bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival Following Chemotherapy in Ovarian Clear Cell Carcinoma Is Not Associated with Pathological Misclassification of Tumor Histotype
Authors: Takenaka Masataka , Köbel Martin , Garsed Dale W. , Fereday Sian , Pandey Ahwan , Etemadmoghadam Dariush , Hendley Joy , Kawabata Ayako , Noguchi Daito , Yanaihara Nozomu , Takahashi Hiroyuki , Kiyokawa Takako , Ikegami Masahiro , Takano Hirokuni , Isonishi Seiji , Ochiai Kazuhiko , Traficante Nadia , Gadipally Sreeja , Semple Timothy , Vassiliadis Dane , Amarasinghe Kausyalya , Li Jason , Mir Arnau Gisela , Okamoto Aikou , Friedlander Michael , Bowtell David D. L. 
Published: April 2019

Abstract

Purpose:
Although ovarian clear cell carcinomas (OCCC) are commonly resistant to platinum-based chemotherapy, good clinical outcomes are observed in a subset of patients. The explanation for this is unknown but may be due to misclassification of high-grade serous ovarian cancer (HGSOC) as OCCC or mixed histology.

Experimental Design:
To discover potential biomarkers of survival benefit following platinum-based chemotherapy, we ascertained a cohort of 68 Japanese and Australian patients in whom progression-free survival (PFS) and overall survival (OS) could be assessed. We performed IHC reclassification of tumors, and targeted sequencing and immunohistochemistry of known driver genes. Exome sequencing was performed in 10 patients who had either unusually long survival (N = 5) or had a very short time to progression (N = 5).

Results:
The majority of mixed OCCC (N = 6, 85.7%) and a small proportion of pure OCCC (N = 3, 4.9%) were reclassified as likely HGSOC. However, the PFS and OS of patients with misclassified samples were similar to that of patients with pathologically validated OCCC. Absent HNF1B expression was significantly correlated with longer PFS and OS (P = 0.0194 and 0.0395, respectively). Mutations in ARID1A, PIK3CA, PPP2R1A, and TP53 were frequent, but did not explain length of PFS and OS. An exploratory exome analysis of patients with favorable and unfavorable outcomes did not identify novel outcome-associated driver mutations.

Conclusions:
Survival benefit following chemotherapy in OCCC was not associated with pathological misclassification of tumor histotype. HNF1B loss may help identify the subset of patients with OCCC with a more favorable outcome.
Medium and large sized mammals of the Boqueirão da Onça, North of Bahia State, Brazil
Authors: Campos Cláudia Bueno de , Esteves Carolina Franco , Dias Douglas De Matos , Rodrigues Flávio Henrique Guimarães 
Published: April 2019

The mosaic of protected areas of Boqueirão da Onça (8.636 km²), created in the north of Bahia state, is located in the Caatinga, an exclusively Brazilian biome, but exposed to a range of anthropic impacts that threaten its species and natural resources. Few data are available for various zoological groups in Caatinga, including mammals. In order to characterize the community of mammals of this region, considering species richness, we installed 80 camera-trap stations. With a sampling effort of 10,370 camera-days we recorded 28 species (22 wild and six domestic). Opportunistically, we recorded four mammals, resulting in a total richness of 32 species, five of which are included in the global list of endangered species, and seven in the national list. The results are significant, since the richness of wild mammals of the Boqueirão da Onça (S = 26) presented a high value when compared to other Caatinga localities. During the study we found evidence of human activities threatening the conservation of the region, such as poaching and deforestation. Therefore, there is an urgent need in the publication of the Management Plan of the recently created Boqueirão da Onça National Park, to minimize negative impacts on biodiversity and ensure the maintenance of ecological processes.
Influence of Baseline Anemia on Dual Antiplatelet Therapy Cessation and Risk of Adverse Events After Percutaneous Coronary Intervention
Authors: Faggioni Michela , Baber Usman , Sartori Samantha , Chandrasekhar Jaya , Cohen David J. , Henry Timothy D. , Claessen Bimmer E. , Dangas George D. , Gibson C. Michael , Krucoff Mitchell W. , Vogel Birgit , Moliterno David J. , Sorrentino Sabato , Colombo Antonio , Chieffo Alaide , Kini Annapoorna , Farhan Serdar , Ariti Cono , Witzenbichler Bernard , Weisz Giora , Steg Philippe Gabriel , Pocock Stuart , Mehran Roxana 
Published: April 2019

Background:
Anemia is a well-recognized risk factor for both bleeding and ischemic events after percutaneous coronary intervention (PCI). We sought to determine the impact of baseline anemia on dual antiplatelet therapy (DAPT) cessation patterns ≤2 years after PCI and the subsequent risk of clinical adverse events.

Methods and Results:
PARIS (Patterns of Non-Adherence to Dual Anti-Platelet Regimen in Stented Patients) was a prospective multicenter observational registry of PCI-treated patients (n=5018). Anemia was defined as baseline Hb (hemoglobin) <12 g/dL for men and <11 g/dL for women. DAPT cessation modes included physician-recommended discontinuation, temporary interruption (≤14 days), and disruption due to bleeding or noncompliance. The primary end point was 2-year major adverse cardiovascular events (MACE), a composite of cardiac death, myocardial infarction, or target vessel revascularization. We identified 824 (18%) anemic and 4194 (82%) nonanemic patients. Anemic patients were older and had a higher rate of diabetes mellitus, hypertension, and prior PCI. DAPT interruption and disruption were significantly more common in anemic patients throughout 2 years after PCI, whereas physician-recommended discontinuation occurred more often in anemic patients during the first year after PCI and in nonanemic patients during the second year. The 2-year adjusted risks of MACE and Bleeding Academic Research Consortium 3 or 5 bleeding events were significantly higher in anemic patients. Compared with uninterrupted DAPT, disruption, but not interruption and physician-recommended discontinuation, was associated with a higher risk of myocardial infarction in nonanemic patients and a higher risk of both myocardial infarction and MACE in anemic patients. There was no significant interaction between anemia and risk of clinical outcomes associated with each DAPT cessation mode.

Conclusions:
Baseline anemia was associated with a significantly higher adjusted risk of MACE and major bleeding. Physicians more frequently recommend DAPT discontinuation to anemic patients during the first year, and to nonanemic patients during the second year after PCI. DAPT disruption was associated with a higher risk of MACE outcomes.
Age at Diagnosis of Type 2 Diabetes Mellitus and Associations With Cardiovascular and Mortality Risks
Authors: Sattar Naveed , Rawshani Araz , Franzén Stefan , Rawshani Aidin , Svensson Ann-Marie , Rosengren Annika , McGuire Darren K. , Eliasson Björn , Gudbjörnsdottir Soffia 
Published: April 2019

Background:
Risk of cardiovascular disease (CVD) and mortality for patients with versus without type 2 diabetes mellitus (T2DM) appears to vary by the age at T2DM diagnosis, but few population studies have analyzed mortality and CVD outcomes associations across the full age range.

Methods:
With use of the Swedish National Diabetes Registry, everyone with T2DM registered in the Registry between 1998 and 2012 was included. Controls were randomly selected from the general population matched for age, sex, and county. The analysis cohort comprised 318 083 patients with T2DM matched with just <1.6 million controls. Participants were followed from 1998 to 2013 for CVD outcomes and to 2014 for mortality. Outcomes of interest were total mortality, cardiovascular mortality, noncardiovascular mortality, coronary heart disease, acute myocardial infarction, stroke, heart failure, and atrial fibrillation. We also examined life expectancy by age at diagnosis. We conducted the primary analyses using Cox proportional hazards models in those with no previous CVD and repeated the work in the entire cohort.

Results:
Over a median follow-up period of 5.63 years, patients with T2DM diagnosed at ≤40 years had the highest excess risk for most outcomes relative to controls with adjusted hazard ratio (95% CI) of 2.05 (1.81–2.33) for total mortality, 2.72 (2.13–3.48) for cardiovascular-related mortality, 1.95 (1.68–2.25) for noncardiovascular mortality, 4.77 (3.86–5.89) for heart failure, and 4.33 (3.82–4.91) for coronary heart disease. All risks attenuated progressively with each increasing decade at diagnostic age; by the time T2DM was diagnosed at >80 years, the adjusted hazard ratios for CVD and non-CVD mortality were <1, with excess risks for other CVD outcomes substantially attenuated. Moreover, survival in those diagnosed beyond 80 was the same as controls, whereas it was more than a decade less when T2DM was diagnosed in adolescence. Finally, hazard ratios for most outcomes were numerically greater in younger women with T2DM.

Conclusions:
Age at diagnosis of T2DM is prognostically important for survival and cardiovascular risks, with implications for determining the timing and intensity of risk factor interventions for clinical decision making and for guideline-directed care. These observations amplify support for preventing/delaying T2DM onset in younger individuals.
In‐Hospital Bleeding Outcomes of Myocardial Infarction in the Era of Warfarin and Direct Oral Anticoagulants for Atrial Fibrillation in the United States: A Report From the National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry
Authors: Feldman Dmitriy N. , Wang Tracy Y. , Chen Anita Y. , Swaminathan Rajesh V. , Kim Luke K. , Wong S. Chiu , Minutello Robert M. , Bergman Geoffrey , Singh Harsimran S. , Madias Christopher 
Published: April 2019

Background
We sought to examine patient characteristics, peri‐infarction invasive and pharmacologic management, and in‐hospital major bleeding in myocardial infarction patients with atrial fibrillation or flutter, based on home anticoagulant use.

Methods and Results

We stratified patients by home anticoagulant: (1) no anticoagulant, (2) warfarin, and (3) direct oral anticoagulants (
DOAC
s) among ST‐segment–elevation myocardial infarction (
STEMI
) and non‐STEMI (NSTEMI) patients with atrial fibrillation or flutter treated at 761
US
hospitals in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry from January 2015 to December 2016. The primary outcome of our study was in‐hospital major bleeding. Multivariable logistic regression was used to examine the independent association between home anticoagulant and in‐hospital major bleeding. Among 6471
STEMI
patients with atrial fibrillation or flutter, 15.7% were on warfarin and 13.0% on
DOAC
s; among 19 954
NSTEMI
patients, 22.8% were on warfarin and 15.4% on
DOAC
s. In
STEMI
, door‐to‐balloon times were slightly higher in those on anticoagulant, with similar rates of angiography within 24 hours in the 3 groups.
NSTEMI
patients on anticoagulant were less likely to undergo angiography (49.3% no anticoagulant, 33.4% on warfarin, 36.4% on
DOAC
s;
P
<0.01) or percutaneous coronary intervention within 24 hours (21.1% no anticoagulant, 14.3% on warfarin, 15.9% on
DOAC
s;
P
<0.01). After multivariate adjustment, use of home warfarin (odds ratio: 1.00 [95%
CI
, 0.79–1.27] in
STEMI
and 1.13 [95%
CI
, 0.97–1.30] in
NSTEMI
) or
DOAC
(odds ratio: 0.93 [95%
CI
, 0.73–1.20] in
STEMI
and 0.97 [95%
CI
, 0.81–1.16] in
NSTEMI
) was not associated with increased in‐hospital major bleeding compared with no anticoagulant.

Conclusions

In routine clinical practice, home warfarin or
DOAC
therapy is not associated with an increased risk of in‐hospital bleeding compared with no anticoagulant.
Combining Neurovascular and Neurodegenerative Magnetic Resonance Imaging Measures in Stroke
Authors: Wyss Annick , Dawson Jesse , Arba Francesco , Wardlaw Joanna M. , Dickie David Alexander ,   on behalf of the VISTA-Prevention Collaborators
Published: April 2019

Background and Purpose—
Individual markers of cerebral small vessel disease and cerebral atrophy explain a small proportion of variance in vascular risk factors and cognitive function. Combining these markers into a single measure of neurovascular and neurodegenerative disease may be more powerful. We assessed this using data contained in the Virtual International Stroke Trials Archive - Prevention sub-archive.

Methods—
We extracted white matter hyperintensities (WMH) and cerebrospinal fluid (CSF) volumes from 317 people with ischemic stroke or transient ischemic attack who had baseline magnetic resonance imaging. We assessed progression of volumes in 208 people who had 2-year follow-up magnetic resonance imaging. WMH and CSF volumes were segmented from fluid attenuated inversion recovery and T1 images. The combined neurovascular and neurodegenerative measure was the sum of WMH and CSF volume normalized by intracranial volume. We assessed (1) the relationship between baseline vascular risk factors and imaging markers; and (2) the relationship between baseline imaging markers and Mini-Mental State Examination score at follow-up using multiple linear regression. We also assessed implications for sample size calculations using n=208 participants with follow-up magnetic resonance imaging.

Results—

Vascular risk factors accounted for 7%, 11%, and 12% of the variance in WMH, CSF, and combined volume, respectively (all
P
<0.001). The association between baseline combined volume and 6-month follow-up Mini-Mental State Examination (β=−0.442; SE, 0.07;
P
<0.0001) was 32% greater than WMH (β=−0.302; SE, 0.06;
P
<0.0001) and 12% greater than CSF (β=−0.391; SE, 0.07;
P
<0.0001) alone. The combined volume required between 207 and 3305 (20%) fewer patients per arm than WMH alone to detect reductions of 10% to 40% in volume progression over 2 years.

Conclusions—
A combined neurovascular and neurodegenerative magnetic resonance imaging measure including WMH and CSF volume was more closely related to vascular risk factors and cognitive function than either WMH or CSF volume alone. The combined volume may be a more sensitive measurement for clinical trials.
Glorious Science or “Dead Dog”? Jean de Jandun and the Quarrel over Astrology in Fourteenth-Century Paris
Authors: Nothaft C. Philipp E. 
Published: April 2019

AbstractThis article edits and examines a little-known epistolary treatise datable to 1322, which survives in a fifteenth-century manuscript in the Herzog-August-Bibliothek, Wolfenbüttel. The author of this work was engaged in a heated argument with the Parisian philosopher Jean de Jandun over the status and rationality of astrology. Jean’s pro-astrological stance is documented in a letter dated 28 October 1321, which survives for having been appended to the main treatise. In responding to Jean de Jandun’s letter, the author delivered a trenchant critique of astrology grounded almost entirely in philosophical, as opposed to theological, ideas, addressing issues such as empirical evidence, causality, and contingency. The author’s way of pointing out ruptures between astrology and Aristotelian natural philosophy marks him out as an intellectual precursor to the much better-known anti-astrological polemics written later in the same century by Parisian thinkers such as Nicole Oresme and Heinrich von Langenstein.
Weather Types and Hourly to Multiday Rainfall Characteristics in Tropical Australia
Authors: Moron Vincent , Barbero Renaud , Evans Jason P. , Westra Seth , Fowler Hayley J. 
Published: April 2019

Abstract
Six weather types (WTs) are computed for tropical Australia during the wet season (November–March 1979–2015) using cluster analysis of 6-hourly low-level winds at 850 hPa. The WTs may be interpreted as a varying combination of at least five distinct phenomena operating at different time scales: the diurnal cycle, fast and recurrent atmospheric phenomena such as transient low pressure, the intraseasonal Madden–Julian oscillation, the annual cycle, and interannual variations mostly associated with El Niño–Southern Oscillation. The WTs are also strongly phase-locked onto the break/active phases of the monsoon; two WTs characterize mostly the trade-wind regime prevalent either at the start and the end of the monsoon or during its breaks, while three monsoonal WTs occur mostly during its core and active phases. The WT influence is strongest for the frequency of wet spells, while the influence on intensity varies according to the temporal aggregation of the rainfall. At hourly time scale, the climatological mean wet intensity tends to be near-constant in space and not systematically larger for the monsoonal WTs compared to other WTs. Nevertheless, one transitional WT, most prevalent around late November and characterized by weak synoptic forcings and overall drier conditions than the monsoonal WTs, is associated with an increased number of high hourly rainfall intensities for some stations, including for the interior of the Cape York Peninsula. When the temporal aggregation exceeds 6–12 h, the mean intensity tends to be larger for some of the monsoonal WTs, in association with more frequent and also slightly longer wet spells.
Thyroidectomy Complications in Patients with Diabetes Mellitus
Authors: Chung Sei Y. , Govindan Aparna , Babu Archana , Tassler Andrew 
Published: April 2019

ObjectiveTo (1) analyze postoperative thyroidectomy outcomes in patients with diabetes mellitus (DM), who are prone to deleterious effects of glucose dysmetabolism, and (2) apply findings to optimize perioperative management of diabetics requiring thyroid surgery.Study DesignRetrospective database analysis.SettingUniversity hospital.Subjects and MethodsThe National Inpatient Sample was queried using International Classification of Diseases, Ninth Revision, Clinical Modification and Procedure Coding System (PCS) codes for patients with benign or malignant thyroid disease who underwent thyroid surgery between 2002 and 2013. An analysis of demographics, comorbidities, and postoperative outcomes was conducted between a DM vs non‐DM cohort using bivariate and multivariate techniques.ResultsIn total, 103,842 cases met inclusion criteria; 14.2% were diabetics. Diabetics had significantly higher rates of baseline comorbid chronic pulmonary disease, hypertension, obesity, and anemia. Following thyroidectomy, patients with DM were more likely to have vocal cord paresis or paralysis compared to non‐DM patients (2.0% vs 1.3%; P <. 001). However, when adjusting for demographics and comorbidities, there was no significant difference in this complication between the 2 groups. Diabetics had independently higher rates of cardiac, pulmonary, and urinary complications, as well as transfusion, reintubation, and in‐hospital mortality. Diabetics had longer hospital stays (2.76 vs 1.97; P <. 001) with higher incurred hospital charges (32,921 vs 25,198; P <. 001).ConclusionAlthough DM often confers metabolic and ischemic derangements secondary to hyperglycemia such as neuropathy, this comorbidity was not independently associated with higher rates of vocal cord paresis or paralysis following thyroid surgery. However, DM predicted other adverse outcomes, including greater cardiac, pulmonary, and urinary complications, as well as transfusion, reintubation, and in‐hospital mortality.
Cancer drug development: The missing links
Authors: Kunnumakkara Ajaikumar B , Bordoloi Devivasha , Sailo Bethsebie Lalduhsaki , Roy Nand Kishor , Thakur Krishan Kumar , Banik Kishore , Shakibaei Mehdi , Gupta Subash C , Aggarwal Bharat B 
Published: April 2019

Although better science and technology has been linked with better health care, however, reality is much different. Although America and most of Europe are equipped with most advanced science and technology, paradoxically cancer incidence is highest in the world. This indicates that science and technology alone is not sufficient in treating diseases like cancer. It is also now well recognized that more than 95% of the drugs/compounds that kill either cancer cells in culture or regress the tumors in animals, fail in phase I clinical trials in humans, indicating that most pre-clinical models of cancer are inadequate. In addition, most of the anticancer drugs that are approved by the regulatory agencies such as FDA either has no effect on the overall survival of the cancer patient or may provide an increase in few months in overall survival. This is despite the fact that most targeted therapies that are currently available are highly expensive; thus suggesting the lack of affordability. This review is meant to focus on some of these problems in detail and then provide potential solutions since most cancers are caused by multiple genes, and thus multi-targeted therapies are needed such as natural products which are inexpensive, safe and have been used for thousands of years for both prevention and treatment of cancer. Impact statement The success rate for cancer drugs which enter into phase 1 clinical trials is utterly less. Why the vast majority of drugs fail is not understood but suggests that pre-clinical studies are not adequate for human diseases. In 1975, as per the Tufts Center for the Study of Drug Development, pharmaceutical industries expended 100 million dollars for research and development of the average FDA approved drug. By 2005, this figure had more than quadrupled, to $1.3 billion. In order to recover their high and risky investment cost, pharmaceutical companies charge more for their products. However, there exists no correlation between drug development cost and actual sale of the drug. This high drug development cost could be due to the reason that all patients might not respond to the drug. Hence, a given drug has to be tested in large number of patients to show drug benefits and obtain significant results.
Patient-centered benefit-risk analysis of transcatheter aortic valve replacement
Authors: Marsh Kevin , Hawken Natalia , Brookes Ella , Kuehn Carrie , Liden Barry 
Published: April 2019

Background: Aortic stenosis (AS) treatments include surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). Choosing between SAVR and TAVR requires patients to trade-off several benefits and risks. The objective of this research was to determine which outcomes associated with TAVR and SAVR patients consider most important, collect quantitative data about how patients weigh these benefits and risks, and evaluate patients’ preferences for SAVR or TAVR. Methods: Patients with aortic stenosis were recruited from advocacy organization databases. An online adapted swing weighting (ASW) method was used to elicit attribute tradeoffs from 93 patients. The ASW exercise consisted of a series of pairwise comparisons of attributes. Survey data were used to estimate the weight that patients put on the AS treatment attributes, which were incorporated into a quantitative benefit-risk analysis (BRA) to evaluate patients’ preferences for TAVR and SAVR. Results: On average, patients put greater value on attributes that favored TAVR than SAVR. The value patients placed on the lower short-term mortality rate, reduced procedural invasiveness, and quicker time to return to normal quality of life associated with TAVR, offset the value they placed on the time over which SAVR has been proven to work. There was substantial heterogeneity in patients’ preferences. This was partly explained by age, with differences in preference observed between patients <60 years to those ≥60 years. A Monte Carlo Simulation found that 75.1% of patients prefer TAVR. Conclusions: Most AS patients are willing to tolerate sizable increases in clinical risk in exchange for the benefits of TAVR, resulting in a large proportion of patients preferring TAVR to SAVR. Further work should be undertaken to characterize the heterogeneity in preferences for AS treatment attributes. Shared decision-making tools based on attributes important to patients can support patients’ selection of the procedure that best meets their needs.