bluuebunny/crossref_metadata_2025 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

The 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

This 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.
Bactericidal Activity of Low‐Dose Ceftizoxime Plus Metronidazole Compared With Cefoxitin and Ampicillin‐Sulbactam
Authors: Freeman Collin D. , Nightingale Charles H. , Nicolau David P. , Belliveau Paul P. , Tessier Pamela R. , Fu Qiang , Xuan Da‐Wei , Quintiliani Richard
Published: October 2023

Eighteen volunteers received ceftizoxime 1 g plus metronidazole 500 mg intravenously every 12 hours, cefoxitin 2 g intravenously every 6 hours, and ampicillin‐sulbactam 3 g every 6 hours in a triple‐crossover, open‐label study to compare serum bactericidal titers (SBTs) against two strains of Escherichia coli and Bacteroides fragilis. Serum was analyzed for drug concentration and bactericidal activity. Ceftizoxime‐metronidazole exhibited a significantly greater (p<0.05) area under the bactericidal curve and percentage of the dosing interval with SBTs of 1:2 or above against E. coli than cefoxitin or ampicillin‐sulbactam. The respective values were equal to those of ampicillin‐sulbactam for one strain of B. fragilis (both greater than cefoxitin) and greater than cefoxitin and ampicillin‐sulbactam for the other strain. A 1‐g dose of ceftizoxime given with metronidazole 500 mg every 12 hours should be an effective alternative to standard antibiotic treatment of mixed aerobic‐anaerobic bacterial infections.
Heparin Monitoring in Acute Thrombosis Associated With Antiphospholipid Antibody Syndrome
Authors: Wittkowsky Ann K. , Kino Kathryn J.
Published: October 2023

Antiphospholipid antibody syndrome is associated with recurrent thromboembolism and the presence of antibodies directed against negatively charged phospholipids. Despite significant hypercoagulability, patients with the disorder often have elevated baseline activated partial thromboplastin times. Although heparin is indicated for the treatment of acute thrombosis, heparin monitoring is complicated by laboratory test interference. A practical treatment approach involves patient‐specific screening for a reagent insensitive to the presence of the inhibitor, and determination of a reagent‐specific therapeutic range in seconds that corresponds to heparin serum concentrations of 0.2‐0.4 U/ml. Other monitoring methods, including using the patient's baseline activated partial thromboplastin time or using an antifactor Xa activity assay, have not been reported or studied but may offer alternatives for heparin monitoring in patients with coagulation laboratory test interference associated with antiphospholipid antibody syndrome.
Amoxapine Overdose in a Young Man: A Transient Mitochondrial Abnormality?
Authors: Mancias Pedro , Kramer Larry , Butler Ian J.
Published: October 2023

Amoxapine is a second‐generation tricyclic antidepressant structurally related to the neuroleptic loxapine. It was previously marketed as an alternative to traditional tricyclic antidepressants because of alleged shorter onset of action and fewer cardiotoxic effects. However, various adverse reactions, including cardiac dysrhythmias, renal failure, coma, seizures, and neuroleptic malignant syndrome, were reported during therapy or after acute overdose. A 14‐year‐old boy ingested 1900 mg of amoxapine and developed seizures, hypertension, hyperpyrexia, altered mental status, myoglobinuria, renal failure, and transient magnetic resonance imaging (MRI) changes suggestive of hypertensive encephalopathy and neuroleptic malignant syndrome. Since mitochondrial disorders can cause multisystem failure, including encephalopathy, renal tubular dysfunction, and myopathy, a transient, toxic disorder of mitochondrial function was considered as the basis for the patient's clinical and MRI changes. (Pharmacotherapy 1995;15(4):528–532)
Drug and Poison Information Resources on the Internet, Part 1: An Introduction
Authors: Marra Carlo A. , Lynd Larry D. , McKerrow Ron , Carleton Bruce C.
Published: October 2023

The Internet is an excellent source of drug and poison information. Despite the relative ease and minimal costs associated with accessing the Internet, many pharmacists and other health care professionals have been slow to adopt this new technology.
Pharmacologic Prophylaxis of Supraventricular Tachyarrhythmias After Coronary Artery Bypass
Authors: Dorovenis Speros A. , Weiner Bruce
Published: October 2023

Coronary artery bypass surgery is an accepted treatment for patients with coronary artery disease. Perioperative morbidity includes development of supraventricular arrhythmias. To prevent this, prophylactic administration of drugs such as calcium channel blockers, digoxin, and β‐blockers have been advised.
Calcitriol in the Management of Secondary Hyperparathyroidism of Renal Failure
Authors: Daisley‐Kydd Racquel E. , Mason Nancy A.
Published: October 2023

Secondary hyperparathyroidism (HPT) is characterized by persistent hypersecretion of parathyroid hormone (PTH), and produces characteristics of hyperparathyroid bone disease and a variety of biochemical and hormonal derangements. Management of uremic secondary HPT involves both prevention and treatment. Among preventive measures are attempts to control serum phosphate and serum calcium concentrations through dietary restriction, administration of phosphate binders, and calcium supplementation. Treatment with a vitamin D analog such as calcitriol returns plasma calcium concentrations toward normal and suppresses PTH secretion. The availability of a parenteral formulation of calcitriol, and new information regarding alternative routes of administration and regimens employing oral pulse dosing have renewed interest in calcitriol for the management of uremic secondary HPT.
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.
QTc‐Interval Prolongation Associated with Slow Intravenous Erythromycin Lactobionate Infusions in Critically Ill Patients: A Prospective Evaluation and Review of the Literature
Authors: Tschida Suzanne J. , Guay David R.P. , Straka Robert J. , Hoey Lori L. , Johanning Rebecca , Vance‐Bryan Kyle
Published: October 2023

Intravenous erythromycin has recently been associated with significant QTc interval prolongation, torsades de pointes, and sudden cardiac death. The prolonged the QTc interval attributed to erythromycin typically is associated with rapid infusion rates in excess of 10 mg/minute. We prospectively assessed the relationship between QTc interval prolongation and erythromycin administration by slow intravenous infusion (mean rate 8.9 ± 3.5 mg/minute, range 3.9–16.7 mg/minute). Electrocardiographic (ECG) rhythm strips were prospectively obtained in 44 critically ill patients receiving intravenous antibiotics (22 received erythromycin and 22 ceftazidime, cefuroxime, cefotaxime, ceftriaxone, or ampicillin‐sulbactam as controls). The ECG recordings were obtained immediately before and within 15 minutes after drug infusions. Only the first available set of ECG strips were evaluated. Two controls had evidence of hepatic dysfunction; no patients receiving erythromycin did. The QTc interval was calculated using Bazett's formula by two blinded investigators. For controls, mean ± 1 SD (range) QTc intervals were 423 ± 96 (300–550) msec at baseline and 419 ± 96 (280–610) msec after infusion (p=0.712). In contrast, in the erythromycin group, the interval was significantly prolonged from 524 ± 105 (360–810) msec at baseline to 555 ± 134 (400–980) msec after infusion (p=0.034). No patients experienced a dysrhythmia as a consequence of erythromycin infusion. Despite slow rates of infusion, QTc interval prolongation was significant. The clinical importance of this finding remains to be determined.
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

In 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

Background

Paclitaxel (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

The 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

Integrated 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

Danuglipron (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

Background

Many 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.

Methods

The 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.

Results

The 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).

Conclusions

In 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

Pleural 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

Background

A 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.

Purpose

To evaluate changes in fetal brain structural connectivity between 23 and 35 weeks postconceptional age using a spatiotemporal atlas of diffusion tensor imaging (DTI).

Study Type

Retrospective.

Population

Publicly 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/Sequence

3.0 Tesla/DTI acquired with diffusion‐weighted echo planar imaging (EPI).

Assessment

We 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 Tests

Linear 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.

Results

Network 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 Conclusion

Extensive network development and refinement occur in the second and third trimesters, marked by a rapid increase in global integration and local segregation.

Level of Evidence

3

Technical Efficacy

Stage 2
Shared and distinct biological mechanisms for anxiety and sensory over‐responsivity in youth with autism versus anxiety disorders
Authors: Cummings Kaitlin K. , Jung Jiwon , Zbozinek Tomislav D. , Wilhelm Frank H. , Dapretto Mirella , Craske Michelle G. , Bookheimer Susan Y. , Green Shulamite A.
Published: October 2023

Sensory over‐responsivity (SOR) is a prevalent cross‐diagnostic condition that is often associated with anxiety. The biological mechanisms underlying the co‐occurrence of SOR and anxiety symptoms are not well understood, despite having important implications for targeted intervention. We therefore investigated the unique associations of SOR and anxiety symptoms with physiological and neural responses to sensory stimulation for youth with anxiety disorders (ANX), autism spectrum disorder (ASD), or typical development (TD). Age/IQ‐matched youth aged 8–18 years (22 ANX; 30 ASD; 22 TD) experienced mildly aversive tactile and auditory stimuli during functional magnetic resonance imaging and then during skin conductance response (SCR) and heart rate (HR) measurements. Caregivers reported on participants' SOR and anxiety symptoms. ASD/ANX youth had elevated SOR and anxiety symptoms compared to TD. ASD/ANX youth showed similar, heightened brain responses to sensory stimulation compared to TD youth, but brain responses were more highly related to SOR symptoms in ASD youth and to anxiety symptoms in ANX youth. Across ASD/ANX youth, anxiety symptoms uniquely related to greater SCR whereas SOR uniquely related to greater HR responses to sensory stimulation. Behavioral and neurobiological over‐responsivity to sensory stimulation was shared across diagnostic groups. However, findings support SOR and anxiety as distinct symptoms with unique biological mechanisms, and with different relationships to neural over‐reactivity dependent on diagnostic group. Results indicate a need for targeted treatment approaches.
White‐rot fungus Phlebia floridensis ITM 12: Laccase production, oxidoreductase profile, and hydrogen‐peroxide independent activity
Authors: Magaña‐Ortiz Denis , López‐Castillo Laura M. , Amezquita‐Novelo Roberto
Published: October 2023

Phlebia genus is a relevant group of fungi with a crucial role in numerous ecosystems. In tropical and subtropical areas this genus allows the efficient degradation of lignin and carbon recovery; however, the majority of these fungal species remain undiscovered. The main purpose of this work was to determine the enzymatic activity of extracellular proteins of a novel Phlebia floridensis strain isolated in Yucatan Peninsula, Mexico. The results that are reported here demonstrate that the soluble protein extract of P. floridensis can degrade a broad spectrum of recalcitrant compounds. This induced protein extract is able to modify not only phenolic and nonphenolic compounds, but also anthroquinone dyes, even without the addition of exogenous hydrogen peroxide. Using liquid chromatography–mass spectrometry (LC‐MS), we were able to identify a novel chloroperoxidase in enzymatic extract. As far as we know, this is the first report about the presence of this type of enzyme in the Phlebia genus.
Therapeutic Ultrasound for Enhanced Corneal Permeability to Macromolecules
Authors: Allison Claire , Jiménez Annette , Ramajayam Krishna , Haemmerich Dieter , Zderic Vesna
Published: October 2023

Objectives

Topically applied macromolecules have the potential to provide vision‐saving treatments for many of the leading causes of blindness in the United States. The aim of this study was to determine if ultrasound can be applied to increase transcorneal drug delivery of macromolecules without dangerously overheating surrounding ocular tissues.

Methods

Dissected corneas of adult rabbits were placed in a diffusion cell between a donor compartment filled with a solution of macromolecules (40, 70 kDa, or 150 kDa) and a receiver compartment. Each cornea was exposed to the drug solution for 60 minutes, with the experimental group receiving 5 minutes of continuous ultrasound or 10 minutes of pulsed ultrasound at a 50% duty cycle (pulse repetition frequency of 500 ms on, 500 ms off) at the beginning of treatment. Unfocused circular ultrasound transducers were operated at 0.5 to 1 W/cm2 intensity and at 600 kHz frequency.

Results

The greatest increase in transcorneal drug delivery seen was 1.2 times (P < .05) with the application of pulsed ultrasound at 0.5 W/cm2 and 600 kHz for 10 minutes with 40 kDa macromolecules. Histological analysis revealed structural damage mostly in the corneal epithelium, with most damage occurring at the epithelial surface.

Conclusions

This study suggests that ultrasound may be used for enhancing transcorneal delivery of macromolecules of lower molecular weights. Further research is needed on the long‐term effects of ultrasound parameters used in this study on human ocular tissues.
Kinetics of direct and water‐mediated tautomerization reactions of nucleobases at low temperatures ⩽200 K
Authors: Würmel Judith , Simmie John M.
Published: October 2023

Detailed chemical kinetic mechanisms for the synthesis of complex organic molecules in the interstellar medium are at an early stage of developement. That such synthesis must take place is well‐known from chemical analysis of sampled asteroids. As molecular complexity increases the number of possible structural isomers also increases with the consequence that the nascent species may adopt a different spatial arrangement, to the lowest energy one. As part of a program of investigations of the hydrogen atom transfer reaction or tautomerization of imidic acid–amide species H‐O=C‐N‐ O=C‐N‐H we have studied the kinetics for a number of nucleobases, namely cytosine, thymine and uracil where a cyclic form of tautomerism (lactim–lactam) is encountered. Together with a fourth, 5‐aza‐uracil (1,3,5‐triazine‐2,4(1H,3H)‐dione), we report on the rates of reaction at low temperatures 50–200 K for both the direct unimolecular process and the similar transformation mediated by an additional water molecule. We show that these tautomerization reactions can be categorized into three classes, and highlight the importance of quantum mechanical tunneling on the rate constants at these low temperatures. We further present some thermochemistry data, such as formation enthalpies, entropies, isobaric heat capacities and enthalpy functions.
Promoting gender diversity in the editorial boards of major otorhinolaryngology journals: A call for inclusion and equal representation
Authors: Ünal Asude , Çeçen Ayşe
Published: October 2023

Objectives

The aim of our study was to investigate the representation of women in the editorial boards of otorhinolaryngology journals indexed in the Science Citation Index‐Expanded (SCIE) database.

Methods

We examined the gender distribution of editors‐in‐chief, editorial board members, and associate/section editors in otorhinolaryngology journals indexed in the Web of Science SCI‐E core collection. We also analyzed the number of years the journals have been publishing, their categories (general otorhinolaryngology, otology‐audiology, phoniatrics, rhinology‐allergy), the country and continent of publication, the Journal Citation Indicator (JCI) 2021 values, 2‐year and 5‐year impact factors (IF), H‐index, and quartile rank of the journals.

Results

Out of the 54 editors‐in‐chief included in our study from a total of 44 journals, only 6 (11.1%) were women. Women constituted 21.6% of the editorial board members and 35.1% of the associate/section editors. The proportion of women in the editorial boards of journals with a 5‐year impact factor >3.0 was significantly higher compared to others. As the 5‐year impact factor of the journals increased, the number of women in the boards showed a linear increase. When evaluated based on journal categories, phoniatrics journals had higher representation of women in both editorial board membership and associate/section editor roles compared to other categories.

Conclusion

The representation of women in the editorial boards of otorhinolaryngology journals is still inadequate. To rectify this situation, it is important for the entire academic community to exhibit a collective attitude rather than individual efforts.

Level of Evidence

2.
Effect of Functionalized Liquid Rubber on Mechanical Properties of an Epoxy Resin
Authors: Vertuccio Luigi , Guadagno Liberata , Barra Giuseppina , Arconati Vincenzo , Catauro Michelina
Published: October 2023

In this study, an epoxy resin has been modified with different weight ratios of carboxyl‐terminated polybutadiene liquid rubber. The introduction of a pre‐reaction catalyst has been necessary to promote the reaction between the epoxy groups and the carboxylic acid groups of carboxyl‐terminated butadiene acrylonitrile copolymer. The occurred reaction has been confirmed by infrared spectroscopy analysis. The analysis of the mechanical properties has shown that the presence of elastomeric domains allows obtaining a matrix with greater flexibility. This allows making the material competitive for many applications such as adhesives and composite matrices where a high fracture toughness is required.
Spectroscopic Investigation of Supramolecular Self‐Healing Resins Based on Covalently Modified Carbon Nanotubes
Authors: Guadagno Liberata , Raimondo Marialuigia , Longo Raffaele , Aliberti Francesca , Passaro Jessica , Piccirillo Annamaria , Calabrese Elisa
Published: October 2023

In this work, Fourier transform infrared spectroscopy (FTIR) is used as a valid method to support the study of supramolecular self‐healing composites, intended for structural applications. These nanocomposites are loaded with covalently functionalized multi wall carbon nanotubes (MWCNTs), which simultaneously impart to the material self‐healing ability, based on supramolecular chemistry, and electrical conductivity. FTIR analysis is carried out to demonstrate the success of the performed covalent modification, by identifying the functional groups bonded to the MWCNTs, and the presence of hydrogen bonding interactions established between the functional groups bonded to nano‐fillers and the hosting matrix.
Different Conformational Properties and Frequencies of Periodic Motion in the β‐ and γ‐Cyclodextrin
Authors: Raffaini Giuseppina , Ganazzoli Fabio
Published: October 2023

Cyclodextrins (CDs) are cyclic oligosaccharides with application in different fields. These systems can encapsulate hydrophobic molecules and allow their solubilization in water. CDs and CD complexes can self‐associate forming aggregate or micelle‐like structures. Theoretical studies based on molecular mechanics (MM) and molecular dynamics (MD) simulations are demonstrated to be a useful tool for understanding the conformational properties, the stability, their host–guest inclusion complexes in the solid state or in aqueous solution in a good agreement with experimental data. The aim of this work is to compare at atomistic level the conformational properties, the flexibility of the native β‐ and γ‐CD. The β‐CD shows very slightly deviation from C7 symmetry, and its glycosidic oxygens are on a flat plane, while in the γ‐CD they are in different arrangement on a curved plane. From the variation of the distance between opposite glycosidic oxygens in these CDs, the frequencies of motion due to periodic motions are calculated during MD run. These frequencies indicate faster periodic motion for the β‐CD and slower for the γ‐CD having larger dimension and less symmetrical structure. MD simulations are an interesting tool for investigating the flexibility of these systems, their possible periodic motion, and their frequencies of motion.
Benzoate‐Based Inhibitor Film to Prevent Chloride‐Induced Corrosion: Simulation Study of Efficiency of Dry or Hydrated Film
Authors: Raffaini Giuseppina , Bolzoni Fabio , Ormellese Marco
Published: October 2023

In the last 30 years, many synthetic organic substances have been proposed as promising inhibitors to prevent chloride‐induced corrosion in reinforced concrete structures. Using molecular mechanics (MM) and molecular dynamics (MD) methods the formation of protective film on steel have been investigated at atomistic level considering different organic inhibitors, comparing the theoretical results with experimental data. In previous work, the interaction between chlorides and both dry and hydrated triethylenetetramine (TETA) film on hydroxylated γ‐FeOOH surface is studied. Using the same simulation protocol, the aim of this work is to investigate the interaction between the Cl− ions and the benzoate inhibitor film to understand how the corrosion process can be avoided. The dry benzoate film efficiently prevents the adsorption of chlorides on lepidocrocite (γ‐FeOOH) surface. At the same time the MD simulations show the hydrated benzoate film have a lower efficiency because some chlorides come into contact with the γ‐FeOOH surface, and moreover, at longer time they cause a depletion of organic inhibitors close to them, then an inhomogeneity in the exposed film. Not only the number of chlorides that penetrate through the protective film must be considered but also the stability of dry or hydrated protective film during the time.
Comparative Studies between Two Plastic Materials Used in 3D Printing
Authors: Năstase Marian‐Sebastian , Costea Mihai , Jiga Gabriel , Alexandru Tudor George
Published: October 2023

This paper deals with the analysis and comparative studies of the two of the most used types of polymer filaments dedicated to the 3D printing industry. The study is focused on the mechanical, elastic, and thermal properties of two different types of plastic materials filaments – acrylonitrile butadiene styrene (ABS) and polylactic acid (PLA) as well as on future development in various categories like industrial, medical, home decoration, and education. For carrying out this study, different specimens are printed using fused filament fabrication (FFF) technique, taking into account an infill percentage of 30% with a triangular shape as pattern type (internal structure).
Effect of Maleic Anhydride and Titanium Dioxide on the Miscibility of the PHBV/PP Mixture
Authors: Hamour Noura , Boukerrou Amar , Beaugrand Johnny
Published: October 2023

This study is interested in blends based on poly (hydroxybutyrate‐co hydroxyvalerate) (PHBV) and polypropylene (PP), using maleic anhydride (AM) as a compatibilizing agent and titanium dioxide (TiO2) acting as a filler in the matrix. In this work, the study of the miscibility of two polymers, as well as their physical mixtures is done. The results reveal that the immiscible PP/PHBV blend can be effectively accounted for by maleic anhydride. The latter is able to create chemical bonds between the macromolecular chains of the two polymers at the interface and therefore improve their properties.
Adaptive Scaling of Components in the Fused Deposition Modeling Process
Authors: Moritzer Elmar , Hecker Felix
Published: October 2023

Currently, the fused deposition modeling (FDM) process is the most common additive manufacturing technology. The principle of the FDM process is the strand wise deposition of molten thermoplastic polymers, by feeding a filament trough a heated nozzle. Due to the strand and layer wise deposition the cooling of the manufactured component is not uniform. This leads to dimensional deviations which may cause the component to be unusable for the desired application. In this paper, a method is described which is based on the shrinkage compensation through the adaption of every single raster line in components manufactured with the FDM process. The shrinkage compensation is based on a model resulting from a DOE which considers the main influencing factors on the shrinkage behavior of raster lines in the FDM process. An in‐house developed software analyzes the component and locally applies the shrinkage compensation with consideration of the boundary conditions, e.g., the position of the raster line in the component and the process parameters. Following, a validation using a simple geometry is conducted to show the effect of the presented adaptive scaling method.
Study of a Microsatelite Hinge Concept Using 3D Printed Prototypes
Authors: Stoica Marilena , Anania Florea Dorel , Zapciu Miron , Georgescu Luminita Elena
Published: October 2023

The CubeSat microsatellites are structures that can be found in many applications of industry and educations, but not only. Based on this, a new concept Card‐Sat structure is used in the present study. For a better understanding of the functionality microstructure Card‐Sat, this paper aims to study the geometry of joints manufactured from plastic materials by using the FFF 3D printing method and assembling to identify the suitable joint for this type of structures.