Major Functions Research Articles

Interstitial brachytherapy for periocular nonmelanoma skin cancers: Impact on organ and function preservation

PurposeTo study the local control, toxicity, organ and functional preservation and cosmetic outcomes after interstitial brachytherapy for periocular nonmelanoma skin cancers. Methods and MaterialsPatients with skin cancers of upper and lower eyelid, medial and lateral canthus and the infra-orbital region treated with high dose rate (HDR) interstitial brachytherapy (ISBT) using 192-Iridium (192Ir) between December 2010 and July 2022 were included and data collected from a prospectively maintained database. Local control, survival outcomes, acute and late RTOG toxicity, functional and cosmetic outcomes were analysed. ResultsSixteen patients were included. Nine patients had lower eyelid tumors, 5 patients had tumors in canthi and two patients had skin tumor in the infra-orbital region. The median dose for definitive ISBT was 49 Gy in 14 fractions. After a median follow up of 73 months, all patients treated with definitive and adjuvant ISBT were locally controlled. Three of the four patients who received salvage ISBT for post-surgical failure had local recurrences and all were effectively managed with salvage re-surgery. Of the two deaths, none were disease related. Organ and function preservation was achieved in 15 (93.7 %) and 13 (81.2 %), respectively, with one patient being lost to follow up. Excellent, good, fair and poor cosmesis was seen in 6 (40 %) patients, 6 (40 %) patients, 2 (14 %) patients and 1(6 %) patient, respectively. ConclusionHDR-ISBT was safe and effective for skin tumors around the eye and resulted in excellent local control and survival outcomes preserving organ and function in majority of patients with good-excellent cosmesis.

325. SURGERY FOR EPIPHRENIC ESOPHAGEAL DIVERTICULUM, SHORT AND LONG TERM RESULTS

Abstract Background and Objectives We present our experience with laparoscopic surgery for epiphrenic oesophageal diverticulum. We wanted to assess our surgical results focusing on the patients’ quality of life. Short- and long-term results of surgical therapy were analysed. Methods 14 patients were examined with a symptomatic causing epiphrenic diverticulum. Patients underwent complex gastroenterological examinations before and after surgery (swallowing x-ray, oesophagogastroscopy, oesophageal manometry/pH monitoring). Surgery: laparoscopic transhiatal epiphrenic diverticulectomy with Heller cardiomyotomy and Dor anterior partial fundoplication were performed in 9 patients; laparoscopic diverticulectomy in 2 patients, laparoscopic Heller-Dor operation without diverticulectomy was 1 case (small (< 3cm) diverticulum) and laparoscopic diverticulectomy + Heller myotomy + Nissen fundoplication in 2 cases. Changes in quality of life with regard to symptoms related to oesophageal function were evaluated in our long-term studies (averaging 60 months, 10–138 months) by Eckardt-Zaninotto score. Results We had no intraoperative complication except one. In one case, a staple line leak developed (1/14 (7%), which was resolved with conservative therapy. Functional check-ups confirmed adequate oesophageal function in majority of the patients. The total symptom score for the patients was 6.3 points before surgery, and it decreased to 1.6 (P .001) after surgery, an average of 74% subjective improvement. During the follow-up period, proton pump inhibitor therapy was started in 4 patients to treat gastroesophageal reflux. In 3 cases, drug therapy was successful; in one case, Nissen antireflux surgery was performed. Conclusion Laparoscopic transhiatal diverticulectomy and Heller–Dor surgery are effective interventions with low morbidity. Patient quality of life significantly improves in the long term, but gastroesophageal reflux disease may occur. Key Words Epiphrenic oesophageal diverticulum, Laparoscopic transhiatal surgery, Long-term results

An efficient nano-design of image processor circuits for morphology operations based on quantum dots

Quantum-dot cellular automata (QCA) are one of the most promising alternatives to traditional VLSI technology despite significant current obstacles. The QCA has the advantages of very low power dissipation, faster switching speed, and extremely low circuit area, which can be used in designing nano-scale image processing circuits. Morphological operations and processing of digital image processing is a significant topic for researchers because it is widely used for analyzing, enhancing, and modifying images to extract meaningful information or improve their visual quality. Image processing is also used for image retrieval and enhancement, image compression, object recognition, machine vision, and medical applications. QCA technology, as a new and leading technology with great potential, can play a fundamental role in morphological operations, processing digital images, image editing, medical imaging, facial recognition, and autonomous vehicles. In recent years, researchers in this field have presented many circuits, but they have many flaws in terms of speed, accuracy, and area consumption, and the need to create more efficient circuits is felt more than ever. Therefore, in this article, a new design for morphological operations and processing digital images is presented using QCA technology. This paper presents a new efficient QCA-based implementation of image processing based on the direct interactions between the QCA cells. This circuit uses two majority gates of five new inputs to produce the output and produces the desired output. In addition, a comparison and analysis of the area and clocking complexity, design cost, and energy dissipation through simulation using QCADesigner and QCADesigner-E are done. The results show that the presented circuit produces the expected and correct output results in 0.75 clock phases, and the obtained results show the high speed and low consumption space of the presented circuit. In addition, the presented circuit performs better than the previous best circuits in terms of quantum cost and delay, and according to the mentioned advantages, it can be used to improve and expand other circuits in image processing.

Hybrid Quantum-Dot Cellular Automata Nanocomputing Circuits

Quantum-dot cellular automata (QCA) is an emerging transistor-less field-coupled nanocomputing (FCN) approach to ultra-scale ‘nanochip’ integration. In QCA, to represent digital circuitry, electrostatic repulsion between electrons and the mechanism of electron tunnelling in quantum dots are used. QCA technology can surpass conventional complementary metal oxide semiconductor (CMOS) technology in terms of clock speed, reduced occupied chip area, and energy efficiency. To develop QCA circuits, irreversible majority gates are typically used as the primary components. Recently, some studies have introduced reversible design techniques, using reversible majority gates as the main building block, to develop ultra-energy-efficient QCA circuits. However, this approach resulted in time delays, an increase in the number of QCA cells used, and an increase in the chip area occupied. This work introduces a novel hybrid design strategy employing irreversible, reversible, and partially reversible QCA gates to establish an optimal balance between power consumption, delay time, and occupied area. This hybrid technique allows the designer to have more control over the circuit characteristics to meet different system needs. A combination of reversible, irreversible, and innovative partially reversible majority gates is used in the proposed hybrid design method. We evaluated the hybrid design method by examining the half-adder circuit as a case study. We developed four hybrid QCA half-adder circuits, each of which simultaneously incorporates various types of majority gates. The QCADesigner-E 2.2 simulation tool was used to simulate the performance and energy efficiency of the half-adders. This tool provides numerical results for the circuit input/output response and heat dissipation at the physical level within a microscopic quantum mechanical model.

Quad-functioning parity layout for nanocomputing: A QCA design

Quantum dot cellular automata (QCA) is considered an alternative to conventional technologies like CMOS (Complementary Metal-Oxide-Semiconductor) technology due to its potential for lower power consumption, higher speed, and increased device density. QCA introduces a novel approach to designing nano communication circuits and systems. Nano communications data mistakes are detected via parity generators and checkers. The parity bit of each data block ensures that the number of 1′s is either even or odd. Consequently, the system requires four circuits: an even parity generator, an odd parity generator, an even parity checker, and an odd parity checker. The whole system requires more space and cell complexity. In this work, we propose a QCA architecture that serves as a generator for both even and odd parities, as well as a checker for both even and odd parities. It is a quad-functioning circuit that performs four distinct operations within a single design, utilizing 118 QCA cells and occupying an area of 0.17 μm2. The recommended approach uses an efficient XOR gate, resulting in improvements across several performance metrics. QCAPro calculates energy dissipation and design parameters. The recommended QCA circuit outperformed similar QCA circuits in size, complexity, and energy dissipation. The circuit's design cost functions are also low. There has been a 17% reduction in latency and an 86% improvement in QCA-specific costs when compared to the optimal existing design. Moreover, it necessitates a 40% reduction in majority gate usage. The proposed design may compete effectively with other equivalent higher-order circuit designs by reducing the need for multiple blocks in conventional circuits to execute the same task. This architecture holds potential benefits for nano processors and nano communication networks.

Design of QCA based memory cell using a novel majority voter with physical validation

Quantum Dot Cellular Automata (QCA) is a unique transistor less paradigm which effectively uses change in cell polarization to perform logical operations with high speed, low power and high intricacy. In recent years, the need of high performance memory cell is increased for improving the system performance. This paper presents the design of a QCA based memory cell with read write capabilities. In recent past, most of the QCA circuits are designed using the conventional three input majority voter. The conventional three input majority gate is not fault tolerant. Thus, we need an alternative design which can serve as the majority voter and also shows the fault tolerance. Moreover, the design of three input majority voter is not much addressed . In this paper, an alternative, simple structure of three input majority voter is presented which is better than the conventional one in terms of fault tolerance. In addition to this, the proposed three input majority voter is power aware and efficient to realize various digital circuits. The correctness of the proposed majority voter is validated through the physical proof. Moreover, the proposed gate is subjected to cell displacement defect to investigate the testability. The proposed gate is further used to implement rudimentary elements such as XOR gate, multiplexer and D latch. Finally, the design of Random Access Memory (RAM) cell with read, write, set and reset capabilities is proposed using the presented majority voter. The proposed circuits are further subjected to comprehensive analyses for estimation of cost functions and energy dissipation. The investigation of presented circuits manifests the use of proposed majority voter for next generation computing circuits.

HIGHLY EFFICIENT INVERTER BLOCKS IN QCA TECHNOLOGY

QCA technology presented as a new paradigm to replace CMOS technology in the nanoscale. QCA technology represents binary information by cell polarization, not as a voltage level. The basic blocks in QCA technology are the majority gate and inverter. Efficient building blocks are important to get whole efficient circuits. This article aims to present novel configurations for the inverter block that offer advantages in terms of temperature tolerance, cell count, and area efficiency. Moreover, a Repeater gate with high efficiency is proposed to demonstrate their versatility. The proposed inverter has efficient improvements by 2%, 4.4%, 11%, and 17.5% over the best-reported inverter block at 10 K, 100 K, 150 K, and 200 K, respectively. The circuits presented in this study were designed and validated using QCADesigner software v 2.0.3, and the energy consumption of the proposed designs was assessed using QCAPro tools.

An Efficient Design of a Three-Layer Magnitude Comparator for Nano-Scale IoT Applications Based on QCA Technology

The difficulty of further downscaling CMOS technology arises from the restriction of feature size reduction. Quantum-dot cellular automata (QCA) emerges as a paradigm-shifting successor to CMOS, heralding a new era of effective digital design at the nanoscale. It stands as an enticing frontier in nanoscale computing, with limited exploration into the realms of smaller QCA cells, elevated processing speeds, and more compact area requirements across diverse circuits. Within the intricate landscape of decoding circuits and process controllers, the binary comparator assumes a role of paramount significance. On the other hand, the quickly developing Internet of Things (IoT) market aims to produce high-speed, low-power gadgets. A comparator is a crucial component in the analog-to-digital conversion process used by IoT devices. In order to meet the power and latency requirements of IoT devices, a high-speed, low-power comparator is greatly required. Consequently, the strategic design of comparators within the QCA framework has ascended to a position of heightened importance in cutting-edge research. This study undertakes the formidable task of conceiving QCA-centric designs for MV32, the majority gate, and the inverter gate, thereby contributing to the development of a sophisticated multi-layered comparator architecture for IoT devices. In the realization of a three-layer comparator implemented in QCA, we attain an impressive feat—a minimal clock zone demanding only a singular clock pulse coupled with exceptional compaction (measuring at a mere 0.03 μm2). Experimental revelations corroborate the substantial advancement of the proposed design over traditional methodologies, particularly in terms of circuit area, cell count, and clock efficiency.

Hybrid Newton-like Inverse Free Algorithms for Solving Nonlinear Equations

Iterative algorithms requiring the computationally expensive in general inversion of linear operators are difficult to implement. This is the reason why hybrid Newton-like algorithms without inverses are developed in this paper to solve Banach space-valued nonlinear equations. The inverses of the linear operator are exchanged by a finite sum of fixed linear operators. Two types of convergence analysis are presented for these algorithms: the semilocal and the local. The Fréchet derivative of the operator on the equation is controlled by a majorant function. The semi-local analysis also relies on majorizing sequences. The celebrated contraction mapping principle is utilized to study the convergence of the Krasnoselskij-like algorithm. The numerical experimentation demonstrates that the new algorithms are essentially as effective but less expensive to implement. Although the new approach is demonstrated for Newton-like algorithms, it can be applied to other single-step, multistep, or multipoint algorithms using inverses of linear operators along the same lines.

Dupilumab prevents nasal epithelial function alteration by IL-4 in vitro: Evidence for its efficacy.

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a typical type 2 inflammation involving interleukin (IL)-4 and IL-13. Dupilumab is a fully human monoclonal antibody targeting IL-4 receptor α subunit, thereby blocking signaling by both cytokines. Our hypothesis was that IL-4 and IL-13, by inducing a severe epithelial dysregulation, are involved in CRSwNP pathogenesis. This study aimed to evaluate the in vitro direct effect of IL-4, IL-13, and dupilumab on nasal epithelial functions. Nasal polyps and control mucosa from 28 patients, as well as human nasal epithelial cells (HNEC) from 35 patients with CRSwNP were used. Three major epithelial functions were investigated: the epithelial barrier function (characterized by transepithelial electrical resistance measurements and tight junction protein expression), the ciliary motion (characterized by the ciliary beating efficiency index), and wound healing (characterized by the wound repair rate) under various stimulations (IL-4, IL-13, and dupilumab). The main outcome was a significant change in epithelial functions following exposure to IL-4, IL-13, and dupilumab for 48h in the basal media. IL-4 (1, 10, and 100ng/mL) but not IL-13 induced a significant decrease in occludin and zonula-occludens protein expression, ciliary beating efficiency, and wound repair rate in HNEC. Dupilumab (0.04mg/mL) had no effect on HNEC and specifically restored all epithelial functions altered when cells were exposed to a 48-h IL-4 stimulation. Dupilumab, in vitro, restored epithelial integrity by counteracting the effect of IL-4 on the epithelial barrier (increased epithelial permeability, decreased ciliary beating efficiency, and decreased wound repair rate).

InR and Pi3K maintain intestinal homeostasis through STAT/EGFR and Notch signaling in enteroblasts.

To maintain the integrity of the adult gut, the proliferation and differentiation of stem cells must be strictly controlled. Several signaling pathways control the proliferation and differentiation of Drosophila intestinal epithelial cells. Although the modulatory effects of insulin pathway components on cell proliferation have been characterized, their specific role in which cell type and how these components interact with other regulatory signaling pathways remain largely unclear. In this study, we found that InR/Pi3K has major functions in enteroblasts (EBs) that were not previously described. The absence of InR/Pi3K in progenitors leads to a decrease in the number of EBs, while it has no significant effect on intestinal stem cells (ISCs). In addition, we found that InR/Pi3K regulates Notch activity in ISCs and EBs in an opposite way. This is also the reason for the decrease in EB. On the one hand, aberrantly low levels of Notch signaling in ISCs inhibit their proper differentiation into EBs; on the other hand, the higher Notch levels in EBs promote their excessive differentiation into enterocytes (ECs), leading to marked increases in abnormal ECs and decreased proliferation. Moreover, we found that Upd/JAK/STAT signaling acts as an effector or modifier of InR/Pi3K function in the midgut and cooperates with EGFR signaling to regulate cell proliferation. Altogether, our results demonstrate that InR and Pi3K are essential for coordinating stem cell differentiation and proliferation to maintain intestinal homeostasis.

Abstract B027: Repurposing ion channel drugs: the Na+ channel modifying drug DPI-201-106 significantly enhances the anti-tumor activity of multiple classes of drugs targeting DNA damage repair

Abstract B027: Repurposing ion channel drugs: the Na+ channel modifying drug DPI-201-106 significantly enhances the anti-tumor activity of multiple classes of drugs targeting DNA damage repair

Design and Analysis of a New Fault-Tolerant QCA-based Nano-Scale Circuit for Morphological Operations in Image Processing

Quantum-dot cellular automata (QCA) is based on traditional cellular automata models in which each cell has one of the finite distinct states at any given time. Cellular automata refer to the use of Coulombic contact rather than wires to connect cells. The discrete character of cellular automata and quantum mechanics have been exploited to develop nano-scale devices that can conduct computations with high switching frequency and low power dissipation. QCA has been utilized in many categories for fault-tolerant and reversible logic computing. On the other hand, the morphology algorithm is an area of image processing that provides a unified methodology and strong tools for image/video processing applications. This work proposes a unique fault-tolerant approach based on QCA to execute the morphological operations in image processing. Two fault-tolerant 5-input majority gates are employed in the implemented QCA architecture, and a control line is used to accomplish dilation and erosion. To assess the capabilities of the proposed fault-tolerant circuit for morphological procedures, its performance is analyzed and confirmed. The proposed design is compared to earlier results, which significantly improve fault-tolerant ability.

Exploiting Flexible and Secure Cryptographic Technique for Multidimensional Image Based on Graph Data Structure and Three-Input Majority Gate

Exploiting Flexible and Secure Cryptographic Technique for Multidimensional Image Based on Graph Data Structure and Three-Input Majority Gate

Research on the Implementation Path of Labor Education in Colleges and Universities from an International Perspective

Universities shoulder the important mission of talent cultivation, scientific research, social service, culturalheritage and innovation, and international exchange and cooperation. International exchange and cooperation have become the fifth major function of universities. Based on the background of the globalization era, undergraduate colleges and universities should pay more attention to the cultivation of students’ intercultural communication and understanding ability while cultivating their professional skills, and take expanding students’ international vision and enhancing the international competitiveness of China’s education as important tasks. Labor education is an important content of the national education system, which has the comprehensive nurturing value of cultivating morality, increasing intelligence, strengthening physical fitness, and cultivating beauty. Higher education institutions should further optimize the system of labor education, expand students’ space and field of thinking in the process of labor education, and broaden students’ international perspectives.

Urinary exosomal mRNA as a biomarker for the diagnosis of bladder cancer.

To study the diagnostic value of mRNA expression in urinary exocrine body in bladder cancer. From February 2022 to December 2022, 60 patients diagnosed with bladder cancer by pathology in the Department of Urology, Affiliated Hospital of Chengde Medical University were selected as the case group. In total, 40 healthy subjects receiving physical examinations were selected as the control group. 100 mL of morning urine samples were collected from the subjects in both groups based on the same standard. Three subjects were randomly selected from each group. Urinary exosomes were extracted by differential ultracentrifugation. High-throughput sequencing (RNA-seq) was used to detect mRNA expression profiles in urinary exosomes and identify differentially expressed genes. Bioinformatic analysis was performed to predict major biological functions of differentially expressed genes and related signaling pathways. RT-PCR validated expression levels of differentially expressed genes in urinary exosomes between the two groups. ROC curves evaluated the diagnostic value of differential genes for bladder cancer. Spearman's correlation analysis determined correlations between differentially expressed genes and the occurrence of bladder cancer. ROC curves speculated the diagnostic value of using combined differentially expressed genes. Compared with normal subjects, there were 189 significantly differentially expressed genes in urinary exosomes of bladder cancer patients, including 33 up-regulated and 156 down-regulated. According to go and kyoto encyclopedia of genes and genomes (KEGG) analysis, the above differentially expressed genes may participate in the occurrence and development of bladder cancer through the MAPK pathway, PPAP signaling pathway, PI3K Akt signaling pathway and Hippo signaling pathway, affect protein and lipid metabolism, RNase activity, polysaccharide synthesis, signal transduction and other biological processes, and participate in cell proliferation, death, movement and adhesion, as well as cell differentiation and signal transduction. RT-PCR verified that the expression of tmeff1, SDPR, ACBD7, SCG2 and COL6A2 in the two groups of samples was statistically significant ( P < 0.05). The ROC curve showed that the area under curve area under the curve of the five differential genes were 0.6934, 0.7746, 0.7239, 0.6396 and 0.6610, respectively. The sensitivity was 42.11%, 64.86%, 47.37%, 73.53% and 76.47%, and the specificity was 90%, 81.36%, 96.36%, 61.02% and 58.18%, respectively. Spearman correlation analysis showed that tmeff1, SDPR and acbd7 were associated with the occurrence of bladder cancer. The ROC curve of the combined diagnosis of the three and the two combined diagnoses suggested that the area under the curve of the combined diagnosis of SDPR and acbd7 was 0.7945, the sensitivity was 89.09%, and the specificity was 60.53%. The gene expression profile in urinary exosomes of bladder cancer patients has changed significantly, and the differential genes may play an important biological role in the occurrence and development of bladder cancer. The combined detection of urinary exosome SDPR and ACBD7 has a certain diagnostic value for bladder cancer.

Overlay databank unlocks data-driven analyses of biomolecules for all

Tools based on artificial intelligence (AI) are currently revolutionising many fields, yet their applications are often limited by the lack of suitable training data in programmatically accessible format. Here we propose an effective solution to make data scattered in various locations and formats accessible for data-driven and machine learning applications using the overlay databank format. To demonstrate the practical relevance of such approach, we present the NMRlipids Databank—a community-driven, open-for-all database featuring programmatic access to quality-evaluated atom-resolution molecular dynamics simulations of cellular membranes. Cellular membrane lipid composition is implicated in diseases and controls major biological functions, but membranes are difficult to study experimentally due to their intrinsic disorder and complex phase behaviour. While MD simulations have been useful in understanding membrane systems, they require significant computational resources and often suffer from inaccuracies in model parameters. Here, we demonstrate how programmable interface for flexible implementation of data-driven and machine learning applications, and rapid access to simulation data through a graphical user interface, unlock possibilities beyond current MD simulation and experimental studies to understand cellular membranes. The proposed overlay databank concept can be further applied to other biomolecules, as well as in other fields where similar barriers hinder the AI revolution.

Digital computerised cognitive training for preventing cognitive decline among hypertensive patients: a study protocol for a multicentre randomised controlled trial (DELIGHT trial)

IntroductionMild cognitive impairment (MCI) is an important intervenable stage for the prevention of dementia. Hypertension is associated with impaired cognition, and when combined with MCI, it may lead to a...

Abstract A023: lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer

Abstract Hormone receptor positive (HR+) breast cancer (BCa) is the most frequently diagnosed BCa type accounting for 70% of all breast cancer cases. A large population of HR+ BCa patients (30-40%) are resistant to mainstay endocrine therapy and develop incurable metastatic disease. Hence, it is imperative to identify viable biomarkers that stratify patients as drug responders or non-responders. Emerging scientific literature highlights the essential role of long non-coding RNAs (lncRNA), a class of RNAs over 200 nucleotides in length that do not encode protein, in cancer drug resistance and metastatic transformation. Major biological functions of lncRNA rely on association with select protein interactors. As lncRNA equally bind proteins with and without canonical RNA-binding motifs, it is unclear what facilitates this lncRNA-protein interaction. Our recent studies show that SUMO post-translational modification (or SUMOylation) of target proteins potentiates binding with lncRNA, particularly at the chromatin. SUMOylation of heterochromatin protein 1 α (HP1α) drives interaction with multiple chromatin-associated lncRNA both within and outside canonical heterochromatin foci. Interaction with lncRNA supports SUMOylated HP1α’s unconventional function as a transcriptional repressor at select euchromatic loci. We now report an inverse relationship in which SUMOylated HP1α directs the stability of its lncRNA binding partner. Specifically, SUMO-modified HP1α directs cell-cycle dependent recruitment of the RNA degradation machinery to the chromatin and facilitates clearance of chromatin-bound lncRNA. This dynamic lncRNA degradation process is disturbed with cancer onset and instead favors aberrant cancer cell transformation. Consistently, restoring lncRNA degradation homeostasis decreases metastatic properties of HR+ BCa cells and increases sensitivity to targeted therapeutics currently in clinical trials. Our studies define a fundamental mechanism that dictates lncRNA stability and/or degradation in BCa cells. In addition, we present viable biomarkers that predict sensitivity to ET and alternative targeted therapies. Citation Format: Kacie D Waiters, Maram Quttina, Ashfia F Khan, Samaneh Karami, Anthony Peidl, Funmi Babajide, Tasneem Bawa-Khalfe. lncRNA-protein interactions that predict response to endocrine therapy in HR+ breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A023.

RAVER1 hinders lethal EMT and modulates miR/RISC activity by the control of alternative splicing.

The RAVER1 protein serves as a co-factor in guiding the polypyrimidine tract-binding protein (PTBP)-dependent control of alternative splicing (AS). Whether RAVER1 solely acts in concert with PTBPs and how it affects cancer cell fate remained elusive. Here, we provide the first comprehensive investigation of RAVER1-controlled AS in cancer cell models. This reveals a pro-oncogenic role of RAVER1 in modulating tumor growth and epithelial-mesenchymal-transition (EMT). Splicing analyses and protein-association studies indicate that RAVER1 guides AS in association with other splicing regulators, including PTBPs and SRSFs. In cancer cells, one major function of RAVER1 is the stimulation of proliferation and restriction of apoptosis. This involves the modulation of AS events within the miR/RISC pathway. Disturbance of RAVER1 impairs miR/RISC activity resulting in severely deregulated gene expression, which promotes lethal TGFB-driven EMT. Among others, RAVER1-modulated splicing events affect the insertion of protein interaction modules in factors guiding miR/RISC-dependent gene silencing. Most prominently, in all three human TNRC6 proteins, RAVER1 controls AS of GW-enriched motifs, which are essential for AGO2-binding and the formation of active miR/RISC complexes. We propose, that RAVER1 is a key modulator of AS events in the miR/RISC pathway ensuring proper abundance and composition of miR/RISC effectors. This ensures balanced expression of TGFB signaling effectors and limits TGFB induced lethal EMT.