Small Nodes Research Articles

Effectiveness of Lymph Node Revealing Solution in Estimation of Lymph Nodes Yield in Radical Specimen of Oral Squamous Cell Carcinoma: A Preliminary Histomorphometric Observational Study

Introduction: Oral cancer poses a serious health challenge globally, particularly for nations undergoing economic transition. The number and size of lymph nodes obtained, along with nodal involvements, are crucial for proper diagnosis, treatment, and prognosis. Aim: To assess the number of lymph nodes obtained before and after treating the specimens with the Lymph Node Revealing Solution (LNRS) along with staining characteristics. Materials and Methods: The present prospective observational study was conducted at the Department of Oral Pathology and Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India, over a period of six months from January 2023 to June 2023 in a tertiary oral healthcare centre in Chennai. Six histologically confirmed Oral Squamous Cell Carcinoma (OSCC) cases with neck dissection were included in the study, involving 32 lymph node levels. Lymph nodes were grossed using both routine procedures of palpation and visualisation and after treatment with LNRS for two days. The number of nodes obtained through both methods was compared along with the staining characteristics. The data were analysed using Statistical Package for Social Sciences (SPSS) software version 26.0. Chi-square and paired t-tests were used to compare the two groups, and any value less than or equal to 0.05 was considered statistically significant. Results: Out of 134 lymph nodes, 21 were positive with conventional fixation, whereas after the application of LNRS, an additional 41 lymph nodes were retrieved. Two nodes showed metastatic deposits; fortunately, the additional positive nodes did not affect the staging. No statistically significant difference was found before and after immersion in LNRS regarding staining characteristics. The mean area of the yielded nodes was 84.71±4.85 mm2 . There was a statistically significant difference between the size of lymph nodes between the manual grossing method and after immersion in LNRS (p-value <0.001). Conclusion: The study confirmed that the LNRS technique identified very small lymph nodes in oral cancer patients, which may contain metastatic deposits. This might change the stage of the disease and influence the mode of treatment.

An Updated Shape Model of Dimorphos from DART Data

Dimorphos was the target of the Double Asteroid Redirection Test (DART) mission. This paper summarizes the properties of an updated shape model of Dimorphos, describes the differences between the updated shape model and an earlier version published by Daly, Ernst, Barnouin et al. (doi:10.1038/s41586-023-05810-5), summarizes the data products associated with this model, and explains where the products can be accessed. The updated shape model benefited from improved methods of incorporating limb information, which will accelerate future shape modeling efforts for other objects with limited imaging data. The updated shape model is similar to the earlier model but slightly smaller (−2.8% change in volume) than the previous Dimorphos global shape model, and the updated shape is slightly more elongated. The additional analysis reported here supports an oblate preimpact shape for Dimorphos. This result indicates that the postimpact elongation of Dimorphos derived from ground-based observations is evidence for a large crater or global reshaping of the asteroid due to the DART impact. The updated global shape model of Dimorphos, as well as the earlier version, will be available in the Planetary Data System Small Bodies Node and through the public Small Body Mapping Tool.

Several Categories of Energy Harvested Routing Protocols, Challenges, and Characteristics in WSN: A Review

The routing protocol is a technique for determining the most efficient channel for data transmission. The route selection procedure, which relies on the kind of network, channel conditions, and measurement systems, presents several challenges. Routing is essential in Wireless Sensor Networks (WSNs) for environmental monitoring, traffic monitoring, and other applications. WSNs are small nodes that can sense, interpret data, and communicate wirelessly. Many routing, power control, and data dissemination techniques have been developed specifically for WSNs, where energy efficiency is a crucial design factor.
 On the other hand, the focus has been on energy harvesting and standard routing methods, which can vary depending on the design and network architecture. In a Wireless Sensor Network (WSN), the data collected by the sensor nodes is typically transferred to the base station, which connects the sensor network to other networks (such as the internet), where it is processed and necessary action is taken. WSN has recently been developed to allow various applications, including traffic enforcement building automation, smart warfare, environmental sensing, and many more.WSN integrates several sensors or nodes deployed around a specific node to perform computational processes.

The Potential of Iron Oxide Nanoparticle-Enhanced MRI at 7 T Compared With 3 T for Detecting Small Suspicious Lymph Nodes in Patients With Prostate Cancer.

Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs. The aim of this study was to explore USPIO-enhanced MRI at 7 T in comparison to 3 T for the detection of small suspicious LNs in the same cohort of patients with PCa. Twenty PCa patients with high-risk primary or recurrent disease were referred to our hospital for an investigational USPIO-enhanced 3 T MRI examination with ferumoxtran-10. With consent, they underwent a 7 T MRI on the same day. Three-dimensional anatomical and T2*-weighted images of both examinations were evaluated blinded, with an interval, by 2 readers who annotated LNs suspicious for metastases. Number, size, and level of suspicion (LoS) of LNs were paired within patients and compared between field strengths. At 7 T, both readers annotated significantly more LNs compared with 3 T (474 and 284 vs 344 and 162), with 116 suspicious LNs on 7 T (range, 1-34 per patient) and 79 suspicious LNs on 3 T (range, 1-14 per patient) in 17 patients. For suspicious LNs, the median short axis diameter was 2.6 mm on 7 T (1.3-9.5 mm) and 2.8 mm for 3 T (1.7-10.4 mm, P = 0.05), with large overlap in short axis of annotated LNs between LoS groups. At 7 T, significantly more suspicious LNs had a short axis <2.5 mm compared with 3 T (44% vs 27%). Magnetic resonance imaging at 7 T provided better image quality and structure delineation and a higher LoS score for suspicious nodes. In the same cohort of patients with PCa, more and more small LNs were detected on 7 T USPIO-enhanced MRI compared with 3 T MRI. Suspicious LNs are generally very small, and increased nodal size was not a good indication of suspicion for the presence of metastases. The high spatial resolution of USPIO-enhanced MRI at 7 T improves structure delineation and the visibility of very small suspicious LNs, potentially expanding the in vivo detection limits of pelvic LN metastases in PCa patients.

(Invited) SAE-MEMS Technology for Electrostatic Vibrational Energy Harvesters

Energy harvesting [1] is expected to be a self-powering technology for small wireless sensor nodes in the next generation Internet-of-Things (IoT). In particular, small vibrational energy harvesters (VEHs) based on micro-electro-mechanical systems (MEMS) technology, which are battery-free and can generate electricity even at night or in the dark, are being investigated worldwide for next-generation power sources for small wireless IoT nodes [2,3]. Electrostatic MEMS VEHs, which use semi-permanent charge-holding dielectrics called "electrets," are useful for power generation using environmental vibrations because they have a higher output power density at lower frequencies than other methods [4]. Further miniaturization, higher performance, and higher productivity will be required to use electret-type MEMS VEHs as power sources for compact wireless IoT nodes and other devices. Although the integration of MEMS VEHs with power management circuits enables miniaturization, higher performance, and improved productivity, the monolithic integration of electret-type MEMS VEHs and electronic circuits is an unexplored area in conventional technology. Conventional electrostatic MEMS VEHs involve corona discharge, electron beam irradiation, X-ray irradiation, or high-temperature treatment as electret charge processing, which imposes restrictions on the design and manufacturing of MEMS structures and the integration of MEMS and electronic circuits. Recently, self-assembled electrets (SAEs), which are electrets that do not require any charging process, have been developed using materials for organic electroluminescent devices [5]. The surface charge density of SAEs is equivalent to those of previously reported electrets for VEHs, and thus SAE is expected to improve the performance of VEH and simplify the manufacturing process. However, there have been no reports of MEMS devices using SAEs.Our proposed method is the first technology to form SAEs inside MEMS structures using only a vacuum evaporation process at room temperature, and we have succeeded in actual vibration power generation [6]. This technology can be integrated into existing semiconductor processes because the electret formation requires only room-temperature deposition, making it possible to monolithically integrate electret-type MEMS VEHs and electronic circuits on the same substrate. In addition, since the SAE surface potential is proportional to the film thickness, the amount of electricity generated can be further increased by increasing the thickness of the SAE film. Therefore, this technology is expected to accelerate the miniaturization, performance, and productivity improvement of MEMS environmental vibration power generation devices. Akinaga, “Recent advances and future prospects in energy harvesting technologies,” Jpn. J. Appl. Phys. 59 (2020) 110201.D. Mitcheson, E. M. Yeatman, G. K. Rao, A. S. Holmes, and T. C. Green, “Energy Harvesting from Human and Machine Motion for Wireless Electronic Devices” Proc. IEEE 96 (2008) 1457–1486.Suzuki, “Recent progress in MEMS electret generator for energy harvesting,” IEEJ Trans. Elec. Electron. Eng. 6 (2011) 101-111.Toshiyoshi, S. Ju, H. Honma, C.-H. Ji, and H. Fujita, “MEMS vibrational energy harvesters,” Sci. Technol. Adv. Mater. 20 (2019) 124-143.Tanaka, N. Matsuura, and H. Ishii, “Self-Assembled Electret for Vibration-Based Power Generator,” Sci. Rep. 10 (2020) 6648.Yamane, H. Kayaguchi, K. Kawashima, H. Ishii, and Y. Tanaka, “MEMS post-processed self-assembled electret for vibratory energy harvesters,” Appl. Phys. Lett. 119 (2021) 254102.

Robust Design of Interdependent Networks Considering Intra-Network Support Flow

Cyber-physical systems comprise multiple interdependent networks supporting each other. This paper considers a combination of power grid and computer network as a typical instance of the interdependent networks. A node in an interdependent network fails if it cannot receive the required volume of support from the nodes in the other interdependent network. Meanwhile, each node supporting the other network is required to receive a sufficient volume of intra-network flow named “support flow”, which corresponds to the flow of electric power in the power grid and the flow of control messages in the computer network. Each sink node of the support flow must terminate a sufficient volume of support flow generated at source nodes in the same network in order to achieve the support of the other network. This means that the support flow is one of the essential elements to make the interdependent networks operable. The conditions related to the support flow increases the possibility of a small initial node failure invoking a cascading failure with a wide range. This paper proposes a robust design method for the interdependent networks to maximize the robustness against the cascading failures while assuring satisfaction of the constraints on the support flow. The method can derive the interdependency to minimize the impact of the cascading failures induced from a given set of possible initial node failures when the configuration of the respective interdependent networks is specified beforehand. The robust design problem is formulated using a mixed integer linear programming model and two kinds of metaheuristic methods are proposed to solve the problem efficiently even if a great number of initial node failures are specified. Several characteristics of the risk of the cascading failures are revealed from the results of the robust design. Simulation experiments demonstrate the effectiveness of the proposed metaheuristic methods.

Distributed cooperative control of mechatronic system driving multiple electrohydraulic actuators with uncertain nonlinearity and communication delay

AbstractBeing different from many centralized mechatronic systems, the distributed transmission mechanism has the significant advantage such that realize cooperative task only based on small amount neighbour nodes with low computational complexity. In this study, a distributed cooperative control is proposed for multiple electrohydraulic system (MEHS) to guarantee the follower electrohydraulic node tracking the leader motion, based on the approach of directed spanning tree. Firstly, the MEHS model is constructed as three‐orders isomorphic nonlinear dynamics. Then, a disturbance observer is adopted to estimate uncertain nonlinearities caused by hydraulic parametric uncertainties and unknown external loads in the MEHS. To address unknown communication delays in the network topology of MEHS, a quasi‐synchronous controller is designed via Lyapunov–Krasovskii technique to guarantee that the synchronous errors asymptotically converge to a zero neighbourhood. Finally, the effectiveness of the proposed distributed synchronous control is verified by simulation results under uncertain nonlinearities and different communication delays.

Homeostatic cytokines reciprocally modulate the emergence of prenatal effector PLZF+CD4+ T cells in humans.

The development of human prenatal adaptive immunity progresses faster than previously appreciated, with the emergence of memory CD4+ T cells alongside regulatory T cells by midgestation. We previously identified a prenatal specific population of promyelocytic leukemia zinc finger-positive (PLZF+) CD4+ T cells with heightened effector potential that were enriched in the developing intestine and accumulated in the cord blood of infants exposed to prenatal inflammation. However, the signals that drive their tissue distribution and effector maturation are unknown. Here, we define the transcriptional and functional heterogeneity of human prenatal PLZF+CD4+ T cells and identify the compartmentalization of T helper-like (Th-like) effector function across the small intestine (SI) and mesenteric lymph nodes (MLNs). IL-7 was more abundant in the SI relative to the MLNs and drove the preferential expansion of naive PLZF+CD4+ T cells via enhanced STAT5 and MEK/ERK signaling. Exposure to IL-7 was sufficient to induce the acquisition of CD45RO expression and rapid effector function in a subset of PLZF+CD4+ T cells, identifying a human analog of memory phenotype CD4+ T cells. Further, IL-7 modulated the differentiation of Th1- and Th17-like PLZF+CD4+ T cells and thus likely contributes to the anatomic compartmentalization of human prenatal CD4+ T cell effector function.

An Efficient Cooperative Routing with ML based Energy Efficiency Model for Distributed Underwater WSN Electricity Meter Warning System

Underwater wireless sensor network that operates underwater, typically in oceans, lakes, and rivers. UWSNs are composed of a large number of small sensor nodes that are equipped with various sensing and communication capabilities. These nodes are deployed in the underwater environment to collect and transmit data, which can be used for a variety of applications such as environmental monitoring, oceanography, and marine biology. The Underwater WSN (UWSN) consists of sensor nodes to sense the data and transmit it to the sink node. These sensor nodes (SN) are equipped with limited batteries, which is the central issue. Therefore, the routing protocols were developed for researchers to save energy. However, the increment of network lifetime remains an open challenge. Forwarding the data to the nearest SN to the sink will reduce the network reliability and stability, draining SN's energy early. To overcome these issues, this paper focused on developing an efficient Cooperative based routing (CR) with a machine learning (ML) model to improve the network's lifetime. The cooperative routing discovers the route path from the sender to the destination. The best possible way from the sender to the receiver has been selected using the ML approach called the Self-organizing network (SON). By identifying congestion-free multi-hop transmission using CRSON, the data packet is transmitted from sender to receiver with reduced energy, increasing the network's lifetime and reliability. This model is simulated and experimented with energy efficiency, packet delivery, loss rate, latency, and throughput metrics.

Time-Limited Bendamustine, Rituximab, and Venetoclax (BR-VR) in Untreated Chronic Lymphocytic Leukemia (CLL): High Rates of Undetectable Minimal Residual Disease Remissions

Background: Despite the efficacy of venetoclax (VEN) in frontline CLL, optimal combination regimens and duration of treatment remain unclear. We hypothesized that cytoreduction with bendamustine/rituximab (BR) induction followed by venetoclax/rituximab (VR) consolidation for a fixed 1-year duration would be associated with an increased rate of undetectable minimal residual disease (uMRD) compared to historical controls and a reduction in the risk of tumor lysis syndrome (TLS). Here we report updated data from a fully-enrolled ongoing phase 2 multicenter, US, single-arm, open-label study (NCT03609593) designed to assess the safety and efficacy of BR-VR in previously untreated CLL patients (pts). Methods: Previously untreated CLL/SLL pts ≥ 18 years requiring therapy per iwCLL criteria initially received 3 cycles of bendamustine 50-90 mg/m 2 daily for 2 days and rituximab 375 mg/m 2 every 28 days for 3 cycles. Following BR, VEN was initiated with a standard dose escalation from 20 mg to 400 mg daily over 5 weeks. This was followed by 6 cycles of VR with rituximab given monthly and 5 cycles of VEN alone (12 cycles of VEN in total). Additional eligibility included: ECOG PS ≤ 2, hemoglobin ≥8g/dL, ANC ≥1000/mm 3, and platelets ≥50,000/mm 3. Response was assessed by 2018 iwCLL criteria with uMRD testing by central flow cytometry at a level of &amp;lt;10 -4 in peripheral blood (PB) and bone marrow (BM). The primary endpoint was objective response rate (ORR). Secondary endpoints included uMRD rate, time to uMRD, and adverse events (AEs) assessed by CTCAE v 5.0. Results: As of data cutoff on 15 July 2023, 42 pts were accrued. Baseline demographics were as follows: male/female (29/13), median age 61.5 yrs (range 38-84). Baseline prognostic studies showed unmutated IGHV in 22 (52%) pts, TP53 aberrant (either del(17p) and/or TP53 mutation) in 2 (5%) pt, del(11q) in 3 (7%) pts, and complex karyotype in 11 (26%) pts. TLS risk among 24 evaluable pts at baseline was high (H) in 9 (21%), medium (M) in 22 (52%), and low (L) in 6 (26%). At a median follow-up of 16.6 mo. (range, 3-40), 37 pts remain on study. Of 29 pts with at least 15 mo. follow-up (completing all therapy), the ORR was 100% (79% CR/CRi, 21% PR [due to small residual nodes]). 3 pts died on study (2 due to COVID-19 and 1 developed newly metastatic squamous cell carcinoma and taken off study after achieving a CR post-VEN ramp-up). 1 pt was lost to follow-up while in a CR. Bendamustine was administered at doses of 50 mg/m 2 in 11%, 70 mg/m 2 in 13%, and 90mg/m 2 in 76% of pts. In 38 evaluable pts, response assessments after cytoreduction with BR demonstrated 16% of pts achieved CR/CRi and 84% achieved PR. For evaluable pts at 16 mo., uMRD (&amp;lt;0.01%) in the PB and BM was observed in 80% (20/25) and 78% (18/23) of pts, respectively. MRD was intermediate (0.01% - &amp;lt;1.0%) in 17% (4 patients) in BM (Figure 1 ORR and MRD). Median time to uMRD was 11 mo. (range 3-15) in PB and 10 mo. (range 2.6-15) in BM. The most common treatment-emergent AEs during BR induction were (any grade/grade ≥3) anemia in 15/4 (36%/10%) pts, nausea in 9/0 (21%/0%), neutropenia in 12/8 (29%/19%), rash in 12/1 (29%/2%), constipation 7/0 (17%/0%), and infusion reactions in 7/1 (17%/2%). 2 pts (5%) developed febrile neutropenia during BR. Emergent AEs during VEN treatment included neutropenia in 21/13 (50%/31%), diarrhea in 18/0 (43%/0%) pts, leukopenia in 14/4 (24%/10%), and nausea in 11/0 (26%/0%). TLS risk was substantially reduced after BR lead-in. Of 9 H-risk pts at baseline, 1 remained H-risk after BR; of 16 M-risk pts, 5 remained M-risk, with the remainder at L-risk (89% reduction in H-risk TLS). Conclusions: BR-VR is a safe and well-tolerated regimen in untreated CLL pts. BR debulking substantially reduces TLS risk, and this sequential strategy achieves high rates of PB and BM uMRD across all prognostic risk groups.

Wireless Sensor Network Based Gas Monitoring System Utilizing ZigBee Technology

This paper presents a ZigBee-based wireless network gas monitoring system, utilizing ZigBee technology to enable reliable and low-cost communication. The system leverages small sensor nodes and ZigBee protocols to collect data on physical phenomena, particularly gas levels, in various environments. The network's low-power consumption and extended range capabilities allow for effective gas sensing within a radius of up to 300 meters. While interoperability with devices from different manufacturers remains a limitation, the system showcases the versatility of ZigBee technology in diverse fields. The study evaluates the system's performance through simulation and experimentation, addresses potential challenges, and proposes future developments to enhance ZigBee-based wireless network gas monitoring systems, offering improved remote monitoring and manipulation capabilities. Furthermore, our research contributes to the advancement of wireless sensor network technology by demonstrating the practicality of ZigBee in gas monitoring. The findings from our experiments and simulations provide valuable insights into the optimization of such systems, which can have far-reaching impacts on environmental monitoring, safety, and industrial processes. In addition, our proposed enhancements pave the way for more reliable and efficient remote monitoring and control, offering substantial benefits for various industries, including environmental management, industrial automation, and beyond.

SAT574 Thyroglossal Duct Papillary Thyroid Cancer With Normal Eutopic Thyroid Gland: A Management Dilemma

Abstract Disclosure: H. Belal: None. J.T. Batch: None. G.Y. Gandhi: None. Background: The incidence of thyroglossal duct cyst carcinomas is less than 1%, the majority being papillary thyroid cancer. One-third arise de novo from the thyroglossal duct. The rest are direct metastasis of eutopic papillary thyroid cancer. Management in the setting of a normal eutopic thyroid gland is challenging. Clinical Case: A 35-year-old female presented with transient right facial paresthesia. CT angiogram revealed an incidental 2.3 cm thyroglossal duct cyst with internal ectopic thyroidal tissue and micro-calcifications. She denied any compressive symptoms, radiation exposure, or family history of thyroid cancer and was euthyroid. Ultrasound noted a normal thyroid gland and complex solid-cystic mass measuring 2.3 x 2.0 x 1.5 cm superior to the isthmus. Satisfactory fine needle aspiration of the mass revealed benign-appearing epithelial cells, macrophage, and colloid-like material. Due to new anterior neck pain, a Sistrunk Procedure (SP) was performed. Pathology revealed a 1.2 cm papillary thyroid carcinoma, conventional type (confirmed by TTF-1 and thyroglobulin stains), arising within the thyroglossal duct cyst. Surgical margins were free of cancer, and there was no lymphovascular invasion. A thyroid ultrasound seven months after the procedure revealed heterogenous thyroid tissue, no thyroid nodules, and several small benign-appearing reniform-shaped cervical lymph nodes in zones 1 and 2. The patient was offered yearly thyroid ultrasound surveillance versus prophylactic thyroidectomy. She elected to proceed with thyroidectomy due to concerns about disease recurrence. Final pathology results revealed right lobe 2 mm papillary microcarcinoma limited to the thyroid. Conclusion: Fine needle aspiration of thyroglossal duct cysts can have a high false negative rate, as in our patient. There is currently no consensus on treatment of thyroid carcinomas arising from thyroglossal duct cysts. There are four possible surgical strategies: 1) SP alone 2) SP with concurrent thyroid lobectomy or pyramidal lobe resection 3) SP with total or near total thyroidectomy in all patients and 4) SP and selective addition of total or near total thyroidectomy in high-risk patients. The role of radio-iodine ablation and levothyroxine suppression after SP is also unclear. Management recommendations are Grade C, relying on case reports, case series, and expert opinion. Whether or not to proceed with total thyroidectomy, especially in the setting of a normal thyroid gland, remains highly controversial. Some experts even argue for an early aggressive surgical approach with SP, total thyroidectomy, and level I lymph node sampling in all patients to provide accurate staging and allow for the use of thyroglobulin and whole-body scintigraphy in surveillance. Multisite comparative data on the long-term outcomes of patients who receive early aggressive versus conservative management is needed. Presentation: Saturday, June 17, 2023

SAT551 Significantly Elevated Thyroglobulin Levels with Negative Whole-Body Scan and PET/CT After Treatment of Thyroid Cancer: A Case Report

Abstract Disclosure: A. Bassatne: None. J.T. Chaiban: None. Background: Thyroglobulin (Tg) levels are used to monitor recurrence or persistence of disease after treatment of differentiated thyroid cancer. Some cases may have persistently elevated Tg and negative whole-body scans (WBS). We present a case of substantially elevated Tg levels despite negative WBS and PET/CT after thyroidectomy and radioactive iodine (RAI) treatment in a patient with papillary thyroid carcinoma (PTC). Clinical Case: A 66 years old lady was referred to the endocrinology clinic almost 5 years ago after incidental findings of calcified thyroid nodules on CT. Thyroid US confirmed 2cm aggregate calcified nodules. FNA revealed PTC for which she underwent thyroidectomy. Pathology showed a unifocal 3.5 cm left lobe conventional PTC without angioinvasion nor extrathyroidal extension, 3/13 positive lymph nodes (LN) on the lateral dissection of the left neck as well as multiple small LN on the central dissection. 6 days postop, her Tg was still significantly high at 40.5ng/mL (Ref 1.2-35 ng/mL) and then increased to 397ng/mL after thyrogen preparation for RAI ablation, antithyroglobulin antibodies were negative. WBS post RAI was negative except for the physiologic neck uptake. Almost a year later, a diagnostic WBS after thyrogen stimulation was still negative but the stimulated Tg increased again to 235 ng/mL with negative thyroglobulin antibodies. Tg result were confirmed by LC-MS method. Heterophile Antibodies were negative. Patient confirmed that every single time she followed at least 2 weeks of low iodine diet in preparation for the WBS. Unfortunately, we were not able to get a 24 hour urine collection for iodine. A PET/CT was reassuring. CT neck/chest did not show any suspicious metastases. TSH was maintained at an adequately suppressed level all through and Tg levels were ranging around 6-8 ng/mL. After another year, a stimulated Tg was 302.4 ng/mL with a TSH of 198 mcU/mL (Ref 0.35-5.0 mcU/mL). At that time, a repeat WBS was negative and a repeat PET/CT demonstrated an interval development of a small thyroid focus thought to be consistent with recurrence of malignancy. However, a CT of neck/chest did not reveal any abnormal thyroid findings or metastases. Patient received 100 mCi of RAI after thyroid hormone withdrawal. Subsequent WBS was negative. Currently her Tg levels are stable at around 8-9ng/mL for the past 6 months with a suppressed TSH. Patient had another PET/CT through her breast surgeon to follow on a previous breast lesion and no thyroid abnormality was noted. Conclusion: Elevated Tg levels despite negative imaging may be seen in patients with PTC as illustrated in this case. We are reporting it due to the extent of elevation of Tg levels seen on more than one occasion in the absence of structural recurrence. Evaluation and treatment of such patients remain controversial. Presentation Date: Saturday, June 17, 2023

SAT546 Papillary Thyroid Cancer Surveillance: Thyroglobulin Levels Affected by HAMA

Abstract Disclosure: J. Sanchez Perez: None. M. Obeid: None. M. Fariduddin: None. D.J. Toft: None. Introduction: Thyroglobulin (TG) measurement is a major means of detecting recurrence of previously treated differentiated thyroid cancers. Human-Anti Mouse Antibodies (HAMA) can interfere with lab measurements of TG levels and affect clinical decisions and treatment for these cancers.Clinical Case: A 65-year-old female was diagnosed with papillary thyroid cancer (PTC). Surgical pathology following total thyroidectomy demonstrated a tumor of 3.5 cm in its greatest dimension, unifocal, without invasion of locoregional tissue classified as Stage I (pT2N0M0) per AJCC 8th edition. Radioiodine whole body scan (WBS) demonstrated iodine uptake in the neck and 126.5 mCi of I-131 was given. In surveillance 5 years later, TSH was found to be 0.17 mcIU/ml (ref range: 0.35 - 4.00) TG 64.7 ng/ml (ref range: 1.3 - 31.8 ng/mL), and anti-Tg antibodies were undetectable. Neck US consistently showed nonspecific findings of stable small nodes with normal morphology in both supraclavicular regions. Given elevated TG levels, 250 mCi of I-131 was given. Follow-up TG levels ranged from 27.8 to 36.4 ng/ml. A repeat WBS did not reveal any uptake, but as TG remained elevated, I-131 (238 mCi) was again given. Subsequent TG throughout the following 15 years ranged from 2.8 - 58.6 ng/ml. Repeat Neck US only showed benign-appearing lymph nodes. WBS did not have any focal activity to suggest recurrent disease and PET/CT did not show any abnormal FDG uptake. The persistently high TG levels without clinical evidence of tumor recurrence raised the suspicion of lab interference. The serum sample was treated with a blocking reagent that contained mouse immunoglobulin after which the TG level decreased to 2.7 ng/ml compared to untreated value of 20.5 ng/ml.Conclusion: HAMA are human antibodies against mouse antibodies which are believed to develop in humans from direct contact with rodents, including mice, and from the recent increase in the use of mouse monoclonal antibodies for diagnostic and therapeutic purposes. These antibodies implicate an unexpected source of interference in immunoassays, as seen in our patient, which can confound laboratory results and create a clinical dilemma. This patient with PTC had a complete radiological response after surgery, but an incomplete biochemical response which caused the patient to be given a total of 614 mCi of I-131. This case highlights the importance of recognizing the possible presence of HAMA when analyzing TG levels, particularly when the TG levels are used for treatment decisions. Presentation Date: Saturday, June 17, 2023

Model cascading overload failure and dynamic vulnerability analysis of facility network of metro station

The existing studies mainly focused on the cascading failure of the whole metro but rarely on stations. In this paper, we map a metro station into a directed and hierarchical network, and propose a cascading overload failure model to study the network dynamic vulnerability. The passenger behavior and node load update are considered based on impedance function and mutual flow redistribution. Without changing the network topology, a flow optimization strategy is proposed to improve the network performance against cascading failure. Yuantong station of Nanjing Metro is studied. The results show the network is vulnerable and global failure occurs easily under small node tolerance. When the node tolerance excesses a critical value, the network can transit abruptly from global failure to balance state. We obtain that the critical node tolerances are 0.17 for the largest degree-based attack(LDA) and 0.19 for the largest load-based attack(LLA). The ranges of the optimal flow redistribution coefficient are identified by the flow optimization strategy, which are [0.15 0.2] for LDA and [0.2 0.25] for LLA. The result indicates that a proper guidance of passenger flow can be beneficial to the network performance while a strong intervention to passenger flow can instead increase the cascading failure risk.

Characterizing First Events in LA-NSCLC Patients Treated with Chemoradiotherapy

Definitive chemoradiotherapy (CRT) is a standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC). After treatment, patients are at risk for local disease recurrence, developing new sites of disease, and death without disease recurrence. Here, we characterize the rates of these events in a modern patient cohort and explore risk factors for each event. The hypothesis is that these rates and risk factors will better inform treatment strategies for local intensification and systemic therapy. We reviewed patients who underwent staging PET/CT and were treated for LA-NSCLC with definitive CRT at our institution between 2010 and 2022. Competing risks analyses were performed to calculate rates of disease progression and death without disease progression. Competing risks analyses were repeated after dividing disease progression into in-field recurrence versus out-of-field progression and after subdividing in-field recurrences into progression of high-risk (large) tumors or lymph nodes (defined as having metabolic tumor volume [MTV] >20 cc on staging PET/CT) versus progression of low-risk (small) tumors or lymph nodes. Predictors of each event type were identified using univariate and multivariable Fine and Gray competing risks regressions. A total of 210 patients met inclusion criteria, and the median follow-up duration is 43 months. Median age was 68 (IQR 60 to 74), and 77% of patients had ECOG performance status 0-1. Median progression-free survival and overall survival durations are 13 and 40 months, respectively. The 3-year cumulative incidence rate (CIR) of disease progression was 58%, and the 3-year CIR of death without disease progression was 18%. The 3-year CIR for out-of-field disease progression was 44%, and the 3-year CIR for in-field recurrence was 14%. The 3-year CIR for in-field recurrence of high-risk lesions was 11%, and the 3-year CIR for low-risk lesions was 4%. Multivariable analyses examining predictors of out-of-field progression revealed two statistically significant factors: total disease burden on PET (SHR 1.03 per 10 cc, p = 0.013) and durvalumab receipt (SHR 0.60, p = 0.031). Multivariable analyses also revealed two predictors of death without disease progression: age (SHR 1.06 per year, p = 0.018) and ECOG performance status (SHR 1.81, p = 0.012). For LA-NSCLC patients treated with definitive CRT, we found that developing new sites of disease is the most common first event, followed by death without disease recurrence. In-field disease recurrence is relatively uncommon, particularly when treating relatively small tumors and lymph nodes. These findings may inform prioritization of strategies to improve systemic therapy, intensify local therapy, and minimize treatment-related toxicity.

Prognostic factor analysis and clinical significance of HER‑2‑positive breast cancers with negative lymph nodes and a tumor diameter ≤1cm.

The 2021 National Comprehensive Cancer Network guidelines recommend that adjuvant chemotherapy combined with trastuzumab be considered for human epidermal growth factor receptor 2 (HER-2)-positive breast cancer patients with small tumors (tumor diameter ≤1 cm) and negative lymph nodes. Additionally, the prognostic factors and clinical significance of HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm remain unclear. In the present study, the clinical data and prognostic factors of 87 patients with HER-2-positive breast cancer with negative lymph nodes and a tumor diameter ≤1 cm admitted to Guangdong Women and Children Hospital from January 2013 to December 2019 were retrospectively analyzed. The median follow-up time was 70 months, the disease-free survival (DFS) of all patients was 94.3% and the overall survival (OS) was 100%. Univariate analysis of prognosis demonstrated that patients aged ≤40 years had significantly lower DFS than those aged >40 (80.8 vs. 100.0%, P<0.001). DFS was significantly improved in patients who were hormone-receptor-positive and patients who received endocrine therapy compared with patients who were estrogen receptor negative and patients who did not receive endocrine therapy (100.0 vs. 89.6%, P=0.039; 100.0 vs. 90.0%, P=0.049). Prognostic univariate analysis demonstrated that patient age, hormone receptor status and use of endocrine therapy were significantly related to the DFS (P<0.05), while none of these were independent factors related to the DFS in the prognostic multivariate analysis (P=0.240, P=0.976 and P=0.925). The proportion of patients with a tumor diameter 0.5-1 cm receiving adjuvant anti-HER-2 treatment was significantly greater compared with patients with tumors with a diameter ≤0.5 cm (46.4 vs. 18.6%, P<0.05). There was no significance difference in the DFS of patients treated with adjuvant chemotherapy with or without anti-HER-2 therapy with tumor diameters ≤0.5 cm (P>0.05), but there was a significant difference in the DFS of patients with a tumor diameter 0.5-1 cm (P<0.05). These results suggested that adjuvant chemotherapy, with or without anti-HER-2 therapy, may affect the prognosis of HER-2-positive breast cancer patients with negative lymph nodes and a tumor diameter of 0.5-1 cm. Therefore, it could be recommended that such patients receive adjuvant chemotherapy and anti-HER-2 therapy in the future.

Outcome of conventional radiotherapy in small centrally located tumours or lymph nodes: minimal toxicity, remarkable survival but challenging loco-regional control

Background In peripheral lung tumours, stereotactic body radiotherapy (SBRT) is superior to conventional RT. SBRT has also shown high loco-regional control (LC) in centrally located tumours, but there is a high risk of severe toxicity. The STRICTSTARLung trial (NCT05354596) examines if risk-adapted SBRT for central tumours is feasible. In this study, we examined overall survival (OS), Disease-free survival (DSF), LC, and toxicity in patients with central tumours that could have been candidates for SBRT but received conventional RT. Material and methods Retrospectively, we evaluated 49 lung cancer patients that between 2008 and 2021 received RT (60–70Gy in 2 Gy fractions) for a solitary tumour or lymph node with a diameter <5cm located <2cm from the bronchial tree, oesophagus, aorta or heart. All tumours were pathologically verified; 30 were primary lung tumours (T1b-T4) and 19 were solitary lymph nodes (T0N1-N2). Chemotherapy was administered as concomitant (29) or sequential (4). OS and LC were analysed using Kaplan Meier. Cox proportional hazards model for OS and disease-free survival (DFS) was performed including tumour volume, histology, sex, T- vs N-site and chemotherapy. Toxicity was scored. Results In 42 patients, the tumour was located <1 cm to mediastinum. Median follow-up time was 44 months (range: 7–123). The median OS was 51 months. OS at 1-, 3- and 5-year was 88% (SE:5), 59% (SE:7) and 50% (SE:8). Loco-regional recurrences occurred in 16 patients resulting in 1-, and 3-year LC rates of 77% (SE:6) and 64% (SE:8). The majority occurred within 3 years after RT. Only stage showed significant impact on OS and DFS. No patients experienced grade 4–5 toxicity. Seven patients developed grade 3 toxicity (5 oesophageal stenosis, 2 pneumonitis). Conclusion Conventional RT for patients with small central lung tumours or solitary lymph nodes is feasible. Median OS was 51 months, and toxicity was low with no grade 4–5 events.

QRT-PCR analysis of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN in colon cancer lymph nodes-An improved method for assessment of tumor stage and prognosis.

One fourth of colorectal cancer patients having curative surgery will relapse of which the majority will die. Lymph node (LN) metastasis is the single most important prognostic factor and a key factor when deciding on postoperative treatment. Presently, LN metastases are identified by histopathological examination, a subjective method analyzing only a small LN volume and giving no information on tumor aggressiveness. To better identify patients at risk of relapse we constructed a qRT-PCR test, ColoNode, that determines levels of CEACAM5, KLK6, SLC35D3, MUC2 and POSTN mRNAs. Combined these biomarkers estimate the tumor cell load and aggressiveness allocating patients to risk categories with low (0, -1), medium (1), high (2) and very high (3) risk of recurrence. Here we present result of a prospective, national multicenter study including 196 colon cancer patients from 8 hospitals. On average, 21 LNs/patient, totally 4698 LNs, were examined by both histopathology and ColoNode. At 3-year follow-up, 36 patients had died from colon cancer or lived with recurrence. ColoNode identified all patients that were identified by histopathology and in addition 9 patients who were undetected by histopathology. Thus, 25% of the patients who recurred were identified by ColoNode only. Multivariate Cox regression analysis proved ColoNode (1, 2, 3 vs 0, -1) as a highly significant risk factor with HR 4.24 [95% confidence interval, 1.42-12.69, P = .01], while pTN-stage (III vs I/II) lost its univariate significance. In conclusion, ColoNode surpassed histopathology by identifying a significantly larger number of patients with future relapse and will be a valuable tool for decisions on postoperative treatment.

The bulbils of Palaeonitella cranii (Charales, Charophyceae) revisited, with notes on other inflated cells of this alga that are not bulbils

Palaeonitella cranii is a charophyte alga (Charophyceae) from the Lower Devonian Rhynie chert of Scotland that consists of an axis of alternating internodes and nodes, with whorls of branchlets arising from the nodes. Conspicuous spherical to ovoid structures believed by most to be the bulbils of P. cranii are often found together with the axes and branchlets; however, they have so far only been insufficiently studied. Here, we revisit the bulbils, along with the rhizoids on which they were formed, based on new material from the Rhynie and Windyfield chert sites. The bulbils are up to 540 μm in diameter and occur singly or in groups on rhizoid nodes. A small node recognizable at the apical end in some specimens is evidence that the bulbils are modified branch rhizoids. There is also evidence of lower-order branch rhizoids extending from the apical node, as well as for sprouting. Palaeonitella cranii thrived in shallow pools and outflow channels of the Rhynie geothermal wetland. The bulbils might have enabled the plant to persist if photosynthesis was limited and to regenerate if the thallus was destroyed, but they might also have served as dispersal units. Other significantly inflated cells, which are not bulbils, may occur in both axes and branchlets of P. cranii, but are generally rare. Some of these cell alterations may be due to parasites. This study complements our understanding of P. cranii, the only fossil charophyte known from both above- and below-ground parts of the thallus, and from reproductive structures.