Evaluation Criteria Research Articles

Parameter estimation of PEM fuel cells using metaheuristic algorithms

Developing an accurate model for precise parameter estimation is crucial for the design of polymer electrolyte membrane fuel cells (PEMFC). While many studies can meet the evaluation criteria for parameter estimation, there is a significant physical inconsistency when applying the Generalized Steady State of Electrochemical Model (GSSEM) prediction in the optimization framework. This study aims to address this inconsistency by adding necessary constraints to the optimization model. It employs the Artificial Hummingbird Algorithm (AHA) and Lévy flight improvement to find unknown parameters by minimizing the sum of squared errors (SSE). The proposed method has been rigorously tested with seven PEMFC cases, demonstrating its robustness and superior accuracy compared to alternative approaches. Notably, the cathode charge transfer coefficient exhibits zero relative percent difference (RPD) between the two sources, confirming its physical consistency. Furthermore, the proposed constrained optimization model lays the groundwork for achieving consistent parameter estimation results for PEMFC when utilizing GSSEM.

A phase II study of osimertinib in patients with NSCLC harboring EGFR exon 20 insertion: A multicenter trial of the Korean Cancer Study Group (LU17-19)

BackgroundEpidermal growth factor receptor (EGFR) exon 20 insertions account for up to 10% of all EGFR mutations. Clinical outcomes in patients receiving approved EGFR exon 20 insertion–specific inhibitors have been variable. Although osimertinib has demonstrated antitumor activity in clinical trials, its clinical efficacy and translational potential remain to be determined in non-small cell lung carcinoma (NSCLC) with EGFR exon 20 insertion. MethodsIn this multicenter phase II study, patients with advanced NSCLC harboring EGFR exon 20 insertions for whom the standard chemotherapy failed received 80 mg osimertinib once daily. The primary endpoint was the investigator-assessed objective response rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety profile. ResultsAmong 15 patients enrolled at stage 1, the best response was most commonly disease stabilization (73.3 %), which did not meet the stage 1 threshold (objective response ≥ 2/15). As of data cutoff, two patients remained on the treatment. The median PFS and OS were 3.8 (95 % confidence interval [CI] = 1.7–5.5) months and 6.5 (95 % CI = 3.9–not reached) months, respectively. Adverse events (≥grade 3) were anemia, hypercalcemia, and pneumonia (13.3 % each), and asthenia, femur fracture, increased alkaline phosphate, hyperkalemia, bone pain, and azotemia (6.7 % each). Pre-existing EGFR C797S mutation detected in plasma limited the efficacy of osimertinib. ConclusionOsimertinib at 80 mg once daily had limited efficacy and mostly showed disease stabilization with an acceptable safety profile in advanced NSCLC harboring EGFR exon 20 insertions.ClinicalTrials.govIdentifier: NCT03414814.

First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors

Rationale of the trialAlthough the use of engineered T cells in cancer immunotherapy has greatly advanced the treatment of hematological malignancies, reaching meaningful clinical responses in the treatment of solid...

Evaluation of Dynamic Multi-Leaf Collimator (MLC) versus Fixed MLC for Intensity Modulated Radiotherapy (IMRT) Using the Agility 160-Leaf Collimator.

This study aimed to evaluate the efficacy of static or step-and-shoot intensity-modulated radiotherapy (ssIMRT) and dynamic intensity-modulated radiotherapy (dIMRT) delivery techniques for various treatment sites. The treatment planning system (TPS) was utilized to develop optimal treatment plans for twenty-seven patients selected for this comparative study, including nine with head and neck cancer, nine with prostate cancer, and nine with cervical cancer. The prescribed doses were 7000cGy/33fr, 7425cGy/33fr, and 5000cGy/25fr for the nasopharynx, prostate, and cervix cases, respectively, in both ssIMRT and dIMRT delivery techniques. Plans were generated using the Monaco treatment planning system with a 6MV photon beam and nine equidistant fields. Plan evaluation criteria included dose-volume histogram analysis, dose homogeneity index, conformity index, radiation delivery time, and monitor unit requirements. All plans were optimized to ensure that 98% of the planning target volume (PTV) received at least 95% of the prescribed dose, while meeting the planning objectives for organs at risk. dIMRT plans exhibited superior conformity (CI = 0.85 ± 0.05) compared to ssIMRT plans (CI = 0.79 ± 0.08), with statistically significant differences (P < 0.01). Inhomogeneity within the PTV was significantly higher in ssIMRT plans (HI = 0.10 ± 0.02) compared to dIMRT plans (HI = 0.09 ± 0.01), with a significant difference (P < 0.01). Delivery time per fraction was significantly lower in dIMRT compared to ssIMRT (P < 0.01). Furthermore, dIMRT plans required a higher mean monitor unit value (1335.4 ± 172.2) compared to ssIMRT plans (974.4 ± 133.6) with a significant difference (P < 0.001). The findings of this study indicate that dIMRT provides improved target coverage, homogeneity, and conformity while reducing treatment delivery time compared to ssIMRT.

Evaluating Safety and Clinical Activity of Front-line Treatment with Cadonilimab plus Chemotherapy in Advanced/Metastatic Nonsmall Cell Lung Cancer Harboring STK11 Genetic Aberration: A Protocol of Phase II Study

BackgroundCadonilimab is a first-in-class bispecific PD-1/CTLA-4 antibody. Serine/threonine kinase (STK11) mutation was shown to be related to low PD-L1 expression and objective response rate (ORR) in nonsmall cell lung cancer (NSCLC), resulting in poor progression-free survival (PFS) and overall survival (OS). Herein, we hypothesized that combining cadonilimab with chemotherapy could enhance antitumor immunity and extend survival in these patients. Consequently, we designed this study to explore the clinical activity and safety of cadonilimab combined with chemotherapy in patients with advanced/metastatic NSCLC harboring STK11 alteration. Trial designThis single-center, open-label, single-arm phase II trial is conducted at the first affiliated hospital of Guangzhou Medical University. Treatment-naïve advanced/metastatic NSCLC patients harboring STK11 mutation will be enrolled in this study. Eligible patients will receive either cadonilimab (10mg/kg on Day 1) plus pemetrexed (500 mg/m2) and carboplatin (AUC = 5) for nonsquamous NSCLC or abraxane (100 mg/m2) and carboplatin (AUC = 5) for squamous NSCLC for 4 cycles, followed by maintenance therapy (cadonilimab plus pemetrexed or abraxane). The treatment will be discontinued when disease progression, intolerability to cadonilimab, and/or chemotherapy occurs. Measurable lesions were assessed according to the Response Evaluation Criteria in Solid Tumors (1.1). The main endpoint is ORR and safety. Subordinate endpoints include PFS, disease control rate, and duration of response. ResultsThe study commenced enrolment in September 2023, with preliminary findings regarding the primary endpoint anticipated by January 2025.

Application of artificial intelligence-based magnetic resonance imaging in diagnosis of cerebral small vessel disease.

Cerebral small vessel disease (CSVD) is an important cause of stroke, cognitive impairment, and other diseases, and its early quantitative evaluation can significantly improve patient prognosis. Magnetic resonance imaging (MRI) is an important method to evaluate the occurrence, development, and severity of CSVD. However, the diagnostic process lacks quantitative evaluation criteria and is limited by experience, which may easily lead to missed diagnoses and misdiagnoses. With the development of artificial intelligence technology based on deep learning, the extraction of high-dimensional features in imaging can assist doctors in clinical decision-making, and it has been widely used in brain function and mental disorders, and cardiovascular and cerebrovascular diseases. This paper summarizes the global research results in recent years and briefly describes the application of deep learning in evaluating CSVD signs in MRI imaging, including recent small subcortical infarcts, lacunes of presumed vascular origin, vascular white matter hyperintensity, enlarged perivascular spaces, cerebral microbleeds, brain atrophy, cortical superficial siderosis, and cortical cerebral microinfarct.

Study on the carbon migration from fossil fuel to liquid methanol by integrating solar energy into the advanced power system

Coupling advanced systems with carbon dioxide (CO2) capture and CO2-to-methanol technologies is a possible solution for both greenhouse gas emissions and low-carbon use of fossil energy. In view of this, this study further develops an advanced molten carbonate fuel cell (MCFC)/steam turbine (ST) hybrid system. The existing single pressurized liquefaction for storing CO2 is expanded to co-exist with liquid methanol synthesis for storing CO2. In detail, the valid thermodynamic models are presented, and the evaluation criteria for energy conversion are described. The case study shows that the energy efficiency of the referenced MCFC/ST system reaches about 62.60%, without cutting down this performance, the photovoltaic methanol efficiency is in the range of about 54% to 63%, which is at a current leading level. This study also investigates the effect of oxygen purity in cryogenic air separation unit (ASU), hydrogen production pressure of proton membrane electrolytic cells (PEMEC), and incident irradiation on CO2-to-methanol conversion. The results indicate that O2 purity of 0.97 in ASU, H2 production pressure of 13.6 bar in PEMEC and a dual-axis tracking method is recommended. These findings provide theoretical guidance for improving the CO2-to-methanol performance and providing a possible solution to the storage of intermittent renewable electricity.

A Randomized, Double-Blind, Phase III Study in India for Comparing Efficacy, Safety, and PK of ZRC-3277 (Pertuzumab Biosimilar) With Perjeta® in Patients With HER2-Positive Metastatic Breast Cancer

IntroductionTo evaluate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of ZRC-3277 (pertuzumab biosimilar) with Perjeta® (pertuzumab) in previously untreated patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and MethodsThis phase III, multicenter, double-blind study across 38 sites in India randomized (1:1) patients with HER2-positive MBC in either the ZRC-3277 or Perjeta® group. Both groups also received trastuzumab and docetaxel. Of 268 enrolled patients, mITT population had 243 patients (119 and 124 in the ZRC-3277 and Perjeta® groups, respectively). The primary objective was to compare the between-group objective response rate (ORR) after 6 cycles of treatment. ORR was determined by evaluating scans of computed tomography or magnetic resonance imaging following Response Evaluation Criteria in Solid Tumor (RECIST 1.1). Two-sided 95% confidence interval (95% CI) for the difference in ORR was determined to evaluate the noninferiority of ZRC-3277 to Perjeta®. The secondary outcomes included the assessment of PK, immunogenicity, and safety between the 2 groups. ResultsIn the mITT population, 104 (87.39%) and 114 (91.94%) participants achieved the ORR in the ZRC-3277 and Perjeta® groups, respectively. For predefined -15% noninferiority margin, obtained 2-sided 95% CIs (−12.19%, 3.11%) for the difference in ORR (−4.55%) between the 2 groups demonstrated the noninferiority of ZRC-3277 to Perjeta®. PK, immunogenicity, and safety were not significantly different between the 2 groups. ConclusionEfficacy, PK, immunogenicity, and safety profiles of ZRC-3277 was found to be similar to those of Perjeta®.

Outcomes in the Asian subgroup of the phase III randomised HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma

Background & AimsIn the global, phase III HIMALAYA study in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) improved overall survival (OS) vs. sorafenib; durvalumab was noninferior to sorafenib. HBV is the predominant HCC aetiology in most of Asia vs. HCV or nonviral aetiologies in Western countries and Japan. This analysis evaluated safety and efficacy outcomes for STRIDE and durvalumab monotherapy vs. sorafenib, in HIMALAYA participants enrolled in Asia, excluding Japan. MethodsIn HIMALAYA, participants were randomised to STRIDE, durvalumab, or sorafenib. The Asian subgroup in this analysis included participants enrolled in Hong Kong, India, South Korea, Taiwan, Thailand, and Vietnam. OS, objective response rate (ORR; per Response Evaluation Criteria in Solid Tumors, version 1.1), and safety were assessed in the Asian subgroup and in an exploratory subgroup of participants in Hong Kong and Taiwan. ResultsThe Asian subgroup included 479 participants randomised to STRIDE (n=156), durvalumab (n=167), or sorafenib (n=156). OS was improved for STRIDE vs. sorafenib (HR 0.68; 95% CI 0.52-0.89]). The OS HR for durvalumab vs. sorafenib was 0.83 (95% CI 0.64-1.06). In Hong Kong and Taiwan (n=141), OS HRs for STRIDE vs. sorafenib and durvalumab vs. sorafenib were 0.44 (95% CI 0.26-0.77) and 0.64 (95% CI 0.37-1.08), respectively. In the Asian subgroup, ORR (including unconfirmed responses) was numerically higher for STRIDE (28.2%) and durvalumab (18.6%) vs. sorafenib (9.0%), and Grade 3/4 treatment-related adverse events were numerically lower for STRIDE (19.9%) and durvalumab (13.3%) vs. sorafenib (30.5%). ConclusionsSTRIDE improved outcomes vs. sorafenib in the Asian subgroup. These results support the benefits of STRIDE for participants with uHCC globally, including the Asia-Pacific region. Clinical trial numberNCT03298451 Impact and implicationsThe global, phase III HIMALAYA study found that the STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen improved overall survival (OS), including long-term OS, vs. sorafenib, and that durvalumab monotherapy was noninferior to sorafenib in participants with unresectable hepatocellular carcinoma (uHCC). However, there are differences in the aetiology and clinical practices related to HCC in parts of Asia, compared to Western countries and Japan, which could lead to differences in treatment outcomes between these regions. The results of this analysis demonstrate the benefits of STRIDE for participants in the Asia-Pacific region, consistent with the full, global study population. Overall, these findings continue to support the use of STRIDE in a diverse population, reflective of uHCC globally.

Organ-Specific Tumor Response to Enfortumab Vedotin for Metastatic Urothelial Carcinoma: A Multicenter Retrospective Study

IntroductionTo evaluate the organ-specific therapeutic effect of enfortumab vedotin (EV) after chemotherapy and immunotherapy failed for advanced urothelial carcinoma. Materials methodsAt 6 institutions between December 2021 and July 2023, we retrospectively analyzed patients with metastatic upper and lower urinary tract cancer who received EV monotherapy after platinum-based chemotherapy and immune checkpoint blockade therapy. Objective response rate (ORR) and organ-specific response rate (OSRR) were evaluated according to the Response Evaluation Criteria in Solid Tumors, version 1.1. ResultsThis study analyzed 58 patients with 210 tumor lesions, of which 24% were females and 48% had upper urinary tract cancer. The ORR and disease control rate were 53.5% and 74.1%. Moreover, we found 15 target lesions in the primary site, 7 in local recurrence, 93 in the lymph nodes, 46 in the lung, 29 in the liver, and 20 in the bone, with OSRRs of 40%, 71.4%, 61.1%, 70.6%, 90.9%, and 18.2%, respectively. Over time from baseline, the reduction rate (median) in tumor burden was 50% or more in the lymph node, lung, and liver metastases. ConclusionThe organ-specific tumor response to EV in patients with metastatic urothelial carcinoma was almost favorable. The antitumor activity of EV monotherapy may be less in bone metastasis than in other organ sites. Conversely, EV showed remarkably high efficacy against liver metastasis.

Экспертные подходы к оценке организации оказания медицинской помощи по профилю «челюстно-лицевая хирургия» на региональном уровне.

Evaluating the effectiveness of healthcare services is an urgent task because it allows us to identify and analyze the existence of health potential risks and organizational difficulties, and it also assesses in developing preventive measures to eliminate them. Currently, there is no regional unified system to evaluate the existing organizational issues of the regional oral and maxillofacial surgery service. Purpose: accordingly, this study aims to determine an evaluation criterion for the organization of regional oral and maxillofacial surgery service and use an expert assessments method. Materials and methods. We conducted a study in 2019–2022 on the base medical organizations of the Volga Federal District using an expert evaluation method. In the first phase, we selected 60 participants in the organization of oral and maxillofacial surgery service, both at the level of the medical organization and at the regional and federal levels. The experts proposed 64 criteria for evaluating the organization of regional oral and maxillofacial services, which were included in the map of expert evaluation. In the second phase, we selected 21 experts by the inclusion criteria and scored the proposed criteria. To evaluate the questionnaire results, 95 percent of the confidence interval (MDI) was calculated using Fisher’s method. Kendall’s coefficient of concordance (W) was used to determine the consistency of experts’ views on the importance of the criteria chosen. The estimation of the concordance coefficient was considered relevant if the probability of the first type of error was less than 0.05. Results and discussion. Analysis of the results and their ranking by experts made it possible to identify the 20 most significant indicators and observe more than 8 points and a concordance correlation coefficient of 0.7 or more. According to experts, for organizing the provision of oral and maxillofacial surgery service, the most important issue is the availability of regulatory documents, regulations for routing patients, rules for the provision and infrastructure of oral and maxillofacial surgery service, the recommended standard of medical equipment and recommended staffing standards, staffing, the availability of emergency round-the-clock dental service, equipping a panel of devices, sets of surgical instruments for surgical interventions in the maxillofacial region, organizing the provision of care in oral and maxillofacial surgery for children and the disabled in the departments, regular monitoring of patient satisfaction by surveys. Conclusions. Significant criteria for assessing the organization of regional maxillofacial surgical service were identified, which made it possible to identify existing shortcomings in the organization of activities and outline ways to eliminate them.

Interference effect on super large twin cooling towers exposed to stationary tornado-like vortices

A comprehensive investigation was conducted aiming at the interference effects on wind pressure distribution, aerodynamics characteristics, structural stability and reinforcement areas of super large twin cooling towers exposed to tornado-like vortices, and the effects of swirl ratios of tornados, grouped tower layouts, and relative central distances between the towers and the tornado were analysed based on a tornado-like vortex simulator. Two types of rigid model wind tunnel experiments were constructed for base forces and wind pressure distribution measurements. The experimental results demonstrate that the interference effects on base forces and local wind pressures are significantly influenced by the swirl ratios, central distances, and grouped tower layouts, etc. Moreover, the layout with a tornado located on the side of tandem twin cooling towers (along with the tornado translation direction being perpendicular to the central axis of the tandem combined twin cooling towers) is the most unfavourable, resulting in obvious amplification effects on base forces and local wind pressures compared with an isolated tower, and the maximum of interference factors (IFs) is 1.68 and 1.41 for the along-wind total wind force coefficient and minimal net mean pressure coefficient respectively. Subsequently, local stability indices and time-variant dynamic reinforcement envelopes were selected as the other evaluation criteria for estimating the interference effects on the cooling towers exposed to the tornado-like vortices, and the interference effects result in enlargements of the structural responses with the maximal IF of 1.36 for the inside meridional reinforcement. Finally, the various interference criteria at aerodynamic loading and structural reinforcement aspects were contrastive analysed, showing that the criterion of time-variant dynamic reinforcement area envelopes is a more reasonable criterion for evaluating the interference effects on the super large cooling towers exposed to the tornado-like vortices. This investigation aims to contribute to a better understanding of the wind-related effects of the cooling towers exposed to extreme non-synoptic winds, particularly tornadic vortex impacts.

METHODOLOGY AND SOFTWARE FOR SEARCHING FOR ANOMALIES IN TELEMETRY DATA OF A SOLAR POWER PLANT BASED ON AN ARTIFICIAL NEURAL NETWORK - AUTOENCODER

Objectives: Development of a new methodology and software for detecting anomalies in the operation of PV-modules based on an artificial neural network type autoencoder trained on telemetry data from a solar power plant. Methods: The methodology is based on statistical studies of deviations of measured from recovered neural network values of current and voltage of all PV-modules of the power plant. Additionally, a criterion for evaluating the presence of faults in the operation of the PV-module based on statistical studies is introduced. Results: Using the developed methodology and software for anomaly detection in telemetry data over six months of observations with different evaluation criteria, from 14 to 45 anomalies were detected in 33 PV-modules. All cases were analyzed for the causes of the anomalies in the operation of the PV-modules. Conclusion: It was established that using four standard deviations for the daily average measured values of current ∆I and voltage ∆U as a criterion for detecting anomalies allows identifying faulty PV-modules. Using three and two standard deviations as a criterion for detecting anomalies helps identify reduced efficiency in PV-module operation due to degradation, excessive shading, and other factors.

Choice of machine learning models for predicting the development of psychological disorders in people with hypothireosis and hyperthireosis

The subject of this article is endocrinological diseases, namely, the analysis of complications in people with hypothyroidism and hyperthyroidism. It is known that these diseases occur asymptomatically or in a way that may indicate other possible diseases, so people do not suspect what exactly they are suffering from. Later, the diseases develop to the point where complications occur in the body, some of the most dangerous of which are psychological disorders: depression, mania, aggression, etc. Therefore, the aim of this work is to develop methods for predicting the occurrence of neurological deterioration in people who have already been diagnosed with endocrinological diseases. The article solves the problem of choosing the best models for predicting the occurrence of psychological disorders in people with endocrinological problems. Machine learning methods that are widespread in the medical field were analyzed and one of them was chosen that more optimally solves all the tasks of the task. The selection of criteria took into account potential problems with medical and psychological data. The method used was linear additive convolution, which is used to select the best alternatives according to the results, with the Pareto principle, which aims to exclude less suitable alternatives because all the features have lower values than in other options. For the experiment, all features were converted into quantitative ones to calculate convolution values. The evaluation criteria are given in the paper. The following results were obtained: the forecasting model in further study of this problem will be a random forest. Conclusions: the forecasting methods were studied and a more optimal model was chosen using linear additive convolution, namely, the random forest algorithm, its advantages and disadvantages were considered. A more detailed analysis of its development will be presented in the following articles. A mathematical description of the chosen forecasting method is provided, which includes potential ways of implementation and steps for building an algorithm for one of these methods.

Метод оценки критериев оптимизации системы электробезопасности в инфраструктуре села

The article provides an analysis of the state of energy availability and equipment of electric installations for infrastructure facilities in rural settlements. The main type of technogenic hazards is marked – the electrical hazard that occurs in emergency modes of operation of electrical installations. The conditions for solving the safety problem and choosing the optimal variant of the electrical safety system are given. The indicators of the technical efficiency of the electrical safety system are determined, characterized by the likelihood of electrical injury to a person and the likelihood of a fire in electrical installations at facilities. The choice of the most appropriate options for the use of electrical protection equipment, providing for the joint use of automatic switches and protective shutdown devices, was made as a result of comparing the likelihood of electrical injury and fire with a normalized risk level of electrical and fire safety. A method for optimizing the electrical safety system is considered according to two particular criteria representing the average values of the probabilities of electrical injury and fire with the equivalence of their values. The task of optimizing the security system is indicated, which consists in constructing a vector criterion of optimality and converting it into a scalar criterion using the "assignment" method to obtain a normalized partial criterion. The normalized private criteria of electrical and fire safety are determined using a scalar criterion for the selection of electrical protection options for an agricultural facility. An algorithm for evaluating the effectiveness of the electrical safety system in dangerous situations of electrical injuries has been built. The description of the construction of an algorithm for modeling the state of fire safety of the system in the event of fires in electrical installations is given. A comprehensive assessment of the normalized criterion for optimizing the electrical safety system was obtained according to two normalized criteria for electrical and fire safety and the choice of optimal electrical protection options at the studied facility. Keywords: TECHNOGENIC HAZARD, ELECTRICAL INSTALLATION, ACCIDENT, ELECTRICAL INJURY, TECHNICAL EFFICIENCY, EVALUATION CRITERIA, OPTIMIZATION OF ELECTRICAL SAFETY SYSTEM, ELECTRICAL PROTECTION

서비스형 버추얼 휴먼의 감성적 디자인 분석 및 UX평가

As the digitization of museums accelerates, service-oriented virtual humans are leading the museum industry's entry into the metaverse. However, compared to other countries, the application of service-oriented virtual humans in Chinese museums is still in its early stages. This study explores ways to enhance the user experience of service-oriented virtual humans in museums through emotional design and UX evaluation. Firstly, the study identifies emotional design elements and UX evaluation factors through prior research. Secondly, it discusses seven elements—visual, auditory, storytelling, interaction, pleasure, satisfaction, and convenience—across the three levels of emotional design(instinctive, behavioral, and reflective) using representative cases from Chinese museums. Thirdly, based on prior research, the study establishes UX evaluation criteria and selects expert interview subjects, identifying key factors affecting user experience: meaningful, pleasurable, convenient, usable, reliable, and interaction. Finally, the study synthesizes insights from case analysis and interview results. From an emotional design perspective, virtual humans are modeled after real people and incorporate traditional Chinese cultural elements in their appearance, using natural dialogue and emotional expression. They explain the background and history of artifacts and enhance participation through diverse interaction methods. Rich knowledge and engaging interactions attract visitor attention and enhance enjoyment. In terms of UX evaluation, diverse interactions increase immersion, while natural language and visual/auditory elements stimulate curiosity and engagement. Concise information delivery and voice interaction improve convenience. Functions such as inquiry response and route planning meet individual needs. Natural voice interaction and data security enhance trust, while improved voice recognition accuracy and facial expression consistency enhance user immersion and interaction experience.

Tislelizumab in previously treated, locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors.

The open-label, phase II RATIONALE-209 study evaluated tislelizumab (anti-programmed cell death protein 1 antibody) as a tissue-agnostic monotherapy for microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR) tumors. Adults with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled. Patients received tislelizumab 200 mg intravenously every 3 weeks. Objective response rate (ORR; primary endpoint), duration of response (DoR), and progression-free survival (PFS) were assessed by independent review committee (Response Evaluation Criteria in Solid Tumors v1.1). Eighty patients were enrolled and treated; 75 (93.8%) patients had measurable disease at baseline. Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease (n=79; 98.8%). At primary analysis (data cutoff July 8, 2021; median follow-up 15.2 months), overall ORR [46.7%; 95% confidence interval (95% CI), 35.1-58.6; one-sided P<0.0001] and ORR across tumor-specific subgroups [colorectal (n=46): 39.1% (95% CI, 25.1-54.6); gastric/gastroesophageal junction (n=9): 55.6% (95% CI, 21.2-86.3); others (n=20): 60.0% (95% CI, 36.1-80.9)] were significantly greater with tislelizumab vs. a prespecified historical control ORR of 10%; five (6.7%) patients had complete responses. Median DoR, PFS, and overall survival were not reached with long-term follow-up (data cutoff December 5, 2022; median follow-up 28.9 months). Tislelizumab was well tolerated with no unexpected safety signals. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 53.8% of patients; 7.5% of patients discontinued treatment due to TRAEs. Tislelizumab demonstrated a significant ORR improvement in patients with previously treated, locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

Hepatic artery infusion pump (HAIP) therapy in combination with targeted delivery of IL-12 for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma: a phase II trial protocol.

Treatment of advanced liver tumors remains challenging. Although immune checkpoint inhibition has revolutionized treatment for many cancers, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. Investigation into additional immunomodulatory therapies for these cancers is needed. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with robust anti-tumor activity, but systemic adverse effects largely terminated therapeutic development of recombinant human IL-12 (rhIL-12). PDS01ADC is a novel human monoclonal antibody (NHS76) conjugated to two IL-12 heterodimers with established safety in phase I trials. The NHS76 antibody specifically targets histone/DNA complexes which are accessible only in regions of cell death and this antibody has been shown to accumulate locally in tumors. Patients with unresectable metastatic colorectal cancer (mCRC) or unresectable intrahepatic cholangiocarcinoma (ICC) will receive synchronization of subcutaneous PDS01ADC with floxuridine delivered via a hepatic artery infusion pump (HAIP). The primary outcome measured in this study will be overall response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Secondary outcomes measured in this study will include hepatic and non-hepatic progression-free survival (PFS), overall survival, and safety of PDS01ADC combination therapy with HAIP. Poor clinical response of these liver tumors to immunotherapy is likely due to various factors, including poor immune infiltrate into the tumor and immunosuppression by the tumor microenvironment. By exploiting the tumor cell death induced by HAIP locoregional therapy in combination with systemic chemotherapy, PDS01ADC is poised to modulate the tumor immune microenvironment to improve outcomes for patients undergoing HAIP therapy. ClinicalTrials.gov (ID NCT05286814 version 2023-10-18); https://clinicaltrials.gov/study/NCT05286814?term=NCT05286814&rank=1.

Efficacy and safety of regorafenib as a first-line agent alone or in combination with an immune checkpoint inhibitor for advanced hepatocellular carcinoma: a retrospective cohort study.

The RESORCE-III trial demonstrated that advanced hepatocellular carcinoma (HCC) patients who progressed on sorafenib and had second-line therapy with regorafenib improved overall survival compared with placebo. Later, immunotherapy with immune checkpoint inhibitors (ICIs) combined with antiangiogenetic antibodies has evolved as the preferred first-line treatment for fit patients. We aimed to explore the efficacy and safety of regorafenib as a first-line agent alone or in combination with ICIs in patients with advanced HCC. We identified 50 patients with advanced HCC treated with regorafenib as a first-line agent. Two patients were lost to follow-up and excluded. Baseline factors, dosing, concomitant use of ICIs, toxicity and outcome of treatment were recorded from electronic medical records. Twenty-six patients received regorafenib as monotherapy and twenty-two received regorafenib + ICI in combination. In the total cohort, the median progression-free survival (mPFS) was 7.7 months and the median overall survival (mOS) was 16.7 months (P=0.02). Objective response rate (ORR) and disease control rate (DCR) assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were 21% and 73%. In the regorafenib monotherapy group, mPFS was 5.9 months, and mOS was 13.9 months; in the combination group, mPFS was 7.8 months, and mOS was 23.6 months. ORR and DCR were 15% and 65% in the monotherapy group, and 27% and 82% in the combined treatment group, respectively. Regorafenib used in combination with ICIs had a mild safety profile and resulted in improved response and an almost doubling of mOS compared to monotherapy, warranting further prospective evaluation in a randomized study.

A pilot study of nintedanib in molecularly selected patients with advanced non-small cell lung cancer.

Nintedanib is a small molecule tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and fibroblast growth factor receptor (FGFR). The purpose of the study was to evaluate the response rate for patients with advanced non-small cell lung cancer (NSCLC) with mutations in TP53, VEGFR1-3, PDGFR-A, PDGFR-B, and FGFR1-3 treated with nintedanib as part of an open-label, single-arm pilot study. Patients with advanced NSCLC previously treated with platinum-doublet chemotherapy with the above mutations were enrolled. Exclusion criteria included necrotic tumors with invasion of blood vessels, history of recent thromboembolic events, increased risk of bleeding or thrombosis, myocardial infarction, and weight loss >10% within past 6 months. Nintedanib was administered at a dose of 200 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Secondary endpoints included progression-free survival (PFS) and correlating outcomes with specific mutations. This study was registered with ClinicalTrials.gov, number NCT02299141. Between 2015 and 2019, 20 patients were enrolled with a median age was 66 years, 15 (75%) were females, 15 (75%) had adenocarcinoma, and 17 patients had a TP53 mutation (85%). Seventeen (85%) had received prior immunotherapy and 11 (55%) had received at least three prior lines of systemic therapy. The ORR was 15% with three partial responses (PR), while 12 patients had stable disease (SD), with disease control rate (DCR) consisting of a PR and SD greater than or equal to 16 weeks of 65% (n=13). Median PFS was 4.3 months [95% confidence interval (CI): 1.8-7.9] and median overall survival (OS) was 11.3 months (95% CI: 3.5-44.2). Three patients experienced prolonged clinical benefit from nintedanib, remaining on treatment for over 1 year and all three had a TP53 mutation and received prior immunotherapy. The most common adverse events of any grade included nausea (80%), fatigue (70%), diarrhea (60%), and anorexia (60%). In this pilot study in heavily pretreated and molecularly selected patients with metastatic NSCLC, nintedanib showed modest activity.