Near-BPS Skyrmions: Non-shell configurations and Coulomb effects

The relatively small binding energy in nuclei suggests that they may be well represented by near-BPS Skyrmions since their mass is roughly proportional to the baryon number $A.$ For that purpose, we propose a generalization of the Skyrme model with terms up to order six in derivatives of the pion fields and treat the nonlinear $\sigma$ and Skyrme terms as small perturbations. For our special choice of mass term (or potential) $V$, we obtain well-behaved analytical BPS-type solutions with non-shell configurations for the baryon density, as opposed to the more complex shell-like configurations found in most extensions of the Skyrme model . Along with static and (iso)rotational energies, we add to the mass of the nuclei the often neglected Coulomb energy and isospin breaking term. Fitting the four model parameters, we find a remarkable agreement for the binding energy per nucleon $B/A$ with respect to experimental data. These results support the idea that nuclei could be near-BPS Skyrmions.Comment: Correction of minors errors, references adde

Considering Predictive Factors in the Diagnosis of Clinically Significant Prostate Cancer in Patients with PI-RADS 3 Lesions

The use of multi-parametric magnetic resonance imaging (mpMRI) in conjunction with the Prostate Imaging Reporting and Data System (PI-RADS) is standard practice in the diagnosis, surveillance, and staging of prostate cancer. The risk associated with lesions graded at a PI-RADS score of 3 is ambiguous. Further characterization of the risk associated with PI-RADS 3 lesions would be useful in guiding further work-up and intervention. This study aims to better characterize the utility of PI-RADS 3 and associated risk factors in detecting clinically significant prostate cancer. From a prospectively maintained IRB-approved dataset of all veterans undergoing mpMRI fusion biopsy at the Southeastern Louisiana Veterans Healthcare System, we identified a cohort of 230 PI-RADS 3 lesions from a dataset of 283 consecutive UroNav-guided biopsies in 263 patients from October 2017 to July 2020. Clinically significant prostate cancer (Gleason Grade ≥ 2) was detected in 18 of the biopsied PI-RADS 3 lesions, representing 7.8% of the overall sample. Based on binomial analysis, PSA densities of 0.15 or greater were predictive of clinically significant disease, as was PSA. The location of the lesion within the prostate was not shown to be a statistically significant predictor of prostate cancer overall (p = 0.87), or of clinically significant disease (p = 0.16). The majority of PI-RADS 3 lesions do not represent clinically significant disease; therefore, it is possible to reduce morbidity through biopsy. PSA density is a potential adjunctive factor in deciding which patients with PI-RADS 3 lesions require biopsy. Furthermore, while the risk of prostate cancer for African-American men has been debated in the literature, our findings indicate that race is not predictive of identifying prostate cancer, with comparable Gleason grade distributions on histology between races

Risk factors for infectious readmissions following radical cystectomy: results from a prospective multicenter dataset

Introduction: Radical cystectomy (RC) is the gold standard treatment for muscle-invasive bladder cancer. This procedure has a high rate of perioperative complications, many of which are infectious in nature. The objective of our study was to evaluate demographic, intrinsic and extrinsic patient variables associated with developing readmission within 30 days due to infectious complications following RC. Methods: We acquired data available from the American College of Surgeons National Surgical Quality Improvement Program. We queried this dataset to identify all patients who underwent RC for muscle-invasive malignant disease (CPT 188.x) in 2012 based on CPT coding. Logistic regression analysis was used to investigate the relationship between preoperative variables and readmissions for infectious complications. Results: Of the 961 patients undergoing cystectomy for malignancy, 159 (17%) required readmission for any indications at a median of 16 days (interquartile range 13–22 days) postoperatively. We identified 71 of a total of 159 (45%) readmissions, which were due to infectious complications. Smoking was more prevalent in the patient population readmitted for an infectious complication compared with the patient population readmitted for a non-infectious complication (37% versus 25%; p = 0.03). Using logistic regression analysis smoking was associated with a significant risk for readmission due to an infectious cause (odds ratio 2.28, 95% confidence interval 1.82–2.97, p = 0.02). Readmission due to an infectious etiology was not associated with other perioperative factors including type of urinary diversion, sex, duration of operation, hypertension, or recent weight loss. Conclusion: Readmission following RC is a common occurrence and infectious complications drive readmission in almost half of the cases. Current smoking was the only independent risk factor for an infectious readmission. Counseling patients in smoking cessation prior to the procedure may provide an avenue for quality improvement to limit readmissions

Prostate Cancer Lesions by Zone and Race: Does Multiparametric MRI Demonstrate Racial Difference in Prostate Cancer Lesions for African American Men?

African American (AA) men have increased risk of prostate cancer diagnosis and mortality, but the cause remains unknown. MRI fusion improves diagnosis of localized prostate cancer, particularly in anterior lesions; however, cost and access are limited in a community practice setting. By utilizing a diverse cohort of veterans with equal access to care in a single payer system, we describe prostate cancer detection. We queried a prospectively maintained institutional review board-approved database of men undergoing prostate biopsy for untreated prostate cancer. We included all consecutive patients from October 2017 to February 2020. Statistical analysis including Kaplan–Meier Curves, Fisher’s exact test, and Forest plot was performed. From 246 consecutive patients, 166 were AA and 80 were non-AA. There were similar distributions of PSA, PSAD, and number of targetable lesions between the AA and non-AA cohort (p > 0.05 for all). We found no difference in location on MRI between race groups. There was similar cancer detection, focusing on anterior lesions and rate of positive Gleason grade (≥GG1) and clinically significant (≥GG2) cancer between cohorts. In a predominant AA cohort of veterans, we found similar distribution of location for MRI-targeted lesions, along with rates of tumor detection and aggressiveness of disease. In this single payer veteran population, we did not identify specific biologic differences inherent to tumor detection between AA and non-AA patients

Combination of Tipifarnib and Sunitinib Overcomes Renal Cell Carcinoma Resistance to Tyrosine Kinase Inhibitors via Tumor-Derived Exosome and T Cell Modulation

Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance. Methods: 786-O, 786-O-SR (sunitinib resistant), A498, A498-SR, Caki-2, Caki-2-SR, and 293T cells were cultured. Exosomes were collected using differential ultracentrifugation. Cell proliferation, Jurkat T cell immune assay, and immunoblot analysis were used for downstream analysis. Results: SR exosomes treatment displayed a cytotoxic effect on immune cells. This cytotoxic effect was associated with increased expression of PD-L1 on SR exosomes when compared to sunitinib-sensitive (SS) exosomes. Additionally, Tipi treatment downregulated PD-L1 expression on exosomes derived from SR cell lines. Tipi’s ability to downregulate PD-L1 in exosomes has a significant application within patients. Exosomes collected from patients with RCC showed increased PD-L1 expression over subjects without RCC. Next, exosome concentrations were then compared after Tipi treatment, with all SS cell lines displaying an even greater reduction. On immunoblot assay, 293T cells showed a dose-dependent increase in Alix with no change in either nSMase or Rab27a. Conversely, all the SS and SR cell lines displayed a decrease in all three markers. After a cell proliferation employed a 48-h treatment on all SS and SR cell lines, the drug combination displayed synergistic ability to decrease tumor growth. Conclusions: Tipifarnib attenuates both the exosome endosomal sorting complex required for endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways, thereby blocking exosome biogenesis and secretion as well as downregulating PD-L1 on SS and SR cells

Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization.

In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 ( -/- ) mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV