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For a hypergraph $\mathcal{H}$, define the minimum positive codegree $\delta_i^+(\mathcal{H})$ to be the largest integer $k$ such that every $i$-set which is contained in at least one edge of $\mathcal{H}$ is contained in at least $k$ edges. For $1\le s\le k,t$ and $t\le r$, we prove that for $n$-vertex $t$-intersecting $r$-graphs $\mathcal{H}$ with $\delta_{r-s}^+(\mathcal{H})>{k-1\choose s}$, the unique hypergraph with the maximum number of edges is the hypergraph $\mathcal{H}$ consisting of every edge which intersects a set of size $2k-2s+t$ in at least $k-s+t$ vertices provided $n$ is sufficiently large. This generalizes work of Balogh, Lemons, and Palmer who proved this for $s=t=1$, as well as the Erd\H{o}s-Ko-Rado theorem when $k=s$., Comment: 10 pages

Exposure to traumatic events is associated with increased risk for negative physical health outcomes, but more work is needed to advance understanding of the mechanisms underlying this relationship. As military deployments frequently involve trauma exposure, this issue has clear implications for veteran populations. This longitudinal study examined the role of mental health symptomatology (i.e., PTSD, depression, and anxiety) in the association between war zone stress and postdeployment physical health in Gulf War veterans.Data were collected in three waves over 7 years from a sample of 2,929 (92% male) Army personnel who were deployed to the 1990-1991 Gulf War. Structural equation modeling (SEM) was used to examine the associations linking war zone stress exposure reported at deployment return with subsequent physical health 6 to 7 years later, including the postdeployment onset of health symptoms and conditions and health functioning. The roles of PTSD, depression, and anxiety symptom severity as potential risk mechanisms linking stress exposure with later health outcomes were examined.Self-reported higher stress exposure was linked with greater severity of PTSD, depression, and anxiety symptoms. SEM analyses revealed that PTSD symptom severity was the only significant mediator of stress exposure on subsequent physical health.Findings support the unique and significant role of PTSD in the development of physical health problems in the wake of war zone stress for Gulf War veterans. These results suggest that targeted PTSD interventions could reduce or prevent future physical health problems that can result from trauma exposure and mental health sequelae linked to military service. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Analysis of premalignant tissue has identified the typical order of somatic events leading to invasive tumors in several cancer types. For other cancers, premalignant tissue is unobtainable, leaving genetic progression unknown. Here, we demonstrate how to infer progression from exome sequencing of primary tumors. Our computational method, PhylogicNDT, recapitulated the previous experimentally determined genetic progression of human papillomavirus-negative (HPV–) head and neck squamous cell carcinoma (HNSCC). We then evaluated HPV+ HNSCC, which lacks premalignant tissue, and uncovered its previously unknown progression, identifying early drivers. We converted relative timing estimates of driver mutations and HPV integration to years before diagnosis based on a clock-like mutational signature. We associated the timing of transitions to aneuploidy with increased intratumor genetic heterogeneity and shorter overall survival. Our approach can establish previously unknown early genetic progression of cancers with unobtainable premalignant tissue, supporting development of experimental models and methods for early detection, interception and prognostication.

Most diseases of the spine disproportionately impact older persons, with the modal (i.e., commonest) patient a female in their 8th decade of life. We examined the corpus of spinal RCTs to determine how many included “average” spine patients. We searched PubMed for randomized clinical trials published in the top 7 spine journals over a period of 5 years from 2016 to 2020 and extracted nominal upper age cut-offs and the distribution of ages actually recruited. We identified 186 trials of 26,238 patients. We found that only 4.8% of trials could be applied to an “average” 75-year-old patient. This age-based exclusion was not dependent on funding source. Age-based exclusion was exacerbated by explicit upper age cut-offs, however, the age-based exclusion went beyond explicit age cut-offs. Only few trials were applicable to older patients even amongst trials with no age cut-off specified. Age-based exclusion from clinical trials starts at late middle age. The mismatch between spinal patient’s age seen in clinical practice and spinal patient’s age in trials was so severe that over the 5 years (2016–2020) almost no RCT evidence was produced applicable to the “average” aged-patient across the body of literature available. In conclusion, age-based exclusion is ubiquitous, multifactorial, and happens on a supratrial level. Eliminating age-based exclusion involves more than an arbitrary lifting of explicitly stated upper age cut-offs. Instead, recommendations include increasing input from geriatricians and ethics committees, establishing updated or new models of cares, and creating new protocols to facilitate further research.

The SUPPORT Act provided resources for developing prescription drug monitoring programs (PDMPs) capable of reporting on four specific opioid quality measures. Therefore, the objective of this pilot study was to map, test, and adapt these claims-based opioid quality measures specified for health plan performance to PDMP data for state-level performance.Maryland PDMP and claims from Maryland Medicaid beneficiaries continuously enrolled from April 1, 2019, to March 31, 2020.The measure rates as specified using claims data are closely aligned with the measure rates when mapped and adapted to PDMP data. The Concurrent Use of Opioids and Benzodiazepines measure rates were 14.49% and 15.31%, the OHD rates were 12.44% and 13.54%, the OHDMP rates were 0.01% and 0.40%, and the Use of Opioids from Multiple Providers in Persons Without Cancer rates were 0.12% and 3.03% for the claims-based and adapted measures, respectively.This is a novel application that may be replicated in other states to support quality improvement and can have a measurable effect on stemming the drug abuse epidemic.This will facilitate data sharing of the opioid quality measure reporting within the Maryland PDMP and stakeholders responsible for caring for Maryland Medicaid beneficiaries. Owing to the encouragement by the Centers for Medicare and Medicaid Services, other states' PDMPs may require the adaptation of these measures. This will open the door for innovative state-level policy and practice interventions. The quantification of outcomes related to these measures will inform our learning healthcare system and help support the Quintuple Aim.

The standard practice for management for asymptomatic severe aortic stenosis with a normal left ventricular systolic function is conservative management with a few exceptions. This practice is challenged by two recent randomized controlled trials (RCT). All the prior data is observational. We performed a meta-analysis of these 2 RCTs to determine if early surgical aortic valve replacement in this patient population is beneficial compared with the standard conservative therapy.

Usutu virus (USUV) is an emerging zoonotic arbovirus in Europe, where it primarily impacts Eurasian blackbirds (Turdus merula). For mosquito-borne viruses to persist in temperate areas, transovarial transmission in vectors or overwintering in either hosts or diapausing vectors must occur to facilitate autochthonous transmission. We undertook surveillance of hosts and vectors in 2021 to elucidate whether USUV had overwintered in the United Kingdom (UK) following its initial detection there in 2020. From 175 dead bird submissions, we detected 1 case of USUV infection, in a blackbird, from which a full USUV genome was derived. Using a molecular clock analysis, we demonstrate that the 2021 detection shared a most recent common ancestor with the 2020 Greater London, UK, USUV sequence. In addition, we identified USUV-specific neutralizing antibodies in 10 out of 86 serum samples taken from captive birds at the index site, demonstrating in situ cryptic infection and potential sustained transmission. However, from 4966 mosquitoes, we detected no USUV RNA suggesting that prevalence in the vector community was absent or low during sampling. Combined, these results suggest that USUV overwintered in the UK, thus providing empirical evidence for the continued northward expansion of this vector-borne viral disease. Currently, our detection indicates geographically restricted virus persistence. Further detections over time will be required to demonstrate long-term establishment. It remains unclear whether the UK, and by extension other high-latitude regions, can support endemic USUV infection.

HRas, KRas, and NRas are GTPases with a common set of effectors that control many cell-signaling pathways, including proliferation through Raf kinase. Their G-domains are nearly identical in sequence, with a few isoform-specific residues that have an effect on dynamics and biochemical properties. Here, we use accelerated molecular dynamics (aMD) simulations consistent with solution x-ray scattering experiments to elucidate mechanisms through which isoform-specific residues associated with each Ras isoform affects functionally important regions connected to the active site. HRas-specific residues cluster in loop 8 to stabilize the nucleotide-binding pocket, while NRas-specific residues on helix 3 directly affect the conformations of switch I and switch II. KRas, the most globally flexible of the isoforms, shows greatest fluctuations in the switch regions enhanced by a KRas-specific residue in loop 7 and a highly dynamic loop 8 region. The analysis of isoform-specific residue effects on Ras proteins is supported by NMR experiments and is consistent with previously published biochemical data.

A tiered pediatric Asthma Population Health Management Program (APHMP), based on evidence-based practices, that differentially targets populations for intervention based on rising risk for high utilization and disease complications was implemented at 6 urban and suburban practices affiliated with an academic medical center. In addition to standard pediatric asthma care, APHMP adds regular administration of the asthma control test (ACT), provider education on performance variation, and monitoring through the electronic health record-based asthma registry. As patients' use of acute health care services and complications increases, APHMP integrates multidisciplinary interventions, including an asthma coach who conducts environmental assessments in addition to addressing social needs, into their primary care. A retrospective cohort study method was used to assess population-level effects on asthma event rates and practice- and provider-level variation from 2017 to 2019. Consistent with well-documented health disparities in pediatric asthma, the analysis demonstrated that patients who were male (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.02-1.43), 4-8 years old (OR = 4.91, 95% CI = 3.27-7.37), Spanish speaking (OR = 1.67, 95% CI = 1.54-1.81), from low-income neighborhoods (OR = 1.56, 95% CI = 1.53-2.46), and with ACT20 (OR = 2.88, 95% CI = 1.97-4.21) had higher odds of having asthma events. Six percent of patients studied were found to be at risk for high health care utilization and disease complications. Study limitations include the absence of a control group, the mixed model data collection approach, and the effects of seasonal variation on asthma events. Future directions include analyzing disease management program outcomes of incorporating an asthma coach into a patient's primary care team and addressing provider-level variation in asthma event rates.

Oral and maxillofacial surgeons frequently encounter patients who require extractions following exposure to head and neck radiation, and they must assess the risk of extraction and consider alternatives such as deliberate root retention. The purpose of this study was to determine whether dose volume would be a better predictor for osteoradionecrosis (ORN) than total dose.This is a retrospective cohort study of patients diagnosed with ORN following head and neck radiation (administered between January 2006 and December 2018) and a comparison group selected based on site and dosage who did not develop ORN. The predictor variables were total radiation dose and mandibular dose volume, and the outcome variable was ORN occurrence. Covariates included age, sex, cancer stage and site, radiation therapy type, smoking status, alcohol use, adjuvant chemotherapy use, medical comorbidities, and concomitant tumor surgery. Logistic regression models were employed and area under receiver operating characteristic curve (AUROC) and model accuracy (Acc) were used to determine the better predictor.A total of 56 patients were included in the study: 27 ORN positive (ORN+) and 29 matched controls who did not develop ORN (ORN-). Most patients were male (76.8%), considered smokers (78.6%), used alcohol (80.4%), were in stage IV (66.1%), received chemotherapy (75.0%), and received intensity modulated radiation therapy radiation (55.4%). The statistical models with V50 Gy (cc) and V65 Gy (cc) dosage variables exhibited greater predictability of ORN occurrence than total dose (AUROC: 0.90 vs 0.76 and model accuracy: 0.82 vs 0.75, respectively).The results suggest that following head and neck radiation, dose volume may be a better predictor of ORN risk than total dose. This finding is significant, both for the oral and maxillofacial surgeon who is preoperatively assessing ORN risk following radiation exposure, and for the radiation oncologist striving to minimize the risk associated with their treatment.

A correction to this paper has been published: https://doi.org/10.1007/JHEP11(2021)100

The Bay of Bengal (BoB) is a 2,600,000 km2 expanse in the Indian Ocean upon which many humans rely. However, the primary producers underpinning food chains here remain poorly characterized. We examined phytoplankton abundance and diversity along strong BoB latitudinal and vertical salinity gradients—which have low temperature variation (27–29°C) between the surface and subsurface chlorophyll maximum (SCM). In surface waters, Prochlorococcus averaged 11.7 ± 4.4 × 104 cells ml−1, predominantly HLII, whereas LLII and ‘rare’ ecotypes, HLVI and LLVII, dominated in the SCM. Synechococcus averaged 8.4 ± 2.3 × 104 cells ml−1 in the surface, declined rapidly with depth, and population structure of dominant Clade II differed between surface and SCM; Clade X was notable at both depths. Across all sites, Ostreococcus Clade OII dominated SCM eukaryotes whereas communities differentiated strongly moving from Arabian Sea-influenced high salinity (southerly; prasinophytes) to freshwater-influenced low salinity (northerly; stramenopiles, specifically, diatoms, pelagophytes, and dictyochophytes, plus the prasinophyte Micromonas) surface waters. Eukaryotic phytoplankton peaked in the south (1.9 × 104 cells ml−1, surface) where a novel Ostreococcus was revealed, named here Ostreococcus bengalensis. We expose dominance of a single picoeukaryote and hitherto ‘rare’ picocyanobacteria at depth in this complex ecosystem where studies suggest picoplankton are replacing larger phytoplankton due to climate change.

BACKGROUND: Enhanced innate immune response is detected in autopsy studies of Parkinson’s disease (PD) but the role of microglia in early pathophysiology is unclear. While the translocator protein 18 kDa (TSPO) that marks glial activation may be high in PD, TSPO expression is not limited to microglia, and ligand binding affinity for newer generation radiotracers for imaging TSPO with PET varies across individuals due to a common single nucleotide polymorphism in TSPO. Imaging the colony stimulating factor 1 receptor (CSF1R) with [(11)C]CPPC PET offers an opportunity to image a complementary in vivo marker of microglial number and/or activity in early PD. OBJECTIVE: To determine whether the binding of [(11)C]CPPC differs across the brains of healthy controls and patients with early PD, and to test for correlation between binding and disease severity in early PD. METHODS: Healthy controls and persons with PD of ≤2 years disease duration and Hoehn & Yahr

Accreting protoplanets are windows into planet formation processes, and high-contrast differential imaging is an effective way to identify them. We report results from the Giant Accreting Protoplanet Survey (GAPlanetS), which collected Hα differential imagery of 14 transitional disk host stars with the Magellan Adaptive Optics System. To address the twin challenges of morphological complexity and point-spread function instability, GAPlanetS required novel approaches for frame selection and optimization of the Karhounen–Loéve Image Processing algorithm pyKLIP. We detect one new candidate, CS Cha “c,” at a separation of 68 mas and a modest Δmag of 2.3. We recover the HD 142527 B and HD 100453 B accreting stellar companions in several epochs, and the protoplanet PDS 70 c in 2017 imagery, extending its astrometric record by nine months. Though we cannot rule out scattered light structure, we also recover LkCa 15 “b,” at Hα; its presence inside the disk cavity, absence in Continuum imagery, and consistency with a forward-modeled point source suggest that it remains a viable protoplanet candidate. Through targeted optimization, we tentatively recover PDS 70 c at two additional epochs and PDS 70 b in one epoch. Despite numerous previously reported companion candidates around GAplanetS targets, we recover no additional point sources. Our moderate Hα contrasts do not preclude most protoplanets, and we report limiting Hα contrasts at unrecovered candidate locations. We find an overall detection rate of ∼36 − 22 + 26 % , considerably higher than most direct imaging surveys, speaking to both GAPlanetS’s highly targeted nature and the promise of Hα differential imaging for protoplanet identification.

This post hoc subgroup analysis examined efficacy and safety outcomes with extended thromboprophylaxis rivaroxaban compared with in-hospital enoxaparin in 2,078 patients from the MAGELLAN study who had a hospitalization for heart failure or a history of heart failure and a lower risk of bleeding. A significant 36% reduction in the composite endpoint of asymptomatic proximal deep vein thrombosis (DVT) in the lower extremity, symptomatic DVT in the lower extremity (proximal or distal), symptomatic nonfatal pulmonary embolism, and venous thromboembolism-related death was observed with rivaroxaban. Major bleeding was low in both groups and not significantly increased with rivaroxaban.

Surface-supported molecular overlayers have demonstrated versatility as platforms for fundamental research and a broad range of applications, from atomic-scale quantum phenomena to potential for electronic, optoelectronic and catalytic technologies. Here, we report a structural and electronic characterisation of self-assembled magnesium phthalocyanine (MgPc) mono and bilayers on the Ag(100) surface, via low-temperature scanning tunneling microscopy and spectroscopy, angle-resolved photoelectron spectroscopy (ARPES), density functional theory (DFT) and tight-binding (TB) modeling. These crystalline close-packed molecular overlayers consist of a square lattice with a basis composed of a single, flat-adsorbed MgPc molecule. Remarkably, ARPES measurements at room temperature on the monolayer reveal a momentum-resolved, two-dimensional (2D) electronic energy band, 1.27 eV below the Fermi level, with a width of ∼20 meV. This 2D band results from in-plane hybridization of highest occupied molecular orbitals of adjacent, weakly interacting MgPc's, consistent with our TB model and with DFT-derived nearest-neighbor hopping energies. This work opens the door to quantitative characterisation – as well as control and harnessing – of subtle electronic interactions between molecules in functional organic nanofilms.

Introduction: When influenza (flu) season arrives, it is easy for emergency department clinicians to anchor on the diagnosis of flu, sending patients on their way with or without anti-influenza medication. It is important not to miss the outlier – the patient who seems to have typical symptoms of influenza but with certain subtleties that should make one consider expanding the differential diagnosis. Case Report: We describe an 11-year-old previously healthy male who presented with eight days of fever, myalgias, cough, congestion, and headache in the context of positive influenza exposure. The length and severity of his symptoms prompted laboratory and imaging investigation. He was positive for influenza type B with elevated inflammatory markers but otherwise normal laboratory workup and normal chest radiograph. He complained of a headache and was given fluids and antipyretics, and was admitted for overnight observation. He specifically did not have any forehead swelling. The next day during his inpatient stay he developed right frontal forehead edema and appeared ill. He was taken for a sinus computed tomography, which showed changes consistent with frontal bone osteomyelitis. Even after drainage by neurosurgery and otolaryngology, the patient subsequently developed repeat abscesses and ultimately a superior sagittal sinus thrombosis. Conclusion: Other sources of infection should be considered in patients who have flu-like symptoms that last longer than expected, present with focality, or appear ill.

This study investigated how adults in the United Kingdom perceived their arts and cultural engagement to facilitate social connectedness over two phases in the first year of the COVID-19 pandemic.The study used the HEartS Survey, a newly designed online survey tool to capture arts engagement in the United Kingdom and its associations with social and mental well-being, over two phases in 2020: March to May (Phase 1) and October (Phase 2).Qualitative data were provided at both phases by 581 respondents, who identified which arts and cultural activity they felt most connected them to others and how during the last month.Thematic analysis revealed that, at both phases, arts and cultural engagement was perceived to facilitate social connectedness through four pathways that were also identified prepandemic: social opportunities, sharing, feelings of commonality and belonging and collective understanding. The subthemes shed light on specific ways that respondents used the arts during the pandemic to connect with others, including using the arts: as a catalyst for conversations, to maintain, reinstate or strengthen relationships during social distancing and to facilitate social interactions (Theme 1); to bring people together through shared experiences and sharing of art (Theme 2); to elicit feelings of direct and indirect proximity to others, to connect people with common interests, to feel a sense of belonging to something and to feel part of a collective 'COVID-19 experience' or to feel collectively distracted from the pandemic (Theme 3); and to learn from and about other people and to relate to others (Theme 4). The activity most frequently cited as connecting was watching a film or drama, followed by listening to recorded music.Engagement in arts and cultural activities supported feelings of social connection among adults in the United Kingdom over two phases in the first year of the COVID-19 pandemic, highlighting the importance of access to the arts and culture to support social connectedness.

Previous research suggests anxious individuals demonstrate hypervigilance for threatening stimuli. Recent controversial studies suggested people's bodies (presentiment) and brain (precognition, Bem, 2011; Bem et al., 2015) can 'predict' biologically salient events, such as threatening stimuli, milliseconds to seconds before they occur. If true, this suggests a possible mechanism for hypervigilance towards threatening stimuli in anxious individuals. We sought to replicate Bem's precognitive avoidance experiment in an independent cohort of adolescents (n = 144), tested whether performance ability is associated with state or trait anxiety, and examined sex-differences in these variables. We hypothesized that trait anxiety would correlate positively with precognitive avoidance performance. We were unable to replicate the 2011 Bem findings in our sample (precognitive avoidance hit rate = 48.95%, p = 0.825), and neither trait nor state anxiety was correlated with precognitive avoidance. We did not detect a sex difference in precognitive avoidance (females > males: t = 1.36, p = 0.175, two sample t-test). We found higher levels of trait anxiety in females in line with previous research. Contrary to our hypotheses, we failed to detect evidence for precognitive avoidance in our sample, possibly because our study was underpowered. Implications are discussed with respect to related literature.

Currently, malignant diseases are one of the leading causes of mortality worldwide. Antarctic yeasts represent a poorly explored source of novel bioactive compounds with antineoplastic activity and expected favourable toxicological profile. The aim of the work was the evaluation of the antiproliferative and proapoptotic potential of extracts obtained from the psychrophilic strain Sporobolomyces roseus AL103. Data from MTT dye reduction assay showed that urothelial cancer cell line T-24 was more sensitive (85--101 μg/mL) than the non-tumour cell line (CCL-1- 343 to 432 μg/mL). Apoptosis analysis after treatment with different yeast extracts revealed strong potential to inhibit various antiapoptotic factors as well as selective induction of apoptosis in tumour cells as confirmed by flow cytometry, too.

Given a graph $F$, we define $\operatorname{ex}(G_{n,p},F)$ to be the maximum number of edges in an $F$-free subgraph of the random graph $G_{n,p}$. Very little is known about $\operatorname{ex}(G_{n,p},F)$ when $F$ is bipartite, with essentially tight bounds known only when $F$ is either $C_4, C_6, C_{10}$, or $K_{s,t}$ with $t$ sufficiently large in terms of $s$, due to work of F\"uredi and of Morris and Saxton. We extend this work by establishing essentially tight bounds when $F$ is a theta graph with sufficiently many paths. Our main innovation is in proving a balanced supersaturation result for vertices, which differs from the standard approach of proving balanced supersaturation for edges.

Microstreams are fluctuations in the solar wind speed and density associated with polarity-reversing folds in the magnetic field (also denoted switchbacks). Despite their long heritage, the origin of these microstreams/switchbacks remains poorly understood. For the first time, we investigated periodicities in microstreams during Parker Solar Probe (PSP) Encounter 10 to understand their origin. Our analysis was focused on the inbound corotation interval on 2021 November 19-21, while the spacecraft dove toward a small area within a coronal hole (CH). Solar Dynamics Observatory remote-sensing observations provide rich context for understanding the PSP in-situ data. Extreme ultraviolet images from the Atmospheric Imaging Assembly reveal numerous recurrent jets occurring within the region that was magnetically connected to PSP during intervals that contained microstreams. The periods derived from the fluctuating radial velocities in the microstreams (approximately 3, 5, 10, and 20 minutes) are consistent with the periods measured in the emission intensity of the jetlets at the base of the CH plumes, as well as in larger coronal jets and in the plume fine structures. Helioseismic and Magnetic Imager magnetograms reveal the presence of myriad embedded bipoles, which are known sources of reconnection-driven jets on all scales. Simultaneous enhancements in the PSP proton flux and ionic ($^3$He, $^4$He, Fe, O) composition during the microstreams further support the connection with jetlets and jets. In keeping with prior observational and numerical studies of impulsive coronal activity, we conclude that quasiperiodic jets generated by interchange/breakout reconnection at CH bright points and plume bases are the most likely sources of the microstreams/switchbacks observed in the solar wind., ApJ Letters, 19 pages, 12 figures

Background Through the evolution of novel wing structures, bats (Order Chiroptera) became the only mammalian group to achieve powered flight. This achievement preceded the massive adaptive radiation of bats into diverse ecological niches. We investigate some of the developmental processes that underlie the origin and subsequent diversification of one of the novel membranes of the bat wing: the plagiopatagium, which connects the fore- and hind limb in all bat species. Results Our results suggest that the plagiopatagium initially arises through novel outgrowths from the body flank that subsequently merge with the limbs to generate the wing airfoil. Our findings further suggest that this merging process, which is highly conserved across bats, occurs through modulation of the programs controlling the development of the periderm of the epidermal epithelium. Finally, our results suggest that the shape of the plagiopatagium begins to diversify in bats only after this merging has occurred. Conclusions This study demonstrates how focusing on the evolution of cellular processes can inform an understanding of the developmental factors shaping the evolution of novel, highly adaptive structures.

Breast cancer (BC) risk models based on electronic health records (EHR) can assist physicians in estimating the probability of an individual with certain risk factors to develop BC in the future. In this retrospective study, we used clinical data combined with machine learning tools to assess the utility of a personalized BC risk model on 13,786 Israeli and 1,695 American women who underwent screening mammography in the years 2012-2018 and 2008-2018, respectively. Clinical features were extracted from EHR, personal questionnaires, and past radiologists’ reports. Using a set of 1,547 features, the predictive ability for BC within 12 months was measured in both datasets and in sub-cohorts of interest. Our results highlight the improved performance of our model over previous established BC risk models, their ultimate potential for risk-based screening policies on first time patients and novel clinically relevant risk factors that can compensate for the absence of imaging history information.

Cancers occur across species. Understanding what is consistent and varies across species can provide new insights into cancer initiation and evolution, with significant implications for animal welfare and wildlife conservation. We build a pan-species cancer digital pathology atlas (panspecies.ai) and conduct a pan-species study of computational comparative pathology using a supervised convolutional neural network algorithm trained on human samples. The artificial intelligence algorithm achieves high accuracy in measuring immune response through single-cell classification for two transmissible cancers (canine transmissible venereal tumour, 0.94; Tasmanian devil facial tumour disease, 0.88). In 18 other vertebrate species (mammalia = 11, reptilia = 4, aves = 2, and amphibia = 1), accuracy (range 0.57–0.94) is influenced by cell morphological similarity preserved across different taxonomic groups, tumour sites, and variations in the immune compartment. Furthermore, a spatial immune score based on artificial intelligence and spatial statistics is associated with prognosis in canine melanoma and prostate tumours. A metric, named morphospace overlap, is developed to guide veterinary pathologists towards rational deployment of this technology on new samples. This study provides the foundation and guidelines for transferring artificial intelligence technologies to veterinary pathology based on understanding of morphological conservation, which could vastly accelerate developments in veterinary medicine and comparative oncology.

Paracoccus denitrificans is a metabolically versatile Gram-negative bacterium that is used as a model for studies of respiratory metabolism. The organism can utilize nitrate as an electron acceptor for anaerobic respiration, reducing it to dinitrogen via nitrite, nitric oxide, and nitrous oxide.