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The objective of this review is to examine the potential benefits and challenges of CT-based lung function imaging in radiotherapy over recent decades. This includes reviewing background information, defining related concepts, classifying and reviewing existing studies, and proposing directions for further investigation. The lung function imaging techniques reviewed herein encompass CT-based methods, specifically utilizing phase-resolved four-dimensional CT (4D-CT) or end-inspiratory and end-expiratory CT scans, to delineate distinct functional regions within the lungs. These methods extract crucial functional parameters, including lung volume and ventilation distribution, pivotal for assessing and characterizing the functional capacity of the lungs. CT-based lung ventilation imaging offers numerous advantages, notably in the realm of thoracic radiotherapy. By utilizing routine CT scans, additional radiation exposure and financial burdens on patients can be avoided. This imaging technique also enables the identification of different functional areas of the lung, which is crucial for minimizing radiation exposure to healthy lung tissue and predicting and detecting lung injury during treatment. In conclusion, CT-based lung function imaging holds significant promise for improving the effectiveness and safety of thoracic radiotherapy. Nevertheless, challenges persist, necessitating further research to address limitations and optimize clinical utilization. Overall, this review highlights the importance of CT-based lung function imaging as a valuable tool in radiotherapy planning and lung injury monitoring.

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Objective: Biochemical recurrence (BCR) after initial management of Prostate Carcinoma (PC) is frequent. Subsequent interventions rely on disease burden and metastasis distribution. 68Ga prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is an excellent imaging modality in BCR. However, 68Ga is radionuclide generator produced and has restricted availability. 99mTc-labeled PSMA could be a potential cost-effective alternative. We compared the performance of 99mTc-PSMA single-photon emission CT (SPECT)/CT and 68Ga-PSMA PET/CT in BCR with a serum prostate surface antigen (PSA) level of <20 ng/mL. Materials and Methods: The prospective study included 25 patients with BCR and at least one lesion on a 68Ga-PSMA PET/CT. All patients underwent 99 mTc-PSMA SPECT/CT, and disease distribution and metastatic burden were compared with 68Ga-PSMA PET/CT. The maximum standard uptake value (SUVmax) and the tumor-to-background ratio (TBR) were computed and analyzed. Results: The mean age and serum PSA (SPSA) were 69.72 ± 6.69 years and 5.65 ± 6.07 ng/mL. Eleven patients (44%) had SPSA ≤2 ng/mL. Recurrent sites were noted in the prostate (19, 76%), prostatic bed (3, 12%), and pelvis lymph nodes (LNs) (13, 52%). Distant metastasis to bones (13, 52%), lungs (5, 20%), and retroperitoneal LNs (2, 8%) were noted. Both modalities were concordant for the recurrent disease at the prostate, prostatic bed, bone, and lung lesions. 99mTc-PSMA could localize pelvis LNs in most patients (10/13, 76.9%). The site-specific sensitivity and specificity between the two modalities were not significantly different (P > 0.05). TBR shows excellent correlation with SUVmax (0.783, P < 0.001). Four (16%) patients were understaged with 99mTc-PSMA due to the nonvisualization of the subcentimeter size LNs. No patient with systemic metastases was understaged. Conclusions: 99mTc-PSMA SPECT/CT has good concordance with 68Ga-PSMA PET/CT in BCR, even at low PSA levels. However, it may miss a few subcentimeter LNs due to lower resolution. 99mTc-PSMA SPECT/CT could be a simple, cost-effective, and readily available imaging alternative to PET/CT.

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Avascular necrosis (AVN) of the femoral head is a condition characterized by limited mobility, discomfort, and changes in walking patterns due to insufficient blood supply in this region. Our objective is to investigate the possible connection between COVID-19 and AVN. In this study, we detail the case of a 41-year-old male patient who developed AVN in both femoral heads after contracting COVID-19. The mere occurrence of a COVID-19 infection and the use of corticosteroids for its treatment may increase the probability of AVN in the femoral head. Hence, post the COVID-19 pandemic, it is crucial to consider AVN vigilantly for timely detection and treatment.

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Superconducting microstrip single photon detectors (SMSPDs) are increasingly attracting the interest of the scientific community as a new platform for large area detectors with unprecedented advantaged in terms of fabrication. However, while their operativity at the telecommunication wavelength was achieved, working beyond 1.55 µm is challenging. Here, we experimentally demonstrate single-photon operation of NbRe microstrips at wavelengths of 1.55 and 2 µm. The devices are structured as pairs of parallel microstrips with widths ranging from 1.4 to 2.2 µm and lengths from 5 to 10 µm. This innovative design may assure large sensitive areas, without affecting the kinetic inductance, namely the time performance of the detectors. The results are discussed in the framework of the hot-spot two-temperature model.

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Single-photon avalanche diodes (SPADs) belong to a family of avalanche photodiodes (APDs) with single-photon detection capability that operate above the breakdown voltage (i.e., Geiger mode). Design and technology constraints, such as dark current, photon detection probability, and power dissipation, impose inherent device limitations on avalanche photodiodes. Moreover, after the detection of a photon, SPADs require dead time for avalanche quenching and recharge before they can detect another photon. The reduction in dead time results in higher efficiency for photon detection in high-frequency applications. In this work, an electronic interface, based on the pole-zero compensation technique for reducing dead time, was investigated. A nanosecond pulse generator was designed and fabricated to generate pulses of comparable voltage to an avalanche transistor. The quenching time constant (τq) is not affected by the compensation capacitance variation, while an increase of about 30% in the τq is related to the properties of the specific op-amp used in the design. Conversely, the recovery time was observed to be strongly influenced by the compensation capacitance. Reductions in the recovery time, from 927.3 ns down to 57.6 ns and 9.8 ns, were observed when varying the compensation capacitance in the range of 5-0.1 pF. The experimental results from an SPAD combined with an electronic interface based on an avalanche transistor are in strong accordance, providing similar output pulses to those of an illuminated SPAD.

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Digital histogram generation for time-resolved measurements with single-photon avalanche diode (SPAD) sensors requires the storage of many timestamp signals. This work presents a mixed-signal time-to-digital converter (TDC) that uses analog storage to achieve an area-efficient design that can be integrated in large SPAD arrays. Fabricated using a 150 nm CMOS process, the prototype occupies an area of only 18.3 µm × 36.5 µm, a notable size reduction compared to conventional designs. The experimental results demonstrated high performance, with an integral nonlinearity (INL) of 0.35/0.14 least significant bit (LSB) and a differential nonlinearity (DNL) of 0.14/-0.12 LSB. In addition, the proposed TDC can support the construction of histograms comprising up to 512 bins, making it an effective solution to accommodate a wide range of resolution requirements. Validated in a point-of-care (PoC) device for fluorescence lifetime measurements, it distinguished between lifetimes of approximately 4.1 ns, 3.6 ns and 80 ns with the Alexa Fluor (AF) 546 and 568 dyes and Quantum Dot (QD) 705, respectively. The analog storage design and area-efficient architecture offer a novel approach to integrating TDCs in SPAD-based systems, with potential applications in medical diagnostics and beyond.

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BACKGROUND: Myocardial perfusion imaging (MPI) with single photon emission computed tomography is an established non-invasive technique for assessing myocardial ischemia. This method involves the intravenous administration of a radiopharmaceutical that accumulates in the heart muscle proportional to regional blood flow. However, image quality and diagnostic accuracy can be compromised by various technical and patient-related factors, including high non-specific radiopharmaceutical uptake in abdominal organs such as the stomach, intestines, liver, and gall-bladder, leading to subdiaphragmatic artifacts. These artifacts are particularly problematic for evaluating inferior wall perfusion and often necessitate repeated imaging, which decreases gamma camera availability and prolongs imaging times. CONCLUSIONS: Despite numerous investigated techniques to reduce interfering gastrointestinal activity, results have been inconsistent, and current MPI guidelines provide scant information on effective procedures to mitigate this issue. Based on our experience, some possible approaches to reducing artifacts include choosing stress testing with an exercise stress test, when possible, late imaging, fluid intake, and consuming carbonated water immediately before imaging.

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The aim of this study is to estimate eye lens exposure dose when handling radiopharmaceuticals and interacting with patients receiving radiopharmaceuticals, and to verify the usefulness of X-ray protective goggles in mitigating such radiation exposure using phantoms. To evaluate radiation exposure during the handling of radiopharmaceuticals, we employed a fluorescent glass dosimeter to measure the radiation doses associated with 99mTc, 123I, 131I, 111In, and 18F at distances of 30 cm and 60 cm, followed by calculation of the 3 mm dose equivalent rate (3DER). We then estimated the dose reduction rates for various scenarios, including the use of syringe shields and X-ray protective goggles with lead equivalences of 0.07, 0.15, 0.75, and 0.88 mmPb, as well as their combined application. X-ray protective goggles with lead equivalence of 0.75 mmPb outperformed those with 0.07 mmPb and 0.15 mmPb, for all radionuclides and at both source distances. X-ray protective goggles with 0.88 mmPb outperformed those with 0.75 mmPb during handling of 131I and 111In at a distance of 30 cm. In the remaining scenarios, X-ray protective goggles with 0.88 mmPb resulted in marginal reductions or no discernible additional effects. The overall shielding effect of X-ray protective goggles was less pronounced for 131I and 18F, but the combined use of a syringe shield with X-ray protective goggles with 0.75 or 0.88 mmPb improved the dose reduction rate for all scenarios. In simulating patient care, X-ray protective goggles with 0.88 mmPb demonstrated a dose reduction effect of approximately 50% or more. X-ray protective goggles could reduce the 3DER for the eye lens, and were more effective when combined with a syringe shield. It is valid to use a lead equivalence of 0.88 mmPb to fully harness the protective capabilities of X-ray shielding goggles when dealing with all five types of nuclides in clinical settings.

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Introduction: Nociplastic pain (NP), classified as a third type of pain alongside nociceptive and neuropathic pain, is chronic pain arising from the amplification of nociceptive stimuli through central sensitization, despite the absence of tissue damage, sensory nerve damage, or disease. An important clinical feature of NP is that it is not only associated with pain but also with sensory hypersensitivity to sound and light and cognitive dysfunction, including mood and attention disorders. Recent studies have suggested that depression and developmental disorders, such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), coexist with NP at high frequency. Additionally, cognitive impairment in individuals with NP may be associated with these psychiatric comorbidities. However, to our knowledge, there are no reports on (1) multidimensional evaluation and diagnostic details of abdominal NP in adults with ADHD/ASD; (2) how ADHD drugs and antidepressants are administered when ADHD and depression coexist with NP; and (3) how central sensitization, brain function, and family relationship problems underlying NP are altered by treatments of ADHD and depression. Case presentation: Herein, we present the case of a 51-year-old woman with abdominal NP. She developed severe right lower abdominal pain and underwent a thorough medical examination; however, the physical, medical cause remained unknown, making treatment challenging. Additionally, she took time off work as she began to complain of insomnia and anxiety. She was referred to our pain center, where a diagnosis of depression, ADHD, and ASD was confirmed, and treatment with ADHD medication was initiated. While ADHD medications alone did not yield sufficient improvement, a combination of methylphenidate and the antidepressant venlafaxine eventually led to improvements in abdominal NP, depression, ADHD symptoms, central sensitization, and family relationship issues. During treatment, cerebral blood flow in the anterior cingulate, prefrontal, and parietal cortices also improved. Conclusion: The treatment of comorbid depression is important while treating NP, and venlafaxine may be effective, especially in cases of comorbid ADHD/ASD. Screening for developmental disorders and depression is required in patients with abdominal NP.

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BACKGROUND: Kidney transplantation provides substantial benefits in extending survival and improving quality of life for patients with end-stage renal disease. The incidence of major adverse cardiac events (MACE) increases with a decline of kidney function in patients with chronic kidney disease. After kidney transplantation, the incidence of MACE remains high. The objective of this study was to assess the prognostic significance of pre-transplant single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in kidney transplant recipients. METHODS: A systematic literature search was performed between January 1st 2015 and March 26th 2024 in PubMed, EMBASE, Web of Science and The Cochrane Library to identify the prognostic value of SPECT MPI for developing MACE (primary outcome) and mortality (secondary outcome) in kidney transplant recipients (PROSPERO CRD42020188610). Risk of bias was assessed. Meta-analyses and subgroup analyses were performed using random-effects models. RESULTS: Six studies comprising 2090 SPECT MPI scans were included. Abnormal SPECT MPI scans were associated with an increased risk of MACE post-transplantation (HR 1.62, 95% CI 1.27-2.06, p < 0.001). Subgroup analyses showed consistent findings across various patient populations and methodological differences. Sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Current evidence showed that pre-transplant SPECT MPI has significant prognostic value in identifying kidney transplant candidates at risk for MACE post-transplantation. Integrating SPECT MPI into preoperative assessments might enhance risk stratification and guide clinical decision-making. Prospective studies are needed to refine risk prediction models.

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BACKGROUND: Positron emission tomography (PET) is an important tool for assessing coronary artery disease (CAD), but its widespread utilization is limited due to various factors, including limited local champion availability. This study aims to compare the frequency of PET procedures and their interpreters with other common CAD assessment modalities. METHODS: Using Medicare data, we examined the number of cardiac PET procedures billed and compared them with single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA), stress magnetic resonance imaging (MRI), and stress echocardiography. Healthcare Common Procedure Coding System codes were used to identify procedures. We calculated the total number of PET myocardial perfusion imaging (MPI) procedures, the proportion of PET/CT and myocardial blood flow (MBF) assessments, and the median number of studies read per physician. We also analyzed the trends in the use of different CAD assessment modalities between 2018 and 2022. Descriptive statistics summarized the data. RESULTS: In 2022, Medicare billed for 212,106 PET MPI scans. SPECT was six times more frequent (1,343,519), whereas stress echocardiography (201,676) and CCTA (118,734) had similar or lower use. Stress MRI (3,932) was least used. Of the PET MPI scans, 46% were PET/CT, and 39% included MBF measurements. Cardiologists interpreted 86% of PET scans, with a median of 58 studies per reader; 23% interpreted ≤25 studies annually. SPECT had a median of 63 studies per reader, and CCTA, stress MRI, and stress echocardiography had medians of 27, 20, and 24, respectively. PET, CT, and MRI use increased from 2018 to 2022, whereas SPECT and stress echocardiography declined. CONCLUSION: In the Medicare population, radionuclide perfusion imaging (SPECT and PET) remained the preferred method for assessment of CAD, with SPECT being the most frequently used modality and PET being the second most frequently used modality for this application. However, PET/CT and MBF are underutilized, limiting diagnostic and prognostic capabilities. Efforts to enhance education and awareness of PET's advantages and to address barriers to its wider adoption are essential to maximize its clinical benefits and improve patient outcomes.

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Surface enhanced fluorescence (SEF) based on noble metal nanoparticles is an effective means to achieve high sensitivity in fluorescence detection. Currently, the physical mechanism behind enhanced fluorescence is not fully understood. This paper measures the fluorescence signals of Dihydroporphyrin f methyl ether (CPD4) under both single-photon and two-photon excitation based on submicrometer silver particles with rough morphologies, achieving enhancement factors of 34 and 45 times, respectively. On this basis, by combining the radiative field characteristics produced by the silver particles, a stimulated radiation model of molecules is established to elucidate the changes in the molecular photophysical process when influenced by silver particles. Moreover, the fluorescence lifetime of the molecules was measured, showing that the presence of silver particles induces an increase in the molecular radiative decay rate, causing the fluorescence lifetime to decay from 3.8 ns to 3 ns. The results indicate that the fluorescence enhancement primarily originates from the submicrometer silver particles' enhancement effect on the excitation light. Additionally, the fluorescence signal emitted by the molecules couples with the silver particles, causing the local surface plasmon resonances generated by the silver particles to also emit light signals of the same frequency. Under the combined effect, the fluorescence of the molecules is significantly enhanced. The findings provide a theoretical foundation for understanding the fluorescence enhancement mechanism of silver particles, adjusting the enhancement effect, and developing enhanced fluorescence detection devices based on submicrometer silver particles, holding significant practical importance.

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Angiotensin-converting enzymes (ACE) are well-known for their roles in both blood pressure regulation via the renin-angiotensin system as well as functions in fertility, immunity, hematopoiesis, and many others. The two main isoforms of ACE include ACE and ACE-2 (ACE2). Both isoforms have similar structures and mediate numerous effects on the cardiovascular system. Most remarkably, ACE2 serves as an entry receptor for SARS-CoV-2. Understanding the interaction between the virus and ACE2 is vital to combating the disease and preventing a similar pandemic in the future. Noninvasive imaging techniques such as positron emission tomography and single photon emission computed tomography could noninvasively and quantitatively assess in vivo ACE2 expression levels. ACE2-targeted imaging can be used as a valuable tool to better understand the mechanism of the infection process and the potential roles of ACE2 in homeostasis and related diseases. Together, this information can aid in the identification of potential therapeutic drugs for infectious diseases, cancer, and many ACE2-related diseases. The present review summarized the state-of-the-art radiotracers for ACE2 imaging, including their chemical design, pharmacological properties, radiochemistry, as well as preclinical and human molecular imaging findings. We also discussed the advantages and limitations of the currently developed ACE2-specific radiotracers.

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BACKGROUND: Patients with low HEART (History, Electrocardiogram, Age, Risk factors, and Troponin level) risk scores who are discharged from the emergency department (ED) may present clinical challenges and diagnostic dilemmas. The use of downstream non-invasive stress imaging (NISI) tests in this population remains uncertain. Therefore, this study aims to investigate the value of NISI in risk stratification and predicting cardiac events in patients with low-risk HEART scores (LRHSs). METHODS: We prospectively included 1384 patients with LRHSs between March 2019 and March 2021. All the patients underwent NISI (involving myocardial perfusion imaging/stress echocardiography). The primary endpoints included cardiac death, non-fatal myocardial infarction and unplanned coronary revascularisation. Secondary endpoints encompassed cardiovascular-related admissions or ED visits. RESULTS: The mean patient age was 64±14 years, with 670 (48.4%) being women. During the 634±104 days of follow-up, 58 (4.2%) patients experienced 62 types of primary endpoints, while 60 (4.3%) developed secondary endpoints. Multivariable Cox models, adjusted for clinical and imaging variables, showed that diabetes (HR: 2.38; p=0.008), HEART score of 3 (HR: 1.32; p=0.01), history of coronary artery disease (HR: 2.75; p=0.003), ECG changes (HR: 5.11; p<0.0001) and abnormal NISI (HR: 16.4; p<0.0001) were primary endpoint predictors, while abnormal NISI was a predictor of secondary endpoints (HR: 3.05; p<0.0001). CONCLUSIONS: NISI significantly predicted primary cardiac events and cardiovascular-related readmissions/ED visits in patients with LRHSs.

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OBJECTIVES: To establish and validate a technetium 99m sestamibi (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) nomogram for predicting non-small cell lung cancer (NSCLC). Comparing the diagnostic performance of early and delayed SPECT/CT nomogram, and compare the diagnostic performance of SPECT/CT radiomics models with single SPECT and CT radiomics models. METHODS: This prospective study included 119 lesions (NSCLC: n = 92, benign pulmonary lesions: n = 27) from 103 patients (mean age: 59.68 ± 8.94 years). Patients underwent dual-phase 99mTc-MIBI SPECT/CT imaging. They were divided into the training (n = 83) and validation (n = 36) cohorts. Logistic regression, support vector machine, random forest, and light-gradient boosting machine were applied to train and determine the optimal machine learning model. Then, combining radiomics score and clinical factors, establish nomograms for diagnosing NSCLC. RESULT: CYFRA21-1 was selected for constructing the clinical model. In early imaging, the areas under the curve (AUCs) of the clinical model, radiomics model, and nomogram were 0.571, 0.830, and 0.875, respectively. The nomogram performed better than the clinical model and similarly to the radiomics model (P=0.020, P=0.216), and there are no statistically significant differences in the predictive performance between the radiomics model and the clinical model (P=0.103). In delayed imaging, the AUC was 0.643, 0.888, and 0.893, respectively. The predictive performance of the nomogram was superior compared to the clinical model and comparable to the radiomics model (P=0.042, P=0.480), and the radiomics model also demonstrated superior diagnostic performance compared to the clinical model (P=0.049). Compared to early SPECT/CT results, the AUC values of the nomogram and radiomics models in the delayed phase were higher, although no statistical differences were found (P=0.831, P=0.568). In delayed imaging, the AUC of the radiomics models for CT and SPECT was 0.696 and 0.768, respectively, SPECT/CT radiomics exhibited significant differences compared with CT and SPECT alone (P=0.042, P=0.038). CONCLUSION: Dual-phase 99mTc-MIBI SPECT/CT nomograms and radiomics models can effectively predict NSCLC, providing an economically and non-invasive imaging method for diagnosing NSCLC, moreover, these findings provide a basis for early diagnosis and treatment strategies in NSCLC patients. Delayed-phase SPECT/CT imaging may offer greater practical value than early-phase imaging for diagnosing NSCLC. However, this novel approach necessitates further validation in larger, multi-center cohorts. CLINICAL RELEVANCE: Radiomics nomogram based on SPECT/CT for discriminating NSCLC from benign lung lesions helps to aid early diagnosis and guide treatment. KEY POINTS: Nomograms, based on dual-phase SPECT/CT, was constructed to discriminate between non-small cell lung cancer and benign lesions. SPECT/CT radiomics model has better predictive performance than SPECT and CT radiomics model.

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Sleep plays an essential role in physiology, allowing the brain and body to restore itself. Despite its critical role, our understanding of the underlying processes in the sleeping human brain is still limited. Sleep comprises several distinct stages with varying depths and temporal compositions. Cerebral blood flow (CBF), which delivers essential nutrients and oxygen to the brain, varies across brain regions throughout these sleep stages, reflecting changes in neuronal function and regulation. This systematic review and meta-analysis assesses global and regional CBF across sleep stages. We included, appraised, and summarized all 38 published sleep studies on CBF in healthy humans that were not or only slightly (<24 h) sleep deprived. Our main findings are that CBF varies with sleep stage and depth, being generally lowest in NREM sleep and highest in REM sleep. These changes appear to stem from sleep stage-specific regional brain activities that serve particular functions, such as alterations in consciousness and emotional processing.

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To address the potential threat to the power grid industry posed by quantum computers and ensure the security of bidirectional communication in smart grids, it is imperative to develop quantum-safe authentication protocols. This paper proposes a semi-quantum bidirectional authentication protocol between a control center (CC) and a neighboring gateway (NG). This method uses single photons to facilitate communication between the CC and the NG. Security analysis demonstrates that the protocol can effectively resist common attack methods, including double CNOT attacks, impersonation attacks, interception-measurement-retransmission attacks, and entanglement-measurement attacks. Comparisons with other protocols reveal that this protocol has significant advantages, making it more appealing and practical for real-world applications. Finally, by simulating the protocol on the IBM quantum simulator, this protocol not only validates the theoretical framework but also confirms the practical feasibility of the protocol.

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Dibenzo[g,p]chrysene can be viewed as a constrained propeller-shaped tetraphenylethylene with reduced curvature and has been utilized to construct dual-pore kagome covalent organic frameworks (COFs) with tightly packed two-dimensional (2D) layers owing to its rigid and more planar structural characteristics. Here, we introduce 2D COFs based on the node 4,4',4″,4‴-(dibenzo[g,p]chrysene-2,7,10,15-tetraphenyl)tetraamine (DBCTPTA) featuring extended conjugation compared to the dibenzo[g,p]chrysene-3,6,11,14-tetraamine (DBCTA) node. We establish two exceptionally crystalline imine-linked 2D COFs with a hexagonal dual-pore kagome structure based on the DBCTPTA core. The newly synthesized thienothiophene (TT) and benzodithiophene (BDT)-based DBCTPTA COFs show a tight stacking behavior between adjacent layers. Furthermore, we obtained an unprecedented, interpenetrated electron-donor/acceptor host-guest system with an electron-donating BDT DBCTPTA COF synthesized in situ with the soluble fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) serving as molecular acceptor. The BDT DBCTPTA COF@PCBM film shows a much shorter amplitude-averaged PL lifetime of 7 ± 2 ps compared to 30 ± 4 ps of the BDT DBCTPTA COF film, indicating the light-induced charge transfer process. The successful in situ formation of interpenetrated donor-acceptor heterojunctions within 2D COFs offers a promising strategy for establishing D-A heterojunctions in diverse framework materials with open channel systems.

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A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using 99mTc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection. This first-in-human study aimed to evaluate the safety and distribution of [99mTc]Tc(CO)3-(HE)3-Ec1 in patients with primary lung cancer. Twelve lung cancer patients were injected with 300.7 ± 103.2 MBq of [99mTc]Tc(CO)3-(HE)3-Ec1. Whole-body planar imaging (at 2, 4, 6 and 24 h after injection) and SPECT/CT of the lung (at 2, 4, and 6 h) were performed. The patients' vital signs and possible side effects were monitored up to 7 days after injection. The patients tolerated the injection of [99mTc]Tc(CO)3-(HE)3-Ec1 well, and their somatic condition remained normal during the entire follow-up period. There were no abnormalities in blood and urine tests after injection of [99mTc]Tc(CO)3-(HE)3-Ec1. The highest absorbed doses were in the kidneys, liver, pancreas, thyroid, gallbladder wall, and adrenals. There was also a relatively high accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 was also noted in regional metastases. [99mTc]Tc(CO)3-(HE)3-Ec1 can potentially be considered a diagnostic tracer for imaging EpCAM expression in lung cancer patients and other tumors with overexpression of EpCAM.