Ret

Non-small cell lung cancers (NSCLCs) in non-smokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in non-smokers, alterations in these "non-smoking-related oncogenes" (NSROs) also occur in smokers. To better understand the clonal architecture and genomic landscape of NSRO-driven tumors in smokers compared to typical-smoking NSCLCs, we investigated genomic and transcriptomic alterations in 173 tumor sectors from 48 NSCLC patients...

Neck lumps can be a symptom of thyroid and parathyroid gland metabolic diseases, and papillary thyroid carcinoma is reported in some cases. It is commonly observed in middle-aged people with a female predominance. Papillary carcinoma of the thyroid is the most common type of thyroid cancer, originating from the thyroid gland cells. It is slow-growing and less aggressive, but it has been reported to have the ability to affect nearby lymph nodes and other organs. It is associated with the RET protooncogene, NTRK1, and MET genes...

INTRODUCTION: Dengue is an arboviral disease causing severe illness in over 500,000 people each year. Currently, there is no way to constrain dengue in the clinic. Host kinase regulators of dengue virus (DENV) infection have the potential to be disrupted by existing therapeutics to prevent infection and/or disease progression. METHODS: To evaluate kinase regulation of DENV infection, we performed kinase regression (KiR), a machine learning approach that predicts kinase regulators of infection using existing drug-target information and a small drug screen...

OBJECTIVE: To investigate the performance of structural MRI cortical and subcortical morphometric data combined with blink-reflex recovery cycle (BRrc) values using machine learning (ML) models in distinguishing between essential tremor (ET) with resting tremor (rET) and classic ET. METHODS: We enrolled 47 ET, 43 rET patients and 45 healthy controls (HC). All participants underwent brain 3 T-MRI and BRrc examination at different interstimulus intervals (ISIs, 100-300 msec)...

BACKGROUND: Ultra-performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) is widely used for concentration detection of many Tyrosine Kinase Inhibitors (TKIs), including afatinib, crizotinib, and osimertinib. In order to analyze whether pralsetinib takes effect in Rearranged during Transfection (RET)-positive patients with central nervous system metastasis, we aimed to develop a method for the detection of pralsetinib concentrations in human plasma and Cerebrospinal Fluid (CSF) by UPLC-MS/MS...

As glacier degradation is intensifying worldwide, understanding how and when glacial runoff becomes imperative for economic planning and societal adaptation in response to climate change. This research highlights a probable emergence of new low-flow periods, ranging from one to several weeks, with an anticipated 50-90 % reduction in runoff even in major rivers originating in glacierized mountains by the mid to late 21th century. While the predicted decline in annual and monthly runoff appears moderate for most glaciated regions globally, the emergence of new deglaciation-induced summer low flow periods could create critical "bottle necks" constraining effective water resources management...

During early development, the enteric nervous system forms from the migration of enteric neural crest cells (ENCCs) from the foregut to the hindgut, where they undergo proliferation and differentiation facilitated by interactions with enteric mesenchymal cells (EMCs). This study investigates the impact on ENCC migration of EMC-ENCC communication mediated by GFRA1b expressed in EMCs. GFRA1-expressing cells in day 11-12 (E11-12) mouse embryos differentiated into smooth muscle cells from E12 onwards. Observations at E12-13...

BACKGROUND: Since the publication of the original work in 2014, significant progress has been made in the characterization of genomic alterations that drive oncogenic addiction of nonsmall cell lung cancer (NSCLC) and how the immune system can leverage non-oncogenic pathways to modulate therapeutic outcomes. This update evaluates and validates the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in NSCLC. DATA SOURCES: We performed a literature search from January 2015 to October 2023 using the keywords non-small cell lung cancer , clinical practice guidelines , gene mutations , genomic assay , immune cancer therapy , circulating tumor DNA , predictive and prognostic biomarkers , and targeted therapies ...

OBJECTIVE: To analyse the expression of BRAF V600E protein and RET gene rearrangement in papillary thyroid carcinoma (PTC) combined with Hashimoto's thyroiditis (HT) and to explore its clinical and pathological significance. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Pathology, East China Normal University (Wuhu No. 2 People's Hospital), Wuhu, China, from January 2019 to July 2022. METHODOLOGY: The study population of 150 patients who underwent central lymph node dissection...

Purpose: Retroperitoneal robotic-assisted pyeloplasty (ret-RAP) for ureteropelvic junction obstruction (UPJO) requires a larger retroperitoneal space (RS) to maintain specified distances between robotic (da Vinci) trocars and between trocars and the region of interest. A modified closed technique (MOT) and conventional closed technique (COT) were compared for creating an adequate RS with optical trocars. Methods: RS access in children with UPJO who underwent ret-RAP ( n  = 30) was MOT ( n  = 15) and COT ( n  = 15)...

Cyanidin-3-O-glucoside (C3G), a natural antioxidant, plays multiple physiological or pathological roles in maintaining human health; thereby, designing advanced sensors to achieve specific recognition and high-sensitivity detection of C3G is significant. Herein, an imprinted-type electrochemiluminescence (ECL) sensing platform was developed using core-shell Ru@SiO2 -CMIPs, which were prepared by covalent organic framework (COF)-based molecularly imprinted polymers (CMIPs) embedded in luminescent Ru@SiO2 cores...

The attenuated phase-shift mask (Att. PSM) is proven to be a promising resolution enhancement technology (RET) to improve the imaging performance in extreme ultraviolet (EUV) lithography. However, due to the reflective nature of the mask structure, the serious shadowing effect can affect the diffraction near field of the mask intensely and further impact the lithography imaging. With the purpose of improving the contrast of lithography imaging, a novel structure of the Att. PSM, to the best of our knowledge, is proposed in this paper...

INTRODUCTION: Available treatments for colorectal cancer are limited. However, in the last few years several advances and new treatment options became available and expanded the continuum of care in metastatic colorectal cancer (mCRC). AREAS COVERED: Fruquintinib, a tyrosine kinase inhibitor, has been shown to be effective in heavily pretreated mCRC progressing to trifluridine-tipiracil (FTD/TPI) or regorafenib or both. Preclinical studies have shown that fruquintinib inhibits with high selectivity VEGFR 1-2-3, leading to a blockade in angiogenesis process, but also acts, with weak inhibition, on RET, FGFR-1, and c-kit kinases...

Introduction: Medullary thyroid carcinoma (MTC) is an aggressive cancer that is often caused by driver mutations in RET . Splice site variants (SSV) reflect changes in mRNA processing, which may alter protein function. RET SSVs have been described in thyroid tumors in general but have not been extensively studied in MTC. Methods: The prevalence of RET SSVs was evaluated in 3,624 cases with next generation sequence reports, including 25 MTCs. Fisher exact analysis was performed to compare RET SSV frequency in cancers with/without a diagnosis of MTC...

INTRODUCTION: Poorly differentiated thyroid cancer (PDTC) remains a challenge not only for pathologists and surgeons because of the difficulties associated with the diagnostic process and the compelling need for difficult thyroidectomy, but it is also of high clinical relevance because it is responsible for mortality in non-anaplastic follicular cell-derived thyroid cancer. MATERIALS AND METHODS: Cases of PDTC within a 30-year period were reviewed by two independent pathologists...

Glioblastoma IDH wild type (GBM) is a very aggressive brain tumour, characterised by an infiltrative growth pattern and by a prominent neoangiogenesis. Its prognosis is unfortunately dismal, and the median overall survival of GBM patients is short (15 months). Clinical management is based on bulk tumour removal and standard chemoradiation with the alkylating drug temozolomide, but the tumour invariably recurs leading to patient's death. Clinical options for GBM patients remained unaltered for almost two decades until the encouraging results obtained by the phase II REGOMA trial allowed the introduction of the multikinase inhibitor regorafenib as a preferred regimen in relapsed GBM treatment by the National Comprehensive Cancer Network (NCCN) 2020 Guideline...

Multiple Endocrine Neoplasia type 2B (MEN2B) is an autosomal dominant cancer syndrome caused by a mutation in rearranged during transfection (RET) proto-oncogene and includes medullary thyroid carcinoma, pheochromocytoma, gastrointestinal neuromas, and mucosal ganglioneuromas. Medullary thyroid carcinoma is the major cause of mortality in MEN2B syndrome. Medullary thyroid carcinoma can often appear during the first years of life. While mucosal neuromas in MEN2B are common, laryngeal neuromas are extremely rare...

MET exon 14 skipping mutation has emerged as a new oncogenic driver in NSCLC with available targeted therapies, including Food and Drug Administration-approved inhibitors capmatinib and tepotinib. Potential resistance mechanisms are beginning to be described and include several on-target and off-target mutations. Here, we report an emergent secondary RET fusion in a patient with a primary MET exon 14 skipping mutation that progressed on capmatinib after the initial response. Subsequently, this patient received both a RET inhibitor (selpercatinib) followed by another MET-targeted treatment (tepotinib) without clinical benefit...

Pulpitis is a common and frequent disease in dental clinics. Although vital pulp therapy and root canal treatment can stop the progression of inflammation, they do not allow for genuine structural regeneration and functional reconstruction of the pulp-dentin complex. In recent years, with the development of tissue engineering and regenerative medicine, research on stem cell-based regenerative endodontic therapy (RET) has achieved satisfactory preliminary results, significantly enhancing its clinical translational prospects...

The aim of this study was to construct an enhanced selection index using the genomic and economic parameters of new health disorders and current production and functional traits. Genomic evaluation for the incidence of clinical mastitis (CM), three claw disease traits, retained placenta (RET), metritis (MET), and cystic ovaries (CYS) was performed using linear animal models based on producer-recorded data. Good correlations among the health disorders were found, and their heritability estimates did not exceed 7%...