bluuebunny/crossref_metadata_2025_split huggingface dataset:
Echocardiographic Parameters Associated With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors
Authors: Caru Maxime , Dubois Pierre , Curnier Daniel , Andelfinger Gregor , Krajinovic Maja , Laverdière Caroline , Sinnett Daniel , Périé Delphine 
Published: October 2023

Background: Children’s exposure to chemotherapeutic agents causes several long-term adverse effects but physical activity has been evidenced to be an effective strategy to improve cardiac function. This cross-sectional study aimed to explore the association between physical activity levels, cardiorespiratory fitness, and cardiac parameters measured by echocardiography. Methods: Participants were 216n childhood acute lymphoblastic leukemia survivors who underwent a maximal cardiopulmonary exercise test and self-reported their daily minutes of moderate to vigorous physical activity. They underwent a complete transthoracic echocardiographic assessment. Systolic and diastolic function analysis and strain images analysis were performed. The associations were studied through the preventive fraction (examined with univariate crude and adjusted logistic regression models) of regular physical activity (≥150 min·wk−1) and adequate cardiorespiratory fitness levels (above the median ≥ 32.0 mL·kg−1·min−1) on cardiac parameters. Results: Crude analysis shows that regular physical activity was associated with a significant preventive fraction in mitral E/A ratio (56%; P = .013), while adjusted analyses highlighted a nonsignificant reduction of 74% to 37% in the prevalence of cardiac parameters associated with physical activity. Similar associations of adequate cardiorespiratory fitness on cardiac parameters were observed. Adjusted analyses revealed a nonsignificant reduction of 7% to 86% in the prevalence of cardiac parameters associated with cardiorespiratory fitness. Conclusion: This study reports that regular physical activity and adequate cardiorespiratory fitness were associated with a higher preventive fraction. Thus, engaging in physical activity prevents childhood acute lymphoblastic leukemia survivors’ cardiac dysfunctions. These findings are novel and clinically relevant in pediatric cardiooncology and provide additional evidence to strengthen the benefits of exercise as long-term care in childhood cancer survivors.
Shaping Policy and Practice: Analyzing the Reach of Highly Cited and High Altmetrics Publications for Broader Impact on Physical Activity
Authors: Ramírez Varela Andrea , Serrano Natalicio , Mejía Grueso Juliana , Nguyen Anita , Salvo Deborah , Brownson Ross C. , Bauman Adrian , Reis Rodrigo , Hallal Pedro , Pratt Michael 
Published: October 2023

Background: A significant gap remains between the availability of physical activity (PA) evidence-based interventions and their application in real-world settings in policy and practice areas. This study aims to describe highly cited and high altmetrics publications in PA research and explore their impact on PA policy and practice. Methods: Mixed-methods sequential explanatory study including the identification and description of the top highly cited and high altmetrics PA publications from the last 10 years (including study design, population, type of PA study, number of citations, and altmetrics score), and interviews with key informants regarding research dissemination and implications on PA policy and practice. Results: When considering publication type, the most frequent highly cited publications were health consequences (40%, altmetrics = 42%), measurement/trends (23%, altmetrics = 10%), and correlates/determinants (21%, altmetrics = 26%) studies. They were predominantly cross-sectional (50%, altmetrics = 28%), systematic reviews (38%, altmetrics = 18%), and longitudinal studies (8%, altmetrics = 37%). All authors who participated in the interviews agreed that the most important factors in disseminating findings and influencing PA policy and practice were the published peer-reviewed manuscript itself, the reputation of the journal, the communication strategy, and the use of online platforms. Conclusions: To have a real-world influence on PA policy and practice, it is not enough to publish the results in scientific journals and participate in media outreach. To successfully involve policymakers and communities in appropriating the evidence and evaluating the extent to which these findings affect policy and practice outcomes, it is critical to lead co-creation, co-dissemination, advocacy, and capacity building efforts.
Antimicrobial effects of Medicines for Malaria Venture Pathogen Box compounds on strains of
Neisseria gonorrhoeae
Authors: Mensah Eric , Fourie P. Bernard , Peters Remco P. H. 
Published: October 2023

ABSTRACT

Therapeutic options for
Neisseria gonorrhoeae
are limited due to emerging global resistance. New agents and treatment options to treat patients with susceptible and multi-extensively drug-resistant
N. gonorrhoeae
is a high priority. This study used an
in vitro
approach to explore the antimicrobial potential, as well as synergistic effects of Medicine for Malaria Venture (MMV) Pathogen Box compounds against ATCC and clinical
N. gonorrhoeae
strains. Microbroth dilution assay was used to determine pathogen-specific minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the Pathogen Box compounds against susceptible and resistant
N. gonorrhoeae
strains, with modification, by adding PrestoBlue HS Cell Viability Reagent. A checkerboard assay was used to determine synergy between the active compounds and in conjunction with ceftriaxone. Time-kill kinetics was performed to determine if the compounds were either bactericidal or bacteriostatic. The Pathogen Box compounds: MMV676501, MMV002817, MMV688327, MMV688508, MMV024937, MMV687798 (levofloxacin), MMV021013, and MMV688978 (auranofin) showed potent activity against resistant strains of
N. gonorrhoeae
at an MIC and MBC of ≤10 µM. Besides the eight compounds, MMV676388 and MMV272144 were active against susceptible
N. gonorrhoeae
strains, also at MIC and MBC of ≤10 µM. All the compounds were bactericidal and were either synergistic or additive with fractional inhibitory concentration index ranging between 0.40 and 1.8. The study identified novel Pathogen Box compounds with potent activity against
N. gonorrhoeae
strains and has the potential to be further investigated as primary or adjunctive therapy to treat gonococcal infections.
Drug distribution and efficacy of the DprE1 inhibitor BTZ-043 in the C3HeB/FeJ mouse tuberculosis model
Authors: Ramey Michelle E. , Kaya Firat , Bauman Allison A. , Massoudi Lisa M. , Sarathy Jansy P. , Zimmerman Matthew D. , Scott Dashick W. L. , Job Alyx M. , Miller-Dawson Jake A. , Podell Brendan K. , Lyons Michael A. , Dartois Véronique , Lenaerts Anne J. , Robertson Gregory T. 
Published: October 2023

ABSTRACT

BTZ-043, a suicide inhibitor of the
Mycobacterium tuberculosis
cell wall synthesis decaprenylphosphoryl-beta-
D
-ribose 2′ epimerase, is under clinical development as a potential new anti-tuberculosis agent. BTZ-043 is potent and bactericidal
in vitro
but has limited activity against non-growing bacilli in rabbit caseum. To better understand its behavior
in vivo
, BTZ-043 was evaluated for efficacy and spatial drug distribution as a single agent in the C3HeB/FeJ mouse model presenting with caseous necrotic pulmonary lesions upon
Mycobacterium tuberculosis
infection. BTZ-043 promoted significant reductions in lung and spleen bacterial burdens in the C3HeB/FeJ mouse model after 2 months of therapy. BTZ-043 penetrates cellular and necrotic lesions and was retained at levels above the serum-shifted minimal inhibitory concentration in caseum. The calculated rate of kill was found to be highest and dose-dependent during the second month of treatment. BTZ-043 treatment was associated with improved histology scores of pulmonary lesions, especially compared to control mice, which experienced advanced fulminant neutrophilic alveolitis in the absence of treatment. These positive treatment responses to BTZ-043 monotherapy in a mouse model of advanced pulmonary disease can be attributed to favorable distribution in tissues and lesions, retention in the caseum, and its high potency and bactericidal nature at drug concentrations achieved in necrotic lesions.
High temperatures augment inhibition of parasites by a honey bee gut symbiont
Authors: Palmer-Young Evan C. , Markowitz Lindsey M. , Huang Wei-Fone , Evans Jay D. 
Published: October 2023

ABSTRACT

Temperature affects growth, metabolism, and interspecific interactions in microbial communities. Within animal hosts, gut bacterial symbionts can provide resistance to parasitic infections. Both infection and populations of symbionts can be shaped by the host body temperature. However, the effects of temperature on the antiparasitic activities of gut symbionts have seldom been explored. The
Lactobacillus
-rich gut microbiota of facultatively endothermic honey bees is subject to seasonal and ontogenetic changes in host temperature that could alter the effects of symbionts against parasites. We used cell cultures of a
Lactobacillus
symbiont and an important trypanosomatid gut parasite of honey bees to test the potential for temperature to shape parasite-symbiont interactions. We found that symbionts showed greater heat tolerance than parasites and chemically inhibited parasite growth via production of acids. Acceleration of symbiont growth and acid production at high temperatures resulted in progressively stronger antiparasitic effects across a temperature range typical of bee colonies. Consequently, the presence of symbionts reduced both the peak growth rate and heat tolerance of parasites. Substantial changes in parasite-symbiont interactions were evident over a temperature breadth that parallels changes in diverse animals exhibiting infection-related fevers and the amplitude of circadian temperature variation typical of endothermic birds and mammals, implying the frequent potential for temperature to alter symbiont-mediated resistance to parasites in endo- and ectothermic hosts. Results suggest that the endothermic behavior of honey bees could enhance the impacts of gut symbionts on parasites, implicating thermoregulation as a reinforcer of core symbioses and possibly microbiome-mediated antiparasitic defense.

IMPORTANCE
Two factors that shape the resistance of animals to infection are body temperature and gut microbiota. However, temperature can also alter interactions among microbes, raising the question of whether and how temperature changes the antiparasitic effects of gut microbiota. Honey bees are agriculturally important hosts of diverse parasites and infection-mitigating gut microbes. They can also socially regulate their body temperatures to an extent unusual for an insect. We show that high temperatures found in honey bee colonies augment the ability of a gut bacterial symbiont to inhibit the growth of a common bee parasite, reducing the parasite’s ability to grow at high temperatures. This suggests that fluctuations in colony and body temperatures across life stages and seasons could alter the protective value of bees’ gut microbiota against parasites, and that temperature-driven changes in gut microbiota could be an underappreciated mechanism by which temperature—including endothermy and fever—alters animal infection.
Ectopic expression of murine CD163 enables cell-culture isolation of lactate dehydrogenase-elevating virus 63 years after its discovery
Authors: Shaw Teressa M. , Maloney Sara M. , Nennig Kylie , Ramuta Mitchell D. , Norton Andrew , Ibarra Rodrigo , Kuehnert Paul , Brinton Margo , Faaberg Kay , Kuhn Jens H. , O'Connor David H. , Warren Cody J. , Bailey Adam L. 
Published: October 2023

ABSTRACT

Arteriviruses are RNA viruses related to coronaviruses but have not yet been associated with human infection. A murine arterivirus, lactate dehydrogenase-elevating virus (LDV), was first described in 1960 and quickly became a promising model for understanding immune failure due to its unique ability to persist in immunocompetent adult mice. However, the inability to culture LDV
in vitro
ultimately limited this system. Here, we demonstrate that the macrophage marker CD163 is essential for LDV infection. Expression of the murine homolog (mCD163) in otherwise mCD163-negative cell lines from mice and nonhuman primates enables productive LDV infection, creating the first immortalized cell-culture system. We also show that mCD163-knockout mice are completely resistant to LDV infection. These findings advance LDV as a model of arterivirus infection and viral persistence while adding to a growing body of literature suggesting that CD163 utilization is a broad feature of arteriviruses.

IMPORTANCE

Mouse models of viral infection play an especially large role in virology. In 1960, a mouse virus, lactate dehydrogenase-elevating virus (LDV), was discovered and found to have the peculiar ability to evade clearance by the immune system, enabling it to persistently infect an individual mouse for its entire lifespan without causing overt disease. However, researchers were unable to grow LDV in culture, ultimately resulting in the demise of this system as a model of failed immunity. We solve this problem by identifying the cell-surface molecule CD163 as the critical missing component in cell-culture systems, enabling the growth of LDV in immortalized cell lines for the first time. This advance creates abundant opportunities for further characterizing LDV in order to study both failed immunity and the family of viruses to which LDV belongs,
Arteriviridae
(aka, arteriviruses).
Palmitoylation of the hemagglutinin of influenza B virus by ER-localized DHHC enzymes 1, 2, 4, and 6 is required for efficient virus replication
Authors: Meng Xiaorong , Veit Michael 
Published: October 2023

ABSTRACT
Covalent attachment of the fatty acid palmitate or stearate to the cytoplasmic domain of viral glycoproteins is often crucial for viral replication. This has previously been studied for the hemagglutinin (HA) of influenza A virus and the responsible enzymes have been identified, but similar studies have not been performed with HA of influenza B virus, which contains palmitate linked to two cysteines. We show here that the modification is required for efficient virus replication since exchange of both cysteines or the cysteine located at the end of the cytoplasmic tail prevented the generation of viable viruses. Viruses with an exchange of the membrane-proximal cysteine rapidly reverted back to wild-type virus. Blocking exit of proteins from the endoplasmic reticulum (ER) revealed that palmitoylation of HA of influenza B virus occurs in the ER, whereas acylation of HA of influenza A virus occurs in the Golgi. Infecting cells deficient in Asp-His-His-Cys (DHHC) palmitoyltransferases revealed that HA of influenza B virus is acylated by the ER-localized DHHCs 1, 2, 4, and 6, which are thus different from the enzymes previously identified for acylation of HA of influenza A virus. A comparison of predicted and experimentally determined protein structures suggests that the exclusive acylation of the HA of influenza B virus with palmitate is not a function of the responsible DHHCs and that the transmembrane region may be critical for the acylation of HA of influenza A and B viruses by different DHHCs.

IMPORTANCE
Influenza viruses are a public health concern since they cause seasonal outbreaks and occasionally pandemics. Our study investigates the importance of a protein modification called “palmitoylation” in the replication of influenza B virus. Palmitoylation involves attaching fatty acids to the viral protein hemagglutinin and has previously been studied for influenza A virus. We found that this modification is important for the influenza B virus to replicate, as mutating the sites where palmitate is attached prevented the virus from generating viable particles. Our experiments also showed that this modification occurs in the endoplasmic reticulum. We identified the specific enzymes responsible for this modification, which are different from those involved in palmitoylation of HA of influenza A virus. Overall, our research illuminates the similarities and differences in fatty acid attachment to HA of influenza A and B viruses and identifies the responsible enzymes, which might be promising targets for anti-viral therapy.
Phosphorylation of CFP10 modulates
Mycobacterium tuberculosis
virulence
Authors: Malakar Basanti , Chauhan Komal , Sanyal Priyadarshini , Naz Saba , Kalam Haroon , Vivek-Ananth R. P. , Singh Lakshya Veer , Samal Areejit , Kumar Dhiraj , Nandicoori Vinay Kumar 
Published: October 2023

ABSTRACT

Virulence effectors secreted by
Mycobacterium tuberculosis
(
Mtb
) help subvert host immune mechanisms and, therefore, are critical for establishing infection and pathogenesis. However, knowledge in terms of signaling mechanisms that modulate the secretion of virulence factors is sparse. We performed high-throughput secretome, phosphoproteome, and phospho-secretome analysis of
Mtb
. We combined the analysis with empirical validations to show regulation of mycobacterial secretion through protein phosphorylation. System level protein-protein interaction network analysis superimposed with the secretome, phosphoproteome, and phospho-secretome profile revealed an intricate relationship between phosphorylation and secretion. At the core of the network was a key virulence factor CFP10. We identified PknA to be the kinase responsible for phosphorylating CFP10. Using genetic tools, we show that phosphomimetic mutation of CFP10 negatively regulates the secretion of virulence mediator ESAT6. Significantly, the dynamics of CFP10 phosphorylation strongly influenced bacterial virulence and survival within macrophages and mice. Together, the results show that the dynamic phosphorylation status of the secretory protein CFP10 regulates the secretion of virulence factors and impacts virulence.

IMPORTANCE

Secreted virulence factors play a critical role in bacterial pathogenesis. Virulence effectors not only help bacteria to overcome the host immune system but also aid in establishing infection.
Mtb
, which causes tuberculosis in humans, encodes various virulence effectors. Triggers that modulate the secretion of virulence effectors in
Mtb
are yet to be fully understood. To gain mechanistic insight into the secretion of virulence effectors, we performed high-throughput proteomic studies. With the help of system-level protein-protein interaction network analysis and empirical validations, we unravelled a link between phosphorylation and secretion. Taking the example of the well-known virulence factor of CFP10, we show that the dynamics of CFP10 phosphorylation strongly influenced bacterial virulence and survival
ex vivo
and
in vivo
. This study presents the role of phosphorylation in modulating the secretion of virulence factors.
A novel, highly sensitive, one-tube nested quantitative real-time PCR for
Brucella
in human blood samples
Authors: Liu Li , Li Mengyao , Liu Gaowen , He Jian , Liu Yang , Chen Xuesong , Tu Yungui , Lin Jie , Feng Yue , Xia Xueshan 
Published: October 2023

ABSTRACT

Brucellosis is a zoonotic disease caused by
Brucella
spp. and is a major threat to human and livestock health. The accurate and rapid detection of
Brucella
DNA is essential for the diagnosis and treatment of this disease. However, traditional diagnostic methods, such as culture and serological tests, have limitations in terms of sensitivity, specificity, and time consumption. To address these challenges, we developed a highly sensitive one-tube nested quantitative real-time PCR (qPCR) method to detect
Brucella
DNA using a closed-tube approach with two primers and two probes that sequentially react with encoding a
Brucella
outer membrane protein. The analytical sensitivity of this one-tube nested qPCR approach was 100 fg/μL, which is 100-fold higher than that of a conventional qPCR. Intra-batch and inter-batch replicates showed low coefficients of variation, both less than 5%. The study included 250 clinical samples, showing that this one-tube nested qPCR method has a specificity of 100% and a sensitivity of 98.6%, exceeding the sensitivity of conventional qPCR (84.1%) at a cycle threshold (CT) cutoff of 38. More importantly, the one-tube nested qPCR reduced the CT values by an average of 6.4 compared to conventional qPCR, significantly improving the detection rate of low-load samples (CT > 35). In conclusion, the
bcsp31
one-tube nested qPCR method is a promising tool for the detection of brucellosis, owing to its high sensitivity and operational simplicity. This study highlights the potential of qPCR-based methods to improve the accuracy and speed of brucellosis diagnoses.

IMPORTANCE

This study developed a highly sensitive and efficient method for the detection of brucellosis by introducing a one-tube nested quantitative real-time PCR (qPCR) approach, representing a remarkable advance in the field. The method demonstrated an impressive analytical sensitivity of 100 fg/μL, surpassing conventional qPCR and enabling the detection of even low levels of
Brucella
DNA. In addition, the study’s comprehensive evaluation of 250 clinical samples revealed a specificity of 100% and a sensitivity of 98.6%, underscoring its reliability and accuracy. Most importantly, the new method significantly improved the detection rate of low-burden samples, reducing cycle threshold values by an average of 6.4. These results underscore the immense potential of this approach to facilitate rapid and accurate brucellosis diagnosis, which is critical for effective disease management and control.
Identifying plutons associated with long-lived volcanism by thermal modeling of contact metamorphic aureoles
Authors: Yamaoka Ken , Wallis Simon R. , Miyake Akira , Annen Catherine 
Published: October 2023

Abstract
A compilation of the thicknesses of contact metamorphic aureoles (CMAs) developed around intermediate to felsic plutons shows many CMAs are far broader than expected by commonly used thermal models for pluton emplacement. Shortfalls in the amount of heat potentially provided based on pluton size, compared to that needed to form the observed CMA, can be accounted for if some hot magma has been lost by volcanic eruption after passing through the pluton domain and replaced by new hot magma. A high ambient temperature may also contribute to broad CMA formation. However, the presence of coeval pairs of both narrow and broad CMAs in the same area requires contrasting types of pluton growth history. Our thermal modeling, constrained by the peak metamorphic temperature, shows the broad CMA of a well-developed pair of CMAs in the Hongusan area of Japan is due to a magmatic history, including magma tapping and replenishment. A global compilation of CMAs suggests more than 30% of plutons are associated with broad CMAs and fed contemporaneous volcanic eruption.