Unsymmetric Ir and RhIr Dinuclear Complexes Supported by a Linear Tetraphosphine -dpmppp, Showing High Reactivity for O, H, and HCl.

Unsymmetric dinuclear Ir(I) complexes, [IrCl(L)(-dpmppp)] (L = XylNC (), BuNC (), CO ()), were synthesized using -PhPCHP(Ph)(CH)P(Ph)CHPPh (-dpmppp), which supports - (M) and (M) metal sites, and exhibited high reactivity for O, H, and HCl. The IrRh heterodinuclear complexes, [MMCl(L)(-dpmppp)] () (MM = IrRh, RhIr; L = XylNC, CO ( = , )), were also synthesized and used together with the Rh complexes () to elucidate the role of each metal site. For the reactions of O, and showed higher reactivity than those of and , giving η-peroxide complexes [{MCl}{M(η-O)(XylNC)}(-dpmppp)] (, ), from which O would not dissociate.

Pharmacist-initiated interventions to test quantitative bone mineral density and prescribe osteoporosis medications to prevent steroid-induced osteoporosis.

Fragility fractures associated with glucocorticoid-induced osteoporosis (GIO) can markedly impair quality of life. However, only 20% of patients are treated in compliance with the relevant management guidelines, and bone mineral density analysis with dual-energy X-ray absorptiometry (DXA) is only rarely performed. We report the intervention methods suggested by pharmacists and describe their efficacy.

Aiming for dynamic behaviours of molecular metal chains.

The dynamical functions of molecular metal chains, that could be derived from unique physical and chemical properties coupled with self-assembly of metal chain components, have largely been unexplored, and this review paper focuses on the dynamic behaviours of Pd chains supported by linear tetraphosphines, - and -PhPCHP(Ph)CHP(Ph)CHPPh recently reported, and the current development on fine-tuning of metal chains by introducing heterometal atoms, heterometallic molecular metal chains, that are considered as promising dynamical components in the next generation.

Intraomental Splenic Implant - An Attempt of Reassessment.

The permanent risk of splenectomized patients to infectious complications, the most severe being overwhelming post splenectomy infection (OPSI), determined the search for solutions in order to diminish these evolutionary possibilities. Therefore, intraomental developsplenic autotransplantation seems to be a viable option which, according to some authors, would have beneficial effects by restoring (at least partially) the functions of the spleen. The article presents the current experience related to this procedure (principles of surgical technique, implant location, complications, post-procedural evaluation) in an attempt to bring it back to the attention of trauma / general surgery surgeons.

Unsymmetric Dinuclear Rh and RhRh Complexes Supported by Tetraphosphine Ligands and Their Reactivity of Oxidative Protonation and Reductive Dechlorination.

Two linear tetradentate phosphine ligands, -PhPCHP(Ph)CHCHP(Ph)CHPPh ( = CH (-dpmppp), NBn (-dpmppmNBn; Bn = benzyl)) were utilized to synthesize unsymmetrical dinuclear Rh complexes, [RhCl(-dpmppp)(L)] (L = XylNC (), CO ()) and [RhCl(-dpmppmNBn)(L)] (L = XylNC (), CO ()), where electron-deficient Rh → Rh centers with 30 valence electrons are supported by a tetraphosphine in an unusual /- coordination mode. The Rh dimers of - were treated with HCl under air to afford the Rh → Rh dimers with 32 e, [RhCl(-dpmppp)(L)] (L = XylNC (), CO ()) and [RhCl(-dpmppmNBn)(L)] (L = XylNC (), CO ()), via intermediate hydride complexes, [{RhCl(μ-H)RhCl(L)}(-dpmppp)] (L = XylNC (), CO ()) and [{RhCl(μ-H)RhCl(L)}(-dpmppmNBn)] (L = XylNC (), CO ()), and [{Rh(H)Cl(μ-Cl)Rh(L)}-dpmppp)] (L = XylNC (), CO ()) and [{Rh(H)Cl(μ-Cl)Rh(L)}-dpmppmNBn)] (L = XylNC (), CO ()). The hydride intermediates and were monitored under nitrogen by H{P} and P{H} NMR techniques to reveal two reaction pathways depending on the terminal auxiliary ligand L.

Chiral Dinuclear Eu , Tb , and Y Complexes Supported by P-Stereogenic Linear Tetraphosphine Tetraoxide.

A P-stereogenic linear tetraphosphine tetraoxide, (R,R)- or (S,S)-dpmppm(=O) , was synthesized to prepare C dinuclear M(hfa) complexes (M=Eu, Tb, Y) as the first example of lanthanide(III) complexes with P-chiral multidentate phosphine oxides. The mononuclear M(hfa) complexes (M=Eu, Y) with a P-chiral diphosphine dioxide, tpdpb(=O) , were also prepared, and comparison of their photophysical properties for the Eu complexes revealed that significant chiral induction from the P-chiral centers arises on the achiral M(hfa) units through intramolecular π-π stacking constraint in the dinuclear system.

Electrochemical hydrogen formation catalysed by a Pd string.

The linear Pd complex supported by tetraphosphines reacted with HBF to give an unprecedented linear tetrapalladium complex with a terminal hydride, which promoted electrocatalytic hydrogen formation from HBF in acetonitrile. The 1D coordination polymer of Pd chain confined within Nafion film was applied to the electrocatalytic H formation.

Octapalladium Strings Trap C and C Fullerenes Affording Metal-Chain-Wired Bucky Balls.

Reactions of Pd strings supported by meso-Ph PCH P(Ph)CH P(Ph)CH PPh (meso-dpmppm) ligands, [Pd (meso-dpmppm) (L) ] (L=CH CN (1), XylNC (2)) with C resulted in the exclusive formation of unprecedented metal-chain-wired C bucky balls, [{Pd (meso-dpmppm) (L)} (C )] (L=CH CN (11), XylNC (12)), in which a C fullerene is trapped in the central Pd-Pd junction, as unambiguously established by spectroscopic, X-ray crystallographic, and theoretical techniques. The similar reaction of Pd strings supported by rac-dpmppm, [Pd (rac-dpmppm) (CH CN) ] (3) also afforded a racemic mixture of [{Pd ((R*,R*)-dpmppm) (CH CN)} (C )] (13) without scrambling the Pd fragments with (R,R)- and (S,S)-dpmppm ligands. Consequently, those of enantiopure chiral Pd strings, [Pd ((R*,R*)-dpmppm) (CH CN) ] , certainly afforded chiral bucky balls of [{Pd ((R*,R*)-dpmppm) (CH CN)} (C )] (13 and 13 ), that exhibit mirror-image circular dichroism spectra.

Fine Tunable, Redox Active Octapalladium Chains Supported by Linear Tetraphosphines, Leading to Dynamically 1D Self-Assembled Coordination Polymers.

A series of the octapalladium chains supported by meso-Ph PCH P(Ph)CH P(Ph)CH PPh (meso-dpmppm) ligands, [Pd (meso-dpmppm) (L) ](BF ) (L=none (1), solvents: CH CN (2 a), dmf (2 b), dmso (2 c), RN≡C: R=Xyl (3 a), Mes (3 b), Dip (3 c), Bu (3 d), Cy (3 e), CH (CH ) (3 f), CH (CH ) (3 g), CH (CH ) (3 h)) and [Pd (meso-dpmppm) (X) ](BF ) (X=Cl (4 a), N (4 b), CN (4 c), SCN (4 d)), were synthesized by using 2 a as a stable good precursor, and characterized by spectroscopic (IR, H and P NMR, UV-vis-NIR, ESI-MS) measurements and X-ray crystallographic analyses (for 1, 2 a, b, 3 a, b, e, f, 4 a-d). On the basis of DFT calculations on the X-ray determined structure of 2 b ([2b-Pd ] ) and the optimized models [Pd (meso-Ph PCH P(H)CH P(H)CH PH ) (CH CN) ] ([Pd Ph ] ) and [Pd (meso-H PCH P(H)CH P(H)CH PH ) (CH CN) ] ([Pd H ] ), with and without empirically calculating dispersion force stabilization energy (B3LYP-D3, B3LYP), the formation energy between the two Pd fragments is assumed to involve mainly noncovalent interactions (ca. -70 kcal/mol) with four sets of interligand C-H/π interactions and Pd⋅⋅⋅Pd metallophilic one, while electron shared covalent interactions are almost canceled out within the Pd chain.

Chiral Octapalladium Chains Supported by Enantiopure -Stereogenic Linear Tetraphosphines, ()- and ()-PhPCHP(Ph)CHP(Ph)CHPPh.

Binuclear Pd(II) and Pt(II) complexes supported by -dpmppm (bis[(diphenylphosphinomethyl)phenylphosphino]methane) in a triply-bridged -form, [MCl(-dpmppm)] (M = Pd (), Pt ()), readily reacted with 2,6-xylyl isocyanide (XylNC) in the presence of NHPF to afford [MCl(-dpmppm)(XylNC)](PF) (M = Pd (), Pt ()), in which each metal center accommodates one isocyanide ligand at the position to the inner P atom of dpmppm. Similarly, treatment of and with axially chiral ()-1,1'-binaphthyl-2,2'-bisisocyanide (-Binac) in the presence of NHOTf gave cyclic tetranuclear complexes, [{MCl(-dpmppm)(-Binac)}](OTf) (M = Pd (), Pt ()), where two {MCl(-dpmppm)} fragments are connected by two -Binac ligands through chirality sorting of ()-dpmppm and ()-Binac. Complex could be transformed into the halide exchanged tetranuclear complexes, [{PdX(-dpmppm)(-Binac)}](OTf) (X = Br (), I ()), to show that the rectangular arrangement of four Pd(II) ions is elongated by repulsive interaction between halide ligands.

High-Level Expression of Alkaline Phosphatase by Adeno-Associated Virus Vector Ameliorates Pathological Bone Structure in a Hypophosphatasia Mouse Model.

Hypophosphatasia (HPP) is a systemic skeletal disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP). We recently reported that survival of HPP model mice can be prolonged using an adeno-associated virus (AAV) vector expressing bone-targeted TNALP with deca-aspartate at the C terminus (TNALP-D); however, abnormal bone structure and hypomineralization remained in the treated mice. Here, to develop a more effective and clinically applicable approach, we assessed whether transfection with TNALP-D expressing virus vector at a higher dose than previously used would ameliorate bone structure defects.

Restricted mean survival time as a summary measure of time-to-event outcome.

Many clinical research studies evaluate a time-to-event outcome, illustrate survival functions, and conventionally report estimated hazard ratios to express the magnitude of the treatment effect when comparing between groups. However, it may not be straightforward to interpret the hazard ratio clinically and statistically when the proportional hazards assumption is invalid. In some recent papers published in clinical journals, the use of restricted mean survival time (RMST) or τ-year mean survival time is discussed as one of the alternative summary measures for the time-to-event outcome.

Determination of hazard ratio for progression-free survival considering the tumor assessment schedule in sample size calculation.

Progression-free survival is recognized as an important endpoint in oncology clinical trials. In clinical trials aimed at new drug development, the target population often comprises patients that are refractory to standard therapy with a tumor that shows rapid progression. This situation would increase the bias of the hazard ratio calculated for progression-free survival, resulting in decreased power for such patients.

Neutropenia and survival outcomes in metastatic colorectal cancer patients treated with trifluridine/tipiracil in the RECOURSE and J003 trials.

Background: The phase II J003 (N = 169) and phase III RECOURSE (N = 800) trials demonstrated a significant improvement in survival with trifluridine (FTD)/tipiracil (TPI) versus placebo in patients with refractory metastatic colorectal cancer. This post hoc analysis investigated pharmacokinetic data of FTD/TPI exposure and pharmacodynamic markers, such as chemotherapy-induced neutropenia (CIN) and clinical outcomes.

Patients And Methods: A total of 210 patients from RECOURSE were enrolled in this substudy.

Facially Dispersed Polyhydride Cu and Cu Clusters Comprising Apex-Truncated Supertetrahedral and Square-Face-Capped Cuboctahedral Copper Frameworks.

By using a linear tetraphosphine, meso-bis[(diphenylphosphinomethyl)phenylphosphino]methane (dpmppm), nona- and hexadecanuclear copper hydride clusters, [Cu H (μ-dpmppm) ]X (X=Cl (1 a), Br (1 b), I (1 c), PF (1 d)) and [Cu H (μ-dpmppm) ]X (X =I (2 c), (4/3) PF ⋅(2/3) OH (2 d)) were synthesized and characterized. They form copper-hydride cages of apex-truncated supertetrahedral {Cu H } and square-face-capped cuboctahedral {Cu H } structures. The hydride positions were estimated by DFT calculations to be facially dispersed around the copper frameworks.

Tetra-, hexa- and octanuclear copper hydride complexes supported by tridentate phosphine ligands.

Multinuclear copper hydride complexes were synthesized by using a triphosphine, bis(diphenylphosphinomethyl)phenylphosphine (dpmp). The reaction of [Cu(MeCN)]PF with dpmp in 2 : 1 ratio in the presence of MeNBH or NaBH yielded a hexanuclear complex, [Cu(μ-H)(μ-dpmp)]PF (1), together with a minor product [Cu(μ-H)(μ-H)(μ-dpmp)](PF) (2) in a very low yield. Complex 1 was also prepared from [CuH(PPh)], [Cu(MeCN)]PF, and dpmp in 87%, but the yield of 2 could not be improved presumably due to its instability in solution.

Synergistic Cu Catalysts for Formic Acid Dehydrogenation.

Hexanuclear copper hydride complexes, [Cu(μ-H)( meso-L)(RNC)](PF) (R = Bu (6a), Cy (6b)), were prepared by using a new linear tetraphosphine, meso-PhPCHP(Ph)(CH)P(Ph)CHPPh ( meso-L), and were converted into active catalysts of [Cu(μ-OCH)( meso-L)(RNC)] under the reaction conditions of formic acid dehydrogenation, where unsymmetric dinuclear copper sites supported by the tetradentate phosphine and isocyanide ligands were essential to demonstrate effective catalytic activity.

Alloyed Tetranuclear Metal Chains of Pd Pt (n=0-3) Scaffolded by a New Linear Tetraphosphine Containing a PNP Bridge.

A new linear tetraphosphine containing a PNP phosphazane bridge, rac-bis[(diphenylphosphinomethyl)phenylphosphino]phenylamine (rac-dpmppan), was synthesized and utilized to support a series of Pd/Pt mixed metal tetranuclear chains, [Pd Pt (μ-rac-dpmppan) (XylNC) ](PF ) (XylNC=xylyl isocyanide; n=0: Pd (1), 1: PtPd (2), 2: PtPd Pt (3), 2: Pt Pd (4), 3: Pt PdPt (5)), in which the number and positions of additional Pt atoms were successfully controlled depending on the respective synthetic procedures using transformations from 1 to 3 through 2 and from 4 to 5 by redox-coupled exchange reactions. The P{ H} NMR and ESI mass spectra and X-ray diffraction analyses revealed almost identical tetranuclear structures, with slight contraction of metal-metal bonds according to incorporation of Pt atoms. The electronic absorption spectra of 1-5 exhibited characteristic bands at 635-510 nm with an energy propensity depending on the number and positions of Pt centres, which were assigned to HOMO (dσ*σσ*) to LUMO (dσ*σ*σ*) transition by theoretical calculations.

Relationship Between Thymidine Kinase 1 Expression and Trifluridine/Tipiracil Therapy in Refractory Metastatic Colorectal Cancer: A Pooled Analysis of 2 Randomized Clinical Trials.

Background: High thymidine kinase 1 (TK1) activity increases the incorporation of trifluridine (FTD) into DNA; thus, FTD antitumor activity is likely to increase in patients with high tumoral TK1 activity. To date, no established predictive biomarker to indicate the clinical benefit of FTD/tipiracil (TPI) has been identified. We aimed to determine the relationship between TK1 expression and FTD/TPI efficacy in refractory metastatic colorectal cancer.

Tri- and Tetranuclear Copper Hydride Complexes Supported by Tetradentate Phosphine Ligands.

Three types of tetradentate phosphine ligands with different central methylene chains and configurations, meso- and rac-PhPCHP(Ph)(CH) P(Ph)CHPPh ( n = 2, meso- and rac-dpmppe; n = 3, meso-dpmppp) were utilized to synthesize a new series of tri- and tetranuclear copper hydride complexes. Reactions of meso-dpmppe or meso-dpmppp with CuCl/NHPF or [Cu(CHCN)]PF in the presence of NaBH afforded trinuclear copper hydride complexes, [Cu(μ-H)( meso-dpmppe)](PF) (1) and [Cu(μ-H)( meso-dpmppp)](PF) (2), while a similar reaction with rac-dpmppe resulted in the formation of a tetranuclear copper dihydride complex, [Cu(μ-H)( rac-dpmppe)](PF) (5). Complexes 1 and 5 further reacted with RNC (R = Bu, Cy, Xyl) to give [Cu(μ-H)( meso-dpmppe)(XylNC)](PF) (3), [Cu(μ-H)( meso-dpmppe)(RNC)](PF) (R = Bu (4a), Cy (4b)) and [Cu(μ-H)( rac-dpmppe)(RNC)](PF) (R = Bu (6a), Cy (6b), Xyl (6c)), respectively.

A Proposal for Progression-Free Survival Assessment in Patients with Early Progressive Cancer.

Background/aim: Progression-free survival (PFS), which is evaluated in oncology clinical trials, is determined based on tumor progression evaluated according to an assessment schedule. There is possibly a bias in median PFS and hazard ratio (HR) for PFS depending on the assessment schedule referring to randomized controlled trials (RCTs) in patients with metastatic colorectal cancer.

Materials And Methods: We re-analyzed the PFS in the FTD/TPI phase 2 trial by changing the assessment schedule.

A Fluxional Cu H Cluster Supported by Bis(diphenylphosphino)methane and its Facile Reaction with CO.

A copper hydride cluster [Cu (μ-H) (μ-dppm) ](PF ) (dppm=bis(diphenylphosphino)methane) was prepared from reaction of [CuH(PPh )] with dppm in the presence of [Cu(CH CN) ]PF and exhibited fluxional behaviors in solution where the hydrides and the phosphines are scrambling around the trans-bicapped octahedral Cu framework. The Cu H complex showed facile reactivity with CO (1 atm, RT) to afford a tricopper complex, [Cu (μ-H)(μ-O CH)(μ-dppm) ]PF , which could be developed to unprecedented hydrosilylation of CO catalyzed by multinuclear CuH species under mild conditions.

Planar PtPd Complexes Stabilized by Three Bridging Silylene Ligands.

A heterobimetallic PtPd complex supported by three bridging diphenylsilylene ligands, [Pt{Pd(dmpe)} (μ -SiPh ) ] (1, dmpe=1,2-bis(dimethylphosphino)ethane), has been synthesized from mononuclear Pd and Pt complexes. The hexagonal core composed of Pt, Pd, and Si atoms is slightly larger than that of the tetrapalladium complex, [Pd{Pd(dmpe)} (μ -SiPh ) ] (2). Reaction of PhSiH with complex 1 in the presence and absence of Ph SiH results in the formation of a tetranuclear complex with silyl and hydride ligands at the Pt center, [PtH(SiPh H){Pd(dmpe)} (μ -SiHPh) ] (3), and an octanuclear complex, [{Pt{Pd(dmpe)} (μ -SiHPh) } (κ -dmpe)] (5), respectively.

Chiral Self-Recognition between Stereogenic Tetrapalladium Units Affording Pd Chains Supported by Homochiral Tetraphosphines.

By using a chiral tetraphosphine, rac-bis[(diphenylphosphinomethyl)phenylphosphino]methane (rac-dpmppm), linear octapalladium chains were synthesized as discrete molecules of [Pd (μ-rac-dpmppm) L ](BF ) (L=CH CN, dmf, XylNC), [Pd (μ-rac-dpmppm) ](BF ) , and [Pd (μ-rac-dpmppm) (Cl) ](BF ) , which are stable in the solution states and characterized by spectroscopic and crystallographic methods to reveal the octapalladium chains supported by homochiral four tetraphosphines. Variable-temperature NMR studies for a 1:1 mixture of [Pd (μ-rac-dpmppm) (dmf) ](BF ) and [Pd (μ-meso-dpmppm) (dmf) ]-(BF ) in [D ]DMF revealed that the Pd chains were dissociated at higher temperature (T≈140 °C) into the Pd units of {Pd (μ-rac-dpmppm) } and {Pd (μ-meso-dpmppm) } , and they were thermodynamically self-aligned to restore the Pd chains at lower temperature (T<60 °C), through perfect chiral self-recognition between the stereogenic tetrapalladium units.