Morpho-physiological traits and tissue burdens of Ecklonia radiata linked to environmental variation in an urban estuary.

Organisms respond to their environment in various ways, including moving, adapting, acclimatising or a combination of responses. Within estuarine habitats, organisms are exposed to naturally variable environmental conditions. In urbanised estuaries, these natural variations can interact with human stressors such as habitat modification and pollution. Here, we investigated trait variation in the golden kelp Ecklonia radiata across an urban estuary - Sydney Harbour, Australia. We found that kelp morphology differed significantly between the more human-modified inner and the less modified outer harbour. Kelp individuals were smaller, had fewer laminae, and lacked spines in the inner harbour where it was warmer, more contaminated and less light was available. Inner harbour populations were characterised by lower tissue nitrogen and higher lead concentrations. These findings provide insights into how environmental variation could affect kelp morphology and physiology, and the high trait variation suggests adaptive capacity in E. radiata.

Acromegaly in humans and cats: Pathophysiological, clinical and management resemblances and differences.

OBJECTIVE: Acromegaly is a disorder associated with excessive levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). In general, GH/IGF-1 excess leads to morphologic craniofacial and acral changes as well as cardiometabolic complications, but the phenotypic changes and clinical presentation of acromegaly differ across species. Here, we review the pathophysiology, clinical presentation and management of acromegaly in humans and cats, and we provide a systematic comparison between this disease across these different species. DESIGN: A comprehensive literature review of pathophysiology, clinical features, diagnosis and management of acromegaly in humans and in cats was performed. RESULTS: Acromegaly is associated with prominent craniofacial changes in both species: frontal bossing, enlarged nose, ears and lips, and protuberant cheekbones are typically encountered in humans, whereas increased width of the head and skull enlargement are commonly found in cats. Malocclusion, prognathism, dental diastema and upper airway obstruction by soft tissue enlargement are reported in both species, as well as continuous growth and widening of extremities resulting in osteoarticular compromise. Increase of articular joint cartilage thickness, vertebral fractures and spine malalignment is more evident in humans, while arthropathy and spondylosis deformans may also occur in cats. Generalized organomegaly is equally observed in both species. Other similarities between humans and cats with acromegaly include heart failure, ventricular hypertrophy, diabetes mellitus, and an overall increased cardiometabolic risk. In GH-secreting pituitary tumours, local compressive effects and behavioral changes are mostly observed in humans, but also present in cats. Cutis verticis gyrata and skin tags are exclusively found in humans, while palmigrade/plantigrade stance may occur in some acromegalic cats. Serum IGF-1 is used for acromegaly diagnosis in both species, but an oral glucose tolerance test with GH measurement is only useful in humans, as glucose load does not inhibit GH secretion in cats. Imaging studies are regularly performed in both species after biochemical diagnosis of acromegaly. Hypophysectomy is the first line treatment for humans and cats, although not always available in veterinary medicine. CONCLUSION: Acromegaly in humans and cats has substantial similarities, as a result of common pathophysiological mechanisms, however species-specific features may be found.

The role of PD-L1 expression in pituitary tumours: lessons from the current literature.

BACKGROUND: Programmed cell death-1 (PD-1) and PD ligand-1 (PD-L1) expression predicts the biological behaviour, aggres-siveness and response to immune checkpoint inhibitors in different cancers. We reviewed the published data on PD-L1 ex-pression in pituitary tumours, from the perspective of its biological role and prognostic usefulness. SUMMARY: A literature review focused on PD-L1 expression in pituitary tumours was performed. Six immunohistochemistry-based studies which assessed PD-L1 positivity in pituitary tumours were included, encompassing 704 patients. The cohort consisted of 384 (54.5%) non-functioning tumours and 320 (43.5%) functioning pituitary tumours. PD-L1 expression was posi-tive in 248 cases (35.2%). PD-L1 positivity rate was higher in functioning than in non-functioning tumours (46.3% vs 26.0%; p<0.001), but also higher in growth hormone-secreting tumours (56.7%) and prolactinomas (53.6%) than in thyrotroph (33.3%) or corticotroph tumours (20.6%). While proliferative pituitary tumours showed higher rate of PD-L1 positivity than non-proliferative tumours (p<0.001), no association with invasion or recurrence was found. KEY MESSAGES: PD-L1 is expressed in a substantial number of pituitary tumours, predominantly in the functioning ones. PD-L1 positivity rates were significantly higher in proliferative pituitary tumours in comparison to non-proliferative tumours, but no differences were found concerning invasive or recurrent pituitary tumours. More studies following homogeneous and standardised methodologies are needed to fully elucidate the role and usefulness of PD-L1 expression in pituitary tumours.

Comprehensive microRNA expression analysis of pediatric gonadal germ cell tumors: unveiling novel biomarkers and signatures.

microRNAs (miRNAs) are small endogenous noncoding RNAs, and alterations in their expression may contribute to oncogenesis. Discovering a unique miRNA pattern holds the potential for early detection and novel treatment possibilities in cancer. This study aimed to evaluate miRNA expression in pediatric patients with gonadal germ cell tumors (GCTs), focusing on characterizing the miRNA profiles of each histological subtype and identifying a distinct histological miRNA signature for a total of 42 samples of pediatric gonadal GCTs. The analysis revealed distinct miRNA expression profiles for all histological types, regardless of the primary site. We identified specific miRNA expression signatures for each histological type, including 34 miRNAs for dysgerminomas, 13 for embryonal carcinomas, 25 for yolk sac tumors, and one for immature teratoma, compared to healthy controls. Furthermore, we identified 26 miRNAs that were commonly expressed in malignant tumors, with six miRNAs (miR-302a-3p, miR-302b-3p, miR-371a-5p, miR-372-3p, miR-373-3p, and miR-367-3p) showing significant overexpression. Notably, miR-302b-3p exhibited a significant association with all the evaluated clinical features. Our findings suggest that miRNAs have the potential to aid in the diagnosis, prognosis, and management of patients with malignant GCTs.

Artificial light at night and warming impact grazing rates and gonad index of the sea urchin Centrostephanus rodgersii.

Artificial light at night (ALAN) is a growing threat to coastal habitats, and is likely to exacerbate the impacts of other stressors. Kelp forests are dominant habitats on temperate reefs but are declining due to ocean warming and overgrazing. We tested the independent and interactive effects of ALAN (dark versus ALAN) and warming (ambient versus warm) on grazing rates and gonad index of the sea urchin Centrostephanus rodgersii. Within these treatments, urchins were fed either 'fresh' kelp or 'treated' kelp. Treated kelp (Ecklonia radiata) was exposed to the same light and temperature combinations as urchins. We assessed photosynthetic yield, carbon and nitrogen content and C : N ratio of treated kelp to help identify potential drivers behind any effects on urchins. Grazing increased with warming and ALAN for urchins fed fresh kelp, and increased with warming for urchins fed treated kelp. Gonad index was higher in ALAN/ambient and dark/warm treatments compared to dark/ambient treatments for urchins fed fresh kelp. Kelp carbon content was higher in ALAN/ambient treatments than ALAN/warm treatments at one time point. This indicates ocean warming and ALAN may increase urchin grazing pressure on rocky reefs, an important finding for management strategies.

Influence of habitat features on the colonisation of native and non-indigenous species.

Marine artificial structures provide substrates on which organisms can settle and grow. These structures facilitate establishment and spread of non-indigenous species, in part due to their distinct physical features (substrate material, movement, orientation) compared to natural habitat analogues such as rocky shores, and because following construction, they have abundant resources (space) for species to colonise. Despite the perceived importance of these habitat features, few studies have directly compared distributions of native and non-indigenous species or considered how functional identity and associated environmental preferences drive associations. We undertook a meta-analysis to investigate whether colonisation of native and non-indigenous species varies between artificial structures with features most closely resembling natural habitats (natural substrates, fixed structures, surfaces oriented upwards) and those least resembling natural habitats (artificial materials, floating structures, downfacing or vertical surfaces), or whether functional identity is the primary driver of differences. Analyses were done at global and more local (SE Australia) scales to investigate if patterns held regardless of scale. Our results suggest that functional group (i.e., algae, ascidians. barnacles, bryozoans, polychaetes) rather than species classification (i.e., native or non-indigenous) are the main drivers of differences in communities between different types of artificial structures. Specifically, there were differences in the abundance of ascidians, barnacles, and polychaetes between (1) upfacing and downfacing/vertical surfaces, and (2) floating and fixed substrates. When differences were detected, taxa were most abundant on features least resembling natural habitats. Results varied between global and SE Australian analyses, potentially due to reduced variability across studies in the SE Australian dataset. Thus, the functional group and associated preferences of the highest threat NIS in the area should be considered in design strategies (e.g., ecological engineering) to limit their establishment on newly built infrastructure.

Variable effects of substrate colour and microtexture on sessile marine taxa in Australian estuaries.

Concrete infrastructure in coastal waters is increasing. While adding complex habitat and manipulating concrete mixtures to enhance biodiversity have been studied, field investigations of sub-millimetre-scale complexity and substrate colour are lacking. Here, the interacting effects of 'colour' (white, grey, black) and 'microtexture' (smooth, 0.5 mm texture) on colonisation were assessed at three sites in Australia. In Townsville, no effects of colour or microtexture were observed. In Sydney, spirorbid polychaetes occupied more space on smooth than textured tiles, but there was no effect of microtexture on serpulid polychaetes, bryozoans and algae. In Melbourne, barnacles were more abundant on black than white tiles, while serpulid polychaetes showed opposite patterns and ascidians did not vary with treatments. These results suggest that microtexture and colour can facilitate colonisation of some taxa. The context-dependency of the results shows that inclusion of these factors into marine infrastructure designs needs to be carefully considered.

Current extent and future opportunities for living shorelines in Australia.

Living shorelines aim to enhance the resilience of coastlines to hazards while simultaneously delivering co-benefits such as carbon sequestration. Despite the potential ecological and socio-economic benefits of living shorelines over conventional engineered coastal protection structures, application is limited globally. Australia has a long and diverse coastline that provides prime opportunities for living shorelines using beaches and dunes, vegetation, and biogenic reefs, which may be either natural ('soft' approach) or with an engineered structural component ('hybrid' approach). Published scientific studies, however, have indicated limited use of living shorelines for coastal protection in Australia. In response, we combined a national survey and interviews of coastal practitioners and a grey and peer-reviewed literature search to (1) identify barriers to living shoreline implementation; and (2) create a database of living shoreline projects in Australia based on sources other than scientific literature. Projects included were those that had either a primary or secondary goal of protection of coastal assets from erosion and/or flooding. We identified 138 living shoreline projects in Australia through the means sampled starting in 1970; with the number of projects increasing through time particularly since 2000. Over half of the total projects (59 %) were considered to be successful according to their initial stated objective (i.e., reducing hazard risk) and 18 % of projects could not be assessed for their success based on the information available. Seventy percent of projects received formal or informal monitoring. Even in the absence of peer-reviewed support for living shoreline construction in Australia, we discovered local and regional increases in their use. This suggests that coastal practitioners are learning on-the-ground, however more generally it was stated that few examples of living shorelines are being made available, suggesting a barrier in information sharing among agencies at a broader scale. A database of living shoreline projects can increase knowledge among practitioners globally to develop best practice that informs technical guidelines for different approaches and helps focus attention on areas for further research.

Complexity-functioning relationships differ across different environmental conditions.

Habitat complexity is widely considered an important determinant of biodiversity, and enhancing complexity can play a key role in restoring degraded habitats. However, the effects of habitat complexity on ecosystem functioning - as opposed to biodiversity and community structure - are relatively poorly understood for artificial habitats, which dominate many coastlines. With Greening of Grey Infrastructure (GGI) approaches, or eco-engineering, increasingly being applied around the globe, it is important to understand the effects that modifying habitat complexity has on both biodiversity and ecological functioning in these highly modified habitats. We assessed how manipulating physical (primary substrate) and/or biogenic habitat (bivalves) complexity on intertidal artificial substrata affected filtration rates, net and gross primary productivity (NPP and GPP, respectively) and community respiration (CR) - as well as abundance of filter feeders and macro-algae and habitat use by cryptobenthic fish across six locations in three continents. We manipulated both physical and biogenic complexity using 1) flat or ridged (2.5 cm or 5 cm) settlement tiles that were either 2) unseeded or seeded with oysters or mussels. Across all locations, increasing physical and biogenic complexity (5 cm seeded tiles) had a significant effect on most ecological functioning variables, increasing overall filtration rates and community respiration of the assemblages on tiles but decreasing productivity (both GPP and NPP) across all locations. There were no overall effects of increasing either type of habitat complexity on cryptobenthic fish MaxN, total time in frame or macro-algal cover. Within each location, there were marked differences in the effects of habitat complexity. In Hobart, we found higher filtration, filter feeder biomass and community respiration on 5 cm tiles compared to flat tiles. However, at this location, both macro-algae cover and GPP decreased with increasing physical complexity. Similarly in Dublin, filtration, filter feeder biomass and community respiration were higher on 5 cm tiles compared to less complex tiles. In Sydney, filtration and filter feeder biomass were higher on seeded than unseeded tiles, and fish MaxN was higher on 5 cm tiles compared to flat tiles. On unseeded tiles in Sydney, filter feeder biomass also increased with increasing physical complexity. Our findings suggest that GGI solutions via increased habitat complexity are likely to have trade-offs among potentially desired functions, such as productivity and filtration rates, and variable effects on cryptobenthic fish communities. Importantly, our results show that the effects of GGI practices can vary markedly according to the environmental context and therefore should not be blindly and uniformly applied across the globe.

Window therapeutic of extraoral photobiomodulation for prevention of oral mucositis in HSCT patients: additional arm.

PURPOSE: This study aimed to evaluate the efficacy of 1W extraoral photobiomodulation (EOPBM) and to compare with our previous results of 2W EOPBM and intraoral photobiomodulation (IOPBM) protocols in the management of oral mucositis (OM) related to hematopoietic stem cell transplantation (HSCT). METHODS: A total of 30 patients underwent autologous or allogenic HSCT. Experimental protocol of 1W EOPBM was performed daily beginning in the first day of the conditioning regimen until 5 days after transplantation. The application areas included six points on the face and three points on the cervical area. Additional application of IOPBM was performed if patients had ulcered mucositis. Its severity was assessed daily according to WHO (World Health Organization) and NCI (National Cancer Institute) scales. Oral and oropharynx pains were scored daily by visual analogue scale (VAS). RESULTS: The 1W EOPBM protocol was well tolerated without any complaints. Of total, 13 patients were male and 17 were female and the mean age was 49.3 years old. Most patients (21 patients - 70%) received autologous HSCT, and 24 patients (80%) underwent myeloablative conditioning (MAC) regime and 6 patients (20%) reduced intensive conditioning regime. Nineteen patients (63.3%) developed OM according to WHO criteria, 3 patients grade I, 10 grade II and 6 grade III. NCI mucositis grades were similar to WHO grades. OM outcomes of 1W EOPBM were similar when compared to our previous groups and no significant differences were observed. No differences were found between pain and the protocols (1W EOPBM, IOPBM and 2W EOPBM). CONCLUSION: This 1W EOPBM protocol seemed to be as effective as IOPBM and 2W EOPBM in the prevention of OM in HSCT patients. In addition, we might assume that there is a window of application on EOPBM.

Clinicopathological Features of Metastasis to the Oral and Maxillofacial Region-Multicenter Study.

BACKGROUND: This study aimed to investigate the clinicopathological features of metastases in the oral and maxillofacial regions. METHODS: In this retrospective study, biopsy records were obtained from referral centers for oral and maxillofacial diagnosis in Brazil, Guatemala, Mexico, and South Africa. RESULTS: A total of 120 cases were evaluated. Of these, 53.78% affected female patients, with a mean age of 57.64 years. Intraosseous lesions were more frequent, particularly in the posterior region of the mandible (49.58%). Clinically, most cases presented with symptomatic swelling, with an average evolution time of 25 months. The clinical diagnostic hypothesis in most instances was that of a malignant lesion. Breast cancer was the most common primary tumor location in females, while lung origin was most common in males. In most cases, the primary cancer was an adenocarcinoma (44.73%). The follow-up period was available for 29 cases, and out of these, 20 had died due to the disease. CONCLUSION: Although this is a rare condition, clinicians should be aware that any oral lesions have the possibility of being metastatic, particularly in individuals with a previous history of cancer. The findings from this study could assist clinicians in prompt diagnosing these lesions and subsequent conducting oncologic assessments and treatment.

The impacts of artificial light at night on the ecology of temperate and tropical reefs.

Despite 22% of the world's coastal regions experiencing some degree of light pollution, and biologically important artificial light at night (ALAN) reaching large portions of the seafloor (greater than 75%) near coastal developments, the impacts of ALAN on temperate and tropical reefs are still relatively unknown. Because many reef species have evolved in response to low-light nocturnal environments, consistent daily, lunar, and seasonal light cycles, and distinct light spectra, these impacts are likely to be profound. Recent studies have found ALAN can decrease reproductive success of fishes, alter predation rates of invertebrates and fishes, and impact the physiology and biochemistry of reef-building corals. In this paper, we integrate knowledge of the role of natural light in temperate and tropical reefs with a synthesis of the current literature on the impacts of ALAN on reef organisms to explore potential changes at the system level in reef communities exposed to ALAN. Specifically, we identify the direct impacts of ALAN on individual organisms and flow on effects for reef communities, and present potential scenarios where ALAN could significantly alter system-level dynamics, possibly even creating novel ecosystems. Lastly, we highlight large knowledge gaps in our understanding of the overall impact of ALAN on reef systems. This article is part of the theme issue 'Light pollution in complex ecological systems'.

Novel Brazilian hop (Humulus lupulus L.) extracts through supercritical CO2 extraction: Enhancing hop processing for greater sustainability.

Hop cultivation has been increasing in the past decade in Brazil, demanding a better understanding of how the processing influences the national hop varieties. Despite the hop process being well-established in the producer countries, there is still room for optimization to reduce energy consumption for a more sustainable process. This study's main purpose was to understand the influence of drying and supercritical CO2 extraction on the quality of hop extracts. The hop quality during drying was evaluated regarding color, bitter acids, xanthohumol, total essential oil content, and volatile profile. Supercritical CO2 extraction yields, and bitter acid recovery were assessed by HPLC in a range of different temperatures (40 or 60 °C) and pressure (15, 20, 25, or 30 MPa) conditions. Hop processing was optimized to produce a greater extract quality from a Brazilian hop variety, saving energy and solvent consumption, and consequently, reducing the process footprint. Furthermore, this study established supercritical CO2 extraction conditions for Brazilian hop extract production, offering the national beer industry an alternative to overpriced products.

High-Throughput Drug Screening Revealed That Ciclopirox Olamine Can Engender Gastric Cancer Stem-like Cells.

Cancer stem cells (CSCs) are relevant therapeutic targets for cancer treatment. Still, the molecular circuits behind CSC characteristics are not fully understood. The low number of CSCs can sometimes be an obstacle to carrying out assays that explore their properties. Thus, increasing CSC numbers via small molecule-mediated cellular reprogramming appears to be a valid alternative tool. Using the SORE6-GFP reporter system embedded in gastric non-CSCs (SORE6-), we performed a high-throughput image-based drug screen with 1200 small molecules to identify compounds capable of converting SORE6- to SORE6+ (CSCs). Here, we report that the antifungal agent ciclopirox olamine (CPX), a potential candidate for drug repurposing in cancer treatment, is able to reprogram gastric non-CSCs into cancer stem-like cells via activation of SOX2 expression and increased expression of C-MYC, HIF-1α, KLF4, and HMGA1. This reprogramming depends on the CPX concentration and treatment duration. CPX can also induce cellular senescence and the metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. We also disclose that the mechanism underlying the cellular reprogramming is similar to that of cobalt chloride (CoCl2), a hypoxia-mimetic agent.

Cardiorespiratory fitness in individuals with type 2 diabetes mellitus: a systematic review and meta-analysis.

Objective: To conduct a systematic review and meta-analysis assessing the cardiorespiratory fitness (CRF) among individuals with and without type 2 diabetes. Materials and methods: The current review was registered in PROSPERO under the number CRD42018082718. MEDLINE, EMBASE, and Cochrane Library databases were searched from inception through February 2022. Eligibility criteria consisted of observational or interventional studies that evaluated CRF through cardiopulmonary exercise testing or six-minute walk test in individuals with type 2 diabetes compared with individuals without type 2 diabetes. For data extraction, we used baseline CRF assessments of randomized clinical trials or follow-up CRF assessments in observational studies. We performed a meta-analysis using maximal oxygen consumption (VO2 max), and distance walked in the 6MWT as primary outcomes. They were extracted and expressed as mean differences (MDs) and 95% CIs between treatment and comparator groups. The meta-analysis was conducted using Review Manager (RevMan) software. Results: Out of 8,347 studies retrieved, 77 were included. Compared with individuals without type 2 diabetes, individuals with diabetes achieved a lower VO2 max (-5.84 mL.kg-1.min-1, 95% CI -6.93, -4.76 mL.kg-1.min-1, p = <0.0001; I2 = 91%, p for heterogeneity < 0.0001), and a smaller distance walked in 6MWT (-93.30 meters, 95% CI -141.2, -45.4 meters, p > 0.0001; I2: 94%, p for heterogeneity < 0.0001). Conclusion: Type 2 diabetes was associated with lower cardiorespiratory fitness, as observed by lower VO2 max on maximal tests, and smaller distance walked in 6MWT, however the quality of studies was low.

Urban shading and artificial light at night alter natural light regimes and affect marine intertidal assemblages.

Urban development in many coastal cities has resulted in altered natural light regimes, with many coastal habitats being artificially shaded during the daytime by built structures such as seawalls and piers, while artificial light emitted from buildings and associated infrastructure creates pollution at night. As a result, these habitats may experience changes to community structure and impacts on key ecological processes such as grazing. This study investigated how changes to light regimes affect the abundance of grazers on natural and artificial intertidal habitats in Sydney Harbour, Australia. We also examined whether differences in patterns of responses to shading or artificial light at night (ALAN) varied across different areas within the Harbour, characterised by different overall levels of urbanisation. As predicted, light intensity was greater during the daytime on rocky shores than seawalls at the more urbanised sites of the harbour. We found a negative relationship between the abundance of grazers and increasing light during the daytime on rocky shores (inner harbour) and seawalls (outer harbour). We found similar patterns at night on rocky shores, with a negative relationship between the abundance of grazers and light. However, on seawalls, grazer abundances increased with increasing night-time lux levels, but this was mainly driven by one site. Overall, we found the opposite patterns for algal cover. Our findings corroborate those of previous studies that found that urbanisation can significantly affect natural light cycles, with consequences to ecological communities.

Molecular Biology of Pediatric and Adult Ovarian Germ Cell Tumors: A Review.

Ovarian germ cell tumors (OGCTs) are rare in adults; indeed, they occur predominantly in children, adolescents, and young adults, and they account for approximately 11% of cancer diagnoses in these groups. Because OGCTs are rare tumors, our current understanding of them is sparse; this is because few studies have investigated the molecular basis of pediatric and adult cancers. Here, we review the etiopathogenesis of OGCTs in children and adults, and we address the molecular landscape of these tumors, including integrated genomic analysis, microRNAs, DNA methylation, the molecular implications of treatment resistance, and the development of in vitro and in vivo models. An elucidation of potential molecular alterations may provide a novel field for understanding the pathogenesis, tumorigenesis, diagnostic markers, and genetic peculiarity of the rarity and complexity of OGCTs.

Somatic mutation detection and KRAS amplification in testicular germ cell tumors.

Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center. Materials and methods: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Results: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable. Conclusion: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.