HER2 Low Expression in Primary Male Breast Cancer.

Purpose: The introduction of HER2-targeting antibody drug conjugates (ADCs) offers new treatment options for female breast cancer patients (FBC) expressing low levels of HER2 (HER2 low). No evidence was found that HER2 low describes a new FBC subtype. There is a lack of studies determining the impact of HER2 low in male breast cancer (MBC). In this study, we evaluate the prevalence of HER2 low in primary MBC and correlate the results with patient characteristics. Patients and Methods: In this study, histological specimens were obtained from 120 male patients diagnosed and treated for primary invasive breast cancer from 1995 to 2022 at Breast Cancer Units in Bergisch Gladbach, Chemnitz, and Zwickau, Germany. HER2 immunostaining and in situ hybridization were performed by central pathology and evaluated based on the ASCO/CAP guidelines. The correlation of expression of HER2 low with tumor biological characteristics and patient outcomes was investigated. Results: Out of all cases, four patients (3.3%) showed HER2 positivity (3+), 39 (32.5%) patients were classified as HER2 low, 7 (5.8%) were HER2 2+ (no amplification), 32 (26.7%) were HER2 1+, and 77 (64.2%) were classified as HER2 zero. Out of 77 HER2 zero cases, 47 tumors (61.0%) showed incomplete staining, with <10% of tumor cells classified as HER2 ultralow. No statistical correlation between HER2 low and tumor biological characteristics and patients' survival was found. Conclusion: Our findings show a notable, albeit lower, prevalence of HER2 low expression in primary MBC. However, tumors expressing HER2 low do not show specific tumor biological features to define a new breast cancer subtype in MBC. Our results suggest that a significant number of MBC patients could benefit from ADCs, as shown in FBC. Further studies are required to better understand HER2 low breast cancer, both generally and in MBC.

Dose-intensified stereotactic body radiotherapy for painful vertebral metastases: A randomized phase 3 trial.

BACKGROUND: The purpose of this randomised study was to determine whether dose-intensified stereotactic body radiotherapy (SBRT) for painful vertebral metastases results in increased rates of pain improvement compared with conventional external beam radiotherapy (cEBRT) (control) 6 months after treatment. METHODS: This randomized, controlled phase 3 trial was conducted between November 2016 and January 2023, when it was stopped early. Patients were eligible if they were aged 18 years or older; had one or two painful, stable, or potentially unstable vertebral metastases; and had a life expectancy of 1 year or longer according to the investigator's estimates. Patients received 48.5 grays (Gy) in 10 fractions (with epidural involvement) or 40 Gy in five fractions (without epidural involvement) in the SBRT group and 30 Gy in 10 fractions or 20 Gy in five fractions in the cEBRT group, respectively. The primary end point was an improvement in the pain score at the treated site by at least 2 points (on a visual analog scale from 0 to 10 points) at 6-month follow-up. Data were analyzed on an intention-to-treat and per-protocol basis. RESULTS: Of 214 patients who were screened for eligibility, 63 were randomized 1:1 between SBRT (33 patients with 36 metastases) and cEBRT (30 patients with 31 metastases). The median age of all patients was 66 years, and 40 patients were men (63.5%). In the intention-to-treat analysis, the 6-month proportion of patients who had metastases with pain reduction by 2 or more points was significantly higher in the SBRT group versus the control group (69.4% vs. 41.9%, respectively; two-sided p = .02). Changes in opioid medication intake relative to baseline were nonsignificant between the groups. No differences were observed in vertebral compression fracture or adverse event rates between the groups. CONCLUSIONS: Dose-intensified SBRT improved pain score more effectively than cEBRT at 6 months.

Converting between the International Prostate Symptom Score (IPSS) and the Expanded Prostate Cancer Index Composite (EPIC) urinary subscales: modeling and external validation.

BACKGROUND: Prostate-related quality of life can be assessed with a variety of different questionnaires. The 50-item Expanded Prostate Cancer Index Composite (EPIC) and the International Prostate Symptom Score (IPSS) are two widely used options. The goal of this study was, therefore, to develop and validate a model that is able to convert between the EPIC and the IPSS to enable comparisons across different studies. METHODS: Three hundred forty-seven consecutive patients who had previously received radiotherapy and surgery for prostate cancer at two institutions in Switzerland and Germany were contacted via mail and instructed to complete both questionnaires. The Swiss cohort was used to train and internally validate different machine learning models using fourfold cross-validation. The German cohort was used for external validation. RESULTS: Converting between the EPIC Urinary Irritative/Obstructive subscale and the IPSS using linear regressions resulted in mean absolute errors (MAEs) of 3.88 and 6.12, which is below the respective previously published minimal important differences (MIDs) of 5.2 and 10 points. Converting between the EPIC Urinary Summary and the IPSS was less accurate with MAEs of 5.13 and 10.45, similar to the MIDs. More complex model architectures did not result in improved performance in this study. The study was limited to the German versions of the respective questionnaires. CONCLUSIONS: Linear regressions can be used to convert between the IPSS and the EPIC Urinary subscales. While the equations obtained in this study can be used to compare results across clinical trials, they should not be used to inform clinical decision-making in individual patients. TRIAL REGISTRATION: This study was retrospectively registered on clinicaltrials.gov on January 14th, 2022, under the registration number NCT05192876.

Mechanisms of SARS-CoV-2 Inactivation Using UVC Laser Radiation.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) has had a tremendous impact on humanity. Prevention of transmission by disinfection of surfaces and aerosols through a chemical-free method is highly desirable. Ultraviolet C (UVC) light is uniquely positioned to achieve inactivation of pathogens. We report the inactivation of SARS-CoV-2 virus by UVC radiation and explore its mechanisms. A dose of 50 mJ/cm2 using a UVC laser at 266 nm achieved an inactivation efficiency of 99.89%, while infectious virions were undetectable at 75 mJ/cm2 indicating >99.99% inactivation. Infection by SARS-CoV-2 involves viral entry mediated by the spike glycoprotein (S), and viral reproduction, reliant on translation of its genome. We demonstrate that UVC radiation damages ribonucleic acid (RNA) and provide in-depth characterization of UVC-induced damage of the S protein. We find that UVC severely impacts SARS-CoV- 2 spike protein's ability to bind human angiotensin-converting enzyme 2 (hACE2) and this correlates with loss of native protein conformation and aromatic amino acid integrity. This report has important implications for the design and development of rapid and effective disinfection systems against the SARS-CoV-2 virus and other pathogens.

Five Fractions versus Seven Fractions SBRT for Intermediate- and High-Risk Prostate Cancer: A Propensity Score Matched Pair Analysis.

PURPOSE: To compare two stereotactic body radiotherapy (SBRT) regimens in patients with intermediate- or high-risk prostate cancer with regards toxicity and efficacy. METHODS/MATERIAL: We retrospectively collected data from 198 patients treated with SBRT for prostate cancer at two different institutions. Patients received either 35-36.25 Gy in five fractions (group A) using Cyberknife robotic platform or 42.7 Gy in seven fractions (group B) using a C-arm LINAC (image-guided). Propensity score matching was done (2:1 nearest neighbor matching without replacement), resulting in 120 patients (80 patients for group A, 40 patients for group B). Toxicity, PSA nadir, biochemical failure and disease-free survival (DFS) were analyzed. RESULTS: Median follow up of all patients was 13 months (range 1-91 months). Overall, 23.3% of patients had ≥G2 acute GU toxicity (21.1% group A versus 30% group B (p = 0.222)) and 6.6% of patients ≥G2 GI toxicity (2.5% versus 15% (p = 0.010)). There was one acute G3 GU toxicity in arm A and one acute G4 rectal bleeding in group B (anticoagulated patient). Regarding late toxicity, 14.1% of patients had ≥G2 late GU toxicity (17.4% versus 6.6% (p = 0.159)) and 5.0% of patients had ≥G2 late GI toxicity (1.4% versus 13.3% (p = 0.013)). There was one G3 late GU toxicity in arm B and two G3 late GI toxicities, one in each arm. Relative median PSA reduction was 92.4% (-53.9-99.9%) from baseline PSA (93.7% (-53.9-99.9%) in group A versus 87.7% (39.8-99.9%) in group B (p = 0.043). In total, 4.2% of patients had biochemical relapse, 5.0% in group A and 2.5% in group B (p = 0.518). One-year DFS in the overall cohort was 97.3%, 98.8% in group A and 94.3% in group B (p = 0.318). CONCLUSION: Both SBRT regimens have acceptable acute and late toxicity and good efficacy. There are significantly more GI toxicities in the seven-fraction regimen. Longer follow-up is warranted for better comparison of long-term efficacy.

Re-irradiation for head and neck cancer: outcome and toxicity analysis using a prospective single institution database.

Purpose: Re-irradiation (re-RT) in head and neck cancer is challenging. This study prospectively explored the feasibility of re-RT in patients with loco-regionally recurrent or second primary head and neck cancer (LRR/SP HNC). Methods: From 2004 to 2021, 61 LRR/SP HNC patients were treated with re-RT, defined as having a second course of RT with curative intent resulting in a cumulative dose of ≥100 Gy in an overlapping volume. Postoperative or definitive dynamic intensity-modulated and/or volumetric modulated re-RT was administered using twice daily hyperfractionation to 60 Gy combined with cisplatin or carboplatin/5-fluorouracil. Overall survival (OS), progression-free survival (PFS), locoregional control (LRC) and distant metastasis control (DMC) were analyzed and prognostic factors evaluated. Toxicity was prospectively recorded and graded. Results: The median follow-up was 9.8 months. In 41 patients (67.1%), complete administration of the intended treatment was not feasible. In 9 patients (15%) re-RT was interrupted prematurely and in other 9, the complete re-RT dose was lower than 60 Gy, and 37 patients (61%) could not receive or complete chemotherapy. Two-year OS, PFS and LRC rates were 19%, 18% and 30%, respectively. 20 patients (33%) received the complete intended treatment, and 1- and 2-year OS rates were 70% and 47%, respectively. Charlson comorbidity index was an important predictor for treatment completion. Multivariate analysis revealed recurrent N stage 0-1, age, chemotherapy administration and re-RT dose of 60 Gy as prognostic factors for clinical outcomes. No grade 5 re-RT-related toxicity was observed. The most common new grade ≥3 acute toxicities were dysphagia (52%) and mucositis (46%). Late toxicity included grade ≥3 dysphagia in 5% and osteoradionecrosis in 10% of evaluable patients, respectively. 6 patients (10%) were alive after 9 years without progression and no late toxicity grade ≥3, except for 2 patients presenting with osteoradionecrosis. Conclusion: Hyperfractionated re-RT with 60 Gy combined with platinum-based chemotherapy was a curative treatment option with acceptable toxicity in LRR/SP patients. Patients with higher comorbidity had a higher probability of failing to receive and complete the intended therapy. Consequently, they derived unsatisfactory benefits from re-RT, highlighting the importance of patient selection.

Dose-Volume Histogram Parameters and Quality of Life in Patients with Prostate Cancer Treated with Surgery and High-Dose Volumetric-Intensity-Modulated Arc Therapy to the Prostate Bed.

INTRODUCTION: Prostate bed radiotherapy (RT) is a major affecter of patients' long-term quality of life (QoL). To ensure the best possible outcome of these patients, dose constraints are key for optimal RT planning and delivery. However, establishing refined dose constraints requires access to patient-level data. Therefore, we aimed to provide such data on the relationship between OAR and gastrointestinal (GI) as well as genitourinary (GU) QoL outcomes of a homogenous patient cohort who received dose-intensified post-operative RT to the prostate bed. Furthermore, we aimed to conduct an exploratory analysis of the resulting data. METHODS: Patients who were treated with prostate bed RT between 2010 and 2020 were inquired about their QoL based on the Expanded Prostate Cancer Index Composite (EPIC). Those (n = 99) who received volumetric arc therapy (VMAT) of at least 70 Gy to the prostate bed were included. Dose-volume histogram (DVH) parameters were gathered and correlated with the EPIC scores. RESULTS: The median age at the time of prostate bed RT was 68.9 years, and patients were inquired about their QoL in the median 2.3 years after RT. The median pre-RT prostate-specific antigen (PSA) serum level was 0.35 ng/mL. The median duration between surgery and RT was 1.5 years. The median prescribed dose to the prostate bed was 72 Gy. A total of 61.6% received prostate bed RT only. For the bladder, the highest level of statistical correlation (p < 0.01) was seen for V10-20Gy, Dmean and Dmedian with urinary QoL. For bladder wall, the highest level of statistically significant correlation (p < 0.01) was seen for V5-25Gy, Dmean and Dmedian with urinary QoL. Penile bulb V70Gy was statistically significantly correlated with sexual QoL (p < 0.05). A larger rectal volume was significantly correlated with improved bowel QoL (p < 0.05). Sigmoid and urethral DVH parameters as well as the surgical approach were not statistically significantly correlated with QoL. CONCLUSION: Specific dose constraints for bladder volumes receiving low doses seem desirable for the further optimization of prostate bed RT. This may be particularly relevant in the context of the aspiration of establishing focal RT of prostate cancer and its local recurrences. Our comprehensive dataset may aid future researchers in achieving these goals.

Orally compensated short bowel patients are thin, potentially malnourished but rarely sarcopenic.

BACKGROUND AND AIM: In short bowel syndrome, insufficient absorptive capacity of the remnant bowel may lead to metabolic and nutritional consequences including electrolyte disturbances, severe diarrhea and malnutrition. While intestinal failure requires parenteral nutrition, short bowel patients with intestinal insufficiency (SB/II) have achieved oral autonomy. The aim of this exploratory study was to assess the nutritional, muscular and functional status of orally compensated SB/II patients. METHODS: 28 orally compensated SB/II patients with a mean of 46 months after termination of parenteral nutrition and 56 age- and sex-matched healthy controls (HC) were compared regarding anthropometric parameters, body composition using bioelectrical impedance analysis, handgrip strength and gait speed, blood parameters as well as nutritional intake and physical activity using validated questionnaires. Malnutrition and sarcopenia were diagnosed according to the criteria of the GLIM or EWGSOP2. RESULTS: SB/II patients had lower body mass index (BMI) and anthropometric parameters than HC but were within the normal weight range. The GLIM algorithm operationally diagnosed malnutrition in 39% (n = 11) of SB/II patients. Reduced skeletal muscle mass index and phase angle were rarely accompanied by a reduction of handgrip strength below cut-off values and the subsequent diagnosis of sarcopenia in SB/II patients (15%, n = 4). Compared to 11% of HC, 37% of SB/II patients had low physical activity level. Female SB/II patients had higher caloric and macronutrient intake. Caloric intake negatively correlated with body weight indicating compensatory hyperphagia in patients with lower body weight. Some of the SB/II patients showed signs of dehydration. CONCLUSIONS: Orally compensated SB/II patients are thinner than HC but have mostly normal BMI. Malnutrition is frequently diagnosed but may be overestimated due to the underlying malabsorption and its interplay with hyperphagia. Muscle mass is often reduced but is rarely accompanied by functional impairment leading to sarcopenia diagnosis. Thus, SB/II patients long term after termination of parenteral support may be malnourished but usually do not develop sarcopenia.

The Apple Watch spO2 sensor and outliers in healthy users.

It is unclear how frequently the Apple Watch produces spO2 measurements outside of the normal range in healthy individuals at rest. We conducted a head-to-head comparison in 38 healthy individuals between two watches and two medical-grade pulse oximeters. Fourteen percent of watch measurements yielded spO2 values below 95%, with no values below 92%. Results suggest that outliers measured by the watch should not be a cause for concern in otherwise healthy individuals.

Accuracy of the Apple Watch Oxygen Saturation Measurement in Adults: A Systematic Review.

The purpose of this review is to summarize the research on the accuracy of oxygen saturation (spO2) measurements using the Apple Watch (Apple Inc., Cupertino, California). The Medline and Google Scholar databases were searched for papers evaluating the spO2 measurements of the Apple Watch vs. any kind of ground truth and records were analyzed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The five publications with 973 total patients that met the inclusion criteria all used the Apple Watch Series 6 and described 95% limits of agreement of +/- 2.7 to 5.9% spO2. However, outliers of up to 15% spO2 were reported. Only one study had patient-level data uploaded to a public repository. The Apple Watch Series 6 does not show a strong systematic bias compared to conventional, medical-grade pulse oximeters. However, outliers do occur and should not cause concern in otherwise healthy individuals. The impact of race on measurement accuracy should be investigated.

Applications of Machine Learning in Palliative Care: A Systematic Review.

Objective: To summarize the available literature on using machine learning (ML) for palliative care practice as well as research and to assess the adherence of the published studies to the most important ML best practices. Methods: The MEDLINE database was searched for the use of ML in palliative care practice or research, and the records were screened according to PRISMA guidelines. Results: In total, 22 publications using machine learning for mortality prediction (n = 15), data annotation (n = 5), predicting morbidity under palliative therapy (n = 1), and predicting response to palliative therapy (n = 1) were included. Publications used a variety of supervised or unsupervised models, but mostly tree-based classifiers and neural networks. Two publications had code uploaded to a public repository, and one publication uploaded the dataset. Conclusions: Machine learning in palliative care is mainly used to predict mortality. Similarly to other applications of ML, external test sets and prospective validations are the exception.

3D Fabrication and Characterisation of Electrically Receptive PCL-Graphene Scaffolds for Bioengineered In Vitro Tissue Models.

Polycaprolactone (PCL) is a well-established biomaterial, offering extensive mechanical attributes along with low cost, biocompatibility, and biodegradability; however, it lacks hydrophilicity, bioactivity, and electrical conductivity. Advances in 3D fabrication technologies allow for these sought-after attributes to be incorporated into the scaffolds during fabrication. In this study, solvent-free Fused Deposition Modelling was employed to fabricate 3D scaffolds from PCL with increasing amounts of graphene (G), in the concentrations of 0.75, 1.5, 3, and 6% (w/w). The PCL+G scaffolds created were characterised physico-chemically, electrically, and biologically. Raman spectroscopy demonstrated that the scaffold outer surface contained both PCL and G, with the G component relatively uniformly distributed. Water contact angle measurement demonstrated that as the amount of G in the scaffold increases (0.75-6% w/w), hydrophobicity decreases; mean contact angle for pure PCL was recorded as 107.22 ± 9.39°, and that with 6% G (PCL+6G) as 77.56 ± 6.75°. Electrochemical Impedance Spectroscopy demonstrated a marked increase in electroactivity potential with increasing G concentration. Cell viability results indicated that even the smallest addition of G (0.75%) resulted in a significant improvement in electroactivity potential and bioactivity compared with that for pure PCL, with 1.5 and 3% exhibiting the highest statistically significant increases in cell proliferation.

Current trends in COVID-19 diagnosis and its new variants in physiological fluids: Surface antigens, antibodies, nucleic acids, and RNA sequencing.

Rapid, highly sensitive, and accurate virus circulation monitoring techniques are critical to limit the spread of the virus and reduce the social and economic burden. Therefore, point-of-use diagnostic devices have played a critical role in addressing the outbreak of COVID-19 (SARS-CoV-2) viruses. This review provides a comprehensive overview of the current techniques developed for the detection of SARS-CoV-2 in various body fluids (e.g., blood, urine, feces, saliva, tears, and semen) and considers the mutations (i.e., Alpha, Beta, Gamma, Delta, Omicron). We classify and comprehensively discuss the detection methods depending on the biomarker measured (i.e., surface antigen, antibody, and nucleic acid) and the measurement techniques such as lateral flow immunoassay (LFIA), enzyme-linked immunosorbent assay (ELISA), reverse transcriptase-polymerase chain reaction (RT-PCR), reverse transcription loop-mediated isothermal amplification (RT-LAMP), microarray analysis, clustered regularly interspaced short palindromic repeats (CRISPR) and biosensors. Finally, we addressed the challenges of rapidly identifying emerging variants, detecting the virus in the early stages of infection, the detection sensitivity, selectivity, and specificity, and commented on how these challenges can be overcome in the future.

Label-free electrochemical immunosensor for picomolar detection of the cervical cancer biomarker MCM5.

An immunosensor for label-free electrochemical detection of MiniChromosome Maintenance Protein 5, MCM5, a protein overexpressed in cervical cancer, based on a gold electrode is reported. The electrode was first modified with a submonolayer (capture layer) of 11-mercaptoundecanoic acid (11-MUA) and then activated with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS) to immobilize the capture antibody. The change in electrode surface properties (wettability) during the formation of the 11-MUA layers was determined using the static water contact angle (WCA). The binding of MCM5 antigens to the capture antibody was monitored by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) using 5 mM [Fe(CN)6]3-/4- in 0.1 M LiClO4(aq) as an electroactive probe. AC Impedance was used to measure charge transfer resistance (Rct), which reflects impeded electron transfer when the antigen is bound to the antibody functionalized surface. After exposing the antibody-functionalized surface to MCM5 antigens, Rct increases linearly with the logarithmic value of MCM5 antigen concentration, with a linear dynamic range of 10-6 to 10-11 g/mL, a correlation coefficient of 0.99, and a detection limit of 2.9 pM (10-11 g/mL). This excellent sensitivity was achieved with simple preparation steps and minimal reagent consumption, without the need for complicated procedures such as enzymatic amplification, fluorescent labeling, or nanoparticle modification.

Data on enhanced wireless cell stimulation using soft and improved bipolar electroactive conducting polymer templates.

Data in this article is associated with our research article "Enhanced wireless cell stimulation using soft and improved bipolar electroactive conducting polymer templates" Qin et al. (2022). Primarily, the present article shows the data of PPy-PMAS/FTO, PPy-PMAS-collagen/FTO and PPy-PMAS-DS-collagen/FTO in conventional electrochemical process and bipolar electrochemical process along with in situ spectrometry for comprehensive supplement and comparison to help with better developing modified conducting polymers based bipolar electrochemistry. Secondly, the presented the complete dataset useful for modelling the soft and improved bipolar electroactive conducting polymers focusing on wireless cell (animal and human) stimulation, which are reported in the main article. All data reported were analysed using Origin 2019b 64Bit.

Correction: Kudura et al. Prediction of Early Response to Immune Checkpoint Inhibition Using FDG-PET/CT in Melanoma Patients. Cancers 2021, 13, 3830.

The authors wish to make the following corrections to this paper [...].

Machine Learning for the Detection and Segmentation of Benign Tumors of the Central Nervous System: A Systematic Review.

Objectives: To summarize the available literature on using machine learning (ML) for the detection and segmentation of benign tumors of the central nervous system (CNS) and to assess the adherence of published ML/diagnostic accuracy studies to best practice. Methods: The MEDLINE database was searched for the use of ML in patients with any benign tumor of the CNS, and the records were screened according to PRISMA guidelines. Results: Eleven retrospective studies focusing on meningioma (n = 4), vestibular schwannoma (n = 4), pituitary adenoma (n = 2) and spinal schwannoma (n = 1) were included. The majority of studies attempted segmentation. Links to repositories containing code were provided in two manuscripts, and no manuscripts shared imaging data. Only one study used an external test set, which raises the question as to whether some of the good performances that have been reported were caused by overfitting and may not generalize to data from other institutions. Conclusions: Using ML for detecting and segmenting benign brain tumors is still in its infancy. Stronger adherence to ML best practices could facilitate easier comparisons between studies and contribute to the development of models that are more likely to one day be used in clinical practice.

Cranial Radiotherapy for Prostate Cancer Patients With Brain Metastases Inaccessible to Stereotactic Radiotherapy.

BACKGROUND/AIM: To evaluate patients and treatment characteristics as well as clinical outcome in patients with intracranial metastases from prostate cancer (PCA) treated with palliative radiotherapy. PATIENTS AND METHODS: Fifteen patients treated for intracranial metastases of PCA were identified. The median age of patients was 69 years. 80% of patients received whole brain radiotherapy and 20% received partial brain radiotherapy. Clinical outcome was assessed. Univariate analysis was performed to analyze the impact of patient specific parameters on survival. RESULTS: There was no >G2 acute or any late toxicity. Median time from the first diagnosis of PCA to first diagnosis of intracranial metastases was 62 months (range=15-160 months). Median survival from first diagnosis of intracranial metastases was 14 weeks (range=0-126 weeks) and 6 weeks (range=0-47 weeks) from the start of radiotherapy. In univariate analysis, survival was significantly better for patients with an Eastern Cooperative Oncology Group (ECOG) performance status 1 compared to ECOG 2-3 [18 weeks (range=5-47 weeks) vs. 3 weeks (range=0-21 weeks), p=0.030] and Recursive Partitioning Analysis (RPA) class 2 compared to RPA class 3 [18 weeks (range=5-47 weeks) vs. 6 weeks (range=0-21 weeks), p=0.045]. CONCLUSION: Overall survival of the patients with wide-spread intracranial metastases from PCA was poor. The decision for a radiotherapy should be done on individual patient basis.

Convolutional Neural Networks to Detect Vestibular Schwannomas on Single MRI Slices: A Feasibility Study.

In this study. we aimed to detect vestibular schwannomas (VSs) in individual magnetic resonance imaging (MRI) slices by using a 2D-CNN. A pretrained CNN (ResNet-34) was retrained and internally validated using contrast-enhanced T1-weighted (T1c) MRI slices from one institution. In a second step, the model was externally validated using T1c- and T1-weighted (T1) slices from a different institution. As a substitute, bisected slices were used with and without tumors originating from whole transversal slices that contained part of the unilateral VS. The model predictions were assessed based on the categorical accuracy and confusion matrices. A total of 539, 94, and 74 patients were included for training, internal validation, and external T1c validation, respectively. This resulted in an accuracy of 0.949 (95% CI 0.935-0.963) for the internal validation and 0.912 (95% CI 0.866-0.958) for the external T1c validation. We suggest that 2D-CNNs might be a promising alternative to 2.5-/3D-CNNs for certain tasks thanks to the decreased demand for computational power and the fact that there is no need for segmentations. However, further research is needed on the difference between 2D-CNNs and more complex architectures.

Electrochemiluminescent detection of epilepsy biomarker miR-134 using a metal complex light switch.

The detection of a key biomarker in epilepsy, miR-134, using an environmentally sensitive electrochemiluminescent luminophore, [Ru(DPPZ)2 PIC]2+, is reported, DPPZ is dipyrido[3,2-a:2',3'-c]phenazine) and PIC is (2,2'-bipyridyl)-2(4-carboxy phenyl) imidazo [4,5][1,10] phenanthroline. A thiolated capture strand is first labelled with [Ru(DPPZ)2 PIC]2+ and then adsorbed onto a gold electrode. No significant electrochemiluminescence, ECL, is observed for immobilised Ru-labelled capture strands which is consistent with the light-switch dye being exposed to the aqueous solution. In sharp contrast, binding of the target turns on ECL. The ECL intensity, IECL, depends on the number of adenine "spacer" bases between the end of the capture sequence and the dye. The ECL intensity for the optimised system increases linearly with increasing miR-134 concentration from 100 nM to approximately 20 µM. Single and double base mismatches produce IECL that are only approximately 30% and 8% respectively of that observed for the fully complementary target reflecting differences in their association constants. Significantly, the presence of BSA protein causes IECL to increase by less 5% in either the single or duplex circumstances. Finally, the ability of the sensor to quantify miR-134 in unprocessed plasma samples from healthy volunteers and people with epilepsy is reported.