Publications by authors named "Swoboda K"

Background: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non-small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells.

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Spinal muscular atrophy (SMA) is caused by mutations in SMN1. SMN2 is a paralogous gene with a C•G-to-T•A transition in exon 7, which causes this exon to be skipped in most SMN2 transcripts, and results in low levels of the protein survival motor neuron (SMN). Here we show, in fibroblasts derived from patients with SMA and in a mouse model of SMA that, irrespective of the mutations in SMN1, adenosine base editors can be optimized to target the SMN2 exon-7 mutation or nearby regulatory elements to restore the normal expression of SMN.

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Article Synopsis
  • The NURTURE study investigated the effects of nusinersen on children with spinal muscular atrophy (SMA) who started treatment before showing symptoms, finding positive outcomes in survival, motor milestones, and safety after 5 years.
  • All participating children remained alive, with significant motor skill achievements, particularly among those with three SMN2 gene copies.
  • Results emphasize the benefits of early treatment for SMA and the importance of considering specific criteria when evaluating trial data.
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Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the gene. Despite the development of various therapies, outcomes can remain suboptimal in SMA infants and the duration of such therapies are uncertain. is a paralogous gene that mainly differs from by a C•G-to-T•A transition in exon 7, resulting in the skipping of exon 7 in most transcripts and production of only low levels of survival motor neuron (SMN) protein.

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Background: Comfort and recovery are major concerns of patients seeking aesthetic surgery. This study aimed to assess postoperative pain and recovery after outpatient breast surgery under sedation, intercostal block, and local anaesthesia.

Methods: This prospective cohort study included all consecutive patients who underwent aesthetic breast surgery between April 2021 and August 2022.

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Background: Cardiovascular safety of marathon running middle-aged amateurs remains unclear. We previously hypothesized that transient release of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in addition to an acute inflammatory response to exercise, may be the cause.

Objectives: To evaluate the effects of running a marathon on inflammatory biomarkers, and its impact on cardiovascular function.

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Stress granules (SGs) are cytoplasmic assemblies in response to a variety of stressors. We report a new neurodevelopmental disorder (NDD) with common features of language problems, intellectual disability, and behavioral issues caused by de novo likely gene-disruptive variants in , which encodes an essential regulator of SG assembly. haploinsufficiency in mouse led to social and cognitive impairments accompanied by disrupted neurogenesis and reduced SG formation during early brain development.

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Article Synopsis
  • Each year, 1 in 294 newborns is identified with a condition through newborn screening (NBS), which can lead to early treatment and potentially life-saving interventions.
  • Advances in genomic technologies are expected to broaden the scope of NBS, but the process of expanding screening occurs slowly and inconsistently across the US.
  • The NBS Expansion Study analyzed current NBS practices and identified four main factors that complicate expansion, averaging a 9.5-year delay for nationwide adoption of new conditions.
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Most children with biallelic SMN1 deletions and three SMN2 copies develop spinal muscular atrophy (SMA) type 2. SPR1NT ( NCT03505099 ), a Phase III, multicenter, single-arm trial, investigated the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated within six postnatal weeks. Of 15 children with three SMN2 copies treated before symptom onset, all stood independently before 24 months (P < 0.

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SPR1NT ( NCT03505099 ) was a Phase III, multicenter, single-arm study to investigate the efficacy and safety of onasemnogene abeparvovec for presymptomatic children with biallelic SMN1 mutations treated at ≤6 weeks of life. Here, we report final results for 14 children with two copies of SMN2, expected to develop spinal muscular atrophy (SMA) type 1. Efficacy was compared with a matched Pediatric Neuromuscular Clinical Research natural-history cohort (n = 23).

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Objective: The US risdiplam expanded access program (EAP; NCT04256265) was opened to provide individuals with Type 1 or 2 spinal muscular atrophy (SMA) who had no satisfactory treatment options access to risdiplam prior to commercial availability. The program was designed to collect safety data during risdiplam treatment.

Methods: Patients were enrolled from 23 non-preselected sites across 17 states and treated with risdiplam orally once daily.

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Background And Purpose: The antisense oligonucleotide nusinersen (Spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression. Nusinersen has improved ventilator-free survival and motor function outcomes in infantile onset forms of spinal muscular atrophy (SMA), treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation.

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Article Synopsis
  • The study focuses on the 10-meter walk/run test (10MWRT) in young individuals with spinal muscular atrophy (SMA) to track changes in walking speed over time and its association with various factors.
  • It examined untreated participants aged 2 to 21 years to establish how 10MWRT time relates to age, SMA type, SMN2 copy number, and body weight.
  • The results indicate that walking speed improves in early childhood, stabilizes for a short period, and then declines in later teenage years, providing important insights for future treatment interpretations.
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This longitudinal cohort study aimed to determine whether circulating neurofilaments (NFs) can monitor response to molecular therapies in newborns with spinal muscular atrophy (SMA; NCT02831296). We applied a mixed-effect model to examine differences in serum NF levels among healthy control infants (n = 13), untreated SMA infants (n = 68), and SMA infants who received the genetic therapies nusinersen and/or onasemnogene abeparvovec (n = 22). Increased NF levels were inversely associated with copy number.

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  • The study examined how cancer cachexia affects oxidative post-translational modifications (Ox-PTMs) in two different muscle types (glycolytic vs. oxidative) in rats.
  • Researchers found muscle wasting primarily in the glycolytic plantaris muscle, with no significant changes in the oxidative soleus muscle in tumor-bearing rats.
  • The results indicated that cancer progression alters metabolic pathways, energy levels, and oxidative stress markers, highlighting that the type of muscle fiber influences how it responds to cancer-induced muscle atrophy.
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Massachusetts began newborn screening (NBS) for Spinal Muscular Atrophy (SMA) following the availability of new treatment options. The New England Newborn Screening Program developed, validated, and implemented a screening algorithm for the detection of SMA-affected infants who show absent Exon 7 by Real-Time™ quantitative PCR (qPCR). We screened 179,467 neonates and identified 9 SMA-affected infants, all of whom were referred to a specialist by day of life 6 (average and median 4 days of life).

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Despite newly available treatments for spinal muscular atrophy (SMA), novel circulating biomarkers are still critically necessary to track SMA progression and therapeutic response. To identify potential biomarkers, we performed whole-blood RNA sequencing analysis in SMA type 1 subjects under 1 year old and age-matched healthy controls. Our analysis revealed the Heat Shock Protein Family A Member 7 (HSPA7)/heat shock 70kDa protein 7 (HSP70B) as a novel candidate biomarker to track SMA progression early in life.

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Spinal muscular atrophy is a progressive, recessively inherited monogenic neurologic disease, the genetic root cause of which is the absence of a functional gene. Onasemnogene abeparvovec (formerly AVXS-101) is an adeno-associated virus serotype 9 vector-based gene therapy that delivers a fully functional copy of the human gene. We report anti-adeno-associated virus serotype 9 antibody titers for patients with spinal muscular atrophy when they were screened for eligibility in the onasemnogene abeparvovec clinical trials (intravenous and intrathecal administration) and managed access programs (intravenous).

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Gene replacement and pre-mRNA splicing modifier therapies represent breakthrough gene targeting treatments for the neuromuscular disease spinal muscular atrophy (SMA), but mechanisms underlying variable efficacy of treatment are incompletely understood. Our examination of severe infantile onset human SMA tissues obtained at expedited autopsy revealed persistence of developmentally immature motor neuron axons, many of which are actively degenerating. We identified similar features in a mouse model of severe SMA, in which impaired radial growth and Schwann cell ensheathment of motor axons began during embryogenesis and resulted in reduced acquisition of myelinated axons that impeded motor axon function neonatally.

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Article Synopsis
  • - Proximal spinal muscular atrophy (SMA) is a severe genetic disorder affecting infants, primarily caused by mutations in the SMN1 gene, with varying impacts based on the number of SMN2 gene copies present.
  • - This study introduces a new method called array digital PCR (dPCR) that accurately measures the copy numbers of SMN1 and SMN2 genes, which is important for assessing disease severity in SMA patients.
  • - The dPCR technique can also detect gene conversion events and partial deletions of SMN1, providing valuable insights for clinical assessments and personalized treatment strategies for SMA.
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Objective: To perform genotype-phenotype, clinical and molecular analysis in a large 3-generation family with autosomal dominant congenital spinal muscular atrophy.

Methods: Using a combined genetic approach including whole genome scanning, next generation sequencing-based multigene panel, whole genome sequencing, and targeted variant Sanger sequencing, we studied the proband and multiple affected individuals of this family who presented bilateral proximal lower limb muscle weakness and atrophy.

Results: We identified a novel heterozygous variant, c.

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Aims: Patients with acute heart failure (AHF) are included into clinical trials regardless of differences in baseline clinical characteristics. The aim of this study was to assess patients with AHF according to the presence of central and/or peripheral congestion at hospital admission and evaluate treatment response and outcomes in studied phenotypes.

Methods And Results: We investigated retrospectively 352 patients (mean age: 68 ± 13 years, 77% men) hospitalized due to AHF with the signs of congestion on admission.

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Purpose: The purpose of this study was to describe stander use in a natural history cohort of drug therapy-naïve children with spinal muscular atrophy (SMA) who are not walking and identify factors associated with consistent stander use.

Methods: Data from 397 children with SMA types 1 and 2 characterized the prevalence and frequency of stander use. Predictors of consistent stander use explored were SMA type, survival motor neuron 2 gene (SMN2) copy number, respiratory support, and motor performance.

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