Creation of a Chiral All-Carbon Quaternary Center Induced by CF and CH Substituents via Cu-Catalyzed Asymmetric Conjugate Addition.

Cu-catalyzed asymmetric construction of a chiral quaternary center bearing CH and CF groups was achieved with high to excellent enantioselectivity using our originally developed ligands. The asymmetric conjugate addition of MeAl to β-CF-substituted enones and unsaturated ketoesters proceeded efficiently. The use of unsaturated ketoesters gives optically active furanones in high yields with high enantioselectivities.

Clinical characterization of patients with gBRCA1/2 mutation-positive unresectable pancreatic cancer: a multicenter prospective study.

Background: Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan.

Ir-Catalyzed Distal Branch-Selective Hydroarylation of Unactivated Internal Alkenes with Benzanilides via C-H Activation along with Consecutive Isomerization.

We herein report a synergistic strategy of C-H activation and consecutive isomerization catalyzed by an Ir catalyst to selectively obtain branched isomers as C-H alkylated products of benzanilide derivatives. A well-tuned ligand and a directing group are crucial to achieve this selectivity. The scope of this reaction is demonstrated by the use of a variety of substituents and complex molecules.

Sulfide-Directed Ir-Catalyzed Vinylic sp and Benzylic sp C-H Activation for the Construction of Sulfur-Containing Medium-Ring System.

Ir-catalyzed transformations initiated by sulfur-directed vinylic sp and benzylic sp  C-H activation are disclosed that achieve the construction of sulfur-containing seven- and eight-membered systems. Allyl 2-alkynylphenyl sulfides were transformed into dihydrobenzothiepines in 30-95 % yield, and 2-alkynylaryl 2-tolyl sulfides were converted into dibenzo[b,f]thiepines in 57-95 % yield along with double bond isomerization. In both reactions, the combination of Ir catalyst and sulfide moiety was a key to the facile cyclization.

Synthesis of Dithia[5]helicenes and Enantioselective Synthesis of Helically Chiral Thia[6]helicenes via Rh-Catalyzed Intramolecular [2 + 2 + 2] Cycloaddition of Triynes.

Dithia[5]helicenes and helically chiral thia[6]helicenes were synthesized in high yields via a cationic Rh-catalyzed intramolecular [2 + 2 + 2] cycloaddition of triynes bearing sulfur-containing 1,6-diynes. Thia[6]helicene could be obtained with a high enantiomeric excess of -isomers by using ()-SEGPHOS as a chiral ligand. This protocol is the first example of the synthesis of thiahelicenes via [2 + 2 + 2] cycloaddition and can also be used for the asymmetric construction of an aza[6]helical skeleton.

Experimental and Theoretical Evidence for Relativistic Catalytic Activity in C-H Activation of -Phenylbenzamide Using a Cationic Iridium Complex.

This study elucidates that relativistic effect plays a key role in catalytic C-H activation using a cationic Ir complex. Experiments show that the cationic Ir(I)-diphosphine catalyst can be used for the deuterium substitution of -phenylbenzamide, whereas a cationic Rh(I)-diphosphine catalyst is scarcely effective. Density functional theory calculations, including the relativistic effect, demonstrate a large difference in the reaction energy diagrams for the C-H activation of -phenylbenzamide between the cationic Ir and Rh catalysts.

Development of a Flexible MEMS Sensor for Subsonic Flow.

Detection and control of flow separation is a key to improving the efficiency of fluid machinery. In this study, we developed a flexible MEMS (microelectromechanical systems) sensor for measuring the wall shear stress and flow angle in subsonic airflow. The developed sensor is made of a flexible polyimide film and a microheater surrounded by three temperature sensor pairs.

Guidelines for cadaver dissection in education and research of clinical medicine (The Japan Surgical Society and The Japanese Association of Anatomists).

This article translates the guidelines for cadaver surgical training (CST) published in 2012 by Japan Surgical Society (JSS) and Japanese Association of Anatomists from Japanese to English. These guidelines are based on Japanese laws and enable the usage of donated cadavers for CST and clinical research. The following are the conditions to implement the activities outlined in the guidelines.

Guidelines for cadaver dissection in education and research of clinical medicine (The Japan Surgical Society and The Japanese Association of Anatomists).

This article translates the guidelines for cadaver surgical training (CST) published in 2012 by Japan Surgical Society (JSS) and Japanese Association of Anatomists from Japanese to English. These guidelines are based on Japanese laws and enable the usage of donated cadavers for CST and clinical research. The following are the conditions to implement the activities outlined in the guidelines.

Ir-Catalyzed Remote Functionalization by the Combination of Deconjugative Chain-Walking and C-H Activation Using a Transient Directing Group.

An Ir-catalyzed reaction of -benzylideneanilines with functionalized alkenes such as α,β-unsaturated esters gave -substituted benzaldehyde derivatives with a functional group at the remote position after acidic treatment. The present transformation involves deconjugative long-range isomerization (chain-walking) up to 11 times and C-H activation using an imino group as a transient directing group.

Ir-Catalyzed Enantioselective Formal C-H Conjugate Addition of Pyrrole and Indoles to α,β-Unsaturated Carbonyl Compounds.

The chiral Ir(I)-catalyzed intermolecular reaction of -carbamoylpyrrole and indole derivatives with α,β-unsaturated carbonyl compounds such as crotonates proceeded with high enantioselectivity. The obtained chirally functionalized pyrroles and indoles are formal C-H conjugate adducts. The reaction mechanism was studied by deuterium labeling experiments.

Enantioselective Cross-Coupling of Electron-Deficient Alkenes via Ir-Catalyzed Vinylic sp C-H Alkylation.

A chiral Ir-catalyzed reaction of α-aryl-α,β-unsaturated amides with β-substituted acrylates proceeded to give formal conjugate adducts in high yield and (up to 99% yield and up to 95% ). This is the first example of the enantioselective cross-coupling of two different electron-deficient alkenes via vinylic sp C-H activation, and polyfunctionalized chiral compounds were obtained.

Ni-catalyzed non-activated C-S bond cleavage at ambient temperature for the synthesis of sulfur-containing polycyclic compounds.

A Ni-catalyzed intramolecular reaction of diarylthioether-tethered 1,8-diynes gave sulfur-containing tetracyclic compounds at ambient temperature. The transformation was initiated by non-activated sp C-S bond cleavage along with consecutive alkyne insertions. A double intramolecular reaction of a tetrayne and an intermolecular reaction of monoynes were also available, and the corresponding polycyclic compounds were obtained.

Exploring the applicability of the robotic seal PARO to support caring for older persons with dementia within the home context.

Objective: To (1) examine the potentiality of using the robot PARO to mediate care provided by the family and (2) identify problems when utilizing PARO in the home context.

Methods: Family members of 7 households were asked to use PARO for at least three times per week, over 1 to 3 months. Research data, including standardized assessments, interviews, and observations, were collected at initial and subsequent monthly visits.

Gold-catalyzed dual C-C bond cleavage of biphenylenes bearing a pendant alkyne at ambient temperature.

We report a catalytic skeletal rearrangement of biphenylenes with a pendant alkyne moiety at room temperature by a cationic gold catalyst, which involves the cleavage of two bonds: the C-C bond of biphenylene and the C(sp)-C(sp2 or sp3) bond. Experimental and theoretical studies revealed that the reaction mechanism included π-activation of the alkyne, ring expansion and 1,2-carbon shift.

A cross-sectional analysis of clinicopathologic similarities and differences between Henoch-Schönlein purpura nephritis and IgA nephropathy.

Introduction: Recent studies noted that Henoch-Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) share the feature of galactose-deficient IgA1 (Gd-IgA1)-oriented pathogenesis, although there are distinct clinical differences. We aimed to clarify the clinicopathologic differences between these 2 diseases.

Methods: We cross-sectionally analyzed adult patients with HSPN (n = 24) or IgAN (n = 56) who underwent renal biopsy (RB) between 2008 and 2018 at Showa University Hospital.

Short-step synthesis and chiroptical properties of polyaza[5]-[9]helicenes with blue to green-colour emission.

We have developed a two- or three-step synthesis of polyaza[5]-[9]helicenes by consecutive N-H/C-H coupling with a hypervalent iodine reagent. We further evaluated their photophysical properties, and circularly polarized luminescence properties and found that g values increase with the number of fused rings up to 2.7 × 10, which is the highest value among [9]helicenes.

Therapeutic Potential of Thrombomodulin in Renal Fibrosis of Nephrotoxic Serum Nephritis in Wistar-Kyoto Rats.

Background: Recombinant human soluble thrombomodulin (rhTM) was approved in 2008 and has been used for treatment of disseminated intravascular coagulation in Japan. The antifibrotic effects of rhTM in acute exacerbation of idiopathic pulmonary fibrosis are well established, but the therapeutic potential of rhTM in renal fibrosis remains poorly understood.

Methods: Nephrotoxic serum nephritis (NTS-N) was induced in 22 female Wistar-Kyoto (WKY) rats on day 0.

Crescentic IgA nephropathy after administration of human monoclonal interleukin-12/23p40 antibody in a patient with Crohn's disease: a case report.

Ustekinumab (UST), an interleukin (IL)-12/IL-23-blocking monoclonal antibody, is a novel therapeutic option for Crohn's disease (CD). We describe a 24-year-old man with CD who showed an abrupt decline in renal function after administration of UST. Twenty-nine months previously, the patient was diagnosed with CD, and abnormal urinalysis findings in health checkup were coincidentally found at that time.

Catalytic Enantioselective Synthesis of Axially Chiral Polycyclic Aromatic Hydrocarbons (PAHs) via Regioselective C-C Bond Activation of Biphenylenes.

Chiral polycyclic aromatic hydrocarbons (PAHs) are expected to have unusual physical properties due to their chirality and expanded π-conjugated system. Indeed, PAHs are promising compounds as chiral recognizers and organic semiconductors. Therefore, an efficient method for the synthesis of chiral PAHs is strongly desired.

Serum uromodulin is associated with the severity of clinicopathological findings in ANCA-associated glomerulonephritis.

Background: Uromodulin (UMOD), also known as Tamm-Horsfall protein, is a kidney-specific protein expressed by epithelial cells lining the thick ascending limb of the loop of Henle. In the current study, we aimed to clarify the clinical significance of UMOD in ANCA-associated glomerulonephritis (AAG).

Materials And Methods: Sixty-one biopsy-proven AAG patients were included in this study.

Proteomics of human glomerulonephritis by laser microdissection and liquid chromatography-tandem mass spectrometry.

Aim: Laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) enable clinicians to analyse proteins from tissue sections. In nephrology, these methods are used to diagnose diseases of abnormal protein deposition, such as amyloidosis, but they are seldom applied to the diagnosis and pathophysiological understanding of human glomerular diseases.

Methods: Renal biopsy specimens were obtained from five patients with IgA nephropathy (IgAN), five patients with membranous nephropathy (MN) and five kidney transplant donors (as controls).

Consecutive HDDA and TDDA reactions of silicon-tethered tetraynes for the synthesis of dibenzosilole-fused polycyclic compounds and their unique reactivity.

Silicon-tethered tetraynes possessing a 1,3-diyne moiety underwent consecutive hexadehydro- and tetradehydro-Diels-Alder reactions to give a series of fused polycyclic aromatic compounds containing a dibenzosilole skeleton. The benzene ring in the product acted as a 1,3-diene and reacted with the active alkyne as well as oxygen to provide [4 + 2] cycloadducts.

Elimination of intravenous alendronate by hemodialysis: A kinetic study.

Introduction: The potential utility of intravenous alendronate for the treatment of osteoporosis in hemodialysis patients was recently reported. However, the pharmacokinetics of intravenous alendronate in patients on hemodialysis is not clear.

Methods: Six hemodialysis patients (mean age, 80.

Iodine-Catalyzed Synthesis of Chiral 4-Imidazolidinones Using α-Amino Acid Derivatives via Dehydrogenative N-H/C(sp)-H Coupling.

An efficient method for the asymmetric synthesis of 4-imidazolidinones via an iodine-catalyzed intramolecular N-H/C(sp)-H activation of readily available and abundant feedstocks, amino acids, and amines is described. The reaction proceeded under visible light irradiation to afford a variety of 4-imidazolidinone derivatives under mild conditions in moderate to excellent yields. Secondary and tertiary C(sp)-H bonds were aminated, and various functional groups were tolerated.