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Biocompatible gold nanoparticles designed to absorb light at wave-lengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance–ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

Tumor heterogeneity is common in cancer, however recent studies have applied single gene expression signatures to classify bladder cancers into distinct subtypes. Such stratification assumes that a predominant transcriptomic signature is sufficient to predict progression kinetics, patient survival and treatment response. We hypothesize that such static classification ignores intra-tumoral heterogeneity and the potential for cellular plasticity occurring during disease development. We have conducted single cell transcriptome analyses of mouse and human model systems of bladder cancer and show that tumor cells with multiple lineage subtypes not only cluster closely together at the transcriptional level but can maintain concomitant gene expression of at least one mRNA subtype. Functional studies reveal that tumor initiation and cellular plasticity can initiate from multiple lineage subtypes. Collectively, these data suggest that lineage plasticity may contribute to innate tumor heterogeneity, which in turn carry clinical implications regarding the classification and treatment of bladder cancer. Recent studies have utilized bulk tumour mRNA sequencing to classify bladder cancers into distinct subgroups. Here, the authors use single cell transcriptomic analysis and cell transplant studies to show that epithelial plasticity can generate basal, luminal and mesenchymal phenotypes in human and murine bladder cancers.

Objective To examine the prevalence of patient preference for male or female urologic provider and explore which patient characteristics influence this preference. Materials and Methods After obtaining hospital Institutional Review Board approval, a 14‐question survey in English and Spanish was administered across four general urology clinic sites in a single hospital system in New York City. The survey asked demographic questions and preference for a male or a female urologist. The survey included questions pertaining to the nature of the clinic visit and subsequent provider preference as well. Statistics were performed using Stata 16 (StataCorp, College Station, TX). Results A total of 540 patients completed the 14‐question survey. The vast majority of survey respondents identified as male (90%). The largest proportion demographic groups were those aged 41–60 (47%), Hispanic or Latino (43%), Catholic (47%), unemployed (40%) and those with a high school level of education (34%). Most patients (60%) did not have a preference for a specific gender provider, whereas 37% preferred a male provider, and 3% preferred a female provider. On univariate analysis, patient age 25–40, less than high school education level and lack of employment were significant predictors of provider gender preference (p < 0.05), with most patients indicating a male provider preference. On multivariate analysis of gender, age, education level and employment status, gender and education level were not significant predictors of preference, whereas age 25–40 and being unemployed were significant predictors (p < 0.05). Conclusion Patient gender, race and religion do not appear to influence their preference to be seen by a male or a female urologist in the clinic setting. However, patient age, unemployment and potentially educational attainment were significantly associated with a provider gender preference.

PurposeTo explore the immune phenotype of peripheral blood mononuclear cells (PBMC) in patients with high-risk non-muscle invasive bladder cancer (NMIBC).MethodsWe prospectively collected blood samples from patients with high-risk NMIBC treated at our institution. PBMC were analyzed by flow cytometry to determine the frequency of T cells and NK cells and the expression of immunoregulatory molecules (Tim-3, TIGIT and PD-1). PBMC from healthy donors (HD) were included for comparison, and associations with response to BCG were investigated.ResultsA total of 38 patients were included, 19 BCG responders and 19 BCG refractory. Compared to 16 PBMC from HD, the frequency of total NK cells was significantly higher in patients with NMIBC [15.2% (IQR: 11.4, 22.2) vs. 5.72% (IQR: 4.84, 9.79); p = 0.05], whereas the frequency of T cells was not statistically different. Both Tim-3 and TIGIT expressions were significantly higher in NMIBC compared to HD, particularly in NK cells [13.8% (11.0; 22.4) vs. 5.56% (4.20; 10.2) and 34.9% (18.9; 53.5) vs. 1.82% (0.63; 5.16), respectively; p < 0.001]. Overall, the expression of PD-1 in all cell types was low in both NMIBC patients and HD. The immune phenotype was not significantly different before and after initiation of BCG. However, the proportion of CD8+ T cells before BCG was significantly higher in responders.ConclusionThe immune phenotype of PBMC from patients with high-risk NMIBC was significantly different from HD, regardless of the presence of disease or the initiation of BCG. Peripheral CD8+ T cells could play a role in response to BCG.

NK cells are innate lymphocytes critical for surveillance of viruses and tumors, however the mechanisms underlying NK cell dysfunction in cancer are incompletely understood. We assessed the effector function of NK cells from bladder cancer patients and found severe dysfunction in NK cells derived from tumors versus peripheral blood. While both peripheral and tumor-infiltrating NK cells exhibited conserved patterns of inhibitory receptor over-expression, this did not explain the observed defects in NK surveillance in bladder tumors. Rather, TME-specific TGF-β and metabolic perturbations such as hypoxia directly suppressed NK cell function. Specifically, an oxygen-dependent reduction in signaling through SLAMF6 was mechanistically responsible for poor NK cell function, as tumor-infiltrating NK cells cultured under normoxic conditions exhibited complete restoration of function, while deletion of SLAMF6 abrogated NK cell cytolytic function even under normoxic conditions. Collectively, this work highlights the role of tissue-specific factors in dictating NK cell function, and implicates SLAMF6 signaling as a rational target for immuno-modulation to improve NK cell function in bladder cancer.

The taxon Haemaphysalis (Kaiseriana) renschi Schulze 1933 (1936), previously known from 2 males and synonymized under H. bispinosa Neumann, is resurrected. The male is redescribed and the female, nymph, and larva are described from numerous specimens parasitizing deer, boars, and domestic cattle, horses, and buffalo in Flores (type locality) and Komodo Islands (Lesser Sunda Islands), Java and nearby small islands, and Sumatra. Each developmental stage of H. (K.) renschi infests these mammals; nymphs are also recorded from a bird. A neotype specimen is deposited in the Rocky Mountain Laboratory. This species is morphologically distinctive and easily separated from H. (K.) bispinosa and other members of the bispinosa group (bispinosa and lagrangei subgroups). The geographic isolation of H. (K.) renschi is noteworthy. All other members of the lagrangei subgroup, except for introduced populations of H. (K.) longicornis, occur in continental Asia and Japan, and none is endemic in the Malay Peninsula close to major islands of Indonesia.

In much of India and neighboring nations, Haemaphysalis (K.) bispinosa parasitizes wild and domestic Carnivora and Artiodactyla alike. However, in the Malay Peninsula, where 12,030 ticks were collected from 459 wild Carnivora and Artiodactyla and 5,555 ticks were taken from 388 domestic animals, H. (K.) bispinosa was represented by 34 (0.28%) specimens from the wild hosts and by 4,907 (88.33%) specimens from the domestic hosts. Although widely distributed in the Malay Peninsula, this parasite has biological characteristics of an introduced species that has not adapted to the Malayan forest environment and fauna. Several old specimens of bispinosa from Borneo [British Museum (Natural History) collections] may represent erroneous labeling or samples of introduced ticks that do not appear to have established a permanent population on this island.

Haemaphysalis (H.) sumatraensis sp. n. is described from adults parasitizing the Sumatran tiger, Felis tigris sumatrae Pocock, wild boar, Sus scrofa vittatus Boie, and sambar deer, Cervus unicolor equinus Cuvier, and swept from vegetation in lowland forests of southern Sumatra. This member of the H. (H.) obesa group of the Oriental Faunal Region is related to H. (H.) obesa Larrousse (NE India to Vietnam, Thailand, N Malaya) and H. (H.) hirsuta Hoogstraal, Trapido, and Kohls (Java, Sumatra), but lacks the unusual setal patches characterizing the related species. The structure of the female external genital area is unique in each species. These species also appear to be related to H. (H.) turturis Nuttall and Warburton of the Indian Subregion, which lacks specialized female genital structure and unusual setae. H. (H.) hirsuta, previously known only by two adult specimens from Java, is recorded from numerous adults, nymphs, and a larva from forest vegetation in western Java and from adults parasitizing a wild boar and nymphs from forest vegetation and a sambar deer in the same localities as H. (H.) sumatraensis in southern Sumatra.