bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating potential program cost savings with a single-dose HPV vaccination schedule: a modeling study
Authors: Slavkovsky Rose , Mvundura Mercy , Debellut Frédéric , Naddumba Teddy 
Published: November 2024

Abstract

Background
There is limited evidence on the magnitude of the potential program cost savings associated with the World Health Organization–endorsed single-dose schedule for the human papillomavirus (HPV) vaccine. The objective of this analysis was to model the delivery and vaccine procurement cost implications of the new schedule.

Methods
The analysis leveraged primary data during a study evaluating the HPV vaccine delivery costs and operational context in 5 countries (Ethiopia, Guyana, Rwanda, Sri Lanka, and Uganda) implementing a two-dose schedule. To estimate the cost for the single-dose schedule, we adjusted the two-dose schedule cost estimates to account for differences in the frequency of activities, whether activities differed by HPV vaccine dose or session, and differences in relative quantity or storage volume of HPV vaccines delivered. We estimated the cost per dose and cost per adolescent receiving the full (single-dose or two-dose) vaccination schedule in 2019 US dollars from a health system perspective.

Results
Modeled results found that cost per dose would increase under a single-dose schedule, whereas cost per adolescent receiving the full schedule would decrease. The financial cost for vaccine procurement and delivery per adolescent receiving the full schedule ranged from $9.64 (Sri Lanka) to $23.43 (Guyana) under a two-dose schedule and decreased to $4.84 and $12.34, respectively, under a single-dose schedule, reflecting savings up to 50%. For economic costs, the range for a single-dose schedule was $7.86 (Rwanda) to $28.53 (Guyana).

Conclusion
A single-dose HPV vaccination schedule could provide cost savings to immunization programs and enhance program affordability and sustainability.
A prospective cohort study comparing efficacy of 1 dose of quadrivalent human papillomavirus vaccine to 2 and 3 doses at an average follow up of 12 years postvaccination
Authors: Malvi Sylla G , Esmy Pulikkottil O , Muwonge Richard , Joshi Smita , Poli Usha Rani Reddy , Lucas Eric , Verma Yogesh , Lucksom Pesona Grace , Shah Anand , Patel Bijal , Zomawia Eric , Pimple Sharmila , Jayant Kasturi , Hingmire Sanjay , Chiwate Aruna , Divate Uma , Vashist Shachi , Mishra Gauravi , Jadhav Radhika , Siddiqi Maqsood , Sauvaget Catherine , Sankaran Subha , Kannan Thiraviam Pillai Rameshwari Ammal , Shastri Surendra S , Pillai M Radhakrishna , Anantharaman Devasena , Bhatla Neerja , Sankaranarayanan Rengaswamy , Basu Partha 
Published: November 2024

Abstract

Background
While recommending a human papillomavirus (HPV) single-dose vaccination schedule in 2022, the World Health Organization highlighted the need for long-term follow-up studies to monitor waning of protection. We report on vaccine efficacy against HPV infections in 1-, 2-, and 3-dose schedules and protection against cervical precancers at a median follow-up of 12 years postvaccination.

Methods
This randomized multicenter study in India was originally designed to vaccinate unmarried girls aged 10-18 years with either 2 or 3 doses of quadrivalent HPV vaccine. A ministerial decree to halt vaccination in trials resulted in the creation of cohorts receiving different doses, including just a single dose. Cohorts were assessed for incident and persistent infections by genotyping cervical samples collected yearly for 4 consecutive years after participants were married. Cervical screening with an HPV test was initiated at age 25 years for married participants. Age- and site-matched unvaccinated married women were recruited to be compared with vaccinated cohorts. Vaccine efficacy was assessed using proportional incidence ratios.

Results
The number of participants in the 1-, 2- (at 0 and 6 months), and 3-dose cohorts was 4949, 4980, and 4348, respectively. Of the recipients, 71%-82% in the different cohorts were eligible to provide samples for genotyping. Vaccine efficacy against persistent HPV 16 and 18 infection was 92.0% (95% confidence interval [CI] = 87.0% to 95.0%) in 3022 recipients of the single dose; and comparable with that observed in the 2-dose arm (94.8%, 95% CI = 90.0% to 97.3%) and the 3-dose arm (95.3%, 95% CI = 90.9% to 97.5%). No high-grade precancer associated with HPV 16 and 18 was detected among vaccinated participants compared with 8 precancers detected among the unvaccinated women.

Conclusion
This observational cohort study has established that a single dose of HPV vaccine provides high protective efficacy against persistent HPV 16 and 18 infections and associated neoplasia 15 years postvaccination.
Evaluation of Visual Disturbances After Mild Traumatic Brain Injury—A One-Year Follow-up Study
Authors: Mona-Lisa Möller , Kaisa Mäki , Taina Nybo , Antti Huovinen , Ivan Marinkovic , Susanna Melkas , Jan Johansson 
Published: November 2024

Objective:
To examine the persistence of visual symptoms in mild traumatic brain injury (MTBI) during the first months after injury. It is important to recognize visual disturbances because they can delay return to normal activities, while they might be simultaneously treated by visual therapy. Here we describe the results from a 1-year follow-up study of visual disturbances after MTBI.

Participants and Measures:
The study group comprised 26 patients from the Brain Injury Clinic of the Helsinki University Hospital. Inclusion criterion was a high score (≥21p) on the Convergence Insufficiency Symptom Survey (CISS) at an appointment with a neurologist within 6 months after injury. The patients underwent baseline vision evaluation at 4 months on average and follow-up at 14 months after injury. The evaluation included tests for visual acuity, near point of convergence, convergence facility, near point of accommodation, accommodative facility, motility, heterophoria, binocular vision, dynamic visual acuity, and fusional vergence width at near and far distances. Further assessments included the Rivermead Post Concussion Questionnaire for posttraumatic symptoms, a visual analog scale for visual fatigue, and the Developmental Eye Movement Test for saccadic eye movements.

Results:
Both CISS and Rivermead Post Concussion Questionnaire scores improved significantly from baseline to follow-up. The overall level of visual fatigue according to visual analog scale score was lower at follow-up, but the increase in visual fatigue (comparing fatigue before and after assessment session) was significant both at baseline and follow-up. In visual function assessments, spontaneous recovery from baseline to follow-up could be seen in vergence facility and pursuit eye movement but not in near point of convergence, near fusion, distance fusion, heterophoria, and dynamic visual acuity.

Conclusion:
The results point out the importance of evaluation of visual disturbances after MTBI. Early detection of these disturbances may provide an opportunity to provide visual therapy.
Consistency in Self-Reported Race-and-Ethnicity Over Time
Authors: Haas Ann , Martino Steven C. , Haviland Amelia M. , Beckett Megan K. , Dembosky Jacob W. , Binion Joy , Hill Torrey , Elliott Marc N. 
Published: November 2024

Background:
Medicare Bayesian Improved Surname and Geocoding (MBISG), which augments an imperfect race-and-ethnicity administrative variable to estimate probabilities that people would self-identify as being in each of 6 mutually exclusive racial-and-ethnic groups, performs very well for Asian American and Native Hawaiian/Pacific Islander (AA&NHPI), Black, Hispanic, and White race-and-ethnicity, somewhat less well for American Indian/Alaska Native (AI/AN), and much less well for Multiracial race-and-ethnicity.

Objectives:
To assess whether temporal inconsistency of self-reported race-and-ethnicity might limit improvements in approaches like MBISG.

Methods:
Using the Medicare Health Outcomes Survey (HOS) baseline (2013–2018) and 2-year follow-up data (2015–2020), we evaluate the consistency of self-reported race-and-ethnicity coded 2 ways: the 6 mutually exclusive MBISG categories and individual endorsements of each racial-and-ethnic group. We compare the consistency of self-reported race-and-ethnicity (HOS) to the accuracy of MBISG (using 2021 Medicare Consumer Assessment of Healthcare Providers and Systems data).

Results:
Concordance (C-statistic) of HOS baseline and follow-up self-reported race-and-ethnicity was 0.95–0.97 for AA&NHPI, Black, Hispanic, and White, 0.83 for AI/AN, and 0.72 for Multiracial using mutually exclusive categories (weighted concordance=0.956). Concordance of MBISG with self-report followed a similar pattern and had similar values, with somewhat lower AI/AN and Multiracial values. The concordance of individual endorsements over time was somewhat higher than for classification (weighted concordance=0.975).

Conclusions:
The concordance of MBISG with self-reported race-and-ethnicity appears to be limited by the consistency of self-report for some racial-and-ethnic groups when employing the 6-mutually-exclusive category approach. The use of individual endorsements can improve the consistency of self-reported data. Reconfiguring algorithms such as MBISG in this form could improve its overall performance.
Asymmetry of Directed Brain Connectivity at Birth in Low-Risk Full-Term Newborns
Authors: Chirumamilla Venkata C. , Mulkey Sarah B. , Anwar Tayyba , Baker Robin , Maxwell G. Larry , De Asis-Cruz Josepheen , Kapse Kushal , Limperopoulos Catherine , du Plessis Adre , Govindan R. B. 
Published: November 2024

Purpose:
Functional connectivity hubs were previously identified at the source level in low-risk full-term newborns by high-density electroencephalography (HD-EEG). However, the directionality of information flow among hubs remains unclear. The aim of this study was to study the directionality of information flow among source level hubs in low-risk full-term newborns using HD-EEG.

Methods:
A retrospective analysis of HD-EEG collected from a prospective study. Subjects included 112 low-risk full-term (37–41 weeks' gestation) newborns born in a large delivery center and studied within 72 hours of life by HD-EEG. The directionality of information flow between hubs at the source level was quantified using the partial directed coherence in the delta frequency band. Descriptive statistics were used to identify the maximum and minimum information flow. Differences in information flow between cerebral hemispheres were assessed using Student t-test.

Results:
There was higher information flow from the left hemisphere to the right hemisphere hubs (p < 0.05, t-statistic = 2). The brainstem had the highest information inflow and lowest outflow among all the hubs. The left putamen received the lowest information, and the right pallidum had the highest information outflow to other hubs.

Conclusions:
In low-risk full-term newborns, there is a significant information flow asymmetry already present, with left hemisphere dominance at birth. The relationship between these findings and the more prevalent left hemisphere dominance observed in full-term newborns, particularly in relation to language, warrants further study.
EEG Infrastructure Within the Veterans Administration: A Survey
Authors: Lu Alisa , Chandra Krishna , Kovalev Dmitri , Savarese Edward N. , Patel Kamakshi , McCarthy David C. , Eisenschenk Stephan , Haneef Zulfi 
Published: November 2024

Purpose:
EEG is a vital tool in the diagnosis and management of neurologic conditions prevalent among veterans such as seizures, epilepsy, and brain injuries. This cross-sectional study aimed to assess the state of EEG infrastructure within the Veterans Administration (VA), focusing on availability, utilization, and the potential avenues to addressing gaps in infrastructure.

Methods:
This survey was distributed to 123 VA hospitals using the Research Electronic Data Capture (REDCap) platform, gathering data on EEG equipment, staffing, and service provision from June to December 2023.

Results:
Of the 123 VA hospitals surveyed, 70 responded (56.9% response rate). Most respondents (88.6%) reported having EEG services, although only 38.7% offering continuous EEG (cEEG). Respondents reported having less EEG technologists, machines, and faculty readers than what they thought would be ideal. Significant correlations were found between the availability of resources (e.g., number of EEG machines) and service capabilities, including remote access and cEEG. The use of alternative EEG technologies such as rapid or quantitative EEG varied greatly. Interest in participating in the VA Tele-EEG program was reported by 59.4% of respondents.

Conclusions:
There is large variability in EEG infrastructure across the VA. Tele-EEG has the potential to maintain continuity of operations through challenges affecting staffing and to improve EEG service access, especially in resource-limited settings. Expanding access to quantitative, rapid, and tele-EEG services may enhance patient management and may be a potential avenue to explore as the VA continues to invest in and grow its capacity for treating neurologic conditions.
Broad thermal tolerance and high mitochondrial genetic connectivity in the pinfish (Lagodon rhomboides)
Authors: Eaton Katherine M. , Samenuk Jacob E. , Thaxton Laurel , Chaves Victoria , Bernal Moisés A. 
Published: November 2024

AbstractPinfish (Lagodon rhomboides) are highly abundant in coastal ecosystems of the Gulf of Mexico and western Atlantic Ocean and serve as a crucial link in marine food webs. Despite their ecological relevance, little is known about this species’ susceptibility to anthropogenic climate change. Here, we characterized patterns of mitochondrial genetic divergence and examined the upper thermal tolerance of pinfish across a large portion of the species’ range. We found little evidence of population genetic differentiation among distant localities with divergent temperature regimes (e.g., Mexico and North Carolina), using two mitochondrial markers (CytBandCOI). This suggests high genetic connectivity, which implies low potential for local adaptation of populations to different thermal conditions along a latitudinal gradient. To further examine population-scale differences in thermal tolerance, we assessed the critical thermal maxima (CTmax) of pinfish from four localities: North Carolina, Florida Keys, Alabama, and Texas. We found that CTmaxwas similar across sites, with all localities showing an average CTmaxwithin a 1°C temperature range (34.5-35.5°C). This suggests that southern populations of pinfish may be more susceptible to the detrimental effects of ocean warming, as individuals in lower latitudes regularly experience temperatures within a few degrees of their CTmax. Finally, we examined the influence of varying salinity on the upper thermal limit of the pinfish and found that pinfish show no variation in CTmaxunder salinity conditions ranging from hypo-to hyper-saline (15-35 ppt). These results show that pinfish can tolerate a wide range of environmental parameters, but may rely on phenotypic plasticity rather than local adaptation to distinct conditions to cope with different environmental regimes.
Comprehensive baseline ctDNA characterization in two biomarker-selected Phase 1/2 studies using genomic and methylation profiling
Authors: Silverman Ian M. , Schonhoft Joseph D. , Herzberg Benjamin , Yablonovitch Arielle , Lagow Errin , Sethuraman Sunantha , Ulanet Danielle , Yang Julia , Kim Insil , Basciano Paul , Cecchini Michael , Lee Elizabeth , Lheureux Stephanie , Fontana Elisa , Carneiro Benedito A. , Reis-Filho Jorge S. , Yap Timothy A. , Zinda Michael , Rosen Ezra Y. , Rimkunas Victoria 
Published: November 2024

ABSTRACTThe development of DNA damage response (DDR)-directed therapies is a major area of clinical investigation, yet to date Poly (ADP-ribose) polymerase (PARP) inhibitors remain the only approved therapy in this space. Major challenges to DDR-targeted therapies in the post-PARPi era are the context dependency of DDR alterations and the presence of pre-existing resistance in this heavily pre-treated population. To that end, we used a contemporary platform to analyze pre-treatment circulating tumor DNA (ctDNA) samples from 173 patients enrolled onto two Phase 1/2 trials harboring pathogenic variants (PVs) in DDR genes. Baseline ctDNA analysis revealed a wealth of insights, including circulating tumor fraction estimation, impact of clonal hematopoiesis, PV allelic status, homologous recombination deficiency (HRD) signatures and presence of pre-existing resistance. HRD reversions were detected in 44% of evaluable patients and included large genomic rearrangements leading to deletion of whole or partial exons. We also discovered reversion ofATMin two patients previously treated with platinum chemotherapy, which has not previously been described. This study showcases the genomic complexity of DDR-altered tumors, revealed through baseline ctDNA profiling, an understanding of which is crucial for the future clinical development of novel DDR-directed therapies and combinations.
Impact of chronic pain on numerous long COVID-like symptoms: A large-scale internet-based epidemiological study in Japan
Authors: Takaoka Saki , Saito Hanako , Kawate Morihiko , Tanaka Chisato , Wu Yihuan , Kosugi Shizuko , Yamada Takashige , Tabuchi Takahiro , Wakaizumi Kenta 
Published: November 2024

AbstractBackgroundIndividuals with chronic pain (CP) not only endure the direct burden of the pain but also experience various symptoms, including sleep disturbances and fatigue, which deteriorate their quality of life. Notably, these symptoms closely resemble those observed in ‘long COVID’, a prolonged health complication that can arise after coronavirus disease 2019 (COVID-19) infection. However, the similarities between them have not yet been explored. Therefore, this study aimed to investigate the relationship between CP and long COVID using Japanese epidemiological data.MethodsUtilizing the Japan COVID-19 and Society Internet Survey in 2022, an Internet-based survey involving 32,000 participants, we analysed data on the presence of CP, history of COVID-19 infection, and presence of 17 long COVID-like symptoms, including gastrointestinal upset, back pain, limb/joint pain, headache, chest pain, shortness of breath, dizziness, sleep disorder, hearing disorder, taste disorder, smell disorder, memory impairment, poor concentration, hair loss, decreased libido, fatigue, and cough.ResultsIndividuals with history of COVID-19 experienced a significantly greater number of long COVID-like symptoms (median: 5) compared to those with neither COVID-19 nor CP (median: 4,p< 0.001). However, individuals with CP alone and those with both COVID-19 and CP exhibited an even greater number of symptoms (median: 8 and 9, respectively). Additionally, individuals with CP exhibited greater prevalence odds for 15 of the 17 symptoms than those without CP or COVID-19 (p< 0.001).ConclusionsAltogether, our study suggests that the long COVID-like symptoms are not specifically related to COVID-19, but CP is an independent risk factor for these symptoms.
Identification of Digital Twins to Guide Interpretable AI for Diagnosis and Prognosis in Heart Failure
Authors: Gu Feng , Meyer Andrew J. , Ježek Filip , Zhang Shuangdi , Catalan Tonimarie , Miller Alexandria , Schenk Noah , Sturgess Victoria , Uceda Domingo , Li Rui , Wittrup Emily , Hua Xinwei , Carlson Brian E. , Tang Yi-Da , Raza Farhan , Najarian Kayvan , Hummel Scott L. , Beard Daniel A. 
Published: November 2024

SummaryBackgroundHeart failure (HF) is a highly heterogeneous and complex condition. Although patient care generates vast amounts of clinical data, robust methods to synthesize available data for individualized management are lacking.MethodsA mechanistic computational model of cardiac and cardiovascular system mechanics was identified for each individual in a cohort of 343 patients with HF. The identifieddigital twins— comprising optimized sets of parameters and corresponding simulations of cardiovascular system function—for patients with HF in the cohort is used to inform both supervised and unsupervised approaches in identifying phenogroups and novel mechanistic drivers of cardiovascular death risk.FindingsThe integration of digital twins into AI-based analyses of patient data enhances the performance and interpretability of prognostics AI models. Prognostics AI models trained with digital twin features are more generalizable than models trained with only clinical variables, as evaluated using an independent prospective cohort. In addition, the digital twin-based approach to phenomapping and predictive AI helps address inconsistencies and inaccuracies in clinical measurements, enables imputation of missing data, and estimates functional parameters that are otherwise unmeasurable directly. This approach provides a more comprehensive and accurate representation of the patient’s disease state than raw clinical data alone.InterpretationThe developed and validated digital twin-based AI framework has the potential to simulate patient-specific pathophysiologic parameters, thereby informing prognosis and guiding therapeutic options.Ultimately, this approach has the potential to enhance the ability to focus on the most critical aspects of a patient’s condition, leading to individualized care and management.FundingNational Institutes of Health and Joint Institute for Translational and Clinical Research (University of Michigan and Peking University Health Science Center)
Loss ofCFHR5function reduces the risk for age-related macular degeneration
Authors: Reeve Mary Pat , Loomis Stephanie , Nissilä Eija , Rausch Tobias , Zheng Zhili , Briotta Parolo Pietro Della , Ben-Isvy Daniel , Aho Elias , Cesetti Emilia , Okunuki Yoko , McLaughlin Helen , Mäkelä Johanna ,   FinnGen, Kurki Mitja , Talkowski Michael E. , Korbel Jan O. , Connor Kip , Meri Seppo , Daly Mark J. , Runz Heiko 
Published: November 2024

AbstractAge-related macular degeneration (AMD) is a prevalent cause of vision loss in the elderly with limited therapeutic options. A single chromosomal region around the complement factor H gene (CFH) is reported to explain nearly 25% of genetic AMD risk. Here, we used association testing, statistical finemapping and conditional analyses in 12,495 AMD cases and 461,686 controls to deconvolute four majorCFHhaplotypes that convey protection from AMD. We show that beyondCFH, two of these are explained by Finn-enriched frameshift and missense variants in theCFHmodulatorCFHR5. We demonstrate through a FinnGen sample recall study thatCFHR5variant carriers exhibit dose-dependent reductions in serum levels of theCFHR5gene product FHR-5 and two functionally related proteins at the locus. Genetic reduction in FHR-5 correlates with higher preserved activities of the classical and alternative complement pathways. Our results propose therapeutic downregulation of FHR-5 as promising to prevent or treat AMD.