bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming Trade for Vaccine Equity: Policy Gaps and Barriers
Authors: Pepperrell Toby , Koivusalo Meri , Grant Liz , McCallum Alison 
Published: June 2024

AbstractThe ongoing Pandemic Agreement negotiations illustrate significant gaps in action required to respond effectively to the lessons of the COVID-19 pandemic and make progress towards public health goals, including Sustainable Development Goals (SDGs). The pandemic revealed vaccine equity as a unifying health need, and international trade as a Commercial Determinant of Health. We explored where policy action could reshape trade relationships, identifying recommendations for vaccine equity within stakeholder literature pertaining to Free Trade Agreements (FTAs).We searched online libraries for stakeholder documents that focused on the interface between FTAs, vaccination, and vaccine equity published between 01/01/2010-31/03/2022. Our analytic framework drew from the rights, regulation, and redistribution (3R) framework, combined with systems analysis, using leverage pointsto categorise recommendations as Technical Mechanisms, Collaborative and Adaptive Mechanisms, or Determinants of Vaccine Equity (DVE). These were then located on a novel systems map to elucidate gaps and actions.No cohesive strategies for change were identified. Technical proposals were reactive, repetitive, and lacked enforcement mechanisms or incentives. There were significant gaps in the articulation of alternative Collaborative Mechanisms to democratise FTA policymaking processes. The underlying DVE and lack of policy coherence were not addressed. These findings are limited by under-representation of low- and middle-income country authorship in the studies, including in ours, reflecting imbalances in international research and policymaking processes.Overall, our research shows how the current trade paradigm has produced and sustained vaccine inequity. We propose potential pathways for action but highlight the importance and urgency of more fundamental change in negotiation and implementation of FTAs. New technologies will be crucial for the global response to emerging, neglected, and non-communicable diseases that are vaccine-preventable or -modifiable. Multilateral organisations must, therefore, prioritise the right to health above FTAs , including through TRIPS waivers on Essential Technologies.
Safety and Effectiveness of LC16m8 for Pre-Exposure Prophylaxis against mpox in a High-Risk Population: An Open-Label Randomized Trial
Authors: Okumura Nobumasa , Morino Eriko , Nomoto Hidetoshi , Yanagi Mashiho , Takahashi Kozue , Iwasaki Haruka , Uemura Yukari , Shimizu Yosuke , Mizushima Daisuke , Fukushima Kazuaki , Kinai Ei , Shiojiri Daisuke , Itoda Ichiro , Onoe Yasuhiko , Kobori Yoshitomo , Nakamura Fukumi , Tokita Daisuke , Sugiura Wataru , Ohmagari Norio , Ujiie Mugen 
Published: June 2024

AbstractBackgroundThe incidence of mpox cases has surged outside endemic regions since May 2022. However, data regarding the safety and efficacy of the LC16m8 vaccine are limited. This study provided opportunities for LC16m8 pre-exposure prophylaxis to high-risk individuals and conducted a randomized controlled trial to assess the effectiveness of LC16m8 in mpox prevention.MethodsThis multicenter, randomized, open-label trial enrolled men and women aged ≥18 with high mpox risk. Participants were randomly assigned 1:1 to early or late vaccination groups, receiving vaccinations approximately 70 days apart. Vaccine effectiveness (VE) against mpox development between early and late vaccinations was the primary endpoint. VE against severe mpox, symptoms, “take” incidence, and adverse events were secondary endpoints.ResultsA total of 570 and 565 patients were assigned to the early and late vaccination groups, respectively, and 530 and 476 were vaccinated. The median age was 41 years; 99.7% were male, 89.7% were Japanese, and 34.4% had human immunodeficiency virus (HIV). No mpox cases occurred, precluding VE calculations. The take rate was 90.3% (HIV-infected) and 94.6% (uninfected). Adverse events were observed in 97.2% and 98.2% of patients with and without HIV, respectively. No fatal adverse events were observed. Serious adverse events (SAE) were observed in 0.6% (HIV-infected) and 0.5% (uninfected) of patients. One participant without HIV reported pulmonary embolism and deep vein thrombosis as causally undeniable SAE. Local skin reactions: 96.6% (HIV-infected) and 97.9% (uninfected); systemic reactions: 63.6% (HIV-infected) and 64.2% (uninfected).ConclusionsThe effectiveness of LC16m8 in mpox remains inconclusive. However, its use in well-controlled HIV-infected and -uninfected individuals showed no significant safety concerns, suggesting the potential for targeted vaccination strategies in at-risk groups. (Japan Registry of Clinical Trials number, jRCT1031230137.)
Temporal trends in test-seeking behaviour during the COVID-19 pandemic
Authors: Eales Oliver , Teo Mingmei , Price David J. , Hao Tianxiao , Ryan Gerard E. , Senior Katharine L. , Carlson Sandra , Dalton Craig , Dawson Peter , Golding Nick , McCaw James M. , Shearer Freya M. 
Published: June 2024

AbstractBackgroundDuring the COVID-19 pandemic, many countries implemented mass community testing programs, where individuals would seek tests due to (primarily) the onset of symptoms. The cases recorded by mass testing programs represent only a fraction of infected individuals, and depend on how many people seek testing. If test-seeking behaviour exhibits heterogeneities or changes over time, and this is not accounted for when analysing case data, then inferred epidemic dynamics used to inform public health decision-making can be biased.MethodsHere we describe temporal trends in COVID-19 test-seeking behaviour in Australia by symptoms, age group, test type, and jurisdiction from November 2021–September 2023. We use data from two surveillance systems: a weekly nationwide behavioural survey (NBS), established by the Australian Government to monitor a range of behavioural responses to COVID-19; and Australia’s FluTracking system, a ‘participatory surveillance system’ designed for monitoring influenza-like illness and health-care seeking behaviour, which was adapted in early 2020 to include questions relevant to COVID-19.ResultsWe found that peaks in test-seeking behaviour generally aligned with peaks in the rate of reported cases. Test-seeking behaviour rapidly increased in early-2022 coinciding with greater availability of rapid antigen tests. There were heterogeneities in test-seeking behaviour by jurisdiction and age-group, which were dynamic through time. Test-seeking behaviour was lowest in older individuals (60+ years) until July 2022, after which there was greater homogeneity across age-groups. Test-seeking behaviour was highest in the Australian Capital Territory and Tasmania and consistently lowest in Queensland. Over the course of the study test-seeking behaviour was highest in individuals who reported symptoms more predictive of COVID-19 infection. There was a greater probability of seeking a test for individuals in FluTracking compared to the NBS, suggesting that participatory surveillance systems such as FluTracking may include a health-conscious subset of the population.ConclusionsOur findings demonstrate the dynamism of test-seeking behaviour, highlighting the importance of the continued collection of behavioural data through dedicated surveillance systems.
Early Detection of an Invasive Alien Plant (Phragmites australis) Using Unoccupied Aerial Vehicles and Artificial Intelligence
Authors: Caron-Guay Antoine , Germain Mickaël , Laliberté Etienne 
Published: June 2024

AbstractThe combination of unoccupied aerial vehicles (UAVs) and artificial intelligence to map vegetation represents a promising new approach to improve the detection of invasive alien plant species (IAPS). The high spatial resolution achievable with UAVs and recent innovations in computer vision, especially with convolutional neural networks, suggest that early detection of IAPS could be possible, thus facilitating their management. In this study, we evaluated the suitability of this approach for mapping the location of common reed (Phragmites australissubsp.australis) within a national park located in southern Quebec, Canada. We collected data on six distinct dates during the growing season, covering environments with different levels of reed invasion. Overall, model performance was high for the different dates and zones, especially for recall (mean of 0.89). The results showed an increase in performance, reaching a peak following the appearance of the inflorescence in September (highest F1-score at 0.98). Furthermore, a decrease in spatial resolution negatively affected recall (18% decrease between a spatial resolution of 0.15 cm pixel−1and 1.50 cm pixel−1) but did not have a strong impact on precision (2% decrease). Despite challenges associated with common reed mapping in a post-treatment monitoring context, the use of UAVs and deep learning shows great potential for IAPS detection when supported by a suitable dataset. Our results show that, from an operational point of view, this approach could be an effective tool for speeding up the work of biologists in the field and ensuring better management of IAPS.
Enhanced Plasmid-Based Transcriptional Activation in Developing Mouse Photoreceptors
Authors: Patierno Brendon M. , Emerson Mark M. 
Published: June 2024

AbstractRod photoreceptor formation in the postnatal mouse is a widely used model system for studying mammalian photoreceptor development. This experimental paradigm provides opportunities for both gain and loss-of-function studies which can be accomplished through in vivo plasmid delivery and electroporation. However, the cis-regulatory elements used to implement this approach have not been fully evaluated or optimized for the unique transcriptional environment of photoreceptors. Here we report that the use of a photoreceptor cis-regulatory element from the Crx gene in combination with broadly active promoter elements can increase the targeting of developing rod photoreceptors in the mouse. This can lead to greater reporter expression, as well as enhanced misexpression and loss-of-function phenotypes in these cells. This study also highlights the importance of identifying and testing relevant cis-regulatory elements when planning cell subtype specific experiments. The use of the specific hybrid elements in this study will provide a more efficacious gene delivery system to study mammalian photoreceptor formation.
The inactive X chromosome drives sex differences in microglial inflammatory activity in human glioblastoma
Authors: Tharp Marla E. , Han Claudia Z. , Balak Chris D. , Fitzpatrick Conor , O’Connor Carolyn , Preissl Sebastian , Buchanan Justin , Nott Alexi , Escoubet Laure , Mavrommatis Konstantinos , Gupta Mihir , Schwartz Marc S. , Hoi Sang U , Jones Pamela S. , Levy Michael L. , Gonda David D. , Ben-Haim Sharona , Ciacci Joseph , Barba David , Khalessi Alexander , Coufal Nicole G. , Chen Clark C. , Glass Christopher K. , Page David C. 
Published: June 2024

SummaryBiological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM.
Global genomics ofAedes aegyptiunveils widespread and novel infectious viruses capable of triggering a small RNA response
Authors: Gupta Shruti , Sharma Rohit , Williams Adeline E. , Sanchez-Vargas Irma , Rose Noah H. , Zhang Chao , Crosbie-Villaseca Alexander , Zhu Zheng , Dayama Gargi , Gloria-Soria Andrea , Brackney Doug E. , Manning Jessica , Wheeler Sarah S. , Caranci Angela , Reyes Trinidad , Sylla Massamba , Badolo Athanase , Akorli Jewelna , Aribodor Ogechukwu B. , Ayala Diego , Liu Wei-Liang , Chen Chun-Hong , Vasquez Chalmers , Acosta Cassandra Gonzalez , Ponlawat Alongkot , Magalhaes Tereza , Carter Brendan , Wesson Dawn , Surin Darred , Younger Meg A. , Costa-da-Silva Andre Luis , DeGennaro Matthew , Bergman Alexander , Lambrechts Louis , McBride Carolyn S. , Olson Ken E. , Calvo Eric , Lau Nelson C. 
Published: June 2024

ABSTRACTThe mosquitoAedes aegyptiis a prominent vector for arboviruses, but the breadth of mosquito viruses that infects this specie is not fully understood. In the broadest global survey to date of over 200Ae. aegyptismall RNA samples, we detected viral small interfering RNAs (siRNAs) and Piwi interacting RNAs (piRNAs) arising from mosquito viruses. We confirmed that most academic laboratory colonies ofAe. aegyptilack persisting viruses, yet two commercial strains were infected by a novel tombus-like virus.Ae. aegyptifrom North to South American locations were also teeming with multiple insect viruses, with Anphevirus and a bunyavirus displaying geographical boundaries from the viral small RNA patterns. AsianAe. aegyptismall RNA patterns indicate infections by similar mosquito viruses from the Americas and reveal the first wild example of dengue virus infection generating viral small RNAs. AfricanAe. aegyptialso contained various viral small RNAs including novel viruses only found in these African substrains. Intriguingly, viral long RNA patterns can differ from small RNA patterns, indicative of viral transcripts evading the mosquitoes’ RNA interference (RNAi) machinery. To determine whether the viruses we discovered via small RNA sequencing were replicating and transmissible, we infected C6/36 and Aag2 cells withAe. aegyptihomogenates. Through blind passaging, we generated cell lines stably infected by these mosquito viruses which then generated abundant viral siRNAs and piRNAs that resemble the native mosquito viral small RNA patterns. This mosquito small RNA genomics approach augments surveillance approaches for emerging infectious diseases.
‘Low’ LRs obtained from DNA mixtures: On calibration and discrimination performance of probabilistic genotyping software
Authors: McCarthy-Allen M. , Bleka Ø. , Ypma R. , Gill P. , Benschop C. 
Published: June 2024

AbstractThe validity of a probabilistic genotyping (PG) system is typically demonstrated by following international guidelines for the developmental and internal validation of PG software. These guidelines mainly focus on discriminatory power. Very few studies have reported with metrics that depend on calibration of likelihood ratio (LR) systems. In this study, discriminatory power as well as various calibration metrics, such as Empirical Cross-Entropy (ECE) plots, pool adjacent violator (PAV) plots, log likelihood ratio cost (Cllr and Cllrcal), fiducial calibration discrepancy plots, and Turing’ expectation were examined using the publicly-available PROVEDIt dataset. The aim was to gain deeper insight into the performance of a variety of PG software in the ‘lower’ LR ranges (∼LR 1-10,000), with focus on DNAStatistX and EuroForMix which use maximum likelihood estimation (MLE). This may be a driving force for the end users to reconsider current LR thresholds for reporting. In previous studies, overstated ‘low’ LRs were observed for these PG software. However, applying (arbitrarily) high LR thresholds for reporting wastes relevant evidential value. This study demonstrates, based on calibration performance, that previously reported LR thresholds can be lowered or even discarded. Considering LRs >1, there was no evidence for miscalibration performance above LR ∼1,000 when using Fst 0.01. Below this LR value, miscalibration was observed. Calibration performance generally improved with the use of Fst 0.03, but the extent of this was dependent on the dataset: results ranged from miscalibration up to LR ∼100 to no evidence of miscalibration alike PG software using different methods to model peak height, HMC and STRmix.This study demonstrates that practitioners using MLE-based models should be careful when low LR ranges are reported, though applying arbitrarily high LR thresholds is discouraged. This study also highlights various calibration metrics that are useful in understanding the performance of a PG system.HighlightsDiscriminatory power and calibration performance of PG software are evaluated.The utility of various calibration metrics are explored in ‘low’ LR ranges.Focus was on DNAStatistX and EuroForMix software using the MLE method.Calibration performance was dependent on Fst value and dataset size.Results suggest reconsideration of lower LR thresholds and cautious reporting of ‘low’ LRs.
ALBA proteins facilitate cytoplasmic YTHDF-mediated reading of m6A in plants
Authors: Reichel Marlene , Tankmar Mathias Due , Rennie Sarah , Arribas-Hernández Laura , Lewinski Martin , Köster Tino , Wang Naiqi , Millar Anthony A. , Staiger Dorothee , Brodersen Peter 
Published: June 2024

ABSTRACTN6-methyladenosine (m6A) exerts many of its regulatory effects on eukaryotic mRNAs by recruiting cytoplasmic YT521-B homology domain family (YTHDF) proteins. Here, we show that in Arabidopsis, the interaction between m6A and the major YTHDF protein ECT2 also involves the mRNA-binding ALBA protein family. ALBA and YTHDF proteins physically associate via a deeply conserved short linear motif in the intrinsically disordered region of YTHDF proteins, their mRNA target sets overlap, and ALBA4 binding sites are juxtaposed to m6A sites. These binding sites correspond to pyrimidine-rich elements previously found to be important for m6A binding of ECT2. Accordingly, both biological functions of ECT2 and its binding to m6A targetsin vivorequire ALBA association. Our results introduce the YTHDF-ALBA complex as the functional cytoplasmic m6A-reader in plants and define a molecular foundation for the concept of facilitated m6A reading that increases the potential for combinatorial control of biological m6A effects.
Structure of fungal tRNA ligase with RNA reveals conserved substrate binding principles
Authors: Köhler Sandra , Kopp Jürgen , Peschek Jirka 
Published: June 2024

AbstractRNA ligases play a vital role in RNA processing and maturation including tRNA splicing, RNA repair and the unfolded protein response (UPR). In fungi and plants, the tripartite tRNA ligase Trl1 catalyzes the joining of TSEN-cleaved pre-tRNA exon halves. Trl1 also functions as ligase in the non-conventionalHAC1mRNA splicing during the UPR. The final ligation step is performed by the N-terminal adenylyltransferase domain (LIG). The spatial arrangement of the exon ends during the ligation reaction has remained elusive. Here, we report the crystal structure of Trl1-LIG in complex with a tRNA-derived substrate. Our structure represents a snapshot of the activated RNA intermediate and defines the conserved substrate binding interface. The underlying enzyme-substrate interplay reveals a general substrate binding principle shared by adenylyltransferases. Moreover, we identify the determinants of RNA end specificity as well as the specific roles of Trl1-LIG’s subdomains during ligase activation, substrate binding and phosphoryltransfer.
Global overview of sea turtle fibropapillomatosis tumors: a survey of expert opinions and trends
Authors: Whilde Jenny , Mashkour Narges , Koda Samantha A. , Eastman Catherine B. , Thompson Drew , Burkhalter Brooke , Frandsen Hilary , Page Annie , Blackburn Nicholas B. , Jones Karina , Ariel Ellen , Dupont Sophie M. , Wood Lawrence , Duffy David J. 
Published: June 2024

AbstractMarine environments offer a wealth of opportunities to improve understanding and treatment options for cancers, through insights into a range of fields from drug discovery to mechanistic insights. By applying One Health principles the knowledge obtained can benefit both human and animal populations, including marine species suffering from cancer. One such species is green sea turtles (Chelonia mydas), which are under threat from fibropapillomatosis (FP), an epizootic tumor disease (animal epidemic) that continues to spread and increase in prevalence globally. In order to effectively address this epizootic, a more thorough understanding is required of the prevalence of the disease and the approaches to treating afflicted turtles. To identify knowledge gaps and assess future needs, we conducted a survey of sea turtle FP experts. The survey consisted of 47 questions designed to assess general perceptions of FP, the areas where more information is needed, local FP trends, the disease status, and mitigation needs, and was voluntarily completed by 44 experts across a broad geographic range. The survey responses provided a valuable overview of the current FP status in sea turtles, FP research, and insight into the approaches currently taken by turtle rehabilitation facilities around the world. Over 70% of respondents both recognized FP as a cancerous panzootic disease, and reported that FP is increasing in prevalence. They report several factors contributing to this increase. Nearly all of the respondents reported that FP research, patient treatment and rehabilitation required more funding in their area, and reported inadequate facilities and capacity for dealing with FP patients. Treatment approaches varied: just over 70% of the medical experts that responded surgically remove FP tumors, either using laser or scalpel. Just under half of respondents use anti-cancer drugs in their treatment of FP. Internal tumors were reported as justification for euthanasia by 61.5% of respondents, and 30.8% reported severe external tumors to be sufficient grounds for euthanasia. Most medical respondents (93.3%) routinely perform necropsy on deceased or euthanized FP-afflicted turtles. Over 80% of respondents considered large-scale multidisciplinary collaboration ‘extremely important’ for advancing the field of FP research. The survey responses provide a valuable insight into the current state of FP treatment, rehabilitation and research, and help to identify critical FP-related research and rehabilitation areas most in need of attention.