Healthcare Utilization Among Persons with HIV and Unhealthy Alcohol Use in St. Petersburg, Russia.

Few studies have examined the association between healthcare utilization and heavy alcohol use in Russia among persons with HIV (PWH), a group with high healthcare needs. This study analyzed the association between unhealthy alcohol use (defined as AUDIT score ≥ 8) and healthcare utilization among PWH with heavy alcohol use and daily smoking in St. Petersburg, Russia.

Respiratory and Cardiometabolic Comorbidities and Stages I to III NSCLC Survival: A Pooled Analysis From the International Lung Cancer Consortium.

Introduction: We explored the association of respiratory and cardiometabolic comorbidities with NSCLC overall survival (OS) and lung cancer-specific survival (LCSS), by stage, in a large, multicontinent NSCLC pooled data set.

Methods: On the basis of patients pooled from 11 International Lung Cancer Consortium studies with available respiratory and cardiometabolic comorbidity data, adjusted hazard ratios (aHRs) were estimated using Cox models for OS. LCSS was evaluated using competing risk Grey and Fine models and cumulative incidence functions.

An overview of genetic services delivery for hereditary breast cancer.

Breast cancer is the most common cancer diagnosed in women worldwide, with approximately 5-10% of cases attributed to high penetrance hereditary breast cancer (HBC) genes. The tremendous advances in precision oncology have broadened indications for germline genetic testing to guide both systemic and surgical treatment, with increasing demand for cancer genetic services. The HBC continuum of care includes (1) identification, access, and uptake of genetic counseling and testing; (2) the delivery of genetic counseling and testing services; and (3) initiation of guideline-adherent follow-up care and family communication of results.

Impact of molecular subtype and race on HR+, HER2- breast cancer survival.

Purpose: There is an urgent need to understand the biological factors contributing to the racial survival disparity among women with hormone receptor-positive (HR+), HER2- breast cancer. In this study, we examined the impact of PAM50 subtype on 10-year mortality rate in women with HR+, HER2- breast cancer by race.

Methods: Women with localized, HR+, HER2- breast cancer diagnosed between 2002 and 2012 from two population-based cohorts were evaluated.

Targeting the PI3K/AKT/mTOR Pathway in Hormone-Positive Breast Cancer.

Approximately 70% of invasive breast cancers have some degree of dependence on the estrogen hormone for cell proliferation and growth. These tumors have estrogen and/or progesterone receptors (ER/PR+), generally referred to as hormone receptor positive (HR+) tumors, as indicated by the presence of positive staining and varying intensity levels of estrogen and/or progesterone receptors on immunohistochemistry. Therapies that inhibit ER signaling pathways, such as aromatase inhibitors (letrozole, anastrozole, exemestane), selective ER modulators (tamoxifen), and ER down-regulators (fulvestrant), are the mainstays of treatment for hormone-receptor-positive breast cancers.

High Xe density, high photon flux, stopped-flow spin-exchange optical pumping: Simulations versus experiments.

Spin-exchange optical pumping (SEOP) can enhance the NMR sensitivity of noble gases by up to five orders of magnitude at Tesla-strength magnetic fields. SEOP-generated hyperpolarised (HP) Xe is a promising contrast agent for lung imaging but an ongoing barrier to widespread clinical usage has been economical production of sufficient quantities with high Xe polarisation. Here, the 'standard model' of SEOP, which was previously used in the optimisation of continuous-flow Xe polarisers, is modified for validation against two Xe-rich stopped-flow SEOP datasets.

Management of toxicity to isoform α-specific PI3K inhibitors.

Alterations in the phosphoinositide 3-kinase (PI3K)/AKT pathway are frequently found in cancer and are especially common in breast cancer, where it is estimated that 70% of tumors have some type of genetic alteration that could lead to pathway hyperactivation. A variety of PI3K pathway inhibitors have been developed in an attempt to target this pathway and improve cancer control. One of the challenges in treating patients with PI3K/AKT pathway inhibitors is the associated toxicity from on-target and off-target effects.

Management of toxicity to isoform α-specific PI3K inhibitors.

Alterations in the phosphoinositide 3-kinase (PI3K)/AKT pathway are frequently found in cancer and are especially common in breast cancer, where it is estimated that 70% of tumors have some type of genetic alteration that could lead to pathway hyperactivation. A variety of PI3K pathway inhibitors have been developed in an attempt to target this pathway and improve cancer control. One of the challenges in treating patients with PI3K/AKT pathway inhibitors is the associated toxicity from on-target and off-target effects.

Effects of Deuteration of C-Enriched Phospholactate on Efficiency of Parahydrogen-Induced Polarization by Magnetic Field Cycling.

We report herein a large-scale (>10 g) synthesis of isotopically enriched 1-C-phosphoenolpyruvate and 1-C-phosphoenolpyruvate-d for application in hyperpolarized imaging technology. The 1-C-phosphoenolpyruvate-d was synthesized with 57% overall yield (over two steps), and >98% H isotopic purity, representing an improvement over the previous report. The same outcome was achieved for 1-C-phosphoenolpyruvate.

F Hyperpolarization of N-3-F-Pyridine Via Signal Amplification by Reversible Exchange.

We report synthesis of N-3-F-pyridine via Zincke salt formation with the overall 35% yield and 84% N isotopic purity. Hyperpolarization studies of Signal Amplification by Reversible Exchange (SABRE) and SABRE in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH) were performed to investigate the mechanism of polarization transfer from parahydrogen-derived hydride protons to F nucleus in milli-Tesla and micro-Tesla magnetic field regimes in N-3-F-pyridine and N-3-F-pyridine. We found the mismatch between N and F magnetic field hyperpolarization profiles in the micro-Tesla regime indicating that the spontaneous hyperpolarization process likely happens directly from parahydrogen-derived hydride protons to F nucleus without spin-relaying via N site.

Parahydrogen-Induced Polarization of 1-C-Acetates and 1-C-Pyruvates Using Sidearm Hydrogenation of Vinyl, Allyl, and Propargyl Esters.

C-hyperpolarized carboxylates, such as pyruvate and acetate, are emerging molecular contrast agents for MRI visualization of various diseases, including cancer. Here we present a systematic study of H and C parahydrogen-induced polarization of acetate and pyruvate esters with ethyl, propyl and allyl alcoholic moieties. It was found that allyl pyruvate is the most efficiently hyperpolarized compound from those under study, yielding 21% and 5.

Geospatial analyses identify regional hot spots of diffuse gastric cancer in rural Central America.

Background: Geospatial technology has facilitated the discovery of disease distributions and etiology and helped target prevention programs. Globally, gastric cancer is the leading infection-associated cancer, and third leading cause of cancer mortality worldwide, with marked geographic variation. Central and South America have a significant burden, particularly in the mountainous regions.

The Multifactorial Etiopathogeneses Interplay of Inflammatory Bowel Disease: An Overview.

The gastrointestinal system where inflammatory bowel disease occurs is central to the immune system where the innate and the adaptive/acquired immune systems are balanced in interactions with gut microbes under homeostasis conditions. This article overviews the high-throughput research screening on multifactorial interplay between genetic risk factors, the intestinal microbiota, urbanization, modernization, Westernization, the environmental influences and immune responses in the etiopathogenesis of inflammatory bowel disease in humans. Inflammatory bowel disease is an expensive multifactorial debilitating disease that affects thousands new people annually worldwide with no known etiology or cure.

A versatile synthetic route to the preparation of N heterocycles.

A robust medium-scale (approximately 3 g) synthetic method for N labeling of pyridine ( N-Py) is reported based on the Zincke reaction. N enrichment in excess of 81% was achieved with approximately 33% yield. N-Py serves as a standard substrate in a wide range of studies employing a hyperpolarization technique for efficient polarization transfer from parahydrogen to heteronuclei; this technique, called SABRE (signal amplification by reversible exchange), employs a simultaneous chemical exchange of parahydrogen and a to-be-hyperpolarized substrate (e.

Novel Agents for the Management of Endocrine Resistant Breast Cancer.

Purpose Of Review: Most women with hormone receptor (HR)-positive, HER2-negative (HR+/HER2-) breast cancer will ultimately develop endocrine-resistant disease, either primary or acquired. This review will discuss the proposed mechanisms underlying endocrine resistance and key advances in the treatment of endocrine-resistant breast cancer.

Recent Findings: Estrogen receptor 1 mutations () occur in the majority of patients with HR+/HER2- metastatic breast cancer after prolonged exposure to aromatase inhibitors.

Heterogeneous Parahydrogen Pairwise Addition to Cyclopropane.

Hyperpolarized gases revolutionize functional pulmonary imaging. Hyperpolarized propane is a promising emerging contrast agent for pulmonary MRI. Unlike hyperpolarized noble gases, proton-hyperpolarized propane gas can be imaged using conventional MRI scanners with proton imaging capability.

Molecular Imaging of Pancreatic Duct Adenocarcinoma Using a Type 2 Cannabinoid Receptor-Targeted Near-Infrared Fluorescent Probe.

Imaging probes targeting type 2 cannabinoid receptor (CBR) overexpressed in pancreatic duct adenocarcinoma (PDAC) tissue have the potential to improve early detection and surgical outcome of PDAC. The aim of our study was to evaluate the molecular imaging potential of a CBR-targeted near-infrared (NIR) fluorescent probe (NIR760-XLP6) for PDAC. CBR overexpression was observed in both PDAC patient tissues and various pancreatic cancer cell lines.

Synthesis of Unsaturated Precursors for Parahydrogen-Induced Polarization and Molecular Imaging of 1-C-Acetates and 1-C-Pyruvates via Side Arm Hydrogenation.

Hyperpolarized forms of 1-C-acetates and 1-C-pyruvates are used as diagnostic contrast agents for molecular imaging of many diseases and disorders. Here, we report the synthetic preparation of 1-C isotopically enriched and pure from solvent acetates and pyruvates derivatized with unsaturated ester moiety. The reported unsaturated precursors can be employed for NMR hyperpolarization of 1-C-acetates and 1-C-pyruvates via parahydrogen-induced polarization (PHIP).

Spin-Lattice Relaxation of Hyperpolarized Metronidazole in Signal Amplification by Reversible Exchange in Micro-Tesla Fields.

Simultaneous reversible chemical exchange of parahydrogen and to-be-hyperpolarized substrate on metal centers enables spontaneous transfer of spin order from parahydrogen singlet to nuclear spins of the substrate. When performed at sub-micro-Tesla magnetic field, this technique of NMR Signal Amplification by Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei (SABRE-SHEATH). SABRE-SHEATH has been shown to hyperpolarize nitrogen-15 sites of a wide range of biologically interesting molecules to a high polarization level ( > 20%) in one minute.

Computer-aided drug design, synthesis and identification of disulfide compounds as novel and potential allosteric PAK1 inhibitors.

p21-activated kinase 1 (PAK1) is an evolutionarily conserved serine/threonine protein kinase, which has been considered as one of the key regulatory factors in signaling network of tumor cells. Therefore, inhibition of PAK1 may be a potential approach to treat many types of solid tumors. Several allosteric inhibitors of PAK1 have been identified, and the most well known one is IPA-3.

Aqueous, Heterogeneous Parahydrogen-Induced N Polarization.

The successful transfer of parahydrogen-induced polarization to N spins using heterogeneous catalysts in aqueous solutions was demonstrated. Hydrogenation of a synthesized unsaturated N-labeled precursor (neurine) with parahydrogen (p-H) over Rh/TiO heterogeneous catalysts yielded a hyperpolarized structural analog of choline. As a result, N polarization enhancements of over two orders of magnitude were achieved for the N-ethyl trimethyl ammonium ion product in deuterated water at elevated temperatures.