bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inertial Parameter Identification for Closed-Loop Mechanisms: Adaptation of Linear Regression for Coordinate Partitioning
Authors: Pyrhönen Lauri , Willems Thijs , Mikkola Aki , Naets Frank 
Published: February 2024

Abstract
This study investigates the use of linear-regression-based identification in rigid multibody system applications. A multibody system model, originally described with differential-algebraic equations (DAE), is transformed into a set of ordinary differential equations using coordinate partitioning. This allows the identification framework (where the system is described with ordinary differential equations) to be applied to rigid multibody systems described with nonminimal coordinates. The methodology is demonstrated via numerical and experimental validation on a slider–crank mechanism. The results show that the presented methodology is capable of accurately identifying the system's inertial parameters even with a short motion trajectory used for training. The presented linear-regression-based identification approach opens new opportunities to develop more accurate multibody models. The resulting updated multibody models can be considered especially useful for state-estimation and the control of multibody systems.
A Decoupling Algorithm for Efficient Estimation of Failure Probability Function Based on Statistical Moment Functions
Authors: Li Hengchao , Lu Zhenzhou , Feng Kaixuan 
Published: February 2024

AbstractFailure probability function (FPF) is an important index that reflects the influence of designable distribution parameters on the safety degree of a structure, and it can be used for decoupling reliability optimization models. Thus, its efficient solution is expected. A decoupling algorithm based on statistical moment functions (SMFs) of performance function is proposed to solve the FPF efficiently in this paper. The proposed algorithm first constructs an extended density weight function (EDWF), which can cover the interested region of the distribution parameters and is independent of the distribution parameters so that the statistical moment integrals corresponding to different realizations of the distribution parameters can share the same EDWF. Then, using the same EDWF, a strategy is dexterously designed to estimate the SMFs by sharing a set of integral characteristic nodes. Finally, the FPF is approximated by the SMFs, which varies with the distribution parameters in the interested design region. In addition, the proposed algorithm introduces the Box–Cox transformation of the performance function to guide the high accuracy of FPF approximated by the SMFs. The main contribution of the proposed algorithm is constructing the EDWF to decouple the dependence of solving SMFs on the realizations of the distribution parameters over the interested region and designing the strategy of estimating the SMFs by sharing the same integral characteristic nodes. Since the proposed algorithm employs a point estimation method to evaluate the FPF, it has higher efficiency than the competitive methods. Numerical and engineering examples demonstrate the superiority of the proposed algorithm.
The Efficiency of Respiratory Exercises in Rehabilitation of Low Back Pain: A Systematic Review and Meta-Analysis
Authors: Zhai Haiting , Zhang Liqing , Xia JiXiang , Li Cheng 
Published: February 2024

Background: Low back pain (LBP) is a common musculoskeletal disorder, and respiratory exercise is considered a nonsurgical management method. Therefore, this systematic review and meta-analysis aims to estimate the results of randomized controlled trials on the effect of respiratory training in reducing LBP and its dose relationship. Methods: The present study was conducted from January 2020 to January 2022, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (2020). Relevant studies were searched in multiple databases including PubMed, Web of Science, the Cochrane Library, EBSCO, Scopus, ScienceDirect, Wan Fang and China Knowledge Network, ClinicalTrials.gov, and Google Scholar, using a combination of MeSH/Emtree terms and free-text words. The heterogeneity of the studies was assessed using the I2 statistic. Results: A total of 14 publications were included in the meta-analysis, with a total sample size of 698 individuals, aged 60–80 years. Respiratory exercise was effective in relieving LBP (standardized mean difference = −0.87, P < .00001) and improving physical disability (standardized mean difference = −0.79, P < .00001). The type of breathing and the total duration of breathing exercises were found to be the source of heterogeneity in this study by subgroup analysis. Subgroup analysis revealed that the most significant effect sizes of breathing resistance exercise to reduce LBP and the most significant effect sizes of breathing relaxation techniques to alleviate physical disability were performed 3 to 5 times per week and period >4 weeks. Respiratory exercise reducing LBP and improving functional disability was most effective when the total duration of the intervention was >500 minutes. Funnel plots showed that the results of the 2 overall studies were reliable without publication bias. Conclusions: Respiratory exercise can effectively reduce LBP and improve physical disability. Therefore, these exercises can be regarded as a part of a LBP management plan. We recommend an exercise program with 30 to 50 minutes, 3 to 5 times per week, and >4 weeks of breathing resistance exercise program as the most effective for treating LBP.
A multi-species outbreak of VIM-producing carbapenem-resistant bacteria in a burn unit and subsequent investigation of rapid development of cefiderocol resistance
Authors: Freiberg Jeffrey A. , Tao Lili , Manuel Carmila , Mike Laura A. , Nelson George E. , Harris Bryan D. , Mathers Amy J. , Talbot Thomas R. , Skaar Eric P. , Humphries Romney M. 
Published: February 2024

ABSTRACT

Carbapenem resistance due to metallo-β-lactamases (MBLs) such as the Verona integron-encoded metallo-β-lactamase (VIM) is particularly problematic due to the limited treatment options. We describe a case series of bacterial infections in a tertiary care hospital due to multi-species acquisition of a VIM gene along with our experience using novel β-lactam antibiotics and antibiotic combinations to treat these infections. Four patients were treated with the combination of ceftazidime-avibactam and aztreonam, with no resistance to the combination detected. However, cefiderocol-resistant
Klebsiella pneumoniae
isolates were detected in two out of the five patients who received cefiderocol within 3 weeks of having started the antibiotic. Strain pairs of sequential susceptible and resistant isolates from both patients were analyzed using whole-genome sequencing. This analysis revealed that the pairs of isolates independently acquired point mutations in both the
cirA
and
fiu
genes, which encode siderophore receptors. These point mutations were remade in a laboratory strain of
K. pneumoniae
and resulted in a significant increase in the MIC of cefiderocol, even in the absence of a beta-lactamase enzyme or a penicillin-binding protein 3 (PBP3) mutation. While newer β-lactam antibiotics remain an exciting addition to the antibiotic armamentarium, their use must be accompanied by diligent monitoring for the rapid development of resistance.
Interspecies variability in protein binding of antibiotics basis for translational PK/PD studies—a case study using cefazolin
Authors: Ahmed Hifza , Böhmdorfer Michaela , Eberl Sabine , Jäger Walter , Zeitlinger Markus 
Published: February 2024

ABSTRACT

For antimicrobial agents in particular, plasma protein binding (PPB) plays a pivotal role in deciphering key properties of drug candidates. Animal models are generally used in the preclinical development of new drugs to predict their effects in humans using translational pharmacokinetics/pharmacodynamics (PK/PD). Thus, we compared the protein binding (PB) of cefazolin as well as bacterial growth under various conditions
in vitro
. The PB extent of cefazolin was studied in human, bovine, and rat plasmas at different antibiotic concentrations in buffer and media containing 20–70% plasma or pure plasma using ultrafiltration (UF) and equilibrium dialysis (ED). Moreover, bacterial growth and time–kill assays were performed in Mueller Hinton Broth (MHB) containing various plasma percentages. The pattern for cefazolin binding to plasma proteins was found to be similar for both UF and ED. There was a significant decrease in cefazolin binding to bovine plasma compared to human plasma, whereas the pattern in rat plasma was more consistent with that in human plasma. Our growth curve analysis revealed considerable growth inhibition of
Escherichia coli
at 70% bovine or rat plasma compared with 70% human plasma or pure MHB. As expected, our experiments with cefazolin at low concentrations showed that
E. coli
grew slightly better in 20% human and rat plasma compared to MHB, most probably due to cefazolin binding to proteins in the plasma. Based on the example of cefazolin, our study highlights the interspecies differences of PB with potential impact on PK/PD. These findings should be considered before preclinical PK/PD data can be extrapolated to human patients.
Methionine oxidation of carbohydrate-active enzymes during white-rot wood decay
Authors: Molinelli Lise , Drula Elodie , Gaillard Jean-Charles , Navarro David , Armengaud Jean , Berrin Jean-Guy , Tron Thierry , Tarrago Lionel 
Published: February 2024

ABSTRACT

White-rot fungi employ secreted carbohydrate-active enzymes (CAZymes) along with reactive oxygen species (ROS), like hydrogen peroxide (H
2
O
2
), to degrade lignocellulose in wood. H
2
O
2
serves as a co-substrate for key oxidoreductases during the initial decay phase. While the degradation of lignocellulose by CAZymes is well documented, the impact of ROS on the oxidation of the secreted proteins remains unclear, and the identity of the oxidized proteins is unknown. Methionine (Met) can be oxidized to Met sulfoxide (MetO) or Met sulfone (MetO
2
) with potential deleterious, antioxidant, or regulatory effects. Other residues, like proline (Pro), can undergo carbonylation. Using the white-rot
Pycnoporus cinnabarinus
grown on aspen wood, we analyzed the Met content of the secreted proteins and their susceptibility to oxidation combining H
2
18
O
2
with deep shotgun proteomics. Strikingly, their overall Met content was significantly lower (1.4%) compared to intracellular proteins (2.1%), a feature conserved in fungi but not in metazoans or plants. We evidenced that a catalase, widespread in white-rot fungi, protects the secreted proteins from oxidation. Our redox proteomics approach allowed the identification of 49 oxidizable Met and 40 oxidizable Pro residues within few secreted proteins, mostly CAZymes. Interestingly, many of them had several oxidized residues localized in hotspots. Some Met, including those in GH7 cellobiohydrolases, were oxidized up to 47%, with a substantial percentage of sulfone (13%). These Met are conserved in fungal homologs, suggesting important functional roles. Our findings reveal that white-rot fungi safeguard their secreted proteins by minimizing their Met content and by scavenging ROS and pinpoint redox-active residues in CAZymes.

IMPORTANCE

The study of lignocellulose degradation by fungi is critical for understanding the ecological and industrial implications of wood decay. While carbohydrate-active enzymes (CAZymes) play a well-established role in lignocellulose degradation, the impact of hydrogen peroxide (H
2
O
2
) on secreted proteins remains unclear. This study aims at evaluating the effect of H
2
O
2
on secreted proteins, focusing on the oxidation of methionine (Met). Using the model white-rot fungi
Pycnoporus cinnabarinus
grown on aspen wood, we showed that fungi protect their secreted proteins from oxidation by reducing their Met content and utilizing a secreted catalase to scavenge exogenous H
2
O
2
. The research identified key oxidizable Met within secreted CAZymes. Importantly, some Met, like those of GH7 cellobiohydrolases, undergone substantial oxidation levels suggesting important roles in lignocellulose degradation. These findings highlight the adaptive mechanisms employed by white-rot fungi to safeguard their secreted proteins during wood decay and emphasize the importance of these processes in lignocellulose breakdown.
Deciphering the metabolism of
Lactobacillus delbrueckii
subsp.
delbrueckii
during soy juice fermentation using phenotypic and transcriptional analysis
Authors: Harlé Olivier , Niay Jérôme , Parayre Sandrine , Nicolas Aurélie , Henry Gwenaële , Maillard Marie-Bernadette , Valence Florence , Thierry Anne , Guédon Éric , Falentin Hélène , Deutsch Stéphanie-Marie 
Published: February 2024

ABSTRACT

In the context of sustainable diet, the development of soy-based yogurt fermented with lactic acid bacteria is an attractive alternative to dairy yogurts. To decipher the metabolism of
Lactobacillus delbrueckii
subsp.
delbrueckii
during soy juice (SJ) fermentation, the whole genome of the strain CIRM-BIA865 (
Ld
865) was sequenced and annotated. Then
Ld
865 was used to ferment SJ. Samples were analyzed throughout fermentation for their cell number, carbohydrate, organic acid, free amino acid, and volatile compound contents. Despite acidification, the number of
Ld
865 cells did not rise, and microscopic observations revealed the elongation of cells from 3.6 µm (inoculation) to 36.9 µm (end of fermentation). This elongation was observed in SJ but not in laboratory-rich medium MRS. Using transcriptomic analysis, we showed that the biosynthesis genes of peptidoglycan and membrane lipids were stably expressed, in line with the cell elongation observed, whereas no genes implicated in cell division were upregulated. Among the main sugars available in SJ (sucrose, raffinose, and stachyose),
Ld
865 only used sucrose. The transcriptomic analysis showed that
Ld
865 implemented the two transport systems that it contains to import sucrose: a PTS system and an ABC transporter. To fulfill its nitrogen needs,
Ld
865 probably first consumed the free amino acids of the SJ and then implemented different oligopeptide transporters and proteolytic/peptidase enzymes. In conclusion, this study showed that
Ld
865 enables fast acidification of SJ, despite the absence of cell division, leads to a product rich in free amino acids, and also leads to the production of aromatic compounds of interest.

IMPORTANCE

To reduce the environmental and health concerns related to food, an alternative diet is recommended, containing 50% of plant-based proteins. Soy juice, which is protein rich, is a relevant alternative to animal milk, for the production of yogurt-like products. However, soy “beany” and “green” off-flavors limit the consumption of such products. The lactic acid bacteria (LAB) used for fermentation can help to improve the organoleptic properties of soy products. But metabolic data concerning LAB adapted to soy juice are lacking. The aim of this study was, thus, to decipher the metabolism of
Lactobacillus delbrueckii
subsp.
delbrueckii
during fermentation of a soy juice, based on a multidisciplinary approach. This result will contribute to give tracks for a relevant selection of starter. Indeed, the improvement of the organoleptic properties of these types of products could help to promote plant-based proteins in our diet.
Proceedings of the Clinical Microbiology Open 2022—assessing clinical laboratory and industry responses to COVID-19 pandemic testing capacity challenges (part 1)
Authors: Peaper David R. , Doern Christopher D. , Sharp Susan ,   On behalf of the ASM Clinical and Public Health Microbiology Committee and the ASM Corporate Council
Published: February 2024

ABSTRACT

As the COVID-19 pandemic winds down, clinical and public health laboratories, along with industry partners, reflect on the successes and failures of the pandemic response. To capture the lessons learned and better prepare for the next pandemic, the Clinical Microbiology Open (CMO) assembled key stakeholders including directors of clinical laboratories, industry partners, and state and federal agencies such as the Centers for Disease Control and Prevention and the Food and Drug Administration. Participants were asked to provide their perspectives on the initial pandemic response, supply chain constraints especially during surges, staffing challenges, test triage and communication strategies, clinical informatics needs, laboratory financial impacts of SARS-CoV-2 testing, and the emergency use authorization process. This manuscript summarizes the diagnostic laboratory and industry perspectives on these issues that were presented and discussed at CMO and proposes some steps that could be taken to improve future pandemic responses.
Influenza D virus utilizes both 9-
O
-acetylated
N
-acetylneuraminic and 9-
O
-acetylated
N
-glycolylneuraminic acids as functional entry receptors
Authors: Uprety Tirth , Yu Jieshi , Nogales Aitor , Naveed Ahsan , Yu Hai , Chen Xi , Liu Yunpeng , Bowman Andrew S. , Martinez-Sobrido Luis , Parrish Colin R. , Melikyan Gregory B. , Wang Dan , Li Feng 
Published: February 2024

ABSTRACT

Influenza D virus (IDV) utilizes bovines as a primary reservoir with periodical spillover to other hosts. We have previously demonstrated that IDV binds both 9-
O
-acetylated
N
-acetylneuraminic acid (Neu5,9Ac
2
) and 9-
O
-acetylated
N
-glycolylneuraminic acid (Neu5Gc9Ac). Bovines produce both Neu5,9Ac
2
and Neu5Gc9Ac, while humans are genetically unable to synthesize Neu5Gc9Ac. 9-
O
-Acetylation of sialic acids is catalyzed by CASD1 via a covalent acetyl-enzyme intermediate. To characterize the role of Neu5,9Ac
2
and Neu5Gc9Ac in IDV infection and determine which form of 9-
O
-acetylated sialic acids drives IDV entry, we took advantage of a CASD1 knockout (KO) MDCK cell line and carried out feeding experiments using synthetic 9-
O
-acetyl sialic acids in combination with the single-round and multi-round IDV infection assays. The data from our studies show that (i) CASD1 KO cells are resistant to IDV infection and lack of IDV binding to the cell surface is responsible for the failure of IDV replication; (ii) feeding CASD1 KO cells with Neu5,9Ac
2
or Neu5Gc9Ac resulted in a dose-dependent rescue of IDV infectivity; and (iii) diverse IDVs replicated robustly in CASD1 KO cells fed with either Neu5,9Ac
2
or Neu5Gc9Ac at a level similar to that in wild-type cells with a functional CASD1. These data demonstrate that IDV can utilize Neu5,9Ac
2
- or non-human Neu5Gc9Ac-containing glycan receptor for infection. Our findings provide evidence that IDV has acquired the ability to infect and transmit among agricultural animals that are enriched in Neu5Gc9Ac, in addition to posing a zoonotic risk to humans expressing only Neu5,9Ac
2
.

IMPORTANCE

Influenza D virus (IDV) has emerged as a multiple-species-infecting pathogen with bovines as a primary reservoir. Little is known about the functional receptor that drives IDV entry and promotes its cross-species spillover potential among different hosts. Here, we demonstrated that IDV binds exclusively to 9-
O
-acetylated
N
-acetylneuraminic acid (Neu5,9Ac
2
) and non-human 9-
O
-acetylated
N
-glycolylneuraminic acid (Neu5Gc9Ac) and utilizes both for entry and infection. This ability in effective engagement of both 9-
O-
acetylated sialic acids as functional receptors for infection provides an evolutionary advantage to IDV for expanding its host range. This finding also indicates that IDV has the potential to emerge in humans because Neu5,9Ac
2
is ubiquitously expressed in human tissues, including lung. Thus, results of our study highlight a need for continued surveillance of IDV in humans, as well as for further investigation of its biology and cross-species transmission mechanism.
Ubiquitin-specific proteinase 1 stabilizes PRRSV nonstructural protein Nsp1β to promote viral replication by regulating K48 ubiquitination
Authors: Zhai Yunyun , Du Yongkun , Yuan Hang , Fan Shuai , Chen Xing , Wang Jiang , He Wenrui , Han Shichong , Zhang Yuhang , Hu Man , Zhang Gaiping , Kong Zhengjie , Wan Bo 
Published: February 2024

ABSTRACT

The porcine reproductive and respiratory syndrome virus (PRRSV) can lead to severe reproductive problems in sows, pneumonia in weaned piglets, and increased mortality, significantly negatively impacting the economy. Post-translational changes are essential for the host-dependent replication and long-term infection of PRRSV. Uncertainty surrounds the function of the ubiquitin network in PRRSV infection. Here, we screened 10 deubiquitinating enzyme inhibitors and found that the ubiquitin-specific proteinase 1 (USP1) inhibitor ML323 significantly inhibited PRRSV replication
in vitro
. Importantly, we found that USP1 interacts with nonstructural protein 1β (Nsp1β) and deubiquitinates its K48 to increase protein stability, thereby improving PRRSV replication and viral titer. Among them, lysine at position 45 is essential for Nsp1β protein stability. In addition, deficiency of USP1 significantly reduced viral replication. Moreover, ML323 loses antagonism to PRRSV rSD16-K45R. This study reveals the mechanism by which PRRSV recruits the host factor USP1 to promote viral replication, providing a new target for PRRSV defense.

IMPORTANCE
Deubiquitinating enzymes are critical factors in regulating host innate immunity. The porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1β (Nsp1β) is essential for producing viral subgenomic mRNA and controlling the host immune system. The host inhibits PRRSV proliferation by ubiquitinating Nsp1β, and conversely, PRRSV recruits the host protein ubiquitin-specific proteinase 1 (USP1) to remove this restriction. Our results demonstrate the binding of USP1 to Nsp1β, revealing a balance of antagonism between PRRSV and the host. Our research identifies a brand-new PRRSV escape mechanism from the immune response.
Absence of CD80 reduces HSV-1 replication in the eye and delays reactivation but not latency levels
Authors: Jaggi Ujjaldeep , Matundan Harry H. , Oh Jay J. , Ghiasi Homayon 
Published: February 2024

ABSTRACT

Herpes simplex virus-1 (HSV-1) infections are among the most frequent serious viral eye infections in the U.S. and are a major cause of viral-induced blindness. HSV-1 infection is known to induce T cell activation, proliferation, and differentiation that play crucial roles in the development of virus-induced inflammatory lesions, leading to eye disease and causing chronic corneal damage. CD80 is a co-stimulatory molecule and plays a leading role in T cell differentiation. Previous efforts to limit lesion severity by controlling inflammation at the cellular level led us to ask whether mice knocked out for CD80 would show attenuated virus replication following reactivation. By evaluating the effects of CD80 activity on primary and latent infection, we found that in the absence of CD80, virus replication in the eyes and virus reactivation in latent trigeminal ganglia were both significantly reduced. However, latency in latently infected CD80
−/−
mice did not differ significantly from that in wild-type (WT) control mice. Reduced virus replication in the eyes of CD80
−/−
mice correlated with significantly expanded CD11c gene expression as compared to WT mice. Taken together, our results indicate that suppression of CD80 could offer significant beneficial therapeutic effects in the treatment of Herpes Stromal Keratitis (HSK).

IMPORTANCE
Of the many problems associated with recurrent ocular infection, reducing virus reactivation should be a major goal of controlling ocular herpes simplex virus-1 (HSV-1) infection. In this study, we have shown that the absence of CD80 reduces HSV-1 reactivation, which marks the establishment of a previously undescribed mechanism underlying viral immune evasion that could be exploited to better manage HSV infection.