Simplified Assessment of Radioiodine Biokinetics for Thyroid Cancer Patients: A Practical Approach Using Continuous External Radiation Monitoring.

INTRODUCTION: The biokinetics of radioiodine (RAI) in thyroid cancer patients are complex. This study aims to develop a practical approach for assessing RAI biokinetics to predict patient discharge time and estimate radiation exposure to caregivers. METHODS: We retrospectively reviewed data from patients with differentiated thyroid carcinoma undergoing RAI treatment. Serial radiation dose rates were dynamically collected during hospitalization and fitted to a biexponential model to assess the biokinetic features: RAI uptake fraction of thyroid tissue (Ft) and effective half-life of extra-thyroid tissue (Tet). Correlations with 99mTc thyroid uptake ratio (TcUR), radiation retention ratio (RR), renal function, and body mass index (BMI) were analyzed. RESULTS: Thirty-five patients were enrolled. The derived Ft was 0.08 ± 0.06 and Tet was 7.57 ± 1.45 h. Pearson's correlation analysis revealed a significant association between Ft and both TcUR and RR (p < 0.05), while Tet correlated with renal function and BMI (p < 0.05). CONCLUSION: This novel and practical method assessing RAI biokinetics demonstrates consistency with other parameters and related studies, enhancing the model reliability. It shows promise in predicting an appropriate discharge time and estimating radiation exposure to caregivers, allowing for modifications to radiation protection precautions to follow ALARA principle and minimize the potential risks from radiation exposure.

Testicular Primary Well-Differentiated Neuroendocrine Tumor: Clinicopathologic, Immunohistochemical, and Molecular Characterization of Two Patients.

Well-differentiated neuroendocrine tumor rarely occurs as a testicular primary tumor, accounting for less than 1% of all testicular cancers, and is rarely reported with sufficient molecular profiles. After searching our departmental database (2003-2023), two testicular primary well-differentiated neuroendocrine tumors were identified in a 35-year-old man and a 23-year-old man, respectively, both of whom had normal serum level of tumor markers. Both tumors grossly exhibited solid, yellow-tan, and homogeneous appearance and histologically displayed a mixture of growth patterns, including organoid, tubular, cribriform, nests, cords, and single cells, were composed of eosinophilic tumor cells with salt-and-pepper chromatin and indistinct cell borders. Immunoreactivity for chromogranin and synaptophysin were detected, with Ki-67 labeling 9% and 2% of tumor cells on counting of 500 tumor cells, respectively. There was no germ cell neoplasia in situ in the background testicular parenchyma. Furthermore, fluorescence in situ hybridization failed to identify the presence of isochromosome 12p in both tumors. A panel-based next-generation sequencing was done in one of tumors and showed no reportable pathogenic variants with a mutation burden of 0.5 mutations per megabase. Although elevated mitotic figures (up to 6 per 10 high power fields), lymphovascular invasion and marked nuclear pleomorphism were present in this tumor, there was no evidence of disease detected in this patient via Dotatate positron emission tomography/computed tomography scan after the surgery. This report expands the spectrum of testicular primary well-differentiated neuroendocrine tumor. Considering its rarity, it may pose a diagnostic challenge or pitfall in certain clinical circumstances. In addition, the literature pertaining to this entity is herein reviewed.

Multi-scale statistical deformation based co-registration of prostate MRI and post-surgical whole mount histopathology.

BACKGROUND: Accurate delineations of regions of interest (ROIs) on multi-parametric magnetic resonance imaging (mpMRI) are crucial for development of automated, machine learning-based prostate cancer (PCa) detection and segmentation models. However, manual ROI delineations are labor-intensive and susceptible to inter-reader variability. Histopathology images from radical prostatectomy (RP) represent the "gold standard" in terms of the delineation of disease extents, for example, PCa, prostatitis, and benign prostatic hyperplasia (BPH). Co-registering digitized histopathology images onto pre-operative mpMRI enables automated mapping of the ground truth disease extents onto mpMRI, thus enabling the development of machine learning tools for PCa detection and risk stratification. Still, MRI-histopathology co-registration is challenging due to various artifacts and large deformation between in vivo MRI and ex vivo whole-mount histopathology images (WMHs). Furthermore, the artifacts on WMHs, such as tissue loss, may introduce unrealistic deformation during co-registration. PURPOSE: This study presents a new registration pipeline, MSERgSDM, a multi-scale feature-based registration (MSERg) with a statistical deformation (SDM) constraint, which aims to improve accuracy of MRI-histopathology co-registration. METHODS: In this study, we collected 85 pairs of MRI and WMHs from 48 patients across three cohorts. Cohort 1 (D1), comprised of a unique set of 3D printed mold data from six patients, facilitated the generation of ground truth deformations between ex vivo WMHs and in vivo MRI. The other two clinically acquired cohorts (D2 and D3) included 42 patients. Affine and nonrigid registrations were employed to minimize the deformation between ex vivo WMH and ex vivo T2-weighted MRI (T2WI) in D1. Subsequently, ground truth deformation between in vivo T2WI and ex vivo WMH was approximated as the deformation between in vivo T2WI and ex vivo T2WI. In D2 and D3, the prostate anatomical annotations, for example, tumor and urethra, were made by a pathologist and a radiologist in collaboration. These annotations included ROI boundary contours and landmark points. Before applying the registration, manual corrections were made for flipping and rotation of WMHs. MSERgSDM comprises two main components: (1) multi-scale representation construction, and (2) SDM construction. For the SDM construction, we collected N = 200 reasonable deformation fields generated using MSERg, verified through visual inspection. Three additional methods, including intensity-based registration, ProsRegNet, and MSERg, were also employed for comparison against MSERgSDM. RESULTS: Our results suggest that MSERgSDM performed comparably to the ground truth (p > 0.05). Additionally, MSERgSDM (ROI Dice ratio = 0.61, landmark distance = 3.26 mm) exhibited significant improvement over MSERg (ROI Dice ratio = 0.59, landmark distance = 3.69 mm) and ProsRegNet (ROI Dice ratio = 0.56, landmark distance = 4.00 mm) in local alignment. CONCLUSIONS: This study presents a novel registration method, MSERgSDM, for mapping ex vivo WMH onto in vivo prostate MRI. Our preliminary results demonstrate that MSERgSDM can serve as a valuable tool to map ground truth disease annotations from histopathology images onto MRI, thereby assisting in the development of machine learning models for PCa detection on MRI.

Immune Response Related to Lymphadenopathy Post COVID-19 Vaccination.

Mass vaccination against coronavirus disease 2019 (COVID-19) is a global health strategy to control the COVID-19 pandemic. With the increasing number of vaccinations, COVID-19 vaccine-associated lymphadenopathy (C19-VAL) has been frequently reported. Current findings emphasize the characteristics of C19-VAL. The mechanism of C19-VAL is complicated to explore. Accumulated reports separately show that C19-VAL incidence is associated with receiver age and gender, reactive change within lymph nodes (LN), etc. We constructed a systematic review to evaluate the associated elements of C19-VAL and provide the mechanism of C19-VAL. Articles were searched from PubMed, Web of Science and EMBASE by using the processing of PRISMA. The search terms included combinations of the COVID-19 vaccine, COVID-19 vaccination and lymphadenopathy. Finally, sixty-two articles have been included in this study. Our results show that days post-vaccination and B cell germinal center response are negatively correlated with C19-VAL incidence. The reactive change within LN is highly related to C19-VAL development. The study results suggested that strong vaccine immune response may contribute to the C19-VAL development and perhaps through the B cell germinal center response post vaccination. From the perspective of imaging interpretation, it is important to carefully distinguish reactive lymph nodes from metastatic lymph node enlargement through medical history collection or evaluation, especially in patients with underlying malignancy.

Reversing "Flip-Flop" Phenomenon of 131 I and Glucose Avidity in RET-Fusion Positive Radioiodine-Refractory Thyroid Cancer Lesions After Treatment of Pralsetinib.

ABSTRACT: A 61-year-old man presented with papillary thyroid cancer in radioiodine-refractory status after high-activity 131 I treatments following thyroidectomy. FDG-avid neck and pulmonary metastases but without 131 I-uptake were detected. CCDC6-RET fusion was identified from the tumor lesion. He was treated with pralsetinib, a RET inhibitor, followed by another high-activity 131 I therapy. Posttherapeutic scan displayed restoration of 131 I avidity at those lesions only shown on previous FDG PET/CT. Reduced FDG avidity of those lesions and decreased serum antithyroglobulin antibody titer were also noticed. This case illustrated successfully reinduced 131 I avidity in papillary thyroid cancer through redifferentiation with target therapy to suppress tumor RET overexpression.

Utilizing Proteomic Approach to Analyze Potential Antioxidant Proteins in Plant against Irradiation.

Gamma-ray irradiation is an effective and clean method of sterilization by inactivating microorganisms. It can also be applied to induce anti-oxidants for future application. In this study, the mung bean (Vigna radiata) was exposed to gamma-ray irradiation under the dose of 0, 5 or 10 kGy. With increasing irradiation doses, the concentrations of malondiadehyde decreased while the levels of total flavonoids and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity increased. It has been shown that consuming flavonoids can provide protective effects. In addition, proteomic analysis identified several proteins having anti-oxidant activities in the 5 kGy irradiated group. These proteins are Apocytochrome f, Systemin receptor SR 160, DELLA protein DWARF8, DEAD-box ATP-dependent RNA helicase 9, ζ-carotene desaturase (ZDS), and Floral homeotic protein AGAMOUS. Our findings indicate that plants contain a variety of phytochemicals and antioxidant proteins which may effectively prevent oxidative stress caused by irradiated peroxidation.

Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI).

Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.

A Rare Adverse Effect of the COVID-19 Vaccine on Autoimmune Encephalitis.

Since countries commenced COVID-19 vaccination around the world, many vaccine-related adverse effects have been reported. Among them, short-term memory loss with autoimmune encephalitis (AE) was reported as a rare adverse effect. Since case numbers are limited, this brief report may draw the attention of the medical community to this uncommon adverse effect and serve as a reference for future vaccine improvement. However, given the high risk of adverse outcomes when infected with SARS-CoV-2 and the clearly favorable safety/tolerability profile of existing vaccines, vaccination is still recommended.

The Effects of Prior Mammography Screening on the Performance of Breast Cancer Detection in Taiwan.

The aim of this study was to investigate the influence of previous mammography screening on the performance of breast cancer detection. The screened women were divided into first-visit and follow-up groups for breast cancer screening. The positive predictive value (PPV), cancer detection rate (CDR), and recall rate were used to evaluate and analyze the overall screening performance among the two groups. Among them, 10,040 screenings (67.2%) were first visits and 4895 screenings (32.8%) were follow-up visits. The proportion of positive screening results for first-visit participants was higher than that for their follow-up counterparts (9.3% vs. 4.0%). A total of 98 participants (74 first-visit and 24 follow-up visit) were confirmed to have breast cancer. The PPV for positive mammography for women who underwent biopsy confirmation was 28.7% overall, reaching 35.8% for the follow-up visit group and 27.0% for the first-visit group. The CDR was 6.6 per 1000 overall, reaching 7.4 per 1000 for first-visit group and 4.9 per 1000 for the follow-up group. The overall recall rate was 7.9%, reaching 9.7% for the first-visit group and 4.2% for the follow-up group. The PPV is improved and the recall rate is decreased if prior mammography images are available for comparison when conducting mammography screening for breast cancer. By this study, we concluded that prior mammography plays an important role for breast cancer screening, while follow-up mammography may increase the diagnostic rate when compared to the prior mammography. We suggest that the public health authority can encourage subjects to undergo screenings in the same health institute where they regularly visit.

Specifically Regional Cerebral Hypoperfusion in a Case of Highly Suspected Sporadic Creutzfeldt-Jakob Disease on 99mTc-ECD SPECT/CT with Easy Z-Score Imaging System Analysis.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rapidly-progressive dementing illness, the challenge of diagnosis during life. We presented a 78-year-old woman reported stupor, right facial palsy, and fluctuations in consciousness. 99mTc-ECD brain SPECT/CT with eZIS analysis revealed significant decreased regional cerebral blood flow mainly in specific regions of Alzheimer's disease as the published article reported with involving frontal region. Brain DWI MRI increased signal intensities corresponding to similar location of 99mTc-ECD brain SPECT/CT. In this case, we reported the pattern of decreased rCBF may correlate to rapidly progressive dementia and associated neurodegenerative symptoms of the highly suspected sCJD patient.

Incidental Finding of Moderna COVID-19 Vaccination-Related Axillary Lymphadenopathy on 201Tl Myocardial Perfusion Imaging.

ABSTRACT: We presented here a 71-year-old man with a history of thyroid cancer post total thyroidectomy and 131I ablation and right renal cell carcinoma post right partial nephrectomy. He reported persistent chest tightness and pain after the first dose of the Moderna COVID-19 (mRNA-1273) vaccine. Thus, coronary heart disease was suspected, and the patient was referred for MPI (myocardial perfusion imaging). Focal 201Tl uptake in the left axillary region was found incidentally on MPI, and SPECT/CT revealed enlarged benign-looking lymph nodes. The diagnostic is in favor of reactive hyperplasia after the intramuscular injection of vaccine into left deltoid muscle.

Presence of Specific Periodontal Pathogens in Prostate Gland Diagnosed With Chronic Inflammation and Adenocarcinoma.

Background Intraprostatic inflammation is frequently observed in the prostate and linked to prostatic diseases, including prostatitis, benign prostatic hyperplasia (BPH), and cancer. The etiology of prostate diseases is unclear. Periodontal diseases are associated with an increased risk of prostate diseases. In men, chronic prostatitis and moderate/severe periodontitis have significantly elevated serum prostate-specific antigen (PSA) levels. Treatment of periodontal disease reduced PSA levels in men. The presence of periodontal pathogens deoxyribonucleic acid (DNA) was identified in the prostate fluid of prostatitis patients. These pathogenic bacteria might have the potential to trigger prostatitis progressing to prostatic adenocarcinoma. The mechanism(s) explaining the etiology of association between periodontal disease and prostate cancer remains unclear. However, the presence of periodontal pathogens has not been analyzed in the prostate gland. Objective To identify and compare the presence of specific periodontal pathogens in the areas of BPH, inflammation, and cancer of the prostate glands diagnosed with malignancy. Materials and methods Whole-mount radical prostatectomy sections from men (n=30) were identified for BPH, inflammation, and cancer areas and marked for tissue procurement. The tissues were subjected to DNA isolation and analysis of microbial DNA and total bacterial load for the following pathogens, including Porphyromonas gingivalis strain ATCC 33277, Prevotella intermedia strain B422, Treponema denticola strain 35405, Fusobacterium nucleatum subsp. fusiform strain, Tannerella forsythia strain ATCC 43037, and Campylobacter​​​​​​​ rectus strain ATCC 33238performed real-time PCR. The universal bacterial primer pairs were used to detect genomic DNA (gDNA) from the total bacteria present in the samples. All species-specific primers were designed to target the variable regions of the 16S ribosomal RNA (rRNA). Data were analyzed using the 2-ΔΔCT method, statistically validated using unpaired t-test and ANOVA test. Results A total of 90 samples of prostate tissue specimens were analyzed for periodontal pathogens; only one pathogen (F. nucleatum subsp. fusiform strain ATCC 51190) showed a significant difference compared to the expression of S. epidermidis (internal control). In particular, F. nucleatum expression was 9, 11.9, and 10.3-fold higher in BPH, inflammation, and cancer, respectively, at p-value <0.05. Moreover, the bacterial load abundance/expression was almost similar in BPH (46.8-fold), inflammation (40.9 fold), and cancer (41.5 fold) higher. There was no significant difference in bacterial load (folder change) among the three areas of BPH, inflammation, and cancer (p-valve>0.05). Similarly, there was no significant difference between F. nucleatum (folder change) among the three areas (p-valve>0.05). Conclusion  Fusobacterium nucleatum is identified in the prostates that harbor cancer, chronic inflammation, and BPH.

Comprehensive review of the incisive branch of the inferior alveolar nerve.

The incisive branch of the inferior alveolar nerve is a vital anatomical structure within the anterior mandible that has not been thoroughly defined and outlined in reports in the literature until recent years. Advances in radiological imaging, particularly the widespread use of cone-beam computed tomography has allowed for accurate visualization of the mandibular incisive canal (MIC) and its associated incisive branch of the inferior alveolar nerve. Surgical damage to the MIC, which could result in hemorrhage and sensory disturbance, may occur in commonly practiced oral and maxillofacial procedures, such as chin bone harvesting, implant placement, fracture repair and removal of pathologic entities of the anterior mandible. Knowledge of both the presence, dimensions and location of the incisive branch is a vital component to pre and peri-operative planning of oral and maxillofacial surgeries performed within the mandible, particularly within the interforaminal zone. In this article, the terminology, anatomy, imaging, surgical consideration, and pathology of the incisive branch will be discussed.

Radioactive Iodine Treatment and the Risk of Long-Term Cardiovascular Morbidity and Mortality in Thyroid Cancer Patients: A Nationwide Cohort Study.

(1) Background: This study aimed to investigate the association between radioactive iodine (RAI) and long-term cardiovascular disease (CVD) morbidity/mortality in thyroid cancer. (2) Methods: The study was conducted using data from the Taiwan National Health Insurance Database during 2000-2015. Thyroid cancer patients aged ≥20 years were categorized into RAI (thyroidectomy with RAI) and non-RAI (thyroidectomy only) groups. The Cox proportional hazard regression model and Kaplan-Meier method were used for analysis. (3) Results: A total of 13,310 patients were included. Kaplan-Meier analysis demonstrated that the two groups had similar cumulative risks of CVD (log-rank p = 0.72) and CVD-specific mortality (log-rank p = 0.62). On Cox regression analysis of different RAI doses, the risk of CVD was higher in the cumulative dosage >3.7 GBq (hazard ratio = 1.69, 95% confidence interval = 1.24-2.40, p < 0.001). (4) Conclusions: RAI was not associated with an increased risk of CVD in thyroid cancer. However, CVD surveillance is indicated in the patients receiving the cumulative RAI dosage above 3.7 GBq.

Clinical anatomy of the inferior labial gland: a narrative review.

OBJECTIVE: In this article we review the literature on the inferior labial gland from a clinical and anatomical perspective. BACKGROUND: Regardless of its importance in clinical practice, there are no medical literature that comprehensively reviewed the inferior labial gland. METHODS: A database search using PubMed and Google Scholar was conducted. The following keywords were used in the search: "lower labial salivary gland", "lower labial gland", "inferior labial salivary gland", AND "inferior labial gland". CONCLUSIONS: The human labial glands are types of minor salivary gland that continuously secrete small amounts of mucous and serous substances to maintain oral health. The inferior labial glands are innervated by the inferior labial branch of the mental nerve, and the inferior labial branch of the facial artery is the main arterial supply to the lower lip. Although they only have an auxiliary role in saliva production compared to the major salivary glands, minor salivary glands provide a certain amount of lubrication in the oral cavity by the continuous outflow of saliva. The inferior labial gland not only promotes moisturization in the oral cavity but also secretes substances with antibacterial effects, which is important for the function of the oral cavity. A recent study showed that the rate of salivary secretion from the inferior labial glands does not change with age, and in some cases the inferior labial glands are used for diagnosing intractable diseases such as Sjogren's syndrome and cystic fibrosis. In addition, since the inferior labial glands themselves can be the site of cyst and/or neoplasia development, we should be careful to distinguish them from other diseases. Elucidation of the anatomy, physiology, and pathology of the inferior labial glands, is important for understanding human health and diseases.

Prognostic Value of 18F-FDG PET/CT Volume-Based Metabolic Parameters in Patients with Node-Negative Stage II Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a major cancer prevalent in Asian males. Pretreatment tumor burden can be prognostic for ESCC. We studied the prognostic value of metabolic parameters of 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the serum squamous cell carcinoma antigen (SCC-Ag) level in node-negative stage II ESCC patients. Eighteen males underwent staging evaluation were included. The volume-based metabolic parameters derived from 18F-FDG PET/CT, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were obtained using the PET Volume Computer Assisted Reading application. The Spearman correlation coefficients were calculated to assess the relationship between metabolic parameters and pretreatment serum SCC-Ag levels. Based on the 5-year follow-up, patients were sub-divided into the demised and the stable groups. Potential prognostic value was assessed by independent t-test and the Mann-Whitney U test. The association of overall survival was assessed using univariate and multivariate Cox regression analyses. The demised group showed significant higher values in serum SCC-Ag, as well as in MTV and TLG, but not SUVmax and SUVmean. The SUVmax, MTV, TLG, and serum SCC-Ag showed significant association with overall survival. Our findings suggest potential usage of pretreatment volume-based metabolic parameters of 18F-FDG PET/CT and serum SCC-Ag as prognostic factors for node-negative stage II ESCC patients.

A rare case of trifid mandibular canal with bilateral retromolar foramina.

There are many reported anatomical variations of the mandibular canal. Consequently, there is great variation in the retromolar area, such as the quantity, size, and location of the retromolar foramen (RMF), the bony entrance of the retromolar canal (RMC). These variations allow for different accessory innervations to the mandibular molars and their adjacent buccal tissue because the RMC contains neurovascular bundles. Consideration of these anatomical variations is crucial for avoiding complications in anesthesia, implant placement, and surgery. However, the rarer canal types are often only imaged by computed tomography (CT) or cone beam computed tomography (CBCT). We present a rare case with bilateral RMF and a unilateral trifid mandibular canal in a cadaver.

Integrative Circuit-Host Modeling of a Genetic Switch in Varying Environments.

Synthetic biology is advancing into a new phase where real-world applications are emphasized. There is hence an urgent need for mathematical modeling that can quantitatively describe the behaviors of genetic devices in natural, fluctuating environments. We utilize an integrative circuit-host modeling framework to examine the dynamics of a genetic switch and its host cell in varying environments. For both steady-state and transient cases, we find increasing nutrient reduces the bistability region of the phase space and eventually drives the switch from bistability to monostability. In response, cellular growth and proteome partitioning experience the same transition. Antibiotic perturbations cause the similar circuit and host responses as nutrient variations. However, one difference is the trend of growth rate, which augments with nutrient but declines with antibiotic levels. The framework provides a mechanistic scheme to account for both the dynamic and static characteristics of the circuit-host system upon environmental perturbations, underscoring the intimacy of gene circuits and their hosts and elucidating the complexity of circuit behaviors arising from environmental variations.

Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases.

OBJECTIVES: To report methods and findings of 2 autopsies with molecular evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals. METHODS: Postmortem examination was completed following Centers for Disease Control and Prevention public guidelines. Numerous formalin-fixed paraffin-embedded (FFPE) tissue types from each case were surveyed for SARS-CoV-2 RNA by quantitative reverse transcription polymerase chain reaction (qRT-PCR). SARS-CoV-2 viral genome was sequenced by next-generation sequencing (NGS) from FFPE lung tissue blocks. RESULTS: Postmortem examinations revealed diffuse alveolar damage, while no viral-associated hepatic, cardiac, or renal damage was observed. Viral RNA was detected in lungs, bronchi, lymph nodes, and spleen in both cases using qRT-PCR method. RNA sequencing using NGS in case 1 revealed mutations most consistent with Western European Clade A2a with ORF1a L3606F mutation. CONCLUSIONS: SARS-CoV-2 testing and viral sequencing can be performed from FFPE tissue. Detection and sequencing of SARS-CoV-2 in combination with morphological findings from postmortem tissue examination can aid in gaining a better understanding of the virus's pathophysiologic effects on human health.

Optimal usage of radium-223 in metastatic castration-resistant prostate cancer.

Radium-223 is a first-in-class α-emitting radiopharmaceutical that targets bone metastases associated with metastatic castration-resistant prostate cancer (mCRPC). In the pivotal phase III trial ALSYMPCA, radium-223 significantly increased overall survival (OS), compared with placebo (median 14.9 vs 11.3 months; hazard ratio 0.70; 95% CI 0.58-0.83; p < 0.001), in patients with mCRPC and symptomatic bone metastases-with a comparable safety profile. To optimize treatment outcomes, selection of appropriate patients is important. As well as osteoblastic bone metastases, mCRPC patients should be well enough to receive six doses of radium-223 as this treatment duration has been shown to greatly improve OS outcomes compared with administration of four or fewer doses. Additionally, alkaline phosphatase and lactate dehydrogenase are emerging as important biomarkers during radium-223 treatment. Optimal concomitant standard-of-care therapies (such as abiraterone or enzalutamide) to be administered with radium-223 have yet to be defined as does the most efficacious dose and duration of radium-223 treatment. In conclusion, radium-223 is an important addition to the mCRPC treatment landscape and marks a paradigm shift in the treatment of bone metastases.