bluuebunny/crossref_metadata_2025_split huggingface dataset:
American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults
Authors: Sekeres Mikkael A. , Guyatt Gordon , Abel Gregory , Alibhai Shabbir , Altman Jessica K. , Buckstein Rena , Choe Hannah , Desai Pinkal , Erba Harry , Hourigan Christopher S. , LeBlanc Thomas W. , Litzow Mark , MacEachern Janet , Michaelis Laura C. , Mukherjee Sudipto , O’Dwyer Kristen , Rosko Ashley , Stone Richard , Agarwal Arnav , Colunga-Lozano L. E. , Chang Yaping , Hao QiuKui , Brignardello-Petersen Romina 
Published: August 2020

Abstract

Background:
Older adults with acute myeloid leukemia (AML) represent a vulnerable population in whom disease-based and clinical risk factors, patient goals, prognosis, and practitioner- and patient-perceived treatment risks and benefits influence treatment recommendations.

Objective:
These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about management of AML in older adults.

Methods:
ASH formed a multidisciplinary guideline panel that included specialists in myeloid leukemia, geriatric oncology, patient-reported outcomes and decision-making, frailty, epidemiology, and methodology, as well as patients. The McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline-development process, including performing systematic evidence reviews (up to 24 May 2019). The panel prioritized clinical questions and outcomes according to their importance to patients, as judged by the panel. The panel used the GRADE approach, including GRADE’s Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.

Results:
The panel agreed on 6 critical questions in managing older adults with AML, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management, the intensity of therapy, the role and duration of postremission therapy, combination vs monotherapy for induction and beyond, duration of less-intensive therapy, and the role of transfusion support for patients no longer receiving antileukemic therapy.

Conclusions:
Treatment is recommended over best supportive management. More-intensive therapy is recommended over less-intensive therapy when deemed tolerable. However, these recommendations are guided by the principle that throughout a patient’s disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment.
Timing of high-dose methotrexate CNS prophylaxis in DLBCL: an analysis of toxicity and impact on R-CHOP delivery
Authors: Wilson Matthew R. , Eyre Toby A. , Martinez-Calle Nicolas , Ahearne Matthew , Parsons Katrina E. , Preston Gavin , Khwaja Jahanzaib , Schofield Jeremy , Elliot Johnathon , Mula Kh Almurtadha , Shah Nimish , Cheung Cheuk-Kie , Timmins Matthew A. , Creasey Thomas , Linton Kim , Smith Jeffery , Fox Christopher P. , Miall Fiona , Cwynarski Kate , McKay Pamela 
Published: August 2020

Abstract
High-dose methotrexate (HD-MTX) is increasingly used as prophylaxis for patients with diffuse large B-cell lymphoma (DLBCL) at high risk of central nervous system (CNS) relapse. However, there is limited evidence to guide whether to intercalate HD-MTX (i-HD-MTX) between R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone given at 21-day intervals) or to give it at the end of treatment (EOT) with R-CHOP-21. We conducted a retrospective, multicenter analysis of 334 patients with DLBCL who received CNS prophylaxis with i-HD-MTX (n = 204) or EOT HD-MTX (n = 130). Primary end points were R-CHOP delay rates and HD-MTX toxicity. Secondary end points were CNS relapse rate, progression-free survival, and overall survival. The EOT group had more patients with a high CNS international prognostic index (58% vs 39%; P &lt; .001) and more concurrent intrathecal prophylaxis (56% vs 34%; P &lt; .001). Of the 409 cycles of i-HD-MTX given, 82 (20%) were associated with a delay of next R-CHOP (median, 7 days). Delays were significantly increased when i-HD-MTX was given after day 9 post–R-CHOP (26% vs 16%; P = .01). On multivariable analysis, i-HD-MTX was independently associated with increased R-CHOP delays. Increased mucositis, febrile neutropenia, and longer median inpatient stay were recorded with i-HD-MTX delivery. Three-year cumulative CNS relapse incidence was 5.9%, with no differences between groups. There was no difference in survival between groups. We report increased toxicity and R-CHOP delay with i-HD-MTX compared with EOT delivery but no difference in CNS relapse or survival. Decisions on HD-MTX timing should be individualized and, where i-HD-MTX is favored, we recommend scheduling before day 10 of R-CHOP cycles.
Oestrogen-mediated upregulation of the Mas receptor contributes to sex differences in acute lung injury and lung vascular barrier regulation
Authors: Erfinanda Lasti , Ravindran Krishnan , Kohse Franziska , Gallo Kathleen , Preissner Robert , Walther Thomas , Kuebler Wolfgang M. 
Published: August 2020

Epidemiological data from the SARS-CoV-2 outbreak suggest sex differences in mortality and vulnerability; however, sex-dependent incidence of acute respiratory distress syndrome (ARDS) remains controversial and the sex-dependent mechanisms of endothelial barrier regulation are unknown. In premenopausal women, increased signalling of angiotensin (Ang)(1–7)viathe Mas receptor has been linked to lower cardiovascular risk. Since stimulation of the Ang(1–7)/Mas axis protects the endothelial barrier in acute lung injury (ALI), we hypothesised that increased Ang(1–7)/Mas signalling may protect females over males in ALI/ARDS.Clinical data were collected from Charité inpatients (Berlin) and sex differences in ALI were assessed in wild-type (WT) and Mas-receptor deficient (Mas−/−) mice. Endothelial permeability was assessed as weight change in isolated lungs and as transendothelial electrical resistance (TEER)in vitro.In 734 090 Charité inpatients (2005–2016), ARDS had a higher incidence in men as compared to women. In murine ALI, male WT mice had more lung oedema, protein leaks and histological evidence of injury than female WT mice. Lung weight change in response to platelet-activating factor (PAF) was more pronounced in male WT and femaleMas−/−mice than in female WT mice, whereas Mas-receptor expression was higher in female WT lungs. Ovariectomy attenuated protection in female WT mice and reduced Mas-receptor expression. Oestrogen increased Mas-receptor expression and attenuated endothelial leakage in response to thrombinin vitro. This effect was alleviated by Mas-receptor blockade.Improved lung endothelial barrier function protects female mice from ALI-induced lung oedema. This effect is partially mediatedviaenhanced Ang(1–7)/Mas signalling as a result of oestrogen-dependent Mas expression.
NADPH oxidase DUOX1 sustains TGF-β1 signalling and promotes lung fibrosis
Authors: Louzada Ruy Andrade , Corre Raphaël , Ameziane El Hassani Rabii , Meziani Lydia , Jaillet Madeleine , Cazes Aurélie , Crestani Bruno , Deutsch Eric , Dupuy Corinne 
Published: August 2020

Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of pulmonary fibrosis, and is governed by transforming growth factor (TGF)-β1/Smad signalling. TGF-β1 and oxidative stress cooperate to drive fibrosis. Cells can produce reactive oxygen species through activation and/or induction of NADPH oxidases, such as dual oxidase (DUOX1/2). Since DUOX enzymes, as extracellular hydrogen peroxide (H2O2­­)-generating systems, are involved in extracellular matrix formation and in wound healing in different experimental models, we hypothesised that DUOX-based NADPH oxidase plays a role in the pathophysiology of pulmonary fibrosis.Ourin vivodata (idiopathic pulmonary fibrosis patients and mouse models of lung fibrosis) showed that the NADPH oxidase DUOX1 is induced in response to lung injury. DUOX1-deficient mice (DUOX1+/−and DUOX1−/−) had an attenuated fibrotic phenotype. In addition to being highly expressed at the epithelial surface of airways, DUOX1 appears to be well expressed in the fibroblastic foci of remodelled lungs. By using primary human and mouse lung fibroblasts, we showed that TGF-β1 upregulates DUOX1 and its maturation factor DUOXA1 and that DUOX1-derived H2O2promoted the duration of TGF-β1-activated Smad3 phosphorylation by preventing phospho-Smad3 degradation. Analysis of the mechanism revealed that DUOX1 inhibited the interaction between phospho-Smad3 and the ubiquitin ligase NEDD4L, preventing NEDD4L-mediated ubiquitination of phospho-Smad3 and its targeting for degradation.These findings highlight a role for DUOX1-derived H2O2in a positive feedback that amplifies the signalling output of the TGF-β1 pathway and identify DUOX1 as a new therapeutic target in pulmonary fibrosis.
Long-term trends of asthma, allergic rhinitis and atopic eczema in young Finnish men: a retrospective analysis, 1926–2017
Authors: Reijula Jere , Latvala Jari , Mäkelä Mika , Siitonen Simo , Saario Mari , Haahtela Tari 
Published: August 2020

The aim of this study was to assess the long-term time trends of the prevalence of asthma, allergic rhinitis and atopic eczema in young Finnish men.A retrospective analysis was carried out on cross-sectional data from the Finnish Defence Forces taken from call-up examinations of candidates for military conscription and examinations of conscripts discharged from service because of poor health. Roughly 1.7 million men aged 18‒19 years (98% of men of conscription age) were examined from 1966 to 2017. A proportional but unknown number of young men were examined from 1926 to 1961.The main outcome measures were asthma recorded at call-up examination as the main diagnosis in 1926‒2017 and any diagnosis in 1997‒2017, exemption or discharge from military service due to asthma, and allergic rhinitis and atopic eczema recorded as the main diagnosis in 1966‒2017 and any diagnosis in 1997‒2017.During 1926–1961 the prevalence of asthma remained low at between 0.02% and 0.08%. A linear rise began between 1961 and 1966, with a 12-fold increase in the prevalence from 0.29% in 1966 to 3.44% in 2001. Thereafter, the prevalence of asthma as the main diagnosis stabilised but continued to increase to 5.19% in 2017 if secondary diagnoses of asthma were included. Exemption rates from military service due to asthma have similarly increased but fluctuated more. The prevalence of allergic rhinitis increased from 0.06% to 10.70% and atopic eczema from 0.15% to 2.90% during the period 1966‒2017.In Finland, an increase in asthma and allergic conditions among young men became evident in the mid-1960s. The increase slowed in the 2000s and may be levelling off in the 2020s.
Giant planktic larvae of anomalan crustaceans and their unusual compound eyes
Authors: Gundi Paula , Cecchin Chiara , Fetzer Lara-Leonie , Haug Carolin , Melzer Roland R. , Haug Joachim T. 
Published: August 2020

AbstractCrustacean larvae are usually recognised as small organisms, below one millimeter body size. However, in different crustacean groups such as Stomatopoda, Polychelida, or Achelata, also very large larvae occur with sizes of 20 mm and beyond. Also from few meiuran species (“short-tailed” crustaceans, including crabs, hermit crabs, or squat lobsters), rather large larvae are known, though still considerably smaller than 20 mm. We present here two specimens of anomalan meiuran larvae, each with a total length of 24 mm, which by far exceed the previously known/reported maximum sizes of meiuran larvae. Yet, both specimens exhibit characters that indicate their identity as zoea larvae (first larval phase with several stages), most likely shortly before the metamorphosis to the megalopa (second larval phase with one stage). Due to this early developmental state, it is difficult to provide a narrower systematic identification of the larvae. In addition to the description of the developmental status of all appendages, we also investigated the gizzard and especially the compound eyes. The latter possess a mixture of hexagonal, intermediate, and square-shaped facets in an unusual arrangement. We documented the exact arrangement of the facets in both specimens and discuss the possible re-structuring during metamorphosis. The arrangement of the different types of facets indicates that transformation to an adult eye structure takes place over several moults and that the facets are being rearranged in this process. The findings demonstrate that also meiuran larvae contribute to the fraction of the macro-plankton.
Modulation of mechanosensory vibrissal responses in the trigeminocervical complex by stimulation of the greater occipital nerve in a rat model of trigeminal neuropathic pain
Authors: García-Magro Nuria , Negredo Pilar , Martin Yasmina B. , Nuñez Ángel , Avendaño Carlos 
Published: August 2020

Abstract
Background
Stimulation of the occipital or trigeminal nerves has been successfully used to treat chronic refractory neurovascular headaches such as migraine or cluster headache, and painful neuropathies. Convergence of trigeminal and occipital sensory afferents in the ‘trigeminocervical complex’ (TCC) from cutaneous, muscular, dural, and visceral sources is a key mechanism for the input-induced central sensitization that may underlie the altered nociception. Both excitatory (glutamatergic) and inhibitory (GABAergic and glycinergic) mechanisms are involved in modulating nociception in the spinal and medullary dorsal horn neurons, but the mechanisms by which nerve stimulation effects occur are unclear. This study was aimed at investigating the acute effects of electrical stimulation of the greater occipital nerve (GON) on the responses of neurons in the TCC to the mechanical stimulation of the vibrissal pad.

Methods
Adult male Wistar rats were used. Neuronal recordings were obtained in laminae II-IV in the TCC in control, sham and infraorbital chronic constriction injury (CCI-IoN) animals. The GON was isolated and electrically stimulated. Responses to the stimulation of vibrissae by brief air pulses were analyzed before and after GON stimulation. In order to understand the role of the neurotransmitters involved, specific receptor blockers of NMDA (AP-5), GABAA (bicuculline, Bic) and Glycine (strychnine, Str) were applied locally.

Results
GON stimulation produced a facilitation of the response to light facial mechanical stimuli in controls, and an inhibition in CCI-IoN cases. AP-5 reduced responses to GON and vibrissal stimulation and blocked the facilitation of GON on vibrissal responses found in controls. The application of Bic or Str significantly reduced the facilitatory effect of GON stimulation on the response to vibrissal stimulation in controls. However, the opposite effect was found when GABAergic or Glycinergic transmission was prevented in CCI-IoN cases.

Conclusions
GON stimulation modulates the responses of TCC neurons to light mechanical input from the face in opposite directions in controls and under CCI-IoN. This modulation is mediated by GABAergic and Glycinergic mechanisms. These results will help to elucidate the neural mechanisms underlying the effectiveness of nerve stimulation in controlling painful craniofacial disorders, and may be instrumental in identifying new therapeutic targets for their prevention and treatment.
Alternative Strategy to Reduce Surface Recombination for InGaN/GaN Micro-light-Emitting Diodes—Thinning the Quantum Barriers to Manage the Current Spreading
Authors: Chang Le , Yeh Yen-Wei , Hang Sheng , Tian Kangkai , Kou Jianquan , Bi Wengang , Zhang Yonghui , Zhang Zi-Hui , Liu Zhaojun , Kuo Hao-Chung 
Published: August 2020

AbstractOwing to high surface-to-volume ratio, InGaN-based micro-light-emitting diodes (μLEDs) strongly suffer from surface recombination that is induced by sidewall defects. Moreover, as the chip size decreases, the current spreading will be correspondingly enhanced, which therefore further limits the carrier injection and the external quantum efficiency (EQE). In this work, we suggest reducing the nonradiative recombination rate at sidewall defects by managing the current spreading effect. For that purpose, we properly reduce the vertical resistivity by decreasing the quantum barrier thickness so that the current is less horizontally spreaded to sidewall defects. As a result, much fewer carriers are consumed in the way of surface nonradiative recombination. Our calculated results demonstrate that the suppressed surface nonradiative recombination can better favor the hole injection efficiency. We also fabricate the μLEDs that are grown on Si substrates, and the measured results are consistent with the numerical calculations, such that the EQE for the proposed μLEDs with properly thin quantum barriers can be enhanced, thanks to the less current spreading effect and the decreased surface nonradiative recombination.
Genome-Wide Association Study for Yield and Yield Related Traits under Reproductive Stage Drought in a Diverse indica-aus Rice Panel
Authors: Bhandari Aditi , Sandhu Nitika , Bartholome Jérôme , Cao-Hamadoun Tuong-Vi , Ahmadi Nourollah , Kumari Nilima , Kumar Arvind 
Published: August 2020

Abstract
Background
Reproductive-stage drought stress is a major impediment to rice production in rainfed areas. Conventional and marker-assisted breeding strategies for developing drought-tolerant rice varieties are being optimized by mining and exploiting adaptive traits, genetic diversity; identifying the alleles, and understanding their interactions with genetic backgrounds for their increased contribution to drought tolerance. Field experiments were conducted in this study to identify marker-trait associations (MTAs) involved in response to yield under reproductive-stage (RS) drought. A diverse set of 280 indica-aus accessions was phenotyped for ten agronomic traits including yield and yield-related traits under normal irrigated condition and under two managed reproductive-stage drought environments. The accessions were genotyped with 215,250 single nucleotide polymorphism markers.

Results
The study identified a total of 219 significant MTAs for 10 traits and candidate gene analysis within a 200 kb window centred from GWAS identified SNP peaks detected these MTAs within/ in close proximity to 38 genes, 4 earlier reported major grain yield QTLs and 6 novel QTLs for 7 traits out of the 10. The significant MTAs were mainly located on chromosomes 1, 2, 5, 6, 9, 11 and 12 and the percent phenotypic variance captured for these traits ranged from 5 to 88%. The significant positive correlation of grain yield with yield-related and other agronomic traits except for flowering time, observed under different environments point towards their contribution in improving rice yield under drought. Seven promising accessions were identified for use in future genomics-assisted breeding programs targeting grain yield improvement under drought.

Conclusion
These results provide a promising insight into the complex genetic architecture of grain yield under reproductive-stage drought in different environments. Validation of major genomic regions reported in the study will enable their effectiveness to develop drought-tolerant varieties following marker-assisted selection as well as to identify genes and understanding the associated physiological mechanisms.
Using full chloroplast genomes of ‘red’ and ‘yellow’ Bixa orellana (achiote) for kmer based identification and phylogenetic inference
Authors: Villacrés-Vallejo Jorge , Aranda-Ventura José , Wallis Anna , Cagle Robin , Handy Sara M. , Davis Jeffery , Reed Elizabeth , Zhang Shu , Strain Errol , Pava-Ripoll Monica , Erickson David , Ramachandran Padmini , Ottesen Andrea 
Published: August 2020

Abstract
Background
Full chloroplast genomes provide high resolution taxonomic discrimination between closely related plant species and are quickly replacing single and multi-locus barcoding regions as reference materials of choice for DNA based taxonomic annotation of plants. Bixa orellana, commonly known as “achiote” and “annatto” is a plant used for both human and animal foods and was thus identified for full chloroplast sequencing for the Center for Veterinary Medicine (CVM) Complete Chloroplast Animal Feed database. This work was conducted in collaboration with the Instituto de Medicina Tradicional (IMET) in Iquitos, Peru. There is a wide range of color variation in pods of Bixa orellana for which genetic loci that distinguish phenotypes have not yet been identified. Here we apply whole chloroplast genome sequencing of “red” and “yellow” individuals of Bixa orellana to provide high quality reference genomes to support kmer database development for use identifying this plant from complex mixtures using shotgun data. Additionally, we describe chloroplast gene content, synteny and phylogeny, and identify an indel and snp that may be associated with seed pod color.

Results
Fully assembled chloroplast genomes were produced for both red and yellow Bixa orellana accessions (158,918 and 158,823 bp respectively). Synteny and gene content was identical to the only other previously reported full chloroplast genome of Bixa orellana (NC_041550). We observed a 17 base pair deletion at position 58,399–58,415 in both accessions, relative to NC_041550 and a 6 bp deletion at position 75,531–75,526 and a snp at position 86,493 in red Bixa orellana.

Conclusions
Our data provide high quality reference genomes of individuals of red and yellow Bixa orellana to support kmer based identity markers for use with shotgun sequencing approaches for rapid, precise identification of Bixa orellana from complex mixtures. Kmer based phylogeny of full chloroplast genomes supports monophylly of Bixaceae consistent with alignment based approaches. A potentially discriminatory indel and snp were identified that may be correlated with the red phenotype.