bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and tolerability of fixed-dose amlodipine/olmesartan medoxomil with or without hydrochlorothiazide in Hispanic and non-Hispanic patients whose blood pressure is uncontrolled on antihypertensive monotherapy
Authors: Punzi Henry , Shojaee Ali , Maa Jen-Fue 
Published: August 2012

Objectives: This is a prespecified subgroup analysis in Hispanic and non-Hispanic patients of a study that evaluated blood pressure (BP) control with fixed-dose amlodipine/olmesartan medoxomil (AML/OM)-based therapy in patients whose condition was uncontrolled on prior monotherapy. Methods: In this prospective, open-label, dose-titration study, patients with uncontrolled BP after at least 1 month of antihypertensive monotherapy were switched to fixed-dose AML/OM 5/20 mg. Patients were uptitrated to AML/OM 5/40 and 10/40 mg, with uptitration to AML/OM + hydrochlorothiazide 10/40 + 12.5 mg and 10/40 + 25 mg to achieve target BP. The primary efficacy endpoint was the cumulative proportion of patients achieving seated cuff systolic BP (SeSBP) less than 140 mmHg (<130 mmHg in patients with diabetes mellitus) at 12 weeks. Secondary endpoints included SeBP goal rates, ambulatory BP (ABP) target rates, and mean change from baseline in seated cuff BP (SeBP) and ABP at weeks 12 and 20. Results: Mean baseline BP was similar in Hispanics (153.6/92.8 mmHg; n = 105) and non-Hispanics (153.7/91.8 mmHg; n = 894). At 12 weeks, 72.0% of Hispanics and 76.3% of non-Hispanics achieved the primary endpoint. At week 12, goal rates for cumulative SeBP (<140/90 mmHg or <130/80 mmHg in patients with diabetes) were 69.0% and 71.5% in Hispanic and non-Hispanic patients, respectively. Mean change in SeBP in Hispanics ranged from −15.3/−7.3 mmHg for AML/OM 5/20 mg to −23.2/−13.8 mmHg for AML/OM 10/40 mg + hydrochlorothiazide 25 mg, and in non-Hispanics from −14.1/−7.8 mmHg to −25.4/−13.7 mmHg (all p < 0.0001 versus baseline). A majority of patients achieved mean 24 h, daytime, and nighttime ABP targets in both subgroups. Greater proportions of Hispanics achieved ABP targets versus non-Hispanics at week 12; however, this trend was reversed at week 20. Treatment was well tolerated. Conclusions: Switching to a fixed-dose combination of AML/OM ± hydrochlorothiazide provided significant BP lowering and effectively controlled BP in a large proportion of Hispanic and non-Hispanic patients with hypertension uncontrolled on previous monotherapy.
Evaluation and Management of Elbow Tendinopathy
Authors: Taylor Samuel A. , Hannafin Jo A. 
Published: August 2012

Context: Elbow tendinopathy is a common cause of pain and disability among patients presenting to orthopaedic surgeons, primary care physicians, physical therapists, and athletic trainers. Prompt and accurate diagnosis of these conditions facilitates a directed treatment regimen. A thorough understanding of the natural history of these injuries and treatment outcomes will enable the appropriate management of patients and their expectations. Evidence Acquisitions: The PubMed database was searched in December 2011 for English-language articles pertaining to elbow tendinopathy. Results: Epidemiologic data as well as multiple subjective and objective outcome measures were investigated to elucidate the incidence of medial epicondylitis, lateral epicondylitis, distal biceps and triceps ruptures, and the efficacy of various treatments. Conclusions: Medial and lateral epicondylitis are overuse injuries that respond well to nonoperative management. Their etiology is degenerative and related to repetitive overuse and underlying tendinopathy. Nonsteroidal anti-inflammatory drugs and localized corticosteroid injections yield moderate symptomatic relief in short term but do not demonstrate benefit on long-term follow-up. Platelet-rich plasma injections may be advantageous in cases of chronic lateral epicondylitis. If 6 to 12 months of nonoperative treatment fails, then surgical intervention can be undertaken. Distal biceps and triceps tendon ruptures, in contrast, have an acute traumatic etiology that may be superimposed on underlying tendinopathy. Prompt diagnosis and treatment improve outcomes. While partial ruptures confirmed with magnetic resonance imaging can be treated nonoperatively with immobilization, complete ruptures should be addressed with primary repair within 3 to 4 weeks of injury.
Prevention of Elbow Injuries in Youth Baseball Pitchers
Authors: Fleisig Glenn S. , Andrews James R. 
Published: August 2012

Context: Although baseball is a relatively safe sport, numerous reports suggest a rapid rise in elbow injury rate among youth baseball pitchers. Evidence Acquisition: PubMed was searched for epidemiologic, biomechanical, and clinical studies of elbow injuries in baseball (keywords: “youth OR adolescent” AND baseball AND pitching AND “ulnar collateral ligament OR elbow”; published January 2000 – April 2012). Studies with relevance to youth baseball pitchers were reviewed. Relevant references from these articles were also retrieved and reviewed. Original data, insight, and recommendations were added. Results: The majority of baseball elbow injuries are noncontact injuries to the dominant arm resulting from repetitive pitching. Five percent of youth pitchers suffer a serious elbow or shoulder injury (requiring surgery or retirement from baseball) within 10 years. The risk factor with the strongest correlation to injury is amount of pitching. Specifically, increased pitches per game, innings pitched per season, and months pitched per year are all associated with increased risk of elbow injury. Pitching while fatigued and pitching for concurrent teams are also associated with increased risk. Pitchers who also play catcher have an increased injury risk, perhaps due to the quantity of throws playing catcher adds to the athlete’s arm. Another risk factor is poor pitching biomechanics. Improper biomechanics may increase the torque and force produced about the elbow during each pitch. Although throwing breaking pitches at a young age has been suggested as a risk factor, existing clinical, epidemiologic, and biomechanical data do not support this claim. Conclusions: Some elbow injuries to youth baseball pitchers can be prevented with safety rules, recommendations, education, and common sense. Scientific and medical organizations have published safety rules and recommendations, with emphasis on prevention of overuse and pitching while fatigued. Strength-of-Recommendation Taxonomy (SORT): A
Induction of IL-4Rα–dependent microRNAs identifies PI3K/Akt signaling as essential for IL-4–driven murine macrophage proliferation in vivo
Authors: Rückerl Dominik , Jenkins Stephen J. , Laqtom Nouf N. , Gallagher Iain J. , Sutherland Tara E. , Duncan Sheelagh , Buck Amy H. , Allen Judith E. 
Published: August 2012

Abstract
Macrophage (MΦ) activation must be tightly controlled to preclude overzealous responses that cause self-damage. MicroRNAs promote classical MΦ activation by blocking antiinflammatory signals and transcription factors but also can prevent excessive TLR signaling. In contrast, the microRNA profile associated with alternatively activated MΦ and their role in regulating wound healing or antihelminthic responses has not been described. By using an in vivo model of alternative activation in which adult Brugia malayi nematodes are implanted surgically in the peritoneal cavity of mice, we identified differential expression of miR-125b-5p, miR-146a-5p, miR-199b-5p, and miR-378-3p in helminth-induced MΦ. In vitro experiments demonstrated that miR-378-3p was specifically induced by IL-4 and revealed the IL-4–receptor/PI3K/Akt-signaling pathway as a target. Chemical inhibition of this pathway showed that intact Akt signaling is an important enhancement factor for alternative activation in vitro and in vivo and is essential for IL-4–driven MΦ proliferation in vivo. Thus, identification of miR-378-3p as an IL-4Rα–induced microRNA led to the discovery that Akt regulates the newly discovered mechanism of IL-4–driven macrophage proliferation. Together, the data suggest that negative regulation of Akt signaling via microRNAs might play a central role in limiting MΦ expansion and alternative activation during type 2 inflammatory settings.
CD25 expression status improves prognostic risk classification in AML independent of established biomarkers: ECOG phase 3 trial, E1900
Authors: Gönen Mithat , Sun Zhuoxin , Figueroa Maria E. , Patel Jay P. , Abdel-Wahab Omar , Racevskis Janis , Ketterling Rhett P. , Fernandez Hugo , Rowe Jacob M. , Tallman Martin S. , Melnick Ari , Levine Ross L. , Paietta Elisabeth 
Published: August 2012

Abstract
We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML.
Genome-wide analysis reveals recurrent structural abnormalities of TP63 and other p53-related genes in peripheral T-cell lymphomas
Authors: Vasmatzis George , Johnson Sarah H. , Knudson Ryan A. , Ketterling Rhett P. , Braggio Esteban , Fonseca Rafael , Viswanatha David S. , Law Mark E. , Kip N. Sertac , Özsan Nazan , Grebe Stefan K. , Frederick Lori A. , Eckloff Bruce W. , Thompson E. Aubrey , Kadin Marshall E. , Milosevic Dragana , Porcher Julie C. , Asmann Yan W. , Smith David I. , Kovtun Irina V. , Ansell Stephen M. , Dogan Ahmet , Feldman Andrew L. 
Published: August 2012

Abstract
Peripheral T-cell lymphomas (PTCLs) are aggressive malignancies of mature T lymphocytes with 5-year overall survival rates of only ∼ 35%. Improvement in outcomes has been stymied by poor understanding of the genetics and molecular pathogenesis of PTCL, with a resulting paucity of molecular targets for therapy. We developed bioinformatic tools to identify chromosomal rearrangements using genome-wide, next-generation sequencing analysis of mate-pair DNA libraries and applied these tools to 16 PTCL patient tissue samples and 6 PTCL cell lines. Thirteen recurrent abnormalities were identified, of which 5 involved p53-related genes (TP53, TP63, CDKN2A, WWOX, and ANKRD11). Among these abnormalities were novel TP63 rearrangements encoding fusion proteins homologous to ΔNp63, a dominant-negative p63 isoform that inhibits the p53 pathway. TP63 rearrangements were seen in 11 (5.8%) of 190 PTCLs and were associated with inferior overall survival; they also were detected in 2 (1.2%) of 164 diffuse large B-cell lymphomas. As TP53 mutations are rare in PTCL compared with other malignancies, our findings suggest that a constellation of alternate genetic abnormalities may contribute to disruption of p53-associated tumor suppressor function in PTCL.
Response to genomic selection: The Bulmer effect and the potential of genomic selection when the number of phenotypic records is limiting
Authors: Van Grevenhof Elizabeth M , Van Arendonk Johan AM , Bijma Piter 
Published: August 2012

AbstractBackgroundOver the last ten years, genomic selection has developed enormously. Simulations and results on real data suggest that breeding values can be predicted with high accuracy using genetic markers alone. However, to reach high accuracies, large reference populations are needed. In many livestock populations or even species, such populations cannot be established when traits are difficult or expensive to record, or when the population size is small. The value of genomic selection is then questionable.MethodsIn this study, we compare traditional breeding schemes based on own performance or progeny information to genomic selection schemes, for which the number of phenotypic records is limiting. Deterministic simulations were performed using selection index theory. Our focus was on the equilibrium response obtained after a few generations of selection. Therefore, we first investigated the magnitude of the Bulmer effect with genomic selection.ResultsResults showed that the reduction in response due to the Bulmer effect is the same for genomic selection as for selection based on traditional BLUP estimated breeding values, and is independent of the accuracy of selection. The reduction in response with genomic selection is greater than with selection based directly on phenotypes without the use of pedigree information, such as mass selection. To maximize the accuracy of genomic estimated breeding values when the number of phenotypic records is limiting, the same individuals should be phenotyped and genotyped, rather than genotyping parents and phenotyping their progeny. When the generation interval cannot be reduced with genomic selection, large reference populations are required to obtain a similar response to that with selection based on BLUP estimated breeding values based on own performance or progeny information. However, when a genomic selection scheme has a moderate decrease in generation interval, relatively small reference population sizes are needed to obtain a similar response to that with selection on traditional BLUP estimated breeding values.ConclusionsWhen the trait of interest cannot be recorded on the selection candidate, genomic selection schemes are very attractive even when the number of phenotypic records is limited, because traditional breeding requires progeny testing schemes with long generation intervals in those cases.
miREvo: an integrative microRNA evolutionary analysis platform for next-generation sequencing experiments
Authors: Wen Ming , Shen Yang , Shi Suhua , Tang Tian 
Published: August 2012

Abstract

Background
MicroRNAs (miRNAs) are small (~19-24nt) non-coding RNAs that play important roles in various biological processes. To date, the next-generation sequencing (NGS) technology has been widely used to discover miRNAs in plants and animals. Although evolutionary analysis is important to reveal the functional dynamics of miRNAs, few computational tools have been developed to analyze the evolution of miRNA sequence and expression across species, especially the newly emerged ones,

Results
We developed miREvo, an integrated software platform with a graphical user interface (GUI), to process deep-sequencing data of small RNAs and to analyze miRNA sequence and expression evolution based on the multiple-species whole genome alignments (WGAs). Three major features are provided by miREvo: (i) to identify novel miRNAs in both plants and animals, based on a modified miRDeep algorithm, (ii) to detect miRNA homologs and measure their pairwise evolutionary distances among multiple species based on a WGA, and (iii) to profile miRNA expression abundances and analyze expression divergence across multiple species (small RNA libraries). Moreover, we demonstrated the utility of miREvo with Illumina data sets from Drosophila melanogaster and Arabidopsis, respectively.

Conclusion
This work presents an integrated pipline, miREvo, for exploring the expressional and evolutionary dynamics of miRNAs across multiple species. MiREvo is standalone, modular, and freely available at http://evolution.sysu.edu.cn/software/mirevo.htm under the GNU/GPL license.
The M5nr: a novel non-redundant database containing protein sequences and annotations from multiple sources and associated tools
Authors: Wilke Andreas , Harrison Travis , Wilkening Jared , Field Dawn , Glass Elizabeth M , Kyrpides Nikos , Mavrommatis Konstantinos , Meyer Folker 
Published: August 2012

Abstract

Background
Computing of sequence similarity results is becoming a limiting factor in metagenome analysis. Sequence similarity search results encoded in an open, exchangeable format have the potential to limit the needs for computational reanalysis of these data sets. A prerequisite for sharing of similarity results is a common reference.

Description
We introduce a mechanism for automatically maintaining a comprehensive, non-redundant protein database and for creating a quarterly release of this resource. In addition, we present tools for translating similarity searches into many annotation namespaces, e.g. KEGG or NCBI's GenBank.

Conclusions
The data and tools we present allow the creation of multiple result sets using a single computation, permitting computational results to be shared between groups for large sequence data sets.
AGORA: Assembly Guided by Optical Restriction Alignment
Authors: Lin Henry C , Goldstein Steve , Mendelowitz Lee , Zhou Shiguo , Wetzel Joshua , Schwartz David C , Pop Mihai 
Published: August 2012

Abstract

Background
Genome assembly is difficult due to repeated sequences within the genome, which create ambiguities and cause the final assembly to be broken up into many separate sequences (contigs). Long range linking information, such as mate-pairs or mapping data, is necessary to help assembly software resolve repeats, thereby leading to a more complete reconstruction of genomes. Prior work has used optical maps for validating assemblies and scaffolding contigs, after an initial assembly has been produced. However, optical maps have not previously been used within the genome assembly process. Here, we use optical map information within the popular de Bruijn graph assembly paradigm to eliminate paths in the de Bruijn graph which are not consistent with the optical map and help determine the correct reconstruction of the genome.

Results
We developed a new algorithm called AGORA: Assembly Guided by Optical Restriction Alignment. AGORA is the first algorithm to use optical map information directly within the de Bruijn graph framework to help produce an accurate assembly of a genome that is consistent with the optical map information provided. Our simulations on bacterial genomes show that AGORA is effective at producing assemblies closely matching the reference sequences.
Additionally, we show that noise in the optical map can have a strong impact on the final assembly quality for some complex genomes, and we also measure how various characteristics of the starting de Bruijn graph may impact the quality of the final assembly. Lastly, we show that a proper choice of restriction enzyme for the optical map may substantially improve the quality of the final assembly.

Conclusions
Our work shows that optical maps can be used effectively to assemble genomes within the de Bruijn graph assembly framework. Our experiments also provide insights into the characteristics of the mapping data that most affect the performance of our algorithm, indicating the potential benefit of more accurate optical mapping technologies, such as nano-coding.
MicroRNA-mRNA interactions in a murine model of hyperoxia-induced bronchopulmonary dysplasia
Authors: Dong Jie , Carey William A , Abel Stuart , Collura Christopher , Jiang Guoqian , Tomaszek Sandra , Sutor Shari , Roden Anja C , Asmann Yan W , Prakash Y S , Wigle Dennis A 
Published: August 2012

Abstract

Background
Bronchopulmonary dysplasia is a chronic lung disease of premature neonates characterized by arrested pulmonary alveolar development. There is increasing evidence that microRNAs (miRNAs) regulate translation of messenger RNAs (mRNAs) during lung organogenesis. The potential role of miRNAs in the pathogenesis of BPD is unclear.

Results
Following exposure of neonatal mice to 80% O2 or room air (RA) for either 14 or 29 days, lungs of hyperoxic mice displayed histological changes consistent with BPD. Comprehensive miRNA and mRNA profiling was performed using lung tissue from both O2 and RA treated mice, identifying a number of dynamically regulated miRNAs and associated mRNA target genes. Gene ontology enrichment and pathway analysis revealed that hyperoxia modulated genes involved in a variety of lung developmental processes, including cell cycle, cell adhesion, mobility and taxis, inflammation, and angiogenesis. MiR-29 was prominently increased in the lungs of hyperoxic mice, and several predicted mRNA targets of miR-29 were validated with real-time PCR, western blotting and immunohistochemistry. Direct miR-29 targets were further validated in vitro using bronchoalveolar stem cells.

Conclusion
In newborn mice, prolonged hyperoxia induces an arrest of alveolar development similar to that seen in human neonates with BPD. This abnormal lung development is accompanied by significant increases in the levels of multiple miRNAs and corresponding decreases in the levels of predicted mRNA targets, many of which have known or suspected roles in pathways altered in BPD. These data support the hypothesis that dynamic regulation of miRNAs plays a prominent role in the pathophysiology of BPD.