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Abstract Earth’s magnetic field exhibits a dominant dipole morphology. Notwithstanding, significant deviations from the dipole are evident today, particularly the South Atlantic Anomaly (SAA), characterized by anomalously low-field intensity and high directional variability, diminishing the field’s shielding effect. To assess the persistence of SAA-like features over multimillion-year scales, we combine paleomagnetic data from Trindade Island (20°30’S, 29°22’W) with an evaluation of paleosecular variation (PSV) over the past 10 Myr. We employ synthetic models to explore how the position and intensity of magnetic flux patches at the core-mantle boundary can influence the long-term field behavior. Here we present results that reveal anomalous field signatures in the South Atlantic and the Atlantic-Pacific hemispheric asymmetries are enduring features, likely linked to a bottom-up control of PSV by the inner core’s heterogeneities but with contributions from mantle anomalies in the long-time range.

Summary: Background: The selective serotonin reuptake inhibitors (SSRIs) fluoxetine and fluvoxamine were repurposed for the treatment of early COVID-19 based on their antiviral activity in vitro, and observational and clinical trial evidence suggesting they prevented progression to severe disease. However, these SSRIs have not been recommended in therapeutic guidelines and their antiviral activity in vivo has not been characterised. Methods: PLATCOV is an open-label, multicentre, phase 2, randomised, controlled, adaptive pharmacometric platform trial running in Thailand, Brazil, Pakistan, and Laos. We recruited low-risk adult outpatients aged 18–50 with early symptomatic COVID-19 (symptoms 2 days follow-up).The viral clearance rate was estimated under a Bayesian hierarchical linear model fitted to the log10 viral densities measured in standardised duplicate oropharyngeal swab eluates taken daily over one week (18 measurements per patient). Secondary endpoints were all-cause hospital admission at 28 days, and time to resolution of fever and symptoms. This ongoing trial is registered at ClinicalTrials.gov (NCT05041907). Findings: 271 patients were concurrently randomised to either fluoxetine (n = 120) or no study drug (n = 151). All patients had received at least one COVID-19 vaccine dose and 67% were female (182/271). In the primary analysis, viral clearance rates following fluoxetine were compatible with a small or no increase relative to the no study drug arm (15% increase; 95% credible interval (CrI): −2 to 34%). There were no deaths or hospitalisations in either arm. There were no significant differences in times to symptom resolution or fever clearance between the fluoxetine and the no study drug arms (although only a quarter of patients were febrile at baseline). Fluoxetine was well tolerated, there were no serious adverse events and only one grade 3 adverse event in the intervention arm. Interpretation: Overall, the evidence from this study is compatible with fluoxetine having a weak in vivo antiviral activity against SARS-CoV-2, although the primary endpoint is also compatible with no effect. This level of antiviral efficacy is substantially less than with other currently available antiviral drugs. Funding: Wellcome Trust Grant ref: 223195/Z/21/Z through the COVID-19 Therapeutics Accelerator.

The size of a protoplanetary disk is a fundamental property, yet most remain unresolved, even in nearby star-forming regions ( d ∼ 140–200 pc). We present the complete continuum size distribution for the 105 brightest protoplanetary disks ( M _dust ≳ 2 M _⊕ ) in the Ophiuchus cloud, obtained from ALMA Band 8 (410 GHz) observations at 0 $\mathop{.}\limits^{\unicode{x02033}}$ 05 (7 au) to 0 $\mathop{.}\limits^{\unicode{x02033}}$ 15 (21 au) resolution. This sample includes 54 Class II and 51 Class I and flat-spectrum sources, providing a comprehensive distribution across evolutionary stages. We measure the half-width at half-maximum and the radius encircling 68% of the flux ( R _68% ) for most nonbinary disks, yielding the largest flux-limited sample of resolved disks in any star-forming region. The distribution is log-normal with a median value of ∼14 au and a logarithmic standard deviation ${\sigma }_{\mathrm{log}}=0.46$ (factor of 2.9 in linear scale). Disks in close-binary systems (

Resumo O propósito do presente texto é comentar a tese de doutorado A recepção do pensamento de Nietzsche na obra literária de Dalcídio Jurandir - defendida por Oclécio das Chagas Lacerda, em 2022, na Escola de Filosofia, Letras e Ciências Humanas da Universidade Federal de São Paulo (Unifesp) - à luz de dois temas centrais por ela desenvolvidos: a interpretação “antropofágica” da crítica nietzschiana ao niilismo cristão e o sentido amazônico de “transvaloração” dela decorrente.

Early antiviral treatments, including intravenous remdesivir (RDV), reduce hospitalization and severe disease caused by COVID-19. An orally bioavailable RDV analog may facilitate earlier treatment of non-hospitalized COVID-19 patients. Here we describe the synthesis and evaluation of alkyl glyceryl ether phosphodiesters of GS-441524 (RVn), lysophospholipid analogs which allow for oral bioavailability and stability in plasma. Oral treatment of SARS-CoV-2-infected BALB/c mice with 1-O-octadecyl-2-O-benzyl-sn-glyceryl-3-phospho-RVn (60 mg/kg orally, once daily for 5 days starting 12h after infection) reduced lung viral load by 1.5 log10 units versus vehicle at day 2 and to below the limit of detection at day 5. Structure/activity evaluation of additional analogs that have hydrophobic ethers at the sn-2 of glycerol revealed improved in vitro antiviral activity by introduction of a 3-fluoro-4-methoxy-substituted benzyl or a 3- or 4-cyano-substituted benzyl. Collectively, our data support the development of RVn phospholipid prodrugs as oral antiviral agents for prevention and treatment of SARS-CoV-2 infections.

Background The morphology and hunting behavior of thresher sharks make them easily distinguishable. These species are distributed across the Tropical Pacific Ocean feeding on squid and small fish. However, ontogenetic changes in their feeding strategies and habitat use are still unknown in this region. Methods We examined the δ13C and δ15N signatures in vertebral collagen from populations of Alopias pelagicus and Alopias superciliosus inhabiting the Galapagos Marine Reserve, focusing on three maturity stages: neonate, juvenile and adult. The vertebrae samples were taken from the seizure of illegal fishing activities carried out by a foreign fleet within the Galapagos archipelago. A total of thirty-three vertebrae from A. pelagicus and twenty-one from A. superciliosus were analyzed. Results Both species displayed significant differences in their δ15N values (p < 0.001), but not in δ13C (p = 0.230), suggesting a similar habitat use, but different prey consumption. Throughout their ontogeny, A. pelagicus displayed isotopic differences (p < 0.001), where neonates showed lower δ13C values and higher δ15N values compared to juveniles, probably because they still reflect the isotopic signatures of their mothers even after the first year of life. This study highlights trophic differences between both species, accompanied by an ontogenetic variation in A. pelagicus, aspects that allow us to understand the role of these species within the dynamics of the Eastern Tropical Pacific ecosystem.

The páramo grassland ecosystem in the high Andes requires definition of spatially explicit and large-scale priorities for bird conservation, especially for lands outside of protected areas. Using surrogate species such as habitat specialists (e.g., páramo specialists), endemic species, or threatened species to identify potential habitat can support conservation decisions. We used MaxEnt to generate habitat suitability models for eighteen surrogate bird species in a high Andean biosphere reserve, the Macizo del Cajas (MCB). The areas of estimated suitable habitat range from 115,500 to 312,700 ha; the proportion predicted inside the national system of protected areas of MCB ranged from 12 to 29 percent. The consolidated map (i.e., the coincidence of predicted pixels for all eighteen surrogate bird species) predicted an area of 94,800 ha, with 70 percent outside the national system of protected areas. The models reveal that there are large suitable areas of MCB potentially occupied by these species outside of protected areas, especially along the eastern flank of the study area. MaxEnt models as a proxy facilitate the recognition of locations of possible habitat suitability for páramo-specialized birds and therefore identify areas of the MCB outside of the protected areas that should be considered for more formal protection.

Decaprenylphosphoryl-β-D-ribose-oxidase (DprE1), a subunit of the essential decaprenylphosphoribose-2′-epimerase, plays a crucial role in the synthesis of cell wall arabinan components in mycobacteria, including the pathogen responsible for tuberculosis, Mycobacterium tuberculosis. In this study, we designed, synthesised, and evaluated 15 (BOK-1–BOK-10 and BOP-1–BOP-5) potential inhibitors of DprE1 from a series of 1,2,3-triazole ligands using a validated DprE1 inhibition assay. Two compounds, BOK-2 and BOK-3, demonstrated significant inhibition with IC50 values of 2.2 ± 0.1 and 3.0 ± 0.6 μM, respectively, whereas the standard drug (TCA-1) showed inhibition at 3.0 ± 0.2 μM. Through molecular modelling and dynamic simulations, we explored the structural relationships between selected 1,2,3-triazole compounds and DprE1, revealing key features for effective drug–target interactions. This study introduces a novel approach for designing ligands against DprE1, offering a potential therapeutic strategy for tuberculosis treatment.

Summary: Safe, effective, and low-cost oral antiviral therapies are needed to treat those at high risk for developing severe COVID-19. To that end, we performed a high-throughput screen to identify non-peptidic, non-covalent inhibitors of the SARS-CoV-2 main protease (Mpro), an essential enzyme in viral replication. NZ-804 was developed from a screening hit through iterative rounds of structure-guided medicinal chemistry. NZ-804 potently inhibits SARS-CoV-2 Mpro (0.009 μM IC50) as well as SARS-CoV-2 replication in human lung cell lines (0.008 μM EC50) and primary human airway epithelial cell cultures. Antiviral activity is maintained against distantly related sarbecoviruses and endemic human CoV OC43. In SARS-CoV-2 mouse and hamster disease models, NZ-804 therapy given once or twice daily significantly diminished SARS-CoV-2 replication and pathogenesis. NZ-804 synthesis is low cost and uncomplicated, simplifying global production and access. These data support the exploration of NZ-804 as a therapy for COVID-19 and future emerging sarbecovirus infections.

En medicina, muchas veces se encuentran situaciones donde la regresión (lineal o logística) no es viable, por contar con constructos latentes o factores que incluyen diversas variables observadas, ya que tratan de reflejar o estimar fenómenos complejos multidimensionales. Esta limitación dio lugar a la búsqueda de metodologías estadísticas alternativas, como un subtipo de Modelos de Ecuaciones Estructurales denominados modelos MIMIC (del inglés, por Multiple Indicators Multiple Causes), utilizado originalmente en neurociencias. En esta entrega se explica qué son estos modelos, para qué sirven, así como se mencionan los programas para su aplicación, y la interpretación de resultados. Se ejemplifica con un estudio sobre la calidad de vida de personas que recibieron un trasplante, destacando la representación gráfica y la importancia de la parsimonia en los modelos. Estos modelos permiten incluir factores y variables sueltas en simultáneo, resolviendo relaciones causales complejas, por lo cual resultan herramientas útiles en la investigación médica.

Bovine alphaherpesvirus 1 (BoAHV1) is prevalent in cattle throughout the world, whereas bovine alphaherpesvirus 5 (BoAHV5) prevalence seems restricted to some countries in South America, Australia, and other regions, mainly in the Southern Hemisphere. BoAHV5 infections occur where water buffalo (Bubalus bubalis) farming is practiced, often close to cattle (Bos taurus) farms. Bubaline alphaherpesvirus 1 (BuAHV1), a virus whose natural host is believed to be the water buffaloes, usually causes asymptomatic infections in that species. Here, evidence is provided confirming the close relationship between BuAHV1 and BoAHV5. Phylogenetic and recombination analyses were used to reveal the evolutionary relationship between all whole-genome sequences of BoAHV1 (n = 52), BoAHV5 (n = 7), and BuAHV1 (n = 6) available to date. It is proposed here that BoAHV5 most likely resulted from multiple recombination events between a BuAHV1-like ancestor and BoAHV1-like viruses. The BoAHV5 whole unique short (US) region and most of the unique long (UL) genomic regions seem to have been derived from a BuAHV1-like parental genome, whereas at least six small segments of the UL (corresponding to nucleotides 8287 to 8624; 10,658 to 14,496; 48,013 to 48,269; 71,379 to 71,927; 81,426 to 85,003; and 94,012 to 96,841 of the BoAHV5 genome) and two small segments of the US (corresponding to nucleotides 107,039 to 107,581 and 131,267 to 131,810) have been derived from a BoAHV1-like parental genome. The hypothesis that the BoAHV5 species may have originated following a series of recombination events between BuAHV1 and BoAHV1 variants is consistent with the geographical distribution of BoAHV5, which seems to be prevalent in the regions where cattle and water buffalo farming overlap.

COVID19 pandemic has compelled educational institutions to re-navigate their learning modalities to that of fully online learning, thus, generating a totally new experience for teachers and learners who are novices in the flexible or blended learning. This study, therefore, attempted to explore the students' experiences of online learning in time of COVID19 via in-depth quantitative method. A total of 171 students from secondary, tertiary, to graduate levels engaged in online learning were selected as participants using purposive sampling technique. The researchers-made questionnaire focusing on students' satisfaction and dissatisfaction with online learning, as well as their desired improvement, was distributed online to these students from which responses were collected. Based on the results, the most common environment and methods for participating classes were student homes and mobile phones (touchscreen/android). Students indicated that they are satisfied with the following features of online classes: selecting a quiet place for online learning, quality classes at home, and being with the family at home while doing online learning. In contrast, students are dissatisfied about the internet connectivity, not getting full attention from teachers, and have difficulty in sharing ideas. Areas that need improvement according to the students were closely related to the causes of complaints, such as improving network connectivity, microphone and sound quality, and smooth communication during online classes. These findings imply that students' educational environments are important and the quality of interactions can vary depending on the teachers and technology used. This study recommends that an improved and effective online learning system, maintaining academic achievement similar to traditional classroom teaching can be designed in preparation for any possible future crisis like COVID19.

Death of one's child is an unfathomable painful situation that a mother may feel. While literature reports different coping strategies across cultures, there has no research yet that explored the grieving process that Meranao mothers go through when they lost a child. Hence, this study explored the grieving process of the bereaved Meranao mothers from the Southern Philippines over the loss of their children and the strategies they used to cope with the feelings of grief. The study was conducted at different barangays located in Marawi City, Lanao del Sur, Philippines. The participants lost children with age range of 18-30 years old. It was discovered that these bereaved mothers ask several questions to themselves emerging after the death of their children. Nonetheless, it was found that after the mothers had worked through their grief brought by their child's death, they were able to restore their life and become stronger and resilient individuals. This paper concludes that bereaved mothers go through a tedious journey wherein the existence of pain, longing, sadness, guilt and anger were felt, but these emotions only strengthen them as mothers.