Segmenting cell nuclei within microscopy images is a ubiquitous task in biological research and clinical applications. Unfortunately, segmenting low-contrast overlapping objects that may be tightly ...packed is a major bottleneck in standard deep learning-based models. We report a Nuclear Segmentation Tool (NuSeT) based on deep learning that accurately segments nuclei across multiple types of fluorescence imaging data. Using a hybrid network consisting of U-Net and Region Proposal Networks (RPN), followed by a watershed step, we have achieved superior performance in detecting and delineating nuclear boundaries in 2D and 3D images of varying complexities. By using foreground normalization and additional training on synthetic images containing non-cellular artifacts, NuSeT improves nuclear detection and reduces false positives. NuSeT addresses common challenges in nuclear segmentation such as variability in nuclear signal and shape, limited training sample size, and sample preparation artifacts. Compared to other segmentation models, NuSeT consistently fares better in generating accurate segmentation masks and assigning boundaries for touching nuclei.
Matching for Fellowship Interviews Melcher, Marc L; Ashlagi, Itai; Wapnir, Irene
JAMA : the journal of the American Medical Association,
2018-Oct-23, Volume:
320, Issue:
16
Journal Article
With increasing metabolic dysfunction-associated steatotic liver disease, the use of steatotic grafts in liver transplantation (LT) and their impact on postoperative graft survival (GS) needs further ...exploration. Analyzing adult LT recipient data (2002-2022) from the United Network for Organ Sharing database, outcomes of LT using steatotic (≥30% macrosteatosis) and nonsteatotic donor livers, donors after circulatory death, and standard-risk older donors (age 45-50) were compared. GS predictors were evaluated using Kaplan-Meier and Cox regression analyses. Of the 35,345 LT donors, 8.9% (3,155) were fatty livers. The initial 30-day postoperative period revealed significant challenges with fatty livers, demonstrating inferior GS. However, the GS discrepancy between fatty and nonfatty livers subsided over time ( p = 0.10 at 5 y). Long-term GS outcomes showed comparable or even superior results in fatty livers relative to nonsteatotic livers, conditional on surviving the initial 90 postoperative days ( p = 0.90 at 1 y) or 1 year ( p = 0.03 at 5 y). In the multivariable Cox regression analysis, the high body surface area (BSA) ratio (≥1.1) (HR 1.42, p = 0.02), calculated as donor BSA divided by recipient BSA, long cold ischemic time (≥6.5 h) (HR 1.72, p < 0.01), and recipient medical condition (intensive care unit hospitalization) (HR 2.53, p < 0.01) emerged as significant adverse prognostic factors. Young (<40 y) fatty donors showed a high BSA ratio, diabetes, and intensive care unit hospitalization as significant indicators of a worse prognosis ( p < 0.01). Our study emphasizes the initial postoperative 30-day survival challenge in LT using fatty livers. However, with careful donor-recipient matching, for example, avoiding the use of steatotic donors with long cold ischemic time and high BSA ratios for recipients in the intensive care unit, it is possible to enhance immediate GS, and in a longer time, outcomes comparable to those using nonfatty livers, donors after circulatory death livers, or standard-risk older donors can be anticipated. These novel insights into decision-making criteria for steatotic liver use provide invaluable guidance for clinicians.
The current liver allocation system may be disadvantaging younger adult recipients as it does not incorporate the donor-recipient age difference. Given the longer life expectancy of younger ...recipients, the influences of older donor grafts on their long-term prognosis should be elucidated. This study sought to reveal the long-term prognostic influence of the donor-recipient age difference in young adult recipients. Adult patients who received initial liver transplants from deceased donors between 2002 and 2021 were identified from the UNOS database. Young recipients (patients 45 years old or below) were categorized into 4 groups: donor age younger than the recipient, 0-9 years older, 10-19 years older, or 20 years older or above. Older recipients were defined as patients 65 years old or above. To examine the influence of the age difference in long-term survivors, conditional graft survival analysis was conducted on both younger and older recipients. Among 91,952 transplant recipients, 15,170 patients were 45 years old or below (16.5%); these were categorized into 6,114 (40.3%), 3,315 (21.9%), 2,970 (19.6%), and 2,771 (18.3%) for groups 1-4, respectively. Group 1 demonstrated the highest probability of survival, followed by groups 2, 3, and 4 for the actual graft survival and conditional graft survival analyses. In younger recipients who survived at least 5 years post-transplant, inferior long-term survival was observed when there was an age difference of 10 years or above (86.9% vs. 80.6%, log-rank p <0.01), whereas there was no difference in older recipients (72.6% vs. 74.2%, log-rank p =0.89). In younger patients who are not in emergent need of a transplant, preferential allocation of younger aged donor offers would optimize organ utility by increasing postoperative graft survival time.
Liver transplantation is a highly successful treatment for liver failure and disease. However, demand continues to outstrip our ability to provide transplantation as a treatment. Many livers ...initially considered for transplantation are not used because of concerns about their viability or logistical issues. Recent clinical trials have shown discarded livers may be viable if they undergo machine perfusion, which allows a more objective assessment of liver quality.
Using the Scientific Registry of Transplant Recipients dataset, we examined discarded and unretrieved organs to determine their eligibility for perfusion. We then used a Markov decision-analytic model to perform a cost-effectiveness analysis of two competing transplant strategies: Static Cold Storage (SCS) alone versus Static Cold Storage and Normothermic Machine Perfusion (NMP) of discarded organs.
The average predicted successful transplants after perfusion was 385, representing a 5.8% increase in the annual yield of liver transplants. Our cost-effectiveness analysis found that the SCS strategy generated 4.64 quality-adjusted life years (QALYs) and cost $479,226. The combined SCS + NMP strategy generated 4.72 QALYs and cost $481,885. The combined SCS + NMP strategy had an incremental cost-effectiveness ratio of $33,575 per additional QALY over the 10-year study horizon.
Machine perfusion of livers currently not considered viable for transplant could increase the number of transplantable grafts by approximately 5% per year and is cost-effective compared to Static Cold Storage alone.
•Five percent more livers available for transplant.•Machine Perfusion is cost-effective.•Wider use of Normothermic Machine Perfusion can improve access to transplant surgery.
Background
The allocation system for livers used the acuity circles (AC) beginning in 2020. In this study, we sought to evaluate the effect of the AC policy on center transplant volumes, from ...geographic and center practice perspectives.
Methods
Using the US national registry data between 2018 and 2022, adult liver transplantations (LTs) were separated into two eras: before AC and after AC.
Results
The number of LT for Model for End‐Stage Liver Disease (MELD) scores ≥29 have significantly increased by 10%, and waitlist times for those patients have been significantly shorter after AC. These benefits were not found in patients with MELD scores <29. The geographic distribution of transplant centers reveals that the majority of centers which increased their transplant volume (18 out of 25 centers) are located in high‐population states while there are seven transplant centers in nonhigh‐population states. The centers in the nonhigh‐population states utilized more marginal donation after brain death (DBD) and donation after circulatory death (DCD) donors by 27% and 155%, respectively. MELD scores were significantly lower in the nonhigh‐population states compared with those in the high‐population states (p < .01).
Conclusion
AC improved the LT access for patients with MELD scores ≥29, which benefited the high‐population states. However, aggressive center practices to utilize marginal DBD and DCD donors were able to increase transplant volume and lower median allocation MELD scores.
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