bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell cycLe inhibitiON to target the EVolution of urOthelial cancer (CLONEVO): A single-arm, open-label window-of-opportunity trial of neoadjuvant abemaciclib in platinum-ineligible muscle invasive bladder cancer patients.
Authors: Nauseef Jones , Vlachostergios Panagiotis J. , Molina Ana M. , Nanus David M. , Sternberg Cora N. , McClure Timothy D , Scherr Douglas , Martin M. Laura , Inghirami Giorgio , Elemento Olivier , Tagawa Scott T. , Faltas Bishoy Morris 
Published: February 2020

TPS606 Background: The standard of care for clinically localized muscle-invasive bladder cancer (MIBC) is neoadjuvant platinum-based combination chemotherapy followed by radical cystectomy (RC). Up to 40% of patients (pts) are ineligible to receive cisplatin and proceed to RC without any neoadjuvant therapy. We and others have demonstrated enrichment of molecular alterations in cell cycle genes in MIBC, including copy number losses of CDKN2A in 41% of pts. Abemaciclib is a unique CDK4/6 inhibitor with single agent activity and a target kinome distinct from other CDK4/6 inhibitors. We have demonstrated that CRISPR knockout of CDKN2A increases susceptibility to abemaciclib in bladder cancer cell lines. Beyond tumor-intrinsic effects, abemaciclib also modulates the tumor microenvironment (TME) via upregulating human endogenous retroviral elements and increasing T cell infiltration. Methods: Cell cycLe inhibitiON to target the EVolution of urOthelial cancer (CLONEVO) is a single arm, window-of-opportunity trial of neoadjuvant abemaciclib which will evaluate tumor cell and TME changes in response to abemaciclib. Enrolled pts must be ineligible for platinum-based neoadjuvant therapy for resectable MIBC. Pts receive abemaciclib (200 mg BID PO) for 4 weeks prior to RC. Tumor tissue collected via transurethral resection of bladder tumor (TURBT) and residual tumor at RC undergo single cell RNA sequencing and whole-exome sequencing. Patient-derived organoids and xenografts are generated for a co-clinical trial of abemaciclib alone or in combination. The primary endpoint is the measurement of changes in cell cycle dynamics. Secondary objectives are assessment of toxicity via NCI CTCAE v 5.0 and pathologic downstaging of MIBC. We will perform targeted sequencing of a panel of cell cycle genes in serial plasma and urine cell free DNA to evaluate changes in the variant allele fractions of somatic alterations. The novel design of this trial allows dynamic in vivo assessment of tumor changes and creates a new paradigm for studying tumor evolution in real time. Clinical trial information: NCT03837821.
PIVOT-09: A phase III randomized open-label study of bempegaldesleukin (NKTR-214) plus nivolumab versus sunitinib or cabozantinib (investigator's choice) in patients with previously untreated advanced renal cell carcinoma (RCC).
Authors: Tannir Nizar M. , Agarwal Neeraj , Pal Sumanta K. , Cho Daniel C. , Formiga Maria , Guo Jun , George Daniel J. , Tagliaferri Mary Ann , Singel Stina Mui , O'Keeffe Bridget A. , Hannah Alison L. , Balbas Minna , Penkov Konstantin 
Published: February 2020

TPS763 Background: Bempegaldesleukin (BEMPEG; NKTR-214) is a first-in-class interleukin-2 (IL-2) receptor pathway agonist that activates and expands effector T cells and natural killer cells in the tumor microenvironment and increases tumor PD-L1 expression, making BEMPEG a promising agent for combination with immune checkpoint inhibitors. In a phase 1/2 study, BEMPEG plus nivolumab (NIVO) demonstrated an encouraging objective response rate (ORR) in first-line advanced RCC (46%) and a manageable safety profile. BEMPEG plus NIVO offers a potential novel immunooncology treatment option for patients with advanced RCC. Methods: A global, multicenter, randomized, open-label phase 3 study is evaluating the efficacy and safety of BEMPEG plus NIVO vs investigator’s choice of tyrosine kinase inhibitor (TKI; sunitinib [SUNI] or cabozantinib [CABO]) in patients with previously untreated advanced or metastatic RCC with a clear-cell component. Patients must not have had prior systemic therapy (including neoadjuvant, adjuvant or vaccine therapy) for RCC. Key exclusion criteria include active brain metastasis and autoimmune disease requiring systemic immunosuppressive agents. Approximately 600 patients will be randomized 1:1 to receive 0.006 mg/kg BEMPEG plus 360 mg NIVO intravenously every 3 weeks or TKI (50 mg SUNI [4 weeks on, 2 weeks off schedule] or 60 mg CABO; orally each day). Patients will be stratified by International Metastatic RCC Database Consortium (IMDC) prognostic score (0 [favorable risk] vs 1-2 [intermediate risk] vs 3-6 [poor risk]) and TKI choice (SUNI vs CABO). Primary objectives are ORR by blinded independent central review (BICR) and overall survival in the IMDC intermediate/poor risk population and the intention-to-treat (ITT) population. Secondary objectives are progression-free survival by BICR in the IMDC intermediate/poor risk population and the ITT population, safety, PD-L1 expression as a predictive biomarker, and quality of life. Enrollment is ongoing. Clinical trial information: NCT03729245.
The correlation between the mineral drinking water composition and the relevance of dentine in health – A pilot study
Authors: Razvan Creteanu , Popa Monica , Incze Ana-Maria , Cristina Creteanu 
Published: February 2020

Objective: This study estimated the concentration of Ca, Mg and F in drinking water from five counties in Transylvania, Romania and correlated these with mineral values found in the dentine of permanent carious teeth. The role of these minerals on the re-mineralization of teeth is broadly analyzed.
Methods: The study consists of two parts: the first part is a pilot study aimed at determining the concentration of Ca, Mg and F in the dentine of permanent carious teeth of 75 male adults with residence in five counties in Transylvania. The second part is an evaluation of the levels of mineral composition in the drinking water from these counties. Mineral concentrations in dentine and drinking water samples, were determined in the laboratories of the public health institute and the research and analysis institute in Cluj Napoca, Romania.
Results: Statistically we found a direct and significant correlation between the Ca, Mg and F contain from the water samples and Ca, Mg and F contain from the dentine samples and an inverse correlation was statistically highlighted between Ca found in water samples and the F concentration in dentine samples. Improperly water mineralization associated with a general lack of fluoride reveals a potential negative impact on consumer health, including the oral-jaw system.
Conclusions: The results of this study indicate the need for improving the prevention of dental caries which is a priority in promoting orthodontic health for children. The variability in dentine minerals indicates the fact that permanent molar dentin represents an important biomarker for exposure. The future research will have to take into consideration the community residency status and the fact that these studies require a large sample to separate individual and community level contributions to dentin fluoride. Considering these notifications, we conclude that minerals are highly associated with caries.
doi: https://doi.org/10.12669/pjms.36.3.1820
How to cite this:Razvan C, Popa M, Incze AM, Cristina C. The correlation between the mineral drinking water composition and the relevance of dentine in health – A pilot study. Pak J Med Sci. 2020;36(3):349-354. doi: https://doi.org/10.12669/pjms.36.3.1820
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Global ageing: successes, challenges and opportunities
Authors: Mitchell Emma , Walker Richard 
Published: February 2020

The world's population is ageing rapidly, with significant increases in the numbers of the oldest old. This places great pressure on societies to adapt to this changing demography. Pertinent issues include provision of education and resource for long-term conditions. The priorities older people hold need to be fully understood and their contributions to society, often diverse and far-reaching, recognised with sincerity. Currently, health systems for older people can often feel reactive, fragmented and disjointed. These systems can harbour inequity and ageism, and leave both patients and health-care providers dissatisfied. Regarding the global context, the most rapidly ageing populations are in low- and middle-income countries. This partly reflects huge successes in the treatment and control of communicable diseases but gives rise to the challenge of the ‘double burden’, managing both communicable and non-communicable diseases simultaneously. Moreover, multimorbidity (suffering two or more chronic conditions) is commonplace and presents further challenges with regards to providing coordinated care. In order to harmonise effective and sustainable change, collaboration at local, national and international levels is key in order to foster a platform for learning and information sharing. Therein lies huge opportunities for countries to share their individual experiences, both past and present, to improve preparedness for global ageing.
How to make norms with drawings: An investigation of normativity beyond the realm of words
Authors: Lorini Giuseppe , Moroni Stefano 
Published: February 2020

AbstractA widespread opinion holds that norms and codes of conduct as such can only be established via words, that is, in some lexical form. This perspective can be criticized: some norms produced by human acts are not word-based at all. For example, many norms are actually conveyed through graphics (e. g. road signs and land-use maps), sounds (e. g. the referee’s whistle), a silent gesture (the traffic warden’s signal to halt). In this article, we will focus on the norms that are created by means of drawings and can be termed “drawn norms” or “graphical norms.” Specifically, we will inquire into the phenomenon of graphical norms with particular regard to traffic signs and land-use plans, and we will discuss the philosophical and legal problems to which these phenomena give rise.
Folding of a peptide continuum: Semiotic approach to protein folding
Authors: Lacková Ľudmila 
Published: February 2020

Abstract
In this paper I attempt to study the notion of “folding of a semiotic continuum” in a direction of a possible application to the biological processes (the process of protein folding). More specifically, the process of obtaining protein structures (protein folding) is compared in this paper to the folding of a semiotic continuum. Consequently, peptide chain is presented as a continuous line potential to be formed (folded) in order to create functional units. The functional units are protein structures having certain function in the cell or organism (semiotic agents). Moreover, protein folding is analyzed in terms of tension between syntax and semantics.
Ser mulher e ser feirante no território-lugar chamado feira
Authors: Quirino Rocha Patricia , Vargas Maria Augusta Mundim 
Published: February 2020

RESUMO: O presente artigo tem por objetivo compreender as territorialidades das mulheres que “botam banca” na feira do município de Euclides da Cunha, sertão baiano. Para isso, construímos nossas referências pela fenomenologia de forma a observar as vivências, as práticas e os saberes das mulheres como feirantes, utilizando como instrumentos da pesquisa, diário de campo e entrevistas concomitante ao aprofundamento de um levantamento e revisão bibliográfica. Foi possível conhecer as trajetórias das feirantes e suas territorialidades, pelas quais identificamos similitudes e diferenças que caracterizam suas práticas. Dentre elas, destacamos os laços de sociabilidade que se desenvolvem com os demais feirantes e com os fregueses, reveladores de que as formas de ser e estar na feira vão além das relações de compra e venda.
PALAVRAS-CHAVE: Territorialidade. Práticas. Saberes. Gênero.
Penentuan Usia Panen Terhadap Karakteristik Eucheuma Cottonii dari Perairan Pulau Pari Kepulauan Seribu
Authors: Novianty Hilda 
Published: February 2020

Eucheuma cottonii adalah salah satu jenis makro alga merah yang memiliki sifat fungsional yang bermanfaat bagi kehidupan manusia seperti pembentuk gel, penstabil, pensuspensi, pembentuk tekstur emulsi yang dapat diaplikasikan dalam industri pangan dan non pangan, oleh sebab itu budidaya jenis makro alga ini sedang dikembangkan oleh Pemerintah dan menjadi salah satu produk unggulan non perikanan. Dalam budidaya makro alga, penentuan umur panen merupakan hal kritis yang dapat mempengaruhi mutu akhir produk. Kriteria penentuan mutu pada produk hasil budidaya Eucheuma dapat diketahui dari sifat fisiknya, salah satunya kekuatan gel yang dapat memunculkan sifat fungsional pembentuk gel pada produk pangan/non pangan. Pada penelitian ini bertujuan untuk menentukan umur panen yang tepat terhadap kekuatan gel Eucheuma. Metode yang digunakan adalah non eksperimental deskriptif. Sample merupakan hasil budidaya dengan metode lone line dengan umur panen yang berbeda (35, 45 dan 55 hari panen) yang diujikan terhadap kekuatan gel. Hasil penelitian menunjukkan bahwa umur panen 35 hari memiliki nilai kekuatan gel terbesar yakni 430 g/cm2 dan kandungan fenol sebesar 77,96 mg/1000g.
Effect of the Gas-lift on the Gas Factor and on Ultimate Production
Authors: Bennett E.O. 
Published: February 2020

Published in Petroleum Transactions, AIME, Volume 77, 1927, pages158–172.
When oil is taken from a subsurface structure it is generally accompanied bygas. The gas thus produced represents the lighter hydrocarbons present in theoriginal petroleum accumulation, which are insoluble at the reduced pressurescreated around a well when it is producing. In some cases the gas accompanyingthe oil may come from a gas-bearing stratum not in immediate contact with theoil. The amount of gas from the formation accompanying each barrel of oil iscalled the natural gas factor.

Energy Causing Well To Flow
The force causing the flow of fluid into a well when it is drilled into anoil-bearing structure is the pressure differential between the well bore andthe formation. A pressure differential between the formation and the well maybe set up in three different ways, as follows:pressure due to gas insolution or in contact with the oil,hydrostatic pressure due to water incontact with the oil (it may be either bottom or edge water);pressuredifference due to force of gravity.
The greatest source of energy for producing oil from most oil fields, andthe one over which the greatest control can be exerted, is the potential energyin the gas under pressure in the formation. In any pool there is but a definiteamount of gas available. Part of this gas may be in solution and a part incontact with oil. The amount of gas in solution in each barrel of oil dependson the pressure and temperature in the formation and the characteristics of theoil. Whether the gas is in solution or in contact with the oil it is necessaryto use the energy it contains as efficiently as possible in order to obtain thegreatest ultimate recovery from the pool. Bush states:
Gas being the most efficient aid in moving the oil, it is important toprevent more of it from escaping than is necessary to remove the maximum amountof oil from the sands. The conservation of this energy is far more important tothe producer of oil than his returns from sales of gas to distributingcompanies.
Well Spacing in the Salt Creek Field
Authors: Wood F.E. 
Published: February 2020

Published in Petroleum Transactions, AIME, Volume 86, 1930, pages160–167.
This paper is written primarily as a discussion of Dr. W.P. Haseman's paperon "A Theory of Well Spacing" and presents briefly the productionrecords, and intensity and rate of development in a large portion of the twoprincipal producing sands in the Salt Creek field, Wyoming. The study includes1350 wells, 160,000,000 bbl. production, well spacings varying from two toseven wells per 40 acres and early and late development.
The general conclusions to be derived from this study are:It is impossible to formulate a mathematical rule to apply to well spacingin the Salt Creek field.Each tract is a separate problem.Tracts first drilled produce the most oil, with many exceptions.Initial production is not a reliable index to the relationship between past, current, or future production.Wells which have produced the most oil in the past are not necessarilyyielding the greatest current production nor will they yield the greatestfuture production. In fact, wells which have yielded the greatest pastproduction will, in at least one-half the cases, make less oil currently or inthe future than wells which have produced a smaller quantity of oil in thepast.The following is a safe rule to apply in well spacing in the Salt Creekfield:if the drilling of an additional well on a tract results in asustained increased production, with prospects of making a profit, the tract isnot overdeveloped and additional wells might be drilled.
If the drilling of an additional well does not effect a sustained increase inthe production of a tract, the tract is fully developed.

Second Wall Creek Sand
The Second Wall Creek sand, covering 20,000 producing acres, is the principalproducing horizon in the Salt Creek field; 1610 wells are producing at thistime from this sand.
Generating gastruloids with somite-like structures from mouse embryonic stem cells
Authors: Batenburg Vincent van , Brink Susanne Carina van den , Blotenburg Marloes , Alemany Anna , Moris Naomi , Baillie-Johnson Peter , Azhar Yasmine el , Sonnen Katharina F. , Arias Alfonso Martinez , Oudenaarden Alexander van 
Published: February 2020

Abstract
Gastruloids are aggregates of mouse embryonic stem cells that can be used to study key aspects of mammalian post-implantation development in vitro1–4. Gastruloids generated with previously published protocols do not generate somite-like structures4–6. Here, we describe a modified version of the gastruloids culture protocol5,6 that results in gastruloids that do generate somite-like structures in vitro (van den Brink et al., Nature, 2020)7. Under these conditions, about 50% of the gastruloids generated form structures with features that are characteristic of somites7.This protocol takes 6 days, with relatively little hands-on time. The protocol starts with the aggregation of the cultured cells. Then, the Wnt-agonist Chiron is added 2 days (48h) later. The medium of the aggregates is replaced 3 days (72h) after aggregation. To induce somite-formation, gastruloids are embedded in Matrigel 4 days (96h) after aggregation. After 5 days (120h) of culture, gastruloids resemble E8.5 mouse embryos. At this timepoint they can be fixed (fixative is added on day 5 and washed away on day 6 after overnight incubation in PFA) to prepare them for staining or microscopy experiments.
The current status and associated factors of fatigue in Chinese patients with gout: A cross-sectional study
Authors: Guo Jiaxin , Zhou Wei , He Mei , Gao Jianlin , Wang Yilin , Zhao Rui , Liu Jiefu , Fu Ting , Ji Juan , Bao Yanfeng , Ge Xingyu , Li Liren , Gu Zhifeng , Dong Chen 
Published: February 2020

Abstract
BackgroundFatigue is a common symptom in patients with rheumatism that is easy to ignore. In the absence of previous studies, our study aims to investigate the fatigue status, explore the potential predictors of fatigue and the effects of fatigue on health-related quality of life (HRQoL) among Chinese gout patients.MethodThis cross-sectional study was conducted from the Affiliated Hospital of Nantong University. A series of questionnaires were applied: Fatigue Scale-14 (FS-14), the 10 cm visual analog scale (VAS), the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder questionnaire (GAD-7), the Pittsburgh Sleep Quality Index (PSQI), Health Assessment Questionnaire(HAQ), the Short Form 36 health survey (SF-36). Laboratory examinations were taken to obtain some biochemical indicators. Independent samples t-test, Mann–Whitney U-test, Chi-square analysis, Pearson /Spearman correlation, Stepwise linear regression and binary logistic regression were used to analyze the data.Results410 gout patients were included in this study. Among them, more than 50% patients reported physical fatigue in FS-14, severe disease, poor psychological status and reduced HRQoL were associated with fatigue. Multiple stepwise linear regression and binary logistic regression were applied and showed that pain, sleep quality, anxiety and depression were the potential predictors of fatigue. In addition, we found that the more severe the fatigue, the lower the patient’s HRQoL.ConclusionsFatigue among gout patients is exceedingly common. The results of this study suggested that rheumatologists should pay closely attention to gout patients who suffer from serious fatigue, especially those with pain, poorer sleep quality, anxiety and depression.
Ultrasensitive Interferons quantification in idiopathic inflammatory myopathies serve as biomarkers of activity in dermatomyositis and anti-synthetase syndrome
Authors: Loïs BOLKO , Anquetil Celine , llibre Alba , Maillard Solene , Amelin Damien , Dorgham Karim , Bondet Vincent , Landon-Cardinal Oceane , Toquet Segolene , Mariampillai Kuberaka , Mahoudeau Alexandrine , Hervier Baptiste , Rodero Mathieu , Gorochov Guy , Duffy Darragh , Benveniste Olivier , Allenbach Yves 
Published: February 2020

Abstract
Objectives Inflammatory idiopathic myopathies (IIM) are a heterogeneous group of disorders, ranging from a muscle-specific autoimmune disease to a systemic one that are difficult to assess. Recent insights into IIM pathogenesis highlighted the role of interferon (IFN) in the pathophysiology. The aim of this study was to test if IFN serum levels can a use as a biomarker of disease activity in IIM. Methods IFN type I and II were measured using an ultrasensitive detection technology and assess the potential of IFN. Results One hundred and fifty-two patients (dermatomyositis (DM); n=50, anti-synthetase syndrome (ASyS); n=46, immune-mediated necrotizing myopathy (IMNM); n=32, inclusion body myositis (IBM); n=24) and 33 age-matched healthy donors were included. IFN-α levels were higher only in DM (0.07 pg/ml [0.03-0.23], p<0.005) and ASyS groups (0.07 [0.02-0.16], p<0.05) compared with controls (0.02 [0.01-0.05]). IFN-β was increased only in DM and IFN-γ among all IIM. IFN-α levels were correlated with disease activity in DM (r=0.76, p<0.0001). The predictive accuracy of IFN-α level to discriminate active and non-active disease was excellent as reflected by an area under the ROC-curve of 0.88. Using an IFN-α level cut-off above 0.11 pg/ml, the sensitivity was 75% and the specificity was 96% in DM patient. IFN-α and IFN-γ were correlated with disease activity in ASyS groups (r=0.55 and r=0.46 p<0.05)). Conclusions IFNs are promising biomarker for DM and ASyS disease activity.