bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting DNA Repair to Drive Immune Responses: It's Time to Reconsider the Strategy for Clinical Translation
Authors: Takahashi Nobuyuki , Surolia Ira , Thomas Anish 
Published: February 2020

AbstractPARP inhibition induces robust local and systemic antitumor immune responses and curative responses when combined with immune checkpoint blockade in many preclinical studies. However, the combination has not markedly improved antitumor effect compared with individual agents in clinical trials to date. We propose that the data from these trials indicate a lack of synergistic interaction of PARP inhibition and immune checkpoint blockade, with implications for reexamining our current strategies for clinical translation. As current mouse models do not recapitulate the genomic heterogeneity or tumor microenvironment of human cancers, better models are urgently needed. Tumor-extrinsic factors modulate immune checkpoint blockade response and they may be better assessed in early-phase clinical trials with frequent tissue and blood sampling. Further work is also needed to uncover the dose and schedule dependency of DNA repair modulation on the immune system. In homologous recombination repair–deficient tumors, randomized trials should be prioritized to address whether the benefit is superior to that of PARP inhibitor monotherapy. In tumors that are not homologous recombination repair deficient, research biopsies should be integrated to early-phase clinical trials to discover biomarkers that can predict clinical benefit. These considerations are relevant to the variety of adjunctive therapeutics being combined with immune checkpoint blockade to improve probability, duration, and potency of antitumor activity.
Filling a gap in Andean Cat Leopardus jacobita (Cornalia, 1865) (Mammalia: Carnivora: Felidae) distribution range: new record in La Rioja province, Argentina
Authors: Tellaeche Cintia Gisele , Guerisoli María de las Mercedes , Napolitano Constanza , Di Nucci Dante Luis , Reppucci Juan Ignacio 
Published: February 2020

A pelt of an Andean Cat specimen was discovered in La Rioja Province, Argentina, a region with no previous data recorded, located in a large distribution gap between the two currently identified evolutionarily significant units (ESU). This new record not only improves our knowledge about the species distribution but can also provide relevant genetic information for a better understanding of the relationship between the two ESU.
Temporal overlap between two sympatric carnivores in northwestern Peru and southwestern Ecuador
Authors: García-Olaechea Alvaro , Hurtado Cindy M. 
Published: February 2020

The coexistence of sympatric species is determined by differences in their ecological niche. Thus, for taxonomically and ecologically similar species to coexist, they must segregate in at least one of the three most important dimensions of the ecological niche: space, time or diet. The Pampas Cat Leopardus colocola and the Sechuran Fox Lycalopex sechurae are sympatric species; and they are the most common medium-sized carnivores in the Sechura Desert and in the lowland seasonally dry tropical forest of Peru and Ecuador. We evaluated the activity pattern of both mesocarnivores using camera trapping and temporal overlap analysis in both arid ecosystems. We found a high degree of activity overlap and no statistically significant difference in the activity pattern of both species (Δ = 0.85 with 95% CI = 0.81 – 0.94; W = 0.531, SD = 2, P = 0.767), both being cathemeral. There is, however, a contrasting pattern in the daytime activity of these species in the dry forest. These results suggest that the different diet composition may be the main dimension that is facilitating the coexistence of both mesocarnivores in the arid ecosystems of northern Peru and southern Ecuador.
Comparison of BNP and NT-proBNP in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Rørth Rasmus , Jhund Pardeep S. , Yilmaz Mehmet B. , Kristensen Søren Lund , Welsh Paul , Desai Akshay S. , Køber Lars , Prescott Margaret F. , Rouleau Jean L. , Solomon Scott D. , Swedberg Karl , Zile Michael R. , Packer Milton , McMurray John J.V. 
Published: February 2020

Background:
Both BNP (B-type natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide) are widely used to aid diagnosis, assess the effect of therapy, and predict outcomes in heart failure and reduced ejection fraction. However, little is known about how these 2 peptides compare in heart failure and reduced ejection fraction, especially with contemporary assays. Both peptides were measured at screening in the PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure).

Methods:

Eligibility criteria in PARADIGM-HF included New York Heart Association functional class II to IV, left ventricular ejection fraction ≤40%, and elevated natriuretic peptides: BNP ≥150 pg/mL or NT-proBNP ≥600 pg/mL (for patients with HF hospitalization within 12 months, BNP ≥100 pg/mL or NT-proBNP ≥400 pg/mL). BNP and NT-proBNP were measured simultaneously at screening and only patients who fulfilled entry criteria for both natriuretic peptides were included in the present analysis. The BNP/NT-proBNP criteria were not different for patients in atrial fibrillation. Estimated glomerular filtration rate <30 mL/min per 1.73 m
2
was a key exclusion criterion.

Results:

The median baseline concentration of NT-proBNP was 2067 (Q1, Q3: 1217–4003) and BNP 318 (Q1, Q3: 207–559), and the ratio, calculated from the raw data, was ≈6.25:1. This ratio varied considerably according to rhythm (atrial fibrillation 8.03:1; no atrial fibrillation 5.75:1) and with age, renal function, and body mass index but not with left ventricular ejection fraction. Each peptide was similarly predictive of death (all-cause, cardiovascular, sudden and pump failure) and heart failure hospitalization, for example, cardiovascular death: BNP hazard ratio, 1.41 (95% CI, 1.33–1.49) per 1 SD increase,
P
<0.0001; NT-proBNP, 1.45 (1.36–1.54);
P
<0.0001.

Conclusions:
The ratio of NT-proBNP to BNP in heart failure and reduced ejection fraction appears to be greater than generally appreciated, differs between patients with and without atrial fibrillation, and increases substantially with increasing age and decreasing renal function. These findings are important for comparison of natriuretic peptide concentrations in heart failure and reduced ejection fraction.
Effects of Percutaneous Coronary Intervention on Death and Myocardial Infarction Stratified by Stable and Unstable Coronary Artery Disease
Authors: Chacko Liza , P. Howard James , Rajkumar Christopher , Nowbar Alexandra N. , Kane Christopher , Mahdi Dina , Foley Michael , Shun-Shin Matthew , Cole Graham , Sen Sayan , Al-Lamee Rasha , Francis Darrel P. , Ahmad Yousif 
Published: February 2020

Background:
In patients presenting with ST-segment–elevation myocardial infarction, percutaneous coronary intervention (PCI) reduces mortality when compared with fibrinolysis. In other forms of coronary artery disease (CAD), however, it has been controversial whether PCI reduces mortality. In this meta-analysis, we examine the benefits of PCI in (1) patients post–myocardial infarction (MI) who did not receive immediate revascularization; (2) patients who have undergone primary PCI for ST-segment–elevation myocardial infarction but have residual coronary lesions; (3) patients who have suffered a non–ST-segment–elevation acute coronary syndrome; and (4) patients with truly stable CAD with no recent infarct. This analysis includes data from the recently presented International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) and Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI (COMPLETE) trials.

Methods and Results:

We systematically identified all randomized trials of PCI on a background of medical therapy for the treatment of CAD. The ISCHEMIA trial, presented in November 2019, was eligible for inclusion. Data were combined using a random-effects meta-analysis. The primary end point was all-cause mortality. Forty-six trials, including 37 757 patients, were eligible. In the 3 unstable scenarios, PCI had the following effects on mortality: unrevascularized post-MI relative risk (RR) 0.68 (95% CI, 0.45–1.03);
P
=0.07; multivessel disease following ST-segment–elevation myocardial infarction (RR, 0.84 [95% CI, 0.69–1.04];
P
=0.11); non–ST-segment–elevation acute coronary syndrome (RR, 0.84 [95% CI, 0.72–0.97];
P
=0.02). Overall, in these unstable scenarios PCI was associated with a significant reduction in mortality (RR, 0.84 [95% CI, 0.75–0.93];
P
=0.02). In unstable CAD, PCI also reduced cardiac death (RR, 0.69 [95% CI, 0.53–0.90];
P
=0.007) and MI (RR, 0.74 [95% CI, 0.62–0.90];
P
=0.002). For stable CAD, PCI did not reduce mortality (RR, 0.98 [95% CI, 0.87–1.11]), cardiac death (RR, 0.89 [95% CI, 0.71–1.12];
P
=0.33), or MI (RR, 0.96 [95% CI, 0.86–1.08];
P
=0.54).

Conclusions:
PCI prevents death, cardiac death, and MI in patients with unstable CAD. For patients with stable CAD, PCI shows no evidence of an effect on any of these outcomes.
T-Cell–Derived miRNA-214 Mediates Perivascular Fibrosis in Hypertension
Authors: Nosalski Ryszard , Siedlinski Mateusz , Denby Laura , McGinnigle Eilidh , Nowak Michal , Cat Aurelie Nguyen Dinh , Medina-Ruiz Laura , Cantini Marco , Skiba Dominik , Wilk Grzegorz , Osmenda Grzegorz , Rodor Julie , Salmeron-Sanchez Manuel , Graham Gerard , Maffia Pasquale , Graham Delyth , Baker Andrew H. , Guzik Tomasz J. 
Published: February 2020

Rationale:
Despite increasing understanding of the prognostic importance of vascular stiffening linked to perivascular fibrosis in hypertension, the molecular and cellular regulation of this process is poorly understood.

Objectives:
To study the functional role of microRNA-214 (miR-214) in the induction of perivascular fibrosis and endothelial dysfunction driving vascular stiffening.

Methods and Results:

Out of 381 miRs screened in the perivascular tissues in response to Ang II (angiotensin II)-mediated hypertension, miR-214 showed the highest induction (8-fold,
P
=0.0001). MiR-214 induction was pronounced in perivascular and circulating T cells, but not in perivascular adipose tissue adipocytes. Global deletion of miR-214
−
/−
prevented Ang II-induced periaortic fibrosis,
Col1a1
,
Col3a1, Col5a1
, and
Tgfb1
expression, hydroxyproline accumulation, and vascular stiffening, without difference in blood pressure. Mechanistic studies revealed that miR-214
−/−
mice were protected against endothelial dysfunction, oxidative stress, and increased Nox2, all of which were induced by Ang II in WT mice. Ang II-induced recruitment of T cells into perivascular adipose tissue was abolished in miR-214
−/−
mice. Adoptive transfer of miR-214
−/−
T cells into RAG1
−/−
mice resulted in reduced perivascular fibrosis compared with the effect of WT T cells. Ang II induced hypertension caused significant change in the expression of 1380 T cell genes in WT, but only 51 in miR-214
−/−
. T cell activation, proliferation and chemotaxis pathways were differentially affected. MiR-214
−/−
prevented Ang II-induction of profibrotic T cell cytokines (
IL-17
,
TNF-α, IL-9
, and
IFN-γ
) and chemokine receptors (CCR1, CCR2, CCR4, CCR5, CCR6, and CXCR3). This manifested in reduced in vitro and in vivo T cell chemotaxis resulting in attenuation of profibrotic perivascular inflammation. Translationally, we show that miR-214 is increased in plasma of patients with hypertension and is directly correlated to pulse wave velocity as a measure of vascular stiffness.

Conclusions:
T-cell–derived miR-214 controls pathological perivascular fibrosis in hypertension mediated by T cell recruitment and local profibrotic cytokine release.
Sex Differences in Primary and Secondary Prevention of Cardiovascular Disease in China
Authors: Xia Shijun , Du Xin , Guo Lizhu , Du Jing , Arnott Clare , Lam Carolyn S.P. , Huffman Mark D. , Arima Hisatomi , Yuan Yiqiang , Zheng Yang , Wu Shulin , Guang Xuefeng , Zhou Xianhui , Lin Hongbo , Cheng Xiaoshu , Anderson Craig S. , Dong Jianzeng , Ma Changsheng 
Published: February 2020

Background:
Despite improvements in diagnostic and therapeutic interventions to combat cardiovascular disease (CVD) in recent decades, there are significant ongoing access gaps and sex disparities in prevention that have not been adequately quantified in China.

Methods:
A representative, cross-sectional, community-based survey of adults (aged ≥45 years) was conducted in 7 geographic regions of China between 2014 and 2016. Logistic regression models were used to determine sex differences in primary and secondary CVD prevention, and any interaction by age, education level, and area of residence. Data are presented as adjusted odds ratios (ORs) and 95% CIs.

Results:
Of 47 841 participants (61.3% women), 5454 (57.2% women) had established CVD and 9532 (70.5% women) had a high estimated 10-year CVD risk (≥10%). Only 48.5% and 48.6% of women and 39.3% and 59.8% of men were on any kind of blood pressure (BP)–lowering medication, lipid-lowering medication, or antiplatelet therapy for primary and secondary prevention, respectively. Women with established CVD were significantly less likely than men to receive BP-lowering medications (OR, 0.79 [95% CI, 0.65–0.95]), lipid-lowering medications (OR, 0.69 [95% CI, 0.56–0.84]), antiplatelets (OR, 0.53 [95% CI, 0.45–0.62]), or any CVD prevention medication (OR, 0.62 [95% CI, 0.52–0.73]). Women with established CVD, however, had better BP control (OR, 1.31 [95% CI, 1.14–1.50]) but less well-controlled low-density lipoprotein cholesterol (OR, 0.66 [95% CI, 0.57–0.76]), and were less likely to smoke (OR, 13.89 [95% CI, 11.24–17.15]) and achieve physical activity targets (OR, 1.92 [95% CI, 1.61–2.29]). Conversely, women with high CVD risk were less likely than men to have their BP, low-density lipoprotein cholesterol, and bodyweight controlled (OR, 0.46 [95% CI, 0.38–0.55]; OR, 0.60 [95% CI, 0.52–0.69]; OR, 0.55 [95% CI, 0.48–0.63], respectively), despite a higher use of BP-lowering medications (OR, 1.21 [95% CI, 1.01–1.45]). Younger patients (<65 years) with established CVD were less likely to be taking CVD preventive medications, but there were no sex differences by area of residence or education level.

Conclusions:
Large and variable gaps in primary and secondary CVD prevention exist in China, particularly for women. Effective CVD prevention requires an improved overall nationwide strategy and a special emphasis on women with established CVD, who have the greatest disparity and the most to benefit.
Body Mass Index in Young Women and Risk of Cardiomyopathy
Authors: Robertson Josefina , Lindgren Martin , Schaufelberger Maria , Adiels Martin , Björck Lena , Lundberg Christina E. , Sattar Naveed , Rosengren Annika , Åberg Maria 
Published: February 2020

Background:
Incidence rates of cardiomyopathies, which are a common cause of heart failure in young people, have increased during the last decades. An association between body weight in adolescence and future cardiomyopathy among men was recently identified. Whether or not this holds true also for women is unknown. The aim was therefore to determine whether for young women being overweight or obese is associated with a higher risk of developing cardiomyopathy.

Methods:
This was a registry-based national prospective cohort study with data collected from the Swedish Medical Birth Register, 1982 to 2014, with up to 33 years of follow-up. Included women were of childbearing age (18–45 years) during the initial antenatal visit in their first or second pregnancy (n=1 393 346). We obtained baseline data on body mass index (BMI), smoking, education, and previous disorders. After exclusions, mainly because of previous disorders, the final sample was composed of 1 388 571 women. Cardiomyopathy cases were identified by linking the Medical Birth Register to the National Patient and Cause of Death registers.

Results:

In total, we identified 1699 cases of cardiomyopathy (mean age at diagnosis, 46.2 [SD 9.1] years) during the follow-up with an incidence rate of 5.9 per 100 000 observation years. Of these, 481 were diagnosed with dilated cardiomyopathy, 246 had hypertrophic cardiomyopathy, 61 had alcohol/drug-induced cardiomyopathy, and 509 had other forms. The lowest risk for being diagnosed with a cardiomyopathy was detected at a BMI of 21 kg/m
2
, with a gradual increase in risk with higher BMI, particularly for dilated cardiomyopathy, where a hazard ratio of 4.71 (95% CI, 2.81–7.89) was found for severely obese subjects (BMI ≥35 kg/m
2
), as compared with BMI 20 to <22.5.

Conclusions:
Elevated BMI among young women was associated with an increased risk of being diagnosed with a subsequent cardiomyopathy, especially dilated cardiomyopathy, starting already at mildly elevated body weight, whereas severe obesity entailed an almost 5-fold increase in risk. With the increasing numbers of persons who are overweight or obese, higher rates of cardiomyopathy can be expected in the future, along with an altered disease burden related to adiposity.
Aromatase Inhibitors and the Risk of Cardiovascular Outcomes in Women With Breast Cancer
Authors: Khosrow-Khavar Farzin , Filion Kristian B. , Bouganim Nathaniel , Suissa Samy , Azoulay Laurent 
Published: February 2020

Background:
The association between aromatase inhibitors and cardiovascular outcomes among women with breast cancer is controversial. Given the discrepant findings from randomized controlled trials and observational studies, additional studies are needed to address this safety concern.

Methods:
We conducted a population-based cohort study using the UK Clinical Practice Research Datalink linked to the Hospital Episode Statistics and Office for National Statistics databases. The study population consisted of women newly diagnosed with breast cancer initiating hormonal therapy with aromatase inhibitors or tamoxifen between April 1, 1998, and February 29, 2016. We usedCox proportional hazards models with inverse probability of treatment and censoring weighting to estimate hazard ratios (HRs) with 95% CIs comparing new users of aromatase inhibitors with new users of tamoxifen for each of the study outcomes (myocardial infarction, ischemic stroke, heart failure, and cardiovascular mortality).

Results:
The study population consisted of 23 525 patients newly diagnosed with breast cancer, of whom 17 922 initiated treatment with either an aromatase inhibitor or tamoxifen (8139 and 9783, respectively). The use of aromatase inhibitors was associated with a significantly increased risk of heart failure (incidence rate, 5.4 versus 1.8 per 1000 person-years; HR, 1.86 [95% CI, 1.14–3.03]) and cardiovascular mortality (incidence rate, 9.5 versus 4.7 per 1000 person-years; HR, 1.50 [95% CI, 1.11–2.04]) compared with the use of tamoxifen. Aromatase inhibitors were associated with elevated HRs, but with CIs including the null value, for myocardial infarction (incidence rate, 3.9 versus 1.8 per 1000 person-years; HR, 1.37 [95% CI, 0.88–2.13]) and ischemic stroke (incidence rate, 5.6 versus 3.2 per 1000 person-years; HR, 1.19 [95% CI, 0.82–1.72]).

Conclusions:
In this population-based study, aromatase inhibitors were associated with increased risks of heart failure and cardiovascular mortality compared with tamoxifen. There were also trends toward increased risks, although nonsignificant, of myocardial infarction and ischemic stroke. The increased risk of cardiovascular events associated with aromatase inhibitors should be balanced with their favorable clinical benefits compared with tamoxifen.
Spatial Trends of Extreme Precipitation Events in the Paraná River Basin
Authors: Abou Rafee Sameh A. , Freitas Edmilson D. , Martins Jorge A. , Martins Leila D. , Domingues Leonardo M. , Nascimento Janaína M. P. , Machado Carolyne B. , Santos Eliane B. , Rudke Anderson P. , Fujita Thais , Souza Rodrigo A. F. , Hallak Ricardo , Uvo Cintia B. 
Published: February 2020

AbstractThis work presents an analysis of the observed trends in extreme precipitation events in the Paraná River basin (PRB) from 1977 to 2016 (40 yr) based on daily records from 853 stations. The Mann–Kendall test and inverse-distance-weighted interpolation were applied to annual and seasonal precipitation and also for four extreme precipitation indices. The results show that the negative trends (significance at 95% confidence level) in annual and seasonal series are mainly located in the northern and northeastern parts of the basin. In contrast, except in the autumn season, positive trends were concentrated in the southern and southeastern regions of the basin, most notably for annual and summer precipitation. The spatial distributions of the indices of annual maximum 5-day precipitation and number of rainstorms indicate that significant positive trends are mostly located in the south-southeast part of the basin and that significant negative trends are mostly located in the north-northeast part. The index of the annual number of dry days shows that 88% of significant trends are positive and that most of these are located in the northern region of the PRB, which is a region with a high number of consecutive dry days (>90). The simple daily intensity index showed the highest number of stations (263) with mostly positive significant trends.
Impact of the Quasi-Biennial Oscillation on the Northern Winter Stratospheric Polar Vortex in CMIP5/6 Models
Authors: Rao Jian , Garfinkel Chaim I. , White Ian P. 
Published: February 2020

AbstractUsing 16 CMIP5/6 models with a spontaneously generated quasi-biennial oscillation (QBO)-like phenomenon, this study investigates the impact of the QBO on the northern winter stratosphere. Eight of the models simulate a QBO with a period similar to that observed (25–31 months), with other models simulating a QBO period of 20–40 months. Regardless of biases in QBO periodicity, the Holton–Tan relationship can be well simulated in CMIP5/6 models with more planetary wave convergence in the polar stratosphere in easterly QBO winters. This wave polar convergence occurs not only due to the Holton–Tan mechanism, but also in the midlatitude upper stratosphere where an Elissen–Palm (E-P) flux divergence dipole (with poleward E-P flux) is simulated in most models. The wave response in the upper stratosphere appears related to changes in the background circulation through a directly excited meridional–vertical circulation cell above the maximum tropical QBO easterly center. The midlatitude upwelling in this anticlockwise cell is split into two branches, and the north branch descends in the Arctic region and warms the stratospheric polar vortex. Most models underestimate the Arctic stratospheric warming in early winter during easterly QBO. Further analysis suggests that this bias is not due to an overly weak response to a given QBO phase, as the models simulate a realistic response if one focuses on similar QBO phases. Rather, the model bias is due to the too-low frequency of strong QBO winds in the lower stratosphere in early winter simulated by the models.