21 research outputs found
The quantum state of light in collective spontaneous emission
Collective spontaneous emission occurs when multiple quantum emitters decay
into common radiation modes, resulting in enhanced or suppressed emission.
Here, we find the quantum state of light collectively emitted from emitters
exhibiting quantum correlations. We unveil under what conditions the quantum
correlations are not lost during the emission but are instead transferred to
the output light. Under these conditions, the inherent nonlinearity of the
emitters can be tailored to create desired photonic states in the form of
traveling single-mode pulses, such as Gottesman-Kitaev-Preskill and
Schr\"odinger-cat states. To facilitate such predictions, our work reveals the
multi-mode nature of collective spontaneous emission, capturing the role of the
emitters' positions, losses, interactions, and beyond-Markov dynamics on the
emitted quantum state of light. We present manifestations of these effects in
different physical systems, with examples in cavity-QED, waveguide-QED, and
atomic arrays. Our findings suggest new paths for creating and manipulating
multi-photon quantum light for bosonic codes in continuous-variable-based
quantum computation, communications, and sensing
A systematic review and meta-analysis of high-quality randomized controlled trials on the role of prehabilitation programs in colorectal surgery.
BACKGROUND
Prehabilitation is gaining popularity in colorectal surgery but lacks high-quality postoperative outcomes data. This meta-analysis explored whether prehabilitation impacts postoperative outcomes.
METHODS
In this meta-analysis, compliant with Preferred Reporting Items for Systematic reviews and Meta-Analyses, we searched PubMed and Scopus through November 2022. High-quality randomized control trials involving adults who underwent colorectal surgery with/without exercise-based prehabilitation were included. The main outcomes were short-term postoperative morbidity, readmissions, and length of stay. Random-effect meta-analyses were performed, and statistical heterogeneity was assessed using the I2 statistic.
RESULTS
Seven high-quality randomized control trials comprising 1,225 patients were included. The median prehabilitation duration was 4 (2-4) weeks. Four studies compared prehabilitation and standard of care, and 3 compared prehabilitation and rehabilitation. Exercise-based prehabilitation did not reduce the odds of short-term complications (odds ratio 0.62, 95% confidence interval 0.27-1.40, P = .25, I2 = 68%) or readmission (odds ratio 1, 95% confidence interval 0.73-1.46, P = .85, I2 = 0%). The prehabilitation group had shorter length of hospital stay (weighted mean difference -0.2, 95% confidence interval -0.25 to -0.14, P < .0001, I2 = 43.3%). Prehabilitation and rehabilitation had similar odds of short-term complications (odds ratio 1.03, 95% confidence interval 0.56-1.89, P = .91, I2 = 33%), length of stay (weighted mean difference -0.16, 95% confidence interval -0.47 to 0.16, P = .33, I2 = 59%), and readmission (odds ratio 1.25, 95% confidence interval 0.28-5.56, P = .77, I2 = 52%). The only benefit of prehabilitation over rehabilitation was better 6-minute walking distance test results at time of surgery (weighted mean difference: -9.4 m; 95% confidence interval -18.04 to 0.79, P = .03, I2 = 42%).
CONCLUSION
Prehabilitation provided decreased postoperative length of hospital stay and improved preoperative functional outcomes, but not reduced odds of complications and/or readmissions. Prehabilitation and rehabilitation had similar clinical outcomes
Trans‑anal minimally invasive surgery (TAMIS) versus rigid platforms for local excision of early rectal cancer: a systematic review and meta-analysis of the literature.
BACKGROUND
Available platforms for local excision (LE) of early rectal cancer are rigid or flexible [trans‑anal minimally invasive surgery (TAMIS)]. We systematically searched the literature to compare outcomes between platforms.
METHODS
PRISMA-compliant search of PubMed and Scopus databases until September 2022 was undertaken in this random-effect meta-analysis. Statistical heterogeneity was assessed using I2 statistic. Studies comparing TAMIS versus rigid platforms for LE for early rectal cancer were included. Main outcome measures were intraoperative and short-term postoperative outcomes and specimen quality.
RESULTS
7 studies were published between 2015 and 2022, including 931 patients (423 females); 402 underwent TAMIS and 529 underwent LE with rigid platforms. Techniques were similar for operative time (WMD 11.1, 95%CI - 2.6 to 25, p = 0.11), percentage of defect closure (OR 0.7, 95%CI 0.06-8.22, p = 0.78), and peritoneal violation (OR 0.41, 95%CI 0.12-1.43, p = 0.16). Rigid platforms had higher rates of short-term complications (19.1% vs 14.2, OR 1.6, 95%CI 1.07-2.4, p = 0.02), although no significant differences were seen for major complications (OR 1.41, 95%CI 0.61-3.23, p = 0.41). Patients in the rigid platforms group were 3-times more likely to be re-admitted within 30 days compared to the TAMIS group (OR 3.1, 95%CI 1.07-9.4, p = 0.03). Rates of positive resection margins (rigid platforms: 7.6% vs TAMIS: 9.34%, OR 0.81, 95%CI 0.42-1.55, p = 0.53) and specimen fragmentation (rigid platforms: 3.3% vs TAMIS: 4.4%, OR 0.74, 95%CI 0.33-1.64, p = 0.46) were similar between the groups. Salvage surgery was required in 5.5% of rigid platform patients and 6.2% of TAMIS patients (OR 0.8, 95%CI 0.4-1.8, p = 0.7).
CONCLUSION
TAMIS or rigid platforms for LE seem to have similar operative outcomes and specimen quality. The TAMIS group demonstrated lower readmission and overall complication rates but did not significantly differ for major complications. The choice of platform should be based on availability, cost, and surgeon's preference
Regulation of Cancer Aggressive Features in Melanoma Cells by MicroRNAs
MicroRNAs (miRNAs) are small non-coding RNAs with regulatory roles, which are involved in a broad spectrum of physiological and pathological processes, including cancer. A common strategy for identification of miRNAs involved in cell transformation is to compare malignant cells to normal cells. Here we focus on identification of miRNAs that regulate the aggressive phenotype of melanoma cells. To avoid differences due to genetic background, a comparative high-throughput miRNA profiling was performed on two isogenic human melanoma cell lines that display major differences in their net proliferation, invasion and tube formation activities. This screening revealed two major cohorts of differentially expressed miRNAs. We speculated that miRNAs up-regulated in the more-aggressive cell line contribute oncogenic features, while the down-regulated miRNAs are tumor suppressive. This assumption was further tested experimentally on five candidate tumor suppressive miRNAs (miR-31, -34a, -184, -185 and -204) and on one candidate oncogenic miRNA (miR-17-5p), all of which have never been reported before in cutaneous melanoma. Remarkably, all candidate Suppressive-miRNAs inhibited net proliferation, invasion or tube formation, while miR-17-5p enhanced cell proliferation. miR-34a and miR-185 were further shown to inhibit the growth of melanoma xenografts when implanted in SCID-NOD mice. Finally, all six candidate miRNAs were detected in 15 different metastatic melanoma specimens, attesting for the physiological relevance of our findings. Collectively, these findings may prove instrumental for understanding mechanisms of disease and for development of novel therapeutic and staging technologies for melanoma
Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries
Abstract
Background
Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres.
Methods
This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries.
Results
In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia.
Conclusion
This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
Novel expression vectors enabling induction of gene expression by small-interfering RNAs and microRNAs.
Small-interfering RNAs and microRNAs are small ∼21-22 nucleotide long RNAs capable of posttranscriptional suppression of gene expression. The synthetic siRNAs are especially designed to target pre-specified genes and are common molecular biology tools. The miRNAs are endogenous regulators of gene expression found in a wide variety of eukaryotes. miRNAs are currently utilized for diagnostics applications. Therapeutically, various miRNA-antagonizing tools are being explored and miRNAs are also utilized for cell-specific inhibition of the expression of gene therapy vectors harboring target sites for specific miRNAs. Here we show, for the first time, that siRNAs and miRNAs can be harnessed to induce gene expression. We designed special expression vectors in which target sites for artificial siRNAs or endogenous miRNAs are located between the transgene and an Upstream Inhibitory Region (UIR). We hypothesized that cleavage of the mRNA by siRNAs or miRNAs will separate the transgene from the UIR and the resulting uncapped mRNA will be capable of being translated. A UIR composed of seven open reading frames was found to be the most efficient inhibitor of the translation of the downstream transgene. We show that under such a configuration both artificial siRNAs and endogenous miRNAs were capable of inducing transgene expression. We show that using the diphtheria toxin A-chain gene, in combination with target sites for highly expressed miRNAs, specific induction of cell-death can be achieved, setting the stage for application to cancer therapy
Decrease in cell viability by siRNA and miRNA dependent induction of DTA.
<p>U251 cells were transfected with the indicated construct (50 ng) with (A) or without (B) siRNAs (10pmol). Cell viability was determined by an XTT assay. The XTT viability value of the “No DTA” construct was set as 100% and the viability value obtained for all other constructs were compared to the No DTA level. (A) DTA dependent decrease in cell viability induced by siRNA in HUH7 cells. The siRNA used were: siCont: control siRNA; S4: siRNA S4; S5: siRNA S5. The numbers above the bars indicated the % viability obtained with each siRNA. P-values are indicated for the specific siRNAs. (B) DTA dependent decrease in cell viability induced by miRNA in U251 cells. The “Const DTA” construct had no UIR, with the DTA transgene directly driven by the CMV promoter. Each bar on the X-axis stands for a construct containing different TS region. The “sTS” control was the 4ORF construct with target sites for siRNAs S4 and S5. The miRNAs for which fully matched target sites were included in the TS are indicated below the bars. The relative level of expression of the miRNAs in the cells (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115327#pone-0115327-t002" target="_blank">Table 2</a>) are marked as L (Low) or H (High). The numbers above the bars of the siRNA indicated the % viability obtained with each siRNA. The experiments were repeated 3 and 4 times, respectively, for A and B. Each experiment was done in triplicates. Statistical analysis was done by T-test and the bars represent standard error. P value for the construct with target sites for miRNAs 21-5p, 125b-5p, 1273g-5p was 1.2*e(−10).</p
Transgene activation by siRNAs in constructs containing varied numbers of upstream ORFs.
<p>(A) Activity of the constructs in HEK293T cells. (B) Activity of the constructs in HUH7 cells. HEK293T cells (1.1×10<sup>5</sup>) were transfected with the indicated DTA construct (30 ng), a luciferase reporter plasmid (170 ng) and the indicated siRNA (10 pmol). HUH7 cells (8×10<sup>4</sup>) were transfected with the indicated DTA construct (50 ng), a luciferase reporter plasmid (150 ng) and the indicated siRNA (10 pmol). The renilla luciferase activity of the “No DTA” construct was set as 100% and the luciferase activity obtained for all other constructs were compared to the No DTA level. All constructs had the CMV promoter. The “No DTA” construct had the UIR but had no transgene. The “Const DTA” construct had no UIR, with the DTA transgene directly driven by the CMV promoter. The siRNAs used were: Sc: control siRNA; S4: siRNA S4; S5: siRNA S5. The numbers above the bars of the S4 and S5 siRNA indicated the DTA induction level calculated by dividing the luciferase activity of the Sc siRNA with that of the S4 or S5 siRNA of the same set. The experiments were repeated twice and each experiment was done in triplicates. Statistical analysis was done by T-test and the bars represent standard error. P values in A were 0.005; 2*10(−19); 2*10(−21) for 2ORF, 3ORF and 4ORF respectively. P values in B were 0.008; 6*10(−11); 6*10(−12) for 2ORF, 3ORF and 4ORF respectively. In both cases comparison was to the siRNA controls (Sc).</p
The effect of various UIR configurations on the activity of the DTA transgene.
<p>All construct had the CMV promoter before the UIR. REN l.u. = Renilla luciferase light units as determined by a luminometer. DTA activity is determined by dividing the REN l.u value of the “NO DTA” construct with that of each of the other constructs.</p><p>The effect of various UIR configurations on the activity of the DTA transgene.</p
Structure of the selected UIR construct.
<p>Each of the 7 ORFs was ∼600 bp long. ORFs 1–4 were in frame 1, ORFS 5–7 were in frame 2, and the DTA transgene ORF was in the 3<sup>rd</sup> frame. T1 and T2 are target sites (TS) for siRNAs. In constructs containing target sites for miRNAs there were usually 3 target sites. Full sequence and information on this construct, with target sites for siRNAs S4 and S5 can be found in the supplementary information).</p