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As AI models continue to advance into many real-life applications, their ability to maintain reliable quality over time becomes increasingly important. The principal challenge in this task stems from the very nature of current machine learning models, dependent on the data as it was at the time of training. In this study, we present the first analysis of AI “aging”: the complex, multifaceted phenomenon of AI model quality degradation as more time passes since the last model training cycle. Using datasets from four different industries (healthcare operations, transportation, finance, and weather) and four standard machine learning models, we identify and describe the main temporal degradation patterns. We also demonstrate the principal differences between temporal model degradation and related concepts that have been explored previously, such as data concept drift and continuous learning. Finally, we indicate potential causes of temporal degradation, and suggest approaches to detecting aging and reducing its impact.

The shortage of recently approved vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for evidence-based tools to prioritize healthcare resources for people at higher risk of severe coronavirus disease (COVID-19). Although age has been identified as the most important risk factor (particularly for mortality), the contribution of underlying comorbidities is often assessed using a pre-defined list of chronic conditions. Furthermore, the count of individual risk factors has limited applicability to population-based “stratify-and-shield” strategies. We aimed to develop and validate a COVID-19 risk stratification system that allows allocating individuals of the general population into four mutually-exclusive risk categories based on multivariate models for severe COVID-19, a composite of hospital admission, transfer to intensive care unit (ICU), and mortality among the general population. The model was developed using clinical, hospital, and epidemiological data from all individuals among the entire population of Catalonia (North-East Spain; 7.5 million people) who experienced a COVID-19 event (i.e., hospitalization, ICU admission, or death due to COVID-19) between March 1 and September 15, 2020, and validated using an independent dataset of 218,329 individuals with COVID-19 confirmed by reverse transcription—polymerase chain reaction (RT-PCR), who were infected after developing the model. No exclusion criteria were defined. The final model included age, sex, a summary measure of the comorbidity burden, the socioeconomic status, and the presence of specific diagnoses potentially associated with severe COVID-19. The validation showed high discrimination capacity, with an area under the curve of the receiving operating characteristics of 0.85 (95% CI 0.85–0.85) for hospital admissions, 0.86 (0.86–0.97) for ICU transfers, and 0.96 (0.96–0.96) for deaths. Our results provide clinicians and policymakers with an evidence-based tool for prioritizing COVID-19 healthcare resources in other population groups aside from those with higher exposure to SARS-CoV-2 and frontline workers.

Nearly two decades ago, pathologic examination results suggested that acoustic factors, such as mid-frequency active naval military sonar (MFAS) could be the cause of acute decompression-like sickness in stranded beaked whales. Acute systemic gas embolism in these whales was reported together with enigmatic cystic liver lesions (CLL), characterized by intrahepatic encapsulated gas-filled cysts, tentatively interpreted as “gas-bubble” lesions in various other cetacean species. Here we provide a pathologic reinterpretation of CLL in odontocetes. Among 1,200 cetaceans necropsied, CLL were only observed in four striped dolphins (Stenella coeruleoalba), with a low prevalence (2%, N = 179). Together, our data strongly suggest that CLL are the result of the combination of a pre-existing or concomitant hepatic vascular disorder superimposed and exacerbated by gas bubbles, and clearly differ from acute systemic gas embolism in stranded beaked whales that is linked to MFAS. Budd-Chiari-like syndrome in dolphins is hypothesized based on the present pathologic findings. Nonetheless, further researched is warranted to determine precise etiopathogenesis(es) and contributing factors for CLL in cetaceans.

Mboumar-9 is an active mariner-transposable element previously isolated in the ant Messor bouvieri. In this work, a mariner-like element, Mboumar, isolated from 22 species of ants, is analyzed. These species belong to nine different subfamilies, including Leptanillinae, the most primitive ant subfamily, and Myrmicinae and Formicidae, the most derived ones. Consequently, Mboumar-like elements seem to be well-represented in ant genomes. The phylogenetic tree drawn for mariner elements is highly inconsistent with the phylogeny of host ants, with almost identical elements found in clearly distant species and, on the contrary, more variable elements in closely related species. The inconsistency between the two phylogenetic trees indicates that these transposable elements have evolved independently from the speciation events of the ants that host them. Besides, we found closer genetic relationships among elements than among their host ants. We also found potential coding copies with an uninterrupted open reading frame of 345 aa in 11 species. The putative transposase codified by them showed a high sequence identity with the active Mboumar-9 transposase. The results of selection tests suggest the intervention of purifying selection in the evolution of these elements. Overall, our study suggests a complex evolutionary history of the Mboumar-like mariner in ants, with important participation of horizontal transfer events. We also suggest that the evolutionary dynamics of Mboumar-like elements can be influenced by the genetic system of their host ants, which are eusocial insects with a haplodiploid genetic system.

Assessing the body condition of wild animals is necessary to monitor the health of the population and is critical to defining a framework for conservation actions. Body condition indices (BCIs) are a non-invasive and relatively simple means to assess the health of individual animals, useful for addressing a wide variety of ecological, behavioral, and management questions. The Antillean manatee (Trichechus manatus manatus) is an endangered subspecies of the West Indian manatee, facing a wide variety of threats from mostly human-related origins. Our objective was to define specific BCIs for the subspecies that, coupled with additional health, genetic and demographic information, can be valuable to guide management decisions. Biometric measurements of 380 wild Antillean manatees captured in seven different locations within their range of distribution were obtained. From this information, we developed three BCIs (BCI1 = UG/SL, BCI2 = W/SL3, BCI3 = W/(SL*UG2)). Linear models and two-way ANCOVA tests showed significant differences of the BCIs among sexes and locations. Although our three BCIs are suitable for Antillean manatees, BCI1 is more practical as it does not require information about weight, which can be a metric logistically difficult to collect under particular circumstances. BCI1 was significantly different among environments, revealing that the phenotypic plasticity of the subspecies have originated at least two ecotypes—coastal marine and riverine—of Antillean manatees.

The better understanding of the safety of biologic DMARDs (bDMARDs), as well as the emergence of new bDMARDs against different therapeutic targets and biosimilars have likely influenced the use patterns of these compounds over time. The aim of this study is to assess changes in demographic characteristics, disease activity and treatment patterns in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) who started a first- or second-line biologic between 2007 and mid-2020. Patients diagnosed with RA, PsA or AS included in the BIOBADASER registry from January 2007 to July 2020 were included. According to the start date of a first- or second-line biologic therapy, patients were stratified into four time periods: 2007–2009; 2010–2013; 2014–2017; 2018–2020 and analyzed cross-sectionally in each period. Demographic and clinical variables, as well as the type of biologic used, were assessed. Generalized linear models were applied to study the evolution of the variables of interest over time periods, the diagnosis, and the interactions between them. A total of 4543 patients initiated a first biologic during the entire time frame of the study. Over the four time periods, disease evolution at the time of biologic initiation (p p p p p p p p p = 0.004), and incremental changes to the therapeutic target between the first and second biologic (p

Ambient temperature may lead to decompensation of cardiovascular diseases and deaths by acute myocardial infarction (AMI). Little is known about this relationship in South American countries located in regions of a hot climate. This study aims to investigate the effects of ambient temperature on mortality due to AMI in six Brazilian micro-regions, which present different climates. We analyzed daily records of deaths by AMI between 1996 and 2013. We estimated the accumulate relative and attributable risks with lags of up to 14 days, using distributed non-linear lag model. Micro-regions that were closest to the equator did not show an association between temperature and mortality. The lowest risk temperatures varied between 22 °C and 28 °C, in the Southern region of Brazil and the Midwest region, respectively. Low temperatures associated with the highest mortality risk were observed in the same areas, varying between 5 °C and 15 °C. The number of deaths attributed to cold temperatures varied from 176/year in Brasilia to 661/year in São Paulo and those deaths attributed to hot temperatures in Rio de Janeiro amounted to 115/year. We showed the relative risk and the attributable risk of warmer and colder days in tropical regions. The estimate of the number of deaths due to climate, varying according to each area, is a way of bringing information to those responsible for health policies based on easily-understood measurements.

Prostate cancer (PCa) patient-derived xenografts (PDXs) are commonly propagated by serial transplantation of “pieces” of tumour in mice, but the cellular composition of pieces is not standardised. Herein, we optimised a microwell platform, the Microwell-mesh, to aggregate precise numbers of cells into arrays of microtissues, and then implanted the Microwell-mesh into NOD-scid IL2γ−/− (NSG) mice to study microtissue growth. First, mesh pore size was optimised using microtissues assembled from bone marrow-derived stromal cells, with mesh opening dimensions of 100×100 μm achieving superior microtissue vascularisation relative to mesh with 36×36 μm mesh openings. The optimised Microwell-mesh was used to assemble and implant PCa cell microtissue arrays (hereafter microtissues formed from cancer cells are referred to as microtumours) into mice. PCa cells were enriched from three different PDX lines, LuCaP35, LuCaP141, and BM18. 3D microtumours showed greater in vitro viability than 2D cultures, but neither proliferated. Microtumours were successfully established in mice 81% (57 of 70), 67% (4 of 6), 76% (19 of 25) for LuCaP35, LuCaP141, and BM18 PCa cells, respectively. Microtumour growth was tracked using live animal imaging for size or bioluminescence signal. If augmented with further imaging advances and cell bar coding, this microtumour model could enable greater resolution of PCa PDX drug response, and lead to the more efficient use of animals. The concept of microtissue assembly in the Microwell-mesh, and implantation in vivo may also have utility in implantation of islets, hair follicles or other organ-specific cells that self-assemble into 3D structures, providing an important bridge between in vitro assembly of mini-organs and in vivo implantation.

Pituitary adenomas (PA) are the second most common intracranial tumors. These neoplasms are classified according to the hormone they produce. The majority of PA occur sporadically, and their molecular pathogenesis is incompletely understood. The present transcriptomic and methylomic analysis of PA revealed that they segregate into three molecular clusters according to the transcription factor driving their terminal differentiation. First cluster, driven by NR5A1, consists of clinically non-functioning PA (CNFPA), comprising gonadotrophinomas and null cell; the second cluster consists of clinically evident ACTH adenomas and silent corticotroph adenomas, driven by TBX19; and the third, POU1F1-driven TSH-, PRL- and GH-adenomas, segregated together. Genes such as CACNA2D4, EPHA4 and SLIT1, were upregulated in each of these three clusters, respectively. Pathway enrichment analysis revealed specific alterations of these clusters: calcium signaling pathway in CNFPA; renin-angiotensin system for ACTH-adenomas and fatty acid metabolism for the TSH-, PRL-, GH-cluster. Non-tumoral pituitary scRNAseq data confirmed that this clustering also occurs in normal cytodifferentiation. Deconvolution analysis identify potential mononuclear cell infiltrate in PA consists of dendritic, NK and mast cells. Our results are consistent with a divergent origin of PA, which segregate into three clusters that depend on the specific transcription factors driving late pituitary cytodifferentiation.

White spot syndrome virus (WSSV) causes major worldwide losses in shrimp aquaculture. The development of resistant shrimp populations is an attractive option for management of the disease. However, heritability for WSSV resistance is generally low and genetic improvement by conventional selection has been slow. This study was designed to determine the power and accuracy of genomic selection to improve WSSV resistance in Litopenaeus vannamei. Shrimp were experimentally challenged with WSSV and resistance was evaluated as dead or alive (DOA) 23 days after infestation. All shrimp in the challenge test were genotyped for 18,643 single nucleotide polymorphisms. Breeding candidates (G0) were ranked on genomic breeding values for WSSV resistance. Two G1 populations were produced, one from G0 breeders with high and the other with low estimated breeding values. A third population was produced from “random” mating of parent stock. The average survival was 25% in the low, 38% in the random and 51% in the high-genomic breeding value groups. Genomic heritability for DOA (0.41 in G1) was high for this type of trait. The realised genetic gain and high heritability clearly demonstrates large potential for further genetic improvement of WSSV resistance in the evaluated L. vannamei population using genomic selection.

The aim was to analyze the effect of fractional flow reserve (FFR), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) on fluoroscopy time (FT), radiation dose (RD) and contrast volume (CV) in patients undergoing coronary angiography. This case-control study included consecutive patients above the age of 18, who underwent coronary angiography. FT, RD, and CV after each procedure were retrospectively recorded. Multivariate models were used to demonstrate the effect of these complementary studies and other factors, on radiation and contrast exposure. A total of 1047 patients were included, 74.5% were men and the mean (SD) age was 62.4 (12.1) years. Complementary studies performed were: IVUS (n = 237), FFR (n = 56) and OCT (n = 37). FFR and IVUS had a small effect on FT (η = 0.008 B = 2.2, p B = 2.5, p B = 2.9, p B = 9.4, p B = 39, p B = 37, p (η = 0.192, Β = 4.2, p 0.001), RD (η = 0.129, Β = 511.8, p 0.001) and CV (η = 0.177, Β = 40.5, p 0.001). The use of complementary studies in hemodynamics did not modify the received RD and had a minor effect on FT and the CV used.

The history of Ecuador was marked by the arrival of Europeans with Africans, resulting in the mixture of Native Americans with Africans and Europeans. The present study contributes to the knowledge of the Ecuadorian mestizo population by offering information about ancestry and ethnic heterogeneity. Forty-six AIM-InDels (Ancestry Informative Insertion/Deletion Markers) were used to obtain information on 240 Ecuadorian individuals from three regions (Amazonia, the Highlands, and the Coast). As a result, the population involved a significant contribution from Native Americans (values up to 51%), followed by Europeans (values up to 33%) and Africans (values up to 13%). Furthermore, we compared the data obtained with nine previously reported scientific articles on autosomal, mitochondrial DNA and Y chromosomes. The admixture results correspond to Ecuador’s historical background and vary slightly between regions.

Methyl benzimidazole carbamate (MBC) fungicides are fungicidal compounds that exert their biological activities by preventing cell division through the inhibition of tubulin polymerization, which is the major component of microtubules. Several mutations in the β-tubulin gene contribute to MBC resistance, the most common and significant of which occur at residues 198 and 200. Despite nearly 50 years of agricultural use, the binding site of MBCs and the precise mechanism by which those mutations affect fungicide efficacy have not been determined. The aim of this work was to clarify the mode of action and the mechanism of resistance to MBC fungicides in Podosphaera xanthii, the primary causal agent of cucurbit powdery mildew, using a combination of biochemical, biophysical and computational approaches. The results allow us to propose an MBC binding site in β-tubulin that lies close to the GTP binding site and does not include residue 198 involved in MBC resistance.

Pain encompasses both sensory and affective dimensions which can be differentially modulated by drugs. Here, we compare the pharmacological sensitivity of the sensory and affective responses using acetic acid-induced abdominal writhings (sensory-reflexive outcome) and acetic acid-induced depression of reward seeking behaviour (RSB, affective-nonreflexive outcome) to a highly palatable food in mice. We found that the expression of RSB critically depends on factors such as sex and previous knowledge and type of the food stimulus. Intraperitoneal administration of acetic acid (iAA) produced a long-lasting (beyond the resolution of writhing behaviour) and concentration-dependent decrease on both appetitive-approach and consummatory dimensions of RSB. Ibuprofen and diclofenac were much more potent in reversing AA-induced changes in RSB: latency to eat (ED50 = 2 and 0.005 mg/kg, intraperinoneally, respectively) and amount consumed (ED50 = 11 and 0.1 mg/kg) than in AA-induced writhing (ED50 = 123 and 60 mg/kg). Morphine and duloxetine inhibited the writhing response (ED50 = 0.8 and 6 mg/kg, respectively) but not the AA-induced changes in RSB. Caffeine was ineffective in both AA-induced writhing and RSB changes. Overall, this study characterized a preclinical mouse model of hedonic deficits induced by pain that can be used to assess affective responses as well as complementary classic reflexive approaches in the evaluation of candidate analgesics.

Childhood obesity is associated with a number of metabolic abnormalities leading to increased cardiovascular risk. Metabolites can be useful as early biomarkers and new targets to promote early intervention beginning in school age. Thus, we aimed to identify metabolomic profiles associated with obesity and obesity-related metabolic traits. We used data from the Obesity Research Study for Mexican children (ORSMEC) in Mexico City and included a case control (n = 1120), cross-sectional (n = 554) and a longitudinal study (n = 301) of 6–12-year-old children. Forty-two metabolites were measured using electrospray MS/MS and multivariate regression models were used to test associations of metabolomic profiles with anthropometric, clinical and biochemical parameters. Principal component analysis showed a serum amino acid signature composed of arginine, leucine/isoleucine, phenylalanine, tyrosine, valine and proline significantly associated with obesity (OR = 1.57; 95%CI 1.45–1.69, P = 3.84 × 10−31) and serum triglycerides (TG) (β = 0.067, P = 4.5 × 10−21). These associations were validated in the cross-sectional study (P P = 0.016). This study shows that an amino acid signature significantly associated with childhood obesity, is an independent risk factor of future hypertriglyceridemia in children.

E-52862 is a selective σ1R antagonist currently undergoing phase II clinical trials for neuropathic pain and represents a potential first-in-class analgesic. Here, we investigated the effect of single and repeated administration of E-52862 on different pain-related behaviours in several neuropathic pain models in rats: mechanical allodynia in cephalic (trigeminal) neuropathic pain following chronic constriction injury of the infraorbital nerve (IoN), mechanical hyperalgesia in streptozotocin (STZ)-induced diabetic polyneuropathy and cold allodynia in oxaliplatin (OX)-induced polyneuropathy. Mechanical hypersensitivity induced after IoN surgery or STZ administration was reduced by acute treatment with E-52862 and morphine, but not by pregabalin. In the OX model, single administration of E-52862 reversed the hypersensitivity to cold stimuli similarly to 100 mg/kg of gabapentin. Interestingly, repeated E-52862 administration twice daily over 7 days did not induce pharmacodynamic tolerance but an increased antinociceptive effect in all three models. Additionally, as shown in the STZ and OX models, repeated daily treatment with E-52862 attenuated baseline pain behaviours, which supports a sustained modifying effect on underlying pain-generating mechanisms. These preclinical findings support a role for σ1R in neuropathic pain and extend the potential for the use of selective σ1R antagonists (e.g., E-52862) to the chronic treatment of cephalic and extra-cephalic neuropathic pain.