bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fabrication of UF‐white cheese: Obtaining a different proteolysis rate, texture, and flavor via using combinations of mesophilic starter culture and Lactobacillus helveticus
Authors: Tondhoush Arash , Soltani Mostafa , Azarikia Fatemeh , Homayouni‐Rad Aziz , Karami Mostafa 
Published: October 2023

AbstractThe effect of using mesophilic starter culture (Lactococcus lactis ssp. lactis and Lactococcus lactis ssp. cremoris) and Lactobacillus helveticus (L. helveticus) at different ratios (100:0, 75:25, 50:50, 25:75, and 0:100) on the quality properties of UF‐white cheese during 90 days of ripening was studied. The results revealed that an increase in L. helveticus ratio caused a significant decrease in the pH and total protein contents of the cheeses (p < .05). No significant changes were observed in the dry matter content of the cheeses (p > .05). The use of higher ratios of L. helveticus led to a noticeable increase in proteolysis and lipolysis indices in the cheeses (p < .05). The cheese produced with higher ratios of L. helveticus had less storage (G′) and loss (G″) moduli compared to other cheeses. The more open structure was seen in the cheeses produced using higher ratios of L. helveticus. Regarding sensory properties, lower scores of body and texture, and higher scores of odor and flavor were assigned to the cheeses produced using higher ratios of L. helveticus. In conclusion, the use of combinations of mesophilic starter culture and L. helveticus at specific ratios (75:25 and 25:75) led to improve quality characteristics of UF‐white cheese.
Maisotsenko Cycle for Heat Recovery in Gas Turbines: A Fundamental Thermodynamic Assessment
Authors: Tariq Rasikh , Caliskan Hakan , Sheikh Nadeem Ahmed 
Published: October 2023

AbstractThis paper reports the Maisotsenko's cycle‐based waste heat recovery system with enhanced humidification to exploit the maximum waste heat recovery potential of the gas turbine. This research uses an integrated methodology coupling thermodynamic balances with heat transfer model of air saturator. The performance of the system is deduced which are assisted with sensitivity analysis indicating the optimal mass flow rate ratio (0.7–0.8) and pressure ratio (4.5–5.0) between the topping and bottoming cycles, and the air saturator split (extraction) ratio (0.5). The net‐work output, energy, and exergy efficiencies of the system are found to be ≈58.39 MW, ≈55.85%, and ≈52.79%, respectively. The maximum exergy destruction ratios are found as 68.2% for the combustion chamber, 16.0% for the topping turbine, 5.7% for topping compressor, 4.9% air saturator. The integration of Maisotsenko's cycle‐based waste heat recovery system with a comprehensive thermodynamic model, as demonstrated in this research, offers valuable insights into enhancing the efficiency, cost‐effectiveness, and environmental impact of gas turbines. By presenting fundamental equations related to thermodynamic balances, this work serves as an invaluable educational resource, equipping future researchers and students with the knowledge and skills needed to advance the study of thermodynamics and sustainable energy solutions.
Evaluation of Two Opioid‐Acetaminophen Combinations and Placebo in Postoperative Oral Surgery Pain
Authors: Forbes James A. , Bates Janet A. , Edquist Irene A. , Burchfield William H. , Smith Frederick G. , Schwartz Michael K. , Kit Victor , Hyatt Julius , Bell Walter E. , Beaver William T. 
Published: October 2023

StudyObjective. To determine the relative analgesic potency and adverse effect liability of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, and placebo in the treatment of pain following oral surgery.Design. Randomized, double‐blind, single‐dose, placebo‐controlled, parallel‐group study with self‐ratings at 30 minutes and then at hourly intervals from hour 1 to hour 6.Setting. Private, oral surgery practice sites.Patients. Three hundred twenty‐four outpatients with moderate or severe pain after the surgical removal of impacted third molars were selected. One was lost to follow‐up and 32 did not need an analgesic; 232 patients had valid efficacy data.Interventions. Patients were treated with a single oral dose of hydrocodone bitartrate 7.5 mg with acetaminophen 500 mg, codeine phosphate 30 mg with acetaminophen 300 mg, or placebo when they experienced steady, moderate or severe pain that, in their opinion, required an analgesic. Using a self‐rating record, subjects rated their pain and its relief for 6 hours after medicating; estimates of peak and total analgesia were derived from these subjective reports.Measurements and Main Results. This study was a valid analgesic assay. Both active treatments were significantly superior to placebo for all measures of analgesic efficacy. The hydrocodone‐acetaminophen combination was significantly superior to the codeine‐acetaminophen combination for total pain relief and the number of evaluations with 50% relief. Both active treatments manifested an analgesic effect within 30 minutes; the effect persisted for 5 hours for the codeine combination and 6 hours for the hydrocodone combination. Adverse effects were transient, consistent with the pharmacologic profiles of opioids, and none required treatment.Conclusions. A slight advantage in analgesic efficacy was demonstrated in this single‐dose study for the hydrocodone‐acetaminophen combination. Repeat‐dose studies, however, should be conducted to determine the clinical significance of the difference in analgesic effect of these opioid combinations.
The Safety, Tolerability, and Pharmacokinetics of Fosphenytoin after Intramuscular and Intravenous Administration in Neurosurgery Patients
Authors: Boucher Bradley A. , Feler Claudio A. , Dean J. Christine , Michie David D. , Tipton Benjamin K. , Smith Kenneth R. , Kramer Ronald E. , Young Byron , Parks Bruce R. , Kugler Alan R. 
Published: October 2023

Study Objective. To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water‐soluble phenytoin prodrug, after intramuscular and intravenous administration.Design. Open‐label study of intramuscular administration, and double‐blind, randomized study of intravenous administration.Setting. Six and ten hospitals throughout the United States for the intramuscular and intravenous multicenter studies, respectively.Patients. Neurosurgical patients who required anticonvulsant prophylaxis or treatment.Interventions. In the intramuscular study, 118 patients received loading doses ranging from 480–1500 mg phenytoin equivalents (PE) and daily maintenance doses ranging from 130–1250 mg PE for 3–14 days. In the intravenous study, 88 patients received fosphenytoin and 28 received phenytoin sodium for 3–14 days. Mean ± SD loading doses and maintenance doses of intravenous fosphenytoin and phenytoin were 1082 ± 299 mg PE and 411 ± 221 mg PE, and 1082 ± 299 mg and 422 ± 197 mg, respectively. Trough phenytoin concentrations were measured daily in all patients.Measurements and Main Results. Intramuscular fosphenytoin was safe and well tolerated, with no irritation found for 99% of all injection site evaluations. Adverse events associated with the drug occurred in 9% of patients, commonly those typical of the parent drug. For intravenous treatment, the frequency of mild irritation at the infusion site was significantly lower in the fosphenytoin group (6%) than in the phenytoin group (25%, p<0.05). Reductions in infusion rates were required in 17% and 36% of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 μg/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days.Conclusion. Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.
Usnic acid attenuates 7,12‐dimethylbenz[a] anthracene (DMBA) induced oral carcinogenesis through inhibiting oxidative stress, inflammation, and cell proliferation in male golden Syrian hamster model
Authors: Azhamuthu Theerthu , Kathiresan Suresh , Senkuttuvan Ilanchitchenni , Abulkalam Asath Nihal Ahamed , Ravichandran Pugazhendhi 
Published: October 2023

AbstractIn this study, we investigated the chemopreventive efficacy of usnic acid (UA), an effective secondary metabolite component of lichens, against 7,12‐dimethylbenz[a]anthracene (DMBA)‐induced oral squamous cell carcinoma (OSCC) in the hamster model. Initially, the buccal pouch carcinogenesis was induced by administering 0.5% DMBA to the HBP (hamster buccal pouch) region about three times a week until the 10th week. Then, UA was orally treated with different concentrations (25, 50, 100 mg/kg b.wt) on alternative days of DMBA exposure, and the experimental process ended in the 16th week. After animal experimentation, we observed 100% tumor incidence with well‐differentiated OSCC, dysplasia, and hyperplasia lesions in the DMBA‐induced HBP region. Furthermore, the UA treatment of DMBA‐induced hamster effectively inhibited tumor growth. In addition, UA upregulated antioxidant levels, interfered with the elevated lipid peroxidation by‐product of thiobarbituric acid reactive substances, and changed the activities of the liver detoxification enzyme (Phase I and II) in DMBA‐induced hamsters. Furthermore, immunohistochemical staining of inflammatory markers (iNOS and COX‐2) and proliferative cell markers (cyclin‐D1 and PCNA) were upregulated in the buccal pouch part of hamster animals induced with DMBA. Notably, the oral administration of UA significantly suppressed these markers during DMBA‐induced hamsters. Collectively, our findings revealed that UA exhibits antioxidant, anti‐inflammatory, antitumor, and apoptosis‐inducing characteristics, demonstrating UA's protective properties against DMBA‐induced HBP carcinogenesis.
Resveratrol augments paclitaxel sensitivity by modulating miR‐671‐5p/STOML2/PINK1/Parkin‐mediated autophagy signaling in A549 cell
Authors: Kong Fanhua , Zhang Lianfu , Zhao Xudong , Zhao Lili , Wang Peng , Zhang Runqi , Tian Hui , Ma Shengjun 
Published: October 2023

AbstractBackgroundPaclitaxel (PTX) resistance has become a notable clinical concern of Non‐small cell lung cancer (NSCLC). Our study aim is to investigate the effects of Resveratrol (RES) on NSCLC cells that have developed resistance to PTX. The NSCLC cell line A549 was employed in this investigation to establish a PTX‐resistant NSCLC cell line, denoted as A549/PTX, and established tumor transplantaton model. The presence of miR‐671‐5p, Stomatin‐like protein 2 (STOML2), and mitophagy biomarkers was evaluated using quantitative teal‐time PCR (qRT‐PCR) and western blot, The assessment of cell proliferation and apoptosis was conducted through the utilisation of colony formation and flow cytometry assays. The investigation of mitochondrial autolysosomes was conducted using transmission electron microscopy (TEM). Our results showed that the application of RES therapy resulted in a substantial improvement in the sansitivity of A549/PTX cells. RES exhibited an augmentation of apoptosis and a suppression of mitophagy in A549/PTX cells. RES induced an upregulation in the expression of miR‐671‐5p. This, in turn, leaded to the inhibition of STOML2, a protein that directly interacts with PINK1. In summary, our research indicates that RES improved the susceptibility of A549/PTX cells to PTX through miR‐671‐5p‐mediated STOML2 inhibition.
The role of p62 in cell death and survival of 5‐fluorouracil and oxaliplatin‐resistant colorectal cancer cells
Authors: Zitkute Vilmante , Jasinevicius Andrius , Vaitiekaite Guoda , Kukcinaviciute Egle , Aleksandraviciute Bernadeta , Eidenaite Eigile , Sudeikis Lukas , Jonusiene Violeta , Sasnauskiene Ausra 
Published: October 2023

AbstractThe protein sequestosome 1 (p62/SQSTM1) is primarily known as a selective autophagy cargo receptor, but due to its multidomain structure, it also has roles in the ubiquitin‐proteasome system, metabolism, cell death and survival signalling. The increase in p62 levels is detected in some types of cancers, including colorectal cancer (CRC). Chemoresistance is the main cause of high mortality rates of CRC patients. Since p62 can regulate both cell survival and death, it is a potential modulator of chemoresistance. The impact of p62 on molecular causes of chemoresistance in CRC cells is insufficiently analysed. Therefore, we aimed to determine the impact of p62 on apoptosis, RIPK1‐pRIPK3 axis, and IL‐8 levels in chemoresistant CRC cells. Our data revealed that p62 levels are higher in the 5‐fluorouracil (5‐FU)‐resistant HCT116/FU subline compared to the parental cell line. 5‐FU and oxaliplatin (OxaPt) treatment decreased p62 protein levels and it correlated with chemoresistance of HCT116 and DLD1 cell lines. The silencing of p62 increased CRC cell sensitivity to 5‐FU and OxaPt, hence p62 is one of the factors supporting chemoresistance. The downregulation of p62 reduced the activation of caspase‐3 and the levels of RIPK1 and pRIPK3. Furthermore, p62 silencing decreased the BAX/BCL2 ratio in the HCT116/FU subline and did not change the levels of apoptosis. Instead, p62 silencing reduced the amount of IL‐8 protein. Our results show that p62 impacts chemoresistance by stimulating prosurvival signalling.
Diverse regulated cell death modes predict the immune microenvironment and drug sensitivity in lung adenocarcinoma
Authors: You Liting , Xin Zhaodan , Zhou Xiaohan , Na Feifei , Zhou Juan , Ying Binwu 
Published: October 2023

AbstractIntegrated action modes of regulated cell death (RCD) in lung adenocarcinoma (LUAD) have not been comprehensively dissected. Here, we adopted 15 RCD modes, including 1350 related genes, and established RCD signature scores. We found that LUAD patients with high RCD scores had a significantly worse prognosis in all four different cohorts (TCGA, KM‐plotter, GSE31210, and GSE30219). Our nomogram established based on the RCD score and clinical characteristics performed well in both the discovery and validation sets. There was a close correlation between the RCD scores and LUAD molecular subtypes identified by unsupervised consensus clustering. Furthermore, we profiled the tumor microenvironment via deconvolution and found significant differences in immune activity, transcription factor activity and molecular pathway enrichment between the RCD‐high and RCD‐low groups. More importantly, we revealed that the regulation of antigen presentation is the crucial mechanism underlying RCD. In addition, higher RCD scores predict poorer sensitivity to multiple therapeutic drugs, which indicates that RCD scores may serve as a promising predictor of chemotherapy and immunotherapy outcomes. In summary, this work is the first to reveal the internal links between RCD modes, LUAD, and cancer immunity and highlights the necessity of RCD scores in personalizing treatment plans.
Effect of Renal Impairment on the Pharmacokinetics of a Single Oral Dose of Danuglipron in Participants With Type 2 Diabetes
Authors: Fediuk Daryl J. , Gorman Donal N. , Stoddard Stephanie‐An , Zhang Yizhong , Ogden Adam G. , Winton Jennifer A. , Saxena Aditi R. 
Published: October 2023

AbstractDanuglipron (PF‐06882961) is an oral, small‐molecule glucagon‐like peptide‐1 receptor agonist in development for the treatment of type 2 diabetes (T2D) and obesity. Impaired renal function is prevalent in patients with T2D. This Phase 1, open‐label study evaluated the effect of renal impairment on the pharmacokinetics, safety, and tolerability of danuglipron (20 mg) in healthy participants with normal renal function (estimated glomerular filtration rate [eGFR] unnormalized for body surface area: ≥90 mL/min), in participants with T2D and normal renal function (eGFR ≥90 mL/min), and in participants with T2D and mild (eGFR 60‐89 mL/min), moderate (eGFR 30‐59 mL/min), or severe (eGFR <30 mL/min) renal impairment (N = 39). Log‐linear regression analyses and analyses of variance showed no evidence of a clinically significant effect of reduced renal function on danuglipron pharmacokinetics. Renal clearance of unchanged danuglipron was minimal (<1% across all renal function groups). Danuglipron pharmacokinetics were similar between healthy participants and participants with T2D and normal renal function. A single 20‐mg oral dose of danuglipron was generally safe and well tolerated in all participant groups. In participants with T2D, renal impairment had no clinically meaningful effect on the pharmacokinetic, safety, and tolerability profiles of danuglipron, indicating that dose adjustment of danuglipron will not be required when administered to patients with T2D and reduced renal function.
Long‐term effect of indomethacin on a rat model of neonatal hypoxia ischemic encephalopathy through behavioral tests
Authors: Tepe Tugay , Satar Mehmet , Ozdemir Mustafa , Yildizdas Hacer Yapicioglu , Ozlü Ferda , Erdogan Seyda , Toyran Tugba , Akillioglu Kübra , Köse Seda , Avci Cagri 
Published: October 2023

AbstractBackgroundMany medical experts prescribe indomethacin because of its anti‐inflammatory, analgesic, tocolytic, and duct closure effects. This article presents an evaluation of the enduring impact of indomethacin on neonatal rats with hypoxic–ischemic (HI) insults, employing behavioral tests as a method of assessment.MethodsThe experiment was conducted on male Wistar‐Albino rats weighing 10 to 15 g, aged between seven and 10 days. The rats were divided into three groups using a random allocation method as follows: hypoxic ischemic encephalopathy (HIE) group, HIE treated with indomethacin group (INDO), and Sham group. A left common carotid artery ligation and hypoxia model was applied in both the HIE and INDO groups. The INDO group was treated with 4 mg/kg intraperitoneal indomethacin every 24 h for 3 days, while the Sham and HIE groups were given dimethylsulfoxide (DMSO). After 72 h, five rats from each group were sacrificed and brain tissue samples were stained with 2,3,5‐Triphenyltetrazolium chloride (TCC) for infarct‐volume measurement. Seven rats from each group were taken to the behavioral laboratory in the sixth postnatal week (PND42) and six from each group were sacrificed for the Evans blue (EB) experiment for blood–brain barrier (BBB) integrity evaluation. The open field (OF) test and Morris water maze (MWM) tests were performed. After behavioral tests, brain tissue were obtained and stained with TCC to assess the infarct volume.ResultsThe significant increase in the time spent in the central area and the frequency of crossing to the center in the INDO group compared with the HIE group indicated that indomethacin decreased anxiety‐like behavior (p < 0.001, p < 0.05). However, the MWM test revealed that indomethacin did not positively affect learning and memory performance (p > 0.05). Additionally, indomethacin significantly reduced infarct volume and neuropathological grading in adolescence (p < 0.05), although not statistically significant in the early period. Moreover, the EB experiment demonstrated that indomethacin effectively increased BBB integrity (p < 0.05).ConclusionsIn this study, we have shown for the first time that indomethacin treatment can reduce levels of anxiety‐like behavior and enhance levels of exploratory behavior in a neonatal rat model with HIE. It is necessary to determine whether nonsteroidal anti‐inflammatory agents, such as indomethacin, should be used for adjuvant therapy in newborns with HIE.
Optimal isolation of extracellular vesicles from pleural fluid and profiling of their microRNA cargo
Authors: Chee Tian Mun , O'Farrell Hannah E. , Lima Luize G. , Möller Andreas , Fong Kwun M. , Yang Ian A. , Bowman Rayleen V. 
Published: October 2023

AbstractPleural effusion occurs in both benign and malignant pleural disease. In malignant pleural effusions, the diagnostic accuracy and sensitivity of pleural fluid cytology is less than perfect, particularly for the diagnosis of malignant pleural mesothelioma, but also in some cases for the diagnosis of metastatic pleural malignancy with primary cancer in the lung, breast or other sites. Extracellular vesicles (EVs) carry an enriched cargo of microRNAs (miRNAs) which are selectively packaged and differentially expressed in pleural disease states. To investigate the diagnostic potential of miRNA cargo in pleural fluid extracellular vesicles (PFEVs), we evaluated methods for isolating the extracellular vesicle (EV) fraction including combinations of ultracentrifugation, size‐exclusion chromatography (SEC) and ultrafiltration (10 kDa filter unit). PFEVs were characterized by total and EV–associated protein, nanoparticle tracking analysis and visualisation by transmission electron microscopy. miRNA expression was analyzed by Nanostring nCounter® in separate EV fractions isolated from pleural fluid with or without additional RNA purification by ultrafiltration (3 kDa filter unit). Optimal PFEV yield, purity and miRNA expression were observed when PFEV were isolated from a larger volume of pleural fluid processed through combined ultracentrifugation and SEC techniques. Purification of total RNA by ultrafiltration further enhanced the detectability of PFEV miRNAs. This study demonstrates the feasibility of isolating PFEVs, and the potential to examine PFEV miRNA cargo using Nanostring technology to discover disease biomarkers.
Population Atlas Analysis of Emerging Brain Structural Connections in the Human Fetus
Authors: Calixto Camilo , Machado‐Rivas Fedel , Karimi Davood , Velasco‐Annis Clemente , Cortes‐Albornoz Maria Camila , Afacan Onur , Warfield Simon K. , Gholipour Ali , Jaimes Camilo 
Published: October 2023

BackgroundA lack of in utero imaging data hampers our understanding of the connections in the human fetal brain. Generalizing observations from postmortem subjects and premature newborns is inaccurate due to technical and biological differences.PurposeTo evaluate changes in fetal brain structural connectivity between 23 and 35 weeks postconceptional age using a spatiotemporal atlas of diffusion tensor imaging (DTI).Study TypeRetrospective.PopulationPublicly available diffusion atlases, based on 60 healthy women (age 18–45 years) with normal prenatal care, from 23 and 35 weeks of gestation.Field Strength/Sequence3.0 Tesla/DTI acquired with diffusion‐weighted echo planar imaging (EPI).AssessmentWe performed whole‐brain fiber tractography from DTI images. The cortical plate of each diffusion atlas was segmented and parcellated into 78 regions derived from the Edinburgh Neonatal Atlas (ENA33). Connectivity matrices were computed, representing normalized fiber connections between nodes. We examined the relationship between global efficiency (GE), local efficiency (LE), small‐worldness (SW), nodal efficiency (NE), and betweenness centrality (BC) with gestational age (GA) and with laterality.Statistical TestsLinear regression was used to analyze changes in GE, LE, NE, and BC throughout gestation, and to assess changes in laterality. The t‐tests were used to assess SW. P‐values were corrected using Holm‐Bonferroni method. A corrected P‐value <0.05 was considered statistically significant.ResultsNetwork analysis revealed a significant weekly increase in GE (5.83%/week, 95% CI 4.32–7.37), LE (5.43%/week, 95% CI 3.63–7.25), and presence of SW across GA. No significant hemisphere differences were found in GE (P = 0.971) or LE (P = 0.458). Increasing GA was significantly associated with increasing NE in 41 nodes, increasing BC in 3 nodes, and decreasing BC in 2 nodes.Data ConclusionExtensive network development and refinement occur in the second and third trimesters, marked by a rapid increase in global integration and local segregation.Level of Evidence3Technical EfficacyStage 2