This work attempts to better understand the significance of morphological diversity among fungal-algal contact zones present in lichens. We used TEM to examine a variety of lichen symbioses involving non-trebouxialean green algae that show intraparietal penetration by the mycobiont. A principal focus was on Endocarpon pusillum, a well-known member of a family (Verrucariaceae; Eurotiomycetes) previously reported to be characterized by unwalled haustoria exposing a naked fungal protoplast. Peg-like haustoria arose from an inner layer(s) of the mycobiont cell wall that broke through outer layers and penetrated a short distance into the wall of the green algal symbiont (Diplosphaera). In both fungal and algal cells at the contact interface, lomasome-like vesicles and tubules occurred as modifications of the plasmalemma intermixed with wall materials at the inner surface of the cell wall. A fungal cell wall was consistently present around the haustorium, which resembled those depicted in earlier TEM studies of Verrucariaceae. Previously published micrographs of Verrucariaceae purporting to show wall-less haustoria surrounded by an empty space are believed to have been misinterpreted. However, in the isidiose Porina and foliicolous Calopadia, Byssoloma and Fellhanera species (Lecanoromycetes), we did observe extreme degrees of reduction in the mycobiont cell wall at symbiont contact interfaces. In those lichens, a broad area of the fungal cell bulged into the adjacent algal symbiont, broadly invaginating the wall of the latter and penetrating it intraparietally without differentiation of a distinct haustorial structure. The mycobiont wall surrounding such protrusions often thinned to near indistinguishability towards its extremity. The protrusion made direct contact with the algal cell wall; no empty space occurred between them. We propose that the short, peg-like intraparietal haustoria bind the symbionts and help maintain cell contacts amid the stresses of tissue expansion and shrinkage, thereby avoiding disruption of the continuous hydrophobic coating that facilitates transfer between them. Broader contact interfaces with extremely thin adjacent walls may facilitate solute flow between symbionts. Reciprocal penetration of algal protrusions into mycobiont cells, noted in Porina as well as other lichens studied previously, is a neglected but potentially significant indication that both symbionts may actively work to maintain functional contact interfaces.

In a combined experimental and numerical effort, we investigate the generation and reduction of airfoil tonal noise. The means of noise control are streak generators in the form of cylindrical roughness elements. These elements are placed periodically along the span of the airfoil at the mid-chord streamwise position. Experiments are performed for a wide range of Reynolds numbers and angles of attack in a companion work (Alva et al., AIAA Aviation Forum, 2023). In the present work, we concentrate on numerical investigations for a further investigation of selected cases. We have performed wall-resolved large-eddy simulations for a NACA 0012 airfoil at zero angle of attack and Mach 0.3. Two Reynolds numbers (${0.8\times 10^{5}}$ and ${1.0 \times 10^{5}}$) have been investigated, showing acoustic results consistent with experiments at the same Reynolds but lower Mach numbers. Roughness elements attenuate tones in the acoustic field and, for the higher Reynolds number, suppress them. Through Fourier decomposition and spectral proper orthogonal decomposition analysis of streamwise velocity data, dominating structures have been identified. Further, the coupling between the structures generated by the surface roughness and the instability modes (Kelvin–Helmholtz) of the shear layer has been identified through stability analysis, suggesting stabilisation mechanisms by which the sound generation by the airfoil is reduced by the roughness elements.

Background: Efgartigimod, a human immunoglobulin G1 (IgG1) antibody Fc fragment, reduces IgG levels through neonatal Fc receptor blockade. Efgartigimod PH20 SC (1000-mg fixed dose, coformulated with recombinant human hyaluronidase PH20) is provided in a vial administered via a separate syringe (V+S). Here, we investigate bioequivalence, safety, and tolerability of efgartigimod PH20 SC administered via prefilled syringe (PFS) vs V+S in healthy participants. Methods: Bioequivalence was assessed in a phase 1, open-label study. Healthy participants (n=72) were randomized to receive one injection of efgartigimod PH20 SC via PFS or V+S in a crossover design. Separate studies evaluated feasibility of different injection speeds and usability of the PFS. Results: Bioequivalence between efgartigimod PH20 SC via PFS or V+S was established, as the 90% CI around the geometric least-squares mean ratio of Cmax and AUC0-inf was within predefined criteria (80.00%-125.00%). Most adverse events were mild to moderate. No observed differences in incidence of reported injection site reactions emerged. No serious adverse events or deaths occurred. Rapid (20-second) administration was feasible and the PFS could be safely prepared and administered by participants/caregivers. Conclusions: Efgartigimod PH20 SC administered via PFS is bioequivalent to efgartigimod PH20 SC administered via V+S, which may provide an additional convenient treatment option.

Background: The complement component C5 inhibitor, ravulizumab, is approved in Canada for the treatment of adults with AQP4-Ab+ NMOSD. Updated efficacy and safety results from the ongoing CHAMPION-NMOSD (NCT04201262) trial are reported. Methods: Participants received IV-administered, weight-based dosing of ravulizumab, with loading on day 1 and maintenance doses on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Outcome measures included safety, time to first adjudicated on-trial relapse (OTR), risk reduction, and disability scores. Results: 56/41 patients entered/completed the LTE as of June 14, 2024. Median follow-up was 170.3 weeks (186.6 patient-years). No patients experienced an OTR. 94.8% (55/58 patients) had stable or improved Hauser Ambulation Index scores. 89.7% (52/58 patients) had no clinically important worsening in Expanded Disability Status Scale scores. Treatment-emergent adverse events (98.4%) were predominantly mild and unrelated to ravulizumab. Serious adverse events occurred in 25.9% of patients. Two cases of meningococcal infection occurred during the PTP, and none in the LTE. One unrelated death (cardiovascular) occurred during the LTE. Conclusions: Ravulizumab demonstrated long-term clinical benefit in AQP4-Ab+ NMOSD relapse prevention while maintaining or improving disability measures, with no new safety concerns.

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP). The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) and open-label extension ADHERE+ (NCT04280718) trials (interim analysis cutoff: February 16, 2024) assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to efgartigimod or placebo for ≤48 weeks (stage-B). Participants with clinical deterioration in stage-B or who completed ADHERE entered ADHERE+. Week 36 changes from run-in baseline (CFB) in adjusted Inflammatory Neuropathy Cause and Treatment (aINCAT), Inflammatory Rasch-built Overall Disability Scale (I-RODS), and grip strength scores were evaluated. Results: Of 322 stage-A participants, 221 were randomized and treated in stage-B, and 99% entered ADHERE+. Mean CFB (SE) in aINCAT, I-RODS, and grip strength scores were -1.2 (0.15) and 8.8 (1.46) and 17.5 (2.02), respectively, at ADHERE+ Week 36 (N=150). Half the participants with clinical deterioration during ADHERE stage-B restabilized on efgartigimod from ADHERE+ Week 4. Conclusions: Interim results from ADHERE+ indicate long-term effectiveness of efgartigimod PH20 SC in clinical outcomes in participants with CIDP.

Background: Efgartigimod, a human immunoglobulin (Ig)G1 antibody Fc fragment, blocks the neonatal Fc receptor, reducing IgGs involved in chronic inflammatory demyelinating polyneuropathy (CIDP), a rare, progressive, immune-mediated disease that can lead to irreversible disability. The multi-stage, double-blinded, placebo-controlled ADHERE (NCT04281472) trial assessed efgartigimod PH20 SC in participants with CIDP. Methods: Participants with active CIDP received open-label, weekly efgartigimod PH20 SC 1000 mg during ≤12-week run-in (stage-A). Responders were randomized (1:1) to weekly efgartigimod or placebo for ≤48 weeks (stage-B). This posthoc analysis evaluated changes from run-in baseline (study enrollment) to stage-B last assessment and items of the Inflammatory Rasch-built Overall Disability Scale (I-RODS). Results: Of 322 participants who entered stage-A, 221 were randomized and treated in stage-B, and 191/221 had data for run-in baseline and post–stage-B timepoints. Mean (SE) I-RODS change at stage-B last assessment vs run-in baseline was 5.7 (1.88) and -4.9 (1.82) in participants randomized to efgartigimod and placebo, respectively. 37/97 (38.1%) and 24/92 (26.1%) participants randomized to efgartigimod and placebo, respectively, experienced ≥4-point improvements in I-RODS score. Efgartigimod-treated participants improved ≥1 point in I-RODS items of clinical interest. Conclusions: Participants who received efgartigimod in stage-B experienced improvements in I-RODS score from study enrollment to stage-B last assessment.

During pregnancy, colonization by genital mycoplasmas may be associated with adverse outcomes. This study was conducted to investigate the prevalence of four species of Mollicutes (Mycoplasma hominis, Mycoplasma genitalium, Ureaplasma parvum, and Ureaplasma urealyticum) in pregnant women receiving high-risk prenatal care and to evaluate possible associated factors. Data collection included the application of a questionnaire and the collection of cervical swabs from pregnant women. Species identification was performed by real-time PCR. The overall prevalence of Mollicutes was 60.97%. 55.9% of pregnant women were colonized by Ureaplasma spp., and 19.51% by Mycoplasma spp. The prevalence rates by species were 48.78% for U. parvum, 11.59% for U. urealyticum, 18.9% for M. hominis, and 1.22% for M. genitalium. Age, 12 years of schooling or more, age at first sexual intercourse up to 14 years, third trimester of pregnancy, having undergone infertility treatment, presence of STI, and groin lymph nodes were associated with a higher prevalence of microorganisms. The results presented are of utmost importance for understanding the prevalence of these microorganisms, the characteristics of colonized pregnant women, and planning screening strategies and interventions that minimize the negative impacts of these infections.

The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.

Parasite biodiversity is underestimated or unknown in many regions, yet information on parasites is critical to understanding ecosystem structure and how this will change into the future. Understanding the diversity and role of parasites is especially important in regions exposed to anthropogenic pressures, such as aquatic ecosystems, as their interactions with other stressors can either exacerbate or mediate negative impacts. Water scarcity in the Brazilian semi-arid has led to a proliferation of reservoirs for human use. These artificial waterbodies host a diversity of taxa, including a large number of fish species; however, fish parasite diversity remains undocumented. This study investigated the parasitological diversity of fishes from reservoirs in the Paraíba and Mamanguape River basins in the Caatinga domain, Brazil – one of the most populated semi-arid regions worldwide. Eight reservoirs were studied, with fish sampled across the two phases of the hydrological cycle (dry and rainy seasons) using gillnets, cast nets, and trawl nets. Endo- and ecto-parasites were identified and enumerated, and parasitological indices (prevalence, intensity, and abundance) were calculated. In total, 1,170 individuals of 21 fish species were examined. Of these individuals, 42% were parasitized with at least one of 54 parasite taxa. We recorded 32 new geographical occurrences of parasites and 23 new fish-parasite interactions, expanding our understanding of ichthyoparasite diversity in the Brazilian semi-arid. Moving forward, it is important to develop knowledge around how anthropogenic changes (e.g., biological invasions, climate, and land use change) influence host-parasite structure and dynamics and ecosystem functioning in these ecosystems.

The description and delineation of trematode species is a major ongoing task. Across the field there has been, and currently still is, great variation in the standard of this work and in the sophistication of the proposal of taxonomic hypotheses. Although most species are relatively unambiguously distinct from their congeners, many are either morphologically very similar, including the major and rapidly growing component of cryptic species, or are highly variable morphologically despite little to no molecular variation for standard DNA markers. Here we review challenges in species delineation in the context provided to us by the historical literature, and the use of morphological, geographical, host, and molecular data. We observe that there are potential challenges associated with all these information sources. As a result, we encourage careful proposal of taxonomic hypotheses with consideration for underlying species concepts and frank acknowledgement of weaknesses or conflict in the data. It seems clear that there is no single source of data that provides a wholly reliable answer to our taxonomic challenges but that nuanced consideration of information from multiple sources (the ‘integrated approach’) provides the best possibility of developing hypotheses that will stand the test of time.

Toxoplasma gondii non-archetypal strains have distinct virulence profiles and immunological activation in the host when compared with archetypal strains. The present work aims to perform an analysis of the inflammatory profile during acute and early chronic infection by T. gondii atypical strain in an experimental murine model. After euthanasia, blood was collected for the quantification of specific IgG antibodies and their subtypes (IgG1/IgG3) by ELISA; bronchoalveolar lavage (BAL) was realized and immunophenotyping of lymphocytes population was performed at 12- and 30-days post infection (dpi); the levels of IFN-γ, IL-12, IL-10, TNF-α, IL-6, IL-17, nitric oxide and total proteins were determined in the BAL supernatant. Tissue cyst burden was determined in the brain homogenate, and the parasite load in the lungs was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Infection with the CK4 strain induced a lower brain cyst load similar parasite burden in the lungs, and higher levels of IgG1 and IgG3, when compared to ME49. The group infected with the CK4 strain presented higher levels of systemic IFN-γ, and both infected groups displayed similarly elevated levels of systemic TNF-α, IL-6 and IL-17 at 30 dpi, as well as higher numbers of CD4+ and CD8+ T lymphocytes in the acute stage of infection, followed by higher numbers of central and effector CD4+ T cells. IFN-γ levels in the BAL fluid were significantly higher in animals infected with the CK4 strain in both the acute and early chronic stage of infection, highlighting the involvement of the lung environment.