The noncircular synchronous belt drive mechanism has demonstrated certain achievements and has been used in special fields. Research regarding noncircular synchronous belt drive mechanisms has ...focused on optimization design and kinematic analysis in China, whereas two pulley noncircular synchronous belt transmissions have been developed overseas. However, owing to the noncircular characteristics of the belt pulley, the real-time variation in the belt length slack during the transmission of the noncircular synchronous belt is significant, resulting in high probabilities of skipping and vibration. In this study, a noncircular tensioning pulley is added to create a stable three-pulley noncircular synchronous belt driving mechanism and a good synchronous belt tensioning, with no skipping; hence, the non-uniform output characteristic of the driven pulley is consistent with the theoretical value. In the circular noncircular noncircular three-pulley noncircular synchronous belt mechanism, the pitch curve of the driving synchronous belt pulley is circular, whereas those of the driven synchronous belt and tensioning pulleys are noncircular. To minimize the slack of the belt length of the synchronous belt and the constraint of the concavity and circumference of the tensioning pulley, an automatic optimization model of the tensioning pulley pitch curve is established. The motion simulation, analysis, and optimization code for a three-belt-pulley noncircular synchronous belt drive mechanism is written, and the variation in belt length slack under different speed ratios is analyzed based on several examples. The testbed for a circular–noncircular–noncircular three-pulley noncircular synchronous belt transmission mechanism is developed. The test shows that the three-pulley noncircular synchronous belt drives well. This study proposes an automatic optimization algorithm for the tensioning pulley pitch curve of a noncircular synchronous belt transmission mechanism; it yields a stable transmission of the noncircular synchronous belt transmission mechanism as well as non-uniform output characteristics.
The noncircular synchronous belt drive mechanism has demonstrated certain achievements and has been used in special fields.Research regarding noncircular synchronous belt drive mechanisms has focused ...on optimization desigr and kinematic analysis in China,whereas two pulley noncircular synchronous belt transmissions have been devel-oped overseas.However,owing to the noncircular characteristics of the belt pulley,the real-time variation in the belt length slack during the transmission of the noncircular synchronous belt is significant,resulting in high probabilities of skipping and vibration.In this study,a noncircular tensioning pulley is added to create a stable three-pulley non-circular synchronous belt driving mechanism and a good synchronous belt tensioning,with no skipping;hence,the non-uniform output characteristic of the driven pulley is consistent with the theoretical value.In the circular noncircu lar noncircular three-pulley noncircular synchronous belt mechanism,the pitch curve of the driving synchronous belt pulley is circular,whereas those of the driven synchronous belt and tensioning pulleys are noncircular.To minimize the slack of the belt length of the synchronous belt and the constraint of the concavity and circumference of the tensioning pulley,an automatic optimization model of the tensioning pulley pitch curve is established.The motion simulation,analysis,and optimization code for a three-belt-pulley noncircular synchronous belt drive mechanism is written,and the variation in belt length slack under different speed ratios is analyzed based on several examples.The testbed for a circular-noncircular-noncircular three-pulley noncircular synchronous belt transmission mechanism is developed.The test shows that the three-pulley noncircular synchronous belt drives well.This study proposes an automatic optimization algorithm for the tensioning pulley pitch curve of a noncircular synchronous belt transmis-sion mechanism;it yields a stable transmission of the noncircular synchronous belt transmission mechanism as well as non-uniform output characteristics.
The deadliest anaplastic thyroid cancer (ATC) often transforms from indolent differentiated thyroid cancer (DTC); however, the complex intratumor transformation process is poorly understood. We ...investigated an anaplastic transformation model by dissecting both cell lineage and cell fate transitions using single-cell transcriptomic and genetic alteration data from patients with different subtypes of thyroid cancer. The resulting spectrum of ATC transformation included stress-responsive DTC cells, inflammatory ATC cells (iATCs), and mitotic-defective ATC cells and extended all the way to mesenchymal ATC cells (mATCs). Furthermore, our analysis identified 2 important milestones: (a) a diploid stage, in which iATC cells were diploids with inflammatory phenotypes and (b) an aneuploid stage, in which mATCs gained aneuploid genomes and mesenchymal phenotypes, producing excessive amounts of collagen and collagen-interacting receptors. In parallel, cancer-associated fibroblasts showed strong interactions among mesenchymal cell types, macrophages shifted from M1 to M2 states, and T cells reprogrammed from cytotoxic to exhausted states, highlighting new therapeutic opportunities for the treatment of ATC.
The aim of this study was to describe the oncologic outcomes of patients with BRAF
-mutated anaplastic thyroid cancer (ATC) who had neoadjuvant BRAF-directed therapy with subsequent surgery. For ...context, we also reviewed patients who received BRAF-directed therapy after surgery, and those who did not have surgery after BRAF-directed therapy.
This was a single-center retrospective cohort study conducted at a tertiary care cancer center in Texas from 2017 to 2021. Fifty-seven consecutive patients with BRAF
-mutated ATC and at least 1 month of BRAF-directed therapy were included. Primary outcomes were overall survival (OS) and progression-free survival (PFS).
All patients had stage IVB (35%) or IVC (65%) ATC. Approximately 70% of patients treated with BRAF-directed therapy ultimately had surgical resection of residual disease. Patients who had neoadjuvant BRAF-directed therapy followed by surgery (
= 32) had 12-month OS of 93.6% confidence interval (CI) 84.9-100 and PFS of 84.4% CI 71.8-96.7. Patients who had surgery before BRAF-directed therapy (
= 12) had 12-month OS of 74.1% CI 48.7-99.5 and PFS of 50% CI 21.7-78.3. Finally, patients who did not receive surgery after BRAF-directed therapy (
= 13) had 12-month OS of 38.5% CI 12.1-64.9 and PFS of 15.4% CI 0-35.0. Neoadjuvant BRAF-directed therapy reduced tumor size, extent of surgery, and surgical morbidity score. Subgroup analysis suggested that any residual ATC in the surgical specimen was associated with significantly worse 12-month OS and PFS (OS = 83.3% CI 62.6-100, PFS = 61.5% CI 35.1-88) compared with patients with pathologic ATC complete response (OS = 100%, PFS = 100%).
We observed that neoadjuvant BRAF-directed therapy reduced extent of surgery and surgical morbidity. While acknowledging potential selection bias, the 12-month OS rate appeared higher in patients who had BRAF-directed therapy followed by surgery as compared with BRAF-directed therapy without surgery; yet, it was not significantly different from surgery followed by BRAF-directed therapy. PFS appeared higher in patients treated with neoadjuvant BRAF-directed therapy relative to patients in the other groups. These promising results of neoadjuvant BRAF-directed therapy followed by surgery for BRAF-mutated ATC should be confirmed in prospective clinical trials.
Anaplastic thyroid carcinoma (ATC) uniformly present with aggressive disease, but the mutational landscape of tumors varies. We aimed to determine whether tumor mutations affect survival outcomes in ...ATC.
Patients who underwent mutation sequencing using targeted gene panels between 2005 and 2019 at a tertiary referral center were included. Associations between mutation status and survival outcomes were assessed using Cox proportional hazards models.
A total of 202 patients were included, where 122 died of ATC (60%). The median follow-up was 31 months (interquartile range, 18-45 months). The most common mutations were in
(59%),
(41%),
promoter (37%), and the
gene family (22%). Clinicopathologic characteristics and overall survival (OS) significantly correlated with mutations in
V600E and
, which were mutually exclusive. The
V600E mutation was associated with the presence of a papillary thyroid carcinoma precursor and significantly better OS (median OS: 24 months).
-mutated patients more commonly presented without cervical lymph node involvement but had the worst OS (median OS: 6 months). Tumors that were wild-type for both
and
were enriched for
and harbored intermediate prognosis (median OS: 15 months). In multivariate analyses,
mutations were associated with a more than 2.5-fold higher risk of death (adjusted hazard ratio, 2.64; 95% CI, 1.66 to 4.20) compared with
V600E. In patients treated with BRAF-directed therapy (n = 60), disease progression occurred in 48% of patients (n = 29). The median progression-free survival was 14 months. The presence of a
mutation was independently associated with reduced progression-free survival in
V600E-mutated patients treated with BRAF-directed therapy (adjusted hazard ratio, 2.89; 95% CI, 1.35 to 6.21).
Mutation analysis provides prognostic information in ATC and should be incorporated into routine clinical care.
PDF
