bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoids inhibit macrophage differentiation towards a pro-inflammatory phenotype upon wounding without affecting their migration
Authors: Xie Yufei , Tolmeijer Sofie , Oskam Jelle M. , Tonkens Tijs , Meijer Annemarie H. , Schaaf Marcel J. M. 
Published: May 2019

ABSTRACT
Glucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited upon glucocorticoid treatment, whereas migration of macrophages is glucocorticoid resistant. We show that wounding-induced increases in the expression of genes that encode neutrophil-specific chemoattractants (Il8 and Cxcl18b) are attenuated by the synthetic glucocorticoid beclomethasone, but that beclomethasone does not attenuate the induction of the genes encoding Ccl2 and Cxcl11aa, which are required for macrophage recruitment. RNA sequencing on FACS-sorted macrophages shows that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas only a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using a tnfa:eGFP-F reporter line and analysis of macrophage morphology. We conclude that differentiation and migration of macrophages are regulated independently, and that glucocorticoids leave the chemotactic migration of macrophages unaffected, but exert their anti-inflammatory effect on these cells by inhibiting their differentiation to an M1 phenotype. The resistance of macrophage-dominated diseases to glucocorticoid therapy can therefore not be attributed to an intrinsic insensitivity of macrophages to glucocorticoids.
Enhancer of Polycomb and the Tip60 complex repress hematological tumor initiation by negatively regulating JAK/STAT pathway activity
Authors: Bailetti Alessandro A. , Negrón-Piñeiro Lenny J. , Dhruva Vishal , Harsh Sneh , Lu Sean , Bosula Aisha , Bach Erika A. 
Published: May 2019

ABSTRACT
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders that cause excessive production of myeloid cells. Most MPN patients have a point mutation in JAK2 (JAK2V617F), which encodes a dominant-active kinase that constitutively triggers JAK/STAT signaling. In Drosophila, this pathway is simplified, with a single JAK, Hopscotch (Hop), and a single STAT transcription factor, Stat92E. The hopTumorous-lethal [hopTum] allele encodes a dominant-active kinase that induces sustained Stat92E activation. Like MPN patients, hopTum mutants have significantly more myeloid cells, which form invasive tumors. Through an unbiased genetic screen, we found that heterozygosity for Enhancer of Polycomb [E(Pc)], a component of the Tip60 lysine acetyltransferase complex (also known as KAT5 in humans), significantly increased tumor burden in hopTum animals. Hematopoietic depletion of E(Pc) or other Tip60 components in an otherwise wild-type background also induced blood cell tumors. The E(Pc) tumor phenotype was dependent on JAK/STAT activity, as concomitant depletion of hop or Stat92E inhibited tumor formation. Stat92E target genes were significantly upregulated in E(Pc)-mutant myeloid cells, indicating that loss of E(Pc) activates JAK/STAT signaling. Neither the hop nor Stat92E gene was upregulated upon hematopoietic E(Pc) depletion, suggesting that the regulation of the JAK/STAT pathway by E(Pc) is dependent on substrates other than histones. Indeed, E(Pc) depletion significantly increased expression of Hop protein in myeloid cells. This study indicates that E(Pc) works as a tumor suppressor by attenuating Hop protein expression and ultimately JAK/STAT signaling. Since loss-of-function mutations in the human homologs of E(Pc) and Tip60 are frequently observed in cancer, our work could lead to new treatments for MPN patients.
This article has an associated First Person interview with the first author of the paper.
SeqAcademy: an educational pipeline for RNA-Seq and ChIP-Seq analysis
Authors: Ather Syed Hussain , Awe Olaitan Igbagbo , Butler Thomas J. , Denka Tamiru , Semick Stephen Andrew , Tang Wanhu , Busby Ben 
Published: May 2019

Quantification of gene expression and characterization of gene transcript structures are central problems in molecular biology. RNA sequencing (RNA-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) are important methods, but can be cumbersome and difficult for beginners to learn. To teach interested students and scientists how to analyze RNA-Seq and ChIP-Seq data, we present a start-to-finish tutorial for analyzing RNA-Seq and ChIP-Seq data: SeqAcademy (source code: https://github.com/NCBI-Hackathons/seqacademy, webpage: http://www.seqacademy.org/). This user-friendly pipeline, fully written in markdown language, emphasizes the use of publicly available RNA-Seq and ChIP-Seq data and strings together popular tools that bridge that gap between raw sequencing reads and biological insight. We demonstrate practical and conceptual considerations for various RNA-Seq and ChIP-Seq analysis steps with a biological use case - a previously published yeast experiment. This work complements existing sophisticated RNA-Seq and ChIP-Seq pipelines designed for advanced users by gently introducing the critical components of RNA-Seq and ChIP-Seq analysis to the novice bioinformatician. In conclusion, this well-documented pipeline will introduce state-of-the-art RNA-Seq and ChIP-Seq analysis tools to beginning bioinformaticians and help facilitate the analysis of the burgeoning amounts of public RNA-Seq and ChIP-Seq data.
How many child deaths can be averted in Nigeria? Assessing state-level prospects of achieving 2030 sustainable development goals for neonatal and under-five mortality
Authors: Ogbuoji Osondu , Yamey Gavin 
Published: May 2019

Background: Nigeria’s neonatal mortality rate (NMR) and under-five mortality rate (U5MR) are 39 per 1,000 and 120 per 1,000 live births, respectively. On average, 0.23 million neonates and 0.7 million under-five children die every year, but some states contribute more to this burden than others. If the country is to meet its sustainable development goal (SDG) targets for NMR and U5MR, it needs to make progress at both the national and subnational levels. Methods: Using the 2016-2017 Nigeria Multiple Indicator Cluster Survey (MICS), we estimated state-level neonatal and under-five mortality rates. Next, we estimated how long it would take for each state to reach the SDG targets for NMR and U5MR. Finally, we estimated the average number of neonatal and under-five deaths that could be averted between 2018 and 2030 in each state under different scenarios. Results: At current average annual rates of decline, Nigeria is unlikely to meet both sustainable development goals targets for NMR and U5MR. At the subnational level, some states are close to or have met both NMR and U5MR targets, while others are projected to meet the targets as late as 2088 (58 years delayed). Between 850,000 and 1.89 million neonatal deaths could be averted between 2018 and 2030, while 3.1 million to 5.96 million under-five deaths could be averted over the same period. Conclusions: Nigeria has the potential to achieve its SDG targets for NMR and U5MR, and in the process avert millions of preventable child deaths. But this will not happen under a business-as-usual approach. The NMR and U5MR trajectories achieved by high-performing states is evidence that achieving these SDG targets is possible. For the country to achieve positive results nationally, systems that encourage peer learning and transfer of technical expertise between states are needed.
Bone reconstruction after malignant tumour resection using a motorized lengthening intramedullary nail in adolescents: Preliminary results
Authors: Accadbled F. , Thévenin Lemoine C. , Poinsot E. , Baron Trocellier T. , Dauzere F. , Sales de Gauzy J. 
Published: May 2019

Purpose Bone reconstruction after malignant tumour of the lower limbs is a challenge. Our aim was to investigate the results of bone lengthening and transport using the Fitbone motorized lengthening nail. Methods Eight patients were included. Two patients had had a tumour involving soft tissue only without bone resection. In six patients, the initial bone defect was 15.5 cm (8 to 24). The first step of reconstruction had consisted of temporary fixation and a cement spacer. The second step had consisted of bone grafting in five patients. One patient was managed with bone transport. Eventually, five patients had a limb-length discrepancy (LLD) managed with bone lengthening only. Two patients had a LLD and a nonunion managed with bone transport and lengthening. Mean age at bone lengthening was 15.2 years (11 to 19). Mean follow-up was 30.5 months (10 to 48). Results In all, 11 nails were implanted in eight patients (eight femurs, three tibias). Mean length gain per procedure was 54.5 mm (30 to 80). Mean healing index was 48.4 days per cm (22.6 to 85.7). The complication rate was 18%. In two cases we observed a loose locking screw, which was revised. In all cases the lengthening involved the short bone (femur or tibia). Mean Musculoskeletal Tumor Society (MSTS) score improved from 52.7 (16.6 to 73.3) to 79.9 (63.3 to 96.6). Conclusions Bone reconstruction using a motorized intramedullary nail stands as a safe and reliable alternative after malignant tumour. It allows biological reconstruction with satisfactory clinical and radiological outcome and low complication rate. Level of evidence III
MODEL PEMBERDAYAAN IBU BALITA TENTANG MP-ASI DI KELURAHAN WONOREJO KABUPATEN KARANGANYAR
Authors: Yunita Fresthy Astrika , Hardiningsih Hardiningsih , Yuneta Agus Eka Nurma 
Published: May 2019

<p><strong>Latar belakang:</strong> Lima tahun pertama usia emas seorang anak (Golden Age) adalah masa yang sangat menentukan. Makanan pendamping ASI perlu di berikan balita usia 6 bulan, ASI bagi bayi tidak lagi mencukupi kebutuhan energi untuk tumbuh dan berkembang, tetapi selama pemberian makanan tambahan pada bayi ASI tetap di berikan pada balita. Masalah kesehatan dan sosial yang dihadapi Indonesia adalah rendahnya status gizi masyarakat Status Gizi balita menurut Rikesdas 2013 adalah 5,7% gizi buruk dan 13,9 % gizi kurang. Tujuan pengabdian masyarakat ini adalah untuk melaksanakan model pemberdayaan pada Ibu Balita tentang MP ASI di Kelurahan Wonorejo sehingga diharapkan ibu balita mampu mengembangkan pola asuh tentang pengetahuan Makanan Pendamping ASI.</p><p><strong>Subjek dan Metode:</strong> Model pemberdayaan ibu balita tentang MP ASI ini dilakukan melalui koordinasi Bidan Koordinator di PKD kelurahan Wonorejo, kader dan personil yang terlibat dalam kegiatan posyandu untuk selanjutnya melakukan penyuluhan kepada ibu balita.</p><p><strong>Hasil:</strong> Hasil pengabdian adalah telah dilaksanakan pemberdayaan MP ASI pada ibu balita di kelurahan wonorejo. Ibu balita mendapatkan pengetahuan tentang MP ASI dan beberapa contoh pengolahan menu MP ASI yang dapat diterapkan dirumah.</p><p><strong>Kesimpulan:</strong> Diharapkan balita mendapatkan gizi yang cukup dengan penerapan MP ASI sesuai dengan tahapannya sehingga proses tumbuh kembang berjalan dengan baik dan normal sesuai perkembangan umurnya.</p>
Characterization and Industrial Performance Evaluation of Duplex-Treated AISI H21 Die Steel during Hot Forging Process
Authors: Chander Subhash , Chawla Vikas 
Published: May 2019

Abstract
Die/tooling failure during the hot forging process is mainly due to repeated varying mechanical loads, rigorous thermal shocks, as well as strong friction and erosion. These cause different failure mechanisms, such as wear, thermal fatigue, and plastic deformation. The enhancement of die service life for a hot forging industry is necessary now in order to be competitive globally. Four nitride coatings—TiN, TiAlN, TiCrN, and AlCrN—were deposited onto plasma-nitrided AISI H21 hot work die steel using the cathodic arc evaporation physical vapor deposition technique. The coatings were characterized by scanning electron microscope (SEM), SEM–energy dispersive x-ray spectroscopy (EDS), x-ray power diffraction (XRD), line scan EDS, and x-ray mapping tests and microhardness tester. The wear characteristics were examined using a pin-on-disk method at high temperature and speed against EN31 bearing steel disk. It was observed that the AlCrN and CrTiN coatings have lower wear rates than other coatings at high temperature (550°C). Also, these coatings performed best during actual industrial practice. The enhancement in die life was reported to be 55 and 76 % in terms of parts being hot forged. The low value of the coefficient of friction for all coatings at 550°C can partly be attributed to lower hardness difference between the pins and disks, decreased plastic deformation in the contact, and, consequently, less ploughing (abrasive wear action). Predominately, wear was the main die failure mode there was; when used, dies were observed microscopically.
Steroid metabolomic signature of liver disease in nonsyndromic childhood obesity
Authors: Gawlik Aneta , Shmoish Michael , Hartmann Michaela F , Wudy Stefan A , Olczak Zbigniew , Gruszczynska Katarzyna , Hochberg Ze’ev 
Published: May 2019

Objective
Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subject’s steroidal fingerprint. Here, we compare the steroidal fingerprints of obese children with or without liver disease to identify the ‘steroid metabolomic signature’ of childhood nonalcoholic fatty liver disease.

Methods
Urinary samples of 85 children aged 8.5–18.0 years with BMI >97% were quantified for 31 steroid metabolites by GC-MS. The fingerprints of 21 children with liver disease (L1) as assessed by sonographic steatosis (L1L), elevated alanine aminotransferases (L1A) or both (L1AL), were compared to 64 children without markers of liver disease (L0). The steroidal signature of the liver disease was generated as the difference in profiles of L1 against L0 groups.

Results
L1 comparing to L0 presented higher fasting triglycerides (P = 0.004), insulin (P = 0.002), INS/GLU (P = 0.003), HOMA-IR (P = 0.002), GGTP (P = 0.006), AST/SGOT (P = 0.002), postprandial glucose (P = 0.001) and insulin (P = 0.011). L1AL showed highest level of T-cholesterol and triglycerides (P = 0.029; P = 0.044). Fasting insulin, postprandial glucose, INS/GLU and HOMA-IR were highest in L1L and L1AL (P = 0.001; P = 0.017; P = 0.001; P = 0.001). The liver disease steroidal signature was marked by lower DHEA and its metabolites, higher glucocorticoids (mostly tetrahydrocortisone) and lower mineralocorticoid metabolites than L0. L1 patients showed higher 5α-reductase and 21-hydroxylase activity (the highest in L1A and L1AL) and lower activity of 11βHSD1 than L0 (P = 0.041, P = 0.009, P = 0.019).

Conclusions
The ‘steroid metabolomic signature’ of liver disease in childhood obesity provides a new approach to the diagnosis and further understanding of its metabolic consequences. It reflects the derangements of steroid metabolism in NAFLD that includes enhanced glucocorticoids and deranged androgens and mineralocorticoids.
Aurélie Choné, Isabelle Hajek, and Philippe Hamman (eds.), Rethinking Nature: Challenging Disciplinary Boundaries
Authors: De Pater Catharina H. 
Published: May 2019

Aurélie Choné, Isabelle Hajek, and Philippe Hamman (eds.), Rethinking Nature:Challenging Disciplinary Boundaries (Abingdon: Routledge, 2017), xiii + 268 pp., £ 31.99(pbk), ISBN: 978-1-138-21493-4.
Astrology as Heresy in Contemporary Belief
Authors: Phillipson Garry 
Published: May 2019

Astrology has been characterised as a heresy by many Christian thinkers, from the time of the early Church Fathers to the present day. In contemporary discourse, astrology is often treated as if it were a heresy against science. I provide examples of astrologers being treated as heretics in the name of science, and an alternative conception of astrology as a form of divination, not dependent on scienti?c substantiation. I argue that the ‘astrology’ often criticised in the name of science may be de?ned as much by scientism’s need for a construction to de?ne itself against, as by the actual views of horoscopic astrologers. The emerging picture is that criticisms of astrology are typically based on a mixture of legitimate objections and scientistic belief. I conclude that scientism’s unspoken aspiration to orthodoxy emerges through the parallels between its approach to astrology and that of the Church.
Living with Fate
Authors: Brady Bernadette 
Published: May 2019

Astrologers are assumed to be a group of people whose lives are dictated by the stars. This position has been encouraged by ad hominem twentieth-century polemics where the astrologer is portrayed as a person of questionable mental ability who takes no responsibility for their life. These assumptions have been informed by the de?nition of fate from the Classical period of Marcus Tullius Cicero (106–43 BCE). In contrast, my research among English-speaking astrologers revealed that their lifestyle was one where beliefs about the nature of fate varied considerably from Cicero’s views and that they used their beliefs in three ways: as an aid for their spiritual development, as a tool for personal re?ection, or as a means for life-planning. The astrologers in my research actively engaged with their lives using their beliefs about fate, understanding it like a life companion rather than a life dictator.
Jesus and the Feminine Genius. The Anthropological Relevance of the Encounters of Jesus with Women in the Fourth Gospel
Authors: Timmermans Marc 
Published: May 2019

Pope John Paul II introduced the expression of the “Feminine Genius” in his Apostolic Letter Mulieris Dignitatem of 1988. If this characteristic belongs to all women in history, there must be traces of it in the Gospel. The article verifies that this is the case in the Gospel of John.Indeed, taking a closer look to the different encounters between Jesus and individual women, we see that the latter have a specific influence on the action of Jesus and participate in a particular way in the mission of Jesus. Two key ideas can help us clarify in which way these women participate in Jesus’ mission. The first is the fruitfulness of faith. Those who believe are born from God himself (1:13), through faith in Christ. This is particularly the case for the Samaritan woman (4:4–42). Her life changes when she comes progressively to faith in Christ: “could he be the Christ?” (4:29). The second key idea is the prophecy of the High Priest Caiaphas: “Jesus was to die for the nation and not for the nation only but also in order to gather into one the scattered children of God.” (11:51–52). Again, the Samaritan woman can serve as an example. She goes back to her town and brings her fellow Samaritans to faith in Jesus (4:39: “Many of that town believed in him”). They represent the first fruits of the great eschatological harvest, the gathering of those who believe in Jesus.Both ideas can shine a light on the specific mission of women in the Fourth Gospel. From Mary in Cana or at the foot of the cross to Mary Magdalene at the tomb, from the Samaritan woman to the adulterous woman and the sisters Martha and Mary, they all influence Jesus in his specific mission of arousing faith and gathering the scattered children of God.These encounters will help us to understand more concretely what John Paul II meant by Feminine Genius and what the role of women in the mission of the Church could be now.
Conformity to Clinical Practice Guidelines at Initial Management in Adult Soft Tissue and Visceral Tumors since the Implementation of the NetSarc Network in Eastern France
Authors: Gantzer Justine , Di Marco Antonio , Fabacher Thibaut , Weingertner Noelle , Delhorme Jean-Baptiste , Brinkert David , Bierry Guillaume , Ghnassia Jean-Pierre , Jégu Jérémie , Kurtz Jean-Emmanuel 
Published: May 2019

Abstract

Background
Soft tissue sarcomas are rare and heterogenous tumors that are hard to diagnose. The aim of this study was to evaluate local practices and conformity to clinical practice guidelines (CPGs) for their initial diagnostic management.

Materials and Methods
Patients were carriers of a soft tissue or visceral tumor, presented at a sarcoma tumor board (STB) between 2010 and 2016. Conformity to CPGs was evaluated using ten criteria designed for this purpose. Associations between different factors and conformity to composite criteria, reflecting the three main diagnostic steps (imaging, biopsy and histological report) were analyzed.

Results
A total of 643 patients were included. A preoperative tumor imaging assessment and a biopsy were performed according to CPGs in 80.8% and 36.8% of the cases, respectively. When done, the first surgical resection was R0 in 30.3% of cases, R1 in 28.6%, and R2 in 10.9%. The rest of the operated patients with sarcoma had a second surgical excision (11.4%), an intraoperative fragmentation (4.3%), or margins were unknown (14.4%). Six of the ten quality criteria presented a conformity rate higher than 70%. Two criteria with a conformity rate lower than 20% were the most controversial: presentation at a STB before biopsy and freezing of a tumor fragment. A multivariate analysis revealed that the common predictor of nonconformity to composite criteria was the initial management in a nonexpert center.

Conclusion
Initial diagnostic management requires improvement, especially outside of specialized centers.
Phase II Study of Bendamustine and Ofatumumab in Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma Who Are Poor Candidates for R-CHOP Chemotherapy
Authors: Flinn Ian W. , Erter Jack , Daniel Davey B. , Mace Joseph R. , Berdeja Jesus G. 
Published: May 2019

Abstract

Lessons Learned
The combination of ofatumumab and bendamustine in elderly patients with diffuse large B-cell lymphoma demonstrated modest efficacy compared with standard of care. The poor response may have been due to patient age and the high rate of treatment discontinuation.

Background
This phase II trial evaluated the efficacy of bendamustine and ofatumumab in elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) who were not candidates for rituximab cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP).

Methods
Patients received IV 90 mg/m2 bendamustine on days 1 and 2 of cycles 1 through 6 and IV 1,000 mg ofatumumab on days 1 and 8 of cycle 1 and on day 1 of cycles 2 through 6. Both drugs were administered at the U.S. Food and Drug Administration-approved dose for combination therapy. All patients received premedications before each infusion of ofatumumab and hematopoietic growth factors. Treatment was administered in 21-day cycles, with restaging after cycle 3 and cycle 6. The primary endpoint was complete response rate (CRR).

Results
Twelve of 21 enrolled patients completed treatment; median age was 83 years. The most common reasons for treatment discontinuation were disease progression (three patients), intercurrent illness (two patients), and death (one patient due to drug-related sepsis and bowel necrosis and one patient due to unknown cause). Thrombocytopenia (14%), neutropenia (10%), diarrhea (10%), vomiting (10%), and dehydration (10%) were the most common grade ≥3 treatment-related adverse events. The overall response rate was 90.5% and the CRR was 33.3%. Median progression-free survival (PFS) and overall survival (OS) were 8.6 and 12.0 months, respectively.

Conclusion
The combination of ofatumumab and bendamustine is feasible in elderly patients with DLBCL.