bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heparin Monitoring with an Anti-Xa Protocol Compared to Activated Clotting Time in Patients on Temporary Mechanical Circulatory Support
Authors: Feih Joel T. , Wallskog Kirsten E. , Rinka Joseph R. G. , Juul Janelle J. , Rein Lisa , Gaglianello Nunzio , Baumann Kreuziger Lisa M. , Joyce David L. , Tawil Justin N. 
Published: August 2021

Background:Temporary mechanical circulatory support (tMCS) devices are used for patients with severe cardiac or respiratory failure; however, these patients are at high risk for clotting and bleeding. The best method to monitor heparin in these patients has not been established.Objective:To determine the risks for bleeding and clotting while monitoring heparin with either anti-Xa or activated clotting time (ACT) in tMCS patients.Methods:A retrospective cohort study was conducted on tMCS patients who received heparin adjusted according to an anti-Xa or ACT protocol. The primary outcome was incidence of major bleeding. Pertinent secondary outcomes were individual components of the primary outcome, clotting events, and time to therapeutic range.Results:There were 103 patients included in the study: 53 in the ACT group and 50 in the anti-Xa group. Overall, there were 30 (56.6%) patients with major bleeding in the ACT group, compared with 16 (32%) patients in the anti-Xa group ( P = 0.017). An anti-Xa–based protocol was associated with a decreased hazard of major bleeding (hazard ratio = 0.388 [0.215-0.701]; P = 0.002) in the univariate analysis. In the multivariable analysis, an anti-Xa protocol remained associated with a significantly lower hazard of bleeding. Findings were similar when broken down into more discrete subgroups of the entire cohort, extracorporeal membrane oxygenation life support (ECMO), and non-ECMO groups.Conclusion and Relevance:Anti-Xa monitoring was associated with a lower hazard of bleeding during tMCS compared to an ACT-based protocol. Further studies should evaluate if anti-Xa monitoring should be preferentially used in tMCS.
Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for the Treatment of Ulcerative Colitis
Authors: Choi David , Stewart Alyssa P. , Bhat Shubha 
Published: August 2021

Objective To review the pharmacological and clinical profile of ozanimod in the treatment of ulcerative colitis (UC). Data Sources A PubMed search was conducted from inception to July 2021 using the keywords ozanimod, ulcerative colitis, and sphingosine 1-phosphate receptor modulator. Information was also extracted from published abstracts and the package insert. Study Selection and Data Extraction Phase 2 and 3 studies and relevant literature on ozanimod pharmacological and clinical profiles were reviewed. Data Synthesis Ozanimod approval was based on True North, a phase 3 trial evaluating ozanimod’s efficacy and safety in the treatment of moderate to severe UC. Compared with placebo, ozanimod led to clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. Additionally, for secondary end points of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing, ozanimod performed significantly better than placebo. Common adverse events included infections, headaches, hypertension, bradycardia, and liver enzyme elevations. Relevance to Patient Care and Clinical Practice Ozanimod is the first sphingosine 1-phosphate modulator to be approved for UC and is administered orally. Its efficacy profile is comparable with other UC medications. However, its safety profile is unique, requiring extensive assessments prior to initiation of and during treatment. Thus, it is unclear how ozanimod will be positioned in UC treatment. Conclusion Ozanimod is another option in the growing arsenal of UC treatment. Although it offers a novel mechanism of action and is administered orally, there are important safety, dosing, and pharmacokinetic factors to consider prior to initiation and use.
Which hip morphology measures and patient factors are associated with age of onset and symptom severity in femoroacetabular impingement syndrome?
Authors: Murphy Nicholas J , Diamond Laura E , Bennell Kim L , Burns Alexander , Dickenson Edward , Eyles Jillian , Fary Camdon , Grieve Stuart M , Griffin Damian R , Kim Young Jo , Linklater James M , Lloyd David G , Molnar Robert , O’Connell Rachel L , O’Donnell John , Randhawa Sunny , J Singh Parminder , Spiers Libby , Tran Phong , Wrigley Tim , Hunter David J 
Published: August 2021

Background: Bony morphology is central to the pathomechanism of femoroacetabular impingement syndrome (FAIS), however isolated radiographic measures poorly predict symptom onset and severity. More comprehensive morphology measurement considered together with patient factors may better predict symptom presentation. This study aimed to determine the morphological parameter(s) and patient factor(s) associated with symptom age of onset and severity in FAIS. Methods: 99 participants (age 32.9 ± 10.5 years; body mass index (BMI 24.3 ± 3.1 kg/m2; 42% females) diagnosed with FAIS received standardised plain radiographs and magnetic resonance scans. Alpha angle in four radial planes (superior to anterior), acetabular version (AV), femoral torsion, lateral centre-edge, anterior centre-edge (ACEA) and femoral neck-shaft angles were measured. Age of symptom onset (age at presentation minus duration of symptoms), international Hip Outcome Tool-33 (iHOT-33) and modified UCLA activity scores were recorded. Backward stepwise regression assessed morphological parameters and patient factors (age, sex, BMI, symptom duration, annual income, private/public healthcare system accessed) to determine variables independently associated with onset age and iHOT-33 score. Results: Earlier symptom onset was associated with larger superoanterior alpha angle ( p = 0.007), smaller AV ( p = 0.023), lower BMI ( p = 0.010) and public healthcare system access ( p = 0.041) (r2 = 0.320). Worse iHOT-33 score was associated with smaller ACEA ( p = 0.034), female sex ( p = 0.040), worse modified UCLA activity score ( p = 0.010) and public healthcare system access ( p < 0.001) (r2 = 0.340). Conclusions: Age of symptom onset was chiefly predicted by femoral and acetabular bony morphology measures, whereas symptom severity predominantly by patient factors. Factors measured explained a small amount of variance in the data; additional unmeasured factors may be more influential.
Voxel-based map of the inter-arterial watershed zones in children
Authors: Barrera Christian A , Chacko Anith , Gonçalves Fabrício Guimarães , Thai Ngoc Jade , Andronikou Savvas 
Published: August 2021

Purpose To create a voxel-based map of the inter-arterial watershed derived from children who have sustained a hypoxic-ischemic injury involving this region at term. Materials and methods Patients 0–18 years of age diagnosed with a hypoxic-ischemic injury of the watershed on magnetic resonance imaging (MRI) were included. Two pediatric neuroradiologists segmented the lesions as visualized on the T2-weighted sequence. All lesion maps were normalized to a brain template and overlapped to create a frequency map in order to highlight the frequency of involvement of portions of the cortical watershed. Results A total of 47 patients (35 boys) were included in the final sample. Their mean age was 7.6 ± 3.6 years. The cortical watershed was successfully mapped. Three watershed regions were defined: the anterior, peri-Sylvian, and posterior watershed zones. The anterior and peri-Sylvian watershed zones are connected through the involvement of the middle frontal gyrus. The peri-Sylvian and the posterior watershed zones are connected through the involvement of the inferior parietal lobule, the posterior aspect of the superior temporal gyrus, and the angular gyrus with the occipital lobe. The temporal lobe and orbital part of the frontal lobe are largely spared in all patients. Conclusion A voxel-based lesion map of children with watershed hypoxic ischemic injury at term was created and three inter-arterial watershed zones defined: anterior, peri-Sylvian, and posterior watersheds.
The association of Greig syndrome and mastocytosis reveals the involvement of the hedgehog pathway in advanced mastocytosis
Authors: Polivka L. , Parietti V. , Bruneau J. , Soucie E. , Madrange M. , Bayard E. , Rignault R. , Canioni D. , Fraitag S. , Lhermitte L. , Feroul M. , Tissandier M. , Rossignol J. , Frenzel L. , Cagnard N. , Meni C. , Bouktit H. , Collange A.-F. , Gougoula C. , Parisot M. , Bader-Meunier B. , Livideanu C. , Laurent C. , Arock M. , Hadj-Rabia S. , Rüther U. , Dubreuil P. , Bodemer C. , Hermine O. , Maouche-Chrétien L. 
Published: August 2021

Abstract
Mastocytosis is a heterogeneous disease characterized by an abnormal accumulation of mast cells (MCs) in 1 or several organs. Although a somatic KIT D816V mutation is detected in ∼85% of patients, attempts to demonstrate its oncogenic effect alone have repeatedly failed, suggesting that additional pathways are involved in MC transformation. From 3 children presenting with both Greig cephalopolysyndactyly syndrome (GCPS, Mendelian Inheritance in Man [175700]) and congenital mastocytosis, we demonstrated the involvement of the hedgehog (Hh) pathway in mastocytosis. GCPS is an extremely rare syndrome resulting from haploinsufficiency of GLI3, the major repressor of Hh family members. From these familial cases of mastocytosis, we demonstrate that the Hh pathway is barely active in normal primary MCs and is overactive in neoplastic MCs. GLI3 and KIT mutations had a synergistic, tumorigenic effect on the onset of mastocytosis in a GCPS mouse model. Finally, Hh inhibitors suppressed neoplastic MC proliferation in vitro and extend the survival time of mice with aggressive systemic mastocytosis (ASM). This work revealed, for the first time, the involvement of Hh signaling in the pathophysiology of mastocytosis and demonstrated the cooperative effects of the KIT and Hh oncogenic pathways in mice with ASM, leading to the identification of new promising therapeutic targets.
Long non-coding RNAs as the critical regulators of doxorubicin resistance in tumor cells
Authors: Khalili-Tanha Ghazaleh , Moghbeli Meysam 
Published: August 2021

AbstractResistance against conventional chemotherapeutic agents is one of the main reasons for tumor relapse and poor clinical outcomes in cancer patients. Various mechanisms are associated with drug resistance, including drug efflux, cell cycle, DNA repair and apoptosis. Doxorubicin (DOX) is a widely used first-line anti-cancer drug that functions as a DNA topoisomerase II inhibitor. However, DOX resistance has emerged as a large hurdle in efficient tumor therapy. Furthermore, despite its wide clinical application, DOX is a double-edged sword: it can damage normal tissues and affect the quality of patients’ lives during and after treatment. It is essential to clarify the molecular basis of DOX resistance to support the development of novel therapeutic modalities with fewer and/or lower-impact side effects in cancer patients. Long non-coding RNAs (lncRNAs) have critical roles in the drug resistance of various tumors. In this review, we summarize the state of knowledge on all the lncRNAs associated with DOX resistance. The majority are involved in promoting DOX resistance. This review paves the way to introducing an lncRNA panel marker for the prediction of the DOX response and clinical outcomes for cancer patients.
Estimation of total mediation effect for high-dimensional omics mediators
Authors: Yang Tianzhong , Niu Jingbo , Chen Han , Wei Peng 
Published: August 2021

AbstractBackgroundEnvironmental exposures can regulate intermediate molecular phenotypes, such as gene expression, by different mechanisms and thereby lead to various health outcomes. It is of significant scientific interest to unravel the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposure and traits. Mediation analysis is an important tool for investigating such relationships. However, it has mainly focused on low-dimensional settings, and there is a lack of a good measure of the total mediation effect. Here, we extend an R-squared (R$$^2$$2) effect size measure, originally proposed in the single-mediator setting, to the moderate- and high-dimensional mediator settings in the mixed model framework.ResultsBased on extensive simulations, we compare our measure and estimation procedure with several frequently used mediation measures, including product, proportion, and ratio measures. Our R$$^2$$2-based second-moment measure has small bias and variance under the correctly specified model. To mitigate potential bias induced by non-mediators, we examine two variable selection procedures, i.e., iterative sure independence screening and false discovery rate control, to exclude the non-mediators. We establish the consistency of the proposed estimation procedures and introduce a resampling-based confidence interval. By applying the proposed estimation procedure, we found that 38% of the age-related variations in systolic blood pressure can be explained by gene expression profiles in the Framingham Heart Study of 1711 individuals. An R package “RsqMed” is available on CRAN.ConclusionR-squared (R$$^2$$2) is an effective and efficient measure for total mediation effect especially under high-dimensional setting.
A graphical, interactive and GPU-enabled workflow to process long-read sequencing data
Authors: Reddy Shishir , Hung Ling-Hong , Sala-Torra Olga , Radich Jerald P. , Yeung Cecilia CS , Yeung Ka Yee 
Published: August 2021

Abstract
Background
Long-read sequencing has great promise in enabling portable, rapid molecular-assisted cancer diagnoses. A key challenge in democratizing long-read sequencing technology in the biomedical and clinical community is the lack of graphical bioinformatics software tools which can efficiently process the raw nanopore reads, support graphical output and interactive visualizations for interpretations of results. Another obstacle is that high performance software tools for long-read sequencing data analyses often leverage graphics processing units (GPU), which is challenging and time-consuming to configure, especially on the cloud.

Results
We present a graphical cloud-enabled workflow for fast, interactive analysis of nanopore sequencing data using GPUs. Users customize parameters, monitor execution and visualize results through an accessible graphical interface. The workflow and its components are completely containerized to ensure reproducibility and facilitate installation of the GPU-enabled software. We also provide an Amazon Machine Image (AMI) with all software and drivers pre-installed for GPU computing on the cloud. Most importantly, we demonstrate the potential of applying our software tools to reduce the turnaround time of cancer diagnostics by generating blood cancer (NB4, K562, ME1, 238 MV4;11) cell line Nanopore data using the Flongle adapter. We observe a 29x speedup and a 93x reduction in costs for the rate-limiting basecalling step in the analysis of blood cancer cell line data.

Conclusions
Our interactive and efficient software tools will make analyses of Nanopore data using GPU and cloud computing accessible to biomedical and clinical scientists, thus facilitating the adoption of cost effective, fast, portable and real-time long-read sequencing.
Describing global pediatric RSV disease at intensive care units in GAVI-eligible countries using molecular point-of-care diagnostics: the RSV GOLD-III study protocol
Authors: Löwensteyn Yvette N. , Mazur Natalie I. , Nair Harish , Willemsen Joukje E. , van Thiel Ghislaine , Bont Louis ,   the RSV GOLD III—ICU Network study group, Garba Maria Ahuoiza , Giwa Fatima Jumai , Rasooly Mohammad Hafiz , Shirpoor Aminullah , Azizyar Merwais , Makalo Lamin , Nyan Ousman , Mohamed Ali , Osman Khalid , Chapagain Ram Hari , Bista Krishna Prasad , Sharma Arun Kumar , Shrestha Prabina , Goka Bamenla , Osman Kwabena , Obodai Evangeline , Mandi Henshaw , Esong Lucas Esuh , Eposse Charlotte Ekoube , Muando Valéria , Mussá Tufária , Said Yasser Habresh , Shoo Aika Abia , Dor Vanessa Jaelle , Gautier Jacqueline , Abicher Lynda 
Published: August 2021

Abstract
Background
Respiratory syncytial virus (RSV) infection is an important cause of hospitalization and death in young children. The majority of deaths (99%) occur in low- and lower-middle-income countries (LMICs). Vaccines against RSV infection are underway. To obtain access to RSV interventions, LMICs depend on support from Gavi, the Vaccine Alliance. To identify future vaccine target populations, information on children with severe RSV infection is required. However, there is a lack of individual patient-level clinical data on instances of life-threatening RSV infection in LMICs. The RSV GOLD III—ICU Network study aims to describe clinical, demographic and socioeconomic characteristics of children with life-threatening RSV infection in Gavi-eligible countries.

Methods
The RSV GOLD-III—ICU Network study is an international, prospective, observational multicenter study and will be conducted in 10 Gavi-eligible countries at pediatric intensive care units and high-dependency units (PICUs/HDUs) during local viral respiratory seasons for 2 years. Children younger than 2 years of age with respiratory symptoms fulfilling the World Health Organization (WHO) “extended severe acute respiratory infection (SARI)” case definition will be tested for RSV using a molecular point-of-care (POC) diagnostic device. Patient characteristics will be collected through a questionnaire. Mortality rates of children admitted to the PICU and/or HDU will be calculated.

Discussion
This multicenter descriptive study will provide a better understanding of the characteristics and mortality rates of children younger than 2 years with RSV infection admitted to the PICU/HDU in LMICs. These results will contribute to knowledge on global disease burden and awareness of RSV and will directly guide decision makers in their efforts to implement future RSV prevention strategies.
Trial registration number: NL9519, May 27, 2021
A comparison of predictors for mortality and bacteraemia in patients suspected of infection
Authors: Andreassen Steen , Møller Jens Kjølseth , Eliakim-Raz Noa , Lisby Gorm , Ward Logan 
Published: August 2021

Abstract
Background
Stratification by clinical scores of patients suspected of infection can be used to support decisions on treatment and diagnostic workup. Seven clinical scores, SepsisFinder (SF), National Early Warning Score (NEWS), Sequential Orgen Failure Assessment (SOFA), Mortality in Emergency Department Sepsis (MEDS), quick SOFA (qSOFA), Shapiro Decision Rule (SDR) and Systemic Inflammatory Response Syndrome (SIRS), were evaluated for their ability to predict 30-day mortality and bacteraemia and for their ability to identify a low risk group, where blood culture may not be cost-effective and a high risk group where direct-from-blood PCR (dfbPCR) may be cost effective.

Methods
Retrospective data from two Danish and an Israeli hospital with a total of 1816 patients were used to calculate the seven scores.

Results
SF had higher Area Under the Receiver Operating curve than the clinical scores for prediction of mortality and bacteraemia, significantly so for MEDS, qSOFA and SIRS. For mortality predictions SF also had significantly higher area under the curve than SDR. In a low risk group identified by SF, consisting of 33% of the patients only 1.7% had bacteraemia and mortality was 4.2%, giving a cost of € 1976 for one positive result by blood culture. This was higher than the cost of € 502 of one positive dfbPCR from a high risk group consisting of 10% of the patients, where 25.3% had bacteraemia and mortality was 24.2%.

Conclusion
This may motivate a health economic study of whether resources spent on low risk blood cultures might be better spent on high risk dfbPCR.
Metagenomic next-generation sequencing for the early diagnosis of talaromycosis in HIV-uninfected patients: five cases report
Authors: Chen Qiuhua , Qiu Ye , Zeng Wen , Wei Xuan , Zhang Jianquan 
Published: August 2021

Abstract
Background
In recent years, talaromycosis is reportedly on the rise in human immunodeficiency virus (HIV)-uninfected patients. However, the misdiagnosis and mistreatment of talaromycosis is more likely in HIV-uninfected patients than in HIV-infected patients because talaromycosis can be easily mistaken for tuberculosis or any other opportunistic infection. Therefore, we used metagenomic next-generation sequencing (mNGS), a novel gene detection method, for the diagnosis of talaromycosis in HIV-uninfected patients.

Case presentation
We report five cases diagnosed as talaromycosis by mNGS in HIV-uninfected patients, which were further confirmed by tissue culture. There were 3 male and 2 female patients. Two patients had a history of rat contact. The misdiagnosis duration ranged from 88 to 245 days. While the results of tissue culture changed from repeated negative to positive, the mNGS result for Talaromyces marneffei was positive earlier in 4 patients. The reads of Talaromyces marneffei in mNGS ranged from 5 to 414. After antifungal therapy, one of the outcomes was death due to the longest duration of misdiagnosis, and the other outcomes were clinical improvement.

Conclusions
mNGS is perhaps a rapid and effective diagnosis approach for the early confirmation of talaromycosis. Antifungal therapy is recommended once Talaromyces marneffei was revealed by mNGS. mNGS might reduce misdiagnosis duration and improve prognosis. Through these findings, we hope to provide some reference for talaromycosis in HIV-uninfected patients diagnosed early with the help of mNGS.
Diagnostic value of combined pleural interleukin-33, adenosine deaminase and peripheral blood tuberculosis T cell spot detection TB for tuberculous pleurisy
Authors: Fenhua Jin , Daohui Wang , Hui Lin , Xiaodong Xia , Wen Huang 
Published: August 2021

AbstractBackgroundTo investigate the correlation between pleural fluid interleukin-33 (IL-33) and adenosine deaminase (ADA) and peripheral blood tuberculosis T cell spot detection (T-SPOT.TB), and the combined value of the three tests for the diagnosis of tuberculous pleurisy.Methods79 patients with pleural effusion admitted from June 2017 to December 2018 were enrolled. They were divided into tuberculous pleural effusion (TPE) group (57 cases, 72.2%) and malignant pleural effusion group (17 cases, 21.5%), pneumonia-like pleural effusion group (5 cases, 6.3%). Correlation between pleural fluid IL-33, pleural effusion ADA and peripheral blood T-SPOT.TB was analyzed, comparison of the three separate and combined diagnostic efficacy was also performed.ResultsThe levels of IL-33, ADA and peripheral blood T-SPOT.TB in patients with TPE were significantly higher than those in non-TPE (P < 0.001). The level of pleural fluid IL-33 was positively correlated with pleural effusion ADA and peripheral blood T-SPOT.TB. The Area under the ROC curve (AUC) of TPE diagnosed by pleural IL-33, ADA and peripheral blood T-SPOT.TB were 0.753, 0.912 and 0.865, respectively. AUC for combined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB is the largest, with a value of 0.962. Specificity is 100% and sensitivity is 88.5%.ConclusionCombined detection of pleural effusion IL-33, ADA and peripheral blood T-SPOT.TB can improve the diagnostic efficacy of tuberculous pleurisy.