Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

Androgen Receptor Splice Variant 7 in Asian Patients With Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Androgen receptor splice variant 7 (ARV-7) is a resistance mechanism to hormonal therapy in metastatic castrate-resistant prostate cancer (mCRPC). It has been associated with poor outcomes. On progression to castrate resistance, ARV-7 positivity has been identified in global populations at an incidence of 17.8%-28.8%. Here, we characterize the incidence of ARV-7 positivity in Asian patients with mCRPC in a prospective fashion and evaluate its implications on treatment outcomes. METHODS: Patients with mCRPC from multiple centers in Southeast and East Asia were enrolled in a prospective manner before initiation of androgen receptor signaling inhibitors or docetaxel. ARV-7 status was evaluated at baseline with three commercially available assays: AdnaTest Prostate Cancer platform, Clearbridge method, and IBN method. Clinical outcomes at progression were assessed. The primary end point of this study was prevalence of ARV-7 positivity; secondary end points were incidence of ARV-7 positivity, prostate specific antigen (PSA) response rate, PSA progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 102 patients with a median age of 72 years at enrollment participated. Overall, an incidence of ARV-7 positivity of between 14.3% and 33.7% in Asian patients with mCRPC was demonstrated depending on the assay used. Patients found to have ARV-7 positivity at enrollment had a numerically worse PSA PFS compared with ARV-7 negative patients. CONCLUSION: In this study, the incidence of ARV-7 positivity in Asian patients with mCRPC was shown to be similar to the global population. Patients with ARV-7 positivity appear to have more aggressive disease with numerically worse PSA PFS and OS. Further prospective studies are needed to fully characterize the relationship that ARV-7 positivity has on prognosis of Asian patients with mCRPC.

"Seeing Is Believing": Additive Utility of 68Ga-PSMA-11 PET/CT in Prostate Cancer Diagnosis.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.

Development of gemcitabine-modified miRNA mimics as cancer therapeutics for pancreatic ductal adenocarcinoma.

Despite the recent advancement in diagnosis and therapy, pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is still the most lethal cancer with a low five-year survival rate. There is an urgent need to develop new therapies to address this issue. In this study, we developed a treatment strategy by modifying tumor suppressor miRNAs, miR-15a and miR-194, with the chemotherapeutic gemcitabine (Gem) to create Gem-modified mimics, Gem-miR-15a and Gem-miR-194, respectively. In a panel of PDAC cell lines, we found that Gem-miR-15a and Gem-miR-194 induce cell-cycle arrest and apoptosis, and these mimics are potent inhibitors with IC50 values up to several hundred fold less than their native counterparts or Gem alone. Furthermore, we found that Gem-miR-15a and Gem-miR-194 retained miRNA function by downregulating the expression of several key targets including WEE1, CHK1, BMI1, and YAP1 for Gem-miR-15a, and FOXA1 for Gem-miR-194. We also found that our Gem-modified miRNA mimics exhibit an enhanced efficacy compared to Gem in patient-derived PDAC organoids. Furthermore, we observed that Gem-miR-15a significantly inhibits PDAC tumor growth in vivo without observing any noticeable signs of toxicity. Overall, our results demonstrate the therapeutic potential of Gem-modified miRNAs as a treatment strategy for PDAC.

Cultivated Meat from Aligned Muscle Layers and Adipose Layers Formed from Glutenin Films.

Cultivated meat production is a promising technology to generate meat while reducing the reliance on traditional animal farming. Biomaterial scaffolds are critical components in cultivated meat production, enabling cell adhesion, proliferation, differentiation, and orientation. In the present work, naturally derived glutenin was fabricated into films with and without surface patterning and in the absence of toxic cross-linking or stabilizing agents for cell culture related to cultivated meat goals. The films were stable in culture media for at least 28 days, and the surface patterns induced cell alignment and guided myoblast organization (C2C12s) and served as a substrate for 3T3-L1 adipose cells. The films supported adhesion, proliferation, and differentiation with mass balance considerations (films, cells, and matrix production). Freeze-thaw cycles were applied to remove cells from glutenin films and monitor changes in glutenin mass with respect to culture duration. Extracellular matrix (ECM) extraction was utilized to quantify matrix deposition and changes in the original biomaterial mass over time during cell cultivation. Glutenin films with C2C12s showed mass increases with time due to cell growth and new collagen-based ECM expression during proliferation and differentiation. All mass balances were compared among cell and noncell systems as controls, along with gelatin control films, with time-dependent changes in the relative content of film, matrix deposition, and cell biomass. These data provide a foundation for cell/biomaterial/matrix ratios related to time in culture as well as nutritional and textural features.

Off-clamp vs on-clamp robot-assisted partial nephrectomy: a systematic review and meta-analysis.

OBJECTIVE: To compare intra- and postoperative outcomes between off-clamp and on-clamp robot-assisted partial nephrectomy (RAPN), using data from randomised controlled trials (RCTs) or covariate-matched studies (propensity score-matched or matched-pair analysis). METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant literature review was conducted on PubMed, EMBASE, Scopus and CENTRAL for relevant studies comparing off-clamp to on-clamp RAPN. Primary outcomes were estimated blood loss, postoperative percentage decrease in estimated glomerular filtration rate (eGFR), and margin positive rate. Secondary outcomes were operative time, postoperative eGFR, length of stay, all postoperative complications, major complications, and need for transfusion. Random-effects meta-analyses were performed to generate mean differences (MDs) or odds ratios (ORs). RESULTS: A total of 10 studies (2307 patients) were shortlisted for analysis. There was no significant difference in estimated operative blood loss between off-clamp and on-clamp RAPN (MD 21.9 mL, 95% confidence interval [CI] -0.9 to 44.7 mL; P = 0.06, I2 = 58%). Off-clamp RAPN yielded a smaller postoperative eGFR deterioration (MD 3.10%, 95% CI 1.05-5.16%; P = 0.008, I2 = 13%) and lower odds of margin positivity (OR 0.62, 95% CI 0.40-0.94; P = 0.03, I2 = 0%). No significant differences were found for all secondary outcomes. CONCLUSIONS: Off-clamp and on-clamp RAPN are similarly effective approaches for selected renal masses. Within the classic trifecta of PN outcomes, off-clamp RAPN yields similar rates of perioperative complications and may possibly offer better preservation of renal function and reduced margin-positive rates.

Oligometastatic Prostate Cancer-The Middle Child Syndrome.

Oligometastatic prostate cancer is an evolving clinical entity as more data from novel imaging tools such as PSMA PET/CT emerges. Recognition of this disease entity allows for unique interventions which differ from conventional treatment of metastatic prostate cancers such as the initiation of chemotherapy. With metastasis-directed therapy (MDT), there is potential for early eradication of limited disease metastases and a delay in systemic treatment with its associated treatment-related toxicities. This review explores the current evidence and outcomes of different metastasis-directed therapies such as the role of radiotherapy in low volume metastasis and the use of PSMA ligands to facilitate pelvic lymph node dissections. With a deeper understanding of this low metastasis state, it has revolutionized the current viable treatment options, and more studies are ongoing to provide further insights into this unique disease entity.

Surveillance one year post focal cryotherapy for clinically significant prostate cancer using mpMRI and PIRADS v2.1: An initial experience from a prospective phase II mandatory biopsy study.

Objectives: Multiparametric magnetic resonance imaging (mpMRI) surveillance post focal cryotherapy (FT) of prostate cancer is challenging as post treatment artefacts alter mpMRI findings. In this initial experience, we assessed diagnostic performance of mpMRI in detecting clinically significant prostate cancer (csPCa) after FT. Materials and methods: This single-centre phase II prospective clinical trial recruited 28 men with localized csPCa for FT between October 2019 and April 2021. 12-months post FT mpMRI were performed prior to biopsy and sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of all mpMRI positive subjects were analysed. Chi square goodness of fit test correlated biopsy positive PIRADS3 (P3) and PIRADS4/5 lesions with histology grade group. One way ANOVA test assessed performance of ADC values in differentiating csPCa, non csPCa and benign lesions. Results: Sensitivity, specificity, PPV and NPV of mpMRI were 100%, 14.28%, 53.84% and 100% for subjects with histologically proven cancer. Correlation of PIRADS v2.1 scores with histologically proven prostate cancer was statistically significant (p < 0.5). Correlation of P3 lesions with non-csPCa was statistically significant (p < 0.02535). Higher ADC value was associated with benign histology (adjusted odds ratio OR 0.97, 95% confidence interval: 0.94, 0.99) (p = 0.008). Among the malignant lesions, higher ADC value was associated with non-csPCa (adjusted OR: 0.97; 95% CI: 0.95, 0.99) (p = 0.032). Conclusion: mpMRI is highly sensitive in detecting residual cancer. ADC values and PIRADS scores may be of value in differentiating csPCa from non-csPCa with a potential for risk stratification of men requiring re-biopsy versus non-invasive surveillance of remnant prostate.

Local Therapy on Clinically Lymph Node-positive Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Patients with clinically lymph node-positive (cN1) prostate cancer (PCa) are traditionally regarded to have metastatic disease, and the role of local therapy (LT) in their treatment remains unclear. OBJECTIVE: To evaluate the outcomes of cN1 PCa patients treated with LT, and secondarily to compare between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). EVIDENCE ACQUISITION: A bibliographic search was performed using Medline, Embase, and the Cochrane Library to identify studies comparing the survival outcomes of cN1 PCa patients treated with LT (RT or RP) with those who did not receive any form of LT (observation or androgen deprivation therapy alone). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations were followed. Survival outcomes of the addition of LT were assessed using a random-effect model. EVIDENCE SYNTHESIS: A total of 8522 patients across eight studies were included. LT significantly improved overall survival (OS) across all time points from 2 to 10 yr compared with patients without LT, most notably providing a durable benefit in 10-yr OS (odds ratio [OR]: 1.49, 95% confidence interval [CI] 1.06-2.10). Both RT and RP were associated with benefits to both OS and recurrence-free survival, with no significant difference in OS between both modalities in medium-term follow-up (4-yr OR: 0.76, 95% CI 0.41-1.40, p = 0.19). CONCLUSIONS: Regardless of modality, the use of LT in cN1 patients improved OS. Future studies should aim to identify patients who could benefit from LT and include more comprehensive survival data including biochemical recurrence. PATIENT SUMMARY: In this study, we evaluated the outcomes of clinically lymph node-positive (cN1) prostate cancer (PCa) patients treated with local therapy (LT) and compared between different modalities of LT, including radiotherapy (RT) and radical prostatectomy (RP). We found that the addition of LT for cN1 PCa patients leads to a significant improvement in survival outcomes, most notably for overall survival, with no significant difference between RT and RP.

Development of Gemcitabine-Modified miRNA Mimics as Cancer Therapeutics for Pancreatic Ductal Adenocarcinoma.

Pancreatic cancer, including its most common subtype, pancreatic adenocarcinoma (PDAC), has the lowest five-year survival rate among patients with pancreatic cancer in the United States. Despite advancements in anticancer treatment, the overall median survival for patients with PDAC has not dramatically improved. Therefore, there is an urgent need to develop new strategies of treatment to address this issue. Non-coding RNAs, including microRNAs (miRNAs), have been found to have major roles in carcinogenesis and the subsequent treatment of various cancer types like PDAC. In this study, we developed a treatment strategy by modifying tumor suppressor miRNAs, hsa-miRNA-15a (miR-15a) and hsa-miRNA-194-1 (miR-194), with the nucleoside analog chemotherapeutic gemcitabine (Gem) to create Gem-modified mimics of miR-15a (Gem-miR-15a) and miR-194 (Gem-miR-194). In a panel of PDAC cell lines, we found that Gem-miR-15a and Gem-miR-194 induce cell cycle arrest and apoptosis, and these mimics are potent inhibitors with IC 50 values up to several hundred fold less than their native counterparts or Gem alone. Furthermore, we found that Gem-miR-15a and Gem-miR-194 retained miRNA function by downregulating the expression of several key targets including WEE1, CHK1, BMI1, and YAP1 for Gem-miR-15a, and FOXA1 for Gem-miR-194. We also found that our Gem-modified miRNA mimics exhibit an enhanced efficacy compared to Gem alone in patient-derived PDAC organoids. Furthermore, we observed that Gem-miR-15a significantly inhibits PDAC tumor growth in vivo without observing any noticeable signs of toxicity. Overall, our results demonstrate the therapeutic potential of Gem-modified miRNAs as a treatment strategy for PDAC. One Sentence Summary: Yuen and Hwang et. al. have developed a potent therapeutic strategy for patients with pancreatic cancer by modifying microRNAs with gemcitabine.

Analysis of MicroRNAs in Ferroptosis.

MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that are involved in a wide range of biological processes, including development, differentiation, and disease. They function by binding to the 3' untranslated region (UTR) of target mRNAs, leading to mRNA degradation or translational repression. miRNAs are involved in the regulation of many cellular processes, including cell proliferation, apoptosis, and metabolism. MiRNAs have been shown to modulate ferroptosis in several ways. Some miRNAs have been shown to promote ferroptosis by increasing the expression of genes involved in lipid peroxidation. Other miRNAs have been shown to inhibit ferroptosis by decreasing the expression of genes involved in iron uptake. The role of miRNAs in ferroptosis is still being studied, but they play a significant role in this cell death pathway. miRNAs may be potential targets for therapeutic intervention in diseases associated with ferroptosis, such as cancer and neurodegenerative diseases. This chapter outlines several methods used to study the connection between miRNAs and ferroptosis through target discovery and validation.

The associations between spiritual well-being, hope and psychological symptoms in Chinese childhood cancer patients: A path analysis.

AIMS: We aimed to test a model in which hope and spiritual well-being acted as protective factors against anxiety and depressive symptoms in childhood cancer patients (CCPs). We hypothesized that hope and spiritual well-being were mutually reinforcing factors that would both reduce anxiety and depressive symptoms. METHODS: Using path analysis, the hypothetical model was tested on a cross-sectional sample of 412 Chinese CCPs aged 8-17 years. Self-reported measures were used to obtain data on participants' social and clinical characteristics, spiritual well-being, hope, anxiety and depressive symptoms. RESULTS: The hypothetical model was supported. Results suggested that sex, treatment type and diagnosis predicted spiritual well-being; diagnosis and time since diagnosis predicted hope. Spiritual well-being and hope were mutually predictive and mutually reinforcing, and were both negatively associated with anxiety and depressive symptoms. This model predicted 40% of the variance in spiritual well-being, 37% in hope, 39% in depressive symptoms, and 28% in anxiety. CONCLUSION: Spiritual well-being and hope were mutually reinforcing and served as protective factors against anxiety and depressive symptoms. These support the value for integrating spiritual and hope elements in developing interventions for CCPs to improve their spiritual and psychological well-being along the disease trajectory.

Intensive sampling of the umbra and penumbra improves clinically significant prostate cancer detection and reduces risk of grade group upgrading at radical prostatectomy.

PURPOSE: Our objective is to evaluate the clinically significant prostate cancer detection rate of overlapping and perilesional systematic biopsy cores and its impact on grade group (GG) concordance at prostatectomy. MATERIALS AND METHODS: Biopsy maps of those undergoing MRI-targeted (TB) and systematic biopsy (SB) were reviewed to reclassify systematic cores. Perilesional (PL) cores were defined as adjacent cores within 10 mm of the target lesion ("penumbra") whilst overlap (OL) cores were defined as cores within the ROI itself ("umbra"). All other cores were designated as distant cores (DC). The incremental csPCa detection rate (GG ≥ 2) and the rate of GG upgrading on prostatectomy as OL, PL and DC sequentially added to TB were determined. RESULTS: Out of the 398 patients included, the median number of OL and PL cores was 5 (IQR 4-7) and 5 (IQR 3-6) respectively. OL cores detected more csPCa than PL cores (31 vs 16%, p < 0.001). OL and PL cores improved the csPCa detection rate of TB from 34 to 39% (p < 0.001) and 37% (p = 0.001) respectively. TB+OL+PL had greater csPCa detection compared to just TB+OL (41 vs 39%, p = 0.016) and TB+PL (41 vs 37%, p < 0.001). Of the 104 patients who underwent prostatectomy, GG upgrading rate for TB+OL+PL was lower compared to TB (21 vs 36%, p < 0.001) and was not significantly different compared to TB+OL+PL+DC (21 vs 19%, p = 0.500). CONCLUSION: A biopsy strategy incorporating both intensive sampling of the umbra and penumbra improved csPCa detection and reduced risk of GG upgrading at prostatectomy.

Far from the truth: Real-world treatment patterns among newly diagnosed metastatic prostate cancer in the era of treatment intensification.

OBJECTIVES: Real-world uptake of treatment intensification (TI) with novel hormonal agents (NHA) or chemotherapy as treatment of metastatic prostate cancer remains low outside of trial settings. We aim to report the prescription patterns and treatment outcomes of de novo metastatic hormone-sensitive prostate cancer (mHSPC) in a tertiary institution. METHODS: This is a retrospective cohort study using real-world data from a prospectively maintained prostate cancer registry. We selected patients newly diagnosed with mHSPC from January 2016 to December 2020. Clinicopathological parameters were recorded to determine their impact on prescription patterns. RESULTS: In total, 585 patients with metastatic prostate cancer were identified. Prescription of NHA increased from 10.5% (2016) to 50.4% (2020), but that of chemotherapy declined. Factors associated with TI were (1) baseline health status: Charlson Comorbidity Index 0-2, ECOG 0-1, age ≤ 65, (2) disease burden: PSA (>400, CHAARTED high volume disease, p = 0.004), development of systemic complications and (3) physician factor: primary physician being uro-oncologist and medical oncologist versus general urologist. Patients with TI had a longer mean time to castration-resistant prostate cancer (45.0 vs. 32.5 months, HR 0.567, 95% CI: 0.441-0.730, p < 0.001) and overall survival (55.3 vs. 46.8 months, HR 0.612, 95% CI, 0.447-0.837, p = 0.001). CONCLUSION: This study demonstrated the trend of treatment prescription of mHSPC and factors contributing to the use of TI. TI improved mean time to CRPC and OS.

Optimization of Culture Media and Cell Ratios for 3D In Vitro Skeletal Muscle Tissues with Endothelial Cells.

A major challenge of engineering larger macroscale tissues in vitro is the limited diffusion of nutrients and oxygen to the interior. For skeletal muscle, this limitation results in millimeter scale outcomes to avoid necrosis. One method to address this constraint may be to vascularize in vitro-grown muscle tissue, to support nutrient (culture media) flow into the interior of the structure. In this exploratory study, we examine culture conditions that enable myogenic development and endothelial cell survival within tissue engineered 3D muscles. Myoblasts (C2C12s), endothelial cells (HUVECs), and endothelial support cells (C3H 10T1/2s) were seeded into Matrigel-fibrin hydrogels and cast into 3D printed frames to form 3D in vitro skeletal muscle tissues. Our preliminary results suggest that the simultaneous optimization of culture media formulation and cell concentrations is necessary for 3D cultured muscles to exhibit robust myosin heavy chain expression and GFP expression from GFP-transfected endothelial cells. The ability to form differentiated 3D muscles containing endothelial cells is a key step toward achieving vascularized 3D muscle tissues, which have potential use as tissue for implantation in a medical setting, as well as for future foods such as cultivated meats.

Family caregivers' lived experience of caring for hospitalised patients with cancer during the COVID-19 lockdown: A descriptive phenomenological study.

AIMS: This study aimed to capture and explore family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown. BACKGROUND: The unprecedented lockdown episodes due to COVID-19 have brought significant changes in the hospital visiting policies and caregiving practices. As part of the precautionary measures for hospital visits, the bedside companion was restricted to one caregiver for patients with cancer in Shanghai hospitals. DESIGN: This study adopted a descriptive phenomenological approach. METHODS: Data were collected among 20 family caregivers recruited from the Oncology department of a tertiary hospital in Shanghai in May 2022, using purposive sampling method and followed by unstructured, open-ended interviews. Colaizzi's seven-step data analysis method was used to analyse the data to reveal the emergent themes and subthemes of the phenomenon. RESULTS: Four themes were generated on family caregivers' lived experience of caring for hospitalised patients with cancer during the lockdown, including (1) Feeling scared for the patient; (2) Living a life feeling trapped under COVID-19 surveillance; (3) Feeling neglected and unseen; (4) Growing resilience and appreciation. CONCLUSIONS: The lockdown exacerbated the burden of family caregivers when they cared for the hospitalised patients with cancer during the lockdown period. However, positive reframing of the lived experience facilitated their coping with the challenging situation. RELEVANCE TO CLINICAL PRACTICE: Findings from this study highlighted the potential proactive roles the healthcare providers could play in improving family caregivers' health and supporting them during and beyond the COVID-19 pandemic. REPORTING METHOD: The study adhered to relevant EQUATOR guidelines; the study was reported according to the COREQ checklist. PATIENT OR PUBLIC CONTRIBUTION: Family caregivers of patients with cancer were involved in data collection and member-checking of the transcripts and interpretations of their experiences.

Immortalized Bovine Satellite Cells for Cultured Meat Applications.

For cultured meat to succeed at scale, muscle cells from food-relevant species must be expanded in vitro in a rapid and reliable manner to produce millions of metric tons of biomass annually. Toward this goal, genetically immortalized cells offer substantial benefits over primary cells, including rapid growth, escape from cellular senescence, and consistent starting cell populations for production. Here, we develop genetically immortalized bovine satellite cells (iBSCs) via constitutive expression of bovine Telomerase reverse transcriptase (TERT) and Cyclin-dependent kinase 4 (CDK4). These cells achieve over 120 doublings at the time of publication and maintain their capacity for myogenic differentiation. They therefore offer a valuable tool to the field, enabling further research and development to advance cultured meat.

Head-to-head Comparison of the Diagnostic Accuracy of Prostate-specific Membrane Antigen Positron Emission Tomography and Conventional Imaging Modalities for Initial Staging of Intermediate- to High-risk Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: Whether prostate-specific membrane antigen positron emission tomography (PSMA-PET) should replace conventional imaging modalities (CIM) for initial staging of intermediate-high risk prostate cancer (PCa) requires definitive evidence on their relative diagnostic abilities. OBJECTIVE: To perform head-to-head comparisons of PSMA-PET and CIM including multiparametric magnetic resonance imaging (mpMRI), computed tomography (CT) and bone scan (BS) for upfront staging of tumour, nodal, and bone metastasis. EVIDENCE ACQUISITION: A search of the PubMed, EMBASE, CENTRAL, and Scopus databases was conducted from inception to December 2021. Only studies in which patients underwent both PSMA-PET and CIM and imaging was referenced against histopathology or composite reference standards were included. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) checklist and its extension for comparative reviews (QUADAS-C). Pairwise comparisons of the sensitivity and specificity of PSMA-PET versus CIM were performed by adding imaging modality as a covariate to bivariate mixed-effects meta-regression models. The likelihood ratio test was applied to determine whether statistically significant differences existed. EVIDENCE SYNTHESIS: A total of 31 studies (2431 patients) were included. PSMA-PET/MRI was more sensitive than mpMRI for detection of extra-prostatic extension (78.7% versus 52.9%) and seminal vesicle invasion (66.7% versus 51.0%). For nodal staging, PSMA-PET was more sensitive and specific than mpMRI (73.7% versus 38.9%, 97.5% versus 82.6%) and CT (73.2% versus 38.5%, 97.8% versus 83.6%). For bone metastasis staging, PSMA-PET was more sensitive and specific than BS with or without single-photon emission computerised tomography (98.0% versus 73.0%, 96.2% versus 79.1%). A time interval between imaging modalities >1 month was identified as a source of heterogeneity across all nodal staging analyses. CONCLUSIONS: Direct comparisons revealed that PSMA-PET significantly outperforms CIM, which suggests that PSMA-PET should be used as a first-line approach for the initial staging of PCa. PATIENT SUMMARY: We reviewed direct comparisons of the ability of a scan method called PSMA-PET (prostate-specific membrane antigen positron emission tomography) and current imaging methods to detect the spread of prostate cancer outside the prostate gland. We found that PSMA-PET is more accurate for detection of the spread of prostate cancer to adjacent tissue, nearby lymph nodes, and bones.

Natural language processing in urology: Automated extraction of clinical information from histopathology reports of uro-oncology procedures.

Objectives: We aimed to automate routine extraction of clinically relevant unstructured information from uro-oncological histopathology reports by applying rule-based and machine learning (ML)/deep learning (DL) methods to develop an oncology focused natural language processing (NLP) algorithm. Methods: Our algorithm employs a combination of a rule-based approach and support vector machines/neural networks (BioBert/Clinical BERT), and is optimised for accuracy. We randomly extracted 5772 uro-oncological histology reports from 2008 to 2018 from electronic health records (EHRs) and split the data into training and validation datasets in an 80:20 ratio. The training dataset was annotated by medical professionals and reviewed by cancer registrars. The validation dataset was annotated by cancer registrars and defined as the gold standard with which the algorithm outcomes were compared. The accuracy of NLP-parsed data was matched against these human annotation results. We defined an accuracy rate of >95% as "acceptable" by professional human extraction, as per our cancer registry definition. Results: There were 11 extraction variables in 268 free-text reports. We achieved an accuracy rate of between 61.2% and 99.0% using our algorithm. Of the 11 data fields, a total of 8 data fields met the acceptable accuracy standard, while another 3 data fields had an accuracy rate between 61.2% and 89.7%. Noticeably, the rule-based approach was shown to be more effective and robust in extracting variables of interest. On the other hand, ML/DL models had poorer predictive performances due to highly imbalanced data distribution and variable writing styles between different reports and data used for domain-specific pre-trained models. Conclusion: We designed an NLP algorithm that can automate clinical information extraction accurately from histopathology reports with an overall average micro accuracy of 93.3%.