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Abstract We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n = 15). All patients received remdesivir and some also received nirmatrelvir-ritonavir (n = 3) or therapeutic monoclonal antibodies (n = 4). Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient sequentially treated with nirmatrelvir-ritonavir and remdesivir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

Abstract Simarouba, a neotropical genus in the family Simaroubaceae, currently lacks comprehensive genomic data in existing databases. This study aims to fill this gap by providing genomic resources for three Simarouba species, S. amara, S. versicolor, and S. glauca. It also aims to perform comparative molecular evolutionary analyses in relation to other species within the order Sapindales. The analysis of these three Simarouba species revealed the presence of the typical quadripartite structure expected in plastomes. However, some pseudogenization events were identified in the psbC, infA, rpl22, and ycf1 genes. In particular, the CDS of the psbC gene in S. amara was reduced from 1422 bp to 584 bp due to a premature stop codon. Nucleotide diversity data pointed to gene and intergenic regions as promising candidates for species and family discrimination within the group, specifically matK, ycf1, ndhF, rpl32, petA-psbJ, and trnS-trnG. Selection signal analyses showed strong evidence for positive selection on the rpl23 gene. Phylogenetic analyses indicated that S. versicolor and S. glauca have a closer phylogenetic relationship than S. amara. We provide chloroplast genomes of three Simaruba species and use them to elucidate plastome evolution, highlight the presence of pseudogenization, and identify potential DNA barcode regions.

Abstract Cerebral vasospasm is determined as a temporary narrowing of cerebral arteries a few days after an aneurysmal subarachnoid hemorrhage. The onset of this vascular event usually evolves with new neurological deficits or progression of ischemic areas. The success of interventions to treat or revert this condition is not satisfying. In addition to cerebral vasospasm, early brain injury plays an important role as a contributor to subarachnoid hemorrhage’s mortality. In this sense, stellate ganglion block appears as an alternative to reduce sympathetic system’s activation, one of the main pathophysiological mechanisms involved in brain injury. Over the past few years, there is growing evidence that stellate ganglion block can contribute to decline patient morbidity from subarachnoid hemorrhage. Is it time to include this procedure as a standard treatment after aneurysm rupture?

Gridded precipitation (PRP) data have been largely used in diagnostic studies on the climate variability in several time scales, as well as to validate model results. The three most used gauge-based PRP datasets are from the Global Precipitation Climatology Centre (GPCC), University of Delaware (UDEL), and Climate Research Unit (CRU). This paper evaluates the performance of these datasets in reproducing spatiotemporal PRP climatological features over the entire South America (SA) for the 1901–2015 period, aiming to identify the differences and similarities among the datasets as well as time intervals and areas with potential uncertainties involved with these datasets. Comparisons of the PRP annual means and variances between the 1901–2015 period and the non-overlapping 30-year subperiods of 1901–1930, 1931–1960, 1961–1990, and the 25-year subperiod of 1991–2015 for each dataset show varying means of the annual PRP over SA depending on the subperiod and dataset. Consistent patterns among datasets are found in most of southeastern SA and southeastern Brazil, where they evolved gradually from less to more rainy conditions from 1901–1930 to the 1991–2015 subperiod. All three datasets present limitations and uncertainties in regions with poor coverage of gauge stations, where the differences among datasets are more pronounced. In particular, the GPCC presents reduced PRP variability in an extensive area west of 50° W and north of 20° S during the 1901–1930 subperiod. In monthly time scale, PRP time series in two areas show differences among the datasets for periods before 1941, which are likely due to spurious or missing data: central Bolivia (CBO), and central Brazil (CBR). The GPCC has less monthly variability before 1940 than the other two datasets in these two areas, and UDEL presents reduced monthly variability before 1940 and spurious monthly values from May to September of the years from 1929 to 1941 in CBO. Thus, studies with these three datasets might lead to different results depending on the study domain and period of analysis, in particular for those including years before 1941. The results here might be relevant for future diagnostic and modelling studies on climate variability from interannual to multidecadal time scales.

Abstract Arterial hypertension (AH) is a multifactorial and asymptomatic disease that affects vital organs such as the kidneys and heart. Considering its prevalence and the associated severe health repercussions, hypertension has become a disease of great relevance for public health across the globe. Conventionally, the classification of an individual as hypertensive or non-hypertensive is conducted through ambulatory blood pressure monitoring over a 24-h period. Although this method provides a reliable diagnosis, it has notable limitations, such as additional costs, intolerance experienced by some patients, and interferences derived from physical activities. Moreover, some patients with significant renal impairment may not present proteinuria. Accordingly, alternative methodologies are applied for the classification of individuals as hypertensive or non-hypertensive, such as the detection of metabolites in urine samples through liquid chromatography or mass spectrometry. However, the high cost of these techniques limits their applicability for clinical use. Consequently, an alternative methodology was developed for the detection of molecular patterns in urine collected from hypertension patients. This study generated a direct discrimination model for hypertensive and non-hypertensive individuals through the amplification of Raman signals in urine samples based on gold nanoparticles and supported by chemometric techniques such as partial least squares-discriminant analysis (PLS-DA). Specifically, 162 patient urine samples were used to create a PLS-DA model. These samples included 87 urine samples from patients diagnosed with hypertension and 75 samples from non-hypertensive volunteers. In the AH group, 35 patients were diagnosed with kidney damage and were further classified into a subgroup termed (RAH). The PLS-DA model with 4 latent variables (LV) was used to classify the hypertensive patients with external validation prediction (P) sensitivity of 86.4%, P specificity of 77.8%, and P accuracy of 82.5%. This study demonstrates the ability of surface-enhanced Raman spectroscopy to differentiate between hypertensive and non-hypertensive patients through urine samples, representing a significant advance in the detection and management of AH. Additionally, the same model was then used to discriminate only patients diagnosed with renal damage and controls with a P sensitivity of 100%, P specificity of 77.8%, and P accuracy of 82.5%.

Adulterating foods, such as milk powder (MP), is a common practice in countries with no rigid policy on food quality control. This study employs Fourier transform near-infrared and mid-infrared (FT-NIR, FT-MIR) spectroscopy and chemometric analysis to detect milk powder adulteration with corn starch (CS) and wheat flour (WF) from 0.00 to 30.00% w/w concentrations. Partial least square regression (PLSR) models were developed, optimized, and compared to quantify corn starch and wheat flour adulterations. According to the results, the root mean square error prediction (RMSEP) for FT-NIR and FT-MIR in corn starch was 0.74 and 1.69% w/w and 0.82 and 2.63% w/w for wheat flour, respectively. FT-NIR spectroscopy, rather than FT-MIR coupled with the appropriate chemometrics models represents a more valuable tool for simple, rapid, and nondestructive detection of adulterants in milk powder. The recent availability of portable instruments, combined with suitable chemometric tools, makes it possible to discriminate adulterated food samples in situ.

In Brazil, young Black males are far more likely to experience criminal violence (e.g., homicide, police lethality and assault) than young White males. However, race might also affect the ex-post scenario; that is, Blacks and Whites may go to the police seeking solutions against criminal violence with different probabilities. In this paper, we identified and quantified the sources of the racial differential in accessing justice between Blacks and Whites in Brazil. Using microdata from the Brazilian Household Survey, we used the Oaxaca-Blinder decomposition to isolate the discriminatory component from social indicators correlated with access to justice. We found that structural attributes explain only part (around 60%) of the racial differential in accessing justice. A significant portion of the discrepancy (at least 40%) provides evidence of racial discrimination. In addition, the spatial dynamics revealed that the Northeast region of Brazil presents the most discriminatory scenario in the country, a region historically characterised by higher social inequalities and violent mortality.

There is little information regarding the acute repercussions of anterior cruciate ligament (ACL) reconstruction on muscle activation, especially on the proximal hip muscles. Thus, this study analyzed the acute effects of ACL reconstruction with doubled semitendinosus/gracilis (ST/G) autografts on lower limb muscle activation. Fourteen male recreational athletes that presented a primary unilateral ACL rupture and underwent the ACL reconstruction with an ST/G graft. Surface electromyographic (sEMG) signal were recorded from each participant during the maximal voluntary isometric contraction (MVIC) of the gluteus maximus and gluteus medius, vastus lateralis and vastus medialis, semitendinosus, biceps femoris, and medial gastrocnemius muscles and also during bipodal mini-squatting with open and closed eyes, before surgery and 15 days postoperatively. (sEMG) signal were normalized to isometric peak electromyography.The postoperative assessment showed reduced muscle activation in the gluteus maximus (p = 0.013, d:0.48) in non-operated limb and also in the muscle gluteus medius (p = 0.013, d:0.79), vastus medialis (p = 0.035, d:0.63) semitendinosus (p = 0.001, d:2.46), biceps femoris (p

African Swine Fever Virus (ASFV) is a large dsDNA virus that encodes at least 150 proteins. The complexity of ASFV and lack of knowledge of effector immune functions and protective antigens have hindered the development of safe and effective ASF vaccines. In this study, we constructed four Orf virus recombinant vectors expressing individual ASFV genes B602L, -CP204L, E184L, and -I73R (ORFVΔ121-ASFV-B602L, -CP204L, -E184L, and -I73R). All recombinant viruses expressed the heterologous ASFV proteins in vitro. We then evaluated the immunogenicity of the recombinants by immunizing four-week-old piglets. In two independent animal studies, we observed high antibody titers against ASFV p30, encoded by CP204L gene. Using Pepscan ELISA, we identified a linear B-cell epitope of 12 amino acids in length (Peptide 15) located in an exposed loop region of p30 as an immunodominant ASFV epitope. Additionally, antibodies elicited against ASFV p30 presented antibody-dependent cellular cytotoxicity (ADCC) activity. These results underscore the role of p30 on antibody responses elicited against ASFV and highlight an important functional epitope that contributes to p30-specific antibody responses.

Melatonin is a hormone secreted by the pineal gland, it can be associated with circadian rhythms, aging and neuroprotection. Melatonin levels are decreased in sporadic Alzheimer's disease (sAD) patients, which suggests a relationship between the melatonergic system and sAD. Melatonin may reduce inflammation, oxidative stress, TAU protein hyperphosphorylation, and the formation of β-amyloid (Aβ) aggregates. Therefore, the objective of this work was to investigate the impact of treatment with 10 mg/kg of melatonin (i.p) in the animal model of sAD induced by the intracerebroventricular (ICV) infusion of 3 mg/kg of streptozotocin (STZ). ICV-STZ causes changes in the brain of rats similar to those found in patients with sAD. These changes include; progressive memory decline, the formation of neurofibrillary tangles, senile plaques, disturbances in glucose metabolism, insulin resistance and even reactive astrogliosis characterized by the upregulation of glucose levels and glial fibrillary acidic protein (GFAP). The results show that ICV-STZ caused short-term spatial memory impairment in rats after 30 days of STZ infusion without locomotor impairment which was evaluated on day 27 post-injury. Furthermore, we observed that a prolonged 30-day treatment with melatonin can improve the cognitive impairment of animals in the Y-maze test, but not in the object location test. Finally, we demonstrated that animals receiving ICV-STZ have high levels of Aβ and GFAP in the hippocampus and that treatment with melatonin reduces Aβ levels but does not reduce GFAP levels, concluding that melatonin may be useful to control the progression of amyloid pathology in the brain.

Abstract Cross-habitat spillover may be the outcome of a process of habitat loss or degradation where the receiving habitat serves as a refuge for organisms. Once surface habitats are lost or degraded, animals can find underground refuge in caves. This paper is focused on testing whether taxonomic order richness inside caves is positively affected by the loss of the native vegetation cover surrounding caves; whether degradation of native vegetation cover predicts cave community composition; and whether there is a pattern of cave community clusters delimited by similarity in the effects of habitat degradation on animal communities. We gathered a comprehensive speleological dataset consisting of occurrence data of thousands of invertebrates and vertebrates sampled in 864 iron caves in the Amazon, to test the effects of both variables measured inside caves and surrounding landscapes on spatial variation in richness and composition of animal communities. We show that caves can work as refuges for the fauna in landscapes where the native vegetation cover surrounding them was degraded, which was evidenced by landcover change increasing the richness of cave communities and clustering caves by similarity in community composition. Therefore, habitat degradation on the surface should be a key variable when characterizing cave ecosystems for conservation prioritization and offset planning. Habitat degradation causing a cross-habitat spillover effect highlights the importance of maintaining the connection between caves by the surface, especially large caves. Our study can help guide industry and stakeholders working on the complex conciliation between land use and biodiversity conservation.

In applications where large-order filters are needed, the computational load of adaptive filtering algorithms can become prohibitively expensive. In this paper, a comprehensive analysis of a selective partial-update least mean squares, named SPU-LMS-M-min, is developed. By employing the partial-update strategy for a non-normalized adaptive scheme, the designer can choose an appropriate number of update blocks considering a trade-off between convergence rate and computational complexity, which can result in a more than 40% reduction in the number of multiplications in some configurations compared to the traditional LMS algorithm. Based on the principle of minimum distortion, a selection criterion is proposed that is based on the input signal’s blocks with the lowest energy, whereas typical Selective Partial Update (SPU) algorithms use a selection criterion based on blocks with highest energy. Stochastic models are developed for the mean weights and mean and mean squared behaviour of the proposed algorithm, which are further extended to accommodate scenarios involving time-varying dynamics and suboptimal filter lengths. Simulation results show that the theoretical predictions are in good agreement with the experimental outcomes. Furthermore, it is demonstrated that the proposed selection criterion can be easily extended to active noise cancellation algorithms as well as algorithms utilizing variable filter length. This allows for the reduction of computational costs for these algorithms without compromising their asymptotic performance.

Water is essential for life on Earth, playing fundamental roles in climate regulation, ecosystem maintenance, and domestic, agricultural, and industrial processes. A total of 70% of the planet is covered by water. However, only 2.5% is fresh water, and much of it is inaccessible. Groundwater is the main source of the planet’s available water resources. For that reason, groundwater is a critically important resource, and is increasingly vulnerable due to the climate crisis and contamination. These challenges threaten the availability of clean and safe water, necessitating an understanding of effective and sustainable management. This review presents an overview of the concepts of aquifers and groundwater. Also, it reflects on the importance of these resources in developing countries such as Colombia (South America). In addition, it considers the characteristics of mineral waters, their uses, and associated risks, as well as their exploration and control policies. Colombia is a country with immense water and biological wealth and is crucial to maintaining the climate and availability of global water resources. Nevertheless, managing Colombia’s aquifers is a challenge, as many have not yet been fully explored. In order to achieve this, it is necessary to study hydrogeochemistry through the application of advanced technologies to analyze the dynamics, distribution, and quality of groundwater, as well as its vulnerability to pollution and climate change. On the other hand, the consumption of mineral groundwater can have health benefits, such as positive cardiovascular and gastrointestinal effects. But geogenic, biogenic, or anthropogenic elements such as heavy metals and microplastics can pose a risk to human health. The need for proper management of water resources to prevent risks to human health and the environment is emphasized. Therefore, an integrated approach to water resource management will ensure conservation and sustainable use, secure a continuous supply of freshwater, and facilitate adaptation to climate change.

Serjania erecta Raldk is an essential genetic resource due to its anti-inflammatory, gastric protection, and anti-Alzheimer properties. However, the genetic and evolutionary aspects of the species remain poorly known. Here, we sequenced and assembled the complete chloroplast genome of S. erecta and used it in a comparative analysis within the Sapindaceae family. S. erecta has a chloroplast genome (cpDNA) of 159,297 bp, divided into a Large Single Copy region (LSC) of 84,556 bp and a Small Single Copy region (SSC) of 18,057 bp that are surrounded by two Inverted Repeat regions (IRa and IRb) of 28,342 bp. Among the 12 species used in the comparative analysis, S. erecta has the fewest long and microsatellite repeats. The genome structure of Sapindaceae species is relatively conserved; the number of genes varies from 128 to 132 genes, and this variation is associated with three main factors: (1) Expansion and retraction events in the size of the IRs, resulting in variations in the number of rpl22, rps19, and rps3 genes; (2) Pseudogenization of the rps2 gene; and (3) Loss or duplication of genes encoding tRNAs, associated with the duplication of trnH-GUG in X. sorbifolium and the absence of trnT-CGU in the Dodonaeoideae subfamily. We identified 10 and 11 mutational hotspots for Sapindaceae and Sapindoideae, respectively, and identified six highly diverse regions (tRNA-Lys — rps16, ndhC – tRNA-Val, petA – psbJ, ndhF, rpl32 – ccsA, and ycf1) are found in both groups, which show potential for the development of DNA barcode markers for molecular taxonomic identification of Serjania. We identified that the psaI gene evolves under neutrality in Sapindaceae, while all other chloroplast genes are under strong negative selection. However, local positive selection exists in the ndhF, rpoC2, ycf1, and ycf2 genes. The genes ndhF and ycf1 also present high nucleotide diversity and local positive selection, demonstrating significant potential as markers. Our findings include providing the first chloroplast genome of a member of the Paullinieae tribe. Furthermore, we identified patterns in variations in the number of genes and selection in genes possibly associated with the family’s evolutionary history.

This article examines the evolution of Israel's religion from the Abrahamic Pre-exilic (approx. 2100-586 BC). The main data of this research is a literature study with a qualitative methodology through an Integrative Critical Analysis (ICA) approach to achieving the aims or objectives of the research. The conclusion or research results obtained are that the evolution of Israel's religion occurred not only in an applicative manner but also substantively. The evolution of Israel's religion can be said to be inseparable from the population, natural, socio-political, marriage, or family factors, where religion is the ultimate concern for survival, aligning life with the universe (aligning one's self with the universe), appeasing the gods including Baal, Asherah, Molok, and others to get their favor (how to placate the deities and secure their favor) with the background of the principle that obedience can be a blessing and disobedience can be a curse. Its significance for Christians is that Israel's religion and Christianity have historical and theological links to deepen understanding of the Bible; as a mirror of faith and Christian life; and how Christians should practice their religion in a pluralist society and the midst of pluralism.

Introducción. Desde el primer reporte en la provincia de Wuhan (China) en el año 2019, el SARS-CoV-2 se ha diseminado por todo el mundo, provocando un enorme impacto en la salud pública. Para su diagnóstico, la Organización Mundial de la Salud ha incentivado el desarrollo de pruebas rápidas, de simple ejecución, sensibles y específicas, que complementan la RT-qPCR como prueba de referencia. La prueba RT-LAMP ha mostrado ser una excelente alternativa para la detección del SARS-CoV-2 en diferentes biofluidos. Objetivo. Validar la técnica RT-LAMP colorimétrica en muestras de hisopado nasofaríngeo previamente confirmadas por RT-qPCR, usando el protocolo Charité, Berlín, Alemania. Materiales y métodos. Un total de 153 muestras de hisopado nasofaríngeo de individuos con sospecha de COVID-19 se sometieron a RT-qPCR y RT-LAMP, usando un estuche comercial colorimétrico (NEB, Germany). La RT-LAMP se practicó con las muestras de ARN extraídas del hisopado nasofaríngeo y con muestras crudas sin previa extracción de ARN. El resultado fue evaluado por un simple cambio de color en la reacción. Resultados. La sensibilidad y especificidad de la técnica RT-LAMP para detectar el gen N del SARS-CoV-2 mediante un set de cebadores previamente reportados (set de Broughton), arrojó valores de 0,97 (0,85-1,00) y 0,81 (0,65-0,92), respectivamente, con un intervalo de confianza del 95%. Otro set de cebadores dirigidos contra otra región del mismo gen (set de Lalli) arrojó valores de sensibilidad y especificidad de 0,96 (0,78-1,00) y 0,77 (0,55-0,92), respectivamente. Sin previa extracción de ARN, se encontró que la sensibilidad fue del 0,95 (0,74-1,00) y la especificidad del 0,88 (0,64-0,99). Conclusiones. Estos resultados evidencian que la técnica RT-LAMP podría considerarse una prueba diagnóstica rápida, de fácil ejecución, libre de equipos sofisticados, sensible y específica, para el diagnóstico del SARS-CoV-2 en muestras de hisopados nasofaríngeos.

The technological evolution allowed the use of a single camera for precise and effective body tracking, reducing the cost and increasing the accessibility of applications in places where depth cameras and wearable sensors are not available. This paper describes and implements a supervised machine learning process consisting of a mobile application used as a motion capture device which also transforms the data into an input for a machine learning model that classifies upper and lower limbs movements (24 types of human movements). The user performs movements in front of the camera, and the trained model classifies them. We designed the system to work in a motor-rehabilitation context to assist the professional while the patient does physical exercises. The implementation can summarize the movements made during the rehabilitation sessions by counting the repetitions and classifying them when done completely or reached a specific range of motion.

The COVID-19 pandemic caused by the SARS-CoV-2 (β-CoV) betacoronavirus has posed a significant threat to global health. Despite the availability of vaccines, the virus continues to spread, and there is a need for alternative strategies to alleviate its impact. Vitamin D, a secosteroid hormone best known for its role in bone health, exhibits immunomodulatory effects in certain viral infections. Here, we have shown that bioactive vitamin D (calcitriol) limits in vitro replication of SARS-CoV-2 and murine coronaviruses MHV-3 and MHV-A59. Comparative studies involving wild-type mice intranasally infected with MHV-3, a model for studying β-CoV respiratory infections, confirmed the protective effect of vitamin D in vivo. Accordingly, mice fed a standard diet rapidly succumbed to MHV-3 infection, whereas those on a vitamin D-rich diet (10,000 IU of Vitamin D3/kg) displayed increased resistance to acute respiratory damage and systemic complications. Consistent with these findings, the vitamin D-supplemented group exhibited lower viral titers in their lungs and reduced levels of TNF, IL-6, IL-1β, and IFN-γ, alongside an enhanced type I interferon response. Altogether, our findings suggest vitamin D supplementation ameliorates β-CoV-triggered respiratory illness and systemic complications in mice, likely via modulation of the host’s immune response to the virus.

To assess whether high-dose coronavirus disease (COVID-19) convalescent plasma (CCP) transfusion may benefit patients with severe COVID-19, we conducted a multicenter randomized trial in Brazil. Patients with severe COVID-19 who were within 10 days of initial symptom onset were eligible. Patients in the CCP group received 3 daily doses of CCP (600 mL/d) in addition to standard treatment; control patients received standard treatment only. Primary outcomes were death rates at days 30 and 60 of study randomization. Secondary outcomes were ventilator-free days and hospital-free days. We enrolled 107 patients: 36 CCP and 71 control. At day 30, death rates were 22% for CCP and 25% for the control group; at day 60, rates were 31% for CCP and 35% for control. Needs for invasive mechanical ventilation and durations of hospital stay were similar between groups. We conclude that high-dose CCP transfused within 10 days of symptom onset provided no benefit for patients with severe COVID-19.

In this study, the bending behavior of Slim-Floor beams was analyzed using FE models developed in the ABAQUS software. The validity of these models was demonstrated by comparing the numerical results obtained with experimental data found in the literature. Through parametric evaluations, the following findings were verified: (i) the connection mechanisms adopted (concrete dowels, reinforcing steel bars, and adherence) were able to activate the composite behavior between steel and concrete; (ii) the spacing between the openings, the number of openings, and the diameter of the reinforcing steel bars determine the behavior of the connection; (iii) adherence contributes little to the strength of the connection, and therefore, its contribution can be neglected; (iv) the connection mechanisms adopted in this study can promote the ductile behavior of the Slim-Floor beams.

Abstract Obtaining an accurate segmentation of images obtained by computed microtomography (micro-CT) techniques is a non-trivial process due to the wide range of noise types and artifacts present in these images. Current methodologies are often time-consuming, sensitive to noise and artifacts, and require skilled people to give accurate results. Motivated by the rapid advancement of deep learning-based segmentation techniques in recent years, we have developed a tool that aims to fully automate the segmentation process in one step, without the need for any extra image processing steps such as noise filtering or artifact removal. To get a general model, we train our network using a dataset made of high-quality three-dimensional micro-CT images from different scanners, rock types, and resolutions. In addition, we use a domain-specific augmented training pipeline with various types of noise, synthetic artifacts, and image transformation/distortion. For validation, we use a synthetic dataset to measure accuracy and analyze noise/artifact sensitivity. The results show a robust and accurate segmentation performance for the most common types of noises present in real micro-CT images. We also compared the segmentation of our method and five expert users, using commercial and open software packages on real rock images. We found that most of the current tools fail to reduce the impact of local and global noises and artifacts. We quantified the variation on human-assisted segmentation results in terms of physical properties and observed a large variation. In comparison, the new method is more robust to local noises and artifacts, outperforming the human segmentation and giving consistent results. Finally, we compared the porosity of our model segmented images with experimental porosity measured in the laboratory for ten different untrained samples, finding very encouraging results.

ABSTRACT The emergence of the SARS-CoV-2 B.1.617.2 lineage (Delta variant) in 2021 was associated with increased case numbers and test positivity rates, including a large number of infections in fully vaccinated individuals. Here, we describe the findings of an investigation conducted in Tompkins County, New York, to evaluate factors underlying a significant uptick in the number of coronavirus disease 2019 (COVID-19) cases observed in the months of July and August 2021. We performed genomic surveillance and genotyping as well as virological assessments to determine infectivity of the virus in a select number of clinical diagnostic samples. Genomic sequence analyses revealed complete replacement of the B.1.1.7 lineage (Alpha variant) with the B.1.617.2 lineage (Delta variant) between July 1 and August 4 2021. We observed a strong association between viral RNA loads detected by real-time reverse transcriptase PCR and infectious virus detected in respiratory secretions by virus titration. A marked increase in positive cases among fully vaccinated individuals was observed. The sequence divergence between two index Delta variant cases in April and May, and the cases after July 1st, revealed independent Delta variant introductions in Tompkins County. Contact tracing information enabled the detection of clusters of connected cases within closely related phylogenetic clusters. We also found evidence of transmission between vaccinated individuals and between vaccinated and unvaccinated individuals. This was confirmed by detection and isolation of infectious virus from a group of individuals within epidemiologically connected transmission clusters, confirming shedding of high viral loads and transmission of the virus by fully vaccinated individuals. IMPORTANCE The SARS-CoV-2 lineage B.1.617.2 (Delta variant) emerged in Asia and rapidly spread to other countries, becoming the dominant circulating lineage. Worldwide infections with B.1.617.2 peaked at a time in which vaccination rates were increasing. In this study, we present data characterizing the emergence of SARS-CoV-2 lineage B.1.617.2 (Delta variant) in Tompkins County, New York, which has one of the highest vaccination rates in the state. We present evidence demonstrating infection, replication, and transmission of SARS-CoV-2 lineage B.1.617.2 (Delta variant) between fully vaccinated individuals. Importantly, infectious virus loads were determined in a subset of samples and demonstrated shedding of high viral titers in respiratory secretions of vaccinated individuals.

We consider open non-twist Hamiltonian systems represented by an area-preserving two-dimensional map describing incompressible planar flows in the reference frame of a propagating wave, and possessing exits through which map orbits can escape. The corresponding escape basins have a fractal nature that can be revealed by the so-called basin entropy, a novel concept developed to quantify final-state uncertainty in dynamical systems. Since the map considered violates locally the twist condition, there is a shearless barrier that prevents global chaotic transport. In this paper, we show that it is possible to determine the shearless barrier breakup by considering the variation in the escape basin entropy with a tunable parameter.

The growing emergence of microbes resistant to commercially available antibiotic therapies poses a threat to healthcare systems worldwide. Multiple factors have been associated with the increasing incidence of hospital-acquired infections caused by antibiotic-resistant pathogens, including the indiscriminate use of broad-spectrum antibiotics, the massive application of antibiotics in hospitals as a prophylactic measure, self-medication, and nonadherence to pharmacological therapies by patients. In this study, we developed a novel treatment to mitigate the impact of microbial resistance. We synthesized a benzoporphyrin derivative, 5,10,15,20-tetrakis (4-ethylphenyl) porphyrin (TEtPP), with a reaction yield close to 50%. TEtPP exhibited excellent photophysical properties (Φf = 0.12 ± 0.04 and ΦΔ = 0.81 ± 0.23) and was thereby assessed as a potential agent for antibacterial photodynamic therapy. The photophysical properties of the synthesized porphyrin derivative were correlated with the assayed antimicrobial activity. TEtPP showed higher activity against the MRSA strain under irradiation than in the absence of irradiation (minimum inhibitory concentration (MIC) = 69.42 µg/mL vs. MIC = 109.30 µg/mL, p < 0.0001). Similar behavior was observed against P. aeruginosa (irradiated MIC = 54.71 µg/mL vs. nonirradiated MIC = 402.90 µg/mL, p < 0.0001). TEtPP exhibited high activity against S. aureus in both the irradiated and nonirradiated assays (MIC = 67.68 µg/mL vs. MIC = 58.26 µg/mL, p = 0.87).

Recently, castellated columns have been increasingly used in buildings because of their flexibility, easy compatibility and potential savings due to less steel consumption. However, there is a lack of research related to the subject. In view of that, this work evaluates the influence of the opening type and size on the resistant capacity of the column, considering a nonlinear plastic analysis by the finite element method (792 simulations). For this, columns without openings were modeled to validate the methodology proposed. After validation, a nonlinear buckling analysis of castellated columns was performed. In this study, different cut patterns of the beam web are evaluated, as well as residual stresses, material and geometric imperfections, based on a statistical design. The loads obtained by castellated columns and columns without web are compared. Also, the resistance reduction factors associated with global buckling (χ) for castellated profiles are compared to the values proposed by ABNR NBR 8800 (2008). Furthermore, statistically, there are no differences between the opening types evaluated. Finally, in order to contribute to the design of castellated columns, equations based on regression models were found to predict the load capacity of these elements.

Here, the authors image twisted bilayer graphene using scanning microwave imaging microscopy, revealing structures with sizes down to 1 nm. They show that is possible by using spontaneously forming nanoscale water menisci that concentrates the microwave fields in small regions.

We report infection of 3 Malayan tigers with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 (Alpha) variant at a zoologic park in Virginia, USA. All tigers exhibited respiratory signs consistent with SARS-CoV-2 infection. These findings show that tigers are susceptible to infection with the SARS-CoV-2 B.1.1.7 variant.

An acute bout of eccentric exercise affects insulin sensitivity and lipid profile, but how the magnitude of muscle damage affects them is not clear. We compared changes in blood insulin sensitivity and lipid markers after the first (EC1) and second (EC2) eccentric exercise bouts. Fifteen sedentary young men performed arm, leg and trunk muscle eccentric exercises, and repeated them 2 weeks later. Fasting blood samples were taken before, 2 h and 1–5 days after each exercise bout to analyze plasma creatine kinase (CK) activity, serum glucose (GLU), insulin, homeostasis model assessment (HOMA), triacylglycerols (TG), total (TC) and low- (LDLC) and high-density lipoprotein cholesterol (HDLC) concentrations as well as TC/HDLC ratio. Changes in these measures were compared between bouts and relationships to peak plasma CK activity were analyzed. Plasma CK activity increased (p < 0.05) after EC1 (peak: 101,668 ± 58,955 IU/L) but not after EC2. The magnitude of changes in GLU (peak after EC1: 26 ± 10% vs. EC2: 7 ± 6%), insulin (46 ± 27% vs. 15 ± 8%), HOMA (86 ± 48% vs. 24 ± 15%), TC (−20 ± 5% vs. −6 ± 4%), TG (−32 ± 11% vs. −6 ± 3%), LDHC (−47 ± 15% vs. −12 ± 9%), HDLC (35 ± 26% vs. 7 ± 4%), and TC/HDLC ratio (−139 ± 13% vs. −11 ± 7%) were significantly greater after EC1 than EC2. Peak plasma CK activity was significantly (p < 0.05) correlated with the peak changes in blood insulin sensitivity and lipid markers for the combined data of EC1 and EC2. These results suggest that the greater the magnitude of muscle damage, the greater the magnitude of changes in the insulin sensitivity to a negative direction and lipid markers to a positive direction.

Abstract Alzheimer’s disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease.

Abstract Background The purpose of this study was to assess the safety and efficacy of percutaneous transcatheter embolization (TCE) for the treatment of pulmonary arteriovenous malformations (PAVMs). Methods Forty-three consecutive patients (n = 17 males; n = 26 females) with 72 untreated PAVMs underwent coil and/or plug embolization between January 2010 and February 2018. The mean patient age was 42 ± 14 years (range 19–71 years). The median size of the feeding artery was 7.9 ± 2.9 mm (range 3.5–14.0 mm). The arterial blood gas level and cardiac function of all patients were analysed. The technical success rate, recanalization rate, and complications were evaluated. Computed tomography angiography (CTA) examinations were scheduled for 12 months after treatment and every 2–4 years thereafter. Results Twenty-five PAVMs were treated with coils alone, twenty-one were treated with plugs alone, and twenty-six were treated with both coils and plugs. The technical success rate was 100%. There were no complications during operation. However, one patient (2.3%) had pulmonary thrombosis and embolism post-operation. The patients’ pre-operative and post-operative PaO2 and SaO2 levels were significantly different (p

Diatoms are one of the main species of interest due to their possible impact on the maintenance of ecosystems, as well as their photosynthetic capacity and biotechnological applications. Reliable, easy, rapid identification of diatoms remains a highly desirable goal to avoid the difficulty for experts in the visual analysis of frustules; a method commonly used to compare the distinctive traits of diatoms, such as ornaments and the marks from images taken by optical and electronic microscopy for identification. This study proposed three simple morphometric methods based on fractal dimension measurements in conjunction with 2D cross-correlation parameters to analyze diatom images. This novel approach demonstrates the differentiation feasibility between a wide variety of diatom species with heterogeneity in their structures and shapes, which could possibly expand the application of this preprocessing process for the identification of new types of images or other biological species.

ABSTRACT: Bees are fundamental in several aspects, especially in relation to plant biodiversity and pollination. Recently, immense losses are being faced in the number of Brazilian colonies, mainly in southern states of the country, which has a strong beekeeping activity. There are indications that, among the reasons for the losses, pathogens that affect the health of bees may be involved. Among them, the microsporidium Nosema and the black queen cell virus (BQCV) stand out for their prevalence. In this study, 92 colonies of 17 apiaries from southern Brazil were evaluated for infection by Nosema ceranae, Nosema apis and BQCV. Nucleic acid extractions and cDNA synthesis were performed from adult bee samples, followed by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and multiplex PCR. Eight BQCV positive samples were subjected to sequencing. The results showed that N. ceranae and BQCV are circulating in the Southern region of the country, which may be the reason for the loss of colonies. N. apis was not found. N. ceranae was found in 57.6% (53/92) of the colonies and BQCV in 32.6% (30/92). Co-infection was found in 25% (23/92) of the colonies studied, a factor that is suggested to be reducing the hosts’ longevity due to the synergistic action of the pathogens. The samples submitted to sequencing indicated similarity of 96.8 to 100% between them, in addition to strong similarity with sequences from Asia, United States, Germany and Peru. This study reports the circulation of N. ceranae and BQCV in apiaries in southern Brazil, in addition to being the first phylogenetic analysis of the Brazilian BQCV sequence.

Low back pain is defined as pain located between the lower rib cage and the gluteal folds, and its etiology is multifactorial, considerably affecting quality of life. The aim of this literature review was to analyze the influence of the Pilates method on the symptoms of patients with nonspecific low back pain, which is considered a promising treatment for this type of pathology. A narrative review of the literature was carried out using the PubMed, Pedro, Scopus and Scielo databases. To perform the search, Pilates AND Low back nonspecific AND Pain were used as keywords. Articles published in the last 5 years, randomized clinical trials that verified the influence of the Pilates method in adult individuals with unspecified low back pain and full text in English were included. Of the 77 articles identified, 7 articles met the inclusion criteria, 7 analyzed the primary outcomes of pain intensity and disability, 5 articles compared Pilates with other rehabilitation techniques and 2 studies compared the effectiveness of Pilates solo with Pilates apparatus. It was concluded that all the techniques that were compared with Pilates are effective, being difficult to affirm the superiority of Pilates over them in relation to the reduction of pain and disability and improvement of quality of life. However, the Pilates method has shown good results in pain perception and intensity, functional capacity, fear of movement and the idea that movement can worsen your condition, muscle strength, range of motion and flexibility.

Abstract Olfactory cues play an important role in mammalian biology, but have been challenging to assess in the field. Current methods pose problematic issues with sample storage and transportation, limiting our ability to connect chemical variation in scents with relevant ecological and behavioral contexts. Real‐time, in‐field analysis via portable gas chromatography–mass spectrometry (GC‐MS) has the potential to overcome these issues, but with trade‐offs of reduced sensitivity and compound mass range. We field‐tested the ability of portable GC‐MS to support two representative applications of chemical ecology research with a wild arboreal primate, common marmoset monkeys (Callithrix jacchus). We developed methods to (a) evaluate the chemical composition of marmoset scent marks deposited at feeding sites and (b) characterize the scent profiles of exudates eaten by marmosets. We successfully collected marmoset scent marks across several canopy heights, with the portable GC‐MS detecting known components of marmoset glandular secretions and differentiating these from in‐field controls. Likewise, variation in the chemical profile of scent marks demonstrated a significant correlation with marmoset feeding behavior, indicating these scents’ biological relevance. The portable GC‐MS also delineated species‐specific olfactory signatures of exudates fed on by marmosets. Despite the trade‐offs, portable GC‐MS represents a viable option for characterizing olfactory compounds used by wild mammals, yielding biologically relevant data. While the decision to adopt portable GC‐MS will likely depend on site‐ and project‐specific needs, our ability to conduct two example applications under relatively challenging field conditions bodes well for the versatility of in‐field GC‐MS.

Abstract Objective To describe our surgical techniques, analyze their safety and their postoperative outcomes for foramen magnum tumors (FMTs). Methods From 1986 to 2014, 34 patients with FMTs underwent surgeries using either the lateral suboccipital approach, standard midline suboccipital craniotomy, or the far lateral approach, depending on the anatomic location of the lesions. Results In the present series, there were 22 (64.7%) female and 12 (35.2%) male patients. The age of the patients ranged from 12 to 63 years old. We observed 1 operative mortality (2.9%). A total of 28 patients (82.3%) achieved a score of 4 or 5 in the Glasgow Outcome Scale (GOS). Gross total resection (GTR) was obtained in 22 (64.7%) patients. After the surgery, 9 (26%) patients developed lower cranial nerve dysfunction (LCNd) weakness. The follow-up varied from 1 to 24 years (mean: 13.2 years). Conclusion The majority of tumors located in the FM can be safely and efficiently removed using either the lateral sub occipital approach, standard middle line sub occipital craniotomy, or the far lateral approach, depending on the anatomic location of the lesions.

Abstract Expansion of agricultural commodity production is driving rapid deforestation in tropical countries. Several strategies including jurisdictional planning and producer or sectoral‐level sourcing/certification have been used to counter this threat, each with its own limitations. There is growing interest in using jurisdictional sourcing (JS) as a hybrid that combines the best elements of each of these strategies. Specifically, JS involves bringing together key stakeholders in a given national or sub‐national political jurisdiction to agree on a land‐use plan that maintains forest ecosystems while promoting enhanced commodity production on degraded lands. Under JS, a key incentive for this agreement is the prospect of preferential sourcing from supply chain actors who want conversion‐free commodities. As with any conservation strategy, the key questions are what defines JS and under what conditions is it likely to work? To help address these questions, we convened a group of practitioners/experts to develop a theory of change that explicitly defines what JS entails from both the perspective of a given jurisdiction as well as a global markets point of view. We also developed generic objectives and indicators that can be used to measure performance. We then vetted our initial drafts with a wider circle of JS practitioners/experts as well as through a review of relevant literature and against seven case studies. It is our hope that this framework can be used to inform the collection of more standardized data across JS strategies being implemented in different locations and conditions. This data could, in turn, inform more systematic assessments of JS strategies and ultimately, revisions to this theory of change as our collective knowledge improves.

Introduction Caustic substance ingestion is a common cause of esophageal stricture in children. The primary treatment is esophageal dilatation. Although it is known that endoscopic esophageal dilatation is a procedure associated with a high rate of bacteremia, current guidelines do not recommend routine throat swab cultures or antibiotic prophylaxis for the general children population. Case Report We describe a case of a 7-year-old boy presenting with refractory headaches who was diagnosed with cranial abscess after multiple esophageal dilatations due to stenosis caused by caustic soda ingestion. The patient was subjected to neurosurgical intervention and intravenous antibiotic treatment for 6 weeks. Streptococcus viridans culture was positive in purulent abscess content. Conclusion We highlight this condition that, although rare, needs immediate diagnosis and proper treatment. We also recommend routine testing of throat swabs and antibiotics prophylaxis to children undergoing esophageal dilatation.

Abstract Vehicular traffic re-routing is the key to provide better traffic mobility. However, taking into account just traffic-related information to recommend better routes for each vehicle is far from achieving the desired requirements of proper transportation management. In this way, context-aware and multi-objective re-routing approaches will play an important role in traffic management. Yet, most procedures are deterministic and cannot support the strict requirements of traffic management applications, since many vehicles potentially will take the same route, consequently degrading overall traffic efficiency. So, we propose an efficient algorithm named as Better Safe Than Sorry (BSTS), based on Pareto-efficiency. Simulation results have shown that our proposal provides a better trade-off between mobility and safety than state-of-the-art approaches and also avoids the problem of potentially creating different congestion spots.

Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevations in serum parathyroid hormone levels in the presence of normal serum calcium concentrations after exclusion of secondary hyperparathyroidism. We have previously demonstrated no differences in the prevalence of clinically active urolithiasis between NPHPT and hypercalcemic asymptomatic PHPT, and that it is significantly higher in postmenopausal osteoporotic women with NPHPT in comparison to women with normal serum PTH and calcium concentrations. Few studies have addressed the occurrence of silent or occult kidney stones in asymptomatic hypercalcemic PHPT, but no data are available for NPHPT. Objective: To determine the presence of occult urolithiasis in NPHPT patients using routine abdominal ultrasonography. Methods and Results: We studied 35 patients with NPHPT (mean age 63.2 ± 10.7 years, 96% women; serum PTH 116.5 ± 39.2 pg/mL, 25OHD 38.5 ± 6.82 ng/mL, total calcium 9.1 ± 0.56 mg/dL; albumin 4.02 ± 0.37 g/dL; BUN 34.35 ±10.23 mg/dL; p = 3.51 ± 0.60 mg/dL; estimated glomerular filtration rate 88.44 ± 32.45 mL/min/1.73 m2, and 24-h urinary calcium excretion 140.6 ± 94.3 mg/24 h). The criteria for the diagnosis of NPHPT were as follows: serum PTH above the reference range (11–65 pg/mL), normal albumin-corrected serum calcium concentrations, normal 24-h urinary calcium excretion, serum 25OHD above 30 ng/mL, estimated GFR (MDRD) above 60 mL/min/1.73 m2 (with the exclusion of medications such as thiazide diuretics, lithium, bisphosphonates, and denosumab), a history of clinical symptoms of urolithiasis, and a family history of kidney stones. Thirty-five patients were evaluated and 25 of them met the inclusion criteria. Five patients presented nephrolithiasis corresponding to 20% of the study population. There were no statistically significant differences in any of the clinical or laboratory variables studied between patients with or without urolithiasis, although mean serum PTH levels were higher in patients with stones (180.06 ± 126.48 vs. 100.72 ± 25.28 pg/mL, p = 0.1). The size of the stones ranged from 0.6 to 0.9 cm and all of the stones were located in the renal pelvis. Conclusion: We found a high prevalence of occult kidney stones in NPHPT patients, similar to what is observed in clinically manifested urolithiasis, in hypercalcemic PHPT.

Arbovirus infections are increasingly important causes of disease, whose spectrum of neurological manifestations are not fully known. This study sought to retrospectively assess the incidence of arboviruses in cerebrospinal fluid samples of patients with neurological symptoms to inform diagnosis of central and peripheral nervous system disorders. A total of 255 cerebrospinal fluid (CSF) samples collected from January 2016 to December 2017 were tested for dengue virus (DENV 1-4), Zika virus (ZIKV), and Chikungunya virus (CHIKV) in addition to other neurotropic arboviruses of interest, using genetic and serologic assays. Of the 255 CSF samples analyzed, 3.53% (09/255) were positive for arboviruses presenting mainly as meningitis, encephalitis, and cerebrovascular events, of which ZIKV was detected in 2.74% (7/255), DENV in 0.78% (2/255), in addition to an identified ILHV infection that was described previously. All the cases were detected in adults aged 18 to 74 years old. Our findings highlight the scientific and clinical importance of neurological syndromes associated with arboviruses and demonstrate the relevance of specific laboratory methods to achieve accurate diagnoses as well as highlight the true dimension of these diseases to ultimately improve public health planning and medical case management.

Surface texturing can improve lubrication and entrap wear debris but increases the effective roughness of the surfaces, which can induce higher contact pressures. On the one hand, this can be detrimental, but on the other hand, the increase in contact pressure could be used to activate the formation of a ZDDP tribofilm from fully-formulated lubricants. This work investigates the synergistic effect between surface texturing via Maskless Electrochemical Texturing (MECT) and ZDDP additive. The surface texture consisted of an array of annular pockets manufactured on a gray cast iron cylinder liner. These textured surfaces were evaluated by scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDX). The results indicated that surface texturing via MECT changes the chemical composition of the surfaces, by inducing a preferential dissolution of the metal matrix. Consequently, it exposed the carbon present in the material. The tribological performance was evaluated by a ring-on-cylinder-liner tribometer in reciprocating sliding under boundary lubrication conditions using both a base oil and a commercial formulated oil containing ZDDP additive. For comparison, a commercially honed liner was also tested. After the tribological tests, the surfaces were evaluated by white light interferometry and SEM/EDX. Although the textured surfaces showed higher friction, they induced more ZDDP-tribofilm formation than conventional cylinder liner finish.

Desde o fim do Império Otomano, o Oriente Médio passou por várias mudanças políticas abruptas e se tornou o palco de uma série de conflitos regionais e disputas entre as grandes potências que impactaram fortemente a forma como este complexo de segurança regional evoluiu. Usando o arcabouço teórico da Escola de Copenhague e da Escola Inglêsa, retraçamos como essas dinâmicas de segurança e insegurança estão em um processo ainda não terminado de constante evolução desde a queda do Império e como esses processos estão inseridos no contexto mais amplo e sistêmico da administração das grandes potências.

ABSTRACT Despite numerous barriers to transmission, zoonoses are the major cause of emerging infectious diseases in humans. Among these, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and ebolaviruses have killed thousands; the human immunodeficiency virus (HIV) has killed millions. Zoonoses and human-to-animal cross-species transmission are driven by human actions and have important management, conservation, and public health implications. The current SARS-CoV-2 pandemic, which presumably originated from an animal reservoir, has killed more than half a million people around the world and cases continue to rise. In March 2020, New York City was a global epicenter for SARS-CoV-2 infections. During this time, four tigers and three lions at the Bronx Zoo, NY, developed mild, abnormal respiratory signs. We detected SARS-CoV-2 RNA in respiratory secretions and/or feces from all seven animals, live virus in three, and colocalized viral RNA with cellular damage in one. We produced nine whole SARS-CoV-2 genomes from the animals and keepers and identified different SARS-CoV-2 genotypes in the tigers and lions. Epidemiologic and genomic data indicated human-to-tiger transmission. These were the first confirmed cases of natural SARS-CoV-2 animal infections in the United States and the first in nondomestic species in the world. We highlight disease transmission at a nontraditional interface and provide information that contributes to understanding SARS-CoV-2 transmission across species. IMPORTANCE The human-animal-environment interface of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an important aspect of the coronavirus disease 2019 (COVID-19) pandemic that requires robust One Health-based investigations. Despite this, few reports describe natural infections in animals or directly link them to human infections using genomic data. In the present study, we describe the first cases of natural SARS-CoV-2 infection in tigers and lions in the United States and provide epidemiological and genetic evidence for human-to-animal transmission of the virus. Our data show that tigers and lions were infected with different genotypes of SARS-CoV-2, indicating two independent transmission events to the animals. Importantly, infected animals shed infectious virus in respiratory secretions and feces. A better understanding of the susceptibility of animal species to SARS-CoV-2 may help to elucidate transmission mechanisms and identify potential reservoirs and sources of infection that are important in both animal and human health.

BackgroundApert, Pfeiffer, and Crouzon syndromes are autosomal dominant diseases characterized by craniosynostosis. They are paternal age effect disorders. The association between paternal age and Beare–Stevenson syndrome (BSS), a very rare and severe craniosynostosis, is uncertain. Gain-of-function mutations in FGFR2 become progressively enriched in testes as men age and were shown to cause these syndromes.Case reportHere, we describe a child affected with BSS, whose father was 36 years old and had congenital bilateral absence of the vas deferens (CBAVD). The child was heterozygous for the pathogenic FGFR2 variant c.1124A > G p.Tyr375Cys. By reviewing the literature, we found that BSS fathers are older than BSS mothers (mean age in years: 39 ± 10 vs 30 ± 6, p = 0.006). Male age greater than 34 years and CBAVD are both factors associated with poor spermogram parameters, which may represent an additional selective pressure to sperm carrying FGFR2 gain-of-function mutations.ConclusionThese findings are consistent with the hypothesis that BSS is a paternal-origin genetic disorder. Further experimental studies would be needed to confirm this hypothesis.