bluuebunny/crossref_metadata_2025_split huggingface dataset:
Topotecan clearance based on a single sample and a population pharmacokinetic model: Application to a pediatric high‐risk neuroblastoma clinical trial
Authors: Campagne Olivia , Wu Huiyun , Wu Jianrong , Naranjo Arlene , Daryani Vinay M. , Gajjar Amar J. , Park Julie R. , Stewart Clinton F. 
Published: September 2023

AbstractBackgroundTopotecan, an antitumor drug with systemic exposure (SE)‐dependent activity against many pediatric tumors has wide interpatient pharmacokinetic variability, making it challenging to attain the desired topotecan SE. The study objectives were to update our topotecan population pharmacokinetic model, to evaluate the feasibility of determining individual topotecan clearance using a single blood sample, and to apply this approach to topotecan data from a neuroblastoma trial to explore exposure–response relationships.ProcedureOur previous population pharmacokinetic and covariate model was updated using data from 13 clinical pediatric studies. A simulation‐based Bayesian analysis was performed to determine if a single blood sample could be sufficient to estimate individual topotecan clearance. Following the Bayesian approach, single pharmacokinetic samples collected from a Children's Oncology Group Phase III clinical trial (ANBL0532; NCT0056767) were analyzed to estimate individual topotecan SE. Associations between topotecan SE and toxicity or early response were then evaluated.ResultsThe updated population model included the impact of patient body surface area (BSA), age, and renal function on topotecan clearance. The Bayesian analysis with the updated model and single plasma samples showed that individual topotecan clearance values were estimated with good precision (mean absolute prediction error ≤16.2%) and low bias (mean prediction error ≤7.2%). Using the same approach, topotecan SE was derived in patients from ANBL0532. The exposure–response analysis showed an increased early response after concomitant cyclophosphamide and topotecan up to a topotecan SE of 45 h ng/mL.ConclusionsA simple single‐sample approach during topotecan therapy could guide dosing for patients, resulting in more patients reaching target attainment.
Facile fabrication and characterization of novel polyvinyl alcohol/polyethylene glycol/aluminum nitride nanocomposites
Authors: Venu Gopala Kumari Satti , Gupta Shiv Prakash Anil , Pakshirajan Kannan , Pugazhenthi G. 
Published: September 2023

AbstractIn the current study, novel polyvinyl alcohol‐based films with polyethylene glycol as a plasticizer and aluminum nitride (AlN) nanoparticles (0.1–0.5 wt%) as a reinforcing agent were fabricated by facile solution casting route. The prepared composite films were characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X‐ray diffraction analysis (XRD), and Fourier transform infrared spectroscopy (FTIR). Additionally, morphology, water contact angle, and optical and mechanical properties were evaluated. FTIR analysis disclosed that the backbone structure of PVA/PEG was not affected by nanofiller loading, and the type of interaction between the PVA/PEG matrix and AlN nanoparticles was physical; furthermore, it was observed that as AlN nanoparticle loading increased in the composite films, water contact angles also increased. Interestingly, the nanocomposite films showed >90% blocking of UV light (200–400 nm) and very high flexibility with an elongation at break of approximately 190%. In comparison with PVA/PEG, the composite films developed by reinforcing 0.3 wt% of AlN (PVA/PEG/0.3AlN) exhibited a 17.94°C increment in thermal degradation temperature and a 7.36°C increment in glass transition temperature, along with a 1.2‐fold increment in tensile strength.Highlights
Fabrication of polyvinyl alcohol/polyethylene glycol/aluminum nitride films.
The composite films showed >90% blocking of UV light.
Thermal stability maximally enhanced at 0.3 wt% loading of aluminum nitride.
The composite films demonstrated very high flexibility.
Towards conservation and sustainable use of an indigenous crop: A large partnership network enabled the genetic diversity assessment of 1539 fonio (Digitaria exilis) accessions
Authors: Kaczmarek Thomas , Causse Sandrine , Abdul Suleiman D. , Abraham Solomon , Achigan‐Dako Enoch G. , Adje Charlotte , Adjebeng‐Danquah Joseph , Agyare Richard Y. , Akanvou Louise , Bakasso Yacoubou , Barry Mamadou B. , Bonsu Samuel K. , Calatayud Caroline , Conde Soukeye , Couderc Marie , Dachi Stephen N. , Diallo Tely , Diop Baye M. , Deu Monique , Gueye Mame C. , Ibrahim Bio Yerima Abdou R. , Issah Abdul R. , Kane Ndjido A. , Keita Yeremakhan , Kombiok James , Ngom Ablaye , Noyer Jean‐Louis , Olodo Katina , Oselebe Happiness O. , Pham Jean‐Louis , Piquet Marie , Puozaa Doris K. , Rivallan Ronan , Saidou Sani , Sekloka Emmanuel , Tengey Theophilus K. , Uyoh Edak A. , Vancoppenolle Sylvie , Vigouroux Yves , Zekraoui Leila , Leclerc Christian , Barnaud Adeline , Billot Claire 
Published: September 2023

Social Impact StatementThe use of neglected and underutilized species (NUS) in agrosystems is a potential solution to the challenges arising from global change. These species could contribute to the equitable diversification of agricultural systems. Providing knowledge on their genetic diversity and fostering access to data and results is essential for the development of strong collaborative future research. The study addressed these issues by assessing the diversity of the largest fonio (Digitaria exilis) collection existing to date. Associated with a user‐friendly Shiny application (https://shinyapps.southgreen.fr/app/foniodiv), our results reinforce research efficiency and broaden the prospects for all actors involved in enhancing fonio and indigenous crops as valuable resources for the future.
Prognostic significance of serum testosterone level in patients with castration‐resistant prostate cancer treated with cabazitaxel
Authors: Fujiwara Shinnosuke , Kosaka Takeo , Nishimoto Yoshinori , Kamisawa Ken , Watanabe Keitaro , Baba Yuto , Takeda Toshikazu , Matsumoto Kazuhiro , Oya Mototsugu 
Published: September 2023

AbstractBackgroundSerum testosterone level is a potential prognostic marker for castration‐resistant prostate cancer. However, its role as a prognostic marker in cabazitaxel chemotherapy remains unclear. This study aimed to elucidate the clinical significance of serum testosterone levels before cabazitaxel chemotherapy.MethodsThis single‐institution, retrospective study included 47 patients with metastatic castration‐resistant prostate cancer (mCRPC) who received cabazitaxel therapy. Serum testosterone levels were measured before the initiation of cabazitaxel therapy.ResultsProgression‐free survival and overall survival (OS) were not significantly different between patients with high and low serum testosterone levels. Analysis of patients aged <70 years revealed that those with high serum testosterone levels (total testosterone level > 0.055 ng/mL) had significantly longer OS than those with low serum testosterone levels (total testosterone level < 0.055 ng/mL, p = 0.012). Multivariate analysis revealed that low serum testosterone levels (hazard ratio [HR] = 11.874, 95% confidence interval [CI] 2.076–67.953, p = 0.005) and high prostate‐specific antigen levels (HR = 18.051, 95% CI 2.462–132.347, p = 0.004) in the pretreatment phase were independent prognostic factors for OS in patients receiving cabazitaxel therapy.ConclusionsSerum testosterone level may be a prognostic marker for cabazitaxel therapy in patients with mCRPC who are younger than 70 years, and high serum testosterone levels may lead to longer survival.
The role of PSMA PET/CT to predict upgrading in patients undergoing radical prostatectomy for ISUP grade group 1 prostate cancer
Authors: Esen Baris , Seymen Hulya , Gurses Bengi , Armutlu Ayse , Koseoglu Ersin , Tarim Kayhan , Ertoy Baydar Dilek , Sarikaya Ahmet Furkan , Canda Abdullah Erdem , Balbay Derya , Kordan Yakup , Tilki Derya , Esen Tarik , Demirkol Mehmet Onur 
Published: September 2023

AbstractIntroduction and ObjectivesTo investigate the additive role of prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) independent from multiparametric magnetic resonance imaging (mpMRI) and clinical‐pathological parameters to predict pathological upgrading in patients with ISUP grade group (GG) 1 prostate cancer (PCa) at prostate biopsy.Materials and MethodsA total of 41 patients who underwent robotic radical prostatectomy (RP) for GG1 disease at prostate biopsy with preoperative PSMA PET/CT and mpMRI images available for central review were included in the study. Univariate and multivariate logistic regression analyses were performed to determine the independent predictors of pathological upgrading (GG ≥ 2).ResultsFinal RP pathology revealed upgrading in 26 patients (65.9%); to GG 2 disease in 25 cases and GG 4 disease in one case. International Society of Urological Pathology (ISUP) upgrading rates for prostate imaging‐reporting and data system (PIRADS)‐5, PIRADS‐4, and PIRADS ≤ 3 lesions were 78%, 74%, and 38%, respectively. Fourteen out of 15 (93.3%) patients with an SUVmax ≥ 5.6 and all patients with an SUVmax ≥ 6.5 (n = 10) had pathological upgrading. The upgrading rate in patients with SUV < 5.6 was 46.2% (12/26). Intraprostatic SUVmax ≥ 5.6 was found as the only independent predictor of pathological upgrading in multivariate analysis.ConclusionHigh prostatic PSMA uptake was found to be a very reliable predictor of pathological upgrading, but low PSMA uptake cannot exclude pathological upgrading. Intraprostatic PSMA uptake along with previously known mpMRI and biopsy‐related parameters should be considered when making a treatment decision in patients with GG1 PCa at prostate biopsy.
Quotient of quotient graph a novel approach to compute π‐conjugated dendrimer and predict its properties
Authors: Xavier D. Antony , Akhila S , Varghese Eddith Sarah , Nair Theertha , Baby Annmaria 
Published: September 2023

AbstractThe role of dendrimers is getting updated and grabbing immense attention in many fields. Dendrimers are used in a broad spectrum, in specific, it is widely utilized in drug delivery, for targeted carrier and specific action. Also, in drug catalysis, it improves the solubility of poorly soluble drugs and increases the stability of active ingredients within the cores. Many researchers are interested in developing new dendrimers by using various compounds. ‐conjugated dendrimers via truxenes and thienylethynylene units, are considered a promising material in the field of medicinal chemistry, bio‐organic, and environmental sciences. In QSAR/QSPR, the structural analysis of chemical compounds is examined by topological descriptors. In this article, the various distance‐based topological indices such as Wiener, Szeged, and Mostar of gradient star‐persistent ‐conjugated dendrimers are determined. Since gradient star‐persistent ‐conjugated dendrimers have odd cycles, the usual cut method is not applicable, therefore we use a new concept, the quotient of quotient graph to determine the numerical expression of various indices. An analysis of linear regression reveals that degree‐based topological descriptors predict better physicochemical properties.
Business modeling under adversity: Resilience in international firms
Authors: Galkina Tamara , Atkova Irina , Gabrielsson Peter 
Published: September 2023

AbstractResearch SummaryThis study employs resilience theory and examines the dynamics of business modeling in international firms that enable them to resist environmental shocks under the adverse conditions of a global pandemic. Our multiple‐case study shows that firms develop various dynamic states of their business models (BMs) during the resilience process; each state differs in terms of the scope of BM change and the concurrent degree of BM innovativeness. Shifts in dynamic states result from attaining certain resilience capabilities. We contribute to the dynamic view on BMs, and the process perspective on organizational resilience; we also advance BM research in the context of internationalization.Managerial SummaryUnder conditions of extreme disruptions that take the form of long‐lasting adversity, international firms need to continuously adjust their BMs to brave force majeure and remain resilient. This study takes a dynamic perspective on business modeling and examines how international firms develop different dynamic states of their BMs to stay resilient under extreme uncertainty; each state differs in terms of the scope of BM change, concurrent degree of BM innovativeness and the attained resilience capabilities. We show that business modeling is a continuous task of international firms that allows them not only to resist adversity but also to open new markets.
Influence of Lithium Diffusion into Copper Current Collectors on Lithium Electrodeposition in Anode‐Free Lithium‐Metal Batteries
Authors: Huang Yu‐Kai , Chen Heyin , Nyholm Leif 
Published: September 2023

AbstractThe development of “anode‐free” lithium‐metal batteries with high energy densities is, at present, mainly limited by the poor control of the nucleation of lithium directly on the copper current collector, especially in conventional carbonate electrolytes. It is therefore essential to improve the understanding of the lithium nucleation process and its interactions with the copper substrate. In this study, it is shown that diffusion of lithium into the copper substrate, most likely via the grain boundaries, can significantly influence the nucleation process. Such diffusion makes it more difficult to obtain a great number of homogeneously distributed lithium nuclei on the copper surface and thus leads to inhomogeneous electrodeposition. It is, however, demonstrated that the nucleation of lithium on copper is significantly improved if an initial chemical prelithiation of the copper surface is performed. This prelithiation saturates the copper surface with lithium and hence decreases the influence of lithium diffusion via the grain boundaries. In this way, the lithium nucleation can be made to take place more homogenously, especially when a short potentiostatic nucleation pulse that can generate a large number of nuclei on the surface of the copper substrate is applied.
Migrating monolithic applications to function as a service
Authors: Würz Hendrik M. , Krämer Michel , Kaster Marvin , Kuijper Arjan 
Published: September 2023

SummaryFunction as a service (FaaS) promises low operating costs, reduced complexity, and good application performance. However, it is still an open question how to migrate monolithic applications to FaaS. In this paper, we present a guideline for software designers to split monolithic applications into smaller functions that can be executed in a FaaS environment. This enables independent scaling of individual parts of the application. Our approach consists of three steps: We first identify the main tasks (and their subtasks) of the application to split. Then, we define the program flow to be able to tell which application tasks can be converted to functions and how they interact with each other. In the final step, we specify actual functions and possibly merge those that are too small and which would produce too much communication overhead or maintenance effort. Compared to existing work, our approach applies to applications of any size and results in functions that are small enough—but not too small—for efficient execution in a FaaS environment. We evaluate the usefulness of our approach by applying it to a real‐world application for the storage of geospatial data. We describe the experiences made and finish the paper with a discussion, conclusions, and ideas for future work.
Rebuttal to Greuter & Rankin‐Rodríguez's (2831) proposal to conserve Exostema against Coutarea (Rubiaceae) and to their expanded circumscription of Exostema
Authors: Delprete Piero G. , Paudyal Sushil K. 
Published: September 2023

AbstractPaudyal & al. performed the most comprehensive phylogenetic study of the tribe Chiococceae (Rubiaceae) using two nuclear and two plastid datasets, and resolved four well‐supported main clades. Within Clade B, Paudyal & al. recognized the genera Exostema, Hintonia, Coutareopsis, Motleyothamnus, Coutarea, Adolphoduckea, and Solenandra. Greuter & Rankin‐Rodríguez interpreted the internal clades of Clade B differently, and instead treated the entire Clade B as the broadly expanded, morphologically diverse genus Exostema. In addition, because the genus Coutarea is positioned within Clade B and its name has nomenclatural priority over Exostema, Greuter & Rankin‐Rodríguez presented a formal proposal (proposal 2831) to conserve the name Exostema against Coutarea. We strongly disagree with Greuter & Rankin‐Rodríguez naming the entire Clade B of Paudyal & al. as a widely circumscribed Exostema, and with their proposal to conserve the name Exostema against Coutarea for the following reasons: (1) their wide delimitation of Exostema and their proposal to reject Coutarea vs. Exostema are and will cause wide disruption in nomenclatural stability of traditional and current usage of generic and specific names within the Chiococceae; (2) their broad synonymisation under Exostema s.l. entails the lumping of six genera (Coutarea, Adolphoduckea, Coutareopsis, Motleyothamnus, Hintonia, Solenandra) into a broadly distributed, highly polymorphic genus, decreasing the value of diagnostic information for each distinct monophyletic taxon and reducing the systematic and morphological information of the species; (3) each of the seven “Clade B” genera of Paudyal & al. corresponds to a well‐resolved clade with a unique set of morphological characters; (4) Paudyal & al.'s genera of Clade B have been accepted by numerous Rubiaceae specialists and managers of specialized websites; (5) the broad expansion of Exostema proposed by Greuter & Rankin‐Rodríguez does not fulfill the principle of maximizing the ease of identification of the c. 40 species included in such a highly polymorphic genus, increasing the difficulty of species identification by the botanical community. In conclusion, we advise the Nomenclature Committee to reject Greuter & Rankin‐Rodríguez's proposal to conserve the generic name Exostema against Coutarea.
Studies on immunotoxicity induced by emamectin benzoate in zebrafish embryos based on metabolomics
Authors: Wei Ziyi , Wang Weiguo , Xu Wenping , Tao Liming , Li Zhong , Zhang Yang , Shao Xusheng 
Published: September 2023

AbstractEmamectin benzoate (EMB) is an insecticide for the control of agricultural lepidoptera pests, and also an anti‐parasiticide for the control of exoparasites in aquaculture industry. Increased studies suggest that EMB could cause toxicity to non‐targeted organisms, but its immunotoxicity to human remains unclear. In this study, zebrafish were used to investigate the immunotoxic effects induced by environmentally relevant doses of EMB. We observed that EMB exposure led to embryo mortality and delayed hatching, as well as increased malformations. Meanwhile, zebrafish exposed to EMB exhibited a significant decrease in the number of neutrophils and macrophages. In addition, untargeted metabolomics approach was developed to elucidate the mechanism of EMB‐induced immunotoxicity. We found that a total of 10 shared biomarkers were identified in response to EMB exposure. Furthermore, pathway analysis identified glycerophospholipid metabolism was the most relevant pathway. Within this pathway, it was observed abnormal increases in glycerol 3‐phosphate content, which could be attributed to the increased expression of GK5 and decreased expression of GPAT3. Our study provided novel and robust perspectives, which showed that EMB exposure to zebrafish embryos could cause metabolic disturbances that adversely affected development and immune system.
Total flavonoids of Rhizoma drynariae improves tendon‐bone healing for anterior cruciate ligament reconstruction in mice and promotes the osteogenic differentiation of bone mesenchymal stem cells by the ERR1/2‐Gga1‐TGF‐β/MAPK pathway
Authors: Han Lei , Wang Canfeng , Wang Tuo , Hu Yungeng , Wang Hongshun 
Published: September 2023

AbstractBackgroundTotal flavonoids of Rhizoma drynariae (TFRD) is broadly used in the treatment of orthopedic diseases. Nevertheless, the effects and underlying mechanism of TFRD on tendon‐bone healing after anterior cruciate ligament reconstruction (ACLR) remain unclear.MethodsThe ACLR mouse model was established. Hematoxylin and Eosin (HE) staining was used for histological analysis of tendon‐bone healing. Western blot was utilized to detect the levels of osteogenic related factors (ALP, OCN, RUNX2). The viability and alkaline phosphatase (ALP) activity of bone mesenchymal stem cells (BMSCs) were determined by Cell Counting Kit‐8 (CCK‐8) and ALP assays. The interaction of estrogen related receptor alpha (ESRRA), estrogen related receptor beta (ESRRB), and golgi‐localized γ‐ear containing ADP ribosylation factor‐binding protein 1 (Gga1) was detected by luciferase reporter assays. The levels of important proteins on the TGF‐β/MAPK pathway were measured by western blot.ResultsTFRD improved tendon‐bone healing, restored biomechanics of ACLR mice and activated the TGF‐β/MAPK pathway. TFRD treatment also enhanced the viability and osteogenic differentiation of BMSCs in vitro. Then, we demonstrated that TFRD targeted ESRRA and ESRRB to transcriptionally activate Gga1 expression. Knockdown of ESRRA, ESRRB, or Gga1 suppressed the viability and osteogenic differentiation of TFRD‐induced BMSCs, which was revealed to be restored by Gga1 overexpression. The overexpression of ESRRA, ESRRB, or Gga1 was demonstrated to promote the BMSC viability and osteogenic differentiation. TGF‐β1 treatment can reverse the impact of Gga1 inhibition on osteogenic differentiation in TFRD‐induced BMSCs.ConclusionTFRD improves tendon‐bone healing in ACLR mouse models and facilitates the osteogenic differentiation of BMSCs through the ERR1/2‐Gga1‐TGF‐β/MAPK pathway, which might deepen our understanding of the underlying mechanism of TFRD in tendon‐bone healing.
Surgical intervention and outcome in a domestic rabbit (Oryctolagus cuniculus domesticus) with dystocia and uterine torsion
Authors: Revay Rebecca , Needleman Abigail 
Published: September 2023

AbstractAn adult female intact rabbit presented through a 24‐h emergency service for exhibiting signs of stage 1 labour for over 5 h. Physical examination findings, delayed progression to stage 2 labour and diagnostic imaging were consistent with dystocia with multiple fetuses present. A laparotomy was performed, during which an en bloc ovariohysterectomy was performed after discovery of an ∼180° counterclockwise uterine torsion. Of the eight kits present in the uterus, five survived to discharge from the hospital. Uterine torsion should be considered a differential diagnosis for any rabbit presenting with dystocia and can carry a good prognosis for the doe and kits with prompt surgical intervention.