Background Spinal muscular atrophy (SMA) is a genetic progressive neuromuscular disease. Nusinersen is the first disease modifying drug approved to treat patients with SMA. Our study aimed to ...evaluate the efficacy of nusinersen treatment on motor function in children with SMA. Methods A retrospective analysis was conducted on the data of 52 genetically confirmed SMA patients from November 2020 to September 2023. Motor function was assessed based on standardized scales from baseline to 14 months of follow-up. Results Of patients in this study, the majority had SMA type 2 (40/52, 76.9%), 5 (9.6%) and 7 (13.5%) patients had SMA types 1 and 3, respectively. The median disease duration was 11 months (range 0–52), and the median age at initiation of treatment was 44.5 months (range 5–192). Motor function of all the patients with SMA improved from baseline to 14 months of follow-up. Mean increases of 4.6-point ( p = 0.173), 4.7-point ( p = 0.021) and 2.7-point ( p = 0.013) were observed from baseline to 14 months of follow-up for the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores, the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM), respectively. Increased disease duration and age of treatment initiation were negatively correlated with the changes in HFMSE scores ( r = −0.567, p = 0.043; r = −0.771 and p = 0.002, respectively). Similar results were observed for the RULM scores ( r = −0.714, p = 0.014; r = −0.638 and p = 0.035, respectively). Conclusion Our study suggested that 14 months of treatment with nusinersen was effective and improved the motor function of children with SMA types 1, 2, or 3. In addition, disease duration and age at treatment initiation were negatively correlated with treatment outcome in the patients.
Epigenetic therapy with hypomethylating drugs is now the standard of care in myelodysplastic syndrome (MDS). Response rates remain low, and mechanism-based dose optimization has not been reported. We ...investigated the clinical and pharmacodynamic results of different dose schedules of decitabine. Adults with advanced MDS or chronic myelomonocytic leukemia (CMML) were randomized to 1 of 3 decitabine schedules: (1) 20 mg/m2 intravenously daily for 5 days; (2) 20 mg/m2 subcutaneously daily for 5 days; and (3) 10 mg/m2 intravenously daily for 10 days. Randomization followed a Bayesian adaptive design. Ninety-five patients were treated (77 with MDS, and 18 with CMML). Overall, 32 patients (34%) achieved a complete response (CR), and 69 (73%) had an objective response by the new modified International Working Group criteria. The 5-day intravenous schedule, which had the highest dose-intensity, was selected as optimal; the CR rate in that arm was 39%, compared with 21% in the 5-day subcutaneous arm and 24% in the 10-day intravenous arm (P < .05). The high dose-intensity arm was also superior at inducing hypomethylation at day 5 and at activating P15 expression at days 12 or 28 after therapy. We conclude that a low-dose, dose-intensity schedule of decitabine optimizes epigenetic modulation and clinical responses in MDS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Supercapacitors with advantages of high-power density, fast charging speed and long cycle life, have very promising application prospects in many fields such as transportation and energy storage. ...Usually, the onboard operation profiles will be recorded and sent to remote monitoring terminal for further study. As the working condition of onboard supercapacitor is complex and fluctuating, it requires high sampling frequency, accuracy, and continuous recording. However, the remote monitoring data usually has the problems of low sampling frequency and fragmented recording, making it difficult to extract the characteristic parameters by traditional parameter identification methods. To solve the problem, this paper makes an extensive investigation on the long-term remote monitoring data of a supercapacitor tram and proposes a set of data processing method that can extract the characteristic parameters of supercapacitors from the sparse and fragmented data. Firstly, a group of proper data segments considering thermal stability of supercapacitor system was selected as effective data from the fragmented daily monitoring data. Secondly, the parameters which can be used to study the aging indicators are extracted by interior point method. With this method, the simulated voltage error is within 0.3% with a sampling frequency of 0.1 Hz. Through analyzing 3.5 years of remote monitoring data, it is found that the characteristic parameters exhibit the feature of seasonal fluctuations, which is highly related to temperature. To further extract the aging trend, a linear fitting model which eliminates the effect of seasonal fluctuations is proposed which can be used for analyzing the evolution characteristic of the studied supercapacitor system.
There has been an increasing interest in the analysis of recurrent event data (Cook and Lawless, 2002, Statistical Methods in Medical Research11, 141–166). In many situations, a terminating event ...such as death can happen during the follow‐up period to preclude further occurrence of the recurrent events. Furthermore, the death time may be dependent on the recurrent event history. In this article we consider frailty proportional hazards models for the recurrent and terminal event processes. The dependence is modeled by conditioning on a shared frailty that is included in both hazard functions. Covariate effects can be taken into account in the model as well. Maximum likelihood estimation and inference are carried out through a Monte Carlo EM algorithm with Metropolis–Hastings sampler in the E‐step. An analysis of hospitalization and death data for waitlisted dialysis patients is presented to illustrate the proposed methods. Methods to check the validity of the proposed model are also demonstrated. This model avoids the difficulties encountered in alternative approaches which attempt to specify a dependent joint distribution with marginal proportional hazards and yields an estimate of the degree of dependence.
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BFBNIB, DOBA, FSPLJ, FZAB, GIS, IJS, INZLJ, IZUM, KILJ, NLZOH, NMLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK, ZRSKP
The journal and authors wish to retract the article entitled 'Prediction of Ovarian Cancer Response to Therapy Based on Deep Learning Analysis of Histopathology Images' cited above ....
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ovarian cancer remains the leading gynecological cause of cancer mortality. Predicting the sensitivity of ovarian cancer to chemotherapy at the time of pathological diagnosis is a goal of precision ...medicine research that we have addressed in this study using a novel deep-learning neural network framework to analyze the histopathological images.
We have developed a method based on the Inception V3 deep learning algorithm that complements other methods for predicting response to standard platinum-based therapy of the disease. For the study, we used histopathological H&E images (pre-treatment) of high-grade serous carcinoma from The Cancer Genome Atlas (TCGA) Genomic Data Commons portal to train the Inception V3 convolutional neural network system to predict whether cancers had independently been labeled as sensitive or resistant to subsequent platinum-based chemotherapy. The trained model was then tested using data from patients left out of the training process. We used receiver operating characteristic (ROC) and confusion matrix analyses to evaluate model performance and Kaplan-Meier survival analysis to correlate the predicted probability of resistance with patient outcome. Finally, occlusion sensitivity analysis was piloted as a start toward correlating histopathological features with a response.
The study dataset consisted of 248 patients with stage 2 to 4 serous ovarian cancer. For a held-out test set of forty patients, the trained deep learning network model distinguished sensitive from resistant cancers with an area under the curve (AUC) of 0.846 ± 0.009 (SE). The probability of resistance calculated from the deep-learning network was also significantly correlated with patient survival and progression-free survival. In confusion matrix analysis, the network classifier achieved an overall predictive accuracy of 85% with a sensitivity of 73% and specificity of 90% for this cohort based on the Youden-J cut-off. Stage, grade, and patient age were not statistically significant for this cohort size. Occlusion sensitivity analysis suggested histopathological features learned by the network that may be associated with sensitivity or resistance to the chemotherapy, but multiple marker studies will be necessary to follow up on those preliminary results.
This type of analysis has the potential, if further developed, to improve the prediction of response to therapy of high-grade serous ovarian cancer and perhaps be useful as a factor in deciding between platinum-based and other therapies. More broadly, it may increase our understanding of the histopathological variables that predict response and may be adaptable to other cancer types and imaging modalities.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract
In order to effectively evaluate the facilities in each airport airfield, this paper proposes four methods: analytic hierarchy process (AHP), subjective weighting method based on Improved ...Analytic Hierarchy Process (AHP), objective weighting method based on entropy weight method and combination weighting method based on game theory. Combined with the actual situation of the airport, the corresponding calculation method is adopted to introduce the mathematical model into the construction of the airport. After verification, the proposed method can be applied to 90% of airports, and the applicability of the index is improved by 50%. The weight of obstacle capability evaluation index provides an important basis.
It is known that complete remission (CR) prolongs survival in acute myeloid leukemia (AML). In 2003, less stringent response categories were introduced, most notably CR with incomplete platelet ...recovery (CRp). Although the significance of CRp for survival remains unclear, reports of AML trials frequently combine CR with CRp rather than considering CR as a separate entity.
This practice led us to retrospectively examine the effect of CR on outcome in newly diagnosed AML, by using data from 6,283 patients treated on Eastern Cooperative Oncology Group (ECOG) and Southwest Oncology Group (SWOG) protocols or at M. D. Anderson Cancer Center. This effect was then contrasted with the effect of CRp in the M. D. Anderson Cancer Center cohort.
At least 94% of patients receiving cytarabine-based therapy and surviving for more than 3 or 5 years achieved a CR with either initial or salvage therapy; limited data suggest the same for patients receiving initial therapies that did not contain cytarabine. Patients with CR were more likely to live beyond 3 or 5 years than patients with CRp. The likelihood of achieving a CR rather than CRp was greater for patients with AML who had better prognosis. After adjustment for covariates, the relapse-free survival of patients achieving CR was longer than that of patients achieving CRp, whereas patients with CRp survived longer than those with resistant disease.
Our data indicate that CR is of unique clinical significance and should be reported as separate response in trials of newly diagnosed AML. Nonetheless, our findings validate CRp as a clinically meaningful response.
Intravitreal injection of conbercept (IVC) is a novel anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP). This study aimed to assess the intraocular ...pressure (IOP) effect of IVC.
All IVC surgeries were performed in the Department of Ophthalmology, Guangdong Women and Children Hospital, from January 2021 to May 2021. In this study, 30 eyes of 15 infants who received intravitreal injections of conbercept at a dose of 0.25 mg/0.025 mL were included. The IOP of all participants was measured prior to administering the injection and subsequently at 2 min, 1 h, 1 day, and 1 week thereafter.
We included 30 eyes (10 boys and 5 girls) with ROP. For the male group, the mean birth weight, mean gestational age at birth, and the mean time of postmenstrual age (PMA) at IVC treatment were 1,174.0 ± 446.0 g, 28.4 ± 3.0 weeks, and 37.1 ± 1.6 weeks, respectively; for the female group, they were 1,108 ± 285.5 g, 28.2 ± 2.5 weeks, and 36.8 ± 2.1 weeks, respectively. For the male group, the IOP at baseline, 2 min, 1 h, 1 day, and 1 week after IVC were 12.4 ± 1.5 mmHg, 49.0 ± 3.1 mmHg, 26.3 ± 2.5 mmHg, 13.4 ± 2.2 mmHg, and 11.6 ± 1.7 mmHg, respectively; for the female group, they were 10.7 ± 2.0 mmHg, 47.3 ± 3.2 mmHg, 26.4 ± 3.2 mmHg, 10.7 ± 1.8 mmHg, and 10.2 ± 1.8 mmHg, respectively. In both groups, the IOP immediately (2 min) after the operation was significantly higher than that at any other time point (
< 0.01). IOP values returned to the preoperative baseline level on the first day after surgery, with no significant difference compared with that before injection (
> 0.05). IOP continued to be maintained at the preoperative baseline level on the first week after surgery, with no significant difference compared with that before surgery (
> 0.05).
Infants with ROP who received IVC experienced a sharp increase in the IOP immediately after injection, which decreased to below 30 mmHg after 1 h and maintain that level for 1 week or longer.
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