bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity and Safety of Geptanolimab (GB226) for Patients with Unresectable, Recurrent, or Metastatic Alveolar Soft Part Sarcoma: A Phase II, Single-arm Study
Authors: Shi Yuankai , Cai Qiqing , Jiang Yu , Huang Gang , Bi Minghong , Wang Baocheng , Zhou Yuhong , Wang Guowen , Ying Hongyan , Tao Zhiwei , Shi Chunmei , Guo Qian , Gao Chao 
Published: October 2020

Abstract

Purpose:
Patients with alveolar soft part sarcoma (ASPS) are rare and have few treatment options. We assessed the activity of geptanolimab (GB226), a fully humanized programmed cell death protein 1 antibody, for patients with unresectable, recurrent, or metastatic ASPS.

Patients and Methods:
We conducted this multicenter, single-arm, phase II study (Gxplore-005, NCT03623581) in patients aged 18–75 years who had unresectable, recurrent, or metastatic ASPS at 11 sites in China. Patients received intravenous geptanolimab (3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by independent review committee (IRC) per RECIST 1.1 in the full analysis set population.

Results:
Between September 6, 2018 and March 6, 2019, we enrolled and treated 37 patients with 23 (62.2%) having received prior systemic treatment. Fourteen [37.8%; 95% confidence interval (CI), 22.5–55.2] of 37 patients had an objective response assessed by IRC with a 6-month duration of response rate of 91.7%. Median progression-free survival was 6.9 months (95% CI, 5.0–not reached) and disease control was achieved in 32 (86.5%; 95% CI, 71.2–95.5) patients. Three of 37 patients reported grade 3 treatment-related adverse events (TRAEs), including anemia, hypophysitis, and proteinuria [one each (2.7%)]. No grade 4 TRAEs were observed. Two (5.4%) patients discontinued treatment due to TRAEs (one with hypophysitis and one with Mobitz type I atrioventricular block). The baseline percentage of CD4+ T cells was adversely associated with patient response (P = 0.031).

Conclusions:
Geptanolimab has clinically meaningful activity and a manageable safety profile in unresectable, recurrent, or metastatic ASPS.
Dephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastoma
Authors: Ali Fahad R. , Marcos Daniel , Chernukhin Igor , Woods Laura M. , Parkinson Lydia M. , Wylie Luke A. , Papkovskaia Tatiana D. , Davies John D. , Carroll Jason S. , Philpott Anna 
Published: October 2020

Abstract

Pediatric cancers often resemble trapped developmental intermediate states that fail to engage the normal differentiation program, typified by high-risk neuroblastoma arising from the developing sympathetic nervous system. Neuroblastoma cells resemble arrested neuroblasts trapped by a stable but aberrant epigenetic program controlled by sustained expression of a core transcriptional circuit of developmental regulators in conjunction with elevated MYCN or MYC (MYC). The transcription factor ASCL1 is a key master regulator in neuroblastoma and has oncogenic and tumor-suppressive activities in several other tumor types. Using functional mutational approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells drives coordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating an enduring gene program driving mitotic exit and neuronal differentiation.

Implications:
These findings indicate that targeting phosphorylation of ASCL1 may offer a new approach to development of differentiation therapies in neuroblastoma.
A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency
Authors: Le Naour Julie , Liu Peng , Zhao Liwei , Adjemian Sandy , Sztupinszki Zsofia , Taieb Julien , Mulot Claire , Silvin Aymeric , Dutertre Charles-Antoine , Ginhoux Florent , Sauvat Allan , Cerrato Giulia , Castoldi Francesca , Martins Isabelle , Stoll Gautier , Paillet Juliette , Mangane Khady , Richter Cornelia , Kepp Oliver , Maiuri Maria Chiara , Pietrocola Federico , Vandenabeele Peter , André Fabrice , Delaloge Suzette , Szallasi Zoltan , Laurent-Puig Pierre , Zucman-Rossi Jessica , Zitvogel Laurence , Pol Jonathan G. , Vacchelli Erika , Kroemer Guido 
Published: October 2020

Abstract

For anthracycline-based chemotherapy to be immunogenic, dying cancer cells must release annexin A1 (ANXA1) that subsequently interacts with the pattern recognition receptor, formyl peptide receptor 1 (FPR1), on the surface of dendritic cells (DC). Approximately 30% of individuals bear loss-of-function alleles of FPR1, calling for strategies to ameliorate their anticancer immune response. Here, we show that immunotherapy with a ligand of Toll-like receptor-3, polyinosinic:polycytidylic acid (pIC), restores the deficient response to chemotherapy of tumors lacking ANXA1 developing in immunocompetent mice or those of normal cancers growing in FPR1-deficient mice. This effect was accompanied by improved DC- and T-lymphocyte–mediated anticancer immunity. Of note, carcinogen-induced breast cancers precociously developed in FPR1-deficient mice as compared with wild-type controls. A similar tendency for earlier cancer development was found in patients carrying the loss-of-function allele of FPR1. These findings have potential implications for the clinical management of FPR1-deficient patients.

Significance:
The loss-of-function variant rs867228 in FPR1, harbored by approximately 30% of the world population, is associated with the precocious manifestation of breast, colorectal, esophageal, and head and neck carcinomas. pIC restores deficient chemotherapeutic responses in mice lacking Fpr1, suggesting a personalized strategy for compensating for the FPR1 defect.
This article is highlighted in the In This Issue feature, p. 211
Coronary Artery Bypass Grafting or Fractional Flow Reserve–Guided Percutaneous Coronary Intervention in Diabetic Patients With Multivessel Disease
Authors: Di Gioia Giuseppe , Soto Flores Nina , Franco Danilo , Colaiori Iginio , Sonck Jeroen , Gigante Carlo , Kodeboina Monika , Bartunek Jozef , Vanderheyden Marc , Van Praet Frank , Casselman Filip , Degriek Ivan , Stockman Bernard , Barbato Emanuele , Collet Carlos , De Bruyne Bernard 
Published: October 2020

Background:
In diabetic patients with multivessel coronary artery disease, coronary artery bypass grafting (CABG) has shown long-term benefits over percutaneous coronary intervention (PCI). Physiology-guided PCI has shown to improve clinical outcomes in multivessel coronary artery disease, though its impact in diabetic patients has never been investigated. We evaluated long-term clinical outcomes of diabetic patients with multivessel coronary artery disease treated with fractional flow reserve (FFR)–guided PCI compared with CABG.

Methods:
From 2010 to 2018, 4622 diabetic patients undergoing coronary angiography were screened for inclusion. The inclusion criterion was the presence of at least 2-vessel disease defined as with diameter stenosis ≥50%, in which at least 1 intermediate stenosis (diameter stenosis, 30%–70%) was treated or deferred according to FFR. Inverse probability of treatment weighting analysis was used to account for baseline differences with a contemporary cohort of patients treated with CABG. The primary end point was major adverse cardiovascular and cerebrovascular events, defined as all-cause death, myocardial infarction, revascularization, or stroke.

Results:

A total of 418 patients were included in the analysis. Among them, 209 patients underwent CABG and 209 FFR-guided PCI. At 5 years, the incidence of major adverse cardiovascular and cerebrovascular events was higher in the FFR-guided PCI versus the CABG group (44.5% versus 31.9%; hazard ratio, 1.60 [95% CI, 1.15–2.22];
P
=0.005). No difference was found in the composite of all-cause death, myocardial infarction, or stroke (28.8% versus 27.5%; hazard ratio, 1.05 [95% CI, 0.72–1.53];
P
=0.81). Repeat revascularization was more frequent with FFR-guided PCI (24.9% versus 8.2%; hazard ratio, 3.51 [95% CI, 1.93–6.40];
P
<0.001).

Conclusions:
In diabetic patients with multivessel coronary artery disease, CABG was associated with a lower rate of major adverse cardiovascular and cerebrovascular events compared with FFR-guided PCI, driven by a higher rate of repeat revascularization. At 5-year follow-up, no difference was observed in the composite of all-cause death, myocardial infarction, or stroke between CABG and FFR-guided PCI.

Graphic Abstract:

A
graphic abstract
is available for this article.
Association of Disease Progression With Cardiovascular and Limb Outcomes in Patients With Peripheral Artery Disease
Authors: Rymer Jennifer A. , Mulder Hillary , Narcisse Dennis I. , Rockhold Frank , Hiatt William R. , Fowkes F. Gerry , Baumgartner Iris , Berger Jeffrey S. , Katona Brian G. , Mahaffey Kenneth , Norgren Lars , Blomster Juuso I. , Jones W. Schuyler , Patel Manesh R. 
Published: October 2020

Background:
Patients with peripheral artery disease have a high risk of future cardiovascular disease events and mortality. Little is known about the changes in symptom classification over time in patients with peripheral artery disease and the association of changes in symptom classification with subsequent cardiovascular disease events.

Methods:
In this analysis of the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease), we examined the changes in Rutherford classification (RC) of patients over 12 months. We examined the baseline characteristics of patients by change in symptom classification at 12 months (improved=decreased RC, no change, or worsened=increased RC), and the association between changes in symptom classification (RC) at 12 months and subsequent cardiovascular disease events.

Results:

Among 12 759 patients, 3240 (25%) were classified as improved by RC at 12 months, 8132 (64%) as no change, and 1387 (11%) as worsened. At 12 months, many patients who were asymptomatic or had mild/moderate claudication at enrollment had no change in symptom classification over 12 months (73.7% and 70.9%). Patients who worsened over 12 months were more likely to have comorbidities (diabetes mellitus and prior myocardial infarction) and more events (myocardial infarction, amputation, and major bleeding) by 12 months postrandomization, all
P
<0.001. Worsened symptom classification over 12 months was associated with increased risk of all-cause death (adjusted hazard ratio, 1.29 [95% CI, 1.03–1.62]), major amputation (adjusted hazard ratio, 4.12 [95% CI, 2.46–6.88]), and a composite of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio, 1.30 [95% CI, 1.05–1.62]), all
P
<0.05 after 12 months postrandomization.

Conclusions:
Patients with comorbidities and prior history of cardiovascular disease events at baseline and within the first 12 months of the trial were more likely to have worsened symptom classification at 12 months. Worsening symptom classification over 12 months was associated subsequently with an increased risk of all-cause death, amputation, and a composite of cardiovascular death, myocardial infarction, or stroke.

Graphic Abstract:

A
graphic abstract
is available for this article.
Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Jhund Pardeep S. , Solomon Scott D. , Docherty Kieran F. , Heerspink Hiddo J.L. , Anand Inder S. , Böhm Michael , Chopra Vijay , de Boer Rudolf A. , Desai Akshay S. , Ge Junbo , Kitakaze Masafumi , Merkley Bela , O'Meara Eileen , Shou Morten , Tereshchenko Sergey , Verma Subodh , Vinh Pham Nguyen , Inzucchi Silvio E. , Køber Lars , Kosiborod Mikhail N. , Martinez Felipe A. , Ponikowski Piotr , Sabatine Marc S. , Bengtsson Olof , Langkilde Anna Maria , Sjöstrand Mikaela , McMurray John J.V. 
Published: October 2020

Background:
Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure). We also examined the effect of dapagliflozin on kidney function after randomization.

Methods:

Patients who have HFrEF with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL·min
–1
·1.73 m
–2
were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) according to eGFR category at baseline (<60 and ≥60 mL·min
–1
·1.73 m
–2
) and used eGFR at baseline as a continuous measure, as well. Secondary cardiovascular outcomes and a prespecified composite renal outcome (≥50% sustained decline eGFR, end-stage renal disease, or renal death) were also examined, along with a decline in eGFR over time.

Results:

Of 4742 patients with a baseline eGFR, 1926 (41%) had eGFR <60 mL·min
–1
·1.73 m
–2
. The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% CI) for the primary end point in patients with chronic kidney disease was 0.71 (0.59–0.86) versus 0.77 (0.64–0.93) in those with an eGFR ≥60 mL·min
–1
·1.73 m
–2
(interaction
P
=0.54). The composite renal outcome was not reduced by dapagliflozin (hazard ratio=0.71 [95% CI, 0.44–1.16];
P
=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, –1.09 (–1.40 to –0.77) versus placebo –2.85 (–3.17 to –2.53) mL·min
–1
·1.73 m
–2
per year (
P
<0.001). This was observed in those with and without type 2 diabetes (
P
for interaction=0.92).

Conclusions:
Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03036124.
Nonstenotic Carotid Plaque in Embolic Stroke of Undetermined Source
Authors: Grosse Gerrit M. , Sieweke Jan-Thorben , Biber Saskia , Ziegler Nora L. , Gabriel Maria M. , Schuppner Ramona , Worthmann Hans , Bavendiek Udo , Weissenborn Karin 
Published: October 2020

Background and Purpose:
Approximately one-sixth of all ischemic strokes are attributable to embolic stroke of undetermined source (ESUS). Recent analyses suggest that atrial cardiopathy and nonstenotic carotid plaque (nsCP) may represent 2 distinct underlying causes in patients with ESUS, although both diseases share common risk factors and are pathophysiologically intertwined. In this study, we, therefore, aimed to search for associations between nsCP and markers of atrial remodeling and function in patients with embolic stroke.

Methods:
Sixty-eight patients with ESUS or atrial fibrillation (AF)-related stroke proven by imaging who underwent comprehensive echocardiographic studies, including measurements of left atrial function and remodeling, were considered. Patients with ESUS underwent a follow-up of at least 1 year after index stroke. For 20 patients with ESUS, NT-proBNP (N-terminal pro-B-type natriuretic peptide) values were available. Presence of nsCP was evaluated considering Duplex sonography and computed tomography angiography and was further categorized in possibly or probably symptomatic nsCP.

Results:

ESUS patients with nsCP tended to have higher values of septal and lateral total atrial conduction times (
P
=0.071 and
P
=0.072, respectively), left atrial volume index (
P
=0.077), and revealed significantly higher strain rates during early diastole (
P
=0.013) as well as higher NT-proBNP values (
P
=0.010) than ESUS patients without nsCP. Moreover, septal total atrial conduction time was significantly longer in ESUS patients with possibly symptomatic nsCP compared with those without (
P
=0.015). Comparison of ESUS with AF patients revealed significantly higher proportions of nsCP (
P
=0.010), possibly symptomatic nsCP (
P
=0.037), and probably symptomatic nsCP (
P
=0.036) in patients with atrial fibrillation-related stroke. In the regression analysis adjusted for vascular risk factors probably symptomatic nsCP remained significantly associated with AF (
P
=0.048, odds ratio: 4.46 [95% CI, 1.02–19.56]).

Conclusions:
Presence of nsCP is associated with AF and markers of left atrial disease in patients with embolic stroke. Therefore, a thorough evaluation regarding atrial cardiopathy and AF in patients with ESUS should not be restricted if nsCP are found, even if high-risk plaque characteristics are evident.
Internet Video Calling and Desktop Sharing (vcds) as an Emerging Research Method for Exploring Pedagogical Reasoning in Lesson Planning
Authors: Hidson Elizabeth 
Published: October 2020

Abstract
This article presents the specific case of video calling and desktop sharing (vcds) used in a small-scale doctoral study exploring the lesson planning processes of teachers as a result of a national curriculum change. Accessing the participants’ actions and live think-aloud exposition of their pedagogical practices also generated dialogue as new data. The study set out to explore how pedagogical content knowledge was enacted through pedagogical reasoning when participant teachers planned Computing lessons. Two central case studies captured using vcds are shared. One presents a dialogic research interview which developed a shared understanding of the impact of the curriculum change on one teacher’s practices. The second case study shows the potential of vcds to capture the verbalised thoughts and observable actions of a second teacher preparing to teach new programming skills. The video data collected provided a rich audio-visual record of the lesson planning process as it happened. This article shares the approach taken, exemplifies the data captured and reflects on vcds as a method for exploring teachers’ pedagogical reasoning. It concludes that, depending on the nature of the research question, vcds may be justified as more suitable than face-to-face, artefact-based interviews.
Vertical Variability of the Raindrop Size Distribution in Typhoons Observed at the Shenzhen 356-m Meteorological Tower
Authors: Chen Baojun , Yang Jun , Gao Ruiquan , Zhu Keping , Zou Chungen , Gong Yi , Zhang Ran 
Published: October 2020

AbstractRaindrop size distribution (DSD) characteristics at various altitudes in two landfalling typhoons in 2017 (Hato and Pakhar) were investigated by using laser-optical disdrometers mounted at four altitudes (10, 40, 160, and 320 m) of the Shenzhen 356-m meteorological tower. Significant differences of the DSD and derived parameters, mass-weighted mean diameter (Dm), normalized intercept parameter (NW), and standard deviation of the mass distribution σm, were observed at different altitudes for the two typhoons, while the rainwater content between the four altitudes had no statistically significant differences. The low-altitude DSDs had more midsize drops (1 < D < 3 mm), fewer large drops (D > 3 mm), and narrower distribution widths than the high-altitude ones, while the concentration of small drops varied nonlinearly with height. The value of NW decreased with height, while Dm and σm increased with height. The gamma distribution parameters N0, μ, and Λ are found to increase with decreasing height. Both the derived μ–Λ and Z–R relations were significantly varied in different altitudes.
Cold Surge Pathways in East Asia and Their Tropical Impacts
Authors: Abdillah Muhammad Rais , Kanno Yuki , Iwasaki Toshiki , Matsumoto Jun 
Published: October 2020

AbstractCold surge occurrences are one of the robust features of winter monsoon in East Asia and are characterized by equatorward outbreaks of cold air from the high latitudes. Beside greatly affecting weather variability across the Far East, cold surges are of importance for Southeast Asian countries because they can propagate far to the tropics and excite convective activities. However, the tropical responses highly depend on the downstream pathways of the surges. To better understand how cold surges influence tropical weather, we investigate 160 cold surges identified using a quantitative approach during 40 winters from 1979/80 to 2018/19, and then classify them into several groups based on their prominent pathways. At the midlatitudes, we find two groups: one for surges that show clear equatorward propagation of cold air to lower latitudes and the other for surges that turn eastward and bring cold air to the North Pacific. These groups arise due to the strength difference of the Siberian high expansion controlled by cold air blocking near the Tibetan Plateau. The tropical impact is evident in the former group. We perform further classification on this group and find four types of surges based on their pathways in the low latitudes: 1) South China Sea (SCS) surges, 2) Philippines Sea (PHS) surges, 3) both SCS and PHS surges, and 4) blocked surges. They exhibit distinct precipitation signatures over the Maritime Continent, which are driven by interactions between the surges and the pre-existing synoptic conditions over the tropics, particularly the Madden–Julian oscillation (MJO).
PERSIANN Dynamic Infrared–Rain Rate (PDIR-Now): A Near-Real-Time, Quasi-Global Satellite Precipitation Dataset
Authors: Nguyen Phu , Ombadi Mohammed , Gorooh Vesta Afzali , Shearer Eric J. , Sadeghi Mojtaba , Sorooshian Soroosh , Hsu Kuolin , Bolvin David , Ralph Martin F. 
Published: October 2020

AbstractThis study presents the Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks–Dynamic Infrared Rain Rate (PDIR-Now) near-real-time precipitation dataset. This dataset provides hourly, quasi-global, infrared-based precipitation estimates at 0.04° × 0.04° spatial resolution with a short latency (15–60 min). It is intended to supersede the PERSIANN–Cloud Classification System (PERSIANN-CCS) dataset previously produced as the near-real-time product of the PERSIANN family. We first provide a brief description of the algorithm’s fundamentals and the input data used for deriving precipitation estimates. Second, we provide an extensive evaluation of the PDIR-Now dataset over annual, monthly, daily, and subdaily scales. Last, the article presents information on the dissemination of the dataset through the Center for Hydrometeorology and Remote Sensing (CHRS) web-based interfaces. The evaluation, conducted over the period 2017–18, demonstrates the utility of PDIR-Now and its improvement over PERSIANN-CCS at all temporal scales. Specifically, PDIR-Now improves the estimation of rain/no-rain days as demonstrated by a critical success index (CSI) of 0.53 compared to 0.47 of PERSIANN-CCS. In addition, PDIR-Now improves the estimation of seasonal and diurnal cycles of precipitation as well as regional precipitation patterns erroneously estimated by PERSIANN-CCS. Finally, an evaluation is carried out to examine the performance of PDIR-Now in capturing two extreme events, Hurricane Harvey and a cluster of summer thunderstorms that occurred over the Netherlands, where it is shown that PDIR-Now adequately represents spatial precipitation patterns as well as subdaily precipitation rates with a correlation coefficient (CORR) of 0.64 for Hurricane Harvey and 0.76 for the Netherlands thunderstorms.