bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiologist Participation in Accountable Care Organizations and Changes in Spending and Quality for Medicare Patients With Cardiovascular Disease
Authors: Sukul Devraj , Ryan Andrew M. , Yan Phyllis , Markovitz Adam A. , Nallamothu Brahmajee K. , Lewis Valerie A. , Hollingsworth John M. 
Published: September 2019

Background:
Despite widespread adoption of Medicare accountable care organizations (ACOs), healthcare spending reductions have been modest. This may relate to variable participation in ACOs by specialist physicians, who disproportionately drive spending. To examine whether specialist participation in Medicare ACOs was associated with changes in healthcare spending and clinical quality, we analyzed national Medicare data.

Methods and Results:

Working with a 20% random sample of Medicare beneficiaries (2008 to 2015), we identified those with cardiovascular disease. We estimated linear regression models at the beneficiary-quarter level to evaluate changes in healthcare spending and clinical quality after the start of the Shared Savings Program in 2012. We then examined whether changes in spending and quality across ACOs were conditional on cardiologist participation. Our study included ≈1.6 million beneficiaries per year. Although the number of ACOs increased over the study period (from 114 in 2012 to 392 in 2015), the proportion with any cardiologist participation remained stable (from 80% in 2012 to 83% in 2015). Compared with unaligned beneficiaries, those cared for by ACOs without cardiologist participation were associated with a spending reduction (per quarter) of −$75 (95% CI, −$105 to −$46;
P
<0.001). Care receipt in an ACO with cardiologist participation was associated with an additional difference in spending of −$56 (95% CI, −$87 to −$25;
P
<0.001), driven by lower spending for skilled nursing facilities, evaluation and management services, procedural care, and testing. While heart failure admission rates were similar among aligned and unaligned beneficiaries, ACO care was associated with fewer all-cause readmissions (
P
<0.001) and emergency department visits (
P
<0.001). Rates of these outcomes did not vary by cardiologist participation.

Conclusions:
Annual spending for beneficiaries with cardiovascular disease was ≈$200 lower when cared for by ACOs with cardiologist participation (compared with those without). These spending reductions did not come at the expense of clinical quality.
Thumos in Aristotle’s Politics VII.7
Authors: Deslauriers Marguerite 
Published: September 2019

Abstract
Aristotle claims that the citizens of the best city should be both intelligent and spirited at Politics VII.7 1327b19-38. While he treats intelligence as an unqualified good, thumos (‘spirit’) is valuable but problematic. This paper has two aims: (i) to consider the political value of spirit in Aristotle’s Politics and in particular to identify the ways in which it is both essential to political excellence and yet insufficient for securing it, and (ii) to use this analysis of the role of spirit in the political realm to explain Aristotle’s exclusion of women from political authority, even in the context of the household. I analyze spirit as a physical phenomenon and as a type of desire, before considering its moral and affective aspects. I then return to the role of spirit in political life and examine its importance for the activity of ruling. In the last section I consider the implications of this analysis of spirit for the social and political roles Aristotle assigns to men and women.
Aristotle’s Best City in the Context of His Concept of Aretē
Authors: Samaras Athanasios 
Published: September 2019

Abstract
The text of the Politics itself establishes beyond reasonable doubt that Aristotle’s best city is, in the philosopher’s own terms, an aristocracy: in Books III and IV Aristotle defines aristocracy as the regime that aims at the best, has virtue as its mark, does not allow citizenship to artisans and wage-earners, and distributes offices by merit. Books VII and VIII unequivocally attribute all these essential characteristics of aristocracy to Aristotle’s best city. In addition, his conception of the virtue of the citizens of this polis conforms to the traditional aristocratic interpretation of the term.
Aristotle – citizenship – kaloskagathos – aristocratic virtue
Politiques VII : un livre anti-platonicien
Authors: Pellegrin Pierre 
Published: September 2019

Abstract
The (quasi)-consensus of interpreters that gives books VII and VIII of the Politics a logical and chronological priority to books IV-VI and that claims that book VII advocates for an aristocratic regime must be abandoned. In fact, these last two books deal with questions which the legislator must know, but which fall short of any constitutional consideration. An image found in Book VII is illuminating: this book deals with the best conditions for life in the city and Aristotle compares it to the material that the craftsman best arranges before giving his product its form. Prior for us, these considerations are therefore posterior by nature to the constitutional analyzes of books IV-VI. In light of the Aristotelian doctrine of two different kinds of priority, we can say that the manuscripts, which place books VII and VIII at the end of the Politics, adopt an Aristotelian order.
Equality for Equals
Authors: Edge Matt 
Published: September 2019

Abstract
Discussions of the liberty of the ancients, in contemporary political theory, treat democratic freedom, and the political equality on which democracy was premised, as anathema to the liberty of the moderns. This article discusses ancient democratic liberty by referencing the theory of arithmetic equality preserved by Aristotle and Plato and suggests that we need to re-investigate this relationship in the interests of modern freedom. The article argues that, in fact, Greek, particularly Athenian, democratic ideas, construe freedom in a negative way and that democratic, arithmetic, accounts of equality are, at root, anti-oppressive and require further investigation in the name of justice for the moderns.
Searching for Statesmanship: a Corpus-Based Analysis of a Translated Political Discourse
Authors: Jones Henry 
Published: September 2019

Abstract
With its connotations of superior moral integrity, exceptional leadership qualities and expertise in the science of government, the modern ideal of statesmanship is most commonly traced back to the ancient Greek concept of πολιτικός (politikos) and the work of Plato and Aristotle in particular. Through an analysis of a large corpus of modern English translations of political works, built as part of the AHRC Genealogies of Knowledge project (http://genealogiesofknowledge.net/), this case-study aims to explore patterns that are specific to this translated discourse, with a view to understanding the crucial role played by translators in shaping its development and reception in society. It ultimately seeks to argue that the model of statesmanship presented in translations from ancient Greek is just as much a product of the receiving culture (and the social anxieties of Victorian Britain especially) as it is inherited from the classical world.
Just Silence in Plato’s Clitophon
Authors: Gassaway Shane 
Published: September 2019

Abstract
Plato’s Clitophon presents a confrontation between two alternative views of justice, one conventional and the other philosophical – and of Clitophon’s inability to move from the one to the other due to his confusion over the relationship between knowledge and virtue and his misconception of the path from ignorance to knowledge, which probably results from his ambition. The nature of this confusion is such that Clitophon can only overcome it by abandoning his submissive stance toward the authority of Socrates (or any other teacher), which fact, combined with the character of his appeal to Socrates for an answer to his difficulties makes any authentic verbal response from Socrates unlikely to help and to risk harm. Silence from Socrates at the conclusion of the dialogue would therefore exemplify the principle that it is not for the just to harm anyone.
La terapia immunosoppressiva nel trapianto di rene
Authors: Tsalouchos Aris , Salvadori Maurizio 
Published: September 2019

Immunosuppressive therapy in renal transplantation Immunosuppressive therapy in renal transplantation can be distinguished in induction therapy and maintenance therapy. Induction therapy is an intense immunosuppressive therapy administered at the time of kidney transplantation to reduce the risk of acute allograft rejection. In general, the induction immunosuppressive strategies used at kidney transplant centers fall into one of these two categories. One strategy relies upon high doses of conventional immunosuppressive agents, while the other utilizes antibodies directed against T-cell antigens in combination with lower doses of conventional agents. Maintenance immunosuppressive therapy is administered to almost all kidney transplant recipients to help prevent acute rejection and loss of the renal allograft. Although an adequate level of immunosuppression is required to dampen the immune response to the allograft, the level of chronic immunosuppression is decreased over time (as the risk of acute rejection decreases) to help lower the overall risk of infection and malignancy; these risks directly correlate with the degree of overall immunosuppression. The optimal maintenance immunosuppressive therapy in kidney transplantation is not established. The major immunosuppressive agents that are available in various combination regimens are glucocorticoids (primarily oral prednisone), azathioprine, mycophenolate mofetil (MMF), enteric-coated mycophenolate sodium (EC-MPS), cyclosporine (in non-modified or modified [microemulsion] form), Tacrolimus, everolimus, rapamycin (sirolimus), and Belatacept.
Medication adherence, hospitalization, and healthcare resource utilization and costs in patients with pulmonary arterial hypertension treated with endothelin receptor antagonists or phosphodiesterase type‐5 inhibitors
Authors: Frantz Robert P. , Hill Jerrold W. , Lickert Cassandra A. , Wade Rolin L. , Cole Michele R. , Tsang Yuen , Drake William 
Published: September 2019

Adherence to therapy for pulmonary arterial hypertension is essential to optimize patient outcomes, but data on real‐world adherence to different pulmonary arterial hypertension drug classes are limited. This retrospective database analysis evaluated relationships between adherence, hospitalization, and healthcare costs in pulmonary arterial hypertension patients treated with endothelin receptor antagonists or phosphodiesterase type‐5 inhibitors. From the IQVIA Adjudicated Health Plan Database, patients with pulmonary arterial hypertension were identified based on diagnostic codes and prescriptions for endothelin receptor antagonists (ambrisentan, bosentan, macitentan) or phosphodiesterase type‐5 inhibitors (sildenafil, tadalafil) approved for pulmonary arterial hypertension. Patients were assigned to the class of their most recently initiated (index) pulmonary arterial hypertension therapy between 1 January 2009 and 30 June 2015. Medication adherence was measured by proportion of days covered; patients with proportion of days covered ≥80% were considered adherent. The proportion of adherent patients was higher for endothelin receptor antagonists (571/755; 75.6%) than for phosphodiesterase type‐5 inhibitors (970/1578; 61.5%; P < 0.0001). In both groups, hospitalizations declined as proportion of days covered increased. Among adherent patients, those on endothelin receptor antagonists had a significantly lower hospitalization rate than those on phosphodiesterase type‐5 inhibitors (23.1% versus 28.5%, P = 0. 0218), fewer hospitalizations (mean (standard deviation) 0.4 (0.8) versus 0.5 (0.9); P = 0.02), and mean hospitalization costs during the six‐month post‐index ($9510 versus $15,726, P = 0.0318). Increasing adherence reduced hospitalization risk more for endothelin receptor antagonists than for phosphodiesterase type‐5 inhibitors (hazard ratio 0.176 versus 0.549, P = 0.001). Rates and numbers of rehospitalizations within 30 days post‐discharge were similar between groups. Mean total costs were higher with endothelin receptor antagonists than phosphodiesterase type‐5 inhibitors in all patients ($91,328 versus $72,401, P = 0.0003) and in adherent patients ($88,867 versus $56,300, P < 0.0001), driven by higher drug costs.
The double-hit signature identifies double-hit diffuse large B-cell lymphoma with genetic events cryptic to FISH
Authors: Hilton Laura K. , Tang Jeffrey , Ben-Neriah Susana , Alcaide Miguel , Jiang Aixiang , Grande Bruno M. , Rushton Christopher K. , Boyle Merrill , Meissner Barbara , Scott David W. , Morin Ryan D. 
Published: September 2019

Abstract
High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements (HGBL-DH/THs) include a group of diffuse large B-cell lymphomas (DLBCLs) with inferior outcomes after standard chemoimmunotherapy. We recently described a gene expression signature that identifies 27% of germinal center B-cell DLBCLs (GCB-DLBCLs) as having a double-hit–like expression pattern (DHITsig) and inferior outcomes; however, only half of these cases have both MYC and BCL2 translocations identifiable using standard breakapart fluorescence in situ hybridization (FISH). Here, 20 DHITsig+ GCB-DLBCLs apparently lacking MYC and/or BCL2 rearrangements underwent whole-genome sequencing. This revealed 6 tumors with MYC or BCL2 rearrangements that were cryptic to breakapart FISH. Copy-number analysis identified 3 tumors with MYC and 6 tumors with MIR17HG gains or amplifications, both of which may contribute to dysregulation of MYC and its downstream pathways. Focal deletions of the PVT1 promoter were observed exclusively among DHITsig+ tumors lacking MYC translocations; this may also contribute to MYC overexpression. These results highlight that FISH fails to identify all HGBL-DH/THs, while revealing a range of other genetic mechanisms potentially underlying MYC dysregulation in DHITsig+ DLBCL, suggesting that gene expression profiling is more sensitive for identifying the biology underlying poor outcomes in GCB-DLBCL.
National surveillance using mobile systems for health monitoring: complexity, functionality and feasibility
Authors: Singh Yages , Jackson Debra , Bhardwaj Sanjana , Titus Natasha , Goga Ameena 
Published: September 2019

Abstract

Background
Although the use of technology viz. mobile phones, personalised digital assistants, smartphones, notebook and tablets to monitor health and health care (mHealth) is mushrooming, only small, localised studies have described their use as a data collection tool. This paper describes the complexity, functionality and feasibility of mHealth for large scale surveillance at national and sub-national levels in South Africa, a high HIV-prevalence setting.

Methods
In 2010, 2011–12 and 2012–13 three nationally representative surveys were conducted amongst infants attending 580 facilities across all 51 districts, within all nine provinces of South Africa, to monitor the effectiveness of the programme to prevent mother-to-child transmission of HIV (PMTCT). In all three surveys a technical protocol and iterative system for mobile data collection was developed. In 2012–13 the system included automated folders to store information about upcoming interviews. Paper questionnaires were used as a back-up, in case of mHealth failure. These included written instructions per question on limits, skips and compulsory questions. Data collectors were trained on both systems.

Results
In the 2010, 2011–12 and 2012–2013 surveys respectively, data from 10,554, 10,071, and 10,536 interviews, and approximately 186 variables per survey were successfully uploaded to 151 mobile phones collecting data from 580 health facilities in 51 districts, across all nine provinces of South Africa. A technician, costing approximately U$D20 000 p.a. was appointed to support field-based staff. Two percent of data were gathered using paper- questionnaires. The time needed for mHealth interviews was approximately 1,5 times less than the time needed for paper questionnaires 30–45 min versus approximately 120 min (including 60–70 min for the interview with an additional 45 min for data capture). In 2012–13, 1172 data errors were identified via the web-based console. There was a four-week delay in resolving data errors from paper-based surveys compared with a 3-day turnaround time following direct capture on mobile phones.

Conclusion
Our experiences demonstrate the feasibility of using mHealth during large-scale national surveys, in the presence of a supportive data management team. mHealth systems reduced data collection time by almost 1.5 times, thus reduced data collector costs and time needed for data management.
Longitudinal adherence to maternal antiretroviral therapy and infant Nevirapine prophylaxis from 6 weeks to 18 months postpartum amongst a cohort of mothers and infants in South Africa
Authors: Larsen Anna , Magasana Vuyolwethu , Dinh Thu-Ha , Ngandu Nobubelo , Lombard Carl , Cheyip Mireille , Ayalew Kassahun , Chirinda Witness , Kindra Gurpreet , Jackson Debra , Goga Ameena 
Published: September 2019

Abstract

Background
Despite improved policies to prevent mother-to-child HIV transmission (MTCT), adherence to maternal antiretroviral therapy (ART) and infant Nevirapine prophylaxis (NVP) is low in South Africa. We describe ART adherence amongst a cohort of HIV-positive mothers and HIV-exposed but uninfected infants from 6 weeks until 18 months post-delivery and identify risk factors for nonadherence.

Methods
Data were collected in 2012–2014 through a nationally representative survey of PMTCT effectiveness. Mother-infant pairs were enrolled during the infant’s first immunization visit at 6 weeks. Mothers and HIV-exposed infants (2811 pairs) were followed to 18 months at 3-month intervals. Mothers who self-reported being on ART at 6 weeks postpartum (N = 1572 (55.9%)) and infants on NVP at 6 weeks (N = 2370 (84.3%)) were eligible for this analysis and information about their adherence was captured at each interview they attended thereafter. We defined nonadherence within each 3-month interval as self-report of missing > 5% of daily ART/NVP doses, estimated adherence using a Cox survival curve with Andersen & Gill setup for recurring events, and identified risk factors for nonadherence with an extended Cox regression model (separately for mothers and infants) in Stata 13. Results are not nationally representative as this is a subgroup analysis of the follow-up cohort.

Results
Amongst mothers on ART at 6 weeks postpartum, cumulative adherence to maternal ART until 18 months was 63.4%. Among infants on NPV at 6 weeks postpartum, adherence to NVP was 74.5%.. Risk factors for nonadherence to maternal ART, controlling for other factors, included mother’s age (16–24 years vs. ≥34 years, adjusted Hazard Ratio (aHR): 1.9, 95% CI: 1.4–2.5), nondisclosure of HIV status to anyone (nondisclosure vs. disclosure: aHR: 1.7, 95% CI: 1.3–2.1), and timing of ART initiation (initiated ART after delivery vs. initiated ART before delivery: aHR: 1.6, 95% CI: 1.3–2.0). Provincial variation was seen in nonadherence to infant NVP, controlling for other factors.

Conclusion
Maintaining ART adherence until 18 months postpartum remains a crucial challenge, with maternal ART adherence among the six week maternal ART cohort below 65% and infant NVP adherence among breastfeeding infants in this cohort below 75%.This is gravely concerning, given the global policy shift to lifelong ART amongst pregnant and lactating women, and the need for extended infant prophylaxis amongst mothers who are not virally suppressed. Our findings suggest that young mothers and mothers who do not disclose their status should be targeted with messages to improve adherence, and that late maternal ART initiation (after delivery) increases the risk of maternal nonadherence.
Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma
Authors: Zhang Jing , Liu Shenglan , Ye Qianyun , Pan Jingxuan 
Published: September 2019

Abstract
Background
Life of patients with uveal melanoma (UM) is largely threatened by liver metastasis. Little is known about the drivers of liver organotropic metastasis in UM. The elevated activity of transcription of oncogenes is presumably to drive aspects of tumors. We hypothesized that inhibition of transcription by cyclin-dependent kinase 7/9 (CDK7/9) inhibitor SNS-032 diminished liver metastasis by abrogating the putative oncogenes in charge of colonization, stemness, cell motility of UM cells in host liver microenvironment.

Methods
The effects of SNS-032 on the expression of the relevant oncogenes were examined by qRT-PCR and Western blotting analysis. Proliferative activity, frequency of CSCs and liver metastasis were evaluated by using NOD-SCID mouse xenograft model and NOG mouse model, respectively.

Results
The results showed that CDK7/9 were highly expressed in UM cells, and SNS-032 significantly suppressed the cellular proliferation, induced apoptosis, and inhibited the outgrowth of xenografted UM cells and PDX tumors in NOD-SCID mice, repressed the cancer stem-like cell (CSC) properties through transcriptional inhibition of stemness-related protein Krüppel-like factor 4 (KLF4), inhibited the invasive phonotypes of UM cells through matrix metalloproteinase 9 (MMP9). Mechanistically, SNS-032 repressed the c-Myc-dependent transcription of RhoA gene, and thereby lowered the RhoA GTPase activity and actin polymerization, and subsequently inhibited cell motility and liver metastasis.

Conclusions
In conclusion, we validate a set of transcription factors which confer metastatic traits (e.g., KLF4 for CSCs, c-Myc for cell motility) in UM cells. Our results identify SNS-032 as a promising therapeutic agent, and warrant a clinical trial in patients with metastatic UM.
Myceliophthora thermophila Xyr1 is predominantly involved in xylan degradation and xylose catabolism
Authors: dos Santos Gomes Ana Carolina , Falkoski Daniel , Battaglia Evy , Peng Mao , Nicolau de Almeida Maira , Coconi Linares Nancy , Meijnen Jean-Paul , Visser Jaap , de Vries Ronald P. 
Published: September 2019

Abstract

Background
Myceliophthora thermophila is a thermophilic ascomycete fungus that is used as a producer of enzyme cocktails used in plant biomass saccharification. Further development of this species as an industrial enzyme factory requires a detailed understanding of its regulatory systems driving the production of plant biomass-degrading enzymes. In this study, we analyzed the function of MtXlr1, an ortholog of the (hemi-)cellulolytic regulator XlnR first identified in another industrially relevant fungus, Aspergillus niger.

Results
The Mtxlr1 gene was deleted and the resulting strain was compared to the wild type using growth profiling and transcriptomics. The deletion strain was unable to grow on xylan and d-xylose, but showed only a small growth reduction on l-arabinose, and grew similar to the wild type on Avicel and cellulose. These results were supported by the transcriptome analyses which revealed reduction of genes encoding xylan-degrading enzymes, enzymes of the pentose catabolic pathway and putative pentose transporters. In contrast, no or minimal effects were observed for the expression of cellulolytic genes.

Conclusions
Myceliophthora thermophila MtXlr1 controls the expression of xylanolytic genes and genes involved in pentose transport and catabolism, but has no significant effects on the production of cellulases. It therefore resembles more the role of its ortholog in Neurospora crassa, rather than the broader role described for this regulator in A. niger and Trichoderma reesei. By revealing the range of genes controlled by MtXlr1, our results provide the basic knowledge for targeted strain improvement by overproducing or constitutively activating this regulator, to further improve the biotechnological value of M. thermophila.