Residual Tissue Research Articles

Intramuscular and oral single-dose pharmacokinetic profiles and multi-tissue distribution of thiamphenicol in Chinese soft-shelled turtle (Trionyx sinensis)

The aim of this investigation was to reveal the pattern of disposal process of thiamphenicol (TAP) in Chinese soft-shelled turtle after oral (PO) and intramuscular (IM) administration routes. TAP concentration levels in Chinese soft-shelled turtle plasma and multi-tissues were measured by HPLC-MS/MS. Pharmacokinetic (PK) parameters of TAP were estimated using WinNolin software based on the non-compartmental analysis. Compared with IM route, higher absorption, longer elimination time and greater AUC0-∞ value for TAP in plasma were observed after PO treatment. It indicated that Chinese soft-shelled turtle has a higher bioavailability for TAP following PO administration than IM medication. For tissue distribution, higher TAP concentrations were also found following PO medication than IM administration. The prescribed medication dosage of TAP (17.5 mg/kg bw) against susceptible strains with MIC should be below 0.22 mg/L (PO) and 0.13 mg/L (IM) based on the values of Cmax/MIC >10 and AUC0–24 h/MIC >125. TAP elimination pattern was investigated, and skirt was suggested as residual target tissue. Withdrawal time (WT) of TAP was calculated using WT 1.4 software, and the recommended WT was 17 d (391 ℃-day). The present investigation can serve as reference data for TAP use in Chinese soft-shelled turtle.

Case Report: Uterine artery embolization after dysfunctional uterine bleeding due to incomplete abortion in female

Dysfunctional uterine bleeding (DUB), a serious clinical challenge caused by incomplete abortion in female, calls for efficient and minimally invasive therapies to treat symptoms and protect reproductive health. Uterine artery embolization (UAE) has been discovered as a viable therapeutic strategy to treat DUB following an incomplete abortion. The existing information and clinical experience of UAE for this particular indication were thoroughly reviewed. A female’s quality of life may be negatively affected by incomplete abortion, which is defined as residual fetal tissue inside the uterine cavity. This frequently results in heavy and continuous uterine bleeding. Medical procedures and traditional management techniques such as dilatation and curettage (D&C) do not always produce the desired effects or might have inherent dangers. UAE, a less invasive technique first developed for treating uterine fibroids, has shown promise as a substitute solution for DUB caused by an incomplete abortion.

Evaluating the utility of ZNF331 promoter methylation as a prognostic and predictive marker in stage III colon cancer: results from CALGB 89803 (Alliance)

ABSTRACT While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of ZNF331 promoter hypermethylation (mZNF331) as a prognostic and predictive marker in colon cancer. We examined the association of mZNF331 with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803). Residual tumour tissue was available for genomic DNA extraction and methylation analysis for 385 patients. ZNF331 promoter methylation status was determined by bisulphite conversion and fluorescence-based real-time polymerase chain reaction. Kaplan-Meier estimator and Cox proportional hazard models were used to assess the prognostic and predictive role of mZNF331 in this well-annotated dataset, adjusting for clinicopathologic features and standard molecular markers. mZNF331 was observed in 267/385 (69.4%) evaluable cases. Histopathologic features were largely similar between patients with mZNF331 compared to unmethylated ZNF331 (unmZNFF31). There was no significant difference in disease-free or overall survival between patients with mZNF331 versus unmZNF331 colon cancers, even when adjusting for clinicopathologic features and molecular marker status. Similarly, there was no difference in disease-free or overall survival across treatment arms when stratified by ZNF331 methylation status. While ZNF331 promoter hypermethylation is frequently observed in CRC, our current study of a small subset of patients with stage III colon cancer suggests limited applicability as a prognostic marker. Larger studies may provide more insight and clarity into the applicability of mZNF331 as a prognostic and predictive marker.

Heterogeneous treatment effect of dose-dense paclitaxel plus carboplatin therapy for advanced ovarian cancer.

A Japanese clinical trial (JGOG3016) showed that dose-dense weekly paclitaxel in combination with carboplatin extensively prolonged overall survival (OS) in patients with advanced ovarian cancer. However, in other clinical trials, dose-dense paclitaxel regimens were not superior to triweekly paclitaxel regimens. In this study, causal tree analysis was applied to explore subpopulations with different treatment effects of dose-dense paclitaxel in a data-driven approach. The 587 participants with stage II-IV ovarian cancer in the JGOG3016 trial were used for model development. The primary endpoint was treatment effect in terms of 3-year OS in patients receiving dose-dense vs. conventional paclitaxel therapies. In patients <50 years, the 3-year OS was similar in both groups; however, it was higher in the dose-dense group in patients ≥50 years. Dose-dense paclitaxel showed strong positive treatment effects in patients ≥50 years with stage II/III disease, BMI <23 kg/m2, non-CC/MC, and residual tumor ≥1 cm. In contrast, although there was no significant difference in OS; the 3-year OS rate was 23% lower in dose-dense paclitaxel than conventional paclitaxel in patients ≥60 years with stage IV cancer. Patients in this group had a particularly lower performance status than other groups. Our causal tree analysis suggested that poor prognosis groups represented by residual tumor tissue ≥1 cm benefit from dose-dense paclitaxel, whereas elderly patients with advanced disease and low-performance status are negatively impacted by dose-dense paclitaxel. These subpopulations will be of interest to future validation studies. Personalized treatments based on clinical features are expected to improve advanced ovarian cancer prognosis.

Single Institution Experience in the Management of Locally Advanced (pT4) Differentiated Thyroid Carcinomas.

Locally infiltrating (T4) differentiated thyroid carcinomas (DTC) represent a challenge. Surgical strategy and adjuvant therapy should be planned balancing morbidity and oncologic outcome. A series of patients with T4 DTC who underwent multidisciplinary evaluation and treatment is reported. The main study endpoints were the oncologic outcome, complication rates, and risk factors for tumor recurrence. All DTC cases operated between 2009 and 2021 were reviewed and T4 DTC cases were identified. En bloc resection of inferior laryngeal nerve (ILN), tracheal, and/or internal jugular vein (IJV) was performed in cases of massive infiltration. In cases of pharyngoesophageal junction (PEJ) invasion, the shaving technique was always applied. Among 4775 DTC cases, 60 were T4. ILN infiltration was documented in 45 cases (en bloc resection in 9), tracheal infiltration in 14 (tracheal resection in 2), PEJ invasion in 11 (R0 resection in 7 cases and < 1 cm residual tissue in 4 cases), IJV resection in 6, and laryngeal in 2. In total, 11 postoperative ILN palsy, 23 transient hypoparathyroidisms, and 2 hematomas requiring reoperation were registered. Final histology showed 7 pN0, 22 pN1a, and 31 pN1b tumors. Aggressive variants were observed in 47 patients. All but 1 patient underwent radioiodine treatment, 12 underwent adjuvant external beam radiation therapy (EBRT), and 2 underwent chemotherapy. At a median follow-up of 58 months, no tumor-related death was registered, and seven patients required reoperation for recurrence. Tracheal invasion was the only significant factor negatively impacting recurrence (p = 0.045). A multidisciplinary approach is essential for the management of T4 DTC. Individualized and balanced surgical strategy and adjuvant treatments, in particular EBRT, ensure control of locally advanced disease with acceptable morbidity.

Do Muscle Mass and Body Fat Differ Between Elite and Amateur Natural Physique Athletes on Competition Day? A Preliminary, Cross-Sectional, Anthropometric Study.

González-Cano, H, Martín-Olmedo, JJ, Baz-Valle, E, Contreras, C, Schoenfeld, BJ, García-Ramos, A, Jiménez-Martínez, P, and Alix-Fages, C. Do muscle mass and body fat differ between elite and amateur natural physique athletes on competition day? A preliminary, cross-sectional, anthropometric study. J Strength Cond Res 38(5): 951-956, 2024-Natural physique athletes strive to achieve low body fat levels while promoting muscle mass hypertrophy for competition day. This study aimed to compare the anthropometric characteristics of natural amateur (AMA) and professional (PRO) World Natural Bodybuilding Federation (WNBF) competitors. Eleven male natural physique athletes (6 PRO and 5 AMA; age = 24.8 ± 2.3 years) underwent a comprehensive anthropometric evaluation following the International Society for the Advancement of Kinanthropometry protocol within a 24-hour time frame surrounding the competition. The 5-component fractionation method was used to obtain the body composition profile of the muscle, adipose, bone, skin, and residual tissues. Five physique athletes exceeded the 5.2 cutoff point of muscle-to-bone ratio (MBR) for natural athletes. Professional physique athletes were older than AMA physique athletes (p = 0.05), and they also presented larger thigh girths (p = 0.005) and bone mass (p = 0.019) compared with AMA physique athletes. Although no statistically significant between-group differences were observed in body mass, height, or body fat levels, PRO physique athletes exhibited a higher body mass index (BMI; AMA: 24.45 ± 0.12; PRO: 25.52 ± 1.01; p = 0.048), lean body mass (LBM; AMA: 64.49 ± 2.35; PRO: 69.80 ± 3.78; p = 0.024), fat-free mass (FFM; AMA: 71.23 ± 3.21; PRO: 76.52 ± 4.31; p = 0.05), LBM index (LBMI; AMA: 20.65 ± 0.52; PRO: 21.74 ± 0.85; p = 0.034), and fat-free mass index index (FFMI; AMA: 22.80 ± 0.22; PRO: 23.83 ± 0.90; p = 0.037) compared with AMA physique athletes. These findings highlight the unique characteristics and anthropometric differences between PRO and AMA natural physique athletes on competition day, emphasizing the significance of age, thigh girth, bone mass, BMI, LBM, FFM, and FFMI in distinguishing these 2 groups. Based on our findings, the established boundaries for muscle mass in natural physique athletes, based on FFMI and MBR, warrant reconsideration.

Raman spectroscopy for esophageal tumor diagnosis and delineation using machine learning and the portable Raman spectrometer

Esophageal cancer is one of the leading causes of cancer-related deaths worldwide. The identification of residual tumor tissues in the surgical margin of esophageal cancer is essential for the treatment and prognosis of cancer patients. But the current diagnostic methods, either pathological frozen section or paraffin section examination, are laborious, time-consuming, and inconvenient. Raman spectroscopy is a label-free and non-invasive analytical technique that provides molecular information with high specificity. Here, we report the use of a portable Raman system and machine learning algorithms to achieve accurate diagnosis of esophageal tumor tissue in surgically resected specimens. We tested five machine learning-based classification methods, including k-Nearest Neighbors, Adaptive Boosting, Random Forest, Principal Component Analysis-Linear Discriminant Analysis, and Support Vector Machine (SVM). Among them, SVM shows the highest accuracy (88.61 %) in classifying the esophageal tumor and normal tissues. The portable Raman system demonstrates robust measurements with an acceptable focal plane shift of up to 3 mm, which enables large-area Raman mapping on resected tissues. Based on this, we finally achieve successful Raman visualization of tumor boundaries on surgical margin specimens, and the Raman measurement time is less than 5 min. This work provides a robust, convenient, accurate, and cost-effective tool for the diagnosis of esophageal cancer tumors, advancing toward Raman-based clinical intraoperative applications.

Comparison of classical method and microdebrider technique for adenoidectomy in pediatric patients with obstructive sleep apnea.

The aim of this study was to evaluate the safety and efficacy of microdebrider adenoidectomy on sleep-disordered breathing among pediatric patients with OSA. In the microdebrider group (Group I), there were 30 Japanese OSA patients consisting of 26 boys and 4 girls. For comparison, we had 15 children (13 boys and 2 girls) who underwent classical adenoidectomy (Group II). Patients in Group I were selected from a pool of 95 pediatric Japanese OSA patients and were matched by age, preoperative AHI, and Kaup index with those in Group II.Parameters such as the amount of residual adenoid tissue, bleeding, duration of the procedure, and sleep-related metrics were compared between the two groups. A significant improvement in postoperative AHI was observed in Group I (p<0.05). The prevalence of AHI <1 was significantly higher in Group I compared with Group II (p<0.05). Additionally, the amount of postoperative residual adenoid was significantly less in Group I (3/30 of Grade 3 and 4 adenoid size) than in Group II (7/15, p<0.05). Furthermore, a reduction in postoperative AHI was proportionally associated with a decrease in residual adenoid. The newly developed microdebrider adenoidectomy technique for pediatric OSA patients with adenotonsillar hypertrophy demonstrated greater accuracy and efficacy in ameliorating sleep apnea symptoms compared with the standard adenoidectomy approach.

Development of rabbit models of ventilator-associated bacterial pneumonia produced by carbapenem-resistant Pseudomonas aeruginosa.

Ventilator-associated bacterial pneumonia (VABP) is among the most intractable of carbapenem-resistant Gram-negative bacterial infections. New antimicrobial agents are critically needed for the treatment of VABP. However, current conventionally used animal model systems are inadequate to meet this challenge. We, therefore, developed rabbit models of VABP caused by carbapenem-resistant Pseudomonas aeruginosa. Persistently neutropenic New Zealand White rabbits were used throughout the study. The early-phase intubated model (0-24 h) received mechanical ventilation, while the late-phase intubated model (72-96 h) was ambulatory. The following outcome parameters were studied: survival, residual tissue bacterial burden (CFU/g), residual BAL bacterial burden (CFU/mL), lung weights, pulmonary lesion score, histology, O2 saturation, radiographic imaging, and histology. Each anesthetized rabbit received a predetermined endotracheal bacterial inoculum, and ventilators were set to FiO2 = 40% and PEEP = 8 mmHg. Within the first 12 h post-inoculation, mean bacterial burdens in lung tissue and BAL fluid, respectively, were established at approximately 107 CFU/g and 106 CFU/mL, persisted through 24 h in the early-phase model and increased in the late-phase model to approximately 108 CFU/g and 107 CFU/mL. Mean max SpO2 was ≥98 mmHg, and mean nadir SpO2 was ≥68 mmHg. Serial thoracic radiographs demonstrated progressive multilobar pneumonic infiltrates. Lung histology revealed progressive focal bronchopneumonia, coagulative necrosis, intra-alveolar hemorrhage, alveolar epithelial cell necrosis, and bacterial microcolonies. The new rabbit model of VABP produced by carbapenem-resistant Pseudomonas aeruginosa recapitulates the pathophysiological, microbiological, diagnostic imaging, and histological patterns of human disease by which to assess critically needed new antimicrobial agents against this lethal infection.

Quantifying Bone and Skin Movement in the Residual Limb-Socket Interface of Individuals With Transtibial Limb Loss Using Dynamic Stereo X-Ray: Protocol for a Lower Limb Loss Cadaver and Clinical Study.

Relative motion between the residual limb and socket in individuals with transtibial limb loss can lead to substantial consequences that limit mobility. Although assessments of the relative motion between the residual limb and socket have been performed, there remains a substantial gap in understanding the complex mechanics of the residual limb-socket interface during dynamic activities that limits the ability to improve socket design. However, dynamic stereo x-ray (DSX) is an advanced imaging technology that can quantify 3D bone movement and skin deformation inside a socket during dynamic activities. This study aims to develop analytical tools using DSX to quantify the dynamic, in vivo kinematics between the residual limb and socket and the mechanism of residual tissue deformation. A lower limb cadaver study will first be performed to optimize the placement of an array of radiopaque beads and markers on the socket, liner, and skin to simultaneously assess dynamic tibial movement and residual tissue and liner deformation. Five cadaver limbs will be used in an iterative process to develop an optimal marker setup. Stance phase gait will be simulated during each session to induce bone movement and skin and liner deformation. The number, shape, size, and placement of each marker will be evaluated after each session to refine the marker set. Once an optimal marker setup is identified, 21 participants with transtibial limb loss will be fitted with a socket capable of being suspended via both elevated vacuum and traditional suction. Participants will undergo a 4-week acclimation period and then be tested in the DSX system to track tibial, skin, and liner motion under both suspension techniques during 3 activities: treadmill walking at a self-selected speed, at a walking speed 10% faster, and during a step-down movement. The performance of the 2 suspension techniques will be evaluated by quantifying the 3D bone movement of the residual tibia with respect to the socket and quantifying liner and skin deformation at the socket-residuum interface. This study was funded in October 2021. Cadaver testing began in January 2023. Enrollment began in February 2024. Data collection is expected to conclude in December 2025. The initial dissemination of results is expected in November 2026. The successful completion of this study will help develop analytical methods for the accurate assessment of residual limb-socket motion. The results will significantly advance the understanding of the complex biomechanical interactions between the residual limb and the socket, which can aid in evidence-based clinical practice and socket prescription guidelines. This critical foundational information can aid in the development of future socket technology that has the potential to reduce secondary comorbidities that result from complications of poor prosthesis load transmission. DERR1-10.2196/57329.

A Case of a Eustachian Tube Hairy Polyp Misdiagnosed as an Adenoid Residual in a Child.

Hairy polyps, considered a highly unusual congenital anomaly of the pharynx, are believed by many scholars to arise from the ectoderm and mesoderm during the embryonic stage. These growths often have a pear or sausage shape, are pedunculated, and their size ranges between 0.5 and 6 cm. They are typically grayish white or pink in color. This article discusses a 12-year-old female who had a growth at the Eustachian tube's entrance on the left side of the nasopharyngeal wall, as identified by a computed tomography scan of the neck soft tissue; it was suspected to be a hairy polyp originating from the left Eustachian tube. The diagnosis of a hairy polyp was confirmed through pathology. The hairy polyp at the Eustachian tube, in this case, showed an irregular form with a wide base, making it look similar to an adenoid; thus, increasing the risk of it being misdiagnosed as residual adenoid tissue.

Isthmocele and Infertility.

Isthmocele is a gynecological condition characterized by a disruption in the uterine scar, often associated with prior cesarean sections. This anatomical anomaly can be attributed to inadequate or insufficient healing of the uterine wall following a cesarean incision. It appears that isthmocele may impact a woman's quality of life as well as her reproductive capacity. The incidence of isthmocele can range from 20% to 70% in women who have undergone a cesarean section. This review aims to sum up the current knowledge about the effect of isthmocele on fertility and the possible therapeutic strategies to achieve pregnancy. However, currently, there is not sufficiently robust evidence to indicate the need for surgical correction in all asymptomatic patients seeking fertility. In cases where surgical correction of isthmocele is deemed necessary, it is advisable to evaluate residual myometrial thickness (RMT). For patients with RMT >2.5-3 mm, hysteroscopy appears to be the technique of choice. In cases where the residual tissue is lower, recourse to laparotomic, laparoscopic, or vaginal approaches is warranted.

Comparison of classical, coblation, and combined adenoidectomy techniques in paediatric patients: a single-blind, prospective study.

Adenoidectomy is one of the most commonly performed surgeries in pediatric otolaryngological practice. This prospective study compared three different adenoidectomy techniques' intra-operative and postoperative outcomes in pediatric patients. The techniques evaluated were classical (blind curettage), coblation, and a combined approach. Ninety pediatric patients undergoing adenoidectomy were enrolled in the study. The patients were divided into three groups based on the technique used: Group A, classical adenoidectomy (blind curettage); Group B, coblation adenoidectomy and Group C, combined (blind curettage + coblation) adenoidectomy. The intra-operative time, degree of bleeding, and complications during and after the operations were recorded. Group A had a significantly shorter operative time than the other groups. However, there was no significant difference in the mean operative time between Groups B and C. The mean amount of intra-operative bleeding differed significantly among the groups. Group B had significantly less bleeding than Group A or Group C. The amount of bleeding also differed significantly between Groups A and C. The postoperative pain scores did not differ significantly among the groups. While complications were infrequent in all groups, Group C did not exhibit a higher complication rate than Groups A and B. The absence of residual or recurrent adenoid tissue in any of the groups during long-term follow-up examinations highlights the effectiveness of all three adenoidectomy techniques in preventing adenoid regrowth. The combined approach, which was one of the techniques studied, demonstrated an intermediate profile in terms of operative time and intra-operative bleeding compared to the classical and coblation techniques. These findings suggest that this combined approach may be a feasible option for adenoidectomy in pediatric patients, considering its similar low incidence of postoperative complications.

Polymeric nanofiber leveraged co-delivery of anti-stromal PAK1 inhibitor and paclitaxel enhances therapeutic effects in stroma-rich 3D spheroid models

The role of tumor stroma in solid tumors has been widely recognized in cancer progression, metastasis and chemoresistance. Cancer-associated fibroblasts (CAFs) play a crucial role in matrix remodeling and promoting cancer cell stemness and resistance via reciprocal crosstalk. Residual tumor tissue after surgical removal as well as unresectable tumors face therapeutic challenges to achieve curable outcome. In this study, we propose to develop a dual delivery approach by combining p21-activated kinase 1 (PAK1) inhibitor (FRAX597) to inhibit tumor stroma and chemotherapeutic agent paclitaxel (PTX) to kill cancer cells using electrospun nanofibers. First, the role of the PAK1 pathway was established in CAF differentiation, migration and contraction using relevant in vitro models. Second, polycaprolactone polymer-based nanofibers were fabricated using a uniaxial electrospinning technique to incorporate FRAX597 and/or PTX, which showed a uniform texture and a prolonged release of both drugs for 16 days. To test nanofibers, stroma-rich 3D heterospheroid models were set up which showed high resistance to PTX nanofibers compared to stroma-free homospheroids. Interestingly, nanofibers containing PTX and FRAX597 showed strong anti-tumor effects on heterospheroids by reducing the growth and viability by > 90 % compared to either of single drug-loaded nanofibers. These effects were reflected by reduced intra-spheroidal expression levels of collagen 1 and α-smooth muscle actin (α-SMA). Overall, this study provides a new therapeutic strategy to inhibit the tumor stroma using PAK1 inhibitor and thereby enhance the efficacy of chemotherapy using nanofibers as a local delivery system for unresectable or residual tumor. Use of 3D models to evaluate nanofibers highlights these models as advanced in vitro tools to study the effect of controlled release local drug delivery systems before animal studies.

Pathology and resection margins following mastectomy prior to immediate breast reconstruction.

Risk of local recurrence (LR) (and even distant disease-free survival) after mastectomy is associated with margin status. Furthermore, the vast majority of LR are located at the anterior (superficial) margin. Margins in mastectomy are considered anatomical borders and not true resection margins; such a conception may erroneously lead to underestimation of the risk of LR after mastectomy. If dissection is accurate along the fascia, only skin, subcutaneous tissue and minimal residual breast gland tissue (rBGT) are expected to remain in the patient. However, the subcutaneous fascia is an inconsistent anatomical structure that may be absent in almost half of patients. Studies and routine clinical practice suggest that resection may frequently, though often focally, be within the breast glandular tissue leaving various amounts of rBGT. Such areas may be nidus for subsequent de novo or recurrent premalignant or malignant disease. There is no consensus on handling of close/positive margins and intervention is extrapolated from studies on breast conserving surgery with subsequent radiotherapy. Handling of a close/positive margin is complicated by poor correlation between the ex vivo findings on the specimen and the attempt to relocate the area of concern in a patient with reconstructed breasts. In this clinical practice review, we strongly advocate for reporting of the lesion-to-margin distance in mastectomies to collect further evidence on the association between LR and margin status.

1228 Comprehensive T-cell Profiling in Chordomas: Single-cell RNA-Seq and TCR Profiling Analysis Uncover Antitumor and Exhaustion Phenotypes for Targeted Immunotherapies

INTRODUCTION: Chordomas, a rare type of tumor, originate from residual notochord tissue. These tumors present important challenges due to the limited treatment options. Investigating the intricacies of T-cell composition and function in chordoma immunity holds the potential to advance immunotherapy strategies for these patients. METHODS: We generated a comprehensive single-cell atlas of T cells of chordomas, incorporating paired single-cell transcriptomic samples from the tumor and blood of five patients and single-cell TCR sequencing data to assess T-cell clonality. Additionally, we analyzed T cells in 33 chordomas (22 newly diagnosed and 11 recurrent tumors) using multiplex immunofluorescence. RESULTS: Our results demonstrate that CD8+ T-cell antitumoral immunity originates in the periphery, marked by clonal expansion of cytotoxic and memory T cells in the blood. However, this immunity experiences progressive exhaustion upon tumor infiltration. Notably, a large percentage of CD8+ T-cells from the tumors and blood shared their TCRs with exhausted CD8+ T-cells known for tumor specificity, confirming the origin of a peripheral antitumor response. We identified specific antigen peptide sequences through TCR analysis that were enriched in exhausted T cell receptors' binding sites that uncovered shared motifs within the reactive tumor-infiltrating compartment. Moreover, we observed that CTLA-expressing central memory and Tregs made up most of the CD4 T-cell tumoral landscape. Interestingly, multiplex immunofluorescence showed a higher abundance of CD3+ T cells in newly diagnosed chordomas compared to recurrent cases. CONCLUSIONS: This study sheds light on the composition and function of T cells in chordomas, revealing the origin and exhaustion of CD8+ T-cell antitumor immunity. These findings contribute to our understanding of chordoma immunity to guide the development of targeted immunotherapies for both newly diagnosed and recurrent cases.

Investigating the Knowledge of Yazd Dental Students about the Taught Factors of Direct Restoration of Endodontically Treated Teeth in 1401

Introduction: Treatment of root-treated teeth depends largely on proper restoration. Direct restorations are a better choice if there is sufficient residual tissue. This study aimed to investigate the knowledge of dental students in School of Dentistry in Yazd City about the taught factors of direct restoration of endodontically treated teeth.&#x0D; Methods: In this descriptive-cross-sectional study, the knowledge of 67 dental students of School of Dentistry in Yazd City about the taught factors of direct restoration of root-treated teeth was studied using a valid and reliable questionnaire containing demographic characteristics (age and gender) and 28 knowledge questions. After collecting the data, using SPSS version 16 software, they were analyzed using descriptive statistics, Chi-square test, Fisher's exact test, Mann-Whitney test, T test and Pearson correlation coefficient.&#x0D; Results: 36 (53.7%) female students and 31 (46.3%) male students with an average age of 25 ± 3.14 participated in this study. The average awareness score was 32.74 ± 9.65. The average knowledge score of female students (35.30±10.27) was higher than that of male students (31.95±8.70), but this difference was not statistically significant (p = 0.156). In the age group under 25, the average score of awareness (34.78 ± 9.94) was higher than the average above 25 (30.43 ± 8.1). There was an inverse and significant relationship between knowledge score and age, r=-0.242 and P 0.049. Conclusion: The average knowledge score of dental students regarding the taught factors of direct restoration of endodontically treated teeth was good. Gender did not have a significant effect on the knowledge of students, and the knowledge of students under 25 years old was higher than ones over 25 years old.

Direct angiographic comparison of different velocity-selective saturation, inversion, and DANTE labeling modules on cerebral arteries.

This study evaluated the velocity-selective (VS) MRA with different VS labeling modules, including double refocused hyperbolic tangent, eight-segment B1-insensitive rotation, delay alternating with nutation for tailored excitation, Fourier transform-based VS saturation, and Fourier transform-based inversion. These five VS labeling modules were evaluated first through Bloch simulations, and then using VSMRA directly on various cerebral arteries of healthy subjects. The relative signal ratios from arterial ROIs and surrounding tissues as well as relative arteria-tissue contrast ratios of different methods were compared. Double refocused hyperbolic tangent and eight-segment B1-insensitive rotation showed very similar labeling effects. Delay alternating with nutation for tailored excitation yielded high arterial signal but with residual tissue signal due to the spatial banding effect. Fourier transform-based VS saturation with half the time of other techniques serves as an efficient nonsubtractive VSMRA method, but the remaining tissue signal still obscured some small distal arteries that were delineated by other subtraction-based VSMRA, allowing more complete cancelation of static tissue. Fourier transform-based inversion produced the highest arterial signal in VSMRA with minimal tissue background. This is the first study that angiographically compared five different VS labeling modules. Their labeling characteristics on arteries and tissue and implications for VSMRA and VS arterial spin labeling are discussed.

Abstract 5899: Evaluation of Up284 as a selective proteasome inhibitor for prostate cancer therapy

Abstract Recent research into prostate cancer treatment has unveiled a promising contender known as Up284. In laboratory experiments, this compound has exhibited a remarkable preference for targeting prostate cancer cells as opposed to normal cells. Specifically, in vitro cell viability assays using MTT have shown that prostate cancer cells display high sensitivity to Up284 at low nanomolar IC50 values, while primary human prostate epithelial cells and mouse keratinocytes exhibit minimal sensitivity. This establishes a notable therapeutic window between cancerous and non-cancerous cells, with Up284 significantly inhibiting colony formation in PC3 cells. Additional functional assays have confirmed Up284's potential, including the 4UbFL Reporter Gene assay, which has revealed robust, dose-dependent proteasome inhibition. This effect is supported by the accumulation of polyubiquitinated proteins in various prostate cancer cell lines following Up284 treatment, suggesting a distinct mechanism of toxicity compared to bortezomib. Furthermore, Up284 has been found to induce apoptosis in PC3 cells, surpassing the efficacy of bortezomib. Competitive binding assays have shown that Up284 exhibits a stronger binding affinity to the proteasomal receptor RPN13 than the prototype inhibitor RA190B. This is further supported by a Cellular Thermo Stabilization Assay (CETSA), which indicates that Up284 stabilizes RPN13 in cells. A preliminary in vivo study utilizing the bone metastatic prostate cancer genetically engineered mouse model(BMPC GEMM) model for metastatic prostate adenocarcinoma has demonstrated that Up284 leads to significant tumor regression and increased levels of poly-ubiquitinated proteins in residual tumor tissues. Moreover, when Up284 is conjugated with an E3 ligase ligand, it successfully degrades RPN13, resulting in the death of PC3 cells. Up284 has also shown favorable pharmacokinetics/pharmacodynamics (PK/PD) profiles and safety in animal models. It is well-tolerated in mice and holds promise for oral administration, demonstrating a proteasome-dependent reporter protein stabilization effect superior to ixazomib. Importantly, Up284 has induced tumor regression and improved survival rates in various cancer models, including ovarian and breast cancers. In conclusion, Up284 emerges as a lead candidate for targeted prostate cancer therapy due to its high specificity, substantial therapeutic index, and potent anti-cancer activity both in vitro and in vivo. Further development and clinical investigation of Up284 are warranted to fully explore its therapeutic potential. Citation Format: Balasubramanyam Karanam, Ravi Anchoori, Yung Chang. Evaluation of Up284 as a selective proteasome inhibitor for prostate cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5899.

Retrospective study on unilateral polyotia combined with microtia utilizing the technique of preserving residual ear tissue

The presence of polyotia in individuals with microtia is a rare deformity. Due to the intricate structure of the auricle, uncertain etiology, and challenging corrective techniques, it has always been a focal point in the field of plastic surgery. The present study presents a technique for correcting the combination of polyotia and microtia by utilizing residual ear tissue as graft material. The retrospective study included 23 patients with polyotia and microtia from 2018 to 2022. The residual ear tissue was used to rectify auricular deformities in all patients. The patients were instructed to evaluate the satisfaction of the auricle shape using a visual analog scale (VAS) both before and 6 months after the surgical procedure. The esthetic outcomes of auricle subunits were simultaneously assessed by a senior physician pre- and postoperatively. The mean duration of follow-up in this study was 8.73 months. The preoperative VAS satisfaction score was recorded as 2.26±0.86, while the post-operative VAS score significantly increased to 7.86±0.86. The preoperative auricle esthetic outcomes score was recorded as 9.95±1.74, while the post-operative score significantly increased to 24.04±2.16. The follow-up period did not present any cases of flap necrosis, hematoma, infection, or wound dehiscence. The study demonstrates that comprehensive utilization of residual auricular tissue can lead to optimal outcomes in correcting polyotia with concha-type microtia. The utilization of residual ear tissue can be maximized to streamline the operation, minimize bodily harm, and enhance patient satisfaction.