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Carabid beetles were sampled by pitfall traps in May–September 2002 and 2003 in an experimental organic strawberry field in seven different mulching row treatments and in fescue-growing row spaces to determine the effect of mulches on carabid activity–density and species composition. There were no differences between treatments or row spaces in total numbers of all carabid species in either season. Of the 67 identified species and 4374 individuals, the most trapped ones were Clivina fossor (11.7% of total catch), Dyschirius globosus (10.2%), Patrobus atrorufus (9.3%), Pterostichus niger (8.8%), Bembidion properans (7.4%), Pterostichus melanarius (6.0%), Bembidion lampros (5.7%), Pterostichus crenatus (5.7%), Amara communis (4.1%), Trechus secalis (3.9%), Pterostichus strenuus (3.9%), Loricera pilicornis (3.1%), Harpalus rufipes (2.8%) and Carabus nemoralis (2.6%). Large carabid species P. niger and P. melanarius were trapped more in all mulched rows than in row spaces, and C. nemoralis was trapped more in the mixture of pine woodchip/buckwheat husk mulch than in row spaces, barley straw and birch woodchip mulch. The small but abundant species P. atrorufus was trapped more in buckwheat husk mulch than in row spaces and B. properans in row spaces than in buckwheat husk mulch. H. rufipes, being also a pest in strawberry, was trapped more in cut grass mulch than in row spaces. The Shannon H′ diversity index was significantly higher in the mixture of pine woodchip/buckwheat husk mulch than in black plastic, buckwheat husk mulch or in row spaces, and in birch woodchip and cut grass mulches than in row spaces. The results of trapping studies show the species preference to the specific mulches, and reflect positive or negative effect of mulches on carabid diversity with consequences to plant protection. [ABSTRACT FROM AUTHOR]

An experiment was carried out using bait cards to assess the contribution of different polyphagous predators in a wheat field to degree of predation. Activity abundancy of predators was measured by pitfall trapping. In June the most abundant carabids were Bembidion guttula, B. properans and Clivina fossor, later Pterostichus melanarius and Trechus discus. Staphylinids and spiders were most abundant in July. The total number of predators increased towards the end of the season. Predatory pressure was assessed using Drosophila melanogaster pupae as bait on small bait cards placed on the soil twice a week from 4/6-6/8. At the beginning of the experiment, predation was lower than later. Degree of predation varied between plots within every two-week period. According to the model obtained, Amara sp. contributed to predation 9/7-7/8. Bembidion guttula contributed to predation in every period, B. properans 4-14/6. Clivina fossor contributed to predation from the middle of June to the beginning of August, as did Trechus discus. Staphylinids contributed to predation 18-27/6 and 23/7-7/8 and spiders 18/6-19/7. Patrobus atrorufus and Synuchus nivalis contributed to predation 23/7-7/8, although not many were caught in the traps. [ABSTRACT FROM AUTHOR]

Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells are associated with myeloid inflammation previously linked to androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting., Competing Interests: Competing interests C.T.A.P.’s employer may gain commercially from licensing data to Artera AI. G.A. received personal fees, grants, and travel support from Janssen and Astellas Pharma; personal fees or travel support from Pfizer, Novartis/AAA, Bayer Healthcare Pharmaceuticals, AstraZeneca, and Sanofi-Aventis; in addition, G.A.’s former employer, The Institute of Cancer Research, receives royalty income from abiraterone and G.A. receives a share of this income through the Institute’s Rewards to Discoverers Scheme. G.A. has received research funding (institutional) from Janssen, Astellas Pharma, and Novartis. All other authors declare no potential conflicts of interest., (© 2024. The Author(s).)

Histopathological investigation of metastasis in core needle axillary lymph node (ALN) biopsies is crucial for the prognosis and treatment planning of breast cancer patients. Biopsies are typically sliced and evaluated as two-dimensional (2D) images. Biopsy sampling errors and the limited view provided by 2D histology are leading factors contributing to false-negative results in the preoperative detection of metastatic lymph nodes and underestimation of metastatic foci.In this proof-of-concept study, we aim to explore the technical feasibility and the potential capacities of tridimensional (3D) X-ray micro-computed tomography imaging to expedite error detection, enhancement of histopathological accuracy, and precise measurement of metastatic lesion on ALN core needle biopsies of two breast cancer patients. Our self-developed micro-CT protocol uses eosin for the first time, a common histological dye, to enhance 3D architecture of ALNs. Performed analysis on the images of the ALN biopsies involves cancer tissue segmentation, swift biopsy evaluation, and measurement of the metastatic longest diameter and deposit volume.The eosin micro-CT protocol shows potential for an improved tumor deposit estimates, offering additional clinical value compared to standard 2D histology, however, further studies for validating this method are needed., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

The percentage of obese people is increasing worldwide, causing versatile health problems. Obesity is connected to diseases such as diabetes and cardiovascular diseases, which are preceded by a state called metabolic syndrome. Diets rich in fruits and vegetables have been reported to decrease the risk of metabolic syndrome and type 2 diabetes. Berries with a high polyphenol content, including lingonberry ( Vaccinium vitis - idaea L.), have also been of interest to possibly prevent obesity-induced metabolic disturbances. In the present study, we prepared an extract from the by-product of a lingonberry juice production process (press cake/pomace) and investigated its metabolic effects in the high-fat diet-induced model of obesity in mice. The lingonberry skin extract partly prevented weight and epididymal fat gain as well as a rise in fasting glucose level in high-fat diet-fed mice. The extract also attenuated high-fat diet-induced glucose intolerance as measured by an intraperitoneal glucose tolerance test (IPGTT). The extract had no effect on the levels of cholesterol, triglyceride or the adipokines adiponectin, leptin, or resistin. The results extend previous data on the beneficial metabolic effects of lingonberry. Further research is needed to explore the mechanisms behind these effects and to develop further health-promoting lingonberry applications.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important., Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan., Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020., Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023., Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group., Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer., Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome., Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Purpose: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen)., Methods: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists., Results: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67)., Conclusions: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial., (© 2024. The Author(s).)

Background: Working memory (WM) deficits are among the most prominent cognitive impairments in attention deficit hyperactivity disorder (ADHD). While functional connectivity is a prevailing approach in brain imaging of ADHD, alterations in WM-related functional brain networks and their malleability by cognitive training are not well known. We examined whole-brain functional connectivity differences between adults with and without ADHD during n-back WM tasks and rest at pretest, as well as the effects of WM training on functional and structural brain connectivity in the ADHD group., Methods: Forty-two adults with ADHD and 36 neurotypical controls performed visuospatial and verbal n-back tasks during functional magnetic resonance imaging (fMRI). In addition, seven-minute resting state fMRI data and diffusion-weighted MR images were collected from all participants. The adults with ADHD continued into a 5-week randomized controlled WM training trial (experimental group training on a dual n-back task, n = 21; active control group training on Bejeweled II video game, n = 21), followed by a posttraining MRI. Brain connectivity was examined with Network-Based Statistic., Results: At the pretest, adults with ADHD had decreased functional connectivity compared with the neurotypical controls during both n-back tasks in networks encompassing fronto-parietal, temporal, occipital, cerebellar, and subcortical brain regions. Furthermore, WM-related connectivity in widespread networks was associated with performance accuracy in a continuous performance test. Regarding resting state connectivity, no group differences or associations with task performance were observed. WM training did not modulate functional or structural connectivity compared with the active controls., Conclusion: Our results indicate large-scale abnormalities in functional brain networks underlying deficits in verbal and visuospatial WM commonly faced in ADHD. Training-induced plasticity in these networks may be limited., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Current knowledge of white matter changes in large-scale brain networks in adult attention-deficit/hyperactivity disorder (ADHD) is scarce. We collected diffusion-weighted magnetic resonance imaging data in 40 adults with ADHD and 36 neurotypical controls and used constrained spherical deconvolution-based tractography to reconstruct whole-brain structural connectivity networks. We used network-based statistic (NBS) and graph theoretical analysis to investigate differences in these networks between the ADHD and control groups, as well as associations between structural connectivity and ADHD symptoms assessed with the Adult ADHD Self-Report Scale or performance in the Conners Continuous Performance Test 2 (CPT-2). NBS revealed decreased connectivity in the ADHD group compared to the neurotypical controls in widespread unilateral networks, which included subcortical and corticocortical structures and encompassed dorsal and ventral attention networks and visual and somatomotor systems. Furthermore, hypoconnectivity in a predominantly left-frontal network was associated with higher amount of commission errors in CPT-2. Graph theoretical analysis did not reveal topological differences between the groups or associations between topological properties and ADHD symptoms or task performance. Our results suggest that abnormal structural wiring of the brain in adult ADHD is manifested as widespread intrahemispheric hypoconnectivity in networks previously associated with ADHD in functional neuroimaging studies., (© 2023 Massachusetts Institute of Technology.)

Objectives: To assess whether mammographic breast density in women diagnosed with breast cancer correlates with the total number of incidental magnetic resonance imaging (MRI)-detected lesions and the likelihood of the lesions being malignant., Methods: Patients diagnosed with breast cancer meeting the EUSOBI and EUSOMA criteria for preoperative breast MRI routinely undergo mammography and ultrasound before MRI at our institution. Incidental suspicious breast lesions detected in MRI are biopsied. We included patients diagnosed with invasive breast cancers between 2014 and 2019 who underwent preoperative breast MRI. One reader retrospectively determined breast density categories according to the 5 th edition of the BI-RADS lexicon., Results: Of 946 patients with 973 malignant primary breast tumors, 166 (17.5%) had a total of 175 (18.0%) incidental MRI-detected lesions (82 (46.9%) malignant and 93 (53.1%) benign). High breast density according to BI-RADS was associated with higher incidence of all incidental enhancing lesions in preoperative breast MRIs: 2.66 (95% confidence interval: 1.03-6.86) higher for BI-RADS density category B, 2.68 (1.04-6.92) for category C, and 3.67 (1.36-9.93) for category D compared to category A (p < 0.05). However, high breast density did not predict higher incidence of malignant incidental lesions (p = 0.741). Incidental MRI-detected lesions in the contralateral breast were more likely benign (p < 0.001): 18 (27.3%)/48 (72.7%) vs. 64 (58.7%)/45 (41.3%) malignant/benign incidental lesions in contralateral vs. ipsilateral breasts., Conclusion: Women diagnosed with breast cancer who have dense breasts have more incidental MRI-detected lesions, but higher breast density does not translate to increased likelihood of malignant incidental lesions., Clinical Relevance Statement: Dense breasts should not be considered as an indication for preoperative breast MRI in women diagnosed with breast cancer., Key Points: • The role of preoperative MRI of patients with dense breasts diagnosed with breast cancer is under debate. • Women with denser breasts have a higher incidence of all MRI-detected incidental breast lesions, but the incidence of malignant MRI-detected incidental lesions is not higher than in women with fatty breasts. • High breast density alone should not indicate preoperative breast MRI., (© 2023. The Author(s).)

Background: Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question., Methods: We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high-risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones., Results: In patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, 5 years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, 3 years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance the identification of key drivers. Evolutionary analysis' potential impact on therapy selection appears positive in these pilot cases., Conclusions: PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Exposure to early life stress (ELS) is associated with a variety of detrimental psychological and neurodevelopmental effects. Importantly, ELS has been associated with regional alterations and aberrant connectivity in the structure and functioning of brain regions involved in emotion processing and self-regulation, creating vulnerability to mental health problems. However, longitudinal research regarding the impact of ELS on functional connectivity between brain regions in the default mode network (DMN) and fronto-limbic network (FLN), both implicated in emotion-related processes, is relatively scarce. Neuroimaging research on ELS has mostly focused on single nodes or bi-nodal connectivity instead of functional networks. We examined how ELS is associated with connectivity patterns within the DMN and FLN during rest in early adulthood. The participants ( n = 86; 47 females) in the current functional magnetic resonance imaging (fMRI) study were young adults (18-21 years old) whose families had participated in a longitudinal study since pregnancy. ELS was assessed both prospectively (parental reports of family relationship problems and mental health problems during pregnancy and infancy) and retrospectively (self-reported adverse childhood experiences). Inter-subject representational similarity analysis (IS-RSA) and multivariate distance matrix regression (MDMR) were used to analyze the association between ELS and the chosen networks. The IS-RSA results suggested that prospective ELS was associated with complex alterations within the DMN, and that retrospective ELS was associated with alterations in the FLN. MDMR results, in turn, suggested that that retrospective ELS was associated with DMN connectivity. Mean connectivity of the DMN was also associated with retrospective ELS. Analyses further showed that ELS-related alterations in the FLN were associated with increased connectivity between the prefrontal and limbic regions, and between different prefrontal regions. These results suggest that exposure to ELS in infancy might have long-lasting influences on functional brain connectivity that persist until early adulthood. Our results also speak for the importance of differentiating prospective and retrospective assessment methods to understand the specific neurodevelopmental effects of ELS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ilomäki, Lindblom, Salmela, Flykt, Vänskä, Salmi, Tolonen, Alho, Punamäki and Wikman.)

Objectives: To evaluate the feasibility of a population-based screening trial using prostate-specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit., Patients and Methods: Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI-RADS] score 3-5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies., Results: Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA-positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]-positive) had a suspicious MRI finding (PI-RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%., Conclusion: The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal., (© 2021 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Pathological gross examination of breast carcinoma samples is sometimes laborious. A tissue pre-mapping method could indicate neoplastic areas to the pathologist and enable focused sampling. Differential Mobility Spectrometry (DMS) is a rapid and affordable technology for complex gas mixture analysis. We present an automated tissue laser analysis system for imaging approaches (iATLAS), which utilizes a computer-controlled laser evaporator unit coupled with a DMS gas analyzer. The system is demonstrated in the classification of porcine tissue samples and three human breast carcinomas. Tissue samples from eighteen landrace pigs were classified with the system based on a pre-designed matrix (spatial resolution 1-3 mm). The smoke samples were analyzed with DMS, and tissue classification was performed with several machine learning approaches. Porcine skeletal muscle (n = 1030), adipose tissue (n = 1329), normal breast tissue (n = 258), bone (n = 680), and liver (n = 264) were identified with 86% cross-validation (CV) accuracy with a convolutional neural network (CNN) model. Further, a panel tissue that comprised all five tissue types was applied as an independent validation dataset. In this test, 82% classification accuracy with CNN was achieved. An analogous procedure was applied to demonstrate the feasibility of iATLAS in breast cancer imaging according to 1) macroscopically and 2) microscopically annotated data with 10-fold CV and SVM (radial kernel). We reached a classification accuracy of 94%, specificity of 94%, and sensitivity of 93% with the macroscopically annotated data from three breast cancer specimens. The microscopic annotation was applicable to two specimens. For the first specimen, the classification accuracy was 84% (specificity 88% and sensitivity 77%). For the second, the classification accuracy was 72% (specificity 88% and sensitivity 24%). This study presents a promising method for automated tissue imaging in an animal model and lays foundation for breast cancer imaging., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Neoadjuvant endocrine therapy is an alternative to neoadjuvant chemotherapy in women with inoperable luminal-like breast cancers. Neoadjuvant cyclin-dependent kinase 4/6 inhibitor treatment combined with endocrine treatment (CDK4/6I + E) is interesting given the combination's utility in the treatment of metastatic breast cancer. Currently, the literature on the radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting is scarce., Purpose: To conduct a radiological response evaluation of patients treated with neoadjuvant CDK4/6I + E in a real-life setting., Material and Methods: We retrospectively reviewed clinical, pathological, and radiological findings of six patients with luminal-like breast cancers treated with neoadjuvant CDK4/6I + E treatment. The radiological neoadjuvant CDK4/6I + E response was evaluated with the RECIST 1.1 criteria and the pathological residual disease was assessed using the Residual Cancer Burden (RBC) criteria., Results: None of the patients achieved a complete radiological magnetic resonance imaging (MRI)-determined response or a complete pathological response; three (50%) patients had a partial radiological response; in the three others, the disease remained stable radiologically. All of the tumors were rendered susceptible to surgical treatment. Two out of six (33.3%) patients had a moderate response (RBC-II); four (66.7%) had an extensive residual disease (RBC-III) in the final surgical sample., Conclusion: Although none of the patients achieved a pathologically complete response, neoadjuvant CDK4/6I + E treatment rendered all tumors operable. MRI appears to be reliable in the assessment of the neoadjuvant CDK4/6I + E treatment response in a real-life setting. Larger studies are warranted to confirm these results., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Doctors Salminen, Sassi, Tervo, Rinta-Kiikka, Tolonen, and Arponen report no conflicts of interest. Doctor Moisander reports consultant and travel fees from Takeda and Roche. Doctor Mäenpää reports consultant fees from Lilly and travel fees from Pfizer. Doctor Tiainen reports consultant and travel fees from Novartis, Roche, and Pfizer., (© The Foundation Acta Radiologica 2021.)

Background: Systematic identification of data essential for outcome prediction in metastatic prostate cancer (mPC) would accelerate development of precision oncology., Objective: To identify novel phenotypes and features associated with mPC outcome, and to identify biomarker and data requirements to be tested in future precision oncology trials., Design Setting and Participants: We analyzed deep longitudinal clinical, neuroendocrine expression, and autopsy data of 33 men who died from mPC between 1995 and 2004 (PELICAN33), and related findings to mPC biomarkers reported in the literature., Intervention: Thirty-three men prospectively consented to participate in an integrated clinical-molecular rapid autopsy study of mPC., Outcome Measurements and Statistical Analysis: Data exploration with correction for multiple testing and survival analysis from the time of diagnosis to time to death and time to first occurrence of severe pain as outcomes were carried out. The effect of seven complications on the modeled probability of dying within 2 yr after presenting with the complication was evaluated using logistic regression., Results and Limitations: Feature exploration revealed novel phenotypes related to mPC outcome. Four complications (pleural effusion, severe anemia, severe or controlled pain, and bone fracture) predict the likelihood of death within 2 yr. Men with Gleason grade group 5 cancers developed severe pain sooner than those with lower-grade tumors. Surprisingly, neuroendocrine (NE) differentiation was frequently observed in the setting of high serum prostate-specific antigen (PSA) levels (≥30 ng/ml). In 4/33 patients, no controlled (requiring analgesics) or severe pain was detected, and strikingly, 14/15 metastatic sites studied in these men did not express NE markers, suggesting an inverse relationship between NE differentiation and pain in mPC. Intracranial subdural metastasis is common (36%) and is usually clinically undetected. Categorization of "skeletal-related events" complications used in recent studies likely obscures the understanding of spinal cord compression and fracture. Early death from prostate cancer was identified in a subgroup of men with a low longitudinal PSA bandwidth. Cachexia is common (body mass index <0.89 in 24/31 patients) but limited to the last year of life. Biomarker review identified 30 categories of mPC biomarkers in need of winnowing in future trials. All findings require validation in larger cohorts, preferably alongside data from this study., Conclusions: The study identified novel outcome subgroups for future validation and provides "vision for mPC precision oncology 2020-2050" draft recommendations for future data collection and biomarker studies., Patient Summary: To better understand variation in metastatic prostate cancer behavior, we assembled and analyzed longitudinal clinical and autopsy records in 33 men. We identified novel outcomes, phenotypes, and aspects of disease burden to be tested and refined in future trials., (© 2021 The Author(s).)

Pathologic examination of clinical tissue samples is time consuming and often does not involve the comprehensive analysis of the whole specimen. Automated tissue analysis systems have potential to make the workflow of a pathologist more efficient and to support in clinical decision-making. So far, these systems have been based on application of mass spectrometry imaging (MSI). MSI provides high fidelity and the results in tissue identification are promising. However, the high cost and need for maintenance limit the adoption of MSI in the clinical setting. Thus, there is a need for new innovations in the field of pathological tissue imaging. In this study, we show that differential ion mobility spectrometry (DMS) is a viable option in tissue imaging. We demonstrate that a DMS-driven solution performs with up to 92% accuracy in differentiating between two grossly distinct animal tissues. In addition, our model is able to classify the correct tissue with 81% accuracy in an eight-class setting. The DMS-based system is a significant innovation in a field dominated by mass-spectrometry-based solutions. By developing the presented platform further, DMS technology could be a cost-effective and helpful tool for automated pathological analysis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The microbes present in bioethanol production processes have been previously studied in laboratory-scale experiments, but there is a lack of information on full-scale industrial processes. In this study, the microbial communities of three industrial bioethanol production processes were characterized using several methods. The samples originated from second-generation bioethanol plants that produce fuel ethanol from biowaste, food industry side streams, or sawdust. Amplicon sequencing targeting bacteria, archaea, and fungi was used to explore the microbes present in biofuel production and anaerobic digestion of wastewater and sludge. Biofilm-forming lactic acid bacteria and wild yeasts were identified in fermentation samples of a full-scale plant that uses biowaste as feedstock. During the 20-month monitoring period, the anaerobic digester adapted to the bioethanol process waste with a shift in methanogen profile indicating acclimatization to high concentrations of ammonia. Amplicon sequencing does not specifically target living microbes. The same is true for indirect parameters, such as low pH, metabolites, or genes of lactic acid bacteria. Since rapid identification of living microbes would be indispensable for process management, a commercial method was tested that detects them by measuring the rRNA of selected microbial groups. Small-scale testing indicated that the method gives results comparable with plate counts and microscopic counting, especially for bacterial quantification. The applicability of the method was verified in an industrial bioethanol plant, inspecting the clean-in-place process quality and detecting viability during yeast separation. The results supported it as a fast and promising tool for monitoring microbes throughout industrial bioethanol processes.

Objective: Plasma, but also urine sample could represent a simple liquid biopsy for ovarian cancer biomarker detection. The miRNA-200 family has been shown to be dysregulated in ovarian cancer. The aim of this study was to isolate three members of miR-200 family from tumor tissue, plasma and urine of high-grade serous ovarian cancer patients in comparison with samples from patients with benign ovarian tumors. This is a methodological pilot study of a prospective ovarian cancer patient cohort investigating the potential of liquid biopsies and the role of miRNAs in ovarian cancer treatment., Results: MiR-200a, miR-200b and miR-200c were isolated from samples of nine ovarian cancer patients and seven patients with benign ovarian tumor. The most significant finding is that all three miRNAs were detectable in all sample types. Tumor tissue and plasma, but not urine analysis was able to discriminate malignant and benign samples. A correlation between the miRNA-200 expression in urine and plasma was observed in malignant samples only. Plasma and urine with respect to miRNA detection show potential according to this study, but larger studies are needed to clarify the usefulness of these liquid biopsies in ovarian cancer., Trial Registration: ClinicalTrials.gov NCT02758652, May 2, 2016.

Immunohistochemistry (IHC) of ER, PR, and Ki-67 are routinely used assays in breast cancer diagnostics. Determination of the proportion of stained cells (labeling index) should be restricted on malignant epithelial cells, carefully avoiding tumor infiltrating stroma and inflammatory cells. Here, we developed a deep learning based digital mask for automated epithelial cell detection using fluoro-chromogenic cytokeratin-Ki-67 double staining and sequential hematoxylin-IHC staining as training material. A partially pre-trained deep convolutional neural network was fine-tuned using image batches from 152 patient samples of invasive breast tumors. Validity of the trained digital epithelial cell masks was studied with 366 images captured from 98 unseen samples, by comparing the epithelial cell masks to cytokeratin images and by visual evaluation of the brightfield images performed by two pathologists. A good discrimination of epithelial cells was achieved (AUC of mean ROC = 0.93; defined as the area under mean receiver operating characteristics), and well in concordance with pathologists' visual assessment (4.01/5 and 4.67/5). The effect of epithelial cell masking on the Ki-67 labeling index was substantial. 52 tumor images initially classified as low proliferation (Ki-67 < 14%) without epithelial cell masking were re-classified as high proliferation (Ki-67 ≥ 14%) after applying the deep learning based epithelial cell mask. The digital epithelial cell masks were found applicable also to IHC of ER and PR. We conclude that deep learning can be applied to detect carcinoma cells in breast cancer samples stained with conventional brightfield IHC.

Purpose: There is a limited amount of studies with results on professional development of paediatric oncology nurses. This study seeks to increase the understanding of the factors associated with the professional development of paediatric oncology nurses through the continuous education programme from the paediatric nurses' perspective., Method: The descriptive, qualitative study used the text of participants' electronic diaries as data during a two-year continuing professional education programme in 2016-2018. The sample consisted of 17 paediatric oncology nurses who were working in three different university hospitals. The data were analysed with the inductive content analysis method., Results: Professional development is linked with a strong knowledge base in nursing, which involves the use of nursing methods and up-to-date nursing practices. Professional development is also linked with the use of medical knowledge, which manifests as a deep understanding of cancers and their treatment., Conclusions: Research results show that a strong knowledge base in nursing alone is not sufficient for the professional development of paediatric oncology nurses. They also need to use their medical knowledge in order to gain an adequately deep understanding of children's cancers and their treatment. Nursing must be organised so that nurses have the opportunity to compare, share, question and argue for the methods they use with their colleagues in their own unit and other hospitals. Further research is needed on the professional development of paediatric oncology nurses and factors affecting it in order for a career development model to be created for this specific yet demanding area of nursing., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: Breast cancer is the most frequent cancer in women worldwide. The primary treatment is breast-conserving surgery or mastectomy with an adequate clearance margin. Diathermy blade is used extensively in breast-conserving surgery. Surgical smoke produced as a side product has cancer-specific molecular features. Differential mobility spectrometry (DMS) is a rapid and affordable technology for analysis of complex gas mixtures. In our study we examined surgical smoke from malignant and benign breast tissue created with a diathermy blade using DMS., Material and Methods: Punch biopsies of 4 mm diameter from breast cancer surgical specimens were taken during gross dissection of fresh surgical specimen and placed in a well plate. The measurement system is a custom-built device called automatic tissue analysis system (ATAS) based on a DMS sensor. Each specimen was incised with a diathermy blade and the surgical smoke was analyzed., Results: We examined 106 carcinoma samples from 21 malignant breast tumors. Benign samples (n = 198) included macroscopically normal mammary gland (n = 82), adipose tissue (n = 88) and vascular tissue (n = 28). The classification accuracy when comparing malignant samples to all benign samples was 87%. The sensitivity was 80% and the specificity was 90%. The classification accuracy of carcinomas to ductal and lobular was 94%, 47%, respectively., Conclusions: Benign and malignant breast tissue can be identified with ATAS. These results lay foundation for intraoperative margin assessment with DMS from surgical smoke., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Keloids have high recurrence rates. Current first-line therapy is triamcinolone (TAC) injection, but it has been suggested that approximately 50% of keloids are steroid resistant. We compared the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinalone injections in a double-blind randomized controlled trial. Forty-three patients with 50 keloid scars were treated with either intralesional TAC or 5-FU-injections over 6 months. There was no statistically significant difference in the remission rate at 6 months between the 5-FU and TAC groups (46% vs 60%, respectively). Local adverse effects were higher in the TAC group compared to the 5-FU group. Occurrence of skin atrophy in TAC group was 44% and in the 5-FU group 8% (p < 0.05). Also the occurrence of telangiectasia in the TAC group was 50% and in the 5-FU 21% (p < 0.05). Vascularity of the keloids, assessed by spectral imaging and immunohistochemical staining for blood vessels, after treatment decreased in the TAC group, but not in the 5-FU group (p < 0.05). Fibroblast proliferation evaluated by Ki-67 staining significantly decreased in the TAC group (p < 0.05) but increased in the 5-FU group (p < 0.05). TAC and 5-FU injections did not differ in their clinical effectivity in this randomized study, but 5-FU injections lead to increased proliferation rate and did not affect vascular density in histological assessment. Due to the greater number of adverse effects observed after TAC treatment, 5-FU injections may be preferable for cosmetically sensitive skin areas., (Copyright © 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Purpose: Paediatric oncology nurses encounter challenges with families on a daily basis. This study explores how nurses describe significant incidents when encountering families and family members during the child's hospitalisation in the paediatric oncology unit., Design and Methods: A qualitative study with a phenomenological approach in which 17 paediatric oncology nurses from three different hospitals described critical incidents related to families. The participants' written descriptions were analysed using inductive content analysis., Results: The results indicate three domains where critical incidents occur: 1) Families' capability and resources, 2) parents' behaviour and 3) emotional labour in paediatric oncology nursing., Conclusion: The results indicate that paediatric oncology nurses face situations with patients' parents that can cause them stress and uncertainty, as well as burden them emotionally. Some of the incidents dealt with difficult ethical questions. Because of the challenges that families are facing, as described in the study, nurses need to focus more on helping families identify their resources and empower themselves in order to adapt to a new situation in their lives., Implications: The results provide important information not only for paediatric nursing but also for education and management. Since the quality of family nursing does not only depend on the competence of nurses or available resources, support from management concerning the work with families of severely sick children would be beneficial to the nurses. In addition, educational interventions need to be developed in order to strengthen the capability of nurses to successfully respond to challenging situations with families., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Cortisol is a steroidal hormone and an important stress marker. Free serum cortisol concentration has been identified to correlate well with free salivary cortisol. In this present work an electrochemical immunosensor was developed to determine cortisol concentration within the physiological concentration range found in human saliva. The immunosensor is based on a direct competitive enzyme linked immunoassay using a home-made cortisol-alkaline phosphatase (AP) conjugate synthesized in our laboratory with disposable graphite screen-printed electrodes (SPEs). 1-nalphtyl phosphate (1-NP) was used as an enzymatic substrate and a square wave voltammetry (SWV) for electrochemical detection. To study method suitability for use with saliva samples, calibration curves were performed both in buffer and saliva. In buffer standard samples showed a limit of detection (LOD) of 0.6 ng/ml and working range (WR) of 0.2-44.6 ng/ml with good reproducibility (RSD 10%). Saliva matrix effect was removed effectively with Salivette Cortisol collection device (polyethylene) and a calibration curve showed similar characteristics as in buffer with LOD 1.7 ng/ml and WR 0.5-55.1 ng/ml (RSD 8%) demonstrating the possibility to determine human salivary cortisol within the desired human physiological range. Spiked saliva samples were analyzed with the developed immunosensor presenting excellent 92-114% recovery. Comparison to liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method showed strong 0.90 correlation between methods indicating good accuracy of the developed immunosensor., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Neuroendocrine differentiation (NED) is a common phenomenon in prostate cancer, and it has been associated with poor prognosis in some studies of primary prostate cancer. Incidence and patterns of NED in metastatic prostate cancer sites have not been examined widely. In this study, we studied expression of three commonly used markers of NED (chromogranin A, neuron specific enolase and synaptophysin) in 89 metastases from 31 men that died of castration-resistant prostate cancer and underwent rapid autopsy, and in 89 hormone-naïve primary tumors removed by radical prostatectomy. In addition, we examined NED association with androgen receptor, ERG and Ki-67 expression in metastatic tumor sites. Morphologically, 1 of 31 cases was classified as small cell carcinoma, and the remaining 30 were classified as usual prostate adenocarcinoma using a recently proposed classification of prostate cancers with NED. Metastases showed more expression of neuron specific enolase and synaptophysin compared to prostatectomies (6.3% of cells vs. 1.0%, p < 0.001 and 4.0% vs. 0.4%, p < 0.001, respectively). At least focal expression of one of the markers was seen in 78% of metastases. Strong expression was relatively uncommon, seen in 3/89 (chromogranin A), 8/89 (neuron specific enolase), and 5/89 (synaptophysin) metastases. Expression of chromogranin A and synaptophysin correlated with each other (r = 0.64, p < 0.001), but expression of neuron specific enolase did not correlate with the two other markers. Extent of NED varied significantly between different metastatic sites in individual patients. Absent androgen receptor expression was associated with strong expression of chromogranin A (p = .02) and neuron specific enolase (p = .02), but not with focal expression of any marker. No clear association was found between expression of NE markers and ERG or Ki-67. In conclusion, NED is a common and heterogeneous phenomenon in metastatic, castration-resistant prostate cancer. NED is more often present in castration-resistant prostate cancer compared to hormone-naïve disease, and it is associated with androgen receptor negativity. More research is needed to understand significance of NED in the progression of prostate cancer., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: Whole slide images (WSIs, digitized histopathology glass slides) are large data files whose long-term storage remains a significant cost for pathology departments. Currently used WSI formats are based on lossy image compression alogrithms, either using JPEG or its more efficient successor JPEG 2000. While the advantages of the JPEG 2000 algorithm (JP2) are commonly recognized, its compression parameters have not been fully optimized for pathology WSIs., Methods: We defined an optimized parametrization for JPEG 2000 image compression, designated JP2-WSI, to be used specifically with histopathological WSIs. Our parametrization is based on allowing a very high degree of compression on the background part of the WSI while using a conventional amount of compression on the tissue-containing part of the image, resulting in high overall compression ratios., Results: When comparing the compression power of JP2-WSI to the commonly used fixed 35:1 compression ratio JPEG 2000 and the default image formats of proprietary Aperio, Hamamatsu, and 3DHISTECH scanners, JP2-WSI produced the smallest file sizes and highest overall compression ratios for all 17 slides tested. The image quality, as judged by visual inspection and peak signal-to-noise ratio (PSNR) measurements, was equal to or better than the compared image formats. The average file size by JP2-WSI amounted to 15, 9, and 16 percent, respectively, of the file sizes of the three commercial scanner vendors' proprietary file formats (3DHISTECH MRXS, Aperio SVS, and Hamamatsu NDPI). In comparison to the commonly used 35:1 compressed JPEG 2000, JP2-WSI was three times more efficient., Conclusions: JP2-WSI allows very efficient and cost-effective data compression for whole slide images without loss of image information required for histopathological diagnosis., Competing Interests: There are no conflicts of interest.

Advances in prostate cancer biology and diagnostics are dependent upon high-fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin-embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied. Our results suggest that it is feasible to use PFPE tissue for routine robot-assisted laparoscopic prostatectomy surgical pathology diagnostics and immunohistochemistry, with the benefit of significantly improvedDNA and RNA quality and RNA picogram yield per nucleus as compared with FFPE tissue. For fresh frozen, FFPE, and PFPE tissues, respectively, the average Genomic Quality Numbers were 7.9, 3.2, and 6.2, average RNA Quality Numbers were 8.7, 2.6, and 6.3, average DNA picogram yields per nucleus were 0.41, 0.69, and 0.78, and average RNA picogram yields per nucleus were 1.40, 0.94, and 2.24. These findings suggest that where DNA and/or RNA analysis of tissue is required, and when tissue size is small, PFPE may provide important advantages over FFPE. The results also suggest several interesting nuances including potential avenues to improve RNA quality in FFPE tissues and confirm recent suggestions that some DNA sequence artifacts associated with FFPE can be avoided.

Global changes in chromatin accessibility may drive cancer progression by reprogramming transcription factor (TF) binding. In addition, histone acetylation readers such as bromodomain-containing protein 4 (BRD4) have been shown to associate with these TFs and contribute to aggressive cancers including prostate cancer (PC). Here, we show that chromatin accessibility defines castration-resistant prostate cancer (CRPC). We show that the deregulation of androgen receptor (AR) expression is a driver of chromatin relaxation and that AR/androgen-regulated bromodomain-containing proteins (BRDs) mediate this effect. We also report that BRDs are overexpressed in CRPCs and that ATAD2 and BRD2 have prognostic value. Finally, we developed gene stratification signature (BROMO-10) for bromodomain response and PC prognostication, to inform current and future trials with drugs targeting these processes. Our findings provide a compelling rational for combination therapy targeting bromodomains in selected patients in which BRD-mediated TF binding is enhanced or modified as cancer progresses., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Quinoa is a crop that originated from the Andes. It has high nutritional value, outstanding agro-ecological adaptability, and low water requirements. Quinoa is an excellent crop alternative to help overcome food shortages, and it can also have a role in the prevention of developed world lifestyle diseases, such as type-2 diabetes, cardiovascular diseases, osteoporosis, inflammatory and autoimmune diseases, etc. In order to expand the traditional uses of quinoa and to provide new, healthier and more nutritious food products, a fermented quinoa-based beverage was developed. Two quinoa varieties (Rosada de Huancayo and Pasankalla) were studied. The fermentation process, viscosity, acidity, and metabolic activity during the preparation and storage of the drink were monitored, as well as the preliminary organoleptic acceptability of the product. The drink had viable and stable microbiota during the storage time and the fermentation proved to be mostly homolactic. Both quinoa varieties were suitable as base for fermented products; Pasankalla, however, has the advantage due to higher protein content, lower saponin concentration, and lower loss of viscosity during the fermentation process. These results suggest that the differences between quinoa varieties may have substantial effects on food processes and on the properties of final products. This is a factor that should be taken into account when planning novel products based on this grain.