Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in patients with acute myeloid leukemia.

We systematically investigate functional and molecular measures of stemness in patients with acute myeloid leukemia (AML) using a cohort of 121 individuals. We confirm that the presence of leukemic stem cells (LSCs) detected through in vivo xenograft transplantation is associated with poor survival. However, the measurement of leukemic progenitor cells (LPCs) through in vitro colony-forming assays provides an even stronger predictor of overall and event-free survival. LPCs not only capture patient-specific mutations but also retain serial re-plating ability, demonstrating their biological relevance. Notably, LPC content represents an independent prognostic factor in multivariate analyses including clinical guidelines of risk stratification. Our findings suggest that LPCs provide a robust functional measure of AML, enabling quantitative and rapid assessment of a wide range of patients. This highlights the potential of LPCs as a valuable prognostic factor in AML management.

Identification of Chemotherapy-Induced Leukemic-Regenerating Cells Reveals a Transient Vulnerability of Human AML Recurrence.

Despite successful remission induction, recurrence of acute myeloid leukemia (AML) remains a clinical obstacle thought to be caused by the retention of dormant leukemic stem cells (LSCs). Using chemotherapy-treated AML xenografts and patient samples, we have modeled patient remission and relapse kinetics to reveal that LSCs are effectively depleted via cell-cycle recruitment, leaving the origins of relapse unclear. Post-chemotherapy, in vivo characterization at the onset of disease relapse revealed a unique molecular state of leukemic-regenerating cells (LRCs) responsible for disease re-growth. LRCs are transient, can only be detected in vivo, and are molecularly distinct from therapy-naive LSCs. We demonstrate that LRC features can be used as markers of relapse and are therapeutically targetable to prevent disease recurrence.

Noninvasive Brain-Computer Interfaces Based on Sensorimotor Rhythms.

Brain-computer interfaces (BCIs) have been explored in the field of neuroengineering to investigate how the brain can use these systems to control external devices. We review the principles and approaches we have taken to develop a sensorimotor rhythm EEG based brain-computer interface (BCI). The methods include developing BCI systems incorporating the control of physical devices to increase user engagement, improving BCI systems by inversely mapping scalp-recorded EEG signals to the cortical source domain, integrating BCI with noninvasive neuromodulation strategies to improve learning, and incorporating mind-body awareness training to enhance BCI learning and performance. The challenges and merits of these strategies are discussed, together with recent findings. Our work indicates that the sensorimotor-rhythm-based noninvasive BCI has the potential to provide communication and control capabilities as an alternative to physiological motor pathways.

Treatment discontinuation and clinical outcomes in the 1-year naturalistic treatment of patients with schizophrenia at risk of treatment nonadherence.

BACKGROUND: This study aimed to improve physicians' understanding of the treatment circumstances and needs of outpatients with schizophrenia at risk of nonadherence, by naturalistically assessing antipsychotic treatment patterns, clinical outcomes, and health care service use in this little-studied patient population. METHODS: In this one-year, prospective, multicenter, noninterventional, observational study, patients considered at risk of nonadherence by their physicians were switched from their primary oral antipsychotic to another oral or a depot antipsychotic at study entry. All cause treatment discontinuation (antipsychotic switch, augmentation, or discontinuation) during the study was assessed using Kaplan-Meier survival analyses and descriptive statistics. Patients' illness severity, quality of life, attitude towards medication, patient-reported adherence, and health care resource utilization were assessed during the study. RESULTS: Of the 406 enrolled patients, 43 (10.6%) were switched to depot and 363 (89.4%) were switched to oral antipsychotics at study entry. During the study, 99 (24.4%) patients switched, augmented, or discontinued their antipsychotic (all cause treatment discontinuation). Of the 99 patients who switched, augmented, or discontinued their antipsychotic, 8 (18.6%) were taking depot and 91 (25.0%) were taking oral antipsychotics. These patients were switched to either depot (n = 15) or oral (n = 78) antipsychotics, or discontinued their antipsychotic medication (n = 6). Inadequate response was the most frequently reported reason for medication discontinuation. During the study, patients' clinical and functional status improved significantly and service use was low. Most patients considered themselves to be adherent at study entry, and this favorable self-perception increased during the study (from 68.5% to 88.1%). CONCLUSION: Although identified as at risk of nonadherence, few patients in this naturalistic study discontinued their prescribed antipsychotic medication during the study. The discrepancy between the physicians' perception of their patient's medication adherence and the patients' self-perceived adherence highlights the need to better understand the underlying reasons for this phenomenon.