bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a Limited Sampling Model to Determine Etoposide Area Under the Curve
Authors: Lum Bert L. , Lane Kevin J. , Synold Timothy W. , Goram Adrian , Charnick Steven B. , Sikic Branimir I.
Published: October 2023

Study Objective. To validate the utility of a previously reported 3‐point limited sampling model (LSM) for determining etoposide area under the curve to infinity (AUC∞).

Design. Secondary analysis of data from two clinical trials of etoposide.

Setting. University medical center clinical research center.

Patients. Thirty‐four patients with different malignancies.

Interventions. Etoposide was administered as a 2‐hour infusion to 34 patients. Serial plasma samples were drawn over 24 hours after the infusion and analyzed for etoposide by high‐performance liquid chromatography.

Measurements and Main Results. The 3‐point LSM AUC was compared with a 14‐point actual AUC calculated by the linear trapezoidal rule. Actual and predicted AUC∞ by the LSM were highly correlated (r=0.97, p<0.0001). The LSM predictions had a mean absolute error of 10.9% (95% CI −14.1, −5.3) and a mean error of −9.7% (95% CI 6.9, 14.9). Nine patients with poor AUC∞ estimations by the LSM (error > 12%) tended to have abnormally low or high peak concentrations.

Conclusion. Our findings suggest the development of more robust LSM using other techniques, such as pharmacostatistical models, that can accommodate a greater degree of pharmacokinetic variability. (Pharmacotherapy 1997;17(5):887–890)
Evaluation of the Safety and Efficacy of Ketorolac versus Morphine by Patient‐Controlled Analgesia for Postoperative Pain
Authors: O'Hara Dorene A. , Fanciullo Gilbert , Hubbard Lex , Maneatis Thomas , Seuffert Patricia , Bynum Lincoln , Shefrin Arna
Published: October 2023

Study Objective. To compare ketorolac tromethamine with morphine for pain management after major abdominal surgery.

Design. Double‐blind, randomized study

Setting. Hospital recovery room and postoperative surgical unit.

Patients. One hundred ninety‐one patients with at least moderate pain after major abdominal surgery.

Interventions. Patients received ketorolac by patient‐controlled analgesia (PCA) bolus alone (Ket B), ketorolac by bolus plus infusion (Ket I), or morphine by PCA bolus (morphine), with injectable morphine available for supplementation.

Measurements and Main Results. Levels of sedation, pain intensity, pain relief, and adverse events were recorded at baseline, at 2, 4, and 6 hours, and at termination. Supplemental morphine was required by 71% of Ket B patients, 67% of Ket I patients, and 38% of morphine patients (p<0.001 for Ket B vs morphine). Although patients receiving ketorolac required more supplemental morphine than the morphine group (6.0 mg Ket I, 6.2 mg Ket B, 4.0 mg morphine), there was a large morphine‐sparing effect in both ketorolac groups (total morphine 6.0 mg Ket I, 6.2 mg Ket B, 33.3 mg morphine). Overall pain relief scores were similar for morphine and Ket I groups, and were lower for Ket B than for morphine (p=0.002). There were no differences among groups in numbers of patients with adverse events.

Conclusion. Ketorolac may be effective when administered by PCA device, and has a clear morphine‐sparing effect. (Pharmacotherapy 1997;17(5):891–899)
A Review of Tissue Plasminogen Activator in the Treatment of Veno‐Occlusive Liver Disease after Bone Marrow Transplantation
Authors: Terra Steven G. , Spitzer Thomas R. , Tsunoda Shirley M.
Published: October 2023

Veno‐occlusive disease (VOD) of the liver is a potentially life‐threatening complication that usually occurs secondary to high dose‐chemotherapy with or without total body irradiation as preparative therapy for bone marrow transplantation. The key event in the development of VOD is damage to the vascular endothelium in the liver, which produces a hypercoagulable state triggering the clotting cascade. Factor VIII and fibrinogen are deposited in the hepatic venules, leading to obliteration of the venules. Tissue plasminogen activator (t‐PA) converts fibrin‐bound plasminogen to plasmin, thereby producing clot lysis. Review of the literature suggests that t‐PA can be administered safely, with some limitations, for the treatment of VOD. (Pharmacotherapy 1997;17(5):929–937)
Interferon, Cortisone, and Antivirals in the Treatment of Chronic Viral Hepatitis: A Review of 30 Years of Therapy
Authors: Malaguarnera Mariano , Restuccia Salvatore , Motta Massimo , Ruello Pasqualina , Trovato Barbara A. , Pistone Giovanni
Published: October 2023

Over the last 30 years many approaches have been adopted to treat chronic hepatitis. We conducted a meta‐analysis to assess the efficacy of various types of treatments. We selected 4 studies of cortisone in chronic hepatitis B; 21 trials of interferon treatment, 6 in chronic hepatitis B, 10 in chronic hepatitis C, and 5 in chronic hepatitis D; and 5 of combined cortisone and interferon treatment in chronic hepatitis B. The Mantel‐Haenszel‐Peto method was applied to extrapolated data. We completed the study by analyzing four studies of cortisone treatment of chronic hepatitis C, two of cortisone plus interferon a (IFN‐α) for chronic hepatitis C, and antiviral therapy for hepatitis B, C, and D. Trials administering cortisone for chronic hepatitis B had an overall OR of 0.29 (CI 0.12‐0.73). No virologic remissions were observed in patients with hepatitis C receiving prednisone, even if those with features of autoimmunity achieved a biohumoral sustained response. Overall ORs in the trials were were as follows: IFN for chronic hepatitis B, 0.27 (CI 0.17‐0.46); IFN for chronic hepatitis C, 0.3 (CI 0.21‐0.44); IFN for chronic hepatitis D, 0.16 (CI 0.06‐0.47); and cortisone plus interferon for chronic hepatitis B, 0.25 (CI 0.15‐0.41). Sustained response rates of chronic hepatitis C ranged from 15–24.2%. The only encouraging results were obtained by antivirals. To date the lack of a specific antiviral drug makes it uncertain as to the preferred agent for this disease.
Comparison of 6‐Hour Infusion versus Bolus Furosemide in Premature Infants
Authors: Reiter Pamela D. , Makhlouf Rita , Stiles Alan D.
Published: October 2023

Study Objective. To compare the renal, hemodynamic, and pulmonary effects of a 6‐hour infusion of furosemide versus conventional bolus administration in premature infants.

Design. Prospective, blinded, placebo‐controlled, randomized study.

Setting. Two level III, university‐based neonatal intensive care units.

Patients. Thirty premature infants with significant lung disease, requiring furosemide after a red cell infusion.

Interventions. Infants received furosemide 1 mg/kg over 2 minutes, followed by a 6‐hour placebo infusion, or a small loading dose of 0.1 mg/kg, followed by a slow infusion of 0.9 mg/kg over 6 hours. Serum and urine were collected to determine percentage fractional excretion of sodium (FENa).

Measurements and Main Results. Urine output and blood pressure were measured every 2 hours after furosemide administration. Percentage FENa was measured immediately before furosemide and compared with pooled urine from an 8‐hour collection after furosemide administration. Serum sodium, creatinine, and calcium were measured before and 24 hours after drug administration. Mean airway pressure and percentage inspired oxygen were compared before, 1–4 hours after, and 4–12 hours after drug administration. No significant differences were detected between the two methods of drug administration.

Conclusion. Our data suggest that a 6‐hour infusion of furosemide does not offer substantial clinical advantage over conventional bolus administration in premature infants when focusing on urine output, blood pressure, FENa, or pulmonary effect.
Albuterol in Acute Bronchiolitis—Continued Therapy Despite Poor Response?
Authors: Lugo Ralph A. , Salyer John W. , Dean J. Michael
Published: October 2023

To determine whether clinicians continue to treat acute bronchiolitis with nebulized albuterol despite lack of clinical improvement after such treatment, we reviewed the medical records of 90 randomly selected infants and children with the primary diagnosis of that disorder who were treated in this 232‐bed tertiary care children's hospital. Clinical improvement and no clinical improvement were defined as improvement and lack of improvement, respectively, in air movement, wheezing, retractions, oxygen saturation, work of breathing, and respiratory rate after administration of nebulized albuterol. Response to nebulized albuterol was determined from explicit written documentation in the medical records. Of 68 children who received nebulized albuterol in the emergency department, 52% had written documentation indicating no clinical improvement; however, 94% had admission orders to continue the therapy. Within 12 hours after admission, 61% were again noted to have no clinical improvement with nebulized albuterol. Eighty‐seven percent of nonresponders continued to receive albuterol throughout hospitalization, and 54% continued to receive it after discharge. Continuing therapy despite lack of response resulted in unnecessary medical expenses.
Increased Expression of a 68‐kDa Protein in the Corpus Cavernosum of Some Men With Erectile Dysfunction
Authors: VAN DER VEN PETER F. M. , WEI AN Y. , JAP PAUL H. K. , VAN DER LEE HEIN A. L. , DEBRUYNE FRANS M. J. , MEULEMAN ERIC J. H.
Published: October 2023

ABSTRACT: Erectile dysfunction (ED) may be caused by abnormalities of intracavemous penile structures. In order to investigate whether specific proteins could be identified that might be related to ED, the composition of structural proteins in cavernous tissues of patients with ED was compared to that of normal cavernous tissues by gel electrophoresis. Increased expression of a 68‐kDa nonionic detergent extraction‐resistant protein was demonstrated in tissues of more than half of the patients with vasculogenic ED, whereas only one out of nine normal cavernous tissues showed the same phenomenon. Increased expression was not related to a specific type of vascular insufficiency, aging, or diabetic constituency. Histochemical and immunochemical studies revealed that the increased amount of the 68‐kDa protein is not merely the result of a surplus of nervous, smooth muscle, or elastic tissues. Furthermore, antibodies specific for 68‐kDa neurofilament and 62‐ to 67.5‐kDa tropoelastin did not recognize the 68‐kDa protein on Western blots. The possibility that the 68‐kDa protein may help us understand the etiology of certain cases of erectile dysfunction is discussed.
Effects of Glucose and Other Energy Substrates on the Hyperactivated Motility of Macaque Sperm and the Zona Pellucida‐Induced Acrosome Reaction
Authors: VANDEVOORT CATHERINE A. , OVERSTREET JAMES W.
Published: October 2023

ABSTRACT: Energy sources in sperm capacitation media have various effects on mammalian sperm and are required for stimulation of hyperactivated motility and/or acrosome reactions in some species. The present experiments were performed to investigate the energy substrate requirement for these two functions of macaque sperm. Semen from six cynomolgus macaques was washed through 60% Percoll, resuspended, and washed with Biggers, Whitten, and Whittingham media. In one set of experiments, sperm were incubated in the complete capacitation medium or in medium without glucose. In another set of experiments, the complete medium was used for comparison with medium containing no energy substrates. The absence of glucose did not affect survival of sperm during a 6‐hour incubation period; however, removal of all energy substrates resulted in a decrease in percent motility by 3 hours. Sperm were incubated for 1 hour prior to evaluation of sperm motility by computer‐aided sperm analysis and sperm‐zona binding experiments. During the last 30 minutes of incubation, half of the aliquots of sperm suspensions were treated with activators (ACT; caffeine and dbcAMP, 1 mM each). As previously reported, when sperm were incubated in complete medium and treated with ACT there were changes in sperm movements that are consistent with hyperactivation. Similar or greater changes were observed in sperm that were incubated prior to treatment with ACT in glucose‐free medium or in medium without any energy substrates. Whether sperm were incubated in complex medium or in glucose‐free medium, sperm binding to zonae was enhanced when the sperm were treated with ACT. The absence of glucose in the incubation medium had no deleterious effect on the zona‐induced acrosome reaction, which could be demonstrated whether or not sperm were treated with ACT. Sperm incubated in medium without energy substrates were also capable of binding to the zona pellucida and of undergoing the acrosome reaction following treatment with ACT. However, the percentage of acrosome‐reacted sperm on the zonae was significantly lower when sperm were incubated in medium without any substrates. These results indicate that macaque sperm, like human sperm, do not require energy substrates in incubation media in order to undergo capacitation in vitro, although energy substrates may be necessary for optimal capacitation.
Enzymatic Digestion of Bradykinin by Rat Sertoli Cell Cultures
Authors: MONSEES THOMAS K. , MISKA WERNER , SCHILL WOLF‐BERNHARD
Published: October 2023

ABSTRACT: Sertoli cells play a key role in spermatogenesis. To study the involvement of the kallikrein‐kinin system in the testis, the pattern of bradykinin‐inactivating kininases in rat Sertoli cells was investigated. Exogenous bradykinin (Arg1‐Pro2‐Pro3‐Gly4‐Phe5‐Ser6‐Pro8‐Phe8‐Arg9) is cleaved at Pro7‐Phe8, Phe5‐Ser6, and Gly4‐Phe5, as demonstrated by high performance liquid chromatography analysis. Degradation of bradykinin was strongly inhibited by phosphoramidon and thiorphan, which are specific inhibitors of neutral metalloendopeptidase‐24.11. The kininase type II‐specific inhibitors, captopril and enalapril, were only partially effective in preventing peptidolysis. This indicates that the main kininases responsible for rapid bradykinin inactivation are neutral metalloendopeptidase and, to a lesser extent, kininase type II. Neutral metalloendopeptidase and kininase type II were shown to be located on Sertoli cell membranes. A low degree of bradykinin degradation was detected by simultaneous inhibition of neutral metalloendopeptidase‐24.11 and kininase II, pointing out the involvement of further peptidases with minor activities. This remaining activity is probably not due to the action of kininase type I or cysteine proteases, as shown by specific inhibitors. The data presented indicate the occurrence of membrane‐bound kininases, which are an important part of the kallikrein‐kinin system, in rat Sertoli cell cultures.
Computerized Imaging and Scanning Electron Microscope (SEM) Analysis of Co‐Cultured Fresh and Frozen Bovine Sperm
Authors: SUZUKI HIROYUKI , FOOTE ROBERT H. , FARRELL PAUL B.
Published: October 2023

ABSTRACT: Fresh and frozen‐thawed bull sperm were incubated with bovine oviductal epithelial cells and segments from the oviducts to examine the usefulness of these culture systems to model sperm changes in vivo. Changes in sperm motion characteristics [computer‐assisted sperm analysis (CASA)] and surface morphology [scanning electron microscopy (SEM)] were evaluated. In Experiment 1, fresh and frozen sperm were suspended in the Brackett and Oliphant medium or modified Tyrodes medium (mTALP) and incubated for 0, 3, 6, and 9 hours in direct contact with bovine oviductal‐epithelial cell (BOEC) monolayers prepared from oviducts of cows in the periovulatory phase of estrus. The percentage of motile sperm decreased gradually in mTALP, but decreased rapidly in Brackett's defined medium after 3 hours of incubation, with overall averages of 55 and 32%, respectively. The percentage of motile fresh sperm exceeded frozen‐thawed sperm under all conditions. In Experiment 2, sperm suspended with mTALP were incubated in dishes without monolayers (control), with monolayers, and within the segments of the oviduct for 0, 3, and 6 hours. In the epithelial cell monolayers, the percentage of motile sperm was similar to the controls throughout incubation, but after 3 hours in the oviductal segments, a decrease, partly associated with more rapid rupture of acrosomal membranes occurred. Sperm velocity was higher (100 μm/seconds) in fresh sperm than in frozen sperm (85 μm/seconds). Acrosomal changes, discernible with SEM after 3 hours of incubation, increased with time and were always found more often in frozen than in fresh sperm. The BOEC‐monolayer system provided a useful in vitro model to study pre‐fertilization changes in sperm.
Leydig Cell Apoptosis in Response to Ethane Dimethanesulphonate After Both In Vivo and In Vitro Treatment
Authors: MORRIS ANDREW J. , TAYLOR MATTHEW F. , MORRIS IAN D.
Published: October 2023

ABSTRACT: The biological effects of ethane dimethanesulphonate (EDS) are unique since cytotoxicity in the adult rat is almost exclusively confined to the Leydig cells. For this reason, EDS has been used extensively to investigate the physiological role of the Leydig cell and its products. Experiments were conducted to determine whether the Leydig cell will undergo apoptosis in response to EDS or methylprednisolone (MP), a glucocorticoid known to cause apoptosis in a number of other cell types. Percoll‐purified Leydig cells were incubated for 24 hours with EDS (750 μg/ml), at which time the cells attached to the culture plate became rounded up while control cells were flattened and polyhedral. Following incubation with EDS or MP (10 μM), cells that became detached from the plate were characteristically apoptotic when stained with the fluorescent DNA dye, acridine orange. These cells had shrunk and the nuclear chromatin had become condensed, which is an early characteristic of apoptosis in other cells; eventually, apoptotic bodies formed, reflecting a later apoptotic stage. Electrophoresis of DNA extracted from the treated Leydig cells exhibited the characteristic ladder of the apoptotic process. Increasing the concentration of EDS or MP resulted in a dose‐dependent increase in the incidence of apoptosis that reached a maximum of 25% (EDS) or 12% (MP) of detached cells. Administration of EDS in vivo caused a 20‐fold increase in the number of apoptotic cells observed in interstitial cell preparations. In conclusion, the data indicates that programmed cell death, apoptosis, can occur in the Leydig cell and that this is the likely mechanism by which EDS kills the cells in vivo and in vitro.
Partial Purification and Localization of Platelet‐Activating Factor Acetylhydrolase From Bovine Seminal Plasma
Authors: HOUGH SHELLEY R. , PARKS JOHN E.
Published: October 2023

ABSTRACT: Platelet‐activating factor (PAF) is a potent lipid mediator that is inactivated by platelet‐activating factor acetylhydrolase (PAF‐AH). Platelet‐activating factor bioactivity has been detected in bovine sperm phospholipids and PAF‐AH activity is extraordinarily high in bovine seminal plasma. The purpose of this study was to purify and characterize partially the PAF‐AH in bovine seminal plasma. Platelet‐activating factor acetylhydrolase was partially purified from bovine seminal plasma using gelatin—agarose and ion‐exchange chromatography and nondenaturing polyacrylamide gel electrophoresis (PAGE). Enzyme activity was increased 11‐fold over seminal plasma with a yield of 11%. Platelet‐activating factor acetylhydrolase activity was eluted from a single band with a Rf of 0.258 from a nondenaturing preparative PAGE gel along with several other proteins of varying molecular weights. Following separation by sodium dodecyl sulfate (SDS)‐PAGE under reducing conditions, PAF‐AH was identified as a ∼60‐kD band by western blotting using antiserum directed against human blood PAF‐AH. N‐terminal sequencing of the ∼60 kD band, followed by amino acid‐sequence similarity searching, demonstrated a single‐sequence match with PAF‐AH from bovine blood. Based on western blotting, a ∼60‐kD band corresponding to PAF‐AH was detected in seminal vesicle fluid but not in samples of washed, sonicated sperm or sperm plasma membranes where activity was low (<5% and <0.3%, respectively, of that in seminal plasma), suggesting that seminal plasma PAF‐AH does not bind tightly to sperm. Specific PAF‐AH activity measured in seminal vesicle fluid was in the lower range of that in seminal plasma. These results demonstrate that PAF‐AH activity in bovine seminal plasma is due to PAF‐AH secreted by the seminal vesicles with sequence homology to the enzyme in human blood.
Effect of Chorionic Gonadotropin and Flutamide on Leydig Cell and Macrophage Populations in the Testosterone‐Estradiol‐Implanted Adult Rat
Authors: DUCKETT RICHARD J. , WREFORD NIGEL G. , MEACHEM SARAH J. , McLACHLAN ROBERT I. , HEDGER MARK P.
Published: October 2023

ABSTRACT: The objective of this study was to investigate the role of androgens and nonandrogenic Leydig cell products in maintaining Leydig cell and macrophage numbers in the testis of the adult rat. Adult male Sprague‐Dawley rats received Silastic implants containing testosterone and estradiol (T‐E) in order to suppress endogenous luteinizing hormone (LH) for 9 weeks. After T‐E treatment, Leydig cell and macrophage numbers, quantified using the optical disector approach, were reduced by 40 and 60%, respectively, compared with controls. Administration of human chorionic gonadotropin (hCG) for a period of 10 days restored Leydig cell numbers to control levels, and macrophage numbers were partially restored. Administration of the antiandrogen, flutamide, in combination with hCG treatment in T‐E implanted animals prevented the restoration of Leydig cell numbers but did not prevent the recovery of macrophage numbers. In the T‐E‐implanted animals, there was a decrease in testicular macrophage nuclear size, which was not restored by either hCG or hCG plus flutamide treatment. The results of this study support the hypothesis that LH is the main pituitary regulator of both Leydig cell and macrophage number in the adult rat testis and further indicate that androgens are responsible for maintaining Leydig cell numbers and/or differentiation, but nonandrogenic Leydig cell factors are primarily responsible for controlling macrophage numbers. Testicular macrophage function, as indicated by nuclear size, does not appear to be influenced by LH or testosterone in the adult rat.
Inherent Variability Among Measures of Fertility of Rats and Its Implications in the Design of Mating Trials
Authors: BERNDTSON WILLIAM E. , JUDD JENNIFER E. , CASTRO ANTONIO C. S.
Published: October 2023

ABSTRACT: Mating trials are used extensively to assess the effects of experimental treatments on the fertility of male or female subjects. Such trials are often insensitive because many measures of fertility are associated with large inherent variability, which makes it difficult to confirm, by statistical significance, that observed differences among treatment means are actually due to treatment rather than due to chance. Unfortunately, and despite this insensitivity, most researchers choose replication arbitrarily on the basis of cost, convenience, or conventional practice and interpret results without assessing the actual power and sensitivity of their experiments. This study was undertaken to characterize the relationship between the number of rats used in fertility trials and experimental power and sensitivity. The variables examined included pregnancy rates, numbers of fetuses per mated or per pregnant female, numbers of fetuses per corpus luteum, and numbers of fetal resorptions. The relationship between replication and experimental power and sensitivity was estimated via statistical approaches utilizing data from Sprague‐Dawley rats used in a mating trial at 105–109 days of age. Tabular data are presented showing the numbers of rats needed per treatment group as a function of the minimal treatment differences to be detected and type II error probability selected. The application of these data in the planning of future studies and in interpreting their outcome is discussed.
Improvement of Cryopreserved Ram Sperm Heterogeneity and Viability by Addition of Seminal Plasma
Authors: OLLERO MARIO , CEBRIAN‐PEREZ JOSE A. , MUIÑO‐BLANCO TERESA
Published: October 2023

ABSTRACT: The effect of seminal plasma, as well as some seminal plasma fractions, on the heterogeneity and viability of frozen‐thawed ram spermatozoa was studied. Fresh and frozen sperm samples were simultaneously assessed by a routine semen‐quality assay and centrifugal countercurrent distribution (CCCD) in an aqueous two‐phase system analysis. All samples used for this study were obtained from Salz rams by an artificial vagina and frozen according to the Fiser method. Sperm samples, consisting of either raw or washed semen, were frozen in the presence of either whole ram seminal plasma (RSP) or >10 kDa seminal plasma fraction. Two control samples were considered: one diluted in Fiser's extender and an undiluted sample. Cell‐membrane integrity (viability), hypoosmotic swelling (HOS) test, and sperm motility were assessed in all cases after collection, before freezing (at 5°C), after thawing, and after removing the diluent before CCCD analysis. Our results show that sperm cell partition behavior was dependent on the sperm treatment and that the freezing‐thawing process accounted for a clear loss of sperm heterogeneity and membrane integrity. These losses were less apparent when seminal plasma had been removed from semen samples before freezing. In addition, washed semen frozen in the presence of either >10 kDa seminal plasma fraction or whole re‐added seminal plasma maintained a higher rate of sperm heterogeneity and viability.
Pharmacologic Inhibition of Myostatin With a Myostatin Antibody Improves the Skeletal Muscle and Bone Phenotype of Male Insulin‐Deficient Diabetic Mice
Authors: Bunn R Clay , Adatorwovor Reuben , Smith Rebecca R , Ray Philip D , Fields Sarah E , Keeble Alexander R , Fry Christopher S , Uppuganti Sasidhar , Nyman Jeffry S , Fowlkes John L , Kalaitzoglou Evangelia
Published: October 2023

Type 1 diabetes (T1D) is associated with low bone and muscle mass, increased fracture risk, and impaired skeletal muscle function. Myostatin, a myokine that is systemically elevated in humans with T1D, negatively regulates muscle mass and bone formation. We investigated whether pharmacologic myostatin inhibition in a mouse model of insulin‐deficient, streptozotocin (STZ)‐induced diabetes is protective for bone and skeletal muscle. DBA/2J male mice were injected with low‐dose STZ (diabetic) or vehicle (non‐diabetic). Subsequently, insulin or palmitate Linbits were implanted and myostatin (REGN647‐MyoAb) or control (REGN1945‐ConAb) antibody was administered for 8 weeks. Body composition and contractile muscle function were assessed in vivo. Systemic myostatin, P1NP, CTX‐I, and glycated hemoglobin (HbA1c) were quantified, and gastrocnemii were weighed and analyzed for muscle fiber composition and gene expression of selected genes. Cortical and trabecular parameters were analyzed (micro‐computed tomography evaluations of femur) and cortical bone strength was assessed (three‐point bending test of femur diaphysis). In diabetic mice, the combination of insulin/MyoAb treatment resulted in significantly higher lean mass and gastrocnemius weight compared with MyoAb or insulin treatment alone. Similarly, higher raw torque was observed in skeletal muscle of insulin/MyoAb‐treated diabetic mice compared with MyoAb or insulin treatment. Additionally, muscle fiber cross‐sectional area (CSA) was lower with diabetes and the combination treatment with insulin/MyoAb significantly improved CSA in type II fibers. Insulin, MyoAb, or insulin/MyoAb treatment improved several parameters of trabecular architecture (eg, bone volume fraction [BV/TV], trabecular connectivity density [Conn.D]) and cortical structure (eg, cortical bone area [Ct. Ar.], minimum moment of inertia [Imin]) in diabetic mice. Lastly, cortical bone biomechanical properties (stiffness and yield force) were also improved with insulin or MyoAb treatment. In conclusion, pharmacologic myostatin inhibition is beneficial for muscle mass, muscle function, and bone properties in this mouse model of T1D and its effects are both independent and additive to the positive effects of insulin. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Effects of oxidant molecules on the thermal decomposition of 4,7‐diaminopyridazino[4,5‐c]furanoxane crystal: Ab initio molecular dynamics simulations
Authors: Cheng Huiming , Zhu Weihua
Published: October 2023

Inserting oxidant molecules into the crystal voids to form oxidant cocrystal can greatly enhance the detonation properties of energetic materials. Therefore, oxidant cocrystals are regarded as one type of potential candidates of high energy density materials. The effects of the oxidants (HNO3 and HClO4) on the thermal decomposition mechanisms of two oxidant cocrystals (DPF(4,7‐diaminopyridazino[4,5‐c] furanoxane):HNO3 and DPF:HClO4) were investigated by ab initio molecular dynamics (AIMD). AIMD simulations are performed using a NVT ensemble. The temperature was controlled by a Nosé thermostat. First, we performed 5 ps simulations at 298.15 K to get an equilibrium system. Then, the simulations were performed at 3000 K with a time step of 1 fs and a total time of 15 ps. The initial degradation pathways of the two cocrystals have the same and involve the cleavage of the N–H and N–O bonds. Five different decay pathways were found in the subsequent reactions: intermolecular H transfer, N–O bond cleavage, N–N bond cleavage, and C–C bond formation and cleavage. Both HNO3 and HClO4 can promote the formation of N2, H2O and CO2, but only have a certain effect. Different oxidant molecules hardly affect the initial and subsequent decomposition paths of DPFH.
Magnetic Resonance Deep Learning Radiomic Model Based on Distinct Metastatic Vascular Patterns for Evaluating Recurrence‐Free Survival in Hepatocellular Carcinoma
Authors: Zhang Cheng , Ma Li‐di , Zhang Xiao‐lan , Lei Cai , Yuan Sha‐sha , Li Jian‐peng , Geng Zhi‐jun , Li Xin‐ming , Quan Xian‐yue , Zheng Chao , Geng Ya‐yuan , Zhang Jie , Zheng Qiao‐li , Hou Jing , Xie Shu‐yi , Lu Liang‐he , Xie Chuan‐miao
Published: October 2023

Background

The metastatic vascular patterns of hepatocellular carcinoma (HCC) are mainly microvascular invasion (MVI) and vessels encapsulating tumor clusters (VETC). However, most existing VETC‐related radiological studies still focus on the prediction of VETC status.

Purpose

This study aimed to build and compare VETC‐MVI related models (clinical, radiomics, and deep learning) associated with recurrence‐free survival of HCC patients.

Study Type

Retrospective.

Population

398 HCC patients (349 male, 49 female; median age 51.7 years, and age range: 22–80 years) who underwent resection from five hospitals in China. The patients were randomly divided into training cohort (n = 358) and test cohort (n = 40).

Field Strength/Sequence

3‐T, pre‐contrast T1‐weighted imaging spoiled gradient recalled echo (T1WI SPGR), T2‐weighted imaging fast spin echo (T2WI FSE), and contrast enhanced arterial phase (AP), delay phase (DP).

Assessment

Two radiologists performed the segmentation of HCC on T1WI, T2WI, AP, and DP images, from which radiomic features were extracted. The RFS related clinical characteristics (VETC, MVI, Barcelona stage, tumor maximum diameter, and alpha fetoprotein) and radiomic features were used to build the clinical model, clinical‐radiomic (CR) nomogram, deep learning model. The follow‐up process was done 1 month after resection, and every 3 months subsequently. The RFS was defined as the date of resection to the date of recurrence confirmed by radiology or the last follow‐up. Patients were followed up until December 31, 2022.

Statistical Tests

Univariate COX regression, least absolute shrinkage and selection operator (LASSO), Kaplan–Meier curves, log‐rank test, C‐index, and area under the curve (AUC). P < 0.05 was considered statistically significant.

Results

The C‐index of deep learning model achieved 0.830 in test cohort compared with CR nomogram (0.731), radiomic signature (0.707), and clinical model (0.702). The average RFS of the overall patients was 26.77 months (range 1–80 months).

Data Conclusion

MR deep learning model based on VETC and MVI provides a potential tool for survival assessment.

Evidence Level

3

Technical Efficacy

Stage 3
Pretreatment gamma‐glutamyl transferase predicts mortality in patients with chronic hepatitis B treated with nucleotide/nucleoside analogs
Authors: Jang Tyng‐Yuan , Liang Po‐Cheng , Jun Dae Won , Jung Jang Han , Toyoda Hidenori , Wang Chih‐Wen , Yuen Man‐Fung , Cheung Ka Shing , Yasuda Satoshi , Kim Sung Eun , Yoon Eileen L. , An Jihyun , Enomoto Masaru , Kozuka Ritsuzo , Chuma Makoto , Nozaki Akito , Ishikawa Toru , Watanabe Tsunamasa , Atsukawa Masanori , Arai Taeang , Hayama Korenobu , Ishigami Masatoshi , Cho Yong Kyun , Ogawa Eiichi , Kim Hyoung Su , Shim Jae‐Jun , Uojima Haruki , Jeong Soung Won , Ahn Sang Bong , Takaguchi Koichi , Senoh Tomonori , Buti Maria , Vargas‐Accarino Elena , Abe Hiroshi , Takahashi Hirokazu , Inoue Kaori , Huang Jee‐Fu , Chuang Wan‐Long , Yeh Ming‐Lun , Dai Chia‐Yen , Huang Chung‐Feng , Nguyen Mindie H. , Yu Ming‐Lung
Published: October 2023

Elevated serum gamma‐glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)‐related hepatocellular carcinoma. However, their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive. Altogether, 2843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month‐6) after initiating NAs were measured to explore their association with all‐cause, liver‐related, and non‐liver‐related mortality. The annual incidence of all‐cause mortality was 0.9/100 person‐years over a follow‐up period of 17,436.3 person‐years. Compared with patients who survived, those who died had a significantly higher pretreatment (89.3 vs. 67.4 U/L, p = 0.002) and Month‐6‐GGT levels (62.1 vs. 38.4 U/L, p < 0.001). The factors associated with all‐cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92–3.70, p < 0.001), pretreatment GGT levels (HR/CI: 1.004/1.003–1.006, p < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994–0.998, p = 0.001), and age (HR/CI: 1.06/1.04–1.07, p < 0.001). Regarding liver‐related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79–6.89, p < 0.001), pretreatment GGT levels (HR/CI: 1.006/1.004–1.008, p < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990–0.997, p = 0.001), age (HR/CI: 1.03/1.01–1.05, p < 0.001), and fatty liver disease (HR/CI: 0.30/0.15–0.59, p = 0.001). Pretreatment GGT levels were also independently predictive of non‐liver‐related mortality (HR/CI: 1.003/1.000–1.005, p = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose‐dependent manner of <25, 25–75, and >75 percentile of pretreatment GGT levels was observed with respect to the all‐cause mortality (trend p < 0.001). Pretreatment serum GGT levels predicted all‐cause, liver‐related, and non‐liver‐related mortality in patients with CHB treated with NAs.
Vegetation patterns affect soil aggregate loss during water erosion
Authors: Zhao Zhun , Shi Peng , Bai Lulu , Dong Jingbing , Li Zhanbin , Li Peng , Wang Wen , Cui Lingzhou
Published: October 2023

Soil aggregates are important for improving the soil quality and structure. Soil erosion causes the fragmentation and migration of soil aggregates. Vegetation restoration is an effective method for controlling soil erosion, and the vegetation distribution on the slope changes the hydrological processes. However, there is a dearth of studies investigating the regulation of vegetation patterns in relation to soil aggregate loss. This study employed a physical model of a slope gully system to examine the characteristics of soil aggregates loss during erosion processes under four distinct vegetation patterns: no vegetation (pattern A), up‐slope vegetation (pattern B), middle‐slope vegetation (pattern C), and down‐slope vegetation (pattern D), utilizing simulated rainfall experiments. The results showed that under various patterns of vegetation, the loss of soil aggregates is predominantly driven by microaggregates (<0.25 mm), A (65.2%) < B (72.4%) < C (77.7%) < D (87.7%). On the contrary, there is an opposite trend of change observed in macroaggregates(>0.25 mm). The vegetation pattern had different effects on the enrichment rate of aggregates in sediments: the enrichment ratio of macroaggregates decreased by 20.9%–64.7% and the enrichment ratio of microaggregates increased by 11.1%–34.5%. The cumulative loss of soil aggregates and the cumulative runoff volume can be described by a linear equation: y = ax + b, where ‘a’ denotes the rate of soil aggregate loss. Vegetation patterns had the capacity to decrease the rate of macroaggregate loss. Among these patterns, pattern D exhibits the lowest rate, followed by patterns C, B, and A. These results indicated that down‐slope vegetation pattern is effective in reducing the loss of soil aggregates especially macroaggregates.
Merging and Band Transition of Bound States in the Continuum in Leaky‐Mode Photonic Lattices
Authors: Lee Sun‐Goo , Kim Seong‐Han , Lee Wook‐Jae
Published: October 2023

Bound states in the continuum (BICs) theoretically have the ability to confine electromagnetic waves in limited regions with infinite radiative quality (Q) factors. However, in practical experiments, resonances can only exhibit finite Q factors due to unwanted scattering losses caused by fabrication imperfections. Recently, it has been shown that ultrahigh‐Q guided‐mode resonances (GMRs), which are robust to fabrication imperfections, can be realized by merging multiple BICs in momentum space. This study analytically and numerically investigates the merging and band transition of accidental BICs in planar photonic lattices. Accidental BICs can merge at the edges of the second stop band, either with or without a symmetry‐protected BIC. The results show that as the thickness of the photonic lattice gradually increases, the merged state of BICs transitions from the upper to the lower band edge. Using coupled‐mode analysis, the analytical merging thickness at which multiple accidental BICs merge at the second‐order Γ point is presented. The coupled‐mode analysis can be beneficial for achieving ultrahigh‐Q GMRs in various photonic lattices composed of materials with different dielectric constants.
Correlation between chemical and physical surface properties and blood compatibility of PPE/EVA‐blends
Authors: Kleem Doris , Severich Birgit , Höcker Hartwig
Published: October 2023

The chemical and physical surface properties of a biomaterial are of high importance for the blood compatibility of an implant. Blends of poly(propylene‐co‐ethylene) with various amounts of poly(ethylene‐co‐vinyl acetate) (PPE/EVA‐blends) were examined because of the varying surface hydrophilicity. Surface characterizations were performed by means of X‐ray Photoelectron Spectroscopy (XPS), Infrared Spectroscopy in Attenuated Totalreflexion Mode (IR‐ATR) in relation to dynamic contact angle and zeta potential measurements. The examination of the blood compatibility of the polymer surfaces was carried out in vitro in a modified BOWRY blood chamber with native whole human blood. A balanced ratio of polar and dispersive surface free energy and a zeta potential of −4 mV are the conditions for a good blood compatibility of the investigated PPE/EVA‐blends.
Modification of catheter materials by coating with polymer layers containing silver
Authors: Coen Martine Collaud , Kressler Jörg , Mülhaupt Rolf
Published: October 2023

The surface of polyurethane based catheter material or of silicon wafers as model surfaces were modified by spin coating of solutions of poly(ethylene oxide) or poly(vinyl alcohol) in water. For the incorporation of silver ions, silver nitrate was added to some of the solutions or the as‐cast surfaces were dipped into AgNO3 solution. Furthermore, samples coated with a thin layer of metallic silver were prepared by deposition of silver vapor in vacuum. The as‐prepared surfaces were studied by atomic force microscopy and X‐ray photoelectron spectroscopy. During the spin coating of the solutions containing AgNO3, clusters of the silver component were formed. They were well dispersed in a poly(vinyl alcohol) matrix but act as nucleation agents in poly(ethylene oxide) where then large spherulites are formed. The surface compositions of coated samples and the depth profiling were carried out by angle dependent X‐ray photoelectron spectroscopy.
KLHDC7B as a novel diagnostic biomarker in urine exosomal mRNA promotes bladder urothelial carcinoma cell proliferation and migration, inhibits apoptosis
Authors: Hou Jiayin , Huang Haiming , Xie Junyi , Yu Wei , Hao Han , Li Haixia
Published: October 2023

Bladder cancer is a common kind of urinary system cancer, in which bladder urothelial carcinoma (BLCA) comprises approximately 90% of all bladder cancer types. In our previous study, we discovered KLHDC7B in urine exosomal messenger RNA (mRNA) as a prospective molecular marker for bladder cancer detection. To systematically study the role and mechanism of KLHDC7B in BLCA, we focused on the most common type of BLCA in this study. First, we used RNA sequencing to discover that KLHDC7B was considerably increased in BLCA patients' urine exosomes compared to healthy controls. Then, we validated this result in an independent cohort and identified it as an effective tool for diagnosing and distinguishing high‐grade and low‐grade BLCA. Finally, we studied the role and mechanism of KLHDC7B in BLCA at the cellular level, providing a functional basis for its expression as a novel laboratory diagnostic biomarker for BLCA exosomal mRNA, which has important theoretical and clinical significance.
LC‐Orbitrap‐HRMS Determination of Two Novel Plastochromanol Homologues
Authors: Hammerschick Tim , Graf Jana , Vetter Walter
Published: October 2023

Scope

The antioxidant plastochromanol‐8 (PC‐8) is a tocochromanol which differs from γ‐tocotrienol in having an unsaturated side chain of eight instead of three isoprene units. The recent isolation of PC‐8 from flaxseed oil indicates the additional presence of lower shares of two previously unknown homologues, plastochromanol‐7 (PC‐7) and plastochromanol‐9 (PC‐9), which feature seven and nine isoprenoid units respectively on the γ‐chromanol backbone. Here, a fast LC‐Orbitrap‐HRMS method is applied for the determination of PC‐7 and PC‐9 in seven plant oils and a plant extract.

Methods and results

The presence of PC‐7, PC‐8, and PC‐9 is confirmed in all eight investigated samples by LC‐Orbitrap‐HRMS analysis after saponification. PC‐8 amounts of ≈315–350 mg kg−1 in two flaxseed oils, ≈75 mg kg−1 in rapeseed oil, ≈38 mg kg−1 in camelina oil, ≈80–120 mg kg−1 in two mustard oils, ≈90 mg kg−1 in candle nut oil, and ≈900 mg kg−1 dry weight in Cecropia leaves are determined by quantification. Semi‐quantification of PC‐7 and PC‐9 indicated the presence of ≈0.1–1% of PC‐7 and PC‐9 in varied relative ratios.

Conclusion

The novel plastochromanol homologues are of particular interest to researchers with focus on vitamin E and other tocochromanols because of their unexplored bioactivity.
A model for the evolution size and composition of olivine crystals
Authors: Haddenhorst Hendrik Holger , Chakraborty Sumit , Hackl Klaus
Published: October 2023

In this proceeding, a material model to describe the evolution of olivine crystals, in particular iron‐based Fayalite crystals, which are affected by the diffusion of magnesium ions, is introduced. These crystals are present in magma and understanding their behavior is an important aspect in improving prediction tools for volcanic eruptions. The model describes the development of the dislocation density, the concentration of magnesium over location and time, as well as the development of the size of the crystal over time. We discuss the model and the corresponding parameters. Furthermore, we present a numerical implementation of the model employing the platform Julia as well as a study on the influence of the various model parameters on the results. The results show a clear threshold between stable and unstable crystals.
Cooperativity and topological hydrogen bonding in aromatic diol complexes
Authors: Rosenberg Robert E. , Lomas John S.
Published: October 2023

Complexes of three aromatic diols, catechol, naphthalene‐1,8‐diol, and fluorene‐4,5‐diol, with a series of hydrogen bond acceptors (HBAs) that have oxygen, nitrogen, and sulfur acceptor atoms, have been studied by density functional theory (DFT) at the B3LYP/6‐311+G(d,p) level. Binding energies, geometries, infrared spectroscopic (IR) frequencies, nuclear magnetic resonance (NMR) shifts, and measures of the electron density distribution from the Quantum Theory of Atoms in Molecules (QTAIM) are evaluated and compared with data for the corresponding monohydroxy compounds (monols), phenol, naphth‐1‐ol, and fluorene‐4‐ol, in order to assess the importance of cooperativity between intramolecular and intermolecular hydrogen bonding. All measures for all complexes show positive cooperativity whereby both the intermolecular and intramolecular hydrogen bonds are strengthened upon complexation. Cooperativity is weak for catechol and strong for the other two diols and, for all diols, increases with the hydrogen bond basicity of the acceptor. Correlations of IR and NMR metrics against binding energies for a single HBA and all six monols and diols are excellent, but attempts to correlate the same metrics for all HBAs and a single donor are frustrated by differences in intermolecular hydrogen bonding, depending notably on the identity of the acceptor atom in the HBA. Atom–atom interaction energies, calculated by the Interacting Quantum Atoms approach, are used to discuss the covalency of both types of hydrogen bond.
The immune response mechanism of Nilaparvata lugens against a combined infection of rice ragged stunt virus and Metarhizium anisopliae
Authors: Lin Sheng , Li Xue‐wen , Liu Jian‐li , Ou‐yang Yu‐ying , Zhang Bang , Zhao Shu‐jiao , Chai Xue‐qing , Ma Yong‐le , Liu Jian
Published: October 2023

BACKGROUND

Previous studies of brown planthopper (BPH), Nilaparvata lugens, showed that carrying the plant pathogenic virus, rice ragged stunt virus (RRSV), enhanced the lethality of the entomopathogenic fungus, Metarhizium anisopliae (YTTR). The underlying mechanism for this was not established but a serine protease cascade was hypothesized to be involved.

RESULTS

Two immune response genes, NlKPI and NlVenomase, were identified and shown to be involved. The synthesized double‐strand RNA (dsRNA) techniques used in this study to explore gene function revealed that treatment with dsRNA to silence either gene led to a higher BPH mortality from M. anisopliae infection than the dsRNA control treatment. NlKPI and NlVenomase play vital roles in BPH immunity to defend against alien pathogens. Both genes participate in the immune response process of BPH against co‐infection with RRSV and M. anisopliae YTTR by regulating the expression of antimicrobial peptides and phenoloxidase activity.

CONCLUSION

Our study provided new targets for BPH biocontrol and laid a solid foundation for further research on the interaction of virus‐insect‐EPF (entomopathogenic fungus). © 2023 Society of Chemical Industry.