bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac complications in beta-thalassemia: From mice to men
Authors: Kumfu Sirinart , Fucharoen Suthat , Chattipakorn Siriporn C. , Chattipakorn Nipon 
Published: May 2017

Beta-thalassemia is an inherited hemoglobin disorder caused by reduced or absent synthesis of the beta globin chains of hemoglobin. This results in variable outcomes ranging from clinically asymptomatic to severe anemia, which then typically requires regular blood transfusion. These regular blood transfusions can result in an iron overload condition. The iron overload condition can lead to iron accumulation in various organs, especially in the heart, leading to iron overload cardiomyopathy, which is the major cause of mortality in patients with thalassemia. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects that iron overload has on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed. The in-depth understanding of biomolecular alterations in the heart of these iron overload thalassemic mice will help give guidance for more effective therapeutic approaches in the near future.Impact statementIron overload cardiomyopathy is a major cause of morbidity and mortality in patients with thalassemia. Since investigation of iron overload cardiomyopathy in thalassemia patients has many limitations, a search for an animal model for this condition has been ongoing for decades. In the past decades, there is no doubt that the use of β-thalassemic mice as a study model to investigate the pathophysiology of iron overload cardiomyopathy and the role of various pharmacological interventions, has shed some light in understanding this serious complication and in improving the associated cardiac dysfunction. In this review, the effects of iron overload on the hearts of β-thalassemic mice under conditions of iron overload as well as the efficacy of pharmacological interventions to combat these adverse effects on the heart are reviewed and discussed.
Circular RNA – New member of noncoding RNA with novel functions
Authors: Hsiao Kuei-Yang , Sun H Sunny , Tsai Shaw-Jenq 
Published: May 2017

A growing body of evidence indicates that circular RNAs are not simply a side product of splicing but a new class of noncoding RNAs in higher eukaryotes. The progression for the studies of circular RNAs is accelerated by combination of several advanced technologies such as next generation sequencing, gene silencing (small interfering RNAs) and editing (CRISPR/Cas9). More and more studies showed that dysregulated expression of circular RNAs plays critical roles during the development of several human diseases. Herein, we review the current advance of circular RNAs for their biosynthesis, molecular functions, and implications in human diseases. Impact statement The accumulating evidence indicate that circular RNA (circRNA) is a novel class of noncoding RNA with diverse molecular functions. Our review summarizes the current hypotheses for the models of circRNA biosynthesis including the direct interaction between upstream and downstream introns and lariat-driven circularization. In addition, molecular functions such as a decoy of microRNA (miRNA) termed miRNA sponge, transcriptional regulator, and protein-like modulator are also discussed. Finally, we reviewed the potential roles of circRNAs in neural system, cardiovascular system as well as cancers. These should provide insightful information for studying the regulation and functions of circRNA in other model of human diseases.
Effect of a near-universal hospitalization-based prophylaxis regimen on annual number of venous thromboembolism events in the US
Authors: Heit John A. , Crusan Daniel J. , Ashrani Aneel A. , Petterson Tanya M. , Bailey Kent R. 
Published: May 2017

Key PointsApproximately 500 000 US VTE events occur annually; approximately one-half are related to current or recent hospitalization. VTE attack rates (2005-2010) did not change despite near-universal in-hospital VTE prophylaxis, possibly due to short prophylaxis duration.
X-ray crystal structure of plasmin with tranexamic acid–derived active site inhibitors
Authors: Law Ruby H. P. , Wu Guojie , Leung Eleanor W. W. , Hidaka Koushi , Quek Adam J. , Caradoc-Davies Tom T. , Jeevarajah Devadharshini , Conroy Paul J. , Kirby Nigel M. , Norton Raymond S. , Tsuda Yuko , Whisstock James C. 
Published: May 2017

Key Points
Plasmin YO inhibitors form extensive interactions with the prime sites, thus anchoring the TXA moiety inside the catalytic pocket. Structural alignment analysis with urokinase and kallikrein gives insights into the molecular basis of the YO inhibitor specificity.
Non-V600BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer
Authors: Jones Jeremy C. , Renfro Lindsay A. , Al-Shamsi Humaid O. , Schrock Alexa B. , Rankin Andrew , Zhang Ben Y. , Kasi Pashtoon M. , Voss Jesse S. , Leal Alexis D. , Sun James , Ross Jeffrey , Ali Siraj M. , Hubbard Joleen M. , Kipp Benjamin R. , McWilliams Robert R. , Kopetz Scott , Wolff Robert A. , Grothey Axel 
Published: May 2017

Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 (non-V600 BRAF mutations). Methods We conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of non-V600 BRAF mutations in metastatic CRC. We pooled patients in whom non-V600 BRAF mutations were identified from NGS databases at three large molecular genetics reference laboratories. Results A total of 9,643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with non-V600 BRAF mutations, which occurred in 2.2% of all patients tested and accounted for 22% of all BRAF mutations identified. Cancers with non-V600 BRAF mutations, compared with cancers with V600E BRAF (V600E BRAF) mutations, were found in patients who were significantly younger (58 v 68 years, respectively), fewer female patients (46% v 65%, respectively), and patients who had fewer high-grade tumors (13% v 64%, respectively) or right-sided primary tumors (36% v 81%, respectively). Median overall survival was significantly longer in patients with non-V600 BRAF-mutant metastatic CRC compared with those with both V600E BRAF-mutant and wild-type BRAF metastatic CRC (60.7 v 11.4 v 43.0 months, respectively; P < .001). In multivariable analysis, non-V600 BRAF mutation was independently associated with improved overall survival (hazard ratio, 0.18; P < .001). Conclusion Non-V600 BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a clinically distinct subtype of CRC with an excellent prognosis.
Clinical Presentation and Gene Expression Profiling of Immunoglobulin M Multiple Myeloma Compared With Other Myeloma Subtypes and Waldenström Macroglobulinemia
Authors: Atrash Shebli , Zhang Qing , Papanikolaou Xenofon , Stein Caleb , Abdallah Al-Ola , Barlogie Bart 
Published: May 2017

PurposeMultiple myeloma (MM) is a clonal bone marrow disease characterized by the neoplastic transformation of differentiated postgerminal B cells. It is a heterogeneous disease both at the genetic level and in terms of clinical outcome. Immunoglobulin M (IgM) MM is a rare subtype of myeloma. Similar to Waldenström macroglobulinemia (WM), patients with MM experience IgM monoclonal gammopathy; however, both diseases are distinct in terms of treatment and clinical behavior.Materials and MethodsTo shed light on the presentation of IgM MM, its prognosis, and its gene expression profiling, we identified and characterized 21 patients with IgM MM from our database.ResultsOne of these patients presented with a rare IgM monoclonal gammopathy of undetermined significance that progressed to smoldering myeloma. The median survival of the 21 patients was 4.9 years, which was comparable to a matched group of patients with non-IgM MM with similar myeloma prognostic factors (age, gender, albumin, creatinine, anemia, lactate dehydrogenase, β2-microglobulin, cytogenetics abnormalities), but much less than the median survival reported for patients with WM (9 years). We identified a cluster of genes that differ in their expression profile between MM and WM and found that the patients with IgM MM displayed a gene expression profile most similar to patients with non-IgM MM, confirming that IgM MM is a subtype of MM that should be differentiated from WM.ConclusionBecause the prognosis of IgM MM and WM differ significantly, an accurate diagnosis is essential. Our gene expression model can assist with the differential diagnosis in controversial cases.
Adherence to and Implementation of ASCO Antiemetic Guidelines in Routine Practice in a Tertiary Cancer Center in India
Authors: Patil Vijay M. , Noronha Vanita , Joshi Amit , Ramaswamy Anant , Gupta Sudeep , Sahu Arvind , Doshi Vipul , Gupta Tarachand , Rath Sushmita , Banavali Shripad , Prabhash Kumar 
Published: May 2017

Background: Nonadherence of antiemetic prescriptions to evidence-based antiemetic guidelines is associated with an increased proportion of chemotherapy-induced nausea and vomiting. The current project was carried out to improve the quality of antiemetic prescriptions at our institute. Methods: We initially performed a retrospective analysis of 1,211 consecutive antiemetic prescription records of adult patients with solid tumors who received outpatient chemotherapy regimens. The antiemetic prescription records were classified as either ASCO-guideline adherent or nonadherent, and the impact on emesis was studied. These data were used to educate clinicians regarding the importance of adherence to guidelines. We then revised our antiemetic prescription policies and made their use mandatory. In addition, a double-check system was introduced to ensure implementation. A reaudit was performed to study the impact of these interventions. Results: ASCO-guideline–adherent prescriptions in the initial part of our study were associated with a lower rate of vomiting (6.6% v 21.9%; P < .001), emergency visits (2.6% v 5.8%; P = .006), and hospitalization for emesis (0.9% v 4.9%; P < .001). The proportion of prescriptions classified as ASCO-guideline adherent in the initial audit and the reaudit were 63.6% and 98.5%, respectively ( P < .001). The proportion of patients for whom antiemetic prescriptions were overused was significantly lower on the reaudit (41.3% v 68.3% before the interventions; P = .001). Conclusion: Mandatory, semirigid corrective steps as carried out in this audit led to an improvement in antiemetic-guideline adherence rate.
Medullary Thyroid Carcinoma in MEN2A: ATA Moderate- or High-Risk RET Mutations Do Not Predict Disease Aggressiveness
Authors: Voss Rachel K , Feng Lei , Lee Jeffrey E , Perrier Nancy D , Graham Paul H , Hyde Samuel M , Nieves-Munoz Frances , Cabanillas Maria E , Waguespack Steven G , Cote Gilbert J , Gagel Robert F , Grubbs Elizabeth G 
Published: May 2017

Abstract

Context
High-risk RET mutations (codon 634) are associated with earlier development of medullary thyroid carcinoma (MTC) and presumed increased aggressiveness compared with moderate-risk RET mutations.

Objective
To determine whether high-risk RET mutations are more aggressive.

Design
Retrospective cohort study using institutional multiple endocrine neoplasia type 2 registry.

Setting
Tertiary cancer care center.

Patients
Patients with MTC and moderate- or high-risk germline RET mutation.

Intervention
None (observational study).

Main Outcome Measures
Proxies for aggressiveness were overall survival (OS) and time to distant metastatic disease (DMD).

Results
A total of 127 moderate-risk and 135 high-risk patients were included (n = 262). Median age at diagnosis was 42.3 years (range, 6.4 to 86.4 years; mean, 41.6 years) for moderate-risk mutations and 23.0 years (range, 3.7 to 66.8 years; mean, 25.6 years) for high-risk mutations (P &lt; 0.0001). Moderate-risk patients had more T3/T4 tumors at diagnosis (P = 0.03), but there was no significant difference for N or M stage and no significant difference in OS (P = 0.40). From multivariable analysis for OS, increasing age [hazard ratio (HR), 1.05/y; 95% confidence interval (CI), 1.03 to 1.08], T3/T4 tumor (HR, 2.73; 95% CI, 1.22 to 6.11), and M1 status at diagnosis (HR, 3.93; 95% CI, 1.61 to 9.59) were significantly associated with worse OS but high-risk mutation was not (P = 0.40). No significant difference was observed for development of DMD (P = 0.33). From multivariable analysis for DMD, only N1 status at diagnosis was significant (HR, 2.10; 95% CI, 1.03 to 4.27).

Conclusions
Patients with high- and moderate-risk RET mutations had similar OS and development of DMD after MTC diagnosis and therefore similarly aggressive clinical courses. High-risk connotes increased disease aggressiveness; thus, future guidelines should consider RET mutation classification by disease onset (early vs late) rather than by risk (high vs moderate).
A Failure to Communicate? Doctors and Nurses in American Hospitals
Authors: Michel Lucie 
Published: May 2017

Abstract
This article showcases the realities and challenges of teamwork in American hospitals based on the in situ comparison with France. Drawing on observation of nurse-physician interactions in hospitals in the two nations, this article highlights a troubling conflict between teamwork rhetoric and realities on the ward. Although the use of informatics systems such as electronic health records is supposed to increase cooperation, the observations presented here show that on the contrary, it inhibits communication that is becoming mainly virtual. While the nursing profession is more developed and provides stronger education in the United States, this story highlights the challenges in creating a shared environment of work and suggests the importance of balancing professional autonomy and effective teamwork.
Closing Kynect and Restructuring Medicaid Threaten Kentucky's Health and Economy
Authors: Wright Charles B. , Vanderford Nathan L. 
Published: May 2017

Abstract
Following passage of the Patient Protection and Affordable Care Act (ACA) in the United States, the Kentucky Health Benefit Exchange, Kynect, began operating in Kentucky in October 2013. Kentucky expanded Medicaid eligibility in January 2014. Together, Kynect and Medicaid expansion provided access to affordable health care coverage to hundreds of thousands of individuals in Kentucky. However, following the Kentucky gubernatorial election in 2015, the newly inaugurated governor moved to dismantle Kynect and restructure the Medicaid expansion, jeopardizing public health gains and the state economy. As the first state to announce both the closure and restructuring of a state health insurance marketplace and Medicaid expansion, Kentucky may serve as a test case for the rest of the nation for reversal of ACA-related health policies. This article describes Kynect and the Kentucky Medicaid expansion and examines the potential short-term and long-term impacts that may occur following changes in state health policy. Furthermore, this article will offer potential strategies to ameliorate the expected negative impacts of disruption of both Kynect and the Medicaid expansion, such as the creation of a new state insurance marketplace under a new governor, the implementation of a private option, and increasing the state minimum wage for workers.
GATA2 expression and biochemical recurrence following salvage radiation therapy for relapsing prostate cancer
Authors: Robinson Jessica L , Tzou Katherine S , Parker Alexander S , Heckman Michael G , Wu Kevin J , Hilton Tracy W , Pisansky Thomas M , Schild Steven E , Peterson Jennifer L , Vallow Laura A , Buskirk Steven J 
Published: May 2017

Objective:
High GATA2 expression has been associated with an increased risk of poor clinical outcomes after radical prostatectomy; however, this has not been studied in relation to risk of biochemical recurrence (BCR) after salvage radiation therapy (SRT) for recurrent prostate cancer after radical prostatectomy. Our aim was to evaluate the association between protein expression levels of GATA2 in primary prostate cancer tumour samples and the risk of BCR after SRT.

Methods:
109 males who were treated with SRT were included. The percentage of cells with nuclear staining and GATA2 staining intensity were both measured. These two measures were multiplied together to obtain a GATA2 H-score (range 0–12) which was our primary GATA2 staining measure.

Results:
In unadjusted analysis, the risk of BCR was higher for patients with a GATA2 H-score &gt;4 (hazard ratio = 2.04, p = 0.033). In multivariable analysis adjusting for SRT dose, pre-SRT PSA, pathological tumour stage and Gleason score, this association weakened substantially (hazard ratio = 1.45, p = 0.31). This lack of an independent association with BCR appears to be the result of correlations between GATA2 H-score &gt;4 and higher pre-SRT PSA (p = 0.021), higher Gleason score (p = 0.044) and more severe pathological tumour stage (p = 0.068).

Conclusion:
Higher levels of GATA2 expression appear to be a marker of prostate cancer severity; however, these do not provide independent prognostic information regarding BCR beyond that of validated clinicopathological risk factors.

Advances in knowledge:
A higher GATA2 expression level appears to be correlated with known measures of prostate cancer severity and therefore is likely not an independent marker of outcome after SRT.
Species delimitation in the recalcitrant moss genus Rhynchostegiella (Brachytheciaceae)
Authors: Patiño Jairo , Hedenäs Lars , Dirkse Gérard M. , Ignatov Michael S. , Papp Beáta , Müller Frank , González-Mancebo Juana M. , Vanderpoorten Alain 
Published: May 2017

AbstractBryophytes, with their reduced morphologies and challenging taxonomy, appear as ideal candidates for the application of the fast‐developing tools of molecular species delimitation. Here, we apply species delimitation techniques to the moss genus Rhynchostegiella, which has long served as a convenient repository for small pleurocarpous species. Species delimitation analyses, including the Generalized Mixed Yule Coalescent approach and its Bayesian variant, congruently identified 13 putative species within Rhynchostegiella. To avoid inflation in the number of species with sympatric distributions that can only be recognized molecularly, we identified only one species when two or more molecular species were monophyletic, sympatric, and morphologically impossible to tell apart. After exclusion of 33 species from the genus based on earlier revisions or studies of type specimens, we recognized 11 Rhynchostegiella species. Eight of these species were already described, but were recircumscribed. In particular, the widespread R. litorea is split into three species with narrower distribution ranges: R. litorea s.str. occurs across continental Europe, western Asia and Africa (excluding Macaronesia), while R. pseudolitorea sp. nov. and R. tubulosa sp. nov. are Macaronesian and Aegean‐Cypriotic endemics, respectively. The Macaronesian endemic R. macilenta is reduced to synonymy with R. teneriffae while the Macaronesian endemic status of R. bourgeana is re‐instated. Altogether, Rhynchostegiella thus includes four Macaronesian endemic species, namely R. azorica, R. bourgeana, R. pseudolitorea, and R. trichophylla, making it the bryophyte genus with the highest number of Macaronesian endemic species. Given the difficulties in identifying some of those species from morphology, as highlighted in the identification key presented here, we describe easy‐to‐use DNA “barcodes” that can be a useful tool for specimen identification when key morphological characters lead to uncertain identification.
Disentangling relationships among the members of the Silene saxífraga alliance (Caryophyllaceae): Phylogenetic structure is geographically rather than taxonomically segregated
Authors: Durovic Sanja , Schönswetter Peter , Niketic Marjan , Tomovic Gordana , Frajman Božo 
Published: May 2017

AbstractOut of ca. 700 species belonging to Silene, 15 to 35 were classified in S. sect. Saxifragoideae. This section has its highest diversity on the Balkan Peninsula, which was the most important European Pleistocene refugium. The most widespread of the species is S. saxifraga ranging from the Pyrenees to the Carpathians. Together with ten morphologically similar taxa it is often treated as the S. saxifraga group, but the relationships among the taxa are unclear and blurred due to the occurrence of transitional forms. In this study, we used sequences of the nuclear ribosomal internal transcribed spacer (ITS) and the plastid rps16 intron as well as amplified fragment length polymorphisms (AFLPs) to elucidate phylogenetic relationships among the taxa belonging to—or hypothesized to be closely related to—S. sect. Saxifragoideae, covering the section’s entire geographical range. Phylogenetic analyses of 112 populations belonging to 33 taxa clarified previous classifications and showed that S. cephallenia, S. congesta, S. linoides, S. multicaulis, S. schwarzenbergeri and S. waldsteinii are clearly differentiated from all other taxa, which in turn form the newly circumscribed S. saxifraga group. Phylogenetic relationships within the latter are unresolved, and are governed by geographic proximity rather than by taxonomic identity. This is likely a result of recent rapid radiation and range expansion, as well as of convergent morphological evolution triggered by similar environmental selection pressures. The southern parts of the Balkan Peninsula are the centre of genetic diversity of the group, underlining the area’s importance as a sanctuary of diversification of European biota.
We’re Number 1: Price Wars for Market Share Leadership
Authors: Cabral Luís 
Published: May 2017

I examine the dynamics of oligopolies when firms derive subjective value from market leadership. In equilibrium, prices alternate in tandem between high levels and occasional price wars, which take place when market leadership is at stake. The stationary distribution of market shares is typically multimodal; that is, much of the time, there is a stable market leader. Even though shareholders do not value market leadership per se, a corporate culture that values market leadership may increase shareholder value. The online appendix is available at https://doi.org/10.1287/mnsc.2017.2725 . This paper was accepted by Bruno Cassiman, business strategy.