bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, Tolerability, and Pharmacokinetics of Single Doses of Exidavnemab (BAN0805), an Anti‐α‐Synuclein Antibody, in Healthy Western, Caucasian, Japanese, and Han Chinese Adults
Authors: Boström Emma , Bachhav Sagar S. , Xiong Hao , Zadikoff Cindy , Li Qingbo , Cohen Eric , Dreher Ingeborg , Torrång Anna , Osswald Gunilla , Moge Mikael , Appelkvist Paulina , Fälting Johanna , Odergren Tomas 
Published: August 2024

AbstractExidavnemab is a monoclonal antibody (mAb) with a high affinity and selectivity for pathological aggregated forms of α‐synuclein and a low affinity for physiological monomers, which is in clinical development as a disease‐modifying treatment for patients with synucleinopathies such as Parkinson's disease. Safety, tolerability, pharmacokinetics, immunogenicity, and exploratory biomarkers were assessed in two separate Phase 1 single ascending dose studies, including single intravenous (IV) (100 to 6000 mg) or subcutaneous (SC) (300 mg) administration of exidavnemab in healthy volunteers (HVs). Across the two studies, a total of 98 Western, Caucasian, Japanese, and Han Chinese HVs were enrolled, of which 95 completed the study. Exidavnemab was generally well tolerated. There were no serious adverse events or safety issues identified in laboratory analyses. Headache, asymptomatic COVID‐19, back pain, and post lumbar puncture syndrome were the most frequently reported treatment‐emergent adverse events. Following IV infusion, the pharmacokinetics of exidavnemab was approximately dose linear in the range 100‐6000 mg. The terminal half‐life was approximately 30 days, and the exposure was comparable across Western, Caucasian, Japanese, and Han Chinese volunteers. The absolute SC bioavailability was ∼71%. Cerebrospinal fluid exposure relative to serum after single dose was within the range expected for mAbs (approximately 0.2%). The anti‐drug antibody rates were low and there was no effect of immunogenicity on the pharmacokinetics or safety. Dose‐dependent reduction of free α‐synuclein in plasma was observed. In summary, exidavnemab was found to have an excellent pharmacokinetic profile and was well tolerated in HVs, supporting the continued clinical development.
Predict the Drug–Drug Interaction of a Novel PI3Kα/δ Inhibitor, TQ‐B3525, and Its Two Metabolites Using Physiologically Based Pharmacokinetic Modeling
Authors: Zhu Shixing , Yu Ding , Wang Xunqiang , Wang Xin 
Published: August 2024

AbstractA novel dual PI3K α/δ inhibitor, TQ‐B3525, has been developed for the targeted treatment of lymphoma and solid tumors. TQ‐B3525 is primarily metabolized by CYP3A4 and FOM3, while also serving as a substrate for the P‐glycoprotein transporter. The aim of this study was to anticipate the drug–drug interaction (DDI) of TQ‐B3525 and its two metabolites with CYP3A4 enzyme potent inducer (rifampicin) and CYP3A4/P‐gp inhibitor (itraconazole) utilizing a physiologically based pharmacokinetic (PBPK) modeling approach. Clinical data from healthy and cancer patient adults were employed to construct and evaluate the PBPK model for TQ‐B3525, M3, and M8‐3. Models involving rifampicin combined with midazolam, itraconazole combined with midazolam or digoxin were utilized to showcase the robustness of evaluating DDI effects. The simulated drug exposure of TQ‐B3525, M3, and M8‐3 in healthy and patient adults were consistent with clinical data, and the mean fold error values were within the acceptable ranges. The simulated results of positive substrates correspond to those reported in the literature. Co‐administration with rifampicin reduces Cmax and AUC of TQ‐B3525 to 76.1% and 46.0%, while increasing the levels of M3 and M8‐3. With itraconazole, Cmax and AUC of TQ‐B3525 rise to 131% and 204%, but decrease substantially for M3 and M8‐3. PBPK model simulation results showed that the systemic exposure of TQ‐B3525 was significantly affected when co‐administered with CYP3A4/P‐gp inducers and inhibitors. This indicates that the combination with strong inducers and inhibitors should be carefully avoided or adjust the dosage of TQ‐B3525 in clinic.
Leveraging the dynamics of microalgal CO2 capture to estimate the maximum inherent photosynthetic potential
Authors: Battula Satyanarayana Reddy , Sen Ramkrishna 
Published: August 2024

AbstractBACKGROUNDNatural photosynthesis, utilizing intelligent molecular machinery to harness sunlight, stands as the benchmark for efficient energy generation. Despite its high quantum efficiency compared to synthetic methods, challenges persist due to dynamic nutritional and light requirements in plant, microalgae, and cyanobacteria‐driven processes. Reported microalgae CO2 uptake rates rely on biomass dry cell weight measurement after certain incubation period and systematic study of required CO2 concentrations for optimal photobioreactor operation remaining unexplored. This research is thus aimed at evaluating the critical dissolved CO2 (Ccrit ∙ CO2) concentration and specific CO2 uptake rates (SCUR) of Chlorella minutissima (CM) culture in the presence of surplus light and other nutrients by online monitoring and measuring the dynamic CO2 uptake rates which will help in maintaining the optimal rate of CO2 delivery for continuous cultivation of microalgae while minimizing the escape of CO2.RESULTSDissolved Ccrit ∙ CO2 was determined to be in the range of 16–20 mg/L, and the maximum SCUR in BBM (Bold Basal Medium) was found to be 0.73 mg CO2 (mg dcw ∙ h)−1. Interestingly, this SCUR value is nearly three times greater than that of the most efficient in vitro artificial photosynthetic novel pathway reported so far.CONCLUSIONFrom the calculated SCUR values, it may be noted that 9.6 g of biomass can be obtained from 1 g of microalgal inoculum in a day, thereby setting a benchmark for the scientists working in the areas of bioprocess engineering, synthetic biology, and metabolic engineering to comply. © 2024 Society of Chemical Industry (SCI).
Development and evaluation of a surgical 3D simulation model on submental flap surgery training
Authors: Tahami Hadis , Rahpeyma Amin , Shooshtari Zahra , Shahri Arsalan , Pourianezhad Bita , Khajehahmadi Saeedeh 
Published: August 2024

AbstractObjectivesThe purpose of the present study was to design and assess a 3D simulation model for submental flap surgery in training oral and maxillofacial surgery (OMFS) residents.MethodsThis quasi‐experimental study involved a total of 20 OMFS residents attending and was conducted from September 2023 to December 2023. A 3D submental flap surgical phantom was designed using Mimics V.21 software and printed using fused deposition modeling technology. Participants were first tested on their knowledge of submental flap surgery before being randomly assigned to experimental or control groups. The experimental group received a lecture and demonstration using the developed phantom, while the control group had traditional lecture education only. Afterward, the same test was administered to all participants post‐training. Pre‐ and post‐test scores were calculated and compared between the two groups. p‐Value < 0.05 was considered statistically significant.ResultsThe average pre‐intervention test scores in the control and experimental group, were 2.5 ± 1.43 and 3 ± 0.816, respectively (p = 0.35). Post‐intervention, the experimental group exhibited significantly higher exam scores compared to the group who had only received academic lecture training (6.9 ± 0.87 vs. 4.9 ± 0.99) (p < 0.001). Irrespective of the applied teaching method, both groups showed a significant increase in exam scores after receiving submental flap training (p < 0.001 for both groups, paired‐sample t‐test).ConclusionThe use of the developed submental flap phantom model significantly improved OMFS residents' test scores and knowledge of the surgical technique, suggesting its potential integration into the conventional resident training curriculum.
A Predictive Model for Initial Platinum‐Based Chemotherapy Efficacy in Patients with Postoperative Epithelial Ovarian Cancer Using Tissue‐Derived Small Extracellular Vesicles
Authors: Shen Shizhen , Wang Conghui , Gu Jiaxin , Song Feifei , Wu Xiaodong , Qian Fangfang , Chen Xiaojing , Wang Lingfang , Peng Qiaohua , Xing Ziyu , Gu Lingkai , Wang Fenfen , Cheng Xiaodong 
Published: August 2024

AbstractEpithelial ovarian cancer (EOC) is an often‐fatal malignancy marked by the development of resistance to platinum‐based chemotherapy. Thus, accurate prediction of platinum drug efficacy is crucial for strategically selecting postoperative interventions to mitigate the risks associated with suboptimal therapeutic outcomes and adverse effects. Tissue‐derived extracellular vesicles (tsEVs), in contrast to their plasma counterparts, have emerged as a powerful tool for examining distinctive attributes of EOC tissues. In this study, 4D data‐independent acquisition (DIA) proteomic sequencing was performed on tsEVs obtained from 58 platinum‐sensitive and 30 platinum‐resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune‐related pathways. Moreover, pivotal immune‐related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression. This model integrated three tsEV IRPs, CCR1, IGHV_35 and CD72, with one clinical parameter, the presence of postoperative residual lesions. Thus, this model could predict the efficacy of initial platinum‐based chemotherapy in patients with EOC post‐surgery, providing prognostic insights even before the initiation of chemotherapy.
Proximity ligation‐based sequencing for the identification of human papillomavirus genomic integration sites in formalin‐fixed paraffin embedded oropharyngeal squamous cell carcinomas
Authors: Demers Imke , Balaji Harini , Feitsma Harma , Stelloo Ellen , Swennenhuis Joost , Sergeeva Irina , Wuerdemann Nora , van den Hout Mari F. C. M. , Wagner Steffen , Kremer Bernd , Klussmann Jens P. , Huebbers Christian U. , Speel Ernst‐Jan M. 
Published: August 2024

AbstractHuman papillomavirus (HPV) infections are an increasing cause of oropharyngeal squamous cell carcinomas (OPSCC). Integration of the viral genome into the host genome is suggested to affect carcinogenesis, however, the correlation with OPSCC patient prognosis is still unclear. Research on HPV integration is hampered by current integration detection technologies and their unsuitability for formalin‐fixed paraffin‐embedded (FFPE) tissues. This study aims to develop and validate a novel targeted proximity‐ligation based sequencing method (targeted locus amplification/capture [TLA/TLC]) for HPV integration detection in cell lines and FFPE OPSCCs. For the identification of HPV integrations, TLA/TLC was applied to 7 cell lines and 27 FFPE OPSCCs. Following preprocessing steps, a polymerase chain reaction (PCR)‐based HPV enrichment was performed on the cell lines and a capture‐based HPV enrichment was performed on the FFPE tissues before paired‐end sequencing. TLA was able to sequence up to hundreds of kb around the target, detecting exact HPV integration loci, structural variants, and chromosomal rearrangements. In all cell lines, one or more integration sites were identified, in accordance with detection of integrated papillomavirus sequences PCR data and the literature. TLC detected integrated HPV in 15/27 FFPE OPSCCs and identified simple and complex integration patterns. In general, TLA/TLC confirmed PCR data and detected additional integration sites. In conclusion TLA/TLC reliably and robustly detects HPV integration in cell lines and FFPE OPSCCs, enabling large, population‐based studies on the clinical relevance of HPV integration. Furthermore, this approach might be valuable for clonality assessment of HPV‐related tumors in clinical diagnostics.
Early postnatal development of the primary visual areas 17 and 18 of the cat cerebral cortex: An SMI‐32 study
Authors: Mikhalkin A. A. , Nikitina N. I. , Merkulyeva N. S. 
Published: August 2024

AbstractUsing anti‐neurofilament H non‐phosphorylated antibodies (SMI‐32) as markers for the neuronal maturation level and Y channel responsible for motion processing, we investigated early postnatal development of the primary visual areas 17 and 18 in cats aged 0, 10, 14, and 34 days and in adults. Two analyzed parameters of SMI‐32‐immunolabeling were used: the total proportion of SMI‐32‐labeling and the density of labeled neurons. (i) The developmental time course of the total proportion of SMI‐32‐labeling shows the general increase in the accumulation of heavy‐chain neurofilaments. This parameter showed a different time course for cortical layer development; the maximal increment in the total labeling in layer V occurred between the second and fifth postnatal weeks and in layers II–III and VI after the fifth postnatal week. In addition, the delay in accumulation of SMI‐32‐labeling was shown in layer V of the area 17 periphery representation during the first two postnatal weeks. (ii) The density of SMI‐32‐labeled neurons decreased in all layers of area 18, but was increased, decreased, or had a transient peak in layers II–III, V, and VI of area 17, respectively. The transient peak is in good correspondence with some transient neurochemical features previously revealed for different classes of cortical and thalamic neurons and reflects the time course of the early development of the thalamocortical circuitry. Some similarities between the time courses for the development of SMI‐32‐labeling in areas 17/18 and in A‐ and C‐laminae of the LGNd allow us to propose heterochronous postnatal development of two Y sub‐channels.
Exercise improves load bearing bone structural properties in female secreted protein acidic and rich in cysteine (SPARC) null mice but not in males
Authors: Kaneda Giselle , Huang Dave , Pham Nathalie , Gonzalez Alfonso R. , Tawackoli Wafa , Lee Seunghwan , Suzuki Miyako , Nelson Trevor J. , Glaeser Juliane D. , Millecamps Magali , Stone Laura S. , Sheyn Dmitriy , Metzger Melodie F. 
Published: August 2024

AbstractSecreted protein acidic and rich in cysteine (SPARC) is the most abundant glycoprotein in bone and is thought to play a critical role in bone remodeling and homeostasis. However, the effect of SPARC in relation to gender and exercise on bone quality is not well understood. The purpose of this study was to quantify differences in the structural and biomechanical properties between calvarial and femoral bone from male and female wild‐type (WT) and SPARC null (SPARC(−/−)) mice as well as the ability of exercise to rescue bone health. Male and female WT and transgenic SPARC(−/−) mice were given either a fixed or rotating running wheel for exercise. Bone structural, biomechanical, and morphological parameters were quantified using micro computed tomography, push out testing for the calvaria, three‐point flexural testing for the femurs, histological and immunofluorescent staining. Similar reductions in structural and biomechanical strength were observed in both male and female SPARC(−/−) calvaria, most of which were not significantly affected by exercise. In femurs, SPARC(−/−) had a significant effect on structural parameters in both sexes, but was more pronounced in females with some properties being rescued with running. Interestingly, the effect of SPARC(−/−) on bone mineral density was only detected in female SPARC(−/−) mice, not males, and was subsequently rescued with exercise. This study emphasizes the differences between sexes in WT and SPARC(−/−) mice in regard to structural parameters and biomechanical properties. Research into gender differences can help inform and personalize treatment options to more accurately meet patient needs.
Influence of biliary and vascular resection types on morbidity in hepatectomies with vascular involvement
Authors: Silva Jonatha C. F. da , Diniz Alessandro L. , Torres Silvio M. , Silva Dante A. , Ribeiro Héber S. d. C. , de Godoy André Luiz , de Farias Igor Correia , Felismino Tiago Cordeiro , da Costa Junior Wilson L. , Coimbra Felipe José F. 
Published: August 2024

AbstractIntroductionHepatectomies associated with vascular resections pose a technical challenge for surgeons, involving multiple reconstruction techniques. Moreover, adding clinical and surgical risks in the postoperative setting of these complex procedures are mainly due to prolonged surgical periods and potential complications inherent to vascular manipulation. Leveraging the expertise of a Cancer Center, we propose an institutional assessment utilizing the case series from A. C. Camargo Cancer Center in hepatectomies associated with vascular resection, evaluating postoperative complications and outcomes while highlighting clinical, laboratory, pathological, and surgical factors that may influence results.ObjectiveTo assess mortality and morbidity associated with hepatectomies involving vascular resection.Materials and MethodsFrom a prospective database, a study was performed evaluating postoperative survival and morbidity using scoring systems such as Clavien−Dindo through a cohort analysis.ResultsFrom a total of 1021 liver resections for a period of 10 years, 31 cases were evaluated from a unique cancer center in Brazil! Factors such as the performance of major hepatectomies, the need for blood transfusion, and the administration of neoadjuvant or adjuvant systemic therapy did not appear to influence the outcome of morbidity or mortality. However, the resection of the associated bile duct and the type of vascular resection seemed to influence morbidity outcomes with statistical significance (p = 0.006+ …).ConclusionHepatectomies associated with vascular resections are safe in selected cases and when performed in referral centers. Factors such as associated bile duct resection and type of vascular resection should be considered for procedure indication.
Comparing cadaveric and 3D‐printed laryngeal models in transcutaneous injection laryngoplasty
Authors: Chandna Megha , Siddiqui Sana , Bertoni Dylan , Sakkal Marah , Belko Sara , Boon Maurits , Spiegel Joseph 
Published: August 2024

AbstractBackgroundThere is increasing focus on the development of high‐quality simulation models for medical education. Cadaveric models, although considered more realistic, may be difficult to obtain and costly. The advent of three‐dimensional (3D) printing has offered a low‐cost, reliable, and reproducible alternative. This study sought to compare the utility of 3D‐printed to cadaveric models for training in transcutaneous injection laryngoplasty (TIL).MethodsA simulation course with a cross‐over design was employed. Video laryngoscopes were utilized for both the 3D and cadaveric models to assess the accuracy of injection into the vocal fold. Pre‐procedure and post‐procedure surveys were administered to evaluate understanding and comfort level on a Likert scale of 1–10. Each model was also rated on a 1–5 Likert scale for self‐efficacy, fidelity, and educational value.ResultsPre‐ and post‐survey data were completed by 15 otolaryngology residents and medical students. Mean pre‐seminar understanding and comfort level were 3.7 and 2.2, respectively, compared to 6.9 and 5.9 (p < .05) following use of the 3D model and 6.4 and 4.7 (p < .05) following use of the cadaver model. When comparing 3D and cadaveric models, no significant differences were observed regarding self‐efficacy, fidelity, and educational value.ConclusionThere was a similar mean increase in understanding and comfort following use of the 3D and cadaveric models. 3D‐printing can provide an excellent adjunct to, and eventually a potential replacement for hands‐on cadaveric training in medical education, particularly for TIL.Level of EvidenceLevel III.
Oropharyngeal reconstruction with buccinator myomucosal island flaps: Functional outcomes and quality of life. A retrospective observational study
Authors: Carnevale C. , Sarría‐Echegaray P. , Morales Olavarría C. , Til‐Pérez G. 
Published: August 2024

AbstractBackgroundThe buccinator myomucosal island flaps are an excellent option for “like with like” oropharyngeal reconstruction in selected cases. We report a series of 15 patients and discuss the functional outcomes.MethodsFrom January 1, 2020 to February 31, 2023, 15 patients underwent oropharyngeal tumor resection and reconstruction with myomucosal island flaps. Buccal artery myomucosal island flap and tunnelized facial artery myomucosal island flap were used in 10 and 5 patients, respectively. In four cases, a total soft palate reconstruction was performed. Before removing the nasogastric tube, a videoendoscopy was performed in all cases to assess postoperative swallowing. Functional assessment was evaluated after a follow‐up of at least 12 months. Speech intelligibility and patient speech perception were assessed using the Hirose's 10‐point scoring system and the Voice Handicap Index. Dysphagia was assessed using the Dysphagia Outcome and Severity Scale and the Dysphagia Handicap Index. Finally, donor site morbidity was analyzed, and quality of life was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ‐C30).ResultsThe median length of hospital stay was 10.5 days. Nasal feeding tube was removed on average in 8.6 days after surgery, and all patients were able to tolerate an oral soft diet. Intelligibility was very good in all cases. No major complications were detected, and donor site morbidity was low. Global quality of life was acceptable in all cases.ConclusionsBuccinator myomucosal island flaps represent a very interesting and versatile option for the functional reconstruction of oropharyngeal defects up to 7–8 cm.Level of EvidenceIV
3D‐printed neck phantoms with detailed anatomy for ultrasound‐guided procedure and device testing
Authors: Hasson Aida M. , Patel Rahul D. , Sissoko Cheick A. , Brattain Laura , Dion Gregory R. 
Published: August 2024

AbstractObjectivesWith rapid advances in ultrasound‐guided procedures, there is an unmet need for echogenic phantoms with sufficient anatomical details for artificial intelligence and ultrasound‐guided device testing. We developed a method for creating neck phantoms for novel otolaryngology‐related device testing. To achieve accurate representation of the anatomy, we utilized CT scans and 3D printing technology to create customized agar molds, thus providing high‐fidelity yet cost‐effective tools.MethodsBased on previous studies, the key components in our neck phantom include the cervical vertebrae, trachea, common carotid arteries, internal jugular veins, thyroid gland, and surrounding soft tissue. Open‐source image analysis software were employed to process CT data to generate high fidelity 3D models of the target structures. Resin molds were 3D printed and filled with various agar mixtures to mimic anatomical echogenicity.ResultsFollowing the method proposed, we successfully assembled the neck phantom which provided a detailed representation of the target structures. To evaluate the results, ultrasound data was collected on the phantom and living tissue and analyzed with ImageJ. We were able to demonstrate echogenicity comparable to that of living tissue.ConclusionThe proposed method for building neck phantoms with detailed anatomical features offers a valuable, detailed, low‐cost tool for medical training and device testing in otolaryngology, particularly for novel devices that involve artificial intelligence (AI) guidance and robotic‐based needle insertion. Additional anatomical refinements and validation studies could further enhance the consistency and accuracy, thus paving the way for future advancements in ultrasound training and research, and ultimately benefiting patient care and safety.