Training to Increase Minority Enrollment in Lupus Clinical Trials With Community Engagement: Enhancing Lupus Clinical Trial Recruitment Through Provider and Community Health Worker Engagement.

Objective: This study evaluates the effectiveness of the Training to Increase Minority Enrollment in Lupus Clinical Trials with Community Engagement (TIMELY) program on enhancing referrals of underrepresented patients to lupus clinical trials. TIMELY leverages two existing American College of Rheumatology online educational initiatives: Materials to Increase Minority Involvement in Clinical Trials (MIMICT), a continuing medical education activity for health care providers, and the community health worker (CHW) Lupus Clinical Trials Training (LuCTT). TIMELY introduced a unique roundtable meeting format to build on the existing online educational programs and facilitate discussions between local clinical trial sites and provider and CHW participants.

A Resorcin[4]arene-Based Phosphite-Phosphine Ligand for the Branched-Selective Hydroformylation of Alkyl Alkenes.

Synthesis of a chelating phosphite-phosphine ligand from a tris(quinoxaline) extended resorcin[4]arene and its application in the rhodium-catalyzed hydroformylation of terminal alkyl alkenes are reported. Rhodium complexes are formed within the cavity of the macrocycle and branched-selective hydroformylation of 1-octene with a / ratio of 5.9 has been achieved at 60 °C under 1:1 H/CO (20 bar).

Copper(I) Catalysed Diboron(4) Reduction of Nitrous Oxide.

A process for the catalytic reduction of nitrous oxide using NHC-ligated copper(I) tert-butoxide precatalysts and Bpin as the reductant is reported. These reactions proceed under mild conditions via copper(I)-boryl intermediates which react with NO by facile O-atom insertion into the Cu-B bond and liberate N. Turnover numbers >800 can be achieved at 80 °C under 1 bar NO.

Synthetic and Mechanistic Studies into the Reductive Functionalization of Nitro Compounds Catalyzed by an Iron(salen) Complex.

We report on the use of a simple, bench-stable [Fe(salen)]-μ-oxo precatalyst in the reduction of nitro compounds. The reaction proceeds at room temperature across a range of substrates, including nitro aromatics and aliphatics. By changing the reducing agent from pinacol borane (HBpin) to phenyl silane (HSiPh), we can chemoselectively reduce nitro compounds while retaining carbonyl functionality.

Students who witness critical events in the clinical setting: Recommendations for prevention of psychological trauma.

Background: Student nurses often do not receive adequate preparation, support, and debriefing related to witnessing or experiencing critical events in the clinical setting.

Purpose: The purpose of this analysis was to describe the experiences of student nurses who have witnessed critical events in the clinical setting, the support and preparation they received, and staff and faculty actions they perceived as facilitating or hindering their processing of the event.

Methods: This is a sub-analysis of a Straussian Grounded Theory qualitative study.

Capture of mechanically interlocked molecules by rhodium-mediated terminal alkyne dimerisation.

The transition metal-mediated dimerisation of terminal alkynes is an attractive and atom-economic method for preparing conjugated 1,3-enynes. Using a phosphine-based macrocyclic pincer ligand, we demonstrate how this transformation can be extended to the synthesis of novel, hydrocarbon-based interlocked molecules: a rotaxane by 'active' metal template synthesis and a catenane by sequential 'active' and 'passive' metal template procedures.

Discovery of KB-0742, a Potent, Selective, Orally Bioavailable Small Molecule Inhibitor of CDK9 for MYC-Dependent Cancers.

Transcriptional deregulation is a hallmark of many cancers and is exemplified by genomic amplifications of the MYC family of oncogenes, which occur in at least 20% of all solid tumors in adults. Targeting of transcriptional cofactors and the transcriptional cyclin-dependent kinase (CDK9) has emerged as a therapeutic strategy to interdict deregulated transcriptional activity including oncogenic MYC. Here, we report the structural optimization of a small molecule microarray hit, prioritizing maintenance of CDK9 selectivity while improving on-target potency and overall physicochemical and pharmacokinetic (PK) properties.

The Complex Reactivity of [(salen)Fe](μ-O) with HBpin and Its Implications in Catalysis.

We report a detailed study into the method of precatalyst activation during alkyne cyclotrimerization. During these studies we have prepared a homologous series of Fe(III)-μ-oxo(salen) complexes and use a range of techniques including UV-vis, reaction monitoring studies, single crystal X-ray diffraction, NMR spectroscopy, and LIFDI mass spectrometry to provide experimental evidence for the nature of the on-cycle iron catalyst. These data infer the likelihood of ligand reduction, generating an iron(salan)-boryl complex as a key on-cycle intermediate.

Vanadium oxide and a sharp onset of cold-trapping on a giant exoplanet.

The abundance of refractory elements in giant planets can provide key insights into their formation histories. Owing to the low temperatures of the Solar System giants, refractory elements condense below the cloud deck, limiting sensing capabilities to only highly volatile elements. Recently, ultra-hot giant exoplanets have allowed for some refractory elements to be measured, showing abundances broadly consistent with the solar nebula with titanium probably condensed out of the photosphere.

Iridium complexes of an -trifluoromethylphenyl substituted PONOP pincer ligand.

The synthesis and iridium coordination chemistry of a new pyridine-based phosphinito pincer ligand 2,6-(ArPO)CHN (PONOP-Ar; Ar = 2-(CF)CH) are described, where the P-donors have -trifluoromethylphenyl substituents. The iridium(III) 2,2'-biphenyl (biph) derivative [Ir(PONOP-Ar)(biph)Cl] was obtained by reaction with [Ir(biph)(COD)Cl] (COD = 1,5-cyclooctadiene) and subsequent halide ion abstraction enabled isolation of [Ir(PONOP-Ar)(biph)] which features an Ir ← F-C bonding interaction in the solid state. Hydrogenolysis of the biphenyl ligand and formation of [Ir(PONOP-Ar)(H)] was achieved by prolonged reaction of [Ir(PONOP-Ar)(biph)] with dihydrogen.

Broken Promises? On the Continued Challenges Faced in Catalytic Hydrophosphination.

In this Perspective, we discuss what we perceive to be the continued challenges faced in catalytic hydrophosphination chemistry. Currently the literature is dominated by catalysts, many of which are highly effective, that generate the same phosphorus architectures, e.g.

Taming PH: State of the Art and Future Directions in Synthesis.

Appetite for reactions involving PH has grown in the past few years. This in part is due to the ability to generate PH cleanly and safely via digestion of cheap metal phosphides with acids, thus avoiding pressurized cylinders and specialized equipment. In this perspective we highlight current trends in forming new P-C/P-OC bonds with PH and discuss the challenges involved with selectivity and product separation encumbering these reactions.

Student Nurses' Experiences of Critical Events in the Clinical Setting: A Grounded Theory.

Background: Nursing students often experience critical events in the clinical setting and clinical instructors may not be prepared to adequately support them. These students often feel alone and abandoned, increasing their risk of psychological distress.

Purpose: A grounded theory study was conducted to explore pre-licensure nursing students' experiences of critical events in the clinical setting.

Island communities and disaster resilience: Applying the EnRiCH community resilience framework.

Objective: To explore the beliefs, attitudes, and perspectives of community resilience in St. Kitts and Nevis.

Design: Qualitative Interpretive Phenomenological Analysis using the EnRiCH Community Resilience Framework for High-Risk Populations (EnRiCH Framework) to identify factors that enhance or create barriers to community resilience to disasters in St.

Synthesis and reactivity of iridium complexes of a macrocyclic PNP pincer ligand.

Having recently reported on the synthesis and rhodium complexes of the novel macrocyclic pincer ligand PNP-14, which is derived from lutidine and features terminal phosphine donors trans-substituted with a tetradecamethylene linker (Dalton Trans., 2020, 49, 2077-2086 and Dalton Trans., 2020, 49, 16649-16652), we herein describe our findings critically examining the chemistry of iridium homologues.

Reactions of Rh(PNP) pincer complexes with terminal alkynes: homocoupling through a ring or not at all.

Through use of a bespoke macrocyclic variant, we demonstrate a novel approach for tuning the reactivity of rhodium PNP pincer complexes that enables formation of conjugated enynes from terminal alkynes, rather than vinylidene derivates. This concept is illustrated using tert-butylacetylene as the substrate and rationalised by a ring-induced switch in mechanism.

TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in AML.

Somatic TP53 mutations and 17p deletions with genomic loss of TP53 occur in 37% to 46% of acute myeloid leukemia (AML) with adverse-risk cytogenetics and correlate with primary induction failure, high risk of relapse, and dismal prognosis. Herein, we aimed to characterize the immune landscape of TP53-mutated AML and determine whether TP53 abnormalities identify a patient subgroup that may benefit from immunotherapy with flotetuzumab, an investigational CD123 × CD3 bispecific dual-affinity retargeting antibody (DART) molecule. The NanoString PanCancer IO360 assay was used to profile 64 diagnostic bone marrow (BM) samples from patients with TP53-mutated (n = 42) and TP53-wild-type (TP53-WT) AML (n = 22) and 45 BM samples from patients who received flotetuzumab for relapsed/refractory (R/R) AML (15 cases with TP53 mutations and/or 17p deletion).

Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response.

Synthesis and rhodium complexes of macrocyclic PNP and PONOP pincer ligands.

The synthesis of macrocyclic variants of commonly employed phosphine-based pincer ligands derived from lutidine (PNP-14) and 2,6-dihydroxypyridine (PONOP-14) is described, where the P-donors are trans-substituted with a tetradecamethylene linker. This was accomplished using an eight-step procedure involving borane protection, ring-closing olefin metathesis, chromatographic separation from the cis-substituted diastereomers, and borane deprotection. The rhodium coordination chemistry of these ligands has been explored, aided by the facile synthesis of 2,2'-biphenyl (biph) adducts [Rh(PNP-14)(biph)][BAr] and [Rh(PONOP-14)(biph)][BAr] (Ar = 3,5-(CF)CH).

Targeted transcriptional profiling of the tumor microenvironment reveals lymphocyte exclusion and vascular dysfunction in metastatic osteosarcoma.

Osteosarcoma (OS) is the most common bone tumor in pediatric and adolescent/young adult patients yet little is known about the microenvironment that supports this aggressive disease. We have used targeted gene expression profiling and immunohistochemistry to characterize the microenvironment of metastatic and non-metastatic OS specimens from pediatric patients exhibiting poor histologic response to chemotherapy. Our results indicate that metastatic specimens exhibit lymphocyte exclusion as T cells are confined to the periphery of the pulmonary lesions.

Synthesis and Structural Dynamics of Five-Coordinate Rh(III) and Ir(III) PNP and PONOP Pincer Complexes.

The synthesis and characterization of a homologous series of five-coordinate rhodium(III) and iridium(III) complexes of PNP (2,6-( tBuPCH)CHN) and PONOP (2,6-( tBuPO)CHN) pincer ligands are described: [M(PNP)(biph)][BAr] (M = Rh, 1a; Ir, 1b; biph = 2,2'-biphenyl; Ar = 3,5-(CF)CH) and [M(PONOP)(biph)][BAr] (M = Rh, 2a; Ir, 2b). These complexes are structurally dynamic in solution, exhibiting pseudorotation of the biph ligand on the H NMR time scale (Δ G ca. 60 kJ mol) and, in the case of the flexible PNP complexes, undergoing interconversion between helical and puckered pincer ligand conformations (Δ G ca.

A convenient method for the generation of {Rh(PNP)} and {Rh(PONOP)} fragments: reversible formation of vinylidene derivatives.

The substitution reactions of [Rh(COD)2][BArF4] with PNP and PONOP pincer ligands 2,6-bis(di-tert-butylphosphinomethyl)pyridine and 2,6-bis(di-tert-butylphosphinito)pyridine in the weakly coordinating solvent 1,2-F2C6H4 are shown to be an operationally simple method for the generation of reactive formally 14 VE rhodium(i) adducts in solution. Application of this methodology enables synthesis of known adducts of CO, N2, H2, previously unknown water complexes, and novel vinylidene derivatives [Rh(pincer)(CCHR)][BArF4] (R = tBu, 3,5-tBu2C6H3), through reversible reactions with terminal alkynes.

Synthesis of a new disulfide Fmoc monomer for creating biologically susceptible linkages in peptide nucleic acid oligomers.

Peptide nucleic acids (PNA) are one of many synthetic mimics of DNA and RNA that have found applications as biological probes, as nano-scaffold components, and in diagnostics. In an effort to use PNA as constructs for cellular delivery we investigated the possibility of installing a biologically susceptible disulfide bond in the backbone of a PNA oligomer. Here we report the synthesis of a new abasic Fmoc monomer containing a disulfide bond that can be incorporated into a PNA oligomer (DS-PNA) using standard solid phase peptide synthesis.