bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 and its impact on the cardiovascular system
Authors: Khawaja Saud Ahmed , Mohan Poornima , Jabbour Richard , Bampouri Theodora , Bowsher Gemma , Hassan Ahmed M M , Huq Farhan , Baghdasaryan Lilit , Wang Brian , Sethi Amarjit , Sen Sayan , Petraco Ricardo , Ruparelia Neil , Nijjer Sukhjinder , Malik Iqbal , Foale Rodney , Bellamy Michael , Kooner Jaspal , Rana Bushra , Cole Graham , Sutaria Nilesh , Kanaganayagam Gajen , Nihoyannopoulos Petros , Fox Kevin , Plymen Carla , Pabari Punam , Howard Luke , Davies Rachel , Haji Gulammehdi , Lo Giudice Francesco , Kanagaratnam Prapa , Anderson Jon , Chukwuemeka Andrew , Khamis Ramzi , Varnava Amanda , Baker Christopher S R , Francis Darrel Parthipan , Asaria Perviz , Al-Lamee Rasha , Mikhail Ghada W 
Published: March 2021

ObjectivesThe clinical impact of SARS-CoV-2 has varied across countries with varying cardiovascular manifestations. We review the cardiac presentations, in-hospital outcomes and development of cardiovascular complications in the initial cohort of SARS-CoV-2 positive patients at Imperial College Healthcare National Health Service Trust, UK.MethodsWe retrospectively analysed 498 COVID-19 positive adult admissions to our institute from 7 March to 7 April 2020. Patient data were collected for baseline demographics, comorbidities and in-hospital outcomes, especially relating to cardiovascular intervention.ResultsMean age was 67.4±16.1 years and 62.2% (n=310) were male. 64.1% (n=319) of our cohort had underlying cardiovascular disease (CVD) with 53.4% (n=266) having hypertension. 43.2%(n=215) developed acute myocardial injury. Mortality was significantly increased in those patients with myocardial injury (47.4% vs 18.4%, p<0.001). Only four COVID-19 patients had invasive coronary angiography, two underwent percutaneous coronary intervention and one required a permanent pacemaker implantation. 7.0% (n=35) of patients had an inpatient echocardiogram. Acute myocardial injury (OR 2.39, 95% CI 1.31 to 4.40, p=0.005) and history of hypertension (OR 1.88, 95% CI 1.01 to 3.55, p=0.049) approximately doubled the odds of in-hospital mortality in patients admitted with COVID-19 after other variables had been controlled for.ConclusionHypertension, pre-existing CVD and acute myocardial injury were associated with increased in-hospital mortality in our cohort of COVID-19 patients. However, only a low number of patients required invasive cardiac intervention.
Association of early versus delayed normalisation of left ventricular ejection fraction with mortality in ischemic cardiomyopathy
Authors: Schiffer Walter B , Perry Andrew , Deych Elena , Brown David L , Adamo Luigi 
Published: March 2021

ObjectiveIn patients with non-ischaemic cardiomyopathy and reduced left ventricular ejection fraction (LVEF), normalisation of LVEF is associated with improved outcomes. However, data on patients with ischaemic cardiomyopathy and recovered LVEF are lacking. The goal of this study was to assess the prognostic significance of normalisation of the LVEF in patients with ischaemic cardiomyopathy.Methods/ResultsWe performed a non-prespecified post hoc analysis of the Surgical Treatment for Ischaemic Heart Failure (STICH) trial to determine the association between normalisation of LVEF (>50%) and mortality during follow-up. Of the 1212 patients with LVEF <35% enroled in the STICH trial, 932 underwent assessment of LVEF at 4 months and/or 2 years after enrolment. Among them, 18 patients experienced normalisation in LVEF at 4-month follow-up and 35 patients experienced recovery in LVEF at 2 years. Recovery of LVEF at 4 months and recovery of LVEF at 2 years were not correlated. Recovery of LVEF at 4 months was not associated with reduced all-cause mortality in unadjusted analysis (log-rank test p=0.54) or in Cox proportional hazards analysis (HR: 0.93; 95% CI: 0.48 to 1.80; p=0.82). Ejection fraction recovery at 2 years was associated with a reduction in all-cause mortality, both in unadjusted analysis (log-rank test p=0.004) and in the Cox proportional hazard model (HR: 0.41; 95% CI: 0.21 to 0.80; p=0.009).ConclusionsIn patients with ischaemic cardiomyopathy, delayed normalisation of LVEF is associated with reduced mortality, whereas early recovery of LVEF is not. Further studies are needed to confirm these findings.
Pleural recurrence after transthoracic needle lung biopsy in stage I lung cancer: a systematic review and individual patient-level meta-analysis
Authors: Hong Hyunsook , Hahn Seokyung , Matsuguma Haruhisa , Inoue Masayoshi , Shintani Yasushi , Honda Osamu , Izumi Yotaro , Asakura Keisuke , Asamura Hisao , Isaka Tetsuya , Lee Kyungjong , Choi Yong Soo , Kim Young Tae , Park Chang Min , Goo Jin Mo , Yoon Soon Ho 
Published: March 2021

Introduction
Conflicting results exist regarding whether preoperative transthoracic biopsy increases the risk of pleural recurrence in early lung cancer. We conducted a systematic, patient-level meta-analysis to evaluate the risk of pleural recurrence in stage I lung cancer after percutaneous transthoracic lung biopsy.

Methods
A systematic search of OVID-MEDLINE, Embase and the Cochrane Database of Systematic Reviews was performed through October 2018. Eligible studies were original articles on the risk of pleural recurrence in stage I lung cancer after transthoracic biopsy. We contacted the corresponding authors of eligible studies to obtain individual patient-level data. We used the Fine-Gray model for time to recurrence and lung cancer-specific survival and a Cox proportional hazards model for overall survival.

Results
We analysed 2394 individual patient data from 6 out of 10 eligible studies. Compared with other diagnostic procedures, transthoracic biopsy was associated with a higher risk for ipsilateral pleural recurrence, which manifested solely (subdistribution HR (sHR), 2.58; 95% CI 1.15 to 5.78) and concomitantly with other metastases (sHR 1.99; 95% CI 1.14 to 3.48). In the analysis of secondary outcomes considering a significant interaction between diagnostic procedures and age groups, reductions of time to recurrence (sHR, 2.01; 95% CI 1.11 to 3.64), lung cancer-specific survival (sHR 2.53; 95% CI 1.06 to 6.05) and overall survival (HR 2.08; 95% CI 1.12 to 3.87) were observed in patients younger than 55 years, whereas such associations were not observed in other age groups.

Discussion
Preoperative transthoracic lung biopsy was associated with increased pleural recurrence in stage I lung cancer and reduced survival in patients younger than 55 years.
Vaidya geometries and scalar fields with null gradients
Authors: Faraoni Valerio , Giusti Andrea , Fahim Bardia H. 
Published: March 2021

AbstractSince, in Einstein gravity, a massless scalar field with lightlike gradient behaves as a null dust, one could expect that it can act as the matter source of Vaidya geometries. We show that this is impossible because the Klein–Gordon equation forces the null geodesic congruence tangent to the scalar field gradient to have zero expansion, contradicting a basic property of Vaidya solutions. By contrast, exact plane waves travelling at light speed and sourced by a scalar field acting as a null dust are possible.
Development of a Histopathology Informatics Pipeline for Classification and Prediction of Clinical Outcomes in Subtypes of Renal Cell Carcinoma
Authors: Marostica Eliana , Barber Rebecca , Denize Thomas , Kohane Isaac S. , Signoretti Sabina , Golden Jeffrey A. , Yu Kun-Hsing 
Published: March 2021

Abstract

Purpose:
Histopathology evaluation is the gold standard for diagnosing clear cell (ccRCC), papillary, and chromophobe renal cell carcinoma (RCC). However, interrater variability has been reported, and the whole-slide histopathology images likely contain underutilized biological signals predictive of genomic profiles.

Experimental Design:
To address this knowledge gap, we obtained whole-slide histopathology images and demographic, genomic, and clinical data from The Cancer Genome Atlas, the Clinical Proteomic Tumor Analysis Consortium, and Brigham and Women's Hospital (Boston, MA) to develop computational methods for integrating data analyses. Leveraging these large and diverse datasets, we developed fully automated convolutional neural networks to diagnose renal cancers and connect quantitative pathology patterns with patients' genomic profiles and prognoses.

Results:
Our deep convolutional neural networks successfully detected malignancy (AUC in the independent validation cohort: 0.964–0.985), diagnosed RCC histologic subtypes (independent validation AUCs of the best models: 0.953–0.993), and predicted stage I ccRCC patients' survival outcomes (log-rank test P = 0.02). Our machine learning approaches further identified histopathology image features indicative of copy-number alterations (AUC &gt; 0.7 in multiple genes in patients with ccRCC) and tumor mutation burden.

Conclusions:
Our results suggest that convolutional neural networks can extract histologic signals predictive of patients' diagnoses, prognoses, and genomic variations of clinical importance. Our approaches can systematically identify previously unknown relations among diverse data modalities.
Dolaflexin: A Novel Antibody–Drug Conjugate Platform Featuring High Drug Loading and a Controlled Bystander Effect
Authors: Yurkovetskiy Aleksandr V. , Bodyak Natalya D. , Yin Mao , Thomas Joshua D. , Clardy Susan M. , Conlon Patrick R. , Stevenson Cheri A. , Uttard Alex , Qin LiuLiang , Gumerov Dmitry R. , Ter-Ovanesyan Elena , Bu Charlie , Johnson Alex J. , Gurijala Venu R. , McGillicuddy Dennis , DeVit Michael J. , Poling Laura L. , Protopopova Marina , Xu Ling , Zhang Qingxiu , Park Peter U. , Bergstrom Donald A. , Lowinger Timothy B. 
Published: March 2021

Abstract
After significant effort over the last 30 years, antibody–drug conjugates (ADC) have recently gained momentum as a therapeutic modality, and nine ADCs have been approved by the FDA to date, with additional ADCs in late stages of development. Here, we introduce dolaflexin, a novel ADC technology that overcomes key limitations of the most common ADC platforms with two key features: a higher drug-to-antibody ratio and a novel auristatin with a controlled bystander effect. The novel, cell permeable payload, auristatin F-hydroxypropylamide, undergoes metabolic conversion to the highly potent, but less cell permeable auristatin F to balance the bystander effect through drug trapping within target cells. We conducted studies in mice, rats, and cynomolgus monkeys to complement in vitro characterization and contrasted the performance of dolaflexin with regard to antitumor activity, pharmacokinetic properties, and safety in comparison with the ADC platform utilized in the approved ADC ado-trastuzumab emtansine (T-DM1). A HER2-targeted dolaflexin ADC was shown to have a much lower threshold of antigen expression for potent cell killing in vitro, was effective in vivo in tumors with low HER2 expression, and induced tumor regressions in a xenograft model that is resistant to T-DM1.
Frondoside A Inhibits an MYC-Driven Medulloblastoma Model Derived from Human-Induced Pluripotent Stem Cells
Authors: Xue Yingchao , Fu Yi , Zhao Fenghong , Gui Gege , Li Yuguo , Rivero-Hinojosa Samuel , Liu Guanshu , Li Yunqing , Xia Shuli , Eberhart Charles G. , Ying Mingyao 
Published: March 2021

Abstract
Medulloblastoma (MB) is the most common malignant pediatric brain tumor. MYC-driven MBs, commonly found in the group 3 MB, are aggressive and metastatic with the worst prognosis. Modeling MYC-driven MB is the foundation of therapeutic development. Here, we applied a synthetic mRNA-driven strategy to generate neuronal precursors from human-induced pluripotent stem cells (iPSCs). These neuronal precursors were transformed by the MYC oncogene combined with p53 loss of function to establish an MYC-driven MB model recapitulating the histologic and transcriptomic hallmarks of group 3 MB. We further show that the marine compound Frondoside A (FA) effectively inhibits this MYC-driven MB model without affecting isogenic neuronal precursors with undetectable MYC expression. Consistent results from a panel of MB models support that MYC levels are positively correlated with FA's antitumor potency. Next, we show that FA suppresses MYC expression and its downstream gene targets in MB cells, suggesting a potential mechanism underlying FA's inhibitory effects on MYC-driven cancers. In orthotopic xenografts of MYC-driven MB, intratumoral FA administration potently induces cytotoxicity in tumor xenografts, significantly extends the survival of tumor-bearing animals, and enhances the recruitment of microglia/macrophages and cytotoxic T lymphocytes to tumors. Moreover, we show that MYC levels also predict FA potency in glioblastoma and non–small cell lung cancer cells. Taken together, this study provides an efficient human iPSC-based strategy for personalizable cancer modeling, widely applicable to mechanistic studies (e.g., genetic predisposition to cancer) and drug discovery. Our preclinical results justify the clinical translation of FA in treating MYC-driven MB and other human cancers.
Implications of Atrial Fibrillation on the Mechanisms of Mitral Regurgitation and Response to MitraClip in the COAPT Trial
Authors: Gertz Zachary M. , Herrmann Howard C. , Lim D. Scott , Kar Saibal , Kapadia Samir R. , Reed Grant W. , Puri Rishi , Krishnaswamy Amar , Gersh Bernard J. , Weissman Neil J. , Asch Federico M. , Grayburn Paul A. , Kosmidou Ioanna , Redfors Björn , Zhang Zixuan , Abraham William T. , Lindenfeld JoAnn , Stone Gregg W. , Mack Michael J. 
Published: March 2021

Background:
Atrial fibrillation (AF), mitral regurgitation (MR), and left ventricular (LV) ejection fraction have a complex interplay. We evaluated the role of AF in patients with heart failure and moderate-to-severe or severe secondary MR enrolled in the randomized COAPT trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) and its impact on mechanisms and outcomes with the MitraClip.

Methods:
Patients in the COAPT trial were stratified by the presence (n=327) or absence (n=287) of a history of AF and by assignment to treatment group. Clinical, echocardiographic, and outcome measures were assessed. The primary outcome was the composite rate of death or heart failure hospitalization at 24 months.

Results:

Patients with history of AF were older and more often male. They had a higher LV ejection fraction, larger left atrial volumes and mitral valve orifice areas, smaller LV volumes, and similar MR severity. Patients with AF compared with those without a history of AF had a higher unadjusted (hazard ratio [HR], 1.32 [95% CI, 1.06–1.64],
P
=0.01) and adjusted (HR, 1.30 [1.03–1.64],
P
=0.03) 2-year rate of the primary outcome. Treatment with the MitraClip compared with guideline-directed medical therapy alone reduced death or heart failure hospitalization in both those with (HR, 0.61 [0.46–0.82]) and without (HR, 0.46 [0.33–0.66]) a history of AF (
P
int
=0.18). Treatment with the MitraClip was associated with a lower risk of stroke in patients with a history of AF (HR, 0.18 [0.04–0.86]) but not in those without a history of AF (HR, 1.64 [0.58–4.62];
P
int
=0.02).

Conclusions:
In the COAPT trial, patients with a history of AF had larger left atrial and mitral valve orifice areas with higher LV ejection fraction and smaller LV volumes, suggesting an atrial mechanism contribution to functional MR. Despite the worse prognosis of heart failure patients with a history of AF, MR reduction with the MitraClip still afforded substantial clinical benefits. Treatment with MitraClip was associated with a lower risk of stroke in patients with a history of AF.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01626079.
Trends in Coded Indications for Percutaneous Coronary Interventions in Medicare and the Veterans Affairs After Implementation of Hospital-Level Reporting of Appropriate Use Criteria
Authors: Dayoub Elias J. , Nathan Ashwin S. , Khatana Sameed Ahmed M. , Wadhera Rishi K. , Kolansky Daniel M. , Yeh Robert W. , Giri Jay , Groeneveld Peter W. 
Published: March 2021

Background:
In 2009, the American College of Cardiology and American Heart Association published Appropriate Use Criteria for Coronary Revascularization (AUC) to aid patient selection for percutaneous coronary intervention (PCI). The subsequent decline in inappropriate PCIs was interpreted as a success of AUC. However, there are concerns clinicians reclassify nonacute PCIs to acute indications to fulfill AUC.

Methods:
A longitudinal, observational difference-in-differences analysis was performed using administrative claims from US Department of Veterans Affairs (VA) beneficiaries coenrolled in Medicare and from a national random sample of Medicare beneficiaries, undergoing PCI from September 30, 2009, to December 31, 2013. Non-VA hospitals participating in the American College of Cardiology CathPCI registry began receiving AUC reports in 2011, while VA hospitals did not receive reports, serving as quasiexperimental and control cohorts, respectively. We measured the proportion of PCIs coded for acute myocardial infarction, unstable angina, and nonacute coronary syndrome indications by quarter.

Results:

There were 87 464 and 30 251 PCIs performed in the Medicare and VA cohorts, respectively. In Medicare, proportion of PCIs coded for acute myocardial infarction and unstable angina changed from 31.9% and 12.6% in quarter 4 2009 to 41.0% and 10.5% in quarter 4 2013, an associated 2.00% (95% CI, 1.56%–2.44%;
P
<0.001) increase per year in PCIs coded for acute coronary syndrome indications. In the VA, proportion of PCIs coded for acute myocardial infarction and unstable angina changed from 26.5% and 15.7% in quarter 4 2009 to 34.3% and 12.3% in quarter 4 2013, an associated 1.20% (95% CI, 0.56%–1.88%;
P
=0.001) increase per year in PCIs coded for acute coronary syndrome indications. Difference-in-differences modeling found no statistically significant change in PCI coded for acute indications between Medicare and VA, pre- and post-AUC reporting.

Conclusions:
After introduction of AUC assessments and reporting, we observed comparable increases in coding for acute myocardial infarction and corresponding decreases in coding for unstable angina and nonacute coronary syndrome indications among national cohorts of Medicare and VA enrollees. The provision of appropriate use reporting did not appear to have a substantial impact on the proportion of PCIs coded for acute indications during this study period.
Elevated Pulmonary Pressure Noted on Echocardiogram: A Simplified Approach to Next Steps
Authors: Kanwar Manreet K. , Tedford Ryan J. , Thenappan Thenappan , De Marco Teresa , Park Myung , McLaughlin Vallerie 
Published: March 2021

Abstract
An elevated right ventricular/pulmonary artery systolic pressure suggestive of pulmonary hypertension (PH) is a common finding noted on echocardiography and is considered a marker for poor clinical outcomes, regardless of the cause. Even mild elevation of pulmonary pressure can be considered a modifiable risk factor, informing the trajectory of patients' clinical outcome. Although guidelines have been published detailing diagnostic and management algorithms, this echocardiographic finding is often underappreciated or not acted upon. Hence, patients with PH are often diagnosed in clinical practice when hemodynamic abnormalities are already moderate or severe. This results in delayed initiation of potentially effective therapies, referral to PH centers, and greater patient morbidity and mortality. This mini‐review presents a succinct, simplified case‐based approach to the “next steps” in the work‐up of PH, once elevated pulmonary pressures have been noted on an echocardiogram. Our goal is for clinicians to develop a good overview of diagnostic approach to PH and recognition of high‐risk features that may require early referral.
Dynamics of the Layered Circulation Inferred from Kinetic Energy Pathway in the South China Sea
Authors: Cai Zhongya , Gan Jianping 
Published: March 2021

AbstractWe investigated the mean kinetic energy (MKE) and eddy kinetic energy (EKE) in the South China Sea to illustrate the dynamics of the vertically rotating cyclonic–anticyclonic–cyclonic (CAC) circulation in the upper, middle, and deep layers. We found that strong MKE along the basin slope and the associated EKE arising from the vertical shear and stratification of the mean current characterize the circulation. In the upper layer, the external MKE input from the Kuroshio intrusion and wind forcing drive the cyclonic circulation, with the wind forcing providing most of the EKE. External forcing, however, does not directly provide the MKE and EKE of the CAC circulation in the semi-enclosed middle and deep layers, where the internal pressure work near Luzon Strait and the vertical buoyancy flux (VBF) in the southern basin and along the western slope maintain the MKE and EKE. The internal pressure work is formed by ageostrophic motion and pressure gradient field associated with circulation. The VBF is generated by vertical motion induced by the geostrophic cross-isobath transport along the slope where variable density field is maintained by the external flow and the internal mixing. The kinetic energy pathway in the CAC circulation indicates that the external forcing dominates upper-layer circulation and the coupling between internal and external dynamics is crucial for maintaining the circulation in the middle and deep layers. This study provides a new interpretation to the maintenance of CAC circulation from energy prospect.
Correction of Monthly SST Forecasts in CFSv2 Using the Local Dynamical Analog Method
Authors: Hou Zhaolu , Li Jianping , Zuo Bin 
Published: March 2021

AbstractNumerical seasonal forecasts in Earth science always contain forecast errors that cannot be eliminated by improving the ability of the numerical model. Therefore, correction of model forecast results is required. Analog correction is an effective way to reduce model forecast errors, but the key question is how to locate analogs. In this paper, we updated the local dynamical analog (LDA) algorithm to find analogs and depicted the process of model error correction as the LDA correction scheme. The LDA correction scheme was first applied to correct the operational seasonal forecasts of sea surface temperature (SST) over the period 1982–2018 from the state-of-the-art coupled climate model named NCEP Climate Forecast System, version 2. The results demonstrated that the LDA correction scheme improves forecast skill in many regions as measured by the correlation coefficient and root-mean-square error, especially over the extratropical eastern Pacific and tropical Pacific, where the model has high simulation ability. El Niño–Southern Oscillation (ENSO) as the focused physics process is also improved. The seasonal predictability barrier of ENSO is in remission, and the forecast skill of central Pacific ENSO also increases due to the LDA correction method. The intensity of the ENSO mature phases is improved. Meanwhile, the ensemble forecast results are corrected, which proves the positive influence from this LDA correction scheme on the probability forecast of cold and warm events. Overall, the LDA correction scheme, combining statistical and model dynamical information, is demonstrated to be readily integrable with other advanced operational models and has the capability to improve forecast results.