bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 Associated Coagulopathy: Thrombosis, Hemorrhage and Mortality Rates with an Escalated-Thromboprophylaxis Strategy
Authors: Daughety Molly , Ortel Thomas L. , Frost Erin , Morgan Andrew , Kao Chester , Hwang Joyce , Patel Bhavik , Welsby Ian J 
Published: February 2021

Introduction: Early studies identified a prothrombotic state associated with novel coronavirus disease 2019 (COVID-19) as well as a survival benefit observed with heparin use in severely ill COVID-19 patients. There is a need to clarify the incidence of thromboembolic events (TEs), as well as major hemorrhage in COVID-19 patients in the context of an escalated-dose thromboprophylaxis strategy.
Methods: We conducted a single center, retrospective study of 192 consecutive patients with COVID-19 admitted to the hospital between March 26th and May 8th 2020. Our study aimed to investigate the rates of thromboembolic events (TEs), hemorrhage and mortality of in the context of an escalated-dose thromboprophylaxis strategy implemented early in our experience with hospitalized patients with COVID-19.
Results: The incidence of radiographically-confirmed venous thromboembolism (VTE) was 7.3% (n=14), and the rate of combined TEs was 12% (n=23). The rate of major hemorrhage was 6.3% (n=12), including one fatal CNS bleed. The overall mortality rate was 27.6% (n=53).
Conclusion: The rate of VTE and overall TE was much lower than was reported in early studies, and the majority of VTEs occurred in ambulatory patients. Our data suggest that an escalated-dose thromboprophylaxis strategy may help reduce the incidence of inpatient VTEs, and that ambulatory COVID-19 patients may benefit from primary thromboprophylaxis. However, the risk of bleeding was not negligible, and must therefore be assessed on an individual and continual basis when using a more aggressive thromboprophylaxis strategy.

Disclosures
No relevant conflicts of interest to declare.
Clinical Utility of Flow Cytometry Immunophenotyping in Acute Lymphoblastic Leukemia
Authors: Silva Alessandra Suelen Jardim , Oliveira Gustavo Henrique de Medeiros , Júnior Lenilton Silva DA Silva , Ferreira Hugo Henrique de Freitas , Araujo Maria das Graças Pereira , Soares Victor lima , Freitas Rodrigo Villar , Bahia Frank , Oliveira Taissa Moura , Silva Dany GKC , Sales Valéria SF , Soares Rodolfo DA , Paiva Hugo Diogenes De Oliveira , Paiva Aldair Sousa , Cavalcanti Geraldo Barroso 
Published: February 2021

The acute lymphoblastic leukemia (ALL) is a malignant disease of the immune system and hematologic characterized by accumulation of neoplastic B lymphoid precursors or T (lymphoblasts) in the bone marrow and / or peripheral blood. The diagnosis of these leukemias occurs by morphological classification of French-American-British (L1, L2 or L3) associated with features of immunological profile T or B cell malignancies, based on the expression profile of monoclonal antibodies (MoAb) directed against the antigens of cell differentiation by flow cytometry (FC). Several studies have shown that blast cell immunophenotypes of cases of acute lymphoblastic leukemia does not always exhibit characteristics of lymphoid differentiation normal but exhibit aberrant immunophenotypes. Thus, blasts some cases of acute lymphoblastic leukemia of B lineage may show myeloid or T antigens. Also blasts of cases of acute lymphoblastic leukemia T cell determinants may possess B or myeloid cells.Objective:To determine the immunophenotypic profile by FC in 88 patients with ALL (B or T lineage) diagnosed in the Laboratory of Flow Cytometry Blood Center of Dalton Cunha - HEMONORTE, from State of Rio Grande do Norte, Brazil.Methods:All samples from peripheral blood and / or bone marrow were subjected to FC immunophenotyping using a panel of MoAb specific for diagnosis of acute leukemia (AL) directly conjugated to fluorochromes as fluorescein isothiocyanate (FITC), phycoerythrin (PE), peridinin-chlorophyll protein (PerCP) and allophycocyanin (APC).Results:The patients' age range was between 1 month and 84 years old, with an average of 20.3 years, with 62.5% of the patients being male. The most frequently observed strain was B and the most evident subtype was the Common Pre-B ALL. Among the cell markers evaluated, the most expressed in lineage B were CD19, CD10, HLADR and cCD79a and the antigens most frequently expressed in lineage T were cytoplasmic CD3 (cCD3) and membrane (mCD3), CD7, CD5 and CD2. A small percentage (6.8%) were doubly positive T cells.Conclusion:It is concluded that individuals with ALL in this study have demographic, clinical and immunophenotypic characteristics similar to those observed in other studies, demonstrating that CF immunophenotyping is an essential methodology in the diagnosis of follow-up of these leukemias.

Disclosures
No relevant conflicts of interest to declare.
Prognostic impact of corticosteroids on efficacy of chimeric antigen receptor T-cell therapy in large B-cell lymphoma
Authors: Strati Paolo , Ahmed Sairah , Furqan Fateeha , Fayad Luis E. , Lee Hun J. , Iyer Swaminathan P. , Nair Ranjit , Nastoupil Loretta J. , Parmar Simrit , Rodriguez Maria A. , Samaniego Felipe , Steiner Raphael E. , Wang Michael , Pinnix Chelsea C. , Horowitz Sandra B. , Feng Lei , Sun Ryan , Claussen Catherine M. , Hawkins Misha C. , Johnson Nicole A. , Singh Prachee , Mistry Haleigh , Johncy Swapna , Adkins Sherry , Kebriaei Partow , Shpall Elizabeth J. , Green Michael R. , Flowers Christopher R. , Westin Jason , Neelapu Sattva S. 
Published: February 2021

AbstractCorticosteroids are commonly used for the management of severe toxicities associated with chimeric antigen receptor (CAR) T-cell therapy. However, it remains unclear whether their dose, duration, and timing may affect clinical efficacy. Here, we determined the impact of corticosteroids on clinical outcomes in patients with relapsed or refractory large B-cell lymphoma treated with standard of care anti-CD19 CAR T-cell therapy. Among 100 patients evaluated, 60 (60%) received corticosteroids for management of CAR T-cell therapy–associated toxicities. The median cumulative dexamethasone-equivalent dose was 186 mg (range, 8-1803) and the median duration of corticosteroid treatment was 9 days (range, 1-30). Corticosteroid treatment was started between days 0 and 7 in 45 (75%) patients and beyond day 7 in 15 (25%). After a median follow-up of 10 months (95% confidence interval, 8-12 months), use of higher cumulative dose of corticosteroids was associated with significantly shorter progression-free survival. More importantly, higher cumulative dose of corticosteroids, and prolonged and early use after CAR T-cell infusion were associated with significantly shorter overall survival. These results suggest that corticosteroids should be used at the lowest dose and for the shortest duration and their initiation should be delayed whenever clinically feasible while managing CAR T-cell therapy–associated toxicities.
NGlyAlign: an automated library building tool to align highly divergent HIV envelope sequences
Authors: Akand Elma H. , Murray John M. 
Published: February 2021

Abstract
Background
The high variability in envelope regions of some viruses such as HIV allow the virus to establish infection and to escape subsequent immune surveillance. This variability, as well as increasing incorporation of N-linked glycosylation sites, is fundamental to this evasion. It also creates difficulties for multiple sequence alignment methods (MSA) that provide the first step in their analysis. Existing MSA tools often fail to properly align highly variable HIV envelope sequences requiring extensive manual editing that is impractical with even a moderate number of these variable sequences.

Results
We developed an automated library building tool NGlyAlign, that organizes similar N-linked glycosylation sites as block constraints and statistically conserved global sites as single site constraints to automatically enforce partial columns in consistency-based MSA methods such as Dialign. This combined method accurately aligns variable HIV-1 envelope sequences. We tested the method on two datasets: a set of 156 founder and chronic gp160 HIV-1 subtype B sequences as well as a set of reference sequences of gp120 in the highly variable region 1. On measures such as entropy scores, sum of pair scores, column score, and similarity heat maps, NGlyAlign+Dialign proved superior against methods such as T-Coffee, ClustalOmega, ClustalW, Praline, HIValign and Muscle. The method is scalable to large sequence sets producing accurate alignments without requiring manual editing. As well as this application to HIV, our method can be used for other highly variable glycoproteins such as hepatitis C virus envelope.

Conclusions
NGlyAlign is an automated tool for mapping and building glycosylation motif libraries to accurately align highly variable regions in HIV sequences. It can provide the basis for many studies reliant on single robust alignments. NGlyAlign has been developed as an open-source tool and is freely available at https://github.com/UNSW-Mathematical-Biology/NGlyAlign_v1.0 .
IUPACpal: efficient identification of inverted repeats in IUPAC-encoded DNA sequences
Authors: Alamro Hayam , Alzamel Mai , Iliopoulos Costas S. , Pissis Solon P. , Watts Steven 
Published: February 2021

AbstractBackgroundAn inverted repeat is a DNA sequence followed downstream by its reverse complement, potentially with a gap in the centre. Inverted repeats are found in both prokaryotic and eukaryotic genomes and they have been linked with countless possible functions. Many international consortia provide a comprehensive description of common genetic variation making alternative sequence representations, such as IUPAC encoding, necessary for leveraging the full potential of such broad variation datasets.ResultsWe presentIUPACpal, an exact tool for efficient identification of inverted repeats in IUPAC-encoded DNA sequences allowing also for potential mismatches and gaps in the inverted repeats.ConclusionWithin the parameters that were tested, our experimental results show thatIUPACpalcompares favourably to a similar application packaged withEMBOSS. We show thatIUPACpalidentifies many previously unidentified inverted repeats when compared withEMBOSS, and that this is also performed with orders of magnitude improved speed.
In silico drug repositioning based on the integration of chemical, genomic and pharmacological spaces
Authors: Chen Hailin , Zhang Zuping , Zhang Jingpu 
Published: February 2021

Abstract
Background
Drug repositioning refers to the identification of new indications for existing drugs. Drug-based inference methods for drug repositioning apply some unique features of drugs for new indication prediction. Complementary information is provided by these different features. It is therefore necessary to integrate these features for more accurate in silico drug repositioning.

Results
In this study, we collect 3 different types of drug features (i.e., chemical, genomic and pharmacological spaces) from public databases. Similarities between drugs are separately calculated based on each of the features. We further develop a fusion method to combine the 3 similarity measurements. We test the inference abilities of the 4 similarity datasets in drug repositioning under the guilt-by-association principle. Leave-one-out cross-validations show the integrated similarity measurement IntegratedSim receives the best prediction performance, with the highest AUC value of 0.8451 and the highest AUPR value of 0.2201. Case studies demonstrate IntegratedSim produces the largest numbers of confirmed predictions in most cases. Moreover, we compare our integration method with 3 other similarity-fusion methods using the datasets in our study. Cross-validation results suggest our method improves the prediction accuracy in terms of AUC and AUPR values.

Conclusions
Our study suggests that the 3 drug features used in our manuscript are valuable information for drug repositioning. The comparative results indicate that integration of the 3 drug features would improve drug-disease association prediction. Our study provides a strategy for the fusion of different drug features for in silico drug repositioning.
Impact of PNPase on the transcriptome of Rhodobacter sphaeroides and its cooperation with RNase III and RNase E
Authors: Spanka Daniel-Timon , Reuscher Carina Maria , Klug Gabriele 
Published: February 2021

Abstract
Background
The polynucleotide phosphorylase (PNPase) is conserved among both Gram-positive and Gram-negative bacteria. As a core part of the Escherichia coli degradosome, PNPase is involved in maintaining proper RNA levels within the bacterial cell. It plays a major role in RNA homeostasis and decay by acting as a 3′-to-5′ exoribonuclease. Furthermore, PNPase can catalyze the reverse reaction by elongating RNA molecules in 5′-to-3′ end direction which has a destabilizing effect on the prolonged RNA molecule. RNA degradation is often initiated by an endonucleolytic cleavage, followed by exoribonucleolytic decay from the new 3′ end.

Results
The PNPase mutant from the facultative phototrophic Rhodobacter sphaeroides exhibits several phenotypical characteristics, including diminished adaption to low temperature, reduced resistance to organic peroxide induced stress and altered growth behavior. The transcriptome composition differs in the pnp mutant strain, resulting in a decreased abundance of most tRNAs and rRNAs. In addition, PNPase has a major influence on the half-lives of several regulatory sRNAs and can have both a stabilizing or a destabilizing effect. Moreover, we globally identified and compared differential RNA 3′ ends in RNA NGS sequencing data obtained from PNPase, RNase E and RNase III mutants for the first time in a Gram-negative organism. The genome wide RNA 3′ end analysis revealed that 885 3′ ends are degraded by PNPase. A fair percentage of these RNA 3′ ends was also identified at the same genomic position in RNase E or RNase III mutant strains.

Conclusion
The PNPase has a major influence on RNA processing and maturation and thus modulates the transcriptome of R. sphaeroides. This includes sRNAs, emphasizing the role of PNPase in cellular homeostasis and its importance in regulatory networks. The global 3′ end analysis indicates a sequential RNA processing: 5.9% of all RNase E-dependent and 9.7% of all RNase III-dependent RNA 3′ ends are subsequently degraded by PNPase. Moreover, we provide a modular pipeline which greatly facilitates the identification of RNA 5′/3′ ends. It is publicly available on GitHub and is distributed under ICS license.
The effects of a preoperative multidisciplinary conference on outcomes for high-risk patients with challenging surgical treatment options: a retrospective study
Authors: Koike Masayoshi , Yoshimura Mie , Mio Yasushi , Uezono Shoichi 
Published: February 2021

Abstract
Background
Surgical options for patients vary with age and comorbidities, advances in medical technology and patients’ wishes. This complexity can make it difficult for surgeons to determine appropriate treatment plans independently. At our institution, final decisions regarding treatment for patients are made at multidisciplinary meetings, termed High-Risk Conferences, led by the Patient Safety Committee.

Methods
In this retrospective study, we assessed the reasons for convening High-Risk Conferences, the final decisions made and treatment outcomes using conference records and patient medical records for conferences conducted at our institution from April 2010 to March 2018.

Results
A total of 410 High-Risk Conferences were conducted for 406 patients during the study period. The department with the most conferences was cardiovascular surgery (24%), and the reasons for convening conferences included the presence of severe comorbidities (51%), highly difficult surgeries (41%) and nonmedical/personal issues (8%). Treatment changes were made for 49 patients (12%), including surgical modifications for 20 patients and surgery cancellation for 29. The most common surgical modification was procedure reduction (16 patients); 4 deaths were reported. Follow-up was available for 21 patients for whom surgery was cancelled, with 11 deaths reported.

Conclusions
Given that some change to the treatment plan was made for 12% of the patients discussed at the High-Risk Conferences, we conclude that participants of these conferences did not always agree with the original surgical plan and that the multidisciplinary decision-making process of the conferences served to allow for modifications. Many of the modifications involved reductions in procedures to reflect a more conservative approach, which might have decreased perioperative mortality and the incidence of complications as well as unnecessary surgeries. High-risk patients have complex issues, and it is difficult to verify statistically whether outcomes are associated with changes in course of treatment. Nevertheless, these conferences might be useful from a patient safety perspective and minimize the potential for legal disputes.
Correlation of the severity of coronary artery disease with patients' metabolic profile- rationale, design and baseline patient characteristics of the CorLipid trial
Authors: Karagiannidis Efstratios , Sofidis Georgios , Papazoglou Andreas S. , Deda Olga , Panteris Eleftherios , Moysidis Dimitrios V. , Stalikas Nikolaos , Kartas Anastasios , Papadopoulos Anastasios , Stefanopoulos Leandros , Karvounis Haralambos , Gika Helen , Theodoridis Georgios , Sianos Georgios 
Published: February 2021

Abstract
Background
Coronary artery disease (CAD) remains one of the leading causes of mortality and morbidity worldwide. As oxygen and nutrient supply to the myocardium significantly decrease during ischemic periods, important changes occur regarding myocardial intermediary energy metabolism. Metabolomics is an emerging field in systems biology, which quantifies metabolic changes in response to disease progression. This study aims to evaluate the diagnostic utility of plasma metabolomics-based biomarkers for determining the complexity and severity of CAD, as it is assessed via the SYNTAX score.

Methods
Corlipid is a prospective, non-interventional cohort trial empowered to enroll 1065 patients with no previous coronary intervention history, who undergo coronary angiography in University Hospital AHEPA, Thessaloniki. Venous blood samples are collected before coronary angiography. State-of the-art analytical methods are performed to calculate the serum levels of novel biomarkers: ceramides, acyl-carnitines, fatty acids, and proteins such as galectin-3, adiponectin, and the ratio of apolipoprotein B/apolipoprotein A1. Furthermore, all patients will be categorized based on the indication for coronary angiography (acute coronary syndrome, chronic coronary syndrome, preoperative coronary angiography) and on the severity of CAD using the SYNTAX score. Follow-up of 12 months after enrollment will be performed to record the occurrence of major adverse cardiovascular events. A risk prediction algorithm will be developed by combining clinical characteristics with established and novel biomarkers to identify patients at high risk for complex CAD based on their metabolite signatures. The first patient was enrolled in July 2019 and completion of enrollment is expected until May 2021.

Discussion
CorLipid is an ongoing trial aiming to investigate the correlation between metabolic profile and complexity of coronary artery disease in a cohort of patients undergoing coronary angiography with the potential to suggest a decision-making tool with high discriminative power for patients with CAD. To our knowledge, Corlipid is the first study aspiring to create an integrative metabolomic biomarkers-based algorithm by combining metabolites from multiple classes, involved in a wide range of pathways with well-established biochemical markers.
Trial registration CorLipid trial registration: ClinicalTrials.gov number: NCT04580173. Registered 8 October 2020—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04580173.
Circulating level of microRNA-142-5p is a potential biomarker for predicting in-stent restenosis: a case–control study
Authors: Pan Chun-Hsu , Chien Shu-Chen , Chen Chang-Jui , Shih Chun-Ming , Hsieh Ming-Hsiung , Huang Chun-Yao , Bi Wei-Fung , Chan Chao-Shun , Kao Yung-Ta , Hsiao Cheng-Yi , Chiang Shuo-Ju , Chiang Kuang-Hsing , Huang Jen-Hung , Liu Yun-Ru , Luo Ji-Dung , Huang Hui-Yu , Wu Chieh-Hsi 
Published: February 2021

Abstract
Background
Patients who receive percutaneous coronary intervention (PCI) have different chances of developing in-stent restenosis (ISR). To date, no predictable biomarker can be applied in the clinic. MicroRNAs (miRNAs or miRs) play critical roles in transcription regulation, and their circulating levels were reported to have potential as clinical biomarkers.

Methods
In total, 93 coronary stent-implanted patients without pregnancy, liver or renal dysfunction, malignancy, hemophilia, or autoimmune diseases were recruited in this clinical study. All recruited participants were divided into an ISR group (n = 45) and a non-ISR group (n = 48) based on their restenotic status as confirmed by cardiologists at the first follow-up visit (6 months after surgery). Blood samples of all participants were harvested to measure circulating levels of miRNA candidates (miR-132, miR-142-5p, miR-15b, miR-24-2, and miR-424) to evaluate whether these circulating miRNAs can be applied as predictive biomarkers of ISR.

Results
Our data indicated that circulating levels of miR-142-5p were significantly higher in the ISR population, and results from the receiver operating characteristic (ROC) curve analysis also demonstrated superior discriminatory ability of miR-142-5p in predicting patients’ restenotic status. In addition, circulating levels of miR-15b, miR-24-2, and miR-424 had differential expressions in participants with diabetes, hyperlipidemia, and hypertension, respectively.

Conclusions
The current study revealed that the circulating level of miR-142-5p has potential application as a clinical biomarker for predicting the development of ISR in stent-implanted patients.
Reliability and validity of an adapted hip abductor strength measure as a potential new fall risk assessment for older persons: a study protocol
Authors: Gafner Simone Chantal , Bastiaenen Caroline Henrice Germaine , Biver Emmanuel , Ferrari Serge , Allet Lara 
Published: February 2021

Abstract
Background
Persons aged ≥ 65 years are currently the world’s fastest growing age group. An important complication of age is the increasing risk of falls. Falls have multifactorial etiology and modifiable risk factors open for interventions in prevention and rehabilitation, are of high interest. In this context, strong hip abductors seem to be important to prevent falls. A newly adapted measurement device to measure hip abductor strength (HAS) in a closed chain position was developed. We aim to assess feasibility, intra- and inter-tester reliability and construct and criterion validity of the new measure.

Methods
In two subsequent parts a feasibility, reliability and validity study with an adapted measurement instrument for the assessment of HAS (index test) in a closed chain position in persons aged ≥ 65 years will be conducted. Part I investigates feasibility of the measure in clinical settings as well as reliability of the new HAS test (n = 26). Part II evaluates construct and criterion validity (n = 169). Construct validity will be assessed cross-sectional, criterion validity by comparison with prospectively followed up fall history for 12 months (external criterion) and other functional fall risk assessments (Short Physical Performance Battery, Timed Up and Go test, usual gait speed and hand grip strength).

Discussion
Results of feasibility, will give insight in its applicability in daily clinical life and clinimetric properties will show if measurements of HAS in a closed chain position should be encouraged to include in fall risk assessments in older adults.