Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of ...mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.
Aim
To compare apical transportation and canal straightening when using three continuous tapered rotary NiTi systems F6 SkyTaper (Komet/Brasseler, Lemgo, Germany), Mtwo (VDW, Munich, Germany) and ...OneShape (Micro Méga, Besançon, France) in severely curved root canals.
Methodology
A total of 60 root canals in extracted human teeth with angles of curvatures ranging between 25° and 35° and radii ranging between 4 and 9 mm were divided into three groups (n = 20). Based on radiographs taken prior to instrumentation, the groups were balanced with respect to the angle and the radius of canal curvature (P = 1.0 and P = 0.994, respectively). All canals were prepared to an apical size 30 according to the manufacturer's instructions. Pre‐ and post‐instrumentation radiographs were superimposed and apical transportation and canal straightening were analysed using a computer imaging program. Preparation time and instrument failure were also recorded. Data were analysed statistically using anova and Student–Newman–Keuls test.
Results
During preparation, no file fractured. All instruments maintained the original canal curvature well with no significant differences between the instruments (P = 0.542). Concerning apical transportation, no significant differences were obtained (P = 0.414). Regarding preparation time, no significant differences were obtained between F6 SkyTaper and OneShape (P > 0.05), but both were significantly faster than Mtwo (P < 0.05).
Conclusion
Under the conditions of this study, all instruments respected the original canal curvature well and apical transportation was negligible. Instruments were safe to use. Preparation with F6 SkyTaper and OneShape was faster than with Mtwo.
Background
The treatment of anal fistula remains a challenge between maintaining continence and radical surgery to prevent recurrence. Fistula-tract Laser Closure (FiLaC
®
) is a sphincter-saving ...technique using a radial emitting laser fibre to close the fistula tract. The aim of this study was to report long-term outcomes in patients who received FiLaC
®
therapy for transsphincteric and intersphincteric anal fistula between January 2011 and December 2017.
Methods
A retrospective study was performed on patients who were treated with FiLaC
®
- for a transsphincteric and intersphincteric anal fistula at our institution between January 2011 and December 2017. In all patients, the FiLaC
®
procedure was combined with a closure of the internal orifice using a simple 3-0 Z stitch. Patient characteristics, previous proctological history, healing rates, failures and postoperative continence were investigated.
Results
The study included 83 patients mean age 50.01 ± 14.59 years. 64 (77.1%) males with a mean follow-up period of 41.99 (± 21.59) months (range 4–87 months). Thirteen patients (15.7%) had a recurrent fistula. 65 patients (78.3%) had undergone prior abscess drainage with insertion of a seton. The primary healing rate was 74.7% (62 of 83 patients) overall. Eleven (13.3%) of the 21 patients (25.3%) who failed FiLaC
®
-therapy underwent a second operation. In eight cases, Re-FiLaC
®
and in three cases, fistulectomy with closure of the internal orifice was performed. Afterwards 6 (54.5%) of these 11 patients could be considered cured: 3 who had fistulectomy and three who had Re-FiLaC
®
treatment. The overall healing rate after second FiLaC
®
was 78.3% (65 of 83 patients) while the overall healing rate for FiLaC
®
therapy combined with any second procedure was 81.9% (68 of 83 patients). The follow-up period in this group of 11 patients who received re-operation was 38 months (range 13–84 months). Changes in continence occurred in eight patients (9.6%). No patient reported major incontinence postoperatively.
Conclusions
The FiLaC
®
procedure is associated with good healing rates in long-term follow-up and should be considered as a treatment option for transsphincteric and intersphincteric anal fistulae, especially due to the low complication rate and low risk of sphincter injury.
Decreased long‐range temporal correlations (LRTC) in brain signals can be used to measure cognitive effort during task execution. Here, we examined how learning a motor sequence affects long‐range ...temporal memory within resting‐state functional magnetic resonance imaging signal. Using the Hurst exponent (HE), we estimated voxel‐wise LRTC and assessed changes over 5 consecutive days of training, followed by a retention scan 12 days later. The experimental group learned a complex visuomotor sequence while a complementary control group performed tightly matched movements. An interaction analysis revealed that HE decreases were specific to the complex sequence and occurred in well‐known motor sequence learning associated regions including left supplementary motor area, left premotor cortex, left M1, left pars opercularis, bilateral thalamus, and right striatum. Five regions exhibited moderate to strong negative correlations with overall behavioral performance improvements. Following learning, HE values returned to pretraining levels in some regions, whereas in others, they remained decreased even 2 weeks after training. Our study presents new evidence of HE's possible relevance for functional plasticity during the resting‐state and suggests that a cortical subset of sequence‐specific regions may continue to represent a functional signature of learning reflected in decreased long‐range temporal dependence after a period of inactivity.
The present study highlights the significance of using long‐range temporal correlations (LRTC) within the rsfMRI BOLD signal as a potential sensitive biomarker for functional neuroplasticity. Our findings demonstrate that decreases in LRTC reflect sequence‐specific motor learning and performance improvements, and that these changes persist even after a two‐week break from training. These results suggest that alterations in functional dynamics represent the newly learned skill and support the use of LRTC as a sensitive measure of functional neuroplasticity resulting from complex motor learning.
In motor learning, sequence specificity, i.e. the learning of specific sequential associations, has predominantly been studied using task-based fMRI paradigms. However, offline changes in resting ...state functional connectivity after sequence-specific motor learning are less well understood. Previous research has established that plastic changes following motor learning can be divided into stages including fast learning, slow learning and retention. A description of how resting state functional connectivity after sequence-specific motor sequence learning (MSL) develops across these stages is missing. This study aimed to identify plastic alterations in whole-brain functional connectivity after learning a complex motor sequence by contrasting an active group who learned a complex sequence with a control group who performed a control task matched for motor execution. Resting state fMRI and behavioural performance were collected in both groups over the course of 5 consecutive training days and at follow-up after 12 days to encompass fast learning, slow learning, overall learning and retention. Between-group interaction analyses showed sequence-specific decreases in functional connectivity during overall learning in the right supplementary motor area (SMA). We found that connectivity changes in a key region of the motor network, the superior parietal cortex (SPC) were not a result of sequence-specific learning but were instead linked to motor execution. Our study confirms the sequence-specific role of SMA that has previously been identified in online task-based learning studies, and extends it to resting state network changes after sequence-specific MSL.
Why is the Winner the Best? Reinke, A.; Tizabi, M. D.; Isensee, F. ...
2023 IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR),
2023-June
Conference Proceeding
Odprti dostop
International benchmarking competitions have become fundamental for the comparative performance assessment of image analysis methods. However, little attention has been given to investigating what ...can be learnt from these competitions. Do they really generate scientific progress? What are common and successful participation strategies? What makes a solution superior to a competing method? To address this gap in the literature, we performed a multicenter study with all 80 competitions that were conducted in the scope of IEEE ISBI 2021 and MICCAI 2021. Statistical analyses performed based on comprehensive descriptions of the submitted algorithms linked to their rank as well as the underlying participation strategies revealed common characteristics of winning solutions. These typically include the use of multi-task learning (63%) and/or multi-stage pipelines (61%), and a focus on augmentation (100%), image preprocessing (97%), data curation (79%), and post-processing (66%). The "typical" lead of a winning team is a computer scientist with a doctoral degree, five years of experience in biomedical image analysis, and four years of experience in deep learning. Two core general development strategies stood out for highly-ranked teams: the reflection of the metrics in the method design and the focus on analyzing and handling failure cases. According to the organizers, 43% of the winning algorithms exceeded the state of the art but only 11% completely solved the respective domain problem. The insights of our study could help researchers (1) improve algorithm development strategies when approaching new problems, and (2) focus on open research questions revealed by this work.
Experience of Solidarity Jäger, Urs P.; Höver, Hendrik; Schröer, Andreas ...
Nonprofit and voluntary sector quarterly,
10/2013, Letnik:
42, Številka:
5
Journal Article
Recenzirano
The more nonprofits become challenged by resource shortages, the higher the demand for highly skilled executive directors. Nevertheless, we do not yet fully understand what motivates executive ...directors to work in nonprofits challenged by market forces. This article explores the career context and individual biographies of executive directors. Introducing a career field and career capital approach to the study of careers in nonprofits, we analyze what influences the career of executive directors of German faith-based social service organizations. The results of 23 interviews and four focus groups with 60 participants are twofold. First, four types of career capital influenced the executive directors’ career: Experience of solidarity, orientation to social service, skills for executive function, and leadership by appointment. Second, all careers were highly influenced by the experience of solidarity. The article ends by explaining why experience of solidarity is important for training and selecting nonprofit executive directors.
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