bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of combined direct oral anticoagulant and antiplatelet among high-risk peripheral arterial disease: a meta-analysis
Authors: Solano S , Obrado G , Balcos K , Heidari M , Gotohio M 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.
Background
Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality and increased risk of limb loss, and despite the wide use of guideline-based antiplatelet therapy, patients remain at high risk for cardiovascular and limb events. There has been increasing interest in novel anticoagulants to improve prevention of complications secondary to PAD.
Purpose
This study aims to determine the effectiveness and safety of combined direct oral anticoagulant plus antiplatelet in reducing MACE, MALE and all-cause mortality among patients with PAD.
Method
Randomized controlled trials with outcomes on major adverse cardiac events (MACE), major adverse limb events (MALE), all-cause mortality and bleeding were searched through PubMed, Cochrane and EBSCOHost.
Result
Pooled analysis of studies on patients peripheral arterial disease showed that anticoagulant combined with antiplatelet have significant benefits compared with antiplatelet alone in reducing major adverse limb events (RR 0.72, 95% CI 0.62 to 0.83) and stroke (RR 0.74, 95% CI 0.57 to 0.97) but had inconclusive results in reducing myocardial infarction (RR 0.85, 95% CI 0.70 to 1.03).There was no significant benefit in reducing cardiovascular death (RR 1.04, 95% CI 0.88 to 1.23) and all-cause mortality (RR 1.02, 95% CI 0.90 to 1.16). Likewise, there was increased risk of bleeding (RR 1.46, 95% CI of 1.18 to 1.80) compared with antiplatelet alone.

Conclusion
Anticoagulant (Rivaroxaban) combined with antiplatelet (aspirin) as alternative to traditional antiplatelet (aspirin) therapy significantly reduced major adverse limb events and stroke. However, there was a higher incidence of bleeding for the combined cohort. Therefore, it is deemed necessary to identify high-risk PAD patients with low risk of bleeding who can benefit the most with the combined intervention.
How to bridge residual distance to target low-density-lipoprotein cholesterol in acute coronary syndrome patients after initial statin therapy?
Authors: Yan B , Lai A , Sun H 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

BACKGROUND
Current guidelines recommend intensive low-density-lipoprotein cholesterol (LDL-C) lowering by ≥50% to target LDL-C &lt;1.4mmol/L after acute coronary syndrome (ACS). Residual distance to LDL-C target can help select treatment strategy after initial statin therapy.

PURPOSE
We aimed to evaluate residual distance to guideline recommended target LDL-C and the proportion of ACS patients who are projected to reach target LDL-C by different statin and non-statin lipid lowering strategies.

METHODS
We retrospectively analyzed 46,114 patients admitted with ACS who survived 1 year from 18 acute hospitals in Hong Kong between Jan 2014 and Dec 2018. Patients were divided into (i) high potency (HP-S; rosuvastatin ≥20mg, atorvastatin ≥40mg or simvastatin ≥80mg); (ii) non-high potency (NHP-S; other statin doses) statin users and (iii) no statin therapy. We calculated the mean distance and percentage LDL-C reduction required to reach dual LDL-C targets (&gt;50% reduction from baseline and &lt;1.4mmol/L). We assumed up-titration from NHP-S to HP-S would further reduce LDL-C by approximately 5-10%; addition of ezetimibe 15-20% and PCSK-9 inhibitor 50-60%.

RESULTS
Of 46,114 patients (60.7% males, mean age 76.2 ± 13.3 years), 80.4% (n = 10945/13614) had LDL-C ≥1.4mmol/L at 12-months after index ACS with 60.2% (n = 18319/30450), 31.9% (n = 9726/30450) and 8.0% (2405/30450) of patients on no statin, NHP-S and HP-S, respectively. 86% of HP-S and 93% of NHP-S users did not reach dual LDL-C targets at 12-months. Among patients on NHP-S and HP-S, the mean LDL-C at 12-months was 2.0 ± 0.7 and2.1 ± 0.9 mmol/L; mean residual distance to target 0.64 ± 0.7 and0.66 ± 0.9 mmol/L; and mean percentage LDL-C reduction required to reach dual LDL-C targets was 22.4 ± 33% and 18.8 ± 36%, respectively. 13% of statin users required &gt;50% further LDL-C reduction to reach targets. Projected proportion of NHP-S users to reach LDL-C targets is 11% (n = 430/3966) by up-titrating to HP-S, 21% (n = 828/3966) by up-titration to HP-S plus ezetimibe and 100% (n = 3966/3966) with PCSK-9 inhibitor plus HP-S and ezetimibe. Projected proportion of HP-S users to reach LDL-C targets is 13% (n = 143/1099) by ezetimibe and 100% (n = 1099/1099) with addition of PCSK-9 inhibitor.

CONCLUSION
The use of high-potency statin was low and almost all statin users did not reach dual LDL-C targets at 12-months after index ACS. High potency statin plus ezetimibe is projected to bridge about a fifth of these patients to target LDL-C. PCSK-9 inhibitor is likely needed in the majority of patients who have not achieved target LDL-C at 12-months after ACS to reach guideline recommendations.
Virtual medical research mentoring and collaboration: breaking the bounds of nationality during the COVID-19 pandemic
Authors: Chan J S K , Lau D H H , King E , Shum Y K L , Roever L , Liu T , Ng K , Dee E C , Ciobanu A , Bazoukis G , Mahmoudi E , Satti D I , Jeevaratnam K , Baranchuk A , Tse G 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

OnBehalf
Cardioovascular Analytics Group

Background
Medical research is critical to professional advancement, and mentoring is an important means of early research engagement in medical training. In contrast to international research collaborations, research mentoring programs are often locally limited. With the COVID-19 pandemic causing drifts to virtual classes and conferences, virtual international medical research mentoring may be viable. We hereby describe our experience with a virtual, international mentorship group for cardiovascular research.

Methods
Our virtual international research mentorship group has been running since 2015. The group focuses on risk stratification and outcomes research in cardiovascular medicine and epidemiology. Mentees from any country or region in all stages of medical careers are welcomed. Considering the increasing emphasis of contemporary research on multidisciplinary healthcare and translational research, our team also includes allied healthcare professionals or students, and graduates from natural sciences (Figure 1). With our members’ diverse backgrounds, we firmly adhere to the principle that all members must be given equal opportunities and treatment, regardless of their age, gender, race, nationality, sexual orientation, family background, and institution of study or practice. We make use of virtual platforms and multi-level mentoring (both senior and peer mentoring), and emphasize active participation, early leadership, open culture, accessible research support, and a distributed research workflow (i.e. an accessible-distributed model).

Results
Since establishment, our group has expanded to include 63 active members from 14 countries (Figure 2), leading a total of 109 peer-reviewed original studies and reviews published. We observed no significant difficulty in communication between team members, nor conflicts due to differences in nationality or ethnicity. Most studies involve cross-country and ethnicity collaborations, and inter-disciplinary and inter-regional knowledge exchanges are frequent. Multi-level mentoring ensured mentoring quality without compromising bonding and communication.

Conclusion
An accessible-distributed model of virtual international medical research collaboration and multi-level mentoring is viable, efficient, and caters to the needs of contemporary healthcare. We hope that others will build similar models and improve medical research mentoring globally. Abstract Figure 1 Abstract Figure 2
Assessment and mitigation of bleeding risk in atrial fibrillation and venous thromboembolism: A Position Paper from the ESC Working Group on Thrombosis, in collaboration with the European Heart Rhythm Association, the Association for Acute CardioVascular Care and the Asia-Pacific Heart Rhythm Society
Authors: Gorog Diana A , Gue Ying X , Chao Tze-Fan , Fauchier Laurent , Ferreiro Jose Luis , Huber Kurt , Konstantinidis Stavros V , Lane Deirdre A , Marin Francisco , Oldgren Jonas , Potpara Tatjana , Roldan Vanessa , Rubboli Andrea , Sibbing Dirk , Tse Hung-Fat , Vilahur Gemma , Lip Gregory Y H 
Published: February 2022

Abstract
Whilst there is a clear clinical benefit of oral anticoagulation (OAC) in patients with atrial fibrillation (AF) and venous thromboembolism (VTE) in reducing the risks of thromboembolism, major bleeding events (especially intracranial bleeds) may still occur and be devastating. The decision to initiate and continue anticoagulation is often based on a careful assessment of both the thromboembolism and bleeding risk. The more common and validated bleeding risk factors have been used to formulate bleeding risk stratification scores, but thromboembolism and bleeding risk factors often overlap. Also, many factors that increase bleeding risk are transient and modifiable, such as variable international normalized ratio values, surgical procedures, vascular procedures, or drug–drug and food–drug interactions. Bleeding risk is also not a static ‘one off’ assessment based on baseline factors but is dynamic, being influenced by ageing, incident comorbidities, and drug therapies. In this Consensus Document, we comprehensively review the published evidence and propose a consensus on bleeding risk assessments in patients with AF and VTE, with the view to summarizing ‘best practice’ when approaching antithrombotic therapy in these patients. We address the epidemiology and size of the problem of bleeding risk in AF and VTE, review established bleeding risk factors, and summarize definitions of bleeding. Patient values and preferences, balancing the risk of bleeding against thromboembolism are reviewed, and the prognostic implications of bleeding are discussed. We propose consensus statements that may help to define evidence gaps and assist in everyday clinical practice.
Genome-wide association study identifies SNP markers and putative candidate genes for terpene traits important forLeptocybe invasaresistance inEucalyptus grandis
Authors: Mhoswa Lorraine , Myburg Alexander A , Slippers Bernard , Külheim Carsten , Naidoo Sanushka 
Published: February 2022

AbstractTerpenes are an important group of plant specialized metabolites influencing, amongst other functions, defence mechanisms against pests. We used a genome-wide association study to identify single nucleotide polymorphism (SNP) markers and putative candidate genes for terpene traits. We tested 15,387 informative SNP markers derived from genotyping 416 Eucalyptus grandis individuals for association with 3 terpene traits, 1,8-cineole, γ-terpinene, and p-cymene. A multilocus mixed model analysis identified 21 SNP markers for 1,8-cineole on chromosomes 2, 4, 6, 7, 8, 9, 10, and 11, that individually explained 3.0%–8.4% and jointly 42.7% of the phenotypic variation. Association analysis of γ-terpinene found 32 significant SNP markers on chromosomes 1, 2, 4, 5, 6, 9, and 11, explaining 3.4–15.5% and jointly 54.5% of phenotypic variation. For p-cymene, 28 significant SNP markers were identified on chromosomes 1, 2, 3, 5, 6, 7, 10, and 11, explaining 3.4–16.1% of the phenotypic variation and jointly 46.9%. Our results show that variation underlying the 3 terpene traits is influenced by a few minor loci in combination with a few major effect loci, suggesting an oligogenic nature of the traits.
Influences of HLH-2 stability on anchor cell fate specification duringCaenorhabditis elegansgonadogenesis
Authors: Benavidez Justin M , Kim Jee Hun , Greenwald Iva 
Published: February 2022

AbstractThe Caenorhabditis elegans E protein ortholog HLH-2 is required for the specification and function of the anchor cell, a unique, terminally differentiated somatic gonad cell that organizes uterine and vulval development. Initially, 4 cells—2 α cells and their sisters, the β cells—have the potential to be the sole anchor cell. The β cells rapidly lose anchor cell potential and invariably become ventral uterine precursor cells, while the 2 α cells interact via LIN-12/Notch to resolve which will be the anchor cell and which will become another ventral uterine precursor cell. HLH-2 protein stability is dynamically regulated in cells with anchor cell potential; initially present in all 4 cells, HLH-2 is degraded in presumptive ventral uterine precursor cells while remaining stable in the anchor cell. Here, we demonstrate that stability of HLH-2 protein is regulated by the activity of lin-12/Notch in both α and β cells. Our analysis provides evidence that activation of LIN-12 promotes degradation of HLH-2 as part of a negative feedback loop during the anchor cell/ventral uterine precursor cell decision by the α cells, and that absence of lin-12 activity in β cells increases HLH-2 stability and may account for their propensity to adopt the anchor cell fate in a lin-12 null background. We also performed an RNA interference screen of 232 ubiquitin-related genes and identified 7 genes that contribute to HLH-2 degradation in ventral uterine precursor cells; however, stabilizing HLH-2 by depleting ubiquitin ligases in a lin-12(+) background does not result in supernumerary anchor cells, suggesting that LIN-12 activation does not oppose hlh-2 activity solely by causing HLH-2 protein degradation. Finally, we provide evidence for lin-12-independent transcriptional regulation of hlh-2 in β cells that correlates with known differences in POP-1/TCF levels and anchor cell potential between α and β cells. Together, our results indicate that hlh-2 activity is regulated at multiple levels to restrict the anchor cell fate to a single cell.
Qiber3D—an open-source software package for the quantitative analysis of networks from 3D image stacks
Authors: Jaeschke Anna , Eckert Hagen , Bray Laura J 
Published: February 2022

Abstract

Background
Optical slice microscopy is commonly used to observe cellular morphology in 3D tissue culture, e.g., the formation of cell-derived networks. The morphometric quantification of these networks is essential to study the cellular phenotype. Commonly, the quantitative measurements are performed on 2D projections of the image stack, resulting in the loss of information in the third dimension. Currently available 3D image analysis tools rely on manual interactions with the software and are therefore not feasible for large datasets.

Findings
Here we present Qiber3D, an open-source image processing toolkit. The software package includes the essential image analysis procedures required for image processing, from the raw image to the quantified data. Optional pre-processing steps can be switched on/off depending on the input data to allow for analyzing networks from a variety of sources. Two reconstruction algorithms are offered to meet the requirements for a wide range of network types. Furthermore, Qiber3D’s rendering capabilities enable the user to inspect each step of the image analysis process interactively to ensure the creation of an optimal workflow for each application.

Conclusions
Qiber3D is implemented as a Python package, and its source code is freely available at https://github.com/theia-dev/Qiber3D. The toolkit was designed using a building block principle to enable the analysis of a variety of structures, such as vascular networks, neuronal structures, or scaffolds from numerous input formats. While Qiber3D can be used interactively in the Python console, it is aimed at unsupervised automation to process large image datasets efficiently.
A super-resolution framework for tensor decomposition
Authors: Li Qiuwei , Prater Ashley , Shen Lixin , Tang Gongguo 
Published: February 2022

Abstract
This work considers a super-resolution framework forovercomplete tensor decomposition. Specifically, we view tensor decomposition as a super-resolution problem of recovering a sum of Dirac measures on the sphere and solve it by minimizing a continuous analog of the $\ell _1$ norm on the space of measures. The optimal value of this optimization defines the tensor nuclear norm. Similar to the separation condition in the super-resolution problem, by explicitly constructing a dual certificate, we develop incoherence conditions of the tensor factors so that they form the unique optimal solution of the continuous analog of $\ell _1$ norm minimization. Remarkably, the derived incoherence conditions are satisfied with high probability by random tensor factors uniformly distributed on the sphere, implying global identifiability of random tensor factors.
Interpolation and stability properties of low-order face and edge virtual element spaces
Authors: Beirão da Veiga L , Mascotto L 
Published: February 2022

AbstractWe analyse the interpolation properties of two-dimensional and three-dimensional low-order virtual element (VE) face and edge spaces, which generalize Nédélec and Raviart–Thomas polynomials to polygonal-polyhedral meshes. Moreover, we investigate the stability properties of the associated $L^2$-discrete bilinear forms, which typically appear in the VE discretization of problems in electromagnetism.
Oral fosfomycin activity against Klebsiella pneumoniae in a dynamic bladder infection in vitro model
Authors: Abbott Iain J. , van Gorp Elke , Wyres Kelly L. , Wallis Steven C. , Roberts Jason A. , Meletiadis Joseph , Peleg Anton Y. 
Published: February 2022

Abstract

Introduction
The use of oral fosfomycin for urinary tract infections (UTIs) caused by non-Escherichia coli uropathogens is uncertain, including Klebsiella pneumoniae, the second most common uropathogen.

Methods
A multicompartment bladder infection in vitro model was used with standard media and synthetic human urine (SHU) to simulate urinary fosfomycin exposure after a single 3 g oral dose (fAUC0–72 16884 mg·h/L, t½ 5.5 h) against 15 K. pneumoniae isolates including ATCC 13883 (MIC 2 to &gt;1024 mg/L) with a constant media inflow (20 mL/h) and 4-hourly voiding of each bladder. The impact of the media (CAMHB + G6P versus SHU) on fosfomycin MIC measurements, drug-free growth kinetics and regrowth after fosfomycin administration was assessed. A low and high starting inoculum (5.5 versus 7.5 log10 cfu/mL) was assessed in the bladder infection model.

Results
Compared with CAMHB, isolates in SHU had a slower growth rate doubling time (37.7 versus 24.1 min) and reduced growth capacity (9.0 ± 0.3 versus 9.4 ± 0.3 log10 cfu/mL), which was further restricted with increased inflow rate (40 mL/h) and more frequent voids (2-hourly). Regrowth was commonly observed in both media with emergence of fosfomycin resistance promoted by a high starting inoculum in CAMHB (MIC rise to ≥1024 mg/L in 13/14 isolates). Resistance was rarely detected in SHU, even with a high starting inoculum (MIC rise to ≥1024 mg/L in 2/14 isolates).

Conclusions
Simulated in an in vitro UTI model, the regrowth of K. pneumoniae urinary isolates was inadequately suppressed following oral fosfomycin therapy. Efficacy was further reduced by a high starting inoculum.
Plasmablastic lymphoma of the rectum: case report of a rare location and literature review
Authors: AlMohamedi Razan Saleh , AlRajban Waleed , AlRikabi Ammar , Arafah Maha 
Published: February 2022

Abstract
Plasmablastic lymphoma (PBL) is an aggressive and rare variant of diffuse large B-cell lymphoma, which is thought to occur in immunocompromised individuals, specifically HIV-positive patients. We report the case of a 27-year-old Saudi male with PBL. The patient had a low CD4 count at presentation, however, he was HIV negative at the time of diagnosis; also Human herpesvirus-8 was negative on immunohistochemical stain, but Epstein–Barr virus showed expression in scattered cells through the utilization of EBV-EBER.
Chronic Wound Infection Model of Acinetobacter baumannii in Outbred Mice
Authors: Ruamsap Nattaya , Thomas Cotrone S , Imerbsin Rawiwan , Reed Matthew C , Gonwong Siriphan , Lurchachaiwong Woradee , Islam Dilara , Wojnarski Mariusz , Vesely Brian A , Lugo-Roman Luis A , Waters Norman C , Zurawski Daniel V , Demons Samandra T 
Published: February 2022

ABSTRACT

Introduction
We established a murine wound infection model with doxycycline treatment against multidrug-resistant Acinetobacter baumannii (AB5075) in Institute of Cancer Research (ICR) outbred mice.

Methods
Using three groups of neutropenic ICR mice, two full-thickness dorsal dermal wounds (6 mm diameter) were made on each mouse. In two groups, wounds were inoculated with 7.0 × 104 colony-forming units of AB5075. Of these two groups, one received a 6-day regimen of doxycycline while the other was sham treated with phosphate-buffered saline as placebo control. Another uninfected/untreated group served as a control. Wound closure, clinical symptoms, bacterial burden in wound beds and organs, and wound histology were investigated.

Results
Doxycycline-treated wounds completely healed by day 21, but untreated, infected wounds failed to heal. Compared to controls, wound infections without treatment resulted in significant reductions in body weight and higher bacterial loads in wound beds, lung, liver, and spleen by day 7. Histological evaluation of wounds on day 21 revealed ulcerated epidermis, muscle necrosis, and bacterial presence in untreated wounds, while wounds treated with doxycycline presented intact epidermis.

Conclusions
Compared to the previously developed BALB/c dermal wound model, this study demonstrates that the mouse strain selected impacts wound severity and resolution. Furthermore, this mouse model accommodates two dorsal wounds rather than only one. These variations offer investigators increased versatility when designing future studies of wound infection. In conclusion, ICR mice are a viable option as a model of dermal wound infection. They accommodate two simultaneous dorsal wounds, and upon infection, these wounds follow a different pattern of resolution compared to BALB/c mice.
The ASTRID simulation: the evolution of supermassive black holes
Authors: Ni Yueying , Di Matteo Tiziana , Bird Simeon , Croft Rupert , Feng Yu , Chen Nianyi , Tremmel Michael , DeGraf Colin , Li Yin 
Published: February 2022

ABSTRACTWe present the evolution of black holes (BHs) and their relationship with their host galaxies in Astrid, a large-volume cosmological hydrodynamical simulation with box size 250 h−1Mpc containing 2 × 55003 particles evolved to z = 3. Astrid statistically models BH gas accretion and active galactic nucleus (AGN) feedback to their environments, applies a power-law distribution for BH seed mass $\, M_{\rm sd}$, uses a dynamical friction model for BH dynamics, and executes a physical treatment of BH mergers. The BH population is broadly consistent with empirical constraints on the BH mass function, the bright end of the luminosity functions, and the time evolution of BH mass and accretion rate density. The BH mass and accretion exhibit a tight correlation with host stellar mass and star formation rate. We trace BHs seeded before z &gt; 10 down to z = 3, finding that BHs carry virtually no imprint of the initial $\, M_{\rm sd}$ except those with the smallest $\, M_{\rm sd}$, where less than 50 per cent of them have doubled in mass. Gas accretion is the dominant channel for BH growth compared to BH mergers. With dynamical friction, Astrid predicts a significant delay for BH mergers after the first encounter of a BH pair, with a typical elapse time of about 200 Myr. There are in total 4.5 × 105 BH mergers in Astrid at z &gt; 3, ∼103 of which have X-ray detectable EM counterparts: a bright $\, {\rm kpc}$ scale dual AGN with LX &gt; 1043 erg s−1. BHs with $\, M_{\rm BH}\sim 10^{7\!-\!8} \, M_{\odot }$ experience the most frequent mergers. Galaxies that host BH mergers are unbiased tracers of the overall $\, M_{\rm BH}\!-\! M_*$ relation. Massive ($\gt 10^{11}\, M_{\odot }$) galaxies have a high occupation number (≳10) of BHs, and hence host the majority of BH mergers.