Effect of different optimization parameters in single isocenter multiple brain metastases radiosurgery.

PURPOSE: Automated treatment planning for multiple brain metastases differs from traditional planning approaches. It is therefore helpful to understand which parameters for optimization are available and how they affect the plan quality. This study aims to provide a reference for designing multi-metastases treatment plans and to define quality endpoints for benchmarking the technique from a scientific perspective. METHODS: In all, 20 patients with a total of 183 lesions were retrospectively planned according to four optimization scenarios. Plan quality was evaluated using common plan quality parameters such as conformity index, gradient index and dose to normal tissue. Therefore, different scenarios with combinations of optimization parameters were evaluated, while taking into account dependence on the number of treated lesions as well as influence of different beams. RESULTS: Different scenarios resulted in minor differences in plan quality. With increasing number of lesions, the number of monitor units increased, so did the dose to healthy tissue and the number of interlesional dose bridging in adjacent metastases. Highly modulated cases resulted in 4-10% higher V10% compared to less complex cases, while monitor units did not increase. Changing the energy to a flattening filter free (FFF) beam resulted in lower local V12Gy (whole brain-PTV) and even though the number of monitor units increased by 13-15%, on average 46% shorter treatment times were achieved. CONCLUSION: Although no clinically relevant differences in parameters where found, we identified some variation in the dose distributions of the different scenarios. Less complex scenarios generated visually more dose overlap; therefore, a more complex scenario may be preferred although differences in the quality metrics appear minor.

Persistent depression of the lambda site with progressive skull deformity may be a sign of suture closure: Case series and pathological consideration.

BACK GROUND: Flat head syndrome (FHS) sometimes occurs when a baby maintains the same head position during the first several months of life causing a skull deformity. FHS usually improves with time and natural growth, however, some shows aggravation against conservative treatment. We reviewed pathologically proved early closure of skull suture that may have seen secondary to FHS. METHODS: The clinical and radiological findings of the patients who showed progressive skull deformity resembling FHS were retrospectively reviewed. All the patients underwent surgical treatment and pathological specimens were obtained. RESULTS: The detected patients included two 5-month-old infants and one 1-year-old infant. The formers were conservatively treated without any obvious premature suture closure on computed tomography (CT), and later developed progressive tower-like skull deformities. The infants were diagnosed with possible premature fusion of Lambda site and underwent removal around lambda depression (LD). The latter showed evident sagittal suture closure on CT with digital markings, and was diagnosed with increased intracranial pressure and underwent cranioplasty of posterior expansion. Histopathological specimens obtained from the patients' resected sutures showed irregularly narrowed suture structure with ossification and fibrous tissue proliferation within them, supporting the diagnosis of premature closure of the sagittal sutures. Their postoperative courses were uneventful, and their skull deformities subsequently improved. CONCLUSIONS: Conservative therapy-resistant progressive occipital skull deformity with LD may be a sign of early suture closure, even if CT does not show obvious suture closure. The findings are helpful for early diagnosis and might lead to minimal invasive surgery if needed.

Subtalar arthroereisis with metallic implant is a safe and effective treatment for pediatric patients with symptomatic flexible flatfeet. A 10-year clinical and radiographic follow-up.

BACKGROUND: Subtalar arthroereisis (SA) is an increasingly applied minimally invasive approach for flexible flat foot (FFF) not responsive to conservative treatment. This study aimed at evaluating the long-term clinical and radiographic outcomes of SA in pediatric patients with symptomatic FFF. METHODS: Thirty-seven patients (11.9 ± 1.6yy) underwent SA (74 feet), with outcomes assessed after a mean 10-year follow-up. Pain, quality of life, foot functionality, and alignment were evaluated using validated tools and radiographic parameters, calculated on weightbearing x-rays pre- and post-operatively. RESULTS: Clinical outcomes reached excellent postoperative results (FFI: 9.1, AOFAS: 94.5) with a low 0.9 NRS pain (p < 0.01) and a 92 % satisfaction. All radiographic parameters improved significantly towards normal values: CP 17.5 ± 3.9, MA 4.3 ± 5.8, TCA 42.8 ± 6.2, TNCA 21.1 ± 8.5, TNU% 26.6 ± 8.4 (all p < 0.01). CONCLUSIONS: SA with a metallic endosinotarsal device provided significant long-term clinical and radiographic improvements, with low complication rates and high patient satisfaction, supporting its efficacy as a treatment option for pediatric symptomatic FFF. LEVEL OF EVIDENCE: IV.

Evaluating the effects of laver cultivation on tidal flat erosion: Toward sustainable environmental practices.

The rapid expansion of laver (Porphyra yezoensis) cultivation on lower tidal flats has become integral to the local economy, yet it also raises concerns regarding its potential impact on the morphological evolution due to increasing human activities. This study utilizes integrated near-bed field measurements to assess morphological dynamics and quantify sediment erosion processes, highlighting the significant impact of laver harvest on tidal flat stability. Our results show that erosion and bed coarsening in the cultivated areas experienced a notable intensification immediately after harvest, with net erosion in cultivated areas reaching approximately -38.2 mm during the first tide post-harvest, markedly higher-more than an order of magnitude-compared to adjacent uncultivated areas. The erosion rate notably spiked with the average bed level change rate increasing to -13.8 × 10-4 mm/s, compared to a rate of +0.3 × 10-4 mm/s during the unharvest period. Subsequently, the cultivated areas entered a recovery phase with a deposition amount of +12.5 mm, while the net cumulative erosion thickness throughout the entire observation period was -25.2 mm. The cultivation method, characterized by consistent harvests every 10 days, means that even minor erosion from continuous harvests can escalate into significant degradation. This study suggests that long-term cultivation cycle practices may result in irreversible changes to the depositional environment, potentially jeopardizing the habitat viability and ecological function. Sustainable agricultural strategies, including site selection, infrastructure planning, monitoring environmental changes, ecological assessments and sustainable practices, are recommended to mitigate the negative impacts of cultivation on regional stability and preserve the coastal ecological balance.

Experimental system and method of aerobic thermal environment simulation based on laser heating.

Considering the superior luminous intensity characteristics of lasers, a thermal simulation platform employing laser-induced heating in an aerobic environment was developed. Achieving a uniformly distributed flat-topped square laser beam output was facilitated through optical fibre bundling techniques, while precise control over laser power output was attained through current modulation. Utilising the aforementioned system, thermal shock simulation experiments were conducted in an aerobic environment, subjecting two types of high-temperature-resistant composites, namely C/C and C/SiC, to temperatures up to 1800 °C. These composites were lightweight, heat-resistant materials designed for hypersonic vehicle applications. The results show that the system and method can be used to simulate high temperatures, rapid temperature increases, and thermal shocks on C/C composite materials, with minimal variation in the coupling coefficient under aerobic conditions. The system and method can also provide key technology support for thermal-force-oxygen coupling testing of high temperature resistant materials.

Pest categorisation of Cenopalpus irani.

The EFSA Panel on Plant Health performed a pest categorisation of Cenopalpus irani (Trombidiformes: Tenuipalpidae), known as the Iranian false spider mite, following the commodity risk assessment of Malus domestica plants from Türkiye, in which C. irani was identified as a pest of possible concern for the territory of the European Union (EU). The pest is only known to be present in Iran and Türkiye and has not been reported from the EU. The mite primarily feeds on Rosaceae plants but is considered polyphagous. Important crops of the EU that are hosts of C. irani include apples (Malus domestica), pears (Pyrus communis) and figs (Ficus carica). Plants for planting and fruits provide potential pathways for entry into the EU. Host availability and climate suitability in southern EU countries would most probably allow this species to successfully establish and spread. This mite is not listed in Annex II of Commission Implementing Regulation (EU) 2019/2072. Phytosanitary measures are available to reduce the likelihood of entry and spread of this species into the EU. The mite C. irani satisfies the criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest, although there is a key uncertainty over the likelihood and magnitude of impact.

Effects of debranched starch on physicochemical properties and in vitro digestibility of flat rice noodles.

Aiming to develop flat rice noodles with both desirable textural quality and lower starch digestibility, we investigated the effect of adding indica rice debranched starch (RDBS) on the quality of flat rice noodles. In this study, adding RDBS to flat rice noodles enhanced their mechanical properties. Cooking characteristic analysis showed that incorporating RDBS into dried flat rice noodles increased the rehydration ratio by 16.1 % and reduced rehydration time by 26.5 %. Scanning electron microscopy (SEM) revealed the presence of microparticles formed through the self-assembly of RDBS within the network of flat rice noodles. X-ray diffraction (XRD) analysis demonstrated that the addition of RDBS elevated the crystallinity of the flat rice noodles, rising from 9.59 % to 22.57 %. In addition, the in vitro simulated digestion test suggested the addition of RDBS led to a threefold increase in the content of slowly digestible starch (SDS) and a ninefold increase in resistant starch (RS) content in flat rice noodles. This study found that adding RDBS into flat rice noodles can effectively reduce their digestion rate and improve their eating quality. It could be a promising approach for creating functional rice noodles aimed at alleviating public health concerns such as diabetes and obesity.

An efficient microchip electromembrane extraction online with high-performance liquid chromatography for the measurement of nicotine in high consumption vegetables.

INTRODUCTION: Nicotine, a highly addictive substance, is naturally produced in the Solanaceae family of plants, particularly tobacco. The presence of nicotine in plant foods has adverse effects on the lungs, kidneys, heart, and reproductive system. OBJECTIVE: A novel three-phase microchip flat electromembrane coupled with online high-performance liquid chromatography (HPLC) was developed to analyze nicotine in tomato, mushroom, eggplant, bell pepper, and red pepper. METHODS: The microchip was connected to the HPLC in online mode. All effective variables were optimized to achieve the best extraction response. The use of electric potential and 2-nitrophenyl octyl ether -5% di(2-ethylhexyl) phosphate as a modified supported liquid membrane (SLM) increased the sensitivity and selectivity. RESULTS: The optimal extraction voltage, extraction time, and ion balance were 40 V, 10 min and 0, respectively. The dynamic linear range was 0.5-1000 ng g-1. The obtained recovery, relative standard deviation, and enrichment factor were 98%, 7%, and 35, respectively. The limits of detection 0.4 ng g-1 and the limits of quantification were obtained 1.3 ng g-1. The highest (105.0 ng g-1) and lowest (3.4 ng g-1) concentrations of nicotine were obtained for eggplant and tomato, respectively. CONCLUSION: Selective electromembrane extraction of nicotine from the donor phase to the acceptor phase was performed by optimizing the main variables influencing the method mechanism. The new channel design in this analytical system and online injection increased efficiency, stability, and repeatability. The results revealed that this method is capable for the efficient determination of trace amount of nicotine in edible vegetables.

Chiral Honeycomb Lattices of Nonplanar π-Conjugated Supramolecules with Protected Dirac and Flat Bands.

The honeycomb lattice is a fundamental two-dimensional (2D) network that gives rise to surprisingly rich electronic properties. While its expansion to 2D supramolecular assembly is conceptually appealing, its realization is not straightforward because of weak intermolecular coupling and the strong influence of a supporting substrate. Here, we show that the application of a triptycene derivative with phenazine moieties, Trip-Phz, solves this problem due to its strong intermolecular π-π pancake bonding and nonplanar geometry. Our scanning tunneling microscopy (STM) measurements demonstrate that Trip-Phz molecules self-assemble on a Ag(111) surface to form chiral and commensurate honeycomb lattices. Electronically, the network can be viewed as a hybrid of honeycomb and kagome lattices. The Dirac and flat bands predicted by a simple tight-binding model are reproduced by total density functional theory (DFT) calculations, highlighting the protection of the molecular bands from the Ag(111) substrate. The present work offers a rational route for creating chiral 2D supramolecules that can simultaneously accommodate pristine Dirac and flat bands.

Features of magnetic structures in perforated films due to the finite thickness of the sample.

The paper examines ferromagnetic films with strong uniaxial anisotropy of the 'easy plane' type, in which vortex-like inhomogeneities can arise in the presence of artificially created perforations. A universal approach has been developed that makes it possible to reduce the problem of calculating demagnetizing fields in a film of arbitrary thickness to the simplest case, when the film thickness is large. It has been shown that the influence of demagnetizing fields causes the magnetization vector to necessarily move out of the sample plane, and the spatial distribution of magnetization corresponding to this effect has been studied. It has been revealed that the contribution of demagnetizing fields to the total energy of the magnet changes slightly during the transition from a homogeneous structure to an inhomogeneous one.

Evaluation of brachycephalic obstructive airway syndrome breeding test results in Finland from 2017 to 2022.

BACKGROUND: Brachycephalic obstructive airway syndrome (BOAS), observed in many flat-faced dog breeds, is one of the most urgent welfare problems in pedigree dogs. Various breeding schemes against BOAS have been implemented in many countries during recent years, but their impact on breed health remains unknown. The BOAS breeding test, used by the Finnish Kennel Club (FKC), includes an exercise component with a recovery assessment, BOAS grading by a veterinarian that evaluates upper respiratory signs before and after exercise, and a nostril stenosis assessment. The aim of our study was to evaluate BOAS breeding test results and estimate the heritability of the BOAS grade using parent-offspring regression from FKC data collected during 2017-2022. RESULTS: The majority (80%) of dogs (n = 957) participating in FKC BOAS testing were English Bulldogs, French Bulldogs, and Pugs. In 2022, 89-100% of the litters from these three breeds registered with the FKC had at least one parent tested for BOAS. The proportion of dogs failing the exercise test was highest in English Bulldogs (11%), followed by French Bulldogs (4%) and Pugs (3%). In these three breeds, moderate to severe BOAS signs were reported in 28%, 22% and 30% of dogs, respectively. The proportion of moderate to severe nostril stenosis was highest (71%) in Pugs, followed by French Bulldogs (55%), and English Bulldogs (40%). Estimates of heritability for BOAS grade were separately calculated for these three breeds and for all dogs, and the estimates were moderate to high, ranging from 0.39 to 0.58. CONCLUSIONS: The exercise test alone did not sufficiently identify dogs with moderate to severe BOAS signs. To better consider the complex nature of BOAS and breed differences, exercise tolerance, the severity of upper respiratory signs (BOAS grade) and nostril stenosis should all be assessed together in breeding animals. The heritability estimates for veterinary-assessed BOAS grade indicated that BOAS grade could be used in selective breeding to obtain less-affected offspring.

Chaos-Assisted Dynamical Tunneling in Flat Band Superwires.

Recent theoretical investigations have revealed unconventional transport mechanisms within high Brillouin zones of two-dimensional superlattices. Electrons can navigate along channels we call superwires, gently guided without brute force confinement. Such dynamical confinement is caused by weak superlattice deflections, markedly different from the static or energetic confinement observed in traditional wave guides or one-dimensional electron wires. The quantum properties of superwires give rise to elastic dynamical tunneling, linking disjoint regions of the corresponding classical phase space, and enabling the emergence of several parallel channels. This paper provides the underlying theory and mechanisms that facilitate dynamical tunneling assisted by chaos in periodic lattices. Moreover, we show that the mechanism of dynamical tunneling can be effectively conceptualized through the lens of a paraxial approximation. Our results further reveal that superwires predominantly exist within flat bands, emerging from eigenstates that represent linear combinations of conventional degenerate Bloch states. Finally, we quantify tunneling rates across various lattice configurations and demonstrate that tunneling can be suppressed in a controlled fashion, illustrating potential implications in future nanodevices.

Twisted graphene superlattices: resonating valence bond states and magnetic properties.

Resonating valence bond (RVB) states are fundamental for understanding quantum spin liquids in two-dimensional (2D) systems. The RVB state is a collective phenomenon in which spins are uncoupled. 2D lattices such as triangular, honeycomb, and dice lattices were investigated using the Hubbard model and exact diagonalization method. We analyzed the total spin, spin-spin correlation functions, local magnetic moments, and spin and charge gaps as a function of on-site Coulomb repulsion, electron concentration, and electronic hopping parameters. Phase diagrams showed that RVB states can live in half-filled and hole-doped anisotropic triangular lattices. We found two types of RVB states: one in the honeycomb sublattice and the other in the centered hexagons in the triangular lattices. Owing to the novel discovery of exotic magnetic ordering in triangular moiré patterns in twisted bilayer graphene and transition metal dichalcogenide systems, our results provide physical insights into the onset of magnetism and possible spin liquid states in these layered materials.

Effects of subtalar arthroereisis in children, assessed on the basis of quality-of-life questionnaires.

INTRODUCTION AND OBJECTIVE: Subtalar arthroereisis is a procedure commonly performed in children with flat feet. The procedure is performed when conservative treatment did not have the desired effect,or when the patient's abnormal symptoms are very severe and make it difficult for them to function normally in daily life. The aim of this study was to assess whether subtalar arthroereisis and physiotherapy improve the quality of life among children with flat feet. MATERIAL AND METHODS: The study comprised 79 patients (140 operated feet) diagnosed with a flat foot defect who underwent a subtalar arthroereisis procedure. A self-administered questionnaire and a shortened version of the standardised WHOQOL-BREF questionnaire were used in the research. RESULTS: The study confirmed that the patients' quality of life after surgery was high in all the areas regarding the somatic, psychological, social and environmental domains. In the group of children assessed 13-24 months after surgery. it was also found that rapid fatigue after exercise (30% ± 9%) and Achilles tendon contracture (7% ± 4%) were significantly reduced. The results of the study confirmed that subtalar arthroereisis contributes to a decreased demand for orthoses in children (9% ± 6%) and for orthopaedic footwear (11% ± 5%) than before surgery. CONCLUSIONS: The employment of subtalars arthroereisis has a positive effect on the quality of life of children with flat feet. The surgery contributes to a reduction in pain and other abnormal symptoms that are associated with flat feet. In addition, physiotherapy performed after the procedure had a positive effect on the healing process and contributed to the improvement of the children's quality of life.

Flat-bands in translated and twisted bilayer Penrose quasicrystals.

Correlated phases in Moiré materials together with the flat-bands in twisted systems play a central role to explain superconductivity in the new twisted bilayer graphene. In this paper, flat-bands are shown to exist in both translated and twisted bilayer of quasicrystals. Such flat-bands arise for different displacements and twisting angles of two-coupled Penrose lattices where Moiré patterns are also shown. Moiré patterns analyzed in this work have at least two inverted worms showing an interference pattern going along the five-fold axes of the pentagon. In order to analyze the behavior of the flat band, our study has been done for fixed interference worm directions but increasing the worm interference density, and for fixed worm interference density but increasing the number of worm directions. In case of rotations, the Moiré patterns that occurs for special angles such asπ/5, 2π/5, 3π/5, 4π/5 andπare discussed in detail because they clearly show flat-bands along with quasicrystalline electronic states at the Fermi level.

Distance of Biopsy-Confirmed High-Risk Breast Lesion from Concurrently Identified Breast Malignancy Associated with Risk of Carcinoma at the High-Risk Lesion Site.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.

Google Bard and ChatGPT in Orthopedics: Which Is the Better Doctor in Sports Medicine and Pediatric Orthopedics? The Role of AI in Patient Education.

BACKGROUND: This study evaluates the potential of ChatGPT and Google Bard as educational tools for patients in orthopedics, focusing on sports medicine and pediatric orthopedics. The aim is to compare the quality of responses provided by these natural language processing (NLP) models, addressing concerns about the potential dissemination of incorrect medical information. METHODS: Ten ACL- and flat foot-related questions from a Google search were presented to ChatGPT-3.5 and Google Bard. Expert orthopedic surgeons rated the responses using the Global Quality Score (GQS). The study minimized bias by clearing chat history before each question, maintaining respondent anonymity and employing statistical analysis to compare response quality. RESULTS: ChatGPT-3.5 and Google Bard yielded good-quality responses, with average scores of 4.1 ± 0.7 and 4 ± 0.78, respectively, for sports medicine. For pediatric orthopedics, Google Bard scored 3.5 ± 1, while the average score for responses generated by ChatGPT was 3.8 ± 0.83. In both cases, no statistically significant difference was found between the platforms (p = 0.6787, p = 0.3092). Despite ChatGPT's responses being considered more readable, both platforms showed promise for AI-driven patient education, with no reported misinformation. CONCLUSIONS: ChatGPT and Google Bard demonstrate significant potential as supplementary patient education resources in orthopedics. However, improvements are needed for increased reliability. The study underscores the evolving role of AI in orthopedics and calls for continued research to ensure a conscientious integration of AI in healthcare education.

Twist Proximity-Endowed Large Figure of Merit in a Band-Modulated CrI3/1T-MoS2 Moiré Superlattice.

Moiré superlattices with a robust twist proximity effect in the low-dimensional regime can facilitate nanoscale thermoelectric devices. In pristine systems, the low efficiency and lack of proficient control of thermoelectric properties impede desirable advancements in the field of energy conversion. In the present study, we demonstrate remarkable macroscopic thermoelectric response as a consequence of microscopic band structure modulation via the twist proximity in an engineered CrI3/1T-MoS2 moiré superlattice. The local twist effect, which leads to the microscopic phenomena of electron localization, results in a comprehensive electronic structure modulation. Consequently, these local effects convolute the macroscopic thermoelectric effect. Additionally, flat bands and angle-dependent metallic to semiconducting transitions are observed at 10.89, 23.41, and 30° twist angles. We correlate the observed phenomenon with the augmented spin-charge transport and interconversion via the twist proximity effect in its semiconducting phase. The estimated ultralow electronic and lattice thermal conductivities further corroborate with the observed large figure of merit and Seebeck coefficient. The maximum values of the Seebeck coefficient and figure of merit are estimated to be ∼413 µV/K and ∼4.3 at 200 K for 30° under the constant time relaxation approach. The twist-endowed outstanding thermoelectric effect in moiré superlattices with band modulation unveils a distinctive approach to establish efficient thermoelectric devices.

Comprehensive literature review on the application of the otological surgical planning software OTOPLAN® for cochlear implantation.

BACKGROUND: The size of the human cochlear, measured by the diameter of the basal turn, varies between 7 and 11 mm. For hearing rehabilitation with cochlear implants (CI), the size of the cochlear influences the individual frequency map and the choice of electrode length. OTOPLAN® (CAScination AG [Bern, Switzerland] in cooperation with MED-EL [Innsbruck, Austria]) is a software tool with CE marking for clinical applications in CI treatment which allows for precise pre-planning based on cochlear size. This literature review aims to analyze all published data on the application of OTOPLAN®. MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to identify relevant studies published in the PubMed search engine between January 2015 and February 2023 using the search terms "otoplan" [title/abstract] OR "anatomy-based fitting" [title/abstract] OR "otological software tool" [title/abstract] OR "computed tomography-based software AND cochlear" [title/abstract]. RESULTS: The systematic review of the literature identified 32 studies on clinical use of OTOPLAN® in CI treatment. Most studies were reported from Germany (7 out of 32), followed by Italy (5), Saudi Arabia (4), the USA (4), and Belgium (3); 2 studies each were from Austria and China, and 1 study from France, India, Norway, South Korea, and Switzerland. In the majority of studies (22), OTOPLAN® was used to assess cochlear size, followed by visualizing the electrode position using postoperative images (5), three-dimensional segmentation of temporal bone structures (4), planning the electrode insertion trajectory (3), creating a patient-specific frequency map (3), planning of a safe drilling path through the facial recess (3), and measuring of temporal bone structures (1). CONCLUSION: To date, OTOPLAN® is the only DICOM viewer with CE marking in the CI field that can process pre-, intra-, and postoperative images in the abovementioned applications.

One Health: Therapies Targeting Genetic Variants in Human and Canine Histiocytic and Dendritic Cell Sarcomas.

The precise cause of HS/DCS is still unknown. The relatively low incidence in humans urges for an animal model with a high incidence to accelerate knowledge about genetics and optimal treatment of HS/DCS. Namely, until now, the therapies targeting genetic variants are still more experimental and sparsely used, while consensus is missing. In addition, the literature about variants and possible mutation-targeted therapies in humans and dogs consists mainly of case reports scattered throughout the literature. Therefore, an overview is provided of all currently known genetic variants in humans and dogs with HS/DCS and its subtypes, their possible mutation-targeted therapies, their efficacy, and a contemplation about the future. Several genetic variants have already been discovered in HS/DCS, of which many are shared between canine and human HS/DCS, but unique variants exist as well. Unfortunately, none of these already found variants seem to be specifically causal for HS/DCS, and the puzzle of its landscape of genetic variation is far from complete. The use of mutation-targeted therapies, including MAPK-/MEK-inhibitors and the future use of PTPN11-, CDK4/6- and PD-1-inhibitors, seems to be promising for these specific variants, but clearly, clinical trials are needed to determine optimal inhibitors and standardised protocols for all variants. It can be concluded that molecular analysis for variants and subsequent mutation-targeted therapy are an essential addition to cancer diagnostics and therapy. A joint effort of humans and dogs in research is urgently needed and will undoubtedly increase knowledge and survival of this devastating disease in dogs and humans.