Characterization of prostate cancer in transgender women

Background: The risk of developing prostate cancer (PC) in transgender women is unknown. Many patients are unaware that the prostate is not removed during male-to-female surgical transition. It is unclear what the exposure of estrogens and androgen blockers in these transgender patients has on the prostate. Our aim was to examine and characterize the different presentations of PC in published cases and augment this with an additional case series from one institute. Methods: A retrospective review of prospectively maintained medical records was performed identifying features of PC diagnoses in transgender women. These included age, duration of feminizing hormone therapy, PSA values at time of diagnosis, Gleason grade, and M stage. These were compared with a series of published cases of PC in transgender women, compiled after a systematic literature review using PubMed to review all literature in the English language reporting a case of prostate cancer in a transgender woman, published between January 1st, 1971 and December 31st, 2021. The review was conducted in accordance with PRISMA guidelines. The keywords used included “prostate cancer,” “transgender,” “transsexual,” “trans,” “male-to-female,” “Gleason score,” and “prostatectomy.” Results: We identified thirteen cases of PC in transgender women; eleven from published cases from 19752021 and two from our database. Several differences were identified between the published cases from the last 50 years and the two from our contemporary database: The average age in each group was 64 and 56, average duration on therapy was 22 years and 5.5 years, PSA values were 61.54 ng/dL and 1.4 ng/dL, and median Gleason grades were 8 and 6, respectively. Of the 9 published cases which discussed metastases, 6 (67%) had metastatic disease on presentation compared to 0% in the contemporary cohort. Conclusions There is a paucity of data describing the risk of prostate cancer in transgender women. The current published data available to inform clinical practice is predominantly comprised of case reports, many of which are dated. Historically, patients present with advanced disease when compared to their recent counterparts, which may be explained by a variety of biopsychosocial factors. There is a need for contemporary data to inform and formalize standards for screening, diagnosis, and treatment within this group

Size-dependent Failure Behavior of Lithium-Iron Phosphate Battery under Mechanical Abuse

The use of battery electric vehicles is one of the green solutions to reduce environmental pollution and save the Earth. Based on the power, speed, and space constraints, the battery geometries (size and shape) are decided in the battery electric vehicles. However, battery failure assessment and abuse testing are much needed to ensure its safe operation. Herein, four types of lithium-iron phosphate batteries viz. 18650, 22650, 26650, and 32650 are considered to conduct lateral, longitudinal compression, and nail penetration tests. The mechanical failure is characterized by the voltage drop and temperature rise at the onset of the first short-circuit is identified by Aurdino-based voltage sensor module and temperature measurement module. The battery failure load and peak temperature at the onset of internal short-circuit during different mechanical abuse conditions are found to rely on the battery size strongly. The failure due to the onset of internal short circuit is observed to be delayed for small-sized 18650 batteries during lateral compression, unlike longitudinal compression and nail penetration test. At the onset of the short circuit, the LFPBs showed variation in temperature above the ambient value of 28 degree C. Among the LFPBs considered, the lowest variation of temperature rise (considering ambient temperature) is found to be 5.25 degree C for type 26650. The outcome of this work is anticipated to demonstrate the significance of the choice of battery sizes for different desired applications safely.Comment: 15 pages, 6 Figures, 2 tabl

Enhanced production surveillance using probabilistic dynamic models

Production surveillance is the task of monitoring oil and gas production from every well in a hydrocarbon field. A key opportunity in this domain is to improve the accuracy of flow measurements per phase (oil, water, gas) from a multi-phase flow. Multi-phase flow sensors are costly and therefore not instrumented for every production well. Instead, several low fidelity surrogate measurements are performed that capture different aspects of the flow. These measurements are then reconciled to obtain per-phase rate estimates. Current practices may not appropriately account for the production dynamics and the sensor issues, thus, fall far short in terms of achieving a desired surveillance accuracy. To improve surveillance accuracy, we pose rate reconciliation as a state estimation problem. We begin with hypothesizing a model that describes the dynamics of production rates and their relationship with the field measurements. The model appropriately accounts for the uncertainties in field conditions and measurements. We then develop robust probabilistic estimators for reconciliation to yield the production estimates and the uncertainties therein. We highlight recent advancements in the area of probabilistic programming that can go a long way in improving the performance and the portability of such estimators. The exposition of our methods is accompanied by experiments in a simulation environment to illustrate improved surveillance accuracy achieved in different production scenarios

Cathepsins B and D drive hepatic stellate cell proliferation and promote their fibrogenic potential

El pdf del artículo es el manuscrito de autor.-- PubMed: PMCID:PMC2670444Cathepsins have been best characterized in tumorigenesis and cell death and implicated in liver fibrosis; however, whether cathepsins directly regulate hepatic stellate cell (HSC) activation and proliferation, hence modulating their fibrogenic potential, is largely unknown. Here, we show that expression of cathepsin B (CtsB) and cathepsin D (CtsD) is negligible in quiescent HSCs but parallels the increase of -smooth muscle actin and transforming growth factor- during in vitro mouse HSC activation. Both cathepsins are necessary for HSC transdifferentiation into myofibroblasts, because their silencing or inhibition decreasedHSC proliferation and the expression of phenotypicmarkers ofHSC activation, with similar results observed with the human HSC cell line LX2. CtsB inhibition blunted AKT phosphorylation in activated HSCs in response to platelet-derived growth factor.Moreover, during in vivo liver fibrogenesis caused by CCl4 administration, CtsB expression increased in HSCs but not in hepatocytes, and its inactivation mitigated CCl4-induced inflammation, HSC activation, and collagen deposition. Conclusion: These findings support a critical role for cathepsins inHSC activation, suggesting that the antagonismof cathepsins inHSCsmay be of relevance for the treatment of liver fibrosis.Financial support: The work was supported by CIBEREHD and grant PI070193 (Instituto de Salud Carlos III); by grant SAF2006-06780 (Plan Nacional de I+D), Spain; and by grant P50-AA-11999 (Research Center for Liver and Pancreatic Diseases, US National Institute on Alcohol Abuse and Alcoholism).Peer reviewe

Epigenomic Alterations in Localized and Advanced Prostate Cancer

AbstractAlthough prostate cancer (PCa) is the second leading cause of cancer death among men worldwide, not all men diagnosed with PCa will die from the disease. A critical challenge, therefore, is to distinguish indolent PCa from more advanced forms to guide appropriate treatment decisions. We used Enhanced Reduced Representation Bisulfite Sequencing, a genome-wide high-coverage single-base resolution DNA methylation method to profile seven localized PCa samples, seven matched benign prostate tissues, and six aggressive castration-resistant prostate cancer (CRPC) samples. We integrated these data with RNA-seq and whole-genome DNA-seq data to comprehensively characterize the PCa methylome, detect changes associated with disease progression, and identify novel candidate prognostic biomarkers. Our analyses revealed the correlation of cytosine guanine dinucleotide island (CGI)-specific hypermethylation with disease severity and association of certain breakpoints (deletion, tandem duplications, and interchromosomal translocations) with DNA methylation. Furthermore, integrative analysis of methylation and single-nucleotide polymorphisms (SNPs) uncovered widespread allele-specific methylation (ASM) for the first time in PCa. We found that most DNA methylation changes occurred in the context of ASM, suggesting that variations in tumor epigenetic landscape of individuals are partly mediated by genetic differences, which may affect PCa disease progression. We further selected a panel of 13 CGIs demonstrating increased DNA methylation with disease progression and validated this panel in an independent cohort of 20 benign prostate tissues, 16 PCa, and 8 aggressive CRPCs. These results warrant clinical evaluation in larger cohorts to help distinguish indolent PCa from advanced disease

Predictive Modeling Techniques in Prostate Cancer

A number of new predictive modeling techniques have emerged in the past several years. These methods can be used independently or in combination with traditional modeling techniques to produce useful tools for the management of prostate cancer. Investigators should be aware of these techniques and avail themselves of their potentially useful properties. This review outlines selected predictive methods that can be used to develop models that may be useful to patients and clinicians for prostate cancer management.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63147/1/10915360152745812.pd

Racial differences in serum prostate-specific antigen (PSA) doubling time, histopathological variables and long-term PSA recurrence between African-American and white American men undergoing radical prostatectomy for clinically localized prostate cancer

To determine if there are significant differences in biochemical characteristics, biopsy variables, histopathological data, and rates of prostate-specific antigen (PSA) recurrence between African-American (AA) and white American (WA) men undergoing radical prostatectomy (RP), as AA men are twice as likely to die from prostate cancer than their white counterparts. PATIENTS AND METHODS We established a cohort of 1058 patients (402 AA, 646 WA) who had RP and were followed for PSA recurrence. Age, race, serum PSA, biopsy Gleason score, clinical stage, pathological stage, and PSA recurrence data were available for the cohort. The chi-square test of proportions and t -tests were used to assess basic associations with race, and log-rank tests and Cox regression models for time to PSA recurrence. Forward stepwise variable selection was used to assess the effect on the risk of PSA recurrence for race, adjusted by the other variables added one at a time. RESULTS The AA men had higher baseline PSA levels, more high-grade prostatic intraepithelial neoplasia (HGPIN) in the biopsy, and more HGPIN in the pathology specimen than WA men. The AA men also had a shorter mean (sd) PSA doubling time before RP, at 4.2 (4.7) vs 5.2 (5.9) years. However, race was not an independent predictor of PSA recurrence ( P  = 0.225). Important predictors for PSA recurrence in a multivariable model were biopsy HGPIN ( P  < 0.014), unilateral vs bilateral cancer ( P  < 0.006), pathology Gleason score and positive margin status (both P  < 0.001). CONCLUSIONS This study indicates that while there are racial differences in baseline serum PSA and incidence of HGPIN, race is not an independent risk factor for PSA recurrence. Rather, other variables such as pathology Gleason score, bilateral cancers, HGPIN and margin positivity are independently associated with PSA recurrence. The PSA doubling time after recurrence may also be important, leading to the increased mortality of AA men with prostate cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74706/1/j.1464-410X.2005.05561.x.pd