for vaping cessation increased.MethodsUsing Tobacco Watcher, a media monitoring platform that automatically identifies and categorises news articles from sources across the globe, we obtained all articles that (a) discussed the outbreak and (b) primarily warned about the dangers of vaping. We obtained internet search trends originating from the USA that mentioned ‘quit’ or ‘stop’ and ‘e cig(s),’ ‘ecig(s),’ ‘e-cig(s),’ ‘e cigarette(s),’ ‘e-cigarette(s),’ ‘electronic cigarette(s),’ ‘vape(s),’ ‘vaping’ or ‘vaper(s)’ from Google Trends (eg, ‘how do I quit vaping?’). All data were obtained from 1 January 2014 to 18 February 2020 and ARIMA models were used with historical trends to forecast the ratio of observed to expected search volumes during the outbreak era.ResultsNews of the vaping-induced pulmonary disease outbreak was first reported on 25 July 2019 with 195 articles, culminating in 44 512 articles by 18 February 2020. On average, news articles warning about the dangers of vaping were 130% (95% prediction
interval (PI): −15 to 417) and searches for vaping cessation were 76% (95% PI: 28 to 182) higher than expected levels for the days during the period when the sources of the outbreak were unknown (25 July to 27 September 2019). News and searches stabilised just after the US Centers for Disease Control and Prevention reported that a primary source of the outbreak was an additive used in marijuana vapes on 27 September 2019. In sum, there were 12 286 articles archived in Tobacco Watcher primarily warning about the dangers of vaping and 1 025 000 cessation searches following the outbreak.ConclusionThe vaping-induced pulmonary disease outbreak spawned increased coverage about the dangers of vaping and internet searches for vaping cessation. Resources and strategies that respond to this elevated interest should become a priority among public health leaders.
Spindle Cell Melanoma Presenting as an Ulcer in a Black Diabetic
Authors: Gaskin D. A. , Brathwaite D. , Depeiza N. , Gaskin P. S. , Ward J. 
Published: October 2020

Background. Melanoma in blacks is uncommon and exceedingly rare in association with a diabetic ulcer. We present a case of a spindle cell melanoma masquerading as a diabetic ulcer. Case Report. A 57-year-old overweight woman presented to The Maria Holder Diabetes Centre for the Caribbean with a nonhealing ulcer of the right heel after being treated by various primary care physicians over the preceding year. Her general and systematic examinations were unremarkable. There was a

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cm ulcer with a necrotic base which bled easily on contact with no evidence of peripheral neuropathy nor arterial insufficiency. Microscopic examination of a biopsy of the lesion showed fascicles of spindle cells with plump nuclei and intracytoplasmic yellow-brown pigment. Immunohistochemistry confirmed a diagnosis of melanoma. Discussion. There should be a high index of suspicion of malignancy with nonhealing diabetic ulcer especially when coupled with short disease duration. This case highlights the importance of a biopsy and histological evaluation in ulcers presenting in recently diagnosed diabetics with no evidence of peripheral neuropathy or vascular disease. Melanoma should be considered in spindle cell lesions especially with pigment and residual nevus cells.
Probabilistic Contextual and Structural Dependencies Learning in Grammar-Based Genetic Programming
Authors: Wong Pak-Kan , Wong Man-Leung , Leung Kwong-Sak 
Published: October 2020

AbstractGenetic Programming is a method to automatically create computer programs based on the principles of evolution. The problem of deceptiveness caused by complex dependencies among components of programs is challenging. It is important because it can misguide Genetic Programming to create suboptimal programs. Besides, a minor modification in the programs may lead to a notable change in the program behaviours and affect the final outputs. This article presents Grammar-Based Genetic Programming with Bayesian Classifiers (GBGPBC) in which the probabilistic dependencies among components of programs are captured using a set of Bayesian network classifiers. Our system was evaluated using a set of benchmark problems (the deceptive maximum problems, the royal tree problems, and the bipolar asymmetric royal tree problems). It was shown to be often more robust and more efficient in searching the best programs than other related Genetic Programming approaches in terms of the total number of fitness evaluation. We studied what factors affect the performance of GBGPBC and discovered that robust variants of GBGPBC were consistently weakly correlated with some complexity measures. Furthermore, our approach has been applied to learn a ranking program on a set of customers in direct marketing. Our suggested solutions help companies to earn significantly more when compared with other solutions produced by several well-known machine learning algorithms, such as neural networks, logistic regression, and Bayesian networks.
Melanophore metachrosis response in amphibian tadpoles: effect of background colour, light and temperature
Authors: Rodríguez-Rodríguez Eduardo José , Beltrán Juan Francisco , Márquez Rafael 
Published: October 2020

Abstract
The developmental and biochemical mechanisms of colour change through chromatophore metachrosis in amphibian tadpoles are relatively well studied, but the environmental factors driving colour change remain unclear. A cryptic response to background colour in order to reduce predation is an intuitively valid explanation, however, other hypotheses need to be explored. In this study, we aimed to investigate the environmental factors driving the melanophore metachrosis process in Alytes dickhilleni tadpoles. First, we tested the response to two backgrounds with clearly distinct reflectance: black and white. The proportion of dark tadpoles became significantly higher when they were located on the black background, and pale tadpole proportion was dominant on the white background, as expected from the crypsis hypothesis. Secondly, we added two new factors, temperature and photoperiod, maintaining the background variation. Our results suggest that lower temperatures, and short photoperiods were significantly driving a change to dark colouration in tadpoles, possibly allowing a more efficient thermoregulation, and in consequence, development and growth. Next we tested whether dark and pale tadpoles selected backgrounds that matched their colouration (black and white background), and found no evidence for behavioral selection. The apparent response in colour change to background appears to be mediated by the background reflectance of light, that there does not seem to be behavioral selection of matching background by the tadpoles, and therefore it suggests that color change is more likely to be a physiological response with thermoregulatory implications.
Some Ancient Greek and Twentieth-Century Theories of Value
Authors: Kraut Richard 
Published: October 2020

Abstract
Plato puts goodness at the center of all practical thinking but offers no definition of it and implies that philosophy must find one. Aristotle demurs, arguing that there is no such thing as universal goodness. What we need, instead, is an understanding of the human good. Plato and Aristotle are alike in the attention they give to the category of the beneficial, and they agree that since some things are beneficial only as means, there must be others that are non-derivatively beneficial. When G. E. Moore proposed in the early twentieth century that goodness is, as Plato had said, the foundation of ethics, he rejected not only the assumption that goodness needs a definition, but also that goodness is beneficial – that is, good for someone. This article traces the development of this debate as it plays out in the writings of Prichard, Ross, Geach, Thomson, and Scanlon.
The Place of Subjectivity
Authors: Halbig Christoph 
Published: October 2020

Abstract
The modern debate on the theory of prudential values is largely structured around the issue of how to accommodate the role of subjectivity: a prudentially good life (unlike, say, a morally good life) seems to be necessarily a life that is good for the person living it. The present article aims at clarifying this crucial role of subjectivity in the ontology of prudential values. It tries to show that this role, rightly understood, can be fully and satisfactorily accounted for by a strong realism in the theory of prudential value. Subjectivist intuitions that prove incompatible with such a realist framework, it is argued, can be convincingly rejected on independent grounds.
The Worst Things in Life
Authors: Sumner Wayne 
Published: October 2020

Abstract
One important test of adequacy for a theory of welfare is completeness. To be complete a theory must cover ill-being as well as well-being. Call this the ill-being test for a theory. The author’s aim in this article is to determine how well equipped the leading theories of welfare are to pass this test. The author reaches three modest conclusions: (1) passing the test is not straightforward for any theory; (2) on the whole, subjective theories do better than objective ones; (3) within the subjective category experiential theories do better than desire theories.
Anti-Realism and Anti-Revisionism in Wittgenstein’s Philosophy of Mathematics
Authors: Nakano Anderson 
Published: October 2020

Abstract
Since the publication of the Remarks on the Foundations of Mathematics, Wittgenstein’s interpreters have endeavored to reconcile his general constructivist/anti-realist attitude towards mathematics with his confessed anti-revisionary philosophy. In this article, the author revisits the issue and presents a solution. The basic idea consists in exploring the fact that the so-called “non-constructive results” could be interpreted so that they do not appear non-constructive at all. The author substantiates this solution by showing how the translation of mathematical results, given by the possibility of translation between logics, can be seen as a tool for partially implementing the solution Wittgenstein had in mind.
Mathematical Philology in the Treatise on Double False Position in an Arabic Manuscript at Columbia University
Authors: Roberts Alexandre M. 
Published: October 2020

Abstract
This article examines an Arabic mathematical manuscript at Columbia University’s Rare Book and Manuscript Library (or. 45), focusing on a previously unpublished set of texts: the treatise on the mathematical method known as Double False Position, as supplemented by Jābir ibn Ibrāhīm al-Ṣābī (tenth century?), and the commentaries by Aḥmad ibn al-Sarī (d. 548/1153–4) and Saʿd al-Dīn Asʿad ibn Saʿīd al-Hamadhānī (12th/13th century?), the latter previously unnoticed. The article sketches the contents of the manuscript, then offers an editio princeps, translation, and analysis of the treatise. It then considers how the Swiss historian of mathematics Heinrich Suter (1848–1922) read Jābir’s treatise (as contained in a different manuscript) before concluding with my own proposal for how to go about reading this mathematical text: as a witness of multiple stages of a complex textual tradition of teaching, extending, and rethinking mathematics—that is, we should read it philologically.
On Original and “Originals”: The “Copy” of the Tashkent Qurʾān Codex in the Rare Collection Books at the Butler Library
Authors: Shalem Avinoam 
Published: October 2020

Abstract
In 1905, Dr. S. Pissareff from St. Petersburg was involved in the production of 50 copies of an earlier Qurʾān codex. The original, namely the Qurʾān codex first discovered to western gaze around the mid 19th century, held in the Khoja Akhrar mosque in Samarqand, is a large-sized Qurʾānic manuscript written in Kufic on parchment with hardly any use of punctuation or vowel marks. This codex has been traditionally regarded as the muṣḥaf of ʿUthmān b. ʿAffān, the third caliph (murdered in 656), and was said to have been brought from Iraq by Timur. This essay presents the ‘Pissareff copy’ kept at the Rare Book and Manuscript Library at Columbia University, discusses its specific status as residing in the grey zone between reproduction and copy, and aims at setting it in the larger context of ‘copies’ of Qurʾān codices.
The association between lithium in drinking water and neuropsychiatric outcomes: A systematic review and meta-analysis from across 2678 regions containing 113 million people
Authors: Eyre-Watt Brenton , Mahendran Eesharnan , Suetani Shuichi , Firth Joseph , Kisely Steve , Siskind Dan 
Published: October 2020

Background: Lithium in drinking water may have significant mental health benefits. We investigated the evidence on the association between lithium concentrations in drinking water and their neuropsychiatric outcomes. Methods: We conducted a systematic review and meta-analysis and searched Pubmed, Embase, Web of Science, PsycINFO and CINAHL up to 19 January 2020, for peer-reviewed research examining the association between lithium concentrations in drinking water and neuropsychiatric outcomes. We used a pairwise analysis and a random effects model to meta-analyse suicide rates and psychiatric hospital admissions. We assessed for publication bias using Egger’s test and Duval and Tweedie’s Trim and Fill analysis. Results: Twenty-seven studies including 113 million subjects were included in this systematic review. Meta-analysis of 14 studies including 94 million people found higher lithium concentrations were associated with reduced suicide rates ( r = −0.191, 95% confidence interval = [−0.287, −0.090], p < 0.001) and meta-analysis of two studies including 5 million people found higher lithium concentrations were associated with fewer hospital admissions ( r = −0.413, 95% confidence interval = [−0.689, −0.031], p = 0.035). We found significant heterogeneity between studies ( Q = 67.4, p < 0.001, I2 = 80.7%) and the presence of publication bias (Egger’s test; t value = 2.90, p = 0.013). Other included studies did not provide sufficient data to analyse other neuropsychiatric outcomes quantitatively. Conclusion: Higher lithium concentrations in drinking water may be associated with reduced suicide rates and inpatient psychiatric admissions. The relationship with other neuropsychiatric outcomes and complications remains unclear. Further research is required before any public health recommendations can be made. Trial registration number: The study was registered with PROSPERO, number CRD42018090145.