bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endurance exercise training changes the limitation on muscle V̇O2max${\dot{V}}_{{{\mathrm{O}}}_{\mathrm{2}}{\mathrm{max}}}$ in normoxia from the capacity to utilize O2 to the capacity to transport O2
Authors: Broxterman Ryan M. , Wagner Peter D. , Richardson Russell S. 
Published: December 2023

AbstractMaximal oxygen (O2) uptake () is an important parameter with utility in health and disease. However, the relative importance of O2 transport and utilization capacities in limiting muscle before and after endurance exercise training is not well understood. Therefore, the present study aimed to identify the mechanisms determining muscle pre‐ and post‐endurance exercise training in initially sedentary participants. In five initially sedentary young males, radial arterial and femoral venous (blood samples), leg blood flow (thermodilution), and myoglobin (Mb) desaturation (1H nuclear magnetic resonance spectroscopy) were measured during maximal single‐leg knee‐extensor exercise (KE) breathing either 12%, 21% or 100% O2 both pre and post 8 weeks of KE training (1 h, 3 times per week). Mb desaturation was converted to intracellular using an O2 half‐saturation pressure of 3.2 mmHg. Pre‐training muscle was not significantly different across inspired O2 conditions (12%: 0.47 ± 0.10; 21%: 0.52 ± 0.13; 100%: 0.54 ± 0.01 L min–1, all q > 0.174), despite significantly greater muscle mean capillary–intracellular gradients in normoxia (34 ± 3 mmHg) and hyperoxia (40 ± 7 mmHg) than hypoxia (29 ± 5 mmHg, both q < 0.024). Post‐training muscle was significantly different across all inspired O2 conditions (12%: 0.59 ± 0.11; 21%: 0.68 ± 0.11; 100%: 0.76 ± 0.09 mmHg, all q < 0.035), as were the muscle mean capillary–intracellular gradients (12%: 32 ± 2; 21%: 37 ± 2; 100%: 45 ± 7 mmHg, all q < 0.029). In these initially sedentary participants, endurance exercise training changed the basis of limitation on muscle in normoxia from the mitochondrial capacity to utilize O2 to the capacity to transport O2 to the mitochondria.
imageKey points
Maximal O2 uptake is an important parameter with utility in health and disease.
The relative importance of O2 transport and utilization capacities in limiting muscle maximal O2 uptake before and after endurance exercise training is not well understood.
We combined the direct measurement of active muscle maximal O2 uptake with the measurement of muscle intracellular before and after 8 weeks of endurance exercise training.
We show that increasing O2 availability did not increase muscle maximal O2 uptake before training, whereas increasing O2 availability did increase muscle maximal O2 uptake after training.
The results suggest that, in these initially sedentary participants, endurance exercise training changed the basis of limitation on muscle maximal O2 uptake in normoxia from the mitochondrial capacity to utilize O2 to the capacity to transport O2 to the mitochondria.
Hydrodynamic Performance of an Array of Stratified Pile Rock Breakwaters Placed on Elevated Seabed
Authors: Dhanunjaya E. , Sanjeeva Rayudu E. , Venkateswarlu V. 
Published: December 2023

Abstract
The present study outlines the hydrodynamic performance of stratified pile-rock breakwaters (SPRBs) in series using the analytical calculation under the framework of linearized potential flow theory. The rubble mounds are separated into two porous layers (surface and bottom layers) and tightly packed within the space available between the seaside and leeside vertical piles. The SPRB is installed on the elevated bed, and it is considered as a bottom rigid layer. The newly proposed breakwater is titled as stratified pile-rock breakwater and vertical piles are suggested to minimize the unwanted displacements of rubble mounds from frequent failures due to the incident wave stroke. The analytical model is developed based on the method of matched eigenfunction expansions (MMEEs) along with suitable boundary conditions to assess the hydrodynamic performance of the SPRB. The study results are compared with the literature based on experimental and analytical methods for specific conditions. The wave reflection, transmission, and energy damping by a series of SPRBs are reported for changes in incident wave properties and breakwater physical properties. The effect of layer porosity, angle of contact, free spacing, and number of breakwaters on the hydrodynamic coefficients is reported. The study suggested that a pair of SPRBs having 80% and 40% porosities for surface and bottom layers, with clear spacing, varied within 1 ≤ w/h1 ≤ 2, and the angle of contact varied within 30 deg ≤ θ ≤ 45 deg to achieve a 90% wave-damping when the relative wavenumber is k10h1 = 1.
A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacy
Authors: Kirkland Marina E. , Patfield Stephanie , Hughes Anna C. , Hernlem Bradley , He Xiaohua 
Published: December 2023

ABSTRACT

Shiga toxin-producing
Escherichia coli
infections are difficult to treat due to the risk of antibiotic-induced stress upregulating the production of toxins, medical treatment is consequently limited to supportive care to prevent the development of hemolytic uremic syndrome (HUS). Here, we introduce a potentially therapeutic humanized mouse monoclonal antibody (Hu-mAb 2-5) targeting Stx2a, the most common Shiga toxin subtype identified from outbreaks. We demonstrate that Hu-mAb 2-5 has low immunogenicity in healthy adults
ex vivo
and high neutralizing efficacy
in vivo
, protecting mice from mortality and HUS-related tissue damage.
Pharmacokinetic and pharmacodynamic evaluation of the atypical tetracyclines chelocardin and amidochelocardin in murine infection models
Authors: Rox Katharina , Jansen Rolf , Lukežič Tadeja , Greweling-Pils Marina , Herrmann Jennifer , Miethke Marcus , Hüttel Stephan , Hennessen Fabienne , Abou Fayad Antoine , Holzhausen Cornelia , Lundberg Carina Vingsbo , Teague Joanne , Sudarman Enge , Bülter Lisa , Hesterkamp Thomas , Stadler Marc , Brönstrup Mark , Müller Rolf 
Published: December 2023

ABSTRACT

The quest for novel anti-infectives against drug-resistant pathogens of the so-called ESKAPE panel is accompanied by intensive research aiming to find treatment options for the future. In this study, we evaluated the pharmacokinetics and pharmacodynamics of the two atypical tetracyclines: chelocardin (CHD) and amidochelocardin (CDCHD). Although CHD was in phase II clinical trials in the 1970s against urinary tract infections (UTI), CDCHD is a novel derivative obtained by biosynthetic engineering. A pharmacokinetic evaluation in uninfected, non-neutropenic CD-1 outbred mice using intravenous, peroral, and subcutaneous routes showed that CHD had higher plasma exposure than CDCHD but underwent an epimerization that was not observed for CDCHD. CDCHD showed persistently high exposure levels in urine lasting for more than 24 hours, whereas CHD urine concentrations decreased faster over time. Pharmacodynamic characterization in the neutropenic thigh infection model with
K. pneumoniae
and
E. coli
as challenge pathogens in CD-1 outbred mice proved that CHD was more effective in reducing bacterial burden in the thigh, in particular against
E. coli
, whereas CDCHD effectively reduced bacterial burden in kidneys affected by hematogenous seeding from the primary inoculation site, that is, thigh. Assessment of both atypical tetracyclines in an ascending UTI model with bladder as the primary inoculation site against gentamicin as positive control revealed high effectiveness of CDCHD. In summary, CDCHD warrants further preclinical exploration for the indication of UTI.

IMPORTANCE
There is a strong need to find novel treatment options against urinary tract infections associated with antimicrobial resistance. This study evaluates two atypical tetracyclines, namely chelocardin (CHD) and amidochelocardin (CDCHD), with respect to their pharmacokinetics and pharmacodynamics. We show CHD and CDCHD are cleared at high concentrations in mouse urine. Especially, CDCHD is highly effective in an ascending urinary tract infection model, suggesting further preclinical evaluation.
Oxygen-driven divergence of marine group II archaea reflected by transitions of superoxide dismutases
Authors: Qu Liping , Li Meng , Gong Fahui , He Lei , Li Minchun , Zhang Chuanlun , Yin Kedong , Xie Wei 
Published: December 2023

ABSTRACT

The superoxide anion radical (O
2•−
), the primary reactive oxygen species (ROS), is detrimental to cellular functions. Marine group II (MGII) archaea predominantly inhabit surface ocean environments that are rich in ROS; however, their defense mechanisms against ROS damage remain unknown. In this study, we integrated the analyses of archaeal 16S rRNA gene amplicons and metagenome-assemblage genomes of MGII archaea from the northern South China Sea and 250 other previously published MGII genomes to investigate their antioxidant mechanisms. The results show that the proportion of oxygen-promoted MGII operational taxonomic units in the iron/manganese superoxide dismutase (Fe/MnSOD) gene-containing group was significantly higher than that in the nickel SOD (NiSOD) group, suggesting that MGII members with Fe/MnSOD may have superior antioxidant capacity relative to members possessing NiSOD. Molecular clock analysis of MGII genomes revealed frequent species divergence correlating to the differentiation of Fe/MnSOD or NiSOD genes. The acquisition/loss of these genes in the MGII genomes was synchronized with the historical changes in atmospheric oxygen and oceanic metal element concentrations over the last 2.4 billion years, suggesting that variations in the antioxidant capacity of MGII archaea in response to changing oxygen levels may have driven their divergences over time.

IMPORTANCE
Reactive oxygen species (ROS), including superoxide anion, is a series of substances that cause oxidative stress for all organisms. Marine group II (MGII) archaea are mainly live in the surface seawater and exposed to considerable ROS. Therefore, it is important to understand the antioxidant capacity of MGII. Our research found that Fe/Mn- superoxide dismutase (Fe/MnSOD) may be more suitable for MGII to resist oxidative damage, and the changes in oxygen concentrations and SOD metallic cofactors play an important role in the selection of SOD by the 17 clades of MGII, which in turn affects the species differentiation of MGII. Overall, this study provides insight into the co-evolutionary history of these uncultivated marine archaea with the earth system.
Systemic and cerebrospinal fluid biomarkers for tuberculous meningitis identification and treatment monitoring
Authors: Yao Xiang-Ping , Hong Jian-Chen , Jiang Zai-Jie , Pan Yu-Ying , Liu Xiao-Feng , Wang Jun-Mei , Fan Rui-Jie , Yang Bi-Hui , Zhang Wei-Qing , Fan Qi-Chao , Li Li-Xiu , Lin Bi-Wei , Zhao Miao 
Published: December 2023

ABSTRACT

Tuberculous meningitis (TBM) is a severe infectious disease affecting the central nervous system, causing high mortality and disability. However, current diagnostic methods for TBM using cerebrospinal fluid (CSF) lack sensitivity and predictive biomarkers for prognosis. We conducted a study on cytokine profiles in CSF and serum samples from TBM patients to identify disease-specific biomarkers. Patients were categorized into three groups: TBM (
n
= 17), cryptococcal meningitis (
n
= 10), and non-infection (
n
= 6), and cytokine levels were quantified using a 48-plex panel. After treatment, we observed a significant reduction in the levels of 12 cytokines, indicating their potential use as biomarkers for treatment monitoring. Among them, monokine induced by interferon-γ (MIG) and interleukin-18 showed significant differences in serum or CSF cytokine levels compared to the control groups. CSF levels of MIG in TBM patients were negatively correlated with the CSF/blood glucose ratio (
r
= −0.4728,
P
= 0.0475). Positive correlations were found between CSF leukocyte counts and several cytokines, including fibroblast growth factor-basic, granulocyte colony-stimulating factor (G-CSF), monocyte chemotactic protein-3, macrophage inflammatory protein 1 alpha (MIP-1α), and tumor necrosis factor alpha. G-CSF and MIP-1α were also positively correlated with CSF protein levels. Receiver operating characteristic curve analysis revealed that MIG exhibited the highest area under the curve of 0.92 [95% confidence interval (CI) 0.82–1.00] with a sensitivity of 0.85 (95% CI 0.58–0.97) and a specificity of 0.87 (95% CI 0.62–0.98), making it a promising diagnostic biomarker for TBM. Our study provides valuable insights into TBM’s pathogenesis and identifies potential biomarkers for diagnosis and evaluating treatment monitoring.

IMPORTANCE
Tuberculous meningitis is a life-threatening infection with high mortality and disability rates. Current diagnostic methods using cerebrospinal fluid (CSF) samples have limited sensitivity and lack predictive biomarkers for evaluating prognosis. This study’s findings reveal excessive activation of the immune response during tuberculous meningitis (TBM) infection. Notably, a strong negative correlation was observed between CSF levels of monokine induced by interferon-γ (MIG) and the CSF/blood glucose ratio in TBM patients. MIG also exhibited the highest area under the curve with high sensitivity and specificity. This study suggests that MIG may serve as a novel biomarker for differentiating TBM infection in CSF or serum, potentially leading to improved diagnostic accuracy and better patient outcomes.
Environmental surveillance of fungi and susceptibility to antifungal agents in tertiary care hospitals
Authors: Badiee Parisa , Ghadimi-Moghadam Abdolkarim , Bayatmanesh Habibeh , Soltani Jafar , Salimi-Khorashad Ali Reza , Ghasemi Fatemeh , Amin Shahidi Maneli , Jafarian Hadis 
Published: December 2023

ABSTRACT

This study aimed to evaluate the epidemiology of fungi in environment of tertiary care hospitals and their susceptibility patterns to seven antifungal agents for controlling and preventing fungal infections in patients. Environmental samplings on the surfaces of different parts of hospitals were collected from four university-affiliated teaching hospitals in Iran. Routine and molecular procedures identified isolated fungi, and antifungal susceptibility tests were performed
in vitro
. Of the 400 samples, 152 presented positive culture results, and 193 fungal species were isolated. Mold fungi accounted for 59.1% (115 species) of isolates. Most isolated fungal species in descending order were 22
Aspergillus flavus
(11.4%), 21
Candida albicans
(10.9%), 17
Mucor
species (8.8%), 16
Penicillium
species (8.3%), 16
Candida famata
(8.3%), 15
Alternaria
species (7.8%), 13
Fusarium
species (6.7%), 11
Candida parapsilosis
(5.7%), and 10
Aspergillus niger sensu stricto
(5.2%). The isolated
Aspergillus
species revealed relatively low susceptibility to itraconazole and posaconazole with MIC90 values of 8 µg/mL. The MIC90 values of amphotericin and luliconazole in
Candida
species were 0.5 and 0.064 µg/mL, respectively. In this study, different species of filamentous and yeast fungi with varying susceptibility to antifungal agents were reported from the environment of the studied hospitals.

IMPORTANCE
Saprophytic fungi can cause nosocomial infections in high-risk patients. These infections are related to high mortality and cost. In the current study, different species of filamentous fungi and yeast were isolated from the environment of the studied hospitals. Some species were resistant to antifungal drugs. We suggest that the future work concentrates on the relationship between the level/quantification of saprophytic contamination in the environment of hospitals and fungal infections in patients.
Immunogenicity and protective efficacy of recombinant adenovirus expressing a novel genotype G2b PEDV spike protein in protecting newborn piglets against PEDV
Authors: Song Xin , Zhou Qun , Zhang Jiaqi , Chen Taoyun , Deng Gunan , Yue Hua , Tang Cheng , Wu Xuejing , Yu Jifeng , Zhang Bin 
Published: December 2023

ABSTRACT
Porcine epidemic diarrhea virus (PEDV) causes porcine epidemic diarrhea (PED). The emergence of the novel G2b strains of PEDV has increased the need for new vaccines. We generated a recombinant adenovirus expressing the spike (S) protein of G2b PEDV based on human adenovirus serotype 5 (Ad5), named rAd5-PEDV-S. Immunization with rAd5-PEDV-S elicited a significant PEDV-specific humoral immune response in sows, including IgA and IgG in colostrum and serum and circulating neutralizing antibodies. The efficacy of rAd5-PEDV-S was superior to that of the commercial inactivated vaccine, and the intramuscular (IM) route was more effective than the intranasal route. Interestingly, there was no significant difference in immunization effect between the twice and once-immunized IM groups (administered 5 weeks before farrowing). Five-day-old piglets born to sows immunized with the rAd5-PEDV-S through the IM route had less diarrhea and weight loss when challenged with PEDV. Fecal PEDV RNA expression in the PEDV-challenged rAd5-PEDV-S IM group piglets was considerably lower than that in the other groups; all five piglets from the rAd5-PEDV-S IM group survived the infection period. Histopathological examination of small intestinal sections revealed evident shedding of ileum intestinal mucosal epithelial cells in the phosphate-buffered saline (PBS) group. These findings suggest that vaccinating pregnant sows with rAd5-PEDV-S induces immune responses in the pregnant sows and passively protects piglets. Our findings highlight the potential of rAd5-PEDV-S as a candidate vaccine for PED.

IMPORTANCE
Porcine epidemic diarrhea (PED) is a highly infectious and economically significant gastrointestinal disorder that affects pigs of all ages. Preventing and controlling PED is achieved by immunizing sows with vaccines, enabling passive piglet immunization via colostrum. The prevalence of G2b porcine epidemic diarrhea virus (PEDV) continues in China despite the use of commercial vaccines, raising questions regarding current vaccine efficacy and the need for novel vaccine development. Adenovirus serotype 5 (Ad5) has several advantages, including high transduction efficiency, a wide range of host cells, and the ability to infect cells at various stages. In this study, we expressed the immunogenic proteins of spike (S) using an Ad5 vector and generated a PED vaccine candidate by inducing significant humoral immunity. The rAd5-PEDV-S prevented PED-induced weight loss, diarrhea, and intestinal damage in piglets. This novel vaccine candidate strain possesses the potential for use in the pig breeding industry.
Mechanical constraints to unbound expansion of
B. subtilis
on semi-solid surfaces
Authors: Krajnc Mojca , Fei Chenyi , Košmrlj Andrej , Kalin Mitjan , Stopar David 
Published: December 2023

ABSTRACT
The effects of surface mechanical constraints that may promote or prevent bacterial expansion on semi-solid surfaces are largely unknown. In this work, we have manufactured agar surfaces with different viscoelasticity, topography, and roughness. To capture the essential biophysics of the bacterial expansion we have developed a continuum model that faithfully reproduces the main patterns of the short-range and long-range expansion with two critical parameters: local interfacial forces and colony viscosity. Cohesive energy of the bacterial colony that determines the extent of exploration was dependent on agar surface viscoelasticity. On soft surfaces, bacteria produce low viscoelastic colonies that allow guided population of bacteria to traverse distances that are six orders of magnitude larger than the size of the individual bacterium. Bacteria growing on stiff surfaces produce colonies with significantly increased viscoelasticity that prevent bacterial exploration of new territory and allow formation of a very steep cliff at the edge of the colony. Upon flooding of the rough surfaces, we have induced aquaplaning and spreading of bacteria. A layer of water between the bacterium and surface results in a loss of traction allowing bacteria to spread across the otherwise inhibitory rough surface. The results shed new light on the bacterial ability to rapidly colonize new territories.

IMPORTANCE
How bacterial cells colonize new territory is a problem of fundamental microbiological and biophysical interest and is key to the emergence of several phenomena of biological, ecological, and medical relevance. Here, we demonstrate how bacteria stuck in a colony of finite size can resume exploration of new territory by aquaplaning and how they fine tune biofilm viscoelasticity to surface material properties that allows them differential mobility. We show how changing local interfacial forces and colony viscosity results in a plethora of bacterial morphologies on surfaces with different physical and mechanical properties.
Targeted amplification-based whole genome sequencing of
Monkeypox virus
in clinical specimens
Authors: Isabel S. , Eshaghi A. , Duvvuri V. R. , Gubbay J. B. , Cronin K. , Li Aimin , Hasso M. , Clark S. T. , Hopkins J. P. , Patel S. N. , Braukmann T. W. A. 
Published: December 2023

ABSTRACT

The 2022 mpox outbreak has led to more than 91,000 cases in 115 countries. Whole genome sequencing (WGS) has been at the forefront of surveillance and outbreak investigations for different pathogens of public health significance. Many institutions performing WGS on
Monkeypox virus
(MPXV) use a resource-intensive metagenomic approach. Here we present a targeted amplification method for WGS of MPXV from clinical specimens. We designed 43 pairs of primers (amplicons ~5 kb) with PrimalScheme to span the ~200 kb viral genome and then added 12 additional primers to optimize amplification. We extracted nucleic acid from clinical specimens and amplified the two primer pools. All libraries were sequenced on the MiniSeq platform. Resulting reads were filtered by quality and then mapped to a MPXV reference genome. Consensus sequences were generated for phylogenetic analysis. A total of 91 specimens with a real-time-PCR cycle threshold (Ct) values ≤27.9 were sequenced using our targeted amplification protocol. The sequenced MPXV genomes were of high quality with mean genome coverage of 99.56% (95% CI 99.32-99.80%), mean depth 1,395× (95% CI 1275–1515), and mean mapping quality of 52.87 (95% CI 52.1–53.6) and allowed for greater multiplexing of samples relative to metagenomics. The MPXV genomes belong to 8 of the 13 clades observed during the 2022 global mpox outbreak. Targeted amplification enrichment provides high coverage, throughput, and short turnaround times. It is an efficient low-cost method for MPXV WGS and can benefit public health surveillance and outbreak management.

IMPORTANCE
We present a protocol to efficiently sequence genomes of the MPXV-causing mpox. This enables researchers and public health agencies to acquire high-quality genomic data using a rapid and cost-effective approach. Genomic data can be used to conduct surveillance and investigate mpox outbreaks. We present 91 mpox genomes that show the diversity of the 2022 mpox outbreak in Ontario, Canada.