bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guiding Dyslipidemia Treatment: A Population Pharmacokinetic–Pharmacodynamic Framework for Obicetrapib
Authors: Dunn Allison , Ditmarsch Marc , Kastelein John J. P. , Kling Douglas , Neild Annie , Davidson Michael H. , Gobburu Joga 
Published: May 2024

AbstractObicetrapib is a selective inhibitor of cholesteryl ester transfer protein that is currently in phase 3 of development for the treatment of dyslipidemia as adjunct therapy. The purpose of this study was to comprehensively characterize the pharmacokinetic (PK) and pharmacodynamic (PD) disposition of obicetrapib. Data from 7 clinical trials conducted in healthy adults and those with varying degrees of dyslipidemia were included for model development. The structural model that best described obicetrapib PK was a 3‐compartment model with 4‐compartment transit absorption and first‐order elimination. Body weight was the only covariate found to significantly explain observed variability and was therefore included using allometric scaling on all disposition parameters. For a typical patient weighing 75 kg, the estimated apparent total body clearance and apparent volume of distribution of the central compartment was 0.81 L/h and 36.1 L, respectively. The final PK model parameters were estimated with good precision and were ultimately leveraged to sequentially inform 2 turnover models that describe obicetrapib's effect on low‐density lipoprotein cholesterol (LDL‐C) and high‐density lipoprotein cholesterol (HDL‐C) concentrations. The maximum stimulatory effect of obicetrapib on LDL‐C loss was estimated to be 1.046, while the maximum inhibitory effect of obicetrapib on HDL‐C loss was 0.691. This corresponds to a predicted typical maximum percent change from baseline LDL‐C and HDL‐C of 51.1% and 224%, respectively. The final sequential model described obicetrapib PKPD well and was ultimately able to both demonstrate evidence of internal consistency and support decision‐making throughout the development lifecycle.
Population Pharmacokinetics of Sertraline in Psychiatric and Substance Use Disorders
Authors: Castillo Cinthya Eloisa Chávez , Garibay Susanna Edith Medellín , Segovia Rosa del Carmen Milán , Guzmán Sergio Zarazúa , Cook Helgi Jung , Contreras Marisol Orocio , Moreno Silvia Romano 
Published: May 2024

AbstractThis study aimed to characterize the population pharmacokinetics of sertraline in Mexican patients with psychiatric and substance use disorders. Fifty‐nine patients (13 to 76 years old) treated with doses of sertraline between 12.5 and 100 mg/day were included. Plasma sertraline concentrations were determined in blood samples and five of the main substances of abuse were determined by rapid tests in urine samples. Demographic, clinical, and pharmacogenetic factors were also evaluated. Population pharmacokinetic analysis was performed using NONMEM software with first‐order conditional estimation method. A one‐compartment model with proportional residual error adequately described the sertraline concentrations versus time. CYP2D6*2 polymorphism and CYP2C19 phenotypes significantly influenced sertraline clearance, which had a population mean value of 66 L/h in the final model. The absorption constant and volume of distribution were fixed at 0.855 1/h and 20.2 L/kg, respectively. The model explained 11.3% of the interindividual variability in sertraline clearance. The presence of the CYP2D6*2 polymorphism caused a 23.1% decrease in sertraline clearance, whereas patients with intermediate and poor phenotype of CYP2C19 showed 19.06% and 48.26% decreases in sertraline clearance, respectively. The model was internally validated by bootstrap and visual predictive check. Finally, stochastic simulations were performed to propose dosing regimens to achieve therapeutic levels that contribute to improving treatment response.
Reduced temporal muscle thickness predicts shorter survival in patients undergoing chronic subdural haematoma drainage
Authors: Korhonen Tommi K. , Arponen Otso , Steinruecke Moritz , Pecorella Ilaria , Mee Harry , Yordanov Stefan , Viaroli Edoardo , Guilfoyle Mathew R. , Kolias Angelos , Timofeev Ivan , Hutchinson Peter , Helmy Adel 
Published: May 2024

AbstractBackgroundChronic subdural haematoma (CSDH) drainage is a common neurosurgical procedure. CSDHs cause excess mortality, which is exacerbated by frailty. Sarcopenia contributes to frailty – its key component, low muscle mass, can be assessed using cross‐sectional imaging. We aimed to examine the prognostic role of temporal muscle thickness (TMT) measured from preoperative computed tomography head scans among patients undergoing surgical CSDH drainage.MethodsWe retrospectively identified all patients who underwent CSDH drainage within 1 year of February 2019. We measured their mean TMT from preoperative computed tomography scans, tested the reliability of these measurements, and evaluated their prognostic value for postoperative survival.ResultsOne hundred and eighty‐eight (122, 65% males) patients (median age 78 years, IQR 70–85 years) were included. Thirty‐four (18%) patients died within 2 years, and 51 (27%) died at a median follow‐up of 39 months (IQR 34–42 months). Intra‐ and inter‐observer reliability of TMT measurements was good‐to‐excellent (ICC 0.85–0.97, P < 0.05). TMT decreased with age (Pearson's r = −0.38, P < 0.001). Females had lower TMT than males (P < 0.001). The optimal TMT cut‐off values for predicting two‐year survival were 4.475 mm for males and 3.125 mm for females. TMT below these cut‐offs was associated with shorter survival in both univariate (HR 3.24, 95% CI 1.85–5.67) and multivariate (HR 1.86, 95% CI 1.02–3.36) analyses adjusted for age, ASA grade and bleed size. The effect of TMT on mortality was not mediated by age.ConclusionsIn patients with CSDH, TMT measurements from preoperative imaging were reliable and contained prognostic information supplemental to previously known predictors of poor outcomes.
Evaluation of Hepatic Glucose and Palmitic Acid Metabolism in Rodents on High‐Fat Diet Using Deuterium Metabolic Imaging
Authors: Ehret Viktoria , Ustsinau Usevalad , Friske Joachim , Scherer Thomas , Fürnsinn Clemens , Helbich Thomas H. , Philippe Cécile , Krššák Martin 
Published: May 2024

BackgroundOne of the main features of several metabolic disorders is dysregulation of hepatic glucose and lipid metabolism. Deuterium metabolic imaging (DMI) allows for assessing the uptake and breakdown of 2H‐labeled substrates, giving specific insight into nutrient processing in healthy and diseased organs. Thus, DMI could be a useful approach for analyzing the differences in liver metabolism of healthy and diseased subjects to gain a deeper understanding of the alterations related to metabolic disorders.PurposeEvaluating the feasibility of DMI as a tool for the assessment of metabolic differences in rodents with healthy and fatty livers (FLs).Study TypeAnimal Model.Population18 male Sprague Dawley rats on standard (SD, n = 9, healthy) and high‐fat diet (HFD, n = 9, FL disease).Field Strength/SequencePhase‐encoded 1D pulse‐acquire sequence and anatomy co‐registered phase‐encoded 3D pulse‐acquire chemical shift imaging for 2H at 9.4T.AssessmentLocalized and nonlocalized liver spectroscopy was applied at eight time points over 104 minutes post injection. The obtained spectra were preprocessed and quantified using jMRUI (v7.0) and the resulting amplitudes translated to absolute concentration (mM) according to the 2H natural abundance water peak.Statistical TestsTwo‐way repeated measures ANOVA were employed to assess between‐group differences, with statistical significance at P < 0.05.ResultsDMI measurements demonstrated no significant difference (P = 0.98) in the uptake of [6,6′‐2H2]glucose between healthy and impaired animals (AUCSD = 1966.0 ± 151.5 mM ‐ minutes vs. AUCHFD = 2027.0 ± 167.6 mM·minutes). In the diseased group, the intrahepatic uptake of palmitic acid d‐31 was higher (AUCHFD = 57.4 ± 17.0 mM·minutes, AUCSD = 33.3 ± 10.5 mM·minutes), but without statistical significance owing to substantial in‐group variation (P = 0.73).Data ConclusionDMI revealed higher concentrations of palmitic acid in rats with FL disease and no difference in hepatic glucose concentration between healthy and impaired animals. Thus, DMI appears to be a useful tool for evaluating metabolism in rodents with FL disease.Level of Evidence2Technical EfficacyStage 3.
Common‐mode current reduction in EMP coupling with the star‐quad cable having a reference conductor
Authors: Lodhi Anmol Abbas , Zhu Yu , Gassab Oussama 
Published: May 2024

AbstractThe coupling of electromagnetic pulse (EMP) with the star‐quad cable having reference conductor is analyzed by using the proposed model, which is based upon multi‐conductor transmission line theory. Expressions for common‐mode (CM) and differential‐mode (DM) currents are developed. Two cases are mainly discussed: the first case is the star‐quad cable with a central reference conductor, and the second case with the outside reference conductor. A rigorous comparison between these two cases shows that when the reference conductor is placed at the center, the magnitude of CM current is reduced dramatically, which is beneficial for electromagnetic compatibility (EMC). The CM current magnitude of the outside reference conductor is relatively very high due to the large CM current loop area, which is the least possible for the central reference conductor. There is no significant change in the DM current magnitude for both cases because the DM current has no direct dependence on the CM current loop area. A commercial software, FEKO, which utilizes the method of momentum (MoM), is used to compare the results of our proposed method, which are in good agreement.
An improved two‐dimensional (2,4) finite‐difference time‐domain method for Lorentz dispersive media
Authors: Zygiridis Theodoros T. , Amanatiadis Stamatios A. , Kantartzis Nikolaos V. 
Published: May 2024

AbstractThe credible solution of discretized Maxwell's equations in spaces occupied by Lorentz dispersive media is the main subject of this work. Specifically, we introduce a finite‐difference time‐domain (FDTD) algorithm with a typical (2,4) structure that features dispersion‐relation‐preserving characteristics and produces reduced numerical errors in two‐dimensional electromagnetic simulations, compared to the standard approach with similar computational requirements. We consider the case of dispersive media with non‐vanishing absorption coefficients and investigate different options for the suitable modification of the spatial approximations, so that the accomplished accuracy is optimized for a given computational overhead. The properties of the proposed FDTD technique are thoroughly examined, both theoretically and in numerical tests, and the performance upgrade compared with the conventional solution is assessed.
Significance of High‐Frequency Sonography for the Subclinical Progression of Rheumatoid Arthritis
Authors: Li Yudan , Zhang Ziteng , Liu Cuicui , Kang Zhilong , Li Zhiyan 
Published: May 2024

ObjectivesThis study aims to investigate the use of high‐frequency sonography as a tool for detecting inflammatory and destructive changes in the hand and foot joints of patients with early and long‐term RA.MethodsThis study employs a prospective cohort design involving 162 patients diagnosed with Rheumatoid arthritis (RA) who meet the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria. Patients were divided into two groups based on disease duration: Group 1 (n = 74) included patients with a disease duration of up to 2 years, or early РА (ERA;), Group 2 (n = 88) consisted of patients with a disease duration exceeding 2 years, or long‐term persistent РА (LtRA). All patients underwent a clinical assessment of their joints, as well as radiography and arthrosonography, at the beginning of the study and again at 6 and 12 months later.ResultsIn the general group of patients, ultrasound examination revealed signs of synovitis in the joints of the hands more frequently (66%) compared with clinical examination (56% by a number of swollen joints [NSJ] and 55% by a number of painful joints [NPJ], P < .01). After 6 months of treatment, 12% of the patients achieved full US remission and 24% achieved partial US remission.ConclusionsWithin the scope of comprehensive RA diagnostics, arthrosonography of the joints of the hands and feet, utilizing a combination of greyscale and power Doppler, may surpass radiography in detecting early RA. This method allows for a more accurate assessment of disease activity and progression rates.
Post‐stapedotomy dizziness after applying topical steroid on footplate: A randomized controlled trial
Authors: Barati Behrouz , Shahzamani Arvin , Tabrizi Ali Goljanian , Asadi Mahboobe 
Published: May 2024

AbstractBackgroundOtosclerosis is characterized by abnormal bone growth in the otie capsule. Nowadays, stapedotomy is commonly used for otosclerosis treatment. Currently, postoperative dizziness has been associated with stapedotomy. In 1981, intratympanic dexamethasone was utilized to manage inner ear disorders like tinnitus and acute sensorineural hearing loss. However, there is much uncertainty regarding the effect and safety of topical steroid therapy in the middle ear during stapedotomy. In the present study, we assessed the effect of topical steroid therapy during stapedotomy on postoperative dizziness.MethodsOtosclerosis patients eligible for stapedotomy were randomly divided into two groups based on dexamethasone administration or placebo. Audiometric and tympanometry results were observed and recorded for the involved frequencies. The Dizziness Handicap Inventory was used to quantify patient perceptions of dizziness and balance issues. Audiometry and dizziness assessments were repeated at discharge and 4 months after the operation.ResultsThe study comprised 72 otosclerosis patients undergoing stapedotomy. At discharge, the intervention group showed a significant reduction in the incidence of dizziness compared to the placebo group. However, in the 4‐month follow‐up after the operation, both groups experienced a decrease in dizziness incidence, with no significant difference between them. There was also no significant difference in audiometric levels between the two groups. Interestingly, the intervention group had a significantly lower need for systemic anti‐dizziness drugs after surgery compared to the control group.ConclusionTopical dexamethasone during stapedotomy effectively minimizes dizziness at discharge and reduces the need for postoperative anti‐dizziness medication.Level of evidence2.
CEO industry tournament, investor attention, and company value
Authors: Jiang Ying , Jiang Xiuqi , Deng Wendan 
Published: May 2024

AbstractBased on the emerging capital market of China, this paper uses the data of Chinese listed companies to test the market value management behavior of CEOs under the incentive of industry tournaments. The empirical results show that the CEOs industry tournament improves the value of listed companies by attracting investor attention. In the test of the incentive mechanism of the industry tournament, we find that in the samples with lower industry mobility and state ownership and where the CEO is new, retiring, or a founder, the industry pay gap has a weaker incentive effect on the CEO. In the test of the CEOs' efforts to manage investor attention, this paper finds that CEOs are incentivized to disclose more financial and nonfinancial information, increase advertising spending, and hold more shareholder meetings. Discussed with other incentives, compensation incentives and equity incentives enhance the motivational role of industry championships for CEOs. This study explores in depth the possible impact of industry tournaments on CEO behavioral decisions and also provides a new perspective for corporate to manage investor attention. This provides important reference value for corporate CEO compensation, information disclosure supervision, and investor decision‐making.
The disease recurrence perception scale for patients with inflammatory bowel disease: Instrument development and cross‐sectional validation study
Authors: Xu Yanhong , Li Xiaona , Liu Wenjing , Jiang Yunxia , Zheng Taohua , Xu Guangyi , Hu Danqing , Liu Ting 
Published: May 2024

AbstractDisease recurrence perception plays a key role in disease management and subsequent disease recurrence prevention. However, there are no specific tools for assessing disease recurrence perception in patients with inflammatory bowel disease (IBD) characterized by alternating remission and recurrence. To develop and validate an instrument for measuring disease recurrence perception of patients with IBD, the study was conducted in two steps: (1) instrument development and (2) psychometric tests. A total of 623 patients with IBD participated in the study. The common sense model of illness self‐regulation (CSM) was used as a framework for instrument development. The administered version contained 48 items intended to be relevant to at least one of the six dimensions of the model. Based on preliminary analyzes, 12 items were deleted leaving 36 items for more detailed psychometric and factor analyzes. The Cronbach's alpha coefficient of the total 36‐item instrument was 0.915. The content validity indexes at item and scale levels were satisfactory. The test‐retest reliability of the total instrument was 0.870. Exploratory principal components analysis (n = 278) was used to identify six components congruent with intended CSM constructs that accounted for 62.6% of total item variance. Confirmatory factor analysis (n = 345) found acceptable fit for the six factor measurement model (χ2/df = 1.999, GFI = 0.846, NFI = 0.855, IFI = 0.922, TLI = 0.910, CFI = 0.921, RMSEA = 0.054). Overall, the DRPSIBD demonstrated satisfactory reliability and validity to warrant further development as a measure of disease recurrence perception of patients with IBD.
Marine bryozoan colonization of terrestrial biomineralized tissues: Taphonomic insights and forensic implications
Authors: Guareschi Edda E. , Magni Paola A. 
Published: May 2024

AbstractThe taphonomy and diagenesis of bone and teeth recovered from any environments provide crucial information for forensic sciences and investigations. This leads to the estimation of the postmortem interval (PMI) and the postmortem submersion interval (PMSI) of the organism/s. Aquatic taxa can induce macroscopic and microscopic alterations in biomineralized tissues (e.g., grooves) or can colonize them by attachment (e.g., Bryozoa). Bryozoa are tiny invertebrates that form colonies in freshwater and saltwater. They can survive for years as suspension feeders in all climates. Most marine Bryozoa species have a biomineralized exoskeleton that can be preserved after their death. This research analyzes eight fragments of archeological elephant ivory with a known PMSI of 314 years, which were inhabited by three distinct bryozoan colonies. The variations in the preservation of the bryozoan exoskeletons and the overgrowth of different marine taxa reveal that one colony (lichenoporid cyclostomatid) was alive at the time of the ivory collection from the submerged archeological site while the two other colonies (cheilostomatid) had previously died at different times. The primary objective of this observation is to contribute to the understanding of the taphonomy of terrestrial mammalian biomineralized tissues recovered in marine environments. Additionally, the study discusses the potential forensic implications of this association, such as the evidence of marine submersion and the PMSI. A secondary objective is to present the Bryozoa colonies within a distinctive depositional context, considering that many bryozoan species of the Western Australian coast remain undescribed. The complexity of the Bryozoa ecobiology is also highlighted, with the need of further research (e.g., minimum time for colonization). Finally, this study highlights the urgency of multidisciplinary collaboration to advance aquatic forensic capabilities.
Megalin‐related mechanism of hemolysis‐induced acute kidney injury and the therapeutic strategy
Authors: Goto Sawako , Hosojima Michihiro , Kabasawa Hideyuki , Arai Kaho , Takemoto Kazuya , Aoki Hiroyuki , Komochi Koichi , Kobayashi Ryota , Sugita Nanako , Endo Taeko , Kaseda Ryohei , Yoshida Yutaka , Narita Ichiei , Hirayama Yoshiaki , Saito Akihiko 
Published: May 2024

AbstractHemolysis‐induced acute kidney injury (AKI) is attributed to heme‐mediated proximal tubule epithelial cell (PTEC) injury and tubular cast formation due to intratubular protein condensation. Megalin is a multiligand endocytic receptor for proteins, peptides, and drugs in PTECs and mediates the uptake of free hemoglobin and the heme‐scavenging protein α1‐microglobulin. However, understanding of how megalin is involved in the development of hemolysis‐induced AKI remains elusive. Here, we investigated the megalin‐related pathogenesis of hemolysis‐induced AKI and a therapeutic strategy using cilastatin, a megalin blocker. A phenylhydrazine‐induced hemolysis model developed in kidney‐specific mosaic megalin knockout (MegKO) mice confirmed megalin‐dependent PTEC injury revealed by the co‐expression of kidney injury molecule‐1 (KIM‐1). In the hemolysis model in kidney‐specific conditional MegKO mice, the uptake of hemoglobin and α1‐microglobulin as well as KIM‐1 expression in PTECs was suppressed, but tubular cast formation was augmented, likely due to the nonselective inhibition of protein reabsorption in PTECs. Quartz crystal microbalance analysis revealed that cilastatin suppressed the binding of megalin with hemoglobin and α1‐microglobulin. Cilastatin also inhibited the specific uptake of fluorescent hemoglobin by megalin‐expressing rat yolk sac tumor‐derived L2 cells. In a mouse model of hemolysis‐induced AKI, repeated cilastatin administration suppressed PTEC injury by inhibiting the uptake of hemoglobin and α1‐microglobulin and also prevented cast formation. Hemopexin, another heme‐scavenging protein, was also found to be a novel ligand of megalin, and its binding to megalin and uptake by PTECs in the hemolysis model were suppressed by cilastatin. Mass spectrometry‐based semiquantitative analysis of urinary proteins in cilastatin‐treated C57BL/6J mice indicated that cilastatin suppressed the reabsorption of a limited number of megalin ligands in PTECs, including α1‐microglobulin and hemopexin. Collectively, cilastatin‐mediated selective megalin blockade is an effective therapeutic strategy to prevent both heme‐mediated PTEC injury and cast formation in hemolysis‐induced AKI. © 2024 The Pathological Society of Great Britain and Ireland.
The impact of levofloxacin prophylaxis on empiric intravenous antibiotic use in pediatric hematopoietic stem cell transplant recipients
Authors: Prodanuk Michael , Timberlake Kathryn , Koo Alicia , Chopra Yogi , Wall Donna A. , Science Michelle 
Published: May 2024

AbstractLevofloxacin prophylaxis during periods of neutropenia in pediatric hematopoietic stem cell transplant (HSCT) may reduce the number of febrile episodes and use of empiric intravenous antibiotics (EIA); however, the literature is conflicting. This retrospective review compared EIA use before and after implementation of levofloxacin prophylaxis at a children's hospital. Levofloxacin prophylaxis was associated with reduced use of certain EIA; however, did not reduce the number of positive blood cultures or clinical deteriorations. Therefore, levofloxacin prophylaxis may have implications for the stewardship of broad‐spectrum intravenous antibiotics used in pediatric HSCT.