miR-371a-3p Predicting Viable Tumor in Patients Undergoing Retroperitoneal Lymph Node Dissection for Metastatic Testicular Cancer: The SWENOTECA-MIR Study.

PURPOSE: The SWENOTECA-MIR prospective multicenter study aims to assess the clinical value of miR-371a-3p as a novel marker in metastatic germ cell tumor patients undergoing retroperitoneal lymph node dissection (RPLND), to predict the presence of viable residual tumor. MATERIALS AND METHODS: A total of 114 patients (86 nonseminomas, 28 seminomas) who underwent surgery for presumed metastatic disease pre chemotherapy (primary RPLND) and post chemotherapy RPLND were included. The expression of miR-371a-3p was evaluated using reverse transcription-digital droplet polymerase chain reaction before and after RPLND. Pre- and postoperative miR-371a-3p levels were statistically compared, and optimism-corrected performance calculations compared with conventional serum tumor markers. Associations were evaluated by logistic regression. Patients who underwent primary RPLND were categorized into seminoma and nonseminoma groups. RESULTS: Among the seminoma patients (n = 24) undergoing primary RPLND, all had normal conventional markers. Six patients received adjuvant treatment before surgery. miR-371a-3p exhibited a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 21% for viable tumor. The levels of miR-371a-3p significantly decreased after surgery. In the nonseminoma group (n = 18) treated with primary RPLND, 22% had elevated conventional markers and 3 had received prior adjuvant treatment. miR-371a-3p showed a sensitivity of 34%, specificity of 88%, positive predictive value of 67%, and negative predictive value of 62% for the primary nonseminoma patients. No association was observed between stage or prior adjuvant treatment and the outcome of the miR test. In the postchemotherapy group (n = 72), the miR-371a-3p sensitivity was 9%, reducing to 0 when excluding patients with seminoma (n = 4). Teratomas and benign histology were essentially negative. CONCLUSIONS: Our study highlights miR-371a-3p as a fairly sensitive and highly specific marker for prechemotherapy seminomas, outperforming conventional markers. However, in prechemotherapy nonseminomas as well as in postchemotherapy patients, we observed low sensitivity and no significant differences in miR-371a-3p levels before and after surgery, suggesting limited utility for miR-371a-3p in this context.

Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988-1989 (n = 52) and during follow-up (median 22.6 years) (n = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.

Serum thymidine kinase 1 concentration as a predictive biomarker in prostate cancer.

BACKGROUND: Thymidine kinase 1 (TK1) recycles DNA before cell division. We do not know if baseline blood concentrations of TK1 predict death in prostate cancer within 30 years. Our objective is to determine if there is an association between baseline levels of TK1 and future prostate cancer-specific mortality. METHODS: With a "proof of concept" approach, we performed a nested case-control study among 1782 individuals screened for prostate cancer between 1988 and 1989. The concentration of TK1 was measured in frozen serum from 330 men, 36 of whom have died of prostate cancer. The primary endpoint was prostate cancer-specific mortality and outcomes after 30 years were analyzed using logistic regression modeling odds ratios (Ors). RESULTS: The estimated OR (adjusted for age) for dying from prostate cancer among the men who had a TK1 value in the upper tertile was 2.39 (95% confidence interval 1.02-5.63). The corresponding OR, regardless of the cause of death, was 2.81 (1.24-6.34). CONCLUSIONS: High levels of TK1 predicts death in prostate cancer within 30 years of follow-up.

Association between one-time prostate-specific antigen (PSA) test with free/total PSA ratio and prostate cancer mortality: A 30-year prospective cohort study.

OBJECTIVES: To explore if there is a long-term association between baseline prostate-specific antigen (PSA), including free/total PSA ratio and long-term (30-year) risk for prostate cancer death. SUBJECTS AND METHODS: In all, 1782 men were screened for prostate cancer through PSA analysis. Some years later, frozen plasma samples were used to calculate the ratio of free to total PSA (f/t PSA). At 30-year follow-up, baseline PSA and f/t PSA were compared with recent data extracts from the Swedish Cause of Death Registry and Swedish Cancer Registry. PSA values and f/t PSA values were treated as continuous variables in a multivariable analysis and also stratified according to their distribution and useful clinical thresholds. RESULTS: Risk of death from prostate cancer after 30 years of follow-up was significantly increased with a higher baseline PSA level, with the hazard ratio being 1.04 (95% confidence interval 1.03-1.09) per increase of one unit of PSA. Adding f/t PSA increased the model's ability to discriminate (concordance index 0.84-0.88). Men with PSA levels <1.0 ng/mL had a very low long-term risk of prostate cancer death (1.2% risk). An f/t PSA ≥ 0.25 extended the low-risk range to PSA < 2.0 ng/mL (1.5% risk). CONCLUSION: Prostate-specific antigen testing can be carried out less frequently or can be discontinued in men aged 55-70 years if their PSA levels are <2.0 ng/mL and the f/t PSA is ≥0.25.

Association between dihydrotestosterone and long-term risk for prostate cancer mortality: A prospective cohort study.

BACKGROUND: The androgen metabolism plays an important role in the progression of prostate cancer. Contradictory to what one might assume given the androgenic potency of dihydrotestosterone (DHT) there are indications that high DHT levels protect from prostate cancer. We want to determine whether there is a long-term association between baseline levels of DHT and death from prostate cancer. METHOD: During the years 1988 and 1989, 1782 men out of 2400 invited were screened for prostate cancer. The invited men were randomly selected from a background population of more than 27 000 men. Serum levels of DHT were analyzed for all 65 men diagnosed in the trial and 130 controls from the same cohort without any signs of prostate cancer. In this study we evaluate outcomes for the whole cohort (n = 195), the men without clinical signs of prostate cancer at beginning of follow up (n = 130) and men with screening detected cancer (n = 65). The cohort was followed up after 30 years and data from the Swedish Cause of Death Registry and the Swedish Cancer Registry were extracted. Hazard ratios (HRs) were calculated using Cox regression models. RESULT: High DHT levels were positively correlated to a lower risk for prostate cancer death in the entire cohort: HR = 0.44 (0.25-0.77 95% confidence interval [CI]). The positive correlation remained significant for the subgroup analysis. HR for the men enrolled in the study without any clinical signs of prostate cancer was 0.25 (0.07-0.88 95% CI) and for the men with a prostate cancer diagnosis at time of inclusion: HR = 0.50 (0.26-0.94 95% CI). CONCLUSION: DHT is negatively associated with long-term prostate cancer death regardless of clinical presentation at time of inclusion.

Maintaining Transparency of a Heated MEMS Membrane for Enabling Long-Term Optical Measurements on Soot-Containing Exhaust Gas.

Ensuring optical transparency over a wide spectral range of a window with a view into the tailpipe of the combustion engine, while it is exposed to the harsh environment of soot-containing exhaust gas, is an essential pre-requisite for introducing optical techniques for long-term monitoring of automotive emissions. Therefore, a regenerable window composed of an optically transparent polysilicon-carbide membrane with a diameter ranging from 100 µm up to 2000 µm has been fabricated in microelectromechanical systems (MEMS) technology. In the first operating mode, window transparency is periodically restored by pulsed heating of the membrane using an integrated resistor for heating to temperatures that result in oxidation of deposited soot (600-700 °C). In the second mode, the membrane is kept transparent by repelling soot particles using thermophoresis. The same integrated resistor is used to yield a temperature gradient by continuous moderate-temperature heating. Realized devices have been subjected to laboratory soot exposure experiments. Membrane temperatures exceeding 500 °C have been achieved without damage to the membrane. Moreover, heating of membranes to ΔT = 40 °C above gas temperature provides sufficient thermophoretic repulsion to prevent particle deposition and maintain transparency at high soot exposure, while non-heated identical membranes on the same die and at the same exposure are heavily contaminated.

Carbon-Based Electrode Materials for Microsupercapacitors in Self-Powering Sensor Networks: Present and Future Development.

There is an urgent need to fulfill future energy demands for micro and nanoelectronics. This work outlines a number of important design features for carbon-based microsupercapacitors, which enhance both their performance and integration potential and are critical for complimentary metal oxide semiconductor (CMOS) compatibility. Based on these design features, we present CMOS-compatible, graphene-based microsupercapacitors that can be integrated at the back end of the line of the integrated circuit fabrication. Electrode materials and their interfaces play a crucial role for the device characteristics. As such, different carbon-based materials are discussed and the importance of careful design of current collector/electrode interfaces is emphasized. Electrode adhesion is an important factor to improve device performance and uniformity. Additionally, doping of the electrodes can greatly improve the energy density of the devices. As microsupercapacitors are engineered for targeted applications, device scaling is critically important, and we present the first steps toward general scaling trends. Last, we outline a potential future integration scheme for a complete microsystem on a chip, containing sensors, logic, power generation, power management, and power storage. Such a system would be self-powering.

Long-Term Outcome of a Single Intervention Population Based Prostate Cancer Screening Study.

PURPOSE: We evaluated the long-term effect of screening for prostate cancer. MATERIALS AND METHODS: In 1988 we randomly selected 2,400 men from a background population of 27,464 men. The 2,400 men were invited to undergo screening, of whom 1,779 (74%) accepted and were examined with digital rectal examination, ultrasound and prostate specific antigen measurement. Biopsy was performed if there were suspicious findings on ultrasound or digital rectal examination, or prostate specific antigen was greater than 10 ng/ml. The subpopulations have now been reassessed after 20 years. RESULTS: Participants had a decreased overall mortality rate compared to the source population (IRR 0.93, 95% CI 0.86-0.98). Nonparticipants had an increased overall mortality rate (IRR 1.25, 95% CI 1.14-1.37). There was no difference between the groups in prostate cancer specific survival. The incidence of prostate cancer remained higher in the screened population throughout followup. CONCLUSIONS: A single screening intervention in men 50 to 75 years old using prostate specific antigen, digital rectal examination and transrectal ultrasound, and a prostate specific antigen cutoff of 10 ng/ml for biopsy carried a significant risk of prostate cancer detection without a concomitant reduction in prostate cancer specific mortality after 20 years. This intervention should not be considered for public screening. Nonparticipants were at greater risk for death of all causes. In addition to being a single intervention trial, the limitations of this study include an outdated prostate specific antigen cutoff for biopsy. Despite the outdated screening method the source population failed to reach the same level of prostate cancer incidence as the screened population even after 20 years.

Influence of Hardwood Lignin Blending on the Electrical and Mechanical Properties of Cellulose Based Carbon Fibers.

Carbon fibers (CFs) are fabricated by blending hardwood kraft lignin (HKL) and cellulose. Various compositions of HKL and cellulose in blended solutions are air-gap spun in 1-ethyl-3-methylimidazolium acetate (EMIM OAc), resulting in the production of virtually bead-free quality fibers. The synthesized HKL-cellulose fibers are thermostabilized and carbonized to achieve CFs, and consequently their electrical and mechanical properties are evaluated. Remarkably, fibers with the highest lignin content (65%) exhibited an electrical conductivity of approximately 42 S/cm, surpassing that of cellulose (approximately 15 S/cm). Moreover, the same fibers demonstrated significantly improved tensile strength (∼312 MPa), showcasing a 5-fold increase compared to pure cellulose while maintaining lower stiffness. Comprehensive analyses, including Auger electron spectroscopy and wide-angle X-ray scattering, show a heterogeneous skin-core morphology in the fibers revealing a higher degree of preferred orientation of carbon components in the skin compared to the core. The incorporation of lignin in CFs leads to increased graphitization, enhanced tensile strength, and a unique skin-core structure, where the skin's graphitized cellulose and lignin contribute stiffness, while the predominantly lignin-rich core enhances carbon content, electrical conductivity, and strength.