bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi-Center “Replica Study” Challenges the Impact of Electronic Cigarette Aerosols on Cisplatin Resistance in Head and Neck Cancer Cells
Authors: Emma R. , Carota G. , Partsinevelos K. , Rust S. , Sun A. , Giordano A. , Volarevic V. , Lesmana R. , Goenawan H. , Barliana M. I. , Arsenijevic A. , Kastratovic N. , Spasic B. , Giardina Chiara , Cantali Miriana , Polosa R. , Caruso M. , Li Volti G. 
Published: January 2025

AbstractBackgroundCisplatin chemoresistance is a critical challenge in the treatment of head and neck squamous cell carcinoma (HNSCC). Since previous research has suggested that nicotine and e-cigarette (e-cig) aerosol might increase cisplatin resistance in oral cancer cells, this multicenter replication study aimed to replicate the work by Manyanga et al. (2021) and evaluate the oncologic implications of e-cigarette exposure during chemotherapy.MethodsThis in vitro study involved standardized and harmonized protocols in international laboratories to examine the effects of cigarette smoke (1R6F) and e-cig aerosols with different concentrations of nicotine (0, 12, and 20 mg/ml nicotine) on cisplatin sensitivity in HNSCC cell lines (SCC-25, FaDu, and UM-SCC-1). Aerosols from 1R6F smoke and e-cig vapor were collected using a smoking and vaping machine, following ISO20778:2018 and ISO20768:2018 puffing regimes. The smoke and vapor were collected in PBS and diluted to 10 puffs/5L for HNSCC cell treatment. Chemosensitivity, clonogenicity, expression of gene for repair of cisplatin-induced DNA damage and gene and protein expression of cisplatin transporters were assessed by MTS, NRU, trypan blue, PCR, and Western blot assays, respectively.ResultsContrary to previous findings, exposure to e-cig aerosols did not significantly modulate cisplatin sensitivity in all cell lines. IC50 values, cytotoxicity assays, and clonogenic survival rates remained similar between e-cig treatments and cisplatin alone. Analysis of gene and protein expression revealed sporadic changes in the levels of transporters and repairs of cisplatin-induced DNA damage.ConclusionsThis study did not fully substantiate previous claims of increased cisplatin resistance due to e-cigarette aerosols and nicotine. The variability in gene and protein expression among different cell lines underscores the need for cautious interpretation and further investigation of the role of e-cigarette components in cancer treatment. These findings provide a critical perspective for shaping public health policies and clinical practices related to e-cigarette use during chemotherapy.
Phase II trial of chemotherapy, cetuximab and erlotinib in patients with metastatic or recurrent squamous cell carcinoma of the head and neck
Authors: Bhatia Aarti , Mehra Ranee , Bauman Jessica , Khan Saad A. , Wei Wei , Neumeister Veronique , Sandoval-Schaefer Teresa , Alpaugh R. Katherine , Lango Miriam , Rimm David L. , Ridge John A. , Burtness Barbara 
Published: January 2025

ABSTRACTPrognosis for patients with recurrent/metastatic (R/M) head and neck squamous cell cancer (HNSCC) remains poor. We hypothesized that the addition of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) to standard therapy would improve responses by inhibiting nuclear translocation of EGFR and designed a phase 2 trial of chemotherapy, cetuximab and erlotinib in patients with R/M HNSCC.24 patients were enrolled and treated with carboplatin, paclitaxel and cetuximab administered in 21-day cycles. Erlotinib was added with cycle 2. Primary end point was objective response rate (ORR). Secondary end points were toxicity, overall survival (OS) and laboratory correlates.Median age was 65.5 years. Median duration on treatment was 4.6 months. ORR with cycle 1 of treatment was 33.3%, and for cycle 2 and beyond was 62.5%. Median progression-free survival (PFS) was 6.2 months, and median OS was 10.6 months. Most common treatment-related adverse events included anemia, neutropenia, skin rash, diarrhea, and hypomagnesemia.Dual EGFR blockade was tolerable and efficacious in this small patient sample. With an ORR of 62.5%, the study met its primary endpoint. PFS and OS were comparable to historical controls. Dual EGFR targeting without the chemotherapy backbone is worthy of further study.Clinical trial information:NCT01316757. Study registered March 8th, 2011
Acceptability of pre-exposure prophylaxis and associated factors among HIV-negative young men in Kagwara fishing community- Serere district: a cross-sectional study
Authors: Omoding Alex , Opito Ronald , Oboth Paul , Okello Francis , Matovu Joseph KB 
Published: January 2025

AbstractBackgroundDespite the potential efficacy of Pre-Exposure Prophylaxis (PrEP) in reducing HIV risk among at-risk populations, PrEP acceptability remains strikingly varied across populations. We assessed PrEP acceptability and associated factors among at-risk HIV-negative young men in Kagwara fishing community, Serere district.MethodsA cross-sectional quantitative study design was used. Data were collected among 409 at-risk HIV-negative young men aged 15-24 years living in Kagwara fishing community, between August and October 2023. Quantitative data were collected on socio-demographic characteristics, sexual-risk behaviors, knowledge, attitudes, and practices regarding PrEP acceptability. PrEP acceptability was defined as the proportion of young men accepting to use PrEP out of those interviewed, based on six constructs adopted from acceptability framework. Data analyzed using Stata version 15.0 statistical software. Summary statistics computed and presented as tables, frequencies and proportions. Bivariate analysis was conducted using penalized logistic regression to identify independent factors associated with PrEP acceptability. All factors that had p<0.10 at the bivariate analysis and suspected confounders were entered into the final logistic regression model. All factors with p<0.05 were significantly associated with the primary outcome.ResultsOf 409 respondents, average age was 21.8(SD=1.9) years. Majority, (97.8%, n=393) had unprotected penetrative sex while 84.6% (n=346) did not know HIV status of their partners. PrEP acceptability was high at 93.6% (n=383) as majority of the participants accepted to use PrEP based on the six constructs of acceptability. At multivariable level, the factors associated with PrEP acceptability were; perceived risk of getting HIV infection, adjusted odds ratio (aOR)(95%CI)=4.23(1.05, 17.04), knowing the partner’s HIV status, aOR (95%CI) = 0.25 (0.07, 0.88), feeling embarrassed to ask for PrEP from the facility, aOR (95%CI) = 0.12 (0.04, 0.39), and having concern of stigma associated with use of PrEP, aOR = 0.13 (95% CI, 0.04-0.41).ConclusionWe found a high level of PrEP acceptability among at-risk HIV-negative young men in Kagwara fishing community. Improving access to PrEP services among at-risk young men in the fishing communities may increase PrEP uptake in this population and across similar settings.
Heart rate fragmentation improves general anesthesia state classification using machine learning
Authors: Fauchereau Clément , Carimalo Fanny , Merienne Axelle , Laffon Marc , Godat Emmanuel , Aude Jean-Christophe 
Published: January 2025

AbstractAccurate assessment of consciousness during general anesthesia is crucial for optimizing anesthetic dosage and patient safety. Current electroencephalogram-based monitoring devices can be inaccurate or unreliable in specific surgical contexts (e.g. cephalic procedures). This study investigated the feasibility of using electrocardiogram (ECG) features and machine learning to differentiate between awake and anesthetized states. A cohort of 48 patients undergoing surgery under general anesthesia at the Tours hospital was recruited. ECG-derived features were extracted, including spectral power, heart rate variability and complexity metrics, as well as heart rate fragmentation indices (HRF). These features were augmented by a range of physiological variables. The aim was to evaluate a number of machine learning algorithms in order to identify the most appropriate method for classifying the awake and anesthetized states. The gradient boosting algorithm achieved the highest accuracy (0.84). Notably, HRF metrics exhibited the strongest predictive power across all models tested. The generalizability of this ECG-based approach was further assessed using public datasets (VitalDB, Fantasia, and MIT-BIH Polysomnographic), achieving accuracies above 0.80. This study provides evidence that ECG-based classification methods can effectively distinguish awake from anesthetized states, with HRF indices playing a pivotal role in this classification.Author summaryGeneral anesthesia monitoring is critical for optimizing patient safety and outcomes. While electroencephalogram (EEG)-based systems are commonly used, they have limitations in accuracy and applicability, particularly in cases where EEG electrodes placement is challenging or impossible, such as during cephalic surgeries or when patients have forehead skin lesions. Here, a novel approach using electrocardiogram (ECG) signals and machine learning techniques was used to differentiate between awake and anesthetized states during surgery. A total of 48 patients undergoing surgical procedures under general anaesthesia at the Tours hospital were selected for inclusion in the study. This investigation focused on heart rate fragmentation indices, metrics designed for assessing biological versus chronological age, derived from ECG recordings. The gradient boosting algorithm demonstrates performance comparable to leading methods reported in the literature for this classification task. Importantly, model generalizability was confirm through successful application to publicly available datasets. This article highlights the potential of ECG signals as an alternative source for deriving depth of anesthesia indices, offering increased versatility in clinical settings where EEG monitoring is challenging or contraindicated.
Lack of evidence for obesity paradox in patients with cardiovascular diseases: A UK BioBank cohort study
Authors: Yu Wenhao , Fan Bingbing , Yang Lin , Si Shucheng , Chen Wei , Zhang Tao , Xue Fuzhong , Li Shengxu 
Published: January 2025

AbstractBackgroundObesity paradox, a phenomenon that obesity seems to be associated with reduced risk of mortality in patients with established cardiovascular disease (CVD), has been controversial. We aimed to use Mendelian randomization to examine the causal relationship between obesity measures and CVD mortality in patients with known CVD in the UK BioBank study cohort.MethodsA total of 58,278 participants with CVD were included. Polygenic risk scores (PRSs) for body mass index (BMI), body fat percentage (BF%), and waist to hip ration adjusted for BMI (WHRadjBMI) were used as instrumental variables. The following sensitivity analyses were performed: 1) using a representative variant rs1558902 in the fat mass and obesity associated gene as an instrumental variable, 2) by sex, and 3) by disease type.ResultsA total of 2203 patients died of CVD causes during a median follow-up period of 8.9 years. BMI in the overweight and class-I obesity range was associated with reduced mortality, with class-II or more severe obesity associated with increased mortality; however, there was a linear trend toward increased mortality with increasing BF% and WHRadjBMI. There was no clear indication that increased obesity-PRSs were associated with reduced risk of CVD mortality among individuals with known CVD. Sensitivity analyses using rs1558902 as an instrumental variable, by sex, and by disease type showed similar results.ConclusionIncreased obesity does not show a protective effect in patients with CVD. Previously reported obesity paradox in observational studies may be a result of confounding or other biases, which needs further investigation.
Are ant-plant mutualisms stronger at lower latitudes? A case study using the castor plant in the Indian subcontinent
Authors: Nathan Pooja , Shahid Arshyaan , Datta Anoushka , Gowda Vinita , Frederickson Megan E. 
Published: January 2025

AbstractThe Biotic Interactions Hypothesis (BIH) predicts that species interactions will intensify from the poles to the tropics. We studied the ant-plant defensive interaction mediated by extrafloral nectaries (EFNs) in the castor bean plant,Ricinus communis,across a ∼21° latitudinal gradient in its naturalized range in India. Among our study sites, we found that the ant-EFN mutualism in castor bean gets stronger from sub-tropical to tropical latitudes. Investment in mutualism by plants and visitation by ants increased from higher to lower latitudes. Further, latitude significantly explained ant community composition. However, contrary to the predictions of the BIH, standing herbivory increased with latitude, perhaps because plants invest less in biotic defence at higher latitudes. To our knowledge, our study is the first to test for the patterns predicted by the BIH for an ant-plant interaction in the Paleotropics. Results from our study can also help inform sustainable pest control practices forR. communissince India is the world’s largest producer of castor oil.
Optimising synthetic cystic fibrosis sputum media for growth of non-typeableHaemophilus influenzae
Authors: Do Carmo Silva Phoebe , Hill Darryl , Harrison Freya 
Published: January 2025

AbstractNon-typeableHaemophilus influenzae(NTHi) is an early pathogen isolated from the lungs of children with cystic fibrosis (CF). However, its role in the progression of CF lung infection is poorly understood. Additionally, whether it forms biofilms in the lungs of people with CF is an open question. The development of synthetic cystic fibrosis sputum media has given key insights into the microbiology of later CF pathogens,Pseudomonas aeruginosaandStaphylococcus aureus, through replicating the chemical composition of CF sputum. However, growth of NTHi in these media has not previously been reported. We show that NTHi grows poorly in three variants of synthetic cystic fibrosis sputum media commonly used to inducein vivo-like growth ofP. aeruginosaandS. aureus(SCFM1, SCFM2 and SCFM3). The addition of NAD and hemin to SCFM1 and SCFM2 promoted the planktonic growth and biofilm formation of both laboratory and clinical NTHi isolates, and we were able to develop a modified variant of SCFM2 that allows culture of NTHis. We show that NTHi cannot be identified in an establishedex-vivomodel of CF infection, which uses SCFM and porcine bronchiolar tissue. This may in part be due to the presence of endogenous bacteria on the pig lung tissue which outcompete NTHi, but the lack of selective agar to isolate NTHi from endogenous bacteria, and the fact that NTHi is an exclusively human pathogen, make it hard to conclude that this is the case. Through spiking modified SCFM2 with filter sterilized lung homogenate, biofilm growth of clinical NTHi isolates was enhanced. Our results highlight that there are crucial components present in the lung tissue which NTHi require for growth, that are not present in any published variant of SCFM from the Palmer et al. 2007 lineage. Our results may inform future modifications to SCFM recipes to truly mimic the environment of CF lung sputum, and thus, to facilitate study of a wide range of CF pathogens.Data SummaryThe authors confirm that all supporting data, code and protocols have been provided within the article or through supplementary data files. All raw data has been uploaded to FigShare (https://doi.org/10.6084/m9.figshare.28175300.v1).
Abundant and active acetogens enhance the carbon dioxide sink of Blue Carbon ecosystems
Authors: Rodriguez Karen , Ricci Francesco , Ni Gaofeng , Iram Naima , Palfreyman Robin , Gonzalez-Garcia Ricardo A. , Heffernan James , Greening Chris , Adame Maria Fernanda , Marcellin Esteban 
Published: January 2025

AbstractBlue Carbon ecosystems, which include all tidal wetlands, mitigate climate change by capturing and storing carbon dioxide (CO2) from the atmosphere. Most carbon fixation in these systems is thought to be driven by plant and microbial photosynthesis, whereas chemosynthetic processes are assumed to play a minor role. However, these ecosystems often contain anoxic environments ideal for chemosynthetic microbes such as acetogens. Here, we show that acetogens are abundant and active mediators of carbon sequestration in tidal wetland soils by pairing gene-and genome-resolved metagenomic analysis with isolation and analysis of gas-fermenting acetogens in bioreactors. Metagenomic profiling revealed that diverse microbes can mediate carbon fixation, primarily through the Calvin-Benson-Bassham cycle and Wood-Ljungdahl pathways. These include various bacteria and archaea capable of reductive acetogenesis. On this basis, we grew bacterial enrichment cultures from tidal wetland soils using the gases hydrogen and CO2as the sole energy and carbon sources. Bioreactor analysis revealed that these enrichments are dominated by clostridial acetogens that grow rapidly by converting CO2into acetate and other products. Collectively, these results reveal Blue Carbon ecosystems harbour communities that can exclusively subsist by using CO2as their sole electron acceptor and for carbon fixation, thereby providing evidence of a novel carbon sink pathway within these ecosystems beyond the known mechanisms of photosynthetic carbon fixation and soil sequestration. Additionally, the discovery and isolation of these chemosynthetic communities provide opportunities for developing further mechanisms of CO2removal through industrial gas fermentation.
Identification of ER:melanosome membrane contact sites in the retinal pigment epithelium
Authors: Burgoyne T. , Doncheva D. , Eden E.R. 
Published: January 2025

AbstractThe retinal pigment epithelium (RPE) forms a monolayer of cells at the blood:retina interface that plays important roles for photoreceptor renewal and function and is central to retinal health. RPE pigment is provided by melanin-containing melanosomes which offer protection against light and oxidative stress. Melanosome migration into the apical processes of the RPE following light onset is thought to contribute to preventing retinal degeneration with age, though the mechanism is not yet clear. Melanosomes are transported along microtubules to the apical surface where they are transferred to actin filaments within the apical processes. Melanosomes are lysosome-related organelles derived from endosomes and endosome transport along microtubules is heavily influenced by the endoplasmic reticulum (ER) through ER:endosome contact sites. Here we describe extensive connection between the ER and melanosomes in the RPE. We further show, in skin melanocytes, that the ER forms contact sites with all stages of melanosome maturation, but ER contact is reduced as melanosomes mature. Finally, we identify tripartite contact sites between the ER, melanosomes and mitochondria in both RPE tissue and cellular models, suggesting that the ER may influence melanosome biogenesis, maturation and interaction with mitochondria.
A chemical genomic screen identifies novel genetic interactors of the methylation-dependentde novo pathwayof phosphatidylcholine biosynthesis inSaccharomyces cerevisiae
Authors: Maliva Amanda , Riekhof Wayne R. 
Published: January 2025

AbstractPhosphatidylcholine (PtdCho) is the most abundant phospholipid in most eukaryotic cell and organelle membranes, and cells must regulate its synthesis and interorganelle transport to maintain correct membrane compositions and biophysical properties. Our knowledge of genes encoding enzymes of PtdCho biosynthesis is largely complete, and a great deal is understood about their localization and regulation, however our understanding of molecular mechanisms regulating PtdCho biosynthesis and trafficking remains incomplete. To identify genes that show epistatic relationships with the methylation pathway of PtdCho biosynthesis, we performed a chemical-genomic screen of aSaccharomyces cerevisiaegene-deletion mutant collection using a phosphatidylethanolamine (PtdEtn) methyltransferase inhibitor, 2-hydroxyethylhydrazine (HEH). HEH functions by selectively inhibiting the PtdEtn methyltransferase enzymes Pem1p/Cho2p and Pem2p/Opi3p. We demonstrate that the addition of exogenous choline or lyso-phosphatidylcholine can recover HEH-mediated growth inhibition, and used this finding to design a functional-genomic screen to identify genes which, when deleted, render the strain unable to grow when the methylation pathway is partially inhibited. We now report the identification of 410S. cerevisiaegene deletion mutants that exhibit HEH hypersensitivity, and identify among those a core set of 21 genes that are known to epistatically interact with genes encoding enzymes of the PtdEtn methylation pathway. This gene set was enriched in functions relating to glycerolipid and sterol biosynthesis and their regulation, the high-osmolarity glycerol (HOG) pathway, and genes involved in chromatin remodeling and transcriptional regulation. These results demonstrate that PtdCho produced by any one of the Kennedy pathway, methylation pathway, or acyltransferase pathway can maintain necessary cellular PtdCho compositions, but that disruption of any one of these pathways leads to epistatic interactions with non-overlapping subsets of genes, thus providing new insights on the specific functions of these pathways. The design and implementation of this screening strategy establishes HEH as a useful tool for specific inhibition of the methylation pathway in high-throughput functional-gnomic screens, which will facilitate further studies on the synthesis, transport, and function of PtdCho.
Research on safety input behaviour decision of tower crane from a collaborative perspective
Authors: Zhang Shibin , Yang Qiying , Yang Feifei 
Published: January 2025

PurposeAs tower cranes are highly dangerous, the problem of insufficient investment in tower safety needs to be solved urgently, and this study aims to solve the problem of insufficient investment in safety caused by the imbalance of interests of tower safety-related subjects and to propose targeted solutions.Design/methodology/approachTower crane rental enterprises, contractors and government departments are selected to construct the game model, calculate the equilibrium point and stability and determine the optimal stabilization strategy. Finally, MATLAB software is used to model and simulate the impact of parameter changes on each party’s choice of strategies.Findings(1) The optimal combination of strategies is safety input by tower companies, leasing of qualified towers by contractors and providing non-financial incentives by the government. (2) The degree of synergistic coefficient γ, the level of government penalty coefficient α and the increase in accident probability p positively affect the adoption of proactive safety measures by tower crane leasing enterprises and contractors. (3) Excessive differences in safety costs may lead firms to adopt hostile safety measures.Originality/valueThis paper creatively uses safety input and tower crane leasing enterprises as the perspective and object of research on tower security. The research results are of great significance in guiding the government to formulate regulatory and incentive policies and in promoting enterprises to implement safety input to ensure construction safety collaboratively. It also provides new research cases for promoting the entire special equipment industry to realize adequate and effective safety input.