bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA Methylation Profiling Reveals Prognostically Significant Groups in Pediatric Adrenocortical Tumors: A Report From the International Pediatric Adrenocortical Tumor Registry
Authors: Clay Michael R. , Pinto Emilia M. , Cline Cynthia , Tran Quynh T. , Lin Tong , Dyer Michael A. , Shi Lei , Wu Huiyun , Pounds Stanley B. , Zambetti Gerard P. , Orr Brent A. , Ribeiro Raul C. 
Published: November 2019

PURPOSE Pediatric adrenocortical carcinomas (ACCs) are aggressive; the overall survival of patients with ACCs is 40%-50%. Appropriate staging and histologic classification are crucial because children with incomplete resections, metastases, or relapsed disease have a dismal prognosis. The clinical course of pediatric adrenocortical tumors (ACTs) is difficult to predict using the current classification schemas, which rely on subjective microscopic and gross macroscopic variables. Recent advances in adult ACT studies have revealed distinct DNA methylation patterns with prognostic significance that have not been systematically interrogated in the pediatric population. PATIENTS AND METHODS We performed DNA methylation analyses on 48 newly diagnosed ACTs from the International Pediatric Adrenocortical Tumor Registry and 12 pediatric adrenal controls to evaluate for distinct methylation groups. Pediatric methylation data were also compared systematically with the adult ACC cohort from The Cancer Genome Atlas (TCGA). RESULTS Two pediatric ACT methylation groups were identified and showed differences in selected clinicopathologic and outcome characteristics. The A1 group was enriched for CTNNB1 variants and unfavorable outcome. The A2 group was enriched for TP53 germline variants, younger age at onset, and favorable outcome. Pediatric ACT methylation groups were maintained when International Pediatric Adrenocortical Tumor Registry cohort data were combined with TCGA cohort data. The CpG-island hypermethylator phenotype characterizing the TCGA cohort was not identified in the pediatric patients. When methylome findings were combined with independent histopathologic review using the Wieneke criteria, a high-risk population was identified with uniform fatal outcome. CONCLUSION Our results indicate DNA methylation analysis can enhance current diagnostic algorithms. A combination of methylation and histologic classification produced the strongest prediction model and may prove useful in future risk-adapted therapeutic trials.
Intravenous Insulin Versus Conservative Management in Hypertriglyceridemia-Associated Acute Pancreatitis
Authors: Dhindsa Sandeep , Sharma Anjul , Al-Khazaali Ali , Sitaula Sujata , Nadella Soumya , McKee Alexis , Albert Stewart , Bourey Raymond , Dandona Paresh 
Published: November 2019

AbstractContext and ObjectiveHypertriglyceridemia is implicated in ~5% of cases of acute pancreatitis. It is assumed that intravenous insulin is effective in lowering triglyceride (TG) concentrations in hypertriglyceridemia-associated acute pancreatitis (HAAP). However, the efficacy of intravenous insulin versus conservative management alone is not known.Design and SettingCharts of 106 patients who were admitted with HAAP and had TG concentrations &gt;1000 mg/dL at admission were reviewed. Patients who received intravenous insulin for at least 8 hours were included in the intravenous insulin group, while the rest were considered to have received conservative management. We compared the change in TG concentrations from baseline in the 2 groups.ResultsFifty-one patients received intravenous insulin while 55 patients were managed conservatively. Baseline TG concentrations were higher in the intravenous insulin group (median [25th, 75th percentile] 3307 [2106, 4425] mg/dL vs 2304 [1416, 2720] mg/dL; P &lt; 0.001). The TG concentrations declined rapidly in both groups, reaching below 1000 mg/dL by day 3 and &lt; 500 mg/dL by day 4. TG concentrations in the intravenous insulin group had decreased by 69% and 85% on days 2 and 4, respectively. The fall in the conservative management group was 63% and 79%, which was not statistically different than the change in the intravenous insulin group.ConclusionOur results show that intravenous insulin did not result in a more rapid fall in TG compared with conservative treatment in patients with HAAP. Fasting and intravenous fluids were effective in lowering TG concentrations rapidly, with no further contribution from insulin.
Metabolomic Analysis of the Effects of Leptin Replacement Therapy in Patients with Lipodystrophy
Authors: Grewal Shivraj , Gubbi Sriram , Fosam Andin , Sedmak Caroline , Sikder Shanaz , Talluru Harsha , Brown Rebecca J , Muniyappa Ranganath 
Published: November 2019

AbstractContext and ObjectiveLeptin treatment has dramatic clinical effects on glucose and lipid metabolism in leptin-deficient patients with lipodystrophy. Further elucidation of metabolic effects of exogenous leptin therapy will shed light on understanding leptin physiology in humans. Our objective was to utilize metabolomic profiling to examine the changes associated with administration of short-term metreleptin therapy in patients with lipodystrophy.Study DesignWe conducted a pre-post-treatment study in 19 patients (75% female) with varying forms of lipodystrophy (congenital generalized lipodystrophy, n = 10; acquired generalized lipodystrophy, n = 1; familial partial lipodystrophy, n = 8) who received daily subcutaneous metreleptin injections for a period of 16 to 23 weeks. A 3-hour oral glucose tolerance test and body composition measurements were conducted before and after the treatment period, and fasting blood samples were used for metabolomic profiling. The study outcome aimed at measuring changes in physiologically relevant metabolites before and after leptin therapy.ResultsMetabolomic analysis revealed changes in pathways involving branched-chain amino acid metabolism, fatty acid oxidation, protein degradation, urea cycle, tryptophan metabolism, nucleotide catabolism, vitamin E, and steroid metabolism. Fold changes in pre- to post-treatment metabolite levels indicated increased breakdown of fatty acids, branched chain amino acids proteins, and nucleic acids.ConclusionsLeptin replacement therapy has significant effects on important metabolic pathways implicated in patients with lipodystrophy. Continued metabolomic studies may provide further insight into the mechanisms of action of leptin replacement therapy and provide novel biomarkers of lipodystrophy.Abbreviations: 1,5-AG, 1,5-anhydroglucitol; 11βHSD1, 11-β hydroxysteroid dehydrogenase 1; BCAA, branched-chain amino acid; FFA, free fatty acid; GC-MS, gas chromatography mass spectrometry; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-γ; m/z, mass to charge ratio; OGTT, oral glucose tolerance test; TDO, tryptophan 2,3-dioxygenase; TNF-α, tumor necrosis factor-α; UPLC-MS/MS, ultra-performance liquid chromatography-tandem mass spectrometry.
C. elegans Runx/CBFβ suppresses POP-1 TCF to convert asymmetric to proliferative division of stem cell-like seam cells
Authors: van der Horst Suzanne E. M. , Cravo Janine , Woollard Alison , Teapal Juliane , van den Heuvel Sander 
Published: November 2019

ABSTRACT
A correct balance between proliferative and asymmetric cell divisions underlies normal development, stem cell maintenance and tissue homeostasis. What determines whether cells undergo symmetric or asymmetric cell division is poorly understood. To gain insight into the mechanisms involved, we studied the stem cell-like seam cells in the Caenorhabditis elegans epidermis. Seam cells go through a reproducible pattern of asymmetric divisions, instructed by divergent canonical Wnt/β-catenin signaling, and symmetric divisions that increase the seam cell number. Using time-lapse fluorescence microscopy we observed that symmetric cell divisions maintain asymmetric localization of Wnt/β-catenin pathway components. Our observations, based on lineage-specific knockout and GFP-tagging of endogenous pop-1, support the model that POP-1TCF induces differentiation at a high nuclear level, whereas low nuclear POP-1 promotes seam cell self-renewal. Before symmetric division, the transcriptional regulator RNT-1Runx and cofactor BRO-1CBFβ temporarily bypass Wnt/β-catenin asymmetry by downregulating pop-1 expression. Thereby, RNT-1/BRO-1 appears to render POP-1 below the level required for its repressor function, which converts differentiation into self-renewal. Thus, we found that conserved Runx/CBFβ-type stem cell regulators switch asymmetric to proliferative cell division by opposing TCF-related transcriptional repression.
The spindle pole body of Aspergillus nidulans is asymmetrical and contains changing numbers of γ-tubulin complexes
Authors: Gao Xiaolei , Schmid Marjorie , Zhang Ying , Fukuda Sayumi , Takeshita Norio , Fischer Reinhard 
Published: November 2019

ABSTRACT
Centrosomes are important microtubule-organizing centers (MTOCs) in animal cells. In addition, non-centrosomal MTOCs (ncMTOCs) are found in many cell types. Their composition and structure are only poorly understood. Here, we analyzed nuclear MTOCs (spindle-pole bodies, SPBs) and septal MTOCs in Aspergillus nidulans. They both contain γ-tubulin along with members of the family of γ-tubulin complex proteins (GCPs). Our data suggest that SPBs consist of γ-tubulin small complexes (γ-TuSCs) at the outer plaque, and larger γ-tubulin ring complexes (γ-TuRC) at the inner plaque. We show that the MztA protein, an ortholog of the human MOZART protein (also known as MZT1), interacted with the inner plaque receptor PcpA (the homolog of fission yeast Pcp1) at SPBs, while no interaction nor colocalization was detected between MztA and the outer plaque receptor ApsB (fission yeast Mto1). Septal MTOCs consist of γ-TuRCs including MztA but are anchored through AspB and Spa18 (fission yeast Mto2). MztA is not essential for viability, although abnormal spindles were observed frequently in cells lacking MztA. Quantitative PALM imaging revealed unexpected dynamics of the protein composition of SPBs, with changing numbers of γ-tubulin complexes over time during interphase and constant numbers during mitosis.
This article has an associated First Person interview with the first author of the paper.
Re-resection in Incidental Gallbladder Cancer: Survival and the Incidence of Residual Disease
Authors: de Savornin Lohman Elise A. J. , van der Geest Lydia G. , de Bitter Tessa J. J. , Nagtegaal Iris D. , van Laarhoven Cornelis J. H. M. , van den Boezem Peter , van der Post Chella S. , de Reuver Philip R. 
Published: November 2019

Abstract
Background
Re-resection for incidental gallbladder cancer (iGBC) is associated with improved survival but little is known about residual disease (RD) and prognostic factors. In this study, survival after re-resection, RD, and prognostic factors are analyzed.

Methods
Patients with iGBC were identified from the Netherlands Cancer Registry, and pathology reports of re-resected patients were reviewed. Survival and prognostic factors were analyzed.

Results
Overall, 463 patients were included; 24% (n = 110) underwent re-resection after a median interval of 66 days. RD was present in 35% of patients and was most frequently found in the lymph nodes (23%). R0 resection was achieved in 93 patients (92%). Median overall survival (OS) of patients without re-resection was 13.7 (95% confidence interval [CI] 11.6–15.6), compared with 52.6 months (95% CI 36.3–68.8) in re-resected patients (p < 0.001). After re-resection, median OS was superior in patients without RD versus patients with RD (not reached vs. 23.1 months; p < 0.001). In patients who underwent re-resection, RD in the liver (hazard ratio [HR] 5.54; p < 0.001) and lymph nodes (HR 2.35; p = 0.005) were the only significant prognostic factors in multivariable analysis. Predictive factors for the presence of RD were pT3 stage (HR 25.3; p = 0.003) and pN1 stage (HR 23.0; p = 0.022).

Conclusion
Re-resection for iGBC is associated with improved survival but remains infrequently used and is often performed after the optimal timing interval. RD is the only significant prognostic factor for survival after re-resection and can be predicted by pT and pN stages.
Coronary artery to aortic luminal attenuation ratio in coronary CT angiography for the diagnosis of haemodynamically significant coronary artery stenosis
Authors: Misaka Tomofumi , Sugitani Yuki , Asato Nobuyuki , Matsukubo Yuko , Uemura Masanobu , Ashikaga Ryuichiro , Ishida Takayuki 
Published: November 2019

Objective:
This study aimed to assess and compare the diagnostic performance of the coronary artery to aortic luminal attenuation ratio (CAR), transluminal attenuation gradient (TAG), and corrected coronary opacification (CCO) difference on coronary CT angiography (cCTA) for detecting haemodynamically significant coronary artery stenosis.

Methods:
33 patients who underwent cCTA, gated SPECT myocardial perfusion imaging (MPI), and invasive coronary angiography within 3 months were included in this retrospective study. The degree of coronary stenosis on cCTA was visually assessed in all patients. Additionally, CAR, TAG, and CCO difference were analyzed and calculated in all patients. Haemodynamically significant coronary stenosis was defined as a vessel with ≥50% luminal stenosis on invasive coronary angiography and an associated abnormal perfusion defect on MPI in the same territory. Diagnostic performance was assessed on a per-vessel basis by the area under the receiver operating characteristic (ROC) curve (AUC).

Results:
Among 99 vessels, 12 were excluded and the remaining 87 were analyzed. 17 (19.5%) vessels were determined as haemodynamically significant coronary artery stenosis. On ROC analysis, the AUC was 0.71 for cCTA, 0.80 for CAR, 0.61 for TAG, 0.74 for CCO, 0.87 for combined CAR and cCTA, 0.77 for combined TAG and cCTA, and 0.75 for combined CCO and cCTA. The AUC for combined CAR and cCTA was significantly greater compared with cCTA alone (p &lt; 0.01).

Conclusion:
Non-invasive CAR derived from 64-detector row CT was feasible and might be helpful for the detection of haemodynamically significant coronary artery stenosis. Still, further investigations such as intra- and inter-reader correlation, evaluation of larger numbers in different settings, and time efficiency are required for applying CAR in various situations.

Advances in knowledge:
CAR could be used as novel noninvasive technique to detect haemodynamically significant coronary artery stenosis.
Analysis of the Arabidopsis organellar rhomboid At1g74140 transcript population uncovered splicing patterns different from its close relative At1g74130
Authors: Ko Kenton , Guenther Jeremy , Ostan Nicholas , Powles Joshua 
Published: November 2019

Background: Four distinct rhomboid genes appear to function in Arabidopsis plastids, two “active” types from the secretases and presenilin-like associated rhomboid-like (PARL) categories (At1g25290 and At5g25752) and two “inactive” rhomboid forms (At1g74130 and At1g74140). The number of working rhomboids is further increased by alternative splicing, two reported for At1g25290 and three for At1g74130. Since At1g25290 and At1g74130 exist as alternative splice variants, it would be necessary to assess the splicing patterns of the other two plastid rhomboid genes, At5g25752 and At1g74140, before studying the Arabidopsis plastid rhomboid system as a whole. Methods: This study thus specifically focused on an analysis of the At1g74140 transcript population using various RT-PCR strategies. Results: The exon mapping results indicate splicing patterns different from the close relative At1g74130, despite similarity between the exonic sequences. The splicing patterns indicate a high level of sequence “discontinuity” in the At1g74140 transcript population with a significant portion of the discontinuity being generated by two regions of the gene. Conclusion: The overall discontinuous splicing pattern of At1g74140 may be reflective of its mode of involvement in activities like controlling gene expression.
Management strategies for lower urinary tract symptoms (LUTS) among people with multiple sclerosis (MS): a qualitative study of the perspectives of people with MS and healthcare professionals
Authors: Al Dandan Hawra B. , Galvin Rose , McClurg Doreen , Coote Susan 
Published: November 2019

Background: Neurogenic lower urinary tract dysfunction (NLUTD) is defined as a lower urinary tract dysfunction secondary to confirmed pathology of the nervous system. NLUTD is common in people with multiple sclerosis (MS), with prevalence estimates ranging from 49% to 92%. Managing NLUTD is complex and can be comprised of pharmacological and non-pharmacological interventions. Qualitative research exploring perspectives of people with MS and healthcare professionals on living with and managing NLUTD symptoms is sparse. This study aims to explore the perspectives of people with MS and healthcare professionals on managing NLUTD symptoms. Methods: A qualitative descriptive approach will be applied in this study using audio-recorded semi structured interviews for people with MS and healthcare professionals. The Consolidated Criteria for Reporting Qualitative Studies (COREQ) guidelines will be used to standardize the conduct and reporting of the research. People with MS will be recruited through a gatekeeper at MS Ireland. Healthcare professionals will be recruited through gatekeepers at Irish Practice Nurses Association, Continence Foundation of Ireland, Irish Society of Chartered Physiotherapists, and Physiotherapists Interested in MS Group. Interviews will be transcribed and exported to NVivo software package (Version 12) for analysis. Data will be collectively synthesised using thematic analysis. Conclusion: It is anticipated that exploring perspectives of people with MS and healthcare professionals on managing symptoms (including current practice) of NLUTD in MS will assist in the development of an evidence-based and stakeholder informed intervention for NLUTD in people with MS.
The association between exaggeration in health-related science news and academic press releases: a replication study
Authors: Bratton Luke , Adams Rachel C. , Challenger Aimée , Boivin Jacky , Bott Lewis , Chambers Christopher D. , Sumner Petroc 
Published: November 2019

Background: Exaggerations in health news were previously found to strongly associate with similar exaggerations in press releases. Moreover, such press release exaggerations did not appear to attract more news. Methods: Here we tested the replicability of these findings in a new cohort of news and press releases based on research in UK universities in 2014 and 2015. Press releases and news were compared to their associated peer-reviewed articles to define exaggeration in advice, causal claims and human inference from non-human studies. Results: We found that the association between news and press releases did not replicate for advice exaggeration, while this association did replicate for causal claims and human inference from non-human studies. There was no evidence for higher news uptake for exaggerated press releases, consistent with previous results. Base exaggeration rates were lower for human inference from non-human studies, possibly reflecting the Concordat on Openness on Animal Research in the UK. Conclusions: Overall, the picture remains that the strength of news statements is normally associated with the strength of press release statements, and without evidence that exaggerated statements get significantly more news.
Initiating a network to support engagement between health researchers and schools: recommendations from an international meeting of schools engagement practitioners held in Kilifi, Kenya
Authors: Davies Alun , Mwango Grace , Appiah Bernard , Callery James J. , Duy Thanh Vu , Gumede Nozibusiso , Inglis Robert , McCracken Shane , Mkoola Kestern , Montjane Kagisho , Ochanda Alice , Shonai Charity , Woods-Townsend Kathryn 
Published: November 2019

Engagement between health researchers and local schools, or School Engagement, has become incorporated into the engagement strategies of many health research institutions worldwide. Innovative initiatives have emerged within Wellcome Trust-funded African and Asian Programmes (APPs) and elsewhere, and continued funding from the Wellcome Trust and other funders is likely to catalyse further innovation. Worldwide, engagement between scientists and schools is well-described in the scientific literature (1-4), however, engagement between health researchers and schools is much newer, particularly in Africa, and rarely documented in the academic literature. In November 2018 the KEMRI-Wellcome Trust Research Programme (KWTRP) hosted an international meeting in Kilifi, Kenya, drawing on an emerging community of School Engagement practitioners towards exploring the broad range of goals for School Engagement, learning about the breadth of evaluation approaches and exploring the usefulness of a practitioner network. The workshop was attended by 29 participants representing 21 institutions in 11 countries and comprised: engagement staff from Wellcome Trust-funded Africa and Asia Programmes (AAPs); facilitators of previously funded Wellcome Trust African School Engagement projects; collaborators of Wellcome Trust funded school engagement projects; and long-established UK and Africa-based School Engagement with research projects. Workshop sessions combining small group discussions with plenary presentations, enabled a range of goals, activities and evaluation approaches to be shared. This report summarises these dicussions, and shares the possible function of a network of School Engagement practitioners. Four broad goals for schools engagement emerged: contributing to science education; capacity strengthening for health research; contributing to goals of community engagement; and health promotion. These aimed ultimately at improving health, but also at supporting development in low- and middle-income countries through promoting science-career uptake. Practitioners identified a range of benefits for creating a network to strengthen School Engagement practice: sharing experiences and resources; facilitating capacity strengthening; and fostering collaboration.
REESCRITURA LITERARIA: MALINCHE BAJO LA MIRADA DE LOS ESTUDIOS POSTCOLONIALES
Authors: Pereira Walquíria Rodrigues , Díaz Merino Ximena Antonia 
Published: November 2019

RESUMEN: La propuesta de este estudio es revelar otra perspectiva sobre la figura de Malinche, reflexiones que serán realizadas a la luz de los estudios postcoloniales. As análisis serán realizadas a partir de la novela Malinche (2006), de Laura Esquivel y del ensayo El laberinto de la soledad (1950), de Octavio Paz. Por medio de una lectura cuestionadora y reflexiva serán observadas las diferentes perspectivas de los dos autores en la construcción de la imagen del símbolo mexicano Malinche, la visión de la mujer rehén de la violencia colonizadora en contrapunto con la visión de la mujer que traicionó a su pueblo. A través de la reescritura de la figura Malinche, encontramos la voz del excluido, que en medio de la colonización busca mantener su identidad, su cultura y sus valores, un nuevo enfoque que permite adoptar estrategias de resistencia como medio de supervivencia en oposición al discurso dominante. Las observaciones se guiarán por los estudios críticos de: Homi K. Bhabha (1998), Thomas Bonnici (2005, 2009), Walter Mignolo (1996, 2008) e Maria Emília Granduque José (2016).PALABRAS CLAVE: Literatura; reescritura; Estudios postcoloniales; Malinche.