bluuebunny/crossref_metadata_2025_split huggingface dataset:
α-Hemolysin-mediated endothelial injury contributes to the development of
Staphylococcus aureus
-induced dermonecrosis
Authors: Yang Ching , Robledo-Avila Frank H. , Partida-Sanchez Santiago , Montgomery Christopher P. 
Published: July 2024

ABSTRACT

Staphylococcus aureus
α-hemolysin (Hla) is a pore-forming toxin critical for the pathogenesis of skin and soft tissue infections, which causes the pathognomonic lesion of cutaneous necrosis (dermonecrosis) in mouse models. To determine the mechanism by which dermonecrosis develops during
S. aureus
skin infection, mice were given control serum, Hla-neutralizing antiserum, or an inhibitor of Hla receptor [A-disintegrin and metalloprotease 10 (ADAM10) inhibitor] followed by subcutaneous infection by
S. aureus,
and the lesions were evaluated using immunohistochemistry and immunofluorescence. Hla induced apoptosis in the vascular endothelium at 6 hours post-infection (hpi), followed by apoptosis in keratinocytes at 24 hpi. The loss of vascular endothelial (VE)-cadherin expression preceded the loss of epithelial-cadherin expression. Hla also induced hypoxia in the keratinocytes at 24 hpi following vascular injury. Treatment with Hla-neutralizing antibody or ADAM10 inhibitor attenuated early cleavage of VE-cadherin, cutaneous hypoxia, and dermonecrosis. These findings suggest that Hla-mediated vascular injury with cutaneous hypoxia underlies the pathogenesis of
S. aureus
-induced dermonecrosis.
When less is more: the art of communicating clinical microbiology results
Authors: Buchan Blake W. 
Published: July 2024

ABSTRACT

The clinical microbiology laboratory is capable of identifying microorganisms in clinical specimens faster and more accurately than ever before. At face value, this should enable patient care providers to make better-informed decisions and target antimicrobial therapies to deliver individualized care. Ironically, more complete and specific reporting of microorganisms isolated from specimens may result in overtreatment based on the presence of a pathogen, even in the absence of clear signs of clinical infection. This conundrum calls into question the role of the laboratory in contributing to care through selective or “exception” reporting whereby some results are selectively withheld when there is a low probability that laboratory findings correlate with the clinical infection. In a recent article published in the
Journal of Clinical Microbiology
, Bloomfield et al. (J Clin Microbiol 62:e00342-24, 2024,
https://doi.org/10.1128/jcm.00342-24
) examine the impact and safety of an exception reporting strategy applied to wound swab specimens. Canonical pathogens associated with skin and soft tissue infections including
S. aureus
and beta-hemolytic streptococci are withheld from the laboratory report if certain patient criteria are met that would put them at low risk of adverse outcomes if untreated, or if treated with guideline-recommended empiric therapy. Their central finding was an approximately 50% reduction in post-laboratory report antibiotic initiation without adverse events or increased 30-day admission rate (indicative of infection-related complications, e.g., disseminated disease). While effectively achieving their goal, the premise of exception reporting and other modified reporting strategies raises questions about the potential risk of underreporting and how to ensure that the message is being interpreted, and acted upon, by care providers as was intended by the laboratory.
The complete genomic sequence of the type strain
Brochothrix thermosphacta
DSM 20171 highlights a diversity of prophages in this species
Authors: Gingras Loic , Piché Laurie C. , Saucier Linda , Vincent Antony T. 
Published: July 2024

ABSTRACT

The bacterium
Brochothrix thermosphacta
is a known muscle food spoiler. Here, the complete genome sequence of the
B. thermosphacta
type strain, DSM 20171, is reported. Prediction of prophages and genomic islands reveals an unsuspected diversity in this bacterial species that deserves further investigation.
Shaping school for childhood myopia: the association between floor area ratio of school environment and myopia in China
Authors: Zeng Danqi , Yang Yahan , Tang Yang , Zhao Lanqin , Wang Xun , Yun Dongyuan , Chen Wenben , Shang Yuanjun , Xu Andi , Liao Huipeng , Zhang Xingying , Lin Duoru , Lin Haotian 
Published: July 2024

Aim
To investigate the association of floor area ratio (FAR), an indicator of built environments, and myopia onset.

Methods
This prospective cohort study recruited 136 753 children aged 6–10 years from 108 schools in Shenzhen, China at baseline (2016–2017). Refractive power was measured with non-cycloplegic autorefraction over a 2-year follow-up period. FAR was objectively evaluated using geographical information system technology. Mixed-effects logistic regression models were constructed to examine the association of FAR with a 2-year cumulative incidence of myopia among individuals without baseline myopia; multiple linear regression model, with a 2-year cumulative incidence rate of myopia at each school.

Results
Of 101 624 non-myopic children (56.3% boys; mean (SE) age, 7.657±1.182 years) included in the study, 26 391 (26.0%) of them developed myopia after 2 years. In the individual-level analysis adjusting for demographic, socioeconomic and greenness factors, an IQR in FAR was associated with a decreased risk of 2-year myopia incidence (OR 0.898, 95% CI 0.866 to 0.932, p<0.001). Similar findings were observed in the analysis additionally adjusted for genetic and behavioural factors (OR 0.821, 95% CI 0.766 to 0.880, p<0.001). In the school-level, an IQR increase in FAR was found to be associated with a 2.0% reduction in the 2-year incidence rate of myopia (95% CI 1.3% to 2.6%, p<0.001).

Conclusions
Exposure to higher FAR was associated with a decreased myopia incidence, providing insights into myopia prevention through school built environments in China.
Effects of vitamin D and L-cysteine cosupplementation on circulating bioavailable and total 25-hydroxy-vitamin D, the free/total testosterone ratio and inflammatory biomarkers in healthy vitamin D-deficient African Americans: a placebo-controlled double-blind clinical trial
Authors: Jain Sushil K , Justin Margret Jeffrey , Zachary Alonzo , Lally Marissa M , Vanchiere John A , Mhanna Maroun J , Shi Runhua , Levine Steven N 
Published: July 2024

BackgroundSubjects with metabolic syndrome and obesity have higher levels of inflammation with depression of the vitamin D (VD) hydroxylase/metabolising genes (CYP2R1/CYP27A1/CYP27B1/VDR) required to convert VD consumed in the diet into 25(OH)VD. Compared with total 25(OH)VD levels, measurement of bioavailable 25(OH)VD is a better method to determine the beneficial effect of VD.ObjectiveThis study investigates whether cosupplementation with VD and L-cysteine (LC), which downregulates inflammation and upregulates VD-regulating genes, provides a better therapeutic benefit than supplementation with VD-alone in African Americans (AA).MethodsAA participants (men/women, aged 18–65 years; n=165) were block randomised into one of four groups and received daily, oral supplementation for 6 months with placebo, LC (1000 mg/day), VD (2000 IU/day) or VD+LC. Fasting blood collected at the baseline and final visits was analysed for total, free and bioavailable 25(OH)VD along with insulin, VD-binding protein (VDBP), sex hormone-binding globulin (SHBG), free and total testosterone, and inflammatory marker levels. Studies were carried out in THP-1 monocytes to elucidate the direct effect of LC and testosterone on VD-regulating genes.ResultsBaseline data showed no differences in age, body mass index, calcium, liver or kidney function among the groups. Compared with levels in the group that received VD-alone supplementation, levels of neutrophil-to-lymphocyte ratio, C reactive protein, HOMA-IR, VDBP and HbA1c were significantly lower in the VD+LC group while the VD+LC group showed a significant increase in bioavailable 25(OH)VD in both sexes, total 25(OH)VD levels were significantly elevated in men but not in women treated with VD+LC. Blood levels of SHBG and free/total testosterone were elevated in the VD+LC group but not in the VD-alone group. LC and testosterone treatment significantly upregulated VD-metabolising genes (CYP2R1/CYP27A1/CYP27B1/VDR) andSHBGin THP-1 monocytes.ConclusionsVD cosupplemented with LC upregulates circulating bioavailable 25(OH)VD and reduces inflammation. Total 25(OH)VD levels were higher in men but not in women in the VD+LC group. This pilot study suggests that compared with supplementation with VD-alone, VD+LC cosupplementation could be a better approach to raising the total 25(OH)VD in men and the bioavailable 25(OH)VD in both sexes and lowering the inflammatory risk in the AA population.Trial registration numberNCT04939792.
High-resolution laser spectroscopy on the hyperfine structure and isotope shift of $$^{237,239}$$Np
Authors: Kaja Magdalena , Urquiza-González Mitzi , Berg Felix , Reich Tobias , Stemmler Matou , Studer Dominik , Weber Felix , Wendt Klaus 
Published: July 2024

AbstractNuclear ground state properties of $$^{237,239}$$

237
,
239

Np were investigated by high-resolution laser spectroscopy at the RISIKO mass separator off-line radioactive beam facility of the University of Mainz. The isotope shifts and the hyperfine parameters were determined in two different atomic ground-state transitions at 398.80 nm and 395.61 nm. The data allowed for calculation of the so far unknown nuclear moments of the short-lived isotope $$^{239}$$

239

Np, i.e. the nuclear magnetic dipole moment of $$\mu _I$$

μ
I

= +3.18(2) $$\mu _N$$

μ
N

and the electric quadrupole moment of $$Q_S$$

Q
S

= +4.05(8) eb, using the known nuclear moments of $$^{237}$$

237

Np as a reference, which were determined by electron paramagnetic resonance and investigations of muonic X-ray hyperfine structures, respectively.
Computing the Heaviest Conflict-free Sub-DAG in DAG-based DLTs
Authors: Bramas Quentin 
Published: July 2024

In this article, we consider DAG-based distributed ledger technologies (DLTs), i.e., DLTs where each block can reference several previous blocks hence forming a directed acyclic graph of blocks (BDAG). Each block has a weight (usually a constant normalized to one) and our goal is to compute the heaviest sub-BDAG that does not contain conflicting blocks.
First, we prove that computing such a sub-BDAG is NP-complete. Then, we show that the difficulty comes from concurrent conflicts and we present an optimal algorithm that is polynomial if the number of concurrent conflicts is bounded. We also give an efficient incremental version of our algorithm. Finally, we evaluate the performance of our algorithm on random BDAGs against an existing algorithm called GHOSTDAG and show that, in addition to being optimal, our algorithm is also more efficient in practice.
Adhesion GPCR ADGRE2 Maintains Proteostasis to Promote Progression in Acute Myeloid Leukemia
Authors: Huang Deyu , Yu Zebin , Lu Huan , Jiang Penglei , Qian Xinyue , Han Yingli , Qian Pengxu 
Published: July 2024

Abstract
Acute myeloid leukemia (AML) is an aggressive and heterogeneous hematologic malignancy. In elderly patients, AML incidence is high and has a poor prognosis due to a lack of effective therapies. G protein–coupled receptors (GPCR) play integral roles in physiologic processes and human diseases. Particularly, one third of adhesion GPCRs, the second largest group of GPCRs, are highly expressed in hematopoietic stem and progenitor cells or lineage cells. Here, we investigate the role of adhesion GPCRs in AML and whether they could be harnessed as antileukemia targets. Systematic screening of the impact of adhesion GPCRs on AML functionality by bioinformatic and functional analyses revealed high expression of ADGRE2 in AML, particularly in leukemic stem cells, which is associated with poor patient outcomes. Silencing ADGRE2 not only exerts antileukemic effects in AML cell lines and cells derived from patients with AML in vitro, but also delays AML progression in xenograft models in vivo. Mechanistically, ADGRE2 activates phospholipase Cβ/protein kinase C/MEK/ERK signaling to enhance the expression of AP1 and transcriptionally drive the expression of DUSP1, a protein phosphatase. DUSP1 dephosphorylates Ser16 in the J-domain of the co-chaperone DNAJB1, which facilitates the DNAJB1–HSP70 interaction and maintenance of proteostasis in AML. Finally, combined inhibition of MEK, AP1, and DUSP1 exhibits robust therapeutic efficacy in AML xenograft mouse models. Collectively, this study deciphers the roles and mechanisms of ADGRE2 in AML and provides a promising therapeutic strategy for treating AML.
Significance: Increased expression of the adhesion GPCR member ADGRE2 in AML supports leukemia stem cell self-renewal and leukemogenesis by modulating proteostasis via an MEK/AP1/DUSP1 axis, which can be targeted to suppress AML progression.
mTORC1-Driven Protein Translation Correlates with Clinical Benefit of Capivasertib within a Genetically Preselected Cohort of PIK3CA-Altered Tumors
Authors: Sobsey Constance A. , Froehlich Bjoern C. , Mitsa Georgia , Ibrahim Sahar , Popp Robert , Zahedi Rene P. , de Bruin Elza C. , Borchers Christoph H. , Batist Gerald 
Published: July 2024

Abstract

Capivasertib is a potent selective inhibitor of AKT. It was recently FDA approved in combination with fulvestrant to treat HR+, HER2-negative breast cancers with certain genetic alteration(s) activating the PI3K pathway. In phase I trials, heavily pretreated patients with tumors selected for activating PI3K pathway mutations treated with capivasertib monotherapy demonstrated objective response rates of &lt;30%. We investigated the proteomic profile associated with capivasertib response in genetically preselected patients and cancer cell lines. We analyzed samples from 16 PIK3CA-mutated patient tumors collected prior to capivasertib monotherapy in the phase I trial. PI3K pathway proteins were precisely quantified with immuno-Matrix-Assisted Laser Desorption/Ionization-mass spectrometry (iMALDI-MS). Global proteomic profiles were also obtained. Patients were classified according to response to capivasertib monotherapy: “clinical benefit (CB)” (≥12 weeks without progression, n = 7) or “no clinical benefit (NCB)” (progression in &lt;12 weeks, n = 9). Proteins that differed between the patient groups were subsequently quantified in AKT1- or PIK3CA-altered breast cancer cell lines with varying capivasertib sensitivity. The measured concentrations of AKT1 and AKT2 varied among the PIK3CA-mutated tumors but did not differ between the CB and NCB groups. However, analysis of the global proteome data showed that translational activity was higher in tumors of the NCB vs. CB group. When reproducibly quantified by validated LC-MRM-MS assays, the same proteins of interest similarly distinguished between capivasertib-sensitive versus -resistant cell lines. The results provide further evidence that increased mTORC1-driven translation functions as a mechanism of resistance to capivasertib monotherapy. Protein concentrations may offer additional insights for patient selection for capivasertib, even among genetically preselected patients.

Significance:
Capivasertib’s first-in-class FDA approval demonstrates its promise, yet there remains an opportunity to optimize its use. Our results provide new evidence that proteomics can stratify genetically preselected patients on clinical benefit. Characterization of the same profile in cell lines furnishes additional validation. Among PIK3CA-altered tumors, increased mTORC1-driven translation appears to confer intrinsic resistance. Assessing mTORC1 activation could therefore prove a useful complement to the existing genetic selection strategy for capivasertib.
In Situ Generation of Planetary Waves in the Mesosphere by Zonally Asymmetric Gravity Wave Drag: A Revisit
Authors: Yoo Ji-Hee , Chun Hye-Yeong , Song In-Sun 
Published: July 2024

Abstract
This study investigates the in situ generation of planetary waves (PWs) by zonally asymmetric gravity wave drag (GWD) in the mesosphere using a fully nonlinear general circulation model extending to the lower thermosphere. To isolate the effects of GWD, we establish a highly idealized but efficient framework that excludes stationary PWs propagating from the troposphere and in situ PWs generated by barotropic and baroclinic instabilities. The GWD is prescribed in a zonally sinusoidal form with a zonal wavenumber (ZWN) of either 1 or 2 in the lower mesosphere of the Northern Hemisphere midlatitude. Our idealized simulations clearly show that zonally asymmetric GWD generates PWs by serving as a nonconservative source Z′ of linearized disturbance quasigeostrophic potential vorticity q′. While Z′ initially amplifies PWs through enhancing q′ tendency, the subsequent zonal advection of q′ gradually balances with Z′, thereby attaining steady-state PWs. The GWD-induced PWs predominantly have the same ZWN as the applied GWD with minor contributions from higher ZWN components attributed to nonlinear processes. The amplitude of the induced PWs increases in proportion with the magnitude of the peak GWD, while it decreases in proportion to the square of ZWN. Moreover, the amplitude of PWs increases as the meridional range of GWD expands and as GWD shifts toward lower latitudes. These PWs deposit substantial positive Eliassen–Palm flux divergence (EPFD) of ∼30 m s−1 day−1 at their origin and negative EPFD of 5–10 m s−1 day−1 during propagation. In addition, the in situ PWs exhibit interhemispheric propagation following westerlies that extend into the Southern Hemisphere.
Resistin as a potential diagnostic biomarker for sepsis: insights from DIA and ELISA analyses
Authors: Lan Youyu , Guo Wentao , Chen Wenhao , Chen Muhu , Li Shaolan 
Published: July 2024

Abstract
Purpose
The primary objective of this investigation is to systematically screen and identify differentially expressed proteins (DEPs) within the plasma of individuals afflicted with sepsis. This endeavor employs both Data-Independent Acquisition (DIA) and enzyme-linked immunosorbent assay (ELISA) methodologies. The overarching goal is to furnish accessible and precise serum biomarkers conducive to the diagnostic discernment of sepsis.

Method
The study encompasses 53 sepsis patients admitted to the Affiliated Hospital of Southwest Medical University between January 2019 and December 2020, alongside a control cohort consisting of 16 individuals devoid of sepsis pathology. Subsequently, a subset comprising 10 randomly selected subjects from the control group and 22 from the sepsis group undergoes quantitative proteomic analysis via DIA. The acquired data undergoes Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses, facilitating the construction of a Protein-Protein Interaction (PPI) network to discern potential markers. Validation of core proteins is then accomplished through ELISA. Comparative analysis between the normal and sepsis groups ensues, characterized by Receiver Operating Characteristic (ROC) curve construction to evaluate diagnostic efficacy.

Result
A total of 187 DEPs were identified through bioinformatic methodologies. Examination reveals their predominant involvement in biological processes such as wound healing, coagulation, and blood coagulation. Functional pathway analysis further elucidates their engagement in the complement pathway and malaria. Resistin emerges as a candidate plasma biomarker, subsequently validated through ELISA. Notably, the protein exhibits significantly elevated levels in the serum of sepsis patients compared to the normal control group. ROC curve analysis underscores the robust diagnostic capacity of these biomarkers for sepsis.

Conclusion
Data-Independent Acquisition (DIA) and Enzyme-Linked Immunosorbent Assay (ELISA) show increased Resistin levels in sepsis patients, suggesting diagnostic potential, warranting further research.
Filter bank temporally local multivariate synchronization index for SSVEP-based BCI
Authors: Xu Tingting , Ji Zhuojie , Xu Xin , Wang Lei 
Published: July 2024

AbstractBackgroundMultivariate synchronization index (MSI) has been successfully applied for frequency detection in steady state visual evoked potential (SSVEP) based brain–computer interface (BCI) systems. However, the standard MSI algorithm and its variants cannot simultaneously take full advantage of the time-local structure and the harmonic components in SSVEP signals, which are both crucial for frequency detection performance. To overcome the limitation, we propose a novel filter bank temporally local MSI (FBTMSI) algorithm to further improve SSVEP frequency detection accuracy. The method explicitly utilizes the temporal information of signal for covariance matrix estimation and employs filter bank decomposition to exploits SSVEP-related harmonic components.ResultsWe employed the cross-validation strategy on the public Benchmark dataset to optimize the parameters and evaluate the performance of the FBTMSI algorithm. Experimental results show that FBTMSI outperforms the standard MSI, temporally local MSI (TMSI) and filter bank driven MSI (FBMSI) algorithms across multiple experimental settings. In the case of data length of one second, the average accuracy of FBTMSI is 9.85% and 3.15% higher than that of the FBMSI and the TMSI, respectively.ConclusionsThe promising results demonstrate the effectiveness of the FBTMSI algorithm for frequency recognition and show its potential in SSVEP-based BCI applications.
SGCP: a spectral self-learning method for clustering genes in co-expression networks
Authors: Aghaieabiane Niloofar , Koutis Ioannis 
Published: July 2024

Abstract
Background
A widely used approach for extracting information from gene expression data employs the construction of a gene co-expression network and the subsequent computational detection of gene clusters, called modules. WGCNA and related methods are the de facto standard for module detection. The purpose of this work is to investigate the applicability of more sophisticated algorithms toward the design of an alternative method with enhanced potential for extracting biologically meaningful modules.

Results
We present self-learning gene clustering pipeline (SGCP), a spectral method for detecting modules in gene co-expression networks. SGCP incorporates multiple features that differentiate it from previous work, including a novel step that leverages gene ontology (GO) information in a self-leaning step. Compared with widely used existing frameworks on 12 real gene expression datasets, we show that SGCP yields modules with higher GO enrichment. Moreover, SGCP assigns highest statistical importance to GO terms that are mostly different from those reported by the baselines.

Conclusion
Existing frameworks for discovering clusters of genes in gene co-expression networks are based on relatively simple algorithmic components. SGCP relies on newer algorithmic techniques that enable the computation of highly enriched modules with distinctive characteristics, thus contributing a novel alternative tool for gene co-expression analysis.