bluuebunny/crossref_metadata_2025_split huggingface dataset:
Life events and donor lapse among blood donors in Denmark
Authors: Piersma Tjeerd W. , Merz Eva‐Maria , Bekkers René , de Kort Wim , Andersen Steffen , Hjalgrim Henrik , Rostgaard Klaus , Nielsen Kaspar René , Ullum Henrik 
Published: October 2019

AbstractBackground and objectivesThe likelihood of donating blood changes over the life course, with life events shown to influence entry to and exit from the donor population. While these previous findings provide valuable insights for donor management, blood collection agencies need to be cautious about generalizing findings to other countries as blood donor behaviour is context‐specific. To examine cross‐country variations in donor behaviour, the repeatability of a previous Dutch study on life events and blood donor lapse is examined by using a sample of Danish donors.Materials and methodsRegister data from Statistics Denmark was linked to the Scandinavian Donations and Transfusions database (n = 152 887). Logistic regressions were conducted to examine the association between life events in 2009–2012 and blood donor lapse in 2013–2014.ResultsOf the total sample, 69 079 (45·2%) donors lapsed. Childbirth and losing a job increased the lapsing risk by 11% and 16%, respectively, while health‐related events in the family (i.e. blood transfusion, disease and death) decreased the lapsing risk by 5%, 7% and 9%, respectively.ConclusionLife events are associated with donor lapse of Danish donors. These results are comparable to previous findings from the Netherlands (i.e. childbirth and labour market transitions increased lapsing risk; health‐related events decreased lapsing risk), with two thirds of the associations being in the same direction. Differences between study results were mainly related to effect sizes and demographic compositions of the donor pools. We argue contextual factors to be of importance in blood donor studies.
Epigenetic Regulation of Myeloid Cells
Authors: Ivashkiv Lionel B. , Park Sung Ho 
Published: October 2019

ABSTRACT
Epigenetic regulation in myeloid cells is crucial for cell differentiation and activation in response to developmental and environmental cues. Epigenetic control involves posttranslational modification of DNA or chromatin, and is also coupled to upstream signaling pathways and transcription factors. In this review, we summarize key epigenetic events and how dynamics in the epigenetic landscape of myeloid cells shape the development, immune activation, and innate immune memory.
Symbiont arrangement and metabolism can explain high δ13C in Eocene planktonic foraminifera
Authors: Gaskell Daniel E. , Hull Pincelli M. 
Published: October 2019

Abstract
An important question in climate modeling is whether carbon cycling is fundamentally different in warm versus cold climate states. A key line of evidence regarding this question comes from the unusually large difference in carbon-isotope values (δ13C) between shallow-dwelling muricate foraminifera and foraminifera living deeper in the water column in the Paleogene. This has been interpreted as evidence that warmer temperatures elevated the metabolic rates of carbon-recycling bacteria, resulting in a steeper gradient in the δ13C of dissolved inorganic carbon (δ13CDIC) and reduced carbon export. However, this interpretation depends on the assumption that vital effects—biological processes that bias foraminiferal δ13C—are constant throughout time. We test this assumption using a chemical model of the foraminiferal microenvironment and find that the hypothesized increase in metabolic rates should also increase vital effects, meaning that both Paleogene δ13CDIC gradients and the temperature dependence of metabolism must have been significantly lower than previously estimated. We further propose that muricate foraminifera may have evolved a novel “mat” strategy for photosymbiosis wherein symbionts rested on the muricae in a thin layer surrounding the shell. This hypothesis can explain both the function of muricae and the observed isotopic data without the need for any change in metabolism. Our work thus challenges existing interpretations of δ13C and provides a path forward to empirically test the magnitude of temperature-dependent metabolic change in the deep past.
Differential bank migration and the maintenance of channel width in meandering river bends
Authors: Mason Jasmine , Mohrig David 
Published: October 2019

AbstractComparison of three bare-earth lidar data sets along 30 consecutive river bends on the Trinity River in Texas, USA, shows that differential migration of river banks in a channel bend counterbalances past bank migrations so that a statistically steady-state channel width is maintained. Two difference maps created from lidar flown in 2011, 2015, and 2017 capture this temporal variability in the relative amounts of inner versus outer bank migration. In 20 of the studied river bends, channel narrowing during 2011–2015 was counterbalanced by widening during the second interval, or vice versa. Only four bends recorded significant (>1%) progressive change in channel width during both measurement periods. Each of these four bends recorded progressive channel narrowing that was connected to floodplain complexity associated with past bend cutoffs or tributaries. Subaerial volumes of sediment deposited on inner banks of bends were smaller for 2015–2017 than for 2011–2015, while erosional volumes associated with the outer banks were similar despite 2015–2017 having had almost twice the number of days under flood conditions. Over time, channel width for the river appears roughly constant because differences in outer and inner bank migration at one time are counterbalanced by compensating differences at a later time. For the Trinity River, this compensation happened over time spans as short as 2–3 yr and would lead to the appearance of invariant channel width at the decadal scale. Tighter river bends with relatively smaller radii of curvature have smaller magnitudes of width change compared to broader bends with larger radii of curvature.
MK5 Regulates YAP Stability and Is a Molecular Target in YAP-Driven Cancers
Authors: Seo Jimyung , Kim Min Hwan , Hong Hyowon , Cho Hyunsoo , Park Seongyeol , Kim Sang Kyum , Kim Joon 
Published: October 2019

Abstract

Transcriptional regulator YAP is activated in multiple human cancers and plays critical roles in tumor initiation, progression, metastasis, and drug resistance. However, therapeutic targeting of the Hippo–YAP pathway has been challenging due to its low druggability and limited knowledge of YAP regulation in cancer. Here we present a functional screen and identify a novel therapeutic target for YAP-driven tumorigenesis. RNAi screening using an oncogenic YAP activation model identified the serine/threonine kinase MK5 as a positive regulator of YAP. MK5 physically interacted with YAP and counteracted CK1δ/ϵ-mediated YAP ubiquitination and degradation independent of LATS1/2. MK5 kinase activity was essential for protecting YAP from ubiquitin-mediated degradation and cytoplasmic retention. Downregulating MK5 expression inhibited the survival of YAP-activated cancer cell lines and mouse xenograft models. MK5 upregulation was associated with high levels of YAP expression and poor prognosis in clinical tumor samples, confirming its important role for YAP activity in human cancer. These results uncover MK5 as a novel factor that regulates YAP stability, and targeting the YAP degradation pathway controlled by MK5 is a potential strategy for suppressing YAP activity in cancer.

Significance:
These findings reveal MK5 is a novel kinase that regulates YAP in a LATS-independent manner and can be targeted for cancer therapy.
Decreased NOTCH1 Activation Correlates with Response to Ibrutinib in Chronic Lymphocytic Leukemia
Authors: Del Papa Beatrice , Baldoni Stefano , Dorillo Erica , De Falco Filomena , Rompietti Chiara , Cecchini Debora , Cantelmi Maria Grazia , Sorcini Daniele , Nogarotto Manuel , Adamo Francesco Maria , Mezzasoma Federica , Silva Barcelos Estevão Carlos , Albi Elisa , Iacucci Ostini Roberta , Di Tommaso Ambra , Marra Andrea , Montanaro Guido , Martelli Maria Paola , Falzetti Franca , Di Ianni Mauro , Rosati Emanuela , Sportoletti Paolo 
Published: October 2019

Abstract

Purpose:
Ibrutinib, a Bruton tyrosine kinase inhibitor (BTKi), has improved the outcomes of chronic lymphocytic leukemia (CLL), but primary resistance or relapse are issues of increasing significance. While the predominant mechanism of action of BTKi is the B-cell receptor (BCR) blockade, many off-target effects are unknown. We investigated potential interactions between BCR pathway and NOTCH1 activity in ibrutinib-treated CLL to identify new mechanisms of therapy resistance and markers to monitor disease response.

Experimental Design:
NOTCH activations was evaluated either in vitro and ex vivo in CLL samples after ibrutinib treatment by Western blotting. Confocal proximity ligation assay (PLA) experiments and analyses of down-targets of NOTCH1 by qRT-PCR were used to investigate the cross-talk between BTK and NOTCH1.

Results:
In vitro ibrutinib treatment of CLL significantly reduced activated NOTCH1/2 and induced dephosphorylation of eIF4E, a NOTCH target in CLL. BCR stimulation increased the expression of activated NOTCH1 that accumulated in the nucleus leading to HES1, DTX1, and c-MYC transcription. Results of in situ PLA experiments revealed the presence of NOTCH1-ICD/BTK complexes, whose number was reduced after ibrutinib treatment. In ibrutinib-treated CLL patients, leukemic cells showed NOTCH1 activity downregulation that deepened over time. The NOTCH1 signaling was restored at relapse and remained activated in ibrutinib-resistant CLL cells.

Conclusions:
We demonstrated a strong clinical activity of ibrutinib in a real-life context. The ibrutinib clinical efficacy was associated with NOTCH1 activity downregulation that deepened over time. Our data point to NOTCH1 as a new molecular partner in BCR signaling with potential to further improve CLL-targeted treatments.
Genetic and Epigenetic Characterization of Growth Hormone–Secreting Pituitary Tumors
Authors: Välimäki Niko , Schalin-Jäntti Camilla , Karppinen Atte , Paetau Anders , Kivipelto Leena , Aaltonen Lauri A. , Karhu Auli 
Published: October 2019

Abstract

Somatic driver mechanisms of pituitary adenoma pathogenesis have remained incompletely characterized; apart from mutations in the stimulatory Gα protein (Gαs encoded by GNAS) causing activated cAMP synthesis, pathogenic variants are rarely found in growth hormone–secreting pituitary tumors (somatotropinomas). The purpose of the current work was to clarify how genetic and epigenetic alterations contribute to the development of somatotropinomas by conducting an integrated copy number alteration, whole-genome and bisulfite sequencing, and transcriptome analysis of 21 tumors. Somatic mutation burden was low, but somatotropinomas formed two subtypes associated with distinct aneuploidy rates and unique transcription profiles. Tumors with recurrent chromosome aneuploidy (CA) were GNAS mutation negative (Gsp−). The chromosome stable (CS) –group contained Gsp+ somatotropinomas and two totally aneuploidy-free Gsp− tumors. Genes related to the mitotic G1–S-checkpoint transition were differentially expressed in CA- and CS-tumors, indicating difference in mitotic progression. Also, pituitary tumor transforming gene 1 (PTTG1), a regulator of sister chromatid segregation, showed abundant expression in CA-tumors. Moreover, somatotropinomas displayed distinct Gsp genotype–specific methylation profiles and expression quantitative methylation (eQTM) analysis revealed that inhibitory Gα (Gαi) signaling is activated in Gsp+ tumors. These findings suggest that aneuploidy through modulated driver pathways may be a causative mechanism for tumorigenesis in Gsp− somatotropinomas, whereas Gsp+ tumors with constitutively activated cAMP synthesis seem to be characterized by DNA methylation activated Gαi signaling.

Implications:
These findings provide valuable new information about subtype-specific pituitary tumorigenesis and may help to elucidate the mechanisms of aneuploidy also in other tumor types.
Reasons for Prehospital Delay in Acute Ischemic Stroke
Authors: Fladt Joachim , Meier Nicole , Thilemann Sebastian , Polymeris Alexandros , Traenka Christopher , Seiffge David J. , Sutter Raoul , Peters Nils , Gensicke Henrik , Flückiger Benjamin , de Hoogh Kees , Künzli Nino , Bringolf‐Isler Bettina , Bonati Leo H. , Engelter Stefan T. , Lyrer Philippe A. , De Marchis Gian Marco 
Published: October 2019

Background
Prehospital delay reduces the proportion of patients with stroke treated with recanalization therapies. We aimed to identify novel and modifiable risk factors for prehospital delay.

Methods and Results

We included patients with an ischemic stroke confirmed by diffusion‐weighted magnetic resonance imaging, symptom onset within 24 hours and hospitalized in the Stroke Center of the University Hospital Basel, Switzerland. Trained study nurses interviewed patients and proxies along a standardized questionnaire. Prehospital delay was defined as >4.5 hours between stroke onset—or time point of wake‐up—and admission. Overall, 336 patients were enrolled. Prehospital delay was observed in 140 patients (42%). The first healthcare professionals to be alarmed were family doctors for 29% of patients (97/336), and a quarter of these patients had a baseline National Institute of Health Stroke Scale score of 4 or higher. The main modifiable risk factor for prehospital delay was a face‐to‐face visit to the family doctor (adjusted odds ratio, 4.19; 95%
CI
, 1.85–9.46). Despite transport by emergency medical services being associated with less prehospital delay (adjusted odds ratio, 0.41; 95%
CI
, 0.24–0.71), a minority of patients (39%) who first called their family doctor were transported by emergency medical services to the hospital. The second risk factor was lack of awareness of stroke symptoms (adjusted odds ratio, 4.14; 95%
CI
, 2.36–7.24).

Conclusions
Almost 1 in 3 patients with a diffusion‐weighted magnetic resonance imaging–confirmed ischemic stroke first called the family doctor practice. Face‐to‐face visits to the family doctor quadrupled the odds of prehospital delay. Efforts to reduce prehospital delay should address family doctors and their staffs as important partners in the prehospital pathway.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02798770.
People’s Intuitions About Innateness
Authors: Berent Iris , Platt Melanie , Sandoboe Gwendolyn M. 
Published: October 2019

Abstract
Few questions in science are as controversial as the origins of knowledge. Whether knowledge (e.g., “objects are cohesive”) is partly innate has been debated for centuries. Here, we ask whether our difficulties with innate knowledge could be grounded in human cognition itself. In eight experiments, we compared reasoning about the innateness of traits that capture knowledge (cognitive traits) with noncognitive (sensorimotor and emotive) traits. Experiments 1–4 examined adult and infant traits; Experiment 5 presented detailed descriptions of published infant experiments. Results showed that people viewed cognitive traits as less likely to be innate in humans—the stronger the association with “thinking,” the lower the rating for “innateness.” Experiments 6–8 explored human, bird, and alien traits that were presented as innate. Participants, however, still considered cognitive traits as less likely to emerge spontaneously (i.e., be innate). These results show that people are selectively biased in reasoning about the origins of knowledge.
The Development of Armeno-Turkish (Hayatar T‘rk‘erēn) in the 19th Century Ottoman Empire
Authors: Der Matossian Bedross 
Published: October 2019

Abstract
Armeno-Turkish played an important role in the lives of Armenians in the Ottoman Empire. At a time in which more than half of the Armenians of the Empire did not speak Armenian, Armeno-Turkish came to fill an important gap. It led to the proliferation of literacy among Armenians and allowed them to mark and strengthen their ethno-religious boundaries vis-à-vis other ethno-religious groups in the Ottoman Empire, while simultaneously allowing for the crossing of these boundaries which, in general, were characterized by fluidity. The 19th century represents an important phase in the development of Armeno-Turkish. Its development cannot be attributed to one factor; rather to a host of factors that include the impact of the Armenian Zart‘ōnk‘ (awakening), the spread of Catholicism and Protestantism, the impact of the Tanzimat Reforms (1839–1876), the development of Armenian ethno-religious boundaries, and the role of print culture. Finally, Armeno-Turkish raises important questions regarding identity formation, belonging, and cross-cultural interaction.
<p><strong><em>Lithophyllum longense</em></strong><strong> (Corallinales, Rhodophyta): a </strong><strong>species with a widespread Indian Ocean distribution</strong></p>
Authors: MANEVELDT G.W. , GABRIELSON P.W. , TOWNSEND R.A. , KANGWE J. 
Published: October 2019

Lithophyllum longense is characterized from Long Reef, Western Australia, Australia and from Chwaka Bay, Zanzibar Island, Tanzania. Both plastid markers psbA and rbcL confirm that L. longense is a distinct species despite its being morpho-anatomically nearly indistinguishable from several other fruticose Lithophyllum species, differing in only one (from L. atlanticum, L. platyphyllum, L. sublicatum, L. yemenense) or two (from L. affine, L. incrustans, L. kotschyanum, L. neocongestum, L. kaiseri, L. pseudoplatyphyllum, L. subreduncum) character states. This is only the second tropical Lithophyllum species and the fourth tropical species confirmed by DNA sequencing to be widely distributed in the Indo-West Pacific.
Unintended consequences in implementing public sector accounting reforms in emerging economies: evidence from Egypt, Nepal and Sri Lanka
Authors: Adhikari Pawan , Kuruppu Chamara , Ouda Hassan , Grossi Giuseppe , Ambalangodage Dayananda 
Published: October 2019

This study investigates the implementation of public sector accounting reforms in Egypt, Nepal and Sri Lanka. Data for the article are derived through document analysis and semi-structured interviews with public administrators, government accountants and members of professional accountancy bodies. The article brings out the factors that have either individually or collectively stifled the diffusion trajectory of public sector accounting reforms in Egypt, Nepal and Sri Lanka at the implementation phase, including the bundling process, pro-innovation biases, informal and interpersonal networks, a boundary-spanning process, organisational communication, power disparity, and dominance. As a result, public sector accounting reforms have resulted in resistance, internal conflicts and unintended consequences, including the fabrication of results, in all three countries without any evidence of yielding better results for public sector governance and accountability. Points for practitioners Public sector accounting practitioners should realise the importance of considering the specific contexts of emerging economies, including the power structures, communication channels, informal networks and communication flows, prior to the diffusion of reforms. When such contextual elements are de-emphasised, reforms would tend to encounter delay and resistance, ongoing reforms in Egypt, Nepal and Sri Lanka serving as examples. Also, instead of delegating power to professional accountants and expert groups, they can be employed as boundary spanners to facilitate communication with government accountants about the technical complexities of public sector accounting reforms. This may help establish an efficient communication network and strengthen interpersonal and informal networks, enabling reforms to pass through the diffusion trajectory without being stifled at the implementation phase.
Fluvoxamine combination therapy with tropisetron for obsessive-compulsive disorder patients: A placebo-controlled, randomized clinical trial
Authors: Shalbafan Mohammadreza , Malekpour Farzaneh , Tadayon Najafabadi Borna , Ghamari Kiandokht , Dastgheib Seyed-Ali , Mowla Arash , Shirazi Elham , Eftekhar Ardebili Mehrdad , Ghazizadeh-Hashemi Maryam , Akhondzadeh Shahin 
Published: October 2019

Background: About 50% of obsessive-compulsive disorder patients still suffer significant symptoms even after the recommended first-line therapy. This demonstrates the necessity to investigate strategies to improve alleviation of symptoms. Objective: The main objective of this study was to investigate the efficacy of a 5-hydroxytryptophan 3 receptor antagonist, tropisetron, as an adjuvant therapy to selective serotonin reuptake inhibitors, in ameliorating obsessive-compulsive disorder symptoms. Methods: Men and women between the ages of 18–60 years diagnosed with obsessive-compulsive disorder, based on DSM5, who had a Yale-Brown obsessive compulsive scale score of more than 21 were recruited in a double-blinded, parallel-group, placebo-controlled, clinical trial of 10 weeks to receive either tropisetron (5 mg twice daily) and fluvoxamine (100 mg daily initially followed by 200 mg daily after week 4) or placebo and fluvoxamine. The primary outcome of interest in this study was the Yale-Brown obsessive compulsive scale total score decrease from baseline. Results: One hundred and eight participants were equally randomized into two groups; 48 participants in each group finished the trial. The Yale-Brown obsessive compulsive total score significantly dropped in both groups while the tropisetron group participants experienced a significantly higher decrease in their scores (Greenhouse-Geisser F(1.53–65.87)=3.516, p-value=0.04). No major adverse effect was observed in any of the groups. Conclusion: This trial showed a significant efficacy for tropisetron over placebo in treatment of obsessive-compulsive disorder symptoms when added to fluvoxamine.