Search Results (18)

Adult patients affected by acute myeloid leukemia who fail to achieve remission after two cycles of intensive chemotherapy based on a combination of anthracyclines and cytarabine are considered chemorefractory and are unlikely to benefit from further induction attempts. Characterized by a poor prognosis, they may still benefit from allogeneic hematopoietic stem cell transplantation, even if long-term survival rarely exceeds 20–30%. Still, the use of sequential high-dose chemotherapy followed by reduced-intensity conditioning, with transplantation performed during aplasia, and the optimization of the alloreactivity of donor leukocytes against leukemia (i.e., the graft-versus-leukemia effect) may ameliorate these results. Optimization of alloreactivity against leukemic cells can be achieved by proper donor selection, by the early withdrawal of immunosuppressive therapy, by post-transplant administration of donor lymphocyte infusions as prophylaxis of leukemia relapse, and by several other maintenance and preemptive therapies. Far from being the final stage of consolidation therapy, allogeneic hematopoietic stem cell transplantation is now considered as the moment when a unique immunological platform can be established in these patients, to be used for additional post-transplant measures. In this study we will critically review the different pre- and post-transplant strategies used in clinical trials to improve long-term survival in adult patients transplanted with chemorefractory leukemia. Full article

This study analyzed the probability of damage in heat transport pipelines buried in urban areas using pipeline attribute information and damage history data and developed an AI-based predictive model. A dataset was constructed by collecting spatial and attribute data of pipelines and defining basic units according to specific standards. Damage trends were analyzed based on pipeline attributes, and correlation analysis was performed to identify influential factors. These factors were applied to three machine learning algorithms: Random Forest, eXtreme gradient boosting (XGBoost), and light gradient boosting machine (LightGBM). The model with optimal performance was selected by comparing evaluation indicators including the F2-score, accuracy, and area under the curve (AUC). The LightGBM model trained on data from pipelines in use for over 20 years showed the best performance (F2-score = 0.804, AUC = 0.837). This model was used to generate a risk map visualizing the probability of pipeline damage. The map can aid in the efficient management of urban heat transport systems by enabling preemptive maintenance in high-risk areas. Incorporating external environmental data and auxiliary facility information in future models could further enhance reliability and support the development of a more effective maintenance decision-making system. Full article

Allogeneic hematopoietic cell transplantation (HCT) remains an important curative-intent treatment for many patients with acute myeloid leukemia (AML), but AML recurrence after allografting is common. Many factors associated with relapse after allogeneic HCT have been identified over the years. Central among these is measurable (“minimal”) residual disease (MRD) as detected by multiparameter flow cytometry, quantitative polymerase chain reaction, and/or next-generation sequencing. Demonstration of a strong, independent prognostic role of pre- and early post-HCT MRD has raised hopes MRD could also serve as a predictive biomarker to inform treatment decision-making, with emerging data indicating the potential value to guide candidacy assessment for allografting as a post-remission treatment strategy, the selection of conditioning intensity, use of small molecule inhibitors as post-HCT maintenance therapy, and preemptive infusion of donor lymphocytes. Monitoring for leukemia recurrence after HCT and surrogacy for treatment response are other considerations for the clinical use of MRD data. In this review, we will outline the current landscape of MRD as a biomarker for patients with AML undergoing HCT and discuss areas of uncertainty and ongoing research. Full article

The ability to preemptively identify potential failures in industrial parts is crucial for minimizing downtime, reducing maintenance costs and ensuring system reliability and safety. However, challenges such as data nonlinearity, temporal dependencies, and imbalanced datasets complicate accurate fault prediction. In this study, we propose a novel combined approach that integrates the Logistic Model Tree Forest (LMT) with Stacked Long Short-Term Memory (LSTM) networks, addressing these challenges effectively. This hybrid method leverages the decision-making capability of the LMT and the temporal sequence learning ability of Stacked LSTM to improve fault prediction accuracy. Additionally, to tackle the issues posed by imbalanced datasets and noise, we employ the ENN-SMOTE (Edited Nearest Neighbors-Synthetic Minority Over-sampling Technique), a technique for data preprocessing, which enhances data balance and quality. Experimental results show that our approach significantly outperforms traditional methods, achieving a fault prediction accuracy of up to 98.2%. This improvement not only demonstrates the effectiveness of the combined model but also highlights its potential for real-world industrial applications, where high accuracy and reliability are paramount. Full article

This paper focuses on predictive maintenance for simple machinery systems monitored by the Internet of Things (IoT). As these systems can be challenging to model due to their complexity, diverse typologies, and limited operational lifespans, traditional predictive maintenance approaches face obstacles due to the lack of extensive historical data. To address this issue, we propose a novel clustering-based process that identifies potential machinery faults. The proposed approach lies in empowering decision-makers to define predictive maintenance policies based on the reliability of the proposed fault classification. Through a case study involving real sensor data from the doors of a transportation vehicle, specifically a bus, we demonstrate the practical applicability and effectiveness of our method in preemptively preventing faults and enhancing maintenance practices. By leveraging IoT sensor data and employing clustering techniques, our approach offers a promising avenue for cost-effective predictive maintenance strategies in simple machinery systems. As part of the quality assurance, a comparison between the predictive maintenance model for a simple machinery system, pattern recognition neural network, and support vector machine approaches has been conducted. For the last two methods, the performance is lower than the first one proposed. Full article

The administration of TKIs after Allo-SCT in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) remains controversial, and the TKI approach (prophylactic, pre-emptive or salvage) is still heterogeneous in transplant centers. In this context, very little is known about the feasibility and safety of third-generation TKIs. In this paper, we analyze the efficacy and safety of ponatinib (PONA) administered after Allo-SCT to prevent cytologic relapse of Ph + ALL. This is a multicenter observational study including 48 patients (pts) with Ph + ALL (median age 49 years) who received PONA after Allo-SCT while in complete cytological remission (cCR); 26 (54%) had positive minimal residual disease (MRD pos) before Allo-SCT. PONA was administered after Allo-SCT prophylactically (starting with MRD neg) in 26 pts or pre-emptively (starting with MRD pos post-SCT and without hematological relapse) in 22 pts. Patients treated prophylactically with PONA started treatment earlier, at a median of 4.3 months (range 1.5–6) after Allo-SCT, than those treated pre-emptively, who started PONA at a median of 7.4 months (range 2–63) after Allo-SCT (p = 0.01). The median starting dose of PONA was 30 mg/day (range 15–45). A dose reduction was required in 10/48 (21%) of cases, but a permanent discontinuation of PONA, due to toxicity, was required in only 5/48 pts (10.5%). No deaths due to PONA-related adverse events (AEs) were reported. The median follow-up time after Allo-SCT was 34 months (range 7.7–118). At the last follow-up, the median duration of PONA therapy was 22 months (range 2–100). The 5-year OS and RFS after Allo-SCT were 92% and 71%, respectively. The 5-year RFS after Allo-SCT of pts who received PONA prophylaxis was 95%, and it was 57% for those who received PONA pre-emptively (log-rank p = 0.02). In conclusion, this multicenter analysis of 48 patients with Ph + ALL undergoing Allo-SCT while in CcR, although with the caution of the retrospective data, supports the feasibility of PONA maintenance strategy after Allo-SCT with a low rate of discontinuations (10.5%) due to PONA-related AE. Full article

There is uncertainty about the best approach to replacement treatment for kidney transplant recipients with chronic terminal graft dysfunction, since a retransplant could be performed before the resumption of dialysis, thus avoiding this treatment and the dilemma of whether or not to suspend immunosuppressive therapy. However, there is limited experience in pre-emptive repeat transplantations, and none from deceased donors. This study aims to assess the results of a pre-emptive retransplantation program with brain-dead deceased donors. We designed a retrospective matched cohort study, including 36 recipients in the pre-dialysis group and 36 controls who were already on dialysis, matched for donor age and transplant date, which could not differ by more than 7 days between pairs. The variables used to standardize the cohorts were donor and recipient age and sex, blood group, duration of the first graft, time on the waitlist to receive the second graft, cold ischemia time, induction and maintenance of immunosuppression, and HLA antibodies (-) prior to retransplantation. The efficacy variables were early graft loss, acute rejection, delay in graft function, renal function at the end of follow-up, survival time, and recipient and graft survival at 24 and 48 months’ follow-up. The pre-dialysis group presented a significantly shorter waitlist time, lower immunization status, and a significantly longer duration of the first graft than the control group. The percentage of recipients who presented early graft loss, delayed renal function, or acute rejection was similar between groups. No significant differences were observed in kidney function or in the survival of the recipient or graft. Retransplantation yields good outcomes in patients with terminal chronic dysfunction, helping to avoid recurrence to dialysis, shortening the time spent on the waitlist, reducing the risk of producing antibodies, and resolving the dilemma of whether or not to stop immunosuppression. Full article

Existing maintenance management systems implement periodic inspections and diagnoses and perform maintenance to restore damaged facilities, making it difficult to establish a long-term and analytical budget plan. The Framework Act on Sustainable Infrastructure Management necessitates specific implementation plans for new implementation items. This study proposes a detailed method for estimating infrastructure management cost to overcome the limitations of the post-response maintenance system and establish a management plan for the Framework Act on Sustainable Infrastructure Management, considering the performance and cost effects in terms of the life cycle. The method was classified into the following stages: analysis of the performance degradation timing by deriving the performance degradation curve, analysis of proper construction methods by performance grade to establish a cost model for each member grade, representative life assessment of the establishment to determine the end-of-life of members, and analysis of optimal action timing for establishing short/mid- to long-term repair and reinforcement plans. The proposed method was applied to a water reservoir (99 reservoirs in Seoul, Korea). The performance degradation and cost prediction models for the target establishment were analyzed. The proposed method can be applied to the maintenance decision making of the management agency and is significant for efficient infrastructure maintenance. Full article

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN. Full article

In South Korea, a water supply enhancement project is being carried out to preemptively respond to drought and water loss by reducing pipeline leakages and supplying stable tap water through the maintenance of an aging water supply network. In order to reduce water leakage, a District Metered Area (DMA) was established to monitor and predict the minimum night flow based on flow data collected from IoT sensors. In this study, a model based on Multi-Layer Perceptron (MLP) and Long Short-Term Memory (LSTM) was constructed to predict the MNF (minimum night flow) of County Y. The prediction of MNF results was compared with the MLP networks and the LSTM model. The outcome showed that the LSTM-MNF model proposed in this study performed better than the MLP-MNF model. Therefore, the research methods of this study can contribute to technical support for leakage reductions by preemptively responding to the expected increase in leakage through the prediction of the minimum flow at night. Full article

Patients with high-risk acute myeloid leukemia are offered allogeneic hematopoietic cell transplantation (allo-HCT) in first remission to reduce risk of relapse. However, disease recurrence remains the major reason of allo-HCT failure, occurring in around 35–45% of patients, and leading to dismal outcomes. Strategies to reduce the risk of relapse are greatly needed, especially in the early post-transplant phase where the graft-versus-leukemia (GVL) effect is not yet activated. Some practices include the use of myeloablative conditioning regimens, close monitoring of measurable residual disease and donor chimerism, rapid tapering of immunosuppression, and implementation of pre-emptive strategies as the use of donor lymphocyte infusion. However, it’s time to consider prophylactic pharmacologic interventions post allo-HCT that aim at maintaining leukemic clones under control by both direct cytotoxic activity and by enhancing the GVL effect. In this current review, available data on drugs targeting epigenetic pathways like azacitidine, or actionable mutations like FLT3 and IDH1/2 inhibitors used as maintenance post allo-HCT, will be discussed. Full article

Regular inspection of railway track health is crucial for maintaining safe and reliable train operations. Factors, such as cracks, ballast issues, rail discontinuity, loose nuts and bolts, burnt wheels, superelevation, and misalignment developed on the rails due to non-maintenance, pre-emptive investigations and delayed detection, pose a grave danger and threats to the safe operation of rail transport. The traditional procedure of manually inspecting the rail track using a railway cart is both inefficient and prone to human error and biases. In a country like Pakistan where train accidents have taken many lives, it is not unusual to automate such approaches to avoid such accidents and save countless lives. This study aims at enhancing the traditional railway cart system to address these issues by introducing an automatic railway track fault detection system using acoustic analysis. In this regard, this study makes two important contributions: data collection on Pakistan railway tracks using acoustic signals and the application of various classification techniques to the collected data. Initially, three types of tracks are considered, including normal track, wheel burnt and superelevation, due to their common occurrence. Several well-known machine learning algorithms are applied such as support vector machines, logistic regression, random forest and decision tree classifier, in addition to deep learning models like multilayer perceptron and convolutional neural networks. Results suggest that acoustic data can help determine the track faults successfully. Results indicate that the best results are obtained by RF and DT with an accuracy of 97%. Full article

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients. Full article

The government of the Republic of Korea has set the minimum service level of bridges as Grade B and has defined the risk management level as higher than 95 percent. To achieve this goal, it is necessary to understand the deterioration process and risk of deficiencies for bridges, and these characteristics should be reflected in the management strategy and budget investment plan. To this end, this study developed deterioration models according to the bridge ages to define heterogeneous deterioration characteristics of aging bridges. To build the deterioration models, this study collected and processed bridge diagnosis data for 10 years, and a Bayesian Markov mixed hazard model was introduced. Analysis results showed that the life expectancy of the aging bridges over 30 years was remarkably short, 1/3 of the average life expectancy of the network, and the probability of failure was seven times higher than that of new bridges within 10 years after completion. In addition, the optimal maintenance demand that satisfies a risk management level of 95 percent illustrated that 44.7 percent of the bridges at Grade C should be continuously maintained annually. The results showed that it is urgent to prepare a preemptive response strategy and budget-securing plan for aging bridges, which will rapidly increase to 39% in the next 10 years and 76% in 20 years. Full article

Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type Ca²⁺ channels (T-channels) and γ-aminobutyric acid A (GABA_A) receptors in the development and maintenance of post-incisional pain. We use neuroactive steroids with distinct effects on GABA_A receptors and/or T-channels: Alphaxalone (combined GABAergic agent and T-channel inhibitor), ECN (T-channel inhibitor), CDNC24 (GABAergic agent), and compared them with an established analgesic, morphine (an opioid agonist without known effect on either T-channels or GABA_A receptors). Adult female rats sustained the skin and muscle incision on the plantar surface of the right paw. We injected the agents of choice intrathecally either before or after the development of post-incisional pain. The pain development was monitored by studying mechanical hypersensitivity. Alphaxalone and ECN, but not morphine, are effective in alleviating mechanical hyperalgesia when administered preemptively whereas morphine provides dose-dependent pain relief only when administered once the pain had developed. CDNC24 on the other hand did not offer any analgesic benefit. Neuroactive steroids that inhibit T-currents—Alphaxalone and ECN—unlike morphine, are effective preemptive analgesics that may offer a promising therapeutic approach to the treatment of post-incisional pain, especially mechanical hypersensitivity. Full article