Miracle-dz/UniFAR-FTUs huggingface dataset:
Exact completions and toposes

Toposes and quasi-toposes have been shown to be useful in mathematics, logic and computer science. Because of this, it is important to understand the different ways in which they can be constructed. Realizability toposes and presheaf toposes are two important classes of toposes. All of the former and many of the latter arise by adding “good” quotients of equivalence relations to a simple category with finite limits. This construction is called the exact completion of the original category. Exact completions are not always toposes and it was not known, not even in the realizability and presheaf cases, when or why toposes arise in this way. Exact completions can be obtained as the composition of two related constructions. The first one assigns to a category with finite limits, the “best” regular category (called its regular completion) that embeds it. The second assigns to a regular category the “best” exact category (called its ex/reg completion) that embeds it. These two constructions are of independent interest. There are quasitoposes that arise as regular completions and toposes, such as those of sheaves on a locale, that arise as ex/reg completions but which are not exact completions. We give a characterization of the categories with finite limits whose exact completions are toposes. This provides a very simple way of presenting realizability toposes, it allows us to give a very simple characterization of the presheaf toposes whose exact completions are themselves toposes and also to find new examples of toposes arising as exact completions. We also characterize universal closure operators in exact completions in terms of topologies, in a way analogous to the case of presheaf toposes and Grothendieck topologies. We then identify two “extreme” topologies in our sense and give simple conditions which ensure that the regular completion of a category is the category of separated objects for one of these topologies. This connection allows us to derive good properties of regular completions such as local cartesian closure. This, in turn, is part of our study of when a regular completion is a quasi-topos. The second extreme topology gives rise, as its category of sheaves, to the category of what we call complete equivalence relations. We then characterize the locally cartesian closed regular categories whose associated category of complete equivalence relations is a topos. Moreover, we observe that in this case the topos is nothing but the ex/reg completion of the original category.
Deterministic small‐scale undulations of image‐based risk predictions from the deep learning of lung tumors in motion

Abstract Introduction Deep learning (DL) models that use medical images to predict clinical outcomes are poised for clinical translation. For tumors that reside in organs that move, however, the impact of motion (i.e., degenerated object appearance or blur) on DL model accuracy remains unclear. We examine the impact of tumor motion on an image‐based DL framework that predicts local failure risk after lung stereotactic body radiotherapy (SBRT). Methods We input pre‐therapy free breathing (FB) computed tomography (CT) images from 849 patients treated with lung SBRT into a multitask deep neural network to generate an image fingerprint signature (or DL score) that predicts time‐to‐event local failure outcomes. The network includes a convolutional neural network encoder for extracting imaging features and building a task‐specific fingerprint, a decoder for estimating handcrafted radiomic features, and a task‐specific network for generating image signature for radiotherapy outcome prediction. The impact of tumor motion on the DL scores was then examined for a holdout set of 468 images from 39 patients comprising: (1) FB CT, (2) four‐dimensional (4D) CT, and (3) maximum‐intensity projection (MIP) images. Tumor motion was estimated using a 3D vector of the maximum distance traveled, and its association with DL score variance was assessed by linear regression. Findings The variance and amplitude in 4D CT image‐derived DL scores were associated with tumor motion (R 2 = 0.48 and 0.46, respectively). Specifically, DL score variance was deterministic and represented by sinusoidal undulations in phase with the respiratory cycle. DL scores, but not tumor volumes, peaked near end‐exhalation. The mean of the scores derived from 4D CT images and the score obtained from FB CT images were highly associated (Pearson r = 0.99). MIP‐derived DL scores were significantly higher than 4D‐ or FB‐derived risk scores (p < 0.0001). Interpretation An image‐based DL risk score derived from a series of 4D CT images varies in a deterministic, sinusoidal trajectory in a phase with the respiratory cycle. These results indicate that DL models of tumors in motion can be robust to fluctuations in object appearance due to movement and can guide standardization processes in the clinical translation of DL models for patients with lung cancer.
Identification and analysis of circRNAs in the prefrontal cortices of wild boar and domestic pig

Abstract Domestication caused significant differences in morphology and behavior between wild and domestic pigs. However, the regulatory role of circRNA in this event is unclear. Here, we analyzed circRNA expression patterns in the prefrontal cortices of wild boar and domestic pigs to determine the potential role of circRNAs in domestication. We identified a total of 11,375 circRNAs and found that 349 and 354 circRNAs were up-regulated in wild boar and Rongchang pig, respectively. Functional enrichment analysis showed that host genes of significantly highly-expressed circRNAs in wild boar were significantly enriched in neural synapse-related categories and the categories of ‘regulation of defense response (p = 0.028)’ and ‘neural retina development (p = 4.32 × 10−3)’. Host genes of significantly highly-expressed circRNAs in Rongchang pig were specifically involved in ‘chordate embryonic development (p = 2.38 × 10−4)’. Additionally, we constructed circRNA-miRNA-mRNA regulatory axes in wild boar and Rongchang pig and found more regulatory axes in wild boar that potentially regulate synaptic activities. We identified multiple circRNAs that may be related to domesticated characteristics, such as ssc_circ_6179 (ssc_circ_6179—ssc-miR-9847—HRH3, related to aggression) and ssc_circ_3027 (ssc_circ_3027—ssc-miR-4334-5p—HCRTR1, related to attention). This study provides a resource for further investigation of the molecular basis of pig domestication.
Secukinumab in enthesitis-related arthritis and juvenile psoriatic arthritis: a randomised, double-blind, placebo-controlled, treatment withdrawal, phase 3 trial

Background Treatment options in patients with enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are currently limited. This trial aimed to demonstrate the efficacy and safety of secukinumab in patients with active ERA and JPsA with inadequate response to conventional therapy. Methods In this randomised, double-blind, placebo-controlled, treatment-withdrawal, phase 3 trial, biologic-naïve patients (aged 2 to <18 years) with active disease were treated with open-label subcutaneous secukinumab (75/150 mg in patients <50/≥50 kg) in treatment period (TP) 1 up to week 12, and juvenile idiopathic arthritis (JIA) American College of Rheumatology 30 responders at week 12 were randomised 1:1 to secukinumab or placebo up to 100 weeks. Patients who flared in TP2 immediately entered open-label secukinumab TP3 that lasted up to week 104. Primary endpoint was time to disease flare in TP2. Results A total of 86 patients (median age, 14 years) entered open-label secukinumab in TP1. In TP2, responders (ERA, 44/52; JPsA, 31/34) received secukinumab or placebo. The study met its primary end point and demonstrated a statistically significant longer time to disease flare in TP2 for ERA and JPsA with secukinumab versus placebo (27% vs 55%, HR, 0.28; 95% CI 0.13 to 0.63; p<0.001). Exposure-adjusted incidence rates (per 100 patient-years (PY), 95% CI) for total patients were 290.7/100 PY (230.2 to 362.3) for adverse events and 8.2/100 PY (4.1 to 14.6) for serious adverse events in the overall JIA population. Conclusions Secukinumab demonstrated significantly longer time to disease flare than placebo in children with ERA and JPsA with a consistent safety profile with the adult indications of psoriatic arthritis and axial spondyloarthritis. Trial registration number NCT03031782.
Outcomes of COVID‐19 vaccination in 323 patients with clonal and non‐clonal mast cell activation disorders

CoV- 2 are proven to be safe and effective. 1 The vaccines are overall well tolerated although hypersensitivity reactions have been reported, which are more frequent in females with atopy and those with a history of anaphylaxis. 2 The reports of anaphylaxis are of concern for patients with mast cell activation disorders (MCAD) and have created vaccine hesitancy. Preliminary data indicate a low risk for vaccination- induced hypersensitivity symptoms, 3– 5 and in a recent study of 30 patients with clonal mast cell disorders who received H1- and H2- antihistamine premedication, none developed symptoms of mast cell activation. 6 The aim of this report was to provide outcomes of the safety and tolerability of COVID- 19 vaccination in a large, international cohort of patients with mast cell disorders. This was a retrospective study conducted across three institu-tions The study was approved by an review board at each institution. Adverse effects were considered “related to vaccine” if symptoms occurred within 2 h of vaccination. Patients with symptoms involving more than one organ system were scored according to the Brighton anaphylaxis scale.
Galactic orbital motions of star clusters: static versus semicosmological time-dependent Galactic potentials

In order to understand the orbital history of Galactic halo objects, such as globular clusters, authors usually assume a static potential for our Galaxy with parameters that appear at the present-day. According to the standard paradigm of galaxy formation, galaxies grow through a continuous accretion of fresh gas and a hierarchical merging with smaller galaxies from high redshift to the present day. This implies that the mass and size of disc, bulge, and halo change with time. We investigate the effect of assuming a live Galactic potential on the orbital history of halo objects and its consequences on their internal evolution. We numerically integrate backwards the equations of motion of different test objects located in different Galactocentric distances in both static and time-dependent Galactic potentials in order to see if it is possible to discriminate between them. We show that in a live potential, the birth of the objects, 13Gyr ago, would have occurred at significantly larger Galactocentric distances, compared to the objects orbiting in a static potential. Based on the direct N-body calculations of star clusters carried out with collisional N-body code, nbody6, we also discuss the consequences of the time-dependence of a Galactic potential on the early- and long-term evolution of star clusters in a simple way, by comparing the evolution of two star clusters embedded in galactic models, which represent the galaxy at present and 12Gyr ago, respectively. We show that assuming a static potential over a Hubble time for our Galaxy as it is often done, leads to an enhancement of mass-loss, an overestimation of the dissolution rates of globular clusters, an underestimation of the final size of star clusters, and a shallower stellar mass function.
Integrating eco‐evolutionary dynamics and modern coexistence theory

Abstract Community ecology typically assumes that competitive exclusion and species coexistence are unaffected by evolution on the time scale of ecological dynamics. However, recent studies suggest that rapid evolution operating concurrently with competition may enable species coexistence. Such findings necessitate general theory that incorporates the coexistence contributions of eco‐evolutionary processes in parallel with purely ecological mechanisms and provides metrics for quantifying the role of evolution in shaping competitive outcomes in both modelling and empirical contexts. To foster the development of such theory, here we extend the interpretation of the two principal metrics of modern coexistence theory—niche and competitive ability differences—to systems where competitors evolve. We define eco‐evolutionary versions of these metrics by considering how invading and resident species adapt to conspecific and heterospecific competitors. We show that the eco‐evolutionary niche and competitive ability differences are sums of ecological and evolutionary processes, and that they accurately predict the potential for stable coexistence in previous theoretical studies of eco‐evolutionary dynamics. Finally, we show how this theory frames recent empirical assessments of rapid evolution effects on species coexistence, and how empirical work and theory on species coexistence and eco‐evolutionary dynamics can be further integrated.
A roadmap for the functional annotation of protein families: a community perspective

Abstract Over the last 25 years, biology has entered the genomic era and is becoming a science of ‘big data’. Most interpretations of genomic analyses rely on accurate functional annotations of the proteins encoded by more than 500 000 genomes sequenced to date. By different estimates, only half the predicted sequenced proteins carry an accurate functional annotation, and this percentage varies drastically between different organismal lineages. Such a large gap in knowledge hampers all aspects of biological enterprise and, thereby, is standing in the way of genomic biology reaching its full potential. A brainstorming meeting to address this issue funded by the National Science Foundation was held during 3–4 February 2022. Bringing together data scientists, biocurators, computational biologists and experimentalists within the same venue allowed for a comprehensive assessment of the current state of functional annotations of protein families. Further, major issues that were obstructing the field were identified and discussed, which ultimately allowed for the proposal of solutions on how to move forward.
Stress Management Interventions to Facilitate Psychological and Physiological Adaptation and Optimal Health Outcomes in Cancer Patients and Survivors

Cancer diagnosis and treatment constitute profoundly stressful experiences involving unique and common challenges that generate uncertainty, fear, and emotional distress. Individuals with cancer must cope with multiple stressors, from the point of diagnosis through surgical and adjuvant treatments and into survivorship, that require substantial psychological and physiological adaptation. This can take a toll on quality of life and well-being and may also promote cellular and molecular changes that can exacerbate physical symptoms and facilitate tumor growth and metastasis, thereby contributing to negative long-term health outcomes. Since modifying responses to stressors might improve psychological and physiological adaptation, quality of life, and clinical health outcomes, several randomized controlled trials have tested interventions that aim to facilitate stress management. We review evidence for the effects of stress management interventions on psychological and physiological adaptation and health outcomes in cancer patients and survivors and summarize emerging research in the field to address unanswered questions.
Autopolyploid inheritance and a heterozygous reciprocal translocation shape chromosome genetic behavior in tetraploid blueberry (Vaccinium corymbosum)

Summary Understanding chromosome recombination behavior in polyploidy species is key to advancing genetic discoveries. In blueberry, a tetraploid species, the line of evidences about its genetic behavior still remain poorly understood, owing to the inter‐specific, and inter‐ploidy admixture of its genome and lack of in depth genome‐wide inheritance and comparative structural studies. Here we describe a new high‐quality, phased, chromosome‐scale genome of a diploid blueberry, clone W85. The genome was integrated with cytogenetics and high‐density, genetic maps representing six tetraploid blueberry cultivars, harboring different levels of wild genome admixture, to uncover recombination behavior and structural genome divergence across tetraploid and wild diploid species. Analysis of chromosome inheritance and pairing demonstrated that tetraploid blueberry behaves as an autotetraploid with tetrasomic inheritance. Comparative analysis demonstrated the presence of a reciprocal, heterozygous, translocation spanning one homolog of chr‐6 and one of chr‐10 in the cultivar Draper. The translocation affects pairing and recombination of chromosomes 6 and 10. Besides the translocation detected in Draper, no other structural genomic divergences were detected across tetraploid cultivars and highly inter‐crossable wild diploid species. These findings and resources will facilitate new genetic and comparative genomic studies in Vaccinium and the development of genomic assisted selection strategy for this crop.
Urinary CD163 is a marker of active kidney disease in childhood-onset lupus nephritis.

OBJECTIVE The objective of this study was to evaluate the utility of urine CD163 for detecting disease activity in childhood-onset systemic lupus erythematosus (cSLE) patients. METHODS Sixty consecutive pediatric patients fulfilling ≥ 4 ACR criteria for SLE and twenty healthy controls were recruited for testing of urinary CD163 using enzyme linked immunosorbent assay. SLE disease activity was assessed using SLEDAI-2000. RESULTS Urine CD163 was significantly higher in patients with active lupus nephritis than inactive SLE patients and healthy controls, with ROC AUC values ranging from 0.93-0.96. Lupus nephritis was ascertained by kidney biopsy. Levels of CD163 significantly correlated strongly with SLEDAI, renal SLEDAI, urinary protein excretion, and C3 complement levels. Urine CD163 was also associated with high renal pathology activity index and chronicity index, correlating strongly with interstitial inflammation and interstitial fibrosis based on examining concurrent kidney biopsies. CONCLUSION Thus, urine CD163 emerges as a promising marker for identifying cSLE patients with active kidney disease. Longitudinal studies are warranted to validate the clinical utility of urine CD163 in tracking kidney disease activity in children with lupus.
Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the RANO resect group

Abstract Background Terminology to describe extent of resection in glioblastoma is inconsistent across clinical trials. A surgical classification system was previously proposed based upon residual contrast-enhancing (CE) tumor. We aimed to (1) explore the prognostic utility of the classification system and (2) define how much removed non-CE tumor translates into a survival benefit. Methods The international RANO resect group retrospectively searched previously compiled databases from 7 neuro-oncological centers in the USA and Europe for patients with newly diagnosed glioblastoma per WHO 2021 classification. Clinical and volumetric information from pre- and postoperative MRI were collected. Results We collected 1,008 patients with newly diagnosed IDHwt glioblastoma. 744 IDHwt glioblastomas were treated with radiochemotherapy per EORTC-26981/22981 (TMZ/RT→TMZ) following surgery. Among these homogenously treated patients, lower absolute residual tumor volumes (in cm3) were favorably associated with outcome: patients with “maximal CE resection” (class 2) had superior outcome compared to patients with “submaximal CE resection” (class 3) or “biopsy” (class 4). Extensive resection of non-CE tumor (≤5 cm3 residual non-CE tumor) was associated with better survival among patients with complete CE resection, thus defining class 1 (“supramaximal CE resection”). The prognostic value of the resection classes was retained on multivariate analysis when adjusting for molecular and clinical markers. Conclusions The proposed “RANO categories for extent of resection in glioblastoma” are highly prognostic and may serve for stratification within clinical trials. Removal of non-CE tumor beyond the CE tumor borders may translate into additional survival benefit, providing a rationale to explicitly denominate such “supramaximal CE resection. ”
Investigational drugs in clinical trials for macular degeneration

ABSTRACT Introduction Intravitreal anti-vascular endothelial growth factor (VEGF) injections for exudative age-related macular degeneration (eAMD) are effective and safe but require frequent injections and have nonresponding patients. Geographic atrophy/dry AMD (gaAMD) remains an unmet medical need. New therapies are needed to address this leading cause of blindness in the increasing aged population. Areas covered This paper reviews the pathogenesis of macular degeneration, current and failed therapeutics, therapies undergoing clinical trials and a rationale for why certain AMD therapies may succeed or fail. Expert Opinion VEGF-inhibitors reduce both vascular leakage and neovascularization. Experimental therapies that only address neovascularization or leakage will unlikely supplant anti-VEGF therapies. The most promising future therapies for eAMD, are those that target, more potently inhibit and have a more sustained effect on the VEGF pathway such as KSI-301, RGX-314, CLS-AX, EYEP-1901, OTX-TKI. GaAMD is a phenotype of phagocytic retinal cell loss. Inhibiting phagocytic activity of retinal microglial/macrophages at the border of geographic atrophy and reducing complement derived activators of microglial/macrophage is the most promising strategy. Complement inhibitors (Pegcetacoplan and Avacincaptad pegol) will likely obtain FDA approval but will serve to pave the way for combined complement and direct phagocytic inhibitors such as AVD-104.