Temporal Genomic Dynamics Shape Clinical Trajectory in Multiple Myeloma.

To comprehensively unravel the temporal relationship between initiating and driver events and its impact on clinical outcomes, we analyzed 421 whole-genome sequencing profiles from 382 patients. Using clock-like mutational signatures, we estimated a time lag of 2-4 decades between initiating events and diagnosis. In patients with hyperdiploidy, we demonstrate that trisomies of odd-numbered chromosomes can be acquired simultaneously with other chromosomal gains, such as 1q gain.

Reirradiation for diffuse intrinsic pontine glioma: prognostic radiomic factors at progression.

Purpose: Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain tumor. Radiation therapy (RT) is the standard treatment, with reirradiation considered in case of progression. However, the prognostic factors for reirradiation are not well understood.

Revisiting the role of radiotherapy in the treatment of neuroblastoma 4S: 30 years of institutional experience and systematic review.

Background And Purpose: Neuroblastoma 4S is a rare subtype of metastatic neuroblastoma found in children younger than 12 months, characterized by liver, skin, or bone marrow metastases. While the prognosis for patients is generally favorable, rapid progression of liver metastases can lead to life-threatening organ insufficiency. In such cases, immediate treatment with chemotherapy or radiotherapy is necessary.

The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma.

Acquisition of a hyperdiploid (HY) karyotype or immunoglobulin heavy chain (IgH) translocations are considered key initiating events in multiple myeloma (MM). To explore if other genomic events can precede these events, we analyzed whole-genome sequencing data from 1173 MM samples. By integrating molecular time and structural variants within early chromosomal duplications, we indeed identified pregain deletions in 9.

Impaired synaptic incorporation of AMPA receptors in a mouse model of fragile X syndrome.

Fragile X syndrome (FXS) is the most common monogenetic cause of inherited intellectual disability and autism in humans. One of the well-characterized molecular phenotypes of KO mice, a model of FXS, is increased translation of synaptic proteins. Although this upregulation stabilizes in adulthood, abnormalities during the critical period of plasticity have long-term effects on circuit formation and synaptic properties.

The rise of negative portrayals of radiation oncology: A textual analysis of media news.

Background And Purpose: There has been growing concern about the media's negative portrayal of radiation oncology in recent years. Our study shows changes in media sentiment toward radiotherapy over the years, identifies prevalent themes, and analyzes their shifts over time.

Materials And Methods: We analyzed articles about radiation oncology published in The New York Times since the journal's inception in 1851.

Genomic and immune signatures predict clinical outcome in newly diagnosed multiple myeloma treated with immunotherapy regimens.

Despite improving outcomes, 40% of patients with newly diagnosed multiple myeloma treated with regimens containing daratumumab, a CD38-targeted monoclonal antibody, progress prematurely. By integrating tumor whole-genome and microenvironment single-cell RNA sequencing from upfront phase 2 trials using carfilzomib, lenalidomide and dexamethasone with daratumumab ( NCT03290950 ), we show how distinct genomic drivers including high APOBEC mutational activity, IKZF3 and RPL5 deletions and 8q gain affect clinical outcomes. Furthermore, evaluation of paired bone marrow profiles, taken before and after eight cycles of carfilzomib, lenalidomide and dexamethasone with daratumumab, shows that numbers of natural killer cells before treatment, high T cell receptor diversity before treatment, the disappearance of sustained immune activation (that is, B cells and T cells) and monocyte expansion over time are all predictive of sustained minimal residual disease negativity.

Impact of Rare Structural Variant Events in Newly Diagnosed Multiple Myeloma.

Purpose: Whole-genome sequencing (WGS) of patients with newly diagnosed multiple myeloma (NDMM) has shown recurrent structural variant (SV) involvement in distinct regions of the genome (i.e., hotspots) and causing recurrent copy-number alterations.

Mechanisms of antigen escape from BCMA- or GPRC5D-targeted immunotherapies in multiple myeloma.

B cell maturation antigen (BCMA) target loss is considered to be a rare event that mediates multiple myeloma (MM) resistance to anti-BCMA chimeric antigen receptor T cell (CAR T) or bispecific T cell engager (TCE) therapies. Emerging data report that downregulation of G-protein-coupled receptor family C group 5 member D (GPRC5D) protein often occurs at relapse after anti-GPRC5D CAR T therapy. To examine the tumor-intrinsic factors that promote MM antigen escape, we performed combined bulk and single-cell whole-genome sequencing and copy number variation analysis of 30 patients treated with anti-BCMA and/or anti-GPRC5D CAR T/TCE therapy.

Risk-Adapted Treatment Strategies with Pre-Irradiation Chemotherapy in Pediatric Medulloblastoma: Outcomes from the Polish Pediatric Neuro-Oncology Group.

Craniospinal irradiation (CSI) has been a major component of the standard of care treatment backbone for childhood medulloblastoma. However, chemotherapy regimens have varied based on protocol, patient age, and molecular subtyping. In one of the largest studies to date, we analyzed treatment outcomes in children with newly-diagnosed medulloblastoma treated with pre-irradiation chemotherapy followed by risk-adapted radiotherapy and maintenance chemotherapy.

Prognostic value of coronary atherosclerosis and CAC score for the risk of chemotherapy-related cardiac dysfunction (CTRCD): The protocol of ANTEC study.

Background: Cardiological complications of oncological treatment, including the most serious one, heart failure, constitute a significant and still unsolved clinical problem. A history of dyslipidemia and complications of atherosclerosis, including coronary artery disease, are established risk factors for cardiotoxicity in cancer patients. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed.

Zeolites with Divalent Ions as Carriers in the Delivery of Epigallocatechin Gallate.

Epigallocatechin gallate (EGCG) is a compound with very high therapeutic potential in the treatment of osteoporosis and cancer. The disadvantages of this compound are its low stability and low bioavailability. Therefore, carriers for EGCG are sought to increase its use.

Mesoporous Silica Modified with Polydopamine and Zinc Ions as a Potential Carrier in the Controlled Release of Mercaptopurine.

Mercaptopurine is one of the drugs used in the treatment of acute lymphoblastic leukemia. A problem with mercaptopurine therapy is its low bioavailability. This problem can be solved by preparing the carrier that releases the drug in lower doses but over a longer period of time.

Impact of rare structural variant events in newly diagnosed multiple myeloma.

Unlabelled: Whole genome sequencing (WGS) of newly diagnosed multiple myeloma patients (NDMM) has shown recurrent structural variant (SV) involvement in distinct regions of the genome (i.e. hotspots) and causing recurrent copy number alterations.

Synergistic Brønsted/Lewis acid catalyzed aromatic alkylation with unactivated tertiary alcohols or di--butylperoxide to synthesize quaternary carbon centers.

Dual Brønsted/Lewis acid catalysis involving environmentally benign, readily accessible protic acid and iron promotes site-selective -butylation of electron-rich arenes using di--butylperoxide. This transformation inspired the development of a synergistic Brønsted/Lewis acid catalyzed aromatic alkylation that fills a gap in the Friedel-Crafts reaction literature by employing unactivated tertiary alcohols as alkylating agents, leading to new quaternary carbon centers. Corroborated by DFT calculations, the Lewis acid serves a role in enhancing the acidity of the Brønsted acid.

Defining genomic events involved in the evolutionary trajectories of myeloma and its precursor conditions.

All patients with a diagnosis of multiple myeloma (MM) have a preceding, asymptomatic expansion of clonal plasma cells, clinically recognized as monoclonal gammopathy of undetermined significance or smoldering multiple myeloma (SMM). While most patients with monoclonal gammopathy of undetermined significance have a very small rate of progression, SMM is a widely heterogeneous condition where a fraction of patients will progress to symptomatic MM rather quickly, while others will experience an indolent clinical course. The differentiation between progressive and stable precursor condition thus represents one of the most important unmet clinical needs in the MM community.

Application of array comparative genomic hybridization (aCGH) for identification of chromosomal aberrations in the recurrent pregnancy loss.

Spontaneous abortion occurs in 8-20% of recognized pregnancies and usually takes place in the first trimester (7-11 weeks). There are many causes of pregnancy loss, but the most important (about 75%) is the presence of chromosomal aberrations. We present the results of oligonucleotide array application in a cohort of 62 miscarriage cases.

COVID-19 Vaccinations: Summary Guidance for Cancer Patients in 28 Languages: Breaking Barriers to Cancer Patient Information.

Background: Covid-19 vaccination has started in the majority of the countries at the global level. Cancer patients are at high risk for infection, serious illness, and death from COVID-19 and need vaccination guidance and support. Guidance availability in the English language only is a major limit for recommendations' delivery and their application in the world's population and generates information inequalities across the different populations.

Radical radiotherapy for paediatric solid tumour metastases: An overview of current European protocols and outcomes of a SIOPE multicenter survey.

Purpose/objective: About 20% of children with solid tumours (ST) present with distant metastases (DM). Evidence regarding the use of radical radiotherapy of these DM is sparse and open for personal interpretation. The aim of this survey was to review European protocols and to map current practice regarding the irradiation of DM across SIOPE-affiliated countries.

Epithelioid Sarcoma-From Genetics to Clinical Practice.

Epithelioid sarcoma is a mesenchymal soft tissue sarcoma often arising in the extremities, usually in young adults with a pick of incidence at 35 years of age. Epithelioid sarcoma (ES) is characterized by the loss of SMARCB1/INI1 (integrase interactor 1) or other proteins of the SWI/SNF complex. Two distinct types, proximal and distal, with varying biology and treatment outcomes, are distinguished.

Smartphone as a monitoring tool for bipolar disorder: a systematic review including data analysis, machine learning algorithms and predictive modelling.

Background: Bipolar disorder (BD) is a chronic illness with a high recurrence rate. Smartphones can be a useful tool for detecting prodromal symptoms of episode recurrence (through real-time monitoring) and providing options for early intervention between outpatient visits.

Aims: The aim of this systematic review is to overview and discuss the studies on the smartphone-based systems that monitor or detect the phase change in BD.

Case report of dysregulation of primary bile acid synthesis in a family with X-linked adrenoleukodystrophy.

Rationale: X-linked adrenoleukodystrophy (X-ALD) is a rare disorder caused by mutations in the ABCD1 gene, coding for peroxisomal membrane transporter adrenoleukodystrophy (ALD) protein. The disease is characterized by accumulation of very long chain fatty acids (VLCFAs) in tissues. Adult adrenomyeloneuropathy (AMN) and the cerebral inflammatory form of ALD are the main phenotypes presenting various symptoms.