bluuebunny/crossref_metadata_2025_split huggingface dataset:
Master Curves for Poroelastic Spherical Indentation With Step Displacement Loading
Authors: Liu Ming , Huang Haiying 
Published: July 2024

Abstract
Theoretical and numerical analyses are conducted to rigorously construct master curves that can be used for interpretation of displacement-controlled poroelastic spherical indentation test. A fully coupled poroelastic solution is first derived within the framework of Biot’s theory using the McNamee–Gibson displacement function method. The fully saturated porous medium is assumed to consist of slightly compressible solid and fluid phases and the surface is assumed to be impermeable over the contact area and permeable everywhere else. In contrast to the cases in our previous studies with an either fully permeable or impermeable surface, the mixed drainage condition yields two coupled sets of dual integral equations instead of one in the Laplace transform domain. The theoretical solutions show that for this class of poroelastic spherical indentation problems, relaxation of the normalized indentation force is affected by material properties through weak dependence on a single-derived material constant only. Finite element analysis is then performed in order to examine the differences between the theoretical solution, obtained by imposing the normal displacement over the contact area, and the numerical results where frictionless contact between a rigid sphere and the poroelastic medium is explicitly modeled. A four-parameter elementary function, an approximation of the theoretical solution with its validity supported by the numerical analysis, is proposed as the master curve that can be conveniently used to aid the interpretation of the poroelastic spherical indentation test. Application of the master curve for the ramp-hold loading scenario is also discussed.
Phase 1 study of the pharmacokinetics and clinical proof-of-concept activity of a biofilm-disrupting human monoclonal antibody in patients with chronic prosthetic joint infection of the knee or hip
Authors: Conway Janet , Delanois Ronald E. , Mont Michael A. , Stavrakis Alexandra , McPherson Edward , Stolarski Edward , Incavo Stephen , Oakes Daniel , Salvagno Ralph , Adams John S. , Kisch-Hancock Adriane , Tenorio Edgar , Leighton Anton , Ryser Stefan , Kauvar Lawrence M. , Bernthal Nicholas M. 
Published: July 2024

ABSTRACT

We report the results of a first-in-human phase 1 clinical study to evaluate TRL1068, a native human monoclonal antibody that disrupts bacterial biofilms with broad-spectrum activity against both Gram-positive and Gram-negative species. The study population consisted of patients with chronic periprosthetic joint infections (PJIs) of the knee or hip, including both monomicrobial and polymicrobial infections, that are highly resistant to antibiotics due to biofilm formation. TRL1068 was administered via a single pre-surgical intravenous infusion in three sequentially ascending dose groups (6, 15, and 30 mg/kg). Concomitant perioperative antibiotics were pathogen-targeted as prescribed by the treating physician. In this double-blinded study, 4 patients were randomized to receive placebo and 11 patients to receive TRL1068 on day 1, as well as targeted antibiotics for 7 days prior to the scheduled removal of the infected implant and placement of an antibiotic-eluting spacer as the first stage of the standard of care two-stage exchange arthroplasty. No adverse events attributable to TRL1068 were reported. TRL1068 serum half-life was 15–18 days. At day 8, the concentration in synovial fluid was approximately 60% of the blood level and thus at least 15-fold above the threshold for biofilm-disrupting activity
in vitro
. Explanted prostheses were sonicated to release adherent bacteria for culture, with elimination of the implant bacteria observed in 3 of the 11 patients who received TRL1068, which compares favorably to prior PJI treatments. None of the patients who received TRL1068 had a relapse of the original infection by the end of the study (day 169).

CLINICAL TRIALS

This study is registered with

ClinicalTrials.gov
as
NCT04763759

.
Biological characterization of the phage lysin AVPL and its efficiency against
Aerococcus viridans
-induced mastitis in a murine model
Authors: Xi Hengyu , Ji Yalu , Fu Yao , Chen Chong , Han Wenyu , Gu Jingmin 
Published: July 2024

ABSTRACT

Aerococcus viridans
(
A. viridans
) is an important opportunistic zoonotic pathogen that poses a potential threat to the animal husbandry industry, such as cow mastitis, due to the widespread development of multidrug-resistant strains. Phage lysins have emerged as a promising alternative antibiotic treatment strategy. However, no lysins have been reported to treat
A. viridans
infections. In this study, the critical active domain and key active sites of the first
A. viridans
phage lysin AVPL were revealed. AVPL consists of an N-terminal N-acetylmuramoyl-L-alanine amidase catalytic domain and a C-terminal binding domain comprising two conserved LysM. H40, N44, E52, W68, H147, T157, F60, F64, I77, N92, Q97, H159, V160, D161, and S42 were identified as key sites for maintaining the activity of the catalytic domain. The LysM motif plays a crucial role in binding AVPL to bacterial cell wall peptidoglycan. AVPL maintains stable activity in the temperature range of 4–45°C and pH range of 4–10, and its activity is independent of the presence of metal ions.
In vitro,
the bactericidal effect of AVPL showed efficient bactericidal activity in milk samples, with 2 µg/mL of AVPL reducing
A. viridans
by approximately 2 Log
10
in 1 h. Furthermore, a single dose (25 µg) of lysin AVPL significantly reduces bacterial load (approximately 2 Log
10)
in the mammary gland of mice, improves mastitis pathology, and reduces the concentration of inflammatory cytokines (TNF-α, IL-1β, and IL-6) in mammary tissue. Overall, this work provides a novel alternative therapeutic drug for mastitis induced by multidrug-resistant
A. viridans
.

IMPORTANCE

A. viridans
is a zoonotic pathogen known to cause various diseases, including mastitis in dairy cows. In recent years, there has been an increase in antibiotic-resistant or multidrug-resistant strains of this pathogen. Phage lysins are an effective approach to treating infections caused by multidrug-resistant strains. This study revealed the biological properties and key active sites of the first
A. viridans
phage lysin named AVPL. AVPL can effectively kill multidrug-resistant
A. viridans
in pasteurized whole milk. Importantly, 25 μg AVPL significantly alleviates the symptoms of mouse mastitis induced by
A. viridans
. Overall, our results demonstrate the potential of lysin AVPL as an antimicrobial agent for the treatment of mastitis caused by
A. viridans
.
Activity for CUREs to increase student understanding and application of responsible authorship and publication practices
Authors: Wilson Kristy J. , Mitchel Alexis 
Published: July 2024

ABSTRACT

Professional development of scientists is enhanced by training students in responsible conduct of research earlier in their careers. One aspect of responsible conduct of research is authorship ethics, which concerns granting of credit to those who make intellectual contributions to the research. The activity discussed in this article emphasizes how authorship ethics can be integrated with Course-based Undergraduate Research Experience (CURE) and includes an adaption that could also be used for independent research students. The activity allows students to reflect upon inequalities and problems seen in scientific authorship, including gender bias, failure to credit effort (ghostwriters), and inclusion of authors that did not meaningfully contribute to the work (honorary/gift authorship). Themes seen in student reflections on how they could demonstrate ethics in authorship included: determining authorship by contribution, appropriate attributions on curriculum vitas (CV) and posters, different credit levels, understanding authorship criteria, and tracking contributions. Themes seen in student reflections on the importance of authorship were proper authorship credit distribution, authorship impacting career opportunities, and accountability in research. In the activity, students also created attributions for a poster to be presented from their research. We found that most students were able to create attributions that were correctly formatted, included the same authors, and positioned authors in the same order as other group members, matching what was presented on the finalized poster. We found that students’ reflection on authorship and this professionalization of their activities in their CURE led to modest increases in their view of themselves as scientists.
Catabolism of β-5 linked aromatics by
Novosphingobium aromaticivorans
Authors: Metz Fletcher , Olsen Abigail M. , Lu Fachuang , Myers Kevin S. , Allemann Marco N. , Michener Joshua K. , Noguera Daniel R. , Donohue Timothy J. 
Published: July 2024

ABSTRACT

Aromatic compounds are an important source of commodity chemicals traditionally produced from fossil fuels. Aromatics derived from plant lignin can potentially be converted into commodity chemicals through depolymerization followed by microbial funneling of monomers and low molecular weight oligomers. This study investigates the catabolism of the β-5 linked aromatic dimer dehydrodiconiferyl alcohol (DC-A) by the bacterium
Novosphingobium aromaticivorans
. We used genome-wide screens to identify candidate genes involved in DC-A catabolism. Subsequent
in vivo
and
in vitro
analyses of these candidate genes elucidated a catabolic pathway composed of four required gene products and several partially redundant dehydrogenases that convert DC-A to aromatic monomers that can be funneled into the central aromatic metabolic pathway of
N. aromaticivorans
. Specifically, a newly identified γ-formaldehyde lyase, PcfL, opens the phenylcoumaran ring to form a stilbene and formaldehyde. A lignostilbene dioxygenase, LsdD, then cleaves the stilbene to generate the aromatic monomers vanillin and 5-formylferulate (5-FF). We also showed that the aldehyde dehydrogenase FerD oxidizes 5-FF before it is decarboxylated by LigW, yielding ferulic acid. We found that some enzymes involved in the β-5 catabolism pathway can act on multiple substrates and that some steps in the pathway can be mediated by multiple enzymes, providing new insights into the robust flexibility of aromatic catabolism in
N. aromaticivorans
. A comparative genomic analysis predicted that the newly discovered β-5 aromatic catabolic pathway is common within the order Sphingomonadales.

IMPORTANCE

In the transition to a circular bioeconomy, the plant polymer lignin holds promise as a renewable source of industrially important aromatic chemicals. However, since lignin contains aromatic subunits joined by various chemical linkages, producing single chemical products from this polymer can be challenging. One strategy to overcome this challenge is using microbes to funnel a mixture of lignin-derived aromatics into target chemical products. This approach requires strategies to cleave the major inter-unit linkages of lignin to release monomers for funneling into valuable products. In this study, we report newly discovered aspects of a pathway by which the
Novosphingobium aromaticivorans
DSM12444 catabolizes aromatics joined by the second most common inter-unit linkage in lignin, the β-5 linkage. This work advances our knowledge of aromatic catabolic pathways, laying the groundwork for future metabolic engineering of this and other microbes for optimized conversion of lignin into products.
Draft genomes of two
Enterobacter hormaechei
strains isolated from catheterized urine samples from females experiencing overactive bladder symptoms
Authors: Appleberry Helen , Patel Richa , Singh Kanishka , Wolfe Alan J. , Putonti Catherine , Kula Alex 
Published: July 2024

ABSTRACT

In this study, we present the draft genome of two
Enterobacter hormaechei
strains isolated from catheterized urine specimens from females with overactive bladder (OAB) symptoms. Through the sequencing of these
E. hormaechei
strains, we aim to better understand its presence and putative role in OAB in the female urinary tract.
Gut microbiome diversity within
Clostridia
is negatively associated with human obesity
Authors: Salazar-Jaramillo Laura , de la Cuesta-Zuluaga Jacobo , Chica Luis A. , Cadavid María , Ley Ruth E. , Reyes Alejandro , Escobar Juan S. 
Published: July 2024

ABSTRACT

Clostridia
are abundant in the human gut and comprise families associated with host health such as
Oscillospiraceae,
which has been correlated with leanness. However, culturing bacteria within this family is challenging, leading to their detection primarily through 16S rRNA amplicon sequencing, which has a limited ability to unravel diversity at low taxonomic levels, or by shotgun metagenomics, which is hindered by its high costs and complexity. In this cross-sectional study involving 114 Colombian adults, we used an amplicon-based sequencing strategy with alternative markers—gyrase subunit B (
gyrB
) and DNA K chaperone heat protein 70 (
dnaK
)—that evolve faster than the 16S rRNA gene. Comparing the diversity and abundance observed with the three markers in our cohort, we found a reduction in the diversity of
Clostridia
, particularly within
Lachnospiraceae
and
Oscillospiraceae
among obese individuals [as measured by the body mass index (BMI)]. Within
Lachnospiraceae
, the diversity of
Ruminococcus_A
negatively correlated with BMI. Within
Oscillospiraceae
, the genera
CAG-170
and
Vescimonas
also exhibited this negative correlation. In addition, the abundance of
Vescimonas
was negatively correlated with BMI. Leveraging shotgun metagenomic data, we conducted a phylogenetic and genomic characterization of 120 metagenome-assembled genomes from
Vescimonas
obtained from a larger sample of the same cohort. We identified 17 of the 72 reported species. The functional annotation of these genomes showed the presence of multiple carbohydrate-active enzymes, particularly glycosyl transferases and glycoside hydrolases, suggesting potential beneficial roles in fiber degradation, carbohydrate metabolism, and butyrate production.

IMPORTANCE

The gut microbiota is diverse across various taxonomic levels. At the intra-species level, it comprises multiple strains, some of which may be host-specific. However, our understanding of fine-grained diversity has been hindered by the use of the conserved 16S rRNA gene. While shotgun metagenomics offers higher resolution, it remains costly, may fail to identify specific microbes in complex samples, and requires extensive computational resources and expertise. To address this, we employed a simple and cost-effective analysis of alternative genetic markers to explore diversity within
Clostridia
, a crucial group within the human gut microbiota whose diversity may be underestimated. We found high intra-species diversity for certain groups and associations with obesity. Notably, we identified
Vescimonas
, an understudied group. Making use of metagenomic data, we inferred functionality, uncovering potential beneficial roles in dietary fiber and carbohydrate degradation, as well as in short-chain fatty acid production.
Thrombectomy alone versus intravenous thrombolysis before thrombectomy for acute basilar artery occlusion
Authors: Guo Meng , Yue Chengsong , Yang Jie , Hu Jinrong , Guo Changwei , Peng Zhouzhou , Xu Rui , Yang Dahong , Kong Weilin , Liu Xiang , Huang Jiacheng , Tian Yan , Li Fengli , Li Chang-Qing 
Published: July 2024

BackgroundEndovascular treatment (EVT) is a well-established approach for acute ischemic stroke. Whether bridging intravenous thrombolysis (IVT) before EVT confers any benefits remains uncertain. The objective of the study was to compare the efficacy and safety of direct EVT with or without bridging IVT in patients with acute basilar artery occlusion (BAO).MethodsThis multicenter cohort study enrolled 647 patients with acute BAO who underwent either bridging IVT before EVT or direct EVT from the BASILAR registry. The primary outcome was an independent functional outcome measured by the modified Rankin Scale (mRS) score of 0–2. Secondary outcomes included excellent functional outcome (mRS 0–1), favorable functional outcome (mRS 0–3), and mortality rate at 90 days, as well as symptomatic intracranial hemorrhage (sICH), and successful reperfusion between the two treatment groups.ResultsDirect EVT and bridging IVT before EVT exhibited similar primary outcomes (27.3% vs 27.7%, respectively) and distributions of mRS scores at 90 days. Moreover, rates of sICH and 90-day mortality were not significantly different between the two groups (7.3% vs 6.0%, adjusted OR (aOR) 0.79, 95% CI 0.34 to 1.86, P=0.84 for sICH; 46.8% vs 43.7%, aOR 0.86, 95% CI 0.54 to 1.38, P=0.53 for mortality).ConclusionsAmong patients with acute BAO, functional outcomes were similar between those treated with bridging IVT before EVT and those treated with direct EVT, and there was no difference between the two groups in terms of sICH and mortality rates.
Modeling a High-Energy, High-Rate Li//CFx Battery with a Capacity-Contributing Electrolyte
Authors: Parke Caitlin D. , Harris Kailot C. , Zhang Xiyue , Baek Minsung , Wang Chunsheng , Albertus Paul 
Published: July 2024

Li//CFx cells have achieved the highest specific energy of commercial batteries, but new applications requiring higher rates (e.g., C/3) and pulsing (e.g., at 5 C/3 rate for 1 min) drive the push for higher energy and power densities. A capacity-contributing electrolyte (CCE) can provide additional capacity at a slightly lower potential than the CFx reaction, increasing cell specific energy. In this work we present a 0D transient model of a primary Li//CFx cell with a CCE composed of both a salt and solvent that provide capacity with a focus on a C/3 rate and pulsing. Novel aspects of our model, in addition to the two CCE reactions, include a variable cathode thickness and porosity (CFx cathode thickness has been measured to expand by >40% at 25 °C) and a detailed presentation of the transient evolution of all species and terms that contribute to cell potential (including how salt and solvent reactions affect ionic polarization and the growth of solid-phase product resistances). Our work quantifies the delicate balance of thermodynamic, kinetic, and transport processes and properties that is needed to obtain specific energy enhancements from CCE reactions, and how changing cathode thickness and porosity affect the mechanisms that cause the end of discharge.
Harnessing Cold Sintering to Fabricate Composite Polymer Electrolytes - A Paradigm Shift in Organic-Inorganic Material Assembly
Authors: Naboulsi Agathe , Dussart Thibaud , Nguyen Giao T. M. , Franger Sylvain , Fichet Odile , Laberty-Robert Christel 
Published: July 2024

The development of composite electrolytes for all-solid-state batteries is an emerging field, but the creation of predominantly inorganic electrolytes remains challenging. In this study, Li6.25Al0.25La3Zr2O12 (Al-LLZO), a ceramic material selected for its high ionic conductivity (1 × 10−4 S.cm−1 at ambient temperature) was shaped by the cold-sintering process (CSP). The organic phase was synthesized by free-radical polymerization of two poly(ethylene oxide) methacrylate derivatives in the presence of lithium bis(trifluoromethanesulfonyl)imide salts (LiTFSI). The polymethacrylate network with dangling poly(ethylene oxide) (PEO) chains was thus obtained. This in situ polymerization allows the one-pot synthesis of the composite electrolyte during CSP. Remarkably, the ionic conductivity of the CSP pellet varied with the nature of the organic phase, ranging from 1 × 10−4 to 1 × 10−5 S.cm−1 for non-grafted and grafted TFSI anion on the PEO-based network, respectively. Additionally, the transport of Li+ remained unaffected by the inorganic material’s nature as long as it contained Li species. Furthermore, a significant enhancement of the ionic conductivity was observed in the composite pellet compared to the TFSI grafted network (10−5 to 10−7 S.cm−1, respectively). Electrochemical impedance spectroscopy measurements revealed changes in the Al-LLZO||PEO-based polymer interface during CSP with the formation of an interphase, confirmed by a low activation energy value (0.1 eV).
The High‐Dietary Insulin Load Score Is Associated With Elevated Level of Fasting Blood Sugar in Iranian Adult Men: Results From Fasa PERSIAN Cohort Study
Authors: Rajaie Seyede Hamide , Khayyatzadeh Sayyed Saeid , Faghih Shiva , Mansoori Yaser , Naghizadeh Mohammad Mehdi , Farjam Mojtaba , Homayounfar Reza , Mozaffari-Khosravi Hassan 
Published: July 2024

Aim: The potential of different foods to induce postprandial hyperinsulinemia may be involved in the development of metabolic syndrome (MetS). We aimed to evaluate the association between dietary insulin indices and MetS in a large population of adults in Iran.Methods: A total of 6356 adults aged 35–70 years were included in the present cross‐sectional study. A validated block‐format 125‐item semiquantitative food frequency questionnaire (FFQ) was used to obtain usual food intakes, and MetS was defined according to the International Diabetes Federation (IDF) and American Heart Association (AHA)/National Heart, Lung, and Blood Institute (NHLBI) criteria.Results: MetS was prevalent in 13.8% of participants. Mean age of the study participants was 46.58 ± 8.82 years, and mean body mass index (BMI) was 25.02 ± 4.60 kg/m2. Mean dietary insulin index (DII) and dietary insulin load (DIL) were 63.15 ± 7.57 and 168.253 ± 52.09, respectively. In the crude model, men in the highest DIL quartile were more likely to have hyperglycemia than those in the lowest quartile (OR: 1.75, 95% CI: 1.12–2.73, p trend = 0.04). This association remained significant and was even stronger after adjusting for potential confounders in model I (OR: 3.64, 95% CI: 1.57–8.47, p trend = 0.005) and further adjustment for BMI in model II (OR: 3.61, 95% CI: 1.55–8.44, p trend = 0.006).Conclusions: In healthy men, adherence to a high‐DIL diet may be associated with a greater likelihood of having hyperglycemia. No statistically significant association was observed between insulin indices and the odds of having MetS.