bluuebunny/crossref_metadata_2025_split huggingface dataset:
Burden of pulmonary hypertension in patients with portal hypertension in the United States: a retrospective database study
Authors: Sahay Sandeep , Tsang Yuen , Flynn Megan , Agron Peter , Dufour Robert 
Published: October 2020

Patients with portal hypertension may develop pulmonary hypertension. The economic implications of these comorbidities have not been systematically assessed. We compared healthcare resource utilization and costs in the United States between patients with co‐existing portal hypertension and pulmonary hypertension (pulmonary hypertension cohort) and a matched cohort of portal hypertension patients without pulmonary hypertension (control cohort). In this retrospective analysis, adult pulmonary hypertension and control patients were identified from the Optum® Clinformatics® Data Mart database between 1 July 2014 and 30 June 2018. All patients had ≥2 claims with diagnosis codes for portal hypertension; pulmonary hypertension patients had ≥2 claims with diagnosis codes for pulmonary hypertension; controls could not have pulmonary hypertension diagnoses or any claims for pulmonary arterial hypertension‐specific medications. Controls were matched to pulmonary hypertension patients by age, sex, Charlson comorbidity index score, and liver diseases. We assessed 12‐month healthcare resource utilization and costs. Each cohort included 146 patients. During follow‐up, pulmonary hypertension cohort patients were more likely than controls to experience a hospitalization (51% vs. 32%, P = 0.0014) and an emergency room visit (55% vs. 41%, P = 0.026). The average annual total cost was higher in pulmonary hypertension patients than for matched controls ($119,912 vs. $81,839, P < 0.0001). After covariate adjustment, costs for pulmonary hypertension cohort patients were 1.47 times higher than those for controls (P = 0.0197). These findings suggest that patients with portal hypertension and co‐existing pulmonary hypertension are at a greater risk for hospitalization and incur higher mean annual total costs than portal hypertension patients without pulmonary hypertension.
Triggering interferon signaling in T cells with avadomide sensitizes CLL to anti-PD-L1/PD-1 immunotherapy
Authors: Ioannou Nikolaos , Hagner Patrick R. , Stokes Matt , Gandhi Anita K. , Apollonio Benedetta , Fanous Mariam , Papazoglou Despoina , Sutton Lesley-Ann , Rosenquist Richard , Amini Rose-Marie , Chiu Hsiling , Lopez-Girona Antonia , Janardhanan Preethi , Awan Farrukh T. , Jones Jeffrey , Kay Neil E. , Shanafelt Tait D. , Tallman Martin S. , Stamatopoulos Kostas , Patten Piers E. M. , Vardi Anna , Ramsay Alan G. 
Published: October 2020

AbstractCancer treatment has been transformed by checkpoint blockade therapies, with the highest anti-tumor activity of anti-programmed death 1 (PD-1) antibody therapy seen in Hodgkin lymphoma. Disappointingly, response rates have been low in the non-Hodgkin lymphomas, with no activity seen in relapsed/refractory chronic lymphocytic leukemia (CLL) with PD-1 blockade. Thus, identifying more powerful combination therapy is required for these patients. Here, we preclinically demonstrate enhanced anti-CLL activity following combinational therapy with anti-PD-1 or anti-PD-1 ligand (PD-L1) and avadomide, a cereblon E3 ligase modulator (CELMoD). Avadomide induced type I and II interferon (IFN) signaling in patient T cells, triggering a feedforward cascade of reinvigorated T-cell responses. Immune modeling assays demonstrated that avadomide stimulated T-cell activation, chemokine expression, motility and lytic synapses with CLL cells, as well as IFN-inducible feedback inhibition through upregulation of PD-L1. Patient-derived xenograft tumors treated with avadomide were converted to CD8+ T cell-inflamed tumor microenvironments that responded to anti-PD-L1/PD-1-based combination therapy. Notably, clinical analyses showed increased PD-L1 expression on T cells, as well as intratumoral expression of chemokine signaling genes in B-cell malignancy patients receiving avadomide-based therapy. These data illustrate the importance of overcoming a low inflammatory T-cell state to successfully sensitize CLL to checkpoint blockade-based combination therapy.
Correntropy induced loss based sparse robust graph regularized extreme learning machine for cancer classification
Authors: Ren Liang-Rui , Gao Ying-Lian , Liu Jin-Xing , Shang Junliang , Zheng Chun-Hou 
Published: October 2020

Abstract
Background
As a machine learning method with high performance and excellent generalization ability, extreme learning machine (ELM) is gaining popularity in various studies. Various ELM-based methods for different fields have been proposed. However, the robustness to noise and outliers is always the main problem affecting the performance of ELM.

Results
In this paper, an integrated method named correntropy induced loss based sparse robust graph regularized extreme learning machine (CSRGELM) is proposed. The introduction of correntropy induced loss improves the robustness of ELM and weakens the negative effects of noise and outliers. By using the L2,1-norm to constrain the output weight matrix, we tend to obtain a sparse output weight matrix to construct a simpler single hidden layer feedforward neural network model. By introducing the graph regularization to preserve the local structural information of the data, the classification performance of the new method is further improved. Besides, we design an iterative optimization method based on the idea of half quadratic optimization to solve the non-convex problem of CSRGELM.

Conclusions
The classification results on the benchmark dataset show that CSRGELM can obtain better classification results compared with other methods. More importantly, we also apply the new method to the classification problems of cancer samples and get a good classification effect.
Impact of data preprocessing on cell-type clustering based on single-cell RNA-seq data
Authors: Wang Chunxiang , Gao Xin , Liu Juntao 
Published: October 2020

Abstract
Background
Advances in single-cell RNA-seq technology have led to great opportunities for the quantitative characterization of cell types, and many clustering algorithms have been developed based on single-cell gene expression. However, we found that different data preprocessing methods show quite different effects on clustering algorithms. Moreover, there is no specific preprocessing method that is applicable to all clustering algorithms, and even for the same clustering algorithm, the best preprocessing method depends on the input data.

Results
We designed a graph-based algorithm, SC3-e, specifically for discriminating the best data preprocessing method for SC3, which is currently the most widely used clustering algorithm for single cell clustering. When tested on eight frequently used single-cell RNA-seq data sets, SC3-e always accurately selects the best data preprocessing method for SC3 and therefore greatly enhances the clustering performance of SC3.

Conclusion
The SC3-e algorithm is practically powerful for discriminating the best data preprocessing method, and therefore largely enhances the performance of cell-type clustering of SC3. It is expected to play a crucial role in the related studies of single-cell clustering, such as the studies of human complex diseases and discoveries of new cell types.
A comparative analysis of chromatin accessibility in cattle, pig, and mouse tissues
Authors: Halstead Michelle M. , Kern Colin , Saelao Perot , Wang Ying , Chanthavixay Ganrea , Medrano Juan F. , Van Eenennaam Alison L. , Korf Ian , Tuggle Christopher K. , Ernst Catherine W. , Zhou Huaijun , Ross Pablo J. 
Published: October 2020

Abstract
Background
Although considerable progress has been made towards annotating the noncoding portion of the human and mouse genomes, regulatory elements in other species, such as livestock, remain poorly characterized. This lack of functional annotation poses a substantial roadblock to agricultural research and diminishes the value of these species as model organisms. As active regulatory elements are typically characterized by chromatin accessibility, we implemented the Assay for Transposase Accessible Chromatin (ATAC-seq) to annotate and characterize regulatory elements in pigs and cattle, given a set of eight adult tissues.

Results
Overall, 306,304 and 273,594 active regulatory elements were identified in pig and cattle, respectively. 71,478 porcine and 47,454 bovine regulatory elements were highly tissue-specific and were correspondingly enriched for binding motifs of known tissue-specific transcription factors. However, in every tissue the most prevalent accessible motif corresponded to the insulator CTCF, suggesting pervasive involvement in 3-D chromatin organization. Taking advantage of a similar dataset in mouse, open chromatin in pig, cattle, and mice were compared, revealing that the conservation of regulatory elements, in terms of sequence identity and accessibility, was consistent with evolutionary distance; whereas pig and cattle shared about 20% of accessible sites, mice and ungulates only had about 10% of accessible sites in common. Furthermore, conservation of accessibility was more prevalent at promoters than at intergenic regions.

Conclusions
The lack of conserved accessibility at distal elements is consistent with rapid evolution of enhancers, and further emphasizes the need to annotate regulatory elements in individual species, rather than inferring elements based on homology. This atlas of chromatin accessibility in cattle and pig constitutes a substantial step towards annotating livestock genomes and dissecting the regulatory link between genome and phenome.
A high-density SNP-based genetic map and several economic traits-related loci in Pelteobagrus vachelli
Authors: Zhang Guosong , Li Jie , Zhang Jiajia , Liang Xia , Wang Tao , Yin Shaowu 
Published: October 2020

Abstract
Background
A high-density genetic linkage map is essential for QTL fine mapping, comparative genome analysis, identification of candidate genes and marker-assisted selection in aquaculture species. Pelteobagrus vachelli is a very popular commercial species in Asia. However, some specific characters hindered achievement of the traditional selective breeding based on phenotypes, such as lack of large-scale genomic resource and short of markers tightly associated with growth, sex determination and hypoxia tolerance related traits.

Results
By making use of 5059 ddRAD markers in P. vachelli, a high-resolution genetic linkage map was successfully constructed. The map’ length was 4047.01 cM by using an interval of 0.11 cm, which is an average marker standard. Comparative genome mapping revealed that a high proportion (83.2%) of markers with a one-to-one correspondence were observed between P. vachelli and P. fulvidraco. Based on the genetic map, 8 significant genome-wide QTLs for 4 weight, 1 body proportion, 2 sex determination, and 1 hypoxia tolerance related traits were detected on 4 LGs. Some SNPs from these significant genome-wide QTLs were observably associated with these phenotypic traits in other individuals by Kompetitive Allele Specific PCR. In addition, two candidate genes for weight, Sipa1 and HSD11B2, were differentially expressed between fast-, medium- and slow-growing P. vachelli. Sema7a, associated with hypoxia tolerance, was induced after hypoxia exposure and reoxygenation.

Conclusions
We mapped a set of suggestive and significant QTLs as well as candidate genes for 12 growth, 1 sex determination and 1 hypoxia tolerance related traits based on a high-density genetic linkage map by making use of SNP markers for P. fulvidraco. Our results have offered a valuable method about the much more efficient production of all-male, fast growth and hypoxia tolerance P. vachelli for the aquaculture industry.
Is salinity the main ecological factor that influences foliar nutrient resorption of desert plants in a hyper-arid environment?
Authors: Wang Lilong , Zhang Xinfang , Xu Shijian 
Published: October 2020

Abstract
Background
Soil salinity is a major abiotic constraint to plant growth and development in the arid and semi-arid regions of the world. However, the influence of soil salinity on the process of nutrient resorption is not well known. We measured the pools of both mature and senesced leaf nitrogen (N), phosphorus (P), potassium (K), and sodium (Na) of desert plants from two types of habitats with contrasting degrees of soil salinity in a hyper-arid environment of northwest China.

Results
N, P, K revealed strict resorption, whereas Na accumulated in senesced leaves. The resorption efficiencies of N, P, and K were positively correlated with each other but not with Na accumulation. The degree of leaf succulence drives both intra-and interspecific variation in leaf Na concentration rather than soil salinity. Both community- and species-level leaf nutrient resorption efficiencies (N, P, K) did not differ between the different habitats, suggesting that soil salinity played a weak role in influencing foliar nutrients resorption.

Conclusions
Our results suggest that plants in hyper-arid saline environments exhibit strict salt ion regulation strategies to cope with drought and ion toxicity and meanwhile ensure the process of nutrient resorption is not affected by salinity.
Improved haemodynamic stability and cerebral tissue oxygenation after induction of anaesthesia with sufentanil compared to remifentanil: a randomised controlled trial
Authors: Poterman Marieke , Kalmar Alain F. , Buisman Pieter L. , Struys Michel M. R. F. , Scheeren Thomas W. L. 
Published: October 2020

Abstract
Background
Balanced anaesthesia with propofol and remifentanil, compared to sufentanil, often decreases mean arterial pressure (MAP), heart rate (HR) and cardiac index (CI), raising concerns on tissue-oxygenation. This distinct haemodynamic suppression might be attenuated by atropine. This double blinded RCT, investigates if induction with propofol-sufentanil results in higher CI and tissue-oxygenation than with propofol-remifentanil and if atropine has more pronounced beneficial effects on CI and tissue-oxygenation in a remifentanil-based anaesthesia.

Methods
In seventy patients scheduled for coronary bypass grafting (CABG), anaesthesia was induced and maintained with propofol target controlled infusion (TCI) with a target effect-site concentration (Cet) of 2.0 μg ml− 1 and either sufentanil (TCI Cet 0.48 ng ml− 1) or remifentanil (TCI Cet 8 ng ml− 1). If HR dropped below 60 bpm, methylatropine (1 mg) was administered intravenously. Relative changes (∆) in MAP, HR, stroke volume (SV), CI and cerebral (SctO2) and peripheral (SptO2) tissue-oxygenation during induction of anaesthesia and after atropine administration were analysed.

Results
The sufentanil group compared to the remifentanil group showed significantly less decrease in MAP (∆ = − 23 ± 13 vs. -36 ± 13 mmHg), HR (∆ = − 5 ± 7 vs. -10 ± 10 bpm), SV (∆ = − 23 ± 18 vs. -35 ± 19 ml) and CI (∆ = − 0.8 (− 1.5 to − 0.5) vs. -1.5 (− 2.0 to − 1.1) l min− 1 m− 2), while SctO2 (∆ = 9 ± 5 vs. 6 ± 4%) showed more increase with no difference in ∆SptO2 (∆ = 8 ± 7 vs. 8 ± 8%). Atropine caused higher ∆HR (13 (9 to 19) vs. 10 ± 6 bpm) and ∆CI (0.4 ± 0.4 vs. 0.2 ± 0.3 l min− 1 m− 2) in sufentanil vs. remifentanil-based anaesthesia, with no difference in ∆MAP, ∆SV and ∆SctO2 and ∆SptO2.

Conclusion
Induction of anaesthesia with propofol and sufentanil results in improved haemodynamic stability and higher SctO2 compared to propofol and remifentanil in patients having CABG. Administration of atropine might be useful to counteract or prevent the haemodynamic suppression associated with these opioids.

Trial registration
Clinicaltrials.gov on June 7, 2013 (trial ID: NCT01871935).
Meigs’ syndrome mimicking heart failure with preserved ejection fraction: a case report
Authors: Murayama Yoko , Kamoi Yoshiro , Yamamoto Hiroyuki , Isogai Jun , Tanaka Takahiro 
Published: October 2020

Abstract
Background
Meigs’ syndrome is a rare disease characterized by a triad of presentations, including benign ovarian tumor, ascites, and pleural effusion. However, a clinical diagnosis of Meigs’ syndrome remains challenging because pleural and ascitic effusions can be common findings in a variety of underlying conditions. Furthermore, these findings can often be misdiagnosed as pleural and peritoneal dissemination caused by potentially malignant tumors, leading to the administration of improper treatment.

Case presentation
We described a case of an 85-year-old postmenopausal female patient with atypical Meigs’ syndrome presenting with right-sided pleural effusion, notable leg edema, and trivial ascites, which was initially mistaken as heart failure with preserved ejection fraction. However, pleural effusion was totally ineffective against diuretic therapy. Subsequently, thoracentesis yielded serosanguineous exudative effusion. Moreover, refractory pleural effusions and abdominal/pelvic computed tomography and magnetic resonance imaging findings strongly suggested bilateral malignant ovarian tumors with pleural dissemination. Repetitive negative cytological results allowed the patient to undergo bilateral salpingo-oophorectomy. Finally, a definitive diagnosis of Meigs’ syndrome was made by confirming the presence of a benign mitotically active cellular fibroma of the ovary by pathology and that pleural effusion resolved following tumor resection.

Conclusions
Our case highlights the clinical importance of assessing Meigs’ syndrome in the diagnostic workup of pleural effusion in postmenopausal female patients. Given the favorable prognosis of Meigs’ syndrome, clinicians should consider surgical resection, even with potentially malignant ovarian tumors with accompanying pleural effusion, ascites, or both.
Interatrial block, P terminal force or fragmented QRS do not predict new-onset atrial fibrillation in patients with severe chronic kidney disease
Authors: Hellman Tapio , Hakamäki Markus , Lankinen Roosa , Koivuviita Niina , Pärkkä Jussi , Kallio Petri , Kiviniemi Tuomas , Airaksinen K. E. Juhani , Järvisalo Mikko J. , Metsärinne Kaj 
Published: October 2020

Abstract
Background
The prevalence of left atrial enlargement (LAE) and fragmented QRS (fQRS) diagnosed using ECG criteria in patients with severe chronic kidney disease (CKD) is unknown. Furthermore, there is limited data on predicting new-onset atrial fibrillation (AF) with LAE or fQRS in this patient group.

Methods
We enrolled 165 consecutive non-dialysis patients with CKD stage 4–5 without prior AF diagnosis between 2013 and 2017 in a prospective follow-up cohort study. LAE was defined as total P-wave duration ≥120 ms in lead II ± > 1 biphasic P-waves in leads II, III or aVF; or duration of terminal negative portion of P-wave > 40 ms or depth of terminal negative portion of P-wave > 1 mm in lead V1 from a baseline ECG, respectively. fQRS was defined as the presence of a notched R or S wave or the presence of ≥1 additional R waves (R’) or; in the presence of a wide QRS complex (> 120 ms), > 2 notches in R or S waves in two contiguous leads corresponding to a myocardial region, respectively.

Results
Mean age of the patients was 59 (SD 14) years, 56/165 (33.9%) were female and the mean estimated glomerular filtration rate was 12.8 ml/min/1.73m2. Altogether 29/165 (17.6%) patients were observed with new-onset AF within median follow-up of 3 [IQR 3, range 2–6] years. At baseline, 137/165 (83.0%) and 144/165 (87.3%) patients were observed with LAE and fQRS, respectively. Furthermore, LAE and fQRS co-existed in 121/165 (73.3%) patients. Neither findings were associated with the risk of new-onset AF within follow-up.

Conclusion
The prevalence of LAE and fQRS at baseline in this study on CKD stage 4–5 patients not on dialysis was very high. However, LAE or fQRS failed to predict occurrence of new-onset AF in these patients.
Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)
Authors: Blennow Nordström Erik , Lilja Gisela , Vestberg Susanna , Ullén Susann , Friberg Hans , Nielsen Niklas , Heimburg Katarina , Evald Lars , Mion Marco , Segerström Magnus , Grejs Anders M. , Keeble Thomas , Kirkegaard Hans , Ljung Hanna , Rose Sofia , Wise Matthew P. , Rylander Christian , Undén Johan , Cronberg Tobias 
Published: October 2020

AbstractBackgroundThis study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA.MethodsThis longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using compositez-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses.DiscussionIn this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA.Trial registrationClinicalTrials.gov,NCT03543371. Registered 1 June 2018