Nucleophilic Functionalization of a Cationic Pentaphosphole Complex-A Systematic Study of Reactivity.

The systematic nucleophilic functionalization of the cationic pentaphosphole ligand complex [Cp*Fe(η-PMe)][OTf] (A) with group 16/17 nucleophiles is reported. This method represents a highly reliable and versatile strategy for the design of novel transition-metal complexes featuring twofold substituted end-deck cyclo-P ligands, bearing unprecedented hetero-element substituents. By the reaction of A with classical group 16 nucleophiles, complexes of the type [Cp*Fe(η-PMeE)] (E=OEt (1), OBu (2), SPh (3), SePh (4)) are obtained.

Perforation of the host cell plasma membrane during invasion requires rhoptry exocytosis.

is an obligate intracellular parasite, and the delivery of effector proteins from the parasite into the host cell during invasion is critical for invasion itself and for parasite virulence. The effector proteins are released from specialized apical secretory organelles known as rhoptries. While much has been learned recently about the structure and composition of the rhoptry exocytic machinery and the function of individual rhoptry effector proteins that are exocytosed, virtually nothing is known about how the released proteins are translocated across the host cell plasma membrane.

Serologic Evidence of Recent Infection with Highly Pathogenic Avian Influenza A(H5) Virus Among Dairy Workers - Michigan and Colorado, June-August 2024.

Since April 2024, sporadic infections with highly pathogenic avian influenza (HPAI) A(H5) viruses have been detected among dairy farm workers in the United States. To date, infections have mostly been detected through worker monitoring, and have been mild despite the possibility of more severe illness. During June-August 2024, CDC collaborated with the Michigan Department of Health and Human Services and the Colorado Department of Public Health and Environment to implement cross-sectional serologic surveys to ascertain the prevalence of recent infection with HPAI A(H5) virus among dairy workers.

Shuttle HAT for mild alkene transfer hydrofunctionalization.

Hydrogen atom transfer (HAT) from a metal-hydride is a reliable and powerful method for functionalizing unsaturated C-C bonds in organic synthesis. Cobalt hydrides (Co-H) have garnered significant attention in this field, where the weak Co-H bonds are most commonly generated in a catalytic fashion through a mixture of stoichiometric amounts of peroxide oxidant and silane reductant. Here we show that the reverse process of HAT to an alkene, i.

The invasion pore induced by .

Obligate intracellular parasites invade host cells to survive. Following host cell contact, the apicomplexan injects proteins required for invasion into the host cell. Here, electrophysiological recordings of host cells acquired at sub-200 ms resolution allowed detection and analysis of a transient increase in host membrane conductance following exposure to .

Enhancing the Reactivity of an Aromatic cyclo-P Ligand via Electrophilic Activation.

Electrophilic activation of the aromatic cyclo-P ligand in [Cp*Fe(η-P)] is demonstrated to drastically enhance its reactivity towards weak nucleophiles. Unprecedented functionalized, contracted as well as complexly aggregated polyphosphorus compounds are accessed utilizing [Cp*Fe(η-PMe)][OTf] (A), highlighting the great potential of this underexplored mode of reactivity. Addition of carbenes to A affords novel 1,2- or 1,1-difunctionalized cyclo-P complexes [Cp*Fe(η-P(1-L)(2-Me)][OTf] (L=IDipp (1), CAAC (2), IPr (3 b)) and [Cp*Fe(η-P(1-IPr)(1-Me)][OTf] (3 a).

Neurocognitive outcomes and functional independence in adult survivors of childhood medulloblastoma diagnosed over 3 decades.

Background: Treatment of childhood medulloblastoma has evolved to reduce neurotoxicity while improving survival. However, the impact of evolving therapies on late neurocognitive outcomes and adult functional independence remains unknown.

Methods: Adult survivors of childhood medulloblastoma (n = 505; median [minimum-maximum] age, 29 [18-46] years) and sibling controls (n = 727; 32 [18-58] years) from the Childhood Cancer Survivor Study completed surveys assessing neurocognitive problems and chronic health conditions (CHCs).

A Radiomic Approach for Evaluating Intra-Subgroup Heterogeneity in SHH and Group 4 Pediatric Medulloblastoma: A Preliminary Multi-Institutional Study.

Medulloblastoma (MB) is the most frequent malignant brain tumor in children with extensive heterogeneity that results in varied clinical outcomes. Recently, MB was categorized into four molecular subgroups, WNT, SHH, Group 3, and Group 4. While SHH and Group 4 are known for their intermediate prognosis, studies have reported wide disparities in patient outcomes within these subgroups.

Resistance, rebound, and recurrence regrowth patterns in pediatric low-grade glioma treated by MAPK inhibition: A modified Delphi approach to build international consensus-based definitions-International Pediatric Low-Grade Glioma Coalition.

Pediatric low-grade glioma (pLGG) is the most common childhood brain tumor group. The natural history, when curative resection is not possible, is one of a chronic disease with periods of tumor stability and episodes of tumor progression. While there is a high overall survival rate, many patients experience significant and potentially lifelong morbidities.

Temporal changes in treatment and late mortality and morbidity in adult survivors of childhood glioma: a report from the Childhood Cancer Survivor Study.

Pediatric glioma therapy has evolved to delay or eliminate radiation for low-grade tumors. This study examined these temporal changes in therapy with long-term outcomes in adult survivors of childhood glioma. Among 2,501 5-year survivors of glioma in the Childhood Cancer Survivor Study diagnosed 1970-1999, exposure to radiation decreased over time.

Safety and pharmacokinetics of ONC201 (dordaviprone) administered two consecutive days per week in pediatric patients with H3 K27M-mutant glioma.

Background: This study evaluated the safety and pharmacokinetics (PK) of oral ONC201 administered twice-weekly on consecutive days (D1D2) in pediatric patients with newly diagnosed DIPG and/or recurrent/refractory H3 K27M glioma.

Methods: This phase 1 dose-escalation and expansion study included pediatric patients with H3 K27M-mutant glioma and/or DIPG following ≥1 line of therapy (NCT03416530). ONC201 was administered D1D2 at 3 dose levels (DLs; -1, 1, and 2).

Consensus framework for conducting phase I/II clinical trials for children, adolescents, and young adults with pediatric low-grade glioma: Guidelines established by the International Pediatric Low-Grade Glioma Coalition Clinical Trial Working Group.

Within the last few decades, we have witnessed tremendous advancements in the study of pediatric low-grade gliomas (pLGG), leading to a much-improved understanding of their molecular underpinnings. Consequently, we have achieved successful milestones in developing and implementing targeted therapeutic agents for treating these tumors. However, the community continues to face many unknowns when it comes to the most effective clinical implementation of these novel targeted inhibitors or combinations thereof.

Relative quantification of progressive changes in healthy and dysferlin-deficient mouse skeletal muscle proteomes.

Introduction/aims: Individuals with dysferlinopathies, a group of genetic muscle diseases, experience delay in the onset of muscle weakness. The cause of this delay and subsequent muscle wasting are unknown, and there are currently no clinical interventions to limit or prevent muscle weakness. To better understand molecular drivers of dysferlinopathies, age-dependent changes in the proteomic profile of skeletal muscle (SM) in wild-type (WT) and dysferlin-deficient mice were identified.

Shedding New Light: Novel Therapies for Common Disorders in Children with Neurofibromatosis Type I.

Neurofibromatosis type I (NF1) is a common dominantly inherited disorder, and one of the most common of the RASopathies. Most individuals with NF1 develop plexiform neurofibromas and cutaneous neurofibromas, nerve tumors caused by NF1 loss of function in Schwann cells. Cell culture models and mouse models of NF1 are being used to test drug efficacy in preclinical trials, which led to Food and Drug Administration approval for use of MEK inhibitors to shrink most inoperable plexiform neurofibromas.

Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma.

Background: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown.

Methods: Adult survivors of childhood glioma diagnosed in 1970-1999 in the Childhood Cancer Survivor Study (n = 1284; median [minimum-maximum] 30 [18-51] years of age at assessment; 22 [15-34] years from diagnosis) self-reported neurocognitive impairment and chronic health conditions.

Opportunities and Advances in Radiomics and Radiogenomics for Pediatric Medulloblastoma Tumors.

Recent advances in artificial intelligence have greatly impacted the field of medical imaging and vastly improved the development of computational algorithms for data analysis. In the field of pediatric neuro-oncology, radiomics, the process of obtaining high-dimensional data from radiographic images, has been recently utilized in applications including survival prognostication, molecular classification, and tumor type classification. Similarly, radiogenomics, or the integration of radiomic and genomic data, has allowed for building comprehensive computational models to better understand disease etiology.

A new era for myelin research in Neurofibromatosis type 1.

Evidence for myelin regulating higher-order brain function and disease is rapidly accumulating; however, defining cellular/molecular mechanisms remains challenging partially due to the dynamic brain physiology involving deep changes during development, aging, and in response to learning and disease. Furthermore, as the etiology of most neurological conditions remains obscure, most research models focus on mimicking symptoms, which limits understanding of their molecular onset and progression. Studying diseases caused by single gene mutations represents an opportunity to understand brain dys/function, including those regulated by myelin.

An unusual presentation of bilateral optic pathway glioma in Crouzon Syndrome.

Crouzon Syndrome is a genetic craniosynostosis disorder associated with a high risk of ophthalmologic sequelae secondary to structural causes. However, ophthalmologic disorders due to intrinsic nerve aberrations in Crouzon Syndrome have not been described. Optic pathway gliomas (OPGs) are low grade gliomas that are intrinsic to the visual pathway, frequently associated with Neurofibromatosis type 1 (NF-1).

The Brain Tumor Segmentation (BraTS) Challenge 2023: .

Pediatric tumors of the central nervous system are the most common cause of cancer-related death in children. The five-year survival rate for high-grade gliomas in children is less than 20%. Due to their rarity, the diagnosis of these entities is often delayed, their treatment is mainly based on historic treatment concepts, and clinical trials require multi-institutional collaborations.

Evaluating Focal Areas of Signal Intensity (FASI) in Children with Neurofibromatosis Type-1 (NF1) Treated with Selumetinib on Pediatric Brain Tumor Consortium (PBTC)-029B.

Background: Understanding the effect of selumetinib on FASI may help elucidate the biology, proliferative potential, and role in neurocognitive changes for these NF1-associated lesions.

Methods: Patients with NF1-associated LGG and FASI treated with selumetinib on PBTC-029B were age-matched to untreated patients with NF1-associated FASI at Cincinnati Children's Hospital Medical Center. Paired bidirectional measurements were compared over time using nonparametric tests.