bluuebunny/crossref_metadata_2025_split huggingface dataset:
TurboID-mediated surface protein biotinylation to inhibit the growth ofStaphylococcus aureus
Authors: Qian Lijuan , He Yuxin , Lian Wenzhe , Ji Zhiyuan , Tian Ziming , Wang Chuyun , Cao Chen , Shern Tyler , Stedman Teagan , Sun Yujun 
Published: June 2024

AbstractStaphylococcus aureus(S. aureus) infection is major cause of nosocomial infections. Antibiotic treatment forS. aureusremains the primary solution for managingS. aureusinfections, which, however, increases the risk of antibiotic resistance. To broaden the resolutions onS. aureusinfection, here we report TurboID-mediated protein proximity technologies to inhibit the growth ofS. aureus. To achieve this goal, we utilized synthetic biology techniques to create a fusion protein named N-AgrD-TurboID (Agr-ID). The N-AgrD domain includes auto-inducer peptide (AIP) which combined to the surface AgrC protein onS. aureus. As such, TurboID then catalyzed the production of biotinoyl-5’-AMP anhydride, triggering the biotinylation of surface proteins onS. aureus25923 which were visualized by using fluorescence microscopy after incubating with Alexa Fluor 647-conjugated streptavidin. The biotinylation of surface protein onS. aureus25923,S. aureus43300, andS. aureus6538 (MRSA) also resulted in growth inhibition and impaired colonization. Moreover, the biotinylation on surface protein further inhibited virulence protein production inS. aureus25923, as indicated by reduced apoptosis of HEK 293T cells after treatment withS. aureus25923 lysates. Overall, our work reveals that the biotinylation of surface proteins can inhibit the growth and toxicity ofS. aureus25923,S. aureus43300, andS. aureus6538 (MRSA), indicating therapeutic potential in clinical treatment.
Synchronized Temporal-spatial Analysis via Microscopy and Phoshoproteomics (STAMP) of Quiescence
Authors: Aziz-Zanjani Mohammad Ovais , Turn Rachel E. , Xu Lucy Artemis , Jackson Peter K. 
Published: June 2024

SUMMARYTightly coordinated cell cycle regulation is essential for homeostasis. G0, or quiescence, is especially crucial for cells to respond to extracellular stimuli. Little is known about the mechanisms that establish the G0program, though the primary cilium (a key signaling hub formed only in G0) is the most widely recognized marker. The study of ciliogenesis is challenging due to its small size, relative to the cell body. To address this gap in our understanding, we developed STAMP (Spatio-Temporal Analysis via Microscopy and Proteomics) to temporally map the changes in cellular landscape occurring in G0and ciliogenesis. Using synchronized RPE cells, we used fixed and live cell imaging combined with phosphoproteomics to uncover new signals and order them in these processes, which also allows further, more targeted, analyses (e.g., using genetic and pharmacological perturbations). We propose that STAMP is broadly applicable for studying temporal-spatial signaling processes and the underlying mechanisms in various biological contexts and cell types.
Highly Sequence-specific, Timing-controllable m6A Demethylation by Modulating RNA-binding Affinity of m6A Erasers
Authors: Otonari Kenko , Asami Yuri , Ogata Kosuke , Ishihama Yasushi , Futaki Shiroh , Imanishi Miki 
Published: June 2024

AbstractIn recent years, significant progress has been made in developing tools that consist of programmable RNA binding proteins and m6A-erasers to selectively demethylate m6A at specific sites. Especially, timing-controllable demethylation tools using stimulus-inducible dimerization show promise in understanding the impact of individual m6A modifications on dynamic physiological processes. However, a critical issue with these technologies is the possible off-target effects, wherein wild-type m6A-erasers constituting the tools may decrease methylation levels at sites other than the intended target m6A. In this study, we addressed this issue by reducing the intrinsic RNA-binding ability of m6A-erasers to prevent off-target effects and by fusing with PUF RNA-binding protein to provide recognition ability of arbitrary RNA sequences. Taking advantage of the reduced RNA-binding ability of the m6A-erasers themselves, we employed a rapamycin-based switching system in the linker connecting the PUF and m6A-eraser domains. The resulting m6A-erasers exhibited superior precision in demethylating targeted sites while minimizing off-target effects, presenting a novel approach for precise temporal control over m6A modification dynamics.
The role of sex hormones in severe mental illness: a genetic exploration
Authors: Veeneman R. R. , Verweij K. J. H. , Sommer I. E. C. , Treur J. L. , Vermeulen J. M. 
Published: June 2024

AbstractIntroductionDespite advances in psychotherapies and pharmacological treatments, the burden of severe mental illness (SMI) remains high. Prominent sex differences exist in SMI, with increasing evidence pointing towards a pivotal role for sex hormones. Elucidation of these hormonal influences is crucial to tailor sex-specific prevention and treatment.MethodsTo investigate potential shared genetics and bi-directional causal effects between sex hormone traits and SMI, we computed genetic correlations using linkage disequilibrium score regression and bi-directional summary-level Mendelian Randomization (MR). A range of sensitivity methods was applied and potential mediators were investigated using multivariable MR. Sex-stratified data from genome-wide association studies (GWAS)s were used, further stratified on menopausal status when available. The main analysis focused on depressive disorder (N women=23,618 and N men=17,336), bipolar disorder (N women=26,573 and N men=22,381), schizophrenia (N women=54,513 and N men=68,287) as SMIs, and oestrogen (N women=229,966 and N men=206,927) and testosterone (N women=230,454 and N men=194,453) as the primary sex hormone traits. Exploratory analyses included other sex hormone traits (progesterone, sex hormone-binding globulin, prolactin, age of menarche, age of menopause). Potential mediators examined included levels of cortisol and CRP, smoking initiation, alcohol dependence, alcohol intake, BMI and body fat distribution. Only individuals of European ancestry were included.ResultsWe found a widespread pattern of significant genetic correlations between oestrogen/testosterone levels and depressive disorder/schizophrenia, in both positive and negative directions in both sexes (ranging between -0.22 and 0.13). There was no significant genetic correlation for bipolar disorder. In the MR analyses, evidence for causal effects was largely lacking; however, there was consistent evidence for a causal, increasing effect of testosterone levels on schizophrenia risk in men, completely mediated by CRP. Conversely, there was evidence for a causal, increasing effect of liability to schizophrenia on testosterone levels in both sexes.ConclusionThis study offers new insights into the complex aetiology of SMI by comprehensively mapping genetic associations with sex hormone traits, emphasizing the need to further investigate sex hormones’ impact on SMI using larger and more precisely phenotyped samples to identify individuals particularly vulnerable to hormonal disturbances.
Empowering Radiologists with ChatGPT-4o: Comparative Evaluation of Large Language Models and Radiologists in Cardiac Cases
Authors: Cesur Turay , Gunes Yasin Celal , Camur Eren , Dağlı Mustafa 
Published: June 2024

ABSTRACTPurposeThis study evaluated the diagnostic accuracy and differential diagnosis capabilities of 12 Large Language Models (LLMs), one cardiac radiologist, and three general radiologists in cardiac radiology. The impact of ChatGPT-4o assistance on radiologist performance was also investigated.Materials and MethodsWe collected publicly available 80 “Cardiac Case of the Month’’ from the Society of Thoracic Radiology website. LLMs and Radiologist-III were provided with text-based information, whereas other radiologists visually assessed the cases with and without ChatGPT-4o assistance. Diagnostic accuracy and differential diagnosis scores (DDx Score) were analyzed using the chi-square, Kruskal-Wallis, Wilcoxon, McNemar, and Mann-Whitney U tests.ResultsThe unassisted diagnostic accuracy of the cardiac radiologist was 72.5%, General Radiologist-I was 53.8%, and General Radiologist-II was 51.3%. With ChatGPT-4o, the accuracy improved to 78.8%, 70.0%, and 63.8%, respectively. The improvements for General Radiologists-I and II were statistically significant (P≤0.006). All radiologists’ DDx scores improved significantly with ChatGPT-4o assistance (P≤0.05). Remarkably, Radiologist-I’s GPT-4o-assisted diagnostic accuracy and DDx Score were not significantly different from the Cardiac Radiologist’s unassisted performance (P>0.05).Among the LLMs, Claude 3.5 Sonnet and Claude 3 Opus had the highest accuracy (81.3%), followed by Claude 3 Sonnet (70.0%). Regarding the DDx Score, Claude 3 Opus outperformed all models and Radiologist-III (P<0.05). The accuracy of the general radiologist-III significantly improved from 48.8% to 63.8% with GPT4o-assistance (P<0.001).ConclusionChatGPT-4o may enhance the diagnostic performance of general radiologists for cardiac imaging, suggesting its potential as a valuable diagnostic support tool. Further research is required to assess its clinical integration.
Reactogenicity Differences between COVID-19 Vaccines: A Pro-spective Observational Study in the United States and Canada
Authors: Rousculp Matthew D. , Hollis Kelly , Ziemiecki Ryan , Odom Dawn , Marchese Anthony M. , Montazeri Mitra , Odak Shardul , Jackson Laurin , Beyhaghi Hadi , Toback Seth 
Published: June 2024

AbstractParticipants in studies investigating COVID-19 vaccines commonly report reactogenicity events, and concerns about side effects may lead to reluctance to receive updated COVID-19 vaccinations. A real-world, post hoc analysis, observational 2019nCoV-406 study, was conducted to examine reactogenicity within the first 2 days after vaccination with either a protein-based vaccine (NVX-CoV2373) or an mRNA vaccine (BNT162b2 or mRNA-1273) in individuals who previously completed a primary series. Propensity score adjustments were conducted to address potential confounding. The analysis included 1130 participants who received a post–primary series dose of NVX-CoV2373 (n = 303) or an mRNA vaccine (n = 827) during the study period. Within the first 2 days after vaccination, solicited systemic reactogenicity events (adjusted) were reported in 60.5% of participants who received NVX-CoV2373 compared with 84.3% of participants who received an mRNA vaccine; moreover, 33.9% and 61.4%, respectively, reported ≥3 systemic reactogenicity symptoms. The adjusted mean (95% CI) number of systemic symptoms was 1.8 (1.6–2.0) and 3.2 (3.0–3.4), respectively. Local reactogenicity events (adjusted) were reported in 73.4% and 91.7% of participants who received NVX-CoV2373 and mRNA vaccines, respectively; the adjusted mean (95% CI) number of local symptoms was 1.5 (1.33–1.61) and 2.4 (2.31–2.52), respectively. These results support the use of adjuvanted, protein-based NVX-CoV2373 as an immunization option with low reactogenicity.
IMPROVE-IT2: Implementing non-invasive circulating tumor DNA analysis to optimize the operative and postoperative treatment for patients with colorectal cancer – Intervention Trial 2: Statistical analysis plan
Authors: Gotschalck Kåre Andersson , Heide-Jørgensen Uffe , Iversen Lene Hjerrild , Andersen Claus Lindbjerg 
Published: June 2024

ABSTRACTBackgroundSurveillance after curative intended surgery and adjuvant chemotherapy for localized colorectal cancer (CRC) aim at detecting recurrence sufficiently early to allow efficient treatment. Minimally invasive blood-based analysis of circulating tumor DNA (ctDNA) has the potential to identify patients with microscopic residual disease early after surgery and adjuvant chemotherapy for CRC, with a median lead time of 9 months compared to standard-of-care CT-based surveillance. The IMPROVE-IT2 study is a randomized controlled trial investigating the effect of ctDNA-guided surveillance compared to standard-of-care CT-based surveillance in high-risk stage II and stage III CRC patients after curative intended surgery and adjuvant chemotherapy. The primary trial endpoint is the fraction of recurrence patients receiving curative intended surgery or local metastasis directed treatment within 3 years after primary surgery for CRC. Secondary endpoints include time-to-clinical-recurrence, overall survival, quality-of-life, and quality-adjusted life-years cost-effectiveness.ObjectiveTo outline a pre-determined statistical analysis plan (SAP) before patients have completed the first year of follow-up after primary surgery.MethodsThe SAP describes the IMPROVE-IT2 study design and endpoints, the randomization procedure, sample size estimation, and the specific statistical procedures and methods for analyzing efficacy outcomes. Health economics and quality of life analyses are not included in this SAP but will be analyzed separately. The SAP outlines the planned primary analyses, subgroup analyses, and a range of specific sensitivity analyses. To avoid bias, the final analyses of the IMPROVE-IT2 trial will adhere to the SAP. The SAP was approved after end of recruitment and before completion of the first 12 months of follow-up after primary surgery.Trial RegistrationClinicaltrials.govNCT04084249, registered in April 2019.
Suboptimal dietary patterns are associated with accelerated biological aging in young adulthood: a twin study
Authors: Ravi Suvi , Kankaanpää Anna , Bogl Leonie H. , Heikkinen Aino , Pietiläinen Kirsi H. , Kaprio Jaakko , Ollikainen Miina , Sillanpää Elina 
Published: June 2024

ABSTRACTBackground & aimsSuboptimal diets increase morbidity and mortality risk. Epigenetic clocks are algorithms that can assess health and lifespan, even at a young age, before clinical manifestations of diseases. We investigated the association between dietary patterns and biological aging in young adult twins.MethodsThe data were drawn from the population-based FinnTwin12 study and consisted of twins aged 21–25 years (n=826). Food and beverage intakes were assessed using a food frequency questionnaire. Biological aging was estimated using the epigenetic clocks GrimAge and DunedinPACE. Latent class analysis was used to identify dietary patterns. The association between dietary patterns and biological aging was assessed using linear regression modeling at the individual level, followed by within–twin pair analyses to account for genetic liabilities and shared familial confounders.ResultsSix dietary patterns were identified: 1) High fast food, low fruits and vegetables (F&V), 2) Plant-based, 3) Health-conscious, 4) Western with infrequent fish, 5) Western with regular fish, and 6) Balanced average. At the individual level, GrimAge acceleration was slower in the Plant-based, Health-conscious, and Balanced-average patterns compared to the High fast food, low F&V, and faster in the Western with infrequent fish pattern compared to the Balanced average, regardless of sex, nonalcoholic energy intake, smoking, and alcohol consumption. After further adjustment for BMI and sports participation, the strengths of the associations modestly decreased; however, the difference between the Balanced-average and High fast food, low F&V patterns remained significant. The pace of aging (DunedinPACE) was slower in the Plant-based pattern compared to the High fast food, low F&V and the Western with infrequent fish patterns after adjustment for sex, nonalcoholic energy intake, smoking, and alcohol. The effect sizes were attenuated and reached a non-significant level when BMI and sports participation were added to the model. Most of the associations were replicated in the within-pair analyses among all twin pairs and among dizygotic twin pairs, but the effect sizes tended to be smaller among monozygotic twin pairs. This suggests that genetics, but not a shared environment, may partially explain the observed associations between diet and biological aging.ConclusionDiets high in fast food, processed red meat, and sugar-sweetened beverages and low in fruits and vegetables are associated with accelerated biological aging in young adulthood. The clustering effect of lifestyle factors and genetic confounders should be considered when interpreting the findings.
Feasibility to virtually generate T2 fat-saturated breast MRI by convolutional neural networks
Authors: Liebert Andrzej , Hadler Dominique , Ehring Chris , Schreiter Hannes , Brock Luise , Kapsner Lorenz A. , Eberle Jessica , Erber Ramona , Emons Julius , Laun Frederik B. , Uder Michael , Wenkel Evelyn , Ohlmeyer Sabine , Bickelhaupt Sebastian 
Published: June 2024

AbstractBackgroundBreast magnetic resonance imaging (MRI) protocols often include T2-weighted fat-saturated (T2w-FS) sequences, which are vital for tissue characterization but significantly increase scan time.PurposeThis study aims to evaluate whether a 2D-U-Net neural network can generate virtual T2w-FS images from routine multiparametric breast MRI sequences.Materials and MethodsThis IRB approved, retrospective study included n=914 breast MRI examinations performed between January 2017 and June 2020. The dataset was divided into training (n=665), validation (n=74), and test sets (n=175). The U-Net was trained on T1-weighted (T1w), diffusion-weighted imaging (DWI), and dynamic contrast-enhanced (DCE) sequences to generate virtual T2w-FS images (VirtuT2). Quantitative metrics and a qualitative multi-reader assessment by two radiologists were used to evaluate the VirtuT2 images.ResultsVirtuT2 images demonstrated high structural similarity (SSIM=0.87) and peak signal-to-noise ratio (PSNR=24.90) compared to original T2w-FS images. High level of the frequency error norm (HFNE=0.87) indicates strong blurring presence in the VirtuT2 images, which was also confirmed in qualitative reading. Radiologists correctly identified VirtuT2 images with 92.3% and 94.2% accuracy, respectively. No significant difference in diagnostic image quality (DIQ) was noted for one reader (p=0.21), while the other reported significantly lower DIQ for VirtuT2 (p<=0.001). Moderate inter-reader agreement was observed for edema detection on T2w-FS images (ƙ=0.43), decreasing to fair on VirtuT2 images (ƙ=0.36).ConclusionThe 2D-U-Net can technically generate virtual T2w-FS images with high similarity to real T2w-FS images, though blurring remains a limitation. Further investigation of other architectures and using larger datasets are needed to improve clinical applicability.Summary StatementVirtual T2-weighted fat-saturated images can be generated from routine breast MRI sequences using convolutional neural networks, showing high structural similarity but with notable blurring, necessitating further refinement for clinical use.Key ResultsImages with T2w-FS characteristics can be virtually generated from T1w and DWI images using deep learningImage blurring occurring in the VirtuT2 image limit clinical use for the current momentFurther investigation of different architectures and with larger datasets are necessary in the future to improve the VirtuT2 performance.
Kidney Protection During Surgery on the Thoracoabdominal Aorta: A Systematic Review
Authors: Bennett James Thomas , Shirley Sarah , Murray Patricia , Wilm Bettina , Field Mark 
Published: June 2024

AbstractBackgroundAcute kidney injury (AKI) is a common complication of surgery to repair the thoracoabdominal aorta, and is associated with risks of dialysis and early mortality. Renal ischaemia, initiated by clamping of the suprarenal aorta, is a major cause. Consequently, perfusion techniques are commonly used to sustain renal blood flow or facilitate hypothermic kidney preservation during surgery. This systematic review provides a comprehensive assessment of renal and mortality outcomes by perfusion techniques, to evaluate their ability to provide effective kidney protection.Methods & ResultsSearches of PubMed, Web of Science,ClinicalTrials.govand ClinicalTrialsRegister.EU were conducted to identify relevant studies published from 1995 to 2024. Included studies were quality assessed, and data were extracted by perfusion techniques. Outcomes of the highest quality studies were used to synthesise a narrative discussion.Forty-five studies were included in our analysis, featuring three extracorporeal strategies: Left heart bypass (LHB; n=24), cardiopulmonary bypass with deep hypothermic circulatory arrest (DHCA; n=19), and partial cardiopulmonary bypass (pCPB; n=12). Three categories of selective renal perfusion strategy were identified: Warm blood, cold blood and cold crystalloid. Our analysis identified operative mortality as 0-23.4% following LHB, 2.2-12.5% following DHCA and 0-42.1% following pCPB. The incidence of renal replacement therapy was 0-40.0% following LHB, 0-15.0% following DHCA and 0-22.2% following pCPB.ConclusionsStrong evidence supports the use of distal aortic perfusion (DAP) with LHB or pCPB, to reduce the risks of dialysis and operative mortality associated with aortic cross clamping. Furthermore, when DAP cannot prevent kidney ischaemia, adjunctive perfusion of the renal arteries with cold histidine-tryptophan-ketoglutarate (HTK) can reduce the risk of AKI. However, no professional guidance on the management of HTK exists, and rates of AKI remain high despite its use. Selective renal perfusion with warm blood is identified as a risk factor for AKI and operative mortality. DHCA is associated with low rates of AKI, warranting further prospective investigation. Finally, intravascular haemolysis and myoglobinaemia are acknowledged as important risk factors that require urgent research to address the problem of AKI.
Estimating young adult uptake of smoking by area across the UK
Authors: Jackson Sarah E. , Tattan-Birch Harry , Hopkinson Nicholas S , Brown Jamie , Shahab Lion , Bunce Laura , Laverty Anthony A , Arnott Deborah 
Published: June 2024

AbstractBackgroundThere is majority support in parliament and across the United Kingdom (UK) to implement a ‘smokefree generation’ policy which would increase the legal age of sale of tobacco from 18 by one year each year from 2027 onwards, such that people born on or after 1 January 2009 could never legally be sold tobacco. To explore the potential impact this policy could have, we estimated the number of young adults (18–25y) currently taking up smoking each year by area across the UK.MethodsUsing data from the Office for National Statistics (ONS), Annual Population Survey (APS), and Smoking Toolkit Study (STS), we estimated the total number of 18–25-year-olds in the UK taking up smoking each year, based on national estimates of population size (ONS) and the proportion who reported ever having been a regular smoker (STS). We used local data on adult smoking rates (APS) to apportion the national estimated number of young adults taking up smoking to specific areas.ResultsAround 127,500 18–25-year-olds in the UK start smoking regularly each year (349 each day); 105,700 each year (290 each day) in England, 11,500 (32) in Scotland, 6,500 (18) in Wales, and 3,800 (10) in Northern Ireland. Estimates of uptake varied across localities: for example, North East Lincolnshire had the highest proportion of young adults taking up smoking each year (3.96%) and Wokingham had the lowest (0.85%).ConclusionsDespite reductions in smoking prevalence over recent decades, hundreds of young adults in the UK start smoking every day. Data on rates of uptake among individual local authorities can be used to focus attention locally prior to the introduction of new age of sale laws.