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QuickProt: A Bioinformatics and Visualization Tool for DIA and PRM Mass Spectrometry-Based Proteomics Datasets.
No full textMass spectrometry (MS)-based proteomics focuses on identifying and quantifying peptides and proteins in biological samples. Processing of MS-derived raw data, including deconvolution, alignment, and peptide-protein prediction, has been achieved through various software platforms. However, the downstream analysis, including quality control, visualizations, and interpretation of proteomics results, remains cumbersome due to the lack of integrated tools to facilitate the analyses. To address this challenge, we developed QuickProt, a series of Python-based Google Colab notebooks for analyzing data-independent acquisition (DIA) and parallel reaction monitoring (PRM) proteomics datasets. These pipelines are designed so that users with no coding expertise can utilize the tool. Furthermore, as open-source code, QuickProt notebooks can be customized and incorporated into existing workflows. As proof of concept, we applied QuickProt to analyze in-house DIA and stable isotope dilution (SID)-PRM MS proteomics datasets from a time-course study of human erythropoiesis. The analysis resulted in annotated tables and publication-ready figures revealing a dynamic rearrangement of the proteome during erythroid differentiation, with the abundance of proteins linked to gene regulation, metabolic, and chromatin remodeling pathways increasing early in erythropoiesis. Altogether, these tools aim to automate and streamline DIA and PRM-MS proteomics data analysis, making it more efficient and less time-consuming
Translating evidence to action to improve care and outcomes in type 2 diabetes and chronic kidney disease.
No full textNurturing Change and Leading With Strategy.
No full textIn today\u27s health care landscape-marked by rapid advancement of medical technology, application of artificial intelligence, strains on workforce supply and demand, and significant changes in organizational structure-nursing professional development specialists find themselves at a pivotal intersection. They carry the responsibility of nurturing individual nursing competence and organizational resilience. To that end, they must meet formidable leadership challenges
Fetal malformations in women with pregestational diabetes mellitus based on pre-pregnancy fasting plasma glucose levels.
No full textTo evaluate the risk of fetal malformation in pregnant women with pregestational diabetes mellitus based on pre-pregnancy fasting plasma glucose (FPG) levels. This cohort study used the Korean Health Insurance Review and Assessment (HIRA) database, including 5,687 women with pre-pregnancy diabetes and FPG measurements within one year before conception. Subjects were grouped into three glycemic level categories: low (FPG \u3c 100 mg/dL [\u3c 5.5 mmol/L]), moderate (FPG: 100-125 mg/dL [5.6-6.9 mmol/L]), and high (FPG ≥ 126 mg/dL [≥ 7.0 mmol/L]). The low glycemic group was divided into four subgroups based on FPG levels. The relative risks of fetal malformations were calculated using multivariable analysis compared to a reference group (FPG \u3c 84 mg/dL [\u3c 4.7 mmol/L]). Fetal malformation rates were 10% in the low, 13.6% in the moderate, and 18.6% in the high glycemic groups (P \u3c 0.001). Teratogenic risks were 1.3 times higher in the moderate glycemic group and 1.8 times higher in the high glycemic group compared to the reference group. The high glycemic group had 2.5 times greater risk of cardiac malformations and 3.3 times greater risk of skeletal malformations. Preconceptional FPG levels ≥ 100 mg/dL [≥ 5.5 mmol/L] in women with pregestational diabetes elevate the risk of fetal malformations, especially cardiac and skeletal malformations at FPG levels ≥ 126 mg/dL [≥ 7.0 mmol/L]
Efficacy of Acoramidis in Wild-Type and Variant Transthyretin Amyloid Cardiomyopathy: Results From ATTRibute-CM and Its Open-Label Extension.
No full textIMPORTANCE: Transthyretin amyloid cardiomyopathy (ATTR-CM), a progressive disease caused by misfolded transthyretin (TTR), occurs as wild-type (ATTRwt-CM) or variant (ATTRv-CM) forms. p.Val142Ile is the most common variant in the US, linked to rapid progression and increased mortality. Acoramidis achieves near-complete (≥90%) TTR stabilization and showed clinical benefit in the 30-month ATTRibute-CM trial and through month 42 in the ongoing open-label extension (OLE).
OBJECTIVE: To evaluate the efficacy of acoramidis in ATTRwt-CM, ATTRv-CM, and variant subgroups (p.Val142Ile and non-p.Val142Ile).
DESIGN, SETTING, AND PARTICIPANTS: This international, multicenter, phase 3, randomized placebo-controlled study took place from April 2019 to May 2023 with ongoing OLE (month 42). ATTRibute-CM enrolled 632 participants with ATTR-CM; 611 of 632 were included in the modified intention-to-treat (mITT) population. There were 380 participants who continued into the OLE. These data were analyzed from January 2025 to July 2025.
INTERVENTIONS: Oral acoramidis, 712 mg, or placebo twice daily for 30 months, followed by 12 months of open-label treatment.
MAIN OUTCOMES AND MEASURES: All-cause mortality (ACM), cardiovascular-related hospitalizations (CVH), serum TTR, 6-minute walk distance, Kansas City Cardiomyopathy Questionnaire Overall Summary score, and N-terminal pro B-type natriuretic peptide in participants with ATTRwt-CM and ATTRv-CM. Post-hoc analyses were conducted in variant subgroups, including p.Val142Ile.
RESULTS: Overall, 552 participants with wild-type ATTR-CM (mean [SD] age, 78 [6.3] years; 92.0% male and 8.0% female) and 59 participants with variant ATTR-CM (mean [SD] age, 73 [7.7] years; 77.3% male and 22.7% female) were randomized (mITT population), including 35 with p.Val142Ile. Consistent efficacy was observed in wild-type and variant subgroups for ACM/CVH through month 30 and ACM through month 42. At month 30, acoramidis reduced the risk of ACM/first CVH vs placebo by 31% in ATTRwt-CM (hazard ratio [HR], 0.69; 95% CI, 0.52-0.90; P = .007) and by 59% in ATTRv-CM (HR, 0.41; 95% CI, 0.21-0.81; P = .01). ACM was reduced through month 42 with HRs of 0.70 (95% CI, 0.50-0.98; P = .04) and 0.41 (95% CI, 0.19-0.93; P = .03) in the ATTRwt-CM and ATTRv-CM groups, respectively. Consistent treatment benefit was observed in participants with ATTRwt-CM and ATTRv-CM for secondary end points. Within variant subgroups (p.Val142Ile vs non-p.Val142Ile), consistent treatment benefits were observed for ACM/CVH through month 30 and ACM through month 42.
CONCLUSIONS AND RELEVANCE: The beneficial effect of acoramidis was observed consistently in ATTRwt-CM and ATTRv-CM groups. These hypothesis-generating results indicate that further studies are warranted to better characterize the therapeutic benefit of acoramidis in variant subgroups.
TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03860935; NCT04988386
Amivantamab-Chemotherapy in Non-Small Cell Lung Cancer with EGFR Exon 20 Insertions: Impact of Treatment Crossover and Other Endpoints from the Phase III PAPILLON Study.
No full textBACKGROUND: In the PAPILLON study, first-line amivantamab-chemotherapy in epidermal growth factor receptor (EGFR) exon 20 insertion-mutated non-small cell lung cancer demonstrated significantly prolonged progression-free survival and favorable overall survival over chemotherapy; a consistent benefit was also observed across some secondary endpoints. However, the complete clinical benefit of first-line amivantamab-chemotherapy is not fully understood, nor is the survival advantage in the presence of per-protocol crossover from chemotherapy to amivantamab after progression.
OBJECTIVE: We aimed to assess time to treatment discontinuation (TTD) and time to subsequent therapy (TTST), at the time of primary analysis for progression-free survival, and the effect of the crossover design on overall survival at the time of interim analysis.
METHODS: In the phase III PAPILLON study, 308 participants were randomized (amivantamab-chemotherapy, n = 153; chemotherapy, n = 155). Intravenous amivantamab was administered every 3 weeks. Chemotherapy was administered as carboplatin for four cycles and pemetrexed until disease progression. TTD and TTST were evaluated using Kaplan-Meier and Cox proportional hazards models. Crossover-adjusted survival estimates were generated using three established statistical methods.
RESULTS: At a median follow-up of 14.9 months, median TTD was 13.2 versus 7.5 months for amivantamab-chemotherapy versus chemotherapy (hazard ratio [HR] 0.38 [95% confidence interval 0.28-0.51]; nominal p \u3c 0.0001). Median TTST was 17.7 versus 9.9 months (HR 0.35 [95% confidence interval 0.25-0.49]; nominal p \u3c 0.0001). A total of 65/155 participants crossed over from chemotherapy to amivantamab after progression. The crossover-adjusted overall survival continued to demonstrate a favorable survival benefit for amivantamab-chemotherapy versus chemotherapy with HRs of 0.52-0.60, which is more pronounced than the planned interim intention-to-treat overall survival (HR of 0.67; 95% confidence interval 0.42-1.09).
CONCLUSIONS: In PAPILLON, TTD and TTST were substantially longer for amivantamab-chemotherapy versus chemotherapy at primary analysis (cut-off on 3 May 2023). Crossover-adjusted analyses of the planned interim overall survival demonstrated a greater benefit for amivantamab-chemotherapy versus chemotherapy, further supporting amivantamab-chemotherapy as the first-line standard of care in EGFR exon 20 insertion-mutated non-small cell lung cancer.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04538664
Implementation of an Alzheimer\u27s Disease Blood Test: Adoption Experience by Memory Care Specialists in a Multi-Center Study.
No full textBackground/Objectives: A high-performing blood biomarker (BBM) test for Alzheimer\u27s disease (AD) represents an accurate, accessible, and scalable tool to aid healthcare professionals (HCPs) evaluating patients presenting with signs or symptoms of mild cognitive impairment (MCI) or dementia. However, implementation of AD blood tests into clinical practice has not been extensively evaluated. The objective of this study was to assess the implementation of the multi-analyte PrecivityAD2™ blood test (C2N Diagnostics, LLC, St. Louis, MO, USA) into the clinical workflow of memory care clinics. Methods: A total of 8 HCPs (neurologists, geriatricians, geriatric psychiatrists) who served as site directors from 8 outpatient sites that evaluated 203 cognitively symptomatic patients were included in this sub-study of the real-world QUIP II Study (NCT06025877). Implementation of this blood test was assessed through surveying these HCPs using published frameworks including the Technology Acceptance Model, net promoter score, and forced choice preference questions. These assessments were analyzed using Wilcoxon signed-rank test, Fisher\u27s Exact test, and Wilcoxon signed-rank test, respectively. Results: HCPs reported acceptance scores that averaged 9.6 out of 10 (p \u3c 0.0001, effect size 0.840): the test\u27s contribution to clinical decision-making as well as the ease of understanding test results received the highest ratings. The net promoter score was 75 (p \u3c 0.0001), exceeding the typical benchmark of 30 reported as good levels of satisfaction in healthcare settings. The APS2 results and individual blood analyte results were rated with similar preference around their roles in HCP clinical decision-making. Conclusions: The results indicate early evidence of user acceptance and recognition by HCPs that this AD blood test can personalize the clinical care pathway for evaluating cognitively symptomatic patients
Effectiveness of Tofacitinib in Patients with Psoriatic Arthritis Initiating Monotherapy Versus Combination Therapy: Results from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.
No full textINTRODUCTION: This study evaluated the real-world effectiveness of tofacitinib monotherapy versus combination therapy in patients with psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry.
METHODS: This study (NCT05195814) included adult patients with PsA initiating tofacitinib (from December 14, 2017 to October 1, 2023) as monotherapy, or in combination with oral small molecules (OSMs: methotrexate, leflunomide, sulfasalazine, hydroxychloroquine, and apremilast). Patients with baseline and 6-month follow-up visits (± 3 months) were included.
OUTCOMES: mean change from baseline (∆) in/proportions achieving, disease activity measures (including body surface area [BSA] = 0%), and patient-reported outcomes. Continuous endpoints at month 6 were analyzed as ∆ with an analysis of covariance model including treatment and baseline value as covariates. ∆ in least squares (LS) means and adjusted LS means/odds ratios are presented.
RESULTS: The study included 141 patients (66/141 monotherapy; 75/141 combination therapy). Patients were predominantly female (61.0%) and white (94.3%), and average age was 56.7 years. More monotherapy initiators were OSM treatment-naïve and had higher mean Patient Global Assessment of Arthritis, compared with combination therapy initiators. By 6 ± 3 months, 28.8% and 25.3% of monotherapy and combination therapy initiators, respectively, discontinued tofacitinib. At 6 ± 3 months, 15.0% of monotherapy initiators achieved minimal disease activity, and 27.1% had BSA = 0%. Corresponding data for combination therapy initiators were 20.7%, and 22.0%, respectively. Differences between groups were not significant. LS mean differences from baseline in overall work impairment/activity impairment were - 13.0/- 21.8 and 1.4/- 2.9 for monotherapy and combination therapy initiators, respectively.
CONCLUSION: Monotherapy and combination therapy initiators demonstrated improvements across effectiveness outcomes. Tofacitinib monotherapy initiators experienced numerical improvements in overall work impairment/activity impairment. This highlights tofacitinib effectiveness as monotherapy/combination therapy for a diverse PsA population. However, the small sample size limited the statistical power, and so results should be interpreted cautiously.
TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT05195814
