bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aptamer-drug conjugates-loaded bacteria for pancreatic cancer synergistic therapy
Authors: Xiao Yu , Pan Tao , Da Wuren , Liu Yuanding , Chen Shuangya , Chen Daiquan , Liu Keying , Zheng Yihan , Xie Daolong , Gao Yuan , Xu Haiyan , Sun Yang , Tan Weihong 
Published: October 2024

AbstractPancreatic cancer is one of the most malignant tumors with the highest mortality rates, and it currently lacks effective drugs. Aptamer-drug conjugates (ApDC), as a form of nucleic acid drug, show great potential in cancer therapy. However, the instability of nucleic acid-based drugs in vivo and the avascularity of pancreatic cancer with dense stroma have limited their application. Fortunately, VNP20009, a genetically modified strain of Salmonella typhimurium, which has a preference for anaerobic environments, but is toxic and lacks specificity, can potentially serve as a delivery vehicle for ApDC. Here, we propose a synergistic therapy approach that combines the penetrative capability of bacteria with the targeting and toxic effects of ApDC by conjugating ApDC to VNP20009 through straightforward, one-step click chemistry. With this strategy, bacteria specifically target pancreatic cancer through anaerobic chemotaxis and subsequently adhere to tumor cells driven by the aptamer’s specific binding. Results indicate that this method prolongs the serum stability of ApDC up to 48 h and resulted in increased drug concentration at tumor sites compared to the free drugs group. Moreover, the aptamer’s targeted binding to cancer cells tripled bacterial colonization at the tumor site, leading to increased death of tumor cells and T cell infiltration. Notably, by integrating chemotherapy and immunotherapy, the effectiveness of the treatment is significantly enhanced, showing consistent results across various animal models. Overall, this strategy takes advantage of bacteria and ApDC and thus presents an effective synergistic strategy for pancreatic cancer treatment.
Regulation of CD8+ T cells by lipid metabolism in cancer progression
Authors: Tang Yong , Chen Ziqing , Zuo Qianying , Kang Yibin 
Published: October 2024

AbstractDysregulation of lipid metabolism is a key characteristic of the tumor microenvironment, where tumor cells utilize lipids for proliferation, survival, metastasis, and evasion of immune surveillance. Lipid metabolism has become a critical regulator of CD8+ T-cell-mediated antitumor immunity, with excess lipids in the tumor microenvironment impeding CD8+ T-cell activities. Considering the limited efficacy of immunotherapy in many solid tumors, targeting lipid metabolism to enhance CD8+ T-cell effector functions could significantly improve immunotherapy outcomes. In this review, we examine recent findings on how lipid metabolic processes, including lipid uptake, synthesis, and oxidation, regulate CD8+ T cells within tumors. We also assessed the impact of different lipids on CD8+ T-cell-mediated antitumor immunity, with a particular focus on how lipid metabolism affects mitochondrial function in tumor-infiltrating CD8+ T cells. Furthermore, as cancer is a systemic disease, we examined systemic factors linking lipid metabolism to CD8+ T-cell effector function. Finally, we summarize current therapeutic approaches that target lipid metabolism to increase antitumor immunity and enhance immunotherapy. Understanding the molecular and functional interplay between lipid metabolism and CD8+ T cells offers promising therapeutic opportunities for cancer treatment.
Cardiovascular and renal effects of apelin in chronic kidney disease: a randomised, double-blind, placebo-controlled, crossover study
Authors: Chapman Fiona A. , Melville Vanessa , Godden Emily , Morrison Beth , Bruce Lorraine , Maguire Janet J. , Davenport Anthony P. , Newby David E. , Dhaun Neeraj 
Published: October 2024

AbstractChronic kidney disease (CKD) affects ~10% of the population and cardiovascular disease is its commonest complication. Despite treatment, patient outcomes remain poor and newer therapies are urgently needed. Here, we investigated the systemic and renal effects of apelin in CKD. In a randomized, double-blind, placebo-controlled, crossover study, 24 subjects (12 patients with CKD and 12 matched healthy subjects) received pyroglutamated apelin-13 ([Pyr1]apelin-13, 1 nmol/min and 30 nmol/min) or matched placebo on two separate visits. Systemic and renal hemodynamics were monitored throughout. The co-primary endpoints were change in systemic vascular resistance index and renal blood flow. Secondary endpoints were change in blood pressure, cardiac output, pulse wave velocity, glomerular filtration rate, natriuresis, free water clearance and urinary protein excretion. In both health and CKD, 30 nmol/min [Pyr1]apelin-13 reduced mean arterial pressure by ~4%, systemic vascular resistance by ~12%, and increased cardiac index by ~10%, compared to placebo (p < 0.05 for all). Both doses of [Pyr1]apelin-13 increased renal blood flow by ~15%, natriuresis by ~20% and free water clearance by ~10%, compared to placebo (p < 0.05 for all). In patients with chronic kidney disease only, glomerular filtration rate fell by ~10%, effective filtration fraction by ~5% and proteinuria by ~25% (p < 0.01 for all). Apelin has short-term cardiovascular and renal benefits in CKD. If maintained longer-term, these should improve patient outcomes. Clinical trials of long-acting oral apelin agonists are justified in CKD and other conditions with impaired salt and water balance. Registration number at www.clinicalTrials.gov: NCT03956576. Funded by Kidney Research UK.
Resilience of genetic diversity in forest trees over the Quaternary
Authors: Milesi Pascal , Kastally Chedly , Dauphin Benjamin , Cervantes Sandra , Bagnoli Francesca , Budde Katharina B. , Cavers Stephen , Fady Bruno , Faivre-Rampant Patricia , González-Martínez Santiago C. , Grivet Delphine , Gugerli Felix , Jorge Véronique , Lesur Kupin Isabelle , Ojeda Dario I. , Olsson Sanna , Opgenoorth Lars , Pinosio Sara , Plomion Christophe , Rellstab Christian , Rogier Odile , Scalabrin Simone , Scotti Ivan , Vendramin Giovanni G. , Westergren Marjana , Lascoux Martin , Pyhäjärvi Tanja ,   On behalf of the GenTree Consortium
Published: October 2024

AbstractThe effect of past environmental changes on the demography and genetic diversity of natural populations remains a contentious issue and has rarely been investigated across multiple, phylogenetically distant species. Here, we perform comparative population genomic analyses and demographic inferences for seven widely distributed and ecologically contrasting European forest tree species based on concerted sampling of 164 populations across their natural ranges. For all seven species, the effective population size, Ne, increased or remained stable over many glacial cycles and up to 15 million years in the most extreme cases. Surprisingly, the drastic environmental changes associated with the Pleistocene glacial cycles have had little impact on the level of genetic diversity of dominant forest tree species, despite major shifts in their geographic ranges. Based on their trajectories of Ne over time, the seven tree species can be divided into three major groups, highlighting the importance of life history and range size in determining synchronous variation in genetic diversity over time. Altogether, our results indicate that forest trees have been able to retain their evolutionary potential over very long periods of time despite strong environmental changes.
HEV ORF2 protein-antibody complex deposits are associated with glomerulonephritis in hepatitis E with reduced immune status
Authors: Leblond Anne-Laure , Helmchen Birgit , Ankavay Maliki , Lenggenhager Daniela , Jetzer Jasna , Helmchen Fritjof , Yurtsever Hueseyin , Parrotta Rossella , Healy Marc E. , Pöschel Amiskwia , Markkanen Enni , Semmo Nasser , Ferrié Martin , Cocquerel Laurence , Seeger Harald , Hopfer Helmut , Müllhaupt Beat , Gouttenoire Jérôme , Moradpour Darius , Gaspert Ariana , Weber Achim 
Published: October 2024

AbstractHepatitis E virus (HEV) infection, one of the most common forms of hepatitis worldwide, is often associated with extrahepatic, particularly renal, manifestations. However, the underlying mechanisms are incompletely understood. Here, we report the development of a de novo immune complex-mediated glomerulonephritis (GN) in a kidney transplant recipient with chronic hepatitis E. Applying immunostaining, electron microscopy, and mass spectrometry after laser-capture microdissection, we show that GN develops in parallel with increasing glomerular deposition of a non-infectious, genome-free and non-glycosylated HEV open reading frame 2 (ORF2) capsid protein. No productive HEV infection of kidney cells is detected. Patients with acute hepatitis E display similar but less pronounced deposits. Our results establish a link between the production of HEV ORF2 protein and the development of hepatitis E-associated GN in the immunocompromised state. The formation of glomerular IgG-HEV ORF2 immune complexes discovered here provides a potential mechanistic explanation of how the hepatotropic HEV can cause variable renal manifestations. These findings directly provide a tool for etiology-based diagnosis of hepatitis E-associated GN as a distinct entity and suggest therapeutic implications.
p53 dependence of senescence markers p21v1 and p21v2 in aging and acute injury
Authors: Kar Parmita , Sivasailam Ashok , Lavarti Rupa , Cai Lun , Thangaraju Muthusamy , Nguyen Emma , Mundluru Bhavishya , Raju Raghavan Pillai 
Published: October 2024

AbstractThe senescence phenotype is heterogeneous, as observed by the context-dependent differential expression of senescence markers. Here, we provide evidence to demonstrate an inverse relationship in the expression pattern of the two murine variants of p21 (p21v1, and p21v2) in aging and hemorrhagic shock. While an upregulation of p21v1 was observed following hemorrhagic shock injury, p21v2 was upregulated in the aged mouse. We further show that the p21v1 response is, at least, partially independent of p53.
PTFE layer formation during brush electroplating of nickel
Authors: Isern L. , Impey S. , Almond H. , Clouser S. J. , Endrino J. L. 
Published: October 2024

AbstractBrush electrodeposition of Ni/PTFE composite coatings was explored using a nickel high speed solution and polytetrafluoroethylene (PTFE) particles 6–9 μm in diameter. A novel bilayer-like, partially intercalated structure was produced, consisting of a rough nickel sublayer covered by an outer, compact, smooth PTFE layer. The study of the coating growth revealed that the PTFE particles bind together on the nickel coating valleys and grow until all the surface is covered by a polymer layer without the need of a baking stage. The resulting coating presents a hydrophobic surface with a low coefficient of friction (0.10) and higher corrosion resistance to salt spray testing than the nodular nickel coating. The coatings were produced using an aqueous nickel plating solution, where the hydrophobic PTFE particles were suspended using different substances: cetrimonium bromide (CTAB) cationic surfactant, isopropyl alcohol premixed with the particles, and ethanol premixed with the particles. High concentrations of the suspending products were detrimental for the deposition process, but optimal values of 0.1 g/l, 3 ml/l and 3 ml/l respectively were found. All compounds successfully suspended the PTFE particles and both alcohols produced the Ni/PTFE coating described before, but the CTAB failed to co-deposit the polymer.
24 Months clinical prospective of proximal restorations with repeated preheating bulk fill composite up to ten cycles: randomized controlled trial
Authors: Ibrahim Islam , Helal Heba , Ibrahim Shereen Hafez , Riad Mona 
Published: October 2024

AbstractThis study aimed to clinically evaluate the performance of non-preheated bulk fill resin composite in class II cavities versus one, five and ten-time preheating cycles at 68 °C. Eighty-four recruited participants were randomly allocated into four groups (21 patients per group). One posterior Bulk-fill proximal restoration was performed for each participant according to the preheating cycles where in group I; teeth were restored with non-heated resin composite, group II: One preheating cycle of composite syringe was performed prior restoration, and group III: five preheating cycles while for group IV: Ten preheating cycles were performed. These restorations were clinically evaluated at 6, 12, 18 and 24 months. Statistical analysis was performed using one way ANOVA, with set p-value < 0.05. The results revealed that there was perfect agreement between both observers and observations WK (95% CI) [0.908 (0.780:1.000)] and [0.940 (0.824:1.000)], respectively. All restorations showed acceptable clinical performance with alpha and bravo scores. No replacement was required for any restoration. No statistically significant differences were detected between the control and intervention groups across all parameters during the various evaluation stages. It could be concluded that the clinical performance of ten cycles of repeated preheated bulk fill resin composite was equivalent to that of non-preheating resin composites after 24 months follow-up period, with great improvement in manipulation. Preheating of resin composite could be performed up to ten cycles prior to placement without any clinical adverse consequences on the performance of the restoration.
Demyelination and neurodegeneration early in experimental autoimmune encephalomyelitis contribute to functional deficits in the anterior visual pathway
Authors: Sekyi Maria T. , Feri Micah , Desfor Shane , Atkinson Kelley C. , Golestany Batis , Beltran Fernando , Tiwari-Woodruff Seema K. 
Published: October 2024

AbstractImpaired visual function is a prevalent feature of optic neuritis (ON) in multiple sclerosis (MS). Abnormal visual evoked potential (VEP) findings of increased latencies, reduced amplitudes and abnormal waveforms as well as decreased retinal nerve fiber layer (RNFL) assessed by optical coherence tomography (OCT) are hallmarks of ON-induced visual dysfunction. Here we utilized the experimental autoimmune encephalomyelitis (EAE) mouse model of MS to investigate the functional and pathological progression during early (before any clinical symptoms), peak (initial maximal clinical symptoms), and late (chronic disease for > 3 weeks) disease stages. Demyelination and initial stages of axon damage were observed in early EAE. Significant demyelination, inflammation, increased axon damage and impaired P1/N2 amplitudes and latencies by VEP were seen in middle and late EAE groups. A decrease in RNFL thickness by OCT was observed only during late EAE. NanoString analysis of optic nerves from late EAE indicated elevated inflammation-related genes, reduced myelin-related genes, and changes in axon degeneration-related genes. Early inflammatory demyelination and functional deficits of the visual pathway, if untreated, may lead to severe irrecoverable axon damage in EAE. These studies potentially help explain the progression of visual dysfunction during MS.
Soft X-ray spectromicroscopic proof of a reversible oxidation/reduction of microbial biofilm structures using a novel microfluidic in situ electrochemical device
Authors: Ingino Pablo , Eraky Haytham , Zhang Chunyang , Hitchcock Adam P. , Obst Martin 
Published: October 2024

AbstractIn situ electrochemistry on micron and submicron-sized individual particles and thin layers is a valuable, emerging tool for process understanding and optimization in a variety of scientific and technological fields such as material science, process technology, analytical chemistry, and environmental sciences. Electrochemical characterization and manipulation coupled with soft X-ray spectromicroscopy helps identify, quantify, and optimize processes in complex systems such as those with high heterogeneity in the spatial and/or temporal domain. Here we present a novel platform optimized for in situ electrochemistry with variable liquid electrolyte flow in soft X-ray scanning transmission X-ray microscopes (STXM). With four channels for fluid control and a modular design, it is suited for a wealth of experimental conditions. We demonstrate its capabilities by proving the reversible oxidation and reduction of individual microbial biofilm structures formed by microaerophilic Fe(II)-oxidizing bacteria, also known as twisted stalks. We show spectromicroscopically the heterogeneity of the redox activity on the submicron scale. Examples are also provided of electrochemical modification of liquid electrolyte species (Fe(II) and Fe(III) cyanides), and in situ studies of electrodeposited copper nanoparticles as CO2 reduction electrocatalysts under reaction conditions.
Comprehensive risk factor-based nomogram for predicting one-year mortality in patients with sepsis-associated encephalopathy
Authors: Jin Guangyong , Zhou Menglu , Chen Jiayi , Ma Buqing , Wang Jianrong , Ye Rui , Fang Chunxiao , Hu Wei , Dai Yanan 
Published: October 2024

AbstractSepsis-associated encephalopathy (SAE) is a frequent and severe complication in septic patients, characterized by diffuse brain dysfunction resulting from systemic inflammation. Accurate prediction of long-term mortality in these patients is critical for improving clinical outcomes and guiding treatment strategies. We conducted a retrospective cohort study using the MIMIC IV database to identify adult patients diagnosed with SAE. Patients were randomly divided into a training set (70%) and a validation set (30%). Least absolute shrinkage and selection operator regression and multivariate logistic regression were employed to identify significant predictors of 1-year mortality, which were then used to develop a prognostic nomogram. The model’s discrimination, calibration, and clinical utility were assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis, respectively. A total of 3,882 SAE patients were included in the analysis. The nomogram demonstrated strong predictive performance with AUCs of 0.881 (95% CI: 0.865, 0.896) in the training set and 0.859 (95% CI: 0.830, 0.888) in the validation set. Calibration plots indicated good agreement between predicted and observed 1-year mortality rates. The decision curve analysis showed that the nomogram provided greater net benefit across a range of threshold probabilities compared to traditional scoring systems such as Glasgow Coma Scale and Sequential Organ Failure Assessment. Our study presents a robust and clinically applicable nomogram for predicting 1-year mortality in SAE patients. This tool offers superior predictive performance compared to existing severity scoring systems and has significant potential to enhance clinical decision-making and patient management in critical care settings.
Efficacy analysis of HAIC combined with lenvatinib plus PD-1 inhibitor vs. first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma
Authors: Lin Zhipeng , Zou Xugong , Hu Xiaolong , Huang Dabei , Chen Yuan , Lin Jiawen , Li Xiaoqun , Zhang Jian 
Published: October 2024

AbstractThis research was intended to compare the clinical efficacy of hepatic arterial infusion chemotherapy (HAIC) in conjunction with lenvatinib and PD-1 inhibitors to first-line systemic chemotherapy for advanced intrahepatic cholangiocarcinoma(ICC). The research enrolled advanced ICC patients who underwent HAIC plus lenvatinib and PD-1 inhibitor(n = 51) or first-line systemic chemotherapy(cisplatin + gemcitabine, n = 39) between July 2020 to January 2023 in Zhongshan People’s Hospital.Their clinical outcomes were assessed through measurement of parameters encompassing objective response rate (ORR), disease control rate (DCR), median overall survival (mOS), median progression-free survival (mPFS), median duration of response (mDOR), and treatment-related adverse events (TRAEs). In accordance with the RECIST1.1, the ORR in the HAIC + L + P and SC groups was 43.1% and 20.5%, while the DCR was 90.2% and 69.2%, respectively (P = 0.04 and = 0.02, respectively). The change in the maximum diameter of intrahepatic target lesions in patients before and after treatment and the diameter of intrahepatic tumors in the HAIC + L + P group were sharply smaller versus the SC group ( P < 0.001). The HAIC + L + P group had prolonged mOS (16.8 months vs. 11.0 months, P = 0.01) and mPFS (12.0 months vs. 6.9 months, P < 0.01) in comparison with the SC group. Compared to first-line systemic chemotherapy(cisplatin + gemcitabine), HAIC plus lenvatinib and PD-1 inhibitors contributes to improvement of tumor response and prolongation of OS and PFS in advanced ICC patients.
Association between dietary inflammatory index and all-cause mortality risk in adults with coronary heart disease in the United States
Authors: Wang Enyang , Fang Caoyang , Zhang Jing , Wang Yuqi 
Published: October 2024

AbstractDiet and inflammation are crucial in the incidence and progression of coronary heart disease (CHD). This study aimed to investigate the correlation between the Dietary inflammatory index (DII) and all-cause mortality in CHD patients. A total of 1,303 CHD patients from the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018 were included. Multivariate Cox regression was used to explore the correlation between the DII and the risk of all-cause mortality in these patients. Restricted cubic spline (RCS) analysis was also utilized to examine the relationship between the DII and all-cause mortality risk in CHD patients. Additionally, subgroup analyses were conducted to determine how the correlation between the DII and all-cause mortality varied across different demographics. During a median follow-up period of 77 months among 1,303 CHD patients, 536 died from all causes. The DII scores were significantly higher in deceased patients compared to survivors. After adjusting for confounding factors, the multivariate Cox regression analysis indicated a strong positive correlation between the DII and all-cause mortality in CHD patients. RCS analysis suggested a non-linear relationship between the DII and all-cause mortality among CHD patients. Additionally, an increase in DII was more pronounced in its impact on female patients. The DII is strongly correlated with the risk of all-cause mortality among CHD patients, particularly among females. Thus, managing dietary inflammation is vital for the prevention and treatment of CHD, especially in female patients.
Quasi-two-dimensional pseudo-sessile drops
Authors: Kärki Tytti , Pääkkönen Into , Kyriakopoulos Nikos , Timonen Jaakko V. I. 
Published: October 2024

AbstractSessile drops are ubiquitous and important in technological applications. While dynamics of liquid drops have been studied under confinement, the possibility of creating sessile drops with reduced dimensionality has not been explored. Here, we demonstrate a quasi-two-dimensional (Q2D) analogy for axisymmetric sessile three-dimensional (3D) drops. The Q2D drops are created by confining liquids between parallel vertical walls, forming low aspect ratio capillary bridges deformed by gravity. Stationary Q2D drops adopt projected shapes analogous to 3D sessile drops, ranging from circular drops to puddles. When moving, the Q2D drops exhibit capillary and fluid mechanical behaviours conceptually analogous to 3D drops, including impacts and sliding. The Q2D drops also exhibit more complex phenomena such as levitation, various instabilities and pattern formation when subjected to external electric, magnetic and flow fields. The 3D-Q2D analogy suggests that the diverse and often complicated phenomena observed in 3D drops can be studied in the simplified Q2D geometry. Additionally, the Q2D confinement analogy allows exploring phenomena arising from the reduced dimensionality and the altered boundary conditions.