UNASSIGNED: Coagulopathies are frequently observed in alveolar rhabdomyosarcoma (ARMS), with disseminated intravascular coagulation (DIC) being the most common presentation. However, hyperfibrinolysis represents a distinct but often overlapping and potentially life-threatening subset of coagulation disorders that requires specific diagnostic and management approaches.
UNASSIGNED: How can clinicians identify hyperfibrinolysis and what are the implications for management?
UNASSIGNED: This case report describes a 25-year-old man with metastatic ARMS arising from the prostate who developed persistent gross hematuria one week after initiating chemotherapy. A comprehensive coagulation workup was performed, including assessment of platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin degradation products. Management included repletion of fibrinogen and the use of anti-fibrinolytic agents.
UNASSIGNED: Recognizing hyperfibrinolysis in ARMS patients is crucial for appropriate management. Clinicians should maintain a high index of suspicion for hyperfibrinolysis in ARMS patients presenting with severe coagulation abnormalities, particularly those with prostatic involvement or undergoing chemotherapy. In cases of primary hyperfibrinolysis, antifibrinolytic agents may be considered, whereas they are generally contraindicated in DIC.

This study focuses on the design and synthesis of two novel coordination polymers (CPs), named 1 and 2, with excellent fluorescent properties. Their structures were characterized by X-ray single-crystal diffraction, revealing that both materials exhibit promising fluorescence performance, indicating their potential as fluorescent detection tools. Additionally, 1 was chosen to be combined with chitosan (CS), resulting in the successful fabrication of a biodegradable and non-toxic efficient drug carrier, termed CS-1@Cisplatin. This carrier possesses a large surface area and good solubility, enabling sustained drug release to target cells. Given that CXC motif chemokine receptor type 4 (CXCR4) is a key marker gene highly expressed in Rhabdomyosarcoma (RMS) cells and tissues, RMS was chosen as the biological model for testing. The results demonstrated that CS-1@Cisplatin effectively inhibited the invasiveness of RMS cells by significantly suppressing CXCR4 expression. Therefore, the system shows great potential for applications in RMS treatment, biometrics, and drug delivery, particularly in its unique advantage of targeting RMS by inhibiting the key marker gene CXCR4.

BACKGROUND: The application of reduced metagenomic sequencing approaches holds promise as a middle ground between targeted amplicon sequencing and whole metagenome sequencing approaches but has not been widely adopted as a technique. A major barrier to adoption is the lack of read simulation software built to handle characteristic features of these novel approaches. Reduced metagenomic sequencing (RMS) produces unique patterns of fragmentation per genome that are sensitive to restriction enzyme choice, and the non-uniform size selection of these fragments may introduce novel challenges to taxonomic assignment as well as relative abundance estimates.
RESULTS: Through the development and application of simulation software, readsynth, we compare simulated metagenomic sequencing libraries with existing RMS data to assess the influence of multiple library preparation and sequencing steps on downstream analytical results. Based on read depth per position, readsynth achieved 0.79 Pearson\'s correlation and 0.94 Spearman\'s correlation to these benchmarks. Application of a novel estimation approach, fixed length taxonomic ratios, improved quantification accuracy of simulated human gut microbial communities when compared to estimates of mean or median coverage.
CONCLUSIONS: We investigate the possible strengths and weaknesses of applying the RMS technique to profiling microbial communities via simulations with readsynth. The choice of restriction enzymes and size selection steps in library prep are non-trivial decisions that bias downstream profiling and quantification. The simulations investigated in this study illustrate the possible limits of preparing metagenomic libraries with a reduced representation sequencing approach, but also allow for the development of strategies for producing and handling the sequence data produced by this promising application.

Rhabdomyosarcoma (RMS) is among the most common pediatric solid malignancies. Fusion-negative, embryonal RMS is the predominant histology among prostate and bladder lesions. Management strategies depend on the clinical stage and risk group. Although the optimal strategy continues to evolve, the field has transitioned from radical upfront resection to organ preservation strategies with multi-modal therapy, including chemotherapy, radiation, and surgery. Survivors frequently develop late complications, including impaired fertility and sexual function, bladder dysfunction, and secondary malignancies. Our case describes an 11-year-old male who developed a radiation-induced prostatic sarcoma. We present a novel surgical technique and highlight the importance of multidisciplinary care.

ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.

UNASSIGNED: The assessment of serum neurofilament light chain (sNFL) has emerged as a diagnostic and prognostic tool in monitoring multiple sclerosis (MS). However, the application of periodic measurement in daily practice remains unclear.
UNASSIGNED: To evaluate the predictive value of individual sNFL levels in determining disease activity in patients with relapsing MS (RMS).
UNASSIGNED: In this two-year prospective study, 129 RMS patients underwent quarterly sNFL assessments and annual MRI scans. The study analyzed the correlation between individual NFL levels and past, current, and future disease activity. Group-level Z-scores were employed as a comparative measure.
UNASSIGNED: Among the 37 participants, a total of 61 episodes of disease activity were observed. sNFL levels proved valuable in distinct ways; they were confirmatory of previous and current clinical and/or radiological activity and demonstrated a high negative predictive value for future 90 days activity. Interestingly, Z-scores marginally outperformed sNFL levels in terms of predictive accuracy, indicating the potential for alternative approaches in disease activity assessment. In our cohort, sNFL cut-offs of 10.8 pg./mL (sensitivity 27%, specificity 90%) and 14.3 pg./mL (sensitivity 15%, specificity 95%) correctly identified 7 and 4 out of 26 cases of radiological activity within 90 days, respectively, with 14 and 15% false negatives. When using lower cut-off values, individuals with sNFL levels below 5 pg/mL (with a sensitivity of 92%, specificity of 25%, and negative predictive value of 94%) were less likely to experience radiological activity within the next 3 months.
UNASSIGNED: Individual sNFL levels may potentially confirm prior or current disease activity and predict short-term future radiological activity in RMS. These findings underscore its periodic measurement as a valuable tool in RMS management and decision-making, enhancing the precision of clinical evaluation in routine practice.

OBJECTIVE: Chemoresistance in rhabdomyosarcoma (RMS) is associated with poor survival, necessitating the development of novel anticancer drugs. Auranofin (AUR), an anti-rheumatic drug, is a thioredoxin reductase (TXNRD) inhibitor with anticancer properties. Although patient-derived xenograft (PDX) models are essential for studying cancer biology, reports on sarcomas using the PDX model are scarce because of their rarity. This study aimed to investigate the effectiveness of AUR treatment in RMS using a PDX model to evaluate its impact on local progression.
METHODS: A 20-year-old woman who was diagnosed with alveolar RMS was used to generate the PDX model. RMS PDX tumors were implanted in nude mice and divided into non-treated (vehicle) and treated (AUR) groups. Tumor volume and weight were evaluated, and immunohistochemical staining was performed to evaluate local progression of the sarcoma. The relationship between the TXNRD-1 expression and survival probability of patients with RMS was evaluated using publicly available expression cohorts.
RESULTS: AUR significantly suppressed RMS tumor progression over time. It also significantly suppressed the tumor size and weight at the time of excision. Histological evaluation showed that AUR induced oxidative stress in the PDX mouse models and inhibited the local progression of RMS by inducing apoptosis. High TXNRD-1 expression was found to be a negative prognostic factor for overall survival in patients with RMS.
CONCLUSIONS: AUR-induced inhibition of TXNRDs can significantly impede the local progression of RMS through the oxidative stress-apoptosis pathway as demonstrated in PDX models. Thus, targeting TXNRD inhibition may be a promising therapeutic strategy for the treatment of RMS.

UNASSIGNED: Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue malignancy, characterized by high clinicalopathological and molecular heterogeneity. Preclinical in vivo models are essential for advancing our understanding of RMS oncobiology and developing novel treatment strategies. However, the diversity of scholarly data on preclinical RMS studies may challenge scientists and clinicians. Hence, we performed a systematic literature survey of contemporary RMS mouse models to characterize their phenotypes and assess their translational relevance.
UNASSIGNED: We identified papers published between 01/07/2018 and 01/07/2023 by searching PubMed and Web of Science databases.
UNASSIGNED: Out of 713 records screened, 118 studies (26.9%) were included in the qualitative synthesis. Cell line-derived xenografts (CDX) were the most commonly utilized (n = 75, 63.6%), followed by patient-derived xenografts (PDX) and syngeneic models, each accounting for 11.9% (n = 14), and genetically engineered mouse models (GEMM) (n = 7, 5.9%). Combinations of different model categories were reported in 5.9% (n = 7) of studies. One study employed a virus-induced RMS model. Overall, 40.0% (n = 30) of the studies utilizing CDX models established alveolar RMS (aRMS), while 38.7% (n = 29) were embryonal phenotypes (eRMS). There were 20.0% (n = 15) of studies that involved a combination of both aRMS and eRMS subtypes. In one study (1.3%), the RMS phenotype was spindle cell/sclerosing. Subcutaneous xenografts (n = 66, 55.9%) were more frequently used compared to orthotopic models (n = 29, 24.6%). Notably, none of the employed cell lines were derived from primary untreated tumors. Only a minority of studies investigated disseminated RMS phenotypes (n = 16, 13.6%). The utilization areas of RMS models included testing drugs (n = 64, 54.2%), studying tumorigenesis (n = 56, 47.5%), tumor modeling (n = 19, 16.1%), imaging (n = 9, 7.6%), radiotherapy (n = 6, 5.1%), long-term effects related to radiotherapy (n = 3, 2.5%), and investigating biomarkers (n = 1, 0.8%). Notably, no preclinical studies focused on surgery.
UNASSIGNED: This up-to-date review highlights the need for mouse models with dissemination phenotypes and cell lines from primary untreated tumors. Furthermore, efforts should be directed towards underexplored areas such as surgery, radiotherapy, and biomarkers.

Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma in children. The present study reports the case of a 2-year-old female who presented with abdominal pain and a palpable abdominal mass. Radiological investigations failed to reveal the tissue origin of the mass and a tru-cut biopsy confirmed the diagnosis of embryonal RMS. Surgical excision was performed after neo-adjuvant chemotherapy. The pelvic end of the mass was observed to continue with the left medial umbilical ligament. The patient\'s postoperative course was uneventful, and follow-up imaging showed no evidence of recurrence. Τhe present case report is the first non-syndromic case with left umbilical medial ligament-originated RMS.

OBJECTIVE: When exercising above the lactic threshold (LT), the slow component of oxygen uptake ([Formula: see text]) appears, mainly ascribed to the progressive recruitment of Type II fibers. However, also the progressive decay of the economy of contraction may contribute to it. We investigated oxygen uptake ([Formula: see text]) during isometric contractions clamping torque (T) or muscular activation to quantify the contributions of the two mechanisms.
METHODS: We assessed for 7 min T of the leg extensors, net oxygen uptake ([Formula: see text]) and root mean square (RMS) from vastus lateralis (VL) in 11 volunteers (21 ± 2 yy; 1.73 ± 0.11 m; 67 ± 14 kg) during cyclic isometric contractions (contraction/relaxation 5 s/5 s): (i) at 65% of maximal voluntary contraction (MVC) (FB-Torque) and; (ii) keeping the level of RMS equal to that at 65% of MVC (FB-EMG).
RESULTS: [Formula: see text] after the third minute in FB-Torque increased with time ([Formula: see text] = 94 × t + 564; R2 = 0.99; P = 0.001), but not during FB-EMG. [Formula: see text]/T increased only during FB-Torque ([Formula: see text]/T = 1.10 × t + 0.57; R2 = 0.99; P = 0.001). RMS was larger in FB-Torque than in FB-EMG and significantly increased in the first three minutes of exercise to stabilize till the end of the trial, indicating that the pool of recruited MUs remained constant despite [Formula: see text].
CONCLUSIONS: The analysis of the RMS, [Formula: see text] and T during FB-Torque suggests that the intrinsic mechanism attributable to the decay of contraction efficiency was responsible for an increase of [Formula: see text] equal to 18% of the total [Formula: see text].