Combination nitazoxanide and auranofin treatment has synergistic anticancer activity in anaplastic thyroid cancer through enhanced activation of oxidative stress that leads to apoptosis.

Anaplastic thyroid cancer (ATC) has one of the highest mortality rates of all human malignancies and has no cure. We used combination drug matrix screening of highly active compounds and identified that combination of nitazoxanide and auranofin was one of those with the highest synergistic anticancer activity. We investigated its synergistic anticancer activity and mechanism of action in preclinical ATC models.

A Retrospective Study of Pregnancy and Fetal Outcomes in Mothers with Hepatitis C Viremia.

Objective: To investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development.

Methods: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected.

Association between ultrasound-based biliary and parenchymal intrahepatic mass-forming cholangiocarcinoma subtypes and clinicopathological features and survival.

Objective: Mass-forming intrahepatic cholangiocarcinomas (MF-ICCs) can be classified into ductal and parenchymal types using magnetic resonance imaging (MRI). We aimed to subclassify MF-ICC into biliary and parenchymal types based on ultrasound (US) findings and to investigate the differences in their contrast-enhanced ultrasound (CEUS) patterns, clinicopathologic features, and prognosis.

Methods: In this study, 141 patients who underwent US with pathologically proven MF-ICC from two hospitals were retrospectively enrolled.

Preoperative identification of hepatocellular carcinoma from focal liver lesions ≤ 20 mm in high-risk patients using clinical and contrast-enhanced ultrasound features.

Objective: We aimed to develop and validate a prediction model to identify HCC in focal liver lesions (FLLs) ≤20 mm among patients at risk for HCC based on clinical and contrast-enhanced ultrasound (CEUS) features.

Methods: Between January 2022 and July 2023, 386 patients (mean age 58 ± 11 years; 277 male) at risk for HCC with FLLs ≤20 mm and clinical and preoperative CEUS data from three centers were retrospectively enrolled. Three prediction models based on clinical data (Cli-M), CEUS features (CEUS-M), and combined clinical and CEUS features (Com-M) were constructed using the training cohort (187 patients).

Distributional Soft Actor-Critic With Three Refinements.

Reinforcement learning (RL) has shown remarkable success in solving complex decision-making and control tasks. However, many model-free RL algorithms experience performance degradation due to inaccurate value estimation, particularly the overestimation of Q-values, which can lead to suboptimal policies. To address this issue, we previously proposed the Distributional Soft Actor-Critic (DSAC or DSACv1), an off-policy RL algorithm that enhances value estimation accuracy by learning a continuous Gaussian value distribution.

Intelligent handheld ultrasound improving the ability of non-expert general practitioners in carotid examinations for community populations: a prospective and parallel controlled trial.

Purpose: The aim of this study was to investigate the feasibility of an intelligent handheld ultrasound (US) device for assisting non-expert general practitioners (GPs) in detecting carotid plaques (CPs) in community populations.

Methods: This prospective parallel controlled trial recruited 111 consecutive community residents. All of them underwent examinations by non-expert GPs and specialist doctors using handheld US devices (setting A, setting B, and setting C).

Construction of a Simplified Bone Age Assessment Model in Chinese Children Aged 3-18 Years.

Context: Bone age assessment (BAA) is critical for pediatric endocrinology. Traditional methods are complex and time-consuming, and current computer-aided systems have made progress but still lacking in robustness.

Objective: Develop simplified BAA methods to aid pediatricians in quick clinical assessments.

Is there an association between eye-level greenness and childhood hypertension using street view? Findings from the Seven Northeastern Cities study in China.

There is a lack of evidence regarding associations of eye-level greenness exposure with blood pressure among children. We aimed to investigate the associations between different types of eye-level greenness and pediatric blood pressure in China. From 2012 to 2013, we recruited 9354 children aged between 5 and 17 years in northeast China.

TFAP2C-DDR1 axis regulates resistance to CDK4/6 inhibitor in breast cancer.

Breast cancer is the predominant malignancy with the majority of cases are characterized as HR+/HER2-subtype. Although cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have shown remarkable efficacy in treating this subtype when combined with endocrine therapy, the development of resistance to these inhibitors remains a significant clinical obstacle. Hence, there is an urgent need to explore innovative therapies and decipher the underlying mechanisms of resistance to CDK4/6i.

A Comprehensive Collection of Pain and Opioid Use Disorder Compounds for High-Throughput Screening and Artificial Intelligence-Driven Drug Discovery.

As part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, the National Center for Advancing Translational Sciences is dedicated to the development of new pharmacological tools and investigational drugs for managing and treating pain as well as the prevention and treatment of opioid misuse and addiction. In line with these objectives, we created a comprehensive, annotated small molecule library including drugs, probes, and tool compounds that act on published pain- and addiction-relevant targets. Nearly 3000 small molecules associated with approximately 200 known and hypothesized HEAL targets have been assembled, curated, and annotated in one collection.

O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer.

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings.

Managing extreme AI risks amid rapid progress.

Preparation requires technical research and development, as well as adaptive, proactive governance.

Secular changes in eruption of primary teeth in Chinese infants and young children from three national cross-sectional surveys.

The eruption of primary teeth is a basic event during physical development of children, which is affected by heredity and environment. This study aimed to analyze the changes in primary teeth eruption among Chinese children with social development. A total of 249,264 healthy children under 2 years were extracted from the 1995, 2005, and 2015 National Survey on the Physical Growth and Development of Children in Nine Cities of China.

Association of height, foot length, and pubertal development in children aged 3-18: a cross-sectional survey in China.

Objective: This study aimed to analyze the growth patterns of height and foot length (FL) among Chinese children aged 3-18 and examine their associations with puberty development.

Methods: A cross-sectional survey was conducted in September 2022 in Beijing. Data were collected through questionnaires and on-site physical examinations.

A deep learning fusion network trained with clinical and high-frequency ultrasound images in the multi-classification of skin diseases in comparison with dermatologists: a prospective and multicenter study.

Background: Clinical appearance and high-frequency ultrasound (HFUS) are indispensable for diagnosing skin diseases by providing internal and external information. However, their complex combination brings challenges for primary care physicians and dermatologists. Thus, we developed a deep multimodal fusion network (DMFN) model combining analysis of clinical close-up and HFUS images for binary and multiclass classification in skin diseases.

A 5G-based telerobotic ultrasound system provides qualified abdominal ultrasound services for patients on a rural island: a prospective and comparative study of 401 patients.

Purpose: To explore the feasibility of a 5G-based telerobotic ultrasound (US) system for providing qualified abdominal US services on a rural island.

Methods: This prospective study involved two medical centers (the tele-radiologist site's hospital and the patient site's hospital) separated by 72 km. Patients underwent 5G-based telerobotic US by tele-radiologists and conventional US by on-site radiologists from September 2020 to March 2021.

Assessment of the Diagnostic Performance of Clinical Examinations and High-Frequency Ultrasound in Patients With Pigmented Skin Tumors.

Objectives: To investigate whether the integration of high-frequency ultrasound (HFUS) to routine clinical examinations could improve diagnostic performance and management decision for pigmented skin tumors.

Methods: Three general practitioners trained previously and a dermatologist independently assessed pigmented skin tumors and rendered management decision based on clinical examinations alone or clinical examinations integrating HFUS.

Results: After integrating HFUS, the diagnostic area under the curve (AUC) (0.

Combination Inhibition with the Multitargeting Tyrosine Kinase Inhibitor Axitinib Shows Additive Anticancer Activity in -Mutant Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is uniformly lethal. mutation is present in 45% of patients with ATC. Targeted therapy with combined BRAF and MEK inhibition in -mutant ATC can be effective, but acquired resistance is common because this combination targets the same pathway.

Height and body mass index trajectories from 1975 to 2015 and prevalence of stunting, underweight and obesity in 2016 among children in Chinese cities: findings from five rounds of a national survey.

Background: A more comprehensive assessment of growth and nutrition in children is required in China due to rapid socioeconomic processes. We aimed to investigate height and body mass index (BMI) trajectories from 1975 to 2015 and the prevalence of stunting and obesity in 2016 among children in Chinese cities.

Methods: A total of 904,263 children from birth to 6.

Risk stratification of gallbladder masses by machine learning-based ultrasound radiomics models: a prospective and multi-institutional study.

Objective: This study aimed to evaluate the diagnostic performance of machine learning (ML)-based ultrasound (US) radiomics models for risk stratification of gallbladder (GB) masses.

Methods: We prospectively examined 640 pathologically confirmed GB masses obtained from 640 patients between August 2019 and October 2022 at four institutions. Radiomics features were extracted from grayscale US images and germane features were selected.

An electrophilic fragment screening for the development of small molecules targeting caspase-2.

Recent Alzheimer's research has shown increasing interest in the caspase-2 (Casp2) enzyme. However, the available Casp2 inhibitors, which have been pentapeptides or peptidomimetics, face challenges for use as CNS drugs. In this study, we successfully screened a 1920-compound chloroacetamide-based, electrophilic fragment library from Enamine.