bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pseudomonas aeruginosametabolite 3-oxo-C12HSL induces apoptosis through T2R14 and the mitochondrial calcium uniporter
Authors: Miller Zoey A. , Mueller Arielle , Thompson Joel C. , Sywanycz Sarah M. , Hill Brianna L. , Carey Ryan M. , Lee Robert J. 
Published: October 2024

AbstractHead and neck squamous cell carcinomas (HNSCCs) arise in the mucosal lining of the upper aerodigestive tract. HNSCCs have high mortality rates and current treatments can be associated with severe morbidities. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. We previously discovered that bitter taste receptor 14 (T2R14), a GPCR, kills HNSCC cells when activated by bitter agonists. We are now investigating endogenous bitter ligands that exist in HNSCC tumor microenvironment (TME). The TME includes cells, signaling molecules, and microbes that can greatly influence treatment responses and overall prognosis in HNSCC.Pseudomonas aeruginosais a gram-negative bacterium that colonizes/infects HNSCC patients. 3-oxo-C12SHL is a quorum-sensing N-acyl homoserine lactone (AHL) secreted byP. aeruginosawhich is also a bitter compound. 3-oxo-C12HSL induces apoptosis but this has never been linked to T2R activation. We hypothesized that 3-oxo-C12HSL induces apoptosis in HNSCC via T2R14. We show that 3-oxo-C12HSL activates intracellular Ca2+responses in HNSCC cells. This is inhibited with T2R14 antagonization. 3-oxo-C12HSL may activate additional Ca2+channels as the Ca2+dynamics are independent from store-operated calcium entry (SOCE). 3-oxo-C12HSL inhibits cell viability, depolarizes mitochondria, and produces ROS. This induces apoptosis in HNSCC cells. In a comparative screen of quorum-sensing AHLs, 3-oxo-C12HSL was the only AHL that elicited both a Ca2+response and reduced cell viability. These results suggest thatP. aeruginosamay play a significant role in modulating an anti-tumor TME through 3-oxo-C12HSL. Moreover, 3-oxo-C12HSL could be a novel, higher-affinity bitter therapeutic for HNSCC. Further research is warranted to elucidate the mechanisms of other endogenous T2R agonists present in the TME.
A comparative network analysis of high-risk MYCN amplified and high-risk MYCN non-amplified neuroblastoma patients
Authors: Chang Erin , Chou Charissa , Chang Wen-I , Honeyman Joshua N , Uzun Alper 
Published: October 2024

AbstractNeuroblastoma is the most common extracranial solid tumor in children. Under contemporary staging guidelines, amplification of MYCN, defined as possessing 10 or more copies of the MYCN gene, is sufficient to classify a patient as high-risk. We aim to investigate the complex genetic landscape of neuroblastoma through a network biology perspective, focusing on complex protein-protein interaction (PPI) networks. Reanalyzing three historical neuroblastoma RNA-Seq datasets, we conducted a comparative network analysis of high-risk MYCN amplified patients and high-risk MYCN non-amplified patients to identify PPI networks that serve as predictive biomarkers for developing high-risk disease. We used R scripts to extract the top 100 most highly expressed genes from each dataset and then analyzed the expression profiles using Proteinarium, a network analysis tool that identifies clusters of patients with shared PPI networks. Statistically significant clusters were annotated and analyzed for network similarity between datasets. Our study isolated four significant clusters with majority high-risk MYCN amplified patients. We annotated the genes unique to high-risk MYCN amplified patients and identified several potential network biomarkers for this particular genotype of neuroblastoma, including ribosome biogenesis (RPL7A, RPL30, RPL35, RPS8), heat shock protein (HSPA8, HSP90AA1, HSP90AB1), matrix metallopeptidase (MMP2, MMP9, MMP13), and collagen (COL2A1, COL5A3, COL6A2, COL11A1, COL16A1) gene networks. The results of this study provide potential therapeutic targets for high-risk MYCN amplified neuroblastoma.
Lactoferrin-Derived Peptide Chimera Induces Caspase-independent Cell Death in Multiple Myeloma
Authors: Jang Young-Saeng , Dehkohneh Shima Barati , Lim Jaewon , Kim Jaehui , Ahn Donghwan , Choi Sun Shim , Kang Seung Goo 
Published: October 2024

AbstractLactoferrin-derived peptide chimera is a synthetic peptide that mimics the functional unit of lactoferrin with antibacterial activity. Antimicrobial peptides are promising candidates for cancer treatment. Although LF is known to have anticancer effects, to the best of our knowledge, its effects on multiple myeloma have not yet been studied. In this study, we explored the potential of lactoferrin-derived chimera for the treatment of multiple myeloma, a malignant clonal plasma cell disease of the bone marrow. Lactoferrin-derived chimera effectively inhibited MM1S, MM1R, and RPMI8226 multiple myeloma cell growth and induced the early and late phases of apoptosis, but not in normal peripheral blood mononuclear cells. Furthermore, lactoferrin-derived chimera modulates the relative expression of genes involved in survival, apoptosis, and mitochondrial dysfunction at the transcriptional level. Mitochondrial analysis revealed that lactoferrin-derived chimera triggered oxidative stress in multiple myeloma cells, leading to the generation of reactive oxygen species and a decline in mitochondrial membrane potential, resulting in mitochondrial dysfunction. Although lactoferrin-derived chimera did not cause caspase-dependent cell death, it induced nuclear translocation of apoptosis-inducing factor and endonuclease G, indicating the initiation of caspase-independent apoptosis. Overall, our data suggest that lactoferrin-derived chimera induces caspase-independent programmed cell death in multiple myeloma cell lines by increasing the nuclear translocation of apoptosis-inducing factor/endonuclease G. Therefore, lactoferrin-derived chimera has potential in multiple myeloma cancer therapies.
The illicit cigarette market in the Democratic Republic of the Congo (DRC): findings from a cross-sectional study of empty cigarette packs
Authors: Mdege Noreen Dadirai , Tchoupe Christelle , Pokothoane Retselisitsoe , Mirindi Didier , Miderho Christus Cito , Sams Kelley , Shamba Patrick , Kandate Emmanuel , Milambo Patrice , Ross Hana 
Published: October 2024

AbstractThis study aimed to estimate the proportion of cigarettes consumed in the Democratic Republic of the Congo (DRC) that are illicit and the extent of cigarette tax evasion; and to identify the origins of and factors associated with illicit cigarettes. Data were collected from May 15 to June 9, 2023. Stratified, multistage sampling was used to select 32 health areas from which empty cigarette packs were collected. Each collected pack was examined and classified as licit if it complied, or illicit if it did not comply, with the DRC’s tax stamp or written health warning requirements, or the requirements to have a notice indicating the prohibition of sale by/to minors or information on tar and nicotine content. We reported frequencies as numbers and percentages, and means for continuous variables. We performed regression analysis and used adjusted odds ratios (aOR) and their 95% confidence intervals (CI) to measure associations. 8.6% of the 10622 empty cigarette packs collected were illicit. All of the illicit packs were also identified as having evaded cigarette tax. Approximately 8.0% of the collected packs did not comply with written health warning requirements, 5.6% did not indicate the prohibition of sale by/to minors, and 4.5% did not have information on tar and nicotine content. Packs from low-income areas were more likely to be illicit than those collected from high-income areas (aOR 1.90; [95% CI: 1.48-2.43]). The likelihood of being an illicit cigarette increased with increasing susceptibility to armed conflict/insecurity. Packs from border provinces were less likely to be illicit than those from non-border provinces (aOR 0.48; [95% CI: 0.25-0.90]). Our results show that the illicit cigarette trade market in the DRC is currently small, and most illicit cigarettes are imported from other countries. There is a need to secure the cigarette supply chain, including strengthening border controls.
Analysis of the progression of cervical cancer in Guatemala- from pre-malignancy to invasive disease
Authors: Robinson Emma , Rodriguez Isabel , Argueta Victor , Xie Yi , Lou Hong , Milano Rose , Lee Hyo Jung , Burdett Laurie , Mishra Sambit K. , Yeager Meredith , Mirabello Lisa , Dean Michael , Orozco Roberto 
Published: October 2024

AbstractTo better understand cervical cancer progression, we analyzed RNA from 262 biopsies from women referred for colposcopy We determined HPV type and analyzed the expression of 51 genes. HPV31 was significantly more prevalent in precancer than stage 1 cancer and invasive cancer (p < 0.0001) and HPV16 increased in invasive disease (p < 0.0001).CCNE1, MELTF, andULBP2were significantly increased in HPV16-positive compared to HPV31 precancers whileNECTIN2andHLA-Eexpression decreased. Markers of the innate immune system, DNA repair genes, and cell cycle genes are significantly increased during cancer progression (p = 0.0001). In contrast, theTP53andRB1tumor suppressor gene expression is significantly decreased in cancer cells. TheT cell markersCD28andFLT3LGexpression decreased in cancer whileFOXP3, IDO1, andULBP2expression increased. There is a significantly higher survival rate in individuals with increased expression ofCD28(p = 0.0005),FOXP3(p = 0.0002),IDO1(p = 0.038),FLT3LG(p = 0.026),APOBEC3B(p = 0.0011), andRUNX3(p = 0.019), and a significantly lower survival rate in individuals with increased expression ofULBP2(p = 0.035). These results will help us understand the molecular factors influencing the progression of cervical precancer to cancer.
Age Prediction based on Blood DNA Methylation
Authors: Rui Liu , Pu Fan , Jing Zhang , Zhao Liu , Hao-yuan Mi 
Published: October 2024

AbstractObjectiveIn the judicial field, traditional DNA methylation age prediction models have low accuracy and poor stability. Additionally, the use of linear regression models for detection is inefficient and costly. This study aims to utilize the prediction principles of the Support Vector Regression (SVR) model, based on preliminary laboratory data from blood DNA methylation detection using the Illumina 850K chip. By selecting low-dimensional and highly linear loci, we aim to establish a highly stable and accurate blood DNA methylation age prediction model.MethodsThis research is based on Illumina 850K chip technology. We conducted a literature review to select CpG sites and related primers, then employed SVR for model construction and age prediction. The model was built on the Matlab2022a platform. Standard parameters were selected, and optimal values for C and g were determined using grid search and cross-validation methods. During data processing, numerical values were normalized before calculation and de-normalized to obtain the predicted values.ResultsThe constructed model achieved an R2of 0.91563 and a Mean Absolute Error (MAE) of 2.77 years. This indicates that the prediction accuracy for blood samples reached 91.56%, with an error of 2.77 years. Moreover, the accuracy of the model’s predictions decreases with increasing age.
Slow-wave sleep is associated with nucleus accumbens volume in elderly adults
Authors: Bán Kitti , Nárai Ádám , Báthori Noémi , Bankó Éva M. , Bihari Adél , Tomacsek Vivien , Kovács Tibor , Weiss Béla , Hermann Petra , Simor Péter , Vidnyánszky Zoltán 
Published: October 2024

AbstractSlow-wave sleep (SWS) is essential for restorative neural processes, and its decline is associated with both healthy and pathological ageing. Building on previous rodent research, this longitudinal study identified a significant association between nucleus accumbens (NAcc) volume and SWS duration in cognitively unimpaired older adults. Our findings support the involvement of the NAcc in ageing-related modulation of SWS and suggest potential therapeutic targets for improving SWS.
Adiponectin Signaling Regulates Urinary Bladder Function by Blunting Smooth Muscle Purinergic Contractility
Authors: Luo Zhaobo , Wu Ali , Robson Simon , Alper Seth , Yu Weiqun 
Published: October 2024

AbstractLower urinary tract symptoms (LUTS) affect ∼ 50% of the population aged >40 years and are strongly associated with obesity and metabolic syndrome. Adipose tissue plays a key role in obesity/metabolic syndrome by releasing adipokines that regulate systemic energy/lipid metabolism, insulin resistance, and inflammation. Adiponectin (ADPN), the most abundant adipokine, modulates energy/metabolism homeostasis through its insulin-sensitizing and anti-inflammatory effects. Human plasma ADPN levels are inversely associated with obesity and diabetes. The role of adipokines such as ADPN in the LUTS associated with obesity/metabolic syndrome remains unknown. We have tested such a possible role in a global ADPN knockout mouse model (Adpn−/−).Adpn−/−mice exhibited increased voiding frequency, small voids, and reduced bladder smooth muscle (BSM) contractility with absence of purinergic contraction. Molecular examination indicated significantly altered metabolic and purinergic pathways. The ADPN receptor agonist AdipoRon was found to abolish acute BSM contraction. Intriguingly, both AMPK activators and inhibitors also abolished BSM purinergic contraction. These data indicate the important contribution of a novel ADPN signaling pathway to the regulation of BSM contractility. Dysregulation of this ADPN signaling pathway might be an important mechanism leading to LUTS associated with obesity/metabolic syndrome.ARTICLE HIGHLIGHTSLower urinary tract symptom (LUTS) is strongly associated with obesity and metabolic syndrome, however, the underlying molecular mechanisms are missing. Dysregulation of adipokine signaling could be the link for this association.Whether adiponectin, the most abundant adipokine, plays a role in regulating bladder function and dysfunction.Mice null for adiponectin exhibited increased voiding frequency, small voids, and reduced bladder smooth muscle contractility, with corresponding metabolic and purinergic pathway changes.Dysregulation of adiponectin signaling might be an important mechanism leading to LUTS associated with obesity/metabolic syndrome.
Optical Clearing with Tartrazine Enables Deep Transscleral Imaging with Optical Coherence Tomography
Authors: Narawane Amit , Trout Robert , Viehland Christian , Kuo Anthony N. , Vajzovic Lejla , Dhalla Al-Hafeez , Toth Cynthia A. 
Published: October 2024

AbstractSuprachoroidal injections are a relatively new method of drug delivery to treat retinal disease. At present, it is difficult to visualize the distribution of injection-delivered product beneath the sclera into the suprachoroidal space. Imaging the suprachoroidal space with OCT is hindered by scattering of light from densely packed collagen fibers of the sclera, limiting depth penetration of the OCT light. In this Letter, we demonstrate the first use of tartrazine (Yellow 5) as an optical clearing agent for suprachoroidal research imaging with OCT in anex vivoeye model. Our results show that this clearing agent dramatically improves visualization of the choroid and suprachoroidal space with transscleral OCT and allows for improved imaging of the location and extent of delivered suprachoroidal fluid. We believe these methods will enable use of optical techniques such as OCT to image through a variety of previously optically inaccessible, highly scattering tissue samples.
Dietary control of peripheral adipose storage capacity through membrane lipid remodelling
Authors: Tol Marcus J. , Shimanaka Yuta , Bedard Alexander H. , Sapia Jennifer , Cui Liujuan , Colaço-Gaspar Mariana , Hofer Peter , Ferrari Alessandra , Qian Kevin , Kennelly John P. , Lee Stephen D. , Gao Yajing , Xiao Xu , Gao Jie , Mack Julia J. , Weston Thomas A. , Pan Calvin , Lusis Aldons J. , Williams Kevin J. , Su Baolong , Pike Daniel P. , Reed Alex , Milosevich Natalia , Cravatt Benjamin F. , Arita Makoto , Young Stephen G. , Ford David A. , Zechner Rudolf , Vanni Stefano , Tontonoz Peter 
Published: October 2024

SummaryComplex genetic and dietary cues contribute to the development of obesity, but how these are integrated on a molecular level is incompletely understood. Here, we show that PPARγ supports hypertrophic expansion of adipose tissue via transcriptional control of LPCAT3, a membrane-bound O-acyltransferase that enriches diet-derived omega-6 (n-6) polyunsaturated fatty acids (PUFAs) in the phospholipidome. In high-fat diet–fed mice, lowering membranen-6 PUFA levels by adipocyte-specificLpcat3knockout (Lpcat3AKO) or by dietary lipid manipulation leads to dysfunctional triglyceride (TG) storage, ectopic fat deposition and insulin resistance. Aberrant lipolysis of stored TGs inLpcat3AKOadipose tissues instigates a non-canonical adaptive response that engages a futile lipid cycle to increase energy expenditure and limit further body weight gain. Mechanistically, we find that adipocyte LPCAT3 activity promotes TG storage by selectively enrichingn-6 arachidonoyl-phosphatidylethanolamine at the ER–lipid droplet interface, which in turn favours the budding of large droplets that exhibit greater resistance to ATGL-dependent hydrolysis. Thus, our study highlights the PPARγ–LPCAT3 pathway as a molecular link between dietaryn-6 PUFA intake, adipose expandability and systemic energy balance.
Evaluation of current practice of antimicrobial use and clinical outcome in the management of children with pneumonia admitted to Jimma Medical Center, Southwest Ethiopia: A prospective observational study
Authors: Wariyo Guyo Abduba , Teshome Derese Berhanu 
Published: October 2024

AbstractBackgroundAntimicrobial resistance is a global crisis that threatens to reverse a century of medical progress; threatening the effective prevention and treatment of common infectious diseases.ObjectivesTo evaluate the current practices of antimicrobial utilization and clinical outcomes of children with pneumonia admitted to Jimma Medical Center, Ethiopia.MethodA prospective observational study design was conducted on children admitted to the pediatric wards of Jimma Medical Center. The study was conducted from February 03, 2022, to June 03, 2022, and patients aged < 18 years and diagnosed with pneumonia were included. A chart review supplemented by a self-administered questionnaire was used to collect data. Descriptive statistics and binary logistic regressions were performed for data analyses.ResultsAmong the total of 146 patients, 61.6% were male, and the mean age was 40.95 (+47.61) months. Microbiologically and radiologically examined patients were 47(32.19%) and 64 (43.8%), respectively. All the treatment approaches were found to be initiated empirically. Ceftriaxone was the most commonly prescribed antimicrobial. In-hospital mortality was 7.5%. Pre-admission antimicrobial use (AOR =3.87; 95% CI:1.34-11.16; P=0.012), antimicrobial change (AOR = 3.74; 95% CI: 1.522-9.22; P=0.004), and hospital stay (> 10 days) (AOR = 6.00; 95% CI: 2.53-14.22; P=0.029) were all independent predictors of poor clinical outcome.ConclusionAn empirically initiated antimicrobial was completed without sufficient evidence of indication, such as microbiological and radiographic findings. More than one-fourth of the patients treated for pneumonia experienced poor outcomes, implicating the need for more attention during treatment.
At-home wearables and machine learning capture motor impairment and progression in adult ataxias
Authors: Manohar Rohin , Yang Faye X. , Stephen Christopher D. , Schmahmann Jeremy D. , Eklund Nicole M. , Gupta Anoopum S. 
Published: October 2024

AbstractA significant barrier to developing disease-modifying therapies for spinocerebellar ataxias (SCAs) and multiple system atrophy of the cerebellar type (MSA-C) is the scarcity of tools to sensitively measure disease progression in clinical trials. Wearable sensors worn continuously during natural behavior at home have the potential to produce ecologically valid and precise measures of motor function by leveraging frequent and numerous high-resolution samples of behavior.Here we test whether movement-building block characteristics (i.e., submovements), obtained from the wrist and ankle during natural behavior at home, can sensitively capture disease progression in SCAs and MSA-C, as recently shown in amyotrophic lateral sclerosis (ALS) and ataxia telangiectasia (A-T).Remotely collected cross-sectional (n= 76) and longitudinal data (n= 27) were analyzed from individuals with ataxia (SCAs 1, 2, 3, and 6, MSA-C) and controls. Machine learning models were trained to produce composite outcome measures based on submovement properties. Two models were trained on data from individuals with ataxia to estimate ataxia rating scale scores. Two additional models, previously trained entirely on longitudinal ALS data to optimize sensitivity to change, were also evaluated.All composite outcomes from both wrist and ankle sensor data had moderate to strong correlations with ataxia rating scales and self-reported function, strongly separated ataxia and control populations, and had high within-week reliability. The composite outcomes trained on longitudinal ALS data most strongly captured disease progression over time.These data demonstrate that outcome measures based on accelerometers worn at home can accurately capture the ataxia phenotype and sensitively measure disease progression. This assessment approach is scalable and can be used in clinical or research settings with relatively low individual burden.
Knowledge, Attitude, and Practices Regarding Dengue Infection: A Community-Based Study in Rural Cox’s Bazar
Authors: Prue Ely , Husna Al Asmaul , Rokony Shazia , Thowai Aung Sain , Moulee Shahra Tanjim , Jahan Afsana , Khatun Aysha , Sarkar Moloy , Bibi Saima , Tabassum Tahsin Tasneem , Nurunnabi Mohammad 
Published: October 2024

AbstractIntroductionDengue, an emerging infectious disease spread by mosquitoes, poses a significant public health challenge, especially in tropical and subtropical areas like Bangladesh.MethodsWe conducted a community-based cross-sectional study to assess the levels of knowledge, attitude, and practice (KAP) towards dengue infection among 484 adult rural people in the purposively selected Shikderpara and Muhuripara villages, Cox’s Bazar. Face-to-face interviews were performed at the convenience of study participants using a pretested, semi-structured questionnaire.ResultsThe mean age of participants were 33.3±13.5 years, with the majority (53.9%) extending between 18 and 34 years. About two-thirds (72.9%) of the residents were literate. Most participants demonstrated average knowledge (84.3%), a positive attitude towards dengue infection (63.0%), and average prevention practices (57.2%). There was a significant association between participants’ practice levels and their knowledge and attitude (p<0.05), along with a statistically significant correlation between their knowledge and dengue prevention practices (p<0.05).ConclusionAlthough the attitude toward dengue infection was positive, knowledge and practices were average. This can be improved by promoting community participation and implementing comprehensive public health measures at all levels.CategoriesCommunicable Disease, Emerging Public Health Issue.