A Utilitarian Perspective on Risk Quantification for Clinical Significance in Binary Outcomes.

Null hypothesis significance testing (NHST) in medical research is increasingly being supplemented by estimation statistics, focusing on effect sizes (ESs) and confidence intervals (CIs). This study evaluates the expression of ESs and CIs for binary outcomes. A utilitarian framework is proposed, emphasizing the number of beneficiaries and the impact level. To evaluate clinical significance, minimal clinically important risk difference (MCIRD) is proposed based on event magnitude (EM). Within this framework, risk difference (RD) is introduced as the primary measure. To assess the performance of RD, we compared its statistical power against other measures (risk ratio, RR; odds ratio, OR; Cohen's h) in individual study scenarios, and visual information conveyance in meta-analysis scenarios. RDs maintain statistical power in comparison to other measures in individual studies. They provide clarity on the true impact of clinical interventions without compromising statistical integrity. Meta-analytic results indicate that using RDs directly enhances transparency, uncovers heterogeneity, and addresses misaligned assumptions. This approach, by quantifying clinical effectiveness under a utilitarian perspective, facilitates the applicability of research to patient care and encourages shared decision-making. The study advocates for reporting baseline risks (BRs) with RDs and recommends a standardized presentation of these statistics. In a utilitarian perspective, adopting RD as the preferred ES can foster a transparent, patient-focused research ethos. This aids in accurately presenting the magnitude and variability of treatment effects, offering a new direction in methodology.

Conversion of the bronchial tree into a conforming electrode to ablate the lung nodule in a porcine model.

BACKGROUND: Radiofrequency ablation (RFA) is one of the treatment options for lung nodules. However, the need for exact delivery of the rigid metal electrode into the center of the target mass often leads to complications or suboptimal results. To overcome these limitations, a concept of conforming electrodes using a flexible material has been tested in this study. METHODS: A bronchoscopy-guided RFA (CAROL) under a temperature-controlled mode was tested in in-vivo and ex-vivo porcine lungs. Gallium-based liquid metal was used for turning the bronchial tree into temporary RF electrodes. A customized bronchoscopy-guided balloon-tipped guiding catheter (CAROL catheter) was used to make the procedure feasible under fluoroscopy imaging guidance. The computer simulation was also performed to gain further insight into the ablation results. Safety was also assessed including the liquid metal remaining in the body. RESULTS: The bronchial electrode injected from the CAROL catheter was able to turn the target site bronchial air pipe into a temporally multi-tined RF electrode. The mean volume of Gallium for each effective CAROL was 0.46 ± 0.47 ml. The ablation results showed highly efficacious and consistent results, especially in the peripheral lung. Most bronchial electrodes were also retrieved by either bronchoscopic suction immediately after the procedure or by natural expectoration thereafter. The liquid metal used in these experiments did not have any significant safety issues. Computer simulation also supports these results. CONCLUSION: The CAROL ablation was very effective and safe in porcine lungs showing encouraging potential to overcome the conventional approaches.

Lung cancer can be treated by inserting a metal device into the lung via the throat and using this to send radio waves into the cancer. However, using a rigid metal device can cause damage to other areas of the lung and can only treat small cancers. Here, we describe an alternative method to treat lung cancers in which liquid metal is used to fill the spaces within the lung closest to the cancer. We demonstrate that this method can be used to treat cancer in a swine model of lung cancer. Given the positive results we obtained, we think this approach should be tested in a clinical trial in human patients with lung cancer, as it might improve cancer treatment.

The Development of a Permanent Implantable Spacer with the Function of Size Adjustability for Customized Treatment of Regurgitant Heart Valve Disease.

The Pivot Mandu is an innovative device featuring a leak-tight adjustable 3D balloon spacer, incorporating inner mesh support, an outer e-PTFE layer, and a compliant balloon in the middle layer with a specialized detachable system. To assess its feasibility, proof of concept was rigorously evaluated through bench testing and survival porcine animal experiments. The results demonstrated successful remote inflation of the balloon system, with the balloon spacer exhibiting sustained patent and functional integrity over an extended observation period of up to 6 months. A noteworthy feature of the newly designed 3D balloon spacer is its capability for easy size adjustment during procedures, enhancing its adaptability and practicality in clinical settings. This three-layered 3D balloon spacer, with its established long-term patency, exhibits highly encouraging outcomes that hold promise in overcoming the current limitations of spacer devices for heart valve diseases. Given the compelling results from preclinical investigations, the translation of the Pivot Mandu into human trials is strongly warranted.

ACGCN: Graph Convolutional Networks for Activity Cliff Prediction between Matched Molecular Pairs.

One of the interesting issues in drug-target interaction studies is the activity cliff (AC), which is usually defined as structurally similar compounds with large differences in activity toward a common target. The AC is of great interest in medicinal chemistry as it may provide clues to understanding the complex properties of the target proteins, paving the way for practical applications aimed at the discovery of more potent drugs. In this paper, we propose graph convolutional networks for the prediction of AC and designate the proposed models as Activity Cliff prediction using Graph Convolutional Networks (ACGCNs). The results show that ACGCNs outperform several off-the-shelf methods when predicting ACs of three popular target data sets for thrombin, Mu opioid receptor, and melanocortin receptor. Finally, we utilize gradient-weighted class activation mapping to visualize activation weights at nodes in the molecular graphs, demonstrating its potential to contribute to the ability to identify important substructures for molecular docking.

A Novel Device for Tricuspid Regurgitation Reduction Featuring 3-Dimensional Leaflet and Atraumatic Anchor: Pivot-TR System.

A new device called the Pivot-TR system was designed to treat tricuspid regurgitation with a novel spacer crossing the valve vertically. Its unique atraumatic anchoring system composed of both the elephant long nose and the inferior vena cava spiral anchor, in addition to the relatively easy implantation mechanism, enabled easy retrieval of the system later on. The system showed promising feasibility and safety results in this swine-based animal experiment, which should encourage human translation study.

The sex-specific effect of the apolipoprotein E allele and methylenetetrahydrofolate reductase gene polymorphism on the biochemical, anatomical, and cognitive profiles of patients clinically diagnosed with probable Alzheimer's disease.

OBJECTIVES: We aimed to evaluate the sex-specific effect of apolipoprotein E (APOE) alleles and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on the biochemical, anatomical, and cognitive profiles of Alzheimer's disease (AD) patients. METHODS: The patient (followed-up for at least 2 years) medical records, which comprised of data on plasma homocysteine and folate levels, lipid profile, HbA1c, MTHFR C677T genotype, APOE allele type, mini-mental state examination (MMSE) and clinical dementia rating (CDR) scores, and brain scans, were retrospectively analyzed. Two trained neurologists scored the white matter lesions (Fazekas scale), medial temporal lobe atrophy (MTA), and microbleeds using brain magnetic resonance imaging scans. RESULTS: This study included 574 patients clinically diagnosed with probable AD (average age, 73.2 years; mean MMSE score, 10.05). The effect of sex on all parameters was evaluated. The triglyceride (TG) and homocysteine levels and the MTA and Fazekas scores were higher in female APOE-ε4/ε4 carriers than in women without APOE-ε4. The TG and homocysteine levels were lower in men with the MTHFR CC allele than in those with the MTHFR TT allele. In contrast, MTHFR polymorphism and APOE-ε4 alleles were not significantly correlated with anatomical lesions and rate of decline in the MMSE and CDR scores. CONCLUSIONS: We demonstrated the sex-specific effect of the APOE allele and MTHFR polymorphism on the serological and anatomical biomarkers in AD patients. The APOE allele and MTHFR mutations did not directly affect cognitive progression, but differentially affected other biochemical factors, between the sexes. These findings will aid in devising novel preventive and therapeutic strategies.