bluuebunny/crossref_metadata_2025_split huggingface dataset:
The potential clinical impact and cost-effectiveness of the updated COVID-19 mRNA Fall 2023 vaccines in the United States
Authors: Kohli M , Maschio M , Joshi K , Lee A , Fust K , Beck E , Van de Velde N , Weinstein MC 
Published: September 2023

AbstractObjectivesTo assess the potential clinical impact and cost-effectiveness of COVID-19 mRNA vaccines updated for Fall 2023 in adults ≥18 years over a 1-year analytic time horizon (September 2023-August 2024).MethodsA compartmental Susceptible-Exposed-Infected-Recovered model was updated to reflect COVID-19 in summer 2023. Numbers of symptomatic infections, COVID-19 related hospitalizations and deaths, and costs and quality-adjusted life-years (QALYs) gained were calculated using a decision tree model. The incremental cost-effectiveness ratio (ICER) of a Moderna updated mRNA Fall 2023 vaccine (Moderna Fall Campaign) was compared to no additional vaccination. Potential differences between the Moderna and the Pfizer-BioNTech Fall 2023 vaccines were examined.ResultsBase case results suggest the Moderna Fall Campaign would decrease the expected 64.2 million symptomatic infections by 7.2 million (11%) to 57.0 million. COVID-19-related hospitalizations and deaths are expected to decline by 343,000 (–29%) and 50,500 (–33%), respectively. The Moderna Fall Campaign would increase QALYs by 740,880 and healthcare costs by $5.7 billion relative to No Vaccine, yielding an ICER of $7,700 per QALY gained. Using a societal cost perspective, the ICER is $2,100. Sensitivity analyses suggest that vaccine effectiveness, COVID-19 incidence, hospitalization rates and costs drive cost-effectiveness. With a relative vaccine effectiveness (rVE) of Moderna versus Pfizer-BioNTech of 5.1% for infection and 9.8% for hospitalization, use of the Moderna vaccine is expected to prevent 24,000 more hospitalizations and 3,300 more deaths than the Pfizer-BioNTech vaccine.Limitations and ConclusionsAs COVID-19 becomes endemic, future incidence, including patterns of infection, are highly uncertain. Vaccine effectiveness of Fall 2023 vaccines is unknown, and it is unclear when a new variant that evades natural or vaccine immunity will emerge. Despite these limitations, the Moderna Fall 2023 vaccine can be considered cost-effective relative to no vaccine.
Prediction of fall-risk factors specific to the old-age Indian population
Authors: Sharma Abhinav , Sharma Mehul , Sharma Ashish Arunkumar 
Published: September 2023

AbstractBackground/ObjectivesThe health care infrastructure of India, designed to treat acute problems, can benefit from preventive medicine-based policies that address chronic and non-communicable issues of relevance to India’s growing elderly population. Unintentional fall related injuries are one such issue whose economic burden can be streamlined with proper preventative public health policies. It is imperative that fall-risk factors specific to the Indian population be identified and analyzed for use in geriatric falls-risk assessment. We aim to determine factors predictive of falls in the aging Indian population in this study using Wave 1 data from the World Health Organization Study on Global Ageing and Adult Health (WHO SAGE) in India.MethodsCross-sectional analysis of results from WHO SAGE Wave 1 was conducted. Multivariate analysis was used to determine risk factors of falls specific to the Indian population in adults over the age of 50. Prediction models were created and evaluated using these risk factors and their performances were evaluated. SAGE Wave 1 India was implemented in six states that together provided nationally representative samples. Multistage stratified sampling was used to select these states and systematic sampling was used to select households from villages and urban districts within these states. Data from all individuals over the age of 50 in selected households was compiled for analysis.Findings34 fall risk factors specific to the Indian population were determined. The model that did not weigh the factors was determined as the best model for possible use in clinically assessing old-age adults at risk for falling. Furthermore, 6 risk factors in the Indian census were used to identify falls risks hotspots on a district-level map of India.ConclusionThis analysis can be used in public health policy recommendations and can form a basis for assessing and addressing falls-risk issues in India.
Identification of Potential EGFR Inhibitors for Type 2 Diabetes and Pancreatic Cancer Treatment: A Computational Approach
Authors: Romero Ricardo 
Published: September 2023

AbstractThis study conducted a differential gene expression analysis in two independent studies of type 2 diabetes using pancreatic samples, specifically Langerhans cells. Through protein-protein interaction network analysis, the Epidermal Growth Factor Receptor (EGFR) emerged as the top hub gene among the upregulated genes in both studies. Furthermore, functional enrichment analysis revealed the involvement of EGFR in pancreatic cancer signaling pathways, indicating its potential role beyond diabetes.To identify potential EGFR inhibitors, a virtual screening approach was employed using tyrosine kinase inhibitors. Two separate deep learning classification models were developed and trained on distinct sets of ligands, one for predicting bioactivity and the other for assessing toxicity. The ligands underwent rigorous filtering based on binding energies and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.This filtering process resulted in the identification of nine hits that demonstrated promising characteristics in terms of both bioactivity and druglikeness, making them viable candidates for further development as EGFR inhibitors.To evaluate the performance of the identified hits, approved drugs including Afatinib, Almonertinib, Erlotinib, Gefitinib, and Osimertinib were used as controls. Notably, the finalist compounds consistently outperformed the control drugs across all evaluated parameters, indicating their superior potential as EGFR inhibitors.This study provides valuable insights into the molecular mechanisms underlying type 2 diabetes by highlighting the significant role of EGFR and its potential association with pancreatic cancer signaling pathways. Moreover, the identified hits from the virtual screening represent promising candidates for further investigation and development of improved drugs targeting EGFR.
Economic analysis of disease and control of multi-field epidemics in agriculture
Authors: Mikaberidze Alexey , Gokhale Chaitanya S. , Bargués-Ribera Maria , Verma Prateek 
Published: September 2023

AbstractEpidemics of plant diseases are estimated to cause significant economic losses in crop production. Fungicide applications are widely used to control crop diseases but incur substantial indirect costs. One essential class of indirect costs arises due to the evolution of fungicide resistance. This indirect cost must be estimated reliably to design economic policy for more sustainable use of fungicides. Such estimation is difficult because the cost depends on economic parameters and the epidemiological/evolutionary properties of crop pathogens. Even a conceptual framework for such estimation is missing. To address this problem, we combined a spatially implicit mathematical model of crop epidemics with an economic analysis at the landscape scale. We investigated how the net economic return from a landscape depends on the proportion of fungicide-treated fields. We discovered a pattern of accelerating (or decelerating) returns, contrary to expected diminishing returns. Next, we calculated the economic cost of the evolution of fungicide resistance as the difference between the optimal net return of the landscape in the absence and presence of resistance. We found that this cost depends strongly on the fungicide price, the degree of resistance, the pathogen’s basic reproduction number and the yield loss due to disease. Surprisingly, the cost declines with the fungicide price and exhibits a non-monotonic pattern as a function of the basic reproduction number. Hence, to calculate the cost, we must estimate these parameters robustly, incorporating variations in environmental conditions, crop varieties and the genetic composition of pathogen populations. Appropriate estimation of the cost of resistance evolution can inform economic policy, design dynamic fungicide pricing, and encourage more sustainable use of fungicides.
Long-term changes in the timing of autumn migration in Alaska’s boreal songbirds
Authors: Scurr April Harding , Hagelin Julie , Pendleton Grey , DuBour Kristin , Blake Tricia , Stuyck Claire , Allaby Eva 
Published: September 2023

ABSTRACTAlaska’s boreal birds face a rapidly changing environment, but we know little about shifts in migratory timing, particularly in autumn. We used quantile regression to quantify long-term changes in autumn capture date in 21 boreal passerines using 22+year datasets from two banding stations in central Alaska. We also quantified differences between sites and explored whether select climate indices during three periods of the annual cycle (breeding, post-fledge, and migration) could predict long-term changes in median capture. Long-term changes in autumn migration were detected in 86% of taxa, 76% of which exhibited advances in capture date (∼2-3 days/decade), particularly long-distance migrants at one field site. However, site-specific differences unexpectedly highlight the need for caution before extrapolating long-term timing patterns over broad spatial extents. Warmer conditions during the breeding period (using the AO climate index) were associated with advances in autumn capture date in the greatest number of species (9). Collectively, we hypothesize that Alaska’s immense size and spatially-variable climate regions impact reproductive timing, often resulting in long-term advances (with warming) and occasionally delays (with cooling). Carry-over effects of reproductive timing may therefore influence the autumn passage of different breeding populations, causing site-specific patterns, such as a species showing long-term advances at one location, but delays at another. Finally, as part of the broader effort to anticipate and reduce declines in boreal migratory birds, our study underscores the conservation value of banding station data in quantifying avian responses to and investigating drivers associated with varied climate indices.
Low albumin status accompanies multi-layered immunosuppressive phenotypes in metastatic breast cancer patients
Authors: Nakamura Yuki , Yoda Mayuko , Izumi Yoshihiro , Kashima Yukie , Takahashi Masatomo , Nakatani Kohta , Bamba Takeshi , He Chenfeng , Konishi Riyo , Saldajeno Don Pietro , Vandenbon Alexis , Suzuki Yutaka , Toi Masakazu , Kawaguchi Kosuke , Kawaoka Shinpei 
Published: September 2023

AbstractLow albumin status is prevalent in advanced cancer patients, but the pathophysiology associated with this anomaly remains largely unexplored. To address this, we aim to search correlations of albumin levels with the transcriptome against peripheral blood mononuclear cells and the plasma metabolome within the same patients having metastatic breast cancers. We confirm that metastatic breast cancer patients exhibit low albumin levels in varying degrees without prominent systemic inflammation. Our data demonstrate that low albumin levels correlate with transcriptome signatures indicative of “neutrophil activation and T-cell down-regulation,” an immunosuppressive phenotype. We also find that immunoregulatory metabolites, such as arginine, are reduced in plasma in an albumin-correlated manner, further corroborating systemic immunosuppression. These results are verified using a mouse model of breast cancer. We conclude that low albumin status in metastatic breast cancer patients accompanies immunosuppressive phenotypes, which is likely unfavorable for anti-cancer immunotherapy and thus can be a cause of unsuccessful treatment outcomes.
The Unexpected Role of GCN2 Kinase Activation in Mediating Pulmonary Arterial Hypertension
Authors: Zhu Maggie M. , Dai Jingbo , Dai Zhiyu , Peng Yi , Zhao You-Yang 
Published: September 2023

ABSTRACTBackgroundPulmonary arterial hypertension (PAH) is characterized by progressive increase of pulmonary vascular resistance and remodeling that result in right heart hypertrophy and failure. Published studies show that recessive mutations ofEIF2AK4gene (encoding GCN2, General control nonderepressibe 2 kinase) are linked to heritable pulmonary veno-occlusive disease (PVOD) in patients andEIF2AK4mutations were also found in PAH patients although very rare. However, the role of GCN2 kinase in the pathogenesis of PAH remains unclear.MethodsEif2ak4-/-mice with genetic disruption of the kinase domain and GCN2 kinase inhibitor A-92 were employed in animal models of PH including chronic hypoxia-exposed mice and monocrotaline-challenged rats. Human lung endothelial cells (HLMVECs) were used for mechanistic studies. Endothelium-targeted nanoparticles were employed to deliver plasmid DNA to adult mice to knockoutEif2ak4or overexpressEndothelin-1 (Edn1)selectively in ECs.ResultsHere we show that loss of GCN2 induced neither spontaneous PVOD nor PH inEif2ak4-/-mice but inhibited hypoxia-induced PH evident by reduced right ventricular systolic pressure, right ventricle hypertrophy and pulmonary vascular remodeling. RNA sequencing analysis suggested Edn1 as the downstream target of GCN2. In cultured HLMVECs, GCN2 was phosphorylated and activated in response to hypoxia, mediating hypoxia-induced Edn1 expression via HIF-2α. RestoredEdn1expression in ECs inGcn2-deficient mice reversed the reduced phenotype of hypoxia-induced PH. Furthermore, loss of endothelialEif2ak4in mice attenuated hypoxia-induced PH. Monocrotaline-induced PH and pulmonary vascular remodeling in rats were inhibited by GCN2 inhibitor A-92 treatment. The clinical relevance of the observation was validated by GCN2 hyperphosphorylation indicative of activation in ECs of pulmonary vascular lesions of PAH patients.ConclusionThese studies demonstrate that GCN2 activation by hypoxia mediates pulmonary vascular remodeling and PAH through Edn1. Thus, targeting GCN2 signaling is a promising therapeutic strategy for treatment of PAH in patients withoutEIF2AK4loss of function mutations.
Exploring the creation or adaptation of knowledge mobilization products for culturally and linguistically diverse audiences: a scoping review
Authors: Elliott Sarah A , Scott Shannon D , Bialy Liza , Wright Kelsey , Hartling Lisa 
Published: September 2023

AbstractIntroductionConnecting end-users to research evidence has the power to improve patient knowledge and inform health decision-making. However, recognized barriers to or determinants of effective knowledge mobilization (KMb) are differences in culture and language among the end users of the evidence. This scoping review set out to understand current processes and practices when creating or adapting KMb products for culturally and linguistically diverse (CALD) audiences.MethodsWe searched 3 databases (Ovid Medline, CINAHL via EBSCOhost, PsychINFO) from 2011 until August 2021. We included any literature about KMb product creation or adaptation processes serving CALD communities. A primary reviewer screened all identified publications and a second reviewer screened publications excluded by the primary. Data were extracted using a standardized form by one reviewer and 10% were verified by a second reviewer. Studies were categorized by type of adaptation (‘surface’ or ‘deep’ structure) and mapped based on type of stakeholder engagement used (i2S model). A search update was run in July 2023, and screening and extraction are in progress.ResultsSeven thousand four hundred and five unique titles and abstracts were reviewed, 319 full-text studies were retrieved and reviewed, and 24 studies were included in final data extraction and mapping. Fifteen studies (63%) created or adapted exclusively text-based KMb products such as leaflets and pamphlets and 9 (38%) produced digital products such as videos (n=4, 16%), mobile applications (n=3, 13%), website (n=1, 4%) and a CD ROM (n=1, 4%). Eight studies (33%) reported following a framework or theory for their creation or adaptation efforts. Only five studies (21%) demonstrated ‘deep structure’ cultural sensitivity and applied all five (Inform, Consult, Involve, Collaborate, and Support) levels of stakeholder engagement. Four (17%) studies included reflections from the research teams on the processes for creating or adapting KMb products for CALD communities.ConclusionIncluded studies cited a variety of methods in creating or adapting KMb products for CALD communities. Successful uptake of created or adapted KMb products was often the result of collaboration with end-users for more applicable, accessible and meaningful products. Further research developing guidance and best practices is needed to support the creation or adaptation of KMb products with CALD communities.
Differential nanoscale organization of excitatory synapses onto excitatory vs inhibitory neurons
Authors: Dharmasri Poorna A. , Levy Aaron D. , Blanpied Thomas A. 
Published: September 2023

AbstractA key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters whose precise alignment across the cleft in a trans-synaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution microscopy to directly compare the organization of shared scaffold proteins at two important excitatory synapses – those forming onto excitatory principal neurons (Ex→Ex synapses) and those forming onto parvalbumin-expressing interneurons (Ex→PV synapses). As in Ex→Ex synapses, we find that in Ex→PV synapses presynaptic Munc13-1 and postsynaptic PSD-95 both form nanoclusters that demonstrate alignment, underscoring synaptic nanostructure and the trans-synaptic nanocolumn as conserved organizational principles of excitatory synapses. Despite the general conservation of these features, we observed specific differences in the characteristics of pre-and postsynaptic Ex→PV nanostructure. Ex→PV synapses contained larger PSDs with fewer PSD-95 NCs when accounting for size than Ex→Ex synapses. Furthermore, the PSD-95 NCs were larger and denser. The identity of the postsynaptic cell also had a retrograde impact on Munc13-1 organization, as Ex→PV synapses hosted larger Munc13-1 puncta that contained less dense but larger and more numerous Munc13-1 NCs. Moreover, we measured the spatial variability of trans-synaptic alignment in these synapse types, revealing protein alignment in Ex→PV synapses over a distinct range of distances compared to Ex→Ex synapses. We conclude that while general principles of nanostructure and alignment are shared, cell-specific elements of nanodomain organization likely contribute to functional diversity of excitatory synapses. Understanding the rules of synapse nanodomain assembly, which themselves are cell-type specific, will be essential for illuminating brain network dynamics.
Curcumin extends the lifespan of aging postmitotic cells with mitochondrial dysfunction
Authors: Naaz Arshia , Zhang Yizhong , Faidzinn Nashrul Afiq , Yogasundaram Sonia , Alfatah Mohammad 
Published: September 2023

AbstractAging is an inevitable biological process intricately linked to age-related diseases, including cardiovascular diseases, neurodegeneration, sarcopenia, and age-related macular degeneration. These ailments are often exacerbated by mitochondrial dysfunction, which plays a pivotal role in postmitotic cells. Curcumin, a natural compound, is explored for its anti-aging potential. This study explores the influence of curcumin on the postmitotic cellular lifespan (PoMiCL) of yeast during chronological aging, examining its potential implications for age-related diseases. Our findings reveal that curcumin significantly extends the lifespan of postmitotic wildtype yeast cells, with maximal effects observed at lower concentrations, displaying a hormetic response. Importantly, curcumin mitigates accelerated aging in cells afflicted by mitochondrial dysfunction. Intriguingly, the hormetic effect is absent under these conditions. Mechanistically, curcumin enhances ATP levels but induces oxidative stress and inhibits TORC1. These findings shed light on curcumin’s potential as an anti-aging modulator and its relevance to age-related diseases, offering insights into novel therapeutic approaches for healthy aging while highlighting the context-dependent nature of its effects.
Global metabolome changes induced by environmentally relevant conditions in a marine-sourcedPenicillium restrictum
Authors: Le Van-Tuyen , Bertrand Samuel , Brandolini-Bunlon Marion , Gentil Emmanuel , Robiou du Pont Thibaut , Rabesaotra Vony , Wielgosz-Collin Gaëtane , Mossion Aurélie , Grovel Olivier 
Published: September 2023

AbstractMarine fungi have been found in all habitats and are able to adapt to their environmental niche conditions. In this study, a combination of LC-HRMS and GC-MS analytical approaches was used to analyse the whole metabolic changes of a marine sourcedPenicillium restrictumstrain isolated from a marine shellfish area. TheP. restrictumMMS417 strain was grown on seven different media including an ecological one with two different water sources (synthetic sea water and distilled water) conditions following the OSMAC approach. Extracts of all media were analysed by LC-HRMS (lipids and specialised metabolites profiling) and GC-MS (fatty acids profiling). Aquired data were analysed using a multiblock strategy to highlight metabolic modification in regards to water conditions and to environmentally relevant conditions (mussel-based culture medium). This revealed that fatty acid composition of lipids was the most altered part of the explored metabolisms either looking to water effect and to environmentally relevant conditions. In particular, data showed thatP. restrictumMMS417 is able to produce lipids that include fatty acids usually produced by the mussel itself. This study also provides insight into theP. restrictumadaptation to marine salinity through fatty acids alteration. and shows that lipid metabolisms if far more altered in an OSMAC approach than the specialized metabolism. This study finally highlights the need for using environnementmimicking culture conditions to reveal the metabolic potentialities of marine microbes.