bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractEconomic 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

Abstract
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

Abstract
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

Abstract
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

Abstract

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 &lt; .001) and lower DNA methylation–estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P &lt; .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

Abstract
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

Abstract
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

Abstract
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.
AI, Art and the Human Condition
Authors: Smith Georgia 
Published: February 2024

Abstract
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.
Artistic Manner as Autonomy: Creative Freedom and the Constraint of Rules in Vasari, Bellori and Kant
Authors: Reiter Aviv 
Published: February 2024

Abstract
§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

Abstract
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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.

Summary
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.