Advancements in Understanding and Preventing Obesity-Related Colon Cancer.

Obesity and colorectal cancer are global public health issues, with the prevalence of both conditions increasing over the last 4 decades. In the United States alone, the prevalence of obesity is greater than 40%, and this percentage is projected to increase past 50% by 2030. This review focuses on understanding the association between obesity and the risk of colorectal cancer while also highlighting hypotheses about molecular mechanisms underlying the link between these disease processes.

A Precision Mixture Risk Model to Identify Adverse Drug Events in Subpopulations Using a Case-Crossover Design.

Despite the success of pharmacovigilance studies in detecting signals of adverse drug events (ADEs) from real-world data, the risks of ADEs in subpopulations warrant increased scrutiny to prevent them in vulnerable individuals. Recently, the case-crossover design has been implemented to leverage large-scale administrative claims data for ADE detection, while controlling both observed confounding effects and short-term fixed unobserved confounding effects. Additionally, as the case-crossover design only includes cases, subpopulations can be conveniently derived.

Electrochemical Bioconjugation of Tryptophan Residues: A Strategy for Peptide Modification.

Interest in electrocatalytic bioconjugation reactions has surged, particularly for modifying tryptophan and tyrosine residues in proteins. We used a cost-effective graphite felt electrode and low-current methodology to achieve selective bioconjugation of tryptophan with thiophenols, yielding up to 92%. This method exclusively labeled tryptophan residues and incorporated fluorinated tryptophan for NMR analysis.

Sildenafil as a Candidate Drug for Alzheimer's Disease: Real-World Patient Data Observation and Mechanistic Observations from Patient-Induced Pluripotent Stem Cell-Derived Neurons.

Background: Alzheimer's disease (AD) is a chronic neurodegenerative disease needing effective therapeutics urgently. Sildenafil, one of the approved phosphodiesterase-5 inhibitors, has been implicated as having potential effect in AD.

Objective: To investigate the potential therapeutic benefit of sildenafil on AD.

Prevalence and trend of central nervous system-active medication polypharmacy among US commercially insured adults with vs without early-onset dementia: a multi-year cross-sectional study.

Background: Limited data exist on the prevalence and trend of central nervous system (CNS)-active medication polypharmacy among adults with early-onset dementia (EOD) and whether these estimates differ for adults without EOD but with chronic pain, depression, or epilepsy, conditions managed by CNS-active medications.

Methods: A multi-year, cross-sectional study using 2012-2021 MarketScan Commercial Claims data was conducted among adults aged 30 to 64 years with EOD and those without EOD but having a diagnosis of chronic pain, depression, or epilepsy as comparison groups. For each disease cohort, the primary outcome was CNS-active medication polypharmacy defined as concurrent use of ≥ 3 CNS-active medications on the US Beers Criteria list that overlapped for > 30 consecutive days during 12 months following a randomly selected medical encounter with the disease diagnosis.

Modeling Path Importance for Effective Alzheimer's Disease Drug Repurposing.

Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs.

Comparing super-utilizers and lower-utilizers among commercial- and Medicare-insured adults with sickle cell disease.

Sickle cell disease (SCD) is a rare but costly condition in the United States. Super-utilizers have been defined as a subset of the population with high health care encounters or expenditures. Although super-utilizers have been described in other disease states, little is known about super-utilizers among adults with SCD.

Modeling Path Importance for Effective Alzheimer's Disease Drug Repurposing.

Recently, drug repurposing has emerged as an effective and resource-efficient paradigm for AD drug discovery. Among various methods for drug repurposing, network-based methods have shown promising results as they are capable of leveraging complex networks that integrate multiple interaction types, such as protein-protein interactions, to more effectively identify candidate drugs. However, existing approaches typically assume paths of the same length in the network have equal importance in identifying the therapeutic effect of drugs.

Generalizability of machine learning methods in detecting adverse drug events from clinical narratives in electronic medical records.

We assessed the generalizability of machine learning methods using natural language processing (NLP) techniques to detect adverse drug events (ADEs) from clinical narratives in electronic medical records (EMRs). We constructed a new corpus correlating drugs with adverse drug events using 1,394 clinical notes of 47 randomly selected patients who received immune checkpoint inhibitors (ICIs) from 2011 to 2018 at The Ohio State University James Cancer Hospital, annotating 189 drug-ADE relations in single sentences within the medical records. We also used data from Harvard's publicly available 2018 National Clinical Challenge (n2c2), which includes 505 discharge summaries with annotations of 1,355 single-sentence drug-ADE relations.

Promotion of -nitrosation of cysteine by a {Co(NO)} complex.

-Nitrosothiols (SNOs) serve as endogenous carriers and donors of NO within living cells, releasing nitrosonium ions (NO), NO, or other nitroso derivatives. In this study, we present a bioinspired {Co(NO)} complex 1 that achieved -nitrosation towards Cys residues. The incorporation of a ferrocenyl group in 1 allowed for fine-tuning of the nitrosation reaction, taking advantage of the redox ability of Cys residues.

Versatile Synthesis of Symmetric and Unsymmetric Imines via Photoelectrochemical Catalysis: Application to N-Terminal Modification of Phenylalanine.

A strategy that combines electrochemical synthesis and photoredox catalysis was reported for the efficient synthesis of imines. This approach was demonstrated to be highly versatile in producing various types of imines, including symmetric and unsymmetric imines, by exploring the impact of different substituents on the benzene ring of the arylamine. Additionally, the method was specifically applied to modify N-terminal phenylalanine residues and was found to be successful in the photoelectrochemical cross-coupling reaction between NH -Phe-OMe and aryl methylamines, leading to the synthesis of phenylalanine-containing imines.

The impact of surgical weight loss procedures on the risk of metachronous colorectal neoplasia: the differential effect of surgery type, sex, and anatomic location.

Patients with prior colorectal polyps are at high risk for metachronous colorectal neoplasia, especially in the presence of obesity. We assessed the impact of 2 common bariatric surgeries, vertical sleeve gastrectomy and roux-n-Y gastric bypass, on the risk of colorectal neoplasia recurrence. This nationally representative analysis included 1183 postbariatric adults and 3193 propensity score-matched controls, who all had prior colonoscopy with polyps and polypectomy.

Photoredox C-H functionalization leads the site-selective phenylalanine bioconjugation.

Site-selectively chemical bioconjugation of peptides and proteins can improve the therapeutic exploration of modified protein drugs. Only 3.8% natural abundance of phenylalanine in protein and nearly 90% of proteins contain at least one phenylalanine residue in their sequenced, showing the potential in biopharmaceutical utility of the phenylalanine bioconjugation.

Incidence and Risk Factors for New-Onset Diabetes Mellitus After Surgical Resection of Pancreatic Cystic Lesions: A MarketScan Study.

Objectives: There is a paucity of literature evaluating new-onset diabetes mellitus (NODM) after resection of pancreatic cystic lesions (PCLs). We sought to characterize the incidence and risk factors associated with NODM after partial pancreatectomy for PCLs.

Methods: We utilized the IBM MarketScan Database (2012-2018) to identify all nondiabetic adults who underwent partial pancreatectomy for PCLs.

PhenoDEF: a corpus for annotating sentences with information of phenotype definitions in biomedical literature.

Background: Adverse events induced by drug-drug interactions are a major concern in the United States. Current research is moving toward using electronic health record (EHR) data, including for adverse drug events discovery. One of the first steps in EHR-based studies is to define a phenotype for establishing a cohort of patients.

Endophenotype-based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease.

We developed an endophenotype disease module-based methodology for Alzheimer's disease (AD) drug repurposing and identified sildenafil as a potential disease risk modifier. Based on retrospective case-control pharmacoepidemiologic analyses of insurance claims data for 7.23 million individuals, we found that sildenafil usage was significantly associated with a 69% reduced risk of AD (hazard ratio = 0.

A comprehensive assessment of statin discontinuation among patients who concurrently initiate statins and CYP3A4-inhibitor drugs; a multistate transition model.

Aims: The aim of this study was to describe the 1-year direct and indirect transition probabilities to premature discontinuation of statin therapy after concurrently initiating statins and CYP3A4-inhibitor drugs.

Methods: A retrospective new-user cohort study design was used to identify (N = 160 828) patients who concurrently initiated CYP3A4 inhibitors (diltiazem, ketoconazole, clarithromycin, others) and CYP3A4-metabolized statins (statin DDI exposed, n = 104 774) vs. other statins (unexposed to statin DDI, n = 56 054) from the MarketScan commercial claims database (2012-2017).

Artificial intelligence framework identifies candidate targets for drug repurposing in Alzheimer's disease.

Background: Genome-wide association studies (GWAS) have identified numerous susceptibility loci for Alzheimer's disease (AD). However, utilizing GWAS and multi-omics data to identify high-confidence AD risk genes (ARGs) and druggable targets that can guide development of new therapeutics for patients suffering from AD has heretofore not been successful.

Methods: To address this critical problem in the field, we have developed a network-based artificial intelligence framework that is capable of integrating multi-omics data along with human protein-protein interactome networks to accurately infer accurate drug targets impacted by GWAS-identified variants to identify new therapeutics.