bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuraminidase-mediated enhancement of
Streptococcus pneumoniae
colonization is associated with altered mucus characteristics and distribution
Authors: Montgomery Matthew T. , Ortigoza Mila , Loomis Cynthia , Weiser Jeffrey N. 
Published: December 2024

ABSTRACT

Upon entry into the upper respiratory tract (URT),
Streptococcus pneumoniae
(Spn) upregulates neuraminidases (NA) that cleave sialic acid (SA) from host glycans. Because sialylation is thought to contribute to the physical properties that determine mucus function, we posited that Spn directly alters host mucus through NA activity. By directly imaging the colonized URT, we demonstrated NA-mediated alterations to the characteristics and distribution of mucus along the respiratory epithelium, where colonizing bacteria are found. Mucus exposed to NA showed increased localization within goblet cells and lining the glycocalyx. By contrast, NA-naïve mucus was more likely to be observed sloughing away from the epithelial surface. We also visualized Spn in the URT and observed that NA promoted efficient bacterial localization to the firm mucus layer overlying the glycocalyx, whereas NA-deficient Spn was associated more with loose mucus. By facilitating tighter association with the glycocalyx, NA promoted increased Spn colonization density. The magnitude of the NA-mediated effect on colonization was widened during late colonization by increased evasion of host-mediated clearance mechanisms. Thus, Spn-encoded NAs directly modify the host environment by desialylating mucus, which allows close interaction with mucus at the epithelium, and this is associated with enhanced bacterial colonization.

IMPORTANCE
Although severe illness and death caused by Spn result from secondary invasive diseases including pneumonia, sepsis, and meningitis, stable colonization of the upper respiratory tract (URT) is a prerequisite to invasive disease. Therefore, understanding host-Spn dynamics during asymptomatic colonization of the URT is warranted with respect to the pathogenesis of Spn disease. In this study, we found that Spn NA activity directly alters mucus characteristics that result in increased density and duration of URT colonization. Therefore, targeting Spn NA activity during URT colonization may be a viable strategy to mitigate Spn infection.
Bacteria-specific modified nucleoside is released and elevated in urine of patients with bacterial infections
Authors: Yamamura Ryosuke , Nagayoshi Yu , Nishiguchi Kayo , Kaneko Hitomi , Yamamoto Keiichi , Matsushita Koki , Shimamura Miho , Kunisawa Akihiro , Sakakida Korin , Chujo Takeshi , Adachi Masataka , Kakizoe Yutaka , Izumi Yuichiro , Kuwabara Takashige , Mukoyama Masashi , Tomizawa Kazuhito 
Published: December 2024

ABSTRACT

Over 170 types of chemical modifications have been identified in cellular RNAs across the three domains of life. Modified RNA is eventually degraded to constituent nucleosides, and in mammals, modified nucleosides are released into the extracellular space. By contrast, the fate of modified nucleosides in bacteria remains unknown. In this study, we performed liquid chromatography-mass spectroscopy (LC-MS) analysis of modified nucleosides from the RNA of 23 pathogenic bacteria, revealing 2-methyladenosine (m
2
A) as a common bacteria-specific modified nucleoside detected in all bacterial RNAs. Under normal culture conditions, bacteria did not actively release most modified nucleoside species, but robustly released nucleosides, including m
2
A, following addition of antibiotics or immune cells. These results indicate that m
2
A is released following bacterial lysis. Intraperitoneal injection of mice with m
2
A increased detectable levels of m
2
A in the urine, indicating that mammals can effectively excrete m
2
A. Additionally, mice infected with wild-type
E. coli
showed higher levels of m
2
A in their urine than mice infected by m
2
A-deficient
rlmN
KO
E. coli
. This suggests that m
2
A from the infected bacteria is excreted in the urine. Lastly, clinical studies using urine samples from febrile patients revealed significantly elevated levels of m
2
A during bacterial infections, and these values did not correlate with inflammation severity markers, such as white blood count (WBC) and C-reactive protein (CRP). This study reports the mammalian metabolism of modified nucleosides derived from bacterial RNA, and the elevation of urinary m
2
A in patients with bacterial infections.

IMPORTANCE

This study reveals the differences in the fate and release of modified nucleosides in bacteria and mammals. Additionally, our study highlights that external bacteria-damaging factors, such as antibiotics and phagocytosis by host immune cells, promote the release of bacteria-specific modified nucleosides. Furthermore, we found that m
2
A was elevated in the urine from animal models of bacterial infection and the urine of patients with bacterial infections. Collectively, this work spans basic biology and clinical science, offering valuable insights into the fate of modified nucleosides in bacterial systems and their relevance to infectious diseases.
Multi-omics analysis reveals the interplay between intratumoral bacteria and glioma
Authors: Li Ting , Zhao Zhanyi , Peng Meichang , Zhang Lu , Wang Cheng , Luo Feiyang , Zeng Meiqin , Sun Kaijian , Fang Zhencheng , Luo Yunhao , Xie Yugu , Lv Cui , Wang Jiaxuan , Huang Jian-Dong , Zhou Hongwei , Sun Haitao 
Published: December 2024

ABSTRACT

Emerging evidence highlights the potential impact of intratumoral microbiota on cancer. However, the microbial composition and function in glioma remains elusive. Consequently, our study aimed to investigate the microbial community composition in glioma tissues and elucidate its role in glioma development. We parallelly performed microbial profiling, transcriptome sequencing, and metabolomics detection on tumor and adjacent normal brain tissues obtained from 50 glioma patients. We employed immunohistochemistry, multicolor immunofluorescence, and fluorescence
in situ
hybridization (FISH) staining to observe the presence and location of bacteria. Furthermore, an animal model was employed to validate the impact of key bacteria on glioma development. Six genera were found to be significantly enriched in glioma tissues compared to adjacent normal brain tissues, including
Fusobacterium
,
Longibaculum
,
Intestinimonas
,
Pasteurella
,
Limosilactobacillus,
and
Arthrobacter
. Both bacterial RNA and lipopolysaccharides (LPS) were observed in glioma tissues. Integrated microbiomics, transcriptomics, and metabolomics revealed that genes associated with intratumoral microbes were enriched in multiple synapse-associated pathways and that metabolites associated with intratumoral microbes were (R)-
N
-methylsalsolinol,
N
-acetylaspartylglutamic acid, and
N
-acetyl-
l
-aspartic acid. Further mediation analysis suggested that the intratumoral microbiome may affect the expression of neuron-related genes through bacteria-associated metabolites. In addition, both
in vivo
and
in vitro
models of glioma show that
Fusobacterium nucleatum
promotes glioma proliferation and upregulates CCL2, CXCL1, and CXCL2 levels. Our findings shed light on the intricate interplay between intratumoral bacteria and glioma.

IMPORTANCE

Our study adopted a multi-omics approach to unravel the impact of intratumoral microbes on neuron-related gene expression through bacteria-associated metabolites. Importantly, we found bacterial RNA and LPS signals within glioma tissues, which were traditionally considered sterile. We identified key microbiota within glioma tissues, including
Fusobacterium nucleatum
(Fn). Through
in vivo
and
in vitro
experiments, we identified the crucial role of Fn in promoting glioma progression, suggesting that Fn could be a potential diagnostic and therapeutic target for glioma patients. These findings offer valuable insights into the intricate interplay between intratumoral bacteria and glioma, offering novel inspiration to the realm of glioma biology.
Association of intratumoral microbiome diversity with hepatocellular carcinoma prognosis
Authors: Jiang Fengle , Dang Yuan , Zhang Zheting , Yan Yanan , Wang Yingchao , Chen Yi , Chen Lihong , Zhang Jialiang , Liu Jingfeng , Wang Jianmin 
Published: December 2024

ABSTRACT

The evidence that intratumoral microbiomes, as a rising hallmark of cancer, have a profound impact on cancer phenotypes is increasingly compelling. However, the impact of the composition and diversity of the intratumoral microbiome on the prognosis of patients undergoing surgical resection for hepatocellular carcinoma (HCC) remains incompletely understood. In this study, we revealed a high abundance of bacteria in the neoplastic tissues. The presence of bacterial lipopolysaccharide and lipoteichoic acid was detected alongside tumor-associated immune cells. By utilizing 16S rRNA gene sequencing, we identified a specific intratumoral microbiome signature that was highly predictive of the prognosis for HCC patients who underwent surgical resection. Specifically, the presence of Intestinimonas, Brachybacterium, and Rothia were identified as independent risk factors for the overall survival of HCC patients who underwent surgical resection.

IMPORTANCE
Although some studies have shown an abundance of bacteria in hepatocellular carcinoma (HCC), there is still limited understanding of the composition and diversity of the intratumoral microbiome that is favorable or adverse to the prognosis of HCC patients. Our results indicated that a greater abundance of bacteria could be observed in the neoplastic tissues than in nonneoplastic tissues. Bacterial cell wall components largely coincided with tumor-associated immune cells. The bacteria in the long overall survival (LOS) group were associated with metabolism and cytokine‒cytokine receptor interaction pathways, while bacteria in the short overall survival (SOS) group were associated with proinflammatory and cell proliferation pathways. Notably, specific taxa could independently predict HCC prognosis. Based on these findings, intratumoral microbiomes facilitate the use of precision medicine in clinical practice.
Prospective clinical performance of CoVarScan in identifying SARS-CoV-2 Omicron subvariants
Authors: Zhu Kenneth , Sah Manoj , Mahimainathan Lenin , Liu Yan , Xing Chao , Roush Karen , Clark Andrew , SoRelle Jeffrey 
Published: December 2024

ABSTRACT

The purpose of this work was to evaluate the performance of CoVarScan, a multiplex fragment analysis approach, in identifying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of the Omicron lineage rapidly and accurately. The ability to identify variants with high fidelity and low turnaround time is important both epidemiologically and clinically for pandemic monitoring and therapeutic monoclonal antibody (mAb) selection. Currently, the gold-standard test for this task is whole-genome sequencing (WGS), which is prohibitively expensive and/or inaccessible due to equipment requirements for many laboratories. Omicron variants have been closely related, so the ability of genotyping tests to differentiate them is an important, outstanding question. CoVarScan uses PCR targeting eight SARS-CoV-2 mutational hot spots. In total, 4,918 SARS-CoV-2-positive cases between 17 December 2021 and 31 January 2024 were included in the analysis. CoVarScan achieved 96.5% concordance with WGS and could detect unique mutational signatures for BA.1, BA.2, BA.2.12.1, BA.4/BA.5, BA.2.75, XBB, and BA.2.86. These are the major variants of concern (VOCs) that have dominated since Omicron originally appeared in December 2021. Lastly, based on panel design, we predict a unique mutational pattern for the newly emergent, highly mutated variant BA.2.87. CoVarScan can rapidly, accurately, and cost-effectively identify all Omicron variants in a scalable manner. Furthermore, CoVarScan does not require design alterations to detect new VOCs. CoVarScan performs as accurately as WGS with higher sensitivity, allowing its use as a tool to quickly identify variants for epidemiological surveillance and clinical decision-making in the selection of effective therapeutic mAbs.

IMPORTANCE
Almost 5 years since the start of the pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern continue to emerge, with mutations conferring new properties like increased transmissibility and resistance to therapeutic monoclonal antibodies and vaccines. Conventionally, whole-genome sequencing (WGS) has characterized new SARS-CoV-2 variants, but results come too late for clinical actionability. WGS suffers from high failure rates for samples with low viral RNA and is inaccessible for lower-resource laboratories. As new variants like Omicron appear, it is necessary to develop rapid and accurate testing to distinguish between variants. Fast and accurate identification of sensitive viral lineages would allow tailored use of monoclonal antibodies that may otherwise have been pulled from the market due to rising overall resistance. Rapid results also allow public health officials to make policy decisions in time to reduce morbidity and mortality for sensitive populations such as patients who are immunocompromised or have significant medical comorbidities.
Navigating the challenge of high-grade cervical lesions (CIN3) in pregnancy: a near miss
Authors: Kulkarni Tithi , Fitch Anthony 
Published: December 2024

In this case, a pregnant Indigenous woman presented with high-grade cervical lesions (high-grade squamous intraepithelial lesion (HSIL), cervical intraepithelial neoplasia grade 3 (CIN2–3) and was lost to follow-up for over 5 years, posing a unique management challenge. Despite higher regression rates in pregnant women, personalised care was crucial due to potential pregnancy-related intervention risks.This case underscores the complexities of managing high-grade cervical lesions in pregnancy and highlights the significant burden of cervical cancer within Aboriginal and Torres Strait Islander communities. It emphasises the urgent need for equitable screening access, patient-centred care and culturally sensitive education among vulnerable populations.Of particular note is the case’s uniqueness, with the patient’s CIN3 diagnosis persisting for over 5 years and spanning three pregnancies without definitive management. Post partum, a subsequent LLETZ revealed extensive HSIL (CIN3) involving ectocervical and endocervical margins. Due to margin involvement, the patient now requires ongoing surveillance, with continued risk of being lost to follow-up due to the factors described.
Timing dilemma: a systematic review and meta-analysis of short-term mortality in patients with COVID-19 undergoing tracheostomy with varied timing, including 7, 10 and 14 days
Authors: Kim Beong Ki , Choi Hangseok , Kim Chi Young 
Published: December 2024

ObjectiveTo analyse the effects of tracheostomy timing on COVID-19 outcomes by comparing mortality rates at different time points (7, 10 and 14 days).DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase, Cochrane Library, Web of Science and Scopus were searched from 31 August 2023 to 6 September 2023.Primary and secondary outcomes measuresThe primary outcome was short-term mortality, defined as intensive care unit (ICU) mortality, hospital mortality and 28-day or 30-day mortality. The secondary outcomes included mechanical ventilation duration, ICU and hospital days.ResultsAmong 3465 patients from 12 studies, the 10-day subgroup analysis revealed higher mortality for earlier tracheostomy than for later tracheostomy (49.7% vs 32.6%, OR 1.91, 95% CI 1.37–2.65). No significant differences were observed at 7- and 14-day marks. Earlier tracheostomy was associated with shorter mechanical ventilation (mean difference=−7.35 days, 95% CI −11.63 to −0.38) and ICU stays (mean difference=−11.24 days, 95% CI −18.50 to −3.97) compared with later tracheostomy. Regarding hospital stay, the later tracheostomy group exhibited a trend towards longer-term inpatients, with no significant difference.ConclusionsNo significant difference in short-term mortality was observed between patients undergoing tracheostomy at 7 and 14 days; however, at 10 days, later tracheostomy resulted in a lower mortality rate. Accordingly, subtle timing differences may impact short-term results in COVID-19 patients. Considering that the later tracheostomy group had longer mechanical ventilation and ICU stays, additional research is required to determine an optimal timing that reduces mortality cost-effectively.
Knowledge, attitude and practice towards postoperative management among patients with type A aortic dissection or their relatives: a cross-sectional study in China
Authors: Zhang Kai , Gao Shiqi , Zhou Chenyu , Xie Enzehua , Song Jian , Wang Zhu , Qiu Juntao , Yu Cuntao 
Published: December 2024

ObjectivesTo assess the knowledge, attitude and practice (KAP) of patients with type A aortic dissection (AD) or their relatives regarding postoperative management.DesignCross-sectional study.SettingThe participants were recruited from three hospitals between October 2022 and February 2023.ParticipantsPatients diagnosed with type A AD or their relatives.InterventionsNo interventions were administered. A structured questionnaire was used to gather the demographic and KAP data from the participants.Primary and secondary outcome measuresThe outcome measures included the levels of KAP regarding postoperative management.ResultsA total of 483 participants were included. They exhibited poor knowledge (15.52±7.67, possible score: 0–32), positive attitude (31.10±5.86, possible score: 9–45) and poor practice (21.96±4.83, possible score: 8–40) towards postoperative management. The multivariable logistic analysis showed that knowledge scores (OR=1.09, 95% CI 1.05 to 1.12, p<0.001), attitude scores (OR=1.22, 95% CI 1.16 to 1.29, p<0.001) and diagnosis for ≤5 years (OR=1.97, 95% CI 1.23 to 3.15, p=0.005) were independently associated with good practice. The structured equation modelling analysis showed that knowledge directly influenced attitudes (β=0.22, p<0.001) and practice (β=0.15, p<0.001), while attitude directly impacted practice (β=0.52, p<0.001) and mediated the relationship between knowledge and practice (β=0.11, p<0.001).ConclusionsPatients with type A AD and their relatives have poor knowledge, positive attitudes and poor practice towards postoperative management. Knowledge might be the prerequisite for practice, and attitudes have a mediating effect.
Improving uptake of COVID-19 testing and vaccination in a homeless population: mixed-methods evaluation of community health worker-led education in a shelter
Authors: Ziolkowski Rebecca A , Balian Lara , Sridhar Shreya , Rodriguez Natalia M 
Published: December 2024

ObjectivesAccess to healthcare and accurate health information is a persistent issue for people experiencing homelessness (PEH), one heightened by the COVID-19 pandemic and exacerbated by issues of health literacy and mistrust. Strategies involving community health workers (CHWs) have the potential to improve education and service delivery for PEH. The objective of this study is to assess PEH knowledge, attitudes and barriers to COVID-19 testing and vaccination, and the impact of CHW-led education within a homeless shelter in Indiana.Design/settingBetween November 2021 and April 2022, 15 sessions were held at a homeless shelter that combined focus group discussions with COVID-19-related education. Pre-/post-tests measured knowledge gains and attitude shifts among PEH. Guided by the socioecological model, thematic analysis of focus group transcripts identified key motivators and barriers to COVID-19 vaccination and testing.Participants78 PEH (73% male, 74% white, mean age=48).Outcome measuresCOVID-19-related knowledge gains and willingness to receive testing and vaccination among PEH.ResultsCompletion of an educational session was associated with a significant increase in knowledge scores (mean pre-test score=10.76/15, SD=2.16; mean post-test score=13.58/15, SD=1.72; p<0.001), with most participants (91%) improving by up to 10 points. The proportion of unvaccinated participants (42%) willing to be vaccinated increased from 21% to 39%. Participants willing to get tested for COVID-19 after a known exposure increased from 83% to 92%. Qualitative findings from the sessions provided insights into key knowledge gaps and revealed participant preferences towards health education format and topics.ConclusionCHW-led COVID-19 education increased knowledge gains and positively influenced attitudes towards vaccination and testing among PEH. Findings highlight the importance of tailored, community-driven interventions for pandemic response and emphasise the crucial role of education in building trust and promoting health literacy to improve health outcomes for vulnerable populations.
Qualitative study on the influence of mealtime screen exposure on children’s feeding practices: perspectives from paediatricians and speech-language pathologists in Chennai, Tamil Nadu
Authors: Fathima Nathira , Venkatraman Krupa , Hariharan Thangatur Sukumar 
Published: December 2024

ObjectiveThis qualitative research study investigates perspectives on the influence of mealtime screen exposure (MTSE) on feeding practices in children through semi-structured interviews with paediatricians and speech-language pathologists (SLPs).DesignThis study used a constructivist paradigm and a qualitative research approach, employing thematic analysis, to understand the research objectives from the lens of practitioners. The researchers used transcripts from semistructured interviews to generate themes.SettingThis was a multisite, in situ research study conducted in healthcare facilities such as hospitals, private clinics and educational institutions in Chennai, Tamil Nadu, India, between March and April 2023.Participants24 participants, 12 SLPs and 12 paediatricians, were interviewed. The researchers selected these participants purposively based on their expertise and experience in dealing with children’s feeding practice-related disorders.ResultsThe study identified six themes: limited awareness of MTSE’s effects, cultural expectations on mothers, screen dependency, sensory deprivation, fragile caregiver–child bonding and picky eating tendencies. Key findings reflect a lack of caregiver awareness, sociocultural pressures and the negative developmental impacts of MTSE on children’s feeding practices.ConclusionsThis study highlights the need for increased awareness among primary caregivers and healthcare professionals regarding the risks of prolonged MTSE. Both paediatricians and SLPs unanimously agree that MTSE can adversely affect feeding practices.