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Molecules that contain a stereogenic phosphorus atom are crucial to medicine, agrochemistry and catalysis. While methods are available for the selective construction of various chiral organophosphorus compounds, catalytic enantioselective approaches for their synthesis are far less common. Given the vastness of possible substituent combinations around a phosphorus atom, protocols for their preparation should also be divergent, providing facile access not only to one but to many classes of phosphorus compounds. Here we introduce a catalytic and enantioselective strategy for the preparation of an enantioenriched phosphorus(V) centre that can be diversified enantiospecifically to a wide range of biologically relevant phosphorus(V) compounds. The process, which involves an enantioselective nucleophilic substitution catalysed by a superbasic bifunctional iminophosphorane catalyst, can accommodate a wide range of carbon substituents at phosphorus. The resulting stable, yet versatile, synthetic intermediates can be combined with a multitude of medicinally relevant O-, N- and S-based nucleophiles.

WNT/β-catenin-activated hepatocellular carcinoma (W/B subclass HCC) is considered as molecularly homogeneous entity and has been linked to resistance to immunotherapy. However, recent studies have indicated possible heterogeneity in the immuno-vascular microenvironment in this subclass. We set out to test the hypothesis that specific immuno-vascular features might stratify W/B subclass HCCs into tumors having distinct aggressive natures.In this study, we analyzed 352 resected HCCs including 78 immunohistochemically defined W/B subclass HCCs. The density of tumor-infiltrating CD3The T-cell density of W/B subclass HCCs was regionally heterogenous within tumor tissues, and focally reduced T-cell density was observed in areas with VETC. VETC-positivity (defined as VETC area ratio greater than 1%) and T-cell infiltration were inversely associated in both W/B subclass and non-W/B subclass HCCs. Fibroblast growth factor 2 (FGF2) gene expression was higher in W/B subclass than in non-W/B subclass HCCs. VETC positivity and low T-cell density correlated with increased expression of FGF2 in W/B subclass HCCs. VETC-positive HCCs showed significantly shorter DFS in W/B subclass HCCs.In conclusion, the immune and vascular microenvironments are interrelated and are also correlated with clinicopathological heterogeneity in W/B subclass HCC. These results may inform clinical practice and translational research on the development of therapeutic stratification of HCCs. This article is protected by copyright. All rights reserved.

Herein we describe the enantioselective intermolecular conjugate addition of nitroalkanes to unactivated α,β-unsaturated esters, catalyzed by a bifunctional iminophosphorane (BIMP) superbase. The transformation provides the most direct access to pharmaceutically relevant enantioenriched γ-nitroesters, utilizing feedstock chemicals, via fundamental reactivity and unprecedented selectivity. The methodology exhibits a broad substrate scope, including β-(fluoro)alkyl, aryl and heteroaryl substituted electrophiles, and was successfully applied on a gram scale with reduced catalyst loading, and additionally catalyst recovery was carried out. The formal synthesis of a range of drugs, and an enantioselective synthesis of (S)-rolipram were achieved. Additionally, computational studies revealed key reaction intermediates and transition states, and provided rationale for high enantioselectivities, in good agreement with experimental results.

Background and Study Aims: The development of minimally invasive endoscopic neurosurgery has enabled widespread application of endoscopic surgery via the ipsilateral transfrontal approach for putaminal hematoma evacuation. However, this approach is unsuitable for putaminal hematomas that extend into the temporal lobe. We adopted the endoscopic trans-middle temporal gyrus approach, instead of the conventional surgical approach, for the management of these complicated cases and determined its safety and feasibility. Patients and Methods: Twenty patients with putaminal hemorrhage underwent surgical treatment at the Shinshu University Hospital between January 2016 and May 2021. Of these, two patients with left putaminal hemorrhage that extended into the temporal lobe underwent surgical treatment using the endoscopic trans-middle temporal gyrus approach. The procedure entailed the use of a thinner transparent sheath to reduce the technique’s invasiveness, a navigation system to determine the location of the middle temporal gyrus and the sheath’s trajectory, and an endoscope with a 4K camera for higher image quality and utility. The Sylvian fissure was compressed superiorly using our novel “port retraction technique” (i.e., by tilting the transparent sheath superiorly) to avoid damage to the middle cerebral artery and the Wernicke’s area. Results: The endoscopic trans-middle temporal gyrus approach allowed sufficient hematoma evacuation and hemostasis under endoscopic observation without any surgical complexities or complications. The postoperative course was uneventful in both patients. Conclusion: The endoscopic trans-middle temporal gyrus approach for putaminal hematoma evacuation helps avoid damage to normal brain tissue, which could result from the wide range of motion of the conventional technique, particularly when the hemorrhage extends to the temporal lobe.

Immune cells and tumor vessels constitute important elements in tumor tissue; however, their detailed relationship in human tumors, including hepatocellular carcinoma (HCC), is still largely unknown. Consequently, we expanded our previous study on the immune microenvironment of HCC and analyzed the relationship among the immune microenvironment, inflammatory/angiostatic factor expression, angiogenic factor expression, and tumor vessel findings, including vessels encapsulating tumor clusters (VETC) and macrotrabecular-massive (MTM) patterns. We classified HCC into four distinct immuno-vascular subtypes (Immune-high/Angiostatic [IH/AS], Immune-mid/Angio-mid [IM/AM], Immune-low/Angiogenic [IL/AG], and Immune-low/Angio-low [IL/AL]). IH/AS, IM/AM, and IL/AG subtypes were associated with decreasing lymphocytic infiltration and increasing angiogenic factor expression and VETC/MTM positivity, reflecting their reciprocal interaction in the tumor microenvironment of HCC. IL/AG subtype was further characterized by CTNNB1 mutation and activation of Wnt/β-catenin pathway. IL/AL subtype was not associated with increased lymphocyte infiltration or angiogenic factor expression. Prognostically, IH/AS subtype and VETC/MTM positivity were independently significant in two independent cohorts. Increased angiogenic factor expression was not necessarily associated with VETC/MTM positivity and poor prognosis, especially when inflammatory/angiostatic milieu co-existed around tumor vessels. These results may provide insights on the therapeutic effects of immunotherapy, anti-angiogenic therapies, and their combinations. The potential of evaluating immuno-vascular microenvironment in predicting the clinical effect of these therapies in non-resectable HCC needs to be analyzed in the future study. CONCLUSION: HCC can be classified into four distinct immuno-vascular subtypes (IH/AS, IM/AM, IL/AG, and IL/AL) that reflect the reciprocal interaction between the anti-tumor immune microenvironment and tumor angiogenesis. In addition to its clinicopathological significance, immuno-vascular classification may also provide pathological insights on the therapeutic effect of immunotherapy, anti-angiogenic therapy, and their combination.

The rhodium(II)-catalyzed, branch-selective C–H alkylation of aryl sulfonamides with vinylsilanes was recently developed by our group, and the unique reactivity and selectivity of the reaction was ...

© 2021 American Chemical Society.An iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3 + 2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using 1 mol% Vaska's complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent regio- and diastereoselective, inter- and intramolecular dipolar cycloaddition reactions with variously substituted electron-deficient alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures, which ultimately control the unusual selectivities observed in certain cases.

The rhodium(III)-catalyzed oxidative C–H alkenylation and coupling sequence of unprotected 1-naphthylamines with α,β-unsaturated esters, which were recently developed by our group, provide an effic...

The branch-selective C–H alkenylation with alkenes using an iridium catalyst is reported. The Ir(III)-catalyzed reaction of aniline derivatives that contain a pyrimidine-directing group with vinyls...

Purpose: Cancer-associated fibroblasts have emerged to be highly heterogenous and can play multifaceted roles in dictating pancreatic ductal adenocarcinoma (PDAC) progression, immunosuppression, and therapeutic response, highlighting the need for a deeper understanding of stromal heterogeneity between patients and even within a single tumor. We hypothesized that image analysis of fibroblast subpopulations and collagen in PDAC tissues might guide stroma-based patient stratification to predict clinical outcomes and tumor characteristics. Experimental Design: A novel multiplex IHC-based image analysis system was established to digitally differentiate fibroblast subpopulations. Using whole-tissue slides from 215 treatment-naïve PDACs, we performed concurrent quantification of principal fibroblast subpopulations and collagen and defined three stroma types: collagen-rich stroma, fibroblast activation protein α (FAP)-dominant fibroblast-rich stroma, and α smooth muscle actin (ACTA2)-dominant fibroblast-rich stroma. These stroma types were assessed for the associations with cancer-specific survival by multivariable Cox regression analyses and with clinicopathologic factors, including CD8+ cell density. Results: FAP-dominant fibroblasts and ACTA2-dominant fibroblasts represented the principal distinct fibroblast subpopulations in tumor stroma. Stroma types were associated with patient survival, SMAD4 status, and transcriptome signatures. Compared with FAP-dominant fibroblast-rich stroma, collagen-rich stroma correlated with prolonged survival [HR, 0.57; 95% confidence interval (CI), 0.33–0.99], while ACTA2-dominant fibroblast-rich stroma exhibited poorer prognosis (HR, 1.65; 95% CI, 1.06–2.58). FAP-dominant fibroblast-rich stroma was additionally characterized by restricted CD8+ cell infiltrates and intense neutrophil infiltration. Conclusions: This study identified three distinct stroma types differentially associated with survival, immunity, and molecular features, thereby underscoring the importance of stromal heterogeneity in subtyping pancreatic cancers and supporting the development of antistromal therapies.

The enantioselective total synthesis of madangamine E has been completed in 30 steps, enabled by a new catalytic and highly enantioselective desymmetrizing intramolecular Michael addition reaction of a prochiral ketone to a tethered β,β’-disubstituted nitroolefin. This key carbon–carbon bond forming reaction efficiently constructed a chiral bicyclic core in near-perfect enantio- and diastereo-selectivity, concurrently established three stereogenic centers, including a quaternary carbon stereocenter, and proved highly scalable. Furthermore, the pathway and origins of enantioselectivity in this catalytic cyclisation were probed using density functional theory (DFT) calculations, which revealed the crucial substrate/catalyst interactions in the enantio-determining step. Following construction of the bicyclic core, the total synthesis of madangamine E could be completed, with key steps including a mild one-pot oxidation-lactamisation, a two-step Z-selective olefination of a sterically hindered ketone, and ring-closing metatheses to install the two macrocyclic rings.

The first metal-free catalytic intermolecular enantioselective Michael addition to unactivated α,β-unsaturated amides is described. Consistently high enantiomeric excesses and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane catalyst. Low catalyst loadings (2.0 mol %) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity via analysis of relevant transition structures and provided substantial support for specific noncovalent activation of the carbonyl group of the α,β-unsaturated amide by the catalyst.

The PRAETORIAN score was developed to evaluate the implant position and predict defibrillation success in patients implanted with a subcutaneous implantable cardioverter-defibrillator (S-ICD). However, usefulness of the PRAETORIAN score for Japanese patients is unknown.We evaluated usefulness of this score, which was determined by width of sub-coil fat, sub-generator fat, and anterior positioning of the S-ICD generator by post-operative chest X-ray, in consecutive 100 Japanese S-ICD implanted patients [78 men, median age 59 (IQR 46.5-67.0) years, median body mass index (BMI) 24.2 (21.3-27.2) kg/mThe median PRAETORIAN score was 30 (30-45) and 93 patients were classified as a low risk of conversion failure. The remaining seven were at an intermediate risk. Almost all patients were classified as an optimal pulse-generator position in the second and third steps of the PRAETORIAN score. The only difference observed was in the width of sub-coil fat in the first step. To further evaluate its significance, patients were divided into the Thicker group (sub-coil fat1 coil width, n = 19) and the Thinner group (sub-coil fat ≤1 coil width, n = 81). BMI and post-shock impedance were both higher in the Thicker group than in the Thinner group [27.1 (25.6-31.6) versus 23.1 (20.9-25.7) kg/mMost Japanese patients were classified as at low risk of conversion failure. The PRAETORIAN score may be useful for the evaluation of conversion failure in Japanese S-ICD implanted patients.

An iridium-catalyzed, reductive alkylation of abundant tertiary lactams and amides using 1-2 mol % of Vaska's complex (IrCl(CO)(PPh3)2), tetramethyldisiloxane (TMDS), and difluoro-Reformatsky reagents (BrZnCF2R) for the general synthesis of medicinally relevant α-difluoroalkylated tertiary amines is described. A broad scope (46 examples), including N-aryl- and N-heteroaryl-substituted lactams, demonstrated an excellent functional group tolerance. Furthermore, late-stage drug functionalizations, a gram-scale synthesis, and common downstream transformations proved the potential synthetic relevance of this new methodology.

The tertiary amide is a ubiquitous functional group and plays an irreplaceable role in medicinal chemistry. Its robust nature has meant—in the past—that selective manipulation of this motif remaine...

The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations., The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual prolinamide/copper(i) catalytic system, is described.

The clinicopathological characteristics of steatosis in hepatocellular carcinoma (HCC) remain unclear. Here, we elucidate the features of macrovesicular steatosis (MaS) and microvesicular steatosis (MiS) in HCC and their relationships with background liver steatosis. A total of 165 HCC lesions were classified as MaS-HCC, MiS-HCC, or conventional HCC (cHCC) according to the cutoff value of 30% MaS or MiS in tumor cells. We analyzed the clinicopathological differences among these groups. MaS-HCC had less portal vein invasion, a higher proportion of HCC with intratumoral fibrosis, and a lower cumulative risk of recurrence than MiS-HCC or cHCC. Moreover, both MaS-HCC and MiS-HCC had lower incidences of hepatitis virus infection and higher levels of HbA1c than cHCC. Background liver steatosis was also higher in MaS-HCC than in cHCC. Immunohistochemical expression of perilipin (Plin1) and adipophilin (ADRP), major proteins expressed on lipid droplet membranes, revealed that almost all lipid droplets in HCC were Plin1 negative, whereas those in background liver were positive. In contrast, ADRP was expressed on lipid droplets in both HCC and background liver. We concluded that MaS-HCC and MiS-HCC were associated with metabolic abnormalities but exhibited different biologic behaviors. Furthermore, lipid droplets in HCC were pathophysiologically different from those in background liver.

Background/Aim: Little is known about the impact of diabetes mellitus (DM) on clinical outcomes in lean patients with acute myocardial infarction (AMI). We conducted this study to evaluate the impact of DM on clinical outcomes in AMI patients based on body mass index (BMI) level. Patients and Methods: A total of 1,282 consecutive AMI patients who underwent emergent percutaneous coronary intervention within 24 hours from onset were retrospectively studied. The patients were divided into 2 groups based on BMI: Underweight group (BMI

AIM Sorafenib inhibits multiple kinase signaling pathways, including the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and is a promising therapy for hepatocellular carcinoma (HCC). However, the role of ERK activation in HCC remains unclear. This study was designed to investigate the potential link between ERK activation and aggressive HCC phenotypes. METHODS We evaluated nuclear ERK expression by immunohistochemistry in 154 resected HCC nodules from 136 patients. We then investigated the associations of ERK expression with the clinicopathological characteristics of HCC, c-MET expression, and the molecular subclass biomarkers Ki-67, keratin 19 (KRT19, CK19, or K19), and sal-like protein 4. Multivariate Cox regression analysis was carried out to determine independent prognostic factors for overall survival and recurrence-free survival. The effects of ERK activation by hepatocyte growth factor (HGF) on eight HCC cell lines were further examined. RESULTS High-level nuclear expression of ERK was observed in 20 (13%) of 154 nodules and was significantly associated with higher serum alpha-fetoprotein levels (P = 0.034), poorer differentiation (P = 0.003), a higher Ki-67 index (P

The metal-free

Various devices exist for glioma image-guided surgery to improve tumor resection. These devices work as stand-alone units, making the flow of operative information complicated and disjointed. A novel networked operating room, the Smart Cyber Operating Theater (SCOT), has been developed, integrating stand-alone medical devices using the OPeLiNK communication interface. We report and evaluate the impact of SCOT for glioma surgery and our initial experiences.Patients with gliomas who underwent tumor resection in SCOT between July 2018 and June 2021 were retrospectively reviewed. Various types of intraoperative information were integrated, managed, and shared with the surgical strategy desk using OPeLiNK. Patients' demographics, tumor characteristics, treatment details, and outcomes were obtained. The impact of the SCOT system was evaluated.Twenty-seven patients, with a mean age of 48.6 years (range, 13-88 years), met the inclusion criteria. We successfully completed all the surgical procedures using SCOT. The mean operation time was 420.6 minutes (range, 225-667 minutes).Gross total resection was accomplished in 13 patients (48.1%), subtotal resection in 4 (14.8%), and partial resection in 10 (37.0%). The main surgeon in the operating room and other neurosurgeons at the strategy desk shared and discussed the information in real time during the procedures.The use of SCOT was shown to be safe and feasible in glioma surgery. This study suggests that SCOT may improve surgical outcomes and educational impact by sharing information in real time with the strategy desk.

Semi-extended tibial nailing techniques include the extra-articular technique (EAT) and the patellar eversion technique (PET). These approaches differ regarding the exposure of the patellar retinaculum and the size of the surgical field. This study compared the postoperative alignment and intramedullary nailing entry points between the EAT and PET for tibial fractures.A total of 54 patients (aged ≥18 years) who had undergone intramedullary nailing by the EAT (n = 29) or PET (n = 25) for a tibial shaft fracture were evaluated. The intramedullary nailing entry point and postoperative alignment were measured, and the 1-year postoperative follow-up results were compared.For the EAT and PET, the intramedullary nailing entry point was located at a mean distance of 4.04 mm medial to the optimal entry point and 0.27 mm lateral to the optimal entry point, respectively. The mean angular deformation observed in anteroposterior radiographs following surgery using the EAT and PET were 2.49° and 0.32° valgus, respectively.The intramedullary nailing entry point affected postoperative alignment. Intramedullary nailing may result in malalignment while performing the EAT due to the interference of the patella at the time of nailing.

A reagent‐controlled stereodivergent carbocyclisation of aryl aldimine‐derived, photocatalytically generated, α‐amino radicals possessing adjacent conjugated alkenes, affording either bicyclic or tetracyclic products, is described. Under net reductive conditions using commercial Hantzsch ester, the α‐amino radical species underwent a single stereoselective cyclisation to give trans‐configured amino‐indane structures in good yield, whereas using a substituted Hantzsch ester as a milder reductant afforded cis‐fused tetracyclic tetrahydroquinoline frameworks, resulting from two consecutive radical cyclisations. Judicious choice of the reaction conditions allowed libraries of both single and dual cyclisation products to be synthesised with high selectivity, notable predictability, and good‐to‐excellent yields. Computational analysis employing DFT revealed the reaction pathway and mechanistic rationale behind this finely balanced yet readily controlled photocatalytic system., Through judicious choice of reductant, a switchable diastereodivergent cyclisation of a single alkene‐tethered imine, to either a trans‐fused amino‐indane or a cis‐fused tetracyclic tetrahydroquinoline structure, is herein described.

The nickel-catalyzed reductive cleavage of esters in the absence of an external reductant, which involves the cleavage of an inert acyl C-O bond in O-alkyl esters is reported. Various groups, such as N-containing heterocycles, esters, amides, and even arene rings can function as a directing group.

The reaction of N-heteroaromatic compounds, such as 2-aryl-pyrrole, benzimidazole, imidazole, indole, and pyrazole derivatives, with alkynes in the presence of a catalytic amount of a nickel complex results in C–H/N–H oxidative annulation. The reaction shows a high functional group compatibility. While both Ni(0) and Ni(II) complexes show a high catalytic activity, Ni(0) is proposed as a key catalytic species in the main catalytic cycle. In the case of the Ni(II) system, the presence of a catalytic amount of a strong base, such as KOBut, is required for the reaction to proceed. In sharp contrast, a base is not required in the case of the Ni(0) system. The proposed mechanism is supported by DFT studies.

Density functional theory (DFT) was used to unveil intimate mechanistic insights on the monodentate-chelation system that is used in the Ni-catalyzed C–H/N–H oxidative annulation of aromatic amides with alkynes, a reaction that was originally reported by our group Chem Sci. 2017, 8, 6650−6655, DOI: 10.1039/C7SC01750B). The proposed reaction mechanism involves two reaction paths. The initial path is initiated by Ni(II), and the other, the main catalytic cycle, is initiated by Ni(0). Both paths require the presence of a catalytic amount of KOBut. The results of the DFT studies presented here indicate that the rate-determining step in the initial Ni(II) system involves a concerted metalation–deprotonation (CMD) mechanism and an anionic Ni(0) ate complex is the key intermediate in the main catalytic cycle. Furthermore, a previously proposed oxidative addition–alkyne insertion sequence is revised to a ligand-to-ligand hydrogen transfer (LLHT) mechanism, which is the rate-determining step in the main catalytic...

An efficient synthesis of enantioenriched hydroquinazoline cores via a novel bifunctional iminophosphorane squaramide catalyzed intramolecular aza-Michael reaction of urea-linked α,β-unsaturated esters is described. The methodology exhibits a high degree of functional group tolerance around the forming hydroquinazoline aryl core and wide structural variance on the nucleophilic N atom of the urea moiety. Excellent yields (up to 99%) and high enantioselectivities (up to 97 : 3 er) using both aromatic and less acidic aliphatic ureas were realized. The potential industrial applicability of the transformation was demonstrated in a 20 mmol scale-up experiment using an adjusted catalyst loading of 2 mol%. The origin of enantioselectivity and reactivity enhancement provided by the squaramide motif has been uncovered computationally using density functional theory (DFT) calculations, combined with the activation strain model (ASM) and energy decomposition analysis (EDA)., The activation of both aromatic and aliphatic ureas as N-centered nucleophiles in intramolecular Michael addition reactions to α,β-unsaturated esters was achieved under bifunctional iminophosphorane squaramide superbase catalysis.

The first metal-free catalytic intermolecular enantioselective sulfa-Michael addition to unactivated α,β- unsaturated amides is described. Consistently high enantiomeric excesses, and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane (BIMP) catalyst. Low catalyst loadings (2 mol%) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity, corresponding transition states, and provided substantial evidence for specific non-covalent activation of the carbonyl group of the α,β-unsaturated amide by the catalyst.

Background Patient-reported outcome measures are widely utilized to assess health-related quality of life (HRQOL) in patients with adolescent idiopathic scoliosis (AIS). However, the association between HRQOL and curve severity is mostly unknown. The aim of this study is to clarify the association between HRQOL and curve severity, and to determine the optimal cutoff values of patient-reported outcomes for major curve severity in female patients with AIS. Methods Female patients with AIS treated conservatively were recruited. The patients’ HRQOL outcomes were examined using the revised Scoliosis Research Society-22 (SRS-22r) and the Scoliosis Japanese Questionnaire-27 (SJ-27). The correlations of the SRS-22r and SJ-27 scores with the major Cobb angle were assessed using Spearman’s correlation coefficient analysis. The association between HRQOL issues in the SJ-27 and the major Cobb angle was evaluated by calculating Akaike’s Information Criterion (AIC). Furthermore, the optimal cutoff values of the SRS-22r and SJ-27 scores for the major Cobb angle were determined by AIC analysis. Results The study cohort comprised 306 female patients with AIS. The SRS-22r and SJ-27 scores were significantly correlated with the major Cobb angle. Questions in the SJ-27 regarding discomfort when wearing clothes showed a lower AIC value in patients with severe scoliosis. The optimal cutoff values were a SRS-22r score of 3.2 for the discrimination of severe scoliosis (Cobb angle ≥48°), and a SJ-27 score of 32 for the discrimination of moderate scoliosis (Cobb angle ≥33°). Conclusion Discomfort when wearing clothes was the most important HRQOL problem caused by severe scoliosis. The SRS-22r and SJ-27 scores are useful for the discrimination of clinical status in female patients with severe scoliosis or moderate scoliosis.

A new iridium-catalyzed reductive generation of both stabilized and unstabilized azomethine ylides and their application to functionalized pyrrolidine synthesis via [3+2] dipolar cycloaddition reactions is described. Proceeding under mild reaction conditions from both amide and lactam precursors possessing a suitably positioned electron-withdrawing or a trimethylsilyl group, using catalytic Vaska’s complex [IrCl(CO)(PPh3)2] and tetramethyldisiloxane (TMDS) as a terminal reductant, a broad range of (un)stabilized azomethine ylides were accessible. Subsequent, regio- and diastereoselective, inter- and intramolecular, dipolar cycloaddition reactions with variously substituted electron-poor alkenes enabled ready and efficient access to structurally complex pyrrolidine architectures. Density functional theory (DFT) calculations of the dipolar cycloaddition reactions uncovered an intimate balance between asynchronicity and interaction energies of transition structures which ultimately control the unusual selectivities observed in certain cases.

An efficient synthesis of enantioenriched hydroquinazoline cores via a novel bifunctional iminophosphorane squaramide catalyzed intramolecular aza-Michael addition of urealinked α,β-unsaturated esters is described. The methodology exhibits a high degree of functional group tolerance around the forming hydroquinazoline aryl core and wide structural variance on the nucleophilic N atom of the urea moiety. Excellent yields (up to 99%) and high enantioselectivities (up to 97:3 e.r.) using both aromatic and less acidic aliphatic ureas were realized. The potential industrial applicability of the transformation was demonstrated in a 20 mmol scale-up experiment using an adjusted catalyst loading of 2 mol%. The origin of enantioselectivity and reactivity enhancement provided by the squaramide motif has been uncovered computationally using density functional theory (DFT) calculations, combined activation strain model (ASM) and energy decomposition analysis (EDA).