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The quantum dynamics of interacting many-body systems has become a unique venue for the realization of novel states of matter. Here, we unveil a new class of nonequilibrium states that are eigenstates of an emergent local Hamiltonian. The latter is explicitly time dependent and, even though it does not commute with the physical Hamiltonian, it behaves as a conserved quantity of the time-evolving system. We discuss two examples of integrable systems in which the emergent eigenstate solution can be applied for an extensive (in system size) time: transport in one-dimensional lattices with initial particle (or spin) imbalance and sudden expansion of quantum gases in optical lattices. We focus on noninteracting spinless fermions, hard-core bosons, and the Heisenberg model. We show that current-carrying states can be ground states of emergent local Hamiltonians, and that they can exhibit a quasimomentum distribution function that is peaked at nonzero (and tunable) quasimomentum. We also show that time-evolving states can be highly excited eigenstates of emergent local Hamiltonians, with an entanglement entropy that does not exhibit volume-law scaling.

Multiple myeloma (MM) is an incurable plasma cell malignancy in which drug resistance remains a significant limitation to treatment. SKP2, the substrate-recognition component of the SCF-SKP2 ubiquitin-protein ligase complex, plays a critical role in the progression of various cancers, including MM. Targeting SKP2 as a therapeutic strategy offers a promising avenue for combating drug resistance in myeloma. Here, we show that SKP2 expression increases as the disease progresses from pre-myeloma to newly diagnosed and relapsed stages. Gene set enrichment analysis (GSEA) and immunoblotting further revealed that SKP2 inhibition by the preclinical chemical inhibitor SkpinC1 leads to decreased STAT3 inflammatory signalling and c-MYC expression in myeloma cells. When tested in SKP2 -overexpressing cells, SkpinC1 retained the ability to reduce activated STAT3, c-MYC, and c-MAF protein levels to impair cell growth and induce apoptosis. Furthermore, SkpinC1 synergistically enhanced the sensitivity of patient myeloma samples to bortezomib. Taken together, these findings underline the potential of SKP2 inhibition to overcome drug resistance in MM.

While majority of the current treatment approaches for cancer remain expensive and are associated with several side effects, development of new treatment modalities takes a significant period of research, time, and expenditure. An alternative novel approach is drug repurposing that focuses on finding new applications for the previously clinically approved drugs. The process of drug repurposing has also been facilitated by current advances in the field of proteomics, genomics, and information computational biology. This approach not only provides cheaper, effective, and potentially safer drugs with less side effects but also increases the processing pace of drug development. In this review, we wish to highlight some recent developments in the area of drug repurposing in cancer with a specific focus on the repurposing potential of anti-psychotic, anti-inflammatory and anti-viral drugs, anti-diabetic, antibacterial, and anti-fungal drugs.

Background: Percutaneous nephrostomy (PCN) is a commonly performed procedure by interventional radiology and urology to treat urinary obstruction. In this procedure, a catheter is percutaneously placed into the renal pelvis for urinary diversion or hemorrhagic cystitis. Material type, catheter size, and catheter shape (anti-dislodgement feature) ultimately contribute to the inherent traits of longevity in drainage catheter device. Reviewing the relative strengths or weaknesses of products in the existing clinical market may help clinicians critically appraise the devices they use with evidence-based findings from this review. Furthermore, a deeper understanding of the relative strengths and weaknesses of existing devices may help inform the next generation of drainage catheter devices to prolong the interval between exchanges without detriment to patient safety. Methods: The following electronic databases will be queried: PubMed, Web of Science, Cochrane from their inception to January 2023 to identify randomized controlled trials (RCTs) and cohort studies to investigate the differences that our interventions of catheter material, size, and dislodgement mechanism will have on the exchange interval (standard of care 90 days vs. 60 days vs. 45 days vs. 30 days). The primary outcomes will be the drainage catheter exchange frequency. Ethics and dissemination: We aim to share our findings through high-impact peer reviewed journals. As drainage catheters and minimally invasive interventional radiology procedures become more popular, it is important for healthcare providers taking case of these populations to understand which variables might optimize patient care and minimize emergent exchanges. Data will be made available to readers. Registration: PROSPERO ( CRD42023432788, 16 June 2023).

Background It is essential to understand the mechanisms responsible for hepatocellular carcinoma (HCC) progression and chemoresistance in order to identify prognostic biomarkers as well as potential therapeutic avenues. Recent findings have shown that SLIT3 appears to function as a novel tumor suppressor gene in various types of cancers, yet its clinical correlation and role in HCC has not been understood clearly. Methods We determined the transcript levels of Slit3 in tumor and adjacent normal tissues within two cohorts ( N  = 40 and 25) of HCC patients, and correlated the gene expression with the clinicopathological data. Subsequently, the functional effects and underlying molecular mechanisms of Slit3 overexpression and/or repression were studied using cell-line and mouse models. Results Our results demonstrated a repression in Slit3 expression in nearly 50% of the HCC patients, while the overall expression of Slit3 inversely correlated with the size of the tumor in both cohorts of patients. Stable down-regulation of Slit3 in HCC cell-lines induced cell proliferation in vitro and tumor growth in vivo, while stable Slit3 overexpression repressed these effects. Molecular investigations showed that the stable Slit3 repression-induced cell proliferation was associated with a higher expression of β-catenin and a repressed GSK3β activity. Moreover, Slit3-repression induced chemoresistance to sorafenib, oxaliplatin and 5-FU through impairment of β-catenin degradation and induction of cyclin D3 and survivin levels. The effects induced by stable Slit3-repression were diminished by transient repression of β-catenin by siRNA approach. Conclusion This study suggests that Slit3 acts as a tumor suppressor in HCC by repressing the tumor growth and thus tumor progression. Low Slit3 level indicates a poor response of HCC cells to chemotherapy. Restoration or overexpression of Slit3 is a potential therapeutic approach to repress the tumor growth and enhance the efficacy of chemotherapeutic agents.

Background Post‐embolization syndrome after transarterial chemoembolization (TACE) and Yttrium‐90 radioembolization (TARE) causes significant morbidity. Understanding whether discharge prescriptions influence short‐term outcomes may guide standardized pain‐management strategies. Methods A retrospective cohort study of 3191 patients (3988 procedures) with hepatocellular carcinoma from the Merative MarketScan Databases (2009–2022) was performed. The composite outcome was 7‐day drug escalation or hospital readmission. Bivariate logistic regression identified candidate variables (p < 0.10); multivariable logistic regression with patient‐clustered robust standard errors estimated adjusted odds ratios (aORs), adjusting for age, sex, and Charlson Comorbidity Index (CCI). Results Compared to patients discharged without opioids post‐chemoembolization, those prescribed opioids at discharge had 83% lower odds of experiencing drug escalation or readmission (odds ratio [aOR] = 0.17, p < 0.001), and those undergoing radioembolization had 59% lower odds (aOR = 0.41, p < 0.001). Being prescribed antiemetics or steroids was also associated with lower odds of escalation/readmission events, with percentages varying by procedure type. Conclusions Prescribing opioids, along with antiemetics and steroids, at discharge may reduce the likelihood of post‐procedural events, such as drug escalation and readmission, in patients undergoing trans‐arterial chemoembolization and radioembolization for hepatocellular carcinoma. These findings highlight the importance of a comprehensive pain management strategy in interventional oncology and warrant consideration in clinical practice guidelines.

Colorectal cancer results from genetic aberrations which accumulate over a long period of time, with malignant and metastatic properties acquired at a relatively late stage. A subpopulation of CD26+ colorectal cancer stem cells are known to be implicated in metastasis. We quantified CD26+ cancer cells in 11 primary tumor samples by flow cytometry, and showed that tumors having confirmed or suspected metastases harbored a relatively high CD26+ level in these samples. We hypothesized that this subpopulation of cancer stem cells arises in the late stage of carcinogenesis from the bulk of tumor daughter cells which are CD26−. The manipulation of PIK3CA and TP53, two genes commonly deregulated in the late stage, had an effect on the maintenance of the CD26+ cell population. When CD26− tumor daughter cells were sorted and cultured, the emergence of tumor spheres containing CD26+ cells occurred. These findings shed light to the origin of colorectal cancer stem cells with metastatic properties, which has an implication on conventional treatments by surgery or adjuvant chemotherapy for tumor debulking.

Purpose The present study aims to evaluate the safety and efficacy of advanced inferior vena cava filter (IVCF) retrieval using laser assistance compared with forceps via systematic review and quantitative aggregation of available data. Methods Pubmed and Embase were queried from establishment to September 2021. Original studies with a sample size ≥ 5 that reported at least one primary outcome of patients who underwent laser- or forceps-assisted IVCF retrieval were included. Primary outcomes included technical success and complication rates. Baseline characteristics were extracted: age, sex, presence of filter thrombus, strut penetration, previous retrieval attempt, filter dwell time, fluoroscopy time, and filter type. Complications were categorized by type and severity. Categorical data was pooled and evaluated with chi-square or Fisher exact tests. Results From the 16 included studies, a total of 673 and 368 patients underwent laser- and forceps-assisted IVCF retrieval, respectively. Successful retrieval was achieved in 98.1 and 93.7% patients from the laser and forceps groups, respectively ( p < 0.001). Major complication rates (1.6 vs 2.1%, p = 0.629) and risk of injury to cava or adjacent organs (1.0 vs 1.4%, p = 0.534) were similar between the two groups. A higher proportion of filters from the laser arm were closed-cell design (75.4 vs 68.1%, p = 0.020). Conclusion Based on limited available evidence, forceps- and laser-assisted complex IVCF retrievals were equally safe. The use of laser sheath is associated with a higher retrieval rate than forceps alone, though the baseline characteristics of two cohorts were not controlled. Future large-scale case-controlled comparative studies with longer clinical follow-up are warranted.

Background Recently the role of microRNAs has been explored immensely as novel regulators and potential biomarkers in several cancers. MiR-509-3p is one such miRNA that has been observed to show a mixed expression in different cancers, while it’s expression and clinical relevance in colorectal cancer (CRC) has not yet been characterized. Methods We used quantitative PCR to evaluate the expression of miR-509-3p in fresh-frozen CRC tumor tissues and the corresponding tumor-adjacent normal (NAT) tissues from 103 patients. Subsequently, functional studies were performed to further interpret the role of the miRNA in CRC. Results MiR-509-3p was found to be overexpressed in CRC tissues in nearly 80% of cases and was associated with an aggressive disease presentation. Notably, a higher expression of the miRNA promoted cell proliferation, migration, and invasion of CRC cells in in vitro and in vivo models. Mechanistically, we confirmed that miR-509-3p directly binds the 3’UTR of the tumor suppressor PHLPP2 and inhibits its expression. Furthermore, within the previous 103 clinical tissue specimens, we observed an overexpression of miR-509-3p within the NAT tissue of patients associated with a poor disease prognosis. Using multivariate analysis, it was observed that the expression of miR-509-3p within the NAT tissue was an independent predictor of prognosis in CRC. At the cellular level, through indirect coculture experiments, miR-509-3p was observed to regulate the proliferative, migratory, and invasive behavior of normal colon cells. Conclusion MiR-509-3p strongly contributes to the development and progression of CRC and can potentially function as a prognostic biomarker in the disease.

Piwi-interacting RNAs (piRNAs) represent a novel class of small non-coding RNAs (ncRNAs) that have been shown to have a deregulated expression in several cancers, although their clinical significance in colorectal cancer (CRC) remains unclear. With an aim of delineating the piRNA distribution in CRC, we conducted a systematic discovery and validation of piRNAs within two clinical cohorts. In the discovery phase, we profiled tumor and adjacent normal tissues from 18 CRC patients by deep sequencing and identified a global piRNA downregulation in CRC. Moreover, we identified piR-24000 as an unexplored piRNA that was significantly overexpressed in CRC. Using qPCR, we validated the overexpression of piR-24000 in 87 CRC patients. Additionally, we identified a significant association between a high expression of piR-24000 and an aggressive CRC phenotype including poor differentiation, presence of distant metastases, and a higher stage. Lastly, ROC analysis demonstrated a strong diagnostic power of piR-24000 in discriminating CRC patients from normal subjects. Taken together, this study provides one of the earliest large-scale reports of the global distribution of piRNAs in CRC. In addition, piR-24000 was identified as a likely oncogene in CRC that can serve as a biomarker or a therapeutic target.