bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling the full impact of SPD_0739: a key effector in
S. pneumoniae
iron homeostasis
Authors: Womack Edroyal , Antone Melina , Eichenbaum Zehava 
Published: October 2024

ABSTRACT

Streptococcus pneumoniae
is a common member of the nasopharynx commensal microflora and the leading etiological agent of bacterial pneumonia in young children and aging adults. SPD_0739, a highly expressed lipoprotein, is the predicted substrate-binding component of an ABC transporter linked to the uptake of nucleosides and heme by independent studies (named PnrA or Spbhp-37, respectively). Here, we demonstrate that SPD_0739 binds heme
in vitro
and contributes to the bacterial binding to hemoglobin. A ∆
spd_0739
strain exhibited growth attenuation that was relieved by the inactivation of the
piuBCDA
transporter. Knocking out
spd_0739
in the wild type, or the Δ
piuBCDA
strain resulted in heme accumulation, higher sensitivity to heme toxicity, and a small growth reduction compared to medium supplemented with a nucleoside mixture. In addition,
spd_0739
loss results in higher iron- and heme-related gene expression and lower H
2
O
2
production. Altogether, the data are consistent with a role in nucleoside import and show that SPD_0739 does not import heme. Instead, it indirectly influences iron and heme metabolism, linking nucleosides and iron status in
S. pneumonia
e.

IMPORTANCE

S. pneumoniae
obtains growth essential iron from hemoglobin and other host hemoproteins. Still, the bacterial mechanisms involved are only partially understood, and there are inconsistent reports regarding the function of several transporters implicated in iron uptake. In this study, we clarified the role of PnrA/Spbhp-37, a ligand-binding protein previously linked to nucleoside or heme by different studies. We present data supporting a role in nucleoside scavenging rather than heme import and reveal that PnrA/Spbhp-37 modulates iron and heme uptake, likely by influencing the nucleoside cellular pool. Hence, this work provides a new understanding of a process critical to the pathophysiology of a significant human pathogen. Moreover, PnrA/Spbhp-37 is an abundant and immunogenic surface protein that is highly conserved. Hence, this study also clarifies the function of a promising vaccine target.
Evolving use and clinical outcomes of coronary intravascular lithotripsy: insights from an international, multicentre registry
Authors: van Oort Martijn J H , Al Amri Ibtihal , Bingen Brian O , Oliveri Federico , Claessen Bimmer E P M , Dimitriu-Leen Aukelien C , Vossenberg Tessel N , Kefer Joelle , Girgis Hany , van der Kley Frank , Jukema J Wouter , Montero-Cabezas Jose M 
Published: October 2024

BackgroundIntravascular lithotripsy (IVL) is increasingly used for treatment of coronary artery calcification. This study aimed to evaluate contemporary utilisation patterns, safety and efficacy of IVL in an unselected real-world patient cohort.MethodsWe included 454 patients undergoing IVL from May 2019 to February 2024 across seven centres in two European countries. Key endpoints included device success, technical success, procedural success, IVL-related complications and major adverse cardiovascular events (MACE) at 1-year follow-up.ResultsThe cohort (mean age 73±9 years, 75% male) had a mean SYNTAX Score of 22.0±13.6. Device, technical and procedural success were achieved in 98%, 91% and 89% of patients, respectively. IVL-related complications occurred in six patients (1%). At 1-year follow-up, MACE was observed in 37 patients (13%). Over time, IVL use increased in patients with acute coronary syndrome (p=0.004) and in combination with intracoronary imaging (p=0.002), while use of other calcium modification devices decreased (p=0.034).ConclusionIn this real-world registry, IVL demonstrated efficacy across diverse clinical and anatomical settings. High success rates, low complication rates and MACE rates were observed acutely and at 1-year follow-up. Utilisation patterns evolved over time, with increased adoption in acute scenarios and alongside intracoronary imaging.
Changes in price, income and e-cigarette affordability for young people in the USA from 2015 to 2021
Authors: Diaz Megan C , Braganza Karl , Minter Tyler , Hair Elizabeth C , Tauras John A. 
Published: October 2024

BackgroundE-cigarette products are the most popular tobacco/nicotine product used among youth and young adults in the USA. While emerging research has shown that e-cigarette taxes increase their price, no study to date has examined e-cigarette tax burdens nor their affordability for youth and young adults.MethodsUsing real (2021 US dollars) prices per mL of e-liquid data from NielsenIQ and annual real (2021 US dollars) personal income data from Integrated Public Use Microdata Series, we calculate relative income prices and examine average annual percentage changes in affordability using Joinpoint trend analysis from 2015 to 2021. In addition, we use tax data to calculate e-cigarette tax burdens as a percentage of price per 1 mL of e-liquid.ResultsIn all states analysed, tax burdens increased from 2015 to 2021. E-cigarette prices decreased considerably from 2019 to 2021; in 2021 the real (2021 US dollars) average price of 1 mL of e-liquid was US$4.45. E-cigarettes on average became more affordable for all age groups and states; however, e-cigarettes tended to be less affordable in states with ad-valorem tax structures. On average, 16–17-year-olds needed 31% of their annual income to purchase 100 mL of e-liquid, whereas 18–19-year-olds, 20–24-year-olds and 25–34-year-olds needed 9%, 3% and 1%, respectively.ConclusionsE-cigarettes have become more affordable for young people, but less so in states with ad-valorem tax structures. Policy efforts should focus on reducing e-cigarette affordability, especially for youth, through tax-induced increases in e-cigarette prices to levels high enough to outpace income growth.
Transformation of the tobacco product market in Japan, 2011–2023
Authors: Cummings K Michael , Roberson Avery , Levy David T , Meza Rafael , Warner Kenneth E , Fong Geoffrey T , Xu Steve Shaowei , Gravely Shannon , Dhungel Bibha , Borland Ron , O'Connor Richard J , Goniewicz Maciej Lukasz , Sweanor David T 
Published: October 2024

ObjectiveThis study updates a previous paper that examined trends in the sale of cigarettes and heated tobacco products (HTPs) in Japan between 2011 and part way through 2019. The current study includes complete unit sales data through 2023.MethodsData on cigarette and HTP sales were obtained from public sources available from the websites and stockholder reports for the Tobacco Institute of Japan, Philip Morris International and Japan Tobacco. We used joinpoint regression using the parametric method to test for trends in both per capita and total sales for the three outcome variables assessed between 2011 and 2023: (1) cigarette sales, (2) HTP sales and (3) combined cigarette and HTP sales. Joinpoint regression identifies changes in trends and estimates the annual per cent change (APC) for each trend segment.ResultsBetween 2011 and 2023, per capita and total cigarette sales declined by 52.6% and 52.7%, respectively. From 2011 to 2015, per capita cigarette sales in Japan decreased −1.5% APC; from 2015 to 2018, the decline accelerated to −10.5% APC and continued to fall −7.3% APC between 2018 and 2023. Between 2016 and 2018, per capita HTP sales increased by 149.0% APC, and since 2018, they have increased by 8.1% APC.ConclusionWhile many factors may account for the decreased sale of cigarettes in Japan over the past 12 years, the increased sale of HTPs appears to be a factor.
Theoretical Calculation of Vacuum Energy Density Based on the Fractal Quantum Gravity Theory
Authors: Li Shuming , Huang Lihua Li , Huang Joyce , Li Shuwei 
Published: October 2024

There has been a huge discrepancy between the vacuum energy density calculated based on the existing quantum theories and the observational values. The calculated vacuum energy density is about 120 orders of magnitude greater than its observational values, which is one of the worst theoretical predictions in the history of modern physics. As a promising quantum gravity theory, the newly developed fractal quantum gravity (FQG) theory has introduced the smallest constant of the product of space, time and energy of Space-Time Quantum of Action (STQA). The product of space, time and energy of every particle is integer times of this smallest constant — STQA. Based on the FQG equation, we have calculated the vacuum energy density which is a perfect match with its observational values. This recent development has shed much insight into the intrinsic nature of vacuum and it will continue to provide guidance of future research in the area of dark energy.
Point-of-Care Sensor Using Modified Nickel-doped Zinc Oxide Nanoparticle Carbon Paste Electrode for Homovanillic Acid Cancer Biomarker Detection in Urine
Authors: Abdalla Rana , Mahmoud Amr M. , Abou Al-Alamein Amal M. , Galal Maha M. , El Mously Dina A. 
Published: October 2024

The prevalence of cancer worldwide has prompted efforts to develop and produce a range of electrochemical biosensors for cancer diagnosis. Efficient cancer diagnosis can be enhanced by the sensitive detection of biomarkers, which can also lower the cost of medical diagnostics. Neuroblastoma is an embryonic cancer arising from neural crest stem cells and is considered the most common malignancy in infants and the extracranial solid tumor in children. In this paper, we describe the construction of a nanoparticle-modified electrochemical sensor for detecting and quantifying homovanillic acid (HVA), a biomarker for neuroblastoma. The electrooxidation of HVA was studied at a carbon paste electrode (CPE) modified with nickel-doped zinc oxide nanoparticles (Ni-ZnO NPs). The use of these nanoparticles enhanced electrochemical sensitivity and the electrocatalytic activity. The differential pulse voltammetric response of HVA was found to be linear in the concentration range of (3.96 × 10−6 to 3.83 × 10−5 M) with a lower detection limit of 1.01 × 10−6 M. The electrode demonstrated good stability in the HVA determination process, with a minor decrease in response after 10 weeks. The proposed sensor was successfully applied to determine HVA in a urine sample with a good detection result and a worthwhile biological impact.
Nursing Faculty Shortage Impact on Nursing Students: A Descriptive Phenomenological Study
Authors: Antig Asia , Arañez Shaniah , Cañazares Chariemae , Palompon Daisy 
Published: October 2024

Background: The nursing education sector has felt the impact of the shortage of nursing clinical instructors (CI) or faculty members. This phenomenon became more profound with the pandemic experience along with the global shortage of nurses in the hospitals.Objective: The study was conducted to explore the lived experiences on learning among undergraduate nursing students in a higher education institution amidst the nursing faculty shortage.Methods: The study was undertaken using a descriptive phenomenological design with seven informants, using Colaizzi’s approach for data analysis.Findings: The findings of the study generated three main themes: disruptions in the learning process and platforms, responses to learning disruptions, and learners’ call to action. It uncovered substantial disruptions in scheduled lectures, activities, and clinical rotations due to the nursing faculty shortage.Conclusion: The findings underscore the critical need for immediate and comprehensive measures to address the nursing faculty shortage. Despite compensatory efforts by the institution, the impact on learning experience remains significant. This study calls for prompt and effective strategies to rectify the nursing faculty shortage, ensuring optimal learning experiences for student nurses.
ITGA1 Promotes Glioma Cell Proliferation and Affects Immune Cell Infiltration in Low‐Grade Glioma
Authors: Ren Yanhong , Xu Jianchang , Zhang Zhengkui , Yu Rutong 
Published: October 2024

Background: Low‐grade glioma (LGG) is a commonly occurring type of central nervous system cancer. Integrin α1 (ITGA1), a family member of integrins, is implied in the malignant development of cancers, but the fundamental role of ITGA1 has not been illustrated yet in glioma. This study aimed to evaluate the prognostic value of ITGA1.Methods: Correlations between ITGA1 and relevant clinical features were analyzed in the LGG datasets based on Chinese Glioma Genome Atlas (CGGA) and Tumor Genome Atlas (TCGA). Glioma clinical samples and glioma cell lines were identified at the level of mRNA and protein level by Western blot. Cox regression were developed to assess the involvement of ITGA1 expression in predicting survival in LGG patients. Application of GSEA enrichment analysis to reveal ITGA1‐mediated biological functions in LGG. Using TIMER 2.0 to analyze correlations between immune cell infiltration. In addition, ITGA1 high expression was analyzed for correlation with immune checkpoint‐related genes and cumulative survival time.Results: ITGA1 was significantly more expressed in LGG than in normal samples. Cox regression indicated that ITGA1 was a risk factor independently for prognosis in LGG patients. GSEA enrichment analysis indicated that ITGA1 was engaged in several immunomodulatory processes. ITGA1 expression was shown to be highly correlated with the immune score, stromal score, and estimate score in LGG. ITGA1 was significantly related to the immune checkpoint‐associated gene expression. In vivo experiments showed that overexpression of ITGA1 promoted glioma cell invasion.Conclusion: High ITGA1 expression is correlated with immune infiltration of the low‐grade tumor, leading to poor prognoses in LGG patients.
SpliceMutr Enables Pan-Cancer Analysis of Splicing-Derived Neoantigen Burden in Tumors
Authors: Palmer Theron , Kessler Michael D. , Shao Xiaoshan M. , Balan Archana , Yarchoan Mark , Zaidi Neeha , Lopez-Vidal Tamara Y. , Saeed Ali M. , Gore Jessica , Azad Nilofer S. , Jaffee Elizabeth M. , Favorov Alexander V. , Anagnostou Valsamo , Karchin Rachel , Gaykalova Daria A. , Fertig Elana J. , Danilova Ludmila 
Published: October 2024

Abstract
Aberrant alternative splicing can generate neoantigens, which can themselves stimulate immune responses and surveillance. Previous methods for quantifying splicing-derived neoantigens are limited by independent references and potential batch effects. Here, we introduce SpliceMutr, a bioinformatics approach and pipeline for identifying splicing-derived neoantigens from tumor and normal data. SpliceMutr facilitates the identification of tumor-specific antigenic splice variants, predicts MHC-binding affinity, and estimates splicing antigenicity scores per gene. By applying this tool to transcriptomic data from The Cancer Genome Atlas, we generate splicing-derived neoantigens and neoantigenicity scores per sample and across all cancer types and find numerous correlations between splicing antigenicity and well-established biomarkers of antitumor immunity. Notably, carriers of mutations within splicing machinery genes have higher splicing antigenicity, which provides support for our approach. Further analysis of splicing antigenicity in cohorts of patients with melanoma treated with mono- or combined immune checkpoint inhibition suggests that the abundance of splicing antigens is reduced post-treatment from baseline in patients who progress. We also observe increased splicing antigenicity in responders to immunotherapy, which may relate to an increased capacity to mount an immune response to splicing-derived antigens. We find the splicing antigenicity to be higher in tumor samples when compared with normal, that mutations in the splicing machinery result in increased splicing antigenicity in some cancers, and higher splicing antigenicity is associated with positive response to immune checkpoint inhibitor therapies. Furthermore, this new computational pipeline provides novel analytical capabilities for splicing antigenicity and is openly available for further immuno-oncology analysis.

Significance:
SpliceMutr shows that splicing antigenicity changes in response to ICI therapies and that native modulation of the splicing machinery through mutations increases the contribution of splicing to the neoantigen load of some The Cancer Genome Atlas cancer subtypes. Future studies of the relationship between splicing antigenicity and immune checkpoint inhibitor response pan-cancer are essential to establish the interplay between antigen heterogeneity and immunotherapy regimen on patient response.
The Significance of Comprehensive Metabolic Phenotypes in Cancer Risk: A Japan Multi-Institutional Collaborative Cohort Study
Authors: Watanabe Takeshi , Nguyen Tien Van , Katsuura-Kamano Sakurako , Arisawa Kokichi , Ishizu Masashi , Unohara Taichi , Tanaka Keitaro , Shimanoe Chisato , Nagayoshi Mako , Tamura Takashi , Kubo Yuko , Kato Yasufumi , Oze Isao , Ito Hidemi , Michihata Nobuaki , Nakamura Yohko , Tanoue Shiroh , Koriyama Chihaya , Suzuki Sadao , Nakagawa-Senda Hiroko , Koyama Teruhide , Tomida Satomi , Kuriki Kiyonori , Takashima Naoyuki , Harada Akiko , Wakai Kenji , Matsuo Keitaro ,   for the J-MICC Study Group
Published: October 2024

Abstract
The present study investigated the relationship between metabolic phenotypes and the risk of cancer in a Japanese population using the criteria of metabolic phenotypes based on an examination and those based on questionnaires. We used data from 25,357 subjects for examination-based analyses and those from 53,042 subjects for questionnaire-based analyses in the Japan Multi-institutional Collaborative Cohort study. Metabolic phenotypes were defined by classifying subjects according to their body mass index (BMI; obesity: BMI  ≥25 kg/m2; normal weight: BMI  &lt;25 kg/m2) and the number of metabolic abnormalities. Metabolic abnormalities were defined according to metabolic syndrome components of the Joint Interim Statement criteria for examination-based analyses and self-reported histories of diabetes, dyslipidemia, and hypertension for questionnaire-based analyses. Cox proportional hazards regression analyses adjusted for potential confounders were performed for total and site-specific cancer incidence rates according to metabolic phenotypes. Metabolically unhealthy obesity (MUHO) was significantly associated with cancer incidence in both examination-based [HR (95% confidence interval), 1.17 (1.01–1.36)] and questionnaire-based analyses [HR (95% confidence interval), 1.15 (1.04–1.26)]. Regarding site-specific cancer in questionnaire-based analyses, metabolically healthy obesity and MUHO were associated with colorectum and liver cancers in all subjects and with breast cancer in female subjects. Subjects with a metabolically unhealthy normal weight had a higher risk of pancreatic cancer. Moreover, MUHO was associated with corpus uteri cancer in female subjects. This prospective cohort study suggests that metabolic phenotypes are important risk factors for total and some site-specific cancers in Japanese adults.

Significance:
The prospective cohort study in a large Japanese population suggested that metabolic phenotypes are important risk factors for total and some site-specific cancers in Japanese adults. Moreover, the risk of each site-specific cancer may differ according to metabolic phenotypes.
Short-term conservation education influences Ugandan adolescents’ knowledge, attitudes and investment decisions
Authors: Bogese Michael , Ho Jackie Y. , O’Donnell Claire , Otali Emily , Tusiime Patrick , Ross Elizabeth , Kahlenberg Sonya , Machanda Zarin , McAuliffe Katherine 
Published: October 2024

Abstract
Environmental education research methods often focus on measuring changes in people’s attitudes toward conservation. While attitudes are an important indicator of change, it is critical to target incentivised behaviour because conservation efforts often involve behavioural changes that are costly to one’s self (e.g., reducing water use, purchasing pricier alternatives). In the present study, we measured both attitudes and behaviours in a short-term conservation education program near the primate-rich Kibale National Forest in Western Uganda. Adolescents () participated in a three-hour curriculum over three weeks integrated into an after-school wildlife club. After almost 30 years of successful primate conservation education in this region, we chose a novel taxonomic group (bats) for this study. Our pre-registered study had two conditions: an experimental condition, in which students learned about bats as an important local pollinator species, and a control condition, in which students learned about the moon. Only the experimental condition emphasised conservation’s delayed benefits. We compared attitudes, knowledge, and behaviours pre- and post- curriculum. To capture behaviour, we employed an investment task in which participants could invest their own resources in a ‘fund’ to support work relating to bats or the moon, depending on condition. Across both conditions, participants showed positive shifts in attitudes and knowledge from pre- to post-measures and showed increased investments in bat- and moon-related funds. These findings reveal that short-term conservation education influences adolescents’ investment decisions as well as their attitudes and knowledge. Our method can easily be edited for conservation education of any species including endangered primates.
Effects of food level and fecal material on the plasticity of metamorphic traits in Asiatic toad, Bufo gargarizans, in Central China
Authors: Yu Tong L. , Gu Chao F. , Yang Tao , Zhang Meng Y. 
Published: October 2024

Abstract
According to Richards’ hypothesis, the presence of a nonpigmented unicellular alga in the intestinal tract of tadpoles is believed to be the inhibitory factor that affects their growth. It is proposed that thecanimals eat their fecal material containing these algal cells, which are then reintroduced into their systems when the alga is shed with the feces and dropped to the bottom. In this study, we aimed to investigate the plasticity of metamorphic traits in the Asiatic toad (Bufo gargarizans) under different combinations of fecal material and food levels. Our findings revealed that B. gargarizans tadpoles reared at high food levels exhibited accelerated larval periods but had smaller metamorphic sizes compared to those reared at low food levels. This suggests that the tadpoles prioritize rapid development at the expense of body mass during metamorphosis. Furthermore, our study discovered evidence supporting the positive effect of fecal material on tadpole growth, as indicated by the investigation of growth rate. Importantly, the presence of feces did not result in smaller body mass on average for Asiatic toad tadpoles compared to those raised in the absence of fecal material. The difference in body mass between fecal material treatments tended to be smaller at low food levels, implying that feces does not inhibit growth in B. gargarizans tadpoles. Therefore, our results contradict Richards’ hypothesis and provide support for a novel mechanism that is selected for in areas where coprophagy is likely to be advantageous, particularly in times of food scarcity.