bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of a Liquid Biopsy-Breast Cancer Methylation (LBx-BCM) Cartridge Assay for Predicting Early Disease Progression and Survival: TBCRC 005 Prospective Trial
Authors: Visvanathan Kala , Cope Leslie , Fackler Mary Jo , Considine Michael , Sokoll Lori , Carey Lisa A. , Forero-Torres Andres , Ingle James N. , Lin Nancy U. , Nanda Rita , Storniolo Anna Maria , Tulac Suzana , Venkatesan Neesha , Wu Natalie C. , Marla Sudhakar , Campbell Scott , Bates Michael , Umbricht Christopher B. , Wolff Antonio C. , Sukumar Saraswati 
Published: December 2022

AbstractPurpose:We previously demonstrated that high levels of circulating methylated DNA are associated with subsequent disease progression in women with metastatic breast cancer (MBC). In this study, we evaluated the clinical utility of a novel liquid biopsy-breast cancer methylation (LBx-BCM) prototype assay using the GeneXpert cartridge system for early assessment of disease progression in MBC.Experimental Design:The 9-marker LBx-BCM prototype assay was evaluated in TBCRC 005, a prospective biomarker study, using plasma collected at baseline, week 4, and week 8 from 144 patients with MBC.Results:At week 4, patients with MBC with high cumulative methylation (CM) had a significantly shorter median PFS (2.88 months vs. 6.60 months, P = 0.001) and OS (14.52 months vs. 22.44 months, P = 0.005) compared with those with low CM. In a multivariable model, high versus low CM was also associated with shorter PFS (HR, 1.90; 95% CI, 1.20–3.01; P = 0.006). Change in CM from baseline to week 4 (OR, 4.60; 95% CI, 1.77–11.93; P = 0.002) and high levels of CM at week 4 (OR, 2.78; 95% CI, 1.29–5.99; P = 0.009) were associated with progressive disease at the time of first restaging. A robust risk model based on week 4 circulating CM levels was developed to predict disease progression as early as 3 months after initiating a new treatment.Conclusions:The automated LBx-BCM prototype assay is a promising clinical tool for detecting disease progression a month after initiating treatment in women with MBC undergoing routine care. The next step is to validate its clinical utility for specific treatments.
Molecular Clusters and Tumor-Immune Drivers of IgM Monoclonal Gammopathies
Authors: Mondello Patrizia , Paludo Jonas , Novak Joseph P. , Wenzl Kerstin , Yang Zhi-Zhang , Jalali Shahrzad , Krull Jordan E. , Braggio Esteban , Dasari Surendra , Manske Michelle K. , Abeykoon Jithma A. , Sarangi Vivekananda , Kapoor Prashant , Paulus Aneel , Reeder Craig B. , Ailawadhi Sikander , Chanan-Khan Asher A. , Kyle Robert A. , Gertz Morie A. , Novak Anne J. , Ansell Stephen M. 
Published: December 2022

AbstractPurpose:IgM monoclonal gammopathy of undetermined significance (MGUS) and Waldenström macroglobulinemia (WM) represent a disease spectrum with highly varied therapeutic management, ranging from observation to chemoimmunotherapy. The current classification relies solely on clinical features and does not explain the heterogeneity that exists within each of these conditions. Further investigation is warranted to shed light on the biology that may account for the clinical differences.Experimental Design:We used bone marrow (BM) clonal CD19+ and/or CD138+ sorted cells, matched BM supernatant, and peripheral blood serum from 32 patients (7 MGUS, 25 WM) to perform the first multi-omics approach including whole-exome sequencing, RNA sequencing, proteomics, metabolomics, and mass cytometry.Results:We identified three clusters with distinct pathway activation, immune content, metabolomic, and clinical features. Cluster 1 included only patients with WM and was characterized by transcriptional silencing of genes involved in cell cycle and immune response, enrichment of mitochondrial metabolism, infiltration of senescent T effector memory cells, and aggressive clinical behavior. Genetic/structural alterations of TNFAIP3 were distinct events of this cluster. Cluster 2 comprised both MGUS and WM patients with upregulation of inflammatory response, senescence and glycolysis signatures, increased activated T follicular helper and T regulatory cells, and indolent clinical behavior. Cluster 3 also included both MGUS and WM patients and exhibited intermediate features, including proliferative and inflammatory signaling, as well as glycolysis and mitochondrial metabolism.Conclusions:We have identified three distinct molecular clusters, suggesting a potential biologic classification that may have therapeutic implications.
Genetic Modeling of B-cell State Transitions for Rational Design of Lymphoma Therapies
Authors: Leveille Etienne , Kothari Shalin , Müschen Markus 
Published: December 2022

Summary:The use of genomic data to analyze primary endpoints for clinical trials in diffuse large B-cell lymphomas (DLBCL) significantly improved the development of rational drug combinations for genetically defined patient subsets. Recent genetic mouse models and their ability to recapitulate transitions between germinal center exit and memory B-cell characteristics in DLBCL will accelerate the development of rationale-based clinical trials.See related article by Flümann et al., p. 78 (3).See related article by Venturutti et al., (5).
Valve‐in‐Valve Transcatheter Aortic Valve Replacement Versus Redo Surgical Aortic Valve Replacement for Failed Surgical Aortic Bioprostheses: A Systematic Review and Meta‐Analysis
Authors: Raschpichler Matthias , de Waha Suzanne , Holzhey David , Schwarzer Guido , Flint Nir , Kaewkes Danon , Bräuchle Paul T. , Dvir Danny , Makkar Raj , Ailawadi Gorav , Abdel‐Wahab Mohamed , Thiele Holger , Borger Michael A. 
Published: December 2022

Background
In the absence of randomized controlled trials, reports from nonrandomized studies comparing valve‐in‐valve implantation (ViV) to redo surgical aortic valve replacement (rAVR) have shown inconsistent results.

Methods and Results

PubMed/MEDLINE, Google Scholar, and CENTRAL (Cochrane Central Register of Controlled Trials) were searched through December 2021. Meta‐Analysis of Observational Studies in Epidemiology guidelines were followed. The protocol was registered at the International Prospective Register of Systematic Reviews. Random effects models were applied. The primary outcomes of interest were short‐term and midterm mortality. Secondary outcomes included stroke, myocardial infarction, acute renal failure, and permanent pacemaker implantation, as well as prosthetic aortic valve regurgitation, mean transvalvular gradient, and severe prosthesis‐patient mismatch. Of 8881 patients included in 15 studies, 4458 (50.2%) underwent ViV and 4423 (49.8%) rAVR. Short‐term mortality was 2.8% in patients undergoing ViV compared with 5.0% in patients undergoing rAVR (risk ratio [RR] 0.55 [95% CI, 0.34–0.91],
P
=0.02). Midterm mortality did not differ in patients undergoing ViV compared with patients undergoing rAVR (hazard ratio, 1.27 [95% CI, 0.72–2.25]). The rate of acute kidney failure was lower following ViV, (RR, 0.54 [95% CI, 0.33–0.88],
P
=0.02), whereas prosthetic aortic valve regurgitation (RR, 4.18 [95% CI, 1.88–9.3],
P
=0.003) as well as severe patient–prothesis mismatch (RR, 3.12 [95% CI, 2.35–4.1],
P
<0.001) occurred more frequently. The mean transvalvular gradient was higher following ViV (standard mean difference, 0.44 [95% CI, 0.15–0.72],
P
=0.008). There were no significant differences between groups with respect to stroke (
P
=0.26), myocardial infarction (
P
=0.93), or pacemaker implantation (
P
=0.21).

Conclusions
Results of this meta‐analysis demonstrate better short‐term mortality after ViV compared with rAVR. Midterm mortality was similar between groups. Given the likely selection bias in these individual reports, an adequately powered multicenter randomized clinical trial with sufficiently long follow‐up in patients with low‐to‐intermediate surgical risk is warranted.

Registration

URL:
crd.york.ac.uk/prospero/
. Unique identifier: CRD42021228752.
Risk and Subtypes of Stroke Following New‐Onset Postoperative Atrial Fibrillation in Coronary Bypass Surgery: A Population‐Based Cohort Study
Authors: Feilberg Rasmussen Louise , Andreasen Jan J. , Riahi Sam , Lundbye‐Christensen Søren , Johnsen Søren P. , Andersen Grethe , Mortensen Janne K. 
Published: December 2022

Background
New‐onset postoperative atrial fibrillation (POAF) develops in approximately one‐third of patients undergoing cardiac surgery and is associated with a higher incidence of ischemic stroke and increased mortality. However, it remains unknown to what extent ischemic stroke events in patients with POAF are cardioembolic and whether anticoagulant therapy is indicated. We investigated the long‐term risk and pathogenesis of postoperative stroke in patients undergoing coronary artery bypass grafting experiencing POAF.

Methods and Results

This was a register‐based cohort study. Data from the WDHR (Western Denmark Heart Registry) were linked with the DNPR (Danish National Patient Register), the Danish National Prescription Register, and the Cause of Death Register. All stroke diagnoses were verified, and ischemic stroke cases were subclassified according to pathogenesis. Furthermore, investigations of all‐cause mortality and the use of anticoagulation medicine for the individual patient were performed. A total of 7813 patients without a preoperative history of atrial fibrillation underwent isolated coronary artery bypass grafting between January 1, 2010, and December 31, 2018, in Western Denmark. POAF was registered in 2049 (26.2%) patients, and a postoperative ischemic stroke was registered in 195 (2.5%) of the patients. After adjustment, there was no difference in the risk of ischemic stroke (hazard ratio [HR], 1.08 [95% CI, 0.74–1.56]) or all‐cause mortality (HR, 1.09 [95% CI, 0.98–1.23]) between patients who developed POAF and non‐POAF patients. Although not statistically significant, patients with POAF had a higher incidence rate (IR; per 1000 patient‐years) of cardioembolic stroke (IR, 1 [95% CI, 0.6–1.6] versus IR, 0.5 [95% CI, 0.3–0.8]), whereas non‐POAF patients had a higher incidence rate of large‐artery occlusion stroke (IR, 1.1 [95% CI, 0.8–1.5] versus IR, 0.7 [95% CI, 0.4–1.4]). Early initiation of anticoagulation medicine was not associated with a lower risk of ischemic stroke. However, patients with POAF were more likely to die of cardiovascular causes than non‐POAF patients (
P
<0.001).

Conclusions
We found no difference in the adjusted risk of postoperative stroke or all‐cause mortality in POAF versus non‐POAF patients. Patients with POAF after coronary artery bypass grafting presented with a higher, although not significant, proportion of ischemic strokes of the cardioembolic type.
Performance of the American Heart Association/American College of Cardiology Guideline‐Recommended Pretest Probability Model for the Diagnosis of Obstructive Coronary Artery Disease
Authors: Winther Simon , Murphy Theodore , Schmidt Samuel Emil , Bax Jeroen J. , Wijns William , Knuuti Juhani , Bøttcher Morten 
Published: December 2022

Background
Substantial differences exist between different guideline‐recommended pretest probability (PTP) models for the detection of obstructive coronary artery disease (CAD). This study was performed to study the performance of the 2021 American Heart Association/American College of Cardiology (AHA/ACC) guideline‐recommended PTP (AHA/ACC‐PTP) model in assessing the likelihood of obstructive CAD compared with previously proposed models.

Methods and Results
Symptomatic patients (N=50 561) referred for coronary computed tomography angiography were included. The reference standard was invasive coronary angiography with optional fractional flow reserve measurements. The AHA/ACC‐PTP values based on sex and age were calculated and compared with the 2019 European Society of Cardiology guideline PTP values based on sex, age, and symptoms as well as the risk factor–weighted clinical likelihood values based on sex, age, symptoms, and risk factors. The AHA/ACC‐PTP maximum values overestimated by a factor of 2.6 the actual prevalence of CAD. Compared with the AHA/ACC‐PTP model (area under the receiver‐operating curve, 71.5 [95% CI, 70.7–72.2]), inclusion of typicality of symptoms in the European Society of Cardiology guideline PTP improved discrimination of CAD (area under the receiver‐operating curve, 75.5 [95% CI, 74.7–76.3]). Inclusion of both symptoms and risk factors in the risk factor–weighted clinical likelihood model further improved discrimination (area under the receiver‐operating curve, 77.7 [95% CI, 77.0–78.5]). The proportion of patients classified as very low PTP was lower using the AHA/ACC‐PTP (5%) compared with the European Society of Cardiology guideline PTP (19%) and the risk factor–weighted clinical likelihood (49%) models.

Conclusions
The new AHA/ACC‐PTP model overestimates the prevalence of obstructive CAD substantially if type of symptoms and risk factors are not taken into account. Inclusion of both symptoms and risk factors improves model performance and identifies more patients with very low likelihood of CAD in whom further testing can be deferred.
Depression and Anxiety Are Associated With Cardiovascular Health in Young Adults
Authors: Patterson Sierra L. , Marcus Michele , Goetz Margarethe , Vaccarino Viola , Gooding Holly C. 
Published: December 2022

Background
Cardiovascular health (CVH) declines in young adulthood, and mood disorders commonly emerge during this life stage. This study examined the association between depression, anxiety, and CVH metrics among young adults.

Methods and Results
We conducted a cross‐sectional analysis of participants aged 18 to 34 years who completed the Emory Healthy Aging Study Health History Questionnaire (n=875). We classified participants as having poor, intermediate, or ideal levels of the 8 CVH metrics using definitions set forth by the American Heart Association with adaptions when necessary. We defined depression and anxiety as absent, mild, or moderate to severe using standard cutoffs for Patient Health Questionnaire and General Anxiety Disorder scales. We used multivariable regression to examine the association between depression and anxiety and CVH, adjusting for age, sex, race and ethnicity, income, and education. The mean participant age was 28.3 years, and the majority identified as women (724; 82.7%); 129 (14.7%) participants had moderate to severe anxiety, and 128 (14.6%) participants had moderate to severe depression. Compared with those without anxiety, participants with moderate to severe anxiety were less likely to meet ideal levels of physical activity (adjusted prevalence ratio [aPR], 0.60 [95% CI, 0.44–0.82]), smoking (aPR, 0.90 [95% CI, 0.82–0.99]), and body mass index (aPR, 0.79 [95% CI, 0.66–0.95]). Participants with moderate to severe depression were less likely than those without depression to meet ideal levels of physical activity (aPR, 0.48 [95% CI, 0.34–0.69]), body mass index (aPR, 0.75 [95% CI, 0.61–0.91]), sleep (aPR, 0.79 [95% CI, 0.66–0.94]), and blood pressure (aPR, 0.92 [95% CI, 0.86–0.99]).

Conclusions
Anxiety and depression are associated with less ideal CVH in young adults. Interventions targeting CVH behaviors such as physical activity, diet, and sleep may improve both mood and CVH.
Understanding the Effects of Constraint and Predictability in ERP
Authors: Stone Kate , Nicenboim Bruno , Vasishth Shravan , Rösler Frank 
Published: December 2022

Abstract
Intuitively, strongly constraining contexts should lead to stronger probabilistic representations of sentences in memory. Encountering unexpected words could therefore be expected to trigger costlier shifts in these representations than expected words. However, psycholinguistic measures commonly used to study probabilistic processing, such as the N400 event-related potential (ERP) component, are sensitive to word predictability but not to contextual constraint. Some research suggests that constraint-related processing cost may be measurable via an ERP positivity following the N400, known as the anterior post-N400 positivity (PNP). The PNP is argued to reflect update of a sentence representation and to be distinct from the posterior P600, which reflects conflict detection and reanalysis. However, constraint-related PNP findings are inconsistent. We sought to conceptually replicate Federmeier et al. (2007) and Kuperberg et al. (2020), who observed that the PNP, but not the N400 or the P600, was affected by constraint at unexpected but plausible words. Using a pre-registered design and statistical approach maximising power, we demonstrated a dissociated effect of predictability and constraint: strong evidence for predictability but not constraint in the N400 window, and strong evidence for constraint but not predictability in the later window. However, the constraint effect was consistent with a P600 and not a PNP, suggesting increased conflict between a strong representation and unexpected input rather than greater update of the representation. We conclude that either a simple strong/weak constraint design is not always sufficient to elicit the PNP, or that previous PNP constraint findings could be an artifact of smaller sample size.
Outdoor Cats: Science, Ethics, and Politics
Authors: Lynn William S. , Santiago-Ávila Francisco J. 
Published: December 2022

Abstract
The relationship between people, outdoor cats, and wildlife is the subject of fraught debate. Some conservationists claim cats are harbingers of chaos – akin to a zombie apocalypse threatening biodiversity and public health. The empirical evidence and scientific reasoning do not bear this out. Cats may or may not be a problem for biodiversity depending on diverse ecological and social contexts. Indeed, while all animals can be vectors or victims of zoonotic disease, cats are not a significant threat to public health. While most of the debate is focused on dueling claims about the science, that is not the primary source of the dispute. Instead, moral disputes drive the debate, and managing the relationship between people, cats, and wildlife is a wicked problem rooted in differing ethical values and worldviews. While wicked problems have no permanent or technical fix, addressing their ethical aspects is key to unlocking productive policy options.
Response to Roundtable Discussion
Authors: Honneth Axel 
Published: December 2022

Abstract
In this text I will deal with three worries that were articulated by my three responders in astounding unanimity: firstly, I will defend the nation-based framework of my history of the idea of recognition on basis of the well-established hypothesis that there is path-dependency of later aesthetic or theoretical productions (1); secondly, I hope to be able to demonstrate that the various theories of subjectivity I investigate can in fact all be subsumed under the concept of “recognition” (2); and thirdly, I will try to clarify the motives I had for synthetizing the three different concepts of recognition in one single approach (3). In an extra step at the end of my article I explain why I don’t see myself making the mistake to assign philosophy the function of something amounting to a leading discipline in the history of ideas (4).
Global Extreme Heat Forecasting Using Neural Weather Models
Authors: Lopez-Gomez Ignacio , McGovern Amy , Agrawal Shreya , Hickey Jason 
Published: December 2022

Abstract
Heatwaves are projected to increase in frequency and severity with global warming. Improved warning systems would help reduce the associated loss of lives, wildfires, power disruptions, and reduction in crop yields. In this work, we explore the potential for deep learning systems trained on historical data to forecast extreme heat on short, medium and subseasonal time scales. To this purpose, we train a set of neural weather models (NWMs) with convolutional architectures to forecast surface temperature anomalies globally, 1 to 28 days ahead, at ∼200-km resolution and on the cubed sphere. The NWMs are trained using the ERA5 reanalysis product and a set of candidate loss functions, including the mean-square error and exponential losses targeting extremes. We find that training models to minimize custom losses tailored to emphasize extremes leads to significant skill improvements in the heatwave prediction task, relative to NWMs trained on the mean-square-error loss. This improvement is accomplished with almost no skill reduction in the general temperature prediction task, and it can be efficiently realized through transfer learning, by retraining NWMs with the custom losses for a few epochs. In addition, we find that the use of a symmetric exponential loss reduces the smoothing of NWM forecasts with lead time. Our best NWM is able to outperform persistence in a regressive sense for all lead times and temperature anomaly thresholds considered, and shows positive regressive skill relative to the ECMWF subseasonal-to-seasonal control forecast after 2 weeks.

Significance Statement
Heatwaves are projected to become stronger and more frequent as a result of global warming. Accurate forecasting of these events would enable the implementation of effective mitigation strategies. Here we analyze the forecast accuracy of artificial intelligence systems trained on historical surface temperature data to predict extreme heat events globally, 1 to 28 days ahead. We find that artificial intelligence systems trained to focus on extreme temperatures are significantly more accurate at predicting heatwaves than systems trained to minimize errors in surface temperatures and remain equally skillful at predicting moderate temperatures. Furthermore, the extreme-focused systems compete with state-of-the-art physics-based forecast systems in the subseasonal range, while incurring a much lower computational cost.
Nexus Between Geopolitical Risk and Tourism Demand in India: Evidence from the ARDL Approach
Authors: Soudager Mohammed Ayub , Wani Suadat Hussain 
Published: December 2022

The present study aims to examine the nexus between geopolitical risk and foreign tourist arrivals in India. In addition, other variables which impact tourist arrival in other parts of the world have also been included. To achieve the objectives of the study, the auto-regressive distributed lag (ARDL) model propounded by Pesaran et al. has been applied using quarterly data from 2001: Q1 to 2019: Q4. The findings of the study reveal that geopolitical risk negatively affects foreign tourist arrival in India. Besides, the study also captures the income and price determinants as propounded by classical economists. JEL Codes: C500; P0; Z30