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Abstract Prior research demonstrates that news-related social media posts using negative language are re-posted more, rewarding users who produce negative content. We investigate whether negative material from external news sites is also introduced to social media through more user posts, offering comparable incentives for journalists to adopt a negative tone. Data from four US and UK news sites (95,282 articles) and two social media platforms (579,182,075 posts on Facebook and Twitter, now X) show social media users are 1.91 times more likely to share links to negative news articles. The impact of negativity varies by news site and social media platform and, for political articles, is moderated by topic focus, with users showing a greater inclination to share negative articles referring to opposing political groups. Additionally, negativity amplifies news dissemination on social media to a greater extent when accounting for the re-sharing of user posts containing article links. These findings suggest a higher prevalence of negatively toned articles on Facebook and Twitter compared to online news sites. Further, should journalists respond to the incentives created by the heightened sharing of negative articles to social media platforms, this could even increase negative news exposure for those who do not use social media.

Abstract Deep learning-assisted digital pathology has demonstrated the potential to profoundly impact clinical practice, even surpassing human pathologists in performance. However, as deep neural network (DNN) architectures grow in size and complexity, their explainability decreases, posing challenges in interpreting pathology features for broader clinical insights into physiological diseases. To better assess the interpretability of digital microscopic images and guide future microscopic system design, we developed a novel method to study the predictive feature length-scale that underpins a DNN’s predictive power. We applied this method to analyze a DNN’s capability in predicting brain metastasis from early-stage non-small-cell lung cancer biopsy slides. This study quantifies DNN’s attention for brain metastasis prediction, targeting features at both the cellular scale and tissue scale in H&E-stained histological whole slide images. At the cellular scale, the predictive power of DNNs progressively increases with higher resolution and significantly decreases when the resolvable feature length exceeds 5 microns. Additionally, DNN uses more macro-scale features associated with tissue architecture and is optimized when assessing visual fields greater than 41 microns. Our study computes the length-scale requirements for optimal DNN learning on digital whole-slide microscopic images, holding the promise to guide future optical microscope designs in pathology applications and facilitating downstream deep learning analysis.

Abstract The rumen microbiome is the focus of a growing body of research, mostly based on investigation of rumen fluid samples collected once from each animal. Exploring the temporal stability of rumen microbiome profiles is imperative, as it enables evaluating the reliability of findings obtained through single-timepoint sampling. We explored the temporal stability of rumen microbiomes considering taxonomic and functional aspects across the 7-month growing-finishing phase spanning 6 timepoints. We identified a temporally stable core microbiome, encompassing 515 microbial genera (e.g., Methanobacterium) and 417 microbial KEGG genes (e.g., K00856—adenosine kinase). The temporally stable core microbiome profiles collected from all timepoints were strongly associated with production traits with substantial economic and environmental impact (e.g., average daily gain, daily feed intake, and methane emissions); 515 microbial genera explained 45–83%, and 417 microbial genes explained 44–83% of their phenotypic variation. Microbiome profiles influenced by the bovine genome explained 54–87% of the genetic variation of bovine traits. Overall, our results provide evidence that the temporally stable core microbiome identified can accurately predict host performance traits at phenotypic and genetic level based on a single timepoint sample taken as early as 7 months prior to slaughter.

Abstract Furthering our knowledge of the skin microbiome is essential to understand health and disease in canines. To date, studies into the canine skin microbiome have focused on 16S rRNA high throughput sequencing however, these lack the granularity of species and strain level taxonomic characterisation and their associated functions. The aim of this study was to provide a comprehensive assessment of the skin microbiome by analysing the skin microbiome of 72 healthy adult colony dogs, across four distinct skin sites and four breeds, using metagenomic sequencing. Our analysis revealed that breed and skin site are drivers of variation, and a core group of taxa and genes are present within the skin microbiome of healthy dogs, comprising 230 taxa and 1219 gene families. We identified 15 species within the core microbiome that are represented by more than one strain. The biosynthesis of secondary metabolites pathway was enriched in the core microbiome suggesting the skin microbiome may play a role in colonisation resistance and protection from invading pathogens. Additionally, we uncovered the novelty of the canine skin microbiome and show that further investigation is required to increase the suitability of current databases for metagenomic sequencing of canine skin samples.

Abstract There is growing evidence that a relationship exists between mental and emotional wellbeing and the gut microbiota. Little is known regarding how the microbiota reacts to repeated acute stress events in dogs, and whether it is a predictor of stress response. In this study, we explored the impact on the gut microbiota and digestive health with two common events many pet dogs find stressful. Twenty healthy adult dogs, living within a colony, were exposed to either car travel or separation three times across eight-week intervals. Faecal samples were collected 24 h before, within 24 h, and 24–48 h after. Faecal quality and pH, and microbiota diversity and composition were analysed in context with wider published work on physiological stress measures. No significant changes were observed in faecal quality or pH with either stress event at any timepoint, indicating all pets remained in good digestive health. Microbiota analysis demonstrated no significant impact on alpha or beta diversity with either stressor. Microbial signatures previously linked to stress were not identified in these dogs and no changes were observed in the functional gut composition. Irrespective of whether the pet was considered “stressed” (i.e., exhibited an increase in serum cortisol), there was no effect on the microbiota and no taxa were predictive of stress response. Collectively, this work demonstrates, for this population, certain acute stress events have no meaningful impact on the canine gut microbiota, and it has no impact on the associated stress response.

Abstract Carbonate sediments are often regarded as problematic in geotechnical engineering due to the high variability of their properties. Understanding and quantifying this variability will become increasingly critical in the years ahead, notably with respect to upcoming developments in offshore renewable energy, for which limited in-situ data are typically available to characterise large areas. Here, six intervals from the North West Shelf of Australia, each composed of similar carbonate grains but accumulated in different environments, are investigated to better understand how the post-depositional cementation, alteration and dissolution of sediments, known as diagenesis, impact their geotechnical properties. Intervals are primarily affected by mineralogy-driven meteoric diagenesis, comprising in-situ dissolution of metastable grains and subsequent precipitation of cement that occurred when the shelf was exposed during lower sea-levels, and by marine diagenesis. In both cases, increased diagenesis results in a higher cement-to-solid ratio and compressive strength. However, while marine diagenesis is associated with a reduction in void ratio, this is not initially observed with mineralogy-driven meteoric diagenesis. Additionally, for a similar cement-to-solid ratio, microcrystalline cement results in higher compressive strength than sparite cement. The data further reveal that the level of meteoric cementation and the compressive strength increase as a function of the duration of exposure and of the regional climate, along with a reduction of the specific gravity related to the replacement of aragonite by calcite. However, increased meteoric diagenesis also leads to the formation of macro-scale heterogeneities such as calcrete layers and karsts that can affect the holistic geotechnical behaviour of such deposits.

Abstract We aimed to characterize the cognitive profile of post-acute COVID-19 syndrome (PACS) patients with cognitive complaints, exploring the influence of biological and psychological factors. Participants with confirmed SARS-CoV-2 infection and cognitive complaints ≥ 8 weeks post-acute phase were included. A comprehensive neuropsychological battery (NPS) and health questionnaires were administered at inclusion and at 1, 3 and 6 months. Blood samples were collected at each visit, MRI scan at baseline and at 6 months, and, optionally, cerebrospinal fluid. Cognitive features were analyzed in relation to clinical, neuroimaging, and biochemical markers at inclusion and follow-up. Forty-nine participants, with a mean time from symptom onset of 10.4 months, showed attention-executive function (69%) and verbal memory (39%) impairment. Apathy (64%), moderate-severe anxiety (57%), and severe fatigue (35%) were prevalent. Visual memory (8%) correlated with total gray matter (GM) and subcortical GM volume. Neuronal damage and inflammation markers were within normal limits. Over time, cognitive test scores, depression, apathy, anxiety scores, MRI indexes, and fluid biomarkers remained stable, although fewer participants (50% vs. 75.5%; p = 0.012) exhibited abnormal cognitive evaluations at follow-up. Altered attention/executive and verbal memory, common in PACS, persisted in most subjects without association with structural abnormalities, elevated cytokines, or neuronal damage markers.

Abstract Settlement is a critical period in the life cycle of marine invertebrates with a planktonic larval stage. For reef-building invertebrates such as oysters and corals, settlement rates are predictive for long-term reef survival. Increasing evidence suggests that marine invertebrates use information from ocean soundscapes to inform settlement decisions. Sessile marine invertebrates with a planktonic stage are particularly reliant on environmental cues to direct them to ideal habitats. As gregarious settlers, oysters prefer to settle amongst members of the same species. It has been hypothesized that oyster larvae from species Crassostrea virginica and Ostrea angasi use distinct conspecific oyster reef sounds to navigate to ideal habitats. In controlled laboratory experiments we exposed Pacific Oyster Magallana gigas larvae to anthropogenic sounds from conspecific oyster reefs, vessels, combined reef-vessel sounds as well as off-reef and no speaker controls. Our findings show that sounds recorded at conspecific reefs induced higher percentages of settlement by about 1.44 and 1.64 times compared to off-reef and no speaker controls, respectively. In contrast, the settlement increase compared to the no speaker control was non-significant for vessel sounds (1.21 fold), combined reef-vessel sounds (1.30 fold), and off-reef sounds (1.18 fold). This study serves as a foundational stepping stone for exploring larval sound feature preferences within this species.

Abstract We report the first detection and prevalence of Beak and feather disease virus (BFDV) in Australia’s Red Goshawk (Erythrotriorchis radiatus). This is a new host for this pervasive pathogen amongst a growing list of non-psittacine species including birds of prey from the orders Accipitriformes (hawks, eagles, kites), Falconiformes (falcons and caracas), and Strigiformes (owls). The Red Goshawk is the first non-psittacine species listed as Endangered to be diagnosed with BFDV. We report an initial case of infection discovered post-mortem in a dead nestling and subsequent surveillance of birds from across northern Australia. We reveal BFDV prevalence rates in a wild raptor population for the first time, with detections in 25% (n = 7/28) of Red Goshawks sampled. Prevalence appears higher in juveniles compared to adults, although not statistically significant, but is consistent with studies of wild psittacines. BFDV genotypes were associated with the Loriinae (lorikeets, budgerigar, and fig parrots), Cacatuini (Cockatoos), and Polytelini (long-tailed parrots) tribes; species which are preyed upon by Red Goshawks. A positive BFDV status may be associated with lower body mass but small sample sizes precluded robust statistical analysis. We postulate the possible impacts of the virus on Red Goshawks and discuss future research priorities given these preliminary observations.

Abstract In natural environments, head movements are required to search for objects outside the field of view (FoV). Here we investigate the power of a salient target in an extended visual search array to facilitate faster detection once this item comes into the FoV by a head movement. We conducted two virtual reality experiments using spatially clustered sets of stimuli to observe target detection and head and eye movements during visual search. Participants completed search tasks with three conditions: (1) target in the initial FoV, (2) head movement needed to bring the target into the FoV, (3) same as condition 2 but the periphery was initially hidden and appeared after the head movement had brought the location of the target set into the FoV. We measured search time until participants found a more salient (O) or less salient (T) target among distractors (L). On average O’s were found faster than T’s. Gaze analysis showed that saliency facilitation occurred due to the target guiding the search only if it was within the initial FoV. When targets required a head movement to enter the FoV, participants followed the same search strategy as in trials without a visible target in the periphery. Moreover, faster search times for salient targets were only caused by the time required to find the target once the target set was reached. This suggests that the effect of stimulus saliency differs between visual search on fixed displays and when we are actively searching through an extended visual field.

Abstract Mycobacterial pathogens present a significant challenge to disease control efforts globally due to their inherent resistance to multiple antibiotics. The rise of drug-resistant strains of Mycobacterium tuberculosis has prompted an urgent need for innovative therapeutic solutions. One promising way to discover new tuberculosis drugs is by utilizing natural products from the vast biochemical space. Multidisciplinary methods can used to harness the bioactivity of these natural products. This study aimed to evaluate the antimycobacterial efficacy of functional crude extracts from bacteria isolated from gold mine tailings in South Africa. Bacterial strains were identified using 16S rRNA sequencing. The crude extracts obtained from the bacteria were tested against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2155, and Mycobacterium aurum A+. Untargeted HPLC-qTOF and molecular networking were used to identify the functional constituents present in extracts that exhibited inhibitory activity. A virtual screening workflow (VSW) was used to filter compounds that were strong binders to Mycobacterium tuberculosis Pks13 and PknG. The ligands returned from the VSW were subjected to optimization using density functional theory (DFT) at M06-2X/6-311++ (d,p) level of theory and basis set implemented in Gaussian16 Rev.C01. The optimized ligands were re-docked against Mycobacterium tuberculosis Pks13 and PknG. Molecular dynamics simulation and molecular mechanics generalized born surface area were used to evaluate the stability of the protein–ligand complexes formed by the identified hits. The hit that showed promising binding characteristics was virtually modified through multiple synthetic routes using reaction-driven enumeration. Three bacterial isolates showed significant activity against the two strains of Mycobacterium, while only two, Bacillus subtilis and Bacillus licheniformis, exhibited activity against both Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis mc2155, and Mycobacterium aurum A+. The tentatively identified compounds from the bacterial crude extracts belonged to various classes of natural compounds associated with antimicrobial activity. Two compounds, cyclo-(L-Pro-4-OH-L-Leu) and vazabitide A, showed strong binding against PknG and Pks13, with pre-MD MM-GBSA values of − 42.8 kcal/mol and − 47.6 kcal/mol, respectively. The DFT-optimized compounds exhibited the same docking scores as the ligands optimized using the OPSL-4 force field. After modifying vazabitide A, its affinity to the Pks13 binding site increased to − 85.8 kcal/mol, as revealed by the post-MD MM-GBSA analysis. This study highlights the potential of bacteria isolates from gold mine tailings as a source of new scaffolds for designing and optimizing anti-Mycobacterium agents. These agents synthesized in-silico can be further tested in-vitro to evaluate their efficacy.

Abstract Antibiotic resistance is recognised as one of the biggest global threats to human and animal health. Understanding the influence of antibiotics on the canine microbiome is important to know the potential mid-to-long term effects on dysbiosis and mitigate side-effects such as antibiotic-associated diarrhoea. In this study, metronidazole was prescribed to 22 dogs for suspected giardiasis after exhibiting gastrointestinal symptoms such as diarrhoea and/or vomiting. Faecal samples were collected before, during seven days of treatment, and six months post-cessation. Faecal microbiota was assessed with 16S rRNA sequencing. Shannon diversity was reduced for up to three days after the treatment ended, and an altered community persisted for four to six weeks. All dogs recovered to a similar microbiome composition as pre-treatment. Immediately after receiving metronidazole, an increase in the relative abundance of the genera Lactobacillus, Bifidobacterium, and Enterococcus was observed. This may be due to antibiotic resistance commonly exhibited by these organisms. One-to-two weeks post-cessation, several other genera that were sensitive to the antibiotic recovered in abundances, with taxa belonging to the Erysipelotrichaceae family particularly driving composition change. Many of the bacteria initially reduced were associated with carbohydrate fermentation. This suggests scope exists to explore interventions to augment gastrointestinal health and support the re-establishment of the microbiome.

Abstract Radiation-attenuated sporozoite (RAS) vaccines can completely prevent blood stage Plasmodium infection by inducing liver-resident memory CD8+ T cells to target parasites in the liver. Such T cells can be induced by ‘Prime-and-trap’ vaccination, which here combines DNA priming against the P. yoelii circumsporozoite protein (CSP) with a subsequent intravenous (IV) dose of liver-homing RAS to “trap” the activated and expanding T cells in the liver. Prime-and-trap confers durable protection in mice, and efforts are underway to translate this vaccine strategy to the clinic. However, it is unclear whether the RAS trapping dose must be strictly administered by the IV route. Here we show that intradermal (ID) RAS administration can be as effective as IV administration if RAS are co-administrated with the glycolipid adjuvant 7DW8-5 in an ultra-low inoculation volume. In mice, the co-administration of RAS and 7DW8-5 in ultra-low ID volumes (2.5 µL) was completely protective and dose sparing compared to standard volumes (10–50 µL) and induced protective levels of CSP-specific CD8+ T cells in the liver. Our finding that adjuvants and ultra-low volumes are required for ID RAS efficacy may explain why prior reports about higher volumes of unadjuvanted ID RAS proved less effective than IV RAS. The ID route may offer significant translational advantages over the IV route and could improve sporozoite vaccine development.

Abstract The stochastic synthesis of extreme, rare climate scenarios is vital for risk and resilience models aware of climate change, directly impacting society in different sectors. However, creating high-quality variations of under-represented samples remains a challenge for several generative models. This paper investigates quantizing reconstruction losses for helping variational autoencoders (VAE) better synthesize extreme weather fields from conventional historical training sets. Building on the classical VAE formulation using reconstruction and latent space regularization losses, we propose various histogram-based penalties to the reconstruction loss that explicitly reinforces the model to synthesize under-represented values better. We evaluate our work using precipitation weather fields, where models usually strive to synthesize well extreme precipitation samples. We demonstrate that bringing histogram awareness to the reconstruction loss improves standard VAE performance substantially, especially for extreme weather events.

Abstract The neurobiological mechanisms that regulate the appetite-stimulatory properties of cannabis sativa are unresolved. This work examined the hypothesis that cannabinoid-1 receptor (CB1R) expressing neurons in the mediobasal hypothalamus (MBH) regulate increased appetite following cannabis vapor inhalation. Here we utilized a paradigm where vaporized cannabis plant matter was administered passively to rodents. Initial studies in rats characterized meal patterns and operant responding for palatable food following exposure to air or vapor cannabis. Studies conducted in mice used a combination of in vivo optical imaging, electrophysiology and chemogenetic manipulations to determine the importance of MBH neurons for cannabis-induced feeding behavior. Our data indicate that cannabis vapor increased meal frequency and food seeking behavior without altering locomotor activity. Importantly, we observed augmented MBH activity within distinct neuronal populations when mice anticipated or consumed food. Mechanistic experiments demonstrated that pharmacological activation of CB1R attenuated inhibitory synaptic tone onto hunger promoting Agouti Related Peptide (AgRP) neurons within the MBH. Lastly, chemogenetic inhibition of AgRP neurons attenuated the appetite promoting effects of cannabis vapor. Based on these results, we conclude that MBH neurons contribute to the appetite stimulatory properties of inhaled cannabis.

Abstract Anopheles arabiensis and Anopheles funestus sensu stricto mosquitoes are major East African malaria vectors. Understanding their dispersal and population structure is critical for developing effective malaria control tools. Three mark-release-recapture (MRR) experiments were conducted for 51 nights to assess daily survival and flight range of An. arabiensis and An. funestus mosquitoes in south-eastern, Tanzania. Mosquitoes were marked with a fluorescent dye as they emerged from breeding sites via a self-marking device. Mosquitoes were collected indoors and outdoors using human landing catches (HLC) and Centers for Disease Control and Prevention light traps (CDC-LT). In total, 4210 An. arabiensis and An. funestus were collected with 316 (7.5%) marked and recaptured (MR). Daily mean MR was 6.8, standard deviation (SD ± 7.6) for An. arabiensis and 8.9 (SD ± 8.3) for An. funestus. Probability of daily survival was 0.76 for An. arabiensis and 0.86 for An. funestus translating into average life expectancy of 3.6 days for An. arabiensis and 6.5 days for An. funestus. Dispersal distance was 654 m for An. arabiensis and 510 m for An. funestus. An. funestus life expectancy was substantially longer than that of An. arabiensis. The MRR method described here could be routinely utilized when evaluating the impact of new vector control tools on mosquito survival.

The aim of this study was to derive a model to predict the risk of dogs developing chronic kidney disease (CKD) using data from electronic health records (EHR) collected during routine veterinary practice. Data from 57,402 dogs were included in the study. Two thirds of the EHRs were used to build the model, which included feature selection and identification of the optimal neural network type and architecture. The remaining unseen EHRs were used to evaluate model performance. The final model was a recurrent neural network with 6 features (creatinine, blood urea nitrogen, urine specific gravity, urine protein, weight, age). Identifying CKD at the time of diagnosis, the model displayed a sensitivity of 91.4% and a specificity of 97.2%. When predicting future risk of CKD, model sensitivity was 68.8% at 1 year, and 44.8% 2 years before diagnosis. Positive predictive value (PPV) varied between 15 and 23% and was influenced by the age of the patient, while the negative predictive value remained above 99% under all tested conditions. While the modest PPV limits its use as a stand-alone diagnostic screening tool, high specificity and NPV make the model particularly effective at identifying patients that will not go on to develop CKD.

Abstract Diastolic dysfunction is increasingly identified as a key, early onset subclinical condition characterizing cardiopathologies of rising prevalence, including diabetic heart disease and heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction characterization has important prognostic value in management of disease outcomes. Validated tools for in vivo monitoring of diastolic function in rodent models of diabetes are required for progress in pre-clinical cardiology studies. 2D speckle tracking echocardiography has emerged as a powerful tool for evaluating cardiac wall deformation throughout the cardiac cycle. The aim of this study was to examine the applicability of 2D speckle tracking echocardiography for comprehensive global and regional assessment of diastolic function in a pre-clinical murine model of cardio-metabolic disease. Type 2 diabetes (T2D) was induced in C57Bl/6 male mice using a high fat high sugar dietary intervention for 20 weeks. Significant impairment in left ventricle peak diastolic strain rate was evident in longitudinal, radial and circumferential planes in T2D mice. Peak diastolic velocity was similarly impaired in the longitudinal and radial planes. Regional analysis of longitudinal peak diastolic strain rate revealed that the anterior free left ventricular wall is particularly susceptible to T2D-induced diastolic dysfunction. These findings provide a significant advance on characterization of diastolic dysfunction in a pre-clinical mouse model of cardiopathology and offer a comprehensive suite of benchmark values for future pre-clinical cardiology studies.

Abstract Naturally occurring canine cancers have remarkable similarities to their human counterparts. To better understand these similarities, we investigated 671 client-owned dogs from 96 breeds with 23 common tumor types, including those whose mutation profile are unknown (anal sac carcinoma and neuroendocrine carcinoma) or understudied (thyroid carcinoma, soft tissue sarcoma and hepatocellular carcinoma). We discovered mutations in 50 well-established oncogenes and tumor suppressors, and compared them to those reported in human cancers. As in human cancer, TP53 is the most commonly mutated gene, detected in 22.5% of canine tumors overall. Canine tumors share mutational hotspots with human tumors in oncogenes including PIK3CA, KRAS, NRAS, BRAF, KIT and EGFR. Hotspot mutations with significant association to tumor type include NRAS G61R and PIK3CA H1047R in hemangiosarcoma, ERBB2 V659E in pulmonary carcinoma, and BRAF V588E (equivalent of V600E in humans) in urothelial carcinoma. Our findings better position canines as a translational model of human cancer to investigate a wide spectrum of targeted therapies.

Abstract Epidemiologic data suggest that the prevalence of hypertension in patients with diabetes mellitus is ∼1.5–2.0 times greater than in matched non-diabetic patients. This co-existent disease burden exacerbates cardiac and vascular injury, leading to structural and functional changes to the myocardium, impaired cardiac function and heart failure. Oxidative stress and persistent low-grade inflammation underlie both conditions, and are identified as major contributors to pathological cardiac remodelling. There is an urgent need for effective therapies that specifically target oxidative stress and inflammation to protect against cardiac remodelling. Animal models are a valuable tool for testing emerging therapeutics, however, there is a notable lack of appropriate animal models of co-morbid diabetes and hypertension. In this study, we describe a novel preclinical mouse model combining diabetes and hypertension to investigate cardiac and vascular pathology of co-morbid disease. Type 1 diabetes was induced in spontaneously hypertensive, 8-week old, male Schlager (BPH/2) mice via 5 consecutive, daily injections of streptozotocin (55 mg/kg in citrate buffer; i.p.). Non-diabetic mice received citrate buffer only. After 10 weeks of diabetes induction, cardiac function was assessed by echocardiography prior to post-mortem evaluation of cardiomyocyte hypertrophy, interstitial fibrosis and inflammation by histology, RT-PCR and flow cytometry. We focussed on the oxidative and inflammatory stress pathways that contribute to cardiovascular remodelling. In particular, we demonstrate that markers of inflammation (monocyte chemoattractant protein; MCP-1), oxidative stress (urinary 8-isoprostanes) and fibrosis (connective tissue growth factor; CTGF) are significantly increased, whilst diastolic dysfunction, as indicated by prolonged isovolumic relaxation time (IVRT), is elevated in this diabetic and hypertensive mouse model. In summary, this pre-clinical mouse model provides researchers with a tool to test therapeutic strategies unique to co-morbid diabetes and hypertension, thereby facilitating the emergence of novel therapeutics to combat the cardiovascular consequences of these debilitating co-morbidities.

Abstract Circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) from whole blood are emerging as important biomarkers that potentially aid in cancer diagnosis and prognosis. The microfilter technology provides an efficient capture platform for them but is confounded by two challenges. First, uneven microfilter surfaces makes it hard for commercial scanners to obtain images with all cells in-focus. Second, current analysis is labor-intensive with long turnaround time and user-to-user variability. Here we addressed the first challenge through developing a customized imaging system and data pre-processing algorithms. Utilizing cultured cancer and CAF cells captured by microfilters, we showed that images from our custom system are 99.3% in-focus compared to 89.9% from a top-of-the-line commercial scanner. Then we developed a deep-learning-based method to automatically identify tumor cells serving to mimic CTC (mCTC) and CAFs. Our deep learning method achieved precision and recall of 94% (± 0.2%) and 96% (± 0.2%) for mCTC detection, and 93% (± 1.7%) and 84% (± 3.1%) for CAF detection, significantly better than a conventional computer vision method, whose numbers are 92% (± 0.2%) and 78% (± 0.3%) for mCTC and 58% (± 3.9%) and 56% (± 3.5%) for CAF. Our custom imaging system combined with deep learning cell identification method represents an important advance on CTC and CAF analysis.

Abstract As part of the COVID-19 pandemic, clinical laboratories have been faced with massive increases in testing, resulting in sample collection systems, reagent, and staff shortages. We utilized self-collected saline gargle samples to optimize high throughput SARS-CoV-2 multiplex polymerase chain reaction (PCR) testing in order to minimize cost and technologist time. This was achieved through elimination of nucleic acid extraction and automation of sample handling on a widely available robotic liquid handler, Hamilton STARlet. A customized barcode scanning script for reading the sample ID by the Hamilton STARlet’s software system was developed to allow primary tube sampling. Use of pre-frozen SARS-CoV-2 assay reaction mixtures reduced assay setup time. In both validation and live testing, the assay produced no false positive or false negative results. Of the 1060 samples tested during validation, 3.6% (39/1060) of samples required retesting as they were either single gene positive, had internal control failure or liquid aspiration error. Although the overall turnaround time was only slightly faster in the automated workflow (185 min vs 200 min), there was a 76% reduction in hands-on time, potentially reducing staff fatigue and burnout. This described process from sample self-collection to automated direct PCR testing significantly reduces the total burden on healthcare systems in terms of human resources and reagent requirements.

Transition-metal dichalcogenides (TMDs) offer an ideal platform to experimentally realize Dirac fermions. However, typically these exotic quasiparticles are located far away from the Fermi level, limiting the contribution of Dirac-like carriers to the transport properties. Here we show that NiTe2 hosts both bulk Type-II Dirac points and topological surface states. The underlying mechanism is shared with other TMDs and based on the generic topological character of the Te p-orbital manifold. However, unique to NiTe2, a significant contribution of Ni d orbital states shifts the energy of the Type-II Dirac point close to the Fermi level. In addition, one of the topological surface states intersects the Fermi energy and exhibits a remarkably large spin splitting of 120 meV. Our results establish NiTe2 as an exciting candidate for next-generation spintronics devices.

Dietary odd-chain saturated fatty acids (OCFAs) are present in trace levels in dairy fat and some fish and plants. Higher circulating concentrations of OCFAs, pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), are associated with lower risks of cardiometabolic diseases, and higher dietary intake of OCFAs is associated with lower mortality. Population-wide circulating OCFA levels, however, have been declining over recent years. Here, we show C15:0 as an active dietary fatty acid that attenuates inflammation, anemia, dyslipidemia, and fibrosis in vivo, potentially by binding to key metabolic regulators and repairing mitochondrial function. This is the first demonstration of C15:0's direct role in attenuating multiple comorbidities using relevant physiological mechanisms at established circulating concentrations. Pairing our findings with evidence that (1) C15:0 is not readily made endogenously, (2) lower C15:0 dietary intake and blood concentrations are associated with higher mortality and a poorer physiological state, and (3) C15:0 has demonstrated activities and efficacy that parallel associated health benefits in humans, we propose C15:0 as a potential essential fatty acid. Further studies are needed to evaluate the potential impact of decades of reduced intake of OCFA-containing foods as contributors to C15:0 deficiencies and susceptibilities to chronic disease.

Abstract Plantago ovata is cultivated for production of its seed husk (psyllium). When wet, the husk transforms into a mucilage with properties suitable for pharmaceutical industries, utilised in supplements for controlling blood cholesterol levels, and food industries for making gluten-free products. There has been limited success in improving husk quantity and quality through breeding approaches, partly due to the lack of a reference genome. Here we constructed the first chromosome-scale reference assembly of P. ovata using a combination of 5.98 million PacBio and 636.5 million Hi-C reads. We also used corrected PacBio reads to estimate genome size and transcripts to generate gene models. The final assembly covers ~ 500 Mb with 99.3% gene set completeness. A total of 97% of the sequences are anchored to four chromosomes with an N50 of ~ 128.87 Mb. The P. ovata genome contains 61.90% repeats, where 40.04% are long terminal repeats. We identified 41,820 protein-coding genes, 411 non-coding RNAs, 108 ribosomal RNAs, and 1295 transfer RNAs. This genome will provide a resource for plant breeding programs to, for example, reduce agronomic constraints such as seed shattering, increase psyllium yield and quality, and overcome crop disease susceptibility.

Abstract A dynamical control of the coupling strengths between dressed states and probe photon states is demonstrated with a transmon-like artificial atom coupled to two closely spaced resonant modes. When the atom is driven with one mode, the atom state and driving photon states form the so-called dressed states. Dressed states with sideband index up to 3 were prepared and probed via the strong coupling to the other resonant mode. Spectroscopy reveals that the coupling strengths are “dressed” and can be modulated by the power and sideband index of the driving. The transmission of the probe tone is modulated by the driving microwave amplitude with a Bessel behavior, displaying multi-photon process associated with the inter-atomic level transitions.

Abstract The menopause can lead to epidermal changes that are alleviated by hormone replacement therapy (HRT). We hypothesise that these changes could relate to altered ceramide production, and that oestrogen may have a role in keratinocyte ceramide metabolism. White Caucasian women were recruited into three groups: pre-menopausal (n = 7), post-menopausal (n = 11) and post-menopausal taking HRT (n = 10). Blood samples were assessed for hormone levels, transepidermal water loss was measured to assess skin barrier function, and stratum corneum lipids were sampled from photoprotected buttock skin. Ceramides and sphingomyelins were analysed by ultraperformance liquid chromatography with electrospray ionisation and tandem mass spectrometry. Post-menopausal stratum corneum contained lower levels of ceramides, with shorter average length; changes that were not evident in the HRT group. Serum oestradiol correlated with ceramide abundance and length. Ceramides had shorter sphingoid bases, indicating altered de novo ceramide biosynthesis. Additionally, post-menopausal women had higher sphingomyelin levels, suggesting a possible effect on the hydrolysis pathway. Treatment of primary human keratinocytes with oestradiol (10 nM) increased production of CER[NS] and CER[NDS] ceramides, confirming an effect of oestrogen on cutaneous ceramide metabolism. Taken together, these data show perturbed stratum corneum lipids post-menopause, and a role for oestrogen in ceramide production.

Abstract ‘Pant-hoot displays’ are a species-typical, multi-modal communicative behaviour in chimpanzees in which pant-hoot vocalisations are combined with varied behavioural displays. In both captivity and the wild, individuals commonly incorporate striking or throwing elements of their environment into these displays. In this case study, we present five videos of an unenculturated, captive, adult male chimpanzee combining a large rubber feeding tub with excelsior (wood wool) in a multi-step process, which was then integrated into the subject’s pant-hoot displays as a percussive tool or ‘instrument’. During the construction process, the subject demonstrated an understanding of the relevant properties of these materials, ‘repairing’ the tub to be a more functional drum when necessary. We supplement these videos with a survey of care staff from the study site for additional detail and context. Although care must be taken in generalising data from a single individual, the behaviour reported here hints at three intriguing features of chimpanzee communicative cognition: (1) it suggests a degree of voluntary control over vocal production, (2) it is a so-far unique example of compound tool innovation and use in communicative behaviour and (3) it may represent an example of forward planning in communicative behaviour. Each of these would represent hitherto undocumented dimensions of flexibility in chimpanzee communication, mapping fertile ground for future research.