bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stepping Into the Night: The Preparedness of Newly Qualified Doctors for Out‐of‐Hours Work
Authors: Synnott David , Cavallari Sarah , Synnott Kevin , Coakley Niamh 
Published: February 2025

ABSTRACTBackgroundThe transition from medical student to doctor is a significantly stressful event with a perceived lack of preparedness. A comprehensive exploration of the facilitators and barriers to preparedness for out‐of‐hours specifically, such as night duty, is lacking. This study aims to investigate the perspectives of newly qualified Irish doctors (interns) regarding their readiness for out‐of‐hours work, the levels of support available and the influence of their medical education on readiness.MethodsA survey using both quantitative and qualitative data was developed and distributed amongst 145 interns in one Irish regional ‘network’ using nonprobability sampling. Quantitative data were analysed using nonparametric methods of Likert scale responses. Qualitative data underwent thematic analysis using Braun and Clarke's approach.FindingsSeventy‐seven respondents met inclusion criteria. Of participants, 88.3% disagreed with feeling prepared for out‐of‐hours, a sentiment corroborated by qualitative expressions of fear and apprehension. Themes emerged regarding general preparedness, support, and the hidden curriculum. Seeking support presented challenges, often met with resistance. Isolation and post‐call anxiety were recurrent sentiments. Participants believed medical education had inadequately prepared them, emphasising theoretical knowledge at the expense of practical skills for real‐world scenarios.ConclusionThis study highlights the anxiety and isolation experienced by new doctors, underscoring a pervasive sense of unpreparedness, inadequate support structures and a disconnect between medical education and the practical demands of out‐of‐hours clinical work. These findings support current literature and emphasise the need for enhanced training, emotional support and better alignment between education and clinical realities for out of hours.
Evaluation of the Effect of Intravenous Mannitol and Hypertonic Saline on Intraocular Pressure and Biometry Parameters in Anesthetized Horses With Experimentally Increased Intracranial Pressure
Authors: Bercovitz Genia R. , Sullivan Stasia N. , Reed Rachel A. , Ryan Clare A. , Diehl Kathryn A. 
Published: February 2025

ABSTRACTObjectiveTo evaluate the effect of intravenous mannitol and hypertonic saline (HS) on intraocular pressure (IOP) and biometry parameters of horses with elevated intracranial pressure (ICP).ProceduresSeven horses with normal ophthalmic exams were anesthetized and placed in lateral recumbency. A subarachnoid transducer was placed, and the head was lowered until ICP measured 40 mmHg +/− 2 mmHg. Five intravenous boluses of mannitol 20% (0.4 g/kg) or HS 7.2% (1 mL/kg) were administered, each 15 min apart. A 2‐day washout period ensued, and the procedure was repeated with the other hyperosmotic agent. IOP via a TonoVet, axial length and vitreous chamber depth via biometry, and ICP via the subarachnoid transducer were monitored.ResultsNo significant correlation between ICP and IOP was identified. Estimated marginal mean (EMM) reduction in IOP (comparing values 5 min post bolus to values at bolus administration) following mannitol and HS was 2.4 mmHg and 0.4 mmHg, respectively. Mean axial length EMM decreased by and increased by 0.1 mm following mannitol and HS, respectively. Mean vitreous chamber depth EMM was unchanged and increased by 0.1 mm following mannitol and HS, respectively. The EMM of the second HS bolus demonstrated an increase of 0.8 mm (95% confidence interval 0.01–1.5 mm) in axial length (p < 0.048), though the remaining individual bolus assessments were not statistically significant.ConclusionsIntravenous mannitol and HS did not cause a significant change in IOP, axial length, or vitreous chamber depth in healthy, anesthetized, laterally recumbent horses in this experimental model of increased ICP.
Pro-inflammatory secreted virulence factors of
Staphylococcus capitis
causing a rare occurrence of severe native hip joint infection
Authors: Schlievert Patrick M. , Kilgore Samuel H. , Ford Bradley , Leung Donald Y. M. , Sekar Poorani 
Published: February 2025

ABSTRACT

Background

Staphylococcus capitis
occasionally causes human infections. We report a case of
S. capitis
infection associated with inflammatory destructive hip abscess/osteomyelitis.

Case Summary

A 63-year-old man with severe hip osteoarthritis and recent left hip replacement presented with 2 months of worsening right hip pain. Radiographic imaging showed right femoral head destruction. The patient had no known hip trauma. His white blood cell count, C-reactive protein, and erythrocyte sedimentation rate were abnormal. Pre-operative aspirate of the hip showed purulent fluid. The examining radiologist believed the changes seen were due to inflammatory arthritis with infection from low-virulence organisms. The patient underwent image-guided biopsies of the synovium and the acetabulum, which showed pure cultures of
S. capitis
and infiltrating neutrophils. The patient’s native hip was removed, and an antibiotic spacer was placed. The patient was treated with intravenous cefazolin (6 weeks), after which he was transitioned to oral cefadroxil. The patient is doing well. The
S. capitis
was analyzed by nucleotide sequencing and biochemically for secreted virulence factors. The strain contained the polysaccharide intercellular adhesin biofilm operon. The strain was negative for urease, hemolysins, and major superantigens. The organism secreted a neutrophil pro-inflammatory autolysin protease and an analog of the immunodominant antigen B of
S. aureus
, previously with no known biological function.

Conclusion

Our data suggest that the inflammatory lesion in the patient’s right hip was due to
S. capitis
subspecies
capitis
, and furthermore, it is likely that two secreted proteins (autolysin and an analog of immunodominant antigen B) contributed to the inflammation.
Diversities of African swine fever virus host-virus dynamics revealed by single-cell profiling
Authors: Zhao Xiaoyang , Zhang Yanyan , Jia Hanying , Lv Lin , Ahsan Md.Asif , Fu Xudong , Hu Rongliang , Shen Zhiqiang , Shen Ning 
Published: February 2025

ABSTRACT

African swine fever virus (ASFV) causes epidemics with high mortality; however, effective vaccines and therapies remain missing. Here, we depict a temporal single-cell landscape of primary porcine alveolar macrophages (PAMs) exposed to three different virulent ASFV strains
in vitro
. We found that attenuated and low-virulence ASFV strains tend to exhibit higher viral loads than highly virulent strain, which may result from upregulated RNA polymerase subunit genes expression. On the host side, our study highlights the IRF7-mediated positive feedback loop to the activation of the interferon signaling pathway in cells exposed to attenuated and low virulent ASFV strains. Moreover, we unraveled the PAMs populations marked by expressions of the
IFI16
and
CD163
, respectively, which produce high levels of interferon-stimulated genes (ISGs) and IL18 to regulate the host response to different virulent ASFV strains. Collectively, our data provide insights into the complex host-virus interactions with various ASFV strain infections, which may shed light on the development of effective antiviral strategies.

IMPORTANCE

There is still no available research on the temporal transcriptional profile of host cells exposed to different virulent ASFV strains at the single-cell level. Here, we first profiled the temporal viral and host transcriptomes in PAMs exposed to high virulent, attenuated virulent, and low virulent ASFV strains. Our analysis revealed that attenuated and low-virulence ASFV strains tend to exhibit higher viral loads than highly virulent strains, which may result from upregulated RNA polymerase subunit genes expression. We also found a positive feedback loop of the interferon signaling pathway mediated through IRF7 and identified the populations of PAMs marked by
IFI6
and
CD163
, respectively, which produce high levels of ISGs and
IL18
to regulate host response to different virulent ASFV strains. Our study delineated a comprehensive single-cell landscape of host-virus dynamics across ASFV strains with different virulences and would provide an important resource for future research.
Begomovirus capsid proteins interact with cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase of its whitefly vector and modulate virus retention within its vector
Authors: Ghosh Saptarshi , Mondal Banani , Jassar Ola , Ghanim Murad , Gautam Saurabh , Reddy Netla Vamsidhar , Srinivasan Rajagopalbabu 
Published: February 2025

ABSTRACT

Begomoviruses are whitefly-transmitted ss-DNA viruses that infect dicotyledonous plants and contribute to major economic losses to global crop production. Invasion and establishment of an aggressive cryptic species of
Bemisia tabaci
, known as the B cryptic species, has severely constrained vegetable production in the southeastern and southwestern United States. Disruption of genes/pathways critical for whitefly-mediated transmission can be effective for the management of begomoviruses. In this study, yeast two-hybrid (Y2H)-based screening of
B. tabaci
cDNA library identified a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase-4 (PDE4) of the whitefly as an interacting partner with capsid proteins (CPs) of old- and new-world begomoviruses. Interactions of PDE4 with begomovirus CPs were validated by glutathione-S-transferase (GST) pull-down assay and co-immunolocalization in whitefly midgut. The PDE4 family of enzymes hydrolyzes cAMP and regulates intracellular cAMP levels. This study conclusively proves that acquisition of begomoviruses downregulates the expression of PDE4 (mRNA and protein) resulting in elevated cAMP levels within the whitefly. The role of cAMP post virus acquisition is further elucidated wherein elevation of cAMP by chemical inhibition or gene (PDE4) silencing resulted in increased retention and transmission of begomoviruses. Similarly, decreased cAMP levels resulted in reduced begomovirus retention. The results of this study demonstrate that whitefly-mediated transmission of begomoviruses is regulated by intracellular cAMP by unknown mechanisms.

IMPORTANCE

Begomoviruses, transmitted by the sweetpotato whitefly (
Bemisia tabaci
Gennadius), are the causal agents of many economically important plant virus diseases. Lack of host plant resistance against begomoviruses, high whitefly abundance, and whitefly’s ability to develop insecticide resistance rapidly often render the commonly used management practice ineffective. This study demonstrates how begomovirus retention within whitefly and its transmission can be modulated by altering cyclic adenosine monophosphate (cAMP) expression of its insect vector. Naturally occurring bio-pesticides that target insect cAMPs are known. Our findings can lead to alternative strategies for the management of begomoviruses by targeting whitefly cAMP using chemicals, botanicals, or RNAi-based insecticides.
Differential mosaicism of recombinant foot-and-mouth disease viruses resulting from heterologous superinfection of cattle
Authors: Stenfeldt Carolina , Fish Ian H. , Rodriguez-Calzada Monica , Medina Gisselle , Richt Juergen A. , Arzt Jonathan 
Published: February 2025

ABSTRACT

Evidence from both field and experimental studies suggests that recombination is a common feature in the evolution of foot-and-mouth disease virus (FMDV). Recent studies have demonstrated that heterologous superinfection of cattle persistently infected with FMDV leads to rapid generation of inter-serotypic recombinant viruses in the upper respiratory tract mucosa. The current study demonstrates that the order of exposure to FMDV strains A24 Cruzeiro and O1 Manisa substantially influenced the patterns of mosaicism of resultant recombinants. FMDV recombinants were isolated from oropharyngeal fluid samples from 7 of 12 cattle following heterologous superinfection at 21 days post-initial infection. There was no apparent competitive advantage of either parental virus. However, recombinant viruses recovered from six of seven animals had gained, or regained through multiple recombination events, the capsid-coding sequence of FMDV O1 Manisa despite the presence of high titers of neutralizing antibodies against that virus. Additionally, a sub-genomic region of high amino acid diversity, spanning the 3′ portion of 3A through 3B, was derived from FMDV A24 in most of the recovered recombinants. Despite the frequent recovery of FMDV recombinants from the upper respiratory tract of superinfected animals, there was no detection of recombinant viruses in blood or lesions in the subset of animals that developed clinical foot-and-mouth disease during superinfection. Overall, these findings confirm the high frequency at which FMDV recombination occurs when persistently infected carrier cattle are exposed to a heterologous virus and reaffirm that superinfection of carriers should be considered as a source of FMDV genetic diversity in endemic regions.

IMPORTANCE
Foot-and-mouth disease virus (FMDV) is a pathogen of domestic livestock with profound global socioeconomic impacts. FMDV causes a subclinical persistent infection in ruminant hosts, such as cattle, during which the animals may become sequentially infected by heterologous variants of the virus. Our previous works have demonstrated that such superinfections frequently lead to emergence of novel recombinant virus variants in the upper respiratory tracts of infected animals. This current investigation demonstrates that the order in which the animals are exposed to two different viruses substantially influences the structure of resultant recombinant genomes and confirms the frequency at which FMDV recombination occurs following heterologous superinfection of persistently infected FMDV carriers.
mGem: A quarter century with the Pirofski–Casadevall damage response framework—a dynamic construct for understanding microbial pathogenesis
Authors: Nosanchuk Joshua D. 
Published: February 2025

ABSTRACT

A quarter of a century ago, Liise-anne Pirofski and Arturo Casadevall shared their concepts of microbial pathogenesis through the lens of a damage-response framework (DRF), which characterizes disease by assessing the dynamic interactions between the host and pathogen as reflected by damage as the readout. This framework has evolved to be a powerful tool for understanding the biology of complex infectious diseases, analyzing emerging and reemerging microbes, and developing therapeutic approaches to combat infections. The DRF is also frequently used to explain research at scientific meetings and to teach microbial pathogenesis to diverse learners. This mGem reviews how the DRF came to be and provides an overview of how it is used. Without a doubt, the scientific community will continue to leverage the DRF to advance research and innovate therapeutic approaches, which is especially important as new and reemerging infectious diseases threaten global health.
mGem: The complexity of viral entry—one virus, many receptors
Authors: Dermody Terence S. , Sutherland Danica M. 
Published: February 2025

ABSTRACT

Binding to cellular receptors initiates viral replication and dictates sites in the host infected by the virus. As illustrated by mammalian orthoreovirus (reovirus), viruses can bind several types of receptors using distinct capsid components to facilitate the viral entry steps of attachment, internalization, and disassembly. The outer of the two concentric capsids of reovirus virions is formed by four viral proteins, three of which bind receptors. These capsid–receptor interactions mediate stepwise entry of reovirus, dictate viral tropism in infected animals, and expand the viral host range. Engagement of independent receptors by different capsid proteins is a property of many pathogenic viruses and illustrates common themes of receptor use in viral entry and disease.
Identification of intratumoral bacteria that enhance breast tumor metastasis
Authors: Gerbec Zachary J. , Serapio-Palacios Antonio , Metcalfe-Roach Avril , Krekhno Zakhar , Bar-Yoseph Haggai , Woodward Sarah E. , Pena-Díaz Jorge , Nemirovsky Oksana , Awrey Shannon , Moreno Sebastian H. , Beatty Sean , Kong Esther , Radisavljevic Nina , Cirstea Mihai , Chafe Shawn , McDonald Paul C. , Aparicio Sam , Finlay B. Brett , Dedhar Shoukat 
Published: February 2025

ABSTRACT

The central, mortality-associated hallmark of cancer is the process of metastasis. It is increasingly recognized that bacteria influence multiple facets of cancer progression, but the extent to which tumor microenvironment-associated bacteria control metastasis in cancer is poorly understood. To identify tumor-associated bacteria and their role in metastasis, we utilized established murine models of non-metastatic and metastatic breast tumors to identify bacteria capable of driving metastatic disease. We found several species of the
Bacillus
genus that were unique to metastatic tumors, and found that breast tumor cells cultured with a
Bacillus
bacterium isolated from metastatic tumors,
Bacillus thermoamylovorans
, produced nearly 3× the metastatic burden as control cells or cells cultured with bacteria from non-metastatic breast tumors. We then performed targeted metabolomics on tumor cells cultured with different bacterial species and found that
B. thermoamylovorans
differentially regulated tumor cell metabolite profiles compared to bacteria isolated from non-metastatic tumors. Using these bacteria, we performed
de novo
sequencing and tested for the presence of genes that were unique to the bacterium isolated from metastatic tumors in a patient population to provide a proof-of-concept for identifying how specific bacterial functions are associated with the metastatic process in cancer independent of bacterial species. Together, our data directly demonstrate the ability of specific bacteria to promote metastasis through interaction with cancer cells.

IMPORTANCE
Metastasis is a major barrier to long-term survival for cancer patients, and therapeutic options for patients with aggressive, metastatic forms of breast cancer remain limited. It is therefore critical to understand the differences between non-metastatic and metastatic disease to identify potential methods for slowing or even stopping metastasis. In this work, we identify a bacterial species present with metastatic breast tumors capable of increasing the metastatic capabilities of tumor cells. We isolated and sequenced this bacteria, as well as a control species which failed to promote metastasis, and identified specific bacterial genes that were unique to the metastasis-promoting species. We tested for the presence of these bacterial genes in patient tumor samples and found they were more likely to be associated with mortality. We also identified enrichment of specific bacterial functions, providing insight into possible sources of bacteria-driven increases in the metastatic potential of multiple cancer types.
C-reactive protein-induced injury in
Mycoplasma pneumoniae
-infected lung epithelial cells is mediated by the P38 MAPK/mitochondrial apoptosis pathway
Authors: Li Lianjia , Zhang Yang , Zhao Lin , Shi Yalin 
Published: February 2025

ABSTRACT

Patients with
Mycoplasma pneumoniae
(MP) infections have markedly higher C-reactive protein (CRP). We investigated how CRP contributes to lung epithelial cell death following MP infection. CRP levels were assessed in children diagnosed with
Mycoplasma pneumoniae
pneumonia (MPP) and A549 lung epithelial cells infected with MP. A549 cells were genetically modified to overexpress CRP. Effects on cell viability, apoptosis, reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨm) were evaluated. The expression of proteins implicated in the p38 MAPK/mitochondrial apoptotic pathway was analyzed. The protective effects of the p38 MAPK inhibitor SB203580 and the mitochondrial protector cyclosporin A (CsA) were assessed. CRP levels were elevated in both MPP patients and MP-infected A549 cells compared to controls. Increased apoptosis and reduced cell viability were observed in MP-infected cells. CRP overexpression led to upregulation of proteins in the p38 MAPK/mitochondrial apoptosis pathway, increased cytoplasmic Cyt C, decreased Tom 20 and ΔΨm, and elevated ROS. Pretreatment with SB203580 or posttreatment with CsA reduced apoptosis and mitochondrial damage and enhanced cell survival. Increased CRP levels during MP infection promote lung epithelial cell death by activating the p38 MAPK/mitochondrial apoptosis pathway. Targeting this pathway could offer therapeutic potential to reduce lung damage in MPP patients.

IMPORTANCE
This study provides critical information in understanding the pathophysiological mechanisms for MP infections concerning CRP in mediating lung epithelial cell injury. This study outlines the significant increase in MP-infected patients and shows its direct involvement in cell apoptosis through the p38 MAPK/mitochondrial apoptosis pathway. By explaining this pathway, the possibility of targeting CRP and its connected signaling mechanisms to devise therapeutic interventions for the amelioration of lung damage in MP-infected patients is brought to light. The implications of such data are not merely in the added knowledge for disease pathobiology but also it brings new promise for novel intervention strategies to result in improved clinical outcomes. The elucidation of specific molecular targets inside the apoptosis pathway heralds a new area regarding the direction of future research and clinical application for humanity in general and concerning the broader relevance and impact of this study on respiratory diseases.