Evaluation of penalty functions for semi-global matching cost aggregation

The stereo matching method semi-global matching (SGM) relies on consistency constraints during the cost aggregation which are enforced by so-called penalty terms. This paper proposes new and evaluates four penalty functions for SGM. Due to mutual dependencies, two types of matching cost calculation, census and rank transform, are considered. Performance is measured using original and degenerated images exhibiting radiometric changes and noise from the Middlebury benchmark. The two best performing penalty functions are inversely proportional and negatively linear to the intensity gradient and perform equally with 6.05 % and 5.91 % average error, respectively. The experiments also show that adaptive penalty terms are mandatory when dealing with difficult imaging conditions. Consequently, for highest algorithmic performance in real-world systems, selection of a suitable penalty function and thorough parametrization with respect to the expected image quality is essential.Stifterverband für die deutsche Wissenschaf

Combining BeEAM with Brentuximab Vedotin for High-Dose Therapy in CD30 Positive Lymphomas before Autologous Transplantation-A Phase I Study.

The prognosis for patients with CD30+ lymphomas (Hodgkin lymphoma and various T-cell lymphomas) relapsing after autologous stem cell transplantation (ASCT) is critical. Brentuximab vedotin (BV), an ADC targeting CD30, is an obvious candidate for inclusion into high-dose chemotherapy (HDCT) regimens to improve outcomes. This single center phase I trial investigated 12 patients with CD30+ lymphoma (AITL: n = 5; relapsed HL: n = 7; median of two previous treatment lines) undergoing ASCT. In a 3 + 3 dose escalation design, 12 patients received a single BV dose at three dose levels (DL) (0.9/1.2/1.8 mg/kg b.w.) prior to standard BeEAM. All patients were treated as planned; no dose limiting toxicities (DLTs) occurred at DL 1 and 2. At DL 3, one DLT (paralytic ileus, fully recovering) occurred. Grade III febrile neutropenia occurred in one patient, and two others had septic complications, all fully recovering. Median hospitalization was 23 days. Hematologic recovery was normal. Six of twelve (50%) patients achieved CR. PFS and OS at 1 year were 67% (n = 8/12) and 83% (n = 10/12), respectively. The addition of brentuximab to standard BeEAM HDCT seems to be safe. We observed a CR rate of 75% post-ASCT in a highly pretreated population. The efficacy of this novel HDCT combination with BV at a 1.8 mg/kg dose level needs to be explored in larger studies

Comparison of methods for donor-derived cell-free DNA quantification in plasma and urine from solid organ transplant recipients.

In allograft monitoring of solid organ transplant recipients, liquid biopsy has emerged as a novel approach using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma. Despite early clinical implementation and analytical validation of techniques, direct comparisons of dd-cfDNA quantification methods are lacking. Furthermore, data on dd-cfDNA in urine is scarce and high-throughput sequencing-based methods so far have not leveraged unique molecular identifiers (UMIs) for absolute dd-cfDNA quantification. Different dd-cfDNA quantification approaches were compared in urine and plasma of kidney and liver recipients: A) Droplet digital PCR (ddPCR) using allele-specific detection of seven common HLA-DRB1 alleles and the Y chromosome; B) high-throughput sequencing (HTS) using a custom QIAseq DNA panel targeting 121 common polymorphisms; and C) a commercial dd-cfDNA quantification method (AlloSeq® cfDNA, CareDx). Dd-cfDNA was quantified as %dd-cfDNA, and for ddPCR and HTS using UMIs additionally as donor copies. In addition, relative and absolute dd-cfDNA levels in urine and plasma were compared in clinically stable recipients. The HTS method presented here showed a strong correlation of the %dd-cfDNA with ddPCR (R 2 = 0.98) and AlloSeq® cfDNA (R 2 = 0.99) displaying only minimal to no proportional bias. Absolute dd-cfDNA copies also correlated strongly (τ = 0.78) between HTS with UMI and ddPCR albeit with substantial proportional bias (slope: 0.25; 95%-CI: 0.19-0.26). Among 30 stable kidney transplant recipients, the median %dd-cfDNA in urine was 39.5% (interquartile range, IQR: 21.8-58.5%) with 36.6 copies/μmol urinary creatinine (IQR: 18.4-109) and 0.19% (IQR: 0.01-0.43%) with 5.0 copies/ml (IQR: 1.8-12.9) in plasma without any correlation between body fluids. The median %dd-cfDNA in plasma from eight stable liver recipients was 2.2% (IQR: 0.72-4.1%) with 120 copies/ml (IQR: 85.0-138) while the median dd-cfDNA copies/ml was below 0.1 in urine. This first head-to-head comparison of methods for absolute and relative quantification of dd-cfDNA in urine and plasma supports a method-independent %dd-cfDNA cutoff and indicates the suitability of the presented HTS method for absolute dd-cfDNA quantification using UMIs. To evaluate the utility of dd-cfDNA in urine for allograft surveillance, absolute levels instead of relative amounts will most likely be required given the extensive variability of %dd-cfDNA in stable kidney recipients

Heat shock protein 90 (HSP90) inhibitors in gastrointestinal cancer: where do we currently stand?-A systematic review.

PURPOSE Dysregulated expression of heat shock proteins (HSP) plays a fundamental role in tumor development and progression. Consequently, HSP90 may be an effective tumor target in oncology, including the treatment of gastrointestinal cancers. METHODS We carried out a systematic review of data extracted from clinicaltrials.gov and pubmed.gov, which included all studies available until January 1st, 2022. The published data was evaluated using primary and secondary endpoints, particularly with focus on overall survival, progression-free survival, and rate of stable disease. RESULTS Twenty trials used HSP90 inhibitors in GI cancers, ranging from phase I to III clinical trials. Most studies assessed HSP90 inhibitors as a second line treatment. Seventeen of the 20 studies were performed prior to 2015 and only few studies have results pending. Several studies were terminated prematurely, due to insufficient efficacy or toxicity. Thus far, the data suggests that HSP90 inhibitor NVP-AUY922 might improve outcome for colorectal cancer and gastrointestinal stromal tumors. CONCLUSION It currently remains unclear which subgroup of patients might benefit from HSP90 inhibitors and at what time point these inhibitors may be beneficial. There are only few new or ongoing studies initiated during the last decade

The impact of perceived donor liver quality on post-transplant outcome.

BACKGROUND We analysed the impact of perceived liver donor quality on transplant recipient outcomes. METHODS this prospective cohort study included all deceased liver donors during 2008-2018 in the Swiss Transplant Cohort Study. Perceived low-quality liver donors were defined when refused for ≥5 top listed recipients or for all recipients in at least one centre before being transplanted. The effect of liver donor quality on relisting or recipient death at 1 week and 1 year after transplantation was analysed using Kaplan-Meier and Cox proportional hazard models. A 1:3 matching was also performed using a recipient score. RESULTS Of 973 liver donors, 187 (19.2%) had perceived poor-quality. Males, obesity, donation after circulatory death and alanine aminotransferase values were significantly associated with perceived poor-quality, with no significant effect of the perceived quality on re-listing or death within the first week and first year post-transplant [(aHR) = 1.45, 95% CI: (0.6, 3.5), P = 0.41 and aHR = 1.52 (95% CI 0.98-2.35), P = 0.06], adjusting by recipient age and gender, obesity, diabetes, prior liver transplantation and model for end-stage liver disease (MELD) score. At 1 year, prior liver transplantation and higher MELD score associated with higher risk of re-listing or death. CONCLUSION Comparable post-transplant outcomes with different perceived quality liver donors stresses the need to improve donor selection in liver transplantation

Comparison of methods for donor-derived cell-free DNA quantification in plasma and urine from solid organ transplant recipients

In allograft monitoring of solid organ transplant recipients, liquid biopsy has emerged as a novel approach using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma. Despite early clinical implementation and analytical validation of techniques, direct comparisons of dd-cfDNA quantification methods are lacking. Furthermore, data on dd-cfDNA in urine is scarce and high-throughput sequencing-based methods so far have not leveraged unique molecular identifiers (UMIs) for absolute dd-cfDNA quantification. Different dd-cfDNA quantification approaches were compared in urine and plasma of kidney and liver recipients: A) Droplet digital PCR (ddPCR) using allele-specific detection of seven common HLA-DRB1 alleles and the Y chromosome; B) high-throughput sequencing (HTS) using a custom QIAseq DNA panel targeting 121 common polymorphisms; and C) a commercial dd-cfDNA quantification method (AlloSeq® cfDNA, CareDx). Dd-cfDNA was quantified as %dd-cfDNA, and for ddPCR and HTS using UMIs additionally as donor copies. In addition, relative and absolute dd-cfDNA levels in urine and plasma were compared in clinically stable recipients. The HTS method presented here showed a strong correlation of the %dd-cfDNA with ddPCR (R2 = 0.98) and AlloSeq® cfDNA (R2 = 0.99) displaying only minimal to no proportional bias. Absolute dd-cfDNA copies also correlated strongly (τ = 0.78) between HTS with UMI and ddPCR albeit with substantial proportional bias (slope: 0.25; 95%-CI: 0.19–0.26). Among 30 stable kidney transplant recipients, the median %dd-cfDNA in urine was 39.5% (interquartile range, IQR: 21.8–58.5%) with 36.6 copies/μmol urinary creatinine (IQR: 18.4–109) and 0.19% (IQR: 0.01–0.43%) with 5.0 copies/ml (IQR: 1.8–12.9) in plasma without any correlation between body fluids. The median %dd-cfDNA in plasma from eight stable liver recipients was 2.2% (IQR: 0.72–4.1%) with 120 copies/ml (IQR: 85.0–138) while the median dd-cfDNA copies/ml was below 0.1 in urine. This first head-to-head comparison of methods for absolute and relative quantification of dd-cfDNA in urine and plasma supports a method-independent %dd-cfDNA cutoff and indicates the suitability of the presented HTS method for absolute dd-cfDNA quantification using UMIs. To evaluate the utility of dd-cfDNA in urine for allograft surveillance, absolute levels instead of relative amounts will most likely be required given the extensive variability of %dd-cfDNA in stable kidney recipients

A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Kaltschmidt C, Banz-Jansen C, Benhidjeb T, et al. A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells. Cancers. 2019;11(5): 655.Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed