bluuebunny/crossref_metadata_2025_split huggingface dataset:
P30 A longitudinal perspective of antimicrobial resistance evolution within urinary tract infection-based clinical trials
Authors: Aldridge Phillip , Tan Aaron , Spencer Alexandra , Vallée Maxime , Harding Chris , Hall Judith 
Published: August 2023

Abstract

Background
The mainstay treatments for urinary tract infections (UTIs) are nitrofurantoin and trimethoprim. The common route to acquire trimethoprim resistance (TriR) is via horizontal transfer of the trimethoprim-insensitive dihydrofolate reductase: dfrA. In contrast, nitrofurantoin resistance (NitR) requires the inactivation of two chromosomally encoded nitroreductases: nfsA and nfsB. The difference in antimicrobial resistance (AMR) evolution is reflected in community surveillance data: NitR incidence = ∼10% and for TriR &gt; 30%. Longitudinal clinical UTI trials provide a unique opportunity to monitor in situ evolution of AMR and correlate its appearance to trial outcomes and the impact on uropathogens.

Objectives
To explore the in situ AMR evolution and its impact in Escherichia coli isolates from patients participating in the clinical trials: AnTIC and ALTAR. AnTIC was an open label randomized trial assessing the efficacy of antibiotic prophylaxis use in clean intermittent self-catheterizing patients. ALTAR compared the efficacy of the non-antibiotic alternative methenamine hippurate to antibiotic prophylaxis to treat recurrent UTIs.

Methods
The investigation of the evolution of nitrofurantoin and trimethoprim resistance in E. coli used general microbiology techniques, bioinformatic genome analysis and genetics to model known AMR mutations in susceptible E. coli strains.

Results
Trimethoprim resistance amongst E. coli trial isolates was driven by 14 out of ∼45 known dfrA allelic variants; the most common being dfrA1 and dfrA17. Growth analysis identified an allelic bias when strains were exposed to sub-MIC concentrations of trimethoprim. Growth rate analysis identified a 2%–10% slower doubling time for nitrofurantoin-resistant strains: NitS: 20.8 ± 0.7 min compared to NitR: 23 ± 0.8 min. Statistically, these data suggested no fitness advantage of evolved strains compared to the sensitive predecessor (P value = 0.13). Genetic manipulation of E. coli to mimic NitR evolution, however, supported a selective advantage.

Conclusions
Longitudinal sampling during antibiotic based clinical trials has provided a new perspective to the response of E. coli to UTI-related antibiotics. Correlation of nitrofurantoin response to pharmacokinetic data suggests that the low incidence of E. coli NitR is driven by selection not fitness. However, fitness correlates to dfrA allele carriage and could potentially be exploited to benefit the use of trimethoprim if other antibiotics are impeded by AMR.
P32 Performance of a novel molecular test designed for point-of-care UTI diagnosis
Authors: van der Goes Ayako , Diggle Joanna , Nieuwland Jeroen , Roula Ali , Hayhurst Emma 
Published: August 2023

Abstract

Objectives
To evaluate the performance of a novel LAMP-based molecular test for the diagnosis of UTIs. The Llusern Scientific UTI test system consists of a panel of six uropathogen tests, positive and negative controls and an analyser, ‘Lodestar DX’ (Figure 1). The analyser will read the reaction data and give the user a simple ‘positive’ or ‘negative’ read out for each uropathogen. The specific aim was to determine the sensitivity and specificity of the test system for the most common uropathogen, Escherichia coli. Figure 1.Lodestar DX.

Methods
In total, 149 urine samples received by Public Health Wales laboratories, Cardiff were randomly selected; 1 μL of each urine sample was added directly to each pre-made E. coli LAMP test. E. coli LAMP tests were placed into the Lodestar DX analyser and run. Results were shown and recorded after 40 minutes as ‘positive’ or ‘negative’ according to the decision of Lodestar's algorithm. LAMP results were compared to standard culture results and sensitivity and specificity calculated.

Results
Overall sensitivity of the E. coli LAMP test was 86.2%. Specificity was 88.3% (Table 1). Of the 14 samples positive in the LAMP test for E. coli but not recorded as E. coli using culture, 11 were from ‘mixed growth’ samples (Table 2). Table 1.Sensitivity and specificity of E. coli LAMP testLAMP positiveLAMP negativeTotalCulture positive25 (true positives)4 (false negatives)29Culture negative14 (false positives)106 (true negatives)120Total39110149Overall sensitivity((25/29) × 100) = 86.2%Overall specificity((106/120) × 100) = 88.3% Table 2.Results of LAMP compared with culture resultsCulture resultnE. coli Lodestar LAMP resultpositiveinconclusivenegativeE. coli positive292504Other pathogen positive121011Mixed growth6111050No growth472045Total149390110

Conclusions
The Llusern Scientific UTI test system shows great promise as a point-of-care diagnostic tool. Sensitivity and specificity for E. coli was high and the test system may be better at diagnosing mixed infections which represent a high proportion of all culture results. The test system is easy to use with no sample processing and minimal training requirements. Test results are available in 40 min, compared to 24–72 h for culture results. The performance of the test system for the detection of other uropathogens (Klebsiella, Enterococcus, Pseudomonas, Proteus and S. saprophyticus) is ongoing. Sensitivity can be further improved by refining the test method.
Optimizing Best Practice Advisory alerts in electronic medical records with a multi-pronged strategy at a tertiary care hospital in Singapore
Authors: Ng Hannah Jia Hui , Kansal Amit , Abdul Naseer Jishana Farhad , Hing Wee Chuan , Goh Carmen Jia Man , Poh Hermione , D’souza Jared Louis Andre , Lim Er Luen , Tan Gamaliel 
Published: August 2023

Abstract

Objective
Clinical decision support (CDS) alerts can aid in improving patient care. One CDS functionality is the Best Practice Advisory (BPA) alert notification system, wherein BPA alerts are automated alerts embedded in the hospital’s electronic medical records (EMR). However, excessive alerts can change clinician behavior; redundant and repetitive alerts can contribute to alert fatigue. Alerts can be optimized through a multipronged strategy. Our study aims to describe these strategies adopted and evaluate the resultant BPA alert optimization outcomes.

Materials and Methods
This retrospective single-center study was done at Jurong Health Campus. Aggregated, anonymized data on patient demographics and alert statistics were collected from January 1, 2018 to December 31, 2021. “Preintervention” period was January 1–December 31, 2018, and “postintervention” period was January 1–December 31, 2021. The intervention period was the intervening period. Categorical variables were reported as frequencies and proportions and compared using the chi-square test. Continuous data were reported as median (interquartile range, IQR) and compared using the Wilcoxon rank-sum test. Statistical significance was defined at P &lt; .05.

Results
There was a significant reduction of 59.6% in the total number of interruptive BPA alerts, despite an increase in the number of unique BPAs from 54 to 360 from pre- to postintervention. There was a 74% reduction in the number of alerts from the 7 BPAs that were optimized from the pre- to postintervention period. There was a significant increase in percentage of overall interruptive BPA alerts with action taken (8 [IQR 7.7–8.4] to 54.7 [IQR 52.5–58.9], P-value &lt; .05) and optimized BPAs with action taken (32.6 [IQR 32.3–32.9] to 72.6 [IQR 64.3–73.4], P-value &lt; .05). We estimate that the reduction in alerts saved 3600 h of providers’ time per year.

Conclusions
A significant reduction in interruptive alert volume, and a significant increase in action taken rates despite manifold increase in the number of unique BPAs could be achieved through concentrated efforts focusing on governance, data review, and visualization using a system-embedded tool, combined with the CDS Five Rights framework, to optimize alerts. Improved alert compliance was likely multifactorial—due to decreased repeated alert firing for the same patient; better awareness due to stakeholders’ involvement; and less fatigue since unnecessary alerts were removed. Future studies should prospectively focus on patients’ clinical chart reviews to assess downstream effects of various actions taken, identify any possibility of harm, and collect end-user feedback regarding the utility of alerts.
Melatonin supplementation promotes muscle fiber hypertrophy and regulates lipid metabolism of skeletal muscle in weaned piglets
Authors: Chen Wentao , Tu Yuang , Cai Peiran , Wang Liyi , Zhou Yanbing , Liu Shiqi , Huang Yuqin , Zhang Shu , Gu Xin , Yi Wuzhou , Shan Tizhong 
Published: August 2023

Abstract
Melatonin has been reported to play crucial roles in regulating meat quality, improving reproductive properties, and maintaining intestinal health in animal production, but whether it regulates skeletal muscle development in weaned piglet is rarely studied. This study was conducted to investigate the effects of melatonin on growth performance, skeletal muscle development, and lipid metabolism in animals by intragastric administration of melatonin solution. Twelve 28-d-old DLY (Duroc × Landrace × Yorkshire) weaned piglets with similar body weight were randomly divided into two groups: control group and melatonin group. The results showed that melatonin supplementation for 23 d had no effect on growth performance, but significantly reduced serum glucose content (P &lt; 0.05). Remarkably, melatonin increased longissimus dorsi muscle (LDM) weight, eye muscle area and decreased the liver weight in weaned piglets (P &lt; 0.05). In addition, the cross-sectional area of muscle fibers was increased (P &lt; 0.05), while triglyceride levels were decreased in LDM and psoas major muscle by melatonin treatment (P &lt; 0.05). Transcriptome sequencing showed melatonin induced the expression of genes related to skeletal muscle hypertrophy and fatty acid oxidation. Enrichment analysis indicated that melatonin regulated cholesterol metabolism, protein digestion and absorption, and mitophagy signaling pathways in muscle. Gene set enrichment analysis also confirmed the effects of melatonin on skeletal muscle development and mitochondrial structure and function. Moreover, quantitative real-time polymerase chain reaction analysis revealed that melatonin supplementation elevated the gene expression of cell differentiation and muscle fiber development, including paired box 7 (PAX7), myogenin (MYOG), myosin heavy chain (MYHC) IIA and MYHC IIB (P &lt; 0.05), which was accompanied by increased insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 5 (IGFBP5) expression in LDM (P &lt; 0.05). Additionally, melatonin regulated lipid metabolism and activated mitochondrial function in muscle by increasing the mRNA abundance of cytochrome c oxidase subunit 6A (COX6A), COX5B, and carnitine palmitoyltransferase 2 (CPT2) and decreasing the mRNA expression of peroxisome proliferator-activated receptor gamma (PPARG), acetyl-CoA carboxylase (ACC) and fatty acid-binding protein 4 (FABP4) (P &lt; 0.05). Together, our results suggest that melatonin could promote skeletal muscle growth and muscle fiber hypertrophy, improve mitochondrial function and decrease fat deposition in muscle.
Direct binding of calmodulin to the cytosolic C-terminal regions of sweet/umami taste receptors
Authors: Yoshida Atsuki , Ito Ayumi , Yasui Norihisa , Yamashita Atsuko 
Published: August 2023

Abstract
Sweet and umami taste receptors recognize chemicals such as sugars and amino acids on their extracellular side and transmit signals into the cytosol of the taste cell. In contrast to ligands that act on the extracellular side of these receptors, little is known regarding the molecules that regulate receptor functions within the cytosol. In this study, we analysed the interaction between sweet and umami taste receptors and calmodulin, a representative Ca2+-dependent cytosolic regulatory protein. High prediction scores for calmodulin binding were observed on the C-terminal cytosolic side of mouse taste receptor type 1 subunit 3 (T1r3), a subunit that is common to both sweet and umami taste receptors. Pull-down assay and surface plasmon resonance analyses showed different affinities of calmodulin to the C-terminal tails of distinct T1r subtypes. Furthermore, we found that T1r3 and T1r2 showed the highest and considerable binding to calmodulin, whereas T1r1 showed weaker binding affinity. Finally, the binding of calmodulin to T1rs was consistently higher in the presence of Ca2+ than in its absence. The results suggested a possibility of the Ca2+-dependent feedback regulation process of sweet and umami taste receptor signaling by calmodulin.
Binding profile of quinonoid-dihydrobiopterin to quinonoid-dihydropteridine reductase examined by in silico and in vitro analyses
Authors: Kono Haruka , Hara Satoshi , Furuta Tadaomi , Ichinose Hiroshi 
Published: August 2023

Abstract
Quinonoid dihydropteridine reductase (QDPR) catalyses the reduction of quinonoid-form dihydrobiopterin (qBH2) to tetrahydrobiopterin (BH4). BH4 metabolism is a drug target for neglected tropical disorders because trypanosomatid protozoans, including Leishmania and Trypanosoma, require exogenous sources of biopterin for growth. Although QDPR is a key enzyme for maintaining intracellular BH4 levels, the precise catalytic properties and reaction mechanisms of QDPR are poorly understood due to the instability of quinonoid-form substrates. In this study, we analysed the binding profile of qBH2 to human QDPR in combination with in silico and in vitro methods. First, we performed docking simulation of qBH2 to QDPR to obtain possible binding modes of qBH2 at the active site of QDPR. Then, among them, we determined the most plausible binding mode using molecular dynamics simulations revealing its atomic-level interactions and confirmed it with the in vitro assay of mutant enzymes. Moreover, it was found that not only qBH2 but also quinonoid-form dihydrofolate (qDHF) could be potential physiological substrates for QDPR, suggesting that QDPR may be a bifunctional enzyme. These findings in this study provide important insights into biopterin and folate metabolism and would be useful for developing drugs for neglected tropical diseases.
Continuity and change in the British diplomatic service in the Levant
Authors: Patrizio Gunning Lucia , Vlami Despina 
Published: August 2023

Abstract
In this article, we examine the organization of the British diplomatic service in the Ottoman Empire and analyse its transition from a prestigious, privately financed, highly individualized public office to a state-funded, but fragmented and poorly paid body. We survey the idiosyncratic character of the diplomatic apparatus set up by the Levant Company to serve its business pursuits, infiltrate local society and obtain political favours. In 1825 the Foreign Office replaced the Levant Company officers with public servants who had no ties or affinities with Levantine society. However, to obtain antiquities for the British Museum, the Foreign Office had to turn once again to British Levantines. Based on our earlier published work,1 as well as recent unpublished archival research, this paper explains how the collecting of antiquities in the Ottoman Empire relied entirely on the British diplomatic service and its Levantine connection.
A common inducer molecule enhances sugar utilization by Shewanella oneidensis MR-1
Authors: Gruenberg Megan C , TerAvest Michaela A 
Published: August 2023

Abstract
Shewanella oneidensis MR-1 is an electroactive bacterium that is a promising host for bioelectrochemical technologies, which makes it a common target for genetic engineering, including gene deletions and expression of heterologous pathways. Expression of heterologous genes and gene knockdown via CRISPRi in S. oneidensis are both frequently induced by β-D-1-thiogalactopyranoside (IPTG), a commonly used inducer molecule across many model organisms. Here, we report and characterize an unexpected phenotype; IPTG enhances the growth of wild-type S. oneidensis MR-1 on the sugar substrate N-acetylglucosamine (NAG). IPTG improves the carrying capacity of S. oneidensis growing on NAG while the growth rate remains similar to cultures without the inducer. Extracellular acetate accumulates faster and to a higher concentration in cultures without IPTG than those with it. IPTG appears to improve acetate metabolism, which combats the negative effect that acetate accumulation has on the growth of S. oneidensis with NAG. We recommend using extensive experimental controls and careful data interpretation when using both NAG and IPTG in S. oneidensis cultures.
NCI Rectal-Anal Task Force consensus recommendations for design of clinical trials in rectal cancer
Authors: Kennecke Hagen F , Auer Rebecca , Cho May , Dasari N Arvind , Davies-Venn Cynthia , Eng Cathy , Dorth Jennifer , Garcia-Aguilar Julio , George Manju , Goodman Karyn A , Kreppel Lillian , Meyer Joshua E , Monzon Jose , Saltz Leonard , Schrag Deborah , Smith J Joshua , Zell Jason A , Das Prajnan ,   the National Cancer Institute Rectal-Anal Task Force, Allegra Carmen , Kennecke Hagen , Auer Rebecca , Kreppel Lillian , Benson Al , Mamon Harvey , Chang George , Meyer Josh , Cho May , Meyerhardt Jeff , Das Prajnan , Monzon Jose , Dasari Arvind , Ou Fang-Shu , Deming Dusty , Rajdev Lakshmi , Dorth Jennifer , Rogers Jane , Eng Cathy , Romak Lindsay , Fisher George , Romesser Paul , Garcia-Aguilar Julio , Saltz Leonard , George Manju , Schrag Deborah , George Thomas , Sheybani Arshin , Goodman Karyn , Shi Qian , Gordon Vallerie , Smith J Joshua , Hall William , VanderWalde Noam , Iqbal Atif , Yothers Greg , Kachnic Lisa , Zell Jason 
Published: August 2023

Abstract
The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established. The task force achieved consensus on several areas, including the following: 1) the use of total neoadjuvant therapy with long-course radiation therapy either before or after chemotherapy, as well as short-course radiation therapy followed by chemotherapy, as the control arm of clinical trials; 2) the need for greater emphasis on patient involvement in treatment choices within the context of trial design; 3) efforts to identify those patients likely, or unlikely, to benefit from nonoperative management or minimally invasive surgery; 4) investigation of the utility of circulating tumor DNA measurements for tailoring treatment and surveillance; and 5) the need for identification of appropriate end points and recognition of challenges of data management for patients who enter nonoperative management trial arms. Substantial agreement was reached on priorities affecting the design of future clinical trials in patients with locally advanced rectal cancer.
Florence Nightingale and the Provincial Response to the Crimean War
Authors: Memel Jonathan Godshaw 
Published: August 2023

Abstract
Florence Nightingale rose to fame early in 1855 at a time when provincialism was assuming unprecedented importance in Victorian culture. The London papers The Times and the Illustrated London News linked Nightingale to the typically provincial domain of the parish and the home: her public image reflecting the wish to extend domestic comfort to soldiers, adrift on foreign land and neglected by uncaring military authorities. Nightingale’s campaigns to improve soldiers’ conditions then galvanized the charitable enthusiasms of households across Britain and its colonies, as the public sent contributions ranging from knitted slippers to bedsheets repurposed as wound dressings on ships to the Crimea. Nightingale subsequently introduced army reading rooms stocked with works of regional and provincial fiction, either as actual volumes or as instalments in periodicals such as Household Words, to bring the imaginative connections between the parish and the Scutari hospitals closer still. While recent work by Stefanie Markovits and Holly Furneaux has shown how the cultural lives of ‘home’ and ‘the East’ were closer than previously thought, I contend that two distinctively provincial features of Nightingale’s place within the conflict have not been sufficiently recognized. First, Nightingale drew on gendered notions of the home and domesticity that were crucial to the provincial as it gained appeal and meaning during the middle of the century. Second, in facilitating imaginative connections between soldiers and the reading public many thousands of miles away, Nightingale showed that the provincial operated most effectively at distance, where its effects were felt most strongly among an increasingly dispersed and fragmented nation.
A meta-analysis of the accuracy of Xpert MTB/RIF in diagnosing intestinal tuberculosis
Authors: Ding Yuan-Lin , Yan Rui-Chao , Chen Hao-Kai , Guo Xu-Guang 
Published: August 2023

Abstract

Objective
A detection method with high efficiency and accuracy is urgently needed in clinical work. The purpose of our study was to determine the diagnostic accuracy of the Xpert MTB/RIF assay for intestinal tuberculosis (ITB).

Methods
We searched PubMed and 4 other databases from their establishment to July 19, 2022, for published essays of diagnostic performance in which Xpert MTB/RIF was used to test patients with clinically suspected ITB. An assessment of the quality of the selected literature was conducted using QUADAS-2. We built forest plots by MetaDiSc software.

Results
The pooled Xpert MTB/RIF sensitivity was 48%, and the specificity was 99%. Moreover, the positive likelihood ratio for ITB diagnosis was 21.61. The negative likelihood ratio was 0.54. There were substantial variations between the study estimates of sensitivity (I2 = 87.6%) and specificity (I2 = 82.4%).

Conclusion
Intestinal TB is detected with limited diagnostic sensitivity by Xpert MTB/RIF but with high specificity. An Xpert-positive result may facilitate the rapid identification of ITB cases. Nevertheless, a negative result has less certainty in excluding the disease.
Temperature influence on the compression and breakage behaviour of yeast cells
Authors: Overbeck Achim , Michel Stephanie , Kampen Ingo , Kwade Arno 
Published: August 2023

Abstract
Industrial biotechnology uses microbial cells to produce a wide range of products. While the genetic and molecular properties of these organisms are well understood, less is known about their mechanical properties. Previous work has established a test procedure for single yeast cells using a nanoindentation instrument equipped with a flat-punch probe, which allows single cells (Saccharomyces cerevisiae) to be compressed between two parallel surfaces. The resulting force–displacement curves clearly showed the bursting of the cells and were used to determine characteristics such as burst force and burst energy. Other studies have investigated the influence of growth conditions and measurement conditions on the mechanical characteristics. The recent study examined the mechanical characteristics according to the temperature during compression. Temperature from 0°C to 25°C has no significant effect on the micromechanical properties. Increasing the temperature up to 35°C causes a reduction in the strength of the cells. At even higher temperatures, up to 50°C, the burst force and burst energy increase significantly. A deformation geometry model was used to calculate the cell wall tensile strength as a function of temperature. The results of these studies may facilitate the identification of efficient conditions for cell disruption and product recovery in downstream biotechnological processes.