bluuebunny/crossref_metadata_2025_split huggingface dataset:
P06 Stewardship potential—the hidden burden of antibiotic prophylaxis in primary care
Authors: Philip Carol , Fullbrook Alexander , Dewar Simon , Evans Morgan , Inverarity Donald , Perry Meghan , Etherson Michelle 
Published: August 2023

Abstract

Background
This study aimed to decrease unnecessary long-term antimicrobial use in primary care by identifying and highlighting patients with long-term or repeated exposure to antibiotics to GP teams for review. The broad spectrum antimicrobial co-amoxiclav was targeted following data showing rising DDD per prescription in our Health Board.

Methods
Community antibiotic prescribing from the national Prescribing Information System (PIS) was searched for NHS Lothian (126 GP practices) using DDD to identify patients. Long courses of co-amoxiclav were defined as ≥63 DDD. Ninety-eight patients were identified with high antimicrobial usage and a data collection form was sent to the Primary Care Pharmacy teams to voluntarily collate data for each patient.

Results
The data collection form had a 97% response rate. Of the 94 patients with full data 62 (66%) patients had co-amoxiclav initiated due to secondary care specialist advice and 26 (28%) had been initiated by primary care. Forty-four patients (47%) were aged 65 or over, putting them at high risk of Clostridioides difficile. Forty-one patients had multiple courses of co-amoxiclav and 39 patients were prescribed co-amoxiclav as prophylaxis; of these 59% were for urinary tract infection (UTI). Thirty-four of 94 patients (36%) had been on prophylaxis for over 5 years with 9 patients on co-amoxiclav for over 20 years. Of note in 39 of 94 patients no microbiology samples were available and where samples were available (n=55), narrower spectrum options were available in 38 patients (69%) and 17 patients (31%) had samples showing resistance to co-amoxiclav. Following this intervention to highlight use, the number of patients on long-term courses or prophylaxis with co-amoxiclav reduced by 70% in the following year.

Conclusions
Patients on long-term antibiotics are priorities for antimicrobial stewardship interventions. This work demonstrated that ongoing appropriateness and efficacy of long-term antibiotic courses were not routinely reviewed. Using pharmacy data proved an effective method to highlight patients and ultimately reduce patient antibiotic exposure. UTI prophylaxis was the majority patient group in this study and interventions to review and decrease long-term UTI prophylaxis in our Board using this method are underway.
P07 Impact of menopausal status and recurrent urinary tract infections (UTIs) on symptoms, severity, and daily life: findings from an online survey of women reporting a recent UTI
Authors: Sanyaolu Leigh , Cooper Emily , Read Brieze , Ahmed Haroon , Lecky Donna M 
Published: August 2023

Abstract

Background
Current UKHSA urinary tract infection (UTI) guidance advises empirical antibiotics if two of the following symptoms are present: cloudy urine, dysuria, and new onset nocturia. Hormonal changes during menopause may affect UTI symptoms. Qualitative studies suggest women with recurrent UTIs may present with different UTI symptoms. This study aims to assess whether menopausal status and a history of recurrent UTIs affects UTI symptoms in women.

Methods
An e-survey was conducted between 13 March 2021 and 13 April 2021. Women aged 16 years or older with a history of a UTI in the past year were eligible for inclusion. We defined menopause as those aged 45–64 years; pre-menopause as those less than 45 years; and post-menopause as those 65 years and older. Recurrent UTIs were defined as three or more UTIs in the last year. Data were weighted to be representative of the UK population. Crude and adjusted ORs were estimated using logistic regression.

Results
A total of 1096 women reported a UTI in the last year. There were significant differences in UTI symptoms based on menopausal status and the presence of recurrent UTIs. Post-menopausal women were more likely to self-report new or worsening incontinence (OR 2.76, 95% CI 1.50, 5.09) with an acute UTI compared with pre-menopausal women. Menopausal women were also more likely to self-report new or worsening incontinence (OR 1.66, 95% CI 1.06, 2.62) and nocturia (OR 1.43, 95% CI 1.05, 1.96) with an acute UTI compared with pre-menopausal women. Women with recurrent UTIs were less likely to self-report dysuria with an acute UTI but reported more severe symptoms (OR 1.93 95% CI 1.37, 2.73) and a greater impact on daily life (OR 1.68, 95% CI 1.19, 2.37) compared with women without recurrent UTIs.

Conclusions
This survey provides evidence that acute UTIs present differently based on menopausal status and in women with recurrent UTIs. This has implications for the diagnosis and treatment of acute UTIs in these patient populations and suggests that a more tailored approach may be required that takes account of menopausal status and history of recurrent UTIs. It is important healthcare professionals are aware of these differences when assessing women presenting with an acute UTI.
P11 Lubricant-infused silver-polytetrafluoroethylene coated urinary catheters inhibit adhesion of host-secreted proteins and biofilm formation
Authors: Zhang Shuai , McCoy Colin P 
Published: August 2023

Abstract

Objectives
The adhesion of specific host-derived proteins (particularly fibrinogen) and subsequent biofilm formation play a central role in the pathogenesis of catheter-associated urinary catheter infections (CAUTIs). However, very few catheter materials have proven to be able to simultaneously prevent both bacterial and protein adhesion in a complex physiological environment (i.e. urine). The aims and objectives of this research were to (i) develop silver-polytetrafluoroethylene (AgF)-based coatings with a wide range of surface energies; (ii) test their antifouling performance; and (iii) investigate the influence of surface energy on biofouling accumulation.

Methods
Standard AgF coatings with tailored surface energies (ranging from 18 mJ/m2 to 42 mJ/m2) were fabricated using an electroless method. By spontaneous polycondensation 1H,1H,2H,2H-perfluorooctyltriethoxysilane (PFOTES) onto the AgF sublayer, a lubricant-infused AgF coating (AgFP) was obtained. The surface morphology, chemical composition, and roughness were characterized by SEM, EDS and AFM, respectively. The surface energy was characterized using a contact angle approach and calculated using the Van Oss method. The anti-adhesion performance of the coated catheters against proteins (fibrinogen [Fgn]; BSA) and bacteria (Escherichia coli; Proteus mirabilis) was examined and compared with commercial all-silicone catheters.

Results
The results showed that there exist two separate optimum surface energies where bacterial (∼25 mJ/m2) and protein adhesion (∼35 mJ/m2) are minimal (Figure 1). The deposition of fibrinogen on surfaces significantly accelerated bacterial attachment and biofilm formation, whereas the AgFP coating with the smoothest surface and ultralow surface energy (∼12 mJ/m2) displayed significant antibiofilm and anti-protein activities compared with uncoated silicone surface traditional AgF coatings (Figure 2). Figure 1.Surface energy on adhesion of bacteria and proteins. Figure 2.Biofilm formation on Si, AgF and AgFP surfaces after 1 day co-culture in pure bacterial suspension and protein-supplemented bacterial suspension. Scale bars correspond to 40 μm.

Conclusions
The inclusion of lubricant into the AgF matrix leads to the formation of a smooth and super-repelling catheter surface, leading to ultralow adhesion for both bacteria and proteins. Surprisingly, our results indicated that there exists an optimum surface energy where the adhesion of both bacteria and proteins is minimal, which further extended the classic ‘Baier curve’.
P21 Development of deep learning models for Sub-Cellular Fluctuation Imaging (SCFI): a 30 min antibiotic susceptibility test for urinary tract infections
Authors: Rama S , Antognozzi M , Szeremeta W , Phonrat K , Eley A , Bermingham C , Kyriakides M , Newman H , Bonney-Bhandal K , Preece J , Dorh N , Dorh J 
Published: August 2023

Abstract

Background
We have developed a phenotypic and label-free antibiotic susceptibility test (AST) termed Sub-Cellular Fluctuation Imaging (SCFI) to address rising rates of antimicrobial resistance.1 SCFI is an advanced machine-learning enabled microscope that monitors real-time fluctuations of bacterial cell membrane in response to antibiotics. By quantifying changes in magnitude and location of light scattering caused by subcellular movement, we can detect metabolic changes that occur when bacteria are challenged with antibiotics.2–5 Here, we show that improvements to SCFI’s deep-learning models can correctly classify metabolic cell states for Escherichia coli (exponential, stationary, dead) and determine cell states for UTI-related species (E. coli, Klebsiella pneumoniae and Proteus mirabilis) with front-line antibiotics (trimethoprim and nitrofurantoin).

Methods
A total of 100 μL per sample is introduced to microfluidic flow chambers and immobilized using a species-specific antibody coating for 10 min. The bacterial suspension is removed, washed (to minimize non-bound cells) and incubated with 100 μL of MHB broth containing either a treated (with antibiotic) or untreated (without antibiotic) condition for 30 min. Images are captured at a laser intensity of 20 Hz for 20 s, for ≥50 individual bacterial cells per test. Convolutional neural networks (CNN) were developed to enable classifications of bacteriostatic antibiotics (trimethoprim and methicillin) on E. coli, K. pneumoniae and P. mirabilis species to determine their respective performance metrics (sensitivity, specificity, PPV and NPV).

Results
CNN models were developed to successfully classify treated, untreated, resistant and susceptible bacterial conditions. All conditions were tested in triplicate (n=150 cells) and demonstrated high accuracy (sensitivity 88%–98%, specificity 88%–99%, PPV 88%–99% and NPV 88%–98%) when compared with known MICs.

Conclusions
In these experiments we successfully demonstrated rapid (30 min) and accurate (≥90%) classification of bacterial resistance states by deep learning techniques. These data also continue to support existing literature that SCFI is an AST that is agnostic to the antibiotic class and bacterial species used. This system is undergoing product development and will be translated into a bespoke hardware system for clinical and antibiotic research applications.
P22 A multifaceted staff-focused approach to improve urinary tract infection management in our Trust
Authors: Abraham Faith , Tawfik Hadeer , Subramanian Bala 
Published: August 2023

Abstract

Background
Urinary tract infection (UTI) is a common diagnostic label given to patients across all medical and surgical specialties. Despite this, there is a great degree of misconception on diagnostic and management aspects of this condition. Following our Trust performance in the NHS UTI CQUIN 2022/2023, where overall compliance was 41% and 48% for quarter 1 and 2, respectively, we embarked on a project to enhance our performance by identifying gaps in knowledge that resulted in over-diagnosis and inappropriate antibiotic treatment.

Objectives
To optimize clinical diagnosis of UTI, reduce reliance on dipsticks in elderly and catheterized patients, and improve antibiotic stewardship.

Methods
We surveyed 76 healthcare workers including doctors, nurses, advanced nurse practitioners and healthcare assistants to understand baseline knowledge and explore areas that required targeted intervention. Based on the survey results, we implemented an educational awareness campaign employing formal teaching sessions on specific wards, informal interactions, UTI flow charts and posters, new antibiotic guidelines and posts on the hospital communications and social media pages

Results
From our survey, we identified 45% believed dipsticks were part of routine investigations, 47% performed dipsticks for catheterized patients and 79% believed that a positive dipstick in elderly patients indicated UTI. The CQUIN data involves five key parameters; including diagnosing UTIs and CA-UTI based on clinical signs and symptoms, establishing the diagnosis without reliance on dipsticks in elderly and catheterized patients, sending urine for culture and microscopy, changing or removing catheters where applicable and treating with an appropriate antibiotic. The individual compliance for each parameter was &gt;60% but our overall compliance was poor. Our survey finding corroborated the initial CQUIN data in demonstrating that the major problem areas were dipstick use in elderly patients and catheterized patients and the use of inappropriate antibiotics for treatment. Following the first wave of our improvement strategies, we recorded a significant improvement in overall Trust CQUIN compliance of 51% and 58% for quarters 3 and 4, respectively, and on the wards where specific implementation strategies were carried out, an overall compliance score of 64%.

Conclusions
The significant improvement we have made so far highlights what can be achieved with staff-focused interventions and the impact on patient care. We intend to continue to involve various specialities across the Trust to optimize UTI management.
P28 Profile of uropathogens and trend of their antimicrobial resistance at a trauma care facility: a 10 year analysis
Authors: Ningombam Aparna , Thakur Arpan Kumar , Srivastava Smriti , Nizam Ahmed M , Kirti Madhavi , Malhotra Rajesh , Mathur Purva 
Published: August 2023

Abstract

Background
Urinary tract infections (UTIs) are one of the most common healthcare-associated infections (HAIs). Trauma patients acquire UTIs almost exclusively due to hospital or treatment-related causes. Healthcare-associated UTIs (HA-UTIs) have increased morbidity, antimicrobial treatment cost and length of stay. Temporal evaluation of HA-UTIs will help in assessing the actual magnitude of the problem and the variation in antibiograms. In this study, we have evaluated the prevalence of uropathogens and their antimicrobial resistance (AMR) pattern over 10 years from patients admitted to a level-1 trauma centre in India.

Methods
The study reports the pathogen profile and their antibiograms from the period 2012 to 2022. Antibiotic susceptibility was done in our laboratory using Vitek 2. In cases where the CLSI guidelines do not recommend Vitek 2, disc diffusion testing was done. The most prevalent organisms with their antimicrobial susceptibility testing were analysed using appropriate statistical measures.

Results
From a total of 3432 isolates, the most common uropathogens were Escherichia coli (1074), Klebsiella pneumoniae (643) and Pseudomonas aeruginosa (638). Amongst Gram-positives, Enterococcus faecium (171) was the most significant. The AMR pattern of the Gram-negative organisms showed that the majority were MDR. Amikacin resistance was consistently in the range of 20%–25% for all E. coli isolates except in 2021 and 2022, where it was 8.47% and 17.82%. K. pneumoniae isolates (&gt;60%) were consistently resistant to amikacin, cefepime, ciprofloxacin and piperacillin/tazobactam. However, there was a slight dip in resistance to amikacin in 2017, which was 52.38%. Imipenem showed consistent resistance in the 30%–60% range, but there has been a spike in resistance (&gt;60%) after the pandemic. Resistance to ceftazidime, cefepime, ciprofloxacin and amikacin was &gt;80% for Pseudomonas isolates except in 2019 and 2020, where their resistance pattern was within 60%–80%. Imipenem resistance was &gt;60% throughout the period except for 2021, where resistance was 53.3% (8/15).

Conclusions
All the antibiotics showed an upward trend in resistance post the pandemic except amikacin in isolates of E. coli. In conclusion, AMR trends are very important, and antibiograms should be revised on a timely basis.
Semantical investigations on non-classical logics with recovery operators: negation
Authors: Fuenmayor David 
Published: August 2023

Abstract
We investigate mathematical structures that provide natural semantics for families of (quantified) non-classical logics featuring special unary connectives, known as recovery operators, that allow us to ‘recover’ the properties of classical logic in a controlled manner. These structures are known as topological Boolean algebras, which are Boolean algebras extended with additional operations subject to specific conditions of a topological nature. In this study, we focus on the paradigmatic case of negation. We demonstrate how these algebras are well-suited to provide a semantics for some families of paraconsistent Logics of Formal Inconsistency and paracomplete Logics of Formal Undeterminedness. These logics feature recovery operators used to earmark propositions that behave ‘classically’ when interacting with non-classical negations. Unlike traditional semantical investigations, which are carried out in natural language (extended with mathematical shorthand), our formal meta-language is a system of higher-order logic (HOL) for which automated reasoning tools exist. In our approach, topological Boolean algebras are encoded as algebras of sets via their Stone-type representation. We use our higher-order meta-logic to define and interrelate several transformations on unary set operations, which naturally give rise to a topological cube of opposition. Additionally, our approach enables a uniform characterization of propositional, first-order and higher-order quantification, including restrictions to constant and varying domains. With this work, we aim to make a case for the utilization of automated theorem proving technology for conducting computer-supported research in non-classical logics. All the results presented in this paper have been formally verified, and in many cases obtained, using the Isabelle/HOL proof assistant.
Distinct roles of two SEC scaffold proteins, AFF1 and AFF4, in regulating RNA polymerase II transcription elongation
Authors: Che Zhuanzhuan , Liu Xiaoxu , Dai Qian , Fang Ke , Guo Chenghao , Yue Junjie , Fang Haitong , Xie Peng , Luo Zhuojuan , Lin Chengqi 
Published: August 2023

Abstract
The super elongation complex (SEC) containing positive transcription elongation factor b plays a critical role in regulating transcription elongation. AFF1 and AFF4, two members of the AF4/FMR2 family, act as central scaffold proteins of SEC and are associated with various human diseases. However, their precise roles in transcriptional control remain unclear. Here, we investigate differences in the genomic distribution patterns of AFF1 and AFF4 around transcription start sites (TSSs). AFF1 mainly binds upstream of the TSS, while AFF4 is enriched downstream of the TSS. Notably, disruption of AFF4 results in slow elongation and early termination in a subset of AFF4-bound active genes, whereas AFF1 deletion leads to fast elongation and transcriptional readthrough in the same subset of genes. Additionally, AFF1 knockdown increases AFF4 levels at chromatin, and vice versa. In summary, these findings demonstrate that AFF1 and AFF4 function antagonistically to regulate RNA polymerase II transcription.
Cell wall dynamics: novel tools and research questions
Authors: Alonso Baez Luis , Bacete Laura 
Published: August 2023

Abstract
Years ago, a classic textbook would define plant cell walls based on passive features. For instance, a sort of plant exoskeleton of invariable polysaccharide composition, and probably painted in green. However, currently, this view has been expanded to consider plant cell walls as active, heterogeneous, and dynamic structures with a high degree of complexity. However, what do we mean when we refer to a cell wall as a dynamic structure? How can we investigate the different implications of this dynamism? While the first question has been the subject of several recent publications, defining the ideal strategies and tools needed to address the second question has proven to be challenging due to the myriad of techniques available. In this review, we will describe the capacities of several methodologies to study cell wall composition, structure, and other aspects developed or optimized in recent years. Keeping in mind cell wall dynamism and plasticity, the advantages of performing long-term non-invasive live-imaging methods will be emphasized. We specifically focus on techniques developed for Arabidopsis thaliana primary cell walls, but the techniques could be applied to both secondary cell walls and other plant species. We believe this toolset will help researchers in expanding knowledge of these dynamic/evolving structures.
Gender in Martin Buber’s Hasidic Tales
Authors: Shonkoff Sam S B 
Published: August 2023

Abstract
Martin Buber’s anthologies of Hasidic tales remain some of his most widely read writings, but few have studied them intertextually vis-à-vis the original Hasidic sources. This article does so, focusing specifically on Buber’s representations of gender in Hasidism. Reading Buber’s tales hermeneutically for gender sheds light on Buber, Hasidism, and the dynamic confluence between them. Firstly, it helps us to identify key aspects of Buber’s representation of Hasidic theology. Regardless of his intentions, when Buber remoulded Hasidic sources to prioritize bodily concreteness over spiritual abstraction, meetings over meditations, and tales over treatises, he subverted theological-metaphysical constructions of gender in Hasidism. Secondly, reading the tales for gender illuminates key aspects of Buber’s representation of Hasidic communities. Buber often softened and omitted sexist elements in the original sources. While this may reveal his egalitarian impulses at times, the article demonstrates that Buber’s efforts to hide misogyny actually rendered women even less visible than they were in the original sources, as images of women dissolved into a sort of gender-blind, neutral (i.e. masculine) humanism. As a whole, Buber’s textual alterations raise thorny questions regarding the ethics of neo-Hasidism or any other movements that gloss over the shadows of historical phenomena.
Diagnosis of Resistance to Thyroid Hormone due to a Rare Mutation in the Thyroid Hormone Receptor Beta Gene in a Patient Previously Presumed to Have Graves’ Disease
Authors: Olatunbosun Samuel T , Kluesner Joseph K , Clerc Philip G , Prasad Shalvin S 
Published: August 2023

ABSTRACT
Clinicians may confuse an impaired sensitivity to thyroid hormone with hyperthyroidism and offer an inappropriate treatment. We report a diagnosis of resistance to thyroid hormone (RTH) caused by a rare mutation in the thyroid hormone receptor beta gene in a patient previously presumed to have Graves’ disease. We have found only one published case of a novel point mutation, c.749T&gt;C (p.Ile250Thr variant) associated with 50% reduction in thyroid hormone receptor binding affinity for triiodothyronine in the I250T mutant; it was found in this patient. A 66-year-old male veteran, with a history of non-ischemic cardiomyopathy and arrhythmias, was referred by a cardiologist with concerns for a possible thyrotropin (TSH) adenoma on account of elevated TSH and free thyroxine (FT4) levels. Pituitary imaging was negative. He was previously treated with radioiodine for presumptive Graves’ disease in the civilian sector. Examination revealed a goiter with no nodules. Repeat TSH and FT4 levels were elevated and also free triiodothyronine (FT3) and reverse triiodothyronine. These findings and other test results were consistent with RTH, which was confirmed by genetic testing. Mutation analysis showed the patient to be heterozygous for the p.Ile250Thr variant. He later developed hypothyroidism. Resistance to thyroid hormone can be misdiagnosed as hyperthyroidism with consequent inappropriate treatment. Treatment is not needed in most RTH-beta patients. Thyroid ablation should generally be avoided. Clinicians must be cautious whenever they encounter concurrent elevation of TSH, FT4, and FT3. This RTH-beta patient has a rare I250T mutant of the thyroid hormone receptor beta gene, the second reported case in the literature.