Response of a Novel KANK1::ALK Fusion to Alectinib in an Advanced Lung Adenocarcinoma: A Case Report.

More than 90 distinct fusion partners of ALK rearrangement have been identified. Different ALK fusions may exhibit different sensitivities to ALK tyrosine kinase inhibitors. The emergence of rare fusions poses significant challenges to targeted therapies. This study aimed to investigate the response of KANK1::ALK fusion to alectinib in an advanced lung adenocarcinoma. A novel KANK1::ALK fusion was identified by next-generation sequencing (NGS) and Ventana immunohistochemistry assessments. A 73-year-old woman who had never smoked was admitted with hemoptysis in May 2020. PET/CT revealed a nodule in the left upper lobe, with bilateral pulmonary and multiple lymph node metastases. The upper lobe nodule of the left lung was diagnosed as adenocarcinoma through bronchofiberscopy biopsy, resulting in a clinical diagnosis of stage IVA (cT1c,N3,M1a). Because the biopsy tissue was insufficient for NGS analysis, a blood-based genetic analysis was performed, revealing the presence of KRAS p.Q61R mutations. The patient received carboplatin and pemetrexed with pembrolizumab as first-line therapy, followed by maintenance therapy of pembrolizumab monotherapy. Although the tumor initially showed significant shrinkage, it unfortunately progressed further after 11 months. Subsequently, the patient was given carboplatin and pemetrexed with pembrolizumab again, but the tumor progression continued. An NGS using a rebiopsy of the left upper lobe tumor suggested a KANK1::ALK fusion. Alectinib was prescribed in January 2022, and a durable partial response was observed after 18 months. ALK rearrangements were observed in the broader spectrum of lung cancers. This study provided a potential treatment option for patients with KANK1::ALK fusions. Further studies are needed to understand the function of these fusions.

Adaptive fuzzy control for tendon-sheath actuated bending-tip system with unknown friction for robotic flexible endoscope.

Introduction: The tendon-sheath actuated bending-tip system (TAB) has been widely applied to long-distance transmission scenes due to its high maneuverability, safety, and compliance, such as in exoskeleton robots, rescue robots, and surgical robots design. Due to the suitability of operation in a narrow or tortuous environment, TAB has demonstrated great application potential in the area of minimally invasive surgery. However, TAB involves highly non-linear behavior due to hysteresis, creepage, and non-linear friction existing on the tendon routing, which is an enormous challenge for accurate control. Methods: Considering the difficulties in the precise modeling of non-linearity friction, this paper proposes a novel fuzzy control scheme for the Euler-Lagrange dynamics model of TAB for achieving tracking performance and providing accurate friction compensation. Finally, the asymptotic stability of the closed-loop system is proved theoretically and the effectiveness of the controller is verified by numerical simulation carried out in MATLAB/Simulink. Results: The desired angle can be reached quickly within 3 s by adopting the proposed controller without overshoot or oscillation in Tracking Experiment, demonstrating the regulation performance of the proposed control scheme. The proposed method still achieves the desired trajectory rapidly and accurately without steady-state errors in Varying-friction Experiment. The angle errors generated by external disturbances are < 1 deg under the proposed controller, which returns to zero in 2 s in Anti-disturbance Experiment. In contrast, comparative controllers take more time to be steady and are accompanied by oscillating and residual errors in all experiments. Discussion: The proposed method is model-free control and has no strict requirement for the dynamics model and friction model. It is proved that advanced tracking performance and real-time response can be guaranteed under the presence of unknown bounded non-linear friction and time-varying non-linear dynamics.

A Novel Cellular Senescence-related lncRNA Signature for Predicting the Prognosis of Breast Cancer Patients.

Background: Long non-coding RNA (lncRNA), a crucial regulator in breast cancer (BC) development, is intricately linked with cellular senescence. However, there is a lack of cellular senescence-related lncRNAs (CSRLs) signature to evaluate the prognosis of BC patients. Methods: Correlation analysis was conducted to identify lncRNAs associated with cellular senescence. Subsequently, a CSRL signature was crafted in the training cohort. The model's accuracy was evaluated through survival analysis and receiver operating characteristic curves. Furthermore, prognostic nomograms amalgamating cellular senescence and clinical characteristics were devised. Tumor microenvironment and checkpoint disparities were compared between low-risk and high-risk groups. The correlation between these signatures and treatment response in BC patients was also investigated. Finally, functional experiments were conducted for validation. Results: A signature comprising nine CSRLs was devised, which demonstrated adept prognostic capability in BC patients. Functional enrichment analysis revealed that tumor and immune-related pathways were predominantly enriched. Compared to the low-risk group, the high-risk group could benefit more from immunotherapy and certain chemotherapeutic agents. The expression of the 9 CSRLs was validated through in vitro experiments in different subtypes of BC cell lines and tissues. AC098484.1 was specifically verified for its association with senescence-associated secretory phenotypes. Conclusion: The CSRLs signature emerges as a promising prognostic biomarker for BC, with implications for immunological studies and treatment strategies. AC098484.1 has potential relevance in the treatment of BC cell senescence, and these findings improve the clinical treatment levels for BC patients.

[The Effect of SIRT5 Deletion on Recovery of Hematopoietic Stem Cells after Injury in Mouse].

OBJECTIVE: To investigate the effect of deacylase Sirtuin 5 in the recovery of hematopoietic stem cells (HSCs) after treated by 5-FU in mouse. METHODS: Flow cytometry was used to analyze the effect of SIRT5 deletion on the proportion of hematopoietic stem/progenitor cells (HSPCs) in bone marrow (BM), the proportion of T cells, B cells and myeloid cells (TBM) in peripheral blood (PB) and spleen, and the development of T cells in thymus. Mouse were treated with 5-FU to study the effect of SIRT5 deletion on the cell cycle, apoptosis and the proportion of HSPCs in BM. The effect of SIRT5 deletion on the proliferation of HSCs was analyzed by flow sorting in vitro. RESULTS: SIRT5 deletion did not affect the development of T cells in thymus and the proportion of TBM cells in PB and spleen compared with wild type mice. SIRT5 deletion increased proportion of HSPCs in BM. After 5-FU treatment, the proportion of HSCs in SIRT5 deletion mice was significant decreased (P < 0.05), the HSPC in SIRT5 deletion mice was activated from G0 to G1 phase (P < 0.05), and the proportion of early apoptosis increased (P < 0.05). By monoclonal culture in vitro, the ability of HSCs to form clones in SIRT5 deletion mice was decreased significantly (P < 0.05). CONCLUSION: SIRT5 deletion lead to a decreased the ability of HSCs to clone in vitro. SIRT5 deletion is not conducive to the recovery of HSPCs injury in mice under hematopoietic stress.

Impact of Silicon Carbide Coating and Nanotube Diameter on the Antibacterial Properties of Nanostructured Titanium Surfaces.

This study aimed to comprehensively assess the influence of the nanotube diameter and the presence of a silicon carbide (SiC) coating on microbial proliferation on nanostructured titanium surfaces. An experiment used 72 anodized titanium sheets with varying nanotube diameters of 50 and 100 nm. These sheets were divided into four groups: non-coated 50 nm titanium nanotubes, SiC-coated 50 nm titanium nanotubes, non-coated 100 nm titanium nanotubes, and SiC-coated 100 nm titanium nanotubes, totaling 36 samples per group. P. gingivalis and T. denticola reference strains were used to evaluate microbial proliferation. Samples were assessed over 3 and 7 days using fluorescence microscopy with a live/dead viability kit and scanning electron microscopy (SEM). At the 3-day time point, fluorescence and SEM images revealed a lower density of microorganisms in the 50 nm samples than in the 100 nm samples. However, there was a consistently low density of T. denticola across all the groups. Fluorescence images indicated that most bacteria were viable at this time. By the 7th day, there was a decrease in the microorganism density, except for T. denticola in the non-coated samples. Additionally, more dead bacteria were detected at this later time point. These findings suggest that the titanium nanotube diameter and the presence of the SiC coating influenced bacterial proliferation. The results hinted at a potential antibacterial effect on the 50 nm diameter and the coated surfaces. These insights contribute valuable knowledge to dental implantology, paving the way for developing innovative strategies to enhance the antimicrobial properties of dental implant materials and mitigate peri-implant infections.

High sensitivity saliva-based biosensor in detection of breast cancer biomarkers: HER2 and CA15-3.

The prevalence of breast cancer in women underscores the urgent need for innovative and efficient detection methods. This study addresses this imperative by harnessing salivary biomarkers, offering a noninvasive and accessible means of identifying breast cancer. In this study, commercially available disposable based strips similar to the commonly used glucose detection strips were utilized and functionalized to detect breast cancer with biomarkers of HER2 and CA15-3. The results demonstrated limits of detection for these two biomarkers reached as low as 1 fg/ml much lower than those of conventional enzyme-linked immunosorbent assay in the range of 1∼4 ng/ml. By employing a synchronized double-pulse method to apply 10 of 1.2 ms voltage pulses to the electrode of sensing strip and drain electrode of the transistor for amplifying the detected signal, and the detected signal was the average of 10 digital output readings corresponding to those 10 voltage pulses. The sensor sensitivities were achieved approximately 70/dec and 30/dec for HER2 and CA15-3, respectively. Moreover, the efficiency of this novel technique is underscored by its swift testing time of less than 15 ms and its minimal sample requirement of only 3 µl of saliva. The simplicity of operation and the potential for widespread public use in the future position this approach as a transformative tool in the early detection of breast cancer. This research not only provides a crucial advancement in diagnostic methodologies but also holds the promise of revolutionizing public health practices.

Sensitive Detection of Oral Leukoplakia: Analyzing P90 Biomarkers in Saliva and Tissue.

Oral cancer represents a significant global public health challenge, contributing substantially to the incidence and mortality of cancer. Despite established risk factors such as tobacco use and alcohol consumption, early detection remains crucial for effective treatment. This study introduces a novel approach using a transistor-based biosensor system for detecting the P90 (CIP2A) protein. We tested the presence of CIP2A in human leukoplakia samples, which can undergo malignant conversion into aggressive oral squamous cell carcinoma. The method used commercially available glucose test strips functionalized with P90 antibodies, providing high sensitivity and a low limit of detection which was five orders lower than that of commercial ELISA kits. A specially designed printed circuit board (PCB) facilitated accurate measurements, and the device's performance was optimized through characteristic tests. Human sample testing validated the biosensor's effectiveness in distinguishing samples after cell lysis. This study contributes to advancing accurate and cost-effective diagnostic approaches for oral pre-cancer and cancer tissues.