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A mathematical model of H5N1 influenza transmission in US dairy cattle

Nat Commun. 2025 May 8;16(1):4308. doi: 10.1038/s41467-025-59554-z.

ABSTRACT

2024 saw a novel outbreak of H5N1 avian influenza in US dairy cattle. Limited surveillance data has made determining the true scale of the epidemic difficult. We present a stochastic metapopulation transmission model that simulates H5N1 influenza transmission through individual dairy cows in 35,974 herds in the continental US. Transmission is enabled through the movement of cattle between herds, as indicated from Interstate Certificates of Veterinary Inspection data. We estimate the rates of under-reporting by state and present the anticipated rates of positivity for cattle tested at the point of exportation over time. We investigate the impact of intervention methods on the underlying epidemiological dynamics, demonstrating that current interventions have had insufficient impact, preventing only a mean 175.2 reported outbreaks. Our model predicts that the majority of the disease burden is, as of January 2025, concentrated within West Coast states. We quantify the uncertainty in the scale of the epidemic, highlighting the most pressing data streams to capture, and which states are expected to see outbreaks emerge next, with Arizona and Wisconsin at greatest risk. Our model suggests that dairy outbreaks will continue to occur in 2025, and that more urgent, farm-focused, biosecurity interventions and targeted surveillance schemes are needed.

PMID:40341525 | DOI:10.1038/s41467-025-59554-z

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Cabergoline’s Promise in Endometriosis: Restoring Molecular Balance to Improve Reproductive Potential

Gynecol Obstet Invest. 2025 May 8:1-23. doi: 10.1159/000546198. Online ahead of print.

ABSTRACT

OBJECTIVES: Endometriosis is a chronic gynecological condition characterized by abnormal angiogenesis and cell adhesion processes driven by VEGF-VEGFR2 signaling. Cabergoline, a dopamine agonist, has been shown to inhibit angiogenesis in endometriosis. This study investigates the therapeutic potential of Cabergoline in modulating these pathways to mitigate endometriotic lesion progression and improve oocyte quality.

DESIGN: A randomized, placebo-controlled study was conducted, involving two groups of participants: one receiving Cabergoline treatment and the other receiving a placebo.

METHODS: Eutopic endometrial tissue from women diagnosed with endometriosis was analyzed. VEGFR-2, FAK, PXN, ITGB3, and ITGAV expression levels were measured using qPCR. DNA methylation at the VEGFR-2 promoter was assessed using High-Resolution Melting (HRM) analysis to examine epigenetic modifications. Western blot analysis was performed to evaluate the phosphorylation status of tyrosine residue 951 on the VEGFR-2 receptor, which is implicated in cell migration and survival. Oocyte quality was also assessed in both groups.

RESULTS: Cabergoline treatment reduced the expression levels of VEGFR-2, FAK, PXN, ITGB3, and ITGAV, with ITGAV showing a statistically significant decrease (p = 0.0174). Hypomethylation of the VEGFR-2 promoter was observed in the treatment group (p = 0.3566). However, phosphorylation of tyrosine residue 951 on VEGFR-2 significantly increased in the Cabergoline-treated group (p = 0.004). Notably, oocyte quality significantly improved in the Cabergoline group (p = 0.0318). A strong correlation was found between reduced VEGFR-2 expression (p = 0.0184), decreased promoter methylation (p = 0.0159), and downregulation of PTK2 expression (p = 0.0057), all of which are associated with improved oocyte quality.

LIMITATIONS: The sample size was limited, and additional long-term studies are needed to confirm the therapeutic potential of Cabergoline in endometriosis treatment.

CONCLUSIONS: Cabergoline may enhance oocyte quality by modulating key regulators of the angiogenic pathway. These findings suggest its potential role in the management of endometriosis-related infertility, warranting further clinical investigation.

PMID:40341516 | DOI:10.1159/000546198

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In-Person and Virtual Clinic Visit Frequency to Rheumatologists for Rheumatoid Arthritis at an Academic Medical Center Before, During, and After COVID Lockdown

Rheumatol Ther. 2025 May 8. doi: 10.1007/s40744-025-00768-4. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to describe outpatient visit volume in a subspecialty clinic before, during, and after COVID lockdown.

METHODS: We assessed monthly in-person and virtual visit volume (telephone-only or video) of 257 patients with rheumatoid arthritis (RA) at one academic center before, during, and post COVID lockdown, November 2018 to September 2021. The primary outcome was monthly visit volume to a rheumatologist. Visit volume, visit type (in-person vs. virtual), and annual visit frequency per patient were assessed. Piecewise Poisson regression models were constructed to examine visit volume trends. Predictors of patient’s visit volume before and after the lockdown were examined using multivariable linear regression.

RESULTS: Median patient age was 58 years; 84% were female; 82% used any disease-modifying anti-rheumatic drug (DMARD), and 62% used a targeted or biologic DMARD. Visit volume was stable 18 months prior to the COVID pandemic [slope 1.00 (95% confidence interval (CI) 0.99-1.01)] and increased at a rate of 2% per month post-lockdown [1.02 (95% CI 1.01-1.03)]. In-person visit volume was greatly reduced during the lockdown, with 61% virtual (51% video, 10% telephone). In the 18 months after lockdown, visit volume rebounded to pre-pandemic levels and continued to increase, with 11% virtual. Older age, serologic status, use of combination DMARDs, and non-steroidal anti-inflammatory drug (NSAID) use predicted greater visit volume during the pre-lockdown period. No variables predicted visit volume post-lockdown.

CONCLUSION: While COVID caused a huge disruption in rheumatology practice, visit volume for RA rebounded in one American academic center, with an increasing slope in visit volume after lockdown.

PMID:40341502 | DOI:10.1007/s40744-025-00768-4

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Associations and Outcomes Comparing First and Second Eye Trabeculectomies in Patients with Glaucoma

J Glaucoma. 2025 May 9. doi: 10.1097/IJG.0000000000002586. Online ahead of print.

ABSTRACT

PRECIS: The present study highlights the high correlation of outcomes of bilateral trabeculectomy in subjects with different types of glaucoma after mid-term follow-up.

PURPOSE: To evaluate the mid-term outcomes of bilateral trabeculectomy and assess the differences and associations in outcome between the first-operated and the second-operated eye.

METHODS: Patients with different types of glaucoma who underwent bilateral trabeculectomy from 2006 to 2022 were included in this retrospective study. All patients were followed for at least 24 months after surgery in each eye. The main outcome measure was surgical success. Complete success was defined according to intraocular pressure (IOP)≤16 mmHg and at least 20% reduction from preoperative baseline IOP without any IOP lowering medications. Cumulative success was defined according to IOP≤16 mmHg and at least 20% reduction from preoperative baseline IOP, with or without IOP-lowering medications. Secondary outcome measures were IOP and the number of IOP-lowering medications.

RESULTS: In total, 186 eyes of 93 patients were included. There was no statistically significant difference in terms of the baseline IOP and number of IOP-lowering medications between the first and second operated eyes before and after surgery (P-value>0.05). The mean follow-up time was 64.35±41.13 months and 57.13±38.41 months for the first operated and the second operated eyes, respectively. At the 24-month follow-up point, among patients whose first operated eyes were considered a complete success, 78.2% of surgeries in second eyes were successful (P-value=0.002). On the other hand, among patients whose first operated eyes were considered a cumulative success, 80.3% of surgeries in second eyes were successful (P value=0.012). In a multivariate analysis of factors affecting cumulative success, the outcome of the surgery in the first operated eye was the only factor that significantly impacted the outcome of surgery in the second operated eye. If the first operated eye achieved cumulative success, the odds of the second operated eye experiencing cumulative success were 6.5 (P-value=0.02). The rates of postoperative complications in the two eyes were similar and did not show statistically significant differences.

CONCLUSION: The present study demonstrates a significant correlation in surgical outcomes of trabeculectomy between the two eyes of the same patient in mid-term follow-up. Surgical success in the first-operated eye increases the odds of success in the second eye 6.5 fold.

PMID:40341455 | DOI:10.1097/IJG.0000000000002586

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The relationship between multiple chronic diseases and sleep quality among the older people ≥ 60 years in China

Sleep Breath. 2025 May 8;29(2):179. doi: 10.1007/s11325-025-03346-8.

ABSTRACT

BACKGROUND: High-quality sleep is essential for both physical well-being and mental health, particularly in promoting the health and longevity of older adults. However, limited evidence exists regarding the relationship between chronic diseases and sleep quality in this population.

METHODS: The study investigated 35 common chronic diseases among 1186 older individuals aged 60 and above from six rural communities in northwest China. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Multiple logistic regression and interaction analyses were employed to explore the relationship between multiple chronic diseases and sleep quality.

RESULTS: Compared with the first quartile (≤ 1) of the number of chronic diseases, the second (2), third (3-4), and fourth (≥ 5) quartile ORs were 1.771 (95% CI: 1.191-2.631, p = 0.005), 2.434 (95% CI: 1.660-3.567, p < 0.001), and 3.180 (95% CI: 2.039-4.959, p < 0.001), respectively. For the duration of chronic diseases, compared with the first quartile (≤ 4.32 years) of duration of chronic diseases, the second (4.33-7.49 years), third (7.50-11.32 years) and fourth (≥ 11.33 years) quartile ORs were 1.350 (95% CI: 0.931-1.957, p = 0.113), 1.381 (95% CI: 0.953-2.000, p = 0.088), and 1.629 (95% CI: 1.122-2.365, p = 0.010), respectively. Older adults with multimorbidity and a longer duration of chronic diseases (≥ 7.5 years) had poorer sleep quality than those without multimorbidity and shorter duration of chronic diseases.

CONCLUSION: The higher number and longer duration of chronic diseases are associated with poorer sleep quality among older adults, with a stronger correlation observed in females compared to males.

PMID:40341452 | DOI:10.1007/s11325-025-03346-8

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The factors affecting breastfeeding self-efficacy, LATCH scores and effect of postnatal breastfeeding education on mothers’ self-efficacy

Rev Esc Enferm USP. 2025 May 2;59:e20240281. doi: 10.1590/1980-220X-REEUSP-2024-0281en. eCollection 2025.

ABSTRACT

OBJECTIVE: To identify the factors affecting breastfeeding self-efficacy and LATCH scores and to assess the impact of postnatal breastfeeding education on mothers’ self-efficacy.

METHOD: This study employed a quasi-experimental pretest-posttest design with a single group. It was completed with 217 mothers who gave birth in a hospital in Turquía between May 2023 and December 2023. Data were collected using Breastfeeding Self-efficacy Scale, and LATCH assessment tool. Breastfeeding education was given to mothers before discharge. Breastfeeding self-efficacy was re-evaluated on the phone four weeks after discharge.

RESULTS: The mean LATCH score among mothers was 9,2 ± 1.3 (min = 3, max = 10). Higher LATCH scores were observed in mothers with primary or secondary education, those who were unemployed, had four or more pregnancies and children, breastfed within the first hour, and had prior breastfeeding experience before discharge. Mothers with breastfeeding experience and those with four pregnancies and three children had higher breastfeeding self-efficacy scores before discharge. Four weeks after discharge was given to mothers, the mean breastfeeding self-efficacy score increased significantly from 58,9 ± 6,7 to 68,4 ± 1,9. A statistically significant improvement in breastfeeding self-efficacy was observed only among mothers with prior breastfeeding experience four weeks after discharge.

CONCLUSION: Regular breastfeeding education in the early postpartum period is crucial, particularly for young, primiparous mothers with higher education levels, those who are employed, with a history of cesarean deliveries, or lack of prior breastfeeding experience. The findings indi-cate that breastfeeding education positively impacts mothers’ breastfeeding self-efficacy.

PMID:40341446 | DOI:10.1590/1980-220X-REEUSP-2024-0281en

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Investigations of Influence of Antibody Binding Kinetics on Tumor Distribution and Anti-Tumor Efficacy

AAPS J. 2025 May 9;27(4):91. doi: 10.1208/s12248-025-01076-z.

ABSTRACT

The pharmacokinetics of antibodies with varied binding kinetics were simulated to assess the role of affinity and binding microconstants (kon, koff) on tumor exposure and intra-tumoral distribution. Anti-HER2 constructs (trastuzumab, pertuzumab, VK3VH6, and conjugates with DM1 and gelonin) were produced, purified, and tested for binding and cytotoxicity in vitro, and for intra-tumoral distribution and anti-tumor efficacy in mice. Simulations demonstrated that homogeneity in intra-tumoral distribution increases with increases in koff and with decreases in kon. Interestingly, simulations also predicted that homogeneity in tumor distribution may be improved by decreasing kon and koff in parallel (without changing affinity). Relative to trastuzumab, pertuzumab exhibits similar affinity but a ~ fivefold smaller kon and koff, while VK3VH6 exhibits a similar koff but a ~ 30-fold lower kon and affinity. Conjugate concentrations associated with 50% inhibition of cell proliferation (IC50s) were found to vary with affinity, where IC50 values were similar for pertuzumab and trastuzumab, and higher for VK3VH6. Consistent with model simulations, VK3VH6 and pertuzumab demonstrated more homogeneous tumor distribution than trastuzumab. Although treatment differences were not statistically significant, pertuzumab and VK3VH6 conjugates showed trends for increased survival time relative to mice treated with trastuzumab conjugates. Our simulation and experimental results demonstrate complex relationships between antibody-antigen binding kinetics, intratumoral distribution, and efficacy. The rate constant of association, kon, is an underappreciated determinant of intra-tumoral distribution; among high-affinity antibodies, those with lower values of kon may be expected to exhibit improved intra-tumoral distribution and, potentially, efficacy.

PMID:40341444 | DOI:10.1208/s12248-025-01076-z

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Harm-Benefit Balance of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

JAMA Oncol. 2025 May 8. doi: 10.1001/jamaoncol.2025.0985. Online ahead of print.

ABSTRACT

IMPORTANCE: The benefits and harms of immune checkpoint inhibitor (ICI) therapy for lung cancer vary across groups, including those typically underrepresented in randomized clinical trials.

OBJECTIVE: To quantify the harms and benefits of ICI-containing regimens in individuals with non-small cell lung cancer and assess heterogeneity across priority subgroups.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study conducted in 2024 used 2013 to 2019 Surveillance, Epidemiology, and End Results (SEER) Medicare data of individuals 66 years or older with non-small cell lung cancer who were exposed to any ICI.

EXPOSURES: ICI + chemotherapy, single ICI (reference group).

MAIN OUTCOMES: Severe immune-related adverse events (irAE; harm) and mortality (when delayed mortality was the benefit). Severe irAEs were defined using validated diagnosis and medication codes. Mortality was ascertained from Medicare data. Hazard ratios (HRs) were estimated and 95% CIs were stratified by whether an ICI was used as the first or second or later systemic anticancer treatment (SACT) and in subgroups defined by preexisting autoimmune disease, sex, and age. The harm-benefit tradeoff was described as excess severe irAEs per year of life gained in which the gain in survival time was assessed using restricted mean survival time.

RESULTS: Of 17 681 Medicare beneficiaries, 8797 (49.5%) were female, and the mean (SD) age was 74 (6.0) years. Compared with a single ICI (14 249 [80.6%]), individuals treated with ICI + chemotherapy (3432 [19.4%]) had an elevated risk of severe irAE in the first SACT setting (hazard ratio [HR], 1.18; 95% CI, 1.06-1.30) but not in the second or later SACT setting (HR, 1.04; 95% CI, 0.92-1.19); there was a decreased risk of mortality in the first SACT setting (HR, 0.66; 95% CI, 0.62-0.72) but not in the second or later SACT setting (HR, 0.94; 95% CI, 0.68-1.03). In the first SACT setting, ICI + chemotherapy delayed mortality more among patients with (vs without) autoimmune disease at baseline. For each 1 year of life gained, the risk of severe irAEs was 0.31 (95% CI, 0.09-0.53) and the tradeoff was also statistically significant in men and patients without autoimmune disease.

CONCLUSIONS: The results of this cohort study suggest that given both treatment-related harms and benefits, ICI + chemotherapy use in the first SACT setting requires informed decision-making; the potential benefits of ICI + chemotherapy vs single ICI in high-risk subgroups is encouraging.

PMID:40338588 | DOI:10.1001/jamaoncol.2025.0985

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Investigating the effect of experience sampling study design on careless and insufficient effort responding identified with a screen-time-based mixture model

Psychol Assess. 2025 May 8. doi: 10.1037/pas0001379. Online ahead of print.

ABSTRACT

When using the experience sampling method (ESM), researchers must navigate a delicate balance between obtaining fine-grained snapshots of phenomena of interest and avoiding undue respondent burden, which can lead to disengagement and compromise data quality. To guide that process, we investigated how questionnaire length and sampling frequency impact careless and insufficient effort responding (C/IER) as an important yet understudied aspect of ESM data quality. To this end, we made use of existing experimental ESM data (Eisele et al., 2022) from 163 students randomly assigned to one of two questionnaire lengths (30/60 items) and one of three sampling frequencies (3/6/9 assessments per day). We employed a novel mixture modeling approach (Ulitzsch, Nestler, et al., 2024) that leverages screen time data to disentangle attentive responding from C/IER and allows investigating how the occurrence of C/IER evolved within and across ESM study days. We found sampling frequency, but not questionnaire length, impacted C/IER, with higher frequencies resulting in higher overall C/IER proportions and sharper increases of C/IER across, but not within days. These effects proved robust across various model specifications. Further, we found no substantial relationships between model-implied C/IER and other engagement measures, such as self-reported attentiveness, attention checks, response-pattern-based attentiveness indicators, and compliance. Our findings contrast previous studies on noncompliance, suggesting that respondents may employ different strategies to lower the different types of burden imposed by questionnaire length and sampling frequency. Implications for designing ESM studies are discussed. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40338562 | DOI:10.1037/pas0001379

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Depression and Heart Failure in US Veterans

JAMA Netw Open. 2025 May 1;8(5):e259246. doi: 10.1001/jamanetworkopen.2025.9246.

ABSTRACT

IMPORTANCE: Depression and heart failure (HF) affect millions of US adults. Incident HF risk following depression diagnosis is understudied.

OBJECTIVE: To examine the association between incident HF and prevalent depression among veterans.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed sociodemographic and clinical data of US veterans participating in the Veterans Affairs (VA) Birth Cohort. Data were obtained from the VA Corporate Data Warehouse between January 1, 2000, and October 1, 2015. Participants were born between 1945 and 1965, were free of HF at baseline, and met a medical home definition (had 3 outpatient visits within 5 years). Statistical analysis was performed from May 2022 to February 2025.

EXPOSURES: Prevalent depression, defined as 1 inpatient or 2 outpatient visits with International Classification of Diseases, Ninth Revision (ICD-9) or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes for depression.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to incident HF, defined as time from baseline to documented date of the first inpatient or second outpatient visit with ICD-9 or ICD-10 codes for HF. A Cox proportional hazards regression model adjusted for relevant covariates was used to assess the association of depression and incident HF.

RESULTS: A total of 2 843 159 veterans (median [SD] age, 54 [49-59] years; 2 677 919 males [94.2%]; 556 914 [19.6%] self-identified as Black, 144 485 [5.1%] as Hispanic, 1 975 068 [69.5%] as White, and 99 011 [3.5%] as other race and ethnicity) were included. Participants were followed up for incident HF over a median (IQR) duration of 6.9 (3.4-11.0) years. Generally, 8.0% of participants (226 247 of 2 843 159) had prevalent depression at baseline. Females made up a larger percentage of those with vs without depression (11.4% vs 5.3%). Participants with depression demonstrated higher unadjusted incident HF rates compared with those without depression (136.9 [95% CI, 132.2-141.7] cases per 10 000 person-years vs 114.6 [95% CI, 113.4-115.9] cases per 10 000 person-years, respectively). After adjusting for sociodemographic and cardiovascular risk factors, depression was associated with an increase in incident HF hazard of 14.0% (hazard ratio [HR], 1.14; 95% CI, 1.13-1.16), with an estimated adjusted median (IQR) incidence rate difference of 16.0 (14.9-18.3) cases per 10 000 person-years. Among patients without comorbidities, depression was associated with a higher increase in incident HF hazard (HR, 1.58; 95% CI, 1.39-1.80), with an estimated adjusted median (IQR) rate difference of 14.2 (9.5-19.5) cases per 10 000 person-years.

CONCLUSIONS AND RELEVANCE: In this cohort study, depression among veterans was associated with an increased hazard of incident HF after controlling for demographic and cardiovascular risk factors. Higher incident HF rates in patients with depression remained consistent in an otherwise low-risk cohort.

PMID:40338547 | DOI:10.1001/jamanetworkopen.2025.9246