bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determinants of Response to Talazoparib in Patients with HER2-Negative, Germline BRCA1/2-Mutated Breast Cancer
Authors: Blum Joanne L. , Laird A. Douglas , Litton Jennifer K. , Rugo Hope S. , Ettl Johannes , Hurvitz Sara A. , Martin Miguel , Roché Henri H. , Lee Kyung-Hun , Goodwin Annabel , Chen Ying , Lanzalone Silvana , Chelliserry Jijumon , Czibere Akos , Hopkins Julia F. , Albacker Lee A. , Mina Lida A. 
Published: January 2022

Abstract

Purpose:
PARP inhibitors (PARPi) have demonstrated efficacy in tumors with germline breast cancer susceptibility genes (gBRCA) 1 and 2 mutations, but further factors influencing response to PARPi are poorly understood.

Experimental Design:
Breast cancer tumor tissue from patients with gBRCA1/2 mutations from the phase III EMBRACA trial of the PARPi talazoparib versus chemotherapy was sequenced using FoundationOne CDx.

Results:
In the evaluable intent-to-treat population, 96.1% (296/308) had ≥1 tumor BRCA (tBRCA) mutation and there was strong concordance (95.3%) between tBRCA and gBRCA mutational status. Genetic/genomic characteristics including BRCA loss of heterozygosity (LOH; identified in 82.6% of evaluable patients), DNA damage response (DDR) gene mutational burden, and tumor homologous recombination deficiency [assessed by genomic LOH (gLOH)] demonstrated no association with talazoparib efficacy.

Conclusions:
Overall, BRCA LOH status, DDR gene mutational burden, and gLOH were not associated with talazoparib efficacy; however, these conclusions are qualified by population heterogeneity and low patient numbers in some subgroups. Further investigation in larger patient populations is warranted.
Nonsustained Ventricular Tachycardia Is Independently Associated With Sustained Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy
Authors: Piers Sebastiaan R. , Androulakis Alexander F. , Yim Kevin S. , van Rein Nienke , Venlet Jeroen , Kapel Gijsbert F. , Siebelink Hans-Marc , Lamb Hildo J. , Cannegieter Suzanne C. , Man Sum-Che , Zeppenfeld Katja 
Published: January 2022

Background:
Spontaneous nonsustained ventricular tachycardia (NSVT) on Holter, VT inducibility during electrophysiology study, and late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) have been associated with sustained ventricular arrhythmias (SVAs) in nonischemic dilated cardiomyopathy (DCM). This study aimed to analyze whether these parameters carry independent prognostic value for spontaneous SVA in DCM.

Methods:
Between 2011 and 2018, patients with the DCM clinical spectrum and documented SVA, suspected SVA, or considered to be at intermediate or high risk for SVA were enrolled in the prospective Leiden Nonischemic Cardiomyopathy Study. Patients underwent a comprehensive evaluation including 24-hour Holter, LGE-CMR, and electrophysiology study. Holters were assessed for the presence of NSVT (≥3 beats; rate, ≥120 bpm; lasting <30 s) and NSVT characteristics (coupling interval, duration, cycle length, morphology, regularity). Patients were followed at 6 to 12 monthly intervals.

Results:

Of all 115 patients (age, 59±12 years; 77% men; left ventricular ejection fraction, 33±13%; history of SVA, 36%; LGE in 63%; median LGE mass, 13 g; interquartile range, 8–23 g), 62 (54%) had NSVT on Holter, and sustained monomorphic VT was inducible in 34 of 114 patients (30%). NSVT was not associated with LGE on CMR or VT inducibility during electrophysiology study nor were its features (all
P
>0.05). During 4.0±1.8 years of follow-up, SVA occurred in 39 patients (34%). NSVT (HR, 4.47 [95% CI, 1.87–10.72];
P
=0.001) and VT inducibility (HR, 3.08 [95% CI, 1.08–8.81];
P
=0.036) were independently associated with SVA during follow-up. A bivariable model including only noninvasively acquired parameters also allowed identification of a high-risk subgroup (ie, those with both NSVT and LGE on CMR). The findings remained similar when only patients without prior SVA were included.

Conclusions:
In patients with DCM, NSVT on Holter and VT inducibility during electrophysiology study predict SVA during follow-up independent of LGE on CMR. NSVTs may serve as an initiator, and sustained VT inducibility indicates the presence of the substrate for SVA in DCM.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01940081.
Integrating Exercise Into Personalized Ventricular Arrhythmia Risk Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy
Authors: Bosman Laurens P. , Wang Weijia , Lie Øyvind H. , van Lint Freyja H.M. , Rootwelt-Norberg Christine , Murray Brittney , Tichnell Crystal , Cadrin-Tourigny Julia , van Tintelen J. Peter , Asselbergs Folkert W. , Calkins Hugh , te Riele Anneline S.J.M. , Haugaa Kristina H. , James Cynthia A. 
Published: January 2022

Background:

Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (
arvcrisk.com
). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise.

Methods:
We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models.

Results:
We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7–9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase <15 to 30 METh/wk. Athlete status, using 3 definitions from literature (>18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53–2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71–0.84) and showed no significant improvement (Akaike information criterion change, <2).

Conclusions:
Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification.
Genetic European Ancestry and Incident Diabetes in Black Individuals: Insights From the SPRINT Trial
Authors: Parcha Vibhu , Heindl Brittain , Kalra Rajat , Bress Adam , Rao Shreya , Pandey Ambarish , Gower Barbara , Irvin Marguerite R. , McDonald Merry-Lynn N. , Li Peng , Arora Garima , Arora Pankaj 
Published: January 2022

Background:
Black individuals have high incident diabetes risk, despite having paradoxically lower triglyceride and higher HDL (high-density lipoprotein) cholesterol levels. The basis of this is poorly understood. We evaluated the participants of SPRINT (Systolic Blood Pressure Intervention Trial) to assess the association of estimated European genetic ancestry with the risk of incident diabetes in self-identified Black individuals.

Methods:
Self-identified non-Hispanic Black SPRINT participants free of diabetes at baseline were included. Black participants were stratified into tertiles (T1–T3) of European ancestry proportions estimated using 106 biallelic ancestry informative genetic markers. The multivariable-adjusted association of European ancestry proportion with indices of baseline metabolic syndrome (ie, fasting plasma glucose, triglycerides, HDL cholesterol, body mass index, and blood pressure) was assessed. Multivariable-adjusted Cox regression determined the risk of incident diabetes (fasting plasma glucose ≥126 mg/dL or self-reported diabetes treatment) across tertiles of European ancestry proportion.

Results:

Among 2466 Black SPRINT participants, a higher European ancestry proportion was independently associated with higher baseline triglyceride and lower HDL cholesterol levels (
P
<0.001 for both). European ancestry proportion was not associated with baseline fasting plasma glucose, body mass index, and blood pressure (
P
>0.05). Compared with the first tertile, those in the second (hazard ratio, 0.64 [95% CI, 0.45–0.90]) and third tertiles (hazard ratio, 0.61 [95% CI, 0.44–0.89]) of the European ancestry proportion had a lower risk of incident diabetes. A 5% point higher European ancestry was associated with a 29% lower risk of incident diabetes (hazard ratio, 0.71 [95% CI, 0.55–0.93]). There was no evidence of a differential association between the European ancestry proportion tertiles and incident diabetes between those randomized to intensive versus standard blood pressure treatment.

Conclusions:
The higher risk of incident diabetes in Black individuals may have genetic determinants in addition to adverse social factors. Further research may help understand the interplay between biological and social determinants of cardiometabolic health in Black individuals.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01206062.
Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns
Authors: Baker Anna D. , Schwamm Lee H. , Sanborn Danita Y. , Furie Karen , Stretz Christoph , Mac Grory Brian , Yaghi Shadi , Kleindorfer Dawn , Sucharew Heidi , Mackey Jason , Walsh Kyle , Flaherty Matt , Kissela Brett , Alwell Kathleen , Khoury Jane , Khatri Pooja , Adeoye Opeolu , Ferioli Simona , Woo Daniel , Martini Sharyl , De Los Rios La Rosa Felipe , Demel Stacie L. , Madsen Tracy , Star Michael , Coleman Elisheva , Slavin Sabreena , Jasne Adam , Mistry Eva A. , Haverbusch Mary , Merkler Alexander E. , Kamel Hooman , Schindler Joseph , Sansing Lauren H. , Faridi Kamil F. , Sugeng Lissa , Sheth Kevin N. , Sharma Richa 
Published: January 2022

Background:
There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018.

Methods:
This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge.

Results:

Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1–6.0%;

I
2

, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%,
P
<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1–3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis.

Conclusions:
Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.
Intraventricular Hemorrhage Expansion in the CLEAR III Trial: A Post Hoc Exploratory Analysis
Authors: Roh David J. , Asonye Ifeyinwa S. , Carvalho Poyraz Fernanda , Magid-Bernstein Jessica R. , Joiner Evan F. , Avadhani Radhika , Awad Issam , Hanley Daniel F. , Ziai Wendy C. , Murthy Santosh B. 
Published: January 2022

Background:
The objective of this study was to evaluate factors associated with intraventricular hemorrhage (IVH) expansion and its association with long-term outcomes.

Methods:
We performed a post hoc analysis of the international, multi-center CLEAR III trial (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) which enrolled IVH patients between September 1, 2009, and January 31, 2015. The exposure was IVH expansion, defined as >1 mL increase in volume between baseline and stability computed tomography scans, before treatment randomization. We assessed factors associated with IVH expansion and secondarily assessed the relationship of IVH expansion with clinical outcomes: composite of death or major disability (modified Rankin Scale score, >3), and mortality alone at 6 months. The relationship of IVH expansion on ventriculoperitoneal shunt placement was additionally explored. Multivariable logistic regression was used for all analyses.

Results:
Of 500 IVH patients analyzed, the mean age was 59 (±11) years old, 44% were female and 135 (27%) had IVH expansion. In multivariable regression models, factors associated with IVH expansion were baseline parenchymal intracerebral hemorrhage (ICH) volume (adjusted odds ratio [OR], 1.04 per 1 mL increase [95% CI, 1.01–1.08]), presence of parenchymal hematoma expansion: >33% (adjusted OR, 6.63 [95% CI, 3.92–11.24]), time to stability head CT (adjusted OR, 0.71 per 1 hour increase [95% CI, 0.54–0.94]), and thalamic hematoma location (adjusted OR, 1.68 [95% CI, 1.01–2.79]) while additionally adjusting for age, sex, and race. In secondary analyses, IVH expansion was associated with higher odds of poor 6-month outcomes (adjusted OR, 1.84 [95% CI, 1.12–3.02]) but not mortality (OR, 1.40 [95% CI, 0.78–2.50]) after adjusting for baseline ICH volume, thalamic ICH location, age, anticoagulant use, Glasgow Coma Scale score, any withdrawal of care order, and treatment randomization arm. However, there were no relationships of IVH expansion on subsequent ventriculoperitoneal shunt placement (adjusted OR, 1.02 [95% CI, 0.58–1.80]) after adjusting for similar covariates.

Conclusions:
In a clinical trial cohort of patients with large IVH, acute hematoma characteristics, specifically larger parenchymal volume, hematoma expansion, and thalamic ICH location were associated with IVH expansion. Given that IVH expansion resulted in poor functional outcomes, exploration of treatment approaches to optimize hemostasis and prevent IVH expansion, particularly in patients with thalamic ICH, require further study.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT00784134.
Word Acquisition in Neural Language Models
Authors: Chang Tyler A. , Bergen Benjamin K. 
Published: January 2022

Abstract
We investigate how neural language models acquire individual words during training, extracting learning curves and ages of acquisition for over 600 words on the MacArthur-Bates Communicative Development Inventory (Fenson et al., 2007). Drawing on studies of word acquisition in children, we evaluate multiple predictors for words’ ages of acquisition in LSTMs, BERT, and GPT-2. We find that the effects of concreteness, word length, and lexical class are pointedly different in children and language models, reinforcing the importance of interaction and sensorimotor experience in child language acquisition. Language models rely far more on word frequency than children, but, like children, they exhibit slower learning of words in longer utterances. Interestingly, models follow consistent patterns during training for both unidirectional and bidirectional models, and for both LSTM and Transformer architectures. Models predict based on unigram token frequencies early in training, before transitioning loosely to bigram probabilities, eventually converging on more nuanced predictions. These results shed light on the role of distributional learning mechanisms in children, while also providing insights for more human-like language acquisition in language models.
Decomposing and Recomposing Event Structure
Authors: Gantt William , Glass Lelia , White Aaron Steven 
Published: January 2022

AbstractWe present an event structure classification empirically derived from inferential properties annotated on sentence- and document-level Universal Decompositional Semantics (UDS) graphs. We induce this classification jointly with semantic role, entity, and event-event relation classifications using a document-level generative model structured by these graphs. To support this induction, we augment existing annotations found in the UDS1.0 dataset, which covers the entirety of the English Web Treebank, with an array of inferential properties capturing fine-grained aspects of the temporal and aspectual structure of events. The resulting dataset (available at decomp.io) is the largest annotation of event structure and (partial) event coreference to date.
The Boy Who Plugs a Dike with His Finger: UN Mediation in the Gaza-Israel Crisis, 2018–2019
Authors: Schiff Amira 
Published: January 2022

Abstract
This article highlights the United Nations’ potential contribution in the niche of crisis management. Drawing from the crisis-based approach’s insights on crisis mediation efficacy, and Carnevale’s conceptualization of the mediator’s various strengths as the sources of leverage in mediation, the study explores UN Special Coordinator for the Middle East Peace Process Nickolay Mladenov’s mediation during the Gaza-Israel crisis in 2018–2019. I argue that a combination of contextual and behavioral factors enabled Mladenov to influence the crisis bargaining environment and pull Israel and Hamas back from the brink. These factors included both parties’ need to avoid further escalation; the mediating skills of the UN envoy; the envoy’s reputation, which led others to perceive him as the right person for the mediation mission; the UN mediator’s use of a blend of strategies and tactics; and Mladenov’s ability to apply a range of strengths, including hard power.
Tropical, Subtropical, and Extratropical Atmospheric Rivers in the Australian Region
Authors: Reid Kimberley J. , King Andrew D. , Lane Todd P. , Hudson Debra 
Published: January 2022

AbstractStudies of atmospheric rivers (ARs) over Australia have, so far, only focused on northwest cloudband–type weather systems. Here we perform a comprehensive analysis of AR climatology and impacts over Australia that includes not only northwesterly systems, but easterly and extratropical ARs also. We quantify the impact of ARs on mean and extreme rainfall including assessing how the origin location of ARs can alter their precipitation outcomes. We found a strong relationship between ARs and extreme rainfall in the agriculturally significant Murray–Daring basin region. We test the hypothesis that the tropical and subtropical originating ARs we observe in Australasia differ from canonical extratropical ARs by examining the vertical structure of ARs grouped by origin location. We found that in the moisture abundant tropics and subtropics, wind speed drives the intensity of ARs, while in the extratropics, the strength of an AR is largely determined by moisture availability. Finally, we examine the modulation of AR frequency by different climate modes. We find weak (but occasionally significant) correlations between ARs frequency and El Niño–Southern Oscillation, the Indian Ocean dipole, and the southern annular mode. However, there is a stronger relationship between the phases of the Madden–Julian oscillation and tropical AR frequency, which is an avenue for potential skill in forecasting ARs on subseasonal time scales.
A Decadal Weakening in the Connection between ENSO and the Following Spring SST over the Northeast Tropical Atlantic after the Mid-1980s
Authors: Chen Wei 
Published: January 2022

AbstractThe north tropical Atlantic (NTA) displays significant sea surface temperature anomalies (SSTA) during the ENSO decaying spring. This study identifies a largely weakened impact of ENSO on the SSTA concentrated over the northeast tropical Atlantic (NETA) after the mid-1980s, while the impacts on the SSTA over the northwest tropical Atlantic (NWTA) are stable during the whole period. Different SST datasets can recognize this weakened connection between ENSO and the NETA SSTA, suggesting the robustness in this decadal variation. The El Niño–related teleconnections shift westward after the mid-1980s, and thus the anomalous southwesterly, leading to the positive NTA SSTA via the wind–evaporation–SST feedbacks, is restricted over the NWTA without extending eastward. As a result, the positive SSTA rises only over the NWTA but is diminished over the NETA. The regime shift in these circulation anomalies is due to the westward shift in the El Niño–induced convection and circulation anomalies from the eastern equatorial Pacific (EEP) to the central equatorial Pacific (CEP). Further analysis indicates that the intensified zonal SST gradient over the equatorial Pacific leads to a westward shift of Pacific Walker circulation after the mid-1980s. The westward shift of Walker circulation contributes to the convergent circulation anomalies over the CEP and thus results in the El Niño–induced precipitation anomalies concentrated there.Significance StatementPrevious studies have indicated a positive connection between ENSO and the succeeding spring SSTA over the north tropical Atlantic (NTA), and this connection tends to be unstable. This study identifies a decadal weakening in the connection between ENSO and the SSTA actually concentrated over the northeast part of tropical Atlantic (NETA) after the mid-1980s. Further analysis indicates that the decadal changes in the ENSO–NETA connection are due to the westward shift in the ENSO-related convection and teleconnections, resulting from the westward shift of Pacific Walker circulation, induced by the intensified zonal SST gradient over the equatorial Pacific after the mid-1980s. The result implies a decadal change in NTA SSTA structure, which may bring different climate anomalies in the surrounding area.