Treatment modalities and survival outcomes in prostate cancer parenchymal brain metastasis.

BACKGROUND: Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes. METHODS: We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan-Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups. RESULTS: At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate-specific antigen (PSA) was 2.2 (0.1-26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6-100.9). The median (IQR) primary Gleason score was 8 (7-9) and over a median (IQR) follow-up time of 2.2 (1.2-16.5) months, 76.5% (n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log-rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16-0.86, p = 0.022). CONCLUSIONS: In our single-institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.

Antibody-Based Therapeutics for the Treatment of Renal Cell Carcinoma: Challenges and Opportunities.

Renal cell carcinoma (RCC) is among the top 10 most common cancers in both men and women with an estimated 75 000 cases each year in the US. Over the last decade, the therapeutic landscape for patients with metastatic RCC has significantly evolved, with immunotherapy emerging as the new front-line therapy. Despite significant improvement in toxicity profile and survival outcomes, key concerns such as patient selection, treatment sequencing, and intrinsic and acquired resistance remain unresolved. Emerging options such as antibody-based therapeutics (eg, anti-CD70, anti-CA9, and anti-ENPP3) are being explored in clinical trials for patients with cancer resistant or refractory to current immunotherapies. Despite positive results for hematological cancers, breast cancer, and more recently bladder cancer, most antibody-based therapies failed to improve the outcomes in patients with advanced RCC. This underscores the need to understand the underlying causes of failed responses to this treatment class, which will ultimately support the rational design of more effective and tolerable treatments. In this review, we summarize the evolving landscape of RCC therapeutics and describe recent clinical trials with emerging antibody-based therapeutics. We also describe the challenges that need to be overcome for the successful creation of therapeutic antibodies for treating RCC.

One-way light flow by spatio-temporal modulation.

The unidirectional flow of electrons that takes place in a conventional electronic diode has been a cornerstone in the development of the field of electronics. Achieving an equivalent one-way flow for light has been a long-standing problem. While a number of concepts have been suggested recently, attaining a unidirectional flow of light in a two-port system (e.g., a waveguiding configuration) is still challenging. Here, we present what we believe to be a novel approach for breaking reciprocity and achieving one-way flow of light. Taking a nanoplasmonic waveguide as an example, we show that a combination of time-dependent interband optical transitions, when in systems exhibiting a backward wave flow, can yield light transmission strictly in one direction. In our configuration, the energy flow is unidirectional: light is fully reflected in one direction of propagation, and is unperturbed in the other. The concept can find use in a range of applications including communications, smart windows, thermal radiation management, and solar energy harvesting.

Effect of COVID-19 Pandemic on Neonatal Sepsis.

BACKGROUND: There is a sudden rise in infectious diseases, with special concern to the most recent SARS-CoV 2 outbreak. A retrospective study was conducted to study the effect of this outbreak on neonatal sepsis as a global issue that poses a challenge for pediatric management and to identify its risk factors, microbial profile, and mortality rate at King Faisal Medical Complex, Taif, KSA, a COVID-19-tertiary care segregation hospital. METHODS: This research included 111 neonates with a culture-proven diagnosis of neonatal sepsis (4 and 62 cases during 2019 and 2020, respectively). RESULTS: During 2019 early onset sepsis (EOS) occurred in 6/49 (12.2%) while in 2020 22/62 (35.5%), and during 2019 late onset sepsis (LOS) occurred in 43/49 (87.7%) while in 2020 40/62 (64.5%). Premature rupture of membrane was the major neonatal risk factor for EOS during 2019 and 2020 with proportions of 4 (66.7%), 20 (90.9%); respectively. As regards LOS, the peripherally inserted central catheters and peripheral lines were the top neonatal risk factors. In the two-year outbreak, the most prevalent causative organism for EOS neonates was Escherichia coli and for LOS neonates it was Klebsiella. There was non-significant change in the mortality rate of neonatal sepsis between 2019 and 2020. However, the mortality rate was higher in EOS 9/22 (40.9%) in 2020 in comparison to 2/6 (33.3%) in 2019. CONCLUSIONS: Neonatal sepsis remains a major health problem causing serious morbidity and mortality, and health care policy makers have to implement EOS preventive measures.

Evaluation of PD-L1 and B7-H3 expression as a predictor of response to adjuvant chemotherapy in bladder cancer.

INTRODUCTION AND OBJECTIVES: PD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher's exact test and postoperative survival using Kaplan-Meier survival curves and Cox regression model. RESULTS: B7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06-5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18-6.04, p = 0.019). CONCLUSIONS: In our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.

Diversity of rhizobial and non-rhizobial bacteria nodulating wild ancestors of grain legume crop plants.

Chickpeas, lentils, and peas are the oldest grain legume species that spread to other regions after their first domestication in Fertile Crescent, and they could reveal the rhizobial evolution in relation to the microsymbionts of wild species in this region. This study investigated the phenotypic and genotypic diversity of the nodule-forming rhizobial bacteria recovered from Pisum sativum subsp., Cicer pinnatifidum, and Lens culinaris subsp. orientalis exhibiting natural distribution in the Gaziantep province of Turkey. PCA analyses of rhizobial isolates, which were tested to be highly resistant to stress conditions, showed that especially pH and salt concentrations had an important effect on these bacteria. Phylogenetic analysis based on 16S rRNA determined that these wild species were nodulated by at least 7 groups including Rhizobium and non-Rhizobium. The largest group comprised of Rhizobium leguminosarum and Rhizobium sp. while R. pusense, which was previously determined as non-symbiotic species, was found to nodulate C. pinnatifidum and L. culinaris subsp. orientalis. In recent studies, Klebsiella sp., which is stated to be able to nodulate different species, strong evidences have been obtained in present study exhibiting that Klebsiella sp. can nodulate C. pinnatifidum and Pseudomonas sp. was able to nodulate C. pinnatifidum and P. sativum subsp. Additionally, L. culinaris subsp. orientalis unlike other plant species, was nodulated by Burkholderia sp. and Serratia sp. associated isolates. Some isolates could not be characterized at the species level since the 16S rRNA sequence similarity rate was low and the fact that they were in a separate group supported with high bootstrap values in the phylogenetic tree may indicate that these isolates could be new species. The REP-PCR fingerprinting provided results supporting the existence of new species nodulating wild ancestors.

Expression of Plasma miRNA-221 in Colorectal Carcinoma Patients and its Diagnostic Significance in Comparison with p53 Expression.

BACKGROUND: Colorectal carcinoma development progresses through a sequence of normal mucosa-polyp-carcinoma. Early detection of premalignancy is crucial for improved outcomes. We evaluated the diagnostic performance of plasma miRNA-221 and its feasibility in discriminating premalignant from malignant neoplasms and correlating it with immunohistochemical p53 expression. METHODS: A total of 109 plasma samples were collected (76 carcinoma, 14 premalignant, and 19 controls). MiRNA221 was quantified by qPCR for calculation of ∆Ct using RNU6B as endogenous control. p53 immunohistochemical staining was performed on corresponding tissue. RESULTS: Plasma miRNA-221 and p53 in tissues were significantly overexpressed in the malignant group when compared with the premalignant and control groups. Plasma miRNA-221 was increased in late-stage tumors with nodal or distant metastasis. ROC curve construction for distinguishing between malignant and premalignant tumors revealed a cutoff value of 2.97 with 74% sensitivity, 79% specificity, 73.7% positive predictive value and 78.6% negative predictive value (AUC = 0.824; p = 0.001). Plasma miRNA-221 significantly correlated with p53 in cancer samples (r = 0.507). CONCLUSIONS: MiRNA-221 could have a diagnostic role in differentiating malignant from premalignant neoplasms and could also serve as a predictive marker indicating tumor progression.

Melatonin attenuates chronic immobilization stress-induced muscle atrophy in rats: Influence on lactate-to-pyruvate ratios and Na+/K+ ATPase activity.

This study assessed the protective effect of melatonin against muscle atrophy provoked by chronic immobilization stress (CIS). CIS was induced in rats by limiting their trunk movement for 90 min daily for 6 weeks. Rats subjected to the CIS procedure demonstrated a substantial decrease in body weight, an increase in serum corticosterone, muscle atrophy, and an increase in atrogin-1 mRNA levels. An increase in the serum lactate-to-pyruvate ratio and the oxidative stress accompanied by a reduction of Na+/K+ ATPase activity could be responsible for these changes. Melatonin efficiently attenuated CIS-induced deleterious effects on the muscle by reducing corticosterone levels, the lactate-to-pyruvate ratio, and oxidative stress, thereby improving Na+/K+ ATPase activity and muscle condition. We conclude that melatonin can contribute to the prevention of CIS-induced muscle atrophy via its anti-stress, anti-oxidant properties and its effect on Na+/K+ ATPase activity.

Diagnostic accuracy of a screening electronic alert tool for severe sepsis and septic shock in the emergency department.

BACKGROUND: Early recognition of severe sepsis and septic shock is challenging. The aim of this study was to determine the diagnostic accuracy of an electronic alert system in detecting severe sepsis or septic shock among emergency department (ED) patients. METHODS: An electronic sepsis alert system was developed as a part of a quality-improvement project for severe sepsis and septic shock. The system screened all adult ED patients for a combination of systemic inflammatory response syndrome and organ dysfunction criteria (hypotension, hypoxemia or lactic acidosis). This study included all patients older than 14 years who presented to the ED of a tertiary care academic medical center from Oct. 1, 2012 to Jan. 31, 2013. As a comparator, emergency medicine physicians or the critical care physician identified the patients with severe sepsis or septic shock. In the ED, vital signs were manually entered into the hospital electronic heath record every hour in the critical care area and every two hours in other areas. We also calculated the time from the alert to the intensive care unit (ICU) referral. RESULTS: Of the 49,838 patients who presented to the ED, 222 (0.4%) were identified to have severe sepsis or septic shock. The electronic sepsis alert had a sensitivity of 93.18% (95% CI, 88.78% - 96.00%), specificity of 98.44 (95% CI, 98.33% - 98.55%), positive predictive value of 20.98% (95% CI, 18.50% - 23.70%) and negative predictive value of 99.97% (95% CI, 99.95% - 99.98%) for severe sepsis and septic shock. The alert preceded ICU referral by a median of 4.02 hours (Q1 - Q3: 1.25-8.55). CONCLUSIONS: Our study shows that electronic sepsis alert tool has high sensitivity and specificity in recognizing severe sepsis and septic shock, which may improve early recognition and management.

Poly-Gamma-Glutamic Acid Nanopolymer Effect against Bacterial Biofilms: In Vitro and In Vivo Study.

In this study, a biodegradable poly-gamma-glutamic-acid nanopolymer (Ɣ-PGA NP) was investigated for its activity against clinical strains of Gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae and Escherichia coli), and reference strains of S. aureus ATCC 6538, S. pyogenes ATCC 19615 (Gram-positive), and Gram-negative E. coli ATCC 25922, and K. pneumoniae ATCC 13884 bacterial biofilms. The minimum inhibitory concentration (MIC) effect of Ɣ-PGA NP showed inhibitory effects of 0.2, 0.4, 1.6, and 3.2 µg/mL for S. pyogenes, S. aureus, E. coli, and K. pneumoniae, respectively. Also, MIC values were 1.6, 0.8, 0.2, and 0.2 µg/mL for K. pneumoniae ATCC 13884, E. coli ATCC 25922, S. aureus ATCC 6538, and S. pyogenes ATCC 19615, respectively. Afterwards, MBEC (minimum biofilm eradication concentration) and MBIC (minimum biofilm inhibitory concentration) were investigated to detect Ɣ-PGA NPs efficiency against the biofilms. MBEC and MBIC increased with increasing Ɣ-PGA NPs concentration or time of exposure. Interestingly, MBIC values were at lower concentrations of Ɣ-PGA NPs than those of MBEC. Moreover, MBEC values showed that K. pneumoniae was more resistant to Ɣ-PGA NPs than E. coli, S. aureus, and S. pyogenes, and the same pattern was observed in the reference strains. The most effective results for MBEC were after 48 h, which were 1.6, 0.8, 0.4, and 0.2 µg/mL for K. pneumoniae, E. coli, S. aureus, and S. pyogenes, respectively. Moreover, MBIC results were the most impactful after 24 h but some were the same after 48 h. MBIC values after 48 h were 0.2, 0.2, 0.2, and 0.1 µg/mL for K. pneumoniae, E. coli, S. aureus, and S. pyogenes, respectively. The most effective results for MBEC were after 24 h, which were 1.6, 0.8, 0.4, and 0.4 µg/mL for K. pneumoniae ATCC 13884, E. coli ATCC 25922, S. aureus ATCC 6538, and S. pyogenes ATCC 19615, respectively. Also, MBIC results were the most impactful after an exposure time of 12 h. MBIC values after exposure time of 12 h were 0.4, 0.4, 0.2, and 0.2 µg/mL for K. pneumoniae ATCC 13884, E. coli ATCC 25922, S. aureus ATCC 6538, and S. pyogenes ATCC 19615, respectively. Besides that, results were confirmed using confocal laser scanning microscopy (CLSM), which showed a decrease in the number of living cells to 80% and 60% for MBEC and MBIC, respectively, for all the clinical bacterial strains. Moreover, living bacterial cells decreased to 70% at MBEC while decreasing up to 50% at MBIC with all bacterial refence strains. These data justify the CFU quantification. After that, ImageJ software was used to count the attached cells after incubating with the NPs, which proved the variation in live cell count between the manual counting and image analysis methods. Also, a scanning electron microscope (SEM) was used to detect the biofilm architecture after incubation with the Ɣ-PGA NP. In in vivo wound healing experiments, treated wounds of mice showed faster healing (p < 0.00001) than both the untreated mice and those that were only wounded, as the bacterial count was eradicated. Briefly, the infected mice were treated faster (p < 0.0001) when infected with S. pyogenes > S. aureus > E. coli > K. pneumoniae. The same pattern was observed for mice infected with the reference strains. Wound lengths after 2 h showed slightly healing (p < 0.001) for the clinical strains, while treatment became more obvious after 72 h > 48 h > 24 h (p < 0.0001) as wounds began to heal after 24 h up to 72 h. For reference strains, wound lengths after 2 h started to heal up to 72 h.

Low PSA radiographic disease progression on C11-choline PET.

Background: For men with prostate cancer, radiographic progression may occur without a concordant rise in prostate-specific antigen (PSA). Our study aimed to assess the prevalence of radiographic progression using C-11 choline positron emission tomography (PET) imaging in patients achieving ultra-low PSA values and to evaluate clinical outcomes in this patient population. Methods: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET metastatic prostate cancer registry to identify patients experiencing radiographic disease progression (rDP) on C-11 choline PET scan while the PSA value was less than 0.5 ng/mL. Disease progression was confirmed by tissue biopsy or response to subsequent therapy. Clinicopathologic variables were abstracted by trained research personnel. Overall survival was estimated using the Kaplan-Meier method. Intergroup differences were assessed using the log-rank test. A univariate and multivariate Cox regression model was performed to investigate variables associated with poor survival after rDP. Results: A total of 1323 patients within the registry experienced rDP between 2011 and 2021, including 220 (16.6%) men with rDP occurring at low PSA level. A median (interquartile range [IQR]) of 54.7 (19.7-106.9) months elapsed between the time of prostate cancer diagnosis and low PSA rDP, during which 173 patients (78%) developed castration-resistant prostate cancer (CRPC). Sites of low PSA rDP included local recurrence (n = 17, 8%), lymph node (n = 90, 41%), bone (n = 94, 43%) and visceral metastases (n = 19, 9%). Biopsy at the time of rDP demonstrated small-cell or neuroendocrine features in 21% of patients with available tissue. Over a median (IQR) follow-up of 49.4 (21.3-95.1) months from the time of low PSA rDP, 46% (n = 102) of patients died. Factors associated with poorer survival outcomes include advanced age at rDP, CRPC status, bone and visceral metastasis (p value <0.05). Visceral metastases were associated with decreased overall survival (p = 0.009 by log-rank) as compared with other sites of rDP. Conclusions: Men with prostate cancer commonly experience metastatic progression at very low or even undetectable PSA levels. Periodic imaging, even at low absolute PSA values, may result in more timely identification of disease progression.

Prostate Cancer Lung Metastasis: Clinical Insights and Therapeutic Strategies.

Prostate cancer lung metastasis represents a clinical conundrum due to its implications for advanced disease progression and the complexities it introduces in treatment planning. As the disease progresses to distant sites such as the lung, the clinical management becomes increasingly intricate, requiring tailored therapeutic strategies to address the unique characteristics of metastatic lesions. This review seeks to synthesize the current state of knowledge surrounding prostate cancer metastasis to the lung, shedding light on the diverse array of clinical presentations encountered, ranging from subtle radiological findings to overt symptomatic manifestations. By examining the diagnostic modalities utilized in identifying this metastasis, including advanced imaging techniques and histopathological analyses, this review aims to provide insights into the diagnostic landscape and the challenges associated with accurately characterizing lung metastatic lesions in prostate cancer patients. Moreover, this review delves into the nuances of therapeutic interventions employed in managing prostate cancer lung metastasis, encompassing systemic treatments such as hormonal therapies and chemotherapy, as well as metastasis-directed therapies including surgery and radiotherapy.

Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going.

Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([177Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [177Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies. Further, the drug development pipeline is deep with variations of PSMA-targeting radionuclides, including higher energy alpha particles conjugated to PSMA-honing vectors. It is safe to assume that an increasing number of patients will be exposed to PSMA-targeted radiopharmaceuticals during the course of their cancer treatment. In this setting, it is important to better understand and mitigate the most commonly encountered toxicities. One particularly vexing side effect is xerostomia. In this review, we discuss the scope of the problem, inventories to better characterize and monitor this troublesome side effect, and approaches to preserve salivary function and effectively palliate symptoms. This article aims to serve as a useful reference for prescribers of PSMA-targeted radiopharmaceuticals, while also commenting on areas of missing data and opportunities for future research.

Optical isolation with epsilon-near-zero metamaterials.

We suggest a principle for isolation of circularly polarized waves in magnetically active extreme-parameter metamaterials. Using theoretical analysis and numerical simulations, we show that metamaterials with extreme parameters, such as epsilon-near-zero materials (ENZ), when merged with magneto-optical materials, become transparent for forward circularly polarized waves of a given handedness and opaque for backward propagating waves of the same handedness. We theoretically study two possible implementations of such hybrid materials: (1) the case of metal-dielectric stacks; and (2) rectangular waveguide near its cut-off frequency. We prove that these structures can be utilized as compact isolators for circularly polarized waves.

Dynamic Translational Landscape Revealed by Genome-Wide Ribosome Profiling under Drought and Heat Stress in Potato.

The yield and quality of potatoes, an important staple crop, are seriously threatened by high temperature and drought stress. In order to deal with this adverse environment, plants have evolved a series of response mechanisms. However, the molecular mechanism of potato's response to environmental changes at the translational level is still unclear. In this study, we performed transcriptome- and ribosome-profiling assays with potato seedlings growing under normal, drought, and high-temperature conditions to reveal the dynamic translational landscapes for the first time. The translational efficiency was significantly affected by drought and heat stress in potato. A relatively high correlation (0.88 and 0.82 for drought and heat stress, respectively) of the fold changes of gene expression was observed between the transcriptional level and translational level globally based on the ribosome-profiling and RNA-seq data. However, only 41.58% and 27.69% of the different expressed genes were shared by transcription and translation in drought and heat stress, respectively, suggesting that the transcription or translation process can be changed independently. In total, the translational efficiency of 151 (83 and 68 for drought and heat, respectively) genes was significantly changed. In addition, sequence features, including GC content, sequence length, and normalized minimal free energy, significantly affected the translational efficiencies of genes. In addition, 28,490 upstream open reading frames (uORFs) were detected on 6463 genes, with an average of 4.4 uORFs per gene and a median length of 100 bp. These uORFs significantly affected the translational efficiency of downstream major open reading frames (mORFs). These results provide new information and directions for analyzing the molecular regulatory network of potato seedlings in response to drought and heat stress.

Early PSA decline after starting second-generation hormone therapy in the post-docetaxel setting predicts cancer-specific survival in metastatic castrate-resistant prostate cancer.

BACKGROUND: The objective of this study was to evaluate the prognostic value of early PSA decline following initiation of second-generation hormone therapy (2nd HT), namely abiraterone acetate or enzalutamide, in patients with taxane-refractory metastatic castrate-resistant prostate cancer (mCRPC) and evaluate utility of this metric in informing intensified surveillance/imaging protocols. METHODS: We retrospectively identified 75 mCRPC patients treated with 2nd HT following docetaxel failure (defined as PSA rise and radiographic progression). Patients were categorized patients into two cohorts based on the first PSA within 3 months after initiation of therapy: PSA reduction ≥50% (Group A) and PSA reduction <50% (Group B). The primary endpoint was cancer-specific mortality (CSM). The secondary endpoint was radiographic disease progression (rDP) on 2nd HT. In univariate and multivariate analyses, we investigated factors associated with rPD and CSM. RESULTS: We included 75 patients (52 in Group A, 23 in Group B) in the analytic cohort. Baseline clinico-demographic characteristics, including median age, primary Gleason score risk group, median pre-treatment PSA, disease burden, site of metastases, and pre-treatment ECOG score were not statistically different between the two groups. Median follow up time was 30 months and the median time to radiographic disease progression was 28.1 and 12.5 months (p = 0.002) in cohorts A and B, respectively. On univariate and multivariate analyses, both PSA reduction ≥50% and volume of metastatic disease were significantly associated with a decreased risk of radiographic disease progression (HR 0.41, 95% CI 0.21-0.80, p = 0.0113) as well as a decreased risk of cancer-specific mortality (HR 0.29, 95% CI 0.09-0.87, p = 0.0325). CONCLUSION: PSA reduction ≥50% within 3 months of starting 2nd HT was associated with significantly improved radiographic disease progression-free survival and 3-year cancer-specific mortality. This suggests using PSA 50%-decline metric in surveillance patients with on 2nd HT and identifies patients who require further evaluation with imaging.

Cytological karyotyping and characterization of a 410 kb minichromosome in Nectria haematococca MPI.

Karyotypes of the cucurbit pathogen Nectria haematococca MPI (anamorph Fusarium solani f. sp. cucurbitae race 1) was studied using the two standard strains ATCC18098 and ATCC18099. Complete separation of all chromosomes was difficult with pulsed field gel electrophoresis due to both the large size and co-migration of chromosomes. In contrast, cytological karyotyping was done successfully with fluorescence microscopy combined with the germ tube burst method for sample preparation to visualize mitotic metaphase chromosomes. For each strain the basic chromosome number (CN) was nine, which revises previous chromosome estimates of n = 4. Chromosomes were morphologically characterized by their sizes, intensely fluorescing segments, and protrusion of rDNA. In addition to the basic chromosome complement, ATCC18098 had a mini-chromosome of ~410 kb present as a single copy in somatic nuclei. Chromosome fluorescence in situ hybridization indicated that this mini-chromosome is not a derivative from the other chromosomes in the genome. In addition, crossing experiments suggested that it was transmitted in a Mendelian manner to the ascospore progeny.

Template-based balloon-marker and guidewire detection for coronary stents in cardiac fluoroscopy.

The placement and visualization of coronary stents during fluoroscopy depends mainly on the detection of balloon markers and their connecting guidewires. In this paper, a novel template-based approach is proposed to detect balloon markers and guidewires in cardiac fluoroscopic images. In particular, guidewires are detected based on balloon markers only, without prior knowledge of the background or guidewire elements. Also, while earlier techniques used circular models of balloon markers, we propose a more realistic elliptical model. Training and the testing datasets for balloon marker and guidewire detection were collected from different Cathlab systems and annotated by an application specialist with 10 years of experience in this field. The balloon-marker detector achieved a precision of 98.5%. Within 3-pixel tolerance, the guidewire detector achieved a matching percentage of 99.5% with the true guidewire using a customized evaluation method. Moreover, the guidewire detector achieved a mean Hausdorff distance of 3.3 pixels (0.6 mm) and a longest-common-substring (LCS) distance with a mean matching percentage of 87% within 1-pixel tolerance. Clinical Relevance- The proposed novel technique of detecting the guidewire offers a constant computational time and insensitivity to the body structures or the guidewire-like elements (such as the surgical wires). This leads to improved stent visualization and reasonable processing times.

Novel silicon bipodal cylinders with controlled resonances and their use as beam steering metasurfaces.

Metasurfaces have paved the way for high performance wavefront shaping and beam steering applications. Phase-gradient metasurfaces (PGM) are of high importance owing to the powerful and relatively systematic tool they offer for manipulating electromagnetic wave fronts and achieving various functionalities. Herein, we numerically present a novel unit cell known as bipodal cylinders (BPC), made of Silicon (Si) and placed on a Silicon dioxide (SiO2) substrate to be compatible with CMOS fabrication techniques and to avoid field leakage into a high index substrate. Owing to its geometrical structure, the BPC structure provides a promising unit cell for electromagnetic wave manipulation. We show that BPC offers a way to shift the electric dipole mode to a frequency higher than that of the magnetic dipole mode. We investigate the effect of varying different geometrical parameters on the performance of such unit cell. Building on that, a metasurface is then presented that can achieve efficient electromagnetic beam steering with high transmission of 0.84 and steering angle of 15.2°; with very good agreement with the theoretically predicted angle covering the whole phase range from 0 to 2[Formula: see text].