Outcomes of Differentiated Thyroid Cancer in Children and Adolescents at King Abdulaziz Medical City, Jeddah.

Objective Differentiated thyroid cancer (DTC) is rare in the pediatric population, with most data from the Western world. We aimed to describe the clinical presentation, treatment intervention, histopathological characteristics, complications, follow-up, and response to treatment in 17 patients with DTC at or below the age of 20 years. Interventions This was a retrospective cohort study at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included patients aged younger than 20 years with DTC. Total or near-total thyroidectomy was performed in 82% of the patients, central and/or lateral neck dissection in 35% of cases, and radioactive iodine (RAI) ablation in 76% of cases. Results The study included 17 patients (14 females), with a median age of 16 years at the time of diagnosis. Thyroid nodules were the main complaint in 88% of the patients. Thyroid ultrasonography was the main method for the initial evaluation. Papillary cancer was the most common type of tumor, and lymph node spread was found in 82% of the patients. Moreover, 40% of the patients exhibited excellent responses to therapy, with 35% showing indeterminate results. Only 23.5% of the patients developed hypocalcemia postoperatively. Conclusions Classical papillary thyroid carcinoma was the predominant histopathological type, and most patients showed excellent responses to therapy, followed by indeterminate in most of the cases. The most common presentation was a neck nodule, signifying the role of thorough physical neck examinations. Finally, recurrence occurred in a minority of patients. However, none of these patients died.

Retinoic acid-induced protein 14 links mechanical forces to Hippo signaling.

Cells sense and respond to various mechanical forces from the extracellular matrix primarily by modulating the actin cytoskeleton. Mechanical forces can be translated into biochemical signals in a process called mechanotransduction. Yes-associated protein (YAP) is an effector of Hippo signaling and a mediator of mechanotransduction, but how mechanical forces regulate Hippo signaling is still an open question. We propose that retinoic acid-induced protein 14 (RAI14) responds to mechanical forces and regulates Hippo signaling. RAI14 positively regulates the activity of YAP. RAI14 interacts with NF2, a key component of the Hippo pathway, and the interaction occurs on filamentous actin. When mechanical forces are kept low in cells, NF2 dissociates from RAI14 and filamentous actin, resulting in increased interactions with LATS1 and activation of the Hippo pathway. Clinical data show that tissue stiffness and expression of RAI14 and YAP are upregulated in tumor tissues and that RAI14 is strongly associated with adverse outcome in patients with gastric cancer. Our data suggest that RAI14 links mechanotransduction with Hippo signaling and mediates Hippo-related biological functions such as cancer progression.

Case Report: A Case of a Patient with Smith-Magenis Syndrome and Early-Onset Parkinson's Disease.

Smith-Magenis Syndrome (SMS) is a rare genetic disorder, characterized by intellectual disability (ID), behavioral impairments, and sleep disturbances, as well as multiple organ anomalies in some affected individuals. The syndrome is caused by a deletion in the chromosome band around 17p11.2, including the Retinoic Acid Induced 1 (RAI1) gene, a multifaceted transcriptional regulator that modulates the expression of genes involved in cellular proliferation and neurodevelopment. This gene has a positive role in regulating BDNF and, importantly, affects several cell mechanisms and pathways such as the nigro-striatal pathway, which is crucial for motor function. Parkinson's disease (PD) is one of the most common neurodegenerative diseases in older populations. It is characterized by various physical symptoms including tremors, loss of balance, bradykinesia, and a stooping posture. We present a case study of a patient diagnosed with both SMS and early-onset PD (at the age of 49). The association between both conditions is as yet ambiguous. Genome-wide association studies (GWAS) implicate an association between the RAI1 gene and PD. Similarly, the co-existence of both SMS and PD in the patient suggests a possible association between RAI1 copy number variations (CNVs) and PD, further indicating that RAI1 has strong implications for PD pathogenesis. Our results suggest that RAI1 CNVs and the pathophysiology of PD may be related, underscoring the need for further research in this field. Therefore, caregivers of SMS patients should pay careful attention to the possibility of their patients developing EOPD and should consider starting treatment for PD as soon as the first symptoms appear.

Clinical factors influencing the success rate of radioiodine treatment for Graves' disease.

AIMS: To investigate the impact of various clinical factors associated with Graves' disease on the success rate of radioiodine (RAI) therapy for Graves' disease within 3 years, and to determine the optimal range of iodine dosage per unit volume that yields the highest cure rate for Graves' disease within 1 year. MATERIALS AND METHODS: This retrospective study included patients diagnosed with Graves' disease who underwent RAI therapy at the Second Affiliated Hospital of Anhui Medical University between October 2012 and October 2022. The cumulative success rate was analysed using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were employed to evaluate factors associated with successful treatment of Graves' disease. Outcomes were categorized as either success or failure for all patients. RESULTS: Overall, 1994 patients were enrolled in this study, including 594 (29.8%) male and 1399 (70.2%) female patients. The success and failure groups comprised 1645 (82.4%) and 349 patients (17.6%), respectively, after a 3-year follow-up period. Multivariate regression analysis demonstrated that sex, antithyroid drug (ATD) use before RAI therapy, age, thyroid receptor antibody (TRAb) levels, iodine dose, thyroid mass, and early ATD use before RAI therapy were independent influencing factors for Graves' disease cure. CONCLUSIONS: We found that female patients and those with TRAbs ≥31.83 IU/L and thyroid mass ≥ 73.42 g had a lower cure rate. Therefore, thyroid size, disease severity, and duration of disease should be comprehensively considered when making treatment decisions and iodine dose selection in clinical practice.

Comparative Uptake Patterns of Radioactive Iodine and [18F]-Fluorodeoxyglucose (FDG) in Metastatic Differentiated Thyroid Cancers.

Background: Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [18F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called "flip-flop" phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. Materials and Methods: A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed. The inclusion criteria included accessible FDG-PET and WBS studies within 1 year of each other. Studies were interpreted by two blinded radiologists for iodine or FDG uptake in extrathyroidal sites including lungs, lymph nodes, and bone. Cases were stratified by BRAF V600E mutation status, histology, and a combination of tumor genotype and histology. The data were analyzed by McNemar's Chi-square test. Results: Lung metastasis FDG uptake was significantly more common than iodine uptake (WBS: 52%, FDG: 84%, p = 0.04), but no significant differences were found for lymph or bone metastases. Lung metastasis FDG uptake was significantly more prevalent in the papillary pattern sub-cohort (WBS: 37%, FDG: 89%, p = 0.02) than the follicular pattern sub-cohort (WBS: 75%, FDG: 75%, p = 1.00). Similarly, BRAF V600E+ tumors with lung metastases also demonstrated a preponderance of FDG uptake (WBS: 29%, FDG: 93%, p = 0.02) than BRAF V600E- tumors (WBS: 83%, FDG: 83%, p = 1.00) with lung metastases. Papillary histology featured higher FDG uptake in lung metastasis (WBS: 39%, FDG: 89%, p = 0.03) compared with follicular histology (WBS: 69%, FDG: 77%, p = 1.00). Patients with papillary pattern disease, BRAF V600E+ mutation, or papillary histology had reduced agreement between both modalities in uptake at all metastatic sites compared with those with follicular pattern disease, BRAF V600E- mutation, or follicular histology. Low agreement in lymph node uptake was observed in all patients irrespective of molecular status or histology. Conclusions: The pattern of FDG-PET and radioiodine uptake is dependent on molecular status and metastatic site, with those with papillary histology or BRAF V600E+ mutation featuring increased FDG uptake in distant metastasis. Further study with an expanded cohort may identify which patients may benefit from specific imaging modalities to recognize and surveil metastases.

Distant lymph node metastasis in differentiated thyroid cancer: A population-based cohort study.

BACKGROUND: Cervical lymph node metastasis (LNM) is the most common clinical event in patients with differentiated thyroid cancer (DTC). However, the incidence, pattern, treatment, and prognosis of distant LNM are yet to be reported. METHODS: DTC patients with distant LNM were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2016 and 2020. Multivariate models and propensity score matching (PSM) were used to account for the effects of covariates. The Kaplan-Meier method was used to evaluate the overall survival (OS) and cancer-specific survival (CSS). A nomogram was established to predict the probability of distant LNM in DTC patients, with calibration and Receiver Operating Characteristic (ROC) curves utilized to validate the nomogram's accuracy. RESULTS: Of the 42,339 DTC patients screened, 100 (0.24 %) patients presented with distant LNM. Risk factors including age, sex, T stage, N stage, bone metastasis, brain metastasis, and lung metastasis were included in the nomogram to predict the probability of distant LNM. The calibration curve of the nomogram was close to the ideal diagonal line and the area under the curve (AUC) of the ROC curve is 0.953. Distant LNM showed a worse prognosis after adjusting for confounders compared with non-distant LNM (P < 0.05). Remarkably, radioactive iodine (RAI) therapy did not improve the OS and CSS in DTC patients with distant LNM in the overall or PSM cohort. CONCLUSIONS: Distant LNM presents as a comparatively rare but grave condition with a substantial negative impact on prognosis in patients with DTC. Identified risk factors of distant LNM are older age, male, advanced T stage and N stage, bone metastasis, brain metastasis, and lung metastasis. Remarkably, the current RAI therapy does not appear to significantly improve the survival outcome of DTC patients with distant LNM.

CRISPR-based genome editing of a diurnal rodent, Nile grass rat (Arvicanthis niloticus).

BACKGROUND: Diurnal and nocturnal mammals have evolved distinct pathways to optimize survival for their chronotype-specific lifestyles. Conventional rodent models, being nocturnal, may not sufficiently recapitulate the biology of diurnal humans in health and disease. Although diurnal rodents are potentially advantageous for translational research, until recently, they have not been genetically tractable. The present study aims to address this major limitation by developing experimental procedures necessary for genome editing in a well-established diurnal rodent model, the Nile grass rat (Arvicanthis niloticus). RESULTS: A superovulation protocol was established, which yielded nearly 30 eggs per female grass rat. Fertilized eggs were cultured in a modified rat 1-cell embryo culture medium (mR1ECM), in which grass rat embryos developed from the 1-cell stage into blastocysts. A CRISPR-based approach was then used for gene editing in vivo and in vitro, targeting Retinoic acid-induced 1 (Rai1), the causal gene for Smith-Magenis Syndrome, a neurodevelopmental disorder. The CRISPR reagents were delivered in vivo by electroporation using an improved Genome-editing via Oviductal Nucleic Acids Delivery (i-GONAD) method. The in vivo approach produced several edited founder grass rats with Rai1 null mutations, which showed stable transmission of the targeted allele to the next generation. CRISPR reagents were also microinjected into 2-cell embryos in vitro. Large deletion of the Rai1 gene was confirmed in 70% of the embryos injected, demonstrating high-efficiency genome editing in vitro. CONCLUSION: We have established a set of methods that enabled the first successful CRISPR-based genome editing in Nile grass rats. The methods developed will guide future genome editing of this and other diurnal rodent species, which will promote greater utility of these models in basic and translational research.

The research status and future direction of polyetheretherketone in dental implant -A comprehensive review.

Currently, dental implants primarily rely on the use of titanium and titanium alloys. However, the extensive utilization of these materials in clinical practice has unveiled various problems including stress shielding, corrosion, allergic reactions, cytotoxicity, and image artifacts. As a result, polyetheretherketone (PEEK) has emerged as a notable alternative due to its favorable mechanical properties, corrosion resistance, wear resistance, biocompatibility, radiation penetrability and MRI compatibility. Meanwhile, the advancement and extensive application of 3D printing technology has expanded the range of medical applications for PEEK, including artificial spines, skulls, ribs, shinbones, hip joints, and temporomandibular joints. In this review, we aim to assess the advantages and disadvantages of PEEK as a dental implant material, summarize the measures taken to address its shortcomings and their effects, and provide insight into the future potential of PEEK in dental implant applications, with the goal of offering guidance and reference for future research endeavors.

Impact of Responsible AI on the Occurrence and Resolution of Ethical Issues: Protocol for a Scoping Review.

BACKGROUND: Responsible artificial intelligence (RAI) emphasizes the use of ethical frameworks implementing accountability, responsibility, and transparency to address concerns in the deployment and use of artificial intelligence (AI) technologies, including privacy, autonomy, self-determination, bias, and transparency. Standards are under development to guide the support and implementation of AI given these considerations. OBJECTIVE: The purpose of this review is to provide an overview of current research evidence and knowledge gaps regarding the implementation of RAI principles and the occurrence and resolution of ethical issues within AI systems. METHODS: A scoping review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines was proposed. PubMed, ERIC, Scopus, IEEE Xplore, EBSCO, Web of Science, ACM Digital Library, and ProQuest (Arts and Humanities) will be systematically searched for articles published since 2013 that examine RAI principles and ethical concerns within AI. Eligibility assessment will be conducted independently and coded data will be analyzed along themes and stratified across discipline-specific literature. RESULTS: The results will be included in the full scoping review, which is expected to start in June 2024 and completed for the submission of publication by the end of 2024. CONCLUSIONS: This scoping review will summarize the state of evidence and provide an overview of its impact, as well as strengths, weaknesses, and gaps in research implementing RAI principles. The review may also reveal discipline-specific concerns, priorities, and proposed solutions to the concerns. It will thereby identify priority areas that should be the focus of future regulatory options available, connecting theoretical aspects of ethical requirements for principles with practical solutions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52349.

Automatic prediction of non-iodine-avid status in lung metastases for radioactive I131 treatment in differentiated thyroid cancer patients.

Objectives: The growing incidence of differentiated thyroid cancer (DTC) have been linked to insulin resistance and metabolic syndrome. The imperative need for developing effective diagnostic imaging tools to predict the non-iodine-avid status of lung metastasis (LMs) in differentiated thyroid cancer (DTC) patients is underscored to prevent unnecessary radioactive iodine treatment (RAI). Methods: Primary cohort consisted 1962 pretreated LMs of 496 consecutive DTC patients with pretreated initially diagnosed LMs who underwent chest CT and subsequent post-treatment radioiodine SPECT. After automatic lesion segmentation by SE V-Net, SE Net deep learning was trained to predict non-iodine-avid status of LMs. External validation cohort contained 123 pretreated LMs of 24 consecutive patients from other two hospitals. Stepwise validation was further performed according to the nodule's largest diameter. Results: The SE-Net deep learning network yielded area under the receiver operating characteristic curve (AUC) values of 0.879 (95% confidence interval: 0.852-0.906) and 0.713 (95% confidence interval: 0.613-0.813) for internal and external validation. With the LM diameter decreasing from ≥10mm to ≤4mm, the AUCs remained relatively stable, for smallest nodules (≤4mm), the model yielded an AUC of 0.783. Decision curve analysis showed that most patients benefited using deep learning to decide radioactive I131 treatment. Conclusion: This study presents a noninvasive, less radioactive and fully automatic approach that can facilitate suitable DTC patient selection for RAI therapy of LMs. Further prospective multicenter studies with larger study cohorts and related metabolic factors should address the possibility of comprehensive clinical transformation.

Risk analysis index predicts mortality and non-home discharge following posterior lumbar interbody fusion: a nationwide inpatient sample analysis of 429,380 patients (2019-2020).

PURPOSE: Frailty is an independent risk factor for adverse postoperative outcomes following spine surgery. The ability of the Risk Analysis Index (RAI) to predict adverse outcomes following posterior lumbar interbody fusion (PLIF) has not been studied extensively and may improve preoperative risk stratification. METHODS: Patients undergoing PLIF were queried from Nationwide Inpatient Sample (NIS) (2019-2020). The relationship between RAI-measured preoperative frailty and primary outcomes (mortality, non-home discharge (NHD)) and secondary outcomes (extended length of stay (eLOS), complication rates) was assessed via multivariate analyses. The discriminatory accuracy of the RAI for primary outcomes was measured in area under the receiver operating characteristic (AUROC) curve analysis. RESULTS: A total of 429,380 PLIF patients (mean age = 61y) were identified, with frailty cohorts stratified by standard RAI convention: 0-20 "robust" (R)(38.3%), 21-30 "normal" (N)(54.3%), 31-40 "frail" (F)(6.1%) and 41+ "very frail" (VF)(1.3%). The incidence of primary and secondary outcomes increased as frailty thresholds increased: mortality (R 0.1%, N 0.1%, F 0.4%, VF 1.3%; p < 0.001), NHD (R 6.5%, N 18.1%, F 36.9%, VF 42.0%; p < 0.001), eLOS (R 18.0%, N 21.9%, F 31.6%, VF 43.8%; p < 0.001) and complication rates (R 6.6%, N 8.8%, F 11.1%, VF 12.2%; p < 0.001). The RAI demonstrated acceptable discrimination for NHD (C-statistic: 0.706) and mortality (C-statistic: 0.676) in AUROC curve analysis. CONCLUSION: Increasing RAI-measured frailty is significantly associated with increased NHD, eLOS, complication rates, and mortality following PLIF. The RAI demonstrates acceptable discrimination for predicting NHD and mortality, and may be used to improve frailty-based risk assessment for spine surgeons.

4Din vivodosimetry for a FLASH electron beam using radiation-induced acoustic imaging.

Objective. The primary goal of this research is to demonstrate the feasibility of radiation-induced acoustic imaging (RAI) as a volumetric dosimetry tool for ultra-high dose rate FLASH electron radiotherapy (FLASH-RT) in real time. This technology aims to improve patient outcomes by accurate measurements ofin vivodose delivery to target tumor volumes.Approach. The study utilized the FLASH-capable eRT6 LINAC to deliver electron beams under various doses (1.2 Gy pulse-1to 4.95 Gy pulse-1) and instantaneous dose rates (1.55 × 105Gy s-1to 2.75 × 106Gy s-1), for imaging the beam in water and in a rabbit cadaver with RAI. A custom 256-element matrix ultrasound array was employed for real-time, volumetric (4D) imaging of individual pulses. This allowed for the exploration of dose linearity by varying the dose per pulse and analyzing the results through signal processing and image reconstruction in RAI.Main Results. By varying the dose per pulse through changes in source-to-surface distance, a direct correlation was established between the peak-to-peak amplitudes of pressure waves captured by the RAI system and the radiochromic film dose measurements. This correlation demonstrated dose rate linearity, including in the FLASH regime, without any saturation even at an instantaneous dose rate up to 2.75 × 106Gy s-1. Further, the use of the 2D matrix array enabled 4D tracking of FLASH electron beam dose distributions on animal tissue for the first time.Significance. This research successfully shows that 4Din vivodosimetry is feasible during FLASH-RT using a RAI system. It allows for precise spatial (∼mm) and temporal (25 frames s-1) monitoring of individual FLASH beamlets during delivery. This advancement is crucial for the clinical translation of FLASH-RT as enhancing the accuracy of dose delivery to the target volume the safety and efficacy of radiotherapeutic procedures will be improved.

Correlation analysis between the quantitative parameters of iodine-131 single-photon emission computed tomography-computed tomography thyroid bed uptake and the efficacy of radioactive iodine adjuvant therapy for papillary thyroid cancer.

Background: Single-photon emission computed tomography-computed tomography (SPECT/CT) quantification has emerged as a valuable tool for assessing disease prognosis by accurately identifying and characterizing abnormal lesions with accumulated radionuclides. Papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, and radioactive iodine (RAI) therapy is a standard treatment following total thyroidectomy. This study aimed to explore the potential utility the quantitative parameters of the thyroid bed under iodine-131 (I-131) SPECT/CT in the efficacy of RAI adjuvant therapy for patients with PTC. Methods: The retrospective cohort study enrolled 107 patients with PTC who underwent RAI adjuvant therapy from June 2020 to January 2023. Three days after the RAI adjuvant therapy, all patients underwent I-131 whole-body scans and SPECT/CT imaging. The quantitative parameters, including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), and percent injected dose (%ID), were measured using image analysis software based on I-131 SPECT/CT thyroid bed uptake. Successful therapy was defined as inhibitory thyroglobulin (Tg) <0.2 ng/mL with negative thyroglobulin antibody (TgAb) and negative imaging examination 6 months after RAI adjuvant therapy. The relationship between the quantitative parameters and the treatment efficacy, in addition to the potential influencing factors, were analyzed. Results: The quantitative parameters from the successful group [SUVmax: median 6.15 g/mL, interquartile range (IQR) 2.34-13.80 g/mL; SUVmean: median 2.02 g/mL, IQR 0.89-4.93 g/mL; %ID: median 2.00%, IQR 1.00-4.00%] were significantly lower than those from the unsuccessful group (SUVmax: median 19.03 g/mL, IQR 5.31-45.10 g/mL, SUVmean 4.64 g/mL, IQR 2.07-19.05 g/mL; %ID: median 8.00%, IQR 3.00-18.00%) (SUVmax: Z=-3.755; SUVmean; Z=-3.671; %ID: Z=-4.070; all P values <0.001). SUVmax, SUVmean and %ID were positively correlated with the stimulated thyroglobulin (sTg) and inhibitory Tg at 6 months after RAI adjuvant therapy, respectively (all P values <0.001). SUVmax [odds ratio (OR) =1.045], SUVmean (OR =1.130), and %ID (OR =1.092) were predictive factors for the failure of RAI adjuvant therapy (all P values <0.001). Conclusions: Our study suggested that quantitative parameters (SUVmax, SUVmean, and %ID) derived from I-131 SPECT/CT imaging of the thyroid bed can serve as useful tools for predicting therapy outcomes following RAI adjuvant therapy.

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.

Allele-Specific Regulation of the Candidate Autism Liability Gene RAI1 by the Enhancer Variant rs4925102 (C/G).

Retinoic acid-induced 1 (RAI1) is a dosage-sensitive gene that causes autistic phenotypes when deleted or duplicated. Observations from clinical cases and animal models also suggest that changes of RAI1 expression levels contribute to autism. Previously, we used a bioinformatic approach to identify several single nucleotide polymorphisms (SNPs) located within the 5'-region of RAI1 that correlate with RAI1 mRNA expression in the human brain. In particular, the SNP rs4925102 was identified as a candidate cis-acting regulatory variant, the genotype of which may affect the binding of transcription factors that influence RAI1 mRNA expression. In this study, we provide experimental evidence based on reporter gene, chromatin immunoprecipitation (ChIP), and chromatin conformation capture (3C) assays that rs4925102 regulates RAI1 mRNA expression in an allele-specific manner in human cell lines, including the neuroblastoma-derived cell line SH-SY5Y. We also describe a statistically significant association between rs4925102 genotype and autism spectrum disorder (ASD) diagnosis in a case-control study and near-statistically significant association in an Autism Genome Project (AGP) transmission disequilibrium (TDT) study using Caucasian subjects.

The Effect of Radioiodine Therapy on the Prognosis of Differentiated Thyroid Cancer with Lung Metastases.

Lung metastasis substantially influences the survival of thyroid cancer (TC) patients. This study sought to investigate factors impacting the survival of differentiated thyroid cancer patients with lung metastases (DTC-LM) undergoing radioiodine therapy (RAI) after thyroid surgery. The retrospective study encompassed 609 TC patients with lung metastases. Survival outcomes-specifically, overall survival (OS) and thyroid cancer-specific survival (TCSS)-were examined through both univariate and multivariate Cox regression analyses. Radioiodine therapy (RAI)'s impact on DTC-LM patient survival was further assessed with the Kaplan-Meier survival curve. Of the 609 TC patients with lung metastases, 434 (71.3%) were found to have undergone thyroid surgery after a median follow-up of 59 months. Anaplastic thyroid cancer (ATC), stage IV, and lung metastases associated with other metastases were identified as risk factors for OS and TCSS in TCLM patients. RAI therapy significantly enhances survival in DTC-LM patients followed by primary site surgery under the age of 55, PTC patients, and those with single organ metastases at lung.

Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer.

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied. Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS. Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041). Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Low-grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis-like syndrome.

Loss-of-function CHD2 (chromodomain helicase DNA-binding protein 2) mutations are associated with a spectrum of neurodevelopmental disorders often including early-onset generalized seizures, photosensitivity, and epileptic encephalopathies. Patients show psychomotor delay/intellectual disability (ID), autistic features, and behavior disorders, such as aggression and impulsivity. Most reported cases are sporadic with description of germline mosaicism only in two families. We detect the first case of parental gonosomal CHD2 mosaicism disclosed by two brothers showing mild ID, born to healthy parents. The eldest brother has a history of drug-controlled generalized tonic-clonic seizures and displays sleep disorder and aggressive behavior suggestive of Smith-Magenis syndrome (SMS). Analysis of brothers' DNAs by next-generation sequencing (NGS) custom gene panel for pediatric epilepsy and/or ID disclosed in both the same pathogenic CHD2 variant. Additional NGS experiment on genomic DNA from parents' peripheral blood and from buccal swab raised the suspicion of low-grade gonosomal mosaicism in the unaffected mother subsequently confirmed by digital polymerase chain reaction (dPCR). This report underlines as worthwhile CHD2 screening in individuals presenting ID/developmental delay, with/without epilepsy, and behavior and sleep disorders suggestive of SMS. Detecting a CHD2 variant should prime testing probands' parents by NGS coupled to dPCR on different tissues to exclude/confirm gonosomal mosaicism and define the recurrence risk.

Radioactive Iodine Therapy of Graves' Disease in Patients Pretreated With Methimazole Without Radioiodine Uptake for Dose Estimation.

OBJECTIVE: To assess response predictors to radioactive iodine (RAI) therapy without using thyroid uptake for dose estimate in patients pretreated with methimazole. METHODS: Retrospective analysis was performed of patients with Graves' disease treated with RAI doses determined without using uptake studies. RESULTS: In 242 patients (median age, 41.9 years; 66.1% female), initial mean free thyroxine (FT4) level was 4.7 ng/dL with an estimated thyroid size of 49.15 g. Prior to RAI therapy, average methimazole dose was 22.7 mg/day. Mean RAI dose was 737.0 ±199.4 MBq (19.9 ± 5.4 mCi). Two hundred eight patients (85.9%) responded to RAI therapy; 185 (88.9%) became hypothyroid and 23 (11.1%) became euthyroid. The majority (90.4%) responded within 6 months of therapy with a quicker response (13.9 ± 8.3 vs 17.5 ± 13.5 weeks) for those treated with doses per gram of ≥14.8 MBq (0.4 mCi). Thirty-four nonresponders had a higher initial FT4 level and larger thyroid size with a lower RAI dose per gram of thyroid tissue. In multivariate analysis, the independent response predictor to therapy was dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) (hazard ratio, 3.18; 95% CI, 1.1-9.7). Doses per gram of 14.8 to 18.1 MBq (0.4-0.5 mCi) achieved maximal response rate without added advantage of higher doses. Thyroid size prior to RAI therapy, FT4 levels at diagnosis, and age were inversely related to response. CONCLUSION: RAI therapy for Graves' disease without uptake studies for dose estimates is an effective treatment method. In patients pretreated with methimazole, an RAI dose per gram of thyroid tissue of ≥14.8 MBq (0.4 mCi) showed high response rate. Prospective studies are needed to confirm the viability of this simplified and cost-effective approach.

Establishment of a non-Westernized gut microbiota in men who have sex with men is associated with sexual practices.

The human gut microbiota is influenced by various factors, including health status and environmental conditions, yet considerable inter-individual differences remain unexplained. Previous studies identified that the gut microbiota of men who have sex with men (MSM) is distinct from that of non-MSM. Here, we reveal through species-level microbiota analysis using shotgun metagenomics that the gut microbiota of many MSM with Western origin resembles gut microbial communities of non-Westernized populations. Specifically, MSM gut microbiomes are frequently dominated by members of the Prevotellaceae family, including co-colonization of species from the Segatella copri complex and unknown Prevotellaceae members. Questionnaire-based analysis exploring inter-individual differences in MSM links specific sexual practices to microbiota composition. Moreover, machine learning identifies microbial features associated with sexual activities in MSM. Together, this study shows associations of sexual activities with gut microbiome alterations in MSM, which may have a large impact on population-based microbiota studies.