bluuebunny/crossref_metadata_2025_split huggingface dataset:
CellVGAE: an unsupervised scRNA-seq analysis workflow with graph attention networks
Authors: Buterez David , Bica Ioana , Tariq Ifrah , Andrés-Terré Helena , Liò Pietro 
Published: November 2021

Abstract

Motivation
Single-cell RNA sequencing allows high-resolution views of individual cells for libraries of up to millions of samples, thus motivating the use of deep learning for analysis. In this study, we introduce the use of graph neural networks for the unsupervised exploration of scRNA-seq data by developing a variational graph autoencoder architecture with graph attention layers that operates directly on the connectivity between cells, focusing on dimensionality reduction and clustering. With the help of several case studies, we show that our model, named CellVGAE, can be effectively used for exploratory analysis even on challenging datasets, by extracting meaningful features from the data and providing the means to visualize and interpret different aspects of the model.

Results
We show that CellVGAE is more interpretable than existing scRNA-seq variational architectures by analysing the graph attention coefficients. By drawing parallels with other scRNA-seq studies on interpretability, we assess the validity of the relationships modelled by attention, and furthermore, we show that CellVGAE can intrinsically capture information such as pseudotime and NF-ĸB activation dynamics, the latter being a property that is not generally shared by existing neural alternatives. We then evaluate the dimensionality reduction and clustering performance on 9 difficult and well-annotated datasets by comparing with three leading neural and non-neural techniques, concluding that CellVGAE outperforms competing methods. Finally, we report a decrease in training times of up to × 20 on a dataset of 1.3 million cells compared to existing deep learning architectures.

Availabilityand implementation
The CellVGAE code is available at https://github.com/davidbuterez/CellVGAE.

Supplementary information
Supplementary data are available at Bioinformatics online.
Comparing outcomes of robotic versus open mesorectal excision for rectal cancer
Authors: Jimenez-Rodriguez Rosa M , Flynn Jessica , Patil Sujata , Widmar Maria , Quezada-Diaz Felipe , Lynn Patricio , Strombom Paul , Temple Larissa , Smith J. Joshua , Wei Iris H , Pappou Emmanouil P , Guillem Jose G , Paty Philip B. , Nash Garrett M , Weiser Martin R , Garcia-Aguilar Julio 
Published: November 2021

Abstract

Background
The outcomes of robot-assisted mesorectal excision for rectal cancer, compared with open resection, have not been fully characterized.

Methods
A retrospective analysis of pathologic, short-term, and long-term outcomes in patients with rectal adenocarcinoma who underwent total or tumour-specific mesorectal excision at a high-volume cancer centre between 2008 and 2017 was conducted. Outcomes after robotic and open surgery were compared on an intention-to-treat basis.

Results
Out of 1048 resections performed, 1018 patients were reviewed, with 638 who underwent robotic surgery and 380 open surgery. Robotic surgery was converted to the open approach in 17 (2.7 per cent) patients. Patients who underwent robotic surgery were younger (median 54 (range 22–91) years versus median 58 (range 18–97) years; P &lt; 0.001), had higher tumours (median 80 (range 0–150) mm from the anal verge versus median 70 (0–150) mm; P = 0.001), and were less likely to have received neoadjuvant therapy (64 per cent versus 73 per cent; P = 0.003). For patients who underwent a robotic total mesorectal excision, the operating time was longer (median 283.5 (range 117–712) min versus median 249 (range 70–661) min; P &lt; 0.001). However, the rate of complications was lower (29 per cent versus 45 per cent; P &lt; 0.001) and length of hospital stay was shorter (median 5 (range 1–32) days versus median 7 (range 0–137) days; P &lt; 0.001). Median follow-up of survivors was 2.9 years. The proportion of patients with a positive circumferential resection margin did not differ between the groups, nor did the rate of local recurrence (robotic versus open: 3.7 per cent, 95 per cent c.i. 1.9 to 5.6 versus 2.8 per cent, 95 per cent c.i. 1.0 to 4.6; P = 0.400), systemic recurrence (robotic versus open: 11.7 per cent, 95 per cent c.i. 8.5 to 14.8 versus 13.0 per cent, 95 per cent c.i. 9.2 to 16.5; P = 0.300), or overall survival (robotic versus open: 97.8 per cent, 95 per cent c.i. 96.3 to 99.3 versus 93.5 per cent, 95 per cent c.i. 90.8 to 96.2; P = 0.050). The same results were documented in a subanalysis of 370 matched patients, including 185 who underwent robotic surgery and 185 open surgery, for the overall incidence of any postoperative complications, overall survival, disease-free survival, local recurrence, and systemic recurrence.

Conclusion
In patients with rectal cancer who are candidates for curative resection, robotic mesorectal excision is associated with lower complication rates, shorter length of stay, and equivalent oncologic outcomes, compared with open mesorectal excision.
Optimal Urine Culture Diagnostic Stewardship Practice—Results from an Expert Modified-Delphi Procedure
Authors: Claeys Kimberly C , Trautner Barbara W , Leekha Surbhi , Coffey K C , Crnich Christopher J , Diekema Dan J , Fakih Mohamad G , Goetz Matthew Bidwell , Gupta Kalpana , Jones Makoto M , Leykum Luci , Liang Stephen Y , Pineles Lisa , Pleiss Ashley , Spivak Emily S , Suda Katie J , Taylor Jennifer M , Rhee Chanu , Morgan Daniel J 
Published: November 2021

Abstract

Background
Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

Methods
A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed.

Results
One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions.

Conclusions
These 18 guidance statements can optimize use of urine cultures for better patient outcomes.
Lessons learnt when accounting for competing events in the external validation of time-to-event prognostic models
Authors: Ramspek Chava L , Teece Lucy , Snell Kym I E , Evans Marie , Riley Richard D , van Smeden Maarten , van Geloven Nan , van Diepen Merel 
Published: November 2021

Abstract

Background
External validation of prognostic models is necessary to assess the accuracy and generalizability of the model to new patients. If models are validated in a setting in which competing events occur, these competing risks should be accounted for when comparing predicted risks to observed outcomes.

Methods
We discuss existing measures of calibration and discrimination that incorporate competing events for time-to-event models. These methods are illustrated using a clinical-data example concerning the prediction of kidney failure in a population with advanced chronic kidney disease (CKD), using the guideline-recommended Kidney Failure Risk Equation (KFRE). The KFRE was developed using Cox regression in a diverse population of CKD patients and has been proposed for use in patients with advanced CKD in whom death is a frequent competing event.

Results
When validating the 5-year KFRE with methods that account for competing events, it becomes apparent that the 5-year KFRE considerably overestimates the real-world risk of kidney failure. The absolute overestimation was 10%age points on average and 29%age points in older high-risk patients.

Conclusions
It is crucial that competing events are accounted for during external validation to provide a more reliable assessment the performance of a model in clinical settings in which competing risks occur.
Medicine acceptability for older people in hospital and care home: the influence of setting
Authors: Jani Yogini H , Liu Fang , Orlu Mine , Desai Neel , du Chayla Florence , Ruiz Fabrice , Vallet Thibault 
Published: November 2021

Abstract

Objective
Medicines acceptability is likely to have a significant impact on older people’s adherence and, consequently, treatment effectiveness. The objective was to explore the influence of setting on medicines acceptability in older people.

Methods
A multi-centre, prospective, cross-sectional, observational study was conducted in one care home and one elderly care hospital ward in London, UK, involving individuals on ≥1 medicine(s) and aged ≥65 years. Data-driven approach was applied using multiple observer-reported outcomes analysis tool to distinguish between positively and negatively accepted medicines.

Key findings
263 observer reports from the care home (n = 97) and hospital ward (n = 166) involving 155 distinct medicinal products were assessed. Collectively, medicines appeared better accepted by patients at the hospital. Differences appeared to be driven by variations in solid oral dosage form (SODF) acceptability. Patients with dysphagia poorly accepted medicines in both settings, as expected. SODFs were unexpectedly better accepted in the hospital than in the care home in patients without dysphagia.

Conclusions
Medicines acceptability was affected by patient’s characteristics, dosage form type and setting. Changes in care practices between care home and hospital may affect medicine administration and lead to variations in the ability and willingness of patients and carers to use the product as intended.
Cubic and Quartic Points on Modular Curves Using Generalised Symmetric Chabauty
Authors: Box Josha , Gajović Stevan , Goodman Pip 
Published: November 2021

Abstract
Answering a question of Zureick-Brown, we determine the cubic points on the modular curves $X_0(N)$ for $N \in \{53,57,61,65,67,73\}$ as well as the quartic points on $X_0(65)$. To do so, we develop a “partially relative” symmetric Chabauty method. Our results generalise current symmetric Chabauty theorems and improve upon them by lowering the involved prime bound. For our curves a number of novelties occur. We prove a “higher-order” Chabauty theorem to deal with these cases. Finally, to study the isolated quartic points on $X_0(65)$, we rigorously compute the full rational Mordell–Weil group of its Jacobian.
A Gonococcal Vaccine Has the Potential to Rapidly Reduce the Incidence of Neisseria gonorrhoeae Infection Among Urban Men Who Have Sex With Men
Authors: Hui Ben B , Padeniya Thilini N , Rebuli Nic , Gray Richard T , Wood James G , Donovan Basil , Duan Qibin , Guy Rebecca , Hocking Jane S , Lahra Monica M , Lewis David A , Whiley David M , Regan David G , Seib Kate L 
Published: November 2021

Abstract

Background
A gonococcal vaccine is urgently needed due to increasing gonorrhea incidence and emerging multidrug-resistant gonococcal strains worldwide. Men who have sex with men (MSM) have among the highest incidences of gonorrhea and may be a key target population for vaccination when available.

Methods
An individual-based, anatomical site-specific mathematical model was used to simulate Neisseria gonorrhoeae transmission in a population of 10 000 MSM. The impact of vaccination on gonorrhea prevalence was assessed.

Results
With a gonococcal vaccine of 100% or 50% protective efficacy, gonorrhea prevalence could be reduced by 94% or 62%, respectively, within 2 years if 30% of MSM are vaccinated on presentation for sexually transmitted infection (STI) testing. Elimination of gonorrhea is possible within 8 years with vaccines of ≥ 50% efficacy lasting 2 years, providing a booster vaccination is available every 3 years on average. A vaccine’s impact may be reduced if it is not effective at all anatomical sites.

Conclusions
Our study indicates that with a vaccine of modest efficacy and an immunization strategy that targets MSM presenting for STI screening, the prevalence of gonorrhea in this population could be rapidly and substantially reduced.
Evolutionary conservative analysis revealed novel functional sites in the efflux pump NorA of Staphylococcus aureus
Authors: Shang Yan , Lv Peiwen , Su Dandan , Li Yaru , Liang Yu , Ma Cuiqing , Yang Chunyu 
Published: November 2021

Abstract

Objectives
The NorA antiporter of Staphylococcus aureus belongs to the major facilitator superfamily (MFS) and extrudes various kinds of drugs. With no structure available for this drug efflux pump, the aim of this study was to explore its important structural elements that contribute to substrate binding and drug transport.

Methods
Evolutionary conservative analyses were conducted on different compilations of NorA homologues to identify conservative motifs and residues. Site-directed mutations were constructed to verify the functional changes in NorA efflux capacities and the conformational changes were further measured by fluorescence resonance energy transfer (FRET) and microscale thermophoresis (MST) analysis.

Results
Besides Motif-A, Motif-B and Motif-C that were reported previously in MFS proteins, two other motifs, Motif-1 and Motif-2, were identified in NorA. Site-directed mutations of Motif-1 and Motif-2 as well as 11 predicted binding sites all caused remarkable reductions in drug resistance and efflux activity. Among these, mutant F16A/E222A/F303A/D307A showed an altered binding affinity for tetraphenylphosphonium chloride when measured by MST and Motif-1 mutant G114D/A117E/D118G/V119I and Motif-2 mutant Q325E/G326E/A328E/G330E displayed obvious conformational alterations when compared with the wild-type NorA in the FRET signal spectra.

Conclusions
The NorA structure agrees well with the typical structures of MFS proteins, with two newly identified motifs (Motif-1 and Motif-2) that are critical to the structural stability of NorA, and sites F16, E222, F303 and D307 are involved in substrate binding.
Genotypic, proteomic, and phenotypic approaches to decipher the response to caspofungin and calcineurin inhibitors in clinical isolates of echinocandin-resistantCandida glabrata
Authors: Ceballos-Garzon Andres , Monteoliva Lucia , Gil Concha , Alvarez-Moreno Carlos , Vega-Vela Nelson E , Engelthaler David M , Bowers Jolene , Le Pape Patrice , Parra-Giraldo Claudia M 
Published: November 2021

AbstractBackgroundEchinocandin resistance represents a great concern, as these drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, pathways are crucial for enabling tolerance, evolution, and maintenance of resistance. Therefore, understanding the biological processes and proteins involved in the response to caspofungin may provide clues indicating new therapeutic targets.ObjectivesWe determined the resistance mechanism and assessed the proteome response to caspofungin exposure. We then evaluated the phenotypic impact of calcineurin inhibition by FK506 and cephalosporine A (CsA) on caspofungin-resistant Candida glabrata isolates.MethodsTwenty-five genes associated with caspofungin resistance were analysed by NGS, followed by studies of the quantitative proteomic response to caspofungin exposure. Then, susceptibility testing of caspofungin in presence of FK506 and CsA was performed. The effects of calcineurin inhibitor/caspofungin combinations on heat stress (40°C), oxidative stress (0.2 and 0.4 mM menadione) and on biofilm formation (polyurethane catheter) were analysed. Finally, a Galleria mellonella model using blastospores (1 × 109 cfu/mL) was developed to evaluate the impact of the combinations on larval survival.ResultsF659-del was found in the FKS2 gene of resistant strains. Proteomics data showed some up-regulated proteins are involved in cell-wall biosynthesis, response to stress and pathogenesis, some of them being members of calmodulin–calcineurin pathway. Therefore, the impact of calmodulin inhibition was explored. Calmodulin inhibition restored caspofungin susceptibility, decreased capacity to respond to stress conditions, and reduced biofilm formation and in vivo pathogenicity.ConclusionsOur findings confirm that calmodulin-calcineurin-Crz1 could provide a relevant target in life-threatening invasive candidiasis.
Cesarean scar pregnancy with devastating profuse vaginal bleeding
Authors: Tjokroprawiro Brahmana Askandar , Akbar Muhammad Ilham Aldika 
Published: November 2021

Abstract
A cesarean scar pregnancy (CSP) is a rare type of ectopic pregnancy that does not have any obvious signs or symptoms. However, the gestational sac in CSP is often embedded in the myometrial scar from the previous cesarean section. We report two cases of CSP in women with a history of cesarean sections who experienced profuse vaginal bleeding. The patients underwent hysterectomy at their own request due to devastating bleeding. CSP is one of the complications of cesarean sections. The patient may present with devastating bleeding, and immediate management is necessary. In a woman who is early into her pregnancy and has a history of cesarean section with profuse vaginal bleeding, CSP is one of the possible diagnoses.
Biomechanics of the parasite–host interaction of the European mistletoe
Authors: Mylo Max D , Hofmann Mara , Balle Frank , Beisel Samuel , Speck Thomas , Speck Olga 
Published: November 2021

AbstractThe European mistletoe (Viscum album) is an epiphytic hemiparasite that attaches to its host by an endophytic system. Two aspects are essential for its survival: the structural integrity of the host–parasite interface must be maintained during host growth and the functional integrity of the interface must be maintained during ontogeny and under mechanical stress. We investigated the mechanical properties of the mistletoe–host interaction. Intact and sliced mistletoe–host samples, with host wood as reference, were subjected to tensile tests up to failure. We quantified the rough fractured surface by digital microscopy and analysed local surface strains by digital image correlation. Tensile strength and deformation energy were independent of mistletoe age but exhibited markedly lower values than host wood samples. Cracks initiated at sites with a major strain of about 30%, especially along the mistletoe–host interface. The risk of sudden failure was counteracted by various sinkers and a lignification gradient that smooths the differences in the mechanical properties between the two species. Our results improve the understanding of the key mechanical characteristics of the host–mistletoe interface and show that the mechanical connection between the mistletoe and its host is age-independent. Thus, functional and structural integrity is ensured over the lifetime of the mistletoe.
X-ray spectra of circumgalactic medium around star-forming galaxies: connecting simulations to observations
Authors: Vijayan Aditi , Li Miao 
Published: November 2021

ABSTRACT
The hot component of the circumgalactic medium (CGM) around star-forming galaxies is detected as diffuse X-ray emission. The X-ray spectra from the CGM depend on the temperature and metallicity of the emitting plasma, providing important information about the feeding and feedback of the galaxy. The observed spectra are commonly fitted using simple one-temperature (1-T) or two-temperature (2-T) models. However, the actual temperature distribution of the gas can be complex because of the interaction between galactic outflows and halo gas. Here, we demonstrate this by analysing 3D hydrodynamical simulations of the CGM with a realistic outflow model. We investigate the physical properties of the simulated hot CGM, which shows a broad distribution in density, temperature, and metallicity. By constructing and fitting the simulated spectra, we show that, while the 1-T and 2-T models are able to fit the synthesized spectra reasonably well, the inferred temperature(s) does not bear much physical meaning. Instead, we propose a lognormal distribution as a more physical model. The lognormal model better fits the simulated spectra while reproducing the gas temperature distribution. We also show that when the star formation rate is high, the spectra inside the biconical outflows are distinct from those outside, as outflows are generally hotter and more metal enriched. Finally, we produce mock spectra for future missions with the eV-level spectral resolution, such as Athena, Lynx, the Hot Universe Baryon Surveyor, and theX-ray Imaging and Spectroscopy Mission.
A low-frequency pilot survey of southern H ii regions in the vela constellation
Authors: Tremblay Chenoa D , Bourke Tyler L , Green James A , Dickey John M , Wong O Ivy , Galvin Tim J 
Published: November 2021

ABSTRACT
Atomic ionized regions with strong continuum emission are often associated with regions of high-mass star formation and low-frequency (&lt;2 GHz) observations of these regions are needed to help build star formation models. The region toward the Vela Supernova Remnant is particularly interesting as it is a complex structure of recent supernova explosions and molecular clouds containing a number of H ii regions that are not well characterized. We searched publicly available catalogues for H ii regions, both candidate and identified, which also have low-frequency emission. In the area of ∼400 square degrees toward the Vela Supernova remnant, we found 10 such H ii regions, some of which have multiple components in catalogues. In this work we use data from the Australian Square Kilometre Array Pathfinder and previously unpublished data from the Murchison Widefield Array and the Australian Telescope Compact Array to analyse these sources. The high-mass star forming region RCW 38, with observations specifically targeted on the source, is used as a pilot study to demonstrate how low-frequency, wide-field continuum observations can identify and study H ii regions in our Galaxy. For the nine other H ii regions, we discuss their properties; including information about which clouds are interacting, their ages, whether they are dominated by infrared or optical H α lines, distances, ionizing photon flux, and upper limits on the infrared luminosity. In future work, these nine regions will be analysed in more detail, similar to the result for RCW 38 presented here.
New photometry of 12 ultrashort-period late-type binary stars
Authors: Koen C 
Published: November 2021

ABSTRACT
Candidate late-type binary stars were selected on the basis of their red g − i and r − z colours, and short (0.1159–0.2059 d) published periods. At least one cycle of variation of each star was observed in the RC and IC bands. For the five brightest stars, observations were also obtained in V. Typically ∼17 standardized photometric measurements of each of the stars, ranging over the optical and infrared, are available from various surveys. These were used to accurately determine the reddenings and effective temperatures. In all but one case Gaia parallaxes are available, so that the luminosities of the binaries could also be estimated. Deduced spectral types are in the range M2–M4.5. Preliminary modelling suggests that half the stars may be in contact configurations.