Association between oral targeted cancer drug net health benefit, uptake, and spending.

BACKGROUND: Targeted cancer drugs (TCDs) have revolutionized oncology but vary in clinical benefit and patient out-out-pocket (OOP) costs. The ASCO Value Framework uses survival, toxicity, and symptom palliation data to quantify the net health benefit (NHB) of cancer drugs. We evaluated associations between NHB, uptake, and spending on oral TCDs. METHODS: We conducted a retrospective cohort study of patients aged 18-64 years with an incident oral TCD pharmacy claim in 2012-2020 in a nationwide de-identified commercial claims dataset. TCDs were categorized as having high (>60), medium (40-60), and low (<40) NHB scores. We plotted the uptake of TCDs by NHB category and used standard descriptive statistics to evaluate patient OOP and total spending. Generalized linear models evaluated the relationship between spending and TCD NHB, adjusted for cancer indication. RESULTS: We included 8,524 patients with incident claims for eight oral TCDs with nine first-line indications in advanced melanoma, breast, lung, and pancreatic cancer. Medium- and high-NHB TCDs accounted for most TCD prescriptions. Median OOP spending was $18.78 for the first 28-day TCD supply (IQR $0.00-$87.57); 45% of patients paid $0 OOP. Median total spending was $10,118.79 (IQR $6,365.95-$10,600.37) for an incident 28-day TCD supply. Total spending increased $1,083.56 for each 10-point increase in NHB score (95% CI $1,050.27-$1,116.84, p < .01 for H0=$0). CONCLUSION: Low-NHB TCDs were prescribed less frequently than medium- and high-NHB TCDs. Total spending on oral TCDs was high and positively associated with NHB. Commercially insured patients were largely shielded from high OOP spending on oral TCDs.

Higher cardiovascular disease risks in people living with HIV: A systematic review and meta-analysis.

Background: The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). Results: We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. Conclusions: People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. Registration: PROSPERO (CRD42021255508).

Identification and functional analysis of a serine protease inhibitor using machine learning strategy.

In the intricate realm of animal biology, a multitude of vital processes heavily rely on precisely orchestrated proteinase cascades, but the potential for havoc makes proteinase inhibitors indispensable, with serine proteinase inhibitors (serpins) at the forefront, serving as custodians of homeostasis and participating in various critical biological processes. Importantly, there are still many unexplored facets of serpin functionality. In this study, we focused on the serpin family proteins from Marsupenaeus japonicus, utilizing a fine-tuned pretrained protein language model. This approach led to the identification and evolutionary validation of 28 serpins, one of which, referred to as Mjserpin-1, was both computationally and experimentally demonstrated to show potential as an antiviral and apoptosis inhibitor. Our research unveils exciting prospects for the fusion of state-of-the-art artificial intelligence and rich bioinformatics, holding the promise of significant discoveries that could pave the way for future therapeutic advancements.

Proanthocyanidins Ameliorate LPS-Inhibited Osteogenesis of PDLSCs by Restoring Lysine Lactylation.

Periodontitis is a bacteria-induced inflammatory disease characterized by the progressive destruction of periodontal supporting tissues. Periodontal ligament stem cells (PDLSCs) are capable of differentiating into osteoblasts, which is an important stem cell source for endogenous periodontal tissue regeneration. Lysine lactylation (Kla) is a novel post-translational modification of proteins that is recently thought to be associated with osteogenic differentiation. Here, we found that lactylation levels are reduced both in the periodontal tissue of rats with periodontitis and lipopolysaccharide (LPS)-stimulated human PDLSCs. Proanthocyanidins were able to promote the osteogenesis of inflamed PDLSCs by restoring lactylation levels. Mechanistically, proanthocyanidins increased lactate production and restored the lactylation levels of PDLSCs, which recovered osteogenesis of inflamed PDLSCs via the Wnt/ß-catenin pathway. These results provide evidence on how epigenetic regulation by pharmacological agents influence the osteogenic phenotype of stem cells and the process of periodontal tissue repair. Our current study highlights the valuable potential of natural product proanthocyanidins in the regenerative engineering of periodontal tissues.

Metagenomic exploration of the rhizosphere soil microbial community and their significance in facilitating the development of wild-simulated ginseng.

Panax ginseng, a prized medicinal herb, has faced increasingly challenging field production due to soil degradation and fungal diseases in Northeast China. Wild-simulated cultivation has prevailed because of its sustainable soil management and low disease incidence. Despite the recognized benefits of rhizosphere microorganisms in ginseng cultivation, their genomic and functional diversity remain largely unexplored. In this work, we utilized shotgun metagenomic analysis to reveal that Pseudomonadota, Actinomycetota, and Acidobacteriota were dominant in the ginseng rhizobiome and recovered 14 reliable metagenome-assembled genomes. Functional analysis indicated an enrichment of denitrification-associated genes, potentially contributing to the observed decline in soil fertility, while genes associated with aromatic carbon degradation may be linked to allelochemical degradation. Further analysis demonstrated enrichment of Actinomycetota in 9-year-old wild-simulated ginseng (WSG), suggesting the need for targeted isolation of Actinomycetota bacteria. Among these, at least three different actinomycete strains were found to play a crucial role in fungal disease resistance, with Streptomyces spp. WY144 standing out for its production of actinomycin natural products active against the pathogenic fungus Ilyonectria robusta. These findings not only enhance our understanding of the rhizobiome of WSG but also present promising avenues for combating detrimental fungal pathogens, underscoring the importance of ginseng in both medicinal and agricultural contexts.IMPORTANCEWild-simulated ginseng, growing naturally without human interference, is influenced by its soil microbiome. Using shotgun metagenomics, we analyzed the rhizospheric soil microbiome of 7- and 9-year-old wild-simulated ginseng. The study aimed to reveal its composition and functions, exploring the microbiome's key roles in ginseng growth. Enrichment analysis identified Streptomycetes in ginseng soil, with three strains inhibiting plant pathogenic fungi. Notably, one strain produced actinomycins, suppressing the ginseng pathogenic fungus Ilyonectria robusta. This research accelerates microbiome application in wild-simulated ginseng cultivation, offering insights into pathogen protection and supporting microbiome utilization in agriculture.

Correction: Enhancing osteogenic differentiation of MC3T3-E1 cells during inflammation using UPPE/ß-TCP/TTC composites via the Wnt/ß-catenin pathway.

[This corrects the article DOI: 10.1039/D3RA05529A.].

Enhancing osteogenic differentiation of MC3T3-E1 cells during inflammation using UPPE/ß-TCP/TTC composites via the Wnt/ß-catenin pathway.

Periodontitis can lead to defects in the alveolar bone, thus increasing the demand for dependable biomaterials to repair these defects. This study aims to examine the pro-osteogenic and anti-bacterial properties of UPPE/ß-TCP/TTC composites (composed of unsaturated polyphosphoester [UPPE], ß-tricalcium phosphate [ß-TCP], and tetracycline [TTC]) under an inflammatory condition. The morphology of MC3T3-E1 cells on the composite was examined using scanning electron microscopy. The toxicity of the composite to MC3T3-E1 cells was assessed using the Alamar-blue assay. The pro-osteogenic potential of the composite was assessed through ALP staining, ARS staining, RT-PCR, and WB. The antimicrobial properties of the composite were assessed using the zone inhibition assay. The results suggest that: (1) MC3T3-E1 cells exhibited stable adhesion to the surfaces of all four composite groups; (2) the UPPE/ß-TCP/TTC composite demonstrated significantly lower toxicity to MC3T3-E1 cells; and (3) the UPPE/ß-TCP/TTC composite had the most pronounced pro-osteogenic effect on MC3T3-E1 cells by activating the WNT/ß-catenin pathway and displaying superior antibacterial properties. UPPE/ß-TCP/TTC, as a biocomposite, has been shown to possess antibacterial properties and exhibit excellent potential in facilitating osteogenic differentiation of MC3T3-E1 cells.

Predictive value of the stress hyperglycemia ratio in dialysis patients with acute coronary syndrome: insights from a multi-center observational study.

BACKGROUND: Various studies have indicated that stress hyperglycemia ratio (SHR) can reflect true acute hyperglycemic status and is associated with poor outcomes in patients with acute coronary syndrome (ACS). However, data on dialysis patients with ACS are limited. The Global Registry of Acute Coronary Events (GRACE) risk score is a well-validated risk prediction tool for ACS patients, yet it underestimates the risk of major events in patients receiving dialysis. This study aimed to evaluate the association between SHR and adverse cardiovascular events in dialysis patients with ACS and explore the potential incremental prognostic value of incorporating SHR into the GRACE risk score. METHODS: This study enrolled 714 dialysis patients with ACS from January 2015 to June 2021 at 30 tertiary medical centers in China. Patients were stratified into three groups based on the tertiles of SHR. The primary outcome was major adverse cardiovascular events (MACE), and the secondary outcomes were all-cause mortality and cardiovascular mortality. RESULTS: After a median follow-up of 20.9 months, 345 (48.3%) MACE and 280 (39.2%) all-cause mortality occurred, comprising 205 cases of cardiovascular death. When the highest SHR tertile was compared to the second SHR tertile, a significantly increased risk of MACE (adjusted hazard ratio, 1.92; 95% CI, 1.48-2.49), all-cause mortality (adjusted hazard ratio, 2.19; 95% CI, 1.64-2.93), and cardiovascular mortality (adjusted hazard ratio, 2.70; 95% CI, 1.90-3.83) was identified in the multivariable Cox regression model. A similar association was observed in both diabetic and nondiabetic patients. Further restricted cubic spline analysis identified a J-shaped association between the SHR and primary and secondary outcomes, with hazard ratios for MACE and mortality significantly increasing when SHR was > 1.08. Furthermore, adding SHR to the GRACE score led to a significant improvement in its predictive accuracy for MACE and mortality, as measured by the C-statistic, net reclassification improvement, and integrated discrimination improvement, especially for those with diabetes. CONCLUSIONS: In dialysis patients with ACS, SHR was independently associated with increased risks of MACE and mortality. Furthermore, SHR may aid in improving the predictive efficiency of the GRACE score, especially for those with diabetes. These results indicated that SHR might be a valuable tool for risk stratification and management of dialysis patients with ACS.

The triglyceride-glucose index predicts 1-year major adverse cardiovascular events in end-stage renal disease patients with coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index has been suggested as a dependable indicator for predicting major adverse cardiovascular events (MACE) in individuals with cardiovascular conditions. Nevertheless, there is insufficient data on the predictive significance of the TyG index in end-stage renal disease (ESRD) patients with coronary artery disease (CAD). METHODS: This study, conducted at multiple centers in China, included 959 patients diagnosed with dialysis and CAD from January 2015 to June 2021. Based on the TyG index, the participants were categorized into three distinct groups. The study's primary endpoint was the combination of MACE occurring within one year of follow-up, including death from any cause, non-fatal myocardial infarction, and non-fatal stroke. We assessed the association between the TyG index and MACE using Cox proportional hazard models and restricted cubic spline analysis. The TyG index value was evaluated for prediction incrementally using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: The three groups showed notable variations in the risk of MACE (16.3% in tertile 1, 23.5% in tertile 2, and 27.2% in tertile 3; log-rank P = 0.003). Following complete adjustment, patients with the highest TyG index exhibited a notably elevated risk of MACE in comparison to those in the lowest tertile (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.14-2.35, P = 0.007). Likewise, each unit increase in the TyG index correlated with a 1.37-fold higher risk of MACE (HR 1.37, 95% CI 1.13-1.66, P = 0.001). Restricted cubic spline analysis revealed a connection between the TyG index and MACE (P for nonlinearity > 0.05). Furthermore, incorporating the TyG index to the Global Registry of Acute Coronary Events risk score or baseline risk model with fully adjusted factors considerably enhanced the forecast of MACE, as demonstrated by the C-statistic, continuous NRI, and IDI. CONCLUSIONS: The TyG index might serve as a valuable and dependable indicator of MACE risk in individuals with dialysis and CAD, indicating its potential significance in enhancing risk categorization in clinical settings.

Association of triglyceride-glucose index with coronary severity and mortality in patients on dialysis with coronary artery disease.

BACKGROUND: The triglyceride-glucose (TyG) index is validated as a reliable biomarker of insulin resistance and an independent predictor of cardiovascular prognosis. However, the prognostic value of the TyG index in patients on dialysis with coronary artery disease (CAD) remained unexplored. This study aimed to determine the association between the TyG index and CAD severity and mortality in these patients. METHODS: A total of 1061 dialysis patients with CAD were enrolled in this multi-center cohort study from January 2015 to June 2021. The extent and severity of CAD were evaluated using the multivessel disease and Gensini score (GS). Patients were followed up for all-cause death and cardiovascular death. RESULTS: The multivariable logistic regression model indicated that the TyG index was significantly associated with multivessel disease (odds ratio [OR] 1.51, 95% confidence interval [CI] 1.18-1.94, P = 0.001), and high GS (OR 1.33, 95% CI 1.10-1.61, P = 0.003). After adjusting for baseline risk factors, the hazards of all-cause death and cardiovascular death were 1.23 (95% CI 1.06-1.43, P = 0.007), and 1.33 (95% CI 1.11-1.59, P = 0.002), independent of CAD severity. Restricted cubic spline analysis identified a dose-response association between the TyG index and both CAD severity and mortality (all P for nonlinearity > 0.05). When modeling the TyG index as a categorical variable, these independent associations remained. Subgroup analyses did not substantially modify the results. Furthermore, incorporating the TyG index into the existing risk prediction model improved the predictive accuracy for all-cause death and cardiovascular death, as evaluated by C-statistic, continuous net reclassification improvement, and integrated discrimination improvement. CONCLUSIONS: In patients on dialysis with CAD, the TyG index was significantly associated with more severe CAD as well as mortality. These results highlight the clinical importance of the TyG index for assessing CAD severity and risk stratification in patients on dialysis with CAD.

THBS1-Mediated Degradation of Collagen via the PI3K/AKT Pathway Facilitates the Metastasis and Poor Prognosis of OSCC.

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by a persistently high incidence and mortality rate. The extracellular matrix (ECM) plays a crucial role in the initiation, progression, and diverse biological behaviors of OSCC, facilitated by mechanisms such as providing structural support, promoting cell migration and invasion, regulating cell morphology, and modulating signal transduction. This study investigated the involvement of ECM-related genes, particularly THBS1, in the prognosis and cellular behavior of OSCC. The analysis of ECM-related gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen ECM-related genes showed a significant correlation with survival. Experimental methods were employed to demonstrate the impact of THBS1 on proliferation, migration, invasion, and ECM degradation in OSCC cells. A risk-prediction model utilizing four differentially prognostic genes demonstrated significant predictive value in overall survival. THBS1 exhibited enrichment of the PI3K/AKT pathway, indicating its potential role in modulating OSCC. In conclusion, this study observed and verified that ECM-related genes, particularly THBS1, have the potential to influence the prognosis, biological behavior, and immunotherapy of OSCC. These findings hold significant implications for enhancing survival outcomes and providing guidance for precise treatment of OSCC.

Exploring associations between built environment and crash risk of children in school commuting.

Understanding how built environment are associated with crash risk (CR) in school commuting is essential to improving travel safety through land use and transportation policies. Scholars often assume that this relationship is consistent across space, but this may lead to inconsistent estimates. To address this issue, using data in Shenzhen, China, the data covers traffic accident data of children taken from police incident reports and supplemented with local land use, transportation network and specific school information. The measurement model of crash scale was conducted to represent crash severity, and the CR was further quantified. The study applies three models, spatial dubin model (SDM), geographically weighted regression (GWR), and mixed GWR (MGWR), to explore spatio-temporal heterogeneity relationships between built environment attributes and CR of children in school commuting. The findings reveal that the crash scale can better represent crash severity of school commuting than a single indicator. Policy interventions should be targeted at specific spatial scales, school types, and time windows to effectively improve travel safety. However, there are some common findings. It is recommended to use a scale of 200 m to explain the relationship between the variables. The MGWR model outperforms the other two models. To reduce CR, it is important to consider lower road network density, a reasonable layout of educational facilities, fewer bus routes, and more on-street parking spaces. Our findings can help to enrich the understanding of associations between land use and CR of children, as well as offer local planning and operating guidance for creating child-friendly environment.

Proanthocyanidin enhances the endogenous regeneration of alveolar bone by elevating the autophagy of PDLSCs.

OBJECTIVE: This study aimed to investigate the effect of proanthocyanidin (PA) on osteogenesis mediated by periodontal ligament stem cells (PDLSCs) and endogenous alveolar bone regeneration. BACKGROUND: Leveraging the osteogenic potential of resident stem cells is a promising strategy for alveolar bone regeneration. PA has been reported to be effective in osteogenesis. However, the effect and mechanism of PA on the osteogenic differentiation of PDLSCs remain elusive. METHODS: Human PDLSCs were treated with various doses of PA to assess the cell proliferation using Cell Counting Kit-8. The osteogenic differentiation ability was detected by qRT-PCR analysis, western blot analysis, Alizarin red S staining, and Alkaline Phosphatase staining. The level of autophagy was evaluated by confocal laser scanning microscopy, transmission electron microscopy, and western blot analysis. RNA sequencing was utilized to screen the potential signaling pathway. The alveolar bone defect model of rats was created to observe endogenous bone regeneration. RESULTS: PA activated intracellular autophagy in PDLSCs, resulting in enhanced osteogenic differentiation. Moreover, this effect could be abolished by the autophagy inhibitor 3-Methyladenine. Mechanistically, the PI3K/Akt/mTOR pathway was negatively correlated with PA-mediated autophagy activation. Lastly, PA promoted the alveolar bone regeneration in vivo, and this effect was reversed when the autophagy process was blocked. CONCLUSION: PA may activate autophagy by inhibiting PI3K/Akt/mTOR signaling pathway to promote the osteogenesis of PDLSCs and enhance endogenous alveolar bone regeneration.

The combined contamination of nano-polystyrene and nanoAg: Uptake, translocation and ecotoxicity effects on willow saplings.

Nanoplastics (NPLs) and nanoAg (AgNPs) are emerging contaminants commonly detected in aquatic and terrestrial environments due to their widespread use in various domains. However, their uptake, translocation, and toxic effects on plants in cooccurrence environments remain largely unexplored. Therefore, a hydroponic experiment was conducted using 100 nm NPLs (1 mg/L and 10 mg/L), AgNPs (100 µg/L and 1000 µg/L) and saplings of willow (Salix matsudana 'J172') to investigate absorption, translocation and the physio-biochemical responses of the plants. The results indicated that NPLs and AgNPs were agglomerated with each other in solutions. NPLs not only penetrated the roots of the saplings but also translocated to the branches and leaves through xylem ducts. However, AgNPs was only detected in the roots, suggesting that the internalization of nanoparticles in plants depends on the properties and types of particles themselves. The combined exposure to NPLs and AgNPs selectively affected the absorption and distribution of K, Ca, Mg and Fe, resulting in inhibited saplings growth and photosynthesis. Furthermore, the presence of NPLs and AgNPs induced oxidative damage and stimulated the antioxidant stress system in the plants. This study provides novel insights into the internalization and ecotoxicological mechanisms of NPLs and AgNPs in woody vascular plants.

Dynamic monitoring of maize grain quality based on remote sensing data.

Remote sensing data have been widely used to monitor crop development, grain yield, and quality, while precise monitoring of quality traits, especially grain starch and oil contents considering meteorological elements, still needs to be improved. In this study, the field experiment with different sowing time, i.e., 8 June, 18 June, 28 June, and 8 July, was conducted in 2018-2020. The scalable annual and inter-annual quality prediction model for summer maize in different growth periods was established using hierarchical linear modeling (HLM), which combined hyperspectral and meteorological data. Compared with the multiple linear regression (MLR) using vegetation indices (VIs), the prediction accuracy of HLM was obviously improved with the highest R 2, root mean square error (RMSE), and mean absolute error (MAE) values of 0.90, 0.10, and 0.08, respectively (grain starch content (GSC)); 0.87, 0.10, and 0.08, respectively (grain protein content (GPC)); and 0.74, 0.13, and 0.10, respectively (grain oil content (GOC)). In addition, the combination of the tasseling, grain-filling, and maturity stages further improved the predictive power for GSC (R 2 = 0.96). The combination of the grain-filling and maturity stages further improved the predictive power for GPC (R 2 = 0.90). The prediction accuracy developed in the combination of the jointing and tasseling stages for GOC (R 2 = 0.85). The results also showed that meteorological factors, especially precipitation, had a great influence on grain quality monitoring. Our study provided a new idea for crop quality monitoring by remote sensing.

Safety and Efficacy of Long-Acting Injectable Agents for HIV-1: Systematic Review and Meta-Analysis.

BACKGROUND: HIV-1 infection continues to affect global health. Although antiretrovirals can reduce the viral load or prevent HIV-1 infection, current drugs require daily oral use with a high adherence level. Long-acting antiretrovirals (LA-ARVs) significantly improve medication adherence and are essential for HIV-1 prophylaxis and therapy. OBJECTIVE: This study aimed to investigate the safety and efficacy of long-acting cabotegravir (CAB-LA) and long-acting rilpivirine (RPV-LA) in the prevention and treatment of HIV-1 infection. METHODS: PubMed, Embase, and the Cochrane Library were searched for studies from database inception to November 12, 2022. We included studies that reported efficacy and safety data on LA-ARV intervention in people living with HIV and excluded reviews, animal studies, and articles with missing or duplicate data. Virological suppression was defined as plasma viral load <50 copies/mL 6 months after antiviral therapy initiation. We extracted outcomes for analysis and expressed dichotomous data as risk ratios (RRs) and continuous data as mean differences. Depending on the heterogeneity assessment, a fixed- or random-effects model was used for data synthesis. We performed subgroup analyses of the partial safety and efficacy outcomes of CAB-LA+RPV-LA. The protocol was registered with the Open Science Framework. RESULTS: We included 12 trials comprising 10,957 individuals, of which 7 were prevention trials and 5 were treatment trials. CAB-LA and RPV-LA demonstrated safety profiles comparable with those of the placebo in terms of adverse event-related withdrawal. Moreover, the efficacy data showed that CAB-LA had a better effect on HIV-1 prevention than tenofovir disoproxil fumarate-emtricitabine (17/5161, 0.33% vs 75/5129, 1.46%; RR 0.21, 95% CI 0.07-0.61; I2=70%). Although CAB-LA+RPV-LA had more drug-related adverse events (556/681, 81.6% vs 37/598, 6.2%; RR 12.50, 95% CI 3.98-39.23; I2=85%), a mild or moderate injection site reaction was the most common reaction, and its frequency decreased over time. The efficacy of CAB-LA+RPV-LA was comparable with that of daily oral drugs at 48 and 96 weeks (1302/1424, 91.43% vs 915/993, 92.2%; RR 0.99, 95% CI 0.97-1.02; I2=0%), and a high level of virological suppression of 80.9% (186/230) was maintained even after 5 years of LA-ARV use. Similar efficacy outcomes were observed in both treatment-naive and treatment-experienced patients (849/911, 93.2% vs 615/654, 94%; RR 0.99, 95% CI 0.96-1.02; I2=0%). According to the questionnaires, more than 85% of people living with HIV favored LA-ARVs. CONCLUSIONS: LA-ARVs showed favorable safety profiles for both the prevention and treatment of HIV-1 infection and were well tolerated. CAB-LA has more satisfactory efficacy than tenofovir disoproxil fumarate-emtricitabine, significantly reducing the rate of HIV-1 infection. CAB-LA+RPV-LA maintains virological suppression for a long time and may be a viable switching strategy with enhanced public health benefits by reducing transmission. However, further trials are required to confirm the efficacy of these drugs.

A Cost Comparison Between Mohs Micrographic Surgery and Conventional Excision for the Treatment of Head and Neck Melanomas In Situ and Thin Melanomas.

BACKGROUND: Variation in operative setting and surgical technique exists when treating specialty site melanomas. There are limited data comparing costs among surgical modalities. OBJECTIVE: To evaluate the costs of head and neck melanoma surgery performed with Mohs micrographic surgery or conventional excision in the operating room or office-based settings. METHODS: A retrospective cohort study was performed on patients aged 18 years and older with surgically treated head and neck melanoma in 2 cohorts, an institutional cohort and an insurance claims cohort, for the years 2008-2019. The primary outcome was total cost of care for a surgical encounter, provided in the form of insurance reimbursement data. A generalized linear model was used to adjust for covariates affecting differences between treatment groups. RESULTS: In the institutional and insurance claims cohorts, average adjusted treatment cost was highest in the conventional excision-operating room treatment group, followed by the Mohs surgery and conventional excision-office setting ( p < .001). CONCLUSION: These data demonstrate the important economic role the office-based setting has for head and neck melanoma surgery. This study allows cutaneous oncologic surgeons to better understand the costs of care involved in head and neck melanoma treatment. Cost awareness is important for shared decision-making discussions with patients.

IL-4/13 expressing CD3γ/δ+ T cells regulate mucosal immunity in response to Flavobacterium columnare infection in grass carp.

Interleukin (IL) 4 and 13 are signature cytokines orchestrating Th2 immune response. Teleost fish have two homologs, termed IL-4/13A and IL-4/13B, and have been functionally characterized. However, what cells express IL-4/13A and IL-4/13B has not been investigated in fish. In this work, the recombinant IL-4/13A and IL-4/13B proteins of grass carp (Ctenopharyngodon idella) were produced in the Escherichia coli (E. coli) cells and purified. Monoclonal antibodies (mAbs) against the recombinant CiIL-4/13A and CiIL-4/13B proteins were prepared and characterized. Western blotting analysis showed that the CiIL-4/13A and CiIL-4/13B mAbs could specifically recognize the recombinant proteins expressed in the E. coli cells and HEK293T cells and did not cross-react with each other. Confocal microscopy revealed that the CiIL-4/13A+ and CiIL-4/13B+ cells were present in the gills, intestine and spleen and could be upregulated in fish infected with Flavobacterium columnare (F. columnare). Interestingly, the cells expressing CiIL-4/13A and CiIL-4/13B were mostly CD3γ/δ+ cells. The CD3γ/δ+/IL-4/13A+ and CD3γ/δ+/IL-4/13B+ cells were significantly upregulated in the gill filaments and the intestinal mucosa after F. columnare infection. Our results imply that the CD3γ/δ+/IL-4/13A+ and CD3γ/δ+/IL-4/13B+ cells are important for homeostasis and the regulation of mucosal immunity.

Factors associated with post-treatment control of viral load in HIV-infected patients: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to investigate the factors associated with maintenance of viral suppression after antiretroviral therapy (ART) discontinuation. METHODS: Databases were searched for studies published between January 01, 2011, and July 01, 2022, that correlated the time of virus rebound with treatment interruption (TI). The corresponding data were extracted from these studies. A fixed-effects model was used to calculate pooled estimates. RESULTS: Thirty-one studies were included in this analysis. Results showed that patients who started ART during acute or early infection had longer viral control than those who started ART during chronic infection. It has been reported that some broadly neutralizing HIV-1-specific antibodies can significantly prolong viral inhibition. The study also found that approximately 7.2% of patients achieved post-treatment control (PTC) approximately a year after TI. CONCLUSION: ART initiation in the acute or early phases can delay viral rebound after TI. Cell-associated HIV RNA and HIV DNA have been difficult to prove as able to predict viral rebound time. Many vaccines and antibodies have also been shown to be effective in prolonging viral control in people without PTC, and more research is needed to develop alternative ART therapies that can effectively inhibit or even eliminate HIV.