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A combination of molecular modelling and experiments was conducted to study the separation of acrylic acid and propionic acid through extractive distillation with polar aprotic entrainers. It was found that acrylic acid and propionic acid can be efficiently separated through extractive distillation with a polar aprotic entrainer, resulting in the entrainment of acrylic acid and making propionic acid the most volatile compound. Vapour-liquid equilibrium experiments were conducted with 25 wt% acrylic acid, 25 wt% propionic, and 50% wt% entrainer. Dimethyl sulfoxide (DMSO) was found to induce the highest relative volatility of 1.56 at 25 mbar, which agrees well with the predicted value of 1.66 using the simulation software COSMO-RS. The difference in pKa (ΔpKa = 0.63) between acrylic acid and propionic acid is the main cause for the enhanced relative volatility. The corresponding difference in hydrogen bonding strength was calculated using COSMO-RS to result in ΔE = 1.8 kJ/mol at 25 °C between acrylic acid and propionic acid with the total mixture. When dodecane was selected as an entrainer, acrylic acid became the most volatile compound instead of propionic acid. This is explained by the fact that propionic acid has two extra hydrogen atoms available to have a Van der Waals interaction with the carbon atoms of dodecane. The difference in total Van der Waals interaction between the two carboxylic acids in the mixture with dodecane is 1.34 kJ/mol at 25 °C. This difference results in a relative volatility of 0.91, which is too small to be exploited in a distillation process, and it was concluded that for this mixture, DMSO was the best entrainer in the study. [Display omitted] ● Acrylic acid and propionic acid were separated by extractive distillation (ED). ● COSMO-RS and Spartan calculations predicted and explained relative volatilities. ● The ΔpKa of 0.63 is sufficient for entrainers to induce relative volatility in ED. ● DMSO induced a relative volatility of 1.56 at 25 mbar using 50 wt% entrainer. ● Alkanes reverse the relative volatility to 0.9. [ABSTRACT FROM AUTHOR]

Aim: The aim of this systematic review was to analyse recurrence rates after different surgical techniques for perineal hernia repair. Method: All original studies (n ≥ 2 patients) reporting recurrence rates after perineal hernia repair after abdominoperineal resection (APR) were included. The electronic database PubMed was last searched in December 2021. The primary outcome was recurrent perineal hernia. A weighted average of the logit proportions was determined by the use of the generic inverse variance method and random effects model. Results: A total of 19 studies involving 172 patients were included. The mean age of patients was 64 ± 5.6 years and the indication for APR was predominantly cancer (99%, 170/172). The pooled percentage of recurrent perineal hernia was 39% (95% CI: 27%–52%) after biological mesh closure, 29% (95% CI: 21%–39%) after synthetic mesh closure, 37% (95% CI: 14%–67%) after tissue flap reconstruction only and 9% (95% CI: 1%–45%) after tissue flap reconstruction combined with mesh. Conclusion: Recurrence rates after mesh repair of perineal hernia are high, without a clear difference between biological and synthetic meshes. The addition of a tissue flap to mesh repair seemed to have a favourable outcome, which warrants further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer is one of the most lethal cancer types and its high refractoriness to therapies, including immunotherapy, has often been associated with the predominantly immune suppressive tumor microenvironment that characterizes pancreatic tumors. Regulatory T cells (Tregs) are generally considered as drivers of immune suppression in cancers. However, an increasing number of reports suggest a paradoxical association between tumor infiltration by Tregs and improved patient prognosis, in particular in gastrointestinal cancers. Here we show that Treg infiltration in pancreatic ductal adenocarcinomas (PDAC) is associated with better overall survival of patients. Pancreatic ductal adenocarcinoma (PDAC) is considered to be a poorly immunogenic cancer type that combines a low mutation burden with a strong immunosuppressive tumor microenvironment. Regulatory T cells (Tregs) are major drivers of immune suppression but their prognostic role, particularly in gastrointestinal malignancies, remains controversial. Lymphocytic infiltration in 122 PDAC samples was assessed by multispectral immunofluorescence with anti-Keratin, -CD3, -CD8, -FOXP3 and -CD163 antibodies. Differential infiltration by Tregs was analyzed in the context of transcriptomic profiles that were available for 65 tumors. High infiltration of CD3+CD8− (mainly CD4+) T cells and, especially, of the subset expressing FOXP3 (Tregs) was associated with improved patient survival, whilst cytotoxic CD3+CD8+ T cell infiltration did not have an impact on overall survival. Transcriptomic analysis revealed three signatures in PDAC tumors comprising of epithelial-mesenchymal transition (EMT)/stromal, metabolic, and secretory/pancreatic signature. However, none of these signatures explained differences in Treg infiltration. We show that Tregs associate with improved overall survival in PDAC patients. This effect was independent of cytotoxic T cell infiltration and the transcriptomic profiles of their respective tumors. These findings provide a new layer of complexity in the study of PDAC tumor microenvironment that must be considered when developing immunotherapeutic interventions for this disease. [ABSTRACT FROM AUTHOR]

Background: Checkpoint blockade immunotherapy has had a significant impact on the survival of a subset of patients with advanced cancers. It has been particularly effective in immunogenic cancer types that present large numbers of somatic mutations in their genomes. To date, all conventional immunotherapies have failed to produce significant clinical benefits for patients diagnosed with pancreatic cancer, probably due to its poor immunogenic properties, including low numbers of neoantigens and highly immune-suppressive microenvironments. Conclusions: Herein, we discuss advances that have recently been made in cancer immunotherapy and the potential of this field to deliver effective treatment options for pancreatic cancer patients. Preclinical investigations, combining different types of therapies, highlight possibilities to enhance anti-tumor immunity and to generate meaningful clinical responses in pancreatic cancer patients. Results from completed and ongoing (pre)clinical trials are discussed. [ABSTRACT FROM AUTHOR]

The use of a wide range of bio-based solvents as entrainers in extractive distillation applications was investigated. The separation of hydrocarbon mixtures containing aromatic and aliphatic compounds is highly relevant, and the use of bio-based solvents for this separation was studied using the model system of methylcyclohexane and toluene. Additionally, the use of bio-based solvents for the difficult olefin/paraffin separation was studied using the model system of n-heptane and 1-heptene. From all of the bio-based solvents studied, Cyrene™ showed the highest relative volatility in the methylcyclohexane–toluene system. At compositions up to 40 wt% of methylcyclohexane in the hydrocarbon mixture, with a relative volatility of 3.17 ± 0.16 at 1000 mbar, the selectivity was comparable with the state-of-the-art industrial solvent Sulfolane™. At higher methylcyclohexane fractions, Cyrene™ outperforms Sulfolane™, resulting in a 43% reduction of the minimum reflux ratio, which is an excellent measure of energy efficiency. With regard to the relative volatility of n-heptane over 1-heptene, Cyrene™ also induces an increase in the relative volatility, but not as much as the industrial benchmark n-methylpyrrolidone (NMP). A relative volatility of 1.20 was measured at a solvent-to-feed ratio of 3 (mass basis), which can be further increased by the addition of extra Cyrene™. This leads to the prospect that Cyrene™ may be used for extractive distillation in olefin/paraffin separations, replacing NMP which is subject to severe environmental restrictions by the REACH agreement due to toxicity. [ABSTRACT FROM AUTHOR]

Highlights • Carboxylic acid extraction process concepts were reviewed. • Process simulations were done to calculate heat duties for the most interesting processes. • Use of a combination of a CO 2 -switchable solvent and a low boiling solvent is highly interesting. Abstract In this manuscript carboxylic acid extraction processes are reviewed and compared on energy efficiency, especially in situations with very low carboxylic acid concentrations. Production of carboxylic acids by fermentation rather than petrochemical routes aims at reducing dependency on petroleum resources. Wastewater streams are potential carbon sources for fermentation. However, their limited carbon content results in low carboxylic acid concentrations (∼1 wt%) that render separation of waste-derived carboxylic acids challenging. This necessitates implementation of cost-effective separation concepts. The incentive to review liquid–liquid extraction (LLX)-based processes for carboxylic acids was to evaluate their applicability to low carboxylic acid concentrations. Although a thorough study of recent solvent developments was beyond the scope of this work, a brief discussion on their families supported the LLX-based process developments that were assessed in terms of energy demand by simulating their thermal unit operations with Aspen Plus. They were simulated both under their reported conditions and with their initial concentration set to 1 wt%. A process proposed by Urbas (1983) that makes use of CO 2 , CO 2 -switchable solvents and low-boiling organic solvents outperformed the others for low carboxylic acid feed concentrations. With a heating duty of about 36 MJ/kg product , it could recover both volatile and non-volatile carboxylic acids from fermentation broths with 1 wt% initial carboxylic acid loading. Future developments in the field may be based on this process design, but with more environmentally friendly solvents such as the bio-based furan derivatives. [ABSTRACT FROM AUTHOR]

Levulinic acid (LA) can be produced from lignocellulosic materials via hydroxylation followed by an acid-catalyzed conversion of hexoses. Inorganic homogeneous catalysts are mostly used, in particular sulphuric acid, yielding a mixture of LA with sulphuric acid, formic acid (FA) and furfural. Significant attention has been paid to optimization of the yield, but purification of the LA is a challenge too. This work focuses on the separation of LA from the complex aqueous mixtures by liquid-liquid extraction. Two aqueous product feeds were considered, reflecting two different processes. One aqueous product stream contains sulphuric acid and LA, while the second product stream also contains formic FA and furfural. Furfural could be removed selectively via liquid-liquid extraction with toluene. For selective extraction of LA and FA without co-extracting sulphuric acid, 30 wt.% of trioctylphosphine oxide (TOPO) in methylisobutylketone (MIBK) was found most suitable, showing a high selectivity over sulphuric acid, and a high equilibrium partitioning of LA. When instead of MIBK, 1-octanol was applied as diluent, the co-extraction of FA was enhanced, while hexanoic acid suppressed the acid extraction. To obtain the LA pure, eventually a distillation is required, and the potential of temperature swing back extraction (TSBE) at 90 °C to pre-concentrate the acid solutions was evaluated for 30 wt.% TOPO in MIBK. This pre-concentration step increased the concentrations of LA and FA by a factor of 2.45 and 2.45 respectively, reducing the distillation reboiler duty from roughly 31.5 to 11.3 GJ per ton LA, at a cost of roughly 4.5 GJ heating duty per ton produced LA. [ABSTRACT FROM AUTHOR]

• 3-Component Margules equation was used to predict vapor–liquid equilibria. • Infinite dilution activity coefficients are the sole input for solvent pre-selection. • Industrial cases were used to validate the approach. • Molecular solvents, ILs and DESs were incorporated in the screening. We present an easily accessible, open-access approach for fast pre-selection of solvents for extractive distillation at isobaric and isothermal conditions. The method uses the three-component Margules equation, which can predict vapor–liquid equilibria (VLE) in ternary systems with the infinite dilution activity coefficients, γ i ∞ , as sole input parameters. This approach is accessible for anybody regardless of the availability of process simulators or other dedicated software to predict VLE, and can be combined with open access γ i ∞ to perform solvent screening. This approach shows a deviation in VLE of <5% for non-hydrogen bond donating mixtures, while for highly dissimilar (e.g. alkane – alcohol) mixtures the deviation can be >10%. The presented method identifies molecular solvents for case studies where the same or similar solvents have also been reported in literature or are already applied on the industrial level, showing realistic pre-selection outcomes. Furthermore, small, cyclic, polar, molecular solvents are identified to induce preferential interactions and several structurally similar solvents, e.g. ethylene carbonate, dihydrolevoglucosenone and y-valerolactone, are identified to be potential alternative solvents. Among the ionic liquids (ILs) and deep eutectic solvents (DESs), the morpholinium and ammonium structures are identified to have the highest potential for increasing relative volatilities, they also show lower toxicity than other cations. This method thus proves to be able to perform early-stage pre-screening among new classes of solvents which generates information on the minimum required solvent to feed ratio (S F min ) for energy-efficient distillation from γ i ∞ obtained by measurement or from literature. [ABSTRACT FROM AUTHOR]

• Infinite dilution activity coefficients (IDACs) were reviewed. • IDACs for a total of 268 solutes in 692 solvents were reviewed. • From the 77.173 IDACs reviewed, solvent effects were visualized. • Utilizing Van 't Hoff's law in an algorithm, IDACs at varying T were compared. • Visualized trends for molecular solvents but also for ionic liquids. The infinite dilution activity coefficient, γ i ∞ , is a frequently used molecular descriptor to pre-select a solvent for various kinds of fluid separations. Unfortunately, information related to these coefficients is scattered through-out the open literature. Therefore, an open-source γ i ∞ -database containing 77.173 γ i ∞ data points over the temperature interval 243 K < T < 555.6 K for 268 solutes and 692 solvents is provided in the electronic supporting information of this work. Additionally, we performed an inter- and extrapolation data analysis algorithm using the Van 't Hoff equation to extend the γ i ∞ data points at 298.15 K. The γ i ∞ for five solutes (n-hexane, benzene, chloroform, acetone and ethanol) in a wide range of molecular solvents and ionic liquids (ILs) were compared. Various trends between the molecular solvent structure and the γ i ∞ are visualized, which allows for not only a pre-selection of solvents for targeted γ i ∞ but also visualizes the effect molecular modification of the solvent will have on the γ i ∞. Overall, the presented methodology is complementary to approaches using simulation software, and helps acquiring a detailed understanding of the effect of the solvent structure on the γ i ∞ , which will facilitate solvent pre-selection in an early process design stage towards greener fluid separations. [ABSTRACT FROM AUTHOR]

[Display omitted] • Acetone and diisopropyl ether form an azeotropic vapor-liquid equilibrium system. • A range of 35 biobased entrainers have been investigated. • DL-Limonene was the only entrainer found to be able to eliminate the azeotrope. • Other entrainers with strong influence were water and ethylene carbonate. • Although shifting the azeotrope, water and ethylene carbonate did not overcome it. This work focuses on the assessment of biobased solvents for the industrial separation of acetone and diisopropyl ether employing extractive distillation. From the experimental screening of 35 (biobased) solvents at 1000 mbar, 84/16 mol ratio acetone/ diisopropyl ether, and a solvent to feed ratio of 1 (mass based) it was observed that DL-limonene entrained diisopropyl ether, resulting in an acetone relative volatility of 1.44. This is a consequence of the selective repulsion of the low-boiling and more polar acetone by DL-limonene. More extensive vapor-liquid equilibrium (VLE) analysis over the entire acetone-diisopropyl ether (pseudo-)binary composition range showed that DL-limonene was the only biobased solvent able to break the azeotrope. The experimentally investigated VLE data of this ternary system was successfully correlated with the NRTL and UNIQUAC models. The other solvents that appeared most interesting in the initial screening were water and ethylene carbonate, entraining acetone with the highest observed diispropyl ether relative volatilities of 2.71 and 11.6. Although the high induced relative volatility for the 84/16 mol ratio acetone/ diisopropyl ether appeared interesting, over the entire composition range this resulted however in a shift in location of the azeotrope rather than removing the azeotrope. Therefore, it was concluded that DL-limonene is for this system the best performing biobased entrainer of the screening study. The observations are in agreement with observations from literature on similar systems, where oxygenated polar solvents were seen to have more affinity towards the ketone than towards the ether, while apolar solvents induce a higher volatility of the ketones. [ABSTRACT FROM AUTHOR]

Development and progression of malignancies are accompanied and influenced by alterations in the surrounding immune microenvironment. Understanding the cellular and molecular interactions between immune cells and cancer cells has not only provided important fundamental insights into the disease, but has also led to the development of new immunotherapies. The C-type lectin Dendritic Cell ImmunoReceptor (DCIR) is primarily expressed by myeloid cells and is an important regulator of immune homeostasis, as demonstrated in various autoimmune, infectious and inflammatory contexts. Yet, the impact of DCIR on cancer development remains largely unknown. Analysis of available transcriptomic data of colorectal cancer (CRC) patients revealed that high DCIR gene expression is associated with improved patients' survival, immunologically "hot" tumors and high immunologic constant of rejection, thus arguing for a protective and immunoregulatory role of DCIR in CRC. In line with these correlative data, we found that deficiency of DCIR1, the murine homologue of human DCIR, leads to the development of significantly larger tumors in an orthotopic murine model of CRC. This phenotype is accompanied by an altered phenotype of tumor-associated macrophages (TAMs) and a reduction in the percentage of activated effector CD4+ and CD8+ T cells in CRC tumors of DCIR1-deficient mice. Overall, our results show that DCIR promotes antitumor immunity in CRC, making it an attractive target for the future development of immunotherapies to fight the second deadliest cancer in the world. [ABSTRACT FROM AUTHOR]

Various solvents such as ionic liquids, deep eutectic solvents, and aqueous two phase systems have been suggested as greener alternatives to existing extraction processes. We propose to add macroscopic complex coacervates to this list. Complex coacervates are liquid-like forms of polyion condensates and consist of a complex of oppositely charged polyions and water. Previous research focussing on the biological significance of these polyion-rich phases has shown that polyion condensates have the ability to extract certain solutes from water and back-extract them by changing parameters such as ionic strength and pH. In this study, we present the distribution coefficients of five commonly used industrial chemicals, namely lactic acid, butanol, and three types of lipase enzymes in poly(ethylenimine)/poly(acrylic acid) complex coacervates. It was found that the distribution coefficients can vary strongly upon variation of tunable parameters such as polyion ratio, ionic strength, polyion and compound concentrations, and temperature. Distribution coefficients ranged from approximately 2 to 50 depending on the tuning of the system parameters. It was also demonstrated that a temperature-swing extraction is possible, with back-extraction of butanol from complex coacervates with a recovery of 21.1%, demonstrating their potential as extraction media. [ABSTRACT FROM AUTHOR]

The eukaryotic genome is highly compacted into a protein-DNAcomplex called chromatin. The cell controls access of transcriptional regulators to chromosomal DNA via several mechanisms that act on chromatin-associated proteins and provide a rich spectrum of epigenetic regulation. Elucidating the mechanisms that fold chromatin fibers into higher-order structures is therefore key to understanding the epigenetic regulation of DNA accessibility. Here, using histone H4-V21C and histone H2A-E64C mutations, we employed single-molecule force spectroscopy to measure the unfolding of individual chromatin fibers that are reversibly cross-linked through the histone H4 tail. Fibers with covalently linked nucleosomes featured the same folding characteristics as fibers containing wild-type histones but exhibited increased stability against stretching forces. By stabilizing the secondary structure of chromatin, we confirmed a nucleosome repeat length (NRL)-dependent folding. Consistent with previous crystallographic and cryo-EM studies, the obtained force-extension curves on arrays with 167-bp NRLs best supported an underlying structure consisting of zig-zag, two-start fibers. For arrays with 197-bp NRLs, we previously inferred solenoidal folding, which was further corroborated by force-extension curves of the cross-linked fibers. The different unfolding pathways exhibited by these two types of arrays and reported here extend our understanding of chromatin structure and its potential roles in gene regulation. Importantly, these findings imply that chromatin compaction by nucleosome stacking protects nucleosomal DNA from external forces up to 4 piconewtons. [ABSTRACT FROM AUTHOR]

Introduction: The subcutaneous implantable cardioverter‐defibrillator (S‐ICD) is most commonly implanted under general anesthesia (GA), due to the intraoperative discomfort associated with tunneling and dissection. Postoperative pain can be substantial and is often managed with opioids. There is a growing interest in transitioning away from the routine use of GA during S‐ICD implantation, while also controlling perioperative discomfort without the use of narcotics. As such, we assessed the feasibility of a multimodal analgesia regimen that included regional anesthesia techniques in patients undergoing S‐ICD implantation. Methods and Results: Twenty patients received truncal plane block (TBL) immediately before S‐ICD implantation. The first 10 patients were implanted under general anesthesia (GA + TBL), and the next 10 patients were implanted under deep sedation (DS + TBL). Additionally, the DS + TBL patients were also prescribed a structured regimen of nonopioid analgesics in the perioperative period. Opioid consumption was calculated as milligram morphine equivalents (MME). In‐hospital opioid consumption was significantly lower in the patients implanted with DS + TBL (MME = 0) as compared with patients receiving GA + TBL (MME = 60; P = 0.004). Conclusions: Subcutaneous ICD implantation with anesthesia‐delivered DS and a multimodal anesthetic regimen that includes TBL is feasible and associated with significantly less perioperative opioid consumption. The subcutaneous implantable cardioverter‐defibrillator (S‐ICD) is most commonly implanted under general anesthesia (GA) due to the intraoperative discomfort associated with tunneling and dissection. Postoperative pain can be substantial, and is often managed with opioids. [ABSTRACT FROM AUTHOR]

It was highlighted that the original article [1] contained a typesetting mistake in the name of Noel Filipe da Cunha Carvalho de Miranda. This was incorrectly captured as Noel Filipe da Cunha Carvahlo de Miranda. It was also highlighted that in Fig. 3C the left panels Y-axis were cropped and in Fig. 5C, CD8 bar was cropped. This Correction article shows the correct Figs. 3 and 5. The original article has been updated. [ABSTRACT FROM AUTHOR]

We introduce quanTIseq, a method to quantify the fractions of ten immune cell types from bulk RNA-sequencing data. quanTIseq was extensively validated in blood and tumor samples using simulated, flow cytometry, and immunohistochemistry data. quanTIseq analysis of 8000 tumor samples revealed that cytotoxic T cell infiltration is more strongly associated with the activation of the CXCR3/CXCL9 axis than with mutational load and that deconvolution-based cell scores have prognostic value in several solid cancers. Finally, we used quanTIseq to show how kinase inhibitors modulate the immune contexture and to reveal immune-cell types that underlie differential patients' responses to checkpoint blockers. Availability: quanTIseq is available at http://icbi.at/quantiseq. [ABSTRACT FROM AUTHOR]