bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and Genomic Epidemiology of Carbapenem-Nonsusceptible
Citrobacter
spp. at a Tertiary Health Care Center over 2 Decades
Authors: Babiker Ahmed , Evans Daniel R. , Griffith Marissa P. , McElheny Christi L. , Hassan Mohamed , Clarke Lloyd G. , Mettus Roberta T. , Harrison Lee H. , Doi Yohei , Shields Ryan K. , Van Tyne Daria 
Published: June 2020

Carbapenem-nonsusceptible
Citrobacter
spp. (CNSC) are increasingly recognized as health care-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000 to 2018 for CNSC, as defined by ertapenem nonsusceptibility. Over this time frame, the proportion of CNSC increased from 4% to 10% (
P =
0.
Recurrent diabetic ketoacidosis and cognitive function among older adults with type 1 diabetes: findings from the Study of Longevity in Diabetes
Authors: Lacy Mary E , Gilsanz Paola , Eng Chloe W , Beeri Michal S , Karter Andrew J , Whitmer Rachel A 
Published: June 2020

IntroductionDiabetic ketoacidosis (DKA) is a serious complication of diabetes. DKA is associated with poorer cognition in children with type 1 diabetes (T1D), but whether this is the case in older adults with T1D is unknown. Given the increasing life expectancy in T1D, understanding the role of DKA on brain health in older adults is crucial.Research design and methodsWe examined the association of DKA with cognitive function in 714 older adults with T1D from the Study of Longevity in Diabetes. Participants self-reported lifetime exposure to DKA resulting in hospitalization; DKA was categorized into 0 hospitalization, 1 hospitalization or ≥2 hospitalizations (recurrent DKA). Global and domain-specific cognition (language, executive function/psychomotor speed, episodic memory and simple attention) were assessed. The association of DKA with cognitive function was evaluated via linear and logistic regression models.ResultsTwenty-eight percent of participants (mean age=67 years; mean age at diagnosis=28 years; average duration of diabetes=39 years) reported a lifetime history of DKA resulting in hospitalization (18.5% single DKA; 9.7% recurrent DKA). In fully adjusted models, those with recurrent DKA had lower global cognitive function (β=−0.13; 95% CI −0.22 to 0.02) and lower scores on the executive function/psychomotor speed domain (β=−0.34; 95% CI −0.51 to 0.17). Individuals with recurrent DKA were also more likely to have the lowest level of cognitive function on the executive function/psychomotor speed domain (defined as 1.5 SD below the population mean; OR=3.26, 95% CI 1.43 to 7.42).ConclusionsAmong 714 older adults with T1D, recurrent DKA was associated with lower global cognitive function, lower scores on the executive function/psychomotor speed domain and 3.3 times greater risk of having the lowest level of cognitive function in our sample on the executive function/psychomotor speed domain. These findings suggest that recurrent DKA may negatively impact the brain health of older patients with T1D and highlight the importance of DKA prevention.
‘I’ve got a little list’—the scourge of a surgical junior. A quality improvement project to change the surgical patient list in a district general hospital
Authors: Khan Hiba , Flesher Elizabeth , Marshman James , Harding Alexander , Bethune Rob , Lawday Samuel 
Published: June 2020

BackgroundJunior doctors at the Royal Devon and Exeter Hospital spend hours every day creating and updating patient lists for all surgical specialties on Microsoft Excel spreadsheets. This not only consumes time that should be spent on clinical tasks, it allows for human errors, system errors and patient safety concerns. Our aim was to reduce time spent on the list and reduce the chance for error.MethodsWe measured the time junior doctors spent creating and updating the surgical lists for one specialty, and on-call shifts. Our first Plan-Do-Study-Act (PDSA) cycle was to introduce clinical secretaries; this reduced the time spent by ward teams on the list but had no effect on the on-call team. We then worked with the hospital application developer to adapt software currently used to suit all surgical teams. Once completed, this software was rolled out alongside the existing spreadsheet method with a view to a switch after a transition period.ResultsThe introduction of clinical secretaries reduced the time spent on the colorectal surgery list from 99.22 min a day to 43.38 min. The on-call team however did not benefit from this intervention. Following the introduction of the new software, the day on-call team time spent on the list changed from 121 min a day to 4.66 min. The night on-call team time changed from 91 min to 7.38 min.ConclusionReducing the time juniors spend compiling surgical lists has clear benefits to patients with extra time for junior doctors to clerk patients. The use of an automated system removes the chance of error in transcription of blood results. Due to the success of this project, colorectal, upper gastrointestinal, urology, vascular and on-call teams have adopted the new list permanently.
Undertriage of the elderly major trauma patient continues in major trauma centre care: a retrospective cohort review
Authors: Hoyle Antonia C , Biant Leela C , Young Mike 
Published: June 2020

BackgroundMajor trauma (Injury Severity Score (ISS) ≥16) in older people is increasing, but concerns persist that major trauma is not always recognised in older patients on triage. This study compared undertriage of older and younger adult major trauma patients in the major trauma centre (MTC) setting to investigate this concern.MethodsA retrospective review of Trauma Audit and Research Network data was conducted for three MTCs in the UK for 3 months in 2014. Age, ISS, injury mechanism and injured areas were examined for all severely injured patients (ISS ≥16) and appropriate major trauma triage rates measured via the surrogate markers of trauma team activation and the presence of a consultant first attender, as per standards for major trauma care set by National Confidential Enquiry into Patient Outcomes and Deaths, Royal College of Surgeons of England and the British Orthopaedic Association. Trends in older (age ≥65) and younger (ages 18–64) adult major trauma presentation, triage and reception were reviewed.ResultsOf 153 severely injured patients, 46 were aged ≥65. Older patients were significantly less likely to receive the attention of a consultant first attender or trauma team. Similar trends were also seen on subgroup analysis by mechanism of injury or number of injured body areas. Older major trauma patients exhibit a higher mortality, despite a lower median ISS (older patient ISS=20 (IQR 16–25), younger patient ISS=25 (IQR 18–29)).ConclusionOlder major trauma patients are at greater risk of undertriage, even in the MTC environment. Existing hospital trauma triage practices should be further investigated to explain and reduce undertriage of elderly trauma patients.
Paramedic experiences of using an enhanced stroke assessment during a cluster randomised trial: a qualitative thematic analysis
Authors: Lally Joanne , Vaittinen Anu , McClelland Graham , Price Christopher I , Shaw Lisa , Ford Gary A , Flynn Darren , Exley Catherine 
Published: June 2020

BackgroundIntravenous thrombolysis is a key element of emergency treatment for acute ischaemic stroke, but hospital service delivery is variable. The Paramedic Acute Stroke Treatment Assessment (PASTA) multicentre cluster randomised controlled trial evaluated whether an enhanced paramedic-initiated stroke assessment pathway could improve thrombolysis volume. This paper reports the findings of a parallel process evaluation which explored intervention paramedics’ experience of delivering the enhanced assessment.MethodsInterviewees were recruited from 453 trained intervention paramedics across three UK ambulance services hosting the trial: North East, North West and Welsh Ambulance Services. A semistructured interview guide aimed to (1) explore the stroke-specific assessment and handover procedures which were part of the PASTA pathway and (2) enable paramedics to share relevant views about expanding their role and any barriers/enablers they encountered. Interviews were audiorecorded, transcribed verbatim and analysed following the principles of the constant comparative method.ResultsTwenty-six interviews were conducted (11 North East, 10 North West and 5 Wales). Iterative data analysis identified four key themes, which reflected paramedics’ experiences at different stages of the care pathway: (1) Enhanced assessment at scene: paramedics felt this improved their skillset and confidence. (2) Prealert to hospital: a mixed experience dependent on receiving hospital staff. (3) Handover to hospital team: standardisation of format was viewed as the primary benefit of the PASTA pathway. (4) Assisting in hospital and feedback: due to professional boundaries, paramedics found these aspects harder to achieve, although feedback from the clinical team was valued when available.ConclusionParamedics believed that the PASTA pathway enhanced their skills and the emergency care of stroke patients, but a continuing clinical role postadmission was challenging. Future studies should consider whether interdisciplinary training is needed to enable more radical extension of professional boundaries for paramedics.
Predicting sudden cardiac death in adults with congenital heart disease
Authors: Oliver Jose M , Gallego Pastora , Gonzalez Ana Elvira , Avila Pablo , Alonso Andres , Garcia-Hamilton Diego , Peinado Rafael , Dos-Subirà Laura , Pijuan-Domenech Antonia , Rueda Joaquín , Rodriguez-Puras Maria-Jose , Garcia-Orta Rocio , Martínez-Quintana Efrén , Datino Tomas , Fernandez-Aviles Francisco , Bermejo Javier 
Published: June 2020

ObjectivesTo develop, calibrate, test and validate a logistic regression model for accurate risk prediction of sudden cardiac death (SCD) and non-fatal sudden cardiac arrest (SCA) in adults with congenital heart disease (ACHD), based on baseline lesion-specific risk stratification and individual’s characteristics, to guide primary prevention strategies.MethodsWe combined data from a single-centre cohort of 3311 consecutive ACHD patients (50% male) at 25-year follow-up with 71 events (53 SCD and 18 non-fatal SCA) and a multicentre case–control group with 207 cases (110 SCD and 97 non-fatal SCA) and 2287 consecutive controls (50% males). Cumulative incidences of events up to 20 years for specific lesions were determined in the prospective cohort. Risk model and its 5-year risk predictions were derived by logistic regression modelling, using separate development (18 centres: 144 cases and 1501 controls) and validation (two centres: 63 cases and 786 controls) datasets.ResultsAccording to the combined SCD/SCA cumulative 20 years incidence, a lesion-specific stratification into four clusters—very-low (<1%), low (1%–4%), moderate (4%–12%) and high (>12%)—was built. Multivariable predictors were lesion-specific cluster, young age, male sex, unexplained syncope, ischaemic heart disease, non-life threatening ventricular arrhythmias, QRS duration and ventricular systolic dysfunction or hypertrophy. The model very accurately discriminated (C-index 0.91; 95% CI 0.88 to 0.94) and calibrated (p=0.3 for observed vs expected proportions) in the validation dataset. Compared with current guidelines approach, sensitivity increases 29% with less than 1% change in specificity.ConclusionsPredicting the risk of SCD/SCA in ACHD can be significantly improved using a baseline lesion-specific stratification and simple clinical variables.
SETD1B-associated neurodevelopmental disorder
Authors: Roston Alexandra , Evans Dan , Gill Harinder , McKinnon Margaret , Isidor Bertrand , Cogné Benjamin , Mwenifumbo Jill , van Karnebeek Clara , An Jianghong , Jones Steven J M , Farrer Matthew , Demos Michelle , Connolly Mary , Gibson William T ,   CAUSES Study
Published: June 2020

BackgroundDysfunction of histone methyltransferases and chromatin modifiers has been implicated in complex neurodevelopmental syndromes and cancers.SETD1Bencodes a lysine-specific methyltransferase that assists in transcriptional activation of genes by depositing H3K4 methyl marks. Previous reports of patients with rare variants inSETD1Bdescribe a distinctive phenotype that includes seizures, global developmental delay and intellectual disability.MethodsTwo of the patients described herein were identified via genome-wide and exome-wide testing, with microarray and research-based exome, through the CAUSES (Clinical Assessment of the Utility of Sequencing and Evaluation as a Service) Research Clinic at the University of British Columbia. The third Vancouver patient had clinical trio exome sequencing through Blueprint Genetics. The fourth patient underwent singleton exome sequencing in Nantes, with subsequent recruitment to this cohort through GeneMatcher.ResultsHere we present clinical reports of four patients with rare coding variants inSETD1Bthat demonstrate a shared phenotype, including intellectual disability, language delay, conserved musculoskeletal findings and seizures that may be treatment-refractory. We include supporting evidence from next-generation sequencing among a cohort of paediatric patients with epilepsy.ConclusionRare coding variants inSETD1Bcan cause a diagnosable syndrome and could contribute as a risk factor for epilepsy, autism and other neurodevelopmental phenotypes. In the long term, some patients may also be at increased risk for cancers and other complex diseases. Thus, longitudinal studies are required to further elucidate the precise role of SETD1B in neurodevelopmental disorders and other systemic disease.
Associations of serum soluble Fas and Fas ligand (FasL) with outcomes in systemic lupus erythematosus
Authors: Vincent Fabien B , Kandane-Rathnayake Rangi , Koelmeyer Rachel , Harris James , Hoi Alberta Y , Mackay Fabienne , Morand Eric F 
Published: June 2020

ObjectiveFas/Fas ligand (FasL) and B cell-activating factor (BAFF) signalling have pivotal roles in SLE pathogenesis. We investigated the clinical associations of serum concentrations of soluble Fas (sFas) and soluble FasL (sFasL) in SLE and their relationship with BAFF.MethodsSerum sFas and sFasL were quantified by multiplex assay, and BAFF by ELISA, in 118 patients with SLE and 17 healthy controls (HC). SLE disease activity and organ damage were assessed using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the Systemic Lupus International Collaborating Clinics Damage Index.ResultssFas, sFasL and BAFF were detectable in all samples. Serum sFas and sFasL were significantly higher in SLE compared with HC. In univariable regression analyses, patients with active renal disease and those with flare had significantly higher levels of sFas compared with those without. High serum BAFF in patients with SLE was associated with increased sFas but not sFasL. The association between sFas and renal disease remained significant after adjusting for BAFF, but the association with flare attenuated. High sFas levels were associated with increased time-adjusted mean SLEDAI-2K, even after adjusting for BAFF, and with higher odds of flare over time. In contrast, high sFasL was associated with reduced organ damage over time. Serum sFasL/sFas ratio was negatively associated with active overall disease, flare and organ damage.ConclusionsSerum sFas is associated with active renal SLE, and active disease and flare over time, while sFasL/sFas ratio is negatively associated with disease activity and organ damage accrual. Treatments correcting abnormal levels of sFas/FasL may be worthy of evaluation in SLE.
Mesenchymal stromal/stem cells modulate response to experimental sepsis-induced lung injury via regulation of miR-27a-5p in recipient mice
Authors: Younes Nadim , Zhou Louis , Amatullah Hajera , Mei Shirley H J , Herrero Raquel , Lorente Jose Angel , Stewart Duncan J , Marsden Philip , Liles W Conrad , Hu Pingzhao , dos Santos Claudia C 
Published: June 2020

IntroductionMesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood.ObjectivesTo identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs.Methods and resultsA total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a statistical estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3′UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation.ConclusionsOur data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome.
Cyclicity of all anti-NMHV and $$\hbox {N}^{2}{\mathrm{MHV}}$$ tree amplitudes in $$\mathcal {N}=4$$ SYM
Authors: Rao Junjie 
Published: June 2020

AbstractThis article proves the cyclicity of anti-NMHV and $$\hbox {N}^{2}{\mathrm{MHV}}$$N2MHV tree amplitudes in planar $$\mathcal {N}=4$$N=4 SYM up to any number of external particles as an interesting application of positive Grassmannian geometry. In this proof the two-fold simplex-like structures of tree amplitudes introduced in 1609.08627 play a key role, as the cyclicity of amplitudes will induce similar simplex-like structures for the boundary generators of homological identities. For this purpose, we only need a part of all distinct boundary generators, and the relevant identities only involve BCFW-like cells. The manifest cyclic invariance in this geometric representation reflects one of the invariant characteristics of amplitudes, though they are obtained by the scheme-dependent BCFW recursion relation.
Alternative to the application of PDG scale factors
Authors: Erler Jens , Ferro-Hernández Rodolfo 
Published: June 2020

AbstractThe Particle Data Group recommends a set of procedures to be applied when discrepant data are to be combined. We introduce an alternative method based on a more general and solid statistical framework, providing a robust way to include possible unknown systematic effects interfering with experimental measurements or their theoretical interpretation. The limit of large data sets and practical cases of interest are discussed in detail.
Photoelectron holography of the H2+ molecule
Authors: Kiss Gellért Zsolt , Borbély Sándor , Tóth Attila , Nagy Ladislau 
Published: June 2020

Abstract

We investigate the photoelectron spectrum of the H2+ target induced by few-cycle XUV laser pulses using first principle calculations. In the photoelectron spectrum, by performing calculations for different internuclear separations, we investigate how the structure of the target is influencing the spatial interference pattern. This interference pattern is created by the coherent superposition of electronic wave packets emitted at the same time, but following different paths. We find that the location of the interference minima in the spectra is dominantly determined by the target’s ionization energy, however, by comparing the H2+ results with model calculations with spherically symmetric potentials, clear differences were observed for the molecular potential relative to the central potentials. Next to the main feature (spatial interference) we have also identified the traces of the two-center interference in the photoelectron spectrum, however, these were mainly washed out due to the complex electronic wave packet dynamics that occurs during the interaction with the considered laser field.

Graphical abstract
Sparse Graph Connectivity for Image Segmentation
Authors: Zhu Xiaofeng , Zhang Shichao , Zhang Jilian , Li Yonggang , Lu Guangquan , Yang Yang 
Published: June 2020

It has been demonstrated that the segmentation performance is highly dependent on both subspace preservation and graph connectivity. In the literature, the full connectivity method linearly represents each data point (
e.g.,
a pixel in one image) by all data points for achieving subspace preservation, while the sparse connectivity method was designed to linearly represent each data point by a set of data points for achieving graph connectivity. However, previous methods only focused on either subspace preservation or graph connectivity. In this article, we propose a Sparse Graph Connectivity (SGC) method for image segmentation to automatically learn the affinity matrix from the low-dimensional space of original data, which aims at simultaneously achieving subspace preservation and graph connectivity. To do this, the proposed SGC simultaneously learns a self-representation affinity matrix for subspace preservation and a sparse affinity matrix for graph connectivity, from the intrinsic low-dimensional feature space of high-dimensional original data. Meanwhile, the self-representation affinity matrix is pushed to be similar to the sparse affinity as well as be the final segmentation results. Experimental result on synthetic and real-image datasets showed that our SGC method achieved the best segmentation performance, compared to state-of-the-art segmentation methods.
Patient Selection Strategies to Maximize Therapeutic Index of Antibody–Drug Conjugates: Prior Approaches and Future Directions
Authors: Williams Marna , Spreafico Anna , Vashisht Kapil , Hinrichs Mary Jane 
Published: June 2020

Abstract
Antibody–drug conjugates (ADC) are targeted agents that have shown promise in treating cancer. A central challenge in development of ADCs is the relatively narrow therapeutic index observed in clinical studies. Patient selection strategies based on expression of the target in tumors have the potential to maximize benefit and provide the best chance of clinical success; however, implementation of biomarker-driven trials can be difficult both practically and scientifically. We conducted a survey of recent clinical experience from early-phase ADC trials completed between 2000 and 2019 to evaluate the different approaches to patient selection currently being used and assess whether there is evidence that target expression is associated with clinical activity. Our analysis of patient selection strategies indicates that optimal trial design for early-stage trials should be based on multiple factors, including prevalence and heterogeneity of target expression among intent-to-treat patients, as well as biological factors influencing expression of cell surface and soluble target. To ensure a high probability of success, early implementation of patient selection strategies centered around target expression are pivotal to development of ADCs. In this review, we propose a strategic approach that can be applied for optimization of trial design.