The Genomic Landscape of Breast Cancer in Young and Older Women.

Background: Young women with breast cancer (YWBC; ≤40 years) often have a poorer prognosis than older women with breast cancer (OWBC; ≥65 years). We explored molecular features of tumors from YWBC and OWBC to identify a biologic connection for these patterns.

Materials And Methods: We retrospectively analyzed the molecular profiles of 1879 breast tumors.

What's the CATCH? A Participatory Learning Model for Case Review Rounds to Support a Culture of Safety and Quality Improvement in Pediatric Hospital Medicine.

Objective: To evaluate the effectiveness of a new model, Case Analysis and Translation to Care in Hospital (CATCH), for the review of pediatric inpatient cases when an adverse event or "close call" had occurred.

Study Design: The curricular intervention consisted of an introductory podcast/workshop, mentorship of presenters, and monthly CATCH rounds over 16 months. The study was conducted with 22 pediatricians at a single tertiary care center.

Integrative Oncology in Young Women With Breast Cancer.

Small studies have demonstrated the benefit of integrative oncology (IO) therapies in patients with breast cancer; however, referral patterns and timing of therapies are unknown. This study describes the referral pattern and utilization of IO services by young women with breast cancer. A retrospective review identified female patients, 40 years or younger, with a breast cancer diagnosis between 2014 and 2019, and a documented IO consultation.

Pembrolizumab in Patients With Metastatic Breast Cancer With High Tumor Mutational Burden: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Purpose: The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported.

Methods: Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks.

Cetuximab in Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Ovarian Cancer Without KRAS, NRAS, or BRAF Mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Background: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a phase II basket study, evaluates anti-tumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known as drug targets.

Objective: With no known genomic targets predictive of sensitivity to cetuximab, cetuximab was evaluated in patients with breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC), without KRAS, NRAS, or BRAF mutations.

Patients And Methods: Eligible patients with advanced BC, NSCLC, and OC received a cetuximab loading dose, then weekly infusions (250 mg/m over 60 min).

Municipal Solid Waste Disposal Operational Performance in Wa Municipality, Ghana.

Background: The generation and management of solid waste pose potential adverse impacts on human health and the environment.

Objective: The present study examines the operational performance of municipal solid waste (MSW) disposal in the Wa Municipality, Ghana.

Methods: The study applied both qualitative and quantitative research methods and modelled the Wa Municipality's MSW disposal system using the municipal solid waste decision support tool (MSW DST).

LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.

Purpose: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM.

Investigating a Relationship between the Mutagenicity of Arylboronic Acids and (11)B NMR Chemical Shifts.

The mutagenicity of arylboronic acids has recently become an important area of research because of their potential to be genotoxic impurities in active pharmaceutical ingredients. There is no known mechanism, so currently all structure-activity relationships have been derived using Ames test data. We present preliminary data supporting a hypothesis that the mutagenicity of arylboronic acids is related to the (11)B NMR chemical shift.

Stereocontrolled protein surface recognition using chiral oligoamide proteomimetic foldamers.

The development of foldamers capable of selective molecular recognition of solvent exposed protein surfaces represents an outstanding challenge in supramolecular chemical biology. Here we introduce an oligoamide foldamer with well-defined conformation that bears all the hallmarks of an information rich oligomer. Specifically, the foldamer recognizes its target protein DM2 leading to inhibition of its protein-protein interaction with p53 in a manner that depends upon the composition, spatial projection and stereochemistry of functional groups appended to the scaffold.

Stabilization of a Bimolecular Triplex by 3'-S-Phosphorothiolate Modifications: An NMR and UV Thermal Melting Investigation.

Triplexes formed from oligonucleic acids are key to a number of biological processes. They have attracted attention as molecular biology tools and as a result of their relevance in novel therapeutic strategies. The recognition properties of single-stranded nucleic acids are also relevant in third-strand binding.

Metallo-cryptophanes decorated with bis-N-heterocyclic carbene ligands: self-assembly and guest uptake into a nonporous crystalline lattice.

Pd3L2 metallo-cryptophane cages with cyclotriveratrylene-type L ligands can be stabilized by use of a bis-N-heterocyclic carbene as an auxiliary cis-protecting ligand, while use of more common protecting chelating ligands such as ethylenediamine saw a Pd3L2 to Pd6L8 rearrangement occur in solution. The crystalline Pd3L2 complexes act as sponges, taking up 1,2-dichorobenzene or iodine in a single-crystal-to-single-crystal fashion despite not exhibiting conventional porosity.

Optimal reaction coordinate as a biomarker for the dynamics of recovery from kidney transplant.

The evolution of disease or the progress of recovery of a patient is a complex process, which depends on many factors. A quantitative description of this process in real-time by a single, clinically measurable parameter (biomarker) would be helpful for early, informed and targeted treatment. Organ transplantation is an eminent case in which the evolution of the post-operative clinical condition is highly dependent on the individual case.

Encapsulation of sodium alkyl sulfates by the cyclotriveratrylene-based, [Pd(6)L(8)](12+) stella octangula cage.

We have previously described a cyclotriveratrylene (CTV)-based complex, [Pd6L8](12+), that forms a highly symmetric stella octangula cage. Here we report on the ability of this system to host sodium salts of three alkyl sulfates; octyl (SOS), dodecyl (SDS) and tetradecyl (STS). (1)H NMR chemical shift and diffusion coefficient measurements reveal that two molecules of alkyl sulfate reside in the cage, though rapid exchange between cage and bulk solvent is apparent.

Solvent-dependent self-assembly behaviour and speciation control of Pd6L8 metallo-supramolecular cages.

The C3-symmetric chiral propylated host-type ligands (±)-tris(isonicotinoyl)-tris(propyl)-cyclotricatechylene (L1) and (±)-tris(4-pyridyl-4-benzoxy)-tris(propyl)-cyclotricatechylene (L2) self-assemble with Pd(II) into [Pd6L8](12+) metallo-cages that resemble a stella octangula. The self-assembly of the [Pd6(L1)8](12+) cage is solvent-dependent; broad NMR resonances and a disordered crystal structure indicate no chiral self-sorting of the ligand enantiomers in DMSO solution, but sharp NMR resonances occur in MeCN or MeNO2. The [Pd6(L1)8](12+) cage is observed to be less favourable in the presence of additional ligand, than is its counterpart, where L=(±)-tris(isonicotinoyl)cyclotriguaiacylene (L1 a).

Development and evaluation of global child health educational modules.

Objectives: To determine if a standardized global child health (GCH) modular course for pediatric residents leads to satisfaction, learning, and behavior change.

Methods: Four 1-hour interactive GCH modules were developed addressing priority GCH topics. "Site champions" from 4 Canadian institutions delivered modules to pediatric residents from their respective programs during academic half-days.

Thermal stabilisation of RNA·RNA duplexes and G-quadruplexes by phosphorothiolate linkages.

The effect of 3'-S-phosphorothiolate linkages on the stability of RNA·RNA duplexes and G-quadruplex structures has been studied. 3'-Thio-2'-deoxyuridine was incorporated into RNA duplexes and thermal melting studies revealed that the resulting 3'-S-phosphorothiolate linkages increased the stability of the duplex to thermal denaturation. Additionally, and contrary to expectation, a similar effect on duplex stability was observed when the same thionucleoside was incorporated into the RNA strand of a RNA·DNA duplex.

Metabolic profiling of follicular fluid and plasma from natural cycle in vitro fertilization patients--a pilot study.

Objective: To investigate changes in follicular fluid (FF) and plasma composition during the follicular and periovulatory phases of the menstrual cycle in patients undergoing assisted conception, using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy-based metabolite profiling.

Design: A pilot prospective laboratory study.

Setting: Assisted conception clinic in a university hospital.

Design, synthesis and binding studies of a novel quadruple ADDA hydrogen-bond array.

The design and synthesis of a novel ADDA hydrogen-bond array is described. The ureidodiimidazole motif (UDIM) 2 engages in interactions with complementary diamidonaphthyridine (DAN) 3 motifs with an association constant K(a) = 825 ± 16 M(-1) in chloroform. (1)H NMR and molecular modelling studies were carried out in order to explain the unexpected behaviour of this new supramolecular motif.

Conformer-independent ureidoimidazole motifs--tools to probe conformational and tautomeric effects on the molecular recognition of triply hydrogen-bonded heterodimers.

Linear arrays of hydrogen bonds are useful for the reversible assembly of "stimuli-responsive" supramolecular materials. There is thus an ongoing requirement for easy-to-synthesise motifs that are capable of presenting hydrogen-bonding functionality in a predictable manner, such that high-affinity and high-fidelity recognition occurs. The design of linear arrays is made challenging as a consequence of their ability to adopt multiple conformational and tautomeric configurations; with each additional hydrogen-bonding heteroatom added to an array, the available tautomeric and conformational space increases and it can be difficult to anticipate where unproductive conformers/tautomers will arise.

Ditopic triply hydrogen-bonded heterodimers.

The synthesis and self-assembly of a stable hydrogen-bonded heterodimer comprising ditopic ureidoimidazole and amidoisocytosine motifs is described. The heterodimer appears to exhibit high stability in deuterochloroform as evidenced by (1)H NMR, DOSY and (1)H-(1)H ROESY.