bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Tumor DNA–Based MRD Assessment in Patients with CLL Treated with Obinutuzumab, Acalabrutinib, and Venetoclax
Authors: Fürstenau Moritz , Weiss Jonathan , Giza Adam , Franzen Fabian , Robrecht Sandra , Fink Anna-Maria , Fischer Kirsten , Schneider Christof , Tausch Eugen , Stilgenbauer Stephan , Ritgen Matthias , Schilhabel Anke , Brüggemann Monika , Eichhorst Barbara , Hallek Michael , Cramer Paula 
Published: June 2022

Abstract

Purpose:
With the advent of highly efficacious time-limited combination treatments of targeted agents in chronic lymphocytic leukemia (CLL), minimal residual disease (MRD) assessment has gained importance as a measure for therapeutic success and as a surrogate for progression-free survival. The currently most widely used method is multicolor flow cytometry, which detects circulating CLL cells in the peripheral blood. However, it seems to be less sensitive for the detection of MRD in the lymph node compartment.

Patients and Methods:
To evaluate whether a cell-free approach can overcome this limitation, we performed serial assessments of circulating tumor DNA (ctDNA) in patients with CLL treated with obinutuzumab, acalabrutinib, and venetoclax in the phase II CLL2-BAAG trial. Patient-specific variability, diversity, joining (VDJ) rearrangements as well as somatic driver mutations were tracked before, during and after treatment by digital droplet PCR in blood plasma. Furthermore, these were systematically compared to matched flow cytometry data.

Results:
In the 381 sample pairs, ctDNA and flow cytometry yielded highly concordant results. However, clone-specific ctDNA was detected in 44 of 152 samples (29%) that were assessed as undetectable MRD (uMRD) by flow cytometry (defined as less than one CLL cell in 10,000 normal leukocytes). 29 ctDNA-negative samples showed detectable MRD &gt;10–4 by flow cytometry. Also, somatic driver mutations were detected with a similar sensitivity compared with patient-specific VDJ rearrangements in plasma. In patients with predominantly nodal residual disease, ctDNA compared favorably with 4-color flow cytometry and seemed to more accurately reflect the entire disease burden across compartments.

Conclusions:
On the basis of these findings, ctDNA-based MRD assessment appears to be a promising method to complement cell-based MRD approaches like flow cytometry that focus on circulating CLL cells in the peripheral blood.
Diurnal Variations in Natriuretic Peptide Levels: Clinical Implications for the Diagnosis of Acute Heart Failure
Authors: Breidthardt Tobias , van Doorn William P.T.M. , van der Linden Noreen , Diebold Matthias , Wussler Desiree , Danier Isabelle , Zimmermann Tobias , Shrestha Samyut , Kozhuharov Nikola , Belkin Maria , Porta Caroline , Strebel Ivo , Michou Eleni , Gualandro Danielle M. , Nowak Albina , Meex S.J.R. , Mueller Christian 
Published: June 2022

Background:
Current guidelines recommend interpreting concentrations of NPs (natriuretic peptides) irrespective of the time of presentation to the emergency department. We hypothesized that diurnal variations in NP concentration may affect their diagnostic accuracy for acute heart failure.

Methods:
In a secondary analysis of a multicenter diagnostic study enrolling patients presenting with acute dyspnea to the emergency department and using central adjudication of the final diagnosis by 2 independent cardiologists, the diagnostic accuracy for acute heart failure of BNP (B-type NP), NT-proBNP (N-terminal pro-B-type NP), and MR-proANP (midregional pro-atrial NP) was compared among 1577 daytime presenters versus 908 evening/nighttime presenters. In a validation study, the presence of a diurnal rhythm in BNP and NT-proBNP concentrations was examined by hourly measurements in 44 stable individuals.

Results:

Among patients adjudicated to have acute heart failure, BNP, NT-proBNP, and MR-proANP concentrations were comparable among daytime versus evening/nighttime presenters (all
P
=nonsignificant). Contrastingly, among patients adjudicated to have other causes of dyspnea, evening/nighttime presenters had lower BNP (median, 44 [18–110] versus 74 [27–168] ng/L;
P
<0.01) and NT-proBNP (median, 212 [72–581] versus 297 [102–902] ng/L;
P
<0.01) concentrations versus daytime presenters. This resulted in higher diagnostic accuracy as quantified by the area under the curve of BNP and NT-proBNP among evening/nighttime presenters (0.97 [95% CI, 0.95–0.98] and 0.95 [95% CI, 0.93–0.96] versus 0.94 [95% CI, 0.92–0.95] and 0.91 [95% CI, 0.90–0.93]) among daytime presenters (both
P
<0.01). These differences were not observed for MR-proANP. Diurnal variation of BNP and NT-proBNP with lower evening/nighttime concentration was confirmed in 44 stable individuals (
P
<0.01).

Conclusions:
BNP and NT-proBNP, but not MR-proANP, exhibit a diurnal rhythm that results in even higher diagnostic accuracy among evening/nighttime presenters versus daytime presenters.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT01831115, NCT02091427, and NCT02210897.
Cardiogenic Shock From Heart Failure Versus Acute Myocardial Infarction: Clinical Characteristics, Hospital Course, and 1-Year Outcomes
Authors: Sinha Shashank S. , Rosner Carolyn M. , Tehrani Behnam N. , Maini Aneel , Truesdell Alexander G. , Lee Seiyon Ben , Bagchi Pramita , Cameron James , Damluji Abdulla A. , Desai Mehul , Desai Shashank S. , Epps Kelly C. , deFilippi Christopher , Flanagan M. Casey , Genovese Leonard , Moukhachen Hala , Park James J. , Psotka Mitchell A. , Raja Anika , Shah Palak , Sherwood Matthew W. , Singh Ramesh , Tang Daniel , Young Karl D. , Welch Timothy , O’Connor Christopher M. , Batchelor Wayne B. 
Published: June 2022

Background:
Little is known about clinical characteristics, hospital course, and longitudinal outcomes of patients with cardiogenic shock (CS) related to heart failure (HF-CS) compared to acute myocardial infarction (AMI; CS related to AMI [AMI-CS]).

Methods:
We examined in-hospital and 1-year outcomes of 520 (219 AMI-CS, 301 HF-CS) consecutive patients with CS (January 3, 2017–December 31, 2019) in a single-center registry.

Results:

Mean age was 61.5±13.5 years, 71% were male, 22% were Black patients, and 63% had chronic kidney disease. The HF-CS cohort was younger (58.5 versus 65.6 years,
P
<0.001), had fewer cardiac arrests (15.9% versus 35.2%,
P
<0.001), less vasopressor utilization (61.8% versus 82.2%,
P
<0.001), higher pulmonary artery pulsatility index (2.14 versus 1.51,
P
<0.01), lower cardiac power output (0.64 versus 0.77 W,
P
<0.01) and higher pulmonary capillary wedge pressure (25.4 versus 22.2 mm Hg,
P
<0.001) than patients with AMI-CS. Patients with HF-CS received less temporary mechanical circulatory support (34.9% versus 76.3%
P
<0.001) and experienced lower rates of major bleeding (17.3% versus 26.0%,
P=
0.02) and in-hospital mortality (23.9% versus 39.3%,
P
<0.001). Postdischarge, 133 AMI-CS and 229 patients with HF-CS experienced similar rates of 30-day readmission (19.5% versus 24.5%,
P
=0.30) and major adverse cardiac and cerebrovascular events (23.3% versus 28.8%,
P
=0.45). Patients with HF-CS had lower 1-year mortality (n=123, 42.6%) compared to the patients with AMI-CS (n=110, 52.9%,
P
=0.03). Cumulative 1-year mortality was also lower in patients with HF-CS (log-rank test,
P
=0.04).

Conclusions:
Patients with HF-CS were younger, and despite lower cardiac power output and higher pulmonary capillary wedge pressure, less likely to receive vasopressors or temporary mechanical circulatory support. Although patients with HF-CS had lower in-hospital and 1-year mortality, both cohorts experienced similarly high rates of postdischarge major adverse cardiovascular and cerebrovascular events and 30-day readmission, highlighting that both cohorts warrant careful long-term follow-up.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03378739.
Transcatheter Recanalization of Atretic Pulmonary Veins in Infants and Children
Authors: Patel Jay D. , Mandhani Mansi , Gray Rosemary , Pettus Joelle , McCracken Courtney E. , Thomas Amanda , Bauser-Heaton Holly , Kim Dennis W. , Petit Christopher J. 
Published: June 2022

Background:
Pulmonary vein stenosis is a progressive disease associated with a high rate of mortality in children. If left untreated, myofibroblastic proliferation can lead to pulmonary vein atresia (PVA). In our experience, transcatheter recanalization has emerged as a favorable interventional option. We sought to determine the acute success rate of recanalization of atretic pulmonary veins and mid-term outcomes of individual veins after recanalization.

Methods:
We reviewed all patients with PVA at our institution between 2008 and 2020 diagnosed by either catheterization or cardiac computed tomography. All veins with successful recanalization were reviewed and procedural success rate and patency rate were noted. Competing risk analysis was performed to demonstrate outcomes of individual atretic veins longitudinally.

Results:
Between 2008 and 2020, our institution diagnosed and treated 131 patients with pulmonary vein stenosis. Of these, 61 patients developed atresia of at least one pulmonary vein. In total, there were 97 atretic pulmonary veins within this group. Successful recanalization was accomplished in 47/97 (48.5%) atretic veins. No atretic pulmonary veins were successfully recanalized before 2012. The majority of veins were recanalized between 2017 and 2020—39/56 (70%). The most common intervention after recanalization was drug-eluting stent placement. At 2-year follow-up 42.6% of recanalized veins (20.6% of all atretic veins) remained patent with a median of 4 reinterventions per person.

Conclusions:
Transcatheter recanalization of PVA can result in successful reestablishment of flow to affected pulmonary veins in many cases. Drug-eluting stent implantation was the most common intervention performed immediately post-recanalization. Vein patency was maintained in 42.6% of patients at 2-year follow-up from recanalization with appropriate surveillance and reintervention. Overall, only a small portion of atretic pulmonary veins underwent successful recanalization with maintained vessel patency at follow-up. Irrespective of successful recanalization, there was no detectable survival difference between the more recently treated PVA cohort and non-PVA cohort.
One-Year Health Status Outcomes Following Early Invasive and Noninvasive Treatment in Symptomatic Peripheral Artery Disease
Authors: Angraal Suveen , Hejjaji Vittal , Tang Yuanyuan , Gosch Kensey L. , Patel Manesh R. , Heyligers Jan , White Christopher J. , Tutein Nolthenius Rudolf , Mena-Hurtado Carlos , Aronow Herbert D. , Moneta Gregory L. , Fitridge Robert , Soukas Peter A. , Abbott J. Dawn , Secemsky Eric A. , Spertus John A. , Smolderen Kim G. 
Published: June 2022

Background:
Lifestyle changes and medications are recommended as the first line of treatment for claudication, with revascularization considered for treatment-resistant symptoms, based on patients’ preferences. Real-world evidence comparing health status outcomes of early invasive with noninvasive management strategies is lacking.

Methods:
In the international multicenter prospective observational PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry, disease-specific health status was assessed by the Peripheral Artery Questionnaire in patients with new-onset or worsening claudication at presentation and 3, 6, and 12 months later. One-year health status trajectories were compared by early revascularization versus noninvasive management on a propensity-matched sample using hierarchical generalized linear models for repeated measures adjusted for baseline health status.

Results:

In a propensity-matched sample of 1000 patients (67.4±9.3 years, 62.8% male, and 82.4% White), 297 (29.7%) underwent early revascularization and 703 (70.3%) were managed noninvasively. Over 1 year of follow-up, patients who underwent early invasive management reported significantly higher health status than patients managed noninvasively (interaction term for time and treatment strategy;
P
<0.001 for all Peripheral Artery Questionnaire domains). The average 1-year change in Peripheral Artery Questionnaire summary scores was 30.8±25.2 in those undergoing early invasive, compared with 16.7±23.4 in those treated noninvasively (
P
<0.001).

Conclusions:
Patients with claudication undergoing early invasive treatment had greater health status improvements over the course of 1 year than those treated noninvasively. These data can be used to support shared decision-making with patients.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01419080.
Transcatheter Myotomy to Relieve Left Ventricular Outflow Tract Obstruction: The Septal Scoring Along the Midline Endocardium Procedure in Animals
Authors: Khan Jaffar M. , Bruce Christopher G. , Greenbaum Adam B. , Babaliaros Vasilis C. , Jaimes Andrea E. , Schenke William H. , Ramasawmy Rajiv , Seemann Felicia , Herzka Daniel A. , Rogers Toby , Eckhaus Michael A. , Campbell-Washburn Adrienne , Guyton Robert A. , Lederman Robert J. 
Published: June 2022

Background:
Left ventricular outflow tract obstruction complicates hypertrophic cardiomyopathy and transcatheter mitral valve replacement. Septal reduction therapies including surgical myectomy and alcohol septal ablation are limited by surgical morbidity or coronary anatomy and high pacemaker rates, respectively. We developed a novel transcatheter procedure, mimicking surgical myotomy, called Septal Scoring Along the Midline Endocardium (SESAME).

Methods:

SESAME was performed in 5 naive pigs and 5 pigs with percutaneous aortic banding–induced left ventricular hypertrophy. Fluoroscopy and intracardiac echocardiography guided the procedures. Coronary guiding catheters and guidewires were used to mechanically enter the basal interventricular septum. Imparting a tip bend to the guidewire enabled intramyocardial navigation with multiple
df
. The guidewire trajectory determined the geometry of SESAME myotomy. The myocardium was lacerated using transcatheter electrosurgery. Cardiac function and tissue characteristics were assessed by cardiac magnetic resonance at baseline, postprocedure, and at 7- or 30-day follow-up.

Results:

SESAME myotomy along the intended trajectory was achieved in all animals. The myocardium splayed after laceration, increasing left ventricular outflow tract area (753 to 854 mm
2
,
P
=0.008). Two naive pigs developed ventricular septal defects due to excessively deep lacerations in thin baseline septa. No hypertrophy model pig, with increased septal thickness and left ventricular mass compared with naive pigs, developed ventricular septal defects. One animal developed left axis deviation on ECG but no higher conduction block was seen in any animal. Coronary artery branches were intact on angiography with no infarction on cardiac magnetic resonance late gadolinium imaging. Cardiac magnetic resonance chamber volumes, function, flow, and global strain were preserved. No myocardial edema was evident on cardiac magnetic resonance T1 mapping.

Conclusions:
This preclinical study demonstrated feasibility of SESAME, a novel transcatheter myotomy to relieve left ventricular outflow tract obstruction. This percutaneous procedure using available devices, with a safe surgical precedent, is readily translatable into patients.
Percutaneous Coronary Intervention With and Without Intravascular Ultrasound for Patients With Complex Lesions: Utilization, Mortality, and Target Vessel Revascularization
Authors: Hannan Edward L. , Zhong Ye , Reddy Pavan , Jacobs Alice K. , Ling Frederick S.K. , King III Spencer B. , Berger Peter B. , Venditti Ferdinand J. , Walford Gary , Tamis-Holland Jacqueline 
Published: June 2022

Background:
Intravascular ultrasound (IVUS) has several benefits during percutaneous coronary interventions (PCIs), including more accurate vessel sizing, improved stent expansion, and better strut apposition. Prior clinical trials have demonstrated a reduction in cardiac events when IVUS is used. However, there is limited information about the utilization of IVUS and the outcomes of IVUS-guided versus angiography-guided PCI in patients with complex lesions in a contemporary population-based setting.

Methods:
New York’s PCI registry was used to identify 44 305 patients with complex lesions (lesions that complicate stenting or that require multiple stents) undergoing PCI with and without IVUS guidance and discharged between December 1, 2013 and November 30, 2018. Trends and inter-hospital variation in IVUS use were examined. Risk-adjusted mortality and target vessel revascularization were compared.

Results:

A total of 6174 (13.9%) PCI patients underwent IVUS-guided PCI. The median follow-up period was 2.5 years. The percent of patients with complex lesions who underwent IVUS-guided PCI rose from 13.4% in 2014 to 16.5% in 2018 (
P
<0.0001 for trend), with the main increases occurring in the last 2 years of the period. Only 31 of 66 hospitals in the study used IVUS for >5% of their study patients. IVUS-guided PCI patients experienced significantly lower mortality (adjusted hazard ratio=0.89 [0.79–0.98] after adjustment using a Cox proportional hazards model, and HR=0.88 [0.78–0.99] for propensity-matched patients). We also found that IVUS-guided PCI patients had a lower rate of target vessel revascularization (adjusted hazard ratio=0.88 [0.80–0.97]) after adjusting using Cox proportional hazards with competing risk of mortality and after propensity matching (0.88 [0.79–0.99]).

Conclusions:
Utilization of IVUS for complex lesions has increased but contemporary rates remain low, and there are large inter-hospital variations. The use of IVUS for complex lesions was associated with lower risk of medium-term mortality and target vessel revascularization.
INFluence of Revascularization Attempts on Clinical Outcomes of Mechanical Thrombectomy Patients and its Economic BURDEN
Authors: Alderson Jack , Herlihy Darragh , Hegarty Aidan , Brennan Paul , Power Sarah , O'Hare Alan , Crockett Matthew , Tong Cindy , Galvain Thibaut , Kocaman Mesut , Ehm Alexandra , Thornton John 
Published: June 2022

BackgroundEmerging evidence suggests that clinical and economic benefits of treatment with mechanical thrombectomy vary by level of reperfusion achieved, and the number of passes required to achieve revascularization. This study aimed to investigate theINFluence of revascularizationAttempts onClinical outcomes of mechanicalThrombectomy and the economicBURDEN (INFACT BURDEN)in Ireland using single center real‐world data from the Irish National Thrombectomy Service database.MethodsPrimary clinical outcomes were reperfusion (modified thrombolysis in cerebral infarction 2b‐3 or <2b) and functional outcome (90‐day modified Rankin Scale ≤2 or modified Rankin Scale >2) among patients treated with 1–3 passes compared with ≥4 passes. Multivariable generalized linear models examined the association between number of passes with outcomes, with adjustment for covariates that may affect outcomes (eg, age, pre‐procedure modified Rankin Scale, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, occlusion site, time from symptom onset to groin puncture). A 90‐day decision‐tree and Markov model with a 5‐year time horizon evaluated the cost‐effectiveness of mechanical thrombectomy from the Irish public healthcare payer perspective.ResultsEight hundred twenty three patients met the inclusion criteria. Compared with patients in the ≥4 passes group, patients in the 1–3 passes group achieved a significantly higher rate of successful reperfusion (94% versus 78%, odds ratio [OR], 4.7;P<0.001) and a higher rate of functional independence (49% versus 33%, OR, 2.0;P<0.001). Patients in the 1–3 passes group had a shorter time from onset to reperfusion, lower incidence of procedural complications, including distal emboli into non‐involved territory and intra‐procedure rupture, as well as lower 90‐day mortality. The cost‐effectiveness analysis demonstrated that patients successfully revascularized in 1–3 passes had 0.19 additional QALYs and lower costs (€3328; $3800) such that 1–3 passes was dominant compared with ≥4 passes over a 5‐year time horizon.ConclusionThis study illustrates that the number of passes has a significant effect on both clinical outcomes and health care costs.
True Few-Shot Learning with Prompts—A Real-World Perspective
Authors: Schick Timo , Schütze Hinrich 
Published: June 2022

Abstract
Prompt-based approaches excel at few-shot learning. However, Perez et al. (2021) recently cast doubt on their performance as they had difficulty getting good results in a “true” few-shot setting in which prompts and hyperparameters cannot be tuned on a dev set. In view of this, we conduct an extensive study of Pet, a method that combines textual instructions with example-based finetuning. We show that, if correctly configured, Pet performs strongly in true few-shot settings without a dev set. Crucial for this strong performance is a number of design choices, including Pet’s ability to intelligently handle multiple prompts. We put our findings to a real-world test by running Pet on RAFT, a benchmark of tasks taken from realistic NLP applications for which no labeled dev or test sets are available. Pet achieves a new state of the art on RAFT and performs close to non-expert humans for 7 out of 11 tasks. These results demonstrate that prompt-based learners can successfully be applied in true few-shot settings and underpin our belief that learning from instructions will play an important role on the path towards human-like few-shot learning capabilities.
Children’s Right to Participate: The Lundy Model Applied to Early Childhood Education and Care
Authors: Correia Nadine , Aguiar Cecília , The participa Consortium  
Published: June 2022

Abstract
Children have the right to express their views in all matters affecting them, and to have them considered and given due weight. Children’s participation is most meaningful when rooted in children’s everyday lives, and its promotion should be encouraged from the youngest ages, especially in early childhood education and care (ecec). In this paper we apply the Lundy model of participation, widely used in policy, practice and professional development initiatives, to the ecec context. Based on examples provided by ecec professionals from Belgium, Greece, Poland, and Portugal, we illustrate the implementation of the elements of space, voice, audience and influence, proposed by the Lundy model. We also discuss the interrelations among these elements and the need for organisational and contextual support to enhance children’s participation. This paper adds to existing literature, highlighting theoretical and practical issues associated with the promotion of children’s right to participate in ecec.
Humboldtia ponmudiana (Fabaceae-Detarioideae), a new species from Kerala, India
Authors: SANTHOSH KUMAR ETTICKAL SUKUMARAN , SHAREEF SAINUDEEN MUHAMMED , VIKRAMAN RAMACHANDRAKURUP RAJ 
Published: June 2022

Humboldtia ponmudiana (Fabaceae-Detarioideae), a new species from Kerala, is described here with photographs. It is closely similar to H. decurrens, but differs in having black coloured bark, densely brown tomentose young shoots, lanceolate or ovate-lanceolate leaflets, sessile or subsessile flowers, large broadly ovate eglandular bracts, connate to middle bracteoles, 1-4 ovuled ovaries and silky tomentose pods with long beak. The IUCN conservation status, ecology, distribution along with a key to the species for the identification of the genus is also provided.