Tailoring the Structure-Property Relationship of Ring-Opened Metathesis Copolymers for CO2-Selective Membranes.

In this work, we explore the use of ring-opening metathesis polymerization (ROMP) facilitated by a second-generation Grubbs catalyst (G2) for the development of advanced polymer membranes aimed at CO2 separation. By employing a novel copolymer blend incorporating 4,4'-oxidianiline (ODA), 1,6-hexanediamine (HDA), 1-adamantylamine (AA), and 3,6,9-trioxaundecylamine (TA), along with a CO2-selective poly(ethylene glycol)/poly(propylene glycol) copolymer (Jeffamine2003) and polydimethylsiloxane (PDMS) units, we have synthesized membranes under ambient conditions with exceptional CO2 separation capabilities. The strategic inclusion of PDMS, up to a 20% composition within the PEG/PPG matrix, has resulted in copolymer membranes that not only surpass the 2008 upper limit for CO2/N2 separation but also meet the commercial targets for CO2/H2 separation. Comprehensive analysis reveals that these membranes adhere to the mixing rule and exhibit percolation behavior across the entire range of compositions (0-100%), maintaining robust antiplasticization performance even under pressures up to 20 atm. Our findings underscore the potential of ROMP in creating precisely engineered membranes for efficient CO2 separation, paving the way for their application in large-scale environmental and industrial processes.

Preoperative C-reactive protein/albumin ratio and mortality of off-pump coronary artery bypass graft.

Background: We sought to investigate the prognostic value of preoperative C-reactive protein (CRP)-to-albumin ratio (CAR) for the prediction of mortality in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Methods: From January 2010 to August 2016, adult patients undergoing OPCAB were analyzed retrospectively. In a total of 2,082 patients, preoperative inflammatory markers including CAR, CRP, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were recorded. Receiver operating characteristic (ROC) curves were used to determine the optimal threshold and compare the predictive values of the markers. The patients were divided into two groups according to the cut-off value of CAR, and then the outcomes were compared. The primary end point was 1-year mortality. Results: During the 1-year follow-up period, 25 patients (1.2%) died after OPCAB. The area under the curve of CAR for 1-year mortality was 0.767, which was significantly higher than other inflammatory markers. According to the calculated cut-off value of 1.326, the patients were divided into two groups: 1,580 (75.9%) patients were placed in the low CAR group vs. 502 (24.1%) patients in the high CAR group. After adjustment with inverse probability weighting, high CAR was significantly associated with increased risk of 1-year mortality after OPCAB (Hazard ratio, 5.01; 95% Confidence interval, 2.01-12.50; p < 0.001). Conclusions: In this study, we demonstrated that preoperative CAR was associated with 1-year mortality following OPCAB. Compared to previous inflammatory markers, CAR may offer superior predictive power for mortality in patients undergoing OPCAB. For validation of our findings, further prospective studies are needed.

PolyMOF nanoparticles constructed from intrinsically microporous polymer ligand towards scalable composite membranes for CO2 separation.

Integrating different modification strategies into a single step to achieve the desired properties of metal-organic frameworks (MOFs) has been very synthetically challenging, especially in developing advanced MOF/polymer mixed matrix membranes (MMMs). Herein, we report a polymer-MOF (polyMOF) system constructed from a carboxylated polymer with intrinsic microporosity (cPIM-1) ligand. This intrinsically microporous ligand could coordinate with metals, leading to ~100 nm-sized polyMOF nanoparticles. Compared to control MOFs, these polyMOFs exhibit enhanced ultramicroporosity for efficient molecular sieving, and they have better dispersion properties in casting solutions to prepare MMMs. Ultimately, integrating coordination chemistries through the cPIM-1 and polymer-based functionality into porous materials results in polyMOF/PIM-1 MMMs that display excellent CO2 separation performance (surpassing the CO2/N2 and CO2/CH4 upper bounds). In addition to exploring the physicochemical and transport properties of this polyMOF system, scalability has been demonstrated by converting the developed MMM material into large-area (400 cm2) thin-film nanocomposite (TFN) membranes.

The utility of the perfusion index as an indicator of anesthetic depth for repeated propofol sedation in children: An observational study.

BACKGROUND: Children receiving proton therapy require repeated sedation. In this study, we aimed to investigate the utility of the perfusion index (PI) for evaluating consciousness level during repeated propofol sedation. METHODS: In this prospective observational study, children aged from birth to 19 years old scheduled for proton therapy under repeated propofol sedation were enrolled. The primary outcome was the equivalence of PI values 5 min after anesthesia induction on consecutive sedation. Total consumption of propofol during sedation, time to reach the University of Michigan sedation scale (UMSS) score 1 after end of proton therapy, and duration of post-anesthesia care unit (PACU) stay were recorded. RESULTS: The PI values measured 5 min after induction of anesthesia were not equivalent to each other in consecutive sedation except for the second versus third (1st vs. 2nd: 97.5% CI: -1.34, 0.91; p = 0.206, 0.034; 2nd vs. 3rd: 97.5% CI: -0.87, 0.94; p = 0.023, 0.036 3rd vs. 4th: 97.5% CI: -2.08, -0.26; p < 0.99, <0.001; 4th vs. 5th: 97.5% CI: 0.21, 2.28; p < 0.001, >0.99; respectively). In consecutive sedation, there was not a significantly different difference in the time to reach UMSS score 1 (p > 0.99, all) for total consumption of propofol, time to reach UMSS score 1 after the end of proton therapy, and duration of PACU stay. CONCLUSIONS: During repeated propofol sedation in children, PI was insufficient to be used as an indicator of consciousness level assessment. However, we suggest that the information related to repeated sedation provided by this study may be helpful in clinical practice.

Effect of preoperative patient education and simulated mouth breathing training on opioid requirements in the post-anesthesia care unit after nasal surgery: a randomized controlled study.

BACKGROUND: A simulated education, prior to surgery about postoperative nasal stuffiness and ease of breathing through the mouth may help patients tolerate discomfort after nasal surgery. This study aimed to investigate the effect of preoperative simulated education on immediate postoperative opioid requirements in patients undergoing elective nasal surgery. METHODS: This randomized controlled trial of 110 patients undergoing nasal surgery randomly allocated patients into either a control (group C) or an education group (group E). One day before surgery, patients in group E were intensively trained to breathe through the mouth by using a nasal clip, with informative explanations about inevitable nasal obstruction and discomfort following surgery. Patients in group C were provided with routine preoperative information. Total intravenous anesthesia (TIVA) with propofol and remifentanil was used for anesthesia. No further opioid was used for analgesia intraoperatively. The primary outcome was index opioid (fentanyl) requirements at the post-anesthesia recovery unit (PACU). Secondary outcomes were emergence agitation, pain scores at the PACU, and postoperative recovery using the Quality of Recovery-15 (QoR15-K). RESULTS: The rate of opioid use in the PACU was 51.0% in the group E and 39.6% in the group C (p = 0.242). Additional request for analgesics other than index opioid was not different between the groups. Emergence agitation, postoperative pain severity, and QoR15-K scores were comparable between the groups. CONCLUSION: Preoperative education with simulated mouth breathing in patients undergoing nasal surgery did not reduce opioid requirements. TRIAL REGISTRATION: KCT0006264; 16/09/2021; Clinical Research Information Services ( https://cris.nih.go.kr ).

Glutathione dynamics is a potential predictive and therapeutic trait for neoadjuvant chemotherapy response in bladder cancer.

Radical cystectomy with preoperative cisplatin-based neoadjuvant chemotherapy (NAC) is the standard care for muscle-invasive bladder cancers (MIBCs). However, the complete response rate to this modality remains relatively low, and current clinicopathologic and molecular classifications are inadequate to predict NAC response in patients with MIBC. Here, we demonstrate that dysregulation of the glutathione (GSH) pathway is fundamental for MIBC NAC resistance. Comprehensive analysis of the multicohort transcriptomes reveals that GSH metabolism and immune-response genes are enriched in NAC-resistant and NAC-sensitive MIBCs, respectively. A machine-learning-based tumor/stroma classifier is applied for high-throughput digitalized immunohistochemistry analysis, finding that GSH dynamics proteins, including glutaminase-1, are associated with NAC resistance. GSH dynamics is activated in cisplatin-resistant MIBC cells, and combination treatment with a GSH dynamics modulator and cisplatin significantly suppresses tumor growth in an orthotopic xenograft animal model. Collectively, these findings demonstrate the predictive and therapeutic values of GSH dynamics in determining the NAC response in MIBCs.

Days alive and out of hospital at 30 days and outcomes of off-pump coronary artery bypass grafting.

Days alive and out of hospital (DAOH) is a simple estimator based on the number of days not in hospital within a defined period. In cases of mortality within the period, DAOH is regarded as zero. It has not been validated solely in off-pump coronary artery bypass grafting (OPCAB). This study aimed to demonstrate a correlation between DAOH and outcome of OPCAB. We identified 2211 OPCAB performed from January 2010 to August 2016. We calculated DAOH at 30 and 60 days. We generated a receiver-operating curve and compared outcomes. The median duration of hospital stay after OPCAB was 6 days. The median DAOH values at 30 and 60 days were 24 and 54 days. The estimated thresholds for 3-year mortality for DAOH at 30 and 60 days were 20 and 50 days. Three-year mortality was higher for short DAOH (1.2% vs. 5.7% and 1.1% vs. 5.6% DAOH at 30 and 60 days). After adjustment, the short DAOH 30 group showed significantly higher mortality during 3-year follow-up (hazard ratio 3.07; 95% confidence interval 1.45-6.52; p = 0.004). DAOH at 30 days after OPCAB showed a correlation with 3-year outcomes. DAOH 30 might be a reliable long-term outcome measure that can be obtained within 30 days after surgery.

Neuregulin-1 reverses anxiety-like behavior and social behavior deficits induced by unilateral micro-injection of CoCl2 into the ventral hippocampus (vHPC).

Neuregulin-1 (NRG1) is an epidermal growth factor family member with essential roles in the developing and adult nervous systems. In recent years, establishing evidence has collectively suggested that NRG1 is a new modulator of central nervous system (CNS) injury and disease, with multifaceted roles in neuroprotection, remyelination, neuroinflammation, and other repair mechanisms. NRG1 signaling exerts its effects via the tyrosine kinase receptors ErbB2-ErbB4. The NRG1/ErbB network in CNS pathology and repair has evolved, primarily in recent years. In the present study, we demonstrated that a unilateral microinjection of CoCl2 into the ventral hippocampus (vHPC) induced hypoxic insult and led to anxiety-related behaviors and deficit sociability in mice. NRG1 treatment significantly alleviated the CoCl2-induced increase of hypoxic-related molecules and behavioral abnormalities. Furthermore, NRG1 reduced the CoCl2-induced neuroinflammation and neuronal deficits in the vHPC or primary hippocampal neurons in mice. Collectively, these results suggest that NRG1 ameliorates hypoxia by alleviating synaptic deficits and behavioral abnormalities of the CoCl2-induced vHPC hypoxic model.

Intratumoral spatial heterogeneity of tumor-infiltrating lymphocytes is a significant factor for precisely stratifying prognostic immune subgroups of microsatellite instability-high colorectal carcinomas.

Although the density of tumor-infiltrating lymphocytes (TILs) is known to be linked to prognosis in various cancers, the prognostic impact and immunologic significance of the spatial heterogeneity of TILs have been rarely investigated. In this study, CD3+ and CD8+ TILs were quantified in independent cohorts (discovery, n = 73; and external validation, n = 93) of colorectal carcinomas (CRCs) with microsatellite instability-high (MSI-H) utilizing whole-slide image analysis of CD3/CD8 immunohistochemistry. The Shannon and Simpson indices, which measure intratumoral patch-to-patch evenness of TIL densities, were used to quantitatively assess the spatial heterogeneity of TILs in each case. To uncover immune-related gene expression signatures of spatial heterogeneity-based TIL subgroups of MSI-H CRCs, representative cases were subjected to GeoMx digital spatial profiler (DSP) analysis. As expected, a low density of TILs was significantly associated with poor disease-free survival (DFS) in MSI-H CRCs. The TIL-low tumors were further classified into two subgroups based on the spatial heterogeneity of TILs: TIL-low/heterogeneity-high and TIL-low/heterogeneity-low subgroups. In both discovery and validation cohorts, the TIL-low/heterogeneity-high, TIL-low/heterogeneity-low, and TIL-high subgroups were significantly associated with poor, intermediate, and good DFS, respectively. In the DSP analysis, the TIL-low/heterogeneity-high subgroup showed higher spatial diversity in the expression of immune-related genes than that of the TIL-low/heterogeneity-low subgroup and exhibited upregulation of genes related to immune checkpoints, chemokine/cytokine receptors, and myeloid cells. TIL-low/heterogeneity-high tumors were also enriched with gene sets related to good response to immune checkpoint inhibitor therapy. In conclusion, TIL-low MSI-H CRCs are prognostically heterogeneous and can be divided into prognostically and immunologically distinct subgroups by considering the spatial heterogeneity of TILs. Our data suggest that intratumoral spatial heterogeneity of TILs can be used as a key element for clinically relevant immunologic subtyping of tumors.

Vasoactive inotropic score as a predictor of long-term mortality in patients after off-pump coronary artery bypass grafting.

Increased vasoactive-inotropic score (VIS) is a reliable predictor of mortality and morbidity after cardiac surgery. Here, we retrospectively evaluated the association between VIS and adverse outcomes in adult patients after off-pump coronary artery bypass grafting (OPCAB). We included 2149 patients who underwent OPCAB. The maximal VIS was calculated for the initial 48 postoperative hours using standard formulae. The primary outcome was 1-year death. The composite adverse outcome was death, resuscitation or mechanical support, myocardial infarction, revascularization, new-onset atrial fibrillation, infection requiring antibacterial therapy, acute kidney injury, and stroke. Path-analysis was conducted using lactate and prognostic nutritional index (PNI). VIS was associated with 1-year death (odds ratio [OR] 1.07 [1.04-1.10], p < 0.001) and 1-year composite outcome (OR 1.02 [1.0-1.03], p = 0.008). In path-analysis, high VIS showed a direct effect on the increased risk of 1-year death and composite outcome. In the pathway using lactate as a mediating variable, VIS showed an indirect effect on the composite outcome but no significant effect on death. Low PNI directly affected the increased risk of 1-year death and composite outcome, and had an indirect effect on both outcomes, even when VIS was used as a mediating variable. In patients undergoing OPCAB, high VIS independently predicted morbidity and 1-year death. Patients with increased lactate levels following high VIS had an increased risk of postoperative complications, although not necessarily resulting in death. However, patients with poor preoperative nutritional status had an increased risk of unfavourable outcomes, including death, implying the importance of preoperative nutritional support.

The Prognostic Reliability of Lymphovascular Invasion for Patients with T3N0 Colorectal Cancer in Adjuvant Chemotherapy Decision Making.

Lymphovascular invasion (LVI) is a high-risk feature guiding decision making for adjuvant chemotherapy. We evaluated the prognostic importance and reliability of LVI as an adjuvant chemotherapy indicator in 1634 patients with pT3N0 colorectal cancer treated with curative radical resection between 2012 and 2016. LVI and perineural invasion (PNI) were identified in 382 (23.5%) and 269 (16.5%) patients, respectively. In total, 772 patients received adjuvant chemotherapy. The five-year recurrence-free survival (RFS) and OS rates were 92% and 94.8%, respectively. Preoperative obstruction, PNI, and positive margins were significantly associated with RFS and OS; however, adjuvant chemotherapy and LVI were not. Pathologic slide central reviews of 242 patients using dual D2-40 and CD31 immunohistochemical staining was performed. In the review cohort, the diagnosis of LVI and PNI was changed in 82 (33.9%) and 61 (25.2%) patients, respectively. Reviewed LVI, encompassing small vessel invasion, lymphatic invasion, and large vessel invasion, was not an independent risk factor associated with OS but was related to RFS. The prognostic importance of LVI and adjuvant chemotherapy was not defined because LVI may be underrecognized in pathologic diagnoses using hematoxylin and eosin staining slides only, leading to low recurrence rate predictions. Using LVI as a guiding factor for adjuvant chemotherapy requires further consideration.

Reevaluation of the expanded indications in undifferentiated early gastric cancer for endoscopic submucosal dissection.

BACKGROUND: Although the criteria for the indication of endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD-EGC) have been recently proposed, accumulating reports on the non-negligible rate of lymph node metastasis (LNM) after indicated ESD raise questions on the reliability of the current criteria. AIM: To investigate the prevalence and risk factors of LNM in UD-EGC cases meeting the expanded indication for ESD. METHODS: We retrospectively reviewed 4780 UD-EGC cases that underwent surgical resection between January 2008 and February 2019 at Asan Medical Center, a tertiary university hospital in Korea. To identify the risk factors of LNM of UD-EGC meeting the expanded criteria for ESD, we performed a case-control study by matching the cases with LNM to those without at a ratio of 1:4. We reviewed the clinical, endoscopic, and histologic features of the cases to identify features with a significant difference according to the presence of LNM. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios (ORs). RESULTS: Of the 4780 UD-EGC cases, 1240 (25.9%) were identified to meet the expanded indication for ESD. Of the 1240 cases, 14 (1.1%) cases had LNM. Among the various clinical, endoscopic, and histopathological features that were evaluated, mixed histology (tumors consisting of 10%-90% of signet ring cells) had a marginally significant association (P = 0.059) with the risk of LNM. Moreover, diffuse blurring of the muscularis mucosae (MM) underneath the tumorous epithelium, a previously unrecognized histologic feature, had a significant association with the absence of LNM (P = 0.028). Multivariate logistic regression analysis showed that the blurring of MM was the only explanatory variable significantly associated with a reduced risk of LNM (OR: 0.12, 95%CI: 0.02-0.95; P = 0.045). CONCLUSION: The risk of LNM is higher than expected when using the current expanded indication for UD-EGC. Histological evaluation could provide useful clues for reducing the risk of LNM.

Surface Modification of Matrimid® 5218 Polyimide Membrane with Fluorine-Containing Diamines for Efficient Gas Separation.

Polyimide membranes have been widely investigated in gas separation applications due to their high separation abilities, excellent processability, relatively low cost, and stabilities. Unfortunately, it is extremely challenging to simultaneously achieve both improved gas permeability and selectivity due to the trade-off relationship in common polymer membranes. Diamine modification is a simple strategy to tune the separation performance of polyimide membranes, but an excessive loss in permeability is also generally observed. In the present work, we reported the effects of diamine type (i.e., non-fluorinated and fluorinated) on the physicochemical properties and the corresponding separation performance of a modified membrane using a commercial Matrimid® 5218 polyimide. Detailed spectroscopic, thermal, and surface analyses reveal that the bulky fluorine groups are responsible for the balanced chain packing modes in the resulting Matrimid membranes compared to the non-fluorinated diamines. Consequently, the modified Matrimid membranes using fluorinated diamines exhibit both higher gas permeability and selectivity than those of pristine Matrimid, making them especially effective for improving the separation performance towards H2/CH4 and CO2/CH4 pairs. The results indicate that the use of fluorinated modifiers may offer new opportunities to tune the gas transport properties of polyimide membranes.

Comprehensive clinicopathologic, molecular, and immunologic characterization of colorectal carcinomas with loss of three intestinal markers, CDX2, SATB2, and KRT20.

Caudal-type homeobox 2 (CDX2), special AT-rich sequence-binding protein 2 (SATB2), and keratin 20 (KRT20) are frequently used as intestinal epithelium-specific markers in immunohistochemical studies. However, subsets of colorectal carcinomas (CRCs) show loss of these markers. We analyzed The Cancer Genome Atlas data to explore molecular correlates of CDX2, SATB2, and KRT20 genes in 390 CRCs. The decreased mRNA expression of each of the three genes commonly correlated with microsatellite instability-high (MSI-H), CpG island methylator phenotype-high (CIMP-H), BRAF/RNF43 mutations, consensus molecular subtype 1, and high tumor mutational burden. The downregulation of CDX2 or SATB2 was dependent on both MSI-H and CIMP-H, whereas that of KRT20 was more dependent on MSI-H than on CIMP-H. Next, we evaluated the immunohistochemical expression of CDX2, SATB2, and KRT20 in 436 primary CRCs. In contrast to RNA-level expression, decreased expression of CDX2 and SATB2 was more dependent on CIMP-H than on MSI-H. However, consistent with RNA-level expression, decreased expression of KRT20 was more dependent on MSI-H than on CIMP-H. CIMP-H and lymphatic invasion were consistently associated with both CDX2 loss and SATB2 loss in CRCs, regardless of MSI status. In microsatellite stable CRCs, CDX2 loss correlated with BRAF mutation, whereas SATB2 loss was associated with KRAS mutations and decreased T-cell infiltration. Cases with concurrent loss of all three markers were found exclusively in MLH1-methylated MSI-H/CIMP-H CRCs. In conclusion, MSI-H and/or CIMP-H are major common correlates of decreased CDX2/SATB2/KRT20 expression in CRCs, but the specific features associated with the loss of each marker are different in CRCs.

Combinatory statuses of tumor stromal percentage and tumor infiltrating lymphocytes as prognostic factors in stage III colorectal cancers.

BACKGROUND AND AIM: Tumor stroma and tumor-infiltrating lymphocytes (TILs) are major constituents of the tumor microenvironment, although they have different effects on the prognosis of patients with colorectal cancer (CRC). Combinatory statuses of tumor-stromal percentage (TSP) and TILs are expected to provide more powerful prognostic information but have never been studied in CRCs. METHODS: Stage III CRCs from patients (n = 487) treated with adjuvant chemotherapy were assessed for their TSP and CD3-TIL or CD8-TIL densities using computer-aided methodology. With cut-off values set at median values for intraepithelial TIL (iTIL) and stromal TIL (sTIL) densities, CRCs were sorted into low and high iTIL or sTIL groups. CRCs were classified into five quintile (Q1-Q5) groups according to their TSP and divided into high TSP (Q5) and low TSP (Q1-4) groups. RESULTS: The combination of CD8 iTIL density and TSP was found to be an independent prognostic parameter in multivariate survival analysis in terms of cancer-specific survival and recurrence-free survival. CRCs with low CD8 iTIL density and high TSP showed the worst survival. The combinatory status showed more prognostic power than CD8 iTIL density or TSP alone. Multivariate survival analysis in an independent cohort of stage III CRC validated the prognostic power of the combinatory statuses. CONCLUSIONS: The findings suggest that the combinatory status might serve as a prognostic parameter in stage III CRCs. Further research in a large-scale cohort of patients with stage III CRC is needed to validate the prognostic power of the combinatory status.

Genomic and transcriptomic characterization of heterogeneous immune subgroups of microsatellite instability-high colorectal cancers.

BACKGROUND: Colorectal cancers (CRCs) with microsatellite instability-high (MSI-H) are hypermutated tumors and are generally regarded as immunogenic. However, their heterogeneous immune responses and underlying molecular characteristics remain largely unexplained. METHODS: We conducted a retrospective analysis of 73 primary MSI-H CRC tissues to characterize heterogeneous immune subgroups. Based on combined tumor-infiltrating lymphocyte (TIL) immunoscore and tertiary lymphoid structure (TLS) activity, MSI-H CRCs were classified into immune-high, immune-intermediate, and immune-low subgroups. Of these, the immune-high and immune-low subgroups were further analyzed using whole-exome and transcriptome sequencing. RESULTS: We found considerable variations in immune parameters between MSI-H CRCs, and immune subgrouping of MSI-H CRCs was performed accordingly. The TIL densities and TLS activities of immune-low MSI-H CRCs were comparable to those of an immune-low or immune-intermediate subgroup of microsatellite-stable CRCs. There were remarkable differences between immune-high and immune-low MSI-H CRCs, including their pathological features (medullary vs mucinous), genomic alterations (tyrosine kinase fusions vs KRAS mutations), and activated signaling pathways (immune-related vs Wnt and Notch signaling), whereas no significant differences were found in tumor mutational burden (TMB) and neoantigen load. The immune-low MSI-H CRCs were subdivided by the consensus molecular subtype (CMS1 vs CMS3) with different gene expression signatures (mesenchymal/stem-like vs epithelial/goblet-like), suggesting distinct immune evasion mechanisms. Angiogenesis and CD200 were identified as potential therapeutic targets in immune-low CMS1 and CMS3 MSI-H CRCs, respectively. CONCLUSIONS: MSI-H CRCs are immunologically heterogeneous, regardless of TMB. The unusual immune-low MSI-H CRCs are characterized by mucinous histology, KRAS mutations, and Wnt/Notch activation, and can be further divided into distinct gene expression subtypes, including CMS4-like CMS1 and CMS3. Our data provide novel insights into precise immunotherapeutic strategies for subtypes of MSI-H tumors.

In Situ Derived Hybrid Carbon Molecular Sieve Membranes with Tailored Ultramicroporosity for Efficient Gas Separation.

Fine control of ultramicroporosity (<7 Å) in carbon molecular sieve (CMS) membranes is highly desirable for challenging gas separation processes. Here, a versatile approach is proposed to fabricate hybrid CMS (HCMS) membranes with unique textural properties as well as tunable ultramicroporosity. The HCMS membranes are formed by pyrolysis of a polymer nanocomposite precursor containing metal-organic frameworks (MOFs) as a carbonizable nanoporous filler. The MOF-derived carbonaceous phase displays good compatibility with the polymer-derived carbon matrix due to the homogeneity of the two carbon phases, substantially enhancing the mechanical robustness of the resultant HCMS membranes. Detailed structural analyses reveal that the in situ pyrolysis of embedded MOFs induces more densified and interconnected carbon structures in HCMS membranes compared to those in conventional CMS membranes, leading to bimodal and narrow pore size distributions in the ultramicroporous region. Eventually, the HCMS membranes exhibit far superior gas separation performances with a strong size-sieving ability than the conventional polymers and CMS membranes, especially for closely sized gas pairs (Δd < 0.5 Å) including CO2 /CH4 and C3 H6 /C3 H8 separations. More importantly, the developed HCMS material is successfully prepared into a thin-film composite (TFC) membrane (≈1 µm), demonstrating its practical feasibility for use in industrial mixed-gas operation conditions.

Atomic-Layer-Deposited SiOx/SnOx Nanolaminate Structure for Moisture and Hydrogen Gas Diffusion Barriers.

High-density SnOx and SiOx thin films were deposited via atomic layer deposition (ALD) at low temperatures (100 °C) using tetrakis(dimethylamino)tin(IV) (TDMASn) and di-isopropylaminosilane (DIPAS) as precursors and hydrogen peroxide (H2O2) and O2 plasma as reactants, respectively. The thin-film encapsulation (TFE) properties of SnOx and SiOx were demonstrated with thickness dependence measurements of the water vapor transmission rate (WVTR) evaluated at 50 °C and 90% relative humidity, and different TFE performance tendencies were observed between thermal and plasma ALD SnOx. The film density, crystallinity, and pinholes formed in the SnOx film appeared to be closely related to the diffusion barrier properties of the film. Based on the above results, a nanolaminate (NL) structure consisting of SiOx and SnOx deposited using plasma-enhanced ALD was measured using WVTR (H2O molecule diffusion) at 2.43 × 10-5 g/m2 day with a 10/10 nm NL structure and time-lag gas permeation measurement (H2 gas diffusion) for applications as passivation layers in various electronic devices.

Liver transplantation of a patient with extreme thrombocytopenia - A case report.

BACKGROUND: Patients with chronic liver disease (CLD) planned for liver transplantation (LT) often show severe thrombocytopenia, but there is a lack of evidence in deciding the threshold for prophylactic platelet transfusion. CASE: A 47-year-old female with acute liver failure was referred for LT. Despite daily transfusion of platelets, platelet counts remained under 10,000/µl. During LT, 2 units of single donor platelets (SDP) were transfused. Although platelet counts remained extremely low (3,000-4,000/µl) no diffuse oozing was observed and the blood loss was 860 ml. Postoperatively, there was no sign of active bleeding or oozing, and the patient received only 1 unit SDP transfusion. CONCLUSIONS: CLD patients may have severe thrombocytopenia. However, primary hemostasis may not be significantly hindered due to the existence of rebalanced hemostasis. Prophylactic platelet transfusion in these patients should not be decided based on platelet counts only, but also take other coagulation tests and clinical signs into consideration.

Tumor microenvironment-adjusted prognostic implications of the KRAS mutation subtype in patients with stage III colorectal cancer treated with adjuvant FOLFOX.

Several studies have reported that the prognostic effect of KRAS mutations on colorectal cancers (CRCs) varies depending on the type of mutation. Considering the effect of KRAS mutations on tumor microenvironment, we analyzed the prognostic significance of KRAS mutation types after adjusting for the tumor-infiltrating lymphocytes (TIL) and tumor-stromal percentage (TSP) statuses. In two independent cohorts, KRAS mutations were analyzed by Sanger sequencing and/or next-generation sequencing. TIL density and the TSP were quantified from whole-slide immunohistochemical images. KRAS-mutant CRCs were divided into three subgroups (G12D/V, other codon 12 mutations and codon 13 mutations) to examine their differential effect on TIL density, the TSP and recurrence-free survival (RFS). Among the KRAS mutations, only the G12D/V subgroups showed significantly less TIL infiltration than the wild-type CRCs. According to survival analysis, G12D/V mutations were associated with short RFS; codon 13 mutations showed discordant trends in the two cohorts, and other codon 12 mutations showed no significant association. Multivariate analysis further supported the prognostic value of G12D/V mutations. This result is not only consistent with a recent study suggesting the immunosuppressive effect of mutant KRAS but also provides insight into the type-specific prognostic effect of KRAS mutations.