Synchronous papillary and follicular thyroid carcinomas: the first retrospective cohort study and literature review.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) contribute to more than 95% of thyroid malignancies. However, synchronous PTC and FTC are less common; it is most commonly discovered incidentally as synchronous malignancies during operation, which adds difficulties to intraoperative decision-making and postoperative treatment. Therefore, we analyzed the clinicopathological characteristics and prognosis of patients with PTC and FTC in our center. Methods: We conducted a search of single PTC, single FTC, and synchronous PTC/FTC patients who received initial surgery treatment at Fudan University Shanghai Cancer Center from 2006 to 2018 and collected paraffin-embedded samples of synchronous patients. Clinicopathological characteristics were collected from the electronic medical record system. Follow-up was performed through telephone contact or medical records. Exome sequencing was performed by ThyroLead panel. Results: Total of 42 synchronous PTC/FTC patients, 244 single FTC patients, and 2,959 single PTC patients were included. It showed a similarity between the clinicopathological features of synchronous thyroid cancer patients and single PTC patients, with a greater proportion of females, higher probabilities of lymph node metastasis, and higher rate of concurrence of Hashimoto's disease. The disease-free survival (DFS) curve indicated a worse prognosis of the synchronous group and single PTC group compared to the single FTC group, who had a propensity for neck lymph node recurrence; however, logistic multivariate regression analysis did not find any factor related to recurrence in the synchronous group. After re-checking pathology, DNA extraction, and quality control, genetic alteration information of 62 samples including primary tumors and metastatic lymph nodes from 35 synchronous cancer patients was displayed. In total, 81 mutations and 1 fusion gene were identified, including mutations related to outcomes and targeted therapy. Besides, some rare mutations in thyroid cancer were found in these patients. Conclusions: To conclude, synchronous PTC/FTC tend to be incidentally discovered during or after operation, behaving more like single PTC. The prognosis of synchronous patients is worse than that of single FTC patients and supplemental cervical lymph node dissection, total thyroidectomy, and postoperative radioiodine therapy should be taken into consideration after diagnosis. The next-generation sequencing (NGS) showed a unique molecular feature of synchronous patients with some rare mutations.

Integrated proteogenomic and metabolomic characterization of papillary thyroid cancer with different recurrence risks.

Although papillary thyroid cancer (PTC) has a good prognosis, its recurrence rate is high and remains a core concern in the clinic. Molecular factors contributing to different recurrence risks (RRs) remain poorly defined. Here, we perform an integrative proteogenomic and metabolomic characterization of 102 Chinese PTC patients with different RRs. Genomic profiling reveals that mutations in MUC16 and TERT promoter as well as multiple gene fusions like NCOA4-RET are enriched by the high RR. Integrative multi-omics analyses further describe the multi-dimensional characteristics of PTC, especially in metabolism pathways, and delineate dominated molecular patterns of different RRs. Moreover, the PTC patients are clustered into four subtypes (CS1: low RR and BRAF-like; CS2: high RR and metabolism type, worst prognosis; CS3: high RR and immune type, better prognosis; CS4: high RR and BRAF-like) based on the omics data. Notably, the subtypes display significant differences considering BRAF and TERT promoter mutations, metabolism and immune pathway profiles, epithelial cell compositions, and various clinical factors (especially RRs and prognosis) as well as druggable targets. This study can provide insights into the complex molecular characteristics of PTC recurrences and help promote early diagnosis and precision treatment of recurrent PTC.

Quantitatively assessing the effect of cervical sagittal alignment on dynamic intervertebral kinematics by video-fluoroscopy technique.

BACKGROUND: Cervical sagittal alignment is crucial for distributing the head load to lower cervical segments and maintaining normal cervical spine function, but its biomechanical effect on the cervical spine was not fully elucidated. OBJECTIVE: To investigate the effect of cervical sagittal alignment on dynamic intervertebral kinematics. DESIGN: Cross-sectional study. METHODS: Healthy participants without neck pain were recruited and divided into lordosis, straight and kyphosis groups according to the C2-C7 Cobb angle at the neutral position. The anti-directional and total joint motions were extracted across 10 epochs of dynamic cervical flexion and extension movements. RESULTS: /findings: The overall anti-directional joint motion during flexion is larger in the kyphosis group when compared with the lordosis group (p = 0.021), while the range of flexion is smaller in the kyphosis group than that in the lordosis group (p = 0.017). The C2/C3 anti-directional joint motion during extension in the straight group is larger than that in the lordosis group (p = 0016). The range of extension in the kyphosis group (p < 0.001) and the straight group (p = 0.002) are larger than that in the lordosis group. The increased range of extension in the kyphosis and straight groups were mainly from the C3/C4, C4/C5, and C5/C6 joints(p < 0.05). CONCLUSION: Changes in cervical sagittal alignment alter both the quality and quantity of the individual joint motions. More adjustments are required by the cervical joints to complete neck movements with the loss of lordosis. The lordotic curvature is a relatively effort-saving mode for the cervical spine from a biomechanical perspective.

A distinct tumor microenvironment makes anaplastic thyroid cancer more lethal but immunotherapy sensitive than papillary thyroid cancer.

Both anaplastic thyroid cancer (ATC) and papillary thyroid cancer (PTC) originate from thyroid follicular epithelial cells, but ATC has a significantly worse prognosis and shows resistance to conventional therapies. However, clinical trials found that immunotherapy works better in ATC than late-stage PTC. Here, we used single-cell RNA sequencing (scRNA-Seq) to generate a single-cell atlas of thyroid cancer. Differences in ATC and PTC tumor microenvironment components (including malignant cells, stromal cells, and immune cells) leading to the polarized prognoses were identified. Intriguingly, we found that CXCL13+ T lymphocytes were enriched in ATC samples and might promote the development of early tertiary lymphoid structure (TLS). Last, murine experiments and scRNA-Seq analysis of a treated patient's tumor demonstrated that famitinib plus anti-PD-1 antibody could advance TLS in thyroid cancer. We displayed the cellular landscape of ATC and PTC, finding that CXCL13+ T cells and early TLS might make ATC more sensitive to immunotherapy.

Historical context, process, and development trends of pediatric thyroid cancer research: a bibliometric analysis.

Objective: At present, the structure of knowledge in the field of childhood thyroid cancer is not clear enough, and scholars lack a sufficient understanding of the developing trends in this field, which has led to a shortage of forward-looking outputs. The purpose of this research is to help scholars construct a complete knowledge framework and identify current challenges, opportunities, and development trends. Methods: We searched the literature in the Web of Science Core Collection database on August 7, 2023 and extracted key information from the top 100 most cited articles, such as the countries, institutions, authors, themes, and keywords. We used bibliometric tools such as bibliometrix, VOSviewer, and CiteSpace for a visualization analysis and Excel for statistical descriptions. Results: The top 100 most cited articles fluctuated over time, and the research was concentrated in European countries, the United States, and Japan, among which scientific research institutions and scholars from the United States made outstanding contributions. Keyword analysis revealed that research has shifted from simple treatment methods for pediatric thyroid cancer (total thyroidectomy) and inducing factors (the Chernobyl power station accident) to the clinical applications of genetic mutations (such as the BRAF and RET genes) and larger-scale genetic changes (mutation studies of the DICER1 gene). The thematic strategy analysis showed an increasing trend towards the popularity of fusion oncogenes, while the popularity of research on traditional treatments and diagnostics has gradually declined. Conclusion: Extensive research has been conducted on the basic problems of pediatric thyroid cancer, and there has been significant outputs in the follow-up and cohort analysis of conventional diagnostic and treatment methods. However, these methods still have certain limitations. Therefore, scholars should focus on exploring fusion genes, the clinical applications of molecular targets, and novel treatment methods. This study provides a strong reference for scholars in this field.

SGLT2i improves kidney senescence by down-regulating the expression of LTBP2 in SAMP8 mice.

Senescent kidney can lead to the maladaptive repairment and predispose age-related kidney diseases. Here, we explore the renal anti-senescence effect of a known kind of drug, sodium-dependent glucose transporters 2 inhibitor (SGLT2i). After 4 months intragastrically administration with dapagliflozin on senescence-accelerated mouse prone 8 (SAMP8) strain mice, the physiologically effects (lowering urine protein, enhancing glomerular blood perfusion, inhibiting expression of senescence-related biomarkers) and structural changes (improving kidney atrophy, alleviating fibrosis, decreasing glomerular mesangial proliferation) indicate the potential value of delaying kidney senescence of SGLT2i. Senescent human proximal tubular epithelial (HK-2) cells induced by H2 O2 also exhibit lower senescent markers after dapagliflozin treatment. Further mechanism exploration suggests LTBP2 have the great possibility to be the target for SGLT2i to exert its renal anti-senescence role. Dapagliflozin down-regulate the LTBP2 expression in kidney tissues and HK-2 cells with senescent phenotypes. Immunofluorescence staining show SGLT2 and LTBP2 exist colocalization, and protein-docking analysis implies there is salt-bridge formation between them; these all indicate the possibility of weak-interaction between the two proteins. Apart from reducing LTBP2 expression in intracellular area induced by H2 O2 , dapagliflozin also decrease the concentration of LTBP2 in cell culture medium. Together, these results reveal dapagliflozin can delay natural kidney senescence in non-diabetes environment; the mechanism may be through regulating the role of LTBP2.

Effects of different ecological restoration methods on the soil physicochemical properties and vegetation community characteristics of the Baotou light rare earth tailings pond in Inner Mongolia, China.

This study investigated the soil physicochemical properties and vegetation community characteristics of the Baotou light rare earth tailings pond after 10 years of aggregate spray seeding ecological restoration (S1) and ordinary soil spray seeding ecological restoration (S2), and the naturally restored dam slope area without human intervention (S3). The results showed that the vegetation community of S1 was dominated by Caragana korshinskii Kom, and its importance and abundance values were 0.40 and 38.4, respectively, while the vegetation communities of S2 and S3 mainly comprised herbaceous plants. Additionally, the vegetation biomass of S1 was significantly higher than that of S2 and S3 by 215.20% and 1345.76%, respectively, and the vegetation diversity index of S1 was the highest among the three treatment groups. The soil porosity (SP), water content (W), electrical conductivity (EC), and available K were significantly improved in S1, while soil bulk density (BD) was significantly reduced compared with that of S2 and S3. In addition, redundancy analysis revealed that SP, EC, W, and K positively correlate with the biomass, Shannon, Pielou, Simpson, and Marglef indices. Principal component analysis further showed that the comprehensive score of S1 (0.983) was higher than that of S2 (- 0.261) and S3 (- 0.648). Collectively, these findings indicate that appropriate ecological restoration can improve soil structure and vegetation community characteristics, thereby accelerating vegetation restoration, ultimately increasing the stability of the ecosystem.

TG468: a text graph convolutional network for predicting clinical response to immune checkpoint inhibitor therapy.

Enhancing cancer treatment efficacy remains a significant challenge in human health. Immunotherapy has witnessed considerable success in recent years as a treatment for tumors. However, due to the heterogeneity of diseases, only a fraction of patients exhibit a positive response to immune checkpoint inhibitor (ICI) therapy. Various single-gene-based biomarkers and tumor mutational burden (TMB) have been proposed for predicting clinical responses to ICI; however, their predictive ability is limited. We propose the utilization of the Text Graph Convolutional Network (GCN) method to comprehensively assess the impact of multiple genes, aiming to improve the predictive capability for ICI response. We developed TG468, a Text GCN model framing drug response prediction as a text classification task. By combining natural language processing (NLP) and graph neural network techniques, TG468 effectively handles sparse and high-dimensional exome sequencing data. As a result, TG468 can distinguish survival time for patients who received ICI therapy and outperforms single gene biomarkers, TMB and some classical machine learning models. Additionally, TG468's prediction results facilitate the identification of immune status differences among specific patient types in the Cancer Genome Atlas dataset, providing a rationale for the model's predictions. Our approach represents a pioneering use of a GCN model to analyze exome data in patients undergoing ICI therapy and offers inspiration for future research using NLP technology to analyze exome sequencing data.

Breast cancer screening and early diagnosis in China: a systematic review and meta-analysis on 10.72 million women.

BACKGROUND: The incidence of breast cancer among Chinese women has gradually increased in recent years. This study aims to analyze the situation of breast cancer screening programs in China and compare the cancer detection rates (CDRs), early-stage cancer detection rates (ECDRs), and the proportions of early-stage cancer among different programs. METHODS: We conducted a systematic review and meta-analysis of studies in multiple literature databases. Studies that were published between January 1, 2010 and June 30, 2023 were retrieved. A random effects model was employed to pool the single group rate, and subgroup analyses were carried out based on screening model, time, process, age, population, and follow-up method. RESULTS: A total of 35 studies, including 47 databases, satisfied the inclusion criteria. Compared with opportunistic screening, the CDR (1.32‰, 95% CI: 1.10‰-1.56‰) and the ECDR (0.82‰, 95% CI: 0.66‰-0.99‰) were lower for population screening, but the proportion of early-stage breast cancer (80.17%, 95% CI: 71.40%-87.83%) was higher. In subgroup analysis, the CDR of population screening was higher in the urban group (2.28‰, 95% CI: 1.70‰-2.94‰), in the breast ultrasonography (BUS) in parallel with mammography (MAM) group (3.29‰, 95% CI: 2.48‰-4.21‰), and in the second screening follow-up group (2.47‰, 95% CI: 1.64‰-3.47‰), and the proportion of early-stage breast cancer was 85.70% (95% CI: 68.73%-97.29%), 88.18% (95% CI: 84.53%-91.46%), and 90.05% (95% CI: 84.07%-94.95%), respectively. CONCLUSION: There were significant differences between opportunistic and population screening programs. The results of these population screening studies were influenced by the screening process, age, population, and follow-up method. In the future, China should carry out more high-quality and systematic population-based screening programs to improve screening coverage and service.

Intra- and Peritumoral Based Radiomics for Assessment of Lymphovascular Invasion in Invasive Breast Cancer.

BACKGROUND: Radiomics has been applied for assessing lymphovascular invasion (LVI) in patients with breast cancer. However, associations between features from peritumoral regions and the LVI status were not investigated. PURPOSE: To investigate the value of intra- and peritumoral radiomics for assessing LVI, and to develop a nomogram to assist in making treatment decisions. STUDY TYPE: Retrospective. POPULATION: Three hundred and sixteen patients were enrolled from two centers and divided into training (N = 165), internal validation (N = 83), and external validation (N = 68) cohorts. FIELD STRENGTH/SEQUENCE: 1.5 T and 3.0 T/dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI). ASSESSMENT: Radiomics features were extracted and selected based on intra- and peritumoral breast regions in two magnetic resonance imaging (MRI) sequences to create the multiparametric MRI combined radiomics signature (RS-DCE plus DWI). The clinical model was built with MRI-axillary lymph nodes (MRI ALN), MRI-reported peritumoral edema (MPE), and apparent diffusion coefficient (ADC). The nomogram was constructed with RS-DCE plus DWI, MRI ALN, MPE, and ADC. STATISTICAL TESTS: Intra- and interclass correlation coefficient analysis, Mann-Whitney U test, and least absolute shrinkage and selection operator regression were used for feature selection. Receiver operating characteristic and decision curve analyses were applied to compare performance of the RS-DCE plus DWI, clinical model, and nomogram. RESULTS: A total of 10 features were found to be associated with LVI, 3 from intra- and 7 from peritumoral areas. The nomogram showed good performance in the training (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.884 vs. 0.695 vs. 0.870), internal validation (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.813 vs. 0.695 vs. 0.794), and external validation (AUCs, nomogram vs. clinical model vs. RS-DCE plus DWI, 0.862 vs. 0.601 vs. 0.849) cohorts. DATA CONCLUSION: The constructed preoperative nomogram might effectively assess LVI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling.

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.

Relationship between scapular elevation exercises with different alignments and activity of the trapezius and levator scapulae muscles.

[Purpose] This study aimed to examine whether scapular elevation exercises in sitting positions with different alignments lead to contractions of the trapezius and levator scapulae muscles. [Participants and Methods] The participants were 25 males, measured in four sitting positions with different alignments. Spine alignment was assessed by measuring the head protrusion, upper thoracic spine tilt, and pelvic tilt angles. Upper limb alignment was evaluated using the scapula tilt angle, scapula rotation angle, and distance between scapular spinous processes. Scapular elevation exercises were measured, and the thickness of the trapezius and levator scapulae muscles were measured in resting and elevated positions, with changes in muscle thickness. [Results] The trapezius muscle thickness was greater in the sitting position with less thoracic spine tilt and scapula tilt angles. Conversely, the levator scapulae muscle thickness was greater in the sitting position with more thoracic spine tilt and scapula tilt angles. [Conclusion] Scapular elevation exercises induce separate contractions of the trapezius and levator scapulae muscles by modifying the alignment of the spine and upper limbs.

LogD7.4 prediction enhanced by transferring knowledge from chromatographic retention time, microscopic pKa and logP.

Lipophilicity is a fundamental physical property that significantly affects various aspects of drug behavior, including solubility, permeability, metabolism, distribution, protein binding, and toxicity. Accurate prediction of lipophilicity, measured by the logD7.4 value (the distribution coefficient between n-octanol and buffer at physiological pH 7.4), is crucial for successful drug discovery and design. However, the limited availability of data for logD modeling poses a significant challenge to achieving satisfactory generalization capability. To address this challenge, we have developed a novel logD7.4 prediction model called RTlogD, which leverages knowledge from multiple sources. RTlogD combines pre-training on a chromatographic retention time (RT) dataset since the RT is influenced by lipophilicity. Additionally, microscopic pKa values are incorporated as atomic features, providing valuable insights into ionizable sites and ionization capacity. Furthermore, logP is integrated as an auxiliary task within a multitask learning framework. We conducted ablation studies and presented a detailed analysis, showcasing the effectiveness and interpretability of RT, pKa, and logP in the RTlogD model. Notably, our RTlogD model demonstrated superior performance compared to commonly used algorithms and prediction tools. These results underscore the potential of the RTlogD model to improve the accuracy and generalization of logD prediction in drug discovery and design. In summary, the RTlogD model addresses the challenge of limited data availability in logD modeling by leveraging knowledge from RT, microscopic pKa, and logP. Incorporating these factors enhances the predictive capabilities of our model, and it holds promise for real-world applications in drug discovery and design scenarios.

Impaired autophagy contributes to the aggravated deterioration of osteoarthritis articular cartilage by peroxisome proliferator-activated receptor α deficiency, associated with decreased ERK and Akt activation.

BACKGROUND: Although the chondroprotection of peroxisome proliferator-activated receptor α (PPARα) activation against osteoarthritis (OA) has been revealed, the regulatory mechanism of PPARα deficiency to aggravate osteoarthritic cartilage deterioration remains unclear. Here, we aimed to investigate whether and how autophagy is involved in OA pathological progression. METHODS: Model of experimental OA was established using destabilization of the medial meniscus in PPARα-KO 129S4/SvJae male mice, followed by histopathological detection of articular cartilage and immunohistochemistry detection of extracellular matrix (ECM) or autophagy-related signal molecules. Meanwhile, human OA chondrocytes obtained from total knee replacement surgery patients with OA were cultured with the pretreatment of IL-1ß, followed with the treatment of PPARα agonist WY14643 and the detection of related signal molecules. RESULTS: PPARα deficiency aggravated cartilage damage with decreased LC3B level in combination with an increase in P62 level, accompanied with reduced p-Akt and p-ERK levels in PPARα-KO mouse model of experimental OA. On the contrary, PPARα activation by WY14643 promoted ECM synthesis in IL-1ß-treated human OA chondrocytes, accompanied with increased LC3B-II/I ratio and Beclin 1 level and decreased P62 and Bcl2 levels. Meanwhile, it was observed that activated ERK and Akt by PPARα activation contributed to the enhancement of autophagy and ECM synthesis in human OA chondrocytes. CONCLUSIONS: Impaired autophagy contributed to the aggravated deterioration of osteoarthritis articular cartilage by PPARα deficiency associated with the suppression of ERK and Akt, with an implication that triggering PPARα activation ought to be a potential promising therapeutic target for OA therapy.

The Comparation of Renal Anti-Senescence Effects and Blood Metabolites between Dapagliflozin and Metformin in Non-Diabetes Environment.

Delaying kidney senescence process will benefit renal physiologic conditions, and prompt the kidney recovering from different pathological states. The renal anti-senescence effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and metformin have been proven in diabetic settings, but the roles of each one and combination of two drugs in natural kidney aging process remain undefined and deserve further research. Senescence-accelerated mouse prone 8 (SAMP8) were orally administered dapagliflozin, metformin, and a combination of them for 16 weeks. Dapagliflozin exhibits better effects than metformin in lowering senescence related markers, and the combination therapy shows the best results. In vitro experiments demonstrate the same results that the combination of dapagliflozin and metformin can exert a better anti-senescence effect. Blood metabolites detection in vivo shows dapagliflozin mainly leads to the change of blood metabolites enriched in choline metabolism, and metformin tends to induce change of blood metabolites enriched in purine metabolism. In conclusion, the results suggest dapagliflozin may have a better renal anti-senescence effect than metformin in non-diabetes environment, and the combination of the two drugs can strengthen the effect. The two drugs can lead to different blood metabolites alteration, which may lead to different systemic effects.

Cost and Effectiveness of Percutaneous Endoscopic Interlaminar Discectomy versus Microscope-Assisted Tubular Discectomy for L5-S1 Lumbar Disc Herniation.

OBJECTIVE: To assess the cost and effectiveness of percutaneous endoscopic interlaminar discectomy (PEID) and microscope-assisted tubular discectomy (MATD) for patients with L5/S1 lumbar disc herniation (LDH). METHODS: The medical and financial records of patients diagnosed with L5/S1 LDH and who underwent either PEID or MATD from April 2021 to April 2022 were retrospectively collected. Demographic and baseline information, perioperative observational index, clinical outcomes, and inpatient costs were analyzed. RESULTS: Sixty patients were included, with 30 patients in the PEID group and 30 patients in the MATD group. No significant difference was found in demographic and baseline information between the 2 groups (P > 0.05). The PEID group showed significantly shorter incision length, less intraoperative blood loss, shorter hospital stays, and higher intraoperative fluoroscopy frequency compared with the MATD group (P < 0.05). There were no significant differences in visual analog scale back/leg score, Oswestry Disability Index, and 36-Item Short-Form Survey score between PEID and MATD groups before the surgery and at any follow-up time points (P > 0.05). The total cost, surgery cost, and surgical instruments/materials cost were significantly higher in the PEID group compared with the MATD group (P < 0.05). In contrast, the drug and nursing costs were significantly higher in the MATD group than in the PEID group (P < 0.05). CONCLUSIONS: PEID and MATD provide equivalent clinical efficacy and safety in treating LDH at L5/S1 segment within a 1-year follow-up. However, PEID is less invasive and MATD is less costly. No one surgical technique is superior in all aspects and patients should make decisions according to their top concern.

TERT accelerates BRAF mutant-induced thyroid cancer dedifferentiation and progression by regulating ribosome biogenesis.

TERT reactivation occurs frequently in human malignancies, especially advanced cancers. However, in vivo functions of TERT reactivation in cancer progression and the underlying mechanism are not fully understood. In this study, we expressed TERT and/or active BRAF (BRAF V600E) specifically in mouse thyroid epithelium. While BRAF V600E alone induced papillary thyroid cancer (PTC), coexpression of BRAF V600E and TERT resulted in poorly differentiated thyroid carcinoma (PDTC). Spatial transcriptome analysis revealed that tumors from mice coexpressing BRAF V600E and TERT were highly heterogeneous, and cell dedifferentiation was positively correlated with ribosomal biogenesis. Mechanistically, TERT boosted ribosomal RNA (rRNA) expression and protein synthesis by interacting with multiple proteins involved in ribosomal biogenesis. Furthermore, we found that CX-5461, an rRNA transcription inhibitor, effectively blocked proliferation and induced redifferentiation of thyroid cancer. Thus, TERT promotes thyroid cancer progression by inducing cancer cell dedifferentiation, and ribosome inhibition represents a potential strategy to treat TERT-reactivated cancers.

Rare case of single left coronary artery in a Japanese cadaver.

A single left coronary artery with a single orifice in the left aortic sinus was observed during anatomical practice in an 81-year-old male Japanese cadaver. The single left coronary artery bifurcated into the anterior interventricular branch (IVa) and circumflex (CXa) branches. The IVa descended into the anterior interventricular sulcus to supply the apex of the heart, leaving a branch that traversed the upper part of the infundibulum to supply the anterior upper region of the right ventricle. The CXa curved leftward in the atrioventricular sulcus to reach the posterior surface, after which it continued to emerge into the anterior surface. The vascular running pattern showed that CXa directly supplied blood to the upper right ventricle (but not the conus branch), with three branches connected to the apex. The atrial arteries showed no anomalous distribution patterns. These findings are useful during surgical procedures, including cardiac catheterization.

Diagnostic Values of Peripheral Blood T-Cell Spot Test for Tuberculosis (T-SPOT.TB) for Spinal Tuberculosis.

Background: The T-cell spot test for tuberculosis (T-SPOT.TB) with false positives and false negatives exists in the diagnosis of spinal infection. The objective of this study was to increase the diagnostic value precision and specificity of T-SPOT.TB in the identification of spinal tuberculosis (TB). Patients and Methods: Fifty-two patients suspected of having spinal TB from April 2020 to December 2021 were included, and all patients received T-SPOT.TB tests and surgical treatment. The composite reference standard was used to diagnose spinal TB. The T-SPOT.TB values were compared according to whether spinal TB was diagnosed, and the optimal cutoff values of diagnosis was determined by receiver operating characteristic (ROC) curve analysis. Results: All patients were followed up for at least one year. The sensitivity, specificity, positive predictive value, and negative predictive value of the T-SPOT.TB test in assisting the diagnosis of spinal TB were 91.67%, 71.43%, 73.33%, and 90.9%, respectively. We determined that the values of early secreted antigen target 6 (ESAT-6) antigen and culture filter protein 10 (CFP-10) antigen were determined to be diagnostic for spinal tuberculosis, with areas under the curve equal to 0.776 and 0.852, respectively; the cutoff values for the diagnosis of ESAT-6 antigen and CFP-10 antigen were calculated as 40.5 spot forming cells (SFCs) per 106 peripheral blood mononuclear cells (PBMCs) and 26.5 SFCs/106 PBMCs, respectively. Follow-up for all patients was 12 months, and in this period, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), visual analog scale (VAS) score, and Oswestry Dysfunction Index (ODI%) were different between groups (p < 0.05). Conclusions: The T-SPOT.TB test is considered a milestone discovery in the diagnosis of TB; there are still many false-positive samples, but the diagnostic specificity was improved in the study, allowing spinal infections to be treated accurately and in a timely manner.