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Distinct attentional characteristics of neurons with visual feature coding in the primate brain
No full textVisual attention and object recognition are two critical cognitive functions that shape our perception of the world. While these neural processes converge in the temporal cortex, the nature of their interactions remains largely unclear. Here, we systematically investigated the interplay between visual attention and stimulus feature coding by training macaques to perform a free-gaze visual search task with natural stimuli. Recording from a large number of units across multiple brain areas, we found that units exhibiting visual feature coding showed stronger attentional modulation of responses and spike-local field potential coherence than units without feature coding. Across brain areas, attention directed toward search targets enhanced the neuronal pattern separation of stimuli, with this enhancement more pronounced for units encoding visual features. Together, our results suggest a complex interplay between visual feature and attention coding in the primate brain, likely driven by interactions between brain areas engaged in these processes
Patient- and community-level characteristics associated with respiratory syncytial virus vaccination
No full textIMPORTANCE: In 2023, the first respiratory syncytial virus (RSV) vaccines were recommended for US adults 60 years or older, but few data are available about which patients were most likely to receive vaccine to inform future RSV vaccine outreach efforts.
OBJECTIVE: To assess patient- and community-level characteristics associated with RSV vaccine receipt and patient knowledge and attitudes related to RSV disease and RSV vaccines.
DESIGN, SETTING, AND PARTICIPANTS: During the first season of RSV vaccine use from October 1, 2023, to April 30, 2024, adults 60 years or older hospitalized with RSV-negative acute respiratory illness were enrolled in this cross-sectional study from 26 hospitals in 20 US states. Sociodemographic and clinical data were abstracted from health records, and structured interviews were conducted for knowledge and attitudes about RSV disease and RSV vaccines.
EXPOSURES: Age, sex, race and ethnicity, pulmonary disease, immunocompromised status, long-term care facility residence, medical insurance, social vulnerability index (SVI), and educational level.
MAIN OUTCOMES AND MEASURES: The exposures were identified a priori as possible factors associated with RSV vaccine receipt and were entered into a modified Poisson regression model accounting for state clustering, to assess for association with RSV vaccine receipt. Knowledge and attitudes were summarized with frequencies and proportions.
RESULTS: Among 6746 hospitalized adults 60 years or older, median age was 73 (IQR, 66-80) years and 3451 (51.2%) were female. Among the 6599 patients with self-reported race and ethnicity, 699 (10.6%) were Hispanic, 1288 (19.5%) were non-Hispanic Black, 4299 (65.1%) were non-Hispanic White, and 313 (4.7%) were other race or ethnicity. There were 700 RSV-vaccinated (10.4%) and 6046 unvaccinated (89.6%) adults. Among 3219 unvaccinated adults who responded to RSV knowledge questions, 1519 (47.2%) had not heard of RSV or were unsure; 2525 of 3218 (78.5%) were unsure if they were eligible for RSV vaccine or thought they were not. In adjusted analyses, characteristics associated with RSV vaccination were being 75 years or older (adjusted risk ratio [ARR], 1.23; 95% CI, 1.10-1.38, P \u3c .001), being male (ARR, 1.15; 95% CI, 1.01-1.30; P = .04), and having pulmonary disease (ARR, 1.39; 95% CI, 1.16-1.67; P \u3c .001), immunocompromised status (ARR, 1.30; 95% CI, 1.14-1.48; P \u3c .001), low (ARR, 1.47; 95% CI, 1.18-1.83, P \u3c .001) or moderate (ARR, 1.47; 95% CI, 1.21-1.79; P \u3c .001) SVI, and educational level consisting of 4 or more years of college (ARR, 2.91; 95% CI, 2.14-3.96; P \u3c .001), at least some college or technical training (ARR, 1.85; 95% CI, 1.35-2.53; P \u3c .001), or grade 12 education or General Educational Development (ARR, 1.44; 95% CI, 1.03-2.00; P = .03). RSV vaccination was less likely among residents of long-term care facilities, patients with Medicaid coverage, and uninsured patients.
CONCLUSIONS AND RELEVANCE: In this cross-sectional study of hospitalized adults, knowledge of RSV disease and RSV vaccine eligibility was low. Older adults and those with certain medical conditions were more likely to have received vaccine, suggesting appropriate prioritization, but sociodemographic differences in vaccine uptake occurred
Cause of death for heart transplant patients, an autopsy study
No full textINTRODUCTION: Heart transplantations are lifesaving for patients with end-stage heart failure. It is pertinent for the multidisciplinary care team to understand how heart transplant patients succumbed to death and the complications that occurred. In this study, we performed a comprehensive retrospective review of all the autopsies performed in our institute for heart transplant patients and report the trend of demographic data, cause of death, and autopsy findings.
MATERIALS AND METHODS: Reports, photos, and slides of autopsies performed at our institute from 1990 to 2023 for heart transplant patients were reviewed. Pertinent demographic data (age, gender, pretransplant diagnosis), clinical data (clinical history of rejection, complication, time interval from transplant to death, clinical cause of death) and pathological findings (allograft pathology, infectious etiology, other findings related to cause of death) were reviewed, documented, and analyzed.
RESULTS: We identified 88 cases, consisting of 53 male and 35 female patients. The median age at transplant was 26 years, while 28.5 years was the median age at death. The median interval from transplant to death was 10 months. The cases were classified in three categories based on length of survival post-transplant: Superacute (\u3c1 month, 21%), Early (1 month-12 months, 30%), and Late (\u3e 12 months, 49%). Slides were unavailable for review in 15 cases, which were excluded from cause of death (COD) evaluation. We categorized 41.1% of cases as allograft-related COD and 58.9% as non-allograft-related COD. Six of the CODs were not perceived premortem. These unexpected CODs included moderate/severe acute cellular rejection in a patient with a recently negative biopsy, dehiscent suture caused by a fungal abscess, an aorto-bronchial fistula, CMV myocarditis, acute abdominal bleeding, and ruptured atherosclerotic plaques with acute myocardial infarction.
CONCLUSION: We systematically reviewed 33 years of heart transplant autopsies. We found that 41.1% of deaths were allograft related, with infection being the most frequent COD. While the rate of unexpected findings was low, the findings demonstrate the continued utility of autopsy in patient evaluation
Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapies
No full textMosunetuzumab, a CD20×CD3 T-cell engaging bispecific antibody, redirects T cells to eliminate malignant B cells. We present updated efficacy and safety data of a pivotal phase 1/2 study after a median follow-up of 37.4 months in 90 patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy treated with fixed-duration mosunetuzumab. Investigator-assessed complete response (CR) rate and objective response rate were 60.0% (95% confidence interval [CI], 49.1-70.2) and 77.8% (95% CI, 67.8-85.9), respectively. Among 70 responders, median duration of response was 35.9 months (95% CI, 20.7 to not estimable [NE]). Among 54 patients who achieved CR, 49 remained in CR at the end of treatment; median duration of CR was not reached (NR; 95% CI, 33.0 to NE); Kaplan-Meier-estimated 30-month remission rate was 72.4% (95% CI, 59.2-85.6). Estimated 36-month overall survival (OS) rate was 82.4% (95% CI, 73.8-91.0); median OS was NR (95% CI, NE to NE). Median progression-free survival was 24.0 months (95% CI, 12.0 to NE). Median time to CD19+ B-cell recovery was 18.4 months (95% CI, 12.8-25.0) after 8 cycles of mosunetuzumab treatment. No new cytokine release syndrome events or fatal, serious, or grade ≥3 adverse events were reported. With extended follow-up, mosunetuzumab demonstrated high response rates, durable remissions, and manageable safety with no long-term concerns. This supports outpatient mosunetuzumab administration as an off-the-shelf, fixed-duration, safe, and effective treatment for patients with R/R FL, including those with high-risk disease. This trial was registered at www.clinicaltrials.gov as #NCT02500407
Engineering adhesive hydrogels for hemostasis and vascular repair
No full textAdhesive hydrogels with tunable mechanical properties and strong adhesion to wet, dynamic tissues have emerged as promising materials for tissue repair, with potential applications in wound closure, hemorrhage control, and surgical adhesives. This review highlights the key design principles, material classifications, and recent advances in adhesive hydrogels designed for vascular repair. The limitations of existing adhesive hydrogels, including insufficient mechanical durability, suboptimal biocompatibility, and challenges in targeted delivery, are critically evaluated. Furthermore, innovative strategies-such as incorporating self-healing capabilities, developing stimuli-responsive systems, integrating functional nanocomposites, and employing advanced fabrication techniques like 3D bioprinting-are discussed to enhance adhesion, mechanical stability, and vascular tissue regeneration. While significant progress has been made, further research and optimization are necessary to advance these materials toward clinical translation, offering a versatile and minimally invasive alternative to traditional vascular repair techniques
Implementation of the Extension for Community Healthcare Outcomes model for hypertension education of frontline health care workers in the Federal Capital Territory, Nigeria: Explanatory sequential mixed methods evaluation
No full textBACKGROUND: The Extension for Community Healthcare Outcomes (ECHO) model was adapted for hypertension education of community health extension workers in the Federal Capital Territory, Nigeria, and delivered as a 7-part series.
OBJECTIVE: This study aims to evaluate implementation outcomes of the hypertension ECHO series mapped to the first 3 levels of the Kirkpatrick model. Outcomes included reach, appropriateness (level 1), effectiveness (level 2), and penetration (level 3).
METHODS: From August 2022 to April 2023, 7 hypertension ECHO sessions were delivered via Zoom (Zoom Video Communications, Inc) to a health care worker audience including targeted community health extension workers at 12 primary health centers (PHCs) in the Hypertension Treatment in Nigeria Program. Health care workers provided demographic information, engaged in pre- and postsession knowledge quizzes, and shared feedback during live sessions. Surveys were sent to health care workers at 12 PHCs approximately 1 month after each session to ask about the use of the presented material and focus group discussions were performed with these health care workers after the ECHO program concluded. Qualitative and quantitative results were evaluated using an explanatory sequential mixed methods design wherein qualitative data were used to help explain outcomes and variability among participants.
RESULTS: Across 7 ECHO sessions, a total of 1407 live participants were documented. Participants largely found the program was acceptable, with more than 97% of respondents reporting that the session was useful. Postsession knowledge scores increased (range: 2.3%-10.5%) relative to presession scores demonstrating moderate effectiveness. Among 12 PHCs, most (more than 70%) health care workers applied information learned in each session to provide patient care. In 6 focus group discussions, with 31 health care workers (n=15; 48% community health extension workers), participants reported that network connectivity and clinical demands were barriers to live participation and expressed preferences for blended training and asynchronous resources.
CONCLUSIONS: Results show that a hypertension ECHO program adapted for community health extension workers effectively increased knowledge among participants and was useful to a majority. Insights gained may inform the scaling of remote hypertension education programs for community health extension workers in similar settings.
TRIAL REGISTRATION: ClinicalTrials.gov NCT04158154; https://clinicaltrials.gov/ct2/show/NCT04158154
Mechanisms of photoreceptor protection upon targeting the Nrl-Nr2e3 pathway
No full textAcute knockout of the rod photoreceptor transcription facto
Subcortical correlates of consciousness with human single neuron recordings
No full textSubcortical brain structures such as the subthalamic nucleus or the thalamus are involved in regulating motor and cognitive behavior. However, their contribution to perceptual consciousness remains unclear, due to the inherent difficulties of recording subcortical neuronal activity in humans. Here, we asked neurological patients undergoing surgery for deep brain stimulation to detect weak vibrotactile stimuli applied on their hand while recording single neuron activity from the tip of a microelectrode. We isolated putative single neurons in the subthalamic nucleus and thalamus. A significant proportion of neurons modulated their activity while participants were expecting a stimulus. We found that the firing rate of 23% of these neurons differed between detected and undetected stimuli. Our results provide direct neurophysiological evidence of the involvement of the subthalamic nucleus and the thalamus for the detection of vibrotactile stimuli, thereby calling for a less cortico-centric view of the neural correlates of consciousness
Simulation-guided pan-cancer analysis identifies a novel regulator of CpG island hypermethylation heterogeneity
No full textCpG island hypermethylation, a hallmark of cancer, exhibits substantial heterogeneity across tumors, presenting both opportunities and challenges for cancer diagnostics and therapeutics. While this heterogeneity offers potential for patient stratification to predict clinical outcomes and personalize treatments, it complicates the development of robust biomarkers for early detection. Understanding the mechanisms driving this heterogeneity is essential for advancing biomarker design. Here, simulation-based analyses demonstrate that tumor purity and the high prevalence of low epi-mutation samples significantly obscure the identification of negative, rather than positive, regulators of CpG island hypermethylation, limiting a comprehensive understanding of heterogeneity sources. By addressing these confounders, we identify impaired DNA methylation maintenance, as indicated by global hypomethylation levels, as the primary contributor to CpG island hypermethylation variability among known regulators. This finding is supported by integrative analyses of datasets from The Cancer Genome Atlas (TCGA) Pan-Cancer Atlas, Genomics of Drug Sensitivity in Cancer (GDSC1000) cancer cell lines, and epi-allele analyses of two independent whole-genome bisulfite sequencing cohorts, using a newly developed method, MeHist (https://github.com/vhang072/MeHist). Furthermore, we assess widely used hypermethylation biomarkers across ten cancer types and find that 65 out of 246 (26.4%) are significantly influenced by impaired methylation maintenance. Incorporating hypomethylation and hypermethylation markers improves the robustness of cancer detection, as validated across multiple plasma cell-free DNA datasets. In summary, our findings highlight the value of simulation-guided integrative analysis in mitigating confounding effects and identify impaired DNA methylation maintenance as a key regulator of CpG island hypermethylation heterogeneity
Active transport enables protein condensation in cells
No full textMultiple factors drive biomolecular condensate formation. In plants, condensation of the transcription factors AUXIN RESPONSE FACTOR 7 (ARF7) and ARF19 attenuates response to the plant hormone auxin. Here, we report that actin-mediated movement of cytoplasmic ARF condensates enhances condensation. Coarse-grained molecular simulations of active polymers reveal that applied forces drive the associations of macromolecules to enhance phase separation while giving rise to dense phases that preferentially accumulate motile molecules. Our study highlights how molecular motility can drive phase separation, with implications for motile condensates while offering insights into cellular mechanisms that can regulate condensate dynamics