bluuebunny/crossref_metadata_2025 huggingface dataset:
Crohn’s Patient Serum Proteomics Reveals Response Signature for Infliximab but not Vedolizumab
Authors: Gonzalez Carlos G , Stevens Toer W , Verstockt Bram , Gonzalez David J , D’Haens Geert , Dulai Parambir S
Published: February 2024

Background

Crohn’s disease is a chronic inflammatory bowel disease that affects the gastrointestinal tract. Common biologic families used to treat Crohn’s are tumor necrosis factor (TNF)-α blockers (infliximab and adalimumab) and immune cell adhesion blockers (vedolizumab). Given their differing mechanisms of action, the ability to monitor response and predict treatment efficacy via easy-to-obtain blood draws remains an unmet need.

Methods

To investigate these gaps in knowledge, we leveraged 2 prospective cohorts (LOVE-CD, TAILORIX) and profiled their serum using high-dimensional isobaric-labeled proteomics before treatment and 6 weeks after treatment initiation with either vedolizumab or infliximab.

Results

The proportion of patients endoscopically responding to treatment was comparable among infliximab and vedolizumab cohorts; however, the impact of vedolizumab on patient sera was negligible. In contrast, infliximab treatment induced a robust response including increased blood-gas regulatory response proteins, and concomitant decreases in inflammation-related proteins. Further analysis comparing infliximab responders and nonresponders revealed a lingering innate immune enrichments in nonresponders and a unique protease regulation signature related to clotting cascades in responders. Lastly, using samples prior to infliximab treatment, we highlight serum protein biomarkers that potentially predict a positive response to infliximab treatment.

Conclusions

These results will positively impact the determination of appropriate patient treatment and inform the selection of clinical trial outcome metrics.
Hierarchical consumption preferences, redistribution, and structural transformation
Authors: Aboobaker Adam
Published: February 2024

In low- and middle-income economies, consumption preferences are hierarchical and the production structure is dualistic. Wage demand correspondingly articulates with the domestic industrial sector in a limited fashion. Where capital accumulation is directed at this modern/industrial sector, downward redistributions are less expansionary than commonly outlined, even if capacity utilization is an adjusting variable influencing investment decisions. Insofar as economic development is underpinned by structural transformation, policies aligned with downward redistributions have important sectoral ramifications neglected in one-sector frameworks. This paper explores these and related propositions formally, drawing from the analysis of a two-sector growth and distribution model.
On the measurement of cause of death inequality
Authors: Permanyer Iñaki , Calazans Júlia Almeida
Published: February 2024

Background

Attempts at assessing heterogeneity in countries’ mortality profiles often rely on measures of cause of death (CoD) diversity. Unfortunately, such indicators fail to take into consideration the degree of (dis)similarity among pairs of causes (e.g. ‘transport injuries’ and ‘unintentional injuries’ are implicitly assumed to be as dissimilar as ‘transport injuries’ and ‘Alzheimer’s disease’)－an unrealistic and unduly restrictive assumption.

Development

We extend diversity indicators proposing a broader class of heterogeneity measures that are sensitive to the similarity between the causes of death one works with. The so-called ‘CoD inequality’ measures are defined as the average expected ‘dissimilarity between any two causes of death’. A strength of the approach is that such measures are decomposable, so that users can assess the contribution of each cause to overall CoD heterogeneity levels—a useful property for the evaluation of public health policies.

Application

We have applied the method to 15 low-mortality countries between 1990 and 2019, using data from the Global Burden of Disease project. CoD inequality and CoD diversity generally increase over time across countries and sex, but with some exceptions. In several cases (notably, Finland), both indicators run in opposite directions.

Conclusions

CoD inequality and diversity indicators capture complementary information about the heterogeneity of mortality profiles, so they should be analysed alongside other population health metrics, such as life expectancy and lifespan inequality.
Development path of a modern rural power grid under dual carbon target based on data analysis
Authors: Ye Linhao , Liu Zhiwen , Liang Yu
Published: February 2024

In China’s economic and social development planning, dual carbon goals and modern rural constructions have become new keywords. It is important to realize the green transformation of energy systems and complete the construction of a modern rural power grid based on data analysis under the guidance of dual carbon goals. Based on the systematic summary of the rural energy structure, this paper assesses the current situation of the scientific and technological development of rural power grids, analyzes the main problems faced by the development of rural power grids, and gives suggestions on the path of energy transformation and the path of rural power grid development. The results show that rural energy transformation plays an important role in the implementation of the dual carbon goals, and the relationship between the long-term and short-term goals of rural energy transformation, top-level design and differentiated development, government regulation and market forces, development stage and energy consumption expenditure must be handled well. In addition, as an important support, rural power grid enterprises should seize the opportunities brought by the construction of rural power grids under the dual carbon goals, make rural power a technology to be valued, and promote the further development of new energy-related technologies.
Privacy and personal information protection in China’s all-seeing state
Authors: Ong Rebecca
Published: February 2024

The proliferation of artificial intelligence (AI)-enabled facial recognition technology (FRT) in the provision of vital services that depend on accurate identification of individuals within China’s public and private sectors prompted an urgent need to foster discussions regarding regulatory, societal, and ethical concerns. While there are safety and efficiency gains to be obtained through the use of FRT where establishing identity is necessary, these result in potential trade-offs against the individuals’ fundamental rights, most notably, the violation of the right to privacy, and personal information where individuals are neither informed of nor consented to the collection, use, or storage. To address such concerns, China has put in place laws. The adequacy of which in addressing the concerns remains. This paper argues that, while significant progress has been made with the promulgation of several legislations, much more needs to be undertaken in terms of ensuring transparency in decision-making on public uses and obtaining prior mandatory authorization before the deployment of FRT. The paper further suggests the engagement of a multi-disciplinary team of experts to support and guide research, development, and deployment of AI-enabled FRT and other biometric technology as a positive step forward together with the possible adoption of adaptive governance as a framework for future policy design.
PI3K-AKT/mTOR Signaling in Psychiatric Disorders: A Valuable Target to Stimulate or Suppress?
Authors: Chen Yan , Guan Wei , Wang Mei-Lan , Lin Xiao-Yun
Published: February 2024

Economic development and increased stress have considerably increased the prevalence of psychiatric disorders in recent years, which rank as some of the most prevalent diseases globally. Several factors, including chronic social stress, genetic inheritance, and autogenous diseases, lead to the development and progression of psychiatric disorders. Clinical treatments for psychiatric disorders include psychotherapy, chemotherapy, and electric shock therapy. Although various achievements have been made researching psychiatric disorders, the pathogenesis of these diseases has not been fully understood yet, and serious adverse effects and resistance to antipsychotics are major obstacles to treating patients with psychiatric disorders. Recent studies have shown that the mammalian target of rapamycin (mTOR) is a central signaling hub that functions in nerve growth, synapse formation, and plasticity. The PI3K-AKT/mTOR pathway is a critical target for mediating the rapid antidepressant effects of these pharmacological agents in clinical and preclinical research. Abnormal PI3K-AKT/mTOR signaling is closely associated with the pathogenesis of several neurodevelopmental disorders. In this review, we focused on the role of mTOR signaling and the related aberrant neurogenesis in psychiatric disorders. Elucidating the neurobiology of the PI3K-AKT/mTOR signaling pathway in psychiatric disorders and its actions in response to antidepressants will help us better understand brain development and quickly identify new therapeutic targets for the treatment of these mental illnesses.
Nodal Decompositions of a Symmetric Matrix
Authors: McKenzie Theo , Urschel John
Published: February 2024

Analyzing nodal domains is a way to discern the structure of eigenvectors of operators on a graph. We give a new definition extending the concept of nodal domains to arbitrary signed graphs, and therefore to arbitrary symmetric matrices. We show that for an arbitrary symmetric matrix, a positive fraction of eigenbases satisfy a generalized version of known nodal bounds for un-signed (that is classical) graphs. We do this through an explicit decomposition. Moreover, we show that with high probability, the number of nodal domains of a bulk eigenvector of the adjacency matrix of a signed Erdős-Rényi graph is $\Omega (n/\log n)$ and $o(n)$.
A Non-Symmetric Kesten Criterion and Ratio Limit Theorem for Random Walks on Amenable Groups
Authors: Dougall Rhiannon , Sharp Richard
Published: February 2024

We consider random walks on countable groups. A celebrated result of Kesten says that the spectral radius of a symmetric walk (whose support generates the group as a semigroup) is equal to one if and only if the group is amenable. We give an analogue of this result for walks that are not symmetric. We also conclude a ratio limit theorem for amenable groups.
Deficient Generation of Spike-Specific Long-Lived Plasma Cells in the Bone Marrow After Severe Acute Respiratory Syndrome Coronavirus 2 Infection
Authors: Tehrani Zahra R , Habibzadeh Parham , Flinko Robin , Chen Hegang , Abbasi Abdolrahim , Yared Jean A , Ciupe Stanca M , Lewis George K , Sajadi Mohammad M
Published: February 2024

Generation of a stable long-lived plasma cell (LLPC) population is the sine qua non of durable antibody responses after vaccination or infection. We studied 20 individuals with a prior coronavirus disease 2019 infection and characterized the antibody response using bone marrow aspiration and plasma samples. We noted deficient generation of spike-specific LLPCs in the bone marrow after severe acute respiratory syndrome coronavirus 2 infection. Furthermore, while the regression model explained 98% of the observed variance in anti-tetanus immunoglobulin G levels based on LLPC enzyme-linked immunospot assay, we were unable to fit the same model with anti-spike antibodies, again pointing to the lack of LLPC contribution to circulating anti-spike antibodies.
Epigenetic Aging and Musculoskeletal Outcomes in a Cohort of Women Living With HIV
Authors: Shiau Stephanie , Zumpano Francesca , Wang Ziyi , Shah Jayesh , Tien Phyllis C , Ross Ryan D , Sharma Anjali , Yin Michael T
Published: February 2024

Background

The relationship between accelerated epigenetic aging and musculoskeletal outcomes in women with HIV (WWH) has not been studied.

Methods

We measured DNA methylation age using the Infinium MethylationEPIC BeadChip in a cohort from the Women's Interagency HIV Study (n = 190) with measures of bone mineral density (BMD) and physical function. We estimated 6 biomarkers of epigenetic aging—epigenetic age acceleration (EAA), extrinsic EAA, intrinsic EAA, GrimAge, PhenoAge, and DNA methylation–estimated telomere length—and evaluated associations of epigenetic aging measures with BMD and physical function. We also performed epigenome-wide association studies to examine associations of DNA methylation signatures with BMD and physical function.

Results

This study included 118 WWH (mean age, 49.7 years; 69% Black) and 72 without HIV (mean age, 48.9 years; 69% Black). WWH had higher EAA (mean ± SD, 1.44 ± 5.36 vs −1.88 ± 5.07; P < .001) and lower DNA methylation–estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P < .001) than women without HIV. There were no significant associations between accelerated epigenetic aging and BMD. Rather, measures of accelerated epigenetic aging were associated with lower physical function.

Conclusions

Accelerated epigenetic aging was observed in WWH as compared with women without HIV and was associated with lower physical function in both groups.
Impact of National Public-Private Mix and Medical Expense Support Program to Control Tuberculosis in South Korea: An Interrupted Time Series Analysis
Authors: Oh In-Sun , Kim Ju Hwan , Huh Kyungmin , Jang Seung Hun , Shin Ju-Young
Published: February 2024

Tuberculosis (TB) remains a major threat to global public health. Various measures at the national level have been implemented to control TB, and no evidence with long-term effectiveness has yet been evaluated on TB control programs. We confirmed the long-term effectiveness of the TB control programs in reducing overall burden in South Korea using interrupted time series analysis. Our finding suggests that, along with the public-private mix, relieving the economic burden of people with TB may complement achieving the End TB Strategy. For countries currently developing strategies for TB control, results may provide important insights in effective TB control.
Hub genes, key miRNAs and interaction analyses in type 2 diabetes mellitus: an integrative in silico approach
Authors: Nematollahi Zeinab , Karimian Shiva , Taghavirashidizadeh Ali , Darvishi Mohammad , Pakmehr SeyedAbbas , Erfan Amin , Teimoury Mohammad Javad , Mansouri Neda , Alipourfard Iraj
Published: February 2024

Diabetes is a rising global metabolic disorder and leads to long-term consequences. As a multifactorial disease, the gene-associated mechanisms are important to know. This study applied a bioinformatics approach to explore the molecular underpinning of type 2 diabetes mellitus through differential gene expression analysis. We used microarray datasets GSE16415 and GSE29226 to identify differentially expressed genes between type 2 diabetes and normal samples using R software. Following that, using the STRING database, the protein-protein interaction network was constructed and further analyzed by Cytoscape software. The EnrichR database was used for Gene Ontology and pathway enrichment analysis to explore key pathways and functional annotations of hub genes. We also used miRTarBase and TargetScan databases to predict miRNAs targeting hub genes. We identified 21 hub genes in type 2 diabetes, some showing more significant changes in the PPI network. Our results revealed that GLUL, SLC32A1, PC, MAPK10, MAPT, and POSTN genes are more important in the PPI network and can be experimentally investigated as therapeutic targets. Hsa-miR-492 and hsa-miR-16-5p are suggested for diagnosis and prognosis by targeting GLUL, SLC32A1, PC, MAPK10, and MAPT genes involved in the insulin signaling pathway.

Insight: Type 2 diabetes, as a rising global and multifactorial disorder, is important to know the gene-associated mechanisms. In an integrative bioinformatics analysis, we integrated different finding datasets to put together and find valuable diagnostic and prognostic hub genes and miRNAs. In contrast, genes, RNAs, and enzymes interact systematically in pathways. Using multiple databases and software, we identified differential expression between hub genes of diabetes and normal samples. We explored different protein-protein interaction networks, gene ontology, key pathway analysis, and predicted miRNAs that target hub genes. This study reported 21 significant hub genes and some miRNAs in the insulin signaling pathway for innovative and potential diagnostic and therapeutic purposes.
The contribution of plasmids to trait diversity in a soil bacterium
Authors: Finks Sarai S , Moudgalya Pranav , Weihe Claudia , Martiny Jennifer B H
Published: February 2024

Plasmids are so closely associated with pathogens and antibiotic resistance that their potential for conferring other traits is often overlooked. Few studies consider how the full suite of traits encoded by plasmids is related to a host’s environmental adaptation, particularly for Gram-positive bacteria. To investigate the role that plasmid traits might play in microbial communities from natural ecosystems, we identified plasmids carried by isolates of Curtobacterium (phylum Actinomycetota) from a variety of soil environments. We found that plasmids were common, but not ubiquitous, in the genus and varied greatly in their size and genetic diversity. There was little evidence of phylogenetic conservation among Curtobacterium plasmids even for closely related bacterial strains within the same ecotype, indicating that horizontal transmission of plasmids is common. The plasmids carried a wide diversity of traits that were not a random subset of the host chromosome. Furthermore, the composition of these plasmid traits was associated with the environmental context of the host bacterium. Together, the results indicate that plasmids contribute substantially to the microdiversity of a soil bacterium and that this diversity may play a role in niche differentiation and a bacterium’s adaptation to its local environment.
Baking the First Business Computer
Authors: Cooper Martin
Published: February 2024

LEO 1 was a pioneering computer that powered a catering empire. The team preserving its memory has won an award for its innovative work. Martin Cooper MBCS reports.
Futurology
Authors: Lucas Matt
Published: February 2024

Matt Lucas FBCS explores the potential afforded by technology to create more transparent and robust food supply chains, improving sustainability while helping to remove unethical practices.
Steering AI in the Right Direction
Authors: Cooper Martin
Published: February 2024

The 43rd BCS Specialist Group for Artificial Intelligence conference saw delegates, keynote speakers, students and academics meet, share, debate and learn. Martin Cooper MBCS reports from Peterhouse, Cambridge.
BCS News, Impact and Influence
Authors: Penketh Claire
Published: February 2024

The BCS Policy and Press team had their finger on the pulse during autumn and the beginning of the year commenting on top technology stories ranging from the Post Office scandal to the AI Summit. Claire Penketh reports.
The Computer Journal: 65th Anniversary
Authors: Cooper Martin
Published: February 2024

In celebrating the 65th anniversary of The Computer Journal, its Deputy Editors reassess key papers which – though sometimes old – continue to influence computer science. Martin Cooper MBCS reports.
AI Spots Crumbling Concrete
Authors: Hall Jon G
Published: February 2024

To keep the public safe, a multi-functional team of building experts and AI developers have created an AI-based imaging system trained to spot problems with ageing concrete buildings.
Formal Languages, Mathematical Models and Bike-Sharing
Authors: Runciman Brian
Published: February 2024

Professor Jane Hillston is one of the winners of 2023's Lovelace Medal. She discusses her work with Brian Runciman MBCS.
How Technology is Saving Coral Reefs
Authors: Powell Grant
Published: February 2024

James Greenhalgh CITP recently spoke to Grant Powell MBCS about bringing together a passion for scuba diving and background in software development to help protect our oceans.
Award Winning Software Testing
Authors: Powell Grant
Published: February 2024

Ryan James, Managing Director of nFocus recently spoke to Grant Powell MBCS about the importance of training top software testing talent and achieving success at the IT Industry Awards.
Mentoring
Authors: Yetim Adem
Published: February 2024

Adem Yetim IntPE FIET FBCS reflects on the integration of technological advancements with sustainable food security through knowledge sharing and collaboration.
Cookie Hijacking
Authors: Clark Tim
Published: February 2024

You set a secure password, composed of random words, numbers and symbols, you turned on biometrics, and set up two-factor authentication. How were you hacked? Tim Clark MBCS explains cookie hijacking.
FeatureTech Tourism: Inside a Data Centre
Authors: Cooper Martin
Published: February 2024

Martin Cooper MBCS slips on his winter coat and visits the Stellium data centre in Newcastle-upon-Tyne, a place famous for football, bridges and – it transpires – highly desirable levels of rain and cold.
Why Data Decarbonisation Matters for Net Zero
Authors: Jackson Tom
Published: February 2024

Thomas Jackson, Ian Hodgkinson and Steven Lockwood from Loughborough University discuss the spiralling relationship between data and carbon dioxide production. They also offer some food for thought on how digital industries can help cut greenhouse gas emissions.
Racing Towards Success: From Education APPS to Formula 1 Systems
Authors: Powell Grant
Published: February 2024

Grant Powell MBCS recently spoke to Enrique Martin Ocaña about achieving a prize at the Young Software Engineer of the Year awards, sponsored by BCS, as well as his inspiring career.
Using VR to Boost Transport Capabilities
Authors: Cooper Martin
Published: February 2024

Gaming technology is key to cost effective virtual reality simulations that are helping improve our transport systems, writes Ian Cornwell of Mott MacDonald.
Task Versus Process Mining: Making the Right Choice
Authors: Major Danny
Published: February 2024

Danny Major FBCS considers task and process mining as mechanisms for gaining powerful organisational insights and explains how to determine which approach might best suit your business needs.
AI, Art and the Human Condition
Authors: Smith Georgia
Published: February 2024

On the 8th of November, BCS held an evening of presentations and discussions with four Lumen artists at our London offices, facilitated by Goldsmiths University's Head of Digital Arts Computing, Rachel Falconer. The panel featured 2023 3D/ Interactive award winner Sarah Selby and shortlister Max Colson, BCS Futures Award shortlister Adam Cole, and Student Award winner Yuqian Sun.
Business Analysis
Authors: Lovelock Christina
Published: February 2024

Christina Lovelock MBCS suggests that most business analysts fall into their role, and explores how professionals can support future BAs to have a planned rather than accidental career.
Strawberry Fields
Authors: Johnstone Emily
Published: February 2024

Food production isn't the first sector that comes to mind when we think of technology. To remedy that, third year PhD student at the University of Reading, Emily Johnstone, explains how tuneable LED lighting is advancing research into fruit crop growth.
Digital Risk
Authors: Hall Jon G
Published: February 2024

Professor Jon G. Hall explains why, as digital risk evolves, it's vital to prepare your teams to mitigate risk against a backdrop of constant fluctuation through a fluid approach to training.
BCS' Royal Charter: The Real 1984
Authors: Runciman Brian
Published: February 2024

Despite the jeremiad feel of the year 1984, it marked a key milestone for BCS. This was when the royal charter, now hitting its 40th anniversary, was granted. Brian Runciman MBCS takes a look back at the process.
Artistic Manner as Autonomy: Creative Freedom and the Constraint of Rules in Vasari, Bellori and Kant
Authors: Reiter Aviv
Published: February 2024

§49 of the Critique of the Power of Judgment concludes with a striking claim regarding the freedom required for artistic expression. Kant classifies Mannerism as aping, but considers manner the only valid means of artistic expression. These opposed uses of maniera echo a historical controversy, which finds reconciliation in Kant in what I call artistic autonomy. For Kant, artistic expression of genuine originality requires autonomous action, the individual manner in which an artist selects, transforms and applies given academic rules, in a way that renders an aesthetic vision meaningful. His grave concern is that artists, in their aspiration to innovate, might make the freedom to modify and transform rules into the very aim of their artistic endeavor. In order to grasp the full significance of Kant’s view, I examine the contradictory attitudes towards maniera articulated by Vasari and Bellori. Kant’s account of artistic autonomy offers an understanding of artistic succession, different from that of his predecessors.
Apophatic Beauty in the Hippias Major and the Symposium
Authors: Wesselinoff Catherine
Published: February 2024

Plato’s discourse on beauty in the Hippias Major and the Symposium is distinctly apophatic in nature. Plato describes beauty in terms of what it is not (an approach sometimes referred to apophasis, or the via negativa). In this paper, I argue that Platonic apophatic practise in the Hippias Major and the Symposium depicts beauty as an ally to certain aspirations of philosophical discourse. In the first section, I offer some brief prefatory remarks on the nature of apophasis and its presence in Plato’s thinking. In the second section, I provide some background to the dialogue of the Hippias Major and highlight the apophatic nature of the descriptions of beauty offered therein. In the third and final section, I discuss the Symposium, a dialogue within which, in addition to representing beauty apophatically, Plato illustrates how we may become able to achieve some positive, or cataphatic, insights into the nature of beauty. I conclude that the purpose of the Platonic apophatic portrayal of beauty in the Hippias Major and the Symposium is to show that, while beauty cannot be reduced to a series of assertive truth statements, it can nevertheless function as an accessory to other dimensions of philosophical thinking.
Identification of a CTX-M-255 β-lactamase containing a G239S substitution selectively conferring resistance to penicillin/β-lactamase inhibitor combinations
Authors: Andreasen Minna Rud , Rick Tim , Alexandersen Nicolai Riff , Hansen Katrine Hartung , Pedersen Martin Schou , Warweitzky Jakob K , Botelho Carolina Mastella , Häussler Susanne , Jelsbak Lotte , Schønning Kristian
Published: February 2024

Objectives

An Escherichia coli isolate, WGS1363, showed resistance to piperacillin/tazobactam but susceptibility to cephalosporins and contained a previously unrecognized β-lactamase, CTX-M-255, as the only acquired β-lactamase. CTX-M-255 was identical to CTX-M-27 except for a G239S substitution. Here, we characterize the hydrolytic spectrum of CTX-M-255 and a previously reported β-lactamase, CTX-M-178, also containing a G239S substitution and compare it to their respective parental enzymes, CTX-M-27 and CTX-M-15.

Methods

All β-lactamase genes were expressed in E. coli TOP10 and MICs to representative β-lactam-antibiotics were determined. Furthermore, blaCTX-M-15,  blaCTX-M-27, blaCTX-M-178 and blaCTX-M-255 with C-terminal His-tag fusions were affinity purified for enzyme kinetic assays determining Michaelis–Menten kinetic parameters against representative β-lactam-antibiotics and IC50s of clavulanate, sulbactam, tazobactam and avibactam.

Results

TOP10-transformants expressing blaCTX-M-178 and blaCTX-M-255 showed resistance to penicillin/β-lactamase combinations and susceptibility to cephalothin and cefotaxime in contrast to transformants expressing blaCTX-M-15 and blaCTX-M-27. Determination of enzyme kinetic parameters showed that CTX-M-178 and CTX-M-255 both lacked hydrolytic activity against cephalosporins and showed impaired hydrolytic efficiency against penicillin antibiotics compared to their parental enzymes. Both enzymes appeared more active against piperacillin compared to benzylpenicillin and ampicillin. Compared to their parental enzymes, IC50s of β-lactamase-inhibitors were increased more than 1000-fold for CTX-M-178 and CTX-M-255.

Conclusions

CTX-M-178 and CTX-M-255, both containing a G239S substitution, conferred resistance to piperacillin/tazobactam and may be characterized as inhibitor-resistant CTX-M β-lactamases. Inhibitor resistance was accompanied by loss of activity against cephalosporins and monobactams. These findings add to the necessary knowledge base for predicting antibiotic susceptibility from genotypic data.
Pilot study to evaluate the need and implementation of a multifaceted nurse-led antimicrobial stewardship intervention in residential aged care
Authors: Jokanovic Natali , Lee Sue J , Haines Terry , Hilmer Sarah N , Jeon Yun-Hee , Travis Laura , Ayton Darshini , Watson Eliza , Tsindos Tess , Stewardson Andrew J , Stuart Rhonda L , Cheng Allen C , Peel Trisha N , Peleg Anton Y ,   START Trial Group, Peleg Anton , Haines Terry , Cheng Allen , Peel Trisha , Holt Kathryn , Hilmer Sarah , Jeon Yun-Hee , Stewardson Andrew , Stuart Rhonda , Lee Sue J , Wilson Daniel , Trauer James , Cruickshank Marilyn , De Maio Nicola , Jokanovic Natali , Roney Janine , Wisniewski Jessica
Published: February 2024

Objectives

To evaluate the need and feasibility of a nurse-led antimicrobial stewardship (AMS) programme in two Australian residential aged care homes (RACHs) to inform a stepped-wedged, cluster randomized controlled trial (SW-cRCT).

Methods

A mixed-methods pilot study of a nurse-led AMS programme was performed in two RACHs in Victoria, Australia (July–December 2019). The AMS programme comprised education, infection assessment and management guidelines, and documentation to support appropriate antimicrobial use in urinary, lower respiratory and skin/soft tissue infections. The programme was implemented over three phases: (i) pre-implementation education and integration (1 month); (ii) implementation of the intervention (3 months); and (iii) post-intervention evaluation (1 month). Baseline RACH and resident data and weekly infection and antimicrobial usage were collected and analysed descriptively to evaluate the need for AMS strategies. Feedback on intervention resources and implementation barriers were identified from semi-structured interviews, an online staff questionnaire and researcher field notes.

Results

Six key barriers to implementation of the intervention were identified and used to refine the intervention: aged care staffing and capacity; access to education; resistance to practice change; role of staff in AMS; leadership and ownership of the intervention at the RACH and organization level; and family expectations. A total of 61 antimicrobials were prescribed for 40 residents over the 3 month intervention. Overall, 48% of antibiotics did not meet minimum criteria for appropriate initiation (respiratory: 73%; urinary: 54%; skin/soft tissue: 0%).

Conclusions

Several barriers and opportunities to improve implementation of AMS in RACHs were identified. Findings were used to inform a revised intervention to be evaluated in a larger SW-cRCT.
Impact of penicillin allergy labels on surgical site infections in a large UK cohort of gastrointestinal surgery patients
Authors: Jones Nick K , Tom Brian , Simillis Constantinos , Bennet John , Gourgiotis Stavros , Griffin Jo , Blaza Helen , Nasser Shuaib , Baker Stephen , Gouliouris Theodore
Published: February 2024

Objectives

Studies in the USA, Canada and France have reported higher surgical site infection (SSI) risk in patients with a penicillin allergy label (PAL). Here, we investigate the association between PALs and SSI in the UK, a country with distinct epidemiology of infecting pathogens and range of antimicrobial regimens in routine use.

Methods

Electronic health records and national SSI surveillance data were collated for a retrospective cohort of gastrointestinal surgery patients at Cambridge University Hospitals NHS Foundation Trust from 1 January 2015 to 31 December 2021. Univariable and multivariable logistic regression were used to examine the effects of PALs and the use of non-β-lactam-based prophylaxis on likelihood of SSI, 30 day post-operative mortality, 7 day post-operative acute kidney injury and 60 day post-operative infection/colonization with antimicrobial-resistant bacteria or Clostridioides difficile.

Results

Our data comprised 3644 patients and 4085 operations; 461 were undertaken in the presence of PALs (11.3%). SSI was detected after 435/4085 (10.7%) operations. Neither the presence of PALs, nor the use of non-β-lactam-based prophylaxis were found to be associated with SSI: adjusted OR (aOR) 0.90 (95% CI 0.65–1.25) and 1.20 (0.88–1.62), respectively. PALs were independently associated with increased odds of newly identified MRSA infection/colonization in the 60 days after surgery: aOR 2.71 (95% CI 1.13–6.49). Negative association was observed for newly identified infection/colonization with third-generation cephalosporin-resistant Gram-negative bacteria: aOR 0.38 (95% CI 0.16–0.89).

Conclusions

No evidence was found for an association between PALs and the likelihood of SSI in this large UK cohort, suggesting significant international variation in the impact of PALs on surgical patients.
Clinical Impacts of Implementing the 2021 Race-Free Chronic Kidney Disease Epidemiology Collaboration Estimated Glomerular Filtration Rate
Authors: Wang Qian , Meeusen Jeffrey W
Published: February 2024

Background

Estimated glomerular filtration rate (eGFR) has become incorporated into multiple clinical management situations. Historically, equations included a Black race coefficient, which lacked biological plausibility and created potential to exacerbate health disparities. A new equation created in 2021 changed the weighting of age, sex, and creatinine by modeling against a diverse cohort and removing the Black race coefficient.

Content

A variety of clinical outcomes including kidney disease risk stratification, medication dosing, patient eligibility for clinical trials, and kidney donation are impacted by implementation of the new equation. Nearly 2 years after its initial publication, many studies have reported on observed analytical performance of the 2021 eGFR determined as diagnostic concordance and percentage of estimates within 30% of measured GFR. Additionally, the potential clinical impacts following adoption of the new eGFR among different patient populations has also been reported. Here we review these studies with a focus on assessing the data associated with the transition from 2009 to 2021 Chronic Kidney Disease Epidemiology Collaboration equations.

The reported interindividual variation in eGFR performance is significantly larger than any potential benefit derived from race coefficients. Both the 2021 eGFR and the 2009 eGFR analytical performance fall short of the validation cohort performance in most cohorts. However, the 2021 analytical is similar or better than the 2009 eGFR in most cohorts. Implementing the 2021 eGFR will remove a systematic overestimation of kidney function among Black patients.
Stability and Analytical Characterization of Voriconazole as Measured by Immunoassay
Authors: Bharti Veni , Jung Benjamin , Lam Sarah , Fabros Ansel , Selvaratnam Rajeevan
Published: February 2024

Background

Voriconazole is a broad-spectrum triazole antifungal agent recommended for invasive fungal diseases, including invasive aspergillosis. Therapeutic drug monitoring via voriconazole target trough concentration is important to ensure efficacy while preventing toxicity. Our aim was to determine the stability of voriconazole as adapted and measured by an immunoassay.

Methods

Plasma from patient samples (n = 45) evaluated by a liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was compared against an ARK immunoassay method, adapted and optimized on the Abbott Alinity c analyzer. Stability of voriconazole and analytical performance of ARK immunoassay was assessed, including functional sensitivity, limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), linearity, and precision.

Results

ARK voriconazole immunoassay was highly correlated (Pearson R = 0.988) to the LC-MS/MS method, with an average bias of 0.09 mg/L (2%). CV at LoQ of 0.5 mg/L was 3.7% while the functional sensitivity was established at 0.05 mg/L. Overall imprecision with liquid quality control material obtained from ARK was 5.0%, 6.3%, and 5.9% at 1 mg/L, 5 mg/L, and 10 mg/L, respectively. Limit of blank and LoD were 0.02 mg/L and 0.05 mg/L, respectively. Voriconazole in lithium heparin plasma separator tube declines over time, with a decrease that is more evident near or above toxic concentrations.

Conclusion

Voriconazole collected in gel separation tubes declines over time, possibly due to absorptive properties. Voriconazole measurements by immunoassay and LC-MS/MS demonstrated acceptable comparability with sufficient level of sensitivity and precision.
Photocontrol of small GTPase Ras fused with a photoresponsive protein
Authors: Nishibe Nobuyuki , Maruta Shinsaku
Published: February 2024

The small GTPase Ras plays an important role in intracellular signal transduction and functions as a molecular switch. In this study, we used a photoresponsive protein as the molecular regulatory device to photoregulate Ras GTPase activity. Photo zipper (PZ), a variant of the photoresponsive protein Aureochrome1 developed by Hisatomi et al. was incorporated into the C-terminus of Ras as a fusion protein. The three constructs of the Ras–PZ fusion protein had spacers of different lengths between Ras and PZ. They were designed using an Escherichia coli expression system. The Ras–PZ fusion proteins exhibited photoisomerization upon blue light irradiation and in the dark. Ras–PZ dimerized upon light irradiation. Moreover, Ras GTPase activity, which is accelerated by the Ras regulators guanine nucleotide exchange factors and GTPase-activating proteins, is controlled by photoisomerization. It has been suggested that light-responsive proteins are applicable to the photoswitching of the enzymatic activity of small GTPases as photoregulatory molecular devices.
An Unusual Pediatric Case of an Insidious Thermal Airway Injury Without Initial Signs of Facial or Intraoral Scalding
Authors: Ohashi Ayaka , Matsubara Daisuke , Mizobe Yoshitaka , Mitani Tadahiro , Ono Marika , Nozawa Miki , Ito Makoto , Tajima Toshihiro , Osaka Hitoshi
Published: February 2024

Thermal airway injuries, usually accompanied by facial burns, require emergency management. We encountered a pediatric case of a late airway-scalding injury without any initial signs of scalding on the face or inside the oral cavity. A 16-month-old boy was accidentally exposed to boiling water from overhead and developed tachypnea and dyspnea at 8 h after the injury. When he visited our hospital at 12 h after the injury, there were no scalding-related findings on his face or inside his oral cavity; however, severe laryngeal edema was observed, which required emergency intubation. Thermal airway injuries can occur later, even if there is no evidence of facial or oral scalding immediately after the injury. Airway injuries should be considered when a patient has been exposed to hot water from overhead.
3D-modeling from hip DXA shows improved bone structure with romosozumab followed by denosumab or alendronate
Authors: Lewiecki E Michael , Betah Donald , Humbert Ludovic , Libanati Cesar , Oates Mary , Shi Yifei , Winzenrieth Renaud , Ferrari Serge , Omura Fumitoshi
Published: February 2024

Romosozumab treatment in women with postmenopausal osteoporosis increases bone formation while decreasing bone resorption, resulting in large BMD gains to reduce fracture risk within 1 yr. DXA-based 3D modeling of the hip was used to assess estimated changes in cortical and trabecular bone parameters and map the distribution of 3D changes in bone parameters over time in patients from 2 randomized controlled clinical trials: FRAME (romosozumab vs placebo followed by denosumab) and ARCH (romosozumab vs alendronate followed by alendronate). For each study, data from a subset of ~200 women per treatment group who had TH DXA scans at baseline and months 12 and 24 and had provided consent for future research were analyzed post hoc. 3D-SHAPER software v2.11 (3D-SHAPER Medical) was used to generate patient-specific 3D models from TH DXA scans. Percentage changes from baseline to months 12 and 24 in areal BMD (aBMD), integral volumetric BMD (vBMD), cortical thickness, cortical vBMD, cortical surface BMD (sBMD), and trabecular vBMD were evaluated. Data from 377 women from FRAME (placebo, 190; romosozumab, 187) and 368 women from ARCH (alendronate, 185; romosozumab, 183) with evaluable 3D assessments at baseline and months 12 and 24 were analyzed. At month 12, treatment with romosozumab vs placebo in FRAME and romosozumab vs alendronate in ARCH resulted in greater increases in aBMD, integral vBMD, cortical thickness, cortical vBMD, cortical sBMD, and trabecular vBMD (P < .05 for all). At month 24, cumulative gains in all parameters were greater in the romosozumab-to-denosumab vs placebo-to-denosumab sequence and romosozumab-to-alendronate vs alendronate-to-alendronate sequence (P < .05 for all). 3D-SHAPER analysis provides a novel technique for estimating changes in cortical and trabecular parameters from standard hip DXA images. These data add to the accumulating evidence that romosozumab improves hip bone density and structure, thereby contributing to the antifracture efficacy of the drug.
Perceived value of computed tomography imaging for patients with inflammatory bowel disease in the emergency department: a Canadian survey
Authors: Roda Caleb A N , Dube Catherine , Macdonald Blair D , Stiell Ian G , Moloo Husein , deBuck van Overstraeten Anthony , Murthy Sanjay , Mallick Ranjeeta , McCurdy Jeffrey D
Published: February 2024

Background

There are high rates of computed tomography (CT) utilization in the emergency department (ED) for patients with inflammatory bowel disease (IBD), despite guidelines recommending judicious use. We performed a national survey to better understand perceptions and practice patterns of Canadian physicians related to CT imaging in the ED.

Methods

Our survey was developed by a multistep iterative process with input from key stakeholders between 2021 and 2022. It evaluated Canadian gastroenterologists’, surgeons’, and emergency physicians’ (1) perceived rates of IBD findings detected by CT, (2) likelihood of performing CT for specific presentations and (3) comfort in diagnosing IBD phenotypes/complications without CT.

Results

A total of 208 physicians responded to our survey: median age 44 years (IQR, 37–50), 63% male, 68% academic, 44% emergency physicians, 39% gastroenterologists, and 17% surgeons. Compared with emergency physicians and surgeons, gastroenterologists more often perceived that CT would detect inflammation alone and less often IBD complications. Based on established rates in the literature, 13 (16%) gastroenterologists, 33 (40%) emergency physicians, and 21 (60%) surgeons overestimated the rates of at least one IBD complication. Although most physicians were more comfortable diagnosing inflammation compared to IBD complications without CT, gastroenterologists were significantly less likely to recommend CT imaging for non-obstructive/penetrating presentations compared with emergency physicians and surgeons with results that varied by IBD subtype.

Conclusion

This national survey demonstrates differences in physician perceptions and practices regarding CT utilization in the ED and can be used as a framework for educational initiatives regarding appropriate usage of this modality.
The influence of GC-biased gene conversion on non-adaptive sequence evolution in short introns of Drosophila melanogaster
Authors: Yıldırım Burçin , Vogl Claus
Published: February 2024

Population genetic inference of selection on the nucleotide sequence level often proceeds by comparison to a reference sequence evolving only under mutation and population demography. Among the few candidates for such a reference sequence is the 5’ part of short introns (5SI) in Drosophila. In addition to mutation and population demography, however, there is evidence for a weak force favouring GC bases, likely due to GC-biased gene conversion (gBGC), and for the effect of linked selection. Here, we use polymorphism and divergence data of Drosophila melanogaster to detect and describe the forces affecting the evolution of the 5SI. We separately analyse mutation classes, compare them between chromosomes, and relate them to recombination rate frequencies. GC-conservative mutations seem to be mainly influenced by mutation and drift, with linked selection mostly causing differences between the central and the peripheral (i.e., telomeric and centromeric) regions of the chromosome arms. Comparing GC-conservative mutation patterns between autosomes and the X chromosome showed differences in mutation rates, rather than linked selection, in the central chromosomal regions after accounting for differences in effective population sizes. On the other hand, GC-changing mutations show asymmetric site frequency spectra, indicating the presence of gBGC, varying among mutation classes and in intensity along chromosomes, but approximately equal in strength in autosomes and the X chromosome.
Metamicrobiome diversity promotes the evolution of host-microbial mutualisms
Authors: Pillai Pradeep , Gouhier Tarik C
Published: February 2024

Ecological theory suggests that a host organism’s internal spatial structure can promote the persistence of mutualistic microbes by allowing for the turnover of tissue occupied by non-beneficial or cheating microbes. This type of regulation, whereby a host preferentially rewards tissue occupied by beneficial members of its microbiome but sanctions tissue occupied by non-beneficial cheaters, is expected to generate a competition–extinction trade-off by allowing beneficial microbes to experience a lower extinction rate than competitively dominant cheaters. Using an adaptive dynamics approach, we demonstrate that although ecologically stable, microbial regulation via sanctioning is not stable in any evolutionary sense, as each individual host will be under pressure to reduce the costs incurred from cheater suppression in order to maximize its own fitness at the expense of the rest of the host population. However, increasing the diversity of non-beneficial cheaters in the host population metamicrobiome can lead to an increase in the relative fitness of hosts that actively sanction non-performing tissue, thus facilitating the evolutionary emergence and persistence of such strategies in host-microbial systems. These counter-intuitive results demonstrate how diversity at multiple levels of biological organization and spatiotemporal scales can interact to facilitate the establishment and maintenance of mutualistic relationships.