Metabolic effects of switching to Biktarvy (B/F/TAF) in patients with HIV-1 treated with antiretroviral regimens that do not include tenofovir disoproxil fumarate (TDF) or tenofovir alafenamide (TAF): The Metabic study.

BACKGROUND: Studies on switching to tenofovir alafenamide (TAF)-based regimens raise concerns about a worse metabolic profile in people with HIV, even though most received tenofovir disoproxil fumarate (TDF) in their previous regimen. This study aims to evaluate changes in lipid fractions, glucose, and serum markers for hepatic steatosis (HS) after switching from a TDF- or TAF-sparing regimen to bictegravir/emtricitabine/TAF (B/F/TAF). METHODS: We performed a retrospective cohort study of people with HIV who switched to B/F/TAF from TDF- or TAF-sparing regimens between January 2019 and May 2022 with at least 6 months of follow-up. The primary endpoint was the absolute change in lipid fractions at 6 months. Secondary outcomes were changes in lipid fractions at 12 months and changes in other metabolic parameters (glucose, creatinine, and HS based on the triglyceride-to-glucose [TyG] ratio at 6 and 12 months). Changes were analysed using mixed linear regression models with random intercept and time as a fixed effect. RESULTS: The study included 259 people with HIV (median age 55 [interquartile range (IQR) 47-60] years; 80% male; 88% Caucasian; CD4+ T-cell count 675 [IQR 450-880] cells/mm3; 84.3% HIV-RNA <50 copies/mL). In total, 63 patients (30%) had hypertension, 93 (44%) dyslipidaemia, 30 (14%) diabetes, and 45% obesity/overweight. Most (60%) switched from integrase inhibitor-based regimens, and 21% switched from a boosted regimen. At 6 months, significant reductions were observed in total cholesterol (-7.64 mg/dL [95% confidence interval (CI) -13.52 to -1.76; p = 0.002]), triglycerides (-23.4 [95% CI -42.07 to -4.65]; p = 0.003), and TyG ratio (-0.14 [95% CI -0.23 to -0.05]; p < 0.001). CONCLUSION: In our real-life cohort, the effect of switching TDF-/TAF-sparing regimens to triple therapy with B/F/TAF improved total cholesterol, triglycerides, and serum markers of HS at 6 months and was neutral for the remaining metabolic parameters at 12 months.

First Study of the

New astronomical observations point to a nucleosynthesis picture that goes beyond what was accepted until recently. The intermediate "i" process was proposed as a plausible scenario to explain some of the unusual abundance patterns observed in metal-poor stars. The most important nuclear physics properties entering i-process calculations are the neutron-capture cross sections and they are almost exclusively not known experimentally. Here we provide the first experimental constraints on the ^{139}Ba(n,γ)^{140}Ba reaction rate, which is the dominant source of uncertainty for the production of lanthanum, a key indicator of i-process conditions. This is an important step towards identifying the exact astrophysical site of stars carrying the i-process signature.

Analysis of hippocampal local field potentials by diffusion mapped delay coordinates.

Spatial navigation through novel spaces and to known goal locations recruits multiple integrated structures in the mammalian brain. Within this extended network, the hippocampus enables formation and retrieval of cognitive spatial maps and contributes to decision making at choice points. Exploration and navigation to known goal locations produce synchronous activity of hippocampal neurons resulting in rhythmic oscillation events in local networks. Power of specific oscillatory frequencies and numbers of these events recorded in local field potentials correlate with distinct cognitive aspects of spatial navigation. Typically, oscillatory power in brain circuits is analyzed with Fourier transforms or short-time Fourier methods, which involve assumptions about the signal that are likely not true and fail to succinctly capture potentially informative features. To avoid such assumptions, we applied a method that combines manifold discovery techniques with dynamical systems theory, namely diffusion maps and Takens' time-delay embedding theory, that avoids limitations seen in traditional methods. This method, called diffusion mapped delay coordinates (DMDC), when applied to hippocampal signals recorded from juvenile rats freely navigating a Y-maze, replicates some outcomes seen with standard approaches and identifies age differences in dynamic states that traditional analyses are unable to detect. Thus, DMDC may serve as a suitable complement to more traditional analyses of LFPs recorded from behaving subjects that may enhance information yield.

Observations of the missing baryons in the warm-hot intergalactic medium.

It has been known for decades that the observed number of baryons in the local Universe falls about 30-40 per cent short1,2 of the total number of baryons predicted 3 by Big Bang nucleosynthesis, as inferred4,5 from density fluctuations of the cosmic microwave background and seen during the first 2-3 billion years of the Universe in the so-called 'Lyman α forest'6,7 (a dense series of intervening H I Lyman α absorption lines in the optical spectra of background quasars). A theoretical solution to this paradox locates the missing baryons in the hot and tenuous filamentary gas between galaxies, known as the warm-hot intergalactic medium. However, it is difficult to detect them there because the largest by far constituent of this gas-hydrogen-is mostly ionized and therefore almost invisible in far-ultraviolet spectra with typical signal-to-noise ratios8,9. Indeed, despite large observational efforts, only a few marginal claims of detection have been made so far2,10. Here we report observations of two absorbers of highly ionized oxygen (O VII) in the high-signal-to-noise-ratio X-ray spectrum of a quasar at a redshift higher than 0.4. These absorbers show no variability over a two-year timescale and have no associated cold absorption, making the assumption that they originate from the quasar's intrinsic outflow or the host galaxy's interstellar medium implausible. The O VII systems lie in regions characterized by large (four times larger than average 11 ) galaxy overdensities and their number (down to the sensitivity threshold of our data) agrees well with numerical simulation predictions for the long-sought warm-hot intergalactic medium. We conclude that the missing baryons have been found.

The expression of ceruloplasmin in astrocytes is essential for postnatal myelination and myelin maintenance in the adult brain.

Ceruloplasmin (Cp) is a ferroxidase enzyme that is essential for cell iron efflux. The absence of this protein in humans and rodents produces progressive neurodegeneration with brain iron accumulation. Astrocytes express high levels of Cp and iron efflux from these cells has been shown to be central for oligodendrocyte maturation and myelination. To explore the role of astrocytic Cp in brain development and aging we generated a specific conditional KO mouse for Cp in astrocytes (Cp cKO). Deletion of Cp in astrocytes during the first postnatal week induced hypomyelination and a significant delay in oligodendrocyte maturation. This abnormal myelin synthesis was exacerbated throughout the first two postnatal months and accompanied by a reduction in oligodendrocyte iron content, as well as an increase in brain oxidative stress. In contrast to young animals, deletion of astrocytic Cp at 8 months of age engendered iron accumulation in several brain areas and neurodegeneration in cortical regions. Aged Cp cKO mice also showed myelin loss and oxidative stress in oligodendrocytes and neurons, and at 18 months of age, developed abnormal behavioral profiles, including deficits in locomotion and short-term memory. In summary, our results demonstrate that iron efflux-mediated by astrocytic Cp-is essential for both early oligodendrocyte maturation and myelin integrity in the mature brain. Additionally, our data suggest that astrocytic Cp activity is central to prevent iron accumulation and iron-induced oxidative stress in the aging CNS.

Study of the

The ^{22}Mg(α,p)^{25}Al reaction rate has been identified as a major source of uncertainty for understanding the nucleosynthesis flow in Type-I x-ray bursts. We report a direct measurement of the energy- and angle-integrated cross sections of this reaction in a 3.3-6.9 MeV center-of-mass energy range using the MUlti-Sampling Ionization Chamber (MUSIC). The new ^{22}Mg(α,p)^{25}Al reaction rate is a factor of ∼4 higher than the previous direct measurement of this reaction within temperatures relevant for x-ray bursts, resulting in the ^{22}Mg waiting point of x-ray burst nucleosynthesis flow to be significantly bypassed via the (α,p) reaction.

The 2021 SIIM-FISABIO-RSNA Machine Learning COVID-19 Challenge: Annotation and Standard Exam Classification of COVID-19 Chest Radiographs.

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including "typical," "indeterminate," and "atypical appearance" for COVID-19, or "negative for pneumonia," adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.

Deep Learning-Based Feature Extraction of Acoustic Emission Signals for Monitoring Wear of Grinding Wheels.

Tool wear monitoring is a critical issue in advanced manufacturing systems. In the search for sensing devices that can provide information about the grinding process, Acoustic Emission (AE) appears to be a promising technology. The present paper presents a novel deep learning-based proposal for grinding wheel wear status monitoring using an AE sensor. The most relevant finding is the possibility of efficient feature extraction form frequency plots using CNNs. Feature extraction from FFT plots requires sound domain-expert knowledge, and thus we present a new approach to automated feature extraction using a pre-trained CNN. Using the features extracted for different industrial grinding conditions, t-SNE and PCA clustering algorithms were tested for wheel wear state identification. Results are compared for different industrial grinding conditions. The initial state of the wheel, resulting from the dressing operation, is clearly identified for all the experiments carried out. This is a very important finding, since dressing strongly affects operation performance. When grinding parameters produce acute wear of the wheel, the algorithms show very good clustering performance using the features extracted by the CNN. Performance of both t-SNE and PCA was very much the same, thus confirming the excellent efficiency of the pre-trained CNN for automated feature extraction from FFT plots.

Clinical profile of patients with lupus psychosis in a Colombian cohort.

The objective of this study is to describe the frequency and the clinical, paraclinical, and treatment profile of patients with lupus psychosis in a Colombian cohort of patients with systemic lupus erythematosus (SLE). This retrospective cohort study evaluated epidemiological and clinical characteristics, results of neuroimaging, analysis of the cerebrospinal fluid, treatment, and disease evolution in patients with lupus psychosis. Among 2,479 patients with SLE, six female patients aged between 20 and 50 years with a diagnosis of lupus psychosis were identified. In two patients, psychosis was present at disease onset and in the other four, SLE was already present, although the majority of them were diagnosed less than two years prior to the onset of psychosis. The entire cohort had high disease activity as measured by SLEDAI-2K. We found concomitant cutaneous, joint, and hematological alterations. Cerebrospinal fluid data were obtained in half of the patients and were normal. We performed brain tomography on most of our patients, which was almost always described as normal. In 5 out of 6 patients, the induction therapy to treat psychosis was based on steroids, and in the majority of them, a resolution of psychiatric symptoms was observed after initiating treatment. Lupus psychosis is a rare event that usually occurs early in the course of the disease and is associated with other manifestations of SLE. This investigation mainly found concomitant cutaneous, joint, and hematological manifestations, with a favorable outcome after treatment, as described in the literature.

The impact of water vapor on the OH reactivity toward CH3CHO at ultra-low temperatures (21.7-135.0 K): Experiments and theory.

The role of water vapor (H2O) and its hydrogen-bonded complexes in the gas-phase reactivity of organic compounds with hydroxyl (OH) radicals has been the subject of many recent studies. Contradictory effects have been reported at temperatures between 200 and 400 K. For the OH + acetaldehyde reaction, a slight catalytic effect of H2O was previously reported at temperatures between 60 and 118 K. In this work, we used Laval nozzle expansions to reinvestigate the impact of H2O on the OH-reactivity with acetaldehyde between 21.7 and 135.0 K. The results of this comprehensive study demonstrate that water, instead, slows down the reaction by factors of ∼3 (21.7 K) and ∼2 (36.2-89.5 K), and almost no effect of added H2O was observed at 135.0 K.

Preservation of protective capacity of hyperimmune anti-Stx2 bovine colostrum against enterohemorrhagic Escherichia coli O157:H7 pathogenicity after pasteurization and spray-drying processes.

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a major etiologic agent that causes bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome (HUS). Shiga toxin (Stx) is the main virulence factor of EHEC responsible for the progression to HUS. Although many laboratories have made efforts to develop an effective treatment for Stx-mediated HUS, a specific therapy has not been found yet. Human consumption of bovine colostrum is known to have therapeutic effects against several gastrointestinal infections because of the peptide and proteins (including antibodies) with direct antimicrobial and endotoxin-neutralizing effects contained in this fluid. We have previously demonstrated that colostrum from Stx type 2 (Stx2)-immunized pregnant cows effectively prevents Stx2 cytotoxicity and EHEC O157:H7 pathogenicity. In this study we evaluated the preservation of the protective properties of hyperimmune colostrum against Stx2 (HIC-Stx2) after pasteurization and spray-drying processes by performing in vitro and in vivo assays. Our results showed that reconstituted HIC-Stx2 colostrum after pasteurization at 60°C for 60 min and spray-dried under optimized conditions preserved specific IgG that successfully neutralized Stx2 cytotoxicity on Vero cells. Furthermore, this pasteurized/dehydrated and reconstituted HIC-Stx2 preserved the protective capacity against EHEC infection in a weaned mice model. The consumption of hyperimmune HIC-Stx2 bovine colostrum could be effective for HUS prevention in humans as well as in EHEC control in calves. However, further studies need to be done to consider its use for controlling EHEC infections.

Developing a Training Web Application for Improving the COVID-19 Diagnostic Accuracy on Chest X-ray.

In December 2019, a new coronavirus known as 2019-nCoV emerged in Wuhan, China. The virus has spread globally and the infection was declared pandemic in March 2020. Although most cases of coronavirus disease 2019 (COVID-19) are mild, some of them rapidly develop acute respiratory distress syndrome. In the clinical management, chest X-rays (CXR) are essential, but the evaluation of COVID-19 CXR could be a challenge. In this context, we developed COVID-19 TRAINING, a free Web application for training on the evaluation of COVID-19 CXR. The application included 196 CXR belonging to three categories: non-pathological, pathological compatible with COVID-19, and pathological non-compatible with COVID-19. On the training screen, images were shown to the users and they chose a diagnosis among those three possibilities. At any time, users could finish the training session and be evaluated through the estimation of their diagnostic accuracy values: sensitivity, specificity, predictive values, and global accuracy. Images were hand-labeled by four thoracic radiologists. Average values for sensitivity, specificity, and global accuracy were .72, .64, and .68. Users who achieved better sensitivity registered less specificity (p < .0001) and those with higher specificity decreased their sensitivity (p < .0001). Users who sent more answers achieved better accuracy (p = .0002). The application COVID-19 TRAINING provides a revolutionary tool to learn the necessary skills to evaluate COVID-19 on CXR. Diagnosis training applications could provide a new original manner of evaluation for medical professionals based on their diagnostic accuracy values, and an efficient method to collect valuable data for research purposes.

The involvement of marine tourism companies in CSR: the case of the island of Tenerife.

Corporate Social Responsibility is a voluntary strategy by companies, which integrates a set of actions that contribute to sustainable development. This study analyzes the degree of involvement of marine tourism companies in human resource management, adaptation to change, environmental management, local community development and collaboration with public and private agents. These areas configure companies' Corporate Social Responsibility strategies. Information was collected from marine tourism companies on the island of Tenerife using quantitative and qualitative methodologies. A binary logistic regression analysis was applied. The results indicate that, in general, marine tourism companies are socio-environmentally responsible. Environmental aspects and adaptation to change through innovation have the greatest weight in these companies' Corporate Social Responsibility strategies. Actions for local community development and collaboration with private agents are also important. However, human resource management influences negatively since marine tourism is a highly regulated sector in this regard. Thus, actions are mandatory and not voluntary, affecting all companies equally whether they have high levels of Corporate Social Responsibility implementation or not. Regarding relations with public authorities, the results indicate that improvement is urgently required, given the low participation of marine tourism companies in policy making.

Nuclear magnetic resonance analysis of female and male pre-hatching embryo metabolites at the embryo-maternal interface.

INTRODUCTION: Bovine female and male embryos differentially release metabolites with signalling effects to culture media. However, it is unknown if the embryo-maternal interface (EMI) metabolome is modified by embryonic sex. OBJECTIVE: To analyse using a combination of 1H NMR and a co-culture of endometrial cells the EMI. RESULTS: Twenty-six metabolites were identified and quantified in the EMI, nine metabolites reflected the sex of the embryo rather than their presence. CONCLUSIONS: 1H NMR is sensitive enough to perform quantitative analysis of sex-induced differences in the EMI. These results may help to understand the embryo-maternal dialogue on the basis of embryonic sex.

Surveying for Batrachochytrium salamandrivorans presence in Spanish captive collections of amphibians.

Batrachochytrium salamandrivorans (Bsal), a pathogenic fungus causing the fatal disease chytridiomycosis in amphibians, was likely introduced to Europe through the trade in pet salamanders from Asia and then escaped into wild populations. Among European countries, Spain has a large number of private breeders and keepers of pet salamanders, and cases of Bsal in wild and captive populations already have been confirmed there. However, surveillance for the pathogen in Spanish collections of amphibians is sparse. Therefore, assisted by private owners and breeders, we surveyed 10 amphibian collections and analysed a total of 317 samples for presence of Bsal. All of our analyses yielded negative results. However, this apparent lack of Bsal cases in captivity should not encourage relaxation of vigilance, quarantine efforts or good practices. Because amphibian collections represent highly dynamic environments (animals are coming in and out), the pathogen could easily be introduced into a collection by new individuals. Any case of Bsal infection in captive animals could lead to its further spread to wild populations of susceptible species, potentially decimating them, and thus should be prevented.

Microgravity effects on frozen human sperm samples.

PURPOSE: Microgravity has severe effects on cellular and molecular structures as well as on metabolic interactions. The aim of this study is to investigate the effects of microgravity (µg) exposure on human frozen sperm samples. METHODS: Sibling samples from 15 normozoospermic healthy donors were frozen using glycerol as cryoprotectant and analyzed under microgravity and ground conditions. Microgravity was obtained by parabolic flights using a CAP10B plane. The plane executed 20 parabolic maneuvers with a mean of 8.5 s of microgravity for each parabola. RESULTS: Frozen sperm samples preserved in cryostraws and stored in a secure and specific nitrogen vapor cryoshipper do not suffer significant alterations after µg exposure. Comparing the study group (µg) and the control group (1 g), similar results were obtained in the main parameters studied: sperm motility (M/ml) 13.72 ± 12.57 vs 13.03 ± 12.13 (- 0.69 95% CI [- 2.9; 1.52]), progressive a + b sperm motility (%) 21.83 ± 11.69 vs 22.54 ± 12.83 (0.03 95% CI [- 0.08; 0.15]), sperm vitality (%) 46.42 ± 10.81 vs 44.62 ± 9.34 (- 0.04 95% CI [- 0.13; 0.05]), morphologically normal spermatozoa (%) 7.03 ± 2.61 vs 8.09 ± 3.61 (0.12 95% CI [0.01; 0.24]), DNA sperm fragmentation by SCD (%) 13.33 ± 5.12 vs 13.88 ± 6.14 (0.03 95% CI [- 0.09; 0.16]), and apoptotic spermatozoa by MACS (%) 15.47 ± 15.04 vs 23.80 ± 23.63 (- 0.20 95% CI [- 0.66; 1.05]). CONCLUSION: The lack of differences obtained between frozen samples exposed to µg and those maintained in ground conditions provides the possibility of considering the safe transport of human male gametes to space. Nevertheless, further research is needed to validate the results and to consider the possibility of creating a human sperm bank outside the Earth. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03760783.

Key

Detection of nuclear-decay γ rays provides a sensitive thermometer of nova nucleosynthesis. The most intense γ-ray flux is thought to be annihilation radiation from the ß^{+} decay of ^{18}F, which is destroyed prior to decay by the ^{18}F(p,α)^{15}O reaction. Estimates of ^{18}F production had been uncertain, however, because key near-threshold levels in the compound nucleus, ^{19}Ne, had yet to be identified. We report the first measurement of the ^{19}F(^{3}He,tγ)^{19}Ne reaction, in which the placement of two long-sought 3/2^{+} levels is suggested via triton-γ-γ coincidences. The precise determination of their resonance energies reduces the upper limit of the rate by a factor of 1.5-17 at nova temperatures and reduces the average uncertainty on the nova detection probability by a factor of 2.1.

The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans.

Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.

Analysis of the regulatory function of natural killer cells from patients with systemic lupus erythematosus.

Natural killer (NK) cells participate in the regulation of the immune response. However, the immunomodulatory function of NK cells in systemic lupus erythematosus (SLE) is not well understood. The aim of this study was to evaluate the regulatory function of NK cells in SLE patients and to identify the NK cells involved in the pathogenesis of this complex disease. We analysed the expression of NK receptors and co-stimulatory molecules in peripheral NK cells (CD3- CD56+ ) from SLE patients, as well as the numbers of human leucocyte antigen D-related (HLA-DR)/CD11c+ NK cells. In addition, NK cell regulatory function was assessed by the detection of NK cell-mediated dendritic cell (DC) lysis. We found that SLE patients showed increased numbers of immunoglobulin-like transcript 2 (ILT2)+ , CD86+ and CD134+ NK cells. Furthermore, NK cells from SLE patients induced higher levels of DC lysis. We were able to identify a new subset of NK cells co-expressing CD11c and HLA-DR. These atypical NK cells were increased in SLE patients when compared with controls. We have identified an expanded new subset of NK cells in SLE patients. This is the first study, to our knowledge, which demonstrates that NK cells in SLE patients have an altered phenotype with a high expression of receptors characteristic of dendritic cells. Our results suggest that the impairment in the regulatory function of NK cells, together with the increased number of DC-like NK cells, could play an important role in the development of SLE and highlight the importance of NK cells as a future therapeutic target.