bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of early definitive management for newly diagnosed malignant pleural effusion related to lung cancer
Authors: Chiang Ka‐Yan , Ho James Chung‐Man , Chong Peony , Tam Terence Chi‐Chun , Lam David Chi‐Leung , Ip Mary Sau‐Man , Lee Yun‐Chor Gary , Lui Macy Mei‐Sze 
Published: April 2020

ABSTRACTBackground and objectiveThe advent of effective anti‐cancer therapy has brought about uncertainty on the benefit of early definitive measures for newly diagnosed MPE from lung cancer. This study aims to investigate the outcomes of MPE in this setting.MethodsLung cancer patients with MPE at first presentation to a tertiary care hospital were followed up till death or censored from 2011 to 2018. Early MPE control measures included chemical pleurodesis or IPC before or shortly after oncological treatment. Predictors of time to MPE re‐intervention were identified with Cox proportional hazard analyses.ResultsOf the 509 records screened, 233 subjects were eligible. One hundred and twenty‐seven subjects received oral targeted therapy as first‐line treatment and 34 (26.8%) underwent early definitive MPE control measures. Early MPE control measures in addition to targeted therapy, as compared to targeted therapy alone, significantly reduced the subsequent need of MPE re‐intervention (23.5% vs 53.8%, P = 0.002). Similar benefits from MPE control measures were found in groups receiving systemic anti‐cancer therapy or best supportive care (0% vs 52%, P = 0.003; 18% vs 56.7%, P = 0.024, respectively). In the group with targetable mutations, both early MPE control measures (HR: 0.25, 95% CI: 0.12–0.53, P < 0.001) and the use of targeted therapy (HR: 0.22, 95% CI: 0.10–0.46, P < 0.001) were independently associated with longer time to MPE re‐interventions.ConclusionEarly MPE control measures in lung cancer has additional benefits on reducing the need and prolonging the time to MPE re‐intervention, independent of anti‐cancer therapies.
Partial anomalous pulmonary venous drainage in patients presenting with suspected pulmonary hypertension: A series of 90 patients from the ASPIRE registry
Authors: Lewis Robert A. , Billings Catherine G. , Bolger Aidan , Bowater Sarah , Charalampopoulos Athanasios , Clift Paul , Elliot Charlie A. , English Kate , Hamilton Neil , Hill Catherine , Hurdman Judith , Jenkins Petra J. , Johns Christopher , MacDonald Simon , Oliver James , Papaioannou Vasilios , Rajaram Smitha , Sabroe Ian , Swift Andy J. , Thompson A.A. Roger , Kiely David G. , Condliffe Robin 
Published: April 2020

ABSTRACTBackground and objectiveThere are limited data regarding patients with PAPVD with suspected and diagnosed PH.MethodsPatients with PAPVD presenting to a large PH referral centre during 2007–2017 were identified from the ASPIRE registry.ResultsNinety patients with PAPVD were identified; this was newly diagnosed at our unit in 71 patients (78%), despite 69% of these having previously undergone CT. Sixty‐seven percent had a single right superior and 23% a single left superior anomalous vein. Patients with an SV‐ASD had a significantly larger RV area, pulmonary artery and L‐R shunt and a higher % predicted DLCO (all P < 0.05). Sixty‐five patients were diagnosed with PH (defined as mPAP ≥ 25 mm Hg), which was post‐capillary in 24 (37%). No additional causes of PH were identified in 28 patients; 17 of these (26% of those patients with PH) had a PVR > 3 WU. Seven of these patients had isolated PAPVD, five of whom (8% of those patients with PH) had anomalous drainage of a single pulmonary vein.ConclusionUndiagnosed PAPVD with or without ASD may be present in patients with suspected PH; cross‐sectional imaging should therefore be specifically assessed whenever this diagnosis is considered. Radiological and physiological markers of L‐R shunt are higher in patients with an associated SV‐ASD. Although many patients with PAPVD and PH may have other potential causes of PH, a proportion of patients diagnosed with PAH have isolated PAPVD in the absence of other causative conditions.
Acral congenital superficial dermal lymphatic malformations in two unrelated cats: clinicopathological, dermoscopic and ultrastructural findings
Authors: Legnani Sara , Abramo Francesca , Zanna Giordana , Graziano Lisa , Cornegliani Luisa , Roccabianca Paola 
Published: April 2020

BackgroundCutaneous vascular malformations (CVM) represent a spectrum of human diseases identified at birth or in paediatric patients and classified according to the type of vessel affected. Confusing classification in human medicine has led to misdiagnoses and frequent nomenclature revision. Cutaneous lymphatic malformations (CLM) are reported sporadically in humans.ObjectiveTo describe the clinicopathological findings of superficial dermal cutaneous lymphatic malformations (SDCLM) in two cats.AnimalsTwo unrelated adult domestic short hair cats.MethodsThe two cats were evaluated clinically and with a dermoscope for recurrent swelling and presence of vesicles oozing serosanguineous fluid affecting the right and left hind foot, respectively, since birth. Skin biopsy specimens were collected for histopathological and immunohistochemical evaluation and electron microscopy.ResultsA CVM was suspected based on the age of onset, clinical signs, results of diagnostic imaging and histopathological findings. Dermoscopy was used to describe the alterations of the skin surface. The involvement of the lymphatic vessels was confirmed using immunohistochemical findings and electron microscopy.Conclusion and clinical importanceTo the best of the authors’ knowledge, this is the first description of the clinical, dermoscopic, histopathological and ultrastructural characteristics of SDCLM in cats resembling the human counterpart. SDCLMs are rare conditions and appropriate histopathological and immunohistochemical confirmation is required to avoid misdiagnosis and mistreatment.
Red‐blood‐cell alloimmunization and prophylactic antigen matching for transfusion in patients with warm autoantibodies
Authors: Delaney Meghan , Apelseth Torunn Oveland , Bonet Bub Carolina , Cohn Claudia S. , Dunbar Nancy M. , Mauro Kutner Jose , Murphy Michael , Perelman Iris , Selleng Kathleen , Staves Julie , Wendel Silvano , Ziman Alyssa ,   the Biomedical Excellence for Safer Transfusion (BEST) Collaborative
Published: April 2020

BackgroundWarm autoantibodies (WAA) are antibodies that react with an antigen on a patient’s own red‐blood‐cells and can complicate compatibility testing whether or not they cause clinical haemolysis. The goal of this study was to understand the overall prevalence of WAA, the risk of RBC alloimmunization and determine whether RBC selection practices have an impact on alloimmunization.Materials and methodsRecords of patients (>1 year of age) with an indirect antibody detection test (IAT) and serologic evidence of WAA over a 10‐year‐period were included. Eight centres from 5 countries collectively reviewed 1 122 245 patients who had an IAT.ResultsOf patients having IAT, 1214 had WAA (0·17%). Transfusion information for 1002 of the patients was available; 631 were transfused after identification of the WAA (63%); of the transfused patients, 390 received prophylactic antigen‐matched (PAM) RBCs and 241 did not. Of the 372 patients with WAA who were transfused and had serologic testing 30+ days following transfusion (30–2765 days), 56 developed new RBC alloimmunization (15·1%). Patients who were transfused using a PAM strategy were not protected from new RBC alloimmunization [14·6% (31 of 212 patients) having PAM transfusion approach compared with those not receiving PAM approach (15·6%, 25 of 160 patients, P = 0·8837)].ConclusionsThe prevalence of WAA in patients having an IAT is low (<1%). A significant portion of patients with WAA form new RBC alloimmunization (15·1%); however, the use of PAM approach for RBC selection was not found to be protective against new alloimmunization.
Bayesian Mixture Poisson Regression for Modeling Spatial Point Pattern of Primary Health Centers in Surabaya
Authors: Murniati Tri , Iriawan Nur , Prastyo Dedy Dwi 
Published: April 2020

Primary Health Centres (PHC) are the first referral health facilities for Indonesian people to seek treatment. The varying distribution of PHC location in central Surabaya, therefore, causes its process to follow the Non-homogeneous Poisson Point Process (NHPP). We use Bayesian analysis coupled with Markov Chain Monte Carlo (MCMC) to model the mixture Poisson regression on NHPP intensity estimation. The result shows that two mixture components are significantly involved in the model along with four variables; i.e., the total population, the number of clean households, Accessibility Index, and the length of road; that produce the smallest Deviance Information Criteria (DIC). Keywords: Bayesian Analysis; Mixture Poisson Regression; NHPP Intensity; Primary Health Centres
Prognostic impacts of changes in left ventricular ejection fraction in heart failure patients with preserved left ventricular ejection fraction
Authors: Yoshihisa Akiomi , Sato Yu , Kanno Yuki , Takiguchi Mai , Yokokawa Tetsuro , Abe Satoshi , Misaka Tomofumi , Sato Takamasa , Oikawa Masayoshi , Kobayashi Atsushi , Yamaki Takayoshi , Kunii Hiroyuki , Takeishi Yasuchika 
Published: April 2020

BackgroundIt has been reported that recovery of left ventricular ejection fraction (LVEF) is associated with better prognosis in heart failure (HF) patients with reduced EF (rEF). However, change of LVEF has not yet been investigated in cases of HF with preserved EF (HFpEF).Methods and resultsConsecutive 1082 HFpEF patients, who had been admitted to hospital due to decompensated HF (EF >50% at the first LVEF assessment at discharge), were enrolled, and LVEF was reassessed within 6 months in the outpatient setting (second LVEF assessment). Among the HFpEF patients, LVEF of 758 patients remained above 50% (pEF group), 138 patients had LVEF of 40%–49% (midrange EF, mrEF group) and 186 patients had LVEF of less than 40% (rEF group). In the multivariable logistic regression analysis, younger age and presence of higher levels of troponin I were predictors of rEF (worsened HFpEF). In the Kaplan-Meier analysis, the cardiac event rate of the groups progressively increased from pEF, mrEF to rEF (log-rank, p<0.001), whereas all-cause mortality did not significantly differ among the groups. In the multivariable Cox proportional hazard analysis, rEF (vs pEF) was not a predictor of all-cause mortality, but an independent predictor of increased cardiac event rates (HR 1.424, 95% CI 1.020 to 1.861, p=0.039).ConclusionAn initial assessment of LVEF and LVEF changes are important for deciding treatment and predicting prognosis in HFpEF patients. In addition, several confounding factors are associated with LVEF changes in worsened HFpEF patients.
Improvements in Clinical Outcomes for BRAFV600E-Mutant Metastatic Colorectal Cancer
Authors: Morris Van K. , Bekaii-Saab Tanios 
Published: April 2020

Abstract
Although the last two decades have seen a broad improvement in overall survival, colorectal cancer is still the second leading cause of cancer deaths worldwide. Patient populations continue to face poor disease prognoses due to the challenges of early detection and the molecular subtypes driving their colorectal cancer. Consequently, many patients present with metastatic colorectal cancer, which often limits options and shifts treatment focus away from curative interventions. BRAFV600E mutations are present in approximately 10% of colorectal cancer tumors and are associated with uninhibited cell proliferation, reduced apoptosis, and resistance to standard therapeutic options. In colorectal cancer, BRAFV600E mutations are associated with decreased overall survival, poor treatment responses, and different patterns of metastatic spread compared with tumors with wild-type BRAF. Success in treating other BRAFV600E-mutant cancers with BRAF inhibitors as monotherapy has not translated into efficacious treatment of metastatic colorectal cancer. Consequently, combination therapy with inhibitors of BRAF, MEK, and EGFR, which overcomes the innate treatment-resistant characteristics of BRAFV600E-mutant colorectal cancer, is now recommended by treatment guidelines.
Radiomics, Tumor Volume, and Blood Biomarkers for Early Prediction of Pseudoprogression in Patients with Metastatic Melanoma Treated with Immune Checkpoint Inhibition
Authors: Basler Lucas , Gabryś Hubert S. , Hogan Sabrina A. , Pavic Matea , Bogowicz Marta , Vuong Diem , Tanadini-Lang Stephanie , Förster Robert , Kudura Ken , Huellner Martin W. , Dummer Reinhard , Guckenberger Matthias , Levesque Mitchell P. 
Published: April 2020

AbstractPurpose:We assessed the predictive potential of positron emission tomography (PET)/CT-based radiomics, lesion volume, and routine blood markers for early differentiation of pseudoprogression from true progression at 3 months.Experimental Design:112 patients with metastatic melanoma treated with immune checkpoint inhibition were included in our study. Median follow-up duration was 22 months. 716 metastases were segmented individually on CT and 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET imaging at three timepoints: baseline (TP0), 3 months (TP1), and 6 months (TP2). Response was defined on a lesion-individual level (RECIST 1.1) and retrospectively correlated with FDG-PET/CT radiomic features and the blood markers LDH/S100. Seven multivariate prediction model classes were generated.Results:Two-year (median) overall survival, progression-free survival, and immune progression–free survival were 69% (not reached), 24% (6 months), and 42% (16 months), respectively. At 3 months, 106 (16%) lesions had progressed, of which 30 (5%) were identified as pseudoprogression at 6 months. Patients with pseudoprogressive lesions and without true progressive lesions had a similar outcome to responding patients and a significantly better 2-year overall survival of 100% (30 months), compared with 15% (10 months) in patients with true progressions/without pseudoprogression (P = 0.002). Patients with mixed progressive/pseudoprogressive lesions were in between at 53% (25 months). The blood prediction model (LDH+S100) achieved an AUC = 0.71. Higher LDH/S100 values indicated a low chance of pseudoprogression. Volume-based models: AUC = 0.72 (TP1) and AUC = 0.80 (delta-volume between TP0/TP1). Radiomics models (including/excluding volume-related features): AUC = 0.79/0.78. Combined blood/volume model: AUC = 0.79. Combined blood/radiomics model (including volume-related features): AUC = 0.78. The combined blood/radiomics model (excluding volume-related features) performed best: AUC = 0.82.Conclusions:Noninvasive PET/CT-based radiomics, especially in combination with blood parameters, are promising biomarkers for early differentiation of pseudoprogression, potentially avoiding added toxicity or delayed treatment switch.
Biomarkers Associated with Beneficial PD-1 Checkpoint Blockade in Non–Small Cell Lung Cancer (NSCLC) Identified Using High-Plex Digital Spatial Profiling
Authors: Zugazagoitia Jon , Gupta Swati , Liu Yuting , Fuhrman Kit , Gettinger Scott , Herbst Roy S. , Schalper Kurt A. , Rimm David L. 
Published: April 2020

Abstract

Purpose:
Only a minority of patients with advanced non–small cell lung cancer (NSCLC) truly benefits from single-agent PD-1 checkpoint blockade, and more robust predictive biomarkers are needed.

Experimental Design:
We assessed tumor samples from 67 immunotherapy-treated NSCLC cases represented in a tissue microarray, 53 of whom had pretreatment samples and received monotherapy. Using GeoMx Digital Spatial Profiling System (NanoString Technologies), we quantified 39 immune parameters simultaneously in four tissue compartments defined by fluorescence colocalization [tumor (panCK+), leucocytes (CD45+), macrophages (CD68+), and nonimmune stroma].

Results:
A total of 156 protein variables were generated per case. In the univariate unadjusted analysis, we found 18 markers associated with outcome in spatial context, five of which remained significant after multiplicity adjustment. In the multivariate analysis, high levels of CD56 and CD4 measured in the CD45 compartment were the only markers that were predictive for all clinical outcomes, including progression-free survival (PFS, HR: 0.24, P = 0.006; and HR: 0.31, P = 0.011, respectively), and overall survival (OS, HR: 0.26, P = 0.014; and HR: 0.23, P = 0.007, respectively). Then, using an orthogonal method based on multiplex immunofluorescence and cell counting (inForm), we validated that high CD56+ immune cell counts in the stroma were associated with PFS and OS in the same cohort.

Conclusions:
This pilot scale discovery study shows the potential of the digital spatial profiling technology in the identification of spatially informed biomarkers of response to PD-1 checkpoint blockade in NSCLC. We identified a number of relevant candidate immune predictors in spatial context that deserve validation in larger independent cohorts.
Epigallocatechin Gallate Induces Hepatic Stellate Cell Senescence and Attenuates Development of Hepatocellular Carcinoma
Authors: Sojoodi Mozhdeh , Wei Lan , Erstad Derek J. , Yamada Suguru , Fujii Tsutomu , Hirschfield Hadassa , Kim Rosa S. , Lauwers Gregory Y. , Lanuti Michael , Hoshida Yujin , Tanabe Kenneth K. , Fuchs Bryan C. 
Published: April 2020

Abstract
Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.
Identification of Functional Variant Enhancers Associated With Atrial Fibrillation
Authors: van Ouwerkerk Antoinette F. , Bosada Fernanda M. , Liu Jia , Zhang Juan , van Duijvenboden Karel , Chaffin Mark , Tucker Nathan R. , Pijnappels Daniel , Ellinor Patrick T. , Barnett Phil , de Vries Antoine A.F. , Christoffels Vincent M. 
Published: April 2020

Rationale:
Genome-wide association studies have identified a large number of common variants (single-nucleotide polymorphisms) associated with atrial fibrillation (AF). These variants are located mainly in noncoding regions of the genome and likely include variants that modulate the function of transcriptional regulatory elements (REs) such as enhancers. However, the actual REs modulated by variants and the target genes of such REs remain to be identified. Thus, the biological mechanisms by which genetic variation promotes AF has thus far remained largely unexplored.

Objective:
To identify REs in genome-wide association study loci that are influenced by AF-associated variants.

Methods and Results:

We screened 2.45 Mbp of human genomic DNA containing 12 strongly AF-associated loci for RE activity using self-transcribing active regulatory region sequencing and a recently generated monoclonal line of conditionally immortalized rat atrial myocytes. We identified 444 potential REs, 55 of which contain AF-associated variants (
P
<10
−8
). Subsequently, using an adaptation of the self-transcribing active regulatory region sequencing approach, we identified 24 variant REs with allele-specific regulatory activity. By mining available chromatin conformation data, the possible target genes of these REs were mapped. To define the physiological function and target genes of such REs, we deleted the orthologue of an RE containing noncoding variants in the
Hcn4
(potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4) locus of the mouse genome. Mice heterozygous for the RE deletion showed bradycardia, sinus node dysfunction, and selective loss of
Hcn4
expression.

Conclusions:

We have identified REs at multiple genetic loci for AF and found that loss of an RE at the
HCN4
locus results in sinus node dysfunction and reduced gene expression. Our approach can be broadly applied to facilitate the identification of human disease-relevant REs and target genes at cardiovascular genome-wide association studies loci.
A Global Probabilistic Dataset for Monitoring Meteorological Droughts
Authors: Turco Marco , Jerez Sonia , Donat Markus G. , Toreti Andrea , Vicente-Serrano Sergio M. , Doblas-Reyes Francisco J. 
Published: April 2020

AbstractAccurate and timely drought information is essential to move from postcrisis to preimpact drought-risk management. A number of drought datasets are already available. They cover the last three decades and provide data in near–real time (using different sources), but they are all “deterministic” (i.e., single realization), and input and output data partly differ between them. Here we first evaluate the quality of long-term and continuous climate data for timely meteorological drought monitoring considering the standardized precipitation index. Then, by applying an ensemble approach, mimicking weather/climate prediction studies, we develop Drought Probabilistic (DROP), a new global land gridded dataset, in which an ensemble of observation-based datasets is used to obtain the best near-real-time estimate together with its associated uncertainty. This approach makes the most of the available information and brings it to the end users. The high-quality and probabilistic information provided by DROP is useful for monitoring applications, and may help to develop global policy decisions on adaptation priorities in alleviating drought impacts, especially in countries where meteorological monitoring is still challenging.