bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better
Authors: Lee Ching-Chi , Chen Po-Lin , Ho Ching-Yu , Hong Ming-Yuan , Hung Yuan-Pin , Ko Wen-Chien 
Published: May 2024

Abstract
Background
Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia.

Methods
The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model.

Results
Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness.

Conclusions
Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.
Deep learning of mammogram images to reduce unnecessary breast biopsies: a preliminary study
Authors: Liu Chang , Sun Min , Arefan Dooman , Zuley Margarita , Sumkin Jules , Wu Shandong 
Published: May 2024

Abstract
Background
Patients with a Breast Imaging Reporting and Data System (BI-RADS) 4 mammogram are currently recommended for biopsy. However, 70–80% of the biopsies are negative/benign. In this study, we developed a deep learning classification algorithm on mammogram images to classify BI-RADS 4 suspicious lesions aiming to reduce unnecessary breast biopsies.

Materials and methods
This retrospective study included 847 patients with a BI-RADS 4 breast lesion that underwent biopsy at a single institution and included 200 invasive breast cancers, 200 ductal carcinoma in-situ (DCIS), 198 pure atypias, 194 benign, and 55 atypias upstaged to malignancy after excisional biopsy. We employed convolutional neural networks to perform 4 binary classification tasks: (I) benign vs. all atypia + invasive + DCIS, aiming to identify the benign cases for whom biopsy may be avoided; (II) benign + pure atypia vs. atypia-upstaged + invasive + DCIS, aiming to reduce excision of atypia that is not upgraded to cancer at surgery; (III) benign vs. each of the other 3 classes individually (atypia, DCIS, invasive), aiming for a precise diagnosis; and (IV) pure atypia vs. atypia-upstaged, aiming to reduce unnecessary excisional biopsies on atypia patients.

Results
A 95% sensitivity for the “higher stage disease” class was ensured for all tasks. The specificity value was 33% in Task I, and 25% in Task II, respectively. In Task III, the respective specificity value was 30% (vs. atypia), 30% (vs. DCIS), and 46% (vs. invasive tumor). In Task IV, the specificity was 35%. The AUC values for the 4 tasks were 0.72, 0.67, 0.70/0.73/0.72, and 0.67, respectively.

Conclusion
Deep learning of digital mammograms containing BI-RADS 4 findings can identify lesions that may not need breast biopsy, leading to potential reduction of unnecessary procedures and the attendant costs and stress.
Effect of genomic and cellular environments on gene expression noise
Authors: Hong Clarice K. Y. , Ramu Avinash , Zhao Siqi , Cohen Barak A. 
Published: May 2024

Abstract
Background
Individual cells from isogenic populations often display large cell-to-cell differences in gene expression. This “noise” in expression derives from several sources, including the genomic and cellular environment in which a gene resides. Large-scale maps of genomic environments have revealed the effects of epigenetic modifications and transcription factor occupancy on mean expression levels, but leveraging such maps to explain expression noise will require new methods to assay how expression noise changes at locations across the genome.

Results
To address this gap, we present Single-cell Analysis of Reporter Gene Expression Noise and Transcriptome (SARGENT), a method that simultaneously measures the noisiness of reporter genes integrated throughout the genome and the global mRNA profiles of individual reporter-gene-containing cells. Using SARGENT, we perform the first comprehensive genome-wide survey of how genomic locations impact gene expression noise. We find that the mean and noise of expression correlate with different histone modifications. We quantify the intrinsic and extrinsic components of reporter gene noise and, using the associated mRNA profiles, assign the extrinsic component to differences between the CD24+ “stem-like” substate and the more “differentiated” substate. SARGENT also reveals the effects of transgene integrations on endogenous gene expression, which will help guide the search for “safe-harbor” loci.

Conclusions
Taken together, we show that SARGENT is a powerful tool to measure both the mean and noise of gene expression at locations across the genome and that the data generatd by SARGENT reveals important insights into the regulation of gene expression noise genome-wide.
Rosace: a robust deep mutational scanning analysis framework employing position and mean-variance shrinkage
Authors: Rao Jingyou , Xin Ruiqi , Macdonald Christian , Howard Matthew K. , Estevam Gabriella O. , Yee Sook Wah , Wang Mingsen , Fraser James S. , Coyote-Maestas Willow , Pimentel Harold 
Published: May 2024

AbstractDeep mutational scanning (DMS) measures the effects of thousands of genetic variants in a protein simultaneously. The small sample size renders classical statistical methods ineffective. For example, p-values cannot be correctly calibrated when treating variants independently. We propose , a Bayesian framework for analyzing growth-based DMS data. leverages amino acid position information to increase power and control the false discovery rate by sharing information across parameters via shrinkage. We also developed for simulating the distributional properties of DMS. We show that is robust to the violation of model assumptions and is more powerful than existing tools.
Development of orthogonal aminoacyl-tRNA synthetase mutant for incorporating a non-canonical amino acid
Authors: Lee Dongheon , Kim Ja Gyung , Kim Tae Wan , Choi Jong-il 
Published: May 2024

AbstractGenetic code expansion involves introducing non-canonical amino acids (ncAAs) with unique functional groups into proteins to broaden their applications. Orthogonal aminoacyl tRNA synthetase (aaRS), essential for genetic code expansion, facilitates the charging of ncAAs to tRNA. In this study, we developed a new aaRS mutant from Methanosaeta concilii tyrosyl-tRNA synthetase (Mc TyrRS) to incorporate para-azido-l-phenylalanine (AzF). The development involved initial site-specific mutations in Mc TyrRS, followed by random mutagenesis. The new aaRS mutant with amber suppression was isolated through fluorescence-activated cell sorting. The M. concilii aaRS mutant structure was further analyzed to interpret the effect of mutations. This research provides a novel orthogonal aaRS evolution pipeline for highly efficient ncAA incorporation that will contribute to developing novel aaRS from various organisms.
Navigating the science policy interface: a co-created mind-map to support early career research contributions to policy-relevant evidence
Authors: Washbourne Carla-Leanne , Murali Ranjini , Saidi Nada , Peter Sophie , Pisa Paola Fontanella , Sarzynski Thuan , Ryu Hyeonju , Filyushkina Anna , Campagne Carole Sylvie , Kadykalo Andrew N. , Ávila-Flores Giovanni , Amiar Taha 
Published: May 2024

AbstractThe interface between science and policy is a complex space, in theory and practice, that sees the interaction of various actors and perspectives coming together to enable policy-relevant evidence to support decision-making. Early Career Researchers (ECRs) are increasingly interested in working at the science-policy interface to support evidence-informed policy, with the number of opportunities to do so increasing at national and international levels. However, there are still many challenges limiting ECRs participation, not least how such a complex space can be accessed and navigated. While recommendations for engaging at the science-policy interface already exist, a practical ‘map’ of the science-policy interface landscape which would allow for ECR participation in evidence co-production and synthesis in science-policy is missing. With the purpose of facilitating the engagement of ECRs producing biodiversity and ecosystem services policy-relevant evidence at the interface between science and policy, the authors have co-created a ‘mind-map’—a tool to review the landscape of and leverage access to the science-policy interface. This tool was developed through reviewing published literature, collating personal experiences of the ECR authors, and validating against wider peer perspectives in an ECR workshop during the 7th Plenary of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). This co-created tool sees ECR engagement in (co-)producing evidence at the science-policy interface as an interaction of three main factors: the environment of the ECR, which mediates their acts of engagement at the science-policy interface leading to outcomes that will ultimately have a reciprocal impact on the ECR’s environment.
Body composition and rupture risk of intracranial aneurysms
Authors: Løvik Katja , Laupsa-Borge Johnny , Logallo Nicola , Helland Christian A. 
Published: May 2024

Abstract
Background
Rupture of an intracranial aneurysm resulting in a subarachnoid hemorrhage (SAH) is a life-threatening situation. Obesity is an increasing health challenge associated with numerous comorbidities. However, recent studies have shown a surprising decreased risk of SAH with increasing body mass index (BMI). The aim was to explore associations between other anthropometric variables and the rupture risk of an intracranial aneurysm, which to our knowledge is lacking in present literature.

Methods
Using a bioelectrical impedance analysis device, we performed body composition analyses on 31 patients admitted with aneurysmal SAH (aSAH) and 28 patients with planned intervention on their unruptured aneurysm. We also collected information on comorbidities and relevant risk factors. Logistic regression was used to explore associations between anthropometric variables and patients with ruptured versus unruptured aneurysms.

Results
Unadjusted estimates showed a significant inverse relationship between body fat percent and aneurysmal rupture (OR [95% CI]: 0.92 [0.86, 0.97], P = 0.009), and between body fat mass and aneurysmal rupture (OR [95% CI]: 0.95 [0.90, 0.99], P = 0.047). These risk relationships remained significant in age- and sex-adjusted analyses for body fat percent (OR [95% CI]: 0.93, [0.87, 0.97], P = 0.028), and body fat mass (OR [95% CI]: 0.95 [0.90, 0.99], P = 0.041).

Conclusions
In recent studies showing a paradoxical relation between aSAH and obesity, BMI was the only parameter investigated. We further explored this “obesity paradox” and found lower body fat in aSAH patients compared to UIA. Future studies should investigate these relationships in larger samples.
Clinical Trial Registration NCT04613427, November 3, 2020, retrospectively registered
Disrupting Na+ ion homeostasis and Na+/K+ ATPase activity in breast cancer cells directly modulates glycolysis in vitro and in vivo
Authors: Michaels Aidan M. , Zoccarato Anna , Hoare Zoe , Firth George , Chung Yu Jin , Kuchel Philip W. , Shah Ajay M. , Shattock Michael J. , Southworth Richard , Eykyn Thomas R. 
Published: May 2024

Abstract
Background
Glycolytic flux is regulated by the energy demands of the cell. Upregulated glycolysis in cancer cells may therefore result from increased demand for adenosine triphosphate (ATP), however it is unknown what this extra ATP turnover is used for. We hypothesise that an important contribution to the increased glycolytic flux in cancer cells results from the ATP demand of Na+/K+-ATPase (NKA) due to altered sodium ion homeostasis in cancer cells.

Methods
Live whole-cell measurements of intracellular sodium [Na+]i were performed in three human breast cancer cells (MDA-MB-231, HCC1954, MCF-7), in murine breast cancer cells (4T1), and control human epithelial cells MCF-10A using triple quantum filtered 23Na nuclear magnetic resonance (NMR) spectroscopy. Glycolytic flux was measured by 2H NMR to monitor conversion of [6,6-2H2]d-glucose to [2H]-labelled l-lactate at baseline and in response to NKA inhibition with ouabain. Intracellular [Na+]i was titrated using isotonic buffers with varying [Na+] and [K+] and introducing an artificial Na+ plasma membrane leak using the ionophore gramicidin-A. Experiments were carried out in parallel with cell viability assays, 1H NMR metabolomics of intracellular and extracellular metabolites, extracellular flux analyses and in vivo measurements in a MDA-MB-231 human-xenograft mouse model using 2-deoxy-2-[18F]fluoroglucose (18F-FDG) positron emission tomography (PET).

Results
Intracellular [Na+]i was elevated in human and murine breast cancer cells compared to control MCF-10A cells. Acute inhibition of NKA by ouabain resulted in elevated [Na+]i and inhibition of glycolytic flux in all three human cancer cells which are ouabain sensitive, but not in the murine cells which are ouabain resistant. Permeabilization of cell membranes with gramicidin-A led to a titratable increase of [Na+]i in MDA-MB-231 and 4T1 cells and a Na+-dependent increase in glycolytic flux. This was attenuated with ouabain in the human cells but not in the murine cells. 18FDG PET imaging in an MDA-MB-231 human-xenograft mouse model recorded lower 18FDG tumour uptake when treated with ouabain while murine tissue uptake was unaffected.

Conclusions
Glycolytic flux correlates with Na+-driven NKA activity in breast cancer cells, providing evidence for the ‘centrality of the [Na+]i-NKA nexus’ in the mechanistic basis of the Warburg effect.
Aberrant myonuclear domains and impaired myofiber contractility despite marked hypertrophy in MYMK-related, Carey-Fineman-Ziter Syndrome
Authors: Dugdale Hannah F. , Levy Yotam , Jungbluth Heinz , Oldfors Anders , Ochala Julien 
Published: May 2024

AbstractCarey Fineman Ziter Syndrome (CFZS) is a rare autosomal recessive disease caused by mutations in the MYMK locus which encodes the protein, myomaker. Myomaker is essential for fusion and concurrent myonuclei donation of muscle progenitors during growth and development. Strikingly, in humans, MYMK mutations appear to prompt myofiber hypertrophy but paradoxically, induce generalised muscle weakness. As the underlying cellular mechanisms remain unexplored, the present study aimed to gain insights by combining myofiber deep-phenotyping and proteomic profiling. Hence, we isolated individual muscle fibers from CFZS patients and performed mechanical, 3D morphological and proteomic analyses. Myofibers from CFZS patients were ~ 4x larger than controls and possessed ~ 2x more myonuclei than those from healthy subjects, leading to disproportionally larger myonuclear domain volumes. These greater myonuclear domain sizes were accompanied by smaller intrinsic cellular force generating-capacities in myofibers from CFZS patients than in control muscle cells. Our complementary proteomic analyses indicated remodelling in 233 proteins particularly those associated with cellular respiration. Overall, our findings suggest that myomaker is somewhat functional in CFZS patients, but the associated nuclear accretion may ultimately lead to non-functional hypertrophy and altered energy-related mechanisms in CFZS patients. All of these are likely contributors of the muscle weakness experienced by CFZS patients.
Emergence of two distinct phase transitions in monolayer CoSe2 on graphene
Authors: Rhee Tae Gyu , Lam Nguyen Huu , Kim Yeong Gwang , Gu Minseon , Hwang Jinwoong , Bostwick Aaron , Mo Sung-Kwan , Chun Seung-Hyun , Kim Jungdae , Chang Young Jun , Choi Byoung Ki 
Published: May 2024

AbstractDimensional modifications play a crucial role in various applications, especially in the context of device miniaturization, giving rise to novel quantum phenomena. The many-body dynamics induced by dimensional modifications, including electron-electron, electron-phonon, electron-magnon and electron-plasmon coupling, are known to significantly affect the atomic and electronic properties of the materials. By reducing the dimensionality of orthorhombic CoSe2 and forming heterostructure with bilayer graphene using molecular beam epitaxy, we unveil the emergence of two types of phase transitions through angle-resolved photoemission spectroscopy and scanning tunneling microscopy measurements. We disclose that the 2 × 1 superstructure is associated with charge density wave induced by Fermi surface nesting, characterized by a transition temperature of 340 K. Additionally, another phase transition at temperature of 160 K based on temperature dependent gap evolution are observed with renormalized electronic structure induced by electron-boson coupling. These discoveries of the electronic and atomic modifications, influenced by electron-electron and electron-boson interactions, underscore that many-body physics play significant roles in understanding low-dimensional properties of non-van der Waals Co-chalcogenides and related heterostructures.
Graphical Abstract
Bayesian earthquake forecasting approach based on the epidemic type aftershock sequence model
Authors: Petrillo Giuseppe , Zhuang Jiancang 
Published: May 2024

AbstractThe epidemic type aftershock sequence (ETAS) model is used as a baseline model both for earthquake clustering and earthquake prediction. In most forecast experiments, the ETAS parameters are estimated based on a short and local catalog, therefore the model parameter optimization carried out by means of a maximum likelihood estimation may be not as robust as expected. We use Bayesian forecast techniques to solve this problem, where non-informative flat prior distributions of the parameters is adopted to perform forecast experiments on 3 mainshocks occurred in Southern California. A Metropolis–Hastings algorithm is employed to sample the model parameters and earthquake events. We also show, through forecast experiments, how the Bayesian inference allows to obtain a probabilistic forecast, differently from one obtained via MLE.
Graphical Abstract
When you need them, they are not there: hedge capacities of cryptocurrencies disappear in downtrend markets
Authors: Bossman Ahmed , Gubareva Mariya , Agyei Samuel Kwaku , Vo Xuan Vinh 
Published: May 2024

AbstractWe provide empirical evidence supporting the economic reasoning behind the impossibility of diversification benefits and the hedge attributes of cryptocurrencies remaining in force during the downside trends observed in bearish financial markets. We employ a spillover connectedness model driven by time-varying parameter vector autoregressions on daily data covering January 2018 to November 2022 to analyze spillover transmissions between conventional and digital markets, focusing on the role of stablecoin issuances. We study the stock, bond, cryptocurrency, and stablecoin markets and find very high connectedness, which varies over time in response to up/down trends in financial markets. The results show that during financial turmoil, cryptocurrencies amplify downside risks rather than serve as diversifiers. In addition to risky assets from conventional financial markets, cryptocurrencies champion the transmission of spillovers to digital and conventional markets. In contrast, changes in stablecoin issuances produce few shocks because of their pegged prices, but they facilitate investors’ switch from volatile cryptos to more stable digital instruments; that is, we observe a phenomenon designated by us as the “flight-to-cryptosafety.” We draw insightful conclusions, provoking new thinking regarding portfolio hedge strategies that could potentially benefit investors when searching for less volatile investment performance.
A case of pediatric Perthes’ disease with unexplained hyperlactatemia at the time of initial surgery and anesthetic management with remimazolam for the subsequent surgery
Authors: Ishikawa Ko , Hiroki Tadanao , Ito Sachiko , Aso Chizu , Saito Shigeru 
Published: May 2024

Abstract
Background
The causes of perioperative hyperlactatemia vary, but they are generally associated with hypoperfusion. Here, we report the case of a pediatric patient who developed unexplained hyperlactatemia during anesthesia with propofol and sevoflurane, which recurred during a second surgery under anesthesia with remimazolam.
Case presentation.
An 8-year-old boy with Perthes disease and no remarkable past or family history was scheduled for an osteotomy. Anesthesia was induced with propofol and rocuronium and then maintained with sevoflurane and remifentanil. The patient developed lactic acidosis without hemodynamic instability during anesthesia, with a normal lactate/pyruvate ratio after surgery, suggesting a lack of hypoperfusion. We used remimazolam instead of propofol during the second surgery 6 months later, considering the possibility of drug-induced lactic acidosis, including malignant hyperthermia and propofol infusion syndrome, where the unexplained hyperlactatemia recurred.

Conclusions
Distinguishing the causes of hyperlactatemia, particularly in the absence of other symptoms, is challenging. The lactate/pyruvate ratio during episodes of hyperlactatemia can provide insights into the underlying pathology.