Gallbladder dysfunction caused by MYPT1 ablation triggers cholestasis-induced hepatic fibrosis in mice.

BACKGROUND: The incidence of gallbladder diseases is as high as 20%, but whether gallbladder diseases contribute to hepatic disorders remains unknown. METHODS: Here, we established an animal model of gallbladder dysfunction and assessed the role of a diseased gallbladder in cholestasis-induced hepatic fibrosis (CIHF). RESULTS: Mice with smooth muscle-specific deletion of Mypt1, the gene encoding the main regulatory subunit of myosin light chain phosphatase (myosin phosphatase target subunit 1 [MYPT1]), had apparent dysfunction of gallbladder motility. This dysfunction was evidenced by abnormal contractile responses, namely, inhibited cholecystokinin 8-mediated contraction and nitric oxide-resistant relaxation. As a consequence, the gallbladder displayed impaired bile filling and biliary tract dilation comparable to the alterations in CIHF. Interestingly, the mutant animals also displayed CIHF features, including necrotic loci by the age of 1 month and subsequently exhibited progressive fibrosis and hyperplastic/dilated bile ducts. This pathological progression was similar to the phenotypes of the animal model with bile duct ligation and patients with CIHF. The characteristic biomarker of CIHF, serum alkaline phosphatase activity, was also elevated in the mice. Moreover, we observed that the myosin phosphatase target subunit 1 protein level was able to be regulated by several reagents, including lipopolysaccharide, exemplifying the risk factors for gallbladder dysfunction and hence CIHF. CONCLUSIONS: We propose that gallbladder dysfunction caused by myosin phosphatase target subunit 1 ablation is sufficient to induce CIHF in mice, resulting in impairment of the bile transport system.

Analysis of stage parameters of low-temperature oxidation of water-soaked coal based on kinetic principles.

Mine fires caused by spontaneous coal combustion are major disasters in coal mines. The staged oxidation kinetic parameters of various coal samples at oxygen concentrations of 21 %, 15 %, 10 %, 5 %, and 3 % were analyzed using a programmed temperature testing system. Herein, the temperature increase rate of coal, the temperature difference between the furnace and coal, and the oxygen consumption characteristics were obtained. Based on the amount of CO produced and the temperature sensitivity coefficient, three characteristic temperatures and four stages of low-temperature oxidation (LTO) were identified. The results showed that at a critical temperature (TC), the amount of CO gas released from the coal samples increased with increasing oxygen concentration, and the difference in the oxygen consumption rate increased. After the limit temperature (Tu), the amount of CO gas increased steadily, and the increase in the oxygen consumption rate stagnated. CO production, the maximum heating rate, and the maximum heat release rate were positively correlated with the oxygen concentration. As the oxygen concentration increased, the activation energy during the oxygen absorption stage gradually decreased. The average reaction enthalpy (ΔH) of pre-oxidized water-immersed coal was 19.37 kJ/kg greater than that of raw coal. The equation for the conservation of energy of the coal oxidation warming process was normalized. The theoretical values of the awakening stage and the stable stage were τν and τν (1-B), respectively. When B was >1, pre-oxidized water-immersed coal at a low oxygen concentration was prone to crossover points during the oxygen absorption stage, which increased the risk of coal spontaneous combustion (CSC). The research results could provide a theoretical basis for the staged control of the spontaneous combustion of water-immersed coal in goaf areas.

Charge-reversal polymeric nanomodulators for ferroptosis-enhanced photodynamic therapy.

The clinical application of photodynamic therapy (PDT) has some limitations including poor tumor targeting properties, a high reductive tumor microenvironment, and inefficient activation of single cell death machinery. We herein report pH-sensitive polymeric nanomodulators (NBS-PDMC NPs) for ferroptosis-enhanced photodynamic therapy. NBS-PDMC NPs were constructed using a positively charged type-I photosensitizer (NBS) coordinated with a demethylcantharidin (DMC)-decorated block copolymer via electrostatic interactions. NBS-PDMC NPs had a negative surface charge, which ensures their high stability in bloodstream circulation, while exposure to lysosomal acidic environments reverses their surface charge to positive for tumor penetration and the release of DMC and NBS. Under NIR light irradiation, NBS generated ROS to induce cell damage; in the meantime, DMC inhibited the expression of the GPX4 protein in tumor cells and promoted ferroptosis of tumor cells. This polymer design concept provides some novel insights into smart drug delivery and combinational action to amplify the antitumor effect.

A fast and smooth one-electron approach for investigating charge transfer states and D1-D0 crossings for systems with odd numbers of electrons.

We propose an efficient version of ensemble Hartree-Fock/density functional theory to calculate a set of two charge-transfer states for systems with odd-numbers of electrons. The approach does require definitions of donor/acceptor fragments; however, the approach is not very sensitive to such definitions-even in the limit of very strong electronic coupling. The key ansatz is that, by mandating that the vector space spanned by the active orbitals projects equally onto the donor and acceptor fragments, such a constraint eliminates all intra-molecular local excitations and makes it far easier to generate potential energy surfaces that are smooth over a wide region of configuration space. The method is fast, working with only two electron configurations, and should be useful for ab initio non-adiabatic dynamics in the near future.

Haloketones: A class of unregulated priority DBPs with high contribution to drinking water cytotoxicity.

Although unregulated aliphatic disinfection byproducts (DBPs) had a much higher concentration and cytotoxicity than known aromatic DBPs, a recent study indicated that seven classes of regulated and unregulated priority DBPs (one and two-carbon-atom DBPs) just accounted for 16.2% of disinfected water cytotoxicity in the U.S., meaning some of the highly toxic aliphatic DBPs may be overlooked. Haloketones (HKs) are an essential class of priority DBPs with a 1-100 µg/L concentration in drinking water but lack cytotoxicity data. This study investigated the cytotoxicity of seven HKs using Chinese hamster ovary (CHO) cells. The order for cytotoxicity of HKs from most to least toxic was: 1,3-dichloroacetone (LC50: 1.0 ± 0.20 µM) ≈ 1,3-dibromoacetone (1.5 ± 0.19 µM) ≈ bromoacetone (1.9 ± 0.49 µM) > chloroacetone (4.3 ± 0.22 µM) > 1,1,3-trichloropropanone (6.6 ± 0.46 µM) > 1,1,1-trichloroacetone (222 ± 7.7 µM) > hexachloroacetone (3269 ± 344 µM). The cytotoxicity of HKs was higher than most regulated and priority aliphatic DBPs in mono-halogenated, di-halogenated, and tri-halogenated categories. A prediction model of HK cytotoxicity was developed based on the quantitative structure-activity relationship (QSAR), optimizing structures and computing descriptors with Gaussian 09 W. The average concentrations of HKs in representative drinking water samples from South Carolina (U.S.) and Suzhou (China) were 12.4 and 0.9 µg/L, respectively, accounting for 18.8% and 1.7% of their specific total DBPs measured (i.e. not TOX). For South Carolina drinking water, their contributions to total calculated additive cytotoxicity of aliphatic DBPs and overall drinking water cytotoxicity were 86.7% and 14.0%, respectively, demonstrating that HKs are an essential class of overlooked DBPs with a high contribution to drinking water cytotoxicity. Our study can help to explain the conflict that why regulated and priority DBPs (except HKs) just accounted for 16% of chlorinated drinking water cytotoxicity even enough they had much higher concentration and cytotoxicity than known aromatic DBPs.

SuperAnimal pretrained pose estimation models for behavioral analysis.

Quantification of behavior is critical in diverse applications from neuroscience, veterinary medicine to animal conservation. A common key step for behavioral analysis is first extracting relevant keypoints on animals, known as pose estimation. However, reliable inference of poses currently requires domain knowledge and manual labeling effort to build supervised models. We present SuperAnimal, a method to develop unified foundation models that can be used on over 45 species, without additional manual labels. These models show excellent performance across six pose estimation benchmarks. We demonstrate how to fine-tune the models (if needed) on differently labeled data and provide tooling for unsupervised video adaptation to boost performance and decrease jitter across frames. If fine-tuned, SuperAnimal models are 10-100× more data efficient than prior transfer-learning-based approaches. We illustrate the utility of our models in behavioral classification and kinematic analysis. Collectively, we present a data-efficient solution for animal pose estimation.

Study on the Formation Mechanism of a Core-Shell Structure during Graphitization of Anthracite.

Graphite is a revolutionary material, and the development of synthetic graphite could potentially solve the shortage of natural graphite in the future. In this paper, the formation of core-shell-structured synthetic graphite prepared from an anthracite-FeO mixture was systematically investigated by a two-step method. First, heat treatment was performed on a layer of almandine (3FeO·Al2O3·3SiO2) particles to obtain a large quantity of uniform-sized glass-phase spheroids. Second, the deashed anthracite was graphitized on the surface of the obtained spheroids to prepare core-shell-structured graphite. Furthermore, the obtained graphite products were systematically characterized by XRD, Raman spectroscopy, SEM-EDS, and TEM. Finally, a model was proposed to illustrate the formation mechanism of the core-shell structure during graphitization of the anthracite-almandine mixture. Under lower temperatures, almandine started to melt into spheroids. Under higher temperatures, the volatile components in the anthracite turned into the gas phase, and the carbon matrix started to bend on the surface of the core material and deposit layer by layer, thus forming the core-shell-structured graphite. The findings could provide theoretical guidance for the synthetic graphite industry and have meaningful implications for the coal chemistry field.

AppleQSM: Geometry-Based 3D Characterization of Apple Tree Architecture in Orchards.

The architecture of apple trees plays a pivotal role in shaping their growth and fruit-bearing potential, forming the foundation for precision apple management. Traditionally, 2D imaging technologies were employed to delineate the architectural traits of apple trees, but their accuracy was hampered by occlusion and perspective ambiguities. This study aimed to surmount these constraints by devising a 3D geometry-based processing pipeline for apple tree structure segmentation and architectural trait characterization, utilizing point clouds collected by a terrestrial laser scanner (TLS). The pipeline consisted of four modules: (a) data preprocessing module, (b) tree instance segmentation module, (c) tree structure segmentation module, and (d) architectural trait extraction module. The developed pipeline was used to analyze 84 trees of two representative apple cultivars, characterizing architectural traits such as tree height, trunk diameter, branch count, branch diameter, and branch angle. Experimental results indicated that the established pipeline attained an R2 of 0.92 and 0.83, and a mean absolute error (MAE) of 6.1 cm and 4.71 mm for tree height and trunk diameter at the tree level, respectively. Additionally, at the branch level, it achieved an R2 of 0.77 and 0.69, and a MAE of 6.86 mm and 7.48° for branch diameter and angle, respectively. The accurate measurement of these architectural traits can enable precision management in high-density apple orchards and bolster phenotyping endeavors in breeding programs. Moreover, bottlenecks of 3D tree characterization in general were comprehensively analyzed to reveal future development.

Understanding the Relationship Between Vascular Smooth Muscle Cell Function and the Efficacy of Acupuncture in Treating Cerebral Ischemic Stroke: A Preclinical Meta-Analysis and Systematic Review.

Background: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models. Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD). Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=-3.75 [95% CI, -5.54 to -1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies. Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.

The relationship between serum resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder.

BACKGROUND: Inflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear. METHODS: Forty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6-8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1ß, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment. RESULTS: Serum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1ß, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1ß, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents. CONCLUSIONS: Our study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.

Bioorthogonal masked acylating agents for proximity-dependent RNA labelling.

RNA localization is highly regulated, with subcellular organization driving context-dependent cell physiology. Although proximity-based labelling technologies that use highly reactive radicals or carbenes provide a powerful method for unbiased mapping of protein organization within a cell, methods for unbiased RNA mapping are scarce and comparably less robust. Here we develop α-alkoxy thioenol and chloroenol esters that function as potent acylating agents upon controlled ester unmasking. We pair these probes with subcellular-localized expression of a bioorthogonal esterase to establish a platform for spatial analysis of RNA: bioorthogonal acylating agents for proximity labelling and sequencing (BAP-seq). We demonstrate that, by selectively unmasking the enol probe in a locale of interest, we can map RNA distribution in membrane-bound and membrane-less organelles. The controlled-release acylating agent chemistry and corresponding BAP-seq method expand the scope of proximity labelling technologies and provide a powerful approach to interrogate the cellular organization of RNAs.

Pneumonic-type lung adenocarcinoma with KRAS G12V mutation and sustained response to Afatinib.

BACKGROUND: Pneumonic-type lung adenocarcinoma (P-ADC) is a rare and challenging subtype of primary lung cancer that can be difficult to distinguish from pneumonia based on radiological images. Furthermore, no drugs are currently available that specifically target KRAS G12V. CASE PRESENTATION: Here we report a case of P-ADC with typical and informative imaging features throughout the course of the disease, including patchy shadows, high-density lesions with aerated bronchus, diffuse ground-glass opacities, and nodular shadows from computed tomography (CT) scan. The KRAS G12V mutation was detected using Next-generation sequencing (NGS). An individualized Afatinib-based therapeutic schedule was prescribed and achieved sustained response after multiple lines of treatment had failed. CONCLUSION: Our case highlights the typical and dynamic changes in imaging features of P-ADC and provides an indicative treatment strategy for KRAS G12V-mutated lung adenocarcinoma.

[Air Microbial Contamination and Risk of Respiratory Exposure of Workers in Chicken Farms].

Animal farms are important sources of microbial contamination in the air environment. However, there are few reports on the time-regularity characteristics of airborne microbial contamination in farms. In the context of this situation, a study was conducted for more than 80 weeks using 16S rRNA gene amplicon sequencing to characterize the bacterial distribution and respiratory exposure in the farm air and fecal environment, respectively, taking a layer farm as an example. The results showed that 16S rRNA concentrations in air and manure samples ranged from 6.08×105-4.90×106 copies·m-3 and 4.27×108-1.15×1010 copies·g-1, respectively. The mean values of airborne bacterial concentrations were significantly higher in winter than in summer, whereas the biodiversity showed the opposite trend. The dominant bacterial phylum in both air and manure in the layer farm was Firmicutes. During the investigated time, the top three dominant genera in the air were relatively stable, in the order of Lactobacillus, Bacteroides, and Faecalibacterium, whereas the dominant genera in feces fluctuated with the increase in breeding time. The correlation between the community structure of bacteria and pathogenic bacteria in both air and manure was not significant, but the concentrations of both target microorganisms in different media were significantly correlated. The bioaerosolization index of bacteria in manure showed an increasing trend with increasing breeding time, whereas the opposite trend was observed for pathogenic bacteria. In this case, [Ruminococcus]_torques_group, Bacteroides, and Faecalibacterium were the top three pathogenic genera that were the most prone to aerosolization. There were seasonal differences in bacterial respiratory exposures of chicken farm workers, with mean intake values of 2.54×107 copies·d-1 and 2.87×105 copies·d-1 for bacteria and pathogenic bacteria, respectively. The results of this study will provide a scientific basis for systematically assessing the contamination characteristics and potential health risks of airborne microorganisms on farms and for developing corresponding industry standards for occupational exposure and prevention and control measures.

A simple one-electron expression for electron rotational factors.

Within the context of fewest-switch surface hopping (FSSH) dynamics, one often wishes to remove the angular component of the derivative coupling between states J and K. In a previous set of papers, Shu et al. [J. Phys. Chem. Lett. 11, 1135-1140 (2020)] posited one approach for such a removal based on direct projection, while we isolated a second approach by constructing and differentiating a rotationally invariant basis. Unfortunately, neither approach was able to demonstrate a one-electron operatorÔ whose matrix element JÔK was the angular component of the derivative coupling. Here, we show that a one-electron operator can, in fact, be constructed efficiently in a semi-local fashion. The present results yield physical insight into designing new surface hopping algorithms and are of immediate use for FSSH calculations.

Practical phase-space electronic Hamiltonians for ab initio dynamics.

Modern electronic structure theory is built around the Born-Oppenheimer approximation and the construction of an electronic Hamiltonian Hel(X) that depends on the nuclear position X (and not the nuclear momentum P). In this article, using the well-known theory of electron translation (Γ') and rotational (Γ″) factors to couple electronic transitions to nuclear motion, we construct a practical phase-space electronic Hamiltonian that depends on both nuclear position and momentum, HPS(X,P). While classical Born-Oppenheimer dynamics that run along the eigensurfaces of the operator Hel(X) can recover many nuclear properties correctly, we present some evidence that motion along the eigensurfaces of HPS(X,P) can better capture both nuclear and electronic properties (including the elusive electronic momentum studied by Nafie). Moreover, only the latter (as opposed to the former) conserves the total linear and angular momentum in general.

Research on reliability index and failure probability of inherent defect insurance from the insurance perspective.

With the continuous improvement of people 's living standards, people have put forward higher requirements for the safety and comfort of housing. Therefore, Inherent Defect Insurance, a financial method to guarantee the quality of construction projects, has also emerged. At present, China 's Inherent Defect Insurance has been gradually promoted, but its claim mechanism has not been analyzed and studied. From the perspective of construction engineering, this paper first makes a bibliometric analysis of the influencing factors of insurance claims that may be caused by construction engineering quality through VOSViewers, and the evaluation index system of inherent defects is constructed. Then, according to the influencing factors, the PSO-LSSVR model is adopted to fit the performance function of the inherent defects. Finally, based on the reliability design principle of engineering structure, the reliability index and failure probability of Inherent Defect Insurance are derived from the performance function of inherent defects. This paper also analyzes its application in insurance practice and determines the relationship between the number of insurance underwriting policies and the initial reserve of insurance at a certain risk level. This paper studies the probability of Inherent Defect Insurance by constructing the reliability model of inherent defect risks in construction quality, and analyzes the anti-risk ability of insurance companies from the perspective of claim, which provides scientific analysis methods and theoretical basis for the scientific decision-making of insurance companies.

An Unusual Presentation of Cobblestone Esophagus From Bisphosphonate Use.

Cobblestone esophagus is a rare finding that has been previously described in cases of eosinophilic esophagitis (EoE), candidiasis, Barrett's esophagus, or severe reflux esophagitis from distal gastrointestinal obstruction. We describe a case of asymptomatic cobblestone esophagus secondary to bisphosphonate use.  A 67-year-old female was seen in the clinic for evaluation of microcytic anemia that was incidentally picked up on routine chronic disease follow-up. She had no gastrointestinal symptoms. She has been taking oral alendronate 70mg once a week for osteoporosis since a year ago. Barium meal was performed as the patient initially opted for non-invasive testing, which incidentally showed a diffuse "cobblestone" appearance. Subsequent oesophago-gastro-duodenoscopy (OGD) showed diffuse white nodular lesions along the esophagus with a cobblestone appearance but no ulcer or mass. Segmental esophageal biopsies were negative for fungal stain and did not show any pathology. In the absence of infection, eosinophilic esophagitis, and dysplasia, her "cobblestone" esophagus was attributed to bisphosphonate use by diagnosis of exclusion. Alendronate acid was held off, and serial barium meals over the next year showed significant interval improvement.  Bisphosphonates, such as alendronate acid, are commonly associated with drug-induced esophagitis. With the cessation of the offending medication, there was indeed a significant improvement in our patient's serial barium meal. It is important to review the medication list when encountering patients who present with cobblestone esophagus, as some of these patients with drug-induced esophagitis may be asymptomatic clinically.

Predicting Risk of Bullying Victimization among Primary and Secondary School Students: Based on a Machine Learning Model.

School bullying among primary and secondary school students has received increasing attention, and identifying relevant factors is a crucial way to reduce the risk of bullying victimization. Machine learning methods can help researchers predict and identify individual risk behaviors. Through a machine learning approach (i.e., the gradient boosting decision tree model, GBDT), the present longitudinal study aims to systematically examine individual, family, and school environment factors that can predict the risk of bullying victimization among primary and secondary school students a year later. A total of 2767 participants (2065 secondary school students, 702 primary school students, 55.20% female students, mean age at T1 was 12.22) completed measures of 24 predictors at the first wave, including individual factors (e.g., self-control, gender, grade), family factors (family cohesion, parental control, parenting style), peer factor (peer relationship), and school factors (teacher-student relationship, learning capacity). A year later (i.e., T2), they completed the Olweus Bullying Questionnaire. The GBDT model predicted whether primary and secondary school students would be exposed to school bullying after one year by training a series of base learners and outputting the importance ranking of predictors. The GBDT model performed well. The GBDT model yielded the top 6 predictors: teacher-student relationship, peer relationship, family cohesion, negative affect, anxiety, and denying parenting style. The protective factors (i.e., teacher-student relationship, peer relationship, and family cohesion) and risk factors (i.e., negative affect, anxiety, and denying parenting style) associated with the risk of bullying victimization a year later among primary and secondary school students are identified by using a machine learning approach. The GBDT model can be used as a tool to predict the future risk of bullying victimization for children and adolescents and to help improve the effectiveness of school bullying interventions.

MET alterations detection platforms and clinical implications in solid tumors: a comprehensive review of literature.

MET alterations, including MET exon 14 skipping variants, MET amplification, MET overexpression, and MET fusion, play pivotal roles in primary tumorigenesis and acquired resistance to targeted therapies, especially EGFR tyrosine kinase inhibitors. They represent important diagnostic, prognostic, and predictive biomarkers in many solid tumor types. However, the detection of MET alterations is challenging due to the complexity of MET alterations and the diversity of platform technologies. Therefore, techniques with high sensitivity, specificity, and reliable molecular detection accuracy are needed to overcome such hindrances and aid in biomarker-guided therapies. The current review emphasizes the role of MET alterations as oncogenic drivers in a variety of cancers and their involvement in the development of resistance to targeted therapies. Moreover, our review provides an overview of and recommendations on the selection of various cross-platform technologies for the detection of MET exon 14 skipping variants, MET amplification, MET overexpression, and MET fusion. Furthermore, challenges and hurdles underlying these common detection platforms are discussed.