bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factor VIIa induces extracellular vesicles from the endothelium: a potential mechanism for its hemostatic effect
Authors: Das Kaushik , Keshava Shiva , Ansari Shabbir A. , Kondreddy Vijay , Esmon Charles T. , Griffin John H. , Pendurthi Usha R. , Rao L. Vijaya Mohan 
Published: February 2021

Abstract
Recombinant factor FVIIa (rFVIIa) is used as a hemostatic agent to treat bleeding disorders in hemophilia patients with inhibitors and other groups of patients. Our recent studies showed that FVIIa binds endothelial cell protein C receptor (EPCR) and induces protease-activated receptor 1 (PAR1)-mediated biased signaling. The importance of FVIIa-EPCR-PAR1–mediated signaling in hemostasis is unknown. In the present study, we show that FVIIa induces the release of extracellular vesicles (EVs) from endothelial cells both in vitro and in vivo. Silencing of EPCR or PAR1 in endothelial cells blocked the FVIIa-induced generation of EVs. Consistent with these data, FVIIa treatment enhanced the release of EVs from murine brain endothelial cells isolated from wild-type (WT), EPCR-overexpressing, and PAR1-R46Q–mutant mice, but not EPCR-deficient or PAR1-R41Q–mutant mice. In vivo studies revealed that administration of FVIIa to WT, EPCR-overexpressing, and PAR1-R46Q–mutant mice, but not EPCR-deficient or PAR1-R41Q–mutant mice, increased the number of circulating EVs. EVs released in response to FVIIa treatment exhibit enhanced procoagulant activity. Infusion of FVIIa-generated EVs and not control EVs to platelet-depleted mice increased thrombin generation at the site of injury and reduced blood loss. Administration of FVIIa-generated EVs or generation of EVs endogenously by administering FVIIa augmented the hemostatic effect of FVIIa. Overall, our data reveal that FVIIa treatment, through FVIIa-EPCR-PAR1 signaling, releases EVs from the endothelium into the circulation, and these EVs contribute to the hemostatic effect of FVIIa.
A combination of cyclophosphamide and interleukin-2 allows CD4+ T cells converted to Tregs to control scurfy syndrome
Authors: Delville Marianne , Bellier Florence , Leon Juliette , Klifa Roman , Lizot Sabrina , Vinçon Hélène , Sobrino Steicy , Thouenon Romane , Marchal Armance , Garrigue Alexandrine , Olivré Juliette , Charbonnier Soëli , Lagresle-Peyrou Chantal , Amendola Mario , Schambach Axel , Gross David , Lamarthée Baptiste , Benoist Christophe , Zuber Julien , André Isabelle , Cavazzana Marina , Six Emmanuelle 
Published: February 2021

Abstract
Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is caused by mutations in forkhead box P3 (FOXP3), which lead to the loss of function of regulatory T cells (Tregs) and the development of autoimmune manifestations early in life. The selective induction of a Treg program in autologous CD4+ T cells by FOXP3 gene transfer is a promising approach for curing IPEX. We have established a novel in vivo assay of Treg functionality, based on adoptive transfer of these cells into scurfy mice (an animal model of IPEX) and a combination of cyclophosphamide (Cy) conditioning and interleukin-2 (IL-2) treatment. This model highlighted the possibility of rescuing scurfy disease after the latter’s onset. By using this in vivo model and an optimized lentiviral vector expressing human Foxp3 and, as a reporter, a truncated form of the low-affinity nerve growth factor receptor (ΔLNGFR), we demonstrated that the adoptive transfer of FOXP3-transduced scurfy CD4+ T cells enabled the long-term rescue of scurfy autoimmune disease. The efficiency was similar to that seen with wild-type Tregs. After in vivo expansion, the converted CD4FOXP3 cells recapitulated the transcriptomic core signature for Tregs. These findings demonstrate that FOXP3 expression converts CD4+ T cells into functional Tregs capable of controlling severe autoimmune disease.
Visual4DTracker: a tool to interact with 3D + t image stacks
Authors: Cordelli Ermanno , Soda Paolo , Iannello Giulio 
Published: February 2021

Abstract
Background
Biological phenomena usually evolves over time and recent advances in high-throughput microscopy have made possible to collect multiple 3D images over time, generating $$3D+t$$

3
D
+
t

(or 4D) datasets. To extract useful information there is the need to extract spatial and temporal data on the particles that are in the images, but particle tracking and feature extraction need some kind of assistance.

Results
This manuscript introduces our new freely downloadable toolbox, the Visual4DTracker. It is a MATLAB package implementing several useful functionalities to navigate, analyse and proof-read the track of each particle detected in any $$3D+t$$

3
D
+
t

stack. Furthermore, it allows users to proof-read and to evaluate the traces with respect to a given gold standard. The Visual4DTracker toolbox permits the users to visualize and save all the generated results through a user-friendly graphical user interface. This tool has been successfully used in three applicative examples. The first processes synthetic data to show all the software functionalities. The second shows how to process a 4D image stack showing the time-lapse growth of Drosophila cells in an embryo. The third example presents the quantitative analysis of insulin granules in living beta-cells, showing that such particles have two main dynamics that coexist inside the cells.

Conclusions
Visual4DTracker is a software package for MATLAB to visualize, handle and manually track $$3D+t$$

3
D
+
t

stacks of microscopy images containing objects such cells, granules, etc.. With its unique set of functions, it remarkably permits the user to analyze and proof-read 4D data in a friendly 3D fashion. The tool is freely available at https://drive.google.com/drive/folders/19AEn0TqP-2B8Z10kOavEAopTUxsKUV73?usp=sharing
DRPnet: automated particle picking in cryo-electron micrographs using deep regression
Authors: Nguyen Nguyen Phuoc , Ersoy Ilker , Gotberg Jacob , Bunyak Filiz , White Tommi A. 
Published: February 2021

AbstractBackgroundIdentification and selection of protein particles in cryo-electron micrographs is an important step in single particle analysis. In this study, we developed a deep learning-based particle picking network to automatically detect particle centers from cryoEM micrographs. This is a challenging task due to the nature of cryoEM data, having low signal-to-noise ratios with variable particle sizes, shapes, distributions, grayscale variations as well as other undesirable artifacts.ResultsWe propose a double convolutional neural network (CNN) cascade for automated detection of particles in cryo-electron micrographs. This approach, entitled Deep Regression Picker Network or “DRPnet”, is simple but very effective in recognizing different particle sizes, shapes, distributions and grayscale patterns corresponding to 2D views of 3D particles. Particles are detected by the first network, a fully convolutional regression network (FCRN), which maps the particle image to a continuous distance map that acts like a probability density function of particle centers. Particles identified by FCRN are further refined to reduce false particle detections by the second classification CNN. DRPnet’s first CNN pretrained with only a single cryoEM dataset can be used to detect particles from different datasets without retraining. Compared to RELION template-based autopicking, DRPnet results in better particle picking performance with drastically reduced user interactions and processing time. DRPnet also outperforms the state-of-the-art particle picking networks in terms of the supervised detection evaluation metrics recall, precision, and F-measure. To further highlight quality of the picked particle sets, we compute and present additional performance metrics assessing the resulting 3D reconstructions such as number of 2D class averages, efficiency/angular coverage, Rosenthal-Henderson plots and local/global 3D reconstruction resolution.ConclusionDRPnet shows greatly improved time-savings to generate an initial particle dataset compared to manual picking, followed by template-based autopicking. Compared to other networks, DRPnet has equivalent or better performance. DRPnet excels on cryoEM datasets that have low contrast or clumped particles. Evaluating other performance metrics, DRPnet is useful for higher resolution 3D reconstructions with decreased particle numbers or unknown symmetry, detecting particles with better angular orientation coverage.
Esmraldi: efficient methods for the fusion of mass spectrometry and magnetic resonance images
Authors: Grélard Florent , Legland David , Fanuel Mathieu , Arnaud Bastien , Foucat Loïc , Rogniaux Hélène 
Published: February 2021

Abstract
Background
Mass spectrometry imaging (MSI) is a family of acquisition techniques producing images of the distribution of molecules in a sample, without any prior tagging of the molecules. This makes it a very interesting technique for exploratory research. However, the images are difficult to analyze because the enclosed data has high dimensionality, and their content does not necessarily reflect the shape of the object of interest. Conversely, magnetic resonance imaging (MRI) scans reflect the anatomy of the tissue. MRI also provides complementary information to MSI, such as the content and distribution of water.

Results
We propose a new workflow to merge the information from 2D MALDI–MSI and MRI images. Our workflow can be applied to large MSI datasets in a limited amount of time. Moreover, the workflow is fully automated and based on deterministic methods which ensures the reproducibility of the results. Our methods were evaluated and compared with state-of-the-art methods. Results show that the images are combined precisely and in a time-efficient manner.

Conclusion
Our workflow reveals molecules which co-localize with water in biological images. It can be applied on any MSI and MRI datasets which satisfy a few conditions: same regions of the shape enclosed in the images and similar intensity distributions.
Intensive care unit discharge: mind the gap!
Authors: Deana Cristian , Sermann Giovanni , De Monte Amato 
Published: February 2021

AbstractMortality after intensive care discharge is a hot topic in critical care medicine. Many factors probably play a role: patient’s comorbidities and severity of the disease may have great impact on mortality. However it should be taken into account also the level of care that characterizes the ward in which the patient is discharged to. A soft transition from intensive care units to the other hospital wards is desirable to avoid the traumatic step that the fragile post-ICU patient has to face with.
Effects of an individualized analgesia protocol on the need for medical interventions after adenotonsillectomy in children: a randomized controlled trial
Authors: Guo Jian , Zhuang Peijun , Liu Kun , Wan Yuanyuan , Wang Xuan 
Published: February 2021

AbstractBackgroundIt has been proposed that the dose of rescue opioids should be individually titrated to the severity of obstructive sleep apnea after adenotonsillectomy. However, a sleep study is not always available before adenotonsillectomy. This randomized, controlled and blinded trial evaluated a strategy of pain control individualized to the results of a fentanyl test, rather than the results of polysomnography, in children after adenotonsillectomy.MethodsA total of 280 children (3–10 years old) undergoing elective adenotonsillectomy were randomized into an individualized protocol (IP) group or a conservative protocol (CP) group. All patients received a fentanyl test before extubation. Pain was assessed every 10 min in the recovery room, and rescue morphine was given when the Children’s Hospital of Eastern Ontario Pain Scale (CHEOPS) score was > 6. In the IP group, the dose of rescue morphine was individualized to the results of the fentanyl test (10 μg/kg in the case of a positive result and 50 μg/kg in the case of a negative result). In the CP group, the dose was fixed (25 μg/kg). The primary outcome was the percentage of patients requiring at least one medical intervention. The secondary outcome was the median duration of CHEOPS scores > 6.ResultsFewer patients in the IP group than in the CP group required medical interventions [11.9% (16/134) vs 22.3% (29/130),P = 0.025]. The median duration of CHEOPS scores > 6 was shorter in the IP group than in the CP group [20 (95% CI: 17 to 23) min vs 30 (95% CI: 28 to 32) min,P <  0.001].ConclusionsCompared with a conservative dosing approach, this individualized protocol may improve analgesia without a significant increase in respiratory adverse events.Trial registrationClinicalTrials.govNCT02990910, registered on 13/12/2016.
Development of an eHealth programme for self-management of persistent physical symptoms: a qualitative study on user needs in general practice
Authors: Rask Mette Trøllund , Jakobsen Pernille Ravn , Clemensen Jane , Rosendal Marianne , Frostholm Lisbeth 
Published: February 2021

Abstract
Background
Persistent physical symptoms (PPS) are estimated to be present in 17% of patients in general practice. Hence, general practitioners (GPs) play a key role in both the diagnostic assessment and the management of PPS. However, research indicates a need to improve their strategies to support self-help in patients, and eHealth tools may serve as an opportunity. This study aimed to explore patients’ and GPs’ needs related to self-management of PPS. The study was designed to inform the future development of eHealth interventions in this field.

Methods
This qualitative study was based on 20 semi-structured interviews (6 GPs and 14 patients with PPS). Interviews were audiotaped, transcribed verbatim and analysed through a five-step thematic analysis approach. First, we conducted an inductive analysis to identify and explore emerging subthemes. Second, using a deductive mapping strategy, we categorised the derived subthemes according to the COM-B behaviour change model and its three domains: capability, opportunity and motivation.

Results
We identified eleven subthemes in the patient interviews and seven subthemes in the GP interviews. Several unmet needs emerged. First, we identified a need to consider PPS early in the illness trajectory by taking a bio-psycho-social approach. Second, both patients and GPs need better skills to manage uncertainty. Third, hope is important for the patients. Fourth, patients need guidance from their GP in how to self-manage their PPS.

Conclusions
This study provides important insight into key issues and needs related to capability, opportunity and motivation that should be addressed in the design of future eHealth self-management interventions targeting patients with PPS in general practice in order to support and improve care.
Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients
Authors: Osawa Yosuke , Yoshio Sachiyo , Aoki Yoshihiko , Korenaga Masaaki , Imamura Masatoshi , Oide Takashi , Okawara Miku , Kawai Hironari , Tsutsui Yuriko , Yoshida Yuichi , Yoshikawa Shiori , Mori Taizo , Yamazoe Taiji , Kanto Tatsuya 
Published: February 2021

Abstract
Background
Pathological angiogenesis is involved in the development of hepatocellular carcinoma. In patients with chronic hepatitis C (CHC), the level of angiogenic factor angiopoietin (ANGP)-2 is reported to be increased in the blood, correlating with fibrosis. In this study, we aimed to clarify whether blood ANGP-2 is useful as a biomarker for liver angiogenesis and fibrosis in CHC patients and to further reveal the relationship between such pathology in a carbon tetrachloride (CCl4)-treated liver fibrosis mouse model.

Methods
Plasma levels of ANGP-2, expression of a liver sinusoidal endothelial cell (LSEC) marker (CD31), collagen deposition (Sirius Red staining) in the liver, clinical fibrosis markers (Mac-2 binding protein glycosylation isomer, virtual touch quantification, and liver stiffness measurement), and liver function (albumin bilirubin score) were examined in CHC patients. To determine the effects of an anti-angiogenic agent on liver fibrosis in vivo, sorafenib was administered to the CCl4-treated mice (BALB/c male).

Results
The plasma levels of ANGP-2 were increased in CHC patients compared to healthy volunteers and decreased by the eradication of hepatitis C with direct-acting antivirals. In addition, plasma ANGP-2 levels were correlated with CD31 expression, collagen deposition, clinical fibrosis markers, and liver function. Sorafenib inhibited liver angiogenesis and fibrosis in the CCl4-treated mice and was accompanied by decreased ANGP-2 expression in LSECs.

Conclusions
ANGP-2 may serve as a useful biomarker for liver angiogenesis and fibrosis in CHC patients. In addition, angiogenesis and fibrosis may be closely related.
Multiple antimicrobial resistance and outcomes among hospitalized patients with complicated urinary tract infections in the US, 2013–2018: a retrospective cohort study
Authors: Zilberberg Marya D. , Nathanson Brian H. , Sulham Kate , Shorr Andrew F. 
Published: February 2021

Abstract
Background
Complicated urinary tract infection (cUTI) is common among hospitalized patients. Though carbapenems are an effective treatment in the face of rising resistance, overuse drives carbapenem resistance (CR). We hypothesized that resistance to routinely used antimicrobials is common, and, despite frequent use of carbapenems, associated with an increased risk of inappropriate empiric treatment (IET), which in turn worsens clinical outcomes.

Methods
We conducted a retrospective cohort study of patients hospitalized with a culture-positive non-CR cUTI. Triple resistance (TR) was defined as resistance to > 3 of the following: 3rd generation cephalosporins, fluoroquinolones, trimethoprim-sulfamethoxazole, fosfomycin, and nitrofurantoin. Multivariable models quantified the impact of TR and inappropriate empiric therapy (IET) on mortality, hospital LOS, and costs.

Results
Among 23,331 patients with cUTI, 3040 (13.0%) had a TR pathogen. Compared to patients with non-TR, those with TR were more likely male (57.6% vs. 47.7%, p < 0.001), black (17.9% vs. 13.6%, p < 0.001), and in the South (46.3% vs. 41.5%, p < 0.001). Patients with TR had higher chronic (median [IQR] Charlson score 3 [2, 4] vs. 2 [1, 4], p < 0.001) and acute (mechanical ventilation 7.0% vs. 5.0%, p < 0.001; ICU admission 22.3% vs. 18.6%, p < 0.001) disease burden. Despite greater prevalence of empiric carbapenem exposure (43.3% vs. 16.2%, p < 0.001), patient with TR were also more likely to receive IET (19.6% vs. 5.4%, p < 0.001) than those with non-TR. Although mortality was similar between groups, TR added 0.38 (95% CI 0.18, 0.49) days to LOS, and $754 (95% CI $406, $1103) to hospital costs. Both TR and IET impacted the outcomes among cUTI patients whose UTI was not catheter-associated (CAUTI), but had no effect on outcomes in CAUTI.

Conclusions
TR occurs in 1 in 8 patients hospitalized with cUTI. It is associated with an increase in the risk of IET exposure, as well as a modest attributable prolongation of LOS and increase in total costs, particularly in the setting of non-CAUTI.
The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing
Authors: Tsutsuura Moeko , Moriyama Hiromu , Kojima Nana , Mizukami Yuki , Tashiro Sho , Osa Sumika , Enoki Yuki , Taguchi Kazuaki , Oda Kazutaka , Fujii Satoshi , Takahashi Yoshiko , Hamada Yukihiro , Kimura Toshimi , Takesue Yoshio , Matsumoto Kazuaki 
Published: February 2021

Abstract
Background
This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety.

Methods
We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs).

Results
Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 μg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47–0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 μg/mL compared to those at 15–20 μg/mL (OR 2.39, 95% CI 1.78–3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18–0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13–3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28–1.01); however, it was not significant in the analysis of mortality.

Conclusions
We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.
Validity and reliability of the Portuguese version of the modified Migraine Disability Assessment
Authors: Ferreira Pedro L. , Luzeiro Isabel , Lopes Margarida , Jorge André , Silva Bruno , Ferreira Lara 
Published: February 2021

Abstract
Background
Migraine Disability Assessment Scale (MIDAS) is a useful tool to measure headache-related disability. Modified MIDAS with 4-week recall period reduces recall bias and improves accuracy of the results. This study aimed at validating mMIDAS in Portuguese.

Methods
Studied population consisted of adult migraine patients attending a headache outpatient clinic. Reliability was assessed by internal consistency and reproducibility in a 3-week test-retest. Content validity was evaluated by two expert panels. Construct validity was tested by comparing mMIDAS-P index in socioeconomic and clinical patient groups and scale unidimensionality was evidenced by factor analysis. Criterion validity was tested using EQ-5D-5L and HADS.

Results
Ninety-two patients, 88% female, mean age of 44 years, participated. They had, in average, 9.7 headache days in previous month, pain averaging 7.5/10. About 69.9% were on a migraine prophylactic treatment, and 42.4% had severe disability; 29.4 and 13.0% showed, respectively, moderate/severe anxiety and depression. Content validity showed that mMIDAS-P is simple and clinically useful. It did not show to be determined by patient’s sociodemographic characteristics and it was correlated with depression scale and EQ-5D-5L. Test-retest demonstrated high reproductive reliability and good internal consistency.

Conclusion
mMIDAS-P is valid and reliable. We strongly recommend it for clinical and research use.