bluuebunny/crossref_metadata_2025_split huggingface dataset:
Draft Genome Sequence of an
Oceanobacillus
sp. Strain Isolated from Soil in a Burial Crypt
Authors: Martínez-Ballesteros Ilargi , Arizaga Ylenia , Bikandi Joseba , Garaizar Javier , Ganau Giulia , Paglietti Bianca , Murgia Manuela , Deligios Massimo , Rubino Salvatore 
Published: July 2016

ABSTRACT

We present the draft genome of an
Oceanobacillus
sp. strain isolated from spores found in soil samples from a burial crypt of the Cathedral of Sant'Antonio Abate in Castelsardo, Italy. The data obtained indicated the closest relation of the strain with
Oceanobacillus caeni
.
Complete Genome Sequence of an Avian Paramyxovirus Representative of Putative New Serotype 13
Authors: Goraichuk Iryna , Sharma Poonam , Stegniy Borys , Muzyka Denys , Pantin-Jackwood Mary J. , Gerilovych Anton , Solodiankin Olexii , Bolotin Vitaliy , Miller Patti J. , Dimitrov Kiril M. , Afonso Claudio L. 
Published: July 2016

ABSTRACT
Here, we report the complete genome sequence of a virus of a putative new serotype of avian paramyxovirus (APMV). The virus was isolated from a white-fronted goose in Ukraine in 2011 and designated white-fronted goose/Ukraine/Askania-Nova/48-15-02/2011. The genomic characterization of the isolate suggests that it represents the novel avian paramyxovirus group APMV 13.
Draft Genome Sequence of
Ustilago trichophora
RK089, a Promising Malic Acid Producer
Authors: Zambanini Thiemo , Buescher Joerg M. , Meurer Guido , Wierckx Nick , Blank Lars M. 
Published: July 2016

ABSTRACT

The basidiomycetous smut fungus
Ustilago trichophora
RK089 produces malate from glycerol.
De novo
genome sequencing revealed a 20.7-Mbp genome (301 gap-closed contigs, 246 scaffolds). A comparison to the genome of
Ustilago maydis
521 revealed all essential genes for malate production from glycerol contributing to metabolic engineering for improving malate production.
Human Rhinovirus B and C Genomes from Rural Coastal Kenya
Authors: Agoti Charles N. , Kiyuka Patience K. , Kamau Everlyn , Munywoki Patrick K. , Bett Anne , van der Hoek Lia , Kellam Paul , Nokes D. James , Cotten Matthew 
Published: July 2016

ABSTRACT
Primer-independent agnostic deep sequencing was used to generate three human rhinovirus (HRV) B genomes and one HRV C genome from samples collected in a household respiratory survey in rural coastal Kenya. The study provides the first rhinovirus genomes from Kenya and will help improve the sensitivity of local molecular diagnostics.
Outpatient management of selected young febrile infants without antibiotics
Authors: Mintegi Santiago , Gomez Borja , Martinez-Virumbrales Lidia , Morientes Oihane , Benito Javier 
Published: July 2016

ObjectiveTo analyse the outpatient management of selected febrile infants younger than 90 days without systematic lumbar puncture and antibiotics.MethodsA prospective registry-based cohort study including all the infants ≤90 days with fever without a source (FWS) who were evaluated in a paediatric emergency department (ED) over a 7-year period (September 2007–August 2014). We analysed the outcome of those infants with low-risk criteria for serious bacterial infection (SBI) managed as outpatients without antibiotics and without undergoing a lumbar puncture. Low-risk criteria: Well appearing, older than 21 days of age, no leucocyturia, absolute neutrophil count ≤10 000, serum C reactive protein ≤20 mg/L, procalcitonin <0.5 ng/mL and no clinical deterioration during the stay in the ED (always <24 hours).Results1472 infants with FWS attended the ED. Of these, 676 were classified to be at low risk for SBI without performing a lumbar puncture. After staying <24 hours in the short-stay unit of the ED, 586 (86.6%) were managed as outpatients without antibiotics. Two patients were diagnosed with SBI: one occult bacteraemia and one bacterial gastroenteritis. Both were afebrile when evaluated again and did well. No patient returned to the ED due to clinical deterioration. Fifty-one infants (8.7%) returned to the ED mainly due to persistence of fever or irritability. None was diagnosed with definite SBI or non-bacterial meningitis.ConclusionsOutpatient management without antibiotics and systematic lumbar puncture is appropriate for selected febrile infants younger than 3 months of age with close follow-up.
Lymphocytic oesophagitis, eosinophilic oesophagitis and compound lymphocytic–eosinophilic oesophagitis I: histological and immunohistochemical findings
Authors: Rubio C A , Ichiya T , Schmidt P T 
Published: July 2016

AimsTo report four histological–immunohistochemical oesophagitis phenotypes.MethodsOesophageal biopsies from 311 patients were stained with H&E and with CD3, a T cell marker. Additional immunohistochemical stains (n=413) were performed in 77 cases.ResultsFour histological–immunohistochemical oesophagitis phenotypes were recorded: lymphocytic oesophagitis (LyE, ≥40 CD3+ lymphocytes/HPF in CD3 immunostain), eosinophilic oesophagitis (EoE, ≥15 eosinophils/HPF in H&E stain), lymphocytic infiltration (≤39 CD3+/HPF) and compound lymphocytic oesophagitis–eosinophilic oesophagitis (Co LyE-EoE). At index biopsy, 28.3% (n=88) had LyE, 21.2% (n=66) EoE, 10.6% (n=33) Co LyE-EoE and 39.9% (n=124) lymphocytic infiltration. A persistent oesophagitis phenotype was found in 42.5% (37/87) in the first follow-up biopsy, in 34.4% (21/61) in the second follow-up biopsy and in 48.1% (26/54) in the third follow-up biopsy. Using βF1 immunostain, two different surface T cell receptors were detected in LyE and Co Lye-EoE: one having ≥40 βF1+/HPF (βF1+ high) and the other having <39 βF1+/HPF (βF1+ low).ConclusionsBased on the literature regarding the significance of intraepithelial lymphocytes (IELs) in the initiation of EoE, we submit that the IEL phenotypes in LyE might differ from those found in EoE as they were unable to elicit the same eosinophilic response. Recent studies disclosed that group 2 innate lymphocytes (ILC2s), enriched in EoE, remain undetected in CD3 immunostain as they lack surface markers for T, B, natural killer (NK) or NK T cells. If ILC2s also participate in the lymphocytic infiltration of EoE, then the frequency of cases with Co LyE-EoE here reported might have been much higher. The four oesophagitis phenotypes described are easy to recognise, provided that the dual staining procedure (H&E-CD3) is implemented.
SpaceJMP
Authors: El Hajj Izzat , Merritt Alexander , Zellweger Gerd , Milojicic Dejan , Achermann Reto , Faraboschi Paolo , Hwu Wen-mei , Roscoe Timothy , Schwan Karsten 
Published: July 2016

Memory-centric computing demands careful organization of the virtual address space, but traditional methods for doing so are inflexible and inefficient. If an application wishes to address larger physical memory than virtual address bits allow, if it wishes to maintain pointer-based data structures beyond process lifetimes, or if it wishes to share large amounts of memory across simultaneously executing processes, legacy interfaces for managing the address space are cumbersome and often incur excessive overheads. We propose a new operating system design that promotes virtual address spaces to first-class citizens, enabling process threads to attach to, detach from, and switch between multiple virtual address spaces. Our work enables data-centric applications to utilize vast physical memory beyond the virtual range, represent persistent pointer-rich data structures without special pointer representations, and share large amounts of memory between processes efficiently.
We describe our prototype implementations in the DragonFly BSD and Barrelfish operating systems. We also present programming semantics and a compiler transformation to detect unsafe pointer usage. We demonstrate the benefits of our work on data-intensive applications such as the GUPS benchmark, the SAMTools genomics workflow, and the Redis key-value store.
Analyzing Behavior Specialized Acceleration
Authors: Nowatzki Tony , Sankaralingam Karthikeyan 
Published: July 2016

Hardware specialization has become a promising paradigm for overcoming the inefficiencies of general purpose microprocessors. Of significant interest are Behavioral Specialized Accelerators (BSAs), which are designed to efficiently execute code with only certain properties, but remain largely configurable or programmable. The most important strength of BSAs -- their ability to target a wide variety of codes -- also makes their interactions and analysis complex, raising the following questions: can multiple BSAs be composed synergistically, what are their interactions with the general purpose core, and what combinations favor which workloads? From a methodological standpoint, BSAs are also challenging, as they each require ISA development, compiler and assembler extensions, and either simulator or RTL models.
To study the potential of BSAs, we propose a novel modeling technique called the Transformable Dependence Graph (TDG) - a higher level alternative to the time-consuming traditional compiler+simulator approach, while still enabling detailed microarchitectural models for both general cores and accelerators. We then propose a multi-BSA organization, called ExoCore, which we model and study using the TDG. A design space exploration reveals that an ExoCore organization can push designs beyond the established energy-performance frontiers for general purpose cores. For example, a 2-wide OOO processor with three BSAs matches the performance of a conventional 6-wide OOO core, has 40% lower area, and is 2.6x more energy efficient.
Individualized Pazopanib Dosing: A Prospective Feasibility Study in Cancer Patients
Authors: Verheijen Remy B. , Bins Sander , Mathijssen Ron H.J. , Lolkema Martijn P. , van Doorn Leni , Schellens Jan H.M. , Beijnen Jos H. , Langenberg Marlies H.G. , Huitema Alwin D.R. , Steeghs Neeltje 
Published: July 2016

Abstract
Purpose: Pazopanib is a tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Retrospective analyses have shown that an increased median progression-free survival and tumor shrinkage appear in patients with higher plasma trough levels (Cmin). Therefore, patients with low Cmin might benefit from pharmacokinetically guided individualized dosing.
Experimental Design: We conducted a prospective multicenter trial in 30 patients with advanced solid tumors. Pazopanib Cmin was measured weekly by LC-MS/MS. At weeks 3, 5, and 7, the pazopanib dose was increased if the measured Cmin was &lt;20 mg/L and toxicity was &lt;grade 3.
Results: In total, 17 patients had at least one Cmin &lt;20 mg/L at weeks 3, 5, and 7. Of these, 10 were successfully treated with a pharmacokinetically guided dose escalation, leading to daily dosages ranging from 1,000 to 1,800 mg. Cmin in these patients increased significantly from 13.2 (38.0%) mg/L [mean (CV%)] to 22.9 mg/L (44.9%). Thirteen patients had all Cmin levels ≥20.0 mg/L. Of these, 9 patients with a high Cmin of 51.3 mg/L (45.1%) experienced ≥grade 3 toxicity and subsequently required a dose reduction to 600 or 400 mg daily, yet in these patients, Cmin remained above the threshold at 28.2 mg/L (25.3%).
Conclusions: A pharmacokinetically guided individualized dosing algorithm was successfully applied and evaluated. The dosing algorithm led to patients being treated at dosages ranging from 400 to 1,800 mg daily. Further studies are needed to show a benefit of individualized dosing on clinical outcomes, such as progression-free survival. Clin Cancer Res; 22(23); 5738–46. ©2016 AACR.
See related commentary by Ornstein and Rini, p. 5626
Ubiquitin Ligase, Fbw7, Targets CDX2 for Degradation via Two Phosphodegron Motifs in a GSK3β-Dependent Manner
Authors: Kumar Yogesh , Shukla Nidhi , Thacker Gatha , Kapoor Isha , Lochab Savita , Bhatt Madan Lal Brahma , Chattopadhyay Naibedya , Sanyal Sabyasachi , Trivedi Arun Kumar 
Published: July 2016

Abstract
Drosophila caudal–related homeobox transcription factor 2 (CDX2) drives differentiation of the intestinal epithelium. Loss of CDX2 expression has been reported in several colorectal cancers and cancer cell lines with a potential inverse correlation between CDX2 levels and tumor stage. Ubiquitination of CDX2 leading to its downregulation has been implicated in several studies; however, the E3 ubiquitin ligases involved in CDX2 ubiquitination have largely remained unknown. Here, it is mechanistically determined that the E3 ubiquitin ligase Fbw7 promotes CDX2 ubiquitination and degradation through two phosphodegron motifs present within CDX2 in a GSK3β-dependent manner leading to its reduced expression and function in colon cancer cells. Fbw7, through its WD domain, interacted with CDX2 both in a heterologous HEK293T cell system and in colon cancer cells. GSK3β was also present in the same complex as determined by coimmunoprecipitation. Furthermore, overexpression of both Fbw7 or GSK3β down regulated endogenous CDX2 expression and function; however, both failed to inhibit endogenous CDX2 when either of them were depleted in colon cancer cells. Fbw7-mediated inhibition of CDX2 expression also led to reduced CDX2 transactivation and growth arrest of colon cancer cells. Both GSK3β and Fbw7 degraded mutant-CDX2 having either of the Cdc4-phosphodegron (CPD) motifs disrupted (CDX2-S60A or CDX-S281A), but were unable to degrade mutant-CDX2 having both CPDs disrupted (CDX2-S60,64,281A).
Implications: Taken together, these findings demonstrate that Fbw7 negatively regulates CDX2 expression in a GSK3β-dependent manner through two CPDs present in CDX2. Mol Cancer Res; 14(11); 1097–109. ©2016 AACR.
E-Selectin Inhibition Mitigates Splenic HSC Activation and Myelopoiesis in Hypercholesterolemic Mice With Myocardial Infarction
Authors: Dutta Partha , Hoyer Friedrich Felix , Sun Yuan , Iwamoto Yoshiko , Tricot Benoit , Weissleder Ralph , Magnani John L. , Swirski Filip K. , Nahrendorf Matthias 
Published: July 2016

Objective—
Atherosclerosis is a chronic disease characterized by lipid accumulation in the arterial wall. After myocardial infarction (MI), atherosclerotic plaques are infiltrated by inflammatory myeloid cells that aggravate the disease and increase the risk of secondary myocardial ischemia. Splenic myelopoiesis provides a steady flow of myeloid cells to inflamed atherosclerotic lesions after MI. Therefore, targeting myeloid cell production in the spleen could ameliorate increased atherosclerotic plaque inflammation after MI.

Approach and Results—
Here we show that MI increases splenic myelopoiesis by driving hematopoietic stem and progenitor cells into the cell cycle. In an atherosclerotic mouse model, E-selectin inhibition decreased hematopoietic stem and progenitor cell proliferation in the spleen after MI. This led to reduced extramedullary myelopoiesis and decreased myeloid cell accumulation in atherosclerotic lesions. Finally, we observed stable atherosclerotic plaque features, including smaller plaque size, reduced necrotic core area, and thicker fibrous cap after E-selectin inhibition.

Conclusions—
Inhibiting E-selectin attenuated inflammation in atherosclerotic plaques, likely by reducing leukocyte recruitment into plaques and by mitigating hematopoietic stem and progenitor cell activation in the spleen of mice with MI.
Hypercholesterolemia Induced by a PCSK9 Gain-of-Function Mutation Augments Angiotensin II–Induced Abdominal Aortic Aneurysms in C57BL/6 Mice—Brief Report
Authors: Lu Hong , Howatt Deborah A. , Balakrishnan Anju , Graham Mark J. , Mullick Adam E. , Daugherty Alan 
Published: July 2016

Objective—
Gain-of-function mutations of PCSK9 (proprotein convertase subtilisin/kexin type 9) lead to hypercholesterolemia. This study was to determine whether infection of normocholesterolemic mice with an adeno-associated viral (AAV) vector expressing a gain-of-function mutation of mouse PCSK9 increased angiotensin II (AngII)–induced abdominal aortic aneurysms.

Approach and Results—

In an initial study, male C57BL/6 mice were injected intraperitoneally with either an empty vector or PCSK9 gain-of-function mutation (D377Y). AAV at 3 doses and fed a saturated fat-enriched diet for 6 weeks. Two weeks after AAV injection, mice were infused with AngII for 4 weeks. Plasma PCSK9 concentrations were increased dose dependently in mice injected with AAV containing PCSK9D377Y mutation and positively associated with elevations of plasma cholesterol concentrations. Infection with intermediate and high doses of PCSK9D377Y.AAV led to equivalent increases of maximal width of abdominal aortas in C57BL/6 mice infused with AngII. Therefore, the intermediate dose was used in subsequent experiments. We then determined effects of PCSK9D377Y.AAV infection on 5 normolipidemic mouse strains, demonstrating that C57BL/6 mice were the most susceptible to this AAV infection. PCSK9D377Y.AAV infected male C57BL/6 mice were also compared with age-matched male low-density lipoprotein receptor
−/−
mice. Although plasma cholesterol concentrations were lower in mice infected with PCSK9D377Y.AAV, these mice had equivalent abdominal aortic aneurysmal formation, compared to low-density lipoprotein receptor
−/−
mice. In a separate study, reduced plasma PCSK9 concentrations by PCSK9 antisense oligonucleotides in male low-density lipoprotein receptor
−/−
mice did not influence AngII-induced abdominal aortic aneurysms.

Conclusion—
AAV-mediated infection with a mouse PCSK9 gain-of-function mutation is a rapid, easy, and efficient approach for inducing hypercholesterolemia and promoting abdominal aortic aneurysms in C57BL/6 mice infused with AngII.
Fibroblast Growth Factor 12 Is a Novel Regulator of Vascular Smooth Muscle Cell Plasticity and Fate
Authors: Song Sun-Hwa , Kim Kyungjong , Jo Eun-Kyung , Kim Young-Wook , Kwon Jin-Sook , Bae Sun Sik , Sung Jong-Hyuk , Park Sang Gyu , Kim Jee Taek , Suh Wonhee 
Published: July 2016

Objective—
Vascular smooth muscle cells (VSMCs) modulate their phenotype between synthetic and contractile states in response to environmental changes; this modulation plays a crucial role in the pathogenesis of restenosis and atherosclerosis. Here, we identified fibroblast growth factor 12 (FGF12) as a novel key regulator of the VSMC phenotype switch.

Approach and Results—
Using murine models and human specimens, we found that FGF12 was highly expressed in contractile VSMCs of normal vessel walls but was downregulated in synthetic VSMCs from injured and atherosclerotic vessels. In human VSMCs, FGF12 expression was inhibited at the transcriptional level by platelet-derived growth factor-BB. Gain- and loss-of-function experiments showed that FGF12 was both necessary and sufficient for inducing and maintaining the quiescent and contractile phenotypes of VSMCs. FGF12 inhibited cell proliferation through the p53 pathway and upregulated the key factors involved in VSMC lineage differentiation, such as myocardin and serum response factor. Such FGF12-induced phenotypic change was mediated by the p38 MAPK (mitogen-activated protein kinase) pathway. Moreover, FGF12 promoted the differentiation of mouse embryonic stem cells and the transdifferentiation of human dermal fibroblasts into SMC-like cells. Furthermore, adenoviral infection of FGF12 substantially decreased neointima hyperplasia in a rat carotid artery injury model.

Conclusions—
In general, FGF family members induce a synthetic VSMC phenotype. Interestingly, the present study showed the unanticipated finding that FGF12 belonging to FGF family, strongly induced the quiescent and contractile VSMC phenotypes and directly promoted VSMC lineage differentiation. These novel findings suggested that FGF12 could be a new therapeutic target for treating restenosis and atherosclerosis.
12(S)-HETrE, a 12-Lipoxygenase Oxylipin of Dihomo-γ-Linolenic Acid, Inhibits Thrombosis via Gα
s
Signaling in Platelets
Authors: Yeung Jennifer , Tourdot Benjamin E. , Adili Reheman , Green Abigail R. , Freedman Cody J. , Fernandez-Perez Pilar , Yu Johnny , Holman Theodore R. , Holinstat Michael 
Published: July 2016

Objective—
Dietary supplementation with polyunsaturated fatty acids has been widely used for primary and secondary prevention of cardiovascular disease in individuals at risk; however, the cardioprotective benefits of polyunsaturated fatty acids remain controversial because of lack of mechanistic and in vivo evidence. We present direct evidence that an omega-6 polyunsaturated fatty acid, dihomo-γ-linolenic acid (DGLA), exhibits in vivo cardioprotection through 12-lipoxygenase (12-LOX) oxidation of DGLA to its reduced oxidized lipid form, 12(S)-hydroxy-8Z,10E,14Z-eicosatrienoic acid (12(S)-HETrE), inhibiting platelet activation and thrombosis.

Approach and Results—

DGLA inhibited ex vivo platelet aggregation and Rap1 activation in wild-type mice, but not in mice lacking 12-LOX expression (12-LOX
−/−
). Similarly, wild-type mice treated with DGLA were able to reduce thrombus growth (platelet and fibrin accumulation) after laser-induced injury of the arteriole of the cremaster muscle, but not 12-LOX
−/−
mice, supporting a 12-LOX requirement for mediating the inhibitory effects of DGLA on platelet-mediated thrombus formation. Platelet activation and thrombus formation were also suppressed when directly treated with 12(S)-HETrE. Importantly, 2 hemostatic models, tail bleeding and arteriole rupture of the cremaster muscle, showed no alteration in hemostasis after 12(S)-HETrE treatment. Finally, the mechanism for 12(S)-HETrE protection was shown to be mediated via a Gα
s
-linked G-protein–coupled receptor pathway in human platelets.

Conclusions—
This study provides the direct evidence that an omega-6 polyunsaturated fatty acid, DGLA, inhibits injury-induced thrombosis through its 12-LOX oxylipin, 12(S)-HETrE, which strongly supports the potential cardioprotective benefits of DGLA supplementation through its regulation of platelet function. Furthermore, this is the first evidence of a 12-LOX oxylipin regulating platelet function in a Gs α subunit–linked G-protein–coupled receptor–dependent manner.
Geographic and Temporal Variation in Cardiac Implanted Electric Devices to Treat Heart Failure
Authors: Hatfield Laura A. , Kramer Daniel B. , Volya Rita , Reynolds Matthew R. , Normand Sharon‐Lise T. 
Published: July 2016

Background

Cardiac implantable electric devices are commonly used to treat heart failure. Little is known about temporal and geographic variation in use of cardiac resynchronization therapy (
CRT
) devices in usual care settings.

Methods and Results

We identified new
CRT
with pacemaker (
CRT
‐P) or defibrillator generators (
CRT
‐D) implanted between 2008 and 2013 in the United States from a commercial claims database. For each implant, we characterized prior medication use, comorbidities, and geography. Among 17 780 patients with
CRT
devices (median age 69, 31% women),
CRT
‐Ps were a small and increasing share of
CRT
devices, growing from 12% to 20% in this study period. Compared to
CRT
‐D recipients,
CRT
‐P recipients were older (median age 76 versus 67), and more likely to be female (40% versus 30%). Pre‐implant use of β‐blockers and angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers was low in both
CRT
‐D (46%) and
CRT
‐P (31%) patients. The fraction of
CRT
‐P devices among all new implants varied widely across states. Compared to the increasing national trend, the share of
CRT
‐P implants was relatively increasing in Kansas and relatively decreasing in Minnesota and Oregon.

Conclusions

In this large, contemporary heart failure population,
CRT
‐D use dwarfed
CRT
‐P, though the latter nearly doubled over 6 years. Practice patterns vary substantially across states and over time. Medical therapy appears suboptimal in real‐world practice.