bluuebunny/crossref_metadata_2025 huggingface dataset:
Stroke Following Coronavirus Disease 2019 Vaccination: Evidence Based on Different Designs of Real-World Studies
Authors: Liu Junyu , Cao Fang , Luo Chun , Guo Yuxin , Yan Junxia
Published: August 2023

Background

We aimed to evaluate whether coronavirus disease 2019 (COVID-19) vaccination was associated with stroke.

Methods

We conducted a systematic meta-analysis of studies using cohort, self-controlled case series (SCCS), and case-crossover study (CCOS) designs to evaluate incidence risk ratios (IRRs) and 95% confidence intervals (CIs) of ischemic stroke (IS), hemorrhagic stroke (HS), and cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination. Risks of stroke were pooled among subpopulations categorized by vaccine type, dose, age, and sex. Sensitivity analysis was performed by different defined risk periods.

Results

Fourteen studies involving 79 918 904 individuals were included. Cohort studies showed decreased risks of IS (IRR, 0.82 [95% CI, .75–.90]) and HS (IRR, 0.75 [95% CI, .67–.85]) postvaccination, but not CVST (IRR, 1.18 [95% CI, .70–1.98]). SCCS identified increased risks 1–21 days postvaccination (IRRIS, 1.05 [95% CI, 1.00–1.10]; IRRHS, 1.16 [95% CI, 1.06–1.26]) or 1–28 days postvaccination (IRRIS, 1.04 [95% CI, 1.00–1.08]; IRRHS, 1.37 [95% CI, 1.15–1.64]), similar to CVST (IRR, 1.58 [95% CI, 1.08–2.32]). CCOS reported an increased risk of CVST after ChAdOx1 vaccination (IRR, 2.9 [95% CI, 1.1–7.2]).

Conclusions

Although different study designs yielded inconsistent findings, considering the relatively low background incidence of stroke and benefits of vaccination, even a potentially increased risk of stroke postvaccination should not justify vaccine hesitancy.
The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence
Authors: Barker Charlotte I S , Kipper Karin , Lonsdale Dagan O , Wright Kirstie , Thompson Georgina , Kim Min , Turner Mark A , Johnston Atholl , Sharland Mike , Standing Joseph F
Published: August 2023

Background

Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care.

Objectives

The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing.

Methods

NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n = 10 000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval.

Results

For the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT>MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h−1 and 1.3 h−1) and bioavailability terms (62.7% and 58.7%, respectively).

Conclusions

NAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.
P02 Strategies for Older People living in care homes to prevent Urinary Tract Infection: the ‘StOP UTI’ realist synthesis of evidence
Authors: Prieto Jacqui , Wilson Jennie , Tingle Alison , Cooper Emily , Handley Melanie , Rycroft-Malone Jo , Bostock Jennifer , Loveday Heather
Published: August 2023

Background

Urinary tract infection (UTI) is the most diagnosed infection in older people living in care homes, accounting for more than 50% of antibiotic prescriptions in this setting. Older people often present with non-specific or atypical symptoms, which may have other origins and are difficult for care home staff to interpret.

Objectives

To identify interventions that could be effective for preventing and recognizing UTI in older people living in care homes in the UK and explore the mechanisms by which they work, for whom and under what circumstances.

Methods

A synthesis of evidence using a realist approach was undertaken to develop, test and refine programme theories, which are the units of analysis within the realist approach. These were expressed as context + mechanism=outcome configurations (CMOc). Their practical relevance and potential for implementation was established through consultation with stakeholders and teacher-learner interviews.

Results

We identified nine CMOc, which describe what needs to happen in care homes to facilitate improvement in practice for the prevention and recognition of UTI. These were arranged under three theory areas: (i) supporting accurate recognition of UTI; (ii) preventing UTI and catheter-associated UTI; and (iii) the infrastructure and systems required to make best practice happen. Our programme theories draw on evidence from a range of areas including infection prevention and control, antimicrobial stewardship, leadership and safety culture in care homes and person-centred care. The findings suggest a whole care team approach, involving residents, their family carers, care home staff and visiting health professionals is needed to develop and implement strategies to improve UTI prevention and recognition. Support at system level, with regulatory and inspection frameworks aligned to evidence on prevention and recognition of UTI, is imperative to ensure the resources and infrastructure are available to enable care home managers and their staff to prioritize this as part of person-centred care.

Conclusions

Our findings have identified the active components of strategies that are effective in preventing and recognizing UTI in older people living in care homes and will help guide delivery of future improvement programmes and research.
P03 Effects of a dietary supplement containing probiotics, cinnamon and cranberry extracts in the prevention of recurrent cystitis
Authors: Ait Abdellah S , Dauchet Q , Leblanc A , Bohbot J M
Published: August 2023

Objectives

A study was conducted to evaluate the effects of a dietary supplement containing two probiotic strains (Lactobacillus helveticus LA201 and Lactobacillus plantarum BL3706, 5×109 cfu per two tablets) and extracts of cinnamon (320 mg) and cranberry (100 mg) in the prevention of recurrent cystitis.

Methods

A total of 80 women (18–65 years) were included who reported at least two episodes of cystitis in the past 6 months, at least one of which was a bacterial cystitis confirmed by a urine cytobacteriological examination or a physician, and for whom the episodes of cystitis had a strong impact on their quality of life (QoL; Acute Cystitis Symptom Score [ACSS] QoL questionnaire >2). Participants took two tablets of the supplement per day for 6 months (n=37; Group 1) or no supplement (n=38; Group 2). The ACSS questionnaire was completed every 15 days, or in case of cystitis, for 8 months (total score ranged from 0 [no urinary discomfort] to 39 [maximum discomfort]). The two groups were comparable at baseline, with a higher proportion of postmenopausal women in Group 1.

Results

During the 6 months, 2/3 of the women in Group 1 had no recurrence of cystitis (0 symptomatic cystitis episodes [SCE]) while 2/3 of the women in Group 2 had at least one SCE (P=0.03 Fisher test). The total ACSS score during SCE was significantly lower in Group 1 (8.4±5.1 versus 12±5.9, P<0.0001 ANOVA), with results in favour of Group 1 for dimensions assessing typical symptoms of acute cystitis and QoL. Compliance and tolerance were excellent.

Conclusions

These results suggest that the supplement may help prevent recurrence of cystitis, particularly in postmenopausal women who are at high risk.
P05 Comparing patients’ and healthcare professionals’ experiences and views on the management of recurrent urinary tract infections: qualitative evidence synthesis and meta-ethnography
Authors: Sanyaolu Leigh , Hayes Catherine , Lecky Donna , Weightman Alison , Ahmed Harry , Cannings-John Rebecca , Edwards Adrian , Wood Fiona
Published: August 2023

Background

Urinary tract infections (UTIs) are common and result in significant morbidity, negative impacts on daily life, reduced quality of life and reduced work attendance. Recurrence is common and recurrent UTIs have an estimated annual prevalence of 3%. The experience of women with recurrent UTIs is not well understood and how this compares to the views of healthcare professionals (HCPs) is unknown.

Objectives

This qualitative evidence synthesis aims to understand the experiences of women with recurrent UTIs and compare them to primary care HCPs.

Methods

We systematically searched MEDLINE, Embase, CINAHL, PsychInfo, ASSIA, Web of Science and the grey literature from inception to June 2022 for primary qualitative studies. Meta-ethnography was conducted to synthesize the studies and the findings for women with recurrent UTIs and HCPs were then compared.

Results

Twelve primary qualitative studies published from 2005 to 2022 and conducted in Europe and the USA were included. Two studies involved primary care staff; nine studies involved women with experience of recurrent UTIs. One study involved both. Patients and HCPs had similar views in terms of the causes of recurrent UTIs and self-management and similar concerns about an underlying cause and antibiotic use. They also had similar views on the impact of recurrent UTIs, however patients felt HCPs did not appreciate the impact of recurrent UTIs. There were conflicts in terms of the expectation for antibiotics and the need for further investigation and referral.

Conclusions

This is the first qualitative evidence synthesis on the experiences of women with recurrent UTIs and the views of primary care HCPs. It demonstrates that women with recurrent UTIs and HCPs share several similar views and concerns but there were significant communication gaps. Further guidance development and a patient decision aid could help address these gaps.
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

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

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

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

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

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 >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

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 (>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 (>60%) after the pandemic. Resistance to ceftazidime, cefepime, ciprofloxacin and amikacin was >80% for Pseudomonas isolates except in 2019 and 2020, where their resistance pattern was within 60%–80%. Imipenem resistance was >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

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

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

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

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

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>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.
The PSZ-MCMF catalogue of Planck clusters over the DES region
Authors: Hernández-Lang D , Klein M , Mohr J J , Grandis S , Melin J-B , Tarrío P , Arnaud M , Pratt G W , Abbott T M C , Aguena M , Alves O , Andrade-Oliveira F , Bacon D , Bertin E , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Castander F J , Costanzi M , da Costa L N , Pereira M E S , Desai S , Diehl H T , Doel P , Everett S , Ferrero I , Flaugher B , Frieman J , García-Bellido J , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hinton S R , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lahav O , Lidman C , Melchior P , Mena-Fernández J , Menanteau F , Miquel R , Palmese A , Paz-Chinchón F , Pieres A , Plazas Malagón A A , Raveri M , Rodriguez-Monroy M , Romer A K , Scarpine V , Sevilla-Noarbe I , Smith M , Suchyta E , Tarle G , Thomas D , Weaverdyck N ,   (DES Collaboration)
Published: August 2023

We present the first systematic follow-up of Planck Sunyaev–Zeldovich effect (SZE) selected candidates down to signal-to-noise (S/N) of 3 over the 5000 deg2 covered by the Dark Energy Survey. Using the MCMF cluster confirmation algorithm, we identify optical counterparts, determine photometric redshifts, and richnesses and assign a parameter, fcont, that reflects the probability that each SZE-optical pairing represents a random superposition of physically unassociated systems rather than a real cluster. The new PSZ-MCMF cluster catalogue consists of 853 MCMF confirmed clusters and has a purity of 90 per cent. We present the properties of subsamples of the PSZ-MCMF catalogue that have purities ranging from 90 per cent to 97.5 per cent, depending on the adopted fcont threshold. Halo mass estimates M500, redshifts, richnesses, and optical centres are presented for all PSZ-MCMF clusters. The PSZ-MCMF catalogue adds 589 previously unknown Planck identified clusters over the DES footprint and provides redshifts for an additional 50 previously published Planck-selected clusters with S/N>4.5. Using the subsample with spectroscopic redshifts, we demonstrate excellent cluster photo-z performance with an RMS scatter in Δz/(1 + z) of 0.47 per cent. Our MCMF based analysis allows us to infer the contamination fraction of the initial S/N>3 Planck-selected candidate list, which is ∼50 per cent. We present a method of estimating the completeness of the PSZ-MCMF cluster sample. In comparison to the previously published Planck cluster catalogues, this new S/N>3 MCMF confirmed cluster catalogue populates the lower mass regime at all redshifts and includes clusters up to z∼1.3.
Testing the cosmological principle with CatWISE quasars: a bayesian analysis of the number-count dipole
Authors: Dam Lawrence , Lewis Geraint F , Brewer Brendon J
Published: August 2023

The Cosmological Principle, that the Universe is homogeneous and isotropic on sufficiently large scales, underpins the standard model of cosmology. However, a recent analysis of 1.36 million infrared-selected quasars has identified a significant tension in the amplitude of the number-count dipole compared to that derived from the cosmic microwave background (CMB), thus challenging the Cosmological Principle. Here, we present a Bayesian analysis of the same quasar sample, testing various hypotheses using the Bayesian evidence. We find unambiguous evidence for the presence of a dipole in the distribution of quasars with a direction that is consistent with the dipole identified in the CMB. However, the amplitude of the dipole is found to be 2.7 times larger than that expected from the conventional kinematic explanation of the CMB dipole, with a statistical significance of 5.7σ. To compare these results with theoretical expectations, we sharpen the ΛCDM predictions for the probability distribution of the amplitude, taking into account a number of observational and theoretical systematics. In particular, we show that the presence of the Galactic plane mask causes a considerable loss of dipole signal due to a leakage of power into higher multipoles, exacerbating the discrepancy in the amplitude. By contrast, we show using probabilistic arguments that the source evolution of quasars improves the discrepancy, but only mildly so. These results support the original findings of an anomalously large quasar dipole, independent of the statistical methodology used.
Assessing the Feasibility of Conducting Smoking Cessation Outreach in Food Pantries: A Pilot Intervention Study
Authors: Kim-Mozeleski Jin E , Smell Adrianna , Castele Madeline C , Ogden Erin , Trapl Erika S
Published: August 2023

Introduction

Smoking prevalence is high among US adults with food insecurity. This study examined how food assistance settings, namely food pantries, can serve as a community-based venue to reach food insecure adults who smoke for smoking cessation.

Methods

Partnering with a local hunger relief organization, we conducted surveys and focus groups of food pantry clients in Greater Cleveland, Ohio, followed by food pantry-based outreach events to connect people who smoke to the Ohio Tobacco Quit Line.

Results

The survey included 132 participants who visited a food pantry (M age = 47; 74% women; 39% Black/African American), of whom 35% were using tobacco and 31% were smoking cigarettes. Among those currently smoking (M cigarettes/day = 9), 76% intended to quit in the next 6 months, and 82% had not used nor heard of the quitline. Informed by focus group themes, we conducted a total of 22 outreach events at four pantries. Among those interested in smoking cessation resources from the outreach events (n = 54), 78% were able to be subsequently contacted. Of them, 74% provided consent for quitline referral. The remainder either declined or were unable to participate.

Conclusions

While it was feasible to leverage food pantries for smoking cessation outreach, the overall reach was low. Despite high interest in quitting, there was limited effectiveness of outreach efforts without adaptations to each pantry setting and in recognition of the immediate food needs and with challenges related to the COVID-19 pandemic. There remains a critical need to address high rates of smoking among populations experiencing food insecurity.

Implications

Tobacco cessation services are increasingly recognizing the need to address food insecurity and other social needs that commonly occur in populations who use tobacco at higher rates. This research underscores both the value and the challenges related to leveraging food pantries as a community-based venue for smoking cessation outreach. In addition to improvements in outreach models, long-term investments in structural interventions are also needed to address underlying poverty and socioeconomic disadvantage that ultimately drive disparities in smoking and in food insecurity.
Successful Treatment of Paecilomyces variotii Pneumonia and Lupus Nephritis With Posaconazole-Cyclophosphamide Co-administration Without Drug Interaction–Induced Toxicity
Authors: Pechacek Joseph , Webb Taura , Ferré Elise M N , Schmitt Monica M , DiMaggio Thomas , Kobrin Dale , Rajasimhan Suraj , Colton Ben , Lewis Russell E , Andes David , Herrera Alejandro , Hammoud Dima , Seyedmousavi Seyedmojtaba , Hasni Sarfaraz , Bolaños Jonathan , Afzali Behdad , Lionakis Michail S
Published: August 2023

Paecilomyces variotii is an opportunistic mold that causes pulmonary infections in immunosuppressed humans that are often treated with triazole therapy. Lupus nephritis is a major cause of progressive kidney disease in patients with systemic lupus erythematosus, often requiring cyclophosphamide-based therapies. Triazole-cyclophosphamide co-administration is challenging as triazoles increase cyclophosphamide concentrations, which can worsen cyclophosphamide toxicity. We describe herein a patient with Paecilomyces variotii pneumonia and concomitant lupus nephritis who was successfully treated with posaconazole and echinocandin-bridged interruptions to allow for cyclophosphamide therapy. This regimen was well-tolerated without cyclophosphamide toxicity and achieved improvements in both fungal pneumonia and renal function.
Pharmacovigilance Study on Eosinophilic Pneumonia Induced by Anti-MRSA Agents: Analysis Based on the FDA Adverse Event Reporting System
Authors: Okada Naoto , Niimura Takahiro , Saisyo Atsuyuki , Kawaguchi Yoshitaka , Ishizawa Keisuke , Kitahara Takashi
Published: August 2023

Background

Eosinophilic pneumonia (EP) is a rare adverse event caused by several types of drugs, such as antibiotics; however, its characteristics remain poorly described. This study aimed to analyze the disproportionality between the occurrence of EP and anti–methicillin-resistant Staphylococcus aureus (anti-MRSA) agents and to characterize anti-MRSA agent–induced EP events using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Method

Disproportionality linking EP and anti-MRSA agents was analyzed through bayesian confidence propagation neural networks of information components and reporting odds ratio methodologies. The FAERS data set for the fourth quarter of 2012 to the fourth quarter of 2022 was used. We also analyzed the characteristics of EP induced by anti-MRSA agents.

Results

A total of 14 805 795 reports were obtained from FAERS. Disproportionality analysis revealed that the EP signal was detected only in cases with the administration of daptomycin (DAP). This disproportionality signal was consistently detected in the sensitivity analysis. When compared with other reports of DAP-related adverse events, the reports of DAP-related EP were characterized by male sex (odds ratio [OR], 1.94; 95% CI, 1.12–3.37), older age (>70 years; OR, 2.70; 95% CI, 1.68–4.33), and longer duration of treatment (>21 days; OR, 5.08; 95% CI, 3.21–8.05).

Conclusions

This study revealed that among the anti-MRSA agents, disproportionality in the occurrence of EP was observed only with DAP. Our results suggest that sex, age, and treatment duration may affect the occurrence of DAP-induced EP. Clinicians should exercise caution regarding EP during DAP administration.
Reappraising Crystallization Kinetics with Overgrowth Chronometry: an in Situ Study of Olivine Growth Velocities
Authors: Welsch Benoît , Faure François , First Emily C
Published: August 2023

We investigated the early stages of olivine crystal growth via in situ seeded experiments in a single plagioclase-hosted melt inclusion, using a heating stage microscope. Each experiment was subjected to a cooling ramp of 7800°C/h followed by an isothermal dwell at 19°C, 38°C, 57°C, 77°C, 96°C or 129°C of undercooling. The seeds (6–16 μm in diameter Ø) grew into large crystals (Ø 80–169 μm) in 3 to 30 min through the symmetrical development of tabular, skeletal, and dendritic overgrowths as the undercooling of the system increased. Time-resolved image processing and incremental measurements of the overgrowth thicknesses indicate up to three stages of crystal growth: an acceleration stage, a linear (constant growth rate) stage, and a deceleration stage. At the isotherm, the growth velocities reach a stable maximum that in all experiments corresponds to the period of linear growth. The highest linear values are measured at the $\left\{101\right\}$ interfaces, from 2.1 × 10−8 m/s at 19°C of undercooling to 4.8 × 10−7 m/s at 129°C of undercooling. Crystal growth is slower at other interfaces, in the ranges 1.9–7.6 × 10−8 m/s and 4.5 × 10−9 – 7.6 × 10−8 m/s for the $\left\{100\right\}$ and $\left\{001\right\}$ forms, respectively. Growth in the $<010>$ dimension appears limited to less than 2.4 × 10−8 m/s at 129°C of undercooling. We constrain the uncertainty on these growth velocities, which includes the environmental conditions (± 8.6°C on the nominal undercooling) and the measurements of crystal lengths (underestimated by <16% at most fast interfaces).

A systematic and comprehensive review of 19 pre-existing datasets indicates that our linear growth velocities are faster than most growth rates determined at comparable undercoolings. Growth rates determined as half crystal lengths divided by total time are intrinsically low estimates of the true maximum, linear growth velocities, because the total time includes periods of slower or non-growth, and measured crystal dimensions are subject to projection foreshortening or truncation. These errors can lead to values that are several times to several orders of magnitude lower than the true maximum growth rates. This study completes and refines previously published data on the crystallization kinetics of olivine, highlighting the sensitivity of growth rates to specific environmental conditions and measurement methods. We emphasize the importance of symmetrical growth and true maximum growth velocities for interpreting olivine growth histories.