Multiple Scans Research Articles

The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump.

Introduction: The increase in bacterial strains resistant to conventional antibiotics is an alarming problem for human health and could lead to pandemics in the future. Among bacterial pathogens responsible for a large variety of severe infections there is Pseudomonas aeruginosa. Therefore, there is an urgent need for new molecules with antimicrobial activity or that can act as adjuvants of antibiotics already in use. In this scenario, antimicrobial peptides (AMPs) hold great promise. Recently, we characterized a frog-skin AMP derived from esculentin-1a, namely Esc(1-21)-1c, endowed with antipseudomonal activity without being cytotoxic to human cells. Methods: The combinatorial effect of the peptide and antibiotics was investigated through the checkerboard assay, differential proteomic and transcriptional analysis. Results: Here, we found that Esc(1-21)-1c can synergistically inhibit the growth of P. aeruginosa cells with three different antibiotics, including tetracycline. We therefore investigated the underlying mechanism implemented by the peptide using a differential proteomic approach. The data revealed a significant decrease in the production of three proteins belonging to the MexAB-OprM efflux pump upon treatment with sub-inhibitory concentration of Esc(1-21)-1c. Down-regulation of these proteins was confirmed by transcriptional analysis and direct measurement of their relative levels in bacterial cells by tandem mass spectrometry analysis in multiple reaction monitoring scan mode. Conclusion: These evidences suggest that treatment with Esc(1-21)-1c in combination with antibiotics would increase the intracellular drug content making bacteria more susceptible to the antibiotic. Overall, these results highlight the importance of characterizing new molecules able to synergize with conventional antibiotics, paving the way for the development of alternative therapeutic strategies based on AMP/antibiotic formulations to counteract the emergence of resistant bacterial strains and increase the use of "old" antibiotics in medical practice.

Integrating Pre-Trained protein language model and multiple window scanning deep learning networks for accurate identification of secondary active transporters in membrane proteins

Secondary active transporters play pivotal roles in regulating ion and molecule transport across cell membranes, with implications in diseases like cancer. However, studying transporters via biochemical experiments poses challenges. We propose an effective computational approach to identify secondary active transporters from membrane protein sequences using pre-trained language models and deep learning neural networks.Our dataset comprised 290 secondary active transporters and 5,420 other membrane proteins from UniProt. Three types of features were extracted - one-hot encodings, position-specific scoring matrix profiles, and contextual embeddings from the ProtTrans language model. A multi-window convolutional neural network architecture scanned the ProtTrans embeddings using varying window sizes to capture multi-scale sequence patterns.The proposed model combining ProtTrans embeddings and multi-window convolutional neural networks achieved 86% sensitivity, 99% specificity and 98% overall accuracy in identifying secondary active transporters, outperforming conventional machine learning approaches.This work demonstrates the promise of integrating pre-trained language models like ProtTrans with multi-scale deep neural networks to effectively interpret transporter sequences for functional analysis. Our approach enables more accurate computational identification of secondary active transporters, advancing membrane protein research.

Electrochemical DNA Sensor for Valrubicin Detection Based on Poly(Azure C) Films Deposited from Deep Eutectic Solvent.

A novel electrochemical DNA sensor was developed for the detection of the anthracycline drug, valrubicin, on the base of poly(Azure C) electropolymerized from the deep eutectic solvent reline and covered with adsorbed DNA from calf thymus. Biosensor assembling was performed by multiple scanning of the potential in one drop (100 µL) of the dye dissolved in reline and placed on the surface of a screen-printed carbon electrode. Stabilization of the coating was achieved by its polarization in the phosphate buffer. The electrochemical characteristics of the electron transfer were determined and compared with a similar coating obtained from phosphate buffer. The use of deep eutectic solvent made it possible to increase the monomer concentration and avoid using organic solvents on the stage of electrode modification. After the contact of the DNA sensor with valrubicin, two signals related to the intrinsic redox activity of the coating and the drug redox conversion were found on voltammogram. Their synchronous changes with the analyte concentration increased the reliability of the detection. In the square-wave mode, the DNA sensor made it possible to determine from 3 µM to 1 mM (limit of detection, 1 µM) in optimal conditions. The DNA sensor was successfully tested in the voltammetric determination of valrubicin in spiked artificial urine, Ringer-Locke solution mimicking plasma electrolytes and biological samples (urine and saliva) with a recovery of 90-110%. After further testing on clinical samples, it can find application in the pharmacokinetics studies and screening of new drugs' interaction with DNA.

Identification of Differences in Body Composition Measures Using 3D-Derived Artificial Intelligence from Multiple CT Scans across the L3 Vertebra Compared to a Single Mid-Point L3 CT Scan.

Body composition analysis in colorectal cancer (CRC) typically utilises a single 2D-abdominal axial CT slice taken at the mid-L3 level. The use of artificial intelligence (AI) allows for analysis of the entire L3 vertebra (non-mid-L3 and mid-L3). The goal of this study was to determine if the use of an AI approach offered any additional information on capturing body composition measures. A total of 2203 axial CT slices of the entire L3 level (4-46 slices were available per patient) were retrospectively collected from 203 CRC patients treated at Western Health, Melbourne (97 males; 47.8%). A pretrained artificial intelligence (AI) model was used to segment muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) on these slices. The difference in body composition measures between mid-L3 and non-mid-L3 scans was compared for each patient, and for males and females separately. Body composition measures derived from non-mid-L3 scans exhibited a median range of 0.85% to 6.28% (average percent difference) when compared to the use of a single mid-L3 scan. Significant variation in the VAT surface area (p = 0.02) was observed in females compared to males, whereas male patients exhibited a greater variation in SAT surface area (p < 0.001) and radiodensity (p = 0.007). Significant differences in various body composition measures were observed when comparing non-mid-L3 slices to only the mid-L3 slice. Researchers should be aware that considering only the use of a single midpoint L3 CT scan slice will impact the estimate of body composition measurements.

Remote Expert DVT Triaging of Novice-User Compression Sonography with AI-Guidance

Compression ultrasonography of the leg is established for triaging proximal lower extremity deep vein thrombosis (DVT). AutoDVT, a machine-learning software, provides a tool for nonspecialists in acquiring compression sequences to be reviewed by an expert for patient triage. The purpose of this study was to test image acquisition and remote triaging in a clinical setting. Patients with a suspected DVT were recruited at 2 centers in Germany and Greece. Enrolled patients underwent an artificial intelligence-guided two-point compression examination by a nonspecialist using a handheld ultrasound device prior to a standard scan. Images collected by the software were uploaded for blind review by 5 qualified physicians. All reviewers rated the quality of all sequences on the American College of Emergency Physicians (ACEP) image quality scale (score 1-5, ≥ 3 defined as adequate imaging quality) and for an ACEP score ≥3, chose "Compressible", "Incompressible", or "Other". Sensitivity and specificity were calculated for adequate quality scans with an assessment as "Compressible" or "Incompressible". We define this group as diagnostic quality. To simulate a triaging clinical algorithm, a post hoc analysis was performed merging the "incomplete", the "low quality", and the "Incompressible" into a high-risk group for proximal DVT. Seventy-three patients (average age 64.2years, 44% females) were eligible for inclusion and scanned by 3 nonultrasound-qualified healthcare professionals. Three patients were excluded from further analysis due to incomplete scans. Sixty two of 70 (88.57%) of the completed scans were judged to be of adequate image quality with an average ACEP score of 3.35. Forty seven of 62 adequate AutoDVT scans were assessed as diagnostic quality, of which 8 were interpreted as positive for proximal DVT by the reviewers resulting in a sensitivity of 100% and specificity of 95.12%. When simulating a triaging algorithm, 34/73 (46.58%) of patients would be triaged as high risk and 8 would be confirmed as positive for proximal DVT (6 in the diagnostic and 2 in the low-quality cohort). Of 39/73 patients triaged as low risk, all were negative for proximal DVT in standard duplex; thus, this triaging algorithm could potentially save 53.42% of standard duplex scans. Machine learning software was able to aid nonexperts in acquiring valid ultrasound images of venous compressions and allowed remote triaging. This strategy allows faster diagnosis and treatment of high-risk patients and can spare the need for multiple unnecessary duplex scans, the vast majority being negative.

A hybrid framework for robust dynamic 3D point clouds removal

When robot creates a map, dynamic objects can change the space and render the map unusable for navigation. Additionally, the vertical resolution of a VLP-16 LiDAR may be insufficient, making dynamic point removal challenging. To address these challenges, we propose a novel method for dynamic point detection and removal consisting of four components. Firstly, we introduce a multi-resolution heightmap to enhance the efficiency and precision of dynamic point recognition by segmenting ground points. Secondly, we address the issue of limited vertical resolution by fusing multiple scans to simulate additional scan lines and leveraging a multi-resolution range image for precise dynamic point elimination. Thirdly, we apply clustering and principal component analysis-based techniques to compute eigenvectors, facilitating the correction of misclassified static points. Lastly, we propose the utilization of a three-dimensional bounding box strategy to reinforce the monitoring of small static clusters with elevated probabilities of misclassification. These four components complement each other and are executed sequentially. We evaluated our method for both dynamic point removal and ground segmentation on the KITTI dataset and real-world environments. The results demonstrate that our method outperforms baseline methods and generates clean maps.

THU465 Significant Improvement In Bone Mineral Density Following Treatment For Tumor Induced Osteomalacia

Abstract Disclosure: L.C. McHan: None. M. Augustine: None. Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting and impaired activation of vitamin D due to excess secretion of FGF23, often from phosphaturic mesenchymal tumors (PMTs). TIO typically presents with months to years of bone pain, muscle weakness, and fractures often leading to functional decline. Given these nonspecific symptoms, diagnosis of TIO can be delayed for years. Removal of the tumor is curative, though it can sometimes be a challenge to localize. For those whose tumors are unable to be localized or removed, medical management with phosphorus and vitamin D is recommended. Patients with TIO have low bone mineral density (BMD) at time of diagnosis. Case Reports: We are presenting two cases of TIO, one managed surgically and one managed medically. Patient 1 is a 45-year-old man with Fabry disease who presented with years of progressive pain, difficulty ambulating, and multiple fractures. Lab workup revealed low serum phosphorus, elevated urinary phosphorus, elevated FGF23, and negative genetic testing for heritable causes of hypophosphatemic osteomalacia. DOTATATE imaging identified a subcutaneous left flank mass, which was excised resulting in improvement in symptoms and resolution of biochemical abnormalities. Additionally, lumbar spine (LS) bone mineral density (BMD) nearly doubled; prior to diagnosis of TIO, LS BMD was 0.601 g/cm2 and 8 months after surgical excision of the tumor, LS BMD was 1.178 g/cm2. Patient 2 is a 55-year-old nonverbal man with autism and intellectual disability who presented with months of progressive difficulty ambulating, presumed pain, functional decline, and multiple fractures. Workup revealed low serum phosphorus, elevated urinary phosphorus, and elevated FGF23 concerning for TIO. He was initiated on phosphorus and vitamin D supplementation, but no culprit tumor has been identified despite multiple scans over the course of years. However, the patient has had a significant improvement in functioning with medical management in addition to a remarkable 48% improvement in LS BMD, from 0.855 g/cm2 prior to diagnosis of TIO and 1.264 g/cm2 following 3 years of medical management. Clinical Lessons: In our review of the literature, there are few case reports and case series documenting the significant improvements in BMD with treatment of TIO. In our experience, two patients who had months to years of debilitating symptoms exhibited remarkable improvements in symptoms and marked improvement in LS BMD following treatment. This emphasizes the importance of recognizing the diagnosis of TIO, as even when the causative tumor is not identified, treatment typically has a significant impact on patient functioning and quality of life. Presentation: Thursday, June 15, 2023

FRI224 A Rare Case Of Recurrent Paraganglioma Presented With Liver Metastasis

Abstract Disclosure: E. Gupta: None. M. Al Mushref: None. Malignant Paragangliomas (PGLs) and Pheochromocytomas (PCC) are extremely rare. Approximately 10% of PCCs and 25% of PGLs are metastatic. Metastatic PGLs typically occur in patients with predisposing genetic mutations. We present a case of recurrent metastatic PGL in a young female with no known genetic predisposition to metastatic disease occurring after surgical resection. Our patient is a 28-year-old female with a history of PGL status post left adrenalectomy and nephrectomy two and a half years prior who presented to the ED for abdominal pain. She was first diagnosed after being admitted for hypertensive emergency. During time of diagnosis, plasma and urinary metanephrines were significantly elevated at 1.13 nmol/L and 907 ug/gCr respectively and plasma and urinary normetanephrines were elevated at 80.2 nmol/L and 52043 ug/gCr respectively. MRI showed a 16 cm left retroperitoneal mass and MIBG scan showed increased uptake in the mass however no evidence of metastatic disease was noted then. The patient had immigrated from Haiti. Her mother had passed away at age 20 of unknown cause and her father has no known history. Genetic testing was negative for hereditary gene mutations including multiple SDHDs, VHL, NF1, MEN1 and MAX. Surgical exploration showed a giant left retroperitoneal neoplasm involving the left kidney and left adrenal and both organs were resected. Pathology revealed PGL, focally extending to peripheral specimen margin and benign retroperitoneal lymph nodes and soft tissues. Post-resection meta- and normetanephrines levels were normal. Unfortunately, the patient was lost to follow up after surgery. On this admission, she endorsed right lower quadrant abdominal pain. Plasma normetanephrine was 1.72 nmol/L, metanephrine was normal, and chromogranin A level was elevated at 545 ng/mL. CT scan revealed multiple hepatic lesions and MIBG scan further showed new increased uptake suggesting metastasis. The patient was asymptomatic and blood pressure remained normal during her hospitalization. Due to concerns of recurrent PGL with metastasis, she established care with Oncology for initiation of treatment. PGL is an extremely rare neuroendocrine tumor and is closely related to PCC. Sympathetic PGLs cause catecholamine surge symptoms but low volume disease may remain asymptomatic. Genetic predisposition is common in malignant PGL particularly succinate dehydrogenase mutation subunit B. Patients should be closely followed up to screen for recurrence and genetic testing should also be done. In our patient’s case, despite surgical resection and negative genetic testing, she developed recurrence of the PGL with new metastasis emphasizing the importance of close surveillance in the case of PGL to monitor for recurrence. Presentation: Friday, June 16, 2023

THU432 Severe Osteoporosis Associated With A Novel Plastin 3 (PLS3) Mutation

Abstract Disclosure: A. Ibrahim: None. L. Esper: None. S.M. Gandhi: None. E.S. Nylen: None. Early Onset Osteoporosis (EOOP) affects children and young adults and can be caused by endocrinopathies, chronic medical conditions, nutritional deficiencies, and/or genetic mutations. The most common inherited cause is osteogenesis imperfecta(OI), and a rare variant linked to OI includes a defect in the X chromosomal gene encoding Plastin 3 (PLS3). In our case, a 34-year-old male was referred for severe osteoporosis. He had been diagnosed with osteopenia at age 21. At age 24, imaging revealed multiple vertebral compression fractures and DXA scan confirmed severe osteoporosis. He required L3-L5 kyphoplasty and started on oral bisphosphonates for presumed OI despite negative gene mutation (i.e., COL1A1/COL1A2). He continued treatment for only 2 years. 8 years later, he had persistent osteoporosis (DXA L2-4 Z-score -3.6, LFN Z-score -3.2). He had no evidence of kyphosis or scoliosis and no extraskeletal manifestations such as blue-grey sclera or any dysmorphic features. The workup was negative for secondary causes of EOOP and he denied a family history of osteoporosis. Labs showed normal 24-hour urine calcium, bone markers, and bone Alkaline Phosphatase. Karyotyping showed normal XY and gene analysis was again negative for OI. He started treatment with intravenous Zoledronic acid, however, had a 2-year gap between doses initially causing BMD to drop by 6.5% in L2-L4 (Z -4.1) and by 5.7% in LFN (Z -3.1). Subsequently, he received a total of 5 doses of Zoledronic acid to date and had no further fractures. DXA significantly improved by 10.4% in L2-4 (Z -2.6), and 16.3% in LFN (Z -2.0). Repeated expanded gene testing showed a novel PLS3 hemizygous mutation (deletion at site C.234_237+10del of Exon 3). This case demonstrates a novel PLS3 mutation variant to be a plausible cause of adulthood EOOP which was responsive to bisphosphonate treatment. PLS3 is an F-actin binding and bundling protein involved in cytoskeletal remodeling and may have roles in calcium homeostasis, cell migration, endocytosis, DNA repair, and membrane trafficking. Currently, less than 30 loss of function variants of PLS3 have been identified and all lead to severe osteoporosis- particularly in children. However, our patient’s known onset of bone loss occurred much later- in his twenties and he had no evidence of extra-skeletal manifestations. The cause for such late presentation is unclear but may be attributed to this specific variant of PLS3. This case highlights that PLS3 mutation should be on the differential for EOOP even in early adulthood. Our patient’s BMD has markedly improved with bisphosphonates and he sustained no further fractures after starting therapy. Timely diagnosis and earlier detection will allow for appropriate genetic counseling, earlier screening, and treatment of affected family members. Presentation: Thursday, June 15, 2023

FRI202 A Curious Case Of Psychosis

Abstract Disclosure: F. Waqar: None. A. Arif: None. A. Muazzam: None. R. Wadood: None. A.S. Khakwani: None. U.A. Khan: None. Ascertaining the cause of mental and behavioral changes can be challenging in patients with complex medical histories. We are sharing a thought-provoking case of psychosis. A 51-year-old woman with past medical history of ESRD, stroke, diabetes, depression, and endometrial cancer was brought to the hospital for lethargy and confusion. It was preceded by some nausea, vomiting, and abdominal pain. Upon admission, she was noted to be hypotensive and minimally responsive. She was given fluids (with subsequent improvement in blood pressure) and started on antibiotics empirically for concerns of sepsis. During her hospital course, her mental status fluctuated from being completely normal to having episodes of becoming still, with total lack of response to any stimulus. During these episodes, she would be awake, breathing spontaneously and vitally stable, but unresponsive, mimicking catatonia however lacked muscle stiffness/ rigidity. Each episode resolved spontaneously after a few hours. Multiple CT scans and a CT Angiogram of the Head &amp; Neck were negative for acute findings. Continuous EEG revealed no epileptic activity. Infectious work-up was unrevealing. Labs were within the expected range of the intra-dialytic period. Two of her medications, gabapentin and mirtazapine were thought to be the contributors and were stopped upon admission, however with little improvement. Her symptoms were ultimately deemed to be psychogenic in origin, and she was started on an anti-psychotic regimen. Fortunately, as part of her workup, a morning cortisol level was checked, which resulted to be quite low at 1.6 mcg/dL, consistent with adrenal insufficiency. Co-syntropin stimulation test confirmed adrenal insufficiency, the actual cause of her presentation. This explained her intermittent hypotension along with mental and behavioral changes. Interestingly, she was found to be on megestrol acetate which is notorious for causing secondary adrenal insufficiency. She was ultimately started on hydrocortisone replacement therapy, with subsequent improvement and stabilization of her mental status, mood, and behavior; and was discharged with outpatient Endocrinology follow-up. This case highlights the importance of the broad differentials to consider for mental and behavioral changes. We want to alert physicians to include adrenal insufficiency in the differentials of acute psychosis as symptoms and electrolyte abnormalities may be atypical and masked in dialysis patients. The exact mechanism of neuropsychiatric symptoms (which may precede metabolic abnormalities) is unknown but is hypothesized to involve elevated levels of endorphins and electrophysiological disturbances as glucocorticoid receptors are widely distributed in the brain, specifically in the hippocampus. Megestrol is an established cause of secondary adrenal insufficiency, and monitoring is essential with long-term use. Presentation: Friday, June 16, 2023

FRI360 A Protracted Course Of Worsening Adrenergic And Neuroglycopenic Symptoms Due To Delay In Diagnosis Of Insulinoma

Abstract Disclosure: A. Karca: None. W. Lai: None. S. Naidoo: None. L.N. Saladi: None. B.C. Jameson: None. A 33-year-old Hispanic male presented with altered mental status, witnessed seizure and hypoglycemia (capillary BG 40mg/dL). Patient and family reported multiple episodes of symptomatic hypoglycemia and progressively worsening adrenergic and neuroglycopenic episodes with altered mental status requiring hospital admissions and evaluation for endogenous hyperinsulinemia in the past several months prior to admission. Patient was admitted to the ICU. Laboratory workup revealed documented hypoglycemia (venous BG 45mg/dL) and inappropriate insulin (17uU/mL, n3-25uU/mL), c-peptide (2.7ng/mL, n0.8-4.2 ng/mL) and pro-insulin (38.3 pmol/L, n&amp;lt;18.8 pmol/L) levels. Sulfonylurea and meglitinide screens were negative. Patient required continuous dextrose infusion as well as octreotide, with enteral feeding, to maintain BG &amp;gt;70mg/dL. Abdominal US, multiple CT scans, endoscopic US failed to locate source of endogenous hyperinsulinemia. Multi-discipline discussion among ICU team, Endocrinology, Interventional Radiology (IR), and Surgery considered MRI versus IR-guided selective arterial calcium stimulation (SACS) vs PET-CT NETSPOT with Ga-68 Dotatate, which had been ordered, but unable to be arranged prior to this admission. Ultimately, MRI with pancreatic protocol revealed 3.5cm exophytic solid mass arising from the tail of the pancreas and patient underwent laparoscopic hand-assisted distal pancreatectomy and splenectomy, with intraoperative ultrasound to confirm the location of the mass. Histologic examination revealed a well-differentiated neuroendocrine tumor. Chart review revealed documented hypoglycemia as far back as eight years prior to this admission, although no further results were available from that time to confirm endogenous source. Possible explanations for delay in diagnosis include patient health literacy, inaccessibility of outpatient testing, limitations of testing modalities, and access to staff skilled in more specialized testing, like PET-CT NETSPOT and SACS. Localizing techniques are divided into pre-operative and intra-operative, with pre-operative techniques further divided into non-invasive and invasive modalities. First line pre-operative testing includes US and CT, which have widely varying sensitivity depending on size and location of the tumor. MRI can have better sensitivity for smaller and distal tumors. PET-CT NETSPOT with Ga-68 Dotatate, has very high sensitivity and specificity in limited studies. If not localized with non-invasive modalities, SACS is an invasive modality with high sensitivity and specificity. Although insulinomas are a rare neuroendocrine tumor with challenging diagnostic workup, higher clinical suspicion with early biochemical workup, patient education, referral to endocrinology, better accessibility of diagnostic testing will help lead to timely diagnosis and management. Presentation: Friday, June 16, 2023

THU538 Use Of Multiple Functional And Structural Imaging Modalities Improves Detection Of Ectopic ACTH Tumors

Abstract Disclosure: H. Elenius: None. R. McGlotten: None. A.M. Gharib: None. L.K. Nieman: None. Introduction: In Ectopic ACTH Syndrome (EAS), Cushing's syndrome (CS) is caused by ACTH secretion from a non-pituitary tumor. Tumor resection reduces CS morbidity and mortality, but up to 38% of tumors remain occult despite repeated structural imaging. We prospectively studied whether functional PET imaging with somatostatin receptor ( 111In-pentetreotide Octreoscan [OCT], vs 68Ga DOTA0-Tyr3 octreotate DOTATATE [DOTA]) or amine precursor (18F-DOPA [F-D]) ligands would improve tumor detection. Methods: From 2014-2022, 22 EAS patients underwent imaging with F-D and DOTA PET/CT and/or MRI (1.5 and/or 3 Tesla, T) of chest/abdomen/pelvis (C/A/P), gated cardiac CT (GC-CT) and/or MRI (GC-MRI), and/or OCT before tumor resection. Pre-surgical imaging results were confirmed by pathology or biochemical cure. Results: Tumors included 16 pulmonary (pulm) neuroendocrine tumors (NET), one thymic NET, one appendiceal NET, one pheochromocytoma and one metastatic NET in mediastinal lymph nodes; two patients had tumorlets. Surgery was done if at least CT or MRI was positive; some lesions were seen only after concurrent PET scan review. Shown in decreasing order, the modalities performed as follows (number of patients = N): Sensitivity (S): CT C/A/P 100%, N 22 ; FDG-PET 100%, N 2 ; 3T MRI C/A/P 93%, N 14 ; F-D 91%, N 22 ; DOTA 86%, N 22 ; 1.5T MRI C/A/P 71%, N 21 ; GC-CT 67%, N 6 ; GC-MRI 50%, N 8 ; OCT 31%, N 13. 95% Confidence intervals (CI) overlapped for all except OCT. Positive predictive value (PPV): GC-MRI 100% ; 3T MRI C/A/P 88% ; 1.5T MRI C/A/P 84% ; DOTA 83% ; CT C/A/P 81% ; GC-CT 80% ; F-D 75% ; OCT 67% ; FDG-PET 67%. All CIs overlapped.1.5T MRI, F-D and DOTA missed a 12 mm pulm NET (false negative, FN) only seen on CT. 1.5T MRI missed three other pulm NET (6, 8 and 10 mm) seen on 3T MRI. 1.5T and 3T MRI missed a 13 mm pulm NET that abutted the heart and was seen on both gated studies - this was the only FN lesion in the 3T MRI cohort. F-D missed the 12 mm pulm NET seen on CT and the retrocardiac NET, which was DOTA +. DOTA missed three other pulm NET (6, 8 and 10 mm); all were positive on F-D. OCT detected 4/10 pulm NET, 6-25 mm, all positive on F-D and DOTA, and missed 9 tumors seen on F-D (N=8) or DOPA (N=8). F-D detected false positive (FP) lesions in seven patients while DOTA detected FP lesions in three, mostly infections or thyroid nodules. All but one patient were localized by DOTA (N=19) and/or F-D (N=20). Conclusions: As reported previously, most EAS tumors were intrathoracic. Among structural modalities, CT was the most sensitive (100%) while cardiac MRI and 3T MRI gave the highest PPV (100% and 88%). Dedicated cardiac imaging found pericardiac lesions missed on routine modalities due to motion artefacts. F-D and DOTA were significantly more sensitive (91% and 86%) than OCT (31%). DOTA detected fewer FP lesions, providing a higher PPV (83%) than F-D (75%), but with lower sensitivity. Use of multiple functional and structural scans improved tumor detection. Presentation: Thursday, June 15, 2023

Impedimetric DNA Sensors for Epirubicin Detection Based on Polythionine Films Electropolymerized from Deep Eutectic Solvent.

An electrochemically active polymer, polythionine (PTN), was synthesized in natural deep eutectic solvent (NADES) via multiple potential scans and characterized using cyclic voltammetry and electrochemical impedance spectroscopy (EIS). NADES consists of citric acid monohydrate, glucose, and water mixed in the molar ratio of 1:1:6. Electrodeposited PTN film was then applied for the electrostatic accumulation of DNA from salmon sperm and used for the sensitive detection of the anticancer drug epirubicin. Its reaction with DNA resulted in regular changes in the EIS parameters that made it possible to determine 1.0-100 µM of epirubicin with the limit of detection (LOD) of 0.3 µM. The DNA sensor developed was successfully applied for the detection of epirubicin in spiked samples of artificial and natural urine and saliva, with recovery ranging from 90 to 109%. The protocol of the DNA sensor assembling utilized only one drop of reactants and was performed with a minimal number of steps. Together with a simple measurement protocol requiring 100 µL of the sample, this offers good opportunities for the further use of the DNA sensor in monitoring the drug level in biological samples, which is necessary in oncology treatment and for the pharmacokinetics studies of new antitumor drugs.

ASIC Implementation for Multiple Scan at Register Transfer Level

Design for testability (DFT) is introduced to reduce the complexity of testing integrated circuit and help improve fault coverage. However, conventional DFT with additional 2-to-1 multiplexer (MUX) might add an increasing amount of delay and area overhead. Therefore, register transfer level (RTL) scan design is introduced to overcome this problem. This paper aims to present the development of an ASIC with RTL scan design by using multiple scan paths instead of the conventional technique, which is gate-level (GL) scan insertion to insert scan cells. This method inserts multiple scan cells by utilizing the existing multiplexer and operational units in order to reduce area overhead and delay. Besides, multiple scan paths are implemented instead of a single scan chain to reduce the complexity of the testing process, where a single scan chain has long test application times due to the high number of clock cycles for the scan chain process. RTL design is also modified by adding an extra gate for multiple scan chain insertion. The graph is derived in order to analyse the connection between registers such that the multiple scan paths can be determined accordingly. Synopsys tool is used for synthesized, placement and routing and performing automatic test pattern generation while static timing analysis is used to verify the results of the setup slack time for ASIC design. The simulation result shows that multiple scan paths insertion at RTL level has an area overhead and slack time of about 3.79% and 0.44ns less compared to multiple scan paths insertion at GL for a finite impulse response circuit with comparable high fault coverage and small delay. A comparison of the performance metrics such as area, setup slack time, and fault coverage of the multiple scan chain is done between the RTL scan and GL scan.

Real-time 3-D reconstruction from multiple simultaneous ultrasound scans for enhanced imaging

Ultrasound imaging offers numerous benefits compared to other modalities, including portability, affordability, and real-time volumetric imaging capabilities. However, its limited field of view hinders image interpretation, significantly limiting its potential clinical applications. This study focuses on creating tomographic ultrasound imaging by automatically registering partially overlapping 3-D ultrasound volumes (coarsely localized in space). This approach can be used to gather a comprehensive field of view of the anatomical area imaged and to enhance the acquired image information. Potential applications involve both tomographic/wide-view imaging using conventional ultrasound probes and future technologies, where multiple ultrasound probes will be able to scan simultaneously the anatomy of interest. This work describes the development of advanced artificial intelligence and image analysis methods to create real-time 3-D anatomical reconstructions of a designated area of interest. Simultaneously (or quasi simultaneously) acquired ultrasound volumes with partial overlap can be spatially aligned using rigid registration, because they present geometrically similar information. We used novel supervised and unsupervised transformers and compared the results with more traditional methods such as mutual information and cross-correlation. This application contributes to creating new imaging processing techniques for ultrasound imaging and making this complex modality more user-friendly and clinically usable.

S2207 Multiple Scans, No Answers: Failure of CTs to Detect Symptomatic Pancreatic Cancer

S2207 Multiple Scans, No Answers: Failure of CTs to Detect Symptomatic Pancreatic Cancer

Chemical profiling of principle active and toxic constituents in herbs containing aristolochic acids

ObjectiveTo clear the amounts of the principal active/toxic components in herbs containing aristolochic acids (HCAAs), which are still used as medicine and/or seasoning in many ethnic minority areas of China. MethodsIn this study, six major active and toxic components in HCAAs were extracted with ultrasonic extraction. With 6-O-methyl guanosine as internal standard, the target compounds were analyzed qualitatively and quantitatively by using ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) with multiple reaction monitoring-information dependent acquisition-enhanced production ion scanning mode (MRM-IDA-EPI) combined with dynamic background subtraction (DBS) function. ResultsThe method showed good linearity in the linear range of the six analytes. The limit range of detection was from 0.01 ng/mL to 0.27 ng/mL. All of the detection repeatability, extraction repeatability and accuracy of the method were good. After extraction, the samples remained stable at 15 °C within 24 h. Six analytes were all found in samples except aristolactam (AL) in sample 2, and the contents varied greatly. The contents of these compounds decreased in fruits, leaves and stems of Aristolochia delavayi successively. ConclusionThis method has the advantages of less sample dosage, simple operation, short analysis cycle, high sensitivity, specificity and accuracy. It laid a good foundation for guiding the safety of HCAAs, the in-depth study of pharmacological and toxicological effects and the scientific and standardized processing and compatibility of HCAAs.

Low Power Compact 3D-Constructed AlScN Piezoelectric MEMS Mirrors for Various Scanning Strategies.

In this paper, the newly developed 3D-constructed AlScN piezoelectric MEMS mirror is presented. This paper describes the structure and driving mechanism of the proposed mirror device, covering its driving characteristics in both quasi-static and resonant scan modes. Particularly, this paper deals with various achievable scan patterns including 1D line scan and 2D area scan capabilities and driving methods to realize each scanning strategy. Bidirectional quasi-static actuation along horizontal, vertical, and diagonal scanning directions was experimentally characterized and even under a low voltage level of ±20 V, a total optical scan angle of 10.4° was achieved. In addition, 1D line scanning methods using both resonant and non-resonant frequencies were included and a total optical scan angle of 14° was obtained with 100 mVpp under out-of-phase actuation condition. Furthermore, 2D scan patterns including Lissajous, circular and spiral, and raster scans were realized. Diverse scan patterns were realized with the presented AlScN-based MEMS mirror device even under a low level of applied voltage. Further experiments using high voltage up to ±120 V to achieve an enhanced quasi-static scan angle of more than 20° are ongoing to ensure repeatability. This multi-functional MEMS mirror possesses the potential to implement multiple scanning strategies suitable for various application purposes.

Cell Lysis, labeling efficacy and biodistribution of intravenously administered Technetium-99 m labeled multifunctional zirconia nanoparticles in animal model

Nanoparticles, to be used in biomedical applications, have been the subject of extensive investigation in recent years. Recently, zirconia and iron have gained significant relevance to the field due to their superior mechanical and structural qualities as well as their numerous biological applications. In this research, Fe3O4-stabilized zirconia nanopowders are fabricated using a low-cost sol–gel approach. Iron oxide sol is added in 1–10 wt% increments to a 0.1 M zirconia sol. The obtained crystallite size values match well with previously reported values for the tetragonally stable (t-zirconia) phase. Hardness values of approximately 1278 HV, along with fracture toughness values of ∼ 24.48 MPa.m-1/2 are observed for stable tetragonal zirconia. Results from cell lysis experiments indicate that the synthesized nanoparticles have the potential to combat cancerous cells. An encapsulation efficacy of up to ∼ 73% is observed after a 120-minute time period. Radio labeling techniques are employed to label the as-synthesized zirconia nanoparticles using Sodium Pertechnetate (Na99mTcO4) labeled radiopharmaceuticals, allowing for biodistribution assessment. Multiple CT scans of rabbits are performed to obtain accurate results and evaluate their survival. Studies show that radiolabeled nanoparticles are highly absorbed in the animals' bladders, making them a promising choice for tumor therapy. Various physical properties of the animals are periodically examined after administration of the nanoparticle-based injection for several months, and no abnormalities are found. The results obtained through these characterizations indicate that these nanoparticles can be used as future therapeutic agents as well as drug carriers.

Building 3D Generative Models from Minimal Data.

We propose a method for constructing generative models of 3D objects from a single 3D mesh and improving them through unsupervised low-shot learning from 2D images. Our method produces a 3D morphable model that represents shape and albedo in terms of Gaussian processes. Whereas previous approaches have typically built 3D morphable models from multiple high-quality 3D scans through principal component analysis, we build 3D morphable models from a single scan or template. As we demonstrate in the face domain, these models can be used to infer 3D reconstructions from 2D data (inverse graphics) or 3D data (registration). Specifically, we show that our approach can be used to perform face recognition using only a single 3D template (one scan total, not one per person). We extend our model to a preliminary unsupervised learning framework that enables the learning of the distribution of 3D faces using one 3D template and a small number of 2D images. Our approach is motivated as a potential model for the origins of face perception in human infants, who appear to start with an innate face template and subsequently develop a flexible system for perceiving the 3D structure of any novel face from experience with only 2D images of a relatively small number of familiar faces.