Commelinid monocotyledons are a monophyletic clade differentiated from other monocotyledons by the presence of cell wall-bound ferulate and p-coumarate. The Poaceae, or grass family, is a member of ...this group, and most of the p-coumarate in the cell walls of this family acylates lignin. Here, we isolated and examined lignified cell wall preparations from 10 species of commelinid monocotyledons from nine families other than Poaceae, including species from all four commelinid monocotyledon orders (Poales, Zingiberales, Commelinales, and Arecales). We showed that, as in the Poaceae, lignin-linked p-coumarate occurs exclusively on the hydroxyl group on the 𝛾-carbon of lignin unit side chains, mostly on syringyl units. Although the mechanism of acylation has not been studied directly in these species, it is likely to be similar to that in the Poaceae and involve BAHD acyl-coenzyme A:monolignol transferases.
The cell walls of leaf base tissues of the Canary Island date palm (Phoenix canariensis) contain lignins with the most complex compositions described to date. The lignin composition varies by tissue ...region and is derived from traditional monolignols (ML) along with an unprecedented range of ML conjugates: ML-acetate, ML-benzoate, ML-p-hydroxybenzoate, ML-vanillate, ML-p-coumarate, and ML-ferulate. The specific functions of such complex lignin compositions are unknown. However, the distribution of the ML conjugates varies depending on the tissue region, indicating that they may play specific roles in the cell walls of these tissues and/or in the plant's defense system.
Angiosperms represent most of the terrestrial plants and are the primary research focus for the conversion of biomass to liquid fuels and coproducts. Lignin limits our access to fibers and represents ...a large fraction of the chemical energy stored in plant cell walls. Recently, the incorporation of monolignol ferulates into lignin polymers was accomplished via the engineering of an exotic transferase into commercially relevant poplar. We report that various angiosperm species might have convergently evolved to natively produce lignins that incorporate monolignol ferulate conjugates. We show that this activity may be accomplished by a BAHD feruloyl-coenzyme A monolignol transferase,
FMT1 (AT5), in rice and its orthologs in other monocots.
What is already known about this topic? Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition typically occurring 2–6 weeks after SARS-CoV-2 infection and ...characterized by fever and multiorgan involvement. What is added by this report? MIS-C incidence has decreased from early in the COVID-19 pandemic (highest in late 2020–early 2021), but cases continue to occur with a recent relative increase in the fall of 2023 after a period of increased COVID-19 activity in the general population. Among 117 patients with MIS-C in 2023, approximately one half required intensive care unit–level care. More than 80% (92 of 112) of MIS-C cases were in vaccine-eligible but unvaccinated children, and among the 20 vaccinated children, 60% likely had waned immunity at the time of MIS-C illness. What are the implications for public health practice? MIS-C cases continue to occur but at low rates, making ongoing surveillance valuable. COVID-19 vaccination remains important for preventing MIS-C.
Abstract
Background
Human immunodeficiency virus (HIV) viral suppression (VS) decreases morbidity, mortality, and transmission risk.
Methods
The Patient-centered HIV Care Model integrated ...community-based pharmacists with HIV medical providers and required them to share patient clinical information, identify therapy-related problems, and develop therapy-related action plans.
Proportions adherent to antiretroviral therapy (proportion of days covered PDC ≥90%) and virally suppressed (HIV RNA <200 copies/mL), before and after model implementation, were compared. Factors associated with postimplementation VS were determined using multivariable logistic regression; participant demographics, baseline viral load, and PDC were explanatory variables. PDC was modified to account for time to last viral load in the year postimplementation, and stratified as <50%, 50% to <80%, 80% to <90%, and ≥90%.
Results
The 765 enrolled participants were 43% non-Hispanic black, 73% male, with a median age of 48 years; 421 and 649 were included in the adherence and VS analyses, respectively. Overall, proportions adherent to therapy remained unchanged. However, VS improved a relative 15% (75% to 86%, P < .001). Higher PDC (adjusted odds ratio AOR, 1.74 per 1-level increase in PDC category 95% confidence interval {CI}, 1.30–2.34) and baseline VS (AOR, 7.69 95% CI, 3.96–15.7) were associated with postimplementation VS. Although non-Hispanic black persons (AOR, 0.29 95% CI, .12–.62) had lower odds of suppression, VS improved a relative 23% (63% to 78%, P < .001).
Conclusions
Integrated care models between community-based pharmacists and primary medical providers may identify and address HIV therapy–related problems and improve VS among persons with HIV.
Although adherence to antiretroviral therapy remained unchanged, before and after Patient-centered Human Immunodeficiency Virus (HIV) Care Model implementation, viral suppression improved 15%. In addition, there was a notable improvement (23% increase) in viral suppression among non-Hispanic black persons.
Poor retention in HIV care is associated with higher morbidity and mortality and greater risk of HIV transmission. The Patient-Centered HIV Care Model (PCHCM) integrated community-based pharmacists ...with medical providers. The model required sharing of patient clinical information and collaborative therapy-related action planning. The proportion of persons retained in care (≥1 medical visit in each 6-month period of a 12-month measurement period with ≥60 days between visits), pre- and post-PCHCM implementation, was modeled using log binomial regression. Factors associated with post-implementation retention were determined using multi-variable regression. Of 765 enrolled persons, the plurality were male (n = 555) and non-Hispanic black (n = 331), with a median age of 48 years (interquartile range = 38-55); 680 and 625 persons were included in the pre- and post-implementation analyses, respectively. Overall, retention improved 12.9% (60.7-68.5%, p = 0.002). The largest improvement was seen among non-Hispanic black persons, 22.6% increase (59.7-73.2%, p < 0.001). Persons who were non-Hispanic black adjusted risk ratio (ARR) 1.27, 95% confidence interval (CI) 1.08-1.48 received one or more pharmacist-clinic developed action plan (ARR 1.51, 95% CI 1.18-1.93), had three or more pharmacist encounters (ARR 1.17, 95% CI 1.05-1.30), were more likely to be retained post-implementation. In the final multi-variable models, only race/ethnicity non-Hispanic black (ARR 1.27, 95% CI 1.09-1.48) and "other or unknown" race/ethnicity (ARR 1.36, 95% CI 1.14-1.63) showed an association with post-implementation retention. PCHCM demonstrated how collaborations between community-based pharmacists and primary medical providers can improve retention in HIV care. This care model may be particularly useful for non-Hispanic black persons who often are less likely to be retained in care.
A critical gap in the adoption of genomic medicine into medical practice is the need for the rigorous evaluation of the utility of genomic medicine interventions.
The Implementing Genomics in ...Practice Pragmatic Trials Network (IGNITE PTN) was formed in 2018 to measure the clinical utility and cost-effectiveness of genomic medicine interventions, to assess approaches for real-world application of genomic medicine in diverse clinical settings, and to produce generalizable knowledge on clinical trials using genomic interventions. Five clinical sites and a coordinating center evaluated trial proposals and developed working groups to enable their implementation.
Two pragmatic clinical trials (PCTs) have been initiated, one evaluating genetic risk APOL1 variants in African Americans in the management of their hypertension, and the other to evaluate the use of pharmacogenetic testing for medications to manage acute and chronic pain as well as depression.
IGNITE PTN is a network that carries out PCTs in genomic medicine; it is focused on diversity and inclusion of underrepresented minority trial participants; it uses electronic health records and clinical decision support to deliver the interventions. IGNITE PTN will develop the evidence to support (or oppose) the adoption of genomic medicine interventions by patients, providers, and payers.
Aims
A recent study examining the specificity of human epidermal growth factor receptor (HER) 2 pharmacodiagnostic antibodies demonstrated that CB11 and 4B5 stain both HER2‐transfected and ...HER4‐transfected cell lines. However, there has been no evidence showing that 4B5 has affinity for HER4 in clinically obtained tissues, and, if so, whether this has any impact on the assessment of HER2. We therefore sought to determine the expression of membrane‐bound HER4 in clinical breast carcinomas, and evaluate its impact on the clinical utility of 4B5 in determining HER2 status.
Methods and results
Breast carcinomas were assessed by immunohistochemistry (IHC) for membrane‐bound HER4 using anti‐HER4 clone E200. HER2 expression in these cases was then assessed using anti‐HER2 clone 4B5, and a reference clone, SP3. In all 117 membrane HER4‐positive cases (out of 241), 4B5 scored equal to or less than the reference anti‐HER2 clone SP3. Eighteen cases were positive for membrane‐bound HER4 by E200 and negative by 4B5, including a membrane HER4 level 3+ case.
Conclusions
No cross‐reactivity of 4B5 with membrane‐bound HER4 was identified in the clinical IHC analysis of formalin‐fixed paraffin‐embedded breast carcinoma cases as evidenced by the HER4 antibody clone E200.
The purpose of this study was to develop and analytically and functionally validate a new human papillomavirus (HPV) in-situ hybridization (ISH) assay and to determine whether the use of this assay ...combined with hemotoxylin and eosin (H&E) staining could potentially improve the diagnostic accuracy of interpreting cervical intraepithelial neoplasia (CIN) in human cervical tissue specimens. An automated HPV ISH assay was developed using probes that targeted the broad spectrum of HPV genotypes most commonly associated with CIN. In an exploratory study, tissue sections (n=118) were stained with H&E alone and H&E with HPV ISH and evaluated by 6 general surgical pathologists. Results were compared with diagnoses established by expert pathologists on H&E alone. The change in specificity (diagnosis of no-CIN) and sensitivity (diagnosis of CIN) using H&E plus HPV versus H&E alone was determined. The HPV ISH assay detected 21 HPV genotypes and demonstrated no cross-reactivity to Epstein-Barr virus, cytomegalovirus, herpes simplex virus (HSV)-1, HSV-2, or human placental DNA. The assay detected HPV in a range of 1 to 600 copies on CaSki, HeLa, and SiHa xenografts. Use of this assay with H&E staining improved the average diagnostic specificity of the surgical pathologists from 68.5% to 89.9% (P<0.001), with fewer false-positive CIN 1 results (122 vs. 39). The diagnostic sensitivity was similar for assessments made with H&E alone and those made with HPV plus H&E (93.1% vs. 93.6%). In conclusion, a new automated broad-spectrum HPV ISH assay combined with H&E-stained slides contributed to better ascertainment of CIN than H&E staining alone.
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