Transcriptomes of the tumor-adjacent normal tissues are more informative than tumors in predicting recurrence in colorectal cancer patients.

BACKGROUND: Previous investigations of transcriptomic signatures of cancer patient survival and post-therapy relapse have focused on tumor tissue. In contrast, here we show that in colorectal cancer (CRC) transcriptomes derived from normal tissues adjacent to tumors (NATs) are better predictors of relapse. RESULTS: Using the transcriptomes of paired tumor and NAT specimens from 80 Korean CRC patients retrospectively determined to be in recurrence or nonrecurrence states, we found that, when comparing recurrent with nonrecurrent samples, NATs exhibit a greater number of differentially expressed genes (DEGs) than tumors. Training two prognostic elastic net-based machine learning models-NAT-based and tumor-based in our Samsung Medical Center (SMC) cohort, we found that NAT-based model performed better in predicting the survival when the model was applied to the tumor-derived transcriptomes of an independent cohort of 450 COAD patients in TCGA. Furthermore, compositions of tumor-infiltrating immune cells in NATs were found to have better prognostic capability than in tumors. We also confirmed through Cox regression analysis that in both SMC-CRC as well as in TCGA-COAD cohorts, a greater proportion of genes exhibited significant hazard ratio when NAT-derived transcriptome was used compared to when tumor-derived transcriptome was used. CONCLUSIONS: Taken together, our results strongly suggest that NAT-derived transcriptomes and immune cell composition of CRC are better predictors of patient survival and tumor recurrence than the primary tumor.

Human Cell-Camouflaged Nanomagnetic Scavengers Restore Immune Homeostasis in a Rodent Model with Bacteremia.

Bloodstream infection caused by antimicrobial resistance pathogens is a global concern because it is difficult to treat with conventional therapy. Here, scavenger magnetic nanoparticles enveloped by nanovesicles derived from blood cells (MNVs) are reported, which magnetically eradicate an extreme range of pathogens in an extracorporeal circuit. It is quantitatively revealed that glycophorin A and complement receptor (CR) 1 on red blood cell (RBC)-MNVs predominantly capture human fecal bacteria, carbapenem-resistant (CR) Escherichia  coli, and extended-spectrum beta-lactamases-positive (ESBL-positive) E. coli, vancomycin-intermediate Staphylococcus aureus (VISA), endotoxins, and proinflammatory cytokines in human blood. Additionally, CR3 and CR1 on white blood cell-MNVs mainly contribute to depleting the virus envelope proteins of Zika, SARS-CoV-2, and their variants in human blood. Supplementing opsonins into the blood significantly augments the pathogen removal efficiency due to its combinatorial interactions between pathogens and CR1 and CR3 on MNVs. The extracorporeal blood cleansing enables full recovery of lethally infected rodent animals within 7 days by treating them twice in series. It is also validated that parameters reflecting immune homeostasis, such as blood cell counts, cytokine levels, and transcriptomics changes, are restored in blood of the fatally infected rats after treatment.

Investigation of the putative role of antisense transcripts as regulators of sense transcripts by correlation analysis of sense-antisense pairs in colorectal cancers.

Antisense transcription occurs widely more expected than when it was first identified in bacteria in the 1980s. However, the functional relevance of antisense transcripts in transcription remains controversial. Here, we investigated the putative role of antisense transcripts in regulating their corresponding sense transcripts by analyzing changes in correlative relationships between sense-antisense pairs under tumor and normal conditions. A total of 3469 sense-antisense gene pairs (SAGPs) downloaded from BioMart mapped to a list of sense and antisense genes in RNA-seq data derived from 80 paired colorectal cancer (CRC) samples were analyzed. As a result, cancer-related genes were significantly enriched in the significantly correlated SAGPs (SCPs). Differentially expressed genes estimated between normal and tumor conditions were also significantly more enriched in SCPs than in non-SCPs. Interestingly, using differential correlation analysis, we found that tumor samples had a significantly larger density of genes with higher correlation coefficients than normal samples, as verified by various cancer transcriptomes from The Cancer Genome Atlas (TCGA). Moreover, we found that the magnitude of the correlation between SAGPs could distinguish poor prognostic CRCs from good prognostic CRCs, showing that correlation coefficients between the SAGPs of CRCs with a poor prognosis were significantly stronger than CRCs with a good prognosis. Consistent with this finding, the Cox proportion hazards model showed that the survival rates were significantly different between patients with high and low expression of genes in the SCPs. All these results strongly support the idea that antisense transcripts are important regulators of their corresponding sense transcripts.

Retraction fibers produced by fibronectin-integrin α5ß1 interaction promote motility of brain tumor cells.

Glioblastoma (GBM) is a refractory disease that has a highly infiltrative characteristic. Over the past decade, GBM perivascular niche (PVN) has been described as a route of dissemination. Here, we investigated that trailed membrane structures, namely retraction fibers (RFs), are formed by perivascular extracellular matrix (ECM) proteins. By using the anatomical GBM database, we validated that the ECM-related genes were highly expressed in the cells within the PVN where fibronectin (FN) induced RF formation. By disrupting candidates of FN-binding integrins, integrin α5ß1 was identified as the main regulator of RF formation. De novo RFs were produced at the trailing edge, and focal adhesions were actively localized in RFs, indicating that adhesive force makes RFs remain at the bottom surface. Furthermore, we observed that GBM cells more frequently migrated along the residual RFs formed by preceding cells in microfluidic channels in comparison to those in the channels without RFs, suggesting that the infiltrative characteristics GBM could be attributed to RFs formed by the preceding cells in concert with chemoattractant cues. Altogether, we demonstrated that shedding membrane structures of GBM cells are maintained by FN-integrin α5ß1 interaction and promoted their motility .

Enhanced Diamagnetic Repulsion of Blood Cells Enables Versatile Plasma Separation for Biomarker Analysis in Blood.

A hemolysis-free and highly efficient plasma separation platform enabled by enhanced diamagnetic repulsion of blood cells in undiluted whole blood is reported. Complete removal of blood cells from blood plasma is achieved by supplementing blood with superparamagnetic iron oxide nanoparticles (SPIONs), which turns the blood plasma into a paramagnetic condition, and thus, all blood cells are repelled by magnets. The blood plasma is successfully collected from 4 mL of blood at flow rates up to 100 µL min-1 without losing plasma proteins, platelets, or exosomes with 83.3±1.64% of plasma volume recovery, which is superior over the conventional microfluidic methods. The theoretical model elucidates the diamagnetic repulsion of blood cells considering hematocrit-dependent viscosity, which allows to determine a range of optimal flow rates to harvest platelet-rich plasma and platelet-free plasma. For clinical validations, it is demonstrated that the method enables the greater recovery of bacterial DNA from the infected blood than centrifugation and the immunoassay in whole blood without prior plasma separation.

Poisson-Gaussian Noise Analysis and Estimation for Low-Dose X-ray Images in the NSCT Domain.

The noise distribution of images obtained by X-ray sensors in low-dosage situations can be analyzed using the Poisson and Gaussian mixture model. Multiscale conversion is one of the most popular noise reduction methods used in recent years. Estimation of the noise distribution of each subband in the multiscale domain is the most important factor in performing noise reduction, with non-subsampled contourlet transform (NSCT) representing an effective method for scale and direction decomposition. In this study, we use artificially generated noise to analyze and estimate the Poisson-Gaussian noise of low-dose X-ray images in the NSCT domain. The noise distribution of the subband coefficients is analyzed using the noiseless low-band coefficients and the variance of the noisy subband coefficients. The noise-after-transform also follows a Poisson-Gaussian distribution, and the relationship between the noise parameters of the subband and the full-band image is identified. We then analyze noise of actual images to validate the theoretical analysis. Comparison of the proposed noise estimation method with an existing noise reduction method confirms that the proposed method outperforms traditional methods.

Denoising Algorithm for CFA Image Sensors Considering Inter-Channel Correlation.

In this paper, a spatio-spectral-temporal filter considering an inter-channel correlation is proposed for the denoising of a color filter array (CFA) sequence acquired by CCD/CMOS image sensors. Owing to the alternating under-sampled grid of the CFA pattern, the inter-channel correlation must be considered in the direct denoising process. The proposed filter is applied in the spatial, spectral, and temporal domain, considering the spatio-tempo-spectral correlation. First, nonlocal means (NLM) spatial filtering with patch-based difference (PBD) refinement is performed by considering both the intra-channel correlation and inter-channel correlation to overcome the spatial resolution degradation occurring with the alternating under-sampled pattern. Second, a motion-compensated temporal filter that employs inter-channel correlated motion estimation and compensation is proposed to remove the noise in the temporal domain. Then, a motion adaptive detection value controls the ratio of the spatial filter and the temporal filter. The denoised CFA sequence can thus be obtained without motion artifacts. Experimental results for both simulated and real CFA sequences are presented with visual and numerical comparisons to several state-of-the-art denoising methods combined with a demosaicing method. Experimental results confirmed that the proposed frameworks outperformed the other techniques in terms of the objective criteria and subjective visual perception in CFA sequences.

On-Site Bioaerosol Sampling and Airborne Microorganism Detection Technologies.

Bioaerosols are small airborne particles composed of microbiological fragments, including bacteria, viruses, fungi, pollens, and/or by-products of cells, which may be viable or non-viable wherever applicable. Exposure to these agents can cause a variety of health issues, such as allergic and infectious diseases, neurological disorders, and cancer. Therefore, detecting and identifying bioaerosols is crucial, and bioaerosol sampling is a key step in any bioaerosol investigation. This review provides an overview of the current bioaerosol sampling methods, both passive and active, as well as their applications and limitations for rapid on-site monitoring. The challenges and trends for detecting airborne microorganisms using molecular and immunological methods are also discussed, along with a summary and outlook for the development of prompt monitoring technologies.

Relationship between female sexual function, vaginal volume, vaginal resting tone, and pelvic floor muscle strength in women with stress urinary incontinence.

OBJECTIVE: Vaginal morphology and pelvic floor muscle (PFM) strength may influence sexual stimulation, sensation, and orgasmic response. This study aimed to determine the relationship between female sexual function and PFM strength and vaginal morphology (represented by vaginal resting tone and vaginal volume) in women with stress urinary incontinence (SUI). METHODS: Forty-two subjects with SUI were recruited for the study. Female sexual function was measured using the female sexual function index (FSFI) questionnaire. PFM strength was measured by digital palpation. Vaginal resting tone (mmHg) and vaginal volume (mL) were measured using a perineometer. The significance of the correlations between female sexual function and PFM function and hip muscle strength was assessed using Pearson's correlation coefficients. If a significant correlation between vaginal morphology and FSFI score was confirmed using Pearson's correlation, the cutoff value was confirmed through a decision tree. RESULTS: PFM strength was significantly correlated with desire (r=0.397), arousal (r=0.388), satisfaction (r=0.326), and total (r=0.315) FSFI scores. Vaginal resting tone (r=-0.432) and vaginal volume (r=0.332) were significantly correlated with the FSFI pain score. The cutoff point of vaginal resting tone for the presence of pain-related sexual dysfunction was >15.2 mmHg. CONCLUSION: PFM strength training should be the first strategy to improve female sexual function. Additionally, because of the relationship between vaginal morphology and pain-related sexual dysfunction, surgical procedures to achieve vaginal rejuvenation should be carefully considered.

Effect of pelvic floor muscle electrical stimulation on lumbopelvic control in women with stress urinary incontinence: randomized controlled trial.

INTRODUCTION: The pelvic floor muscle (PFM) plays a role not only in lumbopelvic stabilization, but also in incontinence and sexual function. OBJECTIVE: This study aimed to determine the effectiveness of PFM training by electrical stimulation (ES) on urinary incontinence, PFM performance (i.e. strength and power), lumbopelvic control, and abdominal muscle thickness in women with stress urinary incontinence (SUI). METHODS: Participants were randomized into ES and control groups. The ES group underwent PFM ES for 8 weeks, whereas the control group underwent only a walking program. The impact of urinary incontinence on quality of life was assessed by the Incontinence Impact Questionnaire (IIQ)-7. PFM strength and power were measured using a perineometer. Lumbopelvic control was measured by one and double-leg-lowering tests. Abdominal muscle thickness was measured by sonography. RESULTS: The ES group showed significantly improved IIQ-7 scores and PFM performance, and had significantly higher values in both one and double-leg lowering tests (p < .05) after 8 weeks of training, indicating significant improvement from pre-session values (p < .005). There were no significant between- or within-group differences at rest in abdominal muscle thickness. CONCLUSION: PFM ES could improve lumbopelvic control and PFM performance, and reduce subjective symptoms of urinary incontinence in women with SUI.

Cosmetic outcome after electrocautery versus non-electrocautery dissection of the temporalis muscle for pterional craniotomy.

OBJECTIVE: Despite the usefulness of pterional craniotomy (PC), its cosmetic outcome is questionable. Electrocautery (EC) causes injuries to adjacent structures, and it could be a factor that affects the cosmetic outcome. Evaluation of cosmetic outcome is difficult because it is often determined by patient's subjective criteria. The objective of this study is to compare the cosmetic outcome after EC versus non-electrocautery (NEC) dissection of the temporalis muscle for PC by analyzing long-term follow-up data determined from both physician and patient's aspects. METHODS: Patients at follow-ups between January 2014 and April 2021 after PCs were enrolled. The keyhole (KH) site, the inferior margin of the temporal line of the frontal bone (ITL), the mid-temporal (mid-T) area, and the posterior incision line (PIL) were inspected by a physician to check the presence of depressions. Patient's cosmetic satisfaction was categorized into satisfactory, intermediate, or unsatisfactory by a survey. The presence of osteolysis was checked from the radiological images. Patients were classified into two groups; one with EC dissection and another with NEC retrograde dissection using a double-ended dissector. RESULTS: The incidences of depression at the mid-T area and osteolysis were higher in the EC group (p=0.001, p＜0.001). The percentage of satisfactory cosmetic outcome was lower in the EC group (p=0.002). The presences of depression at the mid-T area and osteolysis were related with lower rate of satisfactory outcomes (p＜0.001, p＜0.001). Conclusions: NEC dissection causes less destruction to adjacent structures and brings better cosmetic outcome after PC.

Quantitative Fluorescence In Situ Hybridization (FISH) of Magnetically Confined Bacteria Enables Early Detection of Human Bacteremia.

The current diagnosis of bacteremia mainly relies on blood culture, which is inadequate for the rapid and quantitative determination of most bacteria in blood. Here, a quantitative, multiplex, microfluidic fluorescence in situ hybridization method (µFISH) is developed, which enables early and rapid (3-h) diagnosis of bacteremia without the need for prior blood culture. This novel technology employs mannose-binding lectin-coated magnetic nanoparticles, which effectively opsonize a broad range of pathogens, magnetically sequestering them in a microfluidic device. Therein, µFISH probes, based on unique 16S rRNA sequences, enable the identification and quantification of sequestered pathogens both in saline and whole blood, which is more sensitive than conventional polymerase chain reaction. Using µFISH, Escherichia coli (E. coli) is detected in whole blood collected from a porcine disease model and from E. coli-infected patients. Moreover, the proportion of E. coli, relative to other bacterial levels in the blood, is accurately and rapidly determined, which is not possible using conventional diagnostic methods. Blood from E. coli-infected patients is differentiated from healthy donors' blood using cutoff values with a 0.05 significance level. Thus, µFISH is a versatile method that can be used to rapidly identify pathogens and determine their levels relative to other culturable and nonculturable bacteria in biological samples.

Effect of pelvic floor electrical stimulation on diaphragm excursion and rib cage movement during tidal and forceful breathing and coughing in women with stress urinary incontinence: A randomized controlled trial.

BACKGROUND: The pelvic floor muscle (PFM) is associated with respiratory function. We investigated the effects of PFM training by pelvic floor electrical stimulation (PFES) on PFM strength, diaphragm excursion, and upper rib cage movement during tidal and forceful breathing and coughing in women with stress urinary incontinence (SUI). METHODS: In total, 33 participants with SUI were divided into PFES and control groups. The two groups were measured pre- and post-8 weeks of training. Diaphragm excursion and upper rib cage movement during tidal and forceful breathing and coughing and PFM strength were measured using sonography, electromagnetic sensors, and perineometry. RESULTS: There were significant difference of main effect between pre- and post-training and between groups in PFM strength (between groups: P = .001, between time: P < .001) and diaphragm excursion during forceful breathing (between groups: P = .015, between time: P = .026) and coughing (between groups: P = .035, between time: P = .006). There were significant differences in diaphragm excursion during tidal (P = .002) and forceful breathing (P = .005) and coughing (P < .001) between pre- and post-training in the PFES group. Elevation of the upper rib cage during tidal (P < .001) and forceful breathing (P = .001) was significantly decreased after 8 weeks of training in the PFES group. Widening in the horizontal plane in the upper rib cage during forceful breathing (P < .001) was significantly increased after 8 weeks of training in the PFES group. PFM strength (P < .001) was significantly increased after 8 weeks of training in the PFES group. CONCLUSIONS: Pelvic floor muscles training by electrical stimulation can improve diaphragm excursion and breathing patterns in women with SUI.

Pure Cortical Ependymoma With RELA-Fusion Positive in a Young Adult.

A 25-year-old female presented with a generalized tonic-clonic seizure. She had no previous history of seizures. A brain magnetic resonance imaging scan revealed a solitary enhancing mass in the right fronto-parietal cortex. During surgery, the mass was noted to be pure cortical with no connection to the ventricular lining. The tumor was completely resected. After surgery, the patient had no further seizures. The biopsy result showed a supratentorial ependymoma, which was C11orf95-RELA-fusionpositive.

Analysis of Porcine Model of Fecal-Induced Peritonitis Reveals the Tropism of Blood Microbiome.

Recent studies have suggested the existence of a blood microbiome in the healthy host. However, changes in the blood microbiome upon bloodstream infection are not known. Here, we analyzed the dynamics of the blood microbiome in a porcine model of polymicrobial bacteremia induced by fecal peritonitis. Surprisingly, we detected bacterial populations in the bloodstream even before the infection, and these populations were maintained over time. The native blood microbiome was notably taxonomically different from the fecal microbiome that was used to induce peritonitis, reflecting microbial tropism for the blood. Although the population composition after the infection was similar to that of the native blood microbiome, new bacterial strains entered the bloodstream upon peritonitis induction as clinical symptoms relevant to sepsis developed. This indicates that the bacteria detected in the blood before peritonitis induction were derived from the blood rather than a contamination. Comparison of the functional pathways enriched in the blood and fecal microbiomes revealed that communication and stress management pathways are essential for the survival of the blood microbiome.

An inflammatory vascular endothelium-mimicking microfluidic device to enable leukocyte rolling and adhesion for rapid infection diagnosis.

Recruitment of circulating leukocytes to sites of infection is of utmost importance in the development, propagation, and outcome of sepsis. These multi-step processes are mediated by interactions between adhesion receptors of leukocytes and cell adhesion molecules (CAMs) of endothelial cells, such as P-selectin, E-selectin and ICAM-1. However, the potential utility of the CAMs-facilitated leukocyte capture has not been thoroughly investigated as an index of the host response to infection for diagnostic purposes. Here, we report that the systemic infection affects the expression of CAMs ligands on leukocytes, upregulating the expression of P-selectin ligand-1 (PSGL-1) and increasing the number of PSGL-1- and E-selectin ligand-1 (ESL-1)-expressing leukocyte levels in septic blood. We leveraged this finding to determine infection by measuring the increased adhesion of leukocytes to an inflammatory vascular endothelium-mimicking microchannel coated with CAMs. We successfully validated that the proposed method can significantly differentiate infection in bacteremia and endotoxemia models in rats as early as an hour post-infection using a finger-prick volume of blood (50 µL), which were unachievable with the conventional diagnostic methods.

Effects of surface electrical stimulation during sitting on pelvic floor muscle function and sexual function in women with stress urinary incontinence.

OBJECTIVE: Dysfunction of the pelvic floor muscles (PFM) is associated with sexual dysfunction in women with stress urinary incontinence (SUI). The EasyK7 device was developed to stimulate the PFM by surface electrical stimulation during sitting (SESdS). We investigated the effects of SESdS on PFM function and sexual function in women with SUI. METHODS: Women with SUI were randomized into the SESdS and control groups. PFM function and sexual function were assessed using a perineometer and the pelvic organ prolapse-urinary incontinence sexual function questionnaire (PISQ), respectively. After 8 weeks, the groups were compared using either analysis of covariance with the baseline values as covariates or the paired Student's t-test. RESULTS: The final analysis included 16 subjects from each group. There were significant differences between the SESdS and control groups after the intervention, as well as within the SESdS group between the pre- and post-intervention measurements. The P-values for the differences in PFM measurements between the groups, and between the pre- and post- intervention measurements within the SESdS group, were 0.001 and 0.004 for power, 0.015 and 0.011 for strength, and 0.012 and 0.034 for endurance, respectively. In addition, in the PISQ, there were significant differences between the groups and between the pre- and post-intervention measurements within the SESdS group in the partner-related domain (between groups: P=0.003; within SESdS group: P=0.024) and total score (between groups: P<0.001; within SESdS group: P=0.001). CONCLUSION: SESdS can improve PFM function and sexual function in women with SUI.Trial RegistrationClinical Research Information Service Identifier: KCT0003357.

Primary Gliosarcoma with Extracranial Metastasis.

A 69-year-old male presented with a week of worsening headache, mild dizziness and left side weakness, and the radiological work-up of his brain displayed an enhancing mass on the right frontal lobe. The tumor was totally resected. The patient was initially diagnosed with glioblastoma multiforme. His neurologic symptoms recovered after surgery. He underwent adjuvant radiotherapy with concurrent temozolomide. Approximately 7 months after surgery, the patient complained of epigastric pains. Abdominal CT scan showed multiple hepatic metastasis and multiple lymphadenopathy. Chest CT and Torso positron emission tomography-CT scans for additional metastasis study revealed multiple metastatic lesions in the right lung, left pleura, liver, lymph nodes, bones, and muscles. Percutaneous liver biopsy was performed, and associated pathology was consistent with sarcomatous component. After liver biopsy, brain tumor pathology was reviewed, which revealed typical gliomatous and sarcomatous components. The patient was therefore diagnosed with metastatic gliosarcoma. The patient was in a septic condition with aggravated pleural effusion. The patient died 9 months after the diagnosis of primary gliosarcoma.

Which pelvic floor muscle functions are associated with improved subjective and objective symptoms after 8 weeks of surface electrical stimulation in women with stress urinary incontinence?

OBJECTIVE: Stress urinary incontinence (SUI) is defined as involuntary urine loss during effort, sneezing, or coughing. We investigated which pelvic floor muscle (PFM) functions (muscle strength, power, and endurance) are associated with improvement in subjective and objective symptoms after 8 weeks of surface electrical stimulation (SES) training. This study was performed to determine the effects of SES in the seated position on PFM functions and subjective and objective symptoms, and to identify predictors of improved subjective and objective symptoms after 8 weeks of SES training via secondary analysis of females with SUI. STUDY DESIGN: The study was performed between August 2018 and December 2018. Patients with SUI were randomized into an SES group (n = 17) and a control group (n = 17). Both groups were assessed pre-intervention and after 8 weeks of intervention. The outcome measures were PFM functions (strength, power, and endurance) as measured via perineometry, the score on the urogenital distress inventory-6 (UDI-6), and the ultra-short perineal pad test result. RESULTS: Significant differences in all PFM functions, the UDI-6 score, and the pad weight were evident both between the groups (SES vs. control group) and within the groups (pre-SES vs. post-SES). On regression of factors predicting relative changes in subjective and objective symptoms, the relative change in PFM power accounted for 15 and 13 % of the variance in the UDI-6 score (P < 0.05) and pad weight (P < 0.05), respectively. CONCLUSIONS: SES in a seated position improved both subjective and objective symptoms in females with SUI. PFM power, the UDI-6 score, and the pad weight test result should be considered when developing intervention guidelines to improve the subjective and objective symptoms of females with SUI.