bluuebunny/crossref_metadata_2025 huggingface dataset:
Receptor tyrosine kinase MET ligand-interaction classified via machine learning from single-particle tracking data
Authors: Malkusch Sebastian , Rahm Johanna V. , Dietz Marina S. , Heilemann Mike , Sibarita Jean-Baptiste , Lötsch Jörn
Published: February 2022

Internalin B-mediated activation of the membrane-bound receptor tyrosine kinase MET is accompanied by a change in receptor mobility. Conversely, MET receptor mobility can be used to determine reproducibly whether a cell has been treated with internalin B, using machine learning algorithms trained on single-particle tracking data.
Detecting depression in persons living in long-term care: a systematic review and meta-analysis of diagnostic test accuracy studies
Authors: Mele Bria , Watt Jennifer , Wu Pauline , Azeem Feeha , Lew Grace , Holroyd–Leduc Jayna , Goodarzi Zahra
Published: February 2022

Objective

Depressive disorders are common in long-term care (LTC), however, there is no one process used to detect depressive disorders in this setting. Our goal was to describe the diagnostic accuracy of depression detection tools used in LTC settings.

Methods

We conducted a systematic review and meta-analysis of diagnostic accuracy measures. The databases PubMed, EMBASE, PsycINFO and CINAHL were searched from inception to 10 September 2021. Studies involving persons living in LTC, assisted living residences or facilities, comparing diagnostic accuracy of depression tools with a reference standard, were included. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to assess risk of bias.

Results

We identified 8,463 citations, of which 20 studies were included in qualitative synthesis and 19 in meta-analysis. We identified 23 depression detection tools (including different versions) that were validated against a reference standard. At a cut-off point of 6 on the Geriatric Depression Scale-15 (GDS-15), the pooled sensitivity was 73.6% (95% confidence interval (CI) 43.9%–76.5%), specificity was 76.5% (95% CI 62.9%–86.7%), and an area under the curve was 0.83. There was significant heterogeneity in these analyses. There was insufficient data to conduct meta-analysis of other screening tools. The Nursing Homes Short Depression Inventory (NH-SDI) had a sensitivity ranging from 40.0% to 98.0%. The 4-item Cornell Scale for Depression in Dementia (CSDD) had the highest sensitivity (67.0%–90.0%) for persons in LTC living with dementia.

Conclusions

There are 23 tools validated for detection of depressive disorders in LTC, with the GDS-15 being the most studied. Tools developed specifically for use in LTC settings include the NH-SDI and CSDD-4, which provide briefer options to screen for depression. However, more studies of both are needed to examine tool accuracy using meta-analyses.
Slavery and Interethnic Sexual Violence
Authors: Herzig Tamar
Published: February 2022

This article unpacks the 1610 case of a multiple perpetrator rape of enslaved female Jews from Tétouan by Catholic convicts and Muslim slaves in Livorno, early modern Italy’s leading slaving center. Adding to the ongoing attempts to expose the violence inherent to the historical records of slavery, it charts the efforts to silence the slaves and offers a counternarrative to the one their slavers wished to create by erasing their suffering. The article argues that the assault was justified as part of a business strategy. The rape of female slaves by enslaved men as a means of increasing the slavers’ profits, it suggests, was thus a more global phenomenon than has hitherto been assumed and was not limited to women’s systematic raping in Atlantic slavery. Problematizing the scholarly focus on Muslim-Christian reciprocity in early modern Mediterranean slavery, it then proposes that the affluence of Livorno’s Jewish community increased the vulnerability of enslaved Jews in the city to excessive abuse. Complicating historiographic notions regarding religious pluralism and interethnic relations in Livorno, the assault’s analysis underscores the importance of writing Jewish slave women back into not only the history of slavery but also the narratives of Jewish history and Italian history.
MutateX: an automated pipeline for in silico saturation mutagenesis of protein structures and structural ensembles
Authors: Tiberti Matteo , Terkelsen Thilde , Degn Kristine , Beltrame Ludovica , Cremers Tycho Canter , da Piedade Isabelle , Di Marco Miriam , Maiani Emiliano , Papaleo Elena
Published: February 2022

Mutations, which result in amino acid substitutions, influence the stability of proteins and their binding to biomolecules. A molecular understanding of the effects of protein mutations is both of biotechnological and medical relevance. Empirical free energy functions that quickly estimate the free energy change upon mutation (ΔΔG) can be exploited for systematic screenings of proteins and protein complexes. In silico saturation mutagenesis can guide the design of new experiments or rationalize the consequences of known mutations. Often software such as FoldX, while fast and reliable, lack the necessary automation features to apply them in a high-throughput manner. We introduce MutateX, a software to automate the prediction of ΔΔGs associated with the systematic mutation of each residue within a protein, or protein complex to all other possible residue types, using the FoldX energy function. MutateX also supports ΔΔG calculations over protein ensembles, upon post-translational modifications and in multimeric assemblies. At the heart of MutateX lies an automated pipeline engine that handles input preparation, parallelization and outputs publication-ready figures. We illustrate the MutateX protocol applied to different case studies. The results of the high-throughput scan provided by our tools can help in different applications, such as the analysis of disease-associated mutations, to complement experimental deep mutational scans, or assist the design of variants for industrial applications. MutateX is a collection of Python tools that relies on open-source libraries. It is available free of charge under the GNU General Public License from https://github.com/ELELAB/mutatex.
Advanced graph and sequence neural networks for molecular property prediction and drug discovery
Authors: Wang Zhengyang , Liu Meng , Luo Youzhi , Xu Zhao , Xie Yaochen , Wang Limei , Cai Lei , Qi Qi , Yuan Zhuoning , Yang Tianbao , Ji Shuiwang
Published: February 2022

Motivation

Properties of molecules are indicative of their functions and thus are useful in many applications. With the advances of deep-learning methods, computational approaches for predicting molecular properties are gaining increasing momentum. However, there lacks customized and advanced methods and comprehensive tools for this task currently.

Results

Here, we develop a suite of comprehensive machine-learning methods and tools spanning different computational models, molecular representations and loss functions for molecular property prediction and drug discovery. Specifically, we represent molecules as both graphs and sequences. Built on these representations, we develop novel deep models for learning from molecular graphs and sequences. In order to learn effectively from highly imbalanced datasets, we develop advanced loss functions that optimize areas under precision–recall curves (PRCs) and receiver operating characteristic (ROC) curves. Altogether, our work not only serves as a comprehensive tool, but also contributes toward developing novel and advanced graph and sequence-learning methodologies. Results on both online and offline antibiotics discovery and molecular property prediction tasks show that our methods achieve consistent improvements over prior methods. In particular, our methods achieve #1 ranking in terms of both ROC-AUC (area under curve) and PRC-AUC on the AI Cures open challenge for drug discovery related to COVID-19.

Availability and implementation

Our source code is released as part of the MoleculeX library (https://github.com/divelab/MoleculeX) under AdvProp.

Supplementary information

Supplementary data are available at Bioinformatics online.
Autophagy modulation in multiple sclerosis and experimental autoimmune encephalomyelitis
Authors: Shen Donghui , Liu Kang , Wang Hongyan , Wang Haifeng
Published: February 2022

Multiple sclerosis (MS), a white matter demyelinating disease of the central nervous system (CNS), is characterized by neuroinflammatory and neurodegenerative. Experimental autoimmune encephalomyelitis (EAE) is a commonly used animal model for investigating pathogenic mechanisms of MS, representing the destruction of the blood-brain barrier (BBB), the activation of T cells, and the infiltration of myeloid cells. An increasing number of studies have documented that autophagy plays a critical role in the pathogenesis of both MS and EAE. Autophagy maintains CNS homeostasis by degrading the damaged organelles and abnormal proteins. Furthermore, autophagy is involved in inflammatory responses by regulating the activation of immune cells and the secretion of inflammatory factors. However, the specific mechanisms of autophagy involved in MS and EAE are not completely understood. In this review, we will summarize the complex mechanisms of autophagy in MS and EAE, providing potential therapeutic approaches for the management of MS.
Verbal production dynamics and plasticity: functional contributions of language and executive control systems
Authors: Gurunandan Kshipra , Carreiras Manuel , Paz-Alonso Pedro M
Published: February 2022

Bilingual language production requires both language knowledge and language control in order to communicate in a target language. Learning or improving a language in adulthood is an increasingly common undertaking, and this has complex effects on the cognitive and neural processes underlying language production. The current functional magnetic resonance imaging (fMRI) experiment investigated the functional plasticity of verbal production in adult language learners, and examined the dynamics of word retrieval in order to dissociate the contributions of language knowledge and executive control. Thirty four adults who were either intermediate or advanced language learners, underwent MRI scanning while performing verbal fluency tasks in their native and new languages. A multipronged analytical approach revealed (i) time-varying contributions of language knowledge and executive control to verbal fluency performance, (ii) learning-related changes in the functional correlates of verbal fluency in both the native and new languages, (iii) no effect of learning on lateralization, and (iv) greater functional coupling between language and language control regions with greater second language experience. Collectively, our results point to significant functional plasticity in adult language learners that impacts the neural correlates of production in both the native and new languages, and provide new insight into the widely used verbal fluency task.
Reduced Serological Response to COVID-19 Vaccines in Patients with IBD is Further Diminished by TNF Inhibitor Therapy; Early Results of the VARIATION study [VAriability in Response in IBD Against SARS-COV-2 ImmunisatiON]
Authors: Doherty Jayne , Morain Neil O , Stack Roisin , Girod Parker , Tosetto Miriam , Inzitiari Rosanna , Sheridan Juliette , Cullen Garret , McDermott Edel , Buckley Maire , Horgan Gareth , Mulcahy Hugh , Ryan Elizabeth J , Daghfal David , Doran Peter , Morain Colm O , Doherty Glen A
Published: February 2022

Background and Aims

Evidence suggests patients with inflammatory bowel disease [IBD] receiving TNF antagonists have attenuated response to vaccination against COVID-19. We sought to determine the impact of IBD and of various medications for treatment of IBD on antibody responses to vaccination against COVID-19.

Methods

Patients with IBD [n = 270] and healthy controls [HC, n = 116] were recruited prospectively, and quantitative antibody responses were assessed following COVID-19 vaccination. The impact of IBD and of medications for treatment of IBD on vaccine response rates was investigated.

Results

Of HC, 100% seroconverted following complete vaccination with two vaccine doses; 2% of patients with IBD failed to seroconvert. Median anti-spike protein [SP] immunoglobulin [Ig]G levels following complete vaccination in our IBD cohort was significantly lower than among HC [2613 AU/mL versus 6871 AU/mL, p ≤0.001]. A diagnosis of IBD was independently associated with lower anti-SP IgG levels [β coefficient -0.2, p = 0.001]. Use of mRNA vaccines was independently associated with higher anti-SP IgG levels [β coefficient 0.25, p ≤0.001]. Patients with IBD receiving TNF inhibitors had significantly lower anti-SP IgG levels [2445 AU/mL] than IBD patients not receiving TNF inhibitors [3868 AU/mL, p ≤0.001]. Patients with IBD not receiving TNF inhibitors still showed attenuated responses compared with HC [3868 AU/mL versus 8747 AU/mL, p = 0.001].

Conclusions

Patients with IBD have attenuated serological responses to SARS-CoV-2 vaccination. Use of anti-TNF therapy negatively affects anti-SP IgG levels further. Patients who do not seroconvert following vaccination are a particularly vulnerable cohort. Impaired responses to vaccination in our study highlight the importance of booster vaccination programmes for patients with IBD.
Case report of the broad spectrum of late complications in an adult patient with univentricular physiology palliated by the Fontan circulation
Authors: Nederend Marieke , Egorova Anastasia D , Vliegen Hubert W , Roest Arno A W , Ruijter Bastian N , Korteweg Tijmen , Ninaber Maarten K , Zeppenfeld Katja , Hazekamp Mark G , Kiès Philippine , Jongbloed Monique R M
Published: February 2022

Background

At the most severe end of the spectrum of congenital heart disease are patients with an univentricular physiology. They comprise a heterogeneous group of congenital heart malformations that have the common characteristic that the cardiac morphology is not equipped for sustaining a biventricular circulation.

Case summary

Here, we present a case of an adult patient after Fontan palliation, illustrative of the complex clinical course and the broad spectrum of complications that can be encountered during follow-up, highlighting the need for a multidisciplinary approach in the clinical care for these patients.

Discussion

During the surgical Fontan procedure, the inferior vena cava is connected to the pulmonary circulation, after prior connection of the superior vena cava to the pulmonary arterial circulation. The resulting cavopulmonary connection, thus lacking a subpulmonic ventricle, provides non-pulsatile passive flow of oxygen-poor blood from the systemic venous circulation into the lungs, and the functional monoventricle pumps the oxygen-rich pulmonary venous return blood into the aorta. With an operative mortality of <5% and current 30-year survival rates up to 85%, the adult population of patients with a Fontan circulation is growing. This increase in survival is, however, inevitably accompanied by long-term complications affecting multiple organ systems, resulting in decline in cardiovascular performance.

Conclusion

For optimal treatment, the evaluation in a multidisciplinary team is mandatory, using the specific expertise of the team members to timely detect and address late complications and to support quality of life.
Treatment and intention-to-treat propensity score analysis to evaluate the impact of video-assisted thoracic surgery on 90-day mortality after anatomical resection for lung cancer
Authors: Recuero-Díaz Jose Luis , Royo-Crespo Iñigo , Gómez de-Antonio David , Call Sergi , Aguinagalde Borja , Gómez-Hernández María Teresa , Hernández-Ferrández Jorge , Sánchez-Lorente David , Sesma-Romero Julio , Rivo Eduardo , Moreno-Mata Nicolás , Embun Raul
Published: February 2022

OBJECTIVES

The aim of this study was to know the treatment effect of video-assisted thoracic surgery (VATS) on 90-day mortality after anatomical lung resection based on a nationwide cohort.

METHODS

This is a multicentre prospective cohort of 2721 anatomical resections for lung cancer from December 2016 to March 2018. Treatment and intention-to-treat (ITT) analyses were performed after inverse probability score weighting and different propensity score matching algorithms. Covariate balance was assessed by standardized mean differences. The estimators reported were the average treatment effect, the average treatment effect on the treated and odds ratios after conditional logistic models with 95% confidence intervals. The unconfoundedness assumption was evaluated by sensitivity analysis for average treatment effect (c-dependence) and average treatment effect on the treated (Γ).

RESULTS

VATS was the initial approach in 1911 patients (70.2%), though 273 cases (14.3%) had to be converted to thoracotomy. Ninety-day mortality rates were: treatment analysis (VATS 1.16% vs open 3.9%, P < 0.001), ITT analysis (VATS 1.78% vs open 3.36%, P = 0.012). After inverse probability score weighting and propensity score matching, in the treatment analysis, VATS meant absolute risk reductions between 2.25% and 2.96% and relative risk reductions between 65% and 70% [OR = 0.34 (95% confidence interval 0.15–0.79), all P-values <0.004). However, all the estimators turned out to be non-significant in the ITT analyses. A high sensitivity to unobservable confounders was proved (c-dependence 0.135, Γ = 1.5).

CONCLUSIONS

VATS can reduce the risk of 90-day mortality after anatomical lung resection. However, the implications of conversion to thoracotomy, comparing ITT versus treatment analysis, and the potential impact of hidden bias should deserve further attention in the future.
Hospitalization and Mortality Risk for COVID-19 Cases With SARS-CoV-2 AY.4.2 (VUI-21OCT-01) Compared to Non-AY.4.2 Delta Variant Sublineages
Authors: Nyberg Tommy , Harman Katie , Zaidi Asad , Seaman Shaun R , Andrews Nick , Nash Sophie G , Charlett Andre , Lopez Bernal Jamie , Myers Richard , Groves Natalie , Gallagher Eileen , Gharbia Saheer , Chand Meera , Thelwall Simon , De Angelis Daniela , Dabrera Gavin , Presanis Anne M
Published: February 2022

To investigate if the AY.4.2 sublineage of the SARS-CoV-2 delta variant is associated with hospitalization and mortality risks that differ from non-AY.4.2 delta risks, we performed a retrospective cohort study of sequencing-confirmed COVID-19 cases in England based on linkage of routine health care datasets. Using stratified Cox regression, we estimated adjusted hazard ratios (aHR) of hospital admission (aHR = 0.85; 95% confidence interval [CI], .77–.94), hospital admission or emergency care attendance (aHR = 0.87; 95% CI, .81–.94), and COVID-19 mortality (aHR = 0.85; 95% CI, .71–1.03). The results indicate that the risks of hospitalization and mortality are similar or lower for AY.4.2 compared to cases with other delta sublineages.
P11 The ratio and antibiotic resistance profiles of Serratia species among other causative bacteria isolated from blood cultures between 2015 and 2020
Authors: Özcan Nida , Atmaca Selahattin , Özbek Erdal
Published: February 2022

Background

Serratia spp., especially Serratia marcescens, have become one of the main drug-resistant causes of hospital infections in the last five decades.1 There are a limited number of publications on Serratia spp., which cause sporadic infections or outbreaks in ICU patients, especially paediatric patients.2  S. marcescens was reported to have intrinsic resistance to many β-lactam antibiotics, tetracyclines and polymyxins.3–5

Objectives

To investigate the antibiotic resistance profiles of the Serratia spp. and detection rates among blood cultures.

Materials and methods

This retrospective study was approved by Dicle University Medicine Faculty Non-Invasive Clinical Research Committee (no: 361, 1 September 2021). Blood culture samples sent from Dicle University Hospital clinics and ICUs between 2015 and 2020 were included. Blood culture samples were incubated in the BD BACTEC FX (Becton Dickinson, USA) system, and the isolates were identified at genus and/or species level by MS using the MALDI Biotyper 3 (Bruker Daltonics, USA). Antimicrobial susceptibility tests (AST) of the isolates were performed with the BD Phoenix 100 (Becton Dickinson, USA) automated system. AST results were interpreted according to the EUCAST criteria.6

Results

Among 9730 agents isolated from blood cultures over a 6 year period, 69 (0.7%) were identified as Serratia spp., 56 of them being S. marcescens (Table 1). Of patients from whom Serratia spp. were isolated, 37 (54%) were paediatric and 47 (68%) were ICU patients (Table 2). A total of 20 isolates (29%) were resistant to at least one of the carbapenems tested. The most effective antibiotics against Serratia spp. were found to be trimethoprim/sulfamethoxazole, ciprofloxacin and amikacin, with resistance rates of 3%, 4% and 7%, respectively (Table 3).

Conclusions

Serratia species were isolated from blood cultures at a rate of 0.7% in a 6 year period, and increased carbapenem resistance among isolates was noteworthy.
P15 Evaluation of the stability of temocillin in elastomeric infusion devices used for outpatient parenteral antimicrobial therapy in accordance with the requirements of the UK NHS Yellow Cover Document
Authors: Sime Fekade B. , Wallis Steven C. , Jamieson Conor , Hills Tim , Gilchrist Mark , Santillo Mark , Seaton R. Andrew , Drummond Felicity , Roberts Jason A.
Published: February 2022

Background

To assess the feasibility of its use in OPAT via continuous infusion, the stability of temocillin solutions at clinically relevant concentrations in two elastomeric infusion devices (B. Braun Medical Ltd Easypump® II LT 270-27- S and Spirit Ltd Medical Dosi-Fuser® L25915-250D1) was evaluated during 14 days of (2°C–8°C) fridge storage followed by 24 h exposure in-use temperature at 32°C, when reconstituted with 0.3% citrate buffer at pH 7.

Methods

Stability testing was conducted in accordance with the standard protocols for deriving and assessment of stability of small molecule aseptic preparation as per the latest UK National Health Service Pharmaceutical Quality Assurance Committee Yellow Cover Document (YCD) requirements. A stability indicating assay method was developed with an ultra-HPLC (UHPLC) system using photodiode array detector. Temocillin concentrations corresponding to low (500 mg/240 mL), intermediate (4000 mg/240 mL) and high (6000 mg/240 mL) dose in triplicate devices were tested with duplicate samples at 11 timepoints during 14 days of fridge storage followed by 24 h in-use temperature exposure at 32°C.

Results

A total of 396 samples were collected and assayed. The percentage of temocillin remaining after 14 days of fridge storage was greater than 97% in both devices and at all concentrations tested. During in-use temperature, 95% stability limit was achieved for 12 h for all doses and devices tested except for the high concentration in the Dosi-Fuser® device, which met this criterion for only 10 h of in-use temperature exposure.

Conclusions

Temocillin reconstituted with 0.3% citrate buffer at pH 7 in elastomeric infusion devices can be stored in a fridge (2°C–8°C) for 2 weeks, meeting the YCD acceptance criteria of <5% degradation. Within the UK, the current data supports twice daily dosing of temocillin with <5% degradation at in-use temperature of 32°C for 12 h, except at high dose (6000 mg/240 mL) in the Dosi-Fuser® device, which must be limited to 10 h. The limits of accepted degradation do vary in other countries. Temocillin is an important addition to the anti-Gram-negative OPAT armamentarium and may reduce reliance on other broader spectrum, higher consequence agents.
P19 IV antimicrobial duration in practice
Authors: Akintimehin Abisoye O. , Wade Paul , Brown Aisling F.
Published: February 2022

Background

Tackling antimicrobial resistance by reducing unnecessary or inappropriate prescribing is a key priority.

Objectives

To review current clinical practice at Guy's and St Thomas’ Hospital around duration of IV antimicrobial therapy framed with Start Smart Then Focus national guidelines.

Methods

Newly started inpatient prescriptions for IV antimicrobials over three consecutive Mondays were reviewed. Prescriptions not for treatment of acute infections were excluded, as were patients admitted to critical care, obstetrics/gynaecology and paediatric wards. Each patient's record was reviewed at Day 0, 3 and 5. Data were analysed using IBM® SPSS Statistics version 27.

Results

In total, 80 patients with 89 antibiotic prescriptions (71 = β-lactam, 5 = aminoglycoside, 2 = glycopeptide, 1 = ciprofloxacin, 9 = metronidazole, 1 = linezolid) were included. Median age was 66 (IQR 53–75). Documented indications were for suspected or proven infection of urinary tract (15%), respiratory tract (25%), skin/soft tissue (14%), sepsis (1.25%), intra-abdominal (15%), bacteraemia (7.5%), bone and joint infections (2.5%) or other (20%). Median initial NEWS2 on Day 0 was 3 (IQR 1–4), WCC 11.45 (IQR 8.27–14.15) and CRP 121 (IQR 47–208). Median length of stay was 7.5 days. Median duration of IV antimicrobial was 4 (IQR 2–6) days. By D3, 3 patients had died and 16 had been discharged. Of 61 remaining inpatients on D3, 4 had their antimicrobials switched, 14 had been switched to PO antimicrobials, 43 were continued on IV antibiotics. By D5, 17 further patients had been discharged, 44 remained inpatients. Twenty-two had stopped antimicrobials with 22 continuing IV therapy. A number of patients could have been switched from IV to oral therapy by current guidance but were not (D3 x = 11, D5 n = 8). Higher median D0 CRP was seen in those who continued on IV therapy on D3 (139 versus 79 mg/dL) as was higher D3 WCC (13.9 versus 11.9 × 109/L). There was no significant relationship between a NEWS2 score ≥3 and IV to PO switch at D3 or D5. Thirty-two patients had input from the Infection team within 7 days of first prescription. Fifteen patients (21%) received IV antibiotics for more than 7 days, and 14/15 had Infection team input. Three patients were discharged with OPAT.

Conclusions

Median duration of IV therapy for suspected/proven infections in our centre is less than 5 days and only 28% of patients were still receiving IV antibiotics by D5. A number of missed opportunities for earlier switch to oral therapy were identified. The potential for earlier safe discontinuation of IV therapy using patient-specific measures should be explored. A minority of patients received IV therapy for >7 days, and this was almost universally associated with specialist Infection involvement in complex infections with a view to optimizing patient management and antimicrobial stewardship.
P26 Phenotypic and genotypic characterization of antimicrobial resistance in Clostridioides difficile in North Wales
Authors: Thomas R. , Coupe B. , Bull M. , Copsey S. , Morris T. , Perry M. , Morgan C.
Published: February 2022

Background

Clostridioides difficile poses a major infection control challenge and remains a huge burden to our healthcare system. The emergence of hypervirulent strains of C. difficile has highlighted the need for monitoring antimicrobial resistance (AMR) and continual epidemiological vigilance. Agar dilution is the current gold standard method for antimicrobial susceptibility testing of C. difficile and the method routinely utilized in the Public Health Wales (PHW) UK Anaerobe Reference Unit (UKARU) at the University Hospital of Wales, Cardiff. However, this method is laborious and time consuming. Meanwhile, the emergence of WGS introduces the possibility of acquiring rapid genotypic information in terms of AMR.

Methods

In this research project, isolates obtained from faecal samples submitted across the Betsi Cadwalader health board (BCUHB) that were either GDH or PCR positive were sequenced as part of the C. difficile Genomic Sequencing and Typing (DIGEST) pilot project performed at the PHW Pathogen Genomics Unit (PenGU) in Cardiff.

Results

Results highlights include the finding that 93% of the isolates analysed for the presence of AMR genes were found to have the cdeA gene associated with conferring resistance to fluoroquinolones such as ciprofloxacin. Other common genes observed included blaCDD-1 and blaCDD-2, associated with β-lactam resistance.

Conclusions

While further work must be done to link genotypic characterization with phenotype, this study provides a valuable insight into AMR mechanisms in C. difficile and may in future become an important tool providing early indication of shift in C. difficile epidemiology or the emergence of a new hypervirulent and MDR strain.
P29 A retrospective multi-centre review of antimicrobial usage in patients diagnosed with aspiration pneumonia
Authors: Ashtey Blend , Troise Oliver , Hughes Stephen
Published: February 2022

Background

Over-diagnosis of infective aspiration pneumonia is common in healthcare settings and represents a potential for misuse of antimicrobial therapy.

Methods

A retrospective analysis was undertaken of all hospitalized patients treated for aspiration pneumonia within a multicentre Acute NHS Trust (April–May 2021, London, UK). Data collected included: age, initial antibiotics prescribed, duration of therapy, relevant microbiology (sputum samples or blood cultures) and chest X-ray. Treatment response was analysed including body temperature after 24 h of antimicrobials, use of oxygen support after 48 h, any escalation of antimicrobial therapy and 30 day in-hospital mortality. The study was registered as service evaluation project.

Results

In total, 94 patients treated for aspiration pneumonia were included; median age 82 years (IQR 67–89). Co-amoxiclav monotherapy was the most frequently prescribed treatment (67/94); cephalosporins (8/94) and ciprofloxacin (4/94) were also commonly used. Duration (median) of treatment was 4.4 days (IQR 1–6.7); 32/94 patients received <48 h. Radiological evidence of consolidation, O2 support at 48 h and fever at 24 h was present in 32/94, 25/94 and 12/94 patients, respectively. A microbiological diagnosis to confirm infection was present in 12/94. Consolidation [OR 2.36 (95% CI 1.04–10.25); P = 0.037] and O2 support at 48 h [OR 3.22 (95% CI 1.02–10.25); P = 0.044], but not fever at 24 h [OR 0.94 (95% CI 0.18–4.80)], were associated with treatment escalation. No association between O2 support/fever and total duration was evident. The 30 day in-hospital mortality was 17% (16/94).

Conclusions

Aspiration pneumonia has high in-hospital mortality and often necessitates antibacterial treatment. The true incidence of bacterial pneumonia is unclear, and many patients may benefit from early cessation of antibacterial treatment.
P31 Gut colonization of carbapenem-resistant Enterobacteriaceae among patients with haematological malignancies in National Cancer Institute, Sri Lanka
Authors: Suranadee Y. W. S. , Dissanayake Y. , Dissanayake B. M. B. T. , Jyalatharachchi H. R. , Gamage S. , Gunasekara S. P.
Published: February 2022

Background

Carbapenem-resistant Enterobacteriaceae (CRE) are the most critical group of MDR bacteria that pose a threat to human health especially affecting patients with haematological malignancies. Knowledge on the prevalence of CRE colonization of the gut will help healthcare providers to be vigilant in-patient management. However, there are no local studies exploring the gut colonizing CRE among patients with haematological malignancies. Hence, this study aimed to determine the prevalence of CRE genes in colonizing CRE isolates in patients with haematological malignancies and evaluate their antibiotic susceptibility pattern.

Methods

Rectal swab samples collected from patients with haematological malignancies were screened with selective chromogenic agar for CRE. Species identification and ABST of CRE isolates were done using VITEK® 2 system. blaKPC, blaNDM and blaOXA−48 genes were identified using an in-house conventional multiplex PCR, with previously described method and primers.

Results

A total of 264 adult patients with haematological malignancies were included in the study. Prevalence of gut colonization of CRE was 35.2% (93/264). A total of 119 CRE isolates from 93 study subjects were further studied. Klebsiella pneumoniae was the predominant carbapenemase producer [68/119 (57%)] among the isolates. Sixty-one (51.2%) isolates harboured blaNDM, 48 (40.3%) blaOXA−48 and 12 (10%) blaKPC. Three isolates (2.5%) were shown to harbour all three genes and 24 (20%) two genes. Twenty (16.8%) of isolates tested negative for all three genes.

Conclusions

A relatively high prevalence of CRE gene occurrence and co-occurrence was detected in the study population. This indicates a potential challenge to infection prevention and control in the institute as colonization with CRE carries a threat to endogenous infection and cross transfer.

Limitations

In-house conventional PCR method was used to identify CRE genes. Twenty isolates that were negative for all tested genes need to be studied further.
Development of optimal water distribution system design and operation approach considering hydraulic and water quality criteria in many-objective optimization framework
Authors: Choi Young Hwan
Published: February 2022

Water distribution systems (WDSs) are major infrastructure, and it needs to consider economic, hydraulic stability, and water quality safety to optimal design and operation of WDSs. However, the previous studies related to WDS design and operation were focused on each field (i.e. design: optimal pipe diameter, pump sizing, and valve location; operation: optimal pump scheduling, etc.) even though the WDS design and operation have a correlation. Therefore, to achieve economic feasibility, hydraulic stability, and water quality safety under WDS design and operation process, this study develops an optimal WDS design and operation approach considering hydraulic and water quality criteria in the many-objective optimization framework. To consider design and operation, this study applies three objective functions to minimize the total design and operation cost (i.e. the pipe cost, pump construction, and pump operation cost), maximize system robustness, and minimize the amount of chlorine requisition simultaneously under the hydraulic and quality constraints. The proposed optimal WDS design and operation model was applied to the two-stage optimization procedures. The first process determined the optimal pipe diameter set. The second process determined the optimal pump construction and scheduling considering three objective functions such as the total pump cost, the system robustness, and the quantity of the required residual chlorine for determining optimally the available number of pumps, capacity, and scheduling. For the optimization, the self-adaptive multi-objective harmony search is used and a famous benchmark network for the optimal design and pump operation of WDSs is applied to verify the proposed approach. This study can provide a new perspective on WDS design and operation technique considering the essential design factors to the water utility.
Inhibition of retinoid X receptor improved the morphology, localization of desmosomal proteins
and paracellular permeability in three-dimensional cultures of mouse keratinocytes
Authors: Ishikawa Shoko , Nikaido Misaki , Otani Takahito , Ogata Kayoko , Iida Hiroshi , Inai Yuko , Tamaoki Sachio , Inai Tetsuichiro
Published: February 2022

Retinoic acid (RA) plays an important role in epithelial homeostasis and influences the morphology, proliferation, differentiation and permeability of epithelial cells. Mouse keratinocytes, K38, reconstituted non-keratinized stratified epithelium in three-dimensional (3D) cultures with serum, which contains retinol (a source of RA), but the morphology was different from in vivo epithelium. The formed epithelium was thick, with loosened cell–cell contacts. Here, we investigated whether the inhibition of RA receptor (RAR)/retinoid X receptor (RXR)-mediated signaling by an RXR antagonist, HX 531, improved K38 3D cultures in terms of morphology and intercellular junctions. The epithelium formed by 0.5 μM HX531 was thin, and the intercellular space was narrowed because of the restoration of the layer-specific distribution of desmoglein (DSG)-1, DSG3 and plakoglobin (PG). Moreover, the levels of desmosomal proteins and tight junction proteins, including DSG1, DSG2, DSG3, PG, claudin (CLDN)-1 and CLDN4 increased, but the adherens junction protein, E-cadherin, did not show any change. Furthermore, CLDN1 was recruited to occludin-positive cell–cell contacts in the superficial cells and transepithelial electrical resistance was increased. Therefore, K38 3D cultures treated with 0.5 μM HX531 provides a useful in vitro model to study intercellular junctions in the non-keratinized epithelium.
Relational Work and its Pitfalls: Nonprofits’ Participation in Government-Sponsored Voluntary Accreditation
Authors: Luo Wei , Zheng Wenjuan , Long Yan
Published: February 2022

Around the world, voluntary programs are an increasingly prevalent regulatory instrument in governing nonprofit organizations. But accounts of mechanisms driving nonprofits’ participation in those programs are underdeveloped. This article combines and expands insights from voluntary regulation and institutional work theories to examine the impact of government’s informal relational work on nonprofits’ regulatory participation. Drawing on interviews and survey data from a random sample of 203 nonprofits in Shenzhen, China, the authors study the country’s pioneering government-sponsored voluntary accreditation program and its varying receptions among nonprofits. The empirical analysis shows that politically embedded nonprofits, those with closer organizational connections with the local government, are more likely to participate in accreditation. Since government agencies rely on existing regulatory networks to conduct relational work at both organizational and personal levels to persuade or cajole nonprofits to participate, they tend to direct their recruitment efforts towards more politically embedded nonprofits. However, these targeted recruitment practices may generate reactions much more complicated than the dichotomy of acceptance versus resistance, which ultimately facilitates some nonprofits seeking accreditation while deterring others.
Local Group timing argument and virial theorem mass estimators from cosmological simulations
Authors: Hartl Odelia V , Strigari Louis E
Published: February 2022

We identify Local Group (LG) analogues in the IllustrisTNG cosmological simulation, and use these to study two-mass estimators for the LG: One based on the timing argument (TA) and one based on the virial theorem (VT). Including updated measurements of the Milky Way-M31 tangential velocity and the cosmological constant, we show that the TA mass estimator slightly overestimates the true median LG-mass, though the ratio of the TA to the true mass is consistent at the approximate 90 per cent c.l.. These are in broad agreement with previous results using dark matter-only simulations. We show that the VT estimator better estimates the true LG-mass, though there is a larger scatter in the virial mass to true mass ratio relative to the corresponding ratio for the TA. We attribute the broader scatter in the VT estimator to several factors, including the predominantly radial orbits for LG satellite galaxies, which differs from the VT assumption of isotropic orbits. With the systematic uncertainties we derive, the updated measurements of the LG mass at 90 per cent c.l. are $4.75_{-2.41}^{+2.22} \times 10^{12}$ M⊙ from the TA and $2.0_{-1.5}^{+2.1} \times 10^{12}$ M⊙ from the VT. We consider the LMC’s effect on the TA and VT LG mass estimates, and do not find exact LMC–MW–M31 analogues in the Illustris simulations. However, in LG simulations with satellite companions as massive as the LMC, we find that the effect on the TA and VT estimators is small, though we need further studies on a larger sample of LMC–MW–M31 systems to confirm these results.
The spiral density-wave structure of the Milky Way in the 3-kpc-scale solar neighbourhood: line-of-sight velocities of 252 young open clusters
Authors: Griv Evgeny , Gedalin Michael , Jiang Ing-Guey
Published: February 2022

Following Lin and Shu, the spiral structure in the Milky Way disc is considered as an oscillating density-wave pattern. As such, regular enhancements in density are relatedly linked to systematic variations in velocity of young stars and stellar clusters, and interstellar gas. We explain measured line-of-sight velocities of 252 open clusters with ages <100 Myr of Tarricq et al. in the 3-kpc-scale solar neighbourhood in terms of a density wave. New estimates of the parameters of solar peculiar motion and Galactic differential rotation corrected for the effects of small-amplitude density waves, the radial and tangential components of systematic motion of clusters due to the spiral arms as well as the geometrical and dynamical parameters of the waves are suggested.
quokka: a code for two-moment AMR radiation hydrodynamics on GPUs
Authors: Wibking Benjamin D , Krumholz Mark R
Published: February 2022

We present quokka, a new subcycling-in-time, block-structured adaptive mesh refinement (AMR) radiation hydrodynamics (RHD) code optimized for graphics processing units (GPUs). quokka solves the equations of HD with the piecewise parabolic method (PPM) in a method-of-lines formulation, and handles radiative transfer via the variable Eddington tensor (VET) radiation moment equations with a local closure. We use the amrex library to handle the AM management. In order to maximize GPU performance, we combine explicit-in-time evolution of the radiation moment equations with the reduced speed-of-light approximation. We show results for a wide range of test problems for HD, radiation, and coupled RHD. On uniform grids in 3D on a single GPU, our code achieves >250 million hydrodynamic updates per second and almost 40 million radiation hydrodynamic updates per second. For RHD problems on uniform grids in 3D, our code scales from 4 to 256 GPUs with an efficiency of 76 per cent. The code is publicly released under an open-source license on GitHub.
Long term radio and X-ray evolution of the magnetar Swift J1818.0-1607
Authors: Rajwade K M , Stappers B W , Lyne A G , Shaw B , Mickaliger M B , Liu K , Kramer M , Desvignes G , Karuppusamy R , Enoto T , Güver T , Hu Chin-Ping , Surnis M P
Published: February 2022

We report on the the long term monitoring campaign of the seemingly youngest magnetar Swift J1818.0–1607 at radio and X-ray wavelengths over a span of one year. We obtained a coherent timing solution for the magnetar over the same time span. The frequency derivative of the magnetar shows systematic variation with the values oscillating about a mean value of −1.37 × 10−11 Hz s−1. The magnitude of the variation in the frequency derivative reduces with time before converging on the mean value. This corresponds to a characteristic age of ∼ 860 years, 2–4 times more than previously estimated. We were able to identify four states in the spin-frequency derivative that were quantified by the amount of modulation about the mean value and the transition between these states seem to be correlated with the change in the radio emission of the magnetar while no correlation is seen in the average radio profile variability on a shorter time-scale (days). The 0.5–12 keV X-ray flux shows a monotonic decrease that can be attributed to thermal emission from a hot spot on the surface of the neutron star that is reducing in size. Such decrease is consistent with what is seen in other magnetars. The potential correlation between the radio emission mode and the behaviour of the spin-down rate hints to a global change in the magnetopshere of the magnetar akin to the correlation seen in a subset of mode-changing radio pulsars and suggests a physical link between the two sub-populations.
The early afterglow of GRB 190829A
Authors: Dichiara S , Troja E , Lipunov V , Ricci R , Oates S R , Butler N R , Liuzzo E , Ryan G , O’Connor B , Cenko S B , Cosentino R G , Lien A Y , Gorbovskoy E , Tyurina N , Balanutsa P , Vlasenko D , Gorbunov I , Podesta R , Podesta F , Rebolo R , Serra M , Buckley D A H
Published: February 2022

GRB 190829A at z = 0.0785 is the fourth closest long GRB ever detected by the Neil Gehrels Swift observatory, and the third confirmed case with a very high-energy component. We present our multiwavelength analysis of this rare event, focusing on its early stages of evolution, and including data from Swift, the MASTER global network of optical telescopes, ALMA, and ATCA. We report sensitive limits on the linear polarization of the optical emission, disfavouring models of off-axis jets to explain the delayed afterglow peak. The study of the multiwavelength light curves and broad-band spectra supports a model with at least two emission components: a bright reverse shock emission, visible at early times in the optical and X-rays and, later, in the radio band; and a forward shock component dominating at later times and lower radio frequencies. A combined study of the prompt and afterglow properties shows many similarities with cosmological long GRBs, suggesting that GRB 190829A is an example of classical GRBs in the nearby universe.
The vertical structure of debris discs and the impact of gas
Authors: Olofsson Johan , Thébault Philippe , Kral Quentin , Bayo Amelia , Boccaletti Anthony , Godoy Nicolás , Henning Thomas , van Holstein Rob G , Maucó Karina , Milli Julien , Montesinos Matías , Rein Hanno , Sefilian Antranik A
Published: February 2022

The vertical structure of debris discs provides clues about their dynamical evolution and the collision rate of the unseen planetesimals. Thanks to the ever-increasing angular resolution of contemporary instruments and facilities, we are beginning to constrain the scale height of a handful of debris discs, either at near-infrared or millimeter wavelengths. None the less, this is often done for individual targets only. We present here the geometric modeling of eight discs close to edge-on, all observed with the same instrument (SPHERE) and using the same mode (dual-beam polarimetric imaging). Motivated by the presence of CO gas in two out of the eight discs, we then investigate the impact that gas can have on the scale height by performing N-body simulations including gas drag and collisions. We show that gas can quickly alter the dynamics of particles (both in the radial and vertical directions), otherwise governed by gravity and radiation pressure. We find that, in the presence of gas, particles smaller than a few tens of microns can efficiently settle toward the midplane at the same time as they migrate outward beyond the birth ring. For second generation gas (Mgas ≤ 0.1 M⊕), the vertical settling should be best observed in scattered light images compared to observations at millimeter wavelengths. But if the gas has a primordial origin (Mgas ≥ 1 M⊕), the disc will appear very flat both at near-infrared and sub-mm wavelengths. Finally, far beyond the birth ring, our results suggest that the surface brightness profile can be as shallow as ∼−2.25.