Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the therapeutic method with the most potent anti-leukemic activity mediated by the graft versus leukemia effect. However, a ...significant proportion of patients with AML will relapse after allo-SCT. The prognosis for these patients is dismal, with a probability of long-term survival of <20%. Data from previous studies have shown that disease-specific prognostic factors, are in general, the same as those in patients treated with conventional chemotherapy. Minimal residual disease (MRD) and chimerism status monitoring after allo-SCT may be used as predictors of impending relapse and should be part of routine follow-up for AML patients. A significant number of studies have shown that pre-emptive administration of donor lymphocyte infusion (DLI) based on MRD and chimerism monitoring, as well as prophylactic DLI in AML patients at high risk of relapse is effective in preventing relapse. In this review, we discuss strategies for the identification of high-risk patients, review current therapeutic options and provide our recommendations for the management of post-SCT AML.
Sinusoidal obstruction syndrome or veno-occlusive disease (SOS/VOD) is a potentially life-threatening complication of hematopoietic SCT (HSCT). This review aims to highlight, on behalf of the ...European Society for Blood and Marrow Transplantation, the current knowledge on SOS/VOD pathophysiology, risk factors, diagnosis and treatments. Our perspectives on SOS/VOD are (i) to accurately identify its risk factors; (ii) to define new criteria for its diagnosis; (iii) to search for SOS/VOD biomarkers and (iv) to propose prospective studies evaluating SOS/VOD prevention and treatment in adults and children.
Electroencephalography (EEG) is a useful tool to inspect the brain activity in resting state and allows to characterize spontaneous brain activity that is not detected when a subject is cognitively ...engaged. Moreover, taking advantage of the high time resolution in EEG, it is possible to perform fast topographical reference-free analysis, since different scalp potential fields correspond to changes in the underlying sources within the brain. In this study, the spontaneous EEG resting state (eyes closed) was compared between 10 young adults ages 18-30 years with autism spectrum disorder (ASD) and 13 neurotypical controls. A microstate analysis was applied, focusing on four temporal parameters: mean duration, the frequency of occurrence, the ratio of time coverage, and the global explained variance (GEV). Using data that were acquired from a 65-channel EEG system, six resting-state topographies that best describe the dataset across all subjects were identified by running a two-step cluster analysis labeled as microstate classes A-F. The results indicated that microstates B and E displayed statistically significant differences between both groups among the temporal parameters evaluated. Classes B, D, E, and F were consistently more present in ASD, and class C in controls. The combination of these findings with the putative functional significance of the different classes suggests that during resting state, the ASD group was more focused on visual scene reconstruction, while the control group was more engaged with self-memory retrieval. Furthermore, from a connectivity perspective, the resting-state networks that have been previously associated with each microstate class overlap the brain regions implicated in impaired social communication and repetitive behaviors that characterize ASD.
Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although ...SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (>80%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.
Summary
Background
Inflammatory bowel diseases (IBD) are chronic relapsing diseases in which pro‐inflammatory immune cells and cytokines induce intestinal tissue damage and disability. Mesenchymal ...stromal cells (MSCs) exert powerful immunomodulatory effects and stimulate tissue repair.
Aim
To review the current data on mesenchymal stromal cell therapy in IBD.
Method
We searched PubMed and ‘ClinicalTrials.gov’ databases using the terms ‘mesenchymal stromal cells’, ‘mesenchymal stem cell transplantation’, ‘inflammatory bowel diseases’, ‘Crohn disease’ and ‘colitis, ulcerative’. Additional publications were identified from individual article reference lists.
Results
MSCs include inhibition of Th1/Th17 lymphocytes and recruitment of regulatory T lymphocytes, induction of antigen‐presenting cells into a regulatory‐like profile, and stimulation of epithelial cell differentiation and proliferation. More than 200 patients with refractory fistulas have been treated with local injections of MSCs, resulting in complete response in more than half, and in overall response in approximately two thirds of patients. In refractory luminal Crohn's disease, 49 cases of systemic MSC infusions have been reported, while trials with autologous MSCs resulted in mitigated responses, studies using allogeneic MSCs were promising, with around 60% of patients experiencing a response and around 40% achieving clinical remission.
Conclusions
Mesenchymal stromal cells might represent a promising therapy for IBD, especially for Crohn's disease. There remain many unsolved questions concerning the optimal origin and source of mesenchymal stromal cells, dosage and modalities of administration. Moreover, mesenchymal stromal cells still need to prove their effectiveness compared with conventional treatments in randomised controlled trials.
Re-activations of task-dependent patterns of neural activity take place during post-encoding periods of wakeful rest and sleep. However, it is still unclear how the temporal dynamics of brain states ...change during these periods, which are shaped by prior conscious experiences. Here, we examined the very brief periods of wakeful rest immediately after encoding and recognition of auditory and visual stimuli, by applying the EEG microstate analysis, in which the global variance of the EEG is explained by only a few prototypical topographies. We identified the dominant brain states of sub-second duration during the tasks-dependent periods of rest, finding that the temporal dynamics—represented here by two temporal parameters: the frequency of occurrence and the fraction of time coverage—of three task-related microstate classes changed compared to wakeful rest. This study provides evidence of experience-dependent temporal changes in post-encoding periods of resting brain activity, which can be captured using the EEG microstates approach.
TLDR: time lag/delay reconstructor Anderson, M D; Baron, F; Bentz, M C
Monthly notices of the Royal Astronomical Society,
08/2021, Letnik:
505, Številka:
2
Journal Article
Recenzirano
Odprti dostop
ABSTRACT
We present the time lag/delay reconstructor (TLDR), an algorithm for reconstructing velocity delay maps in the maximum a posteriori framework for reverberation mapping. Reverberation mapping ...is a tomographical method for studying the kinematics and geometry of the broad-line region of active galactic nuclei at high spatial resolution. Leveraging modern image reconstruction techniques, including total variation and compressed sensing, TLDR applies multiple regularization schemes to reconstruct velocity delay maps using the alternating direction method of multipliers. Along with the detailed description of the TLDR algorithm we present test reconstructions from TLDR applied to synthetic reverberation mapping spectra as well as a preliminary reconstruction of the Hβ feature of Arp 151 from the 2008 Lick Active Galactic Nuclei Monitoring Project.
ABSTRACT We present near-infrared and optical emission-line and stellar kinematics of the Seyfert 2 galaxy Mrk 573 using the Near-Infrared Field Spectrograph (NIFS) at Gemini North and Dual Imaging ...Spectrograph at Apache Point Observatory, respectively. By obtaining full kinematic maps of the infrared ionized and molecular gas and stellar kinematics in a ∼700 × 2100 pc2 circumnuclear region of Mrk 573, we find that kinematics within the Narrow-Line Region are largely due to a combination of both rotation and in situ acceleration of material originating in the host disk. Combining these observations with large-scale, optical long-slit spectroscopy that traces ionized gas emission out to several kpcs, we find that rotation kinematics dominate the majority of the gas. We find that outflowing gas extends to distances less than 1 kpc, suggesting that outflows in Seyfert galaxies may not be powerful enough to evacuate their entire bulges.
The carbon (C) storage capacity of northern latitude ecosystems may diminish as warming air temperatures increase permafrost thaw and stimulate decomposition of previously frozen soil organic C. ...However, warming may also enhance plant growth so that photosynthetic carbon dioxide (CO2) uptake may, in part, offset respiratory losses. To determine the effects of air and soil warming on CO2 exchange in tundra, we established an ecosystem warming experiment – the Carbon in Permafrost Experimental Heating Research (CiPEHR) project – in the northern foothills of the Alaska Range in Interior Alaska. We used snow fences coupled with spring snow removal to increase deep soil temperatures and thaw depth (winter warming) and open‐top chambers to increase growing season air temperatures (summer warming). Winter warming increased soil temperature (integrated 5–40 cm depth) by 1.5 °C, which resulted in a 10% increase in growing season thaw depth. Surprisingly, the additional 2 kg of thawed soil C m−2 in the winter warming plots did not result in significant changes in cumulative growing season respiration, which may have been inhibited by soil saturation at the base of the active layer. In contrast to the limited effects on growing‐season C dynamics, winter warming caused drastic changes in winter respiration and altered the annual C balance of this ecosystem by doubling the net loss of CO2 to the atmosphere. While most changes to the abiotic environment at CiPEHR were driven by winter warming, summer warming effects on plant and soil processes resulted in 20% increases in both gross primary productivity and growing season ecosystem respiration and significantly altered the age and sources of CO2 respired from this ecosystem. These results demonstrate the vulnerability of organic C stored in near surface permafrost to increasing temperatures and the strong potential for warming tundra to serve as a positive feedback to global climate change.
Allogeneic hematopoietic cell transplantation (HCT) following nonmyeloablative conditioning has been extensively evaluated in patients with hematologic malignancies who are ineligible for ...conventional HCT because of age or medical comorbidities. Nonmyeloablative regimens have led to an initial state of mixed hematopoietic chimerism defined as coexistence of donor- and host-derived hematopoiesis. While nonmyeloablative regimens have been associated with reduced regimen-related toxicities in comparison with conventional myeloablative conditioning, graft rejection, graft-versus-host disease (GVHD), and disease progression have remained significant challenges. In this article, after briefly introducing current techniques for chimerism assessment, we describe factors affecting donor chimerism levels after nonmyeloablative conditioning, and then review data suggesting that chimerism assessment early after HCT might help identify patients at risk for graft rejection, GVHD and relapse/progression. Finally, we discuss how these observations have opened the way to further research protocols evaluating manipulation of postgrafting immunosuppression, and/or infusion of donor immune cells.
PDF
