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A modular "fjord-stitching" reverse strategy has been disclosed to successfully prepare two large-sized B,N-embedded nanographenes: BN-TBTi and BN-TBTo. These two compounds both exhibit excellent stability, nonzero-bandgap and decent photoluminescence quantum yield. Single crystal structure of BN-TBTo features a large C78B2N4 π-skeleton with length and width of approximately 2.4 and 1.5 nm, respectively.

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Breast cancer ranks as one of the most common malignancies among women, with its prognosis and therapeutic efficacy heavily influenced by factors associated with the tumor cell biology, particularly the tumor microenvironment (TME). The diverse elements of the TME are engaged in dynamic bidirectional signaling interactions with various pathways, which together dictate the growth, invasiveness, and metastatic potential of breast cancer. The Hedgehog (Hh) signaling pathway, first identified in Drosophila, has been established as playing a critical role in human development and disease. Notably, the dysregulation of the Hh pathway is recognized as a major driver in the initiation, progression, and metastasis of breast cancer. Consequently, elucidating the mechanisms by which the Hh pathway interacts with the distinct components of the breast cancer TME is essential for comprehensively evaluating the link between Hh pathway activation and breast cancer risk. This understanding is also imperative for devising novel targeted therapeutic strategies and preventive measures against breast cancer. In this review, we delineate the current understanding of the impact of Hh pathway perturbations on the breast cancer TME, including the intricate and complex network of intersecting signaling cascades. Additionally, we focus on the therapeutic promise and clinical challenges of Hh pathway inhibitors that target the TME, providing insights into their potential clinical utility and the obstacles that must be overcome to harness their full therapeutic potential.

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Detection of printed circuit board assembly (PCBA) defects is crucial for improving the efficiency of PCBA manufacturing. This paper proposes PCBA-YOLO, a YOLOv5-based method that can effectively increase the accuracy of PCBA defect detection. First, the spatial pyramid pooling module with cross-stage partial structure is replaced in the neck network of YOLOv5 to capture the resolution features at multiple scales. Second, large kernel convolution is introduced in the backbone network to obtain larger effective receptive fields while reducing computational overhead. Finally, an SIoU loss function that considers the angular cost is utilized to enhance the convergence speed of the model. In addition, an assembled PCBA defect detection dataset named PCBA-DET is created in this paper, containing the corresponding defect categories and annotations of defect locations. The experimental results on the PCB defect dataset demonstrate that the improved method has lower loss values and higher accuracy. Evaluated on the PCBA-DET dataset, the mean average precision reaches 97.3 % , achieving a real-time detection performance of 322.6 frames per second, which considers both the detection accuracy and the model size compared to the YOLO series of detection networks. The source code and PCBA-DET dataset can be accessed at https://github.com/ismh16/PCBA-Dataset .

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The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer.

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Enzyme-induced carbonate precipitation (EICP) has been studied in remediation of heavy metal contaminated water or soil in recent years. This paper aims to investigate the immobilization mechanism of Zn2+, Ni2+, and Cr(VI) in contaminated sand, as well as strength enhancement of sand specimens by using EICP method with crude sword bean urease extracts. A series of liquid batch tests and artificially contaminated sand remediation experiments were conducted to explore the heavy metal immobilization efficacy and mechanisms. Results showed that the urea hydrolysis completion efficiency decreased as the Ca2+ concentration increased and the heavy metal immobilization percentage increased with the concentration of Ca2+ and treatment cycles in contaminated sand. After four treatment cycles with 0.5 mol/L Ca2+ added, the immobilization percentage of Zn2+, Ni2+, and Cr(VI) were 99.99 %, 86.38 %, and 75.18 %, respectively. The microscale analysis results presented that carbonate precipitates and metallic oxide such as CaCO3, ZnCO3, NiCO3, Zn(OH)2, and CrO(OH) were generated in liquid batch tests and sand remediation experiments. The SEM-EDS and FTIR results also showed that organic molecules and CaCO3 may adsorb or complex heavy metal ions. Thus, the immobilization mechanism of EICP method with crude sword bean urease can be considered as biomineralization, as well as adsorption and complexation by organic matter and calcium carbonate. The unconfined compressive strength of EICP-treated contaminated sand specimens demonstrated a positive correlation with the increased generation of carbonate precipitates, being up to 306 kPa after four treatment cycles with shear failure mode. Crude sword bean urease with 0.5 mol/L Ca2+ added is recommended to immobilize multiple heavy metal ions and enhance soil strength.

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Throughout the COVID-19 pandemic, individuals potentially infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were forcibly recalled to local or central hospitals, where the diagnostic results were obtained a couple of days after the liquid biopsies were subjected to conventional polymerase chain reaction (PCR). This slow output of such a complex and time-consuming laboratory procedure hindered its widespread application. To overcome the limitations associated with such a centralized diagnostic system, we developed a hand-held and all-in-one type test kit in which the analytical results can be obtained in only 30 min. The test kit consists of three major steps for on-site SARS-CoV-2 RNA detection: 1) virus lysis by heat, 2) RNA enrichment by membrane, and 3) real-time detection by colorimetric loop-mediated isothermal amplification (c-LAMP). The proposed device operates in a sample-to-answer format, is fully automated, and reduces dependence on traditional laboratory settings, facilitating large-scale population screening.

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Luminescent materials with narrowband emission have extraordinary significance for developing ultrahigh-definition display. B-N-containing multiple resonance thermally activated delayed fluorescence (MR-TADF) materials are strong contenders. However, their device performances pervasively encounter detrimental aggregation-caused quenching effect that is highly vulnerable to doping concentration, complicating device fabrication. Therefore, constructing highly efficient and concentration-independent MR-TADF emitters is of pragmatic importance for improving device controllability and reproducibility, simplifying manufacturing procedures, and conserving production costs. Here, by systematic arrangement of donor triphenylamine and fluorophore BNCz on distinct bridges, a spatial confinement strategy has been developed with a donor-bridge-fluorophore architecture. Structurally fine modulation and progressive evolution to construct molecular entities with congested steric hindrance effect that can suppress intermolecular interactions without substantially affecting the luminescence tone of fluorophore BNCz, resulting in highly efficient and concentration-independent narrowband emitters; through isomer engineering, two isomers BN-PCz-TPA and TPA-PCz-BN with different crystal stacking patterns are synthesized by altering the connection mode between triphenylamine and BNCz. As a result, BN-PCz-TPA-based device showcases maximum external quantum efficiency (EQE) of 36.3% with narrow full-width at half-maximum of 27 nm at 10 wt% doping concentration. Even at 20 wt% doping concentration, the maximum EQE remains at 32.5% and the emission spectrum is almost unchanged.

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Zika virus (ZIKV) is an emerging flavivirus that causes congenital syndromes including microcephaly and fetal demise in pregnant women. No commercial vaccines against ZIKV are currently available. We previously generated a chimeric ZIKV (ChinZIKV) based on the Chaoyang virus (CYV) by replacing the prME protein of CYV with that of a contemporary ZIKV strain GZ01. Herein, we evaluated this vaccine candidate in a mouse model and showed that ChinZIKV was totally safe in both adult and suckling immunodeficient mice. No viral RNA was detected in the serum of mice inoculated with ChinZIKV. All of the mice inoculated with ChinZIKV survived, while mice inoculated with ZIKV succumbed to infection in 8 days. A single dose of ChinZIKV partially protected mice against lethal ZIKV challenge. In contrast, all the control PBS-immunized mice succumbed to infection after ZIKV challenge. Our results warrant further development of ChinZIKV as a vaccine candidate in clinical trials.

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The development of high-performance multiple resonance thermally activated delayed fluorescence (MR-TADF) materials with narrowband yellow emission is highly critical for various applications in industries, such as the automotive, aerospace, and microelectronic industries. However, the modular construction approaches to expeditiously access narrowband yellow-emitting materials is relatively rare. Here, a unique molecular design concept based on frontier molecular orbital engineering (FMOE) of aromatic donor fusion is proposed to strategically address this issue. Donor fusion is a modular approach with a "leveraging effect"; through direct polycyclization of donor attached to the MR parent core, it is facile to achieve red-shifted emission by a large margin. As a result, two representative model molecules, namely BN-Cz and BN-Cb, have been constructed successfully. The BN-Cz- and BN-Cb-based sensitized organic light-emitting diodes (OLEDs) exhibit bright yellow emission with peaks of 560 and 556 nm, full-width at half-maxima (fwhm's) of 49 and 45 nm, Commission Internationale de L'Eclairage coordinates of (0.44, 0.55) and (0.43, 0.56), and maximum external quantum efficiencies (EQEs) of 32.9% and 29.7%, respectively. The excellent optoelectronic performances render BN-Cz and BN-Cb one of the most outstanding yellow-emitting MR-TADF materials.

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We present a statistical simulator, scDesign3, to generate realistic single-cell and spatial omics data, including various cell states, experimental designs and feature modalities, by learning interpretable parameters from real data. Using a unified probabilistic model for single-cell and spatial omics data, scDesign3 infers biologically meaningful parameters; assesses the goodness-of-fit of inferred cell clusters, trajectories and spatial locations; and generates in silico negative and positive controls for benchmarking computational tools.

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Understanding diverse responses of individual cells to the same perturbation is central to many biological and biomedical problems. Current methods, however, do not precisely quantify the strength of perturbation responses and, more importantly, reveal new biological insights from heterogeneity in responses. Here we introduce the perturbation-response score (PS), based on constrained quadratic optimization, to quantify diverse perturbation responses at a single-cell level. Applied to single-cell transcriptomes of large-scale genetic perturbation datasets (e.g., Perturb-seq), PS outperforms existing methods for quantifying partial gene perturbation responses. In addition, PS presents two major advances. First, PS enables large-scale, single-cell-resolution dosage analysis of perturbation, without the need to titrate perturbation strength. By analyzing the dose-response patterns of over 2,000 essential genes in Perturb-seq, we identify two distinct patterns, depending on whether a moderate reduction in their expression induces strong downstream expression alterations. Second, PS identifies intrinsic and extrinsic biological determinants of perturbation responses. We demonstrate the application of PS in contexts such as T cell stimulation, latent HIV-1 expression, and pancreatic cell differentiation. Notably, PS unveiled a previously unrecognized, cell-type-specific role of coiled-coil domain containing 6 (CCDC6) in guiding liver and pancreatic lineage decisions, where CCDC6 knockouts drive the endoderm cell differentiation towards liver lineage, rather than pancreatic lineage. The PS approach provides an innovative method for dose-to-function analysis and will enable new biological discoveries from single-cell perturbation datasets.

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It is of great strategic significance to develop highly efficient narrowband organic electroluminescent materials that can be utilized to manufacture ultra-high-definition (UHD) displays and meet or approach the requirements of Broadcast Television 2020 (B.T.2020) color gamut standards. This motif poses challenges for molecular design and synthesis, especially for developing generality, diversity, scalability, and robustness of molecular structures. The emergence of multiple resonance thermally activated delayed fluorescence (MR-TADF) emitters has ingeniously solved the problems and demonstrated bright application prospects in the field of UHD displays, sparking a research boom. This Minireview summarizes the research endeavors of narrowband organic electroluminescent materials, with emphasis on the tremendous contribution of frontier molecular orbital engineering (FMOE) strategy. It combines the outstanding advantages of MR framework and donor-acceptor (D-A) structure, and can achieve red-shift and narrowband emission simultaneously, which is of great significance in the development of long-wavelength narrowband emitters with emission maxima especially exceeding 500 nm. We hope that this Minireview would provide some inspiration for what could transpire in the future.

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Most natural materials have rotational and hierarchical properties, so they can show excellent mechanical properties such as shear resistance and impact resistance. In order to further improve the energy absorption characteristics of vibration absorbing structures, a new type of honeycomb structure with integral rotation and group rotation is designed and characterized. The effects of the geometrical parameters of rotation Angle on the impact deformation mode, stress response curve and energy absorption characteristics of the honeycomb structure are studied through numerical simulation and experimental design. The results show that the overall honeycomb performance of 15° is better than that of 0°, the specific energy absorption is the results show that the overall honeycomb performance of 15° is better than that of 0°, the specific energy absorption is increased by 6%, the bearing capacity is increased by 320 N, and the crushing force efficiency is increased by 2%. Compared with the whole cell and the group cell, the specific absorption energy increased by 35%, 73% and 71%. The results of this paper provide a new insight into the impact performance of monolithic and grouped rotating honeycomb structures, which is helpful for the results of this paper provide a new insight into the impact performance of monolithic and grouped rotating honeycomb structures, which is helpful for the optimization of crashworthiness structural design.

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Advanced circularly polarized multiple-resonance thermally activated delayed fluorescence (CP-MR-TADF) materials synergize the advantages of circularly polarized luminescence (CPL), narrowband emission, and the TADF characteristic, which can be fabricated into highly efficient circularly polarized organic light-emitting diodes (CP-OLEDs) with high color purity, directly facing the urgent market strategic demand of ultrahigh-definition and 3D displays. In this work, based on an edge-topology molecular-engineering (ETME) strategy, a pair of high-performance CP-MR-TADF enantiomers, (P and M)-BN-Py, is developed, which merges the intrinsically helical chirality into the MR framework. The optimized CP-OLEDs with (P and M)-BN-Py emitters and the newly developed ambipolar transport host PhCbBCz exhibit pure green emission with sharp peaks of 532 nm, full-width at half-maximum (FWHM) of 37 nm, and Commission Internationale de L'Eclairage (CIE) coordinates of (0.29, 0.68). Importantly, they achieve remarkable maximum external quantum efficiencies (EQEs) of 30.6% and 29.2%, and clear circularly polarized electroluminescence (CPEL) signals with electroluminescence dissymmetry factors (gEL s) of -4.37 × 10-4 and +4.35 × 10-4 for (P)-BN-Py and (M)-BN-Py, respectively.

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The genus Flavivirus is a group of arthropod-borne single-stranded RNA viruses, which includes important human and animal pathogens such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), Dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV), and Tick-borne encephalitis virus (TBEV). Reverse genetics has been a useful tool for understanding biological properties and the pathogenesis of flaviviruses. However, the conventional construction of full-length infectious clones for flavivirus is time-consuming and difficult due to the toxicity of the flavivirus genome to E. coli. Herein, we applied a simple, rapid, and bacterium-free circular polymerase extension reaction (CPER) method to synthesize recombinant flaviviruses in vertebrate cells as well as insect cells. We started with the de novo synthesis of the JEV vaccine strain SA-14-14-2 in Vero cells using CPER, and then modified the CPER method to recover insect-specific flaviviruses (ISFs) in mosquito C6/36 cells. Chimeric Zika virus (ChinZIKV) based on the Chaoyang virus (CYV) backbone and the Culex flavivirus reporter virus expressing green fluorescent protein (CxFV-GFP) were subsequently rescued in C6/36 cells. CPER is a simple method for the rapid generation of flaviviruses and other potential RNA viruses. A CPER-based recovery system for flaviviruses of different host ranges was established, which would facilitate the development of countermeasures against flavivirus outbreaks in the future.

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The current study explored the relationships between retrospective parenting styles and food parenting in childhood (≤ 12 years old) and Chinese adults' current maladaptive and adaptive eating behaviors. We recruited 501 Chinese adults (50.30% men, aged 19-46 years). A set of questionnaires were used to measure retrospective parenting styles (i.e., emotional warmth, rejection, and overprotection), food parenting (i.e., parental concern, monitoring, pressure to eat, and restriction), and current maladaptive (i.e., disordered eating) and adaptive (i.e., intuitive eating) eating behaviors. Correlation and mediation analyses were employed to analyze these data. Results revealed that retrospective parenting styles and food parenting were significantly related to current maladaptive and adaptive eating behaviors in both Chinese men and women. Mediation analyses showed that higher retrospective parental warmth was related to higher retrospective parental concern which, in turn, was related to higher current disordered eating in men (indirect effect = 0.14, 95% CI 0.08, 0.24). Furthermore, higher retrospective parental overprotection was related to higher retrospective parental pressure to eat which, in turn, was related to higher current disordered eating in men (indirect effect = 0.06, 95% CI 0.01, 0.14). For women, higher retrospective parental warmth was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.04, 95% CI = -0.10, -0.01). Furthermore, higher retrospective parental overprotection was associated with higher retrospective parental concern which, in turn, was associated with lower current intuitive eating in women (indirect effect = -0.03, 95% CI = -0.08, -0.004). The findings indicate the importance of including childhood parenting styles and food parenting in future research and intervention of adults' current maladaptive and adaptive eating behaviors.

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Plasma-activated water (PAW) is considered a novel sanitizer for the food industry due to the antimicrobial mechanisms exhibited by reactive oxygen and nitrogen species. The plasma operation parameters can affect the chemistry of PAW and can therefore influence its microbial inactivation efficacy. This study statistically optimized the operating conditions of PAW (activation time, distance from nozzle, and volume of water) using response surface methodology. Two optimized conditions of PAW were identified for the inactivation of planktonic cells of the avirulent strain of Salmonella Typhimurium MHM112 providing a minimum reduction of 6.3 log. All three operating parameters significantly affected the physicochemical characteristics (pH, ORP, EC, nitrite, and nitrate) and microbial inactivation efficacy of PAW. Mixing of small batches using the two optimized conditions to obtain larger volumes did not significantly change the microbial inactivation. However, there were significant reductions in nitrite and nitrate concentrations in PAW due to the mixing of batches while the pH and ORP values remained unaffected. The storage of large volumes of PAW for 25 min at 40-46°C, which is the commercial egg washing temperature in the United States, did not significantly impact S. Typhimurium MHM112 inactivation or the physicochemical characteristics of PAW. A validation study using a cocktail of six pathogenic strains of Salmonella revealed no significant differences in inactivation between the avirulent S. Typhimurium MHM112 and the pathogenic strains, suggesting that the avirulent S. Typhimurium MHM112 may serve as a surrogate for sanitation of S. enterica at the optimized conditions of PAW. The results obtained from this study are useful for our long-term goal of evaluating PAW efficacy in surface egg washing to inactivate Salmonella.

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Nitrogen fractions in soil, like organic nitrogen, mineral nitrogen, and free amino acids, are sensitive pointers to the soil nitrogen pools involved in nutrient cycling. As a potential improvement measure, biochar might improve soil fertility and nutrient availability. However, few studies have focused on the long-term effects of biochar retention on the soil nitrogen supply capacity of bulk and rhizosphere soil in brown earth. Therefore, a six-year field experiment was conducted in 2013, concentrating on the impact of biochar retention on soil nitrogen fractions. Four biochar rates were tested: no biochar amendment (CK); 15.75 t ha-1 of biochar (BC1); 31.5 t ha-1 of biochar (BC2); 47.25 t ha-1 of biochar (BC3). Our results showed that the elevated application rates significantly enhanced soil organic matter (SOM), and total nitrogen (TN), and improved pH in both bulk and rhizosphere soils. Acid-hydrolyzable nitrogen (AHN) content in biochar treatments was higher than that of CK in bulk and rhizosphere soil. The content of non-hydrolyzable nitrogen (NHN) was increased in 47.25 t ha-1 of biochar retention. Ammonium nitrogen (AN) and amino sugar nitrogen (ASN) contents were higher in bulk soil than in rhizosphere soil. Neutral amino acid contents were the highest both in bulk and rhizosphere soil. Principal component analysis (PCA) showed that soil organic nitrogen was significantly influenced by BC3 treatment in bulk soil, and largely influenced by other treatments in rhizosphere soil. Partial least square path modeling (PLSPM) revealed that NH4+-N was mainly derived from amino acid nitrogen (AAN) and AN in bulk soil and AAN and ASN in rhizosphere soil. These results indicate that different biochar retention rates contributed to improve soil nutrients. Amino acid nitrogen was the prominent nitrogen source of NH4+-N in bulk and rhizosphere soils.

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Advanced multiple resonance induced thermally activated delayed fluorescence (MR-TADF) emitters have emerged as a privileged motif for applications in organic light-emitting diodes (OLEDs), because they furnish highly tunable TADF characteristics and high color purity emission. Herein, based on the unique nitrogen-atom embedding molecular engineering (NEME) strategy, a series of compounds BN-TP-Nx (x=1, 2, 3, 4) have been customized. The nitrogen-atom anchored at different position of triphenylene hexagonal lattice entails varying degrees of perturbation to the electronic structure. The newly-constructed emitters have demonstrated the precise regulation of emission maxima of MR-TADF emitters to meet the actual industrial demand, and further enormously enriched the MR-TADF molecular reservoir. The BN-TP-N3-based OLED exhibits ultrapure green emission, with peak of 524 nm, full-width at half-maximum (FWHM) of 33 nm, Commission Internationale de L'Eclairage (CIE) coordinates of (0.23, 0.71), and maximum external quantum efficiency (EQE) of 37.3 %.

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BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis of unknown etiology. we report a very rare case of recurrent central nervous system RDD with KRAS gene mutation and review the literature to improve our understanding of this disease. CASE PRESENTATION: A 19-year-old male patient was admitted to our hospital for headache. Cranial magnetic resonance imaging revealed a mass of abnormal signal shadows in the prepontine cistern. The mass was surgically removed and the patient was consequently diagnosed with intracranial Rosai-Dorfman disease. Seven months later, pathological examination confirmed that the RDD had recurred. Next-generation sequencing found KRAS mutation in exon 4 (C.351A > C. P. K117n). CONCLUSION: RDD of the CNS has no distinct clinical manifestations and imaging characteristics, and the final diagnosis should be based on the results of the pathological examination. Although RDD is not currently classified as a neoplastic disorder, some evidence of clonality has changed our understanding of it. Follow up examinations over a long period are necessary to determine the efficacy of treatment.

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