BACKGROUND:The long-term effect of intraoperative usage of carbon nanoparticles (CN) and parathyroid hormone (PTH) test strip using immune colloidal gold technique (ICGT) is unclear. This study aims to compare the effect of intraoperative usage of CN and ICGT test strips on PG function.METHODS:This randomized clinical study involved adult patients who underwent total thyroidectomy. They were randomly allocated into three groups (control, CN, and ICGT group). Clinical data were analyzed.RESULTS:Each group involved 98 patients. Serum calcium and PTH concentrations at 24 h postoperatively (PTH24h) were higher in CN group. The parathyroid function recovered quicker in CN group. Use of CN increased in situ PG preservation and PTH24h. Mediation analysis indicated that 23.05% of the total effect of CN on PTH24h was attributed to PGRIS.CONCLUSION:CN holds promise to improve in situ PG preservation and protect PG vasculature, thereby reducing the incidence of early hypoparathyroidism. The value of ICGT test strips for PG protection is dubious.

Correlations between cannabinoids exposure and clinicopathological parameters.

Figure S2. NOTCH4 expression in si-NOTCH4 cells. NOTCH activity assay, cisplatin viability assay, apoptosis assay and cell cycle analysis in si-NOTCH4 cells.

Primer and siRNA sequences of DOCK5 wide-type and variant

Expression of cannabinoids and their metabolites in plasma samples of HPV positive HNSCC patients identified by LC-MS/MS.

Full list of 580 validated ASEs associated with HPV negative HNSCC

Distribution of 580 validated junctions in each tumor sample

Background:Routine prophylaxis for at-risk patients may reduce the occurrence of postoperative hypocalcemia but is not widely adopted due to a lack of evidence on the efficacy of available prophylactic strategies. In this study, we compared the relative efficacy of prophylactic strategies for postthyroidectomy hypocalcemia with a systematic review and network meta-analysis.Methods:PubMed, Embase, and Cochrane Library were searched, covering the period from 1980 to May 2022, for randomized controlled trials (RCTs) comparing calcium, vitamin D3, activated vitamin D3, teriparatide, steroids, and magnesium with placebo or each other in patients receiving total or completion thyroidectomy. Involved RCTs reporting symptomatic or biochemical hypocalcemia. The primary outcome was symptomatic hypocalcemia, defined as circumoral tingling, and Chvostek and Trousseau signs. The secondary outcome was biochemical hypocalcemia. Risk of bias was assessed using the Cochrane risk of bias assessment tool for randomized trials. Pooled estimates were calculated using a random-effects inverse-variance weighting model. The network meta-analysis was performed under the frequentist framework. This meta-analysis was registered on the PROSPERO (International prospective register of systematic reviews) (CRD42022299982).Results:Twenty-seven RCTs comprising 3382 patients are included. Prophylactic strategies of teriparatide, oral calcium plus vitamin D3, and oral calcium plus activated vitamin D3 are superior to placebo in reducing symptomatic hypocalcemia. Teriparatide emerged as the most effective strategy for symptomatic hypocalcemia [relative risk (RR): 0.18; 95% CI: 0.03-0.98], followed by oral calcium plus activated vitamin D3 (RR: 0.42; 95% CI: 0.25-0.73) and oral calcium plus vitamin D3 (RR: 0.43; 95% CI: 0.26-0.71). Evidence on monotherapy with either oral calcium or vitamin D3 in reducing symptomatic hypocalcemia is insufficient. Intravenous calcium and oral calcium are effective in reducing biochemical hypocalcemia.Conclusions:This network meta-analysis provides information on the relative efficacy of current prophylactic strategies for postthyroidectomy hypocalcemia. Teriparatide performed better than other interventions and would seem appropriate for deployment among high-risk populations.

List of junctions in both HPV negative and positive HNSCC

Correlations between the expression of DOCK5 variant and clinicopathological parameters in TCGA HPV negative HNSCC data

List of differentially expressed genes between patients with higher and lower expression of DOCK5 variant in TCGA HPV negative HNSCC data

Survival analysis of TCGA HPV positive tumors by ecDNA and hybrid classification.

Table S2. NOTCH4 and HEY1 high/low group clinical demographics in TCGA

List of relatively enriched pathways for each transcriptional component forming the Onco-GPS map.

Figure S1: CNR1 and CNR2 affect the proliferation of HPV positive HNSCC cells. Figure S2: High concentrations of cannabinoids inhibit the growth of HPV positive HNSCC cells. Figure S3: Inhibition of CNR1 and CNR2 attenuates the effect of CNR1 / CNR2 agonists on HPV positive HNSCC cells proliferation. Figure S4: CNR1 and CNR2 agonists or antagonists affect the migration of HPV positive HNSCC cells. Figure S5: Cannabinoid receptor agonist activates p38 MAPK pathway. Figure S6: Inhibition of p38 MAPK attenuates the effect of CNR1 / CNR2 agonists on HPV positive HNSCC cells proliferation. Figure S7: Expression of CNR1 and CNR2 in inducible shRNA stably transfected UM-SCC-47 cells. Figure S8: Survival between patients with and without cannabinoids exposure. Figure S9: Gene set enrichment analysis.

Table S1. HNSCC NOTCH mutation samples in TCGA

Figure S5. Comparison of HNSCC CSCs marker genes between NOTCH4, HEY1 high and low groups using the TCGA data set. ALDH1 expression in si-NOTCH4 and si-HEY1 cells.

Figure S1:Distribution of ASEs present within each tumor in TCGA HPV negative HNSCC cohort. Figure S2: Expression of DOCK5 variant within different head and neck regions. Figure S3: Relationship between DOCK5 variant expression and gene mutation. Figure S4: DOCK5 variant expression in HPV negative HNSCC cell lines. Figure S5: Differentially expressed gene and pathway analysis.

Figure S3. Sphere colony shapes. HEY1 expression in si-HEY1 cells and NOTCH4 expressions in sh-NOTCH4 cells

Survival analysis of Institutional HPV positive tumors by ecDNA and hybrid classification.