Assessing Radiation Exposure and Contrast Agent Utilization: A Comparative Analysis of the Woven EndoBridge Device and Stent-Assisted Coil Embolization for Managing Unruptured Wide-Neck Bifurcation Aneurysms.

PURPOSE: In this study, we determined whether there were significant differences in procedure time, radiation dose, fluoroscopy time, and total contrast media dose when unruptured wideneck bifurcation aneurysms (WNBAs) were treated with the Woven EndoBridge (WEB) device and stent-assisted coil (SAC) embolization. MATERIALS AND METHODS: The WEB device and SAC embolization (14:17) were used to treat 31 cases of internal carotid artery bifurcation, anterior communicating artery, middle cerebral artery bifurcation, and basilar bifurcation aneurysms between August 2021 and December 2022. The procedure time, radiation dose, fluoroscopy time, and total contrast medium dose between the 2 treatment groups were compared and analyzed. In the WEB device group, the results between operators were compared, and the follow-up radiologic outcomes were investigated. RESULTS: The procedure and fluoroscopy times were significantly shorter in the WEB device group. Radiation and total contrast media dose were also significantly smaller in the WEB device, but there was no significant difference in results between operators. The follow-up radiological outcome showed adequate occlusion in 83.3% (10/12) of cases. CONCLUSION: The WEB device can be used as an alternative treatment method among the available endovascular treatment methods for WNBAs to reduce radiation exposure and the dose of contrast media when used adequately with appropriate indications.

Deep Learning Super-Resolution Technique Based on Magnetic Resonance Imaging for Application of Image-Guided Diagnosis and Surgery of Trigeminal Neuralgia.

This study aimed to implement a deep learning-based super-resolution (SR) technique that can assist in the diagnosis and surgery of trigeminal neuralgia (TN) using magnetic resonance imaging (MRI). Experimental methods applied SR to MRI data examined using five techniques, including T2-weighted imaging (T2WI), T1-weighted imaging (T1WI), contrast-enhancement T1WI (CE-T1WI), T2WI turbo spin-echo series volume isotropic turbo spin-echo acquisition (VISTA), and proton density (PD), in patients diagnosed with TN. The image quality was evaluated using the peak signal-to-noise ratio (PSNR) and structural similarity index (SSIM). High-quality reconstructed MRI images were assessed using the Leksell coordinate system in gamma knife radiosurgery (GKRS). The results showed that the PSNR and SSIM values achieved by SR were higher than those obtained by image postprocessing techniques, and the coordinates of the images reconstructed in the gamma plan showed no differences from those of the original images. Consequently, SR demonstrated remarkable effects in improving the image quality without discrepancies in the coordinate system, confirming its potential as a useful tool for the diagnosis and surgery of TN.

Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity.

BACKGROUND: Mitochondrial dysfunction is a primary driver of cardiac contractile failure; yet, the cross talk between mitochondrial energetics and signaling regulation remains obscure. Ponatinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia, is among the most cardiotoxic tyrosine kinase inhibitors and causes mitochondrial dysfunction. Whether ponatinib-induced mitochondrial dysfunction triggers the integrated stress response (ISR) to induce ponatinib-induced cardiotoxicity remains to be determined. METHODS: Using human induced pluripotent stem cells-derived cardiomyocytes and a recently developed mouse model of ponatinib-induced cardiotoxicity, we performed proteomic analysis, molecular and biochemical assays to investigate the relationship between ponatinib-induced mitochondrial stress and ISR and their role in promoting ponatinib-induced cardiotoxicity. RESULTS: Proteomic analysis revealed that ponatinib activated the ISR in cardiac cells. We identified GCN2 (general control nonderepressible 2) as the eIF2α (eukaryotic translation initiation factor 2α) kinase responsible for relaying mitochondrial stress signals to trigger the primary ISR effector-ATF4 (activating transcription factor 4), upon ponatinib exposure. Mechanistically, ponatinib treatment exerted inhibitory effects on ATP synthase activity and reduced its expression levels resulting in ATP deficits. Perturbed mitochondrial function resulting in ATP deficits then acts as a trigger of GCN2-mediated ISR activation, effects that were negated by nicotinamide mononucleotide, an NAD+ precursor, supplementation. Genetic inhibition of ATP synthase also activated GCN2. Interestingly, we showed that the decreased abundance of ATP also facilitated direct binding of ponatinib to GCN2, unexpectedly causing its activation most likely because of a conformational change in its structure. Importantly, administering an ISR inhibitor protected human induced pluripotent stem cell-derived cardiomyocytes against ponatinib. Ponatinib-treated mice also exhibited reduced cardiac function, effects that were attenuated upon systemic ISRIB administration. Importantly, ISRIB does not affect the antitumor effects of ponatinib in vitro. CONCLUSIONS: Neutralizing ISR hyperactivation could prevent or reverse ponatinib-induced cardiotoxicity. The findings that compromised ATP production potentiates GCN2-mediated ISR activation have broad implications across various cardiac diseases. Our results also highlight an unanticipated role of ponatinib in causing direct activation of a kinase target despite its role as an ATP-competitive kinase inhibitor.

MRI radiomics may predict early tumor recurrence in patients with sinonasal squamous cell carcinoma.

OBJECTIVES: Sinonasal squamous cell carcinoma (SCC) follows a poor prognosis with high tendency for local recurrence. We aimed to evaluate whether MRI radiomics can predict early local failure in sinonasal SCC. METHODS: Sixty-eight consecutive patients with node-negative sinonasal SCC (January 2005-December 2020) were enrolled, allocated to the training (n = 47) and test sets (n = 21). Early local failure, which occurred within 12 months of completion of initial treatment, was the primary endpoint. For clinical features (age, location, treatment modality, and clinical T stage), binary logistic regression analysis was performed. For 186 extracted radiomic features, different feature selections and classifiers were combined to create two prediction models: (1) a pure radiomics model; and (2) a combined model with clinical features and radiomics. The areas under the receiver operating characteristic curves (AUCs) were calculated and compared using DeLong's method. RESULTS: Early local failure occurred in 38.3% (18/47) and 23.8% (5/21) in the training and test sets, respectively. We identified several radiomic features which were strongly associated with early local failure. In the test set, both the best-performing radiomics model and the combined model (clinical + radiomic features) yielded higher AUCs compared to the clinical model (AUC, 0.838 vs. 0.438, p = 0.020; 0.850 vs. 0.438, p = 0.016, respectively). The performances of the best-performing radiomics model and the combined model did not differ significantly (AUC, 0.838 vs. 0.850, p = 0.904). CONCLUSION: MRI radiomics integrated with a machine learning classifier may predict early local failure in patients with sinonasal SCC. CLINICAL RELEVANCE STATEMENT: MRI radiomics intergrated with machine learning classifiers may predict early local failure in sinonasal squamous cell carcinomas more accurately than the clinical model. KEY POINTS: • A subset of radiomic features which showed significant association with early local failure in patients with sinonasal squamous cell carcinomas was identified. • MRI radiomics integrated with machine learning classifiers can predict early local failure with high accuracy, which was validated in the test set (area under the curve = 0.838). • The combined clinical and radiomics model yielded superior performance for early local failure prediction compared to that of the radiomics (area under the curve 0.850 vs. 0.838 in the test set), without a statistically significant difference.

E2F1 Mediates SOX17 Deficiency-Induced Pulmonary Hypertension.

BACKGROUND: Rare genetic variants and genetic variation at loci in an enhancer in SOX17 (SRY-box transcription factor 17) are identified in patients with idiopathic pulmonary arterial hypertension (PAH) and PAH with congenital heart disease. However, the exact role of genetic variants or mutations in SOX17 in PAH pathogenesis has not been reported. METHODS: SOX17 expression was evaluated in the lungs and pulmonary endothelial cells (ECs) of patients with idiopathic PAH. Mice with Tie2Cre-mediated Sox17 knockdown and EC-specific Sox17 deletion were generated to determine the role of SOX17 deficiency in the pathogenesis of PAH. Human pulmonary ECs were cultured to understand the role of SOX17 deficiency. Single-cell RNA sequencing, RNA-sequencing analysis, and luciferase assay were performed to understand the underlying molecular mechanisms of SOX17 deficiency-induced PAH. E2F1 (E2F transcription factor 1) inhibitor HLM006474 was used in EC-specific Sox17 mice. RESULTS: SOX17 expression was downregulated in the lung and pulmonary ECs from patients with idiopathic PAH. Mice with Tie2Cre-mediated Sox17 knockdown and EC-specific Sox17 deletion induced spontaneously mild pulmonary hypertension. Loss of endothelial Sox17 in EC exacerbated hypoxia-induced pulmonary hypertension in mice. Loss of SOX17 in lung ECs induced endothelial dysfunctions including upregulation of cell cycle programming, proliferative and antiapoptotic phenotypes, augmentation of paracrine effect on pulmonary arterial smooth muscle cells, impaired cellular junction, and BMP (bone morphogenetic protein) signaling. E2F1 signaling was shown to mediate the SOX17 deficiency-induced EC dysfunction. Pharmacological inhibition of E2F1 in Sox17 EC-deficient mice attenuated pulmonary hypertension development. CONCLUSIONS: Our study demonstrated that endothelial SOX17 deficiency induces pulmonary hypertension through E2F1. Thus, targeting E2F1 signaling represents a promising approach in patients with PAH.

Modulation of lncRNA links endothelial glycocalyx to vascular dysfunction of tyrosine kinase inhibitor.

AIMS: Novel cancer therapies leading to increased survivorship of cancer patients have been negated by a concomitant rise in cancer therapies-related cardiovascular toxicities. Sunitinib, a first line multi-receptor tyrosine kinase inhibitor, has been reported to cause vascular dysfunction although the initiating mechanisms contributing to this side effect remain unknown. Long non-coding RNAs (lncRNAs) are emerging regulators of biological processes in endothelial cells (ECs); however, their roles in cancer therapies-related vascular toxicities remain underexplored. METHODS AND RESULTS: We performed lncRNA expression profiling to identify potential lncRNAs that are dysregulated in human-induced pluripotent stem cell-derived ECs (iPSC-ECs) treated with sunitinib. We show that the lncRNA hyaluronan synthase 2 antisense 1 (HAS2-AS1) is significantly diminished in sunitinib-treated iPSC-ECs. Sunitinib was found to down-regulate HAS2-AS1 by an epigenetic mechanism involving hypermethylation. Depletion of HAS2-AS1 recapitulated sunitinib-induced detrimental effects on iPSC-ECs, whereas CRISPR-mediated activation of HAS2-AS1 reversed sunitinib-induced dysfunction. We confirmed that HAS2-AS1 stabilizes the expression of its sense gene HAS2 via an RNA/mRNA heteroduplex formation. Knockdown of HAS2-AS1 led to reduced synthesis of hyaluronic acid (HA) and up-regulation of ADAMTS5, an enzyme involved in extracellular matrix degradation, resulting in disruption of the endothelial glycocalyx which is critical for ECs. In vivo, sunitinib-treated mice showed reduced coronary flow reserve, accompanied by a reduction in Has2os and degradation of the endothelial glycocalyx. Finally, we identified that treatment with high molecular-weight HA can prevent the deleterious effects of sunitinib both in vitro and in vivo by preserving the endothelial glycocalyx. CONCLUSIONS: Our findings highlight the importance of lncRNA-mediated regulation of the endothelial glycocalyx as an important determinant of sunitinib-induced vascular toxicity and reveal potential novel therapeutic avenues to attenuate sunitinib-induced vascular dysfunction.

E-cigarettes Induce Dysregulation of Autophagy Leading to Endothelial Dysfunction in Pulmonary Arterial Hypertension.

Given the increasing popularity of electronic cigarettes (e-cigs), it is imperative to evaluate the potential health risks of e-cigs, especially in users with preexisting health concerns such as pulmonary arterial hypertension (PAH). The aim of the present study was to investigate whether differential susceptibility exists between healthy and patients with PAH to e-cig exposure and the molecular mechanisms contributing to it. Patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) from healthy individuals and patients with PAH were used to investigate whether e-cig contributes to the pathophysiology of PAH and affects EC homeostasis in PAH. Our results showed that PAH iPSC-ECs showed a greater amount of damage than healthy iPSC-ECs upon e-cig exposure. Transcriptomic analyses revealed that differential expression of Akt3 may be responsible for increased autophagic flux impairment in PAH iPSC-ECs, which underlies increased susceptibility upon e-cig exposure. Moreover, knockdown of Akt3 in healthy iPSC-ECs significantly induced autophagic flux impairment and endothelial dysfunction, which further increased with e-cig treatment, thus mimicking the PAH cell phenotype after e-cig exposure. In addition, functional disruption of mTORC2 by knocking down Rictor in PAH iPSC-ECs caused autophagic flux impairment, which was mediated by downregulation of Akt3. Finally, pharmacological induction of autophagy via direct inhibition of mTORC1 and indirect activation of mTORC2 with rapamycin reverses e-cig-induced decreased Akt3 expression, endothelial dysfunction, autophagic flux impairment, and decreased cell viability, and migration in PAH iPSC-ECs. Taken together, these data suggest a potential link between autophagy and Akt3-mediated increased susceptibility to e-cig in PAH.

Contrasting clinical characteristics and treatment patterns in women with newly diagnosed advanced-stage epithelial ovarian cancer in Australia, South Korea and Taiwan.

OBJECTIVE: The real-world INFORM study analyzed sociodemographics, treatment patterns and clinical outcomes for patients with newly diagnosed advanced epithelial ovarian cancer (EOC) in Australia, South Korea (S.Korea) and Taiwan preceding incorporation of poly(ADP-ribose) polymerase inhibitors into clinical practice. METHODS: Retrospective data from patients diagnosed with EOC (high-grade serous EOC for Taiwan) between January 2014 and December 2018 with ≥12 months follow-up from diagnosis were analyzed descriptively. Survival was evaluated by Kaplan-Meier with two-sided 95% confidence interval (CI). RESULTS: Of the 987 patients (Australia, 223; S.Korea, 513; Taiwan, 251), 98% received platinum-based chemotherapy (CT). In S.Korea and Taiwan 76.0% and 78.9% respectively underwent primary cytoreductive surgery; in Australia, 56.5% had interval debulking surgery. Bevacizumab was included in primary/maintenance therapy for 22.4%, 14.6% and 6.8% of patients in Australia, S.Korea and Taiwan, respectively. Patients receiving bevacizumab were high-risk (reimbursement policy) and achieved similar real-world progression-free survival (PFS) compared with CT only. Overall, the median real-world PFS (months; 95% CI) was similar across Australia (16.0 [14.63-18.08]), S.Korea (17.7 [16.18-19.27]) and Taiwan (19.1 [17.56-22.29]). CONCLUSION: This study reveals poor prognosis despite differences in demographics and treatment patterns for patients with EOC across Asia-Pacific suggesting the need for biomarker-driven novel therapies to improve outcomes.

Comparison of the Clinical Effectiveness Between Infrared Thermography and Electrophysiology Tests in Spinal Intradural Extramedullary Schwannoma.

Objective: Subjective pain is experienced differently by each patient; therefore, modalities that can objectify subjective symptoms are useful. Electrophysiology tests and infrared (IR) thermography can present subjective symptoms in an objective manner. This study aimed to compare the effectiveness of electrophysiology tests and IR thermography in patients with intradural extramedullary (IDEM) schwannoma and statistically analyze the results to verify the positive relationship between the subjective neurologic symptoms and test results. Methods: We retrospectively analyzed the data from 23 patients, pathologically confirmed to have IDEM spinal schwannoma after surgery between January 2012 and December 2020. All patients were preoperatively examined using IR thermography and an electrophysiology test. IR thermography was conducted again week after operation. The IR thermography results were classified as either positive or negative. Results: Radiculopathy symptoms were reported in 16 cases and myelopathy in 7 cases. Among the radiculopathy patients, 9 out of 16 (56.2%) showed positive electrophysiology test results. Among the myelopathy patients, 2 out of 7 (28.5%) showed positive electrophysiology test results. In the radiculopathy group, 15 out of 16 (93.7%) patients showed positive IR thermography results. In the myelopathy group, 2 out of 7 (28.5%) patients showed positive IR thermography results. The correlation between the IR thermography and electrophysiology test was analyzed. In the radiculopathy group, positive electrophysiology test result was obtained in 8 out of 15 (53.5%) patients with positive IR thermography result. Conclusion: In patients with IDEM schwannoma presenting radiculopathy symptoms, IR thermography is a complementary tool to objectify the neurological symptoms.

Prognostic factors of dose-response relationship for nodal control in metastatic lymph nodes of cervical cancer patients undergoing definitive radiotherapy with concurrent chemotherapy.

OBJECTIVE: Regional control is occasionally unsatisfactory in cervical cancer, with the optimal radiation dose for nodal metastases in definitive radiotherapy (RT) with concurrent chemotherapy (CRT) remaining controversial. We investigated dose-response relationship for nodal local control in cervical cancer. METHODS: We identified 115 patients with 417 metastatic nodes who received definitive CRT for cervical cancer with nodal metastases. External beam radiation therapy and brachytherapy plans were summated to determine total dose received by each node. Prognostic factors of nodal control and dose-response relationship were investigated using Cox-regression and restricted cubic spline function. RESULTS: The 2-year progression-free survival rate was 69.4%. Among 43 patients with failures, 17 patients (37.5%) had regional failure included in first failure sites of which all except one were in-field only regional failures. Total 30 nodes showed recurrence at initial metastatic site after treatment. Neutrophil-to-lymphocyte ratio (NLR) ≥3.1, total radiation dose (minimum dose received by 98% of the target volume in equivalent dose in 2 Gy per fractions), and initial nodal volume ≥5.29 mL were poor prognostic factors (all p<0.050) of nodal local control. Restricted cubic spline functions revealed strongest dose-response relationship in high NLR (NLR ≥3.1) and initial nodal volume ≥5.29 mL subgroup. CONCLUSION: Initial nodal volume, radiation dose, and NLR were significant factors of nodal local control in cervical cancer; a stronger dose-response relationship was seen in bulky nodes with high NLR. Clinicians may consider these factors when determining the RT dose and the need for boost to nodal metastases in cervical cancer.

Delayed Multiple Intracerebral Hemorrhage After Burr Hole Drainage of Chronic Subdural Hematoma During Failure of Warfarin Resumption in Atrial Fibrillation.

Many elderly people take warfarin due to underlying disease. Warfarin is a risk factor for developing chronic subdural hematomas and other intracranial hematomas. Our patient was on chronic warfarin treatment for longstanding atrial fibrillation and underwent burr hole trephination due to chronic subdural hematoma. Multiple intracerebral hemorrhages developed 7 days after surgery without resumption of warfarin. Here, we report and review this rare case.

Long non-coding RNAs and microRNAs as crucial regulators in cardio-oncology.

Cancer is one of the leading causes of morbidity and mortality worldwide. Significant improvements in the modern era of anticancer therapeutic strategies have increased the survival rate of cancer patients. Unfortunately, cancer survivors have an increased risk of cardiovascular diseases, which is believed to result from anticancer therapies. The emergence of cardiovascular diseases among cancer survivors has served as the basis for establishing a novel field termed cardio-oncology. Cardio-oncology primarily focuses on investigating the underlying molecular mechanisms by which anticancer treatments lead to cardiovascular dysfunction and the development of novel cardioprotective strategies to counteract cardiotoxic effects of cancer therapies. Advances in genome biology have revealed that most of the genome is transcribed into non-coding RNAs (ncRNAs), which are recognized as being instrumental in cancer, cardiovascular health, and disease. Emerging studies have demonstrated that alterations of these ncRNAs have pathophysiological roles in multiple diseases in humans. As it relates to cardio-oncology, though, there is limited knowledge of the role of ncRNAs. In the present review, we summarize the up-to-date knowledge regarding the roles of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in cancer therapy-induced cardiotoxicities. Moreover, we also discuss prospective therapeutic strategies and the translational relevance of these ncRNAs.

Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage III NSCLC patients undergoing maintenance immunotherapy.

PURPOSE: We investigated the dynamics of lymphocyte depletion and recovery during and after definitive concurrent chemoradiotherapy (CCRT), dose to which structures is correlated to them, and how they affect the prognosis of stage III non-small cell lung cancer (NSCLC) patients undergoing maintenance immunotherapy. METHODS AND MATERIALS: In this retrospective study, absolute lymphocyte counts (ALC) of 66 patients were obtained before, during, and after CCRT. Persistent lymphopenia was defined as ALC < 500/µL at 3 months after CCRT. The impact of regional dose on lymphocyte depletion and recovery was investigated using voxel-based analysis (VBA). RESULTS: Most patients (n = 65) experienced lymphopenia during CCRT: 39 patients (59.0%) had grade (G) 3+ lymphopenia. Fifty-nine patients (89.3%) recovered from treatment-related lymphopenia at 3 months after CCRT, whereas 7 (10.6%) showed persistent lymphopenia. Patient characteristics associated with persistent lymphopenia were older age and ALC before and during treatment. In multivariable Cox regression analysis, recovery from lymphopenia was identified as a significant prognostic factor for Progression Free Survival (HR 0.35, 95% CI 0.13-0.93, p = 0.034) and Overall Survival (HR 0.24, 95% CI 0.08-0.68, p = 0.007). Voxel-based analysis showed strong correlation of dose to the upper mediastinum with lymphopenia at the end of CCRT, but not at 3 months after CCRT. CONCLUSION: Recovery from lymphopenia is strongly correlated to improved survival of patients undergoing CCRT and adjuvant immunotherapy, and is correlated to lymphocyte counts pre- and post-CCRT. VBA reveals high correlation of dose to large vessels to lymphopenia at the end of CCRT. Therefore, efforts should be made not only for preventing lymphocyte depletion during CCRT but also for helping lymphocyte recovery after CCRT.

Genome-wide differential expression profiling of lncRNAs and mRNAs in human induced pluripotent stem cell-derived endothelial cells exposed to e-cigarette extract.

BACKGROUND: Electronic-cigarette (e-cig) usage, particularly in the youth population, is a growing concern. It is known that e-cig causes endothelial dysfunction, which is a risk factor for the development of cardiovascular diseases; however, the mechanisms involved remain unclear. We hypothesized that long noncoding RNAs (lncRNAs) may play a role in e-cig-induced endothelial dysfunction. METHODS: Here, we identified lncRNAs that are dysregulated in human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) following 24 h of e-cig aerosol extract treatment via microarray analysis. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analyses of the dysregulated mRNAs following e-cig exposure and constructed co-expression networks of the top 5 upregulated lncRNAs and the top 5 downregulated lncRNAs and the mRNAs that are correlated with them. Furthermore, the functional effects of knocking down lncRNA lung cancer-associated transcript 1 (LUCAT1) on EC phenotypes were determined as it was one of the significantly upregulated lncRNAs following e-cig exposure based on our profiling. RESULTS: 183 lncRNAs and 132 mRNAs were found to be upregulated, whereas 297 lncRNAs and 413 mRNAs were found to be downregulated after e-cig exposure. We also observed that e-cig caused dysregulation of endothelial metabolism resulting in increased FAO activity, higher mitochondrial membrane potential, and decreased glucose uptake and glycolysis. These results suggest that e-cig alters EC metabolism by increasing FAO to compensate for energy deficiency in ECs. Finally, the knockdown of LUCAT1 prevented e-cig-induced EC dysfunction by maintaining  vascular barrier, reducing reactive oxygen species level, and increasing migration capacity. CONCLUSION: This study identifies an expression profile of differentially expressed lncRNAs and several potential regulators and pathways in ECs exposed to e-cig, which provide insights into the regulation of lncRNAs and mRNAs and the role of lncRNA and mRNA networks in ECs associated e-cig exposure.

Desmoid Fibromatosis in the Multifidus Muscle Misdiagnosed as Intramuscular Schwannoma by Incisional Biopsy: A Case Report.

Desmoid fibromatosis is a locally aggressive myofibroblastic neoplasm. In this study, we report a case of desmoid fibromatosis in the paraspinal muscle that was misdiagnosed as intramuscular schwannoma through incisional biopsy at another hospital. We performed total excision of the mass lesion with a clear margin. We found that for an accurate diagnosis, magnetic resonance imaging, incisional biopsy and excisional biopsy were required.

Microporous polymers with cascaded cavities for controlled transport of small gas molecules.

In membrane-based separation, molecular size differences relative to membrane pore sizes govern mass flux and separation efficiency. In applications requiring complex molecular differentiation, such as in natural gas processing, cascaded pore size distributions in membranes allow different permeate molecules to be separated without a reduction in throughput. Here, we report the decoration of microporous polymer membrane surfaces with molecular fluorine. Molecular fluorine penetrates through the microporous interface and reacts with rigid polymeric backbones, resulting in membrane micropores with multimodal pore size distributions. The fluorine acts as angstrom-scale apertures that can be controlled for molecular transport. We achieved a highly effective gas separation performance in several industrially relevant hollow-fibrous modular platform with stable responses over 1 year.

Bacterial extracellular vesicles affect endocrine therapy in MCF7 cells.

BACKGROUND: : The microbiome is important in the development and progression of breast cancer. This study investigated the effects of microbiome derived from Klebsiella on endocrine therapy of breast cancer using MCF7 cells. The bacterial extracellular vesicles (EVs) that affect endocrine therapy were established through experiments focused on tamoxifen efficacy. METHODS: : The microbiomes of breast cancer patients and healthy controls were analyzed using next-generation sequencing. Among microbiome, Klebsiella was selected as the experimental material for the effect on endocrine therapy in MCF7 cells. MCF7 cells were incubated with tamoxifen in the absence/presence of bacterial EVs derived from Klebsiella pneumoniae and analyzed by quantitative real-time polymerase chain reaction and Western blot. RESULTS: : Microbiome derived from Klebsiella is abundant in breast cancer patients especially luminal A subtype compared to healthy controls. The addition of EVs derived from K pneumoniae enhances the anti-hormonal effects of tamoxifen in MCF7 cells. The increased efficacy of tamoxifen is mediated via Cyclin E2 and p-ERK. CONCLUSION: : Based on experiments, the EVs derived from K pneumoniae are important in hormone therapy on MCF7 cells. This result provides new insight into breast cancer mechanisms and hormone therapy using Klebsiella found in the microbiome.

Dosimetric Comparison of Radiation Techniques for Comprehensive Regional Nodal Radiation Therapy for Left-Sided Breast Cancer: A Treatment Planning Study.

PURPOSE: How modern cardiac sparing techniques and beam delivery systems using advanced x-ray and proton beam therapy (PBT) can reduce incidental radiation exposure doses to cardiac and pulmonary organs individually or in any combination is poorly investigated. METHODS: Among 15 patients with left-sided breast cancer, partial wide tangential 3D-conformal radiotherapy (3DCRT) delivered in conventional fractionation (CF) or hypofractionated (HF) schedules; PBT delivered in a CF schedule; and volumetric modulated arc therapy (VMAT) delivered in an HF schedule, each under continuous positive airway pressure (CPAP) and free-breathing (FB) conditions, were examined. Target volume coverage and doses to organs-at-risk (OARs) were calculated for each technique. Outcomes were compared with one-way analysis of variance and the Bonferroni test, with p-values <0.05 considered significant. RESULTS: Target volume coverage was within acceptable levels in all interventions, except for the internal mammary lymph node D95 (99% in PBT, 90% in VMAT-CPAP, 84% in VMAT-FB, and 74% in 3DCRT). The mean heart dose (MHD) was the lowest in PBT (<1 Gy) and VMAT-CPAP (2.2 Gy) and the highest in 3DCRT with CF/FB (7.8 Gy), respectively. The mean lung dose (MLD) was the highest in 3DCRT-CF-FB (20 Gy) and the lowest in both VMAT-HF-CPAP and PBT (approximately 5-6 Gy). VMAT-HF-CPAP and PBT delivered a comparable maximum dose to the left ascending artery (7.2 and 6.13 Gy, respectively). CONCLUSIONS: Both proton and VMAT in combination with CPAP can minimize the radiation exposure to heart and lung with optimal target coverage in regional RT for left-sided breast cancer. The clinical relevance of these differences is yet to be elucidated. Continued efforts are needed to minimize radiation exposures during RT treatment to maximize its therapeutic index.

Fecal microbiota changes with fermented kimchi intake regulated either formation or advancement of colon adenoma.

Gut bacteria might contribute in early stage of colorectal cancer through the development and advancement of colon adenoma, by which exploring either beneficial bacteria, which are decreased in formation or advancement of colon adenoma and harmful bacteria, which are increased in advancement of colon adenoma may result in implementation of dietary interventions or probiotic therapies to functional means for prevention. Korean fermented kimchi is one of representative probiotic food providing beneficiary microbiota and exerting significant inhibitory outcomes in both APC/Min+ polyposis model and colitis-associated cancer. Based on these backgrounds, we performed clinical trial to document the changes of fecal microbiota in 32 volunteers with normal colon, simple adenoma, and advanced colon adenoma with 10 weeks of fermented kimchi intake. Each amplicon is sequenced on MiSeq of Illumina and the sequence reads were clustered into Operational Taxonomic Units using VSEARCH and the Chao Indices, an estimator of richness of taxa per individual, were estimated to measure the diversity of each sample. Though significant difference in α or ß diversity was not seen between three groups, kimchi intake significantly led to significant diversity of fecal microbiome. After genus analysis, Acinobacteria, Cyanobacteria, Clostridium sensu, Turicibacter, Gastronaeophillales, H. pittma were proven to be increased in patients with advanced colon adenoma, whereas Enterococcua Roseburia, Coryobacteriaceau, Bifidobacterium spp., and Akkermansia were proven to be significantly decreased in feces from patients with advanced colon adenoma after kimchi intake. Conclusively, fermented kimchi plentiful of beneficiary microbiota can afford significant inhibition of either formation or advancement of colon adenoma.

Sortase A-Inhibitory Coumarins from the Folk Medicinal Plant Poncirus trifoliata.

Thirteen coumarins (1-13), including five new compounds (1-5), were isolated from the folk medicinal plant Poncirus trifoliata. Combined spectroscopic analyses revealed that coumarins 1-4 are bis-isoprenylated coumarins with diverse oxidation patterns, while 5 is an enantiomeric di-isoprenylated coumarin. The absolute configurations of the stereogenic centers in the isoprenyl chains were assigned through MTPA and MPA methods, and those of the known compounds triphasiol (6) and ponciol (7) were also assigned using similar methods. These coumarins inhibited significantly Staphylococcus aureus-derived sortase A (SrtA), a transpeptidase responsible for anchoring surface proteins to the peptidoglycan cell wall in Gram-positive bacteria. The present results obtained indicated that the bioactivity and underlying mechanism of action of these coumarins are associated with the inhibition of SrtA-mediated S. aureus adhesion to eukaryotic cell matrix proteins including fibrinogen and fibronectin, thus potentially serving as SrtA inhibitors.