Total Regio- and Diastereocontrol in the Aldol Reactions of Dienolborinates

It is reported that appropriate dienolborinates can provide access to both diastereomers of 2-(hydroxymethyl)but-3-enoates through exclusive α-regiocontrol in a non-vinylogous pathway. Contrary to previous reports in which dialkylchloroboranes failed to enolize propanoates, acidity-enhanced but-3-enoates readily undergo enolization, offering unprecedented control over the formation of these valuable synthons. The first example of an aldol reaction in the presence of a phosphine–borane adduct is also reported

Total Regio- and Diastereocontrol in the Aldol Reactions of Dienolborinates

It is reported that appropriate dienolborinates can provide access to both diastereomers of 2-(hydroxymethyl)but-3-enoates through exclusive α-regiocontrol in a non-vinylogous pathway. Contrary to previous reports in which dialkylchloroboranes failed to enolize propanoates, acidity-enhanced but-3-enoates readily undergo enolization, offering unprecedented control over the formation of these valuable synthons. The first example of an aldol reaction in the presence of a phosphine–borane adduct is also reported

Perforated Microcapsules with Selective Permeability Created by Confined Phase Separation of Polymer Blends

Semipermeable microcapsules have a great potential in controlled release of drugs, protection of catalysts, and immunoisolation of cells. However, a method to create such microcapsules with precisely controlled cutoff value and high mechanical stability remains an important challenge. Herein we report microfluidic approach to create microcapsules with size-selective permeability using phase separation of polymer blends in ultrathin middle layer of double-emulsion drops. The blend strongly confined in two-dimensional space exhibit local phase separation, instead of global separation. This enables the perforation of microcapsule membrane by selectively removing one of the phase-separated polymeric domains. The resultant monolithic membrane has uniform pores which connect the interior and the exterior of the microcapsules, thereby providing size-selective permeability. The pore size can be precisely tuned by regulating the extent of phase separation; this enables the control of cutoff value for permeation

Microfluidic Production of Semipermeable Microcapsules by Polymerization-Induced Phase Separation

Semipermeable microcapsules are appealing for controlled release of drugs, study of cell-to-cell communication, and isolation of enzymes or artificial catalysts. Here, we report a microfluidic strategy for creating monodisperse microcapsules with size-selective permeability using polymerization-induced phase separation. Monodisperse water-in-oil-in-water (W/O/W) double-emulsion drops, whose ultrathin middle layer is composed of photocurable resin and inert oil, are generated in a capillary microfluidic device, and irradiated by UV light. Upon UV illumination, the monomers are photopolymerized, which leads to phase separation between the polymerized resin and the oil within the ultrathin shell. Subsequent dissolution of the oil leaves behind regular pores in the polymerized membrane that interconnect the interior and exterior of the microcapsules, thereby providing size-selective permeability. The degree of phase separation can be further tuned by adjusting the fraction of oil in the shell or the affinity of the oil to the monomers, thereby enabling the control of the cutoff value of permeation. High mechanical stability and chemical resistance of the microcapsules, as well as controllable permeability and high encapsulation efficiency, will provide new opportunity in a wide range of applications

Semipermeable Microcapsules with a Block-Polymer-Templated Nanoporous Membrane

Microcapsules with nanoporous membranes can regulate transmembrane transport in a size-dependent fashion while protecting active materials in the core from the surrounding, and are thereby useful as artificial cell models, carriers for cells and catalysts, and microsensors. In this work, we report a pragmatic microfluidic approach to producing such semipermeable microcapsules with precise control of the cutoff threshold of permeation. Using a homogeneous polymerization mixture for the polymerization-induced microphase separation (PIMS) process as the oil phase of water-in-oil-in-water (W/O/W) double emulsions, a densely cross-linked shell composed of a bicontinuous nanostructure that percolates through the entire thickness is prepared, which serves as a template for a monolithic nanoporous membrane of microcapsules with size-selective permeability. We demonstrate that the nanopores with precisely controlled size by the block polymer self-assembly govern molecular diffusion through the membrane and render manipulation of the cutoff threshold

Anisotropic Microparticles Created by Phase Separation of Polymer Blends Confined in Monodisperse Emulsion Drops

Anisotropic microparticles are promising as a new class of colloidal or granular materials due to their advanced functionalities which are difficult to achieve with isotropic particles. However, synthesis of the anisotropic microparticles with a highly controlled size and shape still remains challenging, despite their intense demands. Here, we report a microfluidic approach to create uniform anisotropic microparticles using phase separation of polymer blends confined in emulsion drops. Two different polymers are homogeneously dissolved in organic solvent at low concentration, which is microfluidically emulsified to produce oil-in-water emulsion drops. As the organic solvent diffuses out, small domains are formed in the emulsion drops, which are then merged, forming only two distinct domains. After the drops are fully consolidated, uniform anisotropic microparticles with two compartments are created. The shape of the resulting microparticles is determined by combination of a pair of polymers and type of surfactant. Spherical microparticles with eccentric core and incomplete shell are prepared by consolidation of polystyrene (PS) and poly­(lactic acid) (PLA), and microparticles with single crater are formed by consolidation of PS and poly­(methyl methacrylate) (PMMA); both emulsions are stabilized with poly­(vinyl alcohol) (PVA). With surfactants of triblock copolymer, acorn-shaped Janus microparticles are obtained by consolidating emulsion drops containing PS and PLA. This microfluidic production of anisotropic particles can be further extended to any combination of polymers and colloids to provide a variety of structural and chemical anisotropy

Anisotropic Microparticles Created by Phase Separation of Polymer Blends Confined in Monodisperse Emulsion Drops

Anisotropic microparticles are promising as a new class of colloidal or granular materials due to their advanced functionalities which are difficult to achieve with isotropic particles. However, synthesis of the anisotropic microparticles with a highly controlled size and shape still remains challenging, despite their intense demands. Here, we report a microfluidic approach to create uniform anisotropic microparticles using phase separation of polymer blends confined in emulsion drops. Two different polymers are homogeneously dissolved in organic solvent at low concentration, which is microfluidically emulsified to produce oil-in-water emulsion drops. As the organic solvent diffuses out, small domains are formed in the emulsion drops, which are then merged, forming only two distinct domains. After the drops are fully consolidated, uniform anisotropic microparticles with two compartments are created. The shape of the resulting microparticles is determined by combination of a pair of polymers and type of surfactant. Spherical microparticles with eccentric core and incomplete shell are prepared by consolidation of polystyrene (PS) and poly­(lactic acid) (PLA), and microparticles with single crater are formed by consolidation of PS and poly­(methyl methacrylate) (PMMA); both emulsions are stabilized with poly­(vinyl alcohol) (PVA). With surfactants of triblock copolymer, acorn-shaped Janus microparticles are obtained by consolidating emulsion drops containing PS and PLA. This microfluidic production of anisotropic particles can be further extended to any combination of polymers and colloids to provide a variety of structural and chemical anisotropy

Chameleon-Inspired Mechanochromic Photonic Films Composed of Non-Close-Packed Colloidal Arrays

Chameleons use a non-close-packed array of guanine nanocrystals in iridophores to develop and tune skin colors in the full visible range. Inspired by the biological process uncovered in panther chameleons, we designed photonic films containing a non-close-packed face-centered-cubic array of silica particles embedded in an elastomer. The non-close-packed array is formed by interparticle repulsion exerted by solvation layers on the particle surface, which is rapidly captured in the elastomer by photocuring of the dispersion medium. The artificial skin exhibits a structural color that shifts from red to blue under stretching or compression. The separation between inelastic particles enables tuning without experiencing significant rearrangement of particles, providing elastic deformation and reversible color change, as chameleons do. The simple fabrication procedure consists of film casting and UV irradiation, potentially enabling the continuous high-throughput production. The mechanochromic property of the photonic films enables the visualization of deformation or stress with colors, which is potentially beneficial for various applications, including mechanical sensors, sound–vision transformers, and color display

Table_1_Induction FOLFIRINOX followed by stereotactic body radiation therapy in locally advanced pancreatic cancer.docx

IntroductionFOLFIRINOX (the combination of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) is the preferred systemic regimen for locally advanced pancreatic cancer (LAPC). Furthermore, stereotactic body radiation therapy (SBRT) is a promising treatment option for achieving local control in these patients. However, clinical outcomes in patients with LAPC treated using FOLFIRINOX followed by SBRT have not been clarified. Therefore, we aimed to evaluate clinical outcomes of induction FOLFIRINOX treatment followed by SBRT in patients with LAPC.MethodsTo this end, we retrospectively reviewed the medical records of patients with LAPC treated with induction FOLFIRINOX followed by SBRT in a single tertiary hospital. We evaluated overall survival (OS), progression-free survival (PFS), resection rate, SBRT-related adverse events, and prognostic factors affecting survival.ResultsFifty patients were treated with induction FOLFIRINOX for a median of 8 cycles (range: 3–28), which was followed by SBRT. The median OS and PFS were 26.4 (95% confidence interval [CI]: 22.4–30.3) and 16.7 months (95% CI: 13.0–20.3), respectively. Nine patients underwent conversion surgery (eight achieved R0) and showed better OS than those who did not (not reached vs. 24.1 months, p = 0.022). During a follow-up period of 23.6 months, three cases of grade 3 gastrointestinal bleeding at the pseudoaneurysm site were noted, which were managed successfully. Analysis of the factors affecting clinical outcomes revealed that a high radiation dose (≥ 35 Gy) resulted in a higher rate of conversion surgery (25% [8/32] vs. 5.6% [1/18], respectively) and was an independent favorable prognostic factor for OS in the adjusted analysis (hazard ratio: 2.024, 95% CI: 1.042–3.930, p = 0.037).ConclusionOur findings suggest that induction FOLFIRINOX followed by SBRT in patients with LAPC results in better survival with manageable toxicities. A high total SBRT dose was associated with a high rate of conversion surgery and could afford better survival.</p

Clinical profiles of adverse drug reactions spontaneously reported at a single Korean hospital dedicated to children with complex chronic conditions

<div><p>Children with complex chronic conditions (CCC) are presumed to be vulnerable to adverse drug reactions (ADRs). The clinical profiles of ADRs in CCC are not well known. Herein, we aim to describe the ADR profiles in CCC with regard to typical presentations and vulnerable groups. We accessed the ADR yearly reports at a tertiary children's hospital whose practice is mainly dedicated to CCC and descriptively analyzed their clinical profiles according to the presence of a complex chronic condition, ADR severity, and age groups. A total of 1841 cases were analyzed, among which 1258 (68.3%) were mild, 493 (26.8%) moderate, and 90 (4.9%) cases were severe. A total of 1581 (85.9%) cases of complex chronic condition were reported. The proportion of CCC in each severity group increased as the ADR becomes more severe. In CCC, ADRs were most frequently reported by nurses in the adolescent group and in cases where the symptoms involved the gastrointestinal system. The class of antineoplastic and immunomodulating drugs was the most commonly suspected of causing an ADR, followed by one of the antibiotics. When we focus on the trend across the age groups, the ratio of severe-to-total ADRs decreased with older age. Among severe cases, the ratio of off-label prescription-related cases was the highest in the infant/toddler group and decreased as the groups aged. In conclusion, ADRs of CCCs admitted to a tertiary children’s hospital have a unique profile. These groups are vulnerable to ADRs and thus they should be monitored closely, especially when they are infants or toddlers, so that severe ADRs can be identified and treated immediately.</p></div