Table_1_Diagnostic efficiency of existing guidelines and the AI-SONIC™ artificial intelligence for ultrasound-based risk assessment of thyroid nodules.docx

IntroductionThe thyroid ultrasound guidelines include the American College of Radiology Thyroid Imaging Reporting and Data System, Chinese-Thyroid Imaging Reporting and Data System, Korean Society of Thyroid Radiology, European-Thyroid Imaging Reporting and Data System, American Thyroid Association, and American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi guidelines. This study aimed to compare the efficiency of the six ultrasound guidelines vs. an artificial intelligence system (AI-SONICTM) in differentiating thyroid nodules, especially medullary thyroid carcinoma.MethodsThis retrospective study included patients with medullary thyroid carcinoma, papillary thyroid carcinoma, or benign nodules who underwent nodule resection between May 2010 and April 2020 at one hospital. The diagnostic efficacy of the seven diagnostic tools was evaluated using the receiver operator characteristic curves.ResultsFinally, 432 patients with 450 nodules were included for analysis. The American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi guidelines had the best sensitivity (88.1%) and negative predictive value (78.6%) for differentiating papillary thyroid carcinoma or medullary thyroid carcinoma vs. benign nodules, while the Korean Society of Thyroid Radiology guidelines had the best specificity (85.6%) and positive predictive value (89.6%), and the American Thyroid Association guidelines had the best accuracy (83.7%). When assessing medullary thyroid carcinoma, the American Thyroid Association guidelines had the highest area under the curve (0.78), the American College of Radiology Thyroid Imaging Reporting and Data System guidelines had the best sensitivity (90.2%), and negative predictive value (91.8%), and AI-SONICTM had the best specificity (85.6%) and positive predictive value (67.5%). The Chinese-Thyroid Imaging Reporting and Data System guidelines had the best under the curve (0.86) in diagnosing malignant tumors vs. benign tumors, followed by the American Thyroid Association and Korean Society of Thyroid Radiology guidelines. The best positive likelihood ratios were achieved by the Korean Society of Thyroid Radiology guidelines and AI-SONICTM (both 5.37). The best negative likelihood ratio was achieved by the American Association of Clinical Endocrinologists/American College of Endocrinology/Associazione Medici Endocrinologi guidelines (0.17). The highest diagnostic odds ratio was achieved by the American Thyroid Association guidelines (24.78).DiscussionAll six guidelines and the AI-SONICTM system had satisfactory value in differentiating benign vs. malignant thyroid nodules.</p

Table_1_Association of Coffee, Tea, and Caffeine Consumption With All-Cause Risk and Specific Mortality for Cardiovascular Disease Patients.DOCX

AimThe aim of the study was to examine the relationship between coffee, tea, caffeine consumption and risk of all-cause death and cardiovascular disease (CVD) death in CVD population.MethodsThis cohort study included 626 CVD participants aged ≥18 years old who derived from the National Health and Nutrition Examination Surveys (NHANES) database 2003–2006. The end time of follow-up was 2015, and with a median follow-up time of 113.5 (63, 133) months. CVD death was defined as a death caused by congestive heart failure (CHF), coronary heart disease (CHD), angina pectoris, heart attack or stroke. Cox model and competitive-risk model were used to explore the relationship of coffee, tea, caffeine, decaffeinated coffee/tea on the risk of the all-cause death and CVD death for CVD population, respectively. Additionally, we explored the effect of urinary caffeine and caffeine metabolites on all-cause death.ResultsAll patients were divided into survival group (n = 304), non-CVD death group (n = 223), and CVD death group (n = 99). The incidence of all-cause death and CVD death was ~51.44 and 15.81% in the study. After adjusting age, body mass index (BMI), cancer, estimated glomerular filtration rate (eGFR), energy, the history of CVD medications, carbohydrate and family income to poverty ratio (PIR), the results suggested coffee, caffeine, iced tea and hot tea consumption (≥4 cups per day) were associated with an increased risk of the all-cause death in CVD patients; while hot tea (1–3 cups per day), decaffeinated coffee/iced tea/hot tea could reduce the risk of the all-cause death. Likewise, coffee, caffeine, iced tea (≥4 cups per day), hot tea, decaffeinated iced tea/ hot tea (Always) could enhance the risk of the CVD death in CVD population. We also found that 1-methylxanthine showed a significant positive association on the risk of all-cause death in CVD population.ConclusionOur study indicated that higher consumption of coffee, tea and caffeine could increase the risk of all-cause and CVD death for CVD patients.</p

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention

Double-Cross-Linked Hydrogel with Long-Lasting Underwater Adhesion: Enhancement of Maxillofacial In Situ and Onlay Bone Retention

Bone retention is a usual clinical problem existing in a lot of maxillofacial surgeries involving bone reconstruction and bone transplantation, which puts forward the requirements for bone adhesives that are stable, durable, biosafe, and biodegradable in wet environment. To relieve the suffering of patients during maxillofacial surgery with one-step operation and satisfying repair, herein, we developed a double-cross-linked A-O hydrogel named by its two components: [(3-Aminopropyl) methacrylamide]-co-{[Tris(hydroxymethyl) methyl] acrylamide} and oxidated methylcellulose. With excellent bone adhesion ability, it can maintain long-lasting stable underwater bone adhesion for over 14 days, holding a maximum adhesion strength of 2.32 MPa. Schiff-base reaction and high-density hydrogen bonds endow the hydrogel with strong cohesion and adhesion performance as well as maneuverable properties such as easy formation and injectability. A-O hydrogel not only presents rarely reported long-lasting underwater adhesion of hard tissue but also owns inherent biocompatibility and biodegradation properties with a porous structure that facilitates the survival of bone graft. Compared to the commercial cyanoacrylate adhesive (3 M Vetbond Tissue Adhesive), the A-O hydrogel is confirmed to be safer, more stable, and more effective in calvarial in situ bone retention model and onlay bone retention model of rat, providing a practical solution for the everyday scenario of clinical bone retention

Low-Swelling Adhesive Hydrogel with Rapid Hemostasis and Potent Anti-Inflammatory Capability for Full-Thickness Oral Mucosal Defect Repair

Full-thickness oral mucosal defects are accompanied by significant blood loss and frequent infections. Instead of conventional therapies that separate hemostasis and anti-inflammation in steps, emerging hydrogels can integrate multiple functions for the successive process after defect including hemostasis/inflammatory phase, proliferative phase, and remodeling phase. However, these functions can be easily compromised by rapid swelling and degradation of hydrogels in wet oral environment. Herein, a low-swelling adhesive hydrogel with rapid hemostasis and potent anti-inflammatory capability was developed using a dual cross-linking strategy as well as a safe and facile fabrication method. It was double cross-linked hydrogel consisting of gelatin methacrylate (GelMA), nanoclay, and tannic acid (TA) (referred to as GNT). GNT hydrogel exhibited low-swelling (one-eighth of that of GelMA), excellent stretchability (211.86%), and good adhesive properties (5 times the adhesive strength of GelMA). Physicochemical characterization illuminated the close interactions among the three components. A systematic investigation of the therapeutic effects of GNT hydrogels was performed. In vitro and in vivo experimental results demonstrated the potent hemostatic property and excellent antibacterial and anti-inflammatory effects of GNT hydrogels. The RNA sequencing analysis results for rat full-thickness oral mucosal samples showed that GNT reduced inflammation levels by down-regulating the expression of multiple inflammation-related pathways, including TNF and IL-17 pathways. It also enhanced the expression levels of tissue regeneration-related genes and thus accelerated defective mucosal repair. More importantly, the therapeutic effects of GNT were superior to those of a commercial oral tissue repair membrane when applied for full-thickness oral mucosal defect repair in rabbits. In summary, the prepared low-swelling adhesive GNT hydrogel with rapid hemostasis and potent anti-inflammatory is a promising therapy for full-thickness mucosal defect in the moist and dynamic oral environment

Low-Swelling Adhesive Hydrogel with Rapid Hemostasis and Potent Anti-Inflammatory Capability for Full-Thickness Oral Mucosal Defect Repair

Full-thickness oral mucosal defects are accompanied by significant blood loss and frequent infections. Instead of conventional therapies that separate hemostasis and anti-inflammation in steps, emerging hydrogels can integrate multiple functions for the successive process after defect including hemostasis/inflammatory phase, proliferative phase, and remodeling phase. However, these functions can be easily compromised by rapid swelling and degradation of hydrogels in wet oral environment. Herein, a low-swelling adhesive hydrogel with rapid hemostasis and potent anti-inflammatory capability was developed using a dual cross-linking strategy as well as a safe and facile fabrication method. It was double cross-linked hydrogel consisting of gelatin methacrylate (GelMA), nanoclay, and tannic acid (TA) (referred to as GNT). GNT hydrogel exhibited low-swelling (one-eighth of that of GelMA), excellent stretchability (211.86%), and good adhesive properties (5 times the adhesive strength of GelMA). Physicochemical characterization illuminated the close interactions among the three components. A systematic investigation of the therapeutic effects of GNT hydrogels was performed. In vitro and in vivo experimental results demonstrated the potent hemostatic property and excellent antibacterial and anti-inflammatory effects of GNT hydrogels. The RNA sequencing analysis results for rat full-thickness oral mucosal samples showed that GNT reduced inflammation levels by down-regulating the expression of multiple inflammation-related pathways, including TNF and IL-17 pathways. It also enhanced the expression levels of tissue regeneration-related genes and thus accelerated defective mucosal repair. More importantly, the therapeutic effects of GNT were superior to those of a commercial oral tissue repair membrane when applied for full-thickness oral mucosal defect repair in rabbits. In summary, the prepared low-swelling adhesive GNT hydrogel with rapid hemostasis and potent anti-inflammatory is a promising therapy for full-thickness mucosal defect in the moist and dynamic oral environment