Meta-analysis of transjugular intrahepatic portosystemic shunt creation with intravascular ultrasound guidance.

PURPOSE: To conduct a meta-analysis to assess the efficacy of intravascular ultrasound (IVUS) during transjugular intrahepatic portosystemic shunt (TIPS) creation. METHODS: MEDLINE and Embase databases were queried until July 2022 for comparative studies reporting procedure metrics for TIPS creation with or without IVUS guidance. Meta-analysis was performed with random-effects modeling for total procedural time, time to portal venous access, fluoroscopy time, iodinated contrast volume use, air kerma, dose area product, and number of needle passes. Intraoperative procedure-related complications were also reviewed. RESULTS: Of 95 unique records initially identified, 6 were eligible for inclusion. A total of 194 and 240 patients underwent TIPS with and without IVUS guidance. Pooled analyses indicated that IVUS guidance was associated with reduced total procedure time (SMD -0.76 [95% CI -1.02, -0.50] P < 0.001), time to portal venous access (SMD -0.41 [95% CI -0.67, -0.15] P = 0.002), fluoroscopy time (SMD, -0.54 [95% CI -1.02, -0.07]; P = 0.002), contrast volume use (SMD, -0.89 [95% CI -1.16, -0.63]; P < 0.001), air kerma (SMD, -0.75 [95% CI -1.11, -0.38]; P < 0.001) and dose area product (SMD, -0.98 [95% CI -1.77, -0.20]; P = 0.013). 4.2 and 7.8 needle passes were required in the IVUS and non-IVUS group, respectively (SMD, -0.60 [95% CI -1.42, 0.21]; P = 0.134), whereas pooled complication rates were 15.2% (12/79), and 21.4% (28/131), respectively. CONCLUSION: IVUS guidance during TIPS creation improves procedural metrics including procedural time, contrast usage, and radiation exposure.

Decoding radiology reports: Potential application of OpenAI ChatGPT to enhance patient understanding of diagnostic reports.

PURPOSE: To evaluate the complexity of diagnostic radiology reports across major imaging modalities and the ability of ChatGPT (Early March 2023 Version, OpenAI, California, USA) to simplify these reports to the 8th grade reading level of the average U.S. adult. METHODS: We randomly sampled 100 radiographs (XR), 100 ultrasound (US), 100 CT, and 100 MRI radiology reports from our institution's database dated between 2022 and 2023 (N = 400). These were processed by ChatGPT using the prompt "Explain this radiology report to a patient in layman's terms in second person: ". Mean report length, Flesch reading ease score (FRES), and Flesch-Kincaid reading level (FKRL) were calculated for each report and ChatGPT output. T-tests were used to determine significance. RESULTS: Mean report length was 164 ± 117 words, FRES was 38.0 ± 11.8, and FKRL was 10.4 ± 1.9. FKRL was significantly higher for CT and MRI than for US and XR. Only 60/400 (15%) had a FKRL <8.5. The mean simplified ChatGPT output length was 103 ± 36 words, FRES was 83.5 ± 5.6, and FKRL was 5.8 ± 1.1. This reflects a mean decrease of 61 words (p < 0.01), increase in FRES of 45.5 (p < 0.01), and decrease in FKRL of 4.6 (p < 0.01). All simplified outputs had FKRL <8.5. DISCUSSION: Our study demonstrates the effective use of ChatGPT when tasked with simplifying radiology reports to below the 8th grade reading level. We report significant improvements in FRES, FKRL, and word count, the last of which requires modality-specific context.

Linked cluster expansion on trees.

The linked cluster expansion has been shown to be highly efficient in calculating equilibrium and nonequilibrium properties of a variety of 1D and 2D classical and quantum lattice models. In this article, we extend the linked cluster method to the Cayley tree and its boundaryless cousin the Bethe lattice. We aim to (a) develop the linked cluster expansion for these lattices, a novel application, and (b) to further understand the surprising convergence efficiency of the linked cluster method, as well as its limitations. We obtain several key results. First, we show that for nearest-neighbor Hamiltonians of a specific form, all finite treelike clusters can be mapped to one dimensional finite chains. We then show that the qualitative distinction between the Cayley tree and Bethe lattice appears due to differing lattice constants that is a result of the Bethe lattice being boundaryless. We use these results to obtain the explicit closed-form formula for the zero-field susceptibility for the entire disordered phase up to the critical point for Bethe lattices of arbitrary degree; remarkably, only 1D chainlike clusters contribute. We also obtain the exact zero field partition function for the Ising model on both trees with only the two smallest clusters, similar to the 1D chain. Finally, these results achieve a direct comparison between an infinite lattice with a nonnegligible boundary and one without any boundary, allowing us to show that the linked cluster expansion eliminates boundary terms at each order of the expansion, answering the question about its surprising convergence efficiency. We conclude with some ramifications of these results, and possible generalizations and applications.

Applying CRISPR-Cas9 screens to dissect hematological malignancies.

Bit by bit, over the last few decades, functional genomic tools have been piecing together the molecular puzzle driving tumorigenesis in human patients. Nevertheless, our understanding of the role of several genes and regulatory elements that drive critical cancer-associated physiological processes from disease development to progression to spread is very limited, which significantly affects our ability of applying these insights in the context of improved disease management. The recent advent of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9)-based technology and its application in cancer genomics has, however, allowed the generation of a wealth of knowledge that has helped decipher several critical questions associated with translational cancer research. Precisely, the high-throughput capability coupled with a high level of technological plasticity associated with the CRISPR-Cas9 screens have expanded our horizons from a mere struggle to appreciate cancer as a genetic disease to observing the integrated genomic/epigenomic network of numerous malignancies and correlating it with our present knowledge of drugging strategies to develop innovative approaches for next-generation precision cancer medicine. Specifically, within blood cancers, current CRISPR screens have specifically focused on improving our understanding of drug resistance mechanisms, disease biology, the development of novel therapeutic approaches, and identifying the molecular mechanisms of current therapies, with an underlying aim of improving disease outcomes. Here, we review the development of the CRISPR-Cas9 genome-editing strategy, explicitly focusing on the recent advances in the CRISPR-Cas9-based screening approaches, its current capabilities, limitations, and future applications in the context of hematological malignancies.

Impact of drainage catheter material, size, and anti-dislodgement mechanism on percutaneous nephrostomy exchange intervals: a systematic review protocol.

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).

High Levels of Tumor miR-187-3p-A Potential Tumor-Suppressor microRNA-Are Correlated with Poor Prognosis in Colorectal Cancer.

BACKGROUND: The microRNA miR-187-3p plays antitumor roles in a variety of cancers. We and others have previously identified miR-187-3p as a potential tumor suppressor in colorectal cancer (CRC), but there are also reports revealing that high miR-187-3p levels are associated with poor prognosis among CRC patients. This study further investigated the clinicopathological significance of miR-187-3p in CRC. METHODS: MiR-187-3p levels in paired polyp/CRC/normal specimens or primary CRC/liver metastasis specimens were determined by qPCR, and correlated with the patient's clinicopathological and postoperative survival data. The clinical findings were validated using our validation cohort and data obtained from the TCGA or GEO databases. The functional effects of miR-187-3p were investigated through its overexpression in CRC cell lines. RESULTS: MiR-187-3p was significantly repressed in colorectal polyps and CRC when compared to adjacent normal tissue. Overexpression of miR-187-3p in CRC cell lines impaired colony formation, cell migration, and invasion, and induced chemosensitivity. Clinical analysis revealed that despite miR-187-3p being repressed in CRC, high tumor miR-187-3p levels were positively correlated with tumor stage and disease recurrence. Further analysis showed that miR-187-3p levels were lower in metastatic specimens when compared to paired primary CRC, suggesting that high tumor miR-187-3p levels resulted from the dissemination of metastatic tumor cells. Tumor miR-187-3p levels were positively correlated with peripheral inflammation-related blood markers. Finally, SPRY1 was identified as a novel target gene of miR-187-3p, and was involved in miR-187-3p-impaired CRC metastasis. CONCLUSIONS: This study demonstrated that in spite of its repression and role as a tumor suppressor in CRC, high levels of miR-187-3p in tumors were correlated with poor prognosis and higher levels of peripheral inflammation-related blood markers.

Drug repurposing: re-inventing therapies for cancer without re-entering the development pipeline-a review.

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.

Rigid forceps and excimer laser use for complex inferior cava filter retrieval: a preliminary quantitative analysis of available evidence.

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.

MiR-509-3p is oncogenic, targets the tumor suppressor PHLPP2, and functions as a novel tumor adjacent normal tissue based prognostic biomarker in colorectal cancer.

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.

Investigation of miRNA dysregulation and association with immune cell profile during malignant transformation of colorectal cells.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent and life-threatening cancer among the world. Accumulated somatic mutations during malignant transformation process endow cancer cells with increased growth, invasiveness and immunogenicity. These highly immunogenic cancer cells develop multiple strategies to evade immune attack. Through post-transcriptional regulation, microRNAs (miRNAs) not only participate in cancer development and progression but also manipulate anti-cancer immune response. This study aims to identify miRNAs associated with the colorectal cell malignant transformation process and their association with immune cell population using synchronous adjacent normal, polyp and CRC specimens. METHODS: We conducted a Low Density Array to compare the miRNA expression profile of synchronous colorectal adenoma, adenocarcinoma and adjacent normal colon mucosa collected from 8 patients, in order to identify candidate miRNAs involved in CRC progression. These findings were further validated in 14 additional patients and GEO dataset GSE41655. The relative abundance of dendritic cells, natural killer cells, neutrophil and macrophage was determined and correlated with dysregulated miRNA levels. RESULTS: MicroRNA microarray identified 39 miRNAs aberrantly expressed during the colorectal cell transformation process. Seven novel miRNAs were shortlisted, and dysregulation of miR-149-3p, miR-192-3p, miR-335-5p and miR-425 were further validated by the qPCR validation experiment and data retrieved from the GEO dataset. Furthermore, these miRNAs demonstrated certain associations with level of dendritic cells, natural killer cells, neutrophil and macrophage within the polyp or CRC specimens. CONCLUSION: This study revealed miRNA dysregulated during stepwise malignant transformation of colorectal mucosal cells and their association with immune cell population.

A Pilot Study Investigating the Expression Levels of Pluripotency-Associated Genes in Rectal Swab Samples for Colorectal Polyp and Cancer Diagnosis and Prognosis.

Change in gene expression is inevitable in cancer development. With more studies demonstrating the contributions of cancer stem cells (CSCs) in colorectal cancer (CRC) development, this study is aimed at investigating whether rectal swab specimen serves as a tool for detection of dysregulation of CSC or stem cell (SC) markers and at evaluating its potential as a new promising screening method for high-risk patients. Expression levels of 15 pluripotency-associated genes were assessed by quantitative PCR in 53 rectal swab specimens referred for endoscopic screening. Dysregulated genes and joint panels based on such genes were examined for their diagnostic potentials for both polyp and CRC. Out of 15 genes, Oct4, CD26, c-MYC, and CXCR4 showed significantly differential expression among normal, polyp, and CRC patients. A panel of Oct4 and CD26 showed an AUC value of 0.80 (p = 0.003) in identifying CRC patients from polyp/normal subjects, with sensitivity and specificity of 84.6% and 69.2%. A panel of c-MYC and CXCR4 achieved CRC/polyp identification with an AUC value of 0.79 (p = 0.002), with a sensitivity of 82.8% and specificity of 80.0%. The sensitivity for polyp and CRC was 80.0% and 85.7%, respectively. Further analysis showed that higher c-MYC and CXCR4 level was detected in normal subjects who developed polyps after 5-6 years, in comparison with subjects with no lesion developed, and the AUC of the c-MYC and CXCR4 panel increased to 0.88 (p < 0.001), with sensitivity and specificity of 84.4% and 92.3%, respectively, when these patients were included in the polyp group. This study suggests that the Oct4 and CD26 panel is a promising biomarker for distinguishing CRC from normal and polyp patients, whereas the c-MYC and CXCR4 panel may identify polyp and CRC from normal individuals.

Pathophysiological roles of myristoylated alanine-rich C-kinase substrate (MARCKS) in hematological malignancies.

The myristoylated alanine-rich C-kinase substrate (MARCKS) protein has been at the crossroads of multiple signaling pathways that govern several critical operations in normal and malignant cellular physiology. Functioning as a target of protein kinase C, MARCKS shuttles between the phosphorylated cytosolic form and the unphosphorylated plasma membrane-bound states whilst regulating several molecular partners including, but not limited to calmodulin, actin, phosphatidylinositol-4,5-bisphosphate, and phosphoinositide-3-kinase. As a result of these interactions, MARCKS directly or indirectly modulates a host of cellular functions, primarily including cytoskeletal reorganization, membrane trafficking, cell secretion, inflammatory response, cell migration, and mitosis. Recent evidence indicates that dysregulated expression of MARCKS is associated with the development and progression of hematological cancers. While it is understood that MARCKS impacts the overall carcinogenesis as well as plays a part in determining the disease outcome in blood cancers, we are still at an early stage of interpreting the pathophysiological roles of MARCKS in neoplastic disease. The situation is further complicated by contradictory reports regarding the role of phosphorylated versus an unphosphorylated form of MARCKS as an oncogene versus tumor suppressor in blood cancers. In this review, we will investigate the current body of knowledge and evolving concepts of the physical properties, molecular network, functional attributes, and the likely pathogenic roles of MARCKS in hematological malignancies. Key emphasis will also be laid upon understanding the novel mechanisms by which MARCKS determines the overall disease prognosis by playing a vital role in the induction of therapeutic resistance. Additionally, we will highlight the importance of MARCKS as a valuable therapeutic target in blood cancers and will discuss the potential of existing strategies available to tackle MARCKS-driven blood cancers.

Small RNA Profiling of piRNAs in Colorectal Cancer Identifies Consistent Overexpression of piR-24000 That Correlates Clinically with an Aggressive Disease Phenotype.

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.

Roles of microRNAs as non-invasive biomarker and therapeutic target in colorectal cancer.

MicroRNAs are endogenous, short non-coding RNA molecules that function as critical regulators of various biological processes. There is a strong functional evidence linking the involvement of dysregulated miRNAs to the occurrence, development and progression of colorectal cancer. Studies indicate that while overexpression of oncomiRs, and repression of tumor suppressor miRNAs tends to drive the overall tumorigenic process, the global picture of aberrant miRNA expression in colorectal cancer can classify the disease into multiple molecular phenotypes. Moreover, the expression pattern of miRNAs in colorectal cancer make them viable disease determinants as well as potential therapeutic targets. Through this review, we will summarize the importance of miRNAs in the etiology and progression of colorectal cancer. Specifically, we will explore the key role played by these RNA molecules as likely therapeutic avenues and the strategies presently available to target them. Finally, we will investigate the role of miRNAs as potential non-invasive diagnostic and prognostic biomarkers in colorectal cancer.

Linking stemness with colorectal cancer initiation, progression, and therapy.

The discovery of cancer stem cells caused a paradigm shift in the concepts of origin and development of colorectal cancer. Several unresolved questions remain in this field though. Are colorectal cancer stem cells the cause or an effect of the disease? How do cancer stem cells assist in colorectal tumor dissemination to distant organs? What are the molecular or environmental factors affecting the roles of these cells in colorectal cancer? Through this review, we investigate the key findings until now and attempt to elucidate the origins, physical properties, microenvironmental niches, as well as the molecular signaling network that support the existence, self-renewal, plasticity, quiescence, and the overall maintenance of cancer stem cells in colorectal cancer. Increasing data show that the cancer stem cells play a crucial role not only in the establishment of the primary colorectal tumor but also in the distant spread of the disease. Hence, we will also look at the mechanisms adopted by cancer stem cells to influence the development of metastasis and evade therapeutic targeting and its role in the overall disease prognosis. Finally, we will illustrate the importance of understanding the biology of these cells to develop improved clinical strategies to tackle colorectal cancer.

Suppression of Slit3 induces tumor proliferation and chemoresistance in hepatocellular carcinoma through activation of GSK3ß/ß-catenin pathway.

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 ß-catenin and a repressed GSK3ß activity. Moreover, Slit3-repression induced chemoresistance to sorafenib, oxaliplatin and 5-FU through impairment of ß-catenin degradation and induction of cyclin D3 and survivin levels. The effects induced by stable Slit3-repression were diminished by transient repression of ß-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.

Emergence of CD26+ Cancer Stem Cells with Metastatic Properties in Colorectal Carcinogenesis.

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.

Identification of serum miR-139-3p as a non-invasive biomarker for colorectal cancer.

Aberrant levels of circulating microRNAs are potential biomarkers for the early detection of colorectal cancer. The aim of this study was to study miR-139-3p and miR-622 in serum as a non-invasive biomarker for colorectal cancer diagnosis. We applied quantitative polymerase chain reaction to determine the levels of miR-139-3p and miR-622 in 42 pairs of tumor and adjacent non-tumor tissues, and in serum samples of 117 patients and 90 control subjects. Our results showed that miR-139-3p was silenced whereas miR-622 was overexpressed in colorectal cancer. Similarly, serum miR-139-3p level was significantly lower in colorectal cancer patients than in control subjects whereas miR-622 was more frequently detectable in patients. ROC analysis showed that AUC of miR-139-3p was 0.9935, with a sensitivity of 96.6% and specificity of 97.8%. Serum miR-139-3p level showed high sensitivity and specificity for both early and late stage CRCs and proximal and distal CRCs. Detectable serum miR-622 showed a sensitivity of 87.5% and specificity of 63.5% for discriminating CRC patients, but the sensitivity dropped for late stage patients (72.7%). We also included analyses of the blood CEA level for comparing the diagnostic performance of these blood-based biomarkers. The median level in CRC patients (3.6 ng/ml) was significantly higher than that in control (1.8 ng/ml). The AUC value of CEA in diagnosing CRC patients was 0.7515. CEA showed a positive correlation with tumor stage and age of patients and its level was higher in male. Collectively, serum miR-139-3p has strong potential as a promising non-invasive biomarker in colorectal cancer detection.

Erratum: Optimization of finite-size errors in finite-temperature calculations of unordered phases [Phys. Rev. E 91, 062142 (2015)].

This corrects the article DOI: 10.1103/PhysRevE.91.062142.

Optimization of finite-size errors in finite-temperature calculations of unordered phases.

It is common knowledge that the microcanonical, canonical, and grand-canonical ensembles are equivalent in thermodynamically large systems. Here, we study finite-size effects in the latter two ensembles. We show that contrary to naive expectations, finite-size errors are exponentially small in grand canonical ensemble calculations of translationally invariant systems in unordered phases at finite temperature. Open boundary conditions and canonical ensemble calculations suffer from finite-size errors that are only polynomially small in the system size. We further show that finite-size effects are generally smallest in numerical linked cluster expansions. Our conclusions are supported by analytical and numerical analyses of classical and quantum systems.