Multicenter Retrospective Analysis of Pediatric Differentiated Thyroid Carcinoma: Treatment Practices and Outcomes Prior to Pediatric American Thyroid Association Guidelines Implementation.

Background: Differentiated thyroid carcinoma (DTC) is the most common pediatric thyroid malignancy, with papillary thyroid carcinoma (PTC) representing 90% of the cases. In 2015, the American Thyroid Association (ATA) developed management guidelines for pediatric DTC.

Procedure: Patients less than 21 years of age diagnosed with DTC between 2000 and 2015 at Texas Children's Hospital, Seattle Children's Hospital, Children's Healthcare of Atlanta, Children's Hospital Colorado, and Nationwide Children's Hospital were retrospectively analyzed to evaluate treatment practices before the implementation of the ATA guidelines.

A Strategy To Access Embedded Circuits in a Single-Molecule Bis-Terpyridine Breadboard Junction.

Predictive approaches and rules to connect and combine molecular circuit components are required to realize the potential of molecular electronics and develop miniaturized integrated circuits. To this end, we have recently demonstrated a bis(terpyridine)-based molecular breadboard with four conductance states formed by the superposition of five 2-5 ring circuits. Here, we develop a generic analytical/statistical model to describe break-junction data and use it to extract the conductance of the five embedded circuits in the bis-terpyridine-based molecular breadboard junction.

Tunneling barriers in an extended Marcus theory of electron transfer: Incorporating effects of the bridging medium.

The Marcus semi-classical and quantum theories of electron transfer (ET) have been extensively used to understand and predict tunneling ET reaction rates in the condensed phase. Previously, the traditional Marcus two-state model has been extended to a three-state model, which assumes a harmonic dependence of donor (D), bridge (B), and acceptor (A) free energies on the reaction (e.g.

National virtual tumor boards to inform the management of children with rare cancers.

Purpose Of Review: Due to the infrequent nature of rare pediatric cancers, rigorously studied treatment algorithms are usually nonexistent, and experience with a given tumor may be limited at a single institution. Development of treatment plans for these populations often requires extensive literature review and outreach to experts at other institutions. National or international virtual tumor boards provide a streamlined, collaborative approach to discussing diagnosis and management of these patients through dissemination of collective experience and knowledge.

Implications of Implementing Children's Oncology Group Risk Stratification to Patients With Rhabdomyosarcoma Treated on European Paediatric Soft Tissue Sarcoma Study Group Clinical Trial.

Background: Prognostic factors are crucial in tailoring treatments for patients with rhabdomyosarcoma (RMS). The European paediatric Soft tissue sarcoma Study Group (EpSSG) and the Children's Oncology Group (COG) employ similar prognostic factors, but utilize them differently resulting in diverse stratification systems. This diversity may result in dissimilar treatment approaches for comparable patients and hinder the comparison of clinical trial results.

Late Events Occurring After 5 Years in Pediatric Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma, and 5-year overall survival exceeds 70%. With more long-term survivors, it is critical to understand the frequency of late events, including recurrence, second malignant neoplasm, and death, occurring 5 years after diagnosis, and the variables associated with these events. We report late events in patients enrolled on Intergroup Rhabdomyosarcoma Study Group and Children's Oncology Group trials from 1997 to 2013 including D9602, D9803, D9802, ARST0331, ARST0431, ARST0531, and ARST08P1.

A Mode Evolution Metric to Extract Reaction Coordinates for Biomolecular Conformational Transitions.

The complex, multidimensional energy landscape of biomolecules makes the extraction of suitable, nonintuitive collective variables (CVs) that describe their conformational transitions challenging. At present, dimensionality reduction approaches and machine learning (ML) schemes are employed to obtain CVs from molecular dynamics (MD)/Monte Carlo (MC) trajectories or structural databanks for biomolecules. However, minimum sampling conditions to generate reliable CVs that accurately describe the underlying energy landscape remain unclear.

Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers.

Purpose: Molecular markers, such as fusion genes and and mutations, increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.

Patients And Methods: Clinical variables and somatic mutation data for 20 genes from 641 RMS patients in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS).

The impact of margins and re-resection in pediatric synovial sarcoma.

Introduction: Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re-resection are lacking. We sought to evaluate the adequate resection margin and the role of re-resection in predicting outcomes in children with synovial sarcomas.

Whole Lung Irradiation in Rhabdomyosarcoma With Lung Metastases: A Report From the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

Purpose: Patients with rhabdomyosarcoma with metastatic disease have a poor prognosis despite therapy intensification. The aim of this study was to investigate the efficacy of whole lung irradiation (WLI) in patients with rhabdomyosarcoma and lung metastases.

Methods: Patients with rhabdomyosarcoma with lung metastases enrolled on four Children's Oncology Group protocols (D9802, D9803, ARST08P1, ARST0431) were retrospectively reviewed.

Outcomes for patients with perineal and perianal rhabdomyosarcoma: A report from the Children's Oncology Group Soft Tissue Sarcoma Committee.

Purpose: To describe clinical features, risk factors, and outcomes of patients with perineal and perianal rhabdomyosarcoma.

Methods: The records of 51 patients (38 perineal and 13 perianal) enrolled on Children's Oncology Group clinical trials between 1997 and 2012 were reviewed.

Results: At presentation, 53% were female, 65% were older than 10 years of age, 76% were alveolar histology, 76% were more than 5 cm, 84% were invasive, 65% were regional node positive by imaging, 49% were metastatic, only 16% were grossly resected upfront, and 25% of patients had a delayed excision.

A water-soluble, cell-permeable Mn(ii) sensor enables visualization of manganese dynamics in live mammalian cells.

Central roles of Mn ions in immunity, brain function, and photosynthesis necessitate probes for tracking this essential metal ion in living systems. However, developing a cell-permeable, fluorescent sensor for selective imaging of Mn ions in the aqueous cellular milieu has remained a challenge. This is because Mn is a weak binder to ligand-scaffolds and Mn ions quench fluorescent dyes leading to turn-off sensors that are not applicable for imaging.

Children and young adults with newly diagnosed rhabdomyosarcoma metastatic to bone treated on Children's Oncology Group studies.

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Despite bone metastases being present in 5% of patients at diagnosis, there are limited studies examining these outcomes. We sought to define the prognostic factors, clinical courses, and outcomes of children treated on Children's Oncology Group (COG) clinical trials with RMS metastatic to bone at diagnosis.

Multiple Functional Protein-Protein Interaction Interfaces Allosterically Regulate ATP-Binding in Cyclin-Dependent Kinase-1.

The ATP-dependent phosphorylation activity of cyclin-dependent kinase 1 (CDK1), an essential enzyme for cell cycle progression, is regulated by interactions with Cyclin-B, substrate, and Cks proteins. We have recently shown that active site acetylation in CDK1 abrogated binding to Cyclin-B which posits an intriguing long-range communication between the catalytic site and the protein-protein interaction (PPI) interface. Now, we demonstrate a general allosteric link between the CDK1 active site and all three of its PPI interfaces through atomistic molecular dynamics (MD) simulations.

Addition of temsirolimus to chemotherapy in children, adolescents, and young adults with intermediate-risk rhabdomyosarcoma (ARST1431): a randomised, open-label, phase 3 trial from the Children's Oncology Group.

Background: The Children's Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic FOXO1 fusion-positive disease. Temsirolimus in combination with chemotherapy has shown promising activity in patients with relapsed or refractory rhabdomyosarcoma. We aimed to compare event-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin, and cyclophosphamide alternating with vincristine and irinotecan (VAC/VI) combined with temsirolimus followed by maintenance therapy versus VAC/VI alone with maintenance therapy.

Event-free survival in relapsed and refractory rhabdomyosarcoma treated on cooperative group phase II trials: A report from the Children's Oncology Group.

Background: Novel therapies are needed for relapsed and refractory rhabdomyosarcoma (RRMS). Phase II clinical trials in RRMS have typically utilized radiologic response as the primary activity endpoint, an approach that poses several limitations in RRMS. In this analysis, we aimed to estimate an event-free survival (EFS) endpoint for RRMS that could be used as a benchmark for future studies.

Germline Genetic Testing and Survival Outcomes Among Children With Rhabdomyosarcoma: A Report From the Children's Oncology Group.

Importance: Determining the impact of germline cancer-predisposition variants (CPVs) on outcomes could inform novel approaches to testing and treating children with rhabdomyosarcoma.

Objective: To assess whether CPVs are associated with outcome among children with rhabdomyosarcoma.

Design, Setting, And Participants: In this cohort study, data were obtained for individuals, aged 0.

Outcome of patients with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcomas enrolled in phase 2 cooperative group clinical trials: A report from the Children's Oncology Group.

Background: The aim of this study was to estimate the event-free survival (EFS) of children and young adults with relapsed or refractory nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) treated in nonrandomized phase 2 studies conducted by the Children's Oncology Group (COG) and predecessor groups to establish a benchmark EFS for future phase 2 NRSTS trials evaluating the activity of novel agents.

Methods: A retrospective analysis of patients with recurrent or refractory NRSTS prospectively enrolled in nonrandomized phase 2 COG and predecessor group trials between 1994 and 2015 was conducted. EFS was defined as disease progression/relapse or death and calculated via the Kaplan-Meier method.

Adolescents and young adults with rhabdomyosarcoma: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

Introduction: The impact of established prognostic factors on survival outcomes for childhood rhabdomyosarcoma (RMS) have not been well described in the adolescent and young adult (AYA) RMS patient population.

Methods: This is a retrospective analysis of patients with newly diagnosed RMS enrolled between 1997 and 2016 on seven previously reported Children's Oncology Group (COG) clinical trials. Demographics, clinical features, treatment details, and outcome data were collected.

Prognosis of children and young adults with newly diagnosed rhabdomyosarcoma metastatic to bone marrow treated on Children's Oncology Group studies.

Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Metastatic disease occurs in 16% of all RMS cases and has a poor prognosis. There are limited studies examining the outcomes specific to patients with RMS metastatic to bone marrow despite an incidence of 6% at diagnosis.

Do quantum interference effects manifest in acyclic aliphatic molecules with anchoring groups?

The ability to control single molecule electronic conductance is imperative for achieving functional molecular electronics applications such as insulation, switching, and energy conversion. Quantum interference (QI) effects are generally used to control electronic transmission through single molecular junctions by tuning the molecular structure or the position of the anchoring group(s) in the molecule. While previous studies focussed on the QI between σ and/or π channels of the molecular backbone, here, we show that single molecule electronic devices can be designed based on QI effects originating from the interactions of anchoring groups.