Immune checkpoint inhibitors and anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors with or without transarterial chemoembolization as first-line treatment for advanced hepatocellular carcinoma (CHANCE2201): a target trial emulation study.

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC. Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821. Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group. Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile. Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project.

Healthcare Utilization and Its Correlates in Comorbid Type 2 Diabetes Mellitus and Generalized Anxiety Disorder.

This study investigated the healthcare utilization and medical expenditure of type 2 diabetes mellitus (T2DM) patients with generalized anxiety disorder (GAD) and identified the associated factors. The healthcare utilization and expenditure of T2DM patients with (case group) and without (control group) GAD between 2002 and 2013 were examined using the population-based Taiwan National Health Insurance Research Database. Healthcare utilization included outpatient visits and hospitalization; health expenditure included outpatient, inpatient, and total medical expenditure. Moreover, nonpsychiatric healthcare utilization and medical expenditure were distinguished from total healthcare utilization and medical expenditure. The average healthcare utilization, including outpatient visits and hospitalization, was significantly higher for the case group than for the control group (total and nonpsychiatric). The results regarding differences in average outpatient expenditure (total and nonpsychiatric), inpatient expenditure (total and nonpsychiatric), and total expenditure (total and nonpsychiatric) between the case and control groups are inconsistent. Sex, age, income, comorbidities/complications, and the diabetes mellitus complication severity index were significantly associated with outpatient visits, medical expenditure, and hospitalization in the case group (total and nonpsychiatric). Greater knowledge of factors affecting healthcare utilization and expenditure in comorbid individuals may help healthcare providers intervene to improve patient management and possibly reduce the healthcare burden in the future.

Elevated Levels of Interleukin-18 are Associated with Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates the Th1 immune response. IL-18 exhibits anticancer activity and has been evaluated in clinical trials as a potential cancer treatment. However, evidence suggests that it may also facilitate the development and progression of some cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not been investigated. In this study, we found that the expression of IL-18 was significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18 expression was closely associated with lymphovascular invasion and lymph node metastases. Furthermore, compared to PTC patients with no nodal metastasis, serum IL-18 levels were slightly increased in patients with 1-4 nodal metastases and significantly elevated in patients with 5 or more nodal metastases. The pro-metastatic effect of IL-18 may be attributed to the simultaneous increase in the expression of S100A10, a known factor that is linked to nodal metastasis in PTC. In addition, the activation of several pathways, such as the intestinal immune network for lgA production and Staphylococcus aureus infection, may be involved in the metastasis process. Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore, suppressing the function of IL-18 rather than enhancing it appears to be a reasonable strategy for treating aggressive PTC.

Performance of Generative Artificial Intelligence in Dental Licensing Examinations.

OBJECTIVES: Generative artificial intelligence (GenAI), including large language models (LLMs), has vast potential applications in health care and education. However, it is unclear how proficient LLMs are in interpreting written input and providing accurate answers in dentistry. This study aims to investigate the accuracy of GenAI in answering questions from dental licensing examinations. METHODS: A total of 1461 multiple-choice questions from question books for the US and the UK dental licensing examinations were input into 2 versions of ChatGPT 3.5 and 4.0. The passing rates of the US and UK dental examinations were 75.0% and 50.0%, respectively. The performance of the 2 versions of GenAI in individual examinations and dental subjects was analysed and compared. RESULTS: ChatGPT 3.5 correctly answered 68.3% (n = 509) and 43.3% (n = 296) of questions from the US and UK dental licensing examinations, respectively. The scores for ChatGPT 4.0 were 80.7% (n = 601) and 62.7% (n = 429), respectively. ChatGPT 4.0 passed both written dental licensing examinations, whilst ChatGPT 3.5 failed. ChatGPT 4.0 answered 327 more questions correctly and 102 incorrectly compared to ChatGPT 3.5 when comparing the 2 versions. CONCLUSIONS: The newer version of GenAI has shown good proficiency in answering multiple-choice questions from dental licensing examinations. Whilst the more recent version of GenAI generally performed better, this observation may not hold true in all scenarios, and further improvements are necessary. The use of GenAI in dentistry will have significant implications for dentist-patient communication and the training of dental professionals.

Frequency dependent whole-brain coactivation patterns analysis in Alzheimer's disease.

Background: The brain in resting state has complex dynamic properties and shows frequency dependent characteristics. The frequency-dependent whole-brain dynamic changes of resting state across the scans have been ignored in Alzheimer's disease (AD). Objective: Coactivation pattern (CAP) analysis can identify different brain states. This paper aimed to investigate the dynamic characteristics of frequency dependent whole-brain CAPs in AD. Methods: We utilized a multiband CAP approach to model the state space and study brain dynamics in both AD and NC. The correlation between the dynamic characteristics and the subjects' clinical index was further analyzed. Results: The results showed similar CAP patterns at different frequency bands, but the occurrence of patterns was different. In addition, CAPs associated with the default mode network (DMN) and the ventral/dorsal visual network (dorsal/ventral VN) were altered significantly between the AD and NC groups. This study also found the correlation between the altered dynamic characteristics of frequency dependent CAPs and the patients' clinical Mini-Mental State Examination assessment scale scores. Conclusion: This study revealed that while similar CAP spatial patterns appear in different frequency bands, their dynamic characteristics in subbands vary. In addition, delineating subbands was more helpful in distinguishing AD from NC in terms of CAP.

Ultra-small Mo-Pt subnanoparticles enable CO2 hydrogenation at room temperature and atmospheric pressure.

We present a partially-oxidised bimetallic Mo-Pt subnanoparticle (Mo4Pt8Ox) enabling thermally-driven CO2 hydrogenation to CO at room temperature and atmospheric pressure. A mechanistic study explained the full catalytic cycle of the reaction from CO2 activation to catalyst reactivation. DFT calculations revealed that alloying with Mo lowers the activation barrier by weakening the CO adsorption. This finding could be a first step for low-energy CO2 conversion.

A Systematic Review of the Use of mHealth in Oral Health Education among Older Adults.

Oral diseases are largely preventable. However, as the number of older adults is expected to increase, along with the high cost and various barriers to seeking continuous professional care, a sustainable approach is needed to assist older adults in maintaining their oral health. Mobile health (mHealth) technologies may facilitate oral disease prevention and management through oral health education. This review aims to provide an overview of existing evidence on using mHealth to promote oral health through education among older adults. A literature search was performed across five electronic databases. A total of five studies were identified, which provided low to moderate evidence to support using mHealth among older adults. The selected studies showed that mHealth could improve oral health management, oral health behavior, and oral health knowledge among older adults. However, more quality studies regarding using mHealth technologies in oral health management, oral health behavior, and oral health knowledge among older adults are needed.

Criticality in transient behavior of coupled oscillator system toward chimera and synchronization.

Chimera states in spatiotemporal dynamical systems have been investigated in physical, chemical, and biological systems, while how the system is steering toward different final destinies upon spatially localized perturbation is still unknown. Through a systematic numerical analysis of the evolution of the spatiotemporal patterns of multi-chimera states, we uncover a critical behavior of the system in transient time toward either chimera or synchronization as the final stable state. We measure the critical values and the transient time of chimeras with different numbers of clusters. Then, based on an adequate verification, we fit and analyze the distribution of the transient time, which obeys power-law variation process with the increase in perturbation strengths. Moreover, the comparison between different clusters exhibits an interesting phenomenon, thus we find that the critical value of odd and even clusters will alternatively converge into a certain value from two sides, respectively, implying that this critical behavior can be modeled and enabling the articulation of a phenomenological model.

Study on the proportion of paste filling materials based on fluorogypsum.

A new type of paste filling material was created using fluorogypsum, a byproduct of hydrofluoric acid, as the raw material to address the issue of the filling material's high cost. The effects of five factors, including gangue, fly ash, fluorogypsum, lime content, and mass concentration on the physical and mechanical properties of filling material were also examined. In addition to analyzing slump and extension changes, the filler's mineral composition and microstructure were examined using SEM and XRD examinations. The results show that the best ratio of the developed filling material was 1000g coal gangue, 300g fly ash, 300g fluorogypsum, and 50g lime and mass concentration is 78%, and its compressive strength can reach 4-5MPa at 28 days. Raw materials such as gangue and fly ash will have a certain influence on the mechanical properties of the filling material. The hydration products of the developed filling material prepared by XRD and SEM were ettringite, calcium sulfate dihydrate, and calcium silicate hydrate gel. The new fluorogypsum-based paste filling material can be used to consolidate loose rock strata and fill goaf. It solves the problem of disposal of industrial waste fluoropgypsum and also solves the problem of coal mine gangue stacking, which has a far-reaching influence on ecological environment management.

Enhanced sensing of optomechanically induced nonlinearity by linewidth suppression and optical bistability in cavity-waveguide systems.

We study the enhanced sensing of optomechanically induced nonlinearity (OMIN) in a cavity-waveguide coupled system. The Hamiltonian of the system is anti-PT symmetric, with the two involved cavities being dissipatively coupled via the waveguide. The anti-PT symmetry may break down when a weak waveguide-mediated coherent coupling is introduced. However, we find a strong bistable response of the cavity intensity to the OMIN near the cavity resonance, benefiting from linewidth suppression caused by the vacuum induced coherence. The joint effect of optical bistability and the linewidth suppression is inaccessible by the anti-PT symmetric system involving only dissipative coupling. Due to that, the sensitivity measured by an enhancement factor is greatly enhanced by two orders of magnitude compared to that for the anti-PT symmetric model. Moreover, the enhancement factor shows resistance to a reasonably large cavity decay and robustness to fluctuations in the cavity-waveguide detuning. Based on the integrated optomechanical cavity-waveguide systems, the scheme can be used for sensing different physical quantities related to the single-photon coupling strength and has potential applications in high-precision measurements with systems involving Kerr-type nonlinearity.

Accuracy of Artificial Intelligence-Based Photographic Detection of Gingivitis.

OBJECTIVES: Gingivitis is one of the most prevalent plaque-initiated dental diseases globally. It is challenging to maintain satisfactory plaque control without continuous professional advice. Artificial intelligence may be used to provide automated visual plaque control advice based on intraoral photographs. METHODS: Frontal view intraoral photographs fulfilling selection criteria were collected. Along the gingival margin, the gingival conditions of individual sites were labelled as healthy, diseased, or questionable. Photographs were randomly assigned as training or validation datasets. Training datasets were input into a novel artificial intelligence system and its accuracy in detection of gingivitis including sensitivity, specificity, and mean intersection-over-union were analysed using validation dataset. The accuracy was reported according to STARD-2015 statement. RESULTS: A total of 567 intraoral photographs were collected and labelled, of which 80% were used for training and 20% for validation. Regarding training datasets, there were total 113,745,208 pixels with 9,270,413; 5,711,027; and 4,596,612 pixels were labelled as healthy, diseased, and questionable respectively. Regarding validation datasets, there were 28,319,607 pixels with 1,732,031; 1,866,104; and 1,116,493 pixels were labelled as healthy, diseased, and questionable, respectively. AI correctly predicted 1,114,623 healthy and 1,183,718 diseased pixels with sensitivity of 0.92 and specificity of 0.94. The mean intersection-over-union of the system was 0.60 and above the commonly accepted threshold of 0.50. CONCLUSIONS: Artificial intelligence could identify specific sites with and without gingival inflammation, with high sensitivity and high specificity that are on par with visual examination by human dentist. This system may be used for monitoring of the effectiveness of patients' plaque control.

Novel Indane Derivatives with Antioxidant Activity from the Roots of Anisodus tanguticus.

Four novel indane derivatives, anisotindans A-D (1-4), were isolated from the roots of Anisodus tanguticus. Their structures were established using comprehensive spectroscopic analyses, and their absolute configurations were determined by electronic circular dichroism (ECD) calculations and single-crystal X-ray diffraction analyses. Anisotindans C and D (3 and 4) are two unusual indenofuran analogs. ABTS•+ and DPPH•+ assays of radical scavenging activity reveal that all compounds (1-4) are active. Specifically, the ABTS•+ assay results show that anisotindan A (1) exhibits the best antioxidant activity with an IC50 value of 15.62 ± 1.85 µM (vitamin C, IC50 = 22.54 ± 5.18 µM).

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

Accuracy of artificial intelligence-designed single-molar dental prostheses: A feasibility study.

STATEMENT OF PROBLEM: Computer-aided design and computer-aided manufacturing (CAD-CAM) technology has greatly improved the efficiency of the fabrication of dental prostheses. However, the design process (CAD stage) is still time-consuming and labor intensive. PURPOSE: The purpose of this feasibility study was to investigate the accuracy of a novel artificial intelligence (AI) system in designing biomimetic single-molar dental prostheses by comparing and matching them to the natural molar teeth. MATERIAL AND METHODS: A total of 169 maxillary casts were obtained from healthy dentate participants. The casts were digitized, duplicated, and processed with the removal of the maxillary right first molar. A total of 159 pairs of original and processed casts were input into the Generative Adversarial Networks (GANs) for training. In validation, 10 sets of processed casts were input into the AI system, and 10 AI-designed teeth were generated through backpropagation. Individual AI-designed teeth were then superimposed onto each of the 10 original teeth, and the morphological differences in mean Hausdorff distance were measured. True reconstruction was defined as correct matching between the AI-designed and original teeth with the smallest mean Hausdorff distance. The ratio of true reconstruction was calculated as the Intersection-over-Union. The reconstruction performance of the AI system was determined by the Hausdorff distance and Intersection-over-Union. RESULTS: Data of validation showed that the mean Hausdorff distance ranged from 0.441 to 0.752 mm and the Intersection-over-Union of the system was 0.600 (60%). CONCLUSIONS: This study demonstrated the feasibility of AI in designing single-molar dental prostheses. With further training and optimization of algorithms, the accuracy of biomimetic AI-designed dental prostheses could be further enhanced.

Effects of technology-assisted interventions for people with dementia: A systematic review and meta-analysis.

PURPOSE: The use of technology-assisted interventions in dementia care contributes to increased communication, reduced burden on the caregivers, improved health outcomes, and improved expense management. Technology-assisted interventions can be provided remotely to monitor, improve, and enable home care, benefiting the health of both patients and caregivers. Despite increasing use, the effectiveness of technology-assisted interventions for dementia care remains uncertain, with studies reporting inconclusive findings subject to interpretation. Therefore, the current study investigated the available evidence to explore the efficacy of technology-assisted interventions for people with dementia. DESIGN: Systematic review and meta-analysis. METHODS: The study was preregistered with the PROSPERO international prospective register of systematic reviews using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided protocol. The primary search was conducted in eight databases from database inception to January 29, 2022. Using a random-effects model, the standardized mean differences (SMDs) with 95% confidence intervals (CIs) were synthesized to obtain pooled effect sizes (using Stata 16.0). The updated Cochrane Risk of Bias 2 tool (RoB-2) was used to evaluate the methodological quality of the studies. FINDINGS: A pooled analysis of 12 trials, including 584 people with dementia, showed more improvement associated with technology-assisted interventions compared with standard care, including in the domains of cognitive function (SMD = 0.39; 95% CI: 0.14 to 0.64; p < 0.001) and depression (SMD = -0.75; 95% CI: -1.33 to -0.17; p = 0.01). However, no significant effects were observed for activities of daily living (ADL) or quality of life. CONCLUSION: Technology-assisted interventions appear to improve cognitive function and reduce depression in people with dementia compared with standard care. CLINICAL RELEVANCE: This study may be used to demonstrate that interventions incorporating many modalities or technologies can be used to enhance dementia care, which may improve favorable outcomes when using technology-assisted interventions to remotely initiate appropriate activities for people with dementia. Because technology allows for simultaneous communication and access to shared multimedia, it removes environmental constraints and allows treatment to be administered remotely.

Regulation of Dracocephalum Moldavica total flavonoids on foaming and inflammatory response of RAW264. 7 maerophages / 中国药理学通报

Aim To investigate the effeets of Dracocephalum Moldavica total flavonoids (TFDM) on the foaming lipoprotein (ox-LDL), and to further elucidate the mechanism of anti-atherosclerosis (AS) of TFDM. Methods RAW264. 7 maerophages were cultured in vitro and induced to become foam cells by ox-LDL stimulation, and inflammation of mouse monocyte macrophage leukemia cells (RAW264. 7) induced by oxi-dized low density TFDM(25, 50, 100 mg • L"

Impact of immunosuppression intensified conditioning regimen for patients with strong positive pre-transplantation donor-specific anti-HLA antibodies (DSAs) undergoing haploidentical hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the efficacy of immunosuppression intensified conditioning regimen in patients who have strongly positive donor-specific Anti-HLA antibodies (DSAs) and received a haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Clinical data of 10 patients with strongly positive pretransplant DSAs (defined as MFI ≥10000) were retrospectively analyzed in this study. All of them received a haplo-HSCT in the Hematology Department of Shanghai Zhaxin Traditional Chinese & Western Medicine Hospital. Results: ① Of all ten patients, three were males, and seven were females, with a median age of 53.5 (36-64) years. Of the 10 patients, three were diagnosed with acute myeloid leukemia, two were myelodysplastic syndromes (MDS), two were chronic myelomonocytic leukemia (CMML), two were in an accelerated phase of chronic myeloid leukemia (CML-AP), and one was primary myelofibrosis (PMF). ② Conditioning regimen consisted of fludarabine (Flu) /busulfan (Bu) combined with whole-body irradiation (TBI) /cyclophosphamide (Cy). ③ On the seventh day after transplantation, the median pretransplant DSA level was MFI 15 999 (10 210-23 417) and 10 787 (0-22 720). ④ Eight patients acquired hematopoietic reconstitution; the median time of neutrophil engraftment was 14 (10-16) days; and 18 (14-20) days for platelet engraftment. After a median follow-up of 12.5 (1.5-27) months, primary graft failure was found in one patient and another with poor graft function. Seven patients remained in a disease remission state, and all were DSA-negative. Conclusions: An intensified immunosuppression conditioning regimen can efficiently decrease the level of donor-specific anti-HLA antibodies (DSAs), leading to good short-term efficacy.

A new elemane-type sesquiterpenoid glycoside from Curcuma phaeocaulis / 药学学报

To study the chemical constituents and their biological activities in the rhizomes of Curcuma phaeocaulis, silica gel column chromatography, reverse medium pressure liquid chromatography, preparative thin layer chromatography, and semi-preparative high performance liquid chromatography were used for isolation and purification and modern spectroscopic methods were used to determine the structure of the isolated compound. Moreover, the effect of the compound on the proliferation of HUVECs was determined by the MTT assay. A new elemane-type sesquiterpenoid glycoside was isolated from the n-butanol soluble fraction of 95% ethanolic extract of the rhizomes of Curcuma phaeocaulis. Its structure was identified as (1Z)-2-hydroxy-curzerenone 2-O-β-D-glucoside. It showed no inhibitory effect on the proliferation of HUVECs.