bluuebunny/crossref_metadata_2025_split huggingface dataset:
mSphere of Influence: Seeking the unseen fungi in tumors
Authors: Liu Ning-Ning 
Published: January 2025

ABSTRACT

Ningning Liu works in the field of fungal infection and cancer progression, with a particular focus on the mechanism of host-pathogen interaction. In this mSphere of influence article, he reflects on how papers entitled “The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL,” by B. Aykut, S. Pushalkar, R. Chen, Q. Li, et al. (Nature 574:264–267, 2019,
https://doi.org/10.1038/s41586-019-1608-2
), and “A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors,” by A. B. Dohlman, J. Klug, M. Mesko, I. H. Gao, et al. (Cell 185:3807–3822.E12, 2022,
https://doi.org/10.1016/j.cell.2022.09.015
), emphasized the non-negligible role of fungi in the host and demonstrated a connection between fungi and cancer. These researches arouse his interest in seeking the novel fungal pathogen lurking inside tumors and understanding the unexplored mechanisms behind the severe fungal infections in cancer patients.
Systematic analyses uncover robust salivary microbial signatures and host-microbiome perturbations in oral squamous cell carcinoma
Authors: Han Zewen , Hu Yichen , Lin Xin , Cheng Hongyu , Dong Biao , Liu Xuan , Wu Buling , Xu Zhenjiang Zech 
Published: January 2025

ABSTRACT

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy in the oral-maxillofacial region with a poor prognosis. Oral microbiomes play a potential role in the pathogenesis of this disease. However, findings from individual studies have been inconsistent, and a comprehensive understanding of OSCC-associated microbiome dysbiosis remains elusive. Here, we conducted a large-scale meta-analysis by integrating 11 publicly available data sets comprising salivary microbiome profiles of OSCC patients and healthy controls. After correcting for batch effects, we observed significantly elevated alpha diversity and distinct beta-diversity patterns in the OSCC salivary microbiome compared to healthy controls. Leveraging random effects models, we identified robust microbial signatures associated with OSCC across data sets, including enrichment of taxa such as
Streptococcus
,
Lactobacillus
,
Prevotella
,
Bulleidia moorei
, and
Haemophilus
in OSCC samples. The machine learning models constructed from these microbial markers accurately predicted OSCC status, highlighting their potential as non-invasive diagnostic biomarkers. Intriguingly, our analyses revealed that the age- and gender-associated signatures in normal saliva microbiome were disrupted in the OSCC, suggesting perturbations in the intricate host-microbe interactions. Collectively, our findings uncovered complex alterations in the oral microbiome in OSCC, providing novel insights into disease etiology and paving the way for microbiome-based diagnostic and therapeutic strategies. Given that the salivary microbiome can reflect the overall health status of the host and that saliva sampling is a safe, non-invasive approach, it may be worthwhile to conduct broader screening of the salivary microbiome in high-risk OSCC populations as implications for early detection.

IMPORTANCE
The oral cavity hosts a diverse microbial community that plays a crucial role in systemic and oral health. Accumulated research has investigated significant differences in the saliva microbiota associated with oral cancer, suggesting that microbiome dysbiosis may contribute to the pathogenesis of oral squamous cell carcinoma (OSCC). However, the specific microbial alterations linked to OSCC remain controversial. This meta-analysis reveals robust salivary microbiome alterations. Machine learning models using differential operational taxonomic units accurately predicted OSCC status, highlighting the potential of the salivary microbiome as a non-invasive diagnostic biomarker. Interestingly, age- and gender-associated signatures in the normal salivary microbiome were disrupted in OSCC, suggesting perturbations in host-microbe interactions.
Novel PiuC, PirA, and PiuA mutations leading to
in vivo
cefiderocol resistance progression in IMP-16- and KPC-2-producing
Pseudomonas aeruginosa
from a leukemic patient
Authors: Viñes Joaquim , Herrera Sabina , Vergara Andrea , Roca Ignasi , Vila Jordi , Aiello Tommaso Francesco , Martínez José Antonio , del Río Ana , Lopera Carlos , Garcia-Vidal Carolina , Casals-Pascual Climent , Soriano Àlex , Pitart Cristina 
Published: January 2025

ABSTRACT

Pseudomonas aeruginosa
is an opportunistic pathogen capable of causing severe infections in immunocompromised individuals, who often require prolonged antibiotic therapy. The emergence of carbapenemase-producing
P. aeruginosa
has further complicated the management of nosocomial infections, limiting therapeutic options. Cefiderocol has recently emerged as a promising antipseudomonal agent, using the bacterial iron transport system to gain entry into the cell; however, there have been reports of
P. aeruginosa
resistant to cefiderocol. We describe the
in vivo
cefiderocol resistance progression of four consecutive
P. aeruginosa
isolates from one patient with T-cell acute lymphoblastic leukemia. Analysis of potential genes involved in cefiderocol transport resulted in three genes mutated in two resistant isolates. One isolate presented a S116F substitution in PiuC, and the other presented a deletion of 29 amino acids in the signal peptide of PiuA and a STOP substitution in PirA, resulting in the deletion of a piece of the channel. These mutations increased 24- and 64-folds the cefiderocol minimum inhibitory concentration, respectively. The mutations in the aforementioned genes may directly impact siderophore internalization, thereby contributing to an elevation in the MIC of the antibiotic.

IMPORTANCE

Carbapenem-resistant
Pseudomonas aeruginosa
poses a significant challenge due to its broad antibiotic resistance. Cefiderocol is a novel antibiotic aimed at combating infections caused by such organisms. However, if these pathogens develop resistance to this new drug, it hinders treatment efficacy and options. Therefore, it is crucial to identify and describe mutations in the genes involved in the uptake of cefiderocol to find better treatment strategies for patients infected with multidrug-resistant
P. aeruginosa
.
Characterization of spike S1/S2 processing and entry pathways of lentiviral pseudoviruses bearing seasonal human coronaviruses NL63, 229E, and HKU1 spikes
Authors: Neerukonda Sabari Nath , Vassell Russell , Lusvarghi Sabrina , Liu Shufeng , Akue Adovi , Kukuruga Mark , Wang Tony T. , Weiss Carol D. , Wang Wei 
Published: January 2025

ABSTRACT

Although much has been learned about the entry mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain less well understood. In the present study, we used 293T cell lines stably expressing angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2), which support high-level transduction of lentiviral pseudoviruses bearing spike proteins of seasonal HCoVs, HCoV-NL63, -229E, or -HKU1, respectively, to compare spike processing and virus entry pathways among these viruses. Our results showed that the entry of HCoV-NL63, -229E, and -HKU1 pseudoviruses into cells is sensitive to endosomal acidification inhibitors (chloroquine and NH
4
Cl), indicating entry via the endocytosis route. Although TMPRSS2 expression on target cell surface was required for HCoV-HKU1 spike-mediated entry and cell–cell fusion, we found that only the serine protease domain of TMPRSS2 and not the serine protease activity of TMPRSS2 was required for viral entry via endocytic route. However, the serine protease activity of TMPRSS2 and a furin processing site (RKRR) at the S1/S2 junction were essential for efficient HCoV-HKU1 spike-mediated cell–cell fusion. Additionally, we show that dibasic and monobasic arginine residues at the S1/S2 junctions of spike proteins of HCoV-NL63 and -229E are essential for virus entry, but multi-basic furin processing site at the S1/S2 junction was dispensable for HCoV-HKU1 viral entry. Our findings highlight features of the entry mechanisms of seasonal HCoVs that may support the development of novel treatment strategies.

IMPORTANCE

Details of the entry mechanisms of seasonal human coronaviruses (HCoVs) remain to be fully explored. To investigate spike-mediated virus entry of HCoV-NL63, -229E, and -HKU1 CoVs, we employed 293T cells that stably express angiotensin converting enzyme (ACE2), aminopeptidase N (APN), or transmembrane serine protease 2 (TMPRSS2) to study entry mechanisms of pseudoviruses bearing spike proteins of HCoV-NL63, -229E, and -HKU1, respectively. We found that HCoV-NL63, -229E, and -HKU1 pseudoviruses entered cells via the endocytic route independently of cellular serine protease activity and therefore likely depended on endosomal cathepsin activity. Furthermore, we showed that arginine amino acids in S1/S2 junctions of HCoV-NL63 and -229E spikes were essential for entry but not essential for HCoV-HKU1 entry. Our results provide new insights into the S1/S2 junctional residues, cellular receptors, and protease requirements for seasonal HCoV pseudovirus entry into cells that may support the development of novel inhibitors.
Sellar spine: a rare midline osseous spur
Authors: Rampersad Fidel , Diljohn Jason , Seepersad Sati , Cassim Nicolette 
Published: January 2025

A sellar spine is a rare midline osseous spur, which arises from the dorsum sellae and projects into the pituitary fossa. It can be found incidentally on imaging or may present with symptoms related to optic chiasm compression or hormonal disturbances.Herein, we present the case of an incidentally detected sellar spine in a patient presenting with sudden onset headaches.
Prevalence, predictors and selected outcomes of early sexual initiation among adolescents in secondary schools in Lugbe, Abuja, Nigeria: a mixed methods study
Authors: Okonta Uchechi Grace 
Published: January 2025

BackgroundEarly sexual initiation is the onset of sexual intercourse below 15 years. Despite many negative effects of early sexual initiation, its prevalence has kept increasing globally over the past decades.ObjectiveThis study aims to determine the burden, identify risk factors and examine the selected outcomes of early sexual initiation among secondary school adolescents.DesignThe study was a school-based descriptive cross-sectional survey which employed quantitative and qualitative methods.MethodA descriptive cross-sectional survey was conducted among 300 in-school adolescents aged 15–19 in Lugbe, Abuja. Data were collected using an interviewer-administered questionnaire. Focus group discussion was also conducted in six schools using a structured FGD Guide. The prevalence of early sexual initiation was determined. Descriptive and inferential statistical analysis was done including a binary logistic regression to determine the predictive factors and outcomes of early sexual initiation with statistical inference made at p value <0.05.ResultsThe prevalence of early sexual initiation was 11%; 80% of the respondents who had initiated sex did so before age 15, while 20% had first sex at ages between 15 and 19. Gender, academic performance, communication with parents and peer pressure were significantly associated predictive factors. Pregnancy, abortion, sexually transmitted infections, loss of self-confidence, expulsion from school, poor academic performance and depression were associated outcomes. Four main themes were identified from the qualitative data: being in a romantic relationship, peer pressure, media and lack of parental communication and monitoring.ConclusionThe study concluded that there is high prevalence of early sexual initiation among those who had initiated sex. Predictive factors such as peer pressure, parental communication and media influence can be addressed by the inclusion of sex education in school curriculum and training of peer educators, advocacy and health education for parents of adolescents.
Understanding patient safety during earthquakes: a phenomenological study of disaster response
Authors: Palteki Tunçay , Salimi Saleh , Younas Ahtisham , Taylan Selahattin , Aydın Emre 
Published: January 2025

BackgroundNatural hazards, such as earthquakes, pose a significant risk to both the public and healthcare professionals, jeopardising patient safety due to the disruption of healthcare systems and services. This study aimed to explore the lived experiences of healthcare professionals concerning patient safety during natural hazards, specifically earthquakes.MethodsEmploying a descriptive phenomenological approach, the study followed the Consolidated Criteria for Reporting Qualitative Research guidelines. 23 participants, including doctors, nurses and paramedics, were interviewed using purposive sampling. Data were gathered through semistructured interviews, which were audio recorded and transcribed. Ethical approval was obtained, and Colaizzi’s method was used for data analysis, with findings validated through researcher consensus and participant feedback.ResultsNine overarching themes emerged, such as the emotional toll of communication breakdowns, struggles with patient identification, stress due to resource scarcity, operational chaos, ethical dilemmas and psychological impacts on both patients and staff. The study found that these factors collectively influenced patient safety during the earthquake.ConclusionThe emotional strain caused by communication failures, patient identification issues and resource shortages compounded the challenges of providing safe care during the earthquake. Strengthening disaster preparedness through improved communication systems, resource management, psychological support, interagency coordination and regular realistic disaster drills is essential for safeguarding patient safety in future disasters.
Impact of changes in primary care attachment: a scoping review
Authors: Godfrey Leanda , St-Amant Antoine , Premji Kamila , Fitzsimon Jonathan 
Published: January 2025

ObjectivesPrimary care attachment represents an inclusive, equitable and cost-effective way of enhancing health outcomes globally. However, the growing shortage of family physicians threatens to disrupt patient–provider relationships. Understanding the consequences of these disruptions is essential for guiding future research and policy. The objectives of this study were to map the existing evidence on the impacts of changes in primary care attachment, identify research gaps and recommend areas for further investigation.DesignScoping review following Joanna Briggs Institute (JBI) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews checklist. Two researchers conducted all stages of screening, and study quality was assessed using JBI critical appraisal tools. Key themes included causes of attachment change, direction of change and outcomes aligned with the quintuple aim framework. Both qualitative and quantitative findings were synthesised narratively.Eligibility criteriaPeer-reviewed, English-language articles published between 1999 and 2024 on primary care attachment changes.Information sourcesPubMed, Scopus and Web of Science.ResultsOf 2045 studies screened, 31 met inclusion criteria, with 60% published after 2020. Most studies originated from high-income countries, particularly the USA (35%) and Canada (29%). Attachment losses and transfers were the most frequently studied, while attachment and unattachment durations were less explored. These changes in attachment were consistently shown to impact patients, providers, clinics and the healthcare system, influencing all aims of the quintuple aim framework, including clinical outcomes, healthcare utilisation, costs, equity and patient experience. Commonly assessed outcomes included clinical impact (68%), health equity (48%), patient experience (32%) and costs (23%), with no study assessing provider experience.ConclusionsThis scoping review maps the published literature on changes in primary care attachment and introduces clarifying terminology. Key research gaps include geographical diversity (lack of studies from low- and middle-income countries), attachment gain (limited research on strategies to reconnect unattached patients), attachment duration (insufficient evidence on long-term health outcomes), economic implications (underexplored costs of physician turnover and disruption), provider experiences (lack of studies on how changes in primary care attachment impact provider burnout, job satisfaction and workload) and patient health outcomes (focus on healthcare utilisation rather than direct health outcomes). These findings underscore the need for further research and offer valuable insights for future studies and policy development.
Rapamycin-resistant polyclonal Th1/Tc1 cell therapy (RAPA-201) safely induces disease remissions in relapsed, refractory multiple myeloma
Authors: Dhakal Binod , Hari Parameswaran , Chhabra Saurabh , Szabo Aniko , Lum Lawrence G , Glass Deborah D , Park Jee Hyun , Donato Michele , Siegel David S , Felizardo Tania C , Fowler Daniel H 
Published: January 2025

BackgroundPolyclonal autologous T cells that are epigenetically reprogrammed through mTOR inhibition and IFN-α polarization (RAPA-201) represent a novel approach to the adoptive T cell therapy of cancer. Ex vivo inhibition of mTOR results causes a shift towards T central memory (TCM) whereas ex vivo IFN-α promotes type I cytokines, with each of these functions known to enhance the adoptive T cell therapy of cancer. Rapamycin-resistant T cells polarized for a type II cytokine phenotype were previously evaluated in the allogeneic transplantation context.MethodsThe clinical trial (NCT04176380) evaluated RAPA-201 therapy in combination with fludarabine-sparing low-dose host conditioning for the treatment of patients with relapsed, refractory multiple myeloma (RRMM).ResultsFrom December 2020 to December 2022, 14 patients with RRMM received a median of three RAPA-201 infusions (median dose, 80×106cells). RAPA-201 drug products (DPs) were: polyclonal; enriched for TCMcells; reduced for immune checkpoint expression, including PD1, CD73, and LAIR1; and preferentially secreted Th1 cytokines. The median chemotherapy dose administered per cycle was 1,817 mg total for cyclophosphamide (range, 1,100–2,200) and 2.35 mg/M2for pentostatin (range, 0–16). Nine of 14 patients (64%) achieved disease remission, with eight partial responses and one stringent complete response. Median progression-free survival was 6.0 months (range, 2.1 to>16.8 months). There were no toxicities of any grade attributable to RAPA-201, including no cytokine release syndrome and no immune effector cell-associated neurotoxicity syndrome. Only 4 of 14 patients (29%) had a serious adverse event (≥ grade 3) of any attribution.ConclusionsConsistent with our hypothesis, ex vivo manufacturing using mTOR inhibition and IFN-α polarization consistently yielded a novel RAPA-201 DP that possessed a desirable phenotype relative to cytokine phenotype, memory status, and checkpoint expression. RAPA-201 recipients had preservation of T cell counts and Th1 cytokine secretion yet had increased T cell receptor clonality that associates with antitumor responses in the setting of monoclonal antibody checkpoint therapy. RAPA-201 therapy overcomes previous barriers to effective autologous polyclonal T-cell therapy, as it is feasible to manufacture, exquisitely safe to administer, and mediates remission in patients with RRMM.Trial registration numberClinicalTrials.gov:NCT04176380.
Ischaemia-reperfusion time differences in ST-elevation myocardial infarction in very young patients: a cohort study
Authors: Juan-Salvadores Pablo , De La Torre Fonseca Luis Mariano , Calderon-Cruz Beatriz , Veiga Cesar , Pintos-Rodríguez Samuel , Fernandez Barbeira Saleta , Jimenez Diaz Victor Alfonso , Iñiguez Romo Andres 
Published: January 2025

IntroductionST-elevation myocardial infarction (STEMI) is one of the most prevalent presentations in young patients. It is essential to emphasise that each minute of delay in providing medical care is negatively correlated to the patient’s prognosis. The present study was carried out to evaluate the ischaemia-reperfusion times in patients ≤40 years of age versus individuals >40 years of age and their association with mortality and major adverse cardiac event (MACE) over the long term.MethodsA retrospective, multicentre cohort study was carried out in 6799 patients diagnosed with STEMI. Two groups were established: patients diagnosed with STEMI and aged >40 years, and patients diagnosed with STEMI and aged ≤40 years.ResultsThe patients in the young group had a significantly sooner electrocardiographic diagnosis than the patients >40 years of age. A delay was observed in females, with a relative risk (RR) of 1.21 (95% CI 1.13 to 1.30) (p<0.001). Presenting dyspnoea (RR 1.76, 95% CI 1.5 to 2.06) (p<0.001) or going to a hospital without haemodynamics (RR 1.55, 95% CI 1.45 to 1.67) (p<0.001) was related to increased delay. The occurrence of MACE in the first year of follow-up was related to different risk factors, along with a delay in healthcare (HR 1.25, 95% CI 1.10 to 1.54) (p<0.042).ConclusionThis study shows that young patients with STEMI tend to receive a sooner diagnosis than older individuals. Delays in healthcare represent one of the main factors related to the occurrence of MACE and non-event-free survival.
Detecting higher-order chromosome interactions by polymer modeling
Authors: Conte Mattia , Bianco Simona , Esposito Andrea , Abraham Alex , Guha Sougata , Vercellone Francesca , Fontana Andrea , Di Pierno Florinda 
Published: January 2025

Abstract
Recent experiments have revealed that human chromosomes have an intricate three-dimensional architecture in the cell nucleus, encompassing a hierarchy of interactions across multiple genomic scales. Despite those advances, detecting multiway DNA contacts at the single-molecule level remains challenging. Here, we use polymer physics models to investigate higher-order chromosomal contacts within a key genomic region in human colorectal cancer cells. By running extensive Molecular Dynamics simulations, we test model predictions against available experimental data and show that the model ensemble of single-molecule conformations significantly captures complex multiway chromosomal interactions beyond mere pairwise contacts.
Dynamics of Pinned Pulses in a Class of Nonlinear Reaction–Diffusion Equations with Strong Localized Impurities
Authors: Li Ji , Shen Jianhe , Zhang Qian 
Published: January 2025

For linear reaction–diffusion equations, a general geometric singular perturbation framework was developed, to study the impact of strong, spatially localized, smooth nonlinear impurities on the existence, stability, and bifurcation of localized structure, in the paper [ Doelman et al. , 2018 ]. The multiscale nature enables deriving algebraic conditions determining the existence of pinned single- and multi-pulses. Moreover, linearity enables treating the spectral stability issue for pinned pulses similarly to the problem of existence. In this paper, we move one step further to treat a special type of nonlinear reaction–diffusion equation with the same type of impurity. The additional nonlinear term generates richer and more complex dynamics. We derive algebraic conditions for determining the existence and stability of pinned pulses in terms of Legendre functions.