bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verification and Validation of Turbulence Modeling of Flow Through Triply Periodic Minimal Surfaces Porous Structures
Authors: Piatti Cecilia , Hicks Alex , Gajetti Eleonora , Ward Caleb , Pourghasemi Mahyar , Marocco Luca , Savoldi Laura , Fathi Nima 
Published: June 2024

Abstract
This work is devoted to verification and validation (V&V) activities of modeling and simulation of flow through porous media, with a particular focus on Triply Periodic Minimal Surfaces (TPMS) porous structures. TPMS is a class of porous materials that have attracted significant attention in recent years due to their unique properties, including high porosity, large surface area to volume ratio, and tunable pore structures. Within the context of energy sector decarbonization, several power generation technologies demand components with high heat removal capabilities, as is the case for solar or nuclear fusion machines. TPMS-based devices can be designed to equip heat sinks and heat exchangers introducing significant advantages with respect to traditional solutions. However, accurately predicting the complex flow behavior through TPMS porous media remains a challenge due to the intricate geometry and intricate flow patterns. Consequently, V&V activities play a crucial role in assessing the credibility of various models applied in modeling flow through these structures, establishing a foundation for reliable predictions. This work presents the results of V&V activities on the simulations of three-dimensional CFD using three turbulence models, namely Realizable k-ε two-layer, Lag-EB k-ε and SST (Menter) k-ω. Spatial resolution limitations in the application simulation were identified via solution verification. The experimental data obtained from our experimental setup were used for our validation assessment. All TPMS cases were fabricated using 3D printing technology. The discrepancy between simulation and experiments was evaluated and discussed.
Prevalence and Correlates of Adherence to the Global Total Physical Activity Guideline Based on Step Counting Among 3- to 4-Year-Olds: Evidence From SUNRISE Pilot Studies From 17 Countries
Authors: Mwase-Vuma Tawonga W. , Janssen Xanne , Chong Kar Hau , Okely Anthony D. , Tremblay Mark S. , Draper Catherine E. , Webster E. Kipling , Florindo Alex Antonio , Staiano Amanda E. , Pham Bang Nguyen , Tanaka Chiaki , Koh Denise , Guan Hongyan , Tang Hong K. , Löf Marie , Hossain Mohammad Sorowar , Munambah Nyaradzai E. , Cross Penny , Chathurangana PW Prasad , Reilly John J. 
Published: June 2024

Background: There is limited evidence from globally diverse samples on the prevalence and correlates of meeting the global guideline of 180 minutes per day of total physical activity (TPA) among 3- to 4-year-olds. Methods: Cross-sectional study involving 797 (49.2% girls) 3- to 4-year-olds from 17 middle- and high-income countries who participated in the pilot phases 1 and 2 of the SUNRISE International Study of Movement Behaviours in the Early Years. Daily step count was measured using thigh-worn activPAL accelerometers. Children wore the accelerometers for at least one 24-hour period. Children were categorized as meeting the TPA guideline based on achieving ≥11,500 steps per day. Descriptive analyses were conducted to describe the proportion of meeting the TPA guideline for the overall sample and each of the sociodemographic variables, and 95% CIs were calculated. Multivariable logistic regression was used to determine the sociodemographic correlates of meeting the TPA guideline. Results: Mean daily step count was 10,295 steps per day (SD = 4084). Approximately one-third of the sample (30.9%, 95% CI, 27.6–34.2) met the TPA guideline. The proportion meeting the guideline was significantly lower among girls (adjusted OR [aOR] = 0.70, 95% CI, 0.51–0.96) and 4-year-olds (aOR = 0.50, 95% CI, 0.34–0.75) and higher among rural residents (aOR = 1.78, 95% CI, 1.27–2.49) and those from lower middle-income countries (aOR = 1.35, 95% CI, 0.89–2.04). Conclusions: The findings suggest that a minority of children might meet the TPA guideline globally, and the risk of not meeting the guideline differed by sociodemographic indicators. These findings suggest the need for more surveillance of TPA in young children globally and, possibly, interventions to improve childhood health and development.
Brilacidin, a novel antifungal agent against
Cryptococcus neoformans
Authors: Diehl Camila , Pinzan Camila Figueiredo , de Castro Patrícia Alves , Delbaje Endrews , García Carnero Laura C. , Sánchez-León Eddy , Bhalla Kabir , Kronstad James W. , Kim Dong-gyu , Doering Tamara L. , Alkhazraji Sondus , Mishra Nagendra N. , Ibrahim Ashraf S. , Yoshimura Mami , Vega Isuhuaylas Luis Alberto , Pham Lien Thi Kim , Yashiroda Yoko , Boone Charles , dos Reis Thaila Fernanda , Goldman Gustavo H. 
Published: June 2024

ABSTRACT

Cryptococcus neoformans
causes cryptococcosis, one of the most prevalent fungal diseases, generally characterized by meningitis. There is a limited and not very effective number of drugs available to combat this disease. In this manuscript, we show the host defense peptide mimetic brilacidin (BRI) as a promising antifungal drug against
C. neoformans
. BRI can affect the organization of the cell membrane, increasing the fungal cell permeability. We also investigated the effects of BRI against the model system
Saccharomyces cerevisiae
by analyzing libraries of mutants grown in the presence of BRI. In
S. cerevisiae
, BRI also affects the cell membrane organization, but in addition the cell wall integrity pathway and calcium metabolism.
In vivo
experiments show BRI significantly reduces
C. neoformans
survival inside macrophages and partially clears
C. neoformans
lung infection in an immunocompetent murine model of invasive pulmonary cryptococcosis. We also observed that BRI interacts with caspofungin (CAS) and amphotericin (AmB), potentiating their mechanism of action against
C. neoformans
. BRI + CAS affects endocytic movement, calcineurin, and mitogen-activated protein kinases. Our results indicate that BRI is a novel antifungal drug against cryptococcosis.

IMPORTANCE

Invasive fungal infections have a high mortality rate causing more deaths annually than tuberculosis or malaria. Cryptococcosis, one of the most prevalent fungal diseases, is generally characterized by meningitis and is mainly caused by two closely related species of basidiomycetous yeasts,
Cryptococcus neoformans
and
Cryptococcus gattii
. There are few therapeutic options for treating cryptococcosis, and searching for new antifungal agents against this disease is very important. Here, we present brilacidin (BRI) as a potential antifungal agent against
C. neoformans
. BRI is a small molecule host defense peptide mimetic that has previously exhibited broad-spectrum immunomodulatory/anti-inflammatory activity against bacteria and viruses. BRI alone was shown to inhibit the growth of
C. neoformans
, acting as a fungicidal drug, but surprisingly also potentiated the activity of caspofungin (CAS) against this species. We investigated the mechanism of action of BRI and BRI + CAS against
C. neoformans
. We propose BRI as a new antifungal agent against cryptococcosis.
Genome sequencing of correlated pathogenic
Escherichia coli
and
Enterococcus
associated with recurrent urinary tract infections
Authors: Hogins Jacob , Do Hung P. , Dashti Marjan Ganjali , Zimmern Philippe E. , Reitzer Larry 
Published: June 2024

ABSTRACT

Reported here are the sequences for 11
Escherichia coli
and four
Enterococcus
strains isolated from post-menopausal women with a recurrent urinary tract infection. Each of the
Enterococcus
strains were isolated along with an
E. coli
strain. This provides a resource of high-quality complete genomes from polymicrobial infections.
Coding-complete genome sequence of a bovine viral diarrhea virus isolate NX2023 from a calf in China
Authors: Liu Wei , Shao Junjun , Huang Haiyan , Liu Yijia , Guo Huichen , Chang Huiyun , Wang Jiandong , Shandian Gao 
Published: June 2024

ABSTRACT

The coding-complete genome sequence of bovine viral diarrhea virus (BVDV) isolate NX2023 that originated from a calf in China was determined. Phylogenetic analysis showed that the NX2023 strain belongs to the BVDV-1d subgenotype.
Genomic sequence of three hydrocarbonoclastic pseudomonadaceae strains isolated from marine sediments of the port of Rosarito, Baja California, Mexico
Authors: Millán-López Sofía , Zurita-Artaloitia Juan M. , Silva-Jiménez Hortencia , Pardo-López Liliana , Sanchez-Flores Alejandro 
Published: June 2024

ABSTRACT

We report the draft genome sequence of three marine bacteria belonging to
Pseudomonas
and
Stutzerimonas
genera, with hydrocarbonoclastic metabolism for oil and monoaromatic hydrocarbon degradation. The genomic information of these organisms contributes to the knowledge of natural and polluted marine environments with ubiquitous presence of hydrocarbons as a selective pressure.
Repurposing Hsp90 inhibitors as antimicrobials targeting two-component systems identifies compounds leading to loss of bacterial membrane integrity
Authors: Fernandez-Ciruelos Blanca , Albanese Marco , Adhav Anmol , Solomin Vitalii , Ritchie-Martinez Arabela , Taverne Femke , Velikova Nadya , Jirgensons Aigars , Marina Alberto , Finn Paul W. , Wells Jerry M. 
Published: June 2024

ABSTRACT

The discovery of antimicrobials with novel mechanisms of action is crucial to tackle the foreseen global health crisis due to antimicrobial resistance. Bacterial two-component signaling systems (TCSs) are attractive targets for the discovery of novel antibacterial agents. TCS-encoding genes are found in all bacterial genomes and typically consist of a sensor histidine kinase (HK) and a response regulator. Due to the conserved Bergerat fold in the ATP-binding domain of the TCS HK and the human chaperone Hsp90, there has been much interest in repurposing inhibitors of Hsp90 as antibacterial compounds. In this study, we explore the chemical space of the known Hsp90 inhibitor scaffold 3,4-diphenylpyrazole (DPP), building on previous literature to further understand their potential for HK inhibition. Six DPP analogs inhibited HK autophosphorylation
in vitro
and had good antimicrobial activity against Gram-positive bacteria. However, mechanistic studies showed that their antimicrobial activity was related to damage of bacterial membranes. In addition, DPP analogs were cytotoxic to human embryonic kidney cell lines and induced the cell arrest phenotype shown for other Hsp90 inhibitors. We conclude that these DPP structures can be further optimized as specific disruptors of bacterial membranes providing binding to Hsp90 and cytotoxicity are lowered. Moreover, the X-ray crystal structure of resorcinol, a substructure of the DPP derivatives, bound to the HK CheA represents a promising starting point for the fragment-based design of novel HK inhibitors.

IMPORTANCE
The discovery of novel antimicrobials is of paramount importance in tackling the imminent global health crisis of antimicrobial resistance. The discovery of novel antimicrobials with novel mechanisms of actions, e.g., targeting bacterial two-component signaling systems, is crucial to bypass existing resistance mechanisms and stimulate pharmaceutical innovations. Here, we explore the possible repurposing of compounds developed in cancer research as inhibitors of two-component systems and investigate their off-target effects such as bacterial membrane disruption and toxicity. These results highlight compounds that are promising for further development of novel bacterial membrane disruptors and two-component system inhibitors.
Host-directed therapy with amiodarone in preclinical models restricts mycobacterial infection and enhances autophagy
Authors: Kilinç Gül , Boland Ralf , Heemskerk Matthias T. , Spaink Herman P. , Haks Mariëlle C. , van der Vaart Michiel , Ottenhoff Tom H. M. , Meijer Annemarie H. , Saris Anno 
Published: June 2024

ABSTRACT

Mycobacterium tuberculosis
(
Mtb
) as well as nontuberculous mycobacteria are intracellular pathogens whose treatment is extensive and increasingly impaired due to the rise of mycobacterial drug resistance. The loss of antibiotic efficacy has raised interest in the identification of host-directed therapeutics (HDT) to develop novel treatment strategies for mycobacterial infections. In this study, we identified amiodarone as a potential HDT candidate that inhibited both intracellular
Mtb
and
Mycobacterium avium
in primary human macrophages without directly impairing bacterial growth, thereby confirming that amiodarone acts in a host-mediated manner. Moreover, amiodarone induced the formation of (auto)phagosomes and enhanced autophagic targeting of mycobacteria in macrophages. The induction of autophagy by amiodarone is likely due to enhanced transcriptional regulation, as the nuclear intensity of the transcription factor EB, the master regulator of autophagy and lysosomal biogenesis, was strongly increased. Furthermore, blocking lysosomal degradation with bafilomycin impaired the host-beneficial effect of amiodarone. Finally, amiodarone induced autophagy and reduced bacterial burden in a zebrafish embryo model of tuberculosis, thereby confirming the HDT activity of amiodarone
in vivo
. In conclusion, we have identified amiodarone as an autophagy-inducing antimycobacterial HDT that improves host control of mycobacterial infections.

IMPORTANCE

Due to the global rise in antibiotic resistance, there is a strong need for alternative treatment strategies against intracellular bacterial infections, including
Mycobacterium tuberculosis
(
Mtb
) and non-tuberculous mycobacteria. Stimulating host defense mechanisms by host‐directed therapy (HDT) is a promising approach for treating mycobacterial infections. This study identified amiodarone, an antiarrhythmic agent, as a potential HDT candidate that inhibits the survival of
Mtb
and
Mycobacterium avium
in primary human macrophages. The antimycobacterial effect of amiodarone was confirmed in an
in vivo
tuberculosis model based on
Mycobacterium marinum
infection of zebrafish embryos. Furthermore, amiodarone induced autophagy and inhibition of the autophagic flux effectively impaired the host-protective effect of amiodarone, supporting that activation of the host (auto)phagolysosomal pathway is essential for the mechanism of action of amiodarone. In conclusion, we have identified amiodarone as an autophagy-inducing HDT that improves host control of a wide range of mycobacteria.
Antimicrobial susceptibility of clinical
Helicobacter pylori
isolates and its eradication by standard triple therapy: a study in west central region of Colombia
Authors: Alvarez-Aldana Adalucy , Fernandez Uribe Paula Andrea , Mejía Valencia Tatiana , Guaca-Gonzalez Yina Marcela , Santacruz-Ibarra Jorge Javier , Arturo-Arias Brenda Lucia , Castañeda-Chavez Luis Javier , Pacheco-López Robinson , Londoño-Giraldo Lina María , Moncayo-Ortiz José Ignacio 
Published: June 2024

ABSTRACT

The aim of the present study was first to isolate
Helicobacter pylori
from gastric biopsy specimens and to test their antibiotic susceptibility. Second, it was to evaluate the efficacy of the standard triple therapy from patients of the west central region of Colombia.
H. pylori
positive patients received standard triple therapy with proton pump inhibitor (PPI) (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d.) for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for
H. pylori
by histology or culture. Overall resistance to metronidazole, levofloxacin, rifampicin, clarithromycin, and amoxicillin was 81%, 26.2%, 23.9%, 19%, and 9.5%, respectively. No resistance was found for tetracycline. A total of 54 patients received standard triple therapy, 48 attended follow-ups testing, and of them, 30 had resistance test reports. Overall eradication rate was 81.2%. Second-line treatment was given to eight patients, four of whom were followed up with a 13C urea breath test (UBT) and remained positive for
H. pylori
. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains (95.6% vs 42.8%
P
= 0.001). The updated percentages of resistance to clarithromycin in this geographical area had increased, so this value must be considered when choosing the treatment regimen.

IMPORTANCE

Antibiotic resistance in
Helicobacter pylori
has increased worldwide, as has resistance to multiple antimicrobials (MDRs), which seriously hampers the successful eradication of the infection. The ideal success rate in eradicating
H. pylori
infection (≥90%) was not achieved in this study (81.2%). This is the first time that MDR is reported (14.3%) in the region; the resistance to clarithromycin increased over time (3.8%–19%), and levofloxacin (26.2%) and rifampicin (23%) resistant isolates were detected for the first time. With these results, strain susceptibility testing is increasingly important, and the selection of treatment regimen should be based on local antibiotic resistance patterns.
The diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in critically ill patients with respiratory tract infections
Authors: Hu Xiaohang , Jiang Liqing , Liu Xiaowei , Chang Hong , Dong Haixin , Yan Jinyan , Zhou Xiaoya , Kong Min 
Published: June 2024

ABSTRACT

Metagenomic next-generation sequencing (mNGS) is an unbiased and rapid method for detecting pathogens. This study enrolled 145 suspected severe pneumonia patients who were admitted to the Affiliated Hospital of Jining Medical University. This study primarily aimed to determine the diagnostic performance of mNGS and conventional microbiological tests (CMTs) using bronchoalveolar lavage fluid samples for detecting pathogens. Our findings indicated that mNGS performed significantly higher sensitivity (97.54% vs 28.68%,
P
< 0.001), coincidence (90.34% vs 35.17%,
P
< 0.001), and negative predictive value (80.00% vs 13.21%,
P
< 0.001) but performed lower specificity than CMTs (52.17% vs 87.5%,
P
< 0.001).
Streptococcus pneumoniae
as the most common bacterial pathogen had the largest proportion (22.90%, 30/131) in this study. In addition to bacteria, fungi, and virus, mNGS can detect a variety of atypical pathogens such as
Mycobacterium tuberculosis
and
non-tuberculous
. Mixed infections were common in patients with severe pneumonia, and bacterial-fungal-viral-atypical pathogens were the most complicated infection. After adjustments of antibiotics based on mNGS and CMTs, the clinical manifestation improved in 139 (95.86%, 139/145) patients. Our data demonstrated that mNGS had significant advantage in diagnosing respiratory tract infections, especially atypical pathogens and fungal infections. Pathogens were detected timely and comprehensively, contributing to the adjustments of antibiotic treatments timely and accurately, improving patient prognosis and decreasing mortality potentially.

IMPORTANCE
Metagenomic next-generation sequencing using bronchoalveolar lavage fluid can provide more comprehensive and accurate pathogens for respiratory tract infections, especially when considering the previous usage of empirical antibiotics before admission or complicated clinical presentation. This technology is expected to play an important role in the precise application of antimicrobial drugs in the future.
Insights into the molecular basis of reduced vancomycin susceptibility among three prominent
Staphylococcus aureus
clonal complexes
Authors: Malachowa Natalia , Sturdevant Daniel E. , Porter Adeline R. , Martin Grant , Martens Craig , Nair Vinod , Hansen Bryan , Ricklefs Stacy , Jenkins Stephen G. , Chen Liang , Kreiswirth Barry N. , DeLeo Frank R. 
Published: June 2024

ABSTRACT

Staphylococcus aureus
is a leading cause of healthcare-associated infections globally. Vancomycin-resistant
S. aureus
(VRSA), those with high-level resistance [minimum inhibitory concentration (MIC) of 16–32 µg/mL vancomycin], are uncommon, whereas vancomycin-intermediate
S. aureus
(VISA; MIC of 4–8 µg/mL), are isolated more frequently and develop during long-term and/or repeated use of the antibiotic. VISA can be difficult to eradicate and infections may persist. Our knowledge of mechanisms that underlie the development of VISA is incomplete. We used a genomics approach to investigate the VISA phenotype in three prominent
S. aureus
lineages. All VISA clinical isolates tested had increased cell wall thickness compared with vancomycin-susceptible
S. aureus
strains. Growth rates of clonal complex (CC) 5, CC8, and CC45 clinical isolates were reduced in 2 µg/mL vancomycin compared to media alone. Culture in 2 and 4 µg/mL vancomycin sequentially for two weeks reduced susceptibility to daptomycin, televancin, tigecycline, and vancomycin in a majority of CC5, CC8, and CC45 isolates tested. We identified alleles reported previously to contribute to the VISA phenotype, but unexpectedly, these alleles were unique to each CC. A subtherapeutic concentration of vancomycin elicited changes in the VISA transcriptome—common and unique—among the three CCs tested. Multiple genes, including those encoding a glycerate kinase, an M50 family metallopeptidase, and an uncharacterized membrane protein, were upregulated among all three lineages and not reported previously as associated with VISA. Although there are lineage-specific changes in DNA sequence, our findings suggest changes in the VISA transcriptome constitute a general response to stress that confers reduced susceptibility to multiple antibiotics.

IMPORTANCE

Our understanding of the mechanisms that underlie the development of vancomycin-intermediate
Staphylococcus aureus
(VISA) is incomplete. To provide a more comprehensive view of this process, we compared genome sequences of clonal complex (CC) 5, CC8, and CC45 VISA clinical isolates and measured changes in the transcriptomes of these isolates during culture with a subtherapeutic concentration of vancomycin. Notably, we identified differentially expressed genes that were lineage-specific or common to the lineages tested, including genes that have not been previously reported to contribute to a VISA phenotype. Changes in gene expression were accompanied by reduced growth rate, increased cell wall thickness, and reduced susceptibility to daptomycin, televancin, tigecycline, and vancomycin. Our results provide support to the idea that changes in gene expression contribute to the development of VISA among three CCs that are a prominent cause of human infections.