Although rapid advances in machine learning have made it increasingly applicable to expert decision-making, the delivery of accurate algorithmic predictions alone is insufficient for effective ...human-AI collaboration. In this work, we investigate the key types of information medical experts desire when they are first introduced to a diagnostic AI assistant. In a qualitative lab study, we interviewed 21 pathologists before, during, and after being presented deep neural network (DNN) predictions for prostate cancer diagnosis, to learn the types of information that they desired about the AI assistant. Our findings reveal that, far beyond understanding the local, case-specific reasoning behind any model decision, clinicians desired upfront information about basic, global properties of the model, such as its known strengths and limitations, its subjective point-of-view, and its overall design objective--what it's designed to be optimized for. Participants compared these information needs to the collaborative mental models they develop of their medical colleagues when seeking a second opinion: the medical perspectives and standards that those colleagues embody, and the compatibility of those perspectives with their own diagnostic patterns. These findings broaden and enrich discussions surrounding AI transparency for collaborative decision-making, providing a richer understanding of what experts find important in their introduction to AI assistants before integrating them into routine practice.
Diverse metal–organic complexes (MOCs), shaped as rectangles, triangles, hexagons, prisms, and cages, can be formed by coordination between metal ions (Pt, Pd, Ru, Rh, Ir, Zn, Co, and Cd) and organic ...ligands, with potential applications as alternatives to conventional biomedical materials for therapeutic, sensing, and imaging purposes. MOCs have been investigated as anticancer drugs in the treatment of malignant tumors in lung, cervical, breast, colon, liver, prostate, ovarian, brain, stomach, bone, skin, mouth, thyroid, and other cancers. MOCs with one, two, and three cavities have also been investigated as drug carriers and prepared for the loading and release of different drugs. In addition, MOCs can target proteins by the shape effect and recognize sugars and DNA by electrostatic interactions, as well as estradiol by host–guest interactions, etc. This Perspective mainly covers achievements in the biomedical application of MOCs. We aim to identify some key trends in the reported MOC structures in relation to their biomedical activity and potential applications.
Obiective. Simptomele tractului urinar inferior, condiționate de hiperplazia benignă de prostată constituie unul din cele mai frecvente motive de adresare la medicul urolog a bărbaților în vârstă. În ...pofida existenței unui șir larg de metode conservative, acestea nu întotdeauna pot soluționa manifestările hiperplaziei benigne de prostată și foarte frecvent doar amână tratamentul chirurgical. Scopul lucrării este de a analiza eficiența funcțională a enucleerii transuretrale a prostatei cu utilizarea energiei bipolare și a Thulium:YAG laser. Material și metode. În perioada 2020-2021, 45 pacienți cu hiperplazie benignă de prostată au suportat tratament chirurgical cu utilizarea metodelor de enucleere transuretrală a prostatei: ThuVEP (21 pacienți) și TUEB (24 pacienți). Toți pacienți au fost evaluați preoperator și postoperator (3 și 6 luni):IPSS, QoL, TRUS-P cudeterminarea urinei rezidualeși uroflowmetrie. Criteriile de includere au fost: vârsta ≤80 ani; volumul urinei reziduale ≥ 70ml;IPSS ≥20; Qmax ≤ 8,0ml/s. Rezultate. În perioada de supraveghere a survenit o ameliorare semnificativă la 3 luni postoperator care a continuat să progreseze. Nu au fost observate diferențe semnificative între loturile de cercetare (ThuVEP și TUEB) în ceea ceprivește modificările produse la investigarea prin ultrasunet și uroflowmetrie. O reducere similară a scorurilor simptomatice conform chestionarelor IPSS și QoL a fost raportată de către pacienți. Concluzii. Utilizarea pe larg a enucleerii transuretrale a prostatei, poate substitui metodele clasice de tratament a hiperplaziei benigne de prostată, demonstrând eficiența funcțională înaltă indiferent de volumul preoperator al prostatei.
Targeting exosome biogenesis and release may have potential clinical implications for cancer therapy. Herein, we have optimized a quantitative high throughput screen (qHTS) assay to identify ...compounds that modulate exosome biogenesis and/or release by aggressive prostate cancer (PCa) CD63-GFP-expressing C4-2B cells. A total of 4,580 compounds were screened from the LOPAC library (a collection of 1,280 pharmacologically active compounds) and the NPC library (NCGC collection of 3,300 compounds approved for clinical use). Twenty-two compounds were found to be either potent activators or inhibitors of intracellular GFP signal in the CD63-GFP-expressing C4-2B cells. The activity of lead compounds in modulating the secretion of exosomes was validated by a tunable resistive pulse sensing (TRPS) system (qNano-IZON) and flow cytometry. The mechanism of action of the lead compounds in modulating exosome biogenesis and/or secretion were delineated by immunoblot analysis of protein markers of the endosomal sorting complex required for transport (ESCRT)-dependent and ESCRT-independent pathways. The lead compounds tipifarnib, neticonazole, climbazole, ketoconazole, and triademenol were validated as potent inhibitors and sitafloxacin, forskolin, SB218795, fenoterol, nitrefazole and pentetrazol as activators of exosome biogenesis and/or secretion in PC cells. Our findings implicate the potential utility of drug-repurposing as novel adjunct therapeutic strategies in advanced cancer.
Systematic characterization of the cancer microbiome provides the opportunity to develop techniques that exploit non-human, microorganism-derived molecules in the diagnosis of a major human disease. ...Following recent demonstrations that some types of cancer show substantial microbial contributions
, we re-examined whole-genome and whole-transcriptome sequencing studies in The Cancer Genome Atlas
(TCGA) of 33 types of cancer from treatment-naive patients (a total of 18,116 samples) for microbial reads, and found unique microbial signatures in tissue and blood within and between most major types of cancer. These TCGA blood signatures remained predictive when applied to patients with stage Ia-IIc cancer and cancers lacking any genomic alterations currently measured on two commercial-grade cell-free tumour DNA platforms, despite the use of very stringent decontamination analyses that discarded up to 92.3% of total sequence data. In addition, we could discriminate among samples from healthy, cancer-free individuals (n = 69) and those from patients with multiple types of cancer (prostate, lung, and melanoma; 100 samples in total) solely using plasma-derived, cell-free microbial nucleic acids. This potential microbiome-based oncology diagnostic tool warrants further exploration.
The renal excretion of PSMA radiotracer may render PSMA PET/CT imaging interpretation difficult to identify local recurrence and lymph node metastases in prostate cancer patients.
To evaluate the ...best acquisition method to increase the detection rate of local recurrence and pelvic metastases on PSMA PET/CT by performing dual time-point imaging (delayed imaging) after hyperhydration, diuretics, and contrast enhancement.
Patients with prior history of prostate adenocarcinoma underwent PSMA PET/CT for primary staging or due to biochemical recurrence. PSMA PET/CT acquisition consisted of delayed pelvic imaging after hyperhydration, diuretics, and excretory-phase contrast. SUV values obtained in local recurrence lesions, locoregional lymph node metastases, and bone metastases in the early and delayed PSMA PET/CT images were compared.
A total of 182 patients (medians: age = 66.5; Gleason score = 7.0; total PSA = 1.5) underwent PSMA PET/CT. Twenty-one patients (12%) were scanned due to primary staging, and 161 patients due to biochemical recurrence (88%). Delayed images (with only hyperhydration, without contrast or diuretics) increased diagnostic certainty in identifying local recurrence in 26.6% of patients and locoregional lymph nodes in 25%. There was a significant increase in SUV values in the delayed images compared to early images in the local recurrence (p < 0.0001), locoregional lymph node metastases (p < 0.0001), and bone metastases (p < 0.0199). Adding excretory-phase contrast to the delayed images increased diagnostic certainty in identifying local recurrence in 9.4% of patients and locoregional lymph nodes in 8.3%. The use of diuretics only in delayed images (without excretory-phase contrast) increased diagnostic certainty in identifying local recurrence in 14% of patients; while for identifying pelvic lymph nodes increase was only mild (2.8%). The association of diuretics with excretory-phase contrast increased the diagnostic certainty in identifying local recurrence in 15.6% of patients and locoregional lymph nodes in 5.6%.
Delayed PSMA PET/CT images increase the diagnostic certainty of identifying local recurrence and locoregional metastases in prostate cancer patients. The addition of diuretics increases diagnostic certainty and may be useful in selected cases. However, the addition of excretory-phase contrast (regardless of the use of diuretics) only mildly impacted diagnostic certainty and may be omitted.
Since the re-discovery of sulforaphane in 1992 and the recognition of the bioactivity of this phytochemical, many studies have examined its mode of action in cells, animals and humans. Broccoli, ...especially as young sprouts, is a rich source of sulforaphane and broccoli-based preparations are now used in clinical studies probing efficacy in health preservation and disease mitigation. Many putative cellular targets are affected by sulforaphane although only one, KEAP1-NRF2 signaling, can be considered a validated target at this time. The transcription factor NRF2 is a master regulator of cell survival responses to endogenous and exogenous stressors.
This review summarizes the chemical biology of sulforaphane as an inducer of NRF2 signaling and efficacy as an inhibitor of carcinogenesis. It also provides a summary of the current findings from clinical trials using a suite of broccoli sprout preparations on a series of short-term endpoints reflecting a diversity of molecular actions.
Sulforaphane, as a pure chemical, protects against chemical-induced skin, oral, stomach, colon, lung and bladder carcinogenesis and in genetic models of colon and prostate carcinogenesis. In many of these settings the antitumorigenic efficacy of sulforaphane is dampened in Nrf2-disrupted animals. Broccoli preparations rich in glucoraphanin or sulforaphane exert demonstrable pharmacodynamic action in over a score of clinical trials. Measures of NRF2 pathway response and function are serving as guideposts for the optimization of dose, schedule and formulation as clinical trials with broccoli-based preparations become more commonplace and more rigorous in design and implementation.
•Sulforaphane, an isothioicyante found in cruciferous vegetables, activates the KEAP1-NRF2 cell survival response.•Sulforaphane inhibits carcinogenesis in many animal models; in some cases Nrf2 knockout mice are refractory to protection.•Broccoli preparations rich in sulforaphane have been used in clinical trials examining health preservation and disease mitigation.•Many of these trials utilize pharmacodynamics biomarkers reflective of altered NRF2 signaling, although other markers are also under study.
Organic building blocks are the centerpieces of “one‐for‐all” nanoparticle development. Herein, we report the synthesis of a novel aza‐BODIPY‐lipid building block and its self‐assembly into a ...liposomal nanoparticle (BODIPYsome). We observed optically stable NIR J‐aggregation within the BODIPYsome that is likely attributed to J‐dimerization. BODIPYsomes with cholesterol showed enhanced colloidal stability while maintaining a high extinction coefficient (128 mm−1 cm−1) and high fluorescence quenching (99.70±0.09 %), which enables photoacoustic (PA) properties from its intact structure and recovered NIR fluorescence properties when it is disrupted in cancer cells. Finally, its capabilities for optical imaging (PA/fluorescence) were observed in an orthotopic prostate tumor mouse model 24 h after intravenous administration. Overall, the BODIPYsome opens the door for engineering new building blocks in the design of optically stable biophotonic imaging agents.
BODIPYsome: The synthesis of a novel aza‐BODIPY‐lipid building block and its self‐assembly into BODIPYsome, which has optically stable NIR J‐aggregation that is attributed to J‐dimerization, is presented. BODIPYsomes exhibit a high extinction coefficient and high fluorescence quenching, enabling photoacoustic imaging when intact and recovered NIR fluorescence upon disruption.
Herein, a novel electrochemical ultrasensitive immunosensor was designed for detecting prostate-specific antigen (PSA) with three-dimensional (3D) PtCu hollow nanoframes (PtCu HNFs) as signal ...amplification. The highly opened PtCu HNFs were synthesized by a one-pot solvothermal method with cetyltrimethylammonium chloride (CTAC) and trishydroxymethyl aminomethane (Tris) as co-structuring directors. The architectures enlarged the loading of prostate specific antibodies (Ab) and efficiently catalyzed hydrogen peroxide (H2O2) reaction, ultimately amplifying the signals. And polylysine was used to disperse PtCu HNFs, improve the biocompatibility and bind the Ab on the electrode surface. The fabricated immunosensor exhibited lower detection limit (0.003 ng mL–1, S/N = 3), and wider linear range (0.01–100.0 ng mL–1), along with the improved reproducibility, selectivity and stability for the assay of PSA. Thus, it is a desirable platform for PSA detection in clinical diagnosis and practical applications.
•Uniform PtCu HNFs were synthesized by a simple solvothermal method.•Tris and CTAC acted as the co-structure-directing agents.•Polylysine can well disperse PtCu HNFs with increased biocompatibility.•PtCu HNFs was constructed for PSA immunosensor with excellent analytic performance.
Objectives
This study aims to define consensus-based criteria for acquiring and reporting prostate MRI and establishing prerequisites for image quality.
Methods
A total of 44 leading urologists and ...urogenital radiologists who are experts in prostate cancer imaging from the European Society of Urogenital Radiology (ESUR) and EAU Section of Urologic Imaging (ESUI) participated in a Delphi consensus process. Panellists completed two rounds of questionnaires with 55 items under three headings: image quality assessment, interpretation and reporting, and radiologists’ experience plus training centres. Of 55 questions, 31 were rated for agreement on a 9-point scale, and 24 were multiple-choice or open. For agreement items, there was consensus agreement with an agreement ≥ 70% (score 7–9) and disagreement of ≤ 15% of the panellists. For the other questions, a consensus was considered with ≥ 50% of votes.
Results
Twenty-four out of 31 of agreement items and 11/16 of other questions reached consensus. Agreement statements were (1) reporting of image quality should be performed and implemented into clinical practice; (2) for interpretation performance, radiologists should use self-performance tests with histopathology feedback, compare their interpretation with expert-reading and use external performance assessments; and (3) radiologists must attend theoretical and hands-on courses before interpreting prostate MRI. Limitations are that the results are expert opinions and not based on systematic reviews or meta-analyses. There was no consensus on outcomes statements of prostate MRI assessment as quality marker.
Conclusions
An ESUR and ESUI expert panel showed high agreement (74%) on issues improving prostate MRI quality. Checking and reporting of image quality are mandatory. Prostate radiologists should attend theoretical and hands-on courses, followed by supervised education, and must perform regular performance assessments.
Key Points
• Multi-parametric MRI in the diagnostic pathway of prostate cancer has a well-established upfront role in the recently updated European Association of Urology guideline and American Urological Association recommendations
.
• Suboptimal image acquisition and reporting at an individual level will result in clinicians losing confidence in the technique and returning to the (non-MRI) systematic biopsy pathway. Therefore, it is crucial to establish quality criteria for the acquisition and reporting of mpMRI
.
• To ensure high-quality prostate MRI, experts consider checking and reporting of image quality mandatory. Prostate radiologists must attend theoretical and hands-on courses, followed by supervised education, and must perform regular self- and external performance assessments
.