bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progesterone receptor ligands for the treatment of endometriosis: the mechanisms behind therapeutic success and failure
Authors: Reis Fernando M , Coutinho Larissa M , Vannuccini Silvia , Batteux Frédéric , Chapron Charles , Petraglia Felice 
Published: February 2020

AbstractBACKGROUNDDespite intense research, it remains intriguing why hormonal therapies in general and progestins in particular sometimes fail in endometriosis.OBJECTIVE AND RATIONALEWe review here the action mechanisms of progesterone receptor ligands in endometriosis, identify critical differences between the effects of progestins on normal endometrium and endometriosis and envisage pathways to escape drug resistance and improve the therapeutic response of endometriotic lesions to such treatments.SEARCH METHODSWe performed a systematic Pubmed search covering articles published since 1958 about the use of progestins, estro-progestins and selective progesterone receptor modulators, to treat endometriosis and its related symptoms. Two reviewers screened the titles and abstracts to select articles for full-text assessment.OUTCOMESProgesterone receptor signalling leads to down-regulation of estrogen receptors and restrains local estradiol production through interference with aromatase and 17 beta-hydroxysteroid dehydrogenase type 1. Progestins inhibit cell proliferation, inflammation, neovascularisation and neurogenesis in endometriosis. However, progesterone receptor expression is reduced and disrupted in endometriotic lesions, with predominance of the less active isoform (PRA) over the full-length, active isoform (PRB), due to epigenetic abnormalities affecting the PGR gene transcription. Oxidative stress is another mechanism involved in progesterone resistance in endometriosis. Among the molecular targets of progesterone in the normal endometrium that resist progestin action in endometriotic cells are the nuclear transcription factor FOXO1, matrix metalloproteinases, the transmembrane gap junction protein connexin 43 and paracrine regulators of estradiol metabolism. Compared to other phenotypes, deep endometriosis appears to be more resistant to size regression upon medical treatments. Individual genetic characteristics can affect the bioavailability and pharmacodynamics of hormonal drugs used to treat endometriosis and, hence, explain part of the variability in the therapeutic response.WIDER IMPLICATIONSMedical treatment of endometriosis needs urgent innovation, which should start by deeper understanding of the disease core features and diverse phenotypes and idiosyncrasies, while moving from pure hormonal treatments to drug combinations or novel molecules capable of restoring the various homeostatic mechanisms disrupted by endometriotic lesions.
Investigating Agreement Among HCI Researchers About Human–Computer Interaction in CMMI-DEV Model: A Case Study
Authors: Gonçalves Taisa Guidini , Loslever Pierre , de Oliveira Káthia Marçal , Kolski Christophe 
Published: February 2020

AbstractDo human–computer interaction (HCI) researchers agree about which HCI approaches should be used in the development of an interactive system? To address this question, we performed a study based on the engineering process areas (requirements development, technical solution, product integration, verification and validation) of the CMMI-DEV (Capability Maturity Model Integration for Development), a software engineering model commonly used in the industry. To carry out this study, a literature review was performed, a specific instrument was designed based on CMMI-DEV and interviews with 20 researchers from the HCI domain were conducted. Analyzing the interview data with monovariate and multivariate statistical approach (Multiple Correspondence Analysis - MCA), we find the greatest agreement occurred among researchers for HCI approaches that support verification and validation phases and the use of functional prototypes in some activities of the last phases of software development (technical solution and product integration). However, we identified lack of agreement among researchers regarding requirements development activities.
Impact of the first-line treatment shift from dihydroartemisinin/piperaquine to artesunate/mefloquine on Plasmodium vivax drug susceptibility in Cambodia
Authors: Roesch Camille , Mairet-Khedim Mélissa , Kim Saorin , Lek Dysoley , Popovici Jean , Witkowski Benoit 
Published: February 2020

Abstract

Background
Cambodia is the epicentre of the emergence of Plasmodium falciparum drug resistance. Much less is known regarding the drug susceptibility of the co-endemic Plasmodium vivax. Only in vitro drug assays can determine the parasite’s intrinsic susceptibility, but these are challenging to implement for P. vivax and rarely performed.

Objectives
To evaluate the evolution of Cambodian P. vivax susceptibility to antimalarial drugs and determine their association with putative markers of drug resistance.

Methods
In vitro response to three drugs used in the past decade in Cambodia was measured for 52 clinical isolates from Eastern Cambodia collected between 2015 and 2018 and the sequence and copy number variation of their pvmdr1 and pvcrt genes were analysed. pvmdr1 polymorphism was also determined for an additional 250 isolates collected in Eastern Cambodia between 2014 and 2019.

Results
Among the 52 cryopreserved isolates tested, all were susceptible to the three drugs, with overall median IC50s of 16.1 nM (IQR 11.4–22.3) chloroquine, 3.4 nM (IQR 2.1–5.0) mefloquine and 4.6 nM (IQR 2.7–7.0) piperaquine. A significant increase in chloroquine and piperaquine susceptibility was observed between 2015 and 2018, unrelated to polymorphisms in pvcrt and pvmdr1. Susceptibility to mefloquine was significantly lower in parasites with a single mutation in pvmdr1 compared with isolates with multiple mutations. The proportion of parasites with this single mutation genotype increased between 2014 and 2019.

Conclusions
P. vivax with decreased susceptibility to mefloquine is associated with the introduction of mefloquine-based treatment during 2017–18.
Surgery for Inflammatory Bowel Disease Has Unclear Impact on Female Fertility: A Cochrane Collaboration Systematic Review
Authors: Lee Sangmin , Crowe Megan , Seow Cynthia H , Kotze Paulo G , Kaplan Gilaad G , Metcalfe Amy , Ricciuto Amanda , Benchimol Eric I , Kuenzig M Ellen 
Published: February 2020

Abstract

Background and Aims
Surgical treatment of inflammatory bowel disease (IBD) may impair female fertility. We conducted a systematic review to determine the risk of infertility and pregnancy outcomes in women with IBD who underwent surgery.

Methods
We identified studies evaluating the impact of IBD surgery on infertility and pregnancy outcomes. Risk ratios (RR) and 95% confidence intervals (CIs) were pooled when data were presented using contingency tables. Odds ratios (OR) were pooled when raw numbers were not provided. GRADE was used to evaluate the certainty of evidence.

Results
Sixteen observational studies were included, comparing women with and without surgery, open and laparoscopic surgery and before and after surgery. All studies were of low quality. The effect of surgery on infertility at 12 months (RR 5.45, 95% CI 0.41 to 72.57) was uncertain. Similarly, the fertility effects of laparoscopic versus open surgery method were unclear (RR 0.70, 95% CI 0.38 to 1.27). The impact of IBD surgery on pregnancy outcomes should be interpreted with caution. Surgery was associated with miscarriage (OR 2.03, 95% CI 1.14 to 3.60), use of assisted reproductive technologies (RR 25.09, 95% CI 1.56 to 403.76) and caesarean section (RR 2.23, 95% CI 1.00 to 4.95), but not with stillbirth (RR 1.96, 95% CI 0.42 to 9.18), preterm birth (RR 1.91, 95% CI 0.67 to 5.48), low birth weight (RR 0.61, 95% CI 0.08 to 4.83) or small for gestational age (RR 2.54, 95% CI 0.80 to 8.01).

Conclusion
The effect of surgical therapy for IBD on rates of female infertility and pregnancy-related outcomes was uncertain due to poor quality of existing literature.
Object-oriented integrated algorithms for efficient water pipe network by modified Hardy Cross technique
Authors: Jha Kailash , Mishra Manish Kumar 
Published: February 2020

AbstractIn this work, object-oriented integrated algorithms for an efficient flow analysis of the water pipe network are developed. This is achieved by treating the pipe network as a graph data structure with its nodes as the graph’s nodes and the pipes as the edges. The algorithm for cycle (real cycle or pseudo-cycle) extraction has been developed using nested breadth-first search that gives ordered cycles. Pseudo-loops are found using the shortest path algorithm between the nodes. Pipes are initialized loop by loop using conservation of mass at nodes. A modified Hardy Cross method is used in the proposed work with third-order convergence. The friction factor is updated for every change in discharges. The pressure calculation has been done by the graph traversal algorithm between the reference nodes and node where the pressure is to be calculated using the energy equation. The pressure at all intermediate nodes is obtained in the course of the traversal. Balanced discharges and nodal pressure in the pipe network are compared with the simultaneous loop flow adjustment method and EPANET software. The proposed work gives more efficient flow analysis than the traditional Newton–Raphson-based techniques for complex networks.
Development and Validation of Real-Time PCR Method to Estimate Stored Sperm in the Spermathecae of Ceratitis capitata (Diptera: Tephritidae)
Authors: Catalá-Oltra Marta , Llácer Elena , Urbaneja Alberto , Pérez-Hedo Meritxell 
Published: February 2020

AbstractThe development of polymerase chain reaction (PCR) markers to identify the Y chromosome of Ceratitis capitata Wiedemann has permitted the detection of sperm transferred to females during mating. However, a molecular technique to quantify the sperm transferred has not yet become available. The current method to quantify the amount of sperm has been the direct counting of sperm heads. Thus, the purpose of this research was to develop and validate an accurate molecular method of diagnosis based on the application of an absolute quantitative real-time PCR, which allows the assessment of the quantity of sperm stored in the spermathecae. For this, Y-specific sequences were used to re-design and test distinct sperm markers. From the amplification product of samples detected as strong positives in conventional PCR, a cloning process of the target sequence was carried out to build the required standard curve. A series of known dilutions of this standard material was prepared for the absolute quantification process. A Roche Lightcycler 480 Real-Time PCR System and SYBRGreen fluorescent dye were used to quantify the sperm contained in the spermathecae of 4-d-old mated females and virgins. Wild-type and Vienna-8 strain sterile males were used to quantify the sperm transferred at four mating durations (10, 30, 60, and 90 min) under laboratory conditions. To validate the reported quantitative method, our results were compared by counting sperm heads under a fluorescent microscope using the same experimental design. In addition, DNA samples were also evaluated and compared by conventional PCR.
Response of a remnant marmot population to habitat enhancement yields insights into marmot ecology
Authors: Reynolds-Hogland Melissa J , Ramsey Alan B , Seward August T , Pilgrim Kristine L , Engkjer Cory , Ramsey Philip W 
Published: February 2020

Abstract
We evaluated the response of a remnant population of yellow-bellied marmots (Marmota flaviventris) to targeted habitat enhancement in an ecological system that had been degraded during ~100 years of intensive livestock management, including marmot eradication. We used capture-recapture data and a novel use of a multistate framework to evaluate geographic expansion of the marmot population pre- and post-habitat enhancement. We also estimated age-structured survival, reproduction, and sex ratios. The marmot population appeared to respond positively to new habitat opportunities created by habitat enhancement: the number of marmots captured increased from three marmots pre-habitat enhancement to 54 (28 adults and yearlings, 26 young) post-habitat enhancement at the end of the study. Marmots expanded geographically by transitioning into habitat-enhanced areas, and adult females occupied and reproduced in all habitat-enhanced areas. The sex ratio of the young population in 2019 was strongly female-biased, which may have been influenced by poor body condition of breeding females owing to unusually prolonged snow cover that year. Adult and yearling survival were within the range of that reported for colonial adults and yearlings in Colorado. Our results suggest that active habitat enhancement can assist in the recovery of marmot populations in systems where marmots historically existed.
Direct observation and analysis of TET-mediated oxidation processes in a DNA origami nanochip
Authors: Xing Xiwen , Sato Shinsuke , Wong Nai-Kei , Hidaka Kumi , Sugiyama Hiroshi , Endo Masayuki 
Published: February 2020

Abstract
DNA methylation and demethylation play a key role in the epigenetic regulation of gene expression; however, a series of oxidation reactions of 5-methyl cytosine (5mC) mediated by ten-eleven translocation (TET) enzymes driving demethylation process are yet to be uncovered. To elucidate the relationship between the oxidative processes and structural factors of DNA, we analysed the behavior of TET-mediated 5mC-oxidation by incorporating structural stress onto a substrate double-stranded DNA (dsDNA) using a DNA origami nanochip. The reactions and behaviors of TET enzymes were systematically monitored by biochemical analysis and single-molecule observation using atomic force microscopy (AFM). A reformative frame-like DNA origami was established to allow the incorporation of dsDNAs as 5mC-containing substrates in parallel orientations. We tested the potential effect of dsDNAs present in the tense and relaxed states within a DNA nanochip on TET oxidation. Based on enzyme binding and the detection of oxidation reactions within the DNA nanochip, it was revealed that TET preferred a relaxed substrate regardless of the modification types of 5-oxidated-methyl cytosine. Strikingly, when a multi-5mCG sites model was deployed to further characterize substrate preferences of TET, TET preferred the fully methylated site over the hemi-methylated site. This analytical modality also permits the direct observations of dynamic movements of TET such as sliding and interstrand transfer by high-speed AFM. In addition, the thymine DNA glycosylase-mediated base excision repair process was characterized in the DNA nanochip. Thus, we have convincingly established the system's ability to physically regulate enzymatic reactions, which could prove useful for the observation and characterization of coordinated DNA demethylation processes at the nanoscale.
A multi-layered structure of the interphase chromocenter revealed by proximity-based biotinylation
Authors: Kochanova Natalia Y , Schauer Tamas , Mathias Grusha Primal , Lukacs Andrea , Schmidt Andreas , Flatley Andrew , Schepers Aloys , Thomae Andreas W , Imhof Axel 
Published: February 2020

AbstractDuring interphase centromeres often coalesce into a small number of chromocenters, which can be visualized as distinct, DAPI dense nuclear domains. Intact chromocenters play a major role in maintaining genome stability as they stabilize the transcriptionally silent state of repetitive DNA while ensuring centromere function. Despite its biological importance, relatively little is known about the molecular composition of the chromocenter or the processes that mediate chromocenter formation and maintenance. To provide a deeper molecular insight into the composition of the chromocenter and to demonstrate the usefulness of proximity-based biotinylation as a tool to investigate those questions, we performed super resolution microscopy and proximity-based biotinylation experiments of three distinct proteins associated with the chromocenter in Drosophila. Our work revealed an intricate internal architecture of the chromocenter suggesting a complex multilayered structure of this intranuclear domain.
Mixed milk feeding: a systematic review and meta-analysis of its prevalence and drivers
Authors: Monge-Montero Carmen , van der Merwe Liandré F , Papadimitropoulou Katerina , Agostoni Carlo , Vitaglione Paola 
Published: February 2020

AbstractContextExtensive literature is available on exclusive breastfeeding and formula-feeding practices and health effects. In contrast, limited and unstructured literature exists on mixed milk feeding (MMF), here defined as the combination of breastfeeding and formula feeding during the same period in term infants &gt; 72 hours old (inclusion criterion).ObjectiveA systematic review and meta-analysis were performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, on the global prevalence of MMF (primary outcome) and related drivers and practices (secondary outcomes).Data SourcesThe search of MMF in generally healthy populations was conducted across 6 databases, restricted to publications from January 2000 to August 2018 in English, Spanish, French, and Mandarin.Data ExtractionTwo reviewers independently performed screenings and data extraction according to a priori inclusion and exclusion criteria.Data AnalysisOf the 2931 abstracts identified, 151 full-text publications were included for data extraction and 96 of those were included for data synthesis (the majority of those were cross-sectional and cohort studies). The authors summarized data across 5 different categories (feeding intention prenatally, and 4 age intervals between &gt; 72 hours and &gt; 6–23 months) and 5 regional subgroups. The overall prevalence of MMF across different age intervals and regions varied between 23% and 32%; the highest rate was found for the age group 4–6 months (32%; 95% confidence interval, 27%–38%); regional comparisons indicated highest MMF rates in Asia (34%), North and South America (33%), and Middle East and Africa together (36%), using a random effects meta-analysis model for proportions. Some drivers and practices for MMF were identified.ConclusionMMF is a widespread feeding reality. A shared and aligned definition of MMF will help shed light on this feeding practice and evaluate its influence on the duration of total breastfeeding, as well as on infants’ nutrition status, growth, development, and health status in the short and long terms. PROSPERO registration number CRD42018105337.
Economic theory in an imperfect world: Frank Hahn, general equilibrium, and Keynesian economics
Authors: Backhouse Roger E 
Published: February 2020

Abstract
Frank Hahn was both a Keynesian economist, active in policy debates, and an economic theorist. Placing his work in the context of attempts to make theoretical sense of Keynesian economics, this article explores the way Hahn used abstract general equilibrium theory to draw conclusions relevant to policy in an ‘imperfect’ world that does not conform to the assumptions made in the theory. Hahn’s rigorous approach to theorizing as the route to understanding is assessed in relation to the different approaches of Robert Lucas, Milton Friedman, Paul Samuelson and Axel Leijonhufvud.
Cooperative Intuitionism
Authors: Ingram Stephen 
Published: February 2020

Abstract
According to pluralistic intuitionist theories, some of our moral beliefs are non-inferentially justified, and these beliefs come in both an a priori and an a posteriori variety. In this paper, I present new support for this pluralistic form of intuitionism by examining the deeply social nature of moral inquiry. This is something that intuitionists have tended to neglect. It does play an important role in an intuitionist theory offered by Bengson, Cuneo, and Shafer-Landau, but whilst they invoke the social nature of moral inquiry in order to argue that ordinary moral intuitions are trustworthy, my argument focuses on what I will call the ‘frontiers’ of moral inquiry. I will show that inclusive and cooperative dialogue is necessary at moral inquiry's frontiers, and that intuitionists can expect such dialogue to result in both a priori and a posteriori moral beliefs.
CHARACTERIZATION OF SAND SAMPLES FROM KARACHI BEACHES USING GAMMA SPECTROMETRY AND XRD
Authors: Zeb Jahan , Wasim Mohammad , Shah Sardar A , Khanam Safia , Tahir Hajira , Qadri Masooda 
Published: February 2020

Abstract
Chemical phase and distribution of natural radionuclides (226Ra, 232Th and 40K) were determined for sand samples collected from ten different beaches of Karachi. All samples, except one, were identified with major and minor phases as SiO2 and CaCO3, respectively. The average activity concentrations were 24.9, 25.0 and 239 Bq kg−1 for 226Ra, 232Th and 40K, respectively. Including all samples, the average radium equivalent activity was 79.1 Bq kg−1. The external and internal radiation hazard indices and representative level index were all found below unity. The average air absorbed dose rate at 1 m above the sand due to the natural radionuclides was 18.3 nGy h−1, which was less than the world average for soil. The corresponding annual effective dose rate was 22.4 μSv y−1. It was found that Raeq had positive significant correlation with the amount of quartz present at the beaches.
Bioaccumulation and toxicity of 2-naphthalene sulfonate: an intermediate compound used in textile industry
Authors: Mehra Sukanya , Chadha Pooja 
Published: February 2020

AbstractThe aromatic compounds substituted with sulfonate groups, being xenobiotic, resist biodegradation in the environment and tend to accumulate up to toxic levels. The hydrophilic sulfonated group makes these compounds highly water soluble and they tend to pass through water-treatment plants. The release of untreated effluents from these industries results in pollution of water bodies affecting aquatic fauna. Thus, the toxicity regarding these compounds is of major concern. The 2-naphthalene sulfonate is a sulfonated aromatic compound being widely used in textile industries. Being non-biodegradable concern regarding its toxicity has risen. Thus in the light of above facts, the present study was undertaken to determine the toxicity of 2-naphthalene sulfonate in blood cells of Channa punctatus. For this, LD50 was determined and after selection of sublethal doses oxidative stress, genotoxicity and bioaccumulation were studied. For oxidative stress determination, biochemical markers such as malondialdehyde content and activities of superoxide dismutase, catalase, and glutathione-S-transferase were studied. Genotoxicity was studied using comet and micronucleus assay. Significant increase in oxidative stress and DNA damage in the exposed groups as compared to control group (P ≤ 0.05) was observed till 96 h. However, decreased values of all the studied parameters at 720 h (30 days) indicate repair capacity of fish. Further, the bio accumulative potential of 2-naphthalene sulfonate was assessed in blood plasma using high-performance liquid chromatography. The study revealed the toxic potential of 2-naphthalene sulfonate to aquatic organisms thus stressed on the need for the implementation of stringent policies regarding the management of such toxic compounds.