Population health outcomes of blood-based screening for colorectal cancer in comparison to current screening modalities: insights from a discrete-event simulation model incorporating longitudinal adherence.

Aim: Insufficient adherence to colorectal cancer (CRC) screening impedes individual and population health benefits, with about one-third of individuals non-adherent to available screening options. The impact of poor adherence is inadequately considered in most health economics models, limiting the evaluation of real-world population-level screening outcomes. This study introduces the CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model, utilizing real-world adherence scenarios to assess the effectiveness of a blood-based test (BBT) compared to existing strategies.

A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening.

Background: Colorectal cancer is the third most diagnosed cancer in adults in the United States. Early detection could prevent more than 90% of colorectal cancer-related deaths, yet more than one third of the screening-eligible population is not up to date with screening despite multiple available tests. A blood-based test has the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality.

The Wnt Pathway Inhibitor RXC004 Blocks Tumor Growth and Reverses Immune Evasion in Wnt Ligand-dependent Cancer Models.

Unlabelled: Wnt signaling is implicated in the etiology of gastrointestinal tract cancers. Targeting Wnt signaling is challenging due to on-target toxicity concerns and lack of druggable pathway components. We describe the discovery and characterization of RXC004, a potent and selective inhibitor of the membrane-bound -acyl transferase Porcupine, essential for Wnt ligand secretion.

Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition.

Gastrointestinal cancers are responsible for more cancer deaths than any other system of the body. This review summarises how Wnt pathway dysregulation contributes to the development of the most common gastrointestinal cancers, with a particular focus on the nature and frequency of upstream pathway aberrations. Tumors with upstream aberrations maintain a dependency on the presence of functional Wnt ligand, and are predicted to be tractable to inhibitors of Porcupine, an enzyme that plays a key role in Wnt secretion.

Manganese Carbonyl Complexes as Selective Electrocatalysts for CO Reduction in Water and Organic Solvents.

The electrochemical reduction of CO provides a way to sustainably generate carbon-based fuels and feedstocks. Molecular CO reduction electrocatalysts provide tunable reaction centers offering an approach to control the selectivity of catalysis. Manganese carbonyl complexes, based on [Mn(bpy)(CO)Br] and its derivatives (bpy = 2,2'-bipyridine), are particularly interesting due to their ease of synthesis and the use of a first-row earth-abundant transition metal.

Preexposure Prophylaxis Outcomes in an Urban Community in North Carolina: Discontinuation of Care and Sexually Transmitted Infections.

Background: Few studies have examined long-term outcomes among persons who initiate preexposure prophylaxis (PrEP) in the South, including PrEP discontinuation and sexually transmitted infection (STI) rates.

Methods: Care discontinuation (>6 months without a PrEP appointment) and incident STIs were evaluated for patients at 2 PrEP clinics in Durham, NC. We tested for predictors of discontinuation as a binary variable using logistic regression.

Advancing the HIV Pre-Exposure Prophylaxis Continuum: A Collaboration Between a Public Health Department and a Federally Qualified Health Center in the Southern United States.

Uptake of pre-exposure prophylaxis (PrEP) has been limited among black and Latino men who have sex with men (MSM), especially in the southern United States. Public health departments and federally qualified health centers (FQHCs) serving predominantly uninsured populations are uniquely positioned to improve access. We evaluated a novel PrEP collaboration between a public health department and an FQHC in North Carolina (NC).

Assessing Patient Opinions About Electronic Messaging for Gonorrhea and Chlamydia Result Notification and Partner Services, Durham, North Carolina.

Text or e-mail messages can provide timely notification of sexually transmitted disease results to patients. We assessed sexually transmitted disease clinic patient opinions about text/e-mail notification via a service called Chexout. Among 113 patients who opted in, the majority found results notification via texts/e-mails to be satisfactory (99.

Evolution of asexual and sexual reproduction in the aspergilli.

has long-been used as a model organism to gain insights into the genetic basis of asexual and sexual developmental processes both in other members of the genus , and filamentous fungi in general. Paradigms have been established concerning the regulatory mechanisms of conidial development. However, recent studies have shown considerable genome divergence in the fungal kingdom, questioning the general applicability of findings from , and certain longstanding evolutionary theories have been questioned.

The novel Aspergillus fumigatus MAT1-2-4 mating-type gene is required for mating and cleistothecia formation.

Sexual propagation accompanied by recombination and the formation of spore-containing fruiting bodies is a cornerstone of fungal genetics and biology. In the human pathogen Aspergillus fumigatus sexual identity has previously been shown to be determined by MAT1-1-1 or MAT1-2-1 genes which act as transcriptional regulators and are present within idiomorphs found at the MAT locus. We here report the identification and first characterization of a further novel gene, termed MAT1-2-4, that is present in the MAT1-2 idiomorph of A.

Brain Delivery of Drug and MRI Contrast Agent: Detection and Quantitative Determination of Brain Deposition of CPT-Glu Using LC-MS/MS and Gd-DTPA Using Magnetic Resonance Imaging.

Successful treatment and diagnosis of neurological diseases depend on reliable delivery of molecules across the blood-brain barrier (BBB), which restricts penetration of pharmaceutical drugs and diagnostic agents into the brain. Thus, developing new noninvasive strategies to improve drug delivery across the BBB is critically needed. This study was aimed at evaluating the activity of HAV6 peptide (Ac-SHAVSS-NH2) in improving brain delivery of camptothecin-glutamate (CPT-Glu) conjugate and gadolinium-diethylenetriaminepentaacetate (Gd-DTPA) contrast agent in Sprague-Dawley rats.

Physicians at the executive table.

This article explores factors that influence decision-making by physician leaders, particularly at the executive level. Most physician leaders maintain their clinical practices and some may also have active academic careers, resulting in multiple accountabilities. Managing these accountabilities requires expenditure of time and energy.

BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling.

Objective: Colorectal cancer remains the fourth most common cause of cancer-related mortality worldwide. Here we investigate the role of nuclear factor-κB (NF-κB) co-factor B-cell CLL/lymphoma 3 (BCL-3) in promoting colorectal tumour cell survival.

Design: Immunohistochemistry was carried out on 47 tumour samples and normal tissue from resection margins.

Crystal structure of tetra-kis-(μ-N-phenyl-acetamidato)-κ(4) N:O;κ(4) O:N-bis-[(2-methyl-benzo-nitrile-κN)rhodium(II)](Rh-Rh).

The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(C8H7N)2], exhibits inversion symmetry. The four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner with two N atoms and two O atoms coordinating to each Rh(II) atom trans to one another. The Neq-Rh-Rh-Oeq torsion angles on the acetamidate bridge vary between -4.

(3-Methyl-benzo-nitrile-1κN)-cis-tetra-kis(μ-N-phenyl-acetamidato)-1:2κ(4) N:O;1:2κ(4) O:N-dirhodium(II)(Rh-Rh).

The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(NCC7H7)], has crystallographically-imposed mirror symmetry. The four acetamide ligands bridging the dirhodium core are arranged in a 2,2-cis manner with two N atoms and two O atoms coordinating to the unique Rh(II) atom cis to one another. The Neq-Rh-Rh-Oeq torsion angles on the acetamide bridge are 0.

(3-Methyl-benzo-nitrile-κN)tetra-kis(μ-N-phenyl-acetamidato)-κ(4) N:O;κ(4) O:N-di-rhodium(II)(Rh-Rh).

In the title compound, [Rh2(C8H8NO)4(C8H7N)], the four acetamidate ligands bridging the dirhodium core are arranged in a 2,2-trans manner. One Rh(II) atom is five-coordinate, in a distorted pyramidal geometry, while the other is six-coord-in-ate, with a disorted octa-hedral geometry. For the six-coord-inate Rh(II) atom, the axial nitrile ligand shows a non-linear Rh-nitrile coordination with an Rh-N-C bond angle of 166.

cis-Tetra-kis(μ-N-phenyl-acetamidato)-κ(4) N:O;κ(4) O:N-bis-[(benzo-nitrile-κN)rhodium(II)](Rh-Rh).

The complex molecule of the title compound, [Rh2{N(C6H5)COCH3}4(C6H5CN)2], exhibits crystallographically imposed centrosymmetry. The four acetamide ligands bridging the dirhodium core are arranged in a 2,2-cis manner, with two N atoms and two O atoms coordinating to the unique Rh(II) atom cis to one another. The Neq-Rh-Rh-Oeq torsion angles on the acetamide bridges vary between 1.

Tetra-kis[μ-N-(2,4,6-trimethyl-phen-yl)acetamidato]-κ⁴N:O;κ⁴O:N-bis-[(benzo-nitrile-κN)rhodium(II)](Rh-Rh).

The title structure, [Rh₂(C₁₁H₁₄NO)₄(C₇H₅N)₂], contains a dinuclear Rh complex of point symmetry -4 with an Rh-Rh unit and two benzonitrile ligands located in special positions along the twofold axis passing through -4. Four symmetry-equivalent mesitylacetamidate ligands bridge the Rh-Rh unit. Thus, each Rh(II) atom has an approximately octa-hedral coordination by one Rh [Rh-Rh = 2.

The APC and PreSAP trials: a post hoc noninferiority analysis using a comprehensive new measure for gastrointestinal tract injury in 2 randomized, double-blind studies comparing celecoxib and placebo.

Background: Previous gastrointestinal (GI) outcomes of nonsteroidal anti-inflammatory drug (NSAID) trials have focused on upper GI events, although recent evidence suggests NSAID-related lower GI effects are important and clinically relevant.

Objective: We assessed the long-term GI adverse event (AE) profile of celecoxib in a nonarthritis population. The aim of this post hoc analysis was to determine the incidence of serious GI AEs, using a new Clinically Significant Upper and/or Lower GI Events end point.

Speciation despite globally overlapping distributions in Penicillium chrysogenum: the population genetics of Alexander Fleming's lucky fungus.

Eighty years ago, Alexander Fleming described the antibiotic effects of a fungus that had contaminated his bacterial culture, kick starting the antimicrobial revolution. The fungus was later ascribed to a putatively globally distributed asexual species, Penicillium chrysogenum. Recently, the species has been shown to be genetically diverse, and possess mating-type genes.

A randomized controlled trial of celecoxib to prevent recurrence of nonmuscle-invasive bladder cancer.

Significant morbidity and expense result from frequent recurrences of nonmuscle-invasive bladder cancer (NMIBC) after standard treatment, and carcinoma in situ (Tis) is a poor prognostic factor. Predicated on observational and preclinical data strongly supporting cyclooxygenase-2 (COX-2) in the pathogenesis, and the activity of COX-2 inhibitors, in bladder cancer, we conducted a randomized, double-blind, placebo-controlled trial to determine whether celecoxib could reduce the time-to-recurrence (TTR) in NMIBC patients at high risk for recurrence. A total of 146 patients were randomized to celecoxib (200 mg) or placebo orally twice daily for at least 12 months.

Five-year analysis of the prevention of colorectal sporadic adenomatous polyps trial.

Objectives: Subjects in the Prevention of Colorectal Sporadic Adenomatous Polyps (PreSAP) trial (PRESAP/NCT00141193/www.clinicaltrials.gov) were studied to determine efficacy and safety at a year 5 assessment.