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IntroductionRobot-assisted surgery is becoming increasingly adopted by multiple surgical specialties. There is evidence of inherent risks of utilising new technologies that are unfamiliar early in the learning curve. The development of standardised and validated training programmes is crucial to deliver safe introduction. In this review, we aim to evaluate the current evidence and opportunities to integrate novel technologies into modern digitalised robotic training curricula.MethodsA systematic literature review of the current evidence for novel technologies in surgical training was conducted online and relevant publications and information were identified. Evaluation was made on how these technologies could further enable digitalisation of training.ResultsOverall, the quality of available studies was found to be low with current available evidence consisting largely of expert opinion, consensus statements and small qualitative studies. The review identified that there are several novel technologies already being utilised in robotic surgery training. There is also a trend towards standardised validated robotic training curricula. Currently, the majority of the validated curricula do not incorporate novel technologies and training is delivered with more traditional methods that includes centralisation of training services with wet laboratories that have access to cadavers and dedicated training robots.ConclusionsImprovements to training standards and understanding performance data have good potential to significantly lower complications in patients. Digitalisation automates data collection and brings data together for analysis. Machine learning has potential to develop automated performance feedback for trainees. Digitalised training aims to build on the current gold standards and to further improve the ‘continuum of training’ by integrating PBP training, 3D-printed models, telementoring, telemetry and machine learning.

ContextRetzius sparing robotic assisted radical prostatectomy appears to have better continence rates when compared to conventional robotic assisted radical prostatectomy, however, concern with high positive surgical margin rates exist.ObjectiveTo systematically evaluate evidence comparing functional and oncological outcomes of retzius sparing robotic assisted radical prostatectomy and conventional robotic assisted radical prostatectomy.Evidence acquisitionThe systematic review was performed in accordance with the Cochrane guidelines and the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Bibliographic databases searched were PubMed/MEDLINE, Cochrane central register of controlled trials—CENTRAL (in The Cochrane library—issue 1, 2018). We used the GRADE approach to assess the quality of the evidence.Evidence synthesisThe search retrieved 137 references through electronic searches of various databases. Six were included in the review. RS-RALP was associated with better early continence rates (≤ 1 month) (moderate quality evidence) (RR 1.72, 95% CI 1.27, 2.32, p 0.0005) and at 3 months (low quality evidence) (RR 1.39, 95% CI 1.03, 1.88, p 0.03). Time to continence recovery, number of pads used and pad weight are better with RS-RALP. Based on very low quality evidence, RS-RALP did not alter 6 and 12 months continence rates. Based on very low quality evidence, RS-RALP did not alter T2 positive margin rates (RR 1.67, 95% CI 0.91, 3.06, p 0.10) and T3 positive margin rates (RR 1.08, 95% CI 0.68, 1.70, p = 0.75). Short-term biochemical free survival appears to be similar between the two approaches. Based on low-quality evidence, RS-RALP did not alter overall and major complication rates.ConclusionsRS-RARP appears to have earlier continence recovery when compared to Con-RARP which does not come at a significant oncologic cost. Whilst there was a trend towards higher PSM rates with RS-RALP, this did not achieve statistical significance. Furthermore this trend appeared to be less pronounced with T3 disease, where the PSM rates are almost similar.

Background The ERG oncogene, a member of the ETS family of transcription factor encoding genes, is a genetic driver of prostate cancer. It is activated through a fusion with the androgen-responsive TMPRSS2 promoter in 50% of cases. There is therefore significant interest in developing novel therapeutic agents that target ERG . We have taken an antisense approach and designed morpholino-based oligonucleotides that target ERG by inducing skipping of its constitutive exon 4. Methods We designed antisense morpholino oligonucleotides (splice-switching oligonucleotides, SSOs) that target both the 5′ and 3′ splice sites of ERG’s exon 4. We tested their efficacy in terms of inducing exon 4 skipping in two ERG-positive cell lines, VCaP prostate cancer cells and MG63 osteosarcoma cells. We measured their effect on cell proliferation, migration and apoptosis. We also tested their effect on xenograft tumour growth in mice and on ERG protein expression in a human prostate cancer radical prostatectomy sample ex vivo. Results In VCaP cells, both SSOs were effective at inducing exon 4 skipping, which resulted in a reduction of overall ERG protein levels up to 96 h following a single transfection. SSO-induced ERG reduction decreased cell proliferation, cell migration and significantly increased apoptosis. We observed a concomitant reduction in protein levels for cyclin D1, c-Myc and the Wnt signalling pathway member β-catenin as well as a marker of activated Wnt signalling, p-LRP6. We tested the 3′ splice site SSO in MG63 xenografts in mice and observed a reduction in tumour growth. We also demonstrated that the 3′ splice site SSO caused a reduction in ERG expression in a patient-derived prostate tumour tissue cultured ex vivo. Conclusions We have successfully designed and tested morpholino-based SSOs that cause a marked reduction in ERG expression, resulting in decreased cell proliferation, a reduced migratory phenotype and increased apoptosis. Our initial tests on mouse xenografts and a human prostate cancer radical prostatectomy specimen indicate that SSOs can be effective for oncogene targeting in vivo. As such, this study encourages further in vivo therapeutic studies using SSOs targeting the ERG oncogene.

PIM and PI3K/mTOR pathways are often dysregulated in prostate cancer, and may lead to decreased survival, increased metastasis and invasion. The pathways are heavily interconnected and act on a variety of common effectors that can lead to the development of resistance to drug inhibitors. Most current treatments exhibit issues with toxicity and resistance. We investigated the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, versus a combination of the PIM inhibitor, AZD-1208, and the PI3K/mTOR inhibitor BEZ235 (Dactolisib) to determine their impact on mRNA and phosphoprotein expression, as well as their functional efficacy. We have determined that around 20% of prostate cancer patients overexpress the direct targets of these drugs, and this cohort are more likely to have a high Gleason grade tumour (≥ Gleason 8). A co-targeted inhibition approach offered broader inhibition of genes and phosphoproteins in the PI3K/mTOR pathway, when compared to single kinase inhibition. The preclinical inhibitor AUM302, used at a lower dose, elicited a comparable or superior functional outcome compared with combined AZD-1208 + BEZ235, which have been investigated in clinical trials, and could help to reduce treatment toxicity in future trials. We believe that a co-targeting approach is a viable therapeutic strategy that should be developed further in pre-clinical studies.

Background Partial ablation of the prostate using high-intensity focussed ultrasound (HIFU-PA) is a treatment option for localised prostate cancer. When local recurrence occurs, salvage robot-assisted radical prostatectomy is a treatment option for selected patients, but there is a paucity of data on the peri-operative safety, functional and oncologic outcomes of sRARP.. The objective of this study was therefore to describe peri-operative safety, functional and early oncologic outcomes following salvage robot-assisted radical prostatectomy (sRARP) for local recurrence after HIFU-PA. Methods Retrospective analysis of a prospective database of 53 consecutive men who underwent sRARP after HIFU-PA from 2012 to 2018. Continence and erectile-function were reported pre-HIFU, pre-sRARP, 3-months post-sRARP and 12-months post-sRARP. Complications, PSMs and need for subsequent ADT/radiotherapy were assessed. Results 45 men were suitable for inclusion and had sufficient data for analyses. Median duration from HIFU to sRARP was 30.0 months and median follow-up post-sRARP was 17.7 months. Median age, PSA and ISUP group were 63.0 yrs., 7.2 ng/mL and 2; 88.9% were cT2. Median operative-console time, blood loss and hospital stay were 140 min, 200 ml and 1 day respectively. Clavien-Dindo grade 1, 2 and 3 complications < 90 days occurred in 8.9, 6.7 and 2.2%; late (>90d) complications occurred in 13.2%. At sRARP pathology, ISUP 3–5 occurred in 51.1%, pT3a/b in 64.5%, and PSMs in 44.4% (37.5% for pT2, 48.3% for pT3). Of men with > 3-months follow-up after sRARP, 26.3% underwent adjuvant radiotherapy/ADT for residual disease or adverse pathologic features; 5.3% experienced BCR requiring salvage ADT/radiotherapy. Freedom from ADT/radiotherapy was 66.7% at 12-months. Pad-free rates were 100% pre-HIFU, 95.3% post-HIFU, 29.4% 3-months post-sRARP, and 65.5% 12-months post-sRARP. Median IIEF-5 scores pre-HIFU, post-HIFU, 3- and 12-months post-sRARP were 23.5, 16, 5 and 5, respectively. Potency rates were 81.8, 65.5, 0 and 0%, respectively. Bilateral/unilateral nerve sparing were feasible in 7%/22%. Conclusion Salvage RARP was safe with acceptable but sub-optimal continence and poor sexual-function and poor oncologic outcomes. One in three men required additional treatment within 12-months. This information may aid men and urologists with treatment selection and counselling regarding primary HIFU-PA vs primary RARP and when considering salvage RARP.

The genome sequences of many microbial species from the phytobiomes of several leafy Asian greens remain unknown. Here, we address this gap by reconstructing 910 prokaryotic draft genomes from 24 leaf, 65 root, 12 soil, and 6 compost metagenomes from the seedling and adult developmental stages of three leafy Asian greens – Brassica rapa var. parachinensis, Brassica oleracea var. alboglabra and Amaranthus spp. – grown in a commercial, soil-based urban farm. Of these, 128 are near-complete (>90% completeness, <5% redundancy), 540 are substantially complete (≥70% completeness, <10%, redundancy), while the rest have a completeness ≥50% and redundancy <10%. The draft genomes together span 292 bacterial and 3 archaeal species, a subset of which are from underrepresented genus-level lineages in public databases. We expect our dataset to facilitate a wide range of comparative studies that seek to understand the different functional aspects of vegetable crop phytobiomes and for devising new strategies for microbial cultivation in the future.Measurement(s)Metagenome • metagenomic data • soil metagenome • sequence_assembly • leaf metagenome • root metagenome • compost metagenomeTechnology Type(s)DNA sequencing • sequence assembly processFactor Type(s)green leafy vegetable type • growth stage • plant organsSample Characteristic - OrganismBrassica rapa • Brassica oleracea • AmaranthusSample Characteristic - Environmenturban biome • farm • soilMachine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12472847

Tropical peatlands in South-East Asia are some of the most carbon-dense ecosystems in the world. Extensive repurposing of such peatlands for forestry and agriculture has resulted in substantial microbially-driven carbon emissions. However, we lack an understanding of the microorganisms and their metabolic pathways involved in carbon turnover. Here, we address this gap by reconstructing 764 sub-species-level genomes from peat microbiomes sampled from an oil palm plantation located on a peatland in Indonesia. The 764 genomes cluster into 333 microbial species (245 bacterial and 88 archaeal), of which, 47 are near-complete (completeness ≥90%, redundancy ≤5%, number of unique tRNAs ≥18) and 170 are substantially complete (completeness ≥70%, redundancy ≤10%). The capacity to respire amino acids, fatty acids, and polysaccharides was widespread in both bacterial and archaeal genomes. In contrast, the ability to sequester carbon was detected only in a few bacterial genomes. We expect our collection of reference genomes to help fill some of the existing knowledge gaps about microbial diversity and carbon metabolism in tropical peatlands.

Objective To describe real‐world outcomes of patients with BCG failure undergoing bladder‐sparing treatments (BSTs) vs radical cystectomy in the UK. Patients and Methods A single institution audit was conducted at a tertiary bladder cancer referral service (UCLH, London, UK). Patients with BCG failure treated between January 2017 and September 2022 were included. BSTs included endoscopic surveillance, hyperthermic mitomycin and further BCG. The primary outcome was event free survival (EFS). Complete response (CR) rate and duration of response (DoR) were investigated in patients undergoing BST. The secondary outcomes were 3‐ and 5‐year cancer‐specific (CSS) and overall survival (OS). Results A total of 112 patients were included: 30% (34/112), 32% (36/112) and 27% (30/112) had BCG unresponsive, exposed and intolerant disease and 11% (12/112) had progressed to muscle invasive disease (MIBC). In the BCG unresponsive and exposed groups, 79% (27/34) and 72% (26/36) underwent RC, with the remaining receiving BSTs. Comparing RC vs BST in BCG unresponsive and exposed groups combined, there was a significantly poorer EFS in the BST group (p < 0.001); 35.3% (6/17) patients transitioned to second‐line BST due to recurrence or intolerance and a further 50% (3/6) transitioned a third line BST. There was no significant difference in CSS or OS rates. In BCG intolerance, the EFS rate was 90% as three patients experienced high‐grade recurrence and underwent RC. There were no cancer‐related deaths. In MIBC group, 5/12 presented with metastatic disease and 3‐ and 5‐year CSS rates was 66% and 0%. Conclusion This data reports real‐world practice in a UK centre. BSTs in BCG unresponsive and exposed disease are supported as an alternative to RC providing the increased risk of recurrence is accepted. Additionally, consideration of formal guidance supporting BST is needed in BCG intolerance, which appears to have an excellent outcome in a cohort managed with endoscopic surveillance. Upstaging to MIBC remains a poor prognostic factor and is key to improving survival outcomes in BCG failure.

Introduction: The majority of the open access publishing allows the researchers to publish their articles for a fee and at the same time enables the readers to access the research without paying the expensive journal subscription charges. Under the garb of open access publishing, predatory journals run a scam to dupe the researchers of money. This study was conducted to highlight the characteristics of pseudojournals and increase the awareness about their modus operandi. Methods: The email inboxes of 3 academic urologists (APS, AS, and KP) were searched for emails soliciting articles for open access journals. A list of all such journals was compiled. These journals were checked for metrics from the Journal Citation Reports and the Scimago Journal Rankings. All these journals were then cross-checked with the available whitelists and blacklists. Features pointing toward a pseudo journal were identified as red flag signs for these journals and were noted. A literature search was performed on open access publishing and predatory journals, and the salient points were noted. A checklist of red flag signs was compiled. Results: A total of 71 emails soliciting article submissions from 68 journals were received by the three urologists (APS, AS, KP). Of these, 54 were highly suggestive of being a pseudojournal, 5 journals were operating in the gray zone between genuine open access journals and outright predatory journals, and 9 were genuine open access journals. A total of 33 articles on predatory journals were reviewed after the literature search as per the PRISMA guidelines. The red flag signs identified along with the literature review were used to create the SAFEiMAP checklist, which can be used to identify predatory journals. Conclusion: Predatory journals have infiltrated the whitelists, and the indexing databases like PubMed and no blacklist is all-inclusive. Understanding the concept and the types of open access publishing gives the researchers a better idea on how to differentiate fake journals from the genuine ones. Using a checklist will help to identify the red flag signs of such journals and identify those journals that operate in the gray zone.

Partial cystectomy is a surgical bladder-sparing option for selected patients with muscle-invasive bladder cancer (MIBC), urachal adenocarcinoma and diverticular bladder tumors. Partial cystectomy hold several advantages. It allows for definite pathology and accurate staging while avoiding side effects from radiation therapy and preserves the option for salvage radical therapy (radical cystectomy or radical radiotherapy). Patients should have a CT urogram, prostatic urethral biopsy and mapping biopsies or blue light cystoscopy to rule out multifocal disease or CIS. Small solitary MIBC patients without carcinoma in situ in an area of the bladder where resection can be performed with negative margin would be the ideal candidates for partial cystectomy. Neoadjuvant systemic therapy is recommended for patients undergoing partial cystectomy. Partial cystectomy can be performed either by open or robotic approaches. When compared to radical cystectomy, partial cystectomy affords a lower complication rate and length of stay and better quality of life. Recurrence-free survival, cancer-specific survival and overall survival at 5 years is 39–67%, 62–84% and 45–70%, respectively. Following partial cystectomy, patients should have three monthly cystoscopy and urinary cytology for the first 24 months followed by 6-monthly cystoscopy for year 3 and 4 and then yearly for life. Cross-sectional imaging should be performed every 3–6 months for the first 2–3 years and then annually for 5 years.