Publications by authors named "Breier A"

Isothiocyanates (ITCs) are naturally occurring sulfur-containing compounds with diverse biological effects. This study investigated the effects of sulforaphane (SFN, an aliphatic ITC) and benzyl isothiocyanate (BITC, an aromatic ITC) on human acute myeloid leukemia SKM-1 cells, focusing on cell proliferation, cell death, and drug resistance. Both drug-sensitive SKM-1 cells and their drug-resistant SKM/VCR variant, which overexpresses the drug transporter P-glycoprotein, were used.

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The high resolution ro-vibrational spectrum of the diatomic molecule vanadium oxide (VO) in the gas phase was measured around 1000 cm. In total, 1529 ro-vibrational transitions were assigned, in a spectral range of 984-1036 cm. For many transitions, the hyperfine structure resulting from the nuclear spin of V were resolved and the molecular parameters for the first ( = 1) and second ( = 2) excited vibrational state of VO were derived.

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Oncological diseases represent a significant global health challenge, with high mortality rates. Early detection is crucial for effective treatment, and aptamers, which demonstrate superior specificity and stability compared to antibodies, offer a promising avenue for diagnostic advancement. This study presents the design, development and evaluation of a quartz crystal microbalance (QCM) sensor functionalized with the T2-KK1B10 aptamer for the sensitive and specific detection of Chronic Myeloid Leukemia (CML) K562 cells.

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Schizophrenia is a complex syndrome with taxing symptoms and for which treatment challenges remain. Current dopamine Dreceptor-blocking antipsychotics have well-known limitations, including ineffectively treating across all symptom domains and generating common side effects such as motor disturbances, weight gain, and metabolic dysfunction. New approaches are sorely needed to address the continued unmet treatment needs for individuals living with schizophrenia.

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Article Synopsis
  • The Human Connectome Project for Early Psychosis (HCP-EP) studies how the brain works in people who are starting to experience psychosis, which is when someone has trouble telling what's real and what's not.
  • They collected detailed information from 303 participants aged 16-35 across different hospitals in Massachusetts and Indiana.
  • The study aims to help researchers understand and compare different types of psychosis, and all the data is available for other scientists to use.
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Background: Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies.

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Aptamers are short oligonucleotides with single-stranded regions or peptides that recently started to transform the field of diagnostics. Their unique ability to bind to specific target molecules with high affinity and specificity is at least comparable to many traditional biorecognition elements. Aptamers are synthetically produced, with a compact size that facilitates deeper tissue penetration and improved cellular targeting.

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Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model.

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Article Synopsis
  • There is a critical demand for new antipsychotic medications that are more effective and have fewer side effects; xanomeline, a new muscarinic receptor agonist, shows promise in this area, especially when paired with trospium chloride to minimize side effects.
  • The EMERGENT-3 trial tested xanomeline-trospium against a placebo in adults with schizophrenia experiencing acute psychosis, taking place at multiple sites in the US and Ukraine from April to December 2022.
  • The study aimed to measure changes in psychiatric symptoms using the Positive and Negative Syndrome Scale (PANSS) and assess safety, with results expected to contribute to new treatment options for schizophrenia.
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(hoary cress) is a perennial plant belonging to the family that produces two dominant glucosinolates (GLSs): glucoraphanin (GRN) and sinalbin (SBN). They represent the stored form, which is converted upon the myrosinase (Myr) hydrolysis activity to active compounds, mainly isothiocyanates (ITCs) such as sulforaphane (SFN) or -hydroxybenzyl isothiocyanate (pHBITC). Research on ITCs that have proven anticancer, antimicrobial, and chemoprotective properties is usually conducted with pure commercially available compounds.

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Intracellular calcium, as a second messenger, is involved in multilevel cellular regulatory pathways and plays a role (among other processes) in switching between survival and initiation of cell death in neoplastic cells. The development of multidrug resistance (MDR) in neoplastic cells is associated with the ability of cells to escape programmed cell death, in which dysregulation of intracellular calcium may play an important role. Therefore, reliable monitoring of intracellular calcium levels is necessary.

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Article Synopsis
  • Despite decades of drug development, finding effective treatments for schizophrenia remains tough, with most antipsychotics providing only modest benefits.
  • Most currently approved medications mainly target dopamine D receptors, showing limited effectiveness, especially for cognitive and negative symptoms.
  • There is growing interest in developing new treatments that target muscarinic acetylcholine receptors, with promising research suggesting that drugs like xanomeline may improve outcomes for people with schizophrenia.
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Decades of psychosis research highlight the prevalence and the clinical significance of negative emotions, such as fear and anxiety. Translational evidence demonstrates the pivotal role of the amygdala in fear and anxiety. However, most of these approaches have used hypothesis-driven analyses with predefined regions of interest.

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Background: Psychomotor disturbances are observed across psychiatric disorders and often manifest as psychomotor slowing, agitation, disorganized behavior, or catatonia. Psychomotor function includes both cognitive and motor components, but the neural circuits driving these subprocesses and how they relate to symptoms have remained elusive for centuries.

Methods: We analyzed data from the HCP-EP (Human Connectome Project for Early Psychosis), a multisite study of 125 participants with early psychosis and 58 healthy participants with resting-state functional magnetic resonance imaging and clinical characterization.

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Molecules containing short-lived, radioactive nuclei are uniquely positioned to enable a wide range of scientific discoveries in the areas of fundamental symmetries, astrophysics, nuclear structure, and chemistry. Recent advances in the ability to create, cool, and control complex molecules down to the quantum level, along with recent and upcoming advances in radioactive species production at several facilities around the world, create a compelling opportunity to coordinate and combine these efforts to bring precision measurement and control to molecules containing extreme nuclei. In this manuscript, we review the scientific case for studying radioactive molecules, discuss recent atomic, molecular, nuclear, astrophysical, and chemical advances which provide the foundation for their study, describe the facilities where these species are and will be produced, and provide an outlook for the future of this nascent field.

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Article Synopsis
  • New treatments for schizophrenia are needed, as current options mostly block dopamine receptors, whereas xanomeline offers a different approach as a muscarinic receptor agonist without this blockade.
  • The EMERGENT-2 trial tested KarXT, a combination of xanomeline and trospium, for efficacy and safety in hospitalized patients experiencing acute psychosis, assessing changes in the PANSS score over 5 weeks.
  • Participants received varying doses of KarXT or a placebo, with results analyzed to determine the effectiveness of the treatment in improving symptoms compared to the placebo group.
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We present an empirically benchmarked framework for sex-specific normative modeling of brain morphometry that can inform about the biological and behavioral significance of deviations from typical age-related neuroanatomical changes and support future study designs. This framework was developed using regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) following a comparative evaluation of eight algorithms and multiple covariate combinations pertaining to image acquisition and quality, parcellation software versions, global neuroimaging measures, and longitudinal stability. The Multivariate Factorial Polynomial Regression (MFPR) emerged as the preferred algorithm optimized using nonlinear polynomials for age and linear effects of global measures as covariates.

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Article Synopsis
  • - The study focused on individuals with early phase psychosis (EPP) and found that a significant portion (about 25%) reported a history of legal issues like arrests or incarceration shortly after joining a treatment clinic.
  • - Data analysis revealed that 39% of participants had multiple traffic violations or criminal convictions, which is more than double the national average, with drug and alcohol-related offenses being the most frequent types.
  • - The findings suggest that specialty clinics should collaborate with experts in criminal behavior management, and future research should look into the risk factors associated with criminal convictions in individuals with EPP.
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Three AML cell variants (M/A, M/A* from MOLM-13 and S/A from SKM-1) were established for resistance by the same protocol using 5-azacytidine (AZA) as a selection agent. These AZA-resistant variants differ in their responses to other cytosine nucleoside analogs, including 5-aza-2'-deoxycytidine (DAC), as well as in some molecular features. Differences in global DNA methylation, protein levels of DNA methyltransferases, and phosphorylation of histone H2AX were observed in response to AZA and DAC treatment in these cell variants.

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Background: Alterations in brain connectivity may underlie neuropsychiatric conditions such as schizophrenia. We here assessed the degree of convergence of frontostriatal fiber projections in 56 young adult healthy controls (HCs) and 108 matched Early Psychosis-Non-Affective patients (EP-NAs) using our novel fiber cluster analysis of whole brain diffusion magnetic resonance imaging tractography.

Methods: Using whole brain tractography and our fiber clustering methodology on harmonized diffusion magnetic resonance imaging data from the Human Connectome Project for Early Psychosis we identified 17 white matter fiber clusters that connect frontal cortex (FCtx) and caudate (Cd) per hemisphere in each group.

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Dialuminum monoxide, AlO, has been investigated in the laboratory at mid-IR wavelengths around 10 μm at high spectral resolution. The molecule was produced by laser ablation of an aluminum target with the addition of gaseous nitrous oxide, NO. Subsequent adiabatic cooling of the gas in a supersonic beam expansion led to rotationally cold spectra.

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Successful anterior cruciate ligament (ACL) reconstructions strive for a firm bone-ligament integration. With the aim to establish an enthesis-like construct, embroidered functionalized scaffolds were colonized with spheroids of osteogenically differentiated human mesenchymal stem cells (hMSCs) and lapine (l) ACL fibroblasts in this study. These triphasic poly(L-lactide-co-ε-caprolactone) and polylactic acid (P(LA-CL)/PLA) scaffolds with a bone-, a fibrocartilage transition- and a ligament zone were colonized with spheroids directly after assembly (DC) or with 14-day pre-cultured lACL fibroblast and 14-day osteogenically differentiated hMSCs spheroids (=longer pre-cultivation, LC).

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