bluuebunny/crossref_metadata_2025 huggingface dataset:
Tactile bill-tip organs in seabirds suggest conservation of a deep avian symplesiomorphy
Authors: du Toit Carla J. , Bond Alexander L. , Cunningham Susan J. , Field Daniel J. , Portugal Steven J.
Published: September 2024

Birds’ bills are their main tactile interface with the outside world. Tactile bill-tip organs associated with specialized foraging techniques are present in several bird groups, yet remain understudied in most clades. One example is Austrodyptornithes, the major seabird clade uniting Procellariiformes (albatrosses and petrels) and Sphenisciformes (penguins). Here, we describe the mechanoreceptor arrangement and neurovascular anatomy in the premaxillae of Austrodyptornithes. Using a wide phylogenetic sample of extant birds (361 species), we show that albatrosses and penguins exhibit complex tactile bill-tip anatomies, comparable to birds with known bill-tip organs, despite not being known to use tactile foraging. Petrels (Procellariidae, Hydrobatidae and Oceanitidae) lack these morphologies, indicating an evolutionary transition in bill-tip mechanosensitivity within Procellariiformes. The bill-tip organ in Austrodyptornithes may be functionally related to nocturnal foraging and prey detection under water, or courtship displays involving tactile stimulation of the bill. Alternatively, these organs may be vestigial as is likely the case in most palaeognaths (e.g. ostriches and emu). Ancestral state reconstructions fail to reject the hypothesis that the last common ancestor of Austrodyptornithes had a bill-tip organ; thus, tactile foraging may be ancestral for this major extant clade, perhaps retained from a deeper point in crown bird evolutionary history.
How domestication, feralization and experience-dependent plasticity affect brain size variation in
Sus scrofa
Authors: Cucchi T. , Neaux D. , Féral L. , Goussard F. , Adriensen H. , Elleboudt F. , Sansalone G. , Schafberg R.
Published: September 2024

Among domestic species, pigs experienced the greatest brain size reduction, but the extent and factors of this reduction remain unclear. Here, we used the brain endocast volume collected from 92 adult skulls of wild, captive, feral and domestic
Sus scrofa
to explore the effects of domestication, feralization and captivity over the brain size variation of this species. We found a constant brain volume increase over 24 months, while body growth slowed down from month 20. We observed an 18% brain size reduction between wild boars and pigs, disagreeing with the 30%–40% reduction previously mentioned. We did not find significant sexual differences in brain volume, refuting the theory of the attenuation of male secondary sexual characteristics through the selection for reduced male aggression. Feralization in Australia led to brain size reduction—probably as an adaptation to food scarcity and drought, refuting the reversal to wild ancestral brain size. Finally, free-born wild boars raised in captivity showed a slight increase in brain size, potentially due to a constant and high-quality food supply as well as new allospecific interactions. These results support the need to further explore the influence of diet, environment and experience on brain size evolution during animal domestication.
Economic foraging in a floral marketplace: asymmetrically dominated decoy effects in bumblebees
Authors: Hemingway Claire T. , DeVore Jennie E. , Muth Felicity
Published: September 2024

While most models of decision-making assume that individuals assign options absolute values, animals often assess options comparatively, violating principles of economic rationality. Such ‘irrational’ preferences are especially common when two rewards vary along multiple dimensions of quality and a third, ‘decoy’ option is available. Bumblebees are models of decision-making, yet whether they are subject to decoy effects is unknown. We addressed this question using bumblebees (
Bombus impatiens
) choosing between flowers that varied in their nectar concentration and reward rate. We first gave bees a choice between two flower types, one higher in concentration and the other higher in reward rate. Bees were then given a choice between these flowers and either a ‘concentration’ or ‘rate’ decoy, designed to be asymmetrically dominated on each axis. The rate decoy increased bees’ preference in the expected direction, while the concentration decoy did not. In a second experiment, we manipulated choices along two single reward dimensions to test whether this discrepancy was explained by differences in how concentration versus reward rate were evaluated. We found that low-concentration decoys increased bees’ preference for the medium option as predicted, whereas low-rate decoys had no effect. Our results suggest that both low- and high-value flowers can influence pollinator preferences in ways previously unconsidered.
Effects of visual diet on colour discrimination and preference
Authors: Skelton Alice E. , Maule John , Floyd Simeon , Wozniak Beata , Majid Asifa , Bosten Jenny M. , Franklin Anna
Published: September 2024

To what extent is perception shaped by low-level statistical regularities of our visual environments and on what time scales? We characterized the chromatic ‘visual diets’ of people living in remote rainforest and urban environments, using calibrated head-mounted cameras worn by participants as they went about their daily lives. All environments had chromatic distributions with the most variance along a blue–yellow axis, but the extent of this bias differed across locations. If colour perception is calibrated to the visual environments in which participants are immersed, variation in the extent of the bias in scene statistics should have a corresponding impact on perceptual judgements. To test this, we measured colour discrimination and preferences for distributions of colour for people living in different environments. Group differences in the extent of blue–yellow bias in colour discrimination were consistent with perceptual learning in local environments. Preferences for colour distributions aligned with scene statistics, but not specifically to local environments, and one group preferred distributions along an unnatural colour axis orthogonal to that dominant in natural scenes. Our study shows the benefits of conducting psychophysics with people at remote locations for understanding the commonalities and diversity in human perception.
Small populations of Palaeolithic humans in Cyprus hunted endemic megafauna to extinction
Authors: Bradshaw Corey J. A. , Saltré Frédérik , Crabtree Stefani A. , Reepmeyer Christian , Moutsiou Theodora
Published: September 2024

The hypothesized main drivers of megafauna extinctions in the late Quaternary have wavered between over-exploitation by humans and environmental change, with recent investigations demonstrating more nuanced synergies between these drivers depending on taxon, spatial scale, and region. However, most studies still rely on comparing archaeologically based chronologies of timing of initial human arrival into naïve ecosystems and palaeontologically inferred dates of megafauna extinctions. Conclusions arising from comparing chronologies also depend on the reliability of dated evidence, dating uncertainties, and correcting for the low probability of preservation (Signor–Lipps effect). While some models have been developed to test the susceptibility of megafauna to theoretical offtake rates, none has explicitly linked human energetic needs, prey choice, and hunting efficiency to examine the plausibility of human-driven extinctions. Using the island of Cyprus in the terminal Pleistocene as an ideal test case because of its late human settlement (~14.2–13.2 ka), small area (~11 000 km
2
), and low megafauna diversity (2 species), we developed stochastic models of megafauna population dynamics, with offtake dictated by human energetic requirements, prey choice, and hunting-efficiency functions to test whether the human population at the end of the Pleistocene could have caused the extinction of dwarf hippopotamus (
Phanourios minor
) and dwarf elephants (
Palaeoloxodon cypriotes
). Our models reveal not only that the estimated human population sizes (
n
= 3000–7000) in Late Pleistocene Cyprus could have easily driven both species to extinction within < 1000 years, the model predictions match the observed, Signor–Lipps-corrected chronological sequence of megafauna extinctions inferred from the palaeontological record (
P. minor
at ~12–11.1 ka, followed by
P. cypriotes
at ~10.3–9.1 ka).
Chronic and acute thermal stressors have non-additive effects on fertility
Authors: Pilakouta Natalie , Allan Daniel , Moore Ellie , Russell Alison A.
Published: September 2024

Climate change is driving both higher mean temperatures and a greater likelihood of heatwaves, which are becoming longer and more intense. Previous work has looked at these two types of thermal stressors in isolation, focusing on the effects of either a small, long-term increase in temperature or a large, short-term increase in temperature. Yet, a fundamental gap in our understanding is the combined effect of chronic and acute thermal stressors and, in particular, its impact on vital processes such as reproduction. Here, we investigated the independent and interactive effects of higher constant temperatures and short-term heatwave events on reproductive success and offspring fitness in an insect study system, the burying beetle
Nicrophorus vespilloides
. We found a substantial reduction in key fitness traits (fecundity, hatching success and offspring size) after exposure to both a heatwave and higher constant temperatures, but not after exposure to only one of these thermal stressors. This indicates that the effects of chronic and acute thermal stressors are amplified when they act in combination, as is very likely to occur in natural populations. Our findings, therefore, suggest that, by not considering the potential multiplicative effects of different types of thermal stressors, we may be underestimating the effects of climate change on animal fertility.
Mechanisms of transcriptional regulation in
Anopheles gambiae
revealed by allele-specific expression
Authors: Dyer Naomi A. , Lucas Eric R. , Nagi Sanjay C. , McDermott Daniel P. , Brenas Jon H. , Miles Alistair , Clarkson Chris S. , Mawejje Henry D. , Wilding Craig S. , Halfon Marc S. , Asma Hasiba , Heinz Eva , Donnelly Martin J.
Published: September 2024

Malaria control relies on insecticides targeting the mosquito vector, but this is increasingly compromised by insecticide resistance, which can be achieved by elevated expression of detoxifying enzymes that metabolize the insecticide. In diploid organisms, gene expression is regulated both in
cis
, by regulatory sequences on the same chromosome, and by
trans
acting factors, affecting both alleles equally. Differing levels of transcription can be caused by mutations in
cis
-regulatory modules (CRM), but few of these have been identified in mosquitoes. We crossed bendiocarb-resistant and susceptible
Anopheles gambiae
strains to identify
cis
-regulated genes that might be responsible for the resistant phenotype using RNAseq, and CRM sequences controlling gene expression in insecticide resistance relevant tissues were predicted using machine learning. We found 115 genes showing allele-specific expression (ASE) in hybrids of insecticide susceptible and resistant strains, suggesting
cis
-regulation is an important mechanism of gene expression regulation in
A. gambiae
. The genes showing ASE included a higher proportion of
Anopheles
-specific genes on average younger than genes with balanced allelic expression.
Phylogenomic and molecular marker based studies to clarify the evolutionary relationships amongst Anoxybacillus species and demarcation of the family Anoxybacillaceae and some of its constituent genera
Authors: Patel Isha , Bello Sarah , Gupta Radhey S.
Published: September 2024

The family Anoxybacillaceae was recently proposed encompassing the genera Anoxybacillus, Geobacillus, Parageobacillus, Saccharococcus and Thermolongibacillus. Of these genera, Anoxybacillus contains >50% of the Anoxybacillaceae species. However, Anoxybacillus species form multiple unrelated clades in phylogenetic trees and their evolutionary relationships are unclear. To clarify the evolutionary relationships of Anoxybacillus and other Anoxybacillaceae species, detailed phylogenomic and comparative analyses were conducted on 38 Anoxybacillaceae species with available genomes. In a phylogenomic tree based on 1148 core proteins, all Anoxybacillus, Geobacillus, Parageobacillus, Saccharococcus and Thermolongibacillus species, excepting Anoxybacillus sediminis, formed a strongly supported clade representing the family Anoxybacillaceae. Five conserved signature indels (CSIs) reported here are also uniquely found in these species, providing robust means for the demarcation of family Anoxybacillaceae in molecular terms. In our phylogenomic tree and in the Genomic Taxonomy Database, Anoxybacillus species formed four distinct clades designated as Anoxybacillus sensu stricto (containing the type species A. pushchinoensis), Anoxybacillus_A, Anoxybacillus_B and Anoxybacillus_C. Our analyses have identified 17 novel CSIs which offer means to reliably distinguish species from these clades based upon multiple uniquely shared molecular characteristics. Additionally, we have identified three and seven CSIs specific for the genera Geobacillus and Brevibacillus, respectively. All seven Brevibacillus-specific CSIs are also shared by Anoxybacillus sediminis, which branches reliably with this genus. Based on the strong phylogenetic and molecular evidence presented here, we are proposing that the genus Anoxybacillus should be restricted to only the species from Anoxybacillus sensu stricto clade, whereas the species from Anoxybacillus_A, Anoxybacillus_B, and Anoxybacillus_C clades should be transferred into three novel genera Anoxybacteroides gen. nov., Paranoxybacillus gen. nov. and Thermaerobacillus gen. nov., respectively. Additionally, we are also proposing the transfer of Anoxybacillus sediminis to the genus Brevibacillus. The proposed changes, which reliably depict the evolutionary relationships among Anoxybacillaceae species, should be helpful in the studies of these organisms.
EbsA is essential for both motility and biofilm formation in the filamentous cyanobacterium Nostoc punctiforme
Authors: Hassan Aya S. , Heflen Ethan S. , Nguyen Khoa D. , Parrett Gabriel A. , Risser Douglas D.
Published: September 2024

Many cyanobacteria, both unicellular and filamentous, exhibit surface motility driven by type IV pili (T4P). While the component parts of the T4P machinery described in other prokaryotes are largely conserved in cyanobacteria, there are also several T4P proteins that appear to be unique to this phylum. One recently discovered component is EbsA, which has been characterized in two unicellular cyanobacteria. EbsA was found to form a complex with other T4P proteins and is essential for motility. Additionally, deletion of ebsA in one of these strains promoted the formation of biofilms. To expand the understanding of ebsA in cyanobacteria, its role in motility and biofilm formation were investigated in the model filamentous cyanobacterium Nostoc punctiforme. Expression of ebsA was strictly limited to hormogonia, the motile filaments of N. punctiforme. Deletion of ebsA did not affect hormogonium development but resulted in the loss of motility and the failure to accumulate surface pili or produce hormogonium polysaccharide (HPS), consistent with pervious observations in unicellular cyanobacteria. Protein-protein interaction studies indicated that EbsA directly interacts with PilB, and the localization of EbsA-GFP resembled that previously shown for both PilB and Hfq. Collectively, these results support the hypothesis that EbsA forms a complex along with PilB and Hfq that is essential for T4P extension. In contrast, rather than enhancing biofilm formation, deletion of both ebsA and pilB abolish biofilm formation in N. punctiforme, implying that distinct modalities for the relationship between motility, T4P function and biofilm formation may exist in different cyanobacteria.
Variation in bacterial pathotype is consistent with the sit-and-wait hypothesis
Authors: Rayner Eliza , Lavenir Amelie , Murray Gemma G. R. , Matusewska Marta , Tucker Alexander W. , Welch John J. , Weinert Lucy A.
Published: September 2024

The sit-and-wait hypothesis predicts that bacteria can become more virulent when they survive and transmit outside of their hosts due to circumventing the costs of host mortality. While this hypothesis is largely supported theoretically and through comparative analysis, experimental validation is limited. Here we test this hypothesis in Streptococcus suis, an opportunistic zoonotic pig pathogen, where a pathogenic ecotype proliferated during the change to intensive pig farming that amplifies opportunities for fomite transmission. We show in an in vitro environmental survival experiment that pathogenic ecotypes survive for longer than commensal ecotypes, despite similar rates of decline. The presence of a polysaccharide capsule has no consistent effect on survival. Our findings suggest that extended survival in the food chain may augment the zoonotic capability of S. suis. Moreover, eliminating the long-term environmental survival of bacteria could be a strategy that will both enhance infection control and curtail the evolution of virulence.
Accelerating Ligand Discovery for Insect Odorant Receptors
Authors: Comte Arthur , Lalis Maxence , Brajon Ludvine , Moracci Riccardo , Montagné Nicolas , Topin Jérémie , Jacquin Joly Emmanuelle , Fiorucci Sébastien
Published: September 2024

Odorant receptors (ORs) are main actors of the insects peripheral olfactory system, making them prime targets for pest control through olfactory disruption. Traditional methods employed in the context of chemical ecology for identifying OR ligands rely on analyzing compounds present in the insect’s environment or screening molecules with structures similar to known ligands. However, these approaches can be time-consuming and constrained by the limited chemical space they explore. Recent advances in OR structural understanding, coupled with scientific breakthroughs in protein structure prediction, have facilitated the application of structure-based virtual screening (SBVS) techniques for accelerated ligand discovery. Here, we report the first successful application of SBVS to insect ORs. We developed a unique workflow that combines molecular docking predictions,in vivovalidation and behavioral assays to identify new behaviorally active volatiles for non-pheromonal receptors. This work serves as a proof of concept, laying the groundwork for future studies and highlighting the need for improved computational approaches. Finally, we propose a simple model for predicting receptor response spectra based on the hypothesis that the binding pocket properties partially encode this information, as suggested by our results onSpodoptera littoralisORs.
Thermal adaptation in worldwide collections of a major fungal pathogen
Authors: Miñana-Posada Silvia , Lorrain Cécile , McDonald Bruce A. , Feurtey Alice
Published: September 2024

Adaptation to new climates poses a significant challenge for plant pathogens during range expansion, highlighting the importance of understanding their response to climate to accurately forecast future disease outbreaks. The wheat pathogenZymoseptoria triticiis ubiquitous across most wheat production regions distributed across diverse climate zones. We explored the genetic architecture of thermal adaptation using a global collection of 411Z. triticistrains that were phenotyped across a wide range of temperatures and then included in a genome-wide association study. Our analyses provided evidence for local thermal adaptation inZ. triticipopulations worldwide, with a significant positive correlation between bioclimatic variables and optimal growth temperatures. We also found a high variability in thermal performance amongZ. triticistrains coming from the same field populations, reflecting the high evolutionary potential of this pathogen at the field scale. We identified 69 genes putatively involved in thermal adaptation, including one high-confidence candidate potentially involved in cold adaptation. These results highlight the complex polygenic nature of thermal adaptation inZ. triticiand suggest that this pathogen is likely to adapt well when confronted with climate change.
Developmental transcriptomics inPristionchusreveals the logic of a plasticity gene regulatory network
Authors: Reich Shelley , Loschko Tobias , Jung Julie , Nestel Samantha , Sommer Ralf J. , Werner Michael S.
Published: September 2024

Developmental plasticity enables the production of alternative phenotypes in response to different environmental conditions. While significant advances in understanding the ecological and evolutionary implications of plasticity have been made, understanding its genetic basis has lagged. However, a decade of genetic screens in the model nematodePristionchus pacificushas culminated in 30 genes which affect mouth-form plasticity. We also recently reported the critical window of environmental sensitivity, and therefore have clear expectations for when differential gene expression should matter. Here, we collated previous data into a gene-regulatory network (GRN), and performed developmental transcriptomics across different environmental conditions, genetic backgrounds, and mouth-form mutants to assess the regulatory logic of plasticity. We found that only two genes in the GRN (eud-1andseud-1/sult-1) are sensitive to the environment during the critical window. Interestingly, the time points of their sensitivity differ, suggesting that they act as sequential checkpoints. We also observed temporal constraint upon the transcriptional effects of mutating the GRN and revealed unexpected feedback between mouth-form genes. Surprisingly, expression ofseud-1/sult-1, but noteud-1, correlated with mouth form biases across different strains and species. Finally, a comprehensive analysis of all samples identified metabolism as a shared pathway for regulating mouth-form plasticity. These data are presented in a Shiny app to facilitate gene-expression comparisons across development in up to 14 different conditions. Collectively, our results suggest that mouth-form plasticity evolved a constrained, two-tiered logic to integrate environmental information leading up to the final developmental decision.
Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells
Authors: Kim Justin , Brunetti Bryce , Kumar Ayanesh , Mangla Ankit , Honda Kord , Yoshida Akihiro
Published: September 2024

The cyclin D1-Cyclin-Dependent Kinases 4 and 6 (CDK4/6) complex is crucial for the development of melanoma. We previously demonstrated that targeting CDK4/6 using small molecule inhibitors (CDK4/6i) suppresses BrafV600Emelanoma growthin vitroandin vivothrough induction of cellular senescence. Clinical trials investigating CDK4/6i in melanoma have not yielded successful outcomes, underscoring the necessity to enhance the therapeutic efficacy of CDK4/6i. Accumulated research has shown that while senescence initially suppresses cell proliferation, a prolonged state of senescence eventually leads to tumor relapse by altering the tumor microenvironment, suggesting that removal of those senescent cells (in a process referred to as senolysis) is of clinical necessity to facilitate clinical response. We demonstrate that glutaminase 1 (GLS1) expression is specifically upregulated in CDK4/6i-induced senescent BrafV600Emelanoma cells. Upregulated GLS1 expression renders BrafV600Emelanoma senescent cells vulnerable to GLS1 inhibitor (GLS1i). Furthermore, we demonstrate that this senolytic approach targeting upregulated GLS1 expression is applicable even though those cells developed resistance to the BrafV600Einhibitor vemurafenib, a frequently encountered substantial clinical challenge to treating patients. Thus, this novel senolytic approach may revolutionize current CDK4/6i mediated melanoma treatment if melanoma cells undergo senescence prior to developing resistance to CDK4/6i. Given that we demonstrate that a low dose of vemurafenib induced senescence, which renders BrafV600Emelanoma cells susceptible to GLS1i and recent accumulated research shows many cancer cells undergo senescence in response to chemotherapy, radiation, and immunotherapy, this senolytic therapy approach may prove applicable to a wide range of cancer types once senescence and GLS1 expression are induced.

Key points

Upregulated GLS1 expression renders senescent BrafV600Emelanoma cells induced by CDK4/6 inhibitor (CDK4/6i) or vemurafenib susceptible to GLS1 inhibitor (GLS1i) even with BrafV600Einhibitor resistance. This senolytic therapy combining CDK4/6i and GLS1i provides insights into potential novel therapeutic strategies for metastatic melanoma and may be applicable to various types of cancers providing alternative therapy options.
PSMA+ Extracellular Vesicles are a Biomarker for SABR in Oligorecurrent Prostate Cancer Analysis from the STOMP-like and ORIOLE trial cohorts
Authors: Andrews Jack , Kim Yohan , Horjeti Edlira , Arafa Ali , Gunn Heather , De Bruycker Aurélie , Phillips Ryan , Song Daniel , Childs Daniel S. , Sartor Oliver A. , Orme Jacob J. , Chaudhuri Aadel A. , Tran Phuoc , Kiess Ana , Sutera Philip , Mercier Carole , Ost Piet , Park Sean S. , Lucien Fabrice
Published: September 2024

Purpose

Two randomized clinical trials (STOMP and ORIOLE) demonstrated that stereotactic ablative radiotherapy (SABR) can prolong ADT-free survival or progression-free survival (PFS) in patients with metachronous oligometastatic prostate cancer (omCSPC) patients. While most omCSPC patients have a more modest delay in progression, a small subset achieves a durable response following SABR. We investigated the prognostic and predictive value of circulating PSMA-positive extracellular vesicles (PSMA+EV) and prostate specific antigen (PSA) in a biomarker correlative study using blood samples from three independent patient cohorts.

Methods

Plasma samples from 46 patients on the ORIOLE trial and 127 patietns on the STOMP trial protocol with omCSPC patients treated with SABR. Pre-SABR PSMA+EV levels (EVs/ml) were measured by nanoscale flow cytometry. Kaplan-Meier curves and logistic regression models were used to determine the association of PSMA+EV and PSA levels with clinical outcomes.

Results

In the pooled cohorts, median bPFS were 26.1 and 15.0 months (p=0.005) and median rPFS were 36.0 and 25.0 months (p=0.003) for PSMA+EV low and high groups, respectively. The combination of pre-SABR low levels of both PSMA+EV and PSA was associated with lower risk of radiographic progression (HR=0.34, 95% CI: 0.18-0.58, p=0.0002). In the ORIOLE cohort, which included both a SABR arm and an observation arm, low PSMA+EV was predictive of benefit from SABR (p=0.012).

Conclusions

PSMA+EV is a novel prognostic and predictive biomarker of radiographically occult tumor burden in omCSPC. PSMA+EV may inform clinical decisions regarding which patients achieve a durable benefit from consolidative SABR alone.
Leveraging an Online Dashboard to Inform on Infectious Disease Surveillance: A case Study of COVID-19 in Kenya
Authors: Mwanga Mike J. , Guzman-Rincon Laura M. , Kingwara Leonard , Odhiambo Don B. , Gathuri Henry , Lambisia Arnold , Mwita John Morobe , Moraa Edidah , Kutima Bernadette , Gitonga John , Mugo Daisy , Agoti Charles N. , Nyagwange James , Warimwe George , Oyier Isabella , Nokes D. James , Agweyu Ambrose , Kagucia E Wangeci , Etyang Anthony , Kiiru John , Githinji George
Published: September 2024

A multi-pronged approach to combating the COVID-19 pandemic in Kenya resulted in the formation of multidisciplinary research initiatives including genomic sequencing, syndromic surveillance, sero-surveillance, vaccination, and mathematical modelling. These initiatives generated an overwhelming amount of data that posed a challenge to researchers and public health officials, to effectively manage, analyse and promptly interpret for immediate pandemic response. As a result, there was demand for a platform to collate and integrate these datasets with interpretable findings to aid in pandemic management. In response, we developed a web-based dashboard, and integrated multidisciplinary datasets collected by the Ministry of Health-Kenya (MoH-K) and other research organizations, to support surveillance and monitoring of COVID-19 in Kenya. The developed dashboard combines genomics, epidemiological, seroprevalence, modelling, vaccination, syndromic and phylogenetic data and provides real-time updates to the public and health sector experts. The dashboard provides temporal trends of reported COVID-19 cases, fatalities, variants, and vaccination, in addition to summary reports from multiple cross-sectional seroprevalence studies and ongoing facility-based inpatient syndromic surveillance from 15 health facilities across Kenya. This is the first detailed interactive dashboard in Kenya that combines multiple datasets from a disease outbreak to provide valuable insights to researchers, health policy makers, the media and public not only during pandemic but also during routine surveillance. This resource is a model for digital platform for infectious disease surveillance and for informing public health planning and intervention.

Dashboard Link

https://kcd.kemri-wellcome.org/
INCIDENCE OF BENIGN PROSTATIC HYPERPLASIA IN TESTICULAR CANCER SURVIVORS IN THE VETERANS AFFAIRS HEALTH SYSTEM
Authors: Pandit Kshitij , Morgan Kylie , Riviere Paul , Cortez-Ryes Josue , Meagher Margaret , Nelson Tyler , Puri Dhruv , Yodkhunnatham Nuphat , Millard Frederick , Mckay Rana R. , Rose Brent , Bagrodia Aditya
Published: September 2024

Testosterone and prostatic inflammation have been postulated to influence the development of benign prostatic hyperplasia (BPH). Our study aims to evaluate the incidence of BPH in Testicular Cancer (TCa) survivors, focusing on the impact of chemotherapy and post TCa diagnosed hypogonadism. We conducted a retrospective cohort analysis of US veterans diagnosed with TCa between 1990 to 2021, using the Veterans affairs database. BPH was defined using International Classification of Diseases (ICD) codes, Current Procedural Terminology (CPT) codes, or a 6-month prescription of medications. Associations with BPH were analysed, stratifying the cohort by receipt of chemotherapy and presence of hypogonadism. Multivariable cox regression models were used to determine statistical significance (p-value <0.05). Our cohort included 2038 TCa survivors with a median age at diagnosis of 41 years. On multivariable cox regression analysis, receipt of chemotherapy wasn’t significantly associated with incidence of BPH (p-value= 0.13). When stratified by diagnosis of hypogonadism prior to BPH, no significant associations were found on univariable (p=0.81) as well as multivariable (p=0.65) analyses. In the multivariable model, age at diagnosis was significantly associated with an increased incidence of BPH (Hazard ratio: 1.06, p<0.001). Our findings demonstrate that age is a significant factor associated with development of BPH in this population, while suggesting that chemotherapy for TCa and hypogonadism might not substantially alter the development of BPH.

Patient summary

In this study, we looked at whether testicular cancer survivors are more likely to develop an enlarged prostate (Benign Prostatic Hyperplasia), especially if they received chemotherapy or had low testosterone afterward. We found that age, rather than cancer treatment or testosterone levels, was the main factor linked to developing an enlarged prostate.
In computer explore The neutralization mechanism of Amubarvimab and Romlusevimab against SARS-COV-2 mutants
Authors: Huan Xinkang , Gao Hongwei
Published: September 2024

Since the end of 2019, The coronavirus disease 2019 (COVID-19) has been endemic worldwide for three years, causing more than 6.95 million deaths and having a massive impact on the global political economy. With time, the Severe acute respiratory syndrome coronavirus 2(SARS-COV-2) is also constantly mutating. Mutations lead to stronger infectivity or virulence of the virus, and some monoclonal antibodies against wild-type SARS-COV-2 are also challenging to play a role. Amubarvimab and Romlusevimab were originally developed against wild-type SARS-COV-2; however, these monoclonal antibodies’ neutralizing efficacy and mechanism against these mutants are unknown. In this study, the binding ability of Amubarvimab and Romlusevimab to 7 mutant strains were tested by computer method and the interaction mechanism was explored. Our experimental data show that Amubarvimab can effectively bind most mutations and maintain the stability of the complexes mainly through hydrogen bond interaction; However, the binding efficiency of Romlusevimab was lower than that of Amubarvimab, and the stability of the complexes was maintained mainly through electrostatic interaction. Both Amubarvimab and Romlusevimab show low binding potency against E406W and Q498Y mutations, so there is a certain probability of immune escape in the face of variants carrying E406W and Q498Y mutations when Amubarvimab and Romlusevimab are used in combination.
Whole-exome sequencing study of opioid dependence offers novel insights into the contributions of exome variants
Authors: Wang Lu , Nuñez Yaira Z. , Kranzler Henry R. , Zhou Hang , Gelernter Joel
Published: September 2024

Opioid dependence (OD) is epidemic in the United States and it is associated with a variety of adverse health effects. Its estimated heritability is ∼50%, and recent genome-wide association studies have identified more than a dozen common risk variants. However, there are no published studies of rare OD risk variants. In this study, we analyzed whole-exome sequencing data from the Yale-Penn cohort, comprising 2,100 participants of European ancestry (EUR; 1,321 OD cases) and 1,790 of African ancestry (AFR; 864 cases). A novel low-frequency variant (rs746301110) in theRUVBL2gene was identified in EUR (p=6.59×10-10). Suggestive associations (p<1×10-5) were observed inTMCO3in EUR, inNEIL2andCFAP44in AFR, and inFAM210Bin the cross-ancestry meta-analysis. Gene-based collapsing tests identifiedSLC22A10,TMCO3,FAM90A1,DHX58,CHRND,GLDN,PLAT,H1-4,COL3A1,GPHB5andQPCTLas top genes (p<1×10-4) with most associations attributable to rare variants and driven by the burden of predicted loss-of-function and missense variants. This study begins to fill the gap in our understanding of the genetic architecture of OD, providing insights into the contribution of rare coding variants and potential targets for future functional studies and drug development.
Hospital-onset bacteraemia and fungaemia as a novel automated surveillance indicator: results from four European university hospitals
Authors: Aghdassi Seven J.S. , van der Werff Suzanne D. , Catho Gaud , Brekelmans Manon , Peña Diaz Luis A. , Buetti Niccolò , Rüther Ferenc D. , Teixeira Daniel Dinis , Sjöholm Daniel , Nauclér Pontus , Behnke Michael , van Mourik Maaike S.M.
Published: September 2024

Background

Conventional manual surveillance of healthcare-associated infections is labour-intensive and therefore often restricted to areas with high-risk patients. Fully automated surveillance of hospital-onset bacteraemia and fungaemia (HOB) may facilitate hospital-wide surveillance.

Aim

To develop an algorithm and minimal dataset (MDS) required for automated surveillance of HOB and apply it to real-life routine data in four European hospitals.

Methods

Through consensus discussion a HOB definition with MDS suitable for automated surveillance was developed and applied in a retrospective multicentre observational study including all admitted adult patients (2018-2022). HOB was defined as a positive blood culture with a recognised pathogen two or more days after hospital admission. For common commensals, two blood cultures with the same commensal within two days were required. Annual HOB rates were calculated per 1,000 patient days for the hospital and for intensive care units (ICU) and non-ICU.

Results

HOB rates were comparable between the four hospitals (1.0 to 2.2 per 1,000 patient days). HOB rates were substantially higher in ICU than non-ICU across the four hospitals, and HOB with common commensals accounted for 14.8-28.2% of all HOB. HOB rates per 1,000 patient days were rather consistent over time, but were higher in 2020 and 2021. HOB caused by Staphylococcus aureus accounted for 8.4-16.0% of all HOB.

Conclusion

Automated HOB surveillance using a common definition was feasible and reproducible across four European hospitals. Future studies should investigate clinical relevance and preventability of HOB, and focus on strategies to make the automated HOB metric an actionable infection control tool.
Electroencephalographic (EEG) Changes Accompanying Normal Breathing of Concentrated Oxygen (Hyperoxic Ventilation) by Healthy Adults: A Systematic Review
Authors: Barnes Lachlan D. , Hallum Luke E. , Vrijdag Xavier C.E.
Published: September 2024

Introduction

Divers often increase their fraction of inspired oxygen (FiO2) to decrease their risk of decompression sickness. However, breathing concentrated oxygen can cause hyperoxia, and central nervous system oxygen toxicity (CNS-OT). This study aims to review the literature describing hyperoxic ventilation’s effect on the electroencephalogram (EEG), thus exploring the potential for real-time detection of impending CNS-OT seizure.

Methods

We searched Medline, Embase, Scopus, and Web of Science for articles that reported EEG measures accompanying hyperoxic ventilation (FiO2= 1.0) in healthy participants. We included peer-reviewed journal articles, books, and government reports with no language or date restrictions. Randomised controlled trials and cross-over studies were included; case reports were excluded. We used the Newcastle-Ottawa scale to evaluate evidence quality.

Results

Our search strategy returned 1025 unique abstracts; we analysed the full text of 40 articles; 22 articles (16 studies) were included for review. Study cohorts were typically small, and comprised of male non-divers. We discovered a variety of EEG analysis methods: studies performed spectral analysis (n= 12), the analysis of sensory-evoked potentials (n= 4), connectivity/complexity analysis (n= 3), source localization (n= 1), and expert qualitative analyses (n= 4). Studies of severe exposures (long duration at hyperbaric pressure) typically reported qualitative measures, and studies of mild exposures typically reported quantitative measures.

Conclusions

There is a need for a large randomised controlled trial (RCT) reporting quantitative measures to better understand hyperoxic ventilation’s effect on EEG, thus enabling the development of real-time monitoring of CNS-OT risk.
In-utero exposure to PM2.5 and adverse birth outcomes in India: Geostatistical modelling using remote sensing and demographic health survey data 2019-21
Authors: Jana Arup , Pramanik Malay , Maiti Arabinda , Chattopadhyay Aparajita , Abed Al Ahad Mary
Published: September 2024

Rapid urbanization in India is contributing to heightened poor air quality. Yet research on the impact of poor air on adverse birth outcomes (ABOs) especially in the public health aspect is less in India. This study investigates the influence of air quality on birth weight (LBW) and preterm birth (PTB). Utilizing data from the National Family Health Survey and satellite images, the study employs various statistical analyses and spatial models to elucidate the connection between in-utero exposure to air pollution and birth outcomes, both at the individual and district levels. It was observed that approximately 13% of children were born prematurely, and 17% were born with low birth weight. Increased ambient PM2.5 concentrations during pregnancy were associated with higher odds of LBW (AOR: 1.4; 95% CI: 1.29–1.45). Mothers exposed to PM2.5 during pregnancy had a heightened likelihood of delivering prematurely (AOR: 1.7; 95% CI: 1.57–1.77) in comparison to unexposed mothers. Climatic factors such as rainfall and temperature had a greater association with ABOs. Children residing in the Northern districts of India appeared to be more susceptible to the adverse effects of ambient air pollution. Furthermore, indoor air pollution was found to be associated with LBW. Employing a distributed spline approach, the study identified a discernible upward trend in the risk of adverse birth outcomes as the level of exposure increased, particularly following an exposure level of 40 PM2.5 ug/m3. Among the spatial models employed, the MGWR spatial model exhibited the highest level of goodness of fit. In addition to addressing immediate determinants such as nutrition and maternal healthcare, it is imperative to collaboratively address distal factors encompassing both indoor and outdoor pollution to attain lasting enhancements in child health.
Postoperative 20% Albumin and Cardiac Surgery Associated Kidney Injury, Statistical Analysis Plan and Updated Protocol
Authors: Balachandran Mayurathan , Pakavakis Adrian , Al-Bassam Wisam , Collins David , Mandarano Raffaele , Sarode Vineet , Bellomo Rinaldo , Brown Alastair , Bihari Shailesh , Li Mozhu , Brown Alana , Shehabi Yahya
Published: September 2024

Background

The incidence of cardiac surgery associated acute kidney injury (CS-AKI) remains high. Patients who develop AKI after cardiac surgery are at higher risk of persistent renal dysfunction and increased long-term mortality. The risk of CS-AKI is significantly increased in patients with chronic kidney disease and in patients having prolonged bypass for complex surgery. Previous trials of albumin did not show any benefit in prevention of CS-AKI. These trials, however, did not focus on high-risk patients and used albumin as a resuscitation strategy. The aim of ALBICS-AKI is to demonstrate the effect of concentrated albumin infusion on CS-AKI in high-risk patients undergoing cardiac surgery compared with standard care.

Methods

ALBICS-AKI is an investigator initiated, multicentre, randomised, open label trial. Seven centres in Australia and Italy will participate in the trial. We will randomise 620 adult patients who will undergo on-pump cardiac surgery with one of the following: an estimated glomerular filtration rate <60 ml/min/1.73m2, combined valve/s, coronary artery, or surgery involving thoracic aorta. Within 6 hours after surgery, a 20% albumin infusion will commence at 20ml/h for 15 hours. All patients will receive standard care as per institutional protocols. The primary outcome is the proportion of patients with AKI according to creatinine based KDIGO definition at hospital discharge or day 28, whichever comes first. Secondary outcomes include Major Adverse Kidney Events at day 28, AKI stage II and III, need for renal replacement therapy, and hospital mortality.

Ethics and dissemination

The trial was approved by Monash Health Lead Research Committee for Australian sites and by the Italian Medicine Agency for Italian sites. The estimated study completion date is Sep 2024. The results will be presented at major conferences and submitted for publication in peer-reviewed journals.

Trial registration number

Australian New Zealand Clinical Trials Registry ACTRN12619001355167
A Strategic Blend of Stabilizing Polymers to Control Particle Surface Charge for Enhanced Mucus Transport and Cell Binding
Authors: Stevens Corey A. , Sevarika Boris , Wilson Brian K. , Wang Chia-Ming , Cárcamo-Oyarce Gerardo , Degen George , Kassis Timothy , Lehr Claus Michael , Carrier Rebecca , Ribbeck Katharina , Prud’homme Robert K.
Published: September 2024

Mucus layers, viscoelastic gels abundant in anionic mucin glycoproteins, obstruct therapeutic delivery across all mucosal surfaces. We found that strongly positively charged nanoparticles (NPs) rapidly adsorb a mucin protein corona in mucus, impeding cell binding and uptake. To overcome this, we developed mucus-evading, cell-adhesive (MECS) NPs with variable surface charge using Flash NanoPrecipitation, by blending a neutral poly(ethylene glycol) (PEG) corona for mucus transport with a small amount, 5 wt%, of polycationic dimethylaminoethyl methacrylate (PDMAEMA) for increased cell targeting.In vitroexperiments confirmed rapid mucus penetration and binding to epithelial cells by MECS NPs, suggesting a breakthrough in mucosal drug delivery.
Evidence for vertical line nodes in
Sr2RuO4
from nonlocal electrodynamics
Authors: Landaeta J. F. , Semeniuk K. , Aretz J. , Shirer K. R. , Sokolov D. A. , Kikugawa N. , Maeno Y. , Bonalde I. , Schmalian J. , Mackenzie A. P. , Hassinger E.
Published: September 2024

By determining the superconducting lower and upper critical fields Hc1(T) and Hc2(T), respectively, in a high-purity spherical Sr2RuO4 sample via ac-susceptibility measurements, we obtain the temperature dependence of the coherence length ξ and the penetration depth λ down to 0.04Tc. Given the high sample quality, the observed T2 dependence of λ at low temperatures cannot be explained in terms of impurity effects. Instead, we argue that the weak type-II superconductor Sr2RuO4 has to be treated in the nonlocal limit. By comparing our data with existing theory in that limit, the penetration depth in Sr2RuO4 agrees with a gap structure having vertical line nodes, while horizontal line nodes cannot account for the observation. The work highlights the potential benefits of purifying other unconventional superconductors in order to access the fascinating nonlocal regime in more materials and to determine their Cooper pair wave functions.

Published by the American Physical Society
2024
Studies of
Z
boson decay into double
ϒ
mesons at the NLO QCD accuracy
Authors: Li Cong , Jiang Ying-Zhao , Sun Zhan
Published: September 2024

In this paper, we employ the nonrelativistic quantum chromodynamics (QCD) factorization to conduct a comprehensive examination of the Z boson decay into a pair of ϒ mesons, achieving accuracy at the next-to-leading-order (NLO) in αs. Our calculations demonstrate that the quantum electrodynamics (QED) diagrams are indispensable in comparison to the pure QCD diagrams, and the implementation of QCD corrections markedly enhances the QCD results, whereas it substantially diminishes the QED results. To ensure consistency with the experimental methodology, we have taken into account the feed-down transitions originating from higher excited states, which exhibit significant relevance. Combining all the contributions, we arrive at the NLO prediction of BZ→ϒ(nS)+ϒ(mS)∼10−11, which is notably lower than the upper limits set by CMS.

Published by the American Physical Society
2024
Exploring axionlike particle couplings through single top
tW
-channel and top pair production at the LHC
Authors: Hosseini Yasaman , Mohammadi Najafabadi Mojtaba
Published: September 2024

In this paper, we explore the interactions between light axionlike particles (ALPs) and top quarks, gluons, and W-bosons. Utilizing high-energy probes at the LHC, we probe these couplings in the context of single top quark production associated with a W-boson and an ALP. We analyze the latest LHC Run II data on tt¯ spin correlation measurements to establish constraints on these couplings. Additionally, we compare these constraints with those derived from loop-induced couplings and indirect searches involving B-meson decays. Furthermore, we derive two-dimensional limits on the ALP couplings with top quarks and gluons.

Published by the American Physical Society
2024