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We explore the relationship between mid-infrared (mid-IR) and CO rotational line emission from massive star-forming galaxies, which is one of the tightest scalings in the local universe. We assemble a large set of unresolved and moderately (∼1 kpc) spatially resolved measurements of CO (1–0) and CO (2–1) intensity, I _CO , and mid-IR intensity, I _MIR , at 8, 12, 22, and 24 μ m. The I _CO versus I _MIR relationship is reasonably described by a power law with slopes 0.7–1.2 and normalization I _CO ∼ 1 K km s ^−1 at I _MIR ∼ 1 MJy sr ^−1 . Both the slopes and intercepts vary systematically with choice of line and band. The comparison between the relations measured for CO (1–0) and CO (2–1) allow us to infer that ${R}_{21}\propto {I}_{\mathrm{MIR}}^{0.2}$ , in good agreement with other work. The 8 μ m and 12 μ m bands, with strong polycyclic aromatic hydrocarbon (PAH) features, show steeper CO versus mid-IR slopes than the 22 and 24 μ m, consistent with PAH emission arising not just from CO-bright gas but also from atomic or CO-dark gas. The CO-to-mid-IR ratio correlates with global galaxy stellar mass ( M _⋆ ) and anticorrelates with star formation rate/ M _⋆ . At ∼1 kpc resolution, the first four PHANGS–JWST targets show CO-to-mid-IR relationships that are quantitatively similar to our larger literature sample, including showing the steep CO-to-mid-IR slopes for the JWST PAH-tracing bands, although we caution that these initial data have a small sample size and span a limited range of intensities.

We present maps tracing the fraction of dust in the form of polycyclic aromatic hydrocarbons (PAHs) in IC 5332, NGC 628, NGC 1365, and NGC 7496 from JWST/MIRI observations. We trace the PAH fraction by combining the F770W (7.7 μ m) and F1130W (11.3 μ m) filters to track ionized and neutral PAH emission, respectively, and comparing the PAH emission to F2100W, which traces small, hot dust grains. We find the average R _PAH = (F770W + F1130W)/F2100W values of 3.3, 4.7, 5.1, and 3.6 in IC 5332, NGC 628, NGC 1365, and NGC 7496, respectively. We find that H ii regions traced by MUSE H α show a systematically low PAH fraction. The PAH fraction remains relatively constant across other galactic environments, with slight variations. We use CO+H i +H α to trace the interstellar gas phase and find that the PAH fraction decreases above a value of ${{\rm{I}}}_{{\rm{H}}\alpha }/{{\rm{\Sigma }}}_{{\rm{H}}{\rm\small{I}}+{{\rm{H}}}_{2}}\sim {10}^{37.5}\,\mathrm{erg}\,{{\rm{s}}}^{-1}\,{\mathrm{kpc}}^{-2}\,{({M}_{\odot }\,{\mathrm{pc}}^{-2})}^{-1}$ in all four galaxies. Radial profiles also show a decreasing PAH fraction with increasing radius, correlated with lower metallicity, in line with previous results showing a strong metallicity dependence to the PAH fraction. Our results suggest that the process of PAH destruction in ionized gas operates similarly across the four targets.

Large-scale bars can fuel galaxy centers with molecular gas, often leading to the development of dense ringlike structures where intense star formation occurs, forming a very different environment compared to galactic disks. We pair ∼0.″3 (30 pc) resolution new JWST/MIRI imaging with archival ALMA CO(2–1) mapping of the central ∼5 kpc of the nearby barred spiral galaxy NGC 1365 to investigate the physical mechanisms responsible for this extreme star formation. The molecular gas morphology is resolved into two well-known bright bar lanes that surround a smooth dynamically cold gas disk ( R _gal ∼ 475 pc) reminiscent of non-star-forming disks in early-type galaxies and likely fed by gas inflow triggered by stellar feedback in the lanes. The lanes host a large number of JWST-identified massive young star clusters. We find some evidence for temporal star formation evolution along the ring. The complex kinematics in the gas lanes reveal strong streaming motions and may be consistent with convergence of gas streamlines expected there. Indeed, the extreme line widths are found to be the result of inter-“cloud” motion between gas peaks; ScousePy decomposition reveals multiple components with line widths of 〈 σ _CO,scouse 〉 ≈ 19 km s ^−1 and surface densities of $\langle \,{{\rm{\Sigma }}}_{{{\rm{H}}}_{2},\mathrm{scouse}}\rangle \,\approx \,800\,{M}_{\odot }\,{\mathrm{pc}}^{-2}$ , similar to the properties observed throughout the rest of the central molecular gas structure. Tailored hydrodynamical simulations exhibit many of the observed properties and imply that the observed structures are transient and highly time-variable. From our study of NGC 1365, we conclude that it is predominantly the high gas inflow triggered by the bar that is setting the star formation in its CMZ.

PHANGS–JWST mid-infrared (MIR) imaging of nearby spiral galaxies has revealed ubiquitous filaments of dust emission in intricate detail. We present a pilot study to systematically map the dust filament network (DFN) at multiple scales between 25 and 400 pc in NGC 628. MIRI images at 7.7, 10, 11.3, and 21 μ m of NGC 628 are used to generate maps of the filaments in emission, while PHANGS–HST B -band imaging yields maps of dust attenuation features. We quantify the correspondence between filaments traced by MIR thermal continuum/polycyclic aromatic hydrocarbon (PAH) emission and filaments detected via extinction/scattering of visible light; the fraction of MIR flux contained in the DFN; and the fraction of H ii regions, young star clusters, and associations within the DFN. We examine the dependence of these quantities on the physical scale at which the DFN is extracted. With our highest-resolution DFN maps (25 pc filament width), we find that filaments in emission and attenuation are cospatial in 40% of sight lines, often exhibiting detailed morphological agreement; that ∼30% of the MIR flux is associated with the DFN; and that 75%–80% of the star formation in H ii regions and 60% of the mass in star clusters younger than 5 Myr are contained within the DFN. However, the DFN at this scale is anticorrelated with looser associations of stars younger than 5 Myr identified using PHANGS–HST near-UV imaging. We discuss the impact of these findings on studies of star formation and the interstellar medium, and the broad range of new investigations enabled by multiscale maps of the DFN.

Ratios of polycyclic aromatic hydrocarbon (PAH) vibrational bands are a promising tool for measuring the properties of the PAH population and their effect on star formation. The photometric bands of the MIRI and NIRCam instruments on JWST provide the opportunity to measure PAH emission features across entire galaxy disks at unprecedented resolution and sensitivity. Here we present the first results of this analysis in a sample of three nearby galaxies: NGC 628, NGC 1365, and NGC 7496. Based on the variations observed in the 3.3, 7.7, and 11.3 μ m features, we infer changes to the average PAH size and ionization state across the different galaxy environments. High values of F335M _PAH /F1130W and low values of F1130W/F770W are measured in H ii regions in all three galaxies. This suggests that these regions are populated by hotter PAHs, and/or that the PAH ionization fraction is larger. We see additional evidence of heating and/or changes in PAH size in regions with higher molecular gas content as well as increased ionization in regions with higher H α intensity.

We present new 0.3–21 μ m photometry of SN 2021aefx in the spiral galaxy NGC 1566 at +357 days after B -band maximum, including the first detection of any Type Ia supernova (SN Ia) at >15 μ m. These observations follow earlier JWST observations of SN 2021aefx at +255 days after the time of maximum brightness, allowing us to probe the temporal evolution of the emission properties. We measure the fraction of flux emerging at different wavelengths and its temporal evolution. Additionally, the integrated 0.3–14 μ m decay rate of Δ m _0.3–14 = 1.35 ± 0.05 mag/100 days is higher than the decline rate from the radioactive decay of ^56 Co of ∼1.2 mag/100 days. The most plausible explanation for this discrepancy is that flux is shifting to >14 μ m, and future JWST observations of SNe Ia will be able to directly test this hypothesis. However, models predicting nonradiative energy loss cannot be excluded with the present data.

We measure empirical relationships between the local star formation rate (SFR) and properties of the star-forming molecular gas on 1.5 kpc scales across 80 nearby galaxies. These relationships, commonly referred to as “star formation laws,” aim at predicting the local SFR surface density from various combinations of molecular gas surface density, galactic orbital time, molecular cloud free fall time, and the interstellar medium dynamical equilibrium pressure. Leveraging a multiwavelength database built for the Physics at High Angular Resolution in Nearby Galaxies (PHANGS) survey, we measure these quantities consistently across all galaxies and quantify systematic uncertainties stemming from choices of SFR calibrations and the CO-to-H _2 conversion factors. The star formation laws we examine show 0.3–0.4 dex of intrinsic scatter, among which the molecular Kennicutt–Schmidt relation shows a ∼10% larger scatter than the other three. The slope of this relation ranges β ≈ 0.9–1.2, implying that the molecular gas depletion time remains roughly constant across the environments probed in our sample. The other relations have shallower slopes ( β ≈ 0.6–1.0), suggesting that the star formation efficiency per orbital time, the star formation efficiency per free fall time, and the pressure-to-SFR surface density ratio (i.e., the feedback yield) vary systematically with local molecular gas and SFR surface densities. Last but not least, the shapes of the star formation laws depend sensitively on methodological choices. Different choices of SFR calibrations can introduce systematic uncertainties of at least 10%–15% in the star formation law slopes and 0.15–0.25 dex in their normalization, while the CO-to-H _2 conversion factors can additionally produce uncertainties of 20%–25% for the slope and 0.10–0.20 dex for the normalization.

A silvopasture system intentionally integrates trees, forages, and livestock, allowing dual land use. These systems can provide high-quality habitat for broiler chickens; however, such systems have not been widely adopted by the broiler industry in the United States. The objective of this study was to examine the effect of silvopasture versus open pasture access on fearfulness and leg health in fast-growing broiler chickens. A total of 886 mixed-sex Ross 708 chicks in Experiment 1 (Exp 1) and 648 chicks in Experiment 2 (Exp 2) were housed in coops and had access to 16 (Exp 1) or 12 (Exp 2) 125m2 silvopasture plots (x̄ = 32% canopy cover) or open pasture plots (no canopy cover) from day 24 of age. Fearfulness was measured using a tonic immobility test (tonic immobility duration), and leg health was assessed by quantifying footpad dermatitis, hock burns, gait, and performing a latency-to-lie test on days 37-39 of age. Birds in the silvopasture treatment were less fearful than birds in the open pasture treatment. Overall, birds in both silvopasture and open pasture systems had excellent leg health. Silvopasture birds had lower footpad dermatitis scores than open pasture birds. Silvopasture birds tended to have worse gait than open pasture birds in Exp 1, but not in Exp 2. Hock burn scores and latency-to-lie did not differ between treatments in Exp 1 or Exp 2. Raising birds in silvopasture reduced fear and improved footpad health compared to birds raised in open pastures, which indicates that silvopasture systems provide some benefits for affective state and leg health in fast-growing broilers.

BackgroundHIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya.MethodsWe conducted a nested study of 62 HIV-uninfected and 64 healthy women living with HIV, as well as their HIV-exposed uninfected (N = 61) and HIV-unexposed (N = 64) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between May 1, 2020-February 1, 2022 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on available stool samples from seropositive participants.ResultsSARS-CoV-2 seropositivity was found in 66% of the 126 mothers and in 44% of the 125 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR] = 0.810, 95% CI: 0.517-1.27) or infant HIV exposure (HR = 1.47, 95% CI: 0.859-2.53). Maternal SARS-CoV-2 was associated with a two-fold increased risk of infant infection (HR = 2.31, 95% CI: 1.08-4.94). Few participants (13% mothers, 33% infants) had symptoms; no participant experienced severe COVID-19 or death. Seroreversion occurred in about half of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants.ConclusionsThese data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection and that antibody responses waned over an average of 8-10 months. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.

Objective: To compare the relative value of 3 analgesic pathways for total knee arthroplasty (TKA). Patients and Methods: Time-driven activity-based costing analyses were performed on 3 common analgesic pathways for patients undergoing TKA: periarticular infiltration (PAI) only, PAI and single-injection adductor canal blockade (SACB), and PAI and continuous adductor canal blockade (CACB). Additionally, adult patients who underwent elective primary TKA from November 1, 2017, to May 1, 2018, were retrospectively identified to analyze analgesic (pain score, opiate use) and hospital outcomes (distance walked, length of stay) after TKA based on analgesic pathway. Results: There was no difference in patient demographic characteristics, specifically complexity (American Society of Anesthesiologists score) or preoperative opiate use, between groups. Compared with PAI, total cost (labor and material) was 1.4-times greater for PAI plus SACB and 2.3-times greater for PAI plus CACB. The addition of SACB to PAI resulted in lower average and maximum pain scores and opiate use on the day of operation compared with PAI alone. Average and maximum pain scores and opiate use between SACB and CACB were not significantly different. Walking distance and hospital length of stay were not significantly different between groups. Conclusion: Perioperative care teams should consider the cost and relative value of pain management when selecting the optimal analgesic strategy for TKA. Despite slightly higher relative cost, the combination of SACB with PAI may offer short-term analgesic benefit compared with PAI alone, which could enhance its relative value in TKA.

Abstract Washed textiles can remain malodorous and dingy due to the recalcitrance of soils. Recent work has found that ‘invisible’ soils such as microbial extracellular DNA (eDNA) play a key role in the adhesion of extracellular polymeric substances that form matrixes contributing to these undesirable characteristics. Here we report the application of an immunostaining method to illustrate the cleaning mechanism of a nuclease (DNase I) acting upon eDNA. Extending previous work that established a key role for eDNA in anchoring these soil matrixes, this work provides new insights into the presence and effective removal of eDNA deposited on fabrics using high-resolution in-situ imaging. Using a monoclonal antibody specific to Z-DNA, we showed that when fabrics are washed with DNase I, the incidence of microbial eDNA is reduced. As well as a quantitative reduction in microbial eDNA, the deep cleaning benefits of this enzyme are shown using confocal microscopy and imaging analysis of T-shirt fibers. To the best of our knowledge, this is the first time the use of a molecular probe has been leveraged for fabric and homecare-related R&D to visualize eDNA and evaluate its removal from textiles by a new-to-laundry DNase enzyme. The approaches described in the current work also have scope for re-application to identify further cleaning technology.

Summary: The development of therapeutics to prevent or treat COVID-19 remains an area of intense focus. Protein biologics, including monoclonal antibodies and nanobodies that neutralize virus, have potential for the treatment of active disease. Here, we have used yeast display of a synthetic nanobody library to isolate nanobodies that bind the receptor-binding domain (RBD) of SARS-CoV-2 and neutralize the virus. We show that combining two clones with distinct binding epitopes within the RBD into a single protein construct to generate biparatopic reagents dramatically enhances their neutralizing capacity. Furthermore, the biparatopic nanobodies exhibit enhanced control over clinically relevant RBD variants that escaped recognition by the individual nanobodies. Structural analysis of biparatopic binding to spike (S) protein revealed a unique binding mode whereby the two nanobody paratopes bridge RBDs encoded by distinct S trimers. Accordingly, biparatopic nanobodies offer a way to rapidly generate powerful viral neutralizers with enhanced ability to control viral escape mutants.

Abstract Neuroinflammation, particularly in the dorsolateral prefrontal cortex, is well-established in a subset of people with schizophrenia, with significant increases in inflammatory markers including several cytokines. Yet the cause(s) of cortical inflammation in schizophrenia remains unknown. Clues as to potential microenvironmental triggers and/or intracellular deficits in immunoregulation may be gleaned from looking further upstream of effector immune molecules to transcription factors that control inflammatory gene expression. Here, we focus on the ‘master immune regulator’ nuclear factor kappa B (NF-κB) and review evidence in support of NF-κB dysregulation causing or contributing to neuroinflammation in patients. We discuss the utility of ‘immune biotyping’ as a tool to analyse immune-related transcripts and proteins in patient tissue, and the insights into cortical NF-κB in schizophrenia revealed by immune biotyping compared to studies treating patients as a single, homogenous group. Though the ubiquitous nature of NF-κB presents several hurdles for drug development, targeting this key immunoregulator with novel or repurposed therapeutics in schizophrenia is a relatively underexplored area that could aid in reducing symptoms of patients with active neuroinflammation.

Abstract In this paper, we study the fragmentation of a heavy quark into a jet near threshold, meaning that final state jet carries most of the energy of the fragmenting heavy quark. Using the heavy quark fragmentation function, we simultaneously resum large logarithms of the jet radius R and 1 − z, where z is the ratio of the jet energy to the initiating heavy quark energy. There are numerically significant corrections to the leading order rate due to this resummation. We also investigate the heavy quark fragmentation to a groomed jet, using the soft drop grooming algorithm as an example. In order to do so, we introduce a collinear-ultrasoft mode sensitive to the grooming region determined by the algorithm’s z cut parameter. This allows us to resum large logarithms of z cut /(1 − z), again leading to large numerical corrections near the endpoint. A nice feature of the analysis of the heavy quark fragmenting to a groomed jet is the heavy quark mass m renders the algorithm infrared finite, allowing a perturbative calculation. We analyze this for E J R ∼ m and E J R » m, where E J is the jet energy. To do the latter case, we introduce an ultracollinear-soft mode, allowing us to resum large logarithms of E J R/m. Finally, as an application we calculate the rate for e + e − collisions to produce a heavy quark jet in the endpoint region, where we show that grooming effects have a sizable contribution near the endpoint.

Although antibody-inducing split virus vaccines (SV) are currently the most effective way to combat seasonal influenza, their efficacy can be modest, especially in immunologically-naïve individuals. We investigated immune responses towards inactivated whole influenza virus particle vaccine (WPV) formulations, predicated to be more immunogenic, in a non-human primate model, as an important step towards clinical testing in humans. Comprehensive analyses were used to capture 46 immune parameters to profile how WPV-induced responses differed to those elicited by antigenically-similar SV formulations. Naïve cynomolgus macaques vaccinated with either monovalent or quadrivalent WPV consistently induced stronger antibody responses and hemagglutination inhibition (HI) antibody titres against vaccine-matched viruses compared to SV formulations, while acute reactogenic effects were similar. Responses in WPV-primed animals were further increased by boosting with the same formulation, conversely to modest responses after priming and boosting with SV. 28-parameter multiplex bead array defined key antibody features and showed that while both WPV and SV induced elevated IgG responses against A/H1N1 nucleoprotein, only WPV increased IgG responses against A/H1N1 hemagglutinin (HA) and HA-Stem, and higher IgA responses to A/H1N1-HA after each vaccine dose. Antibodies to A/H1N1-HA and HA-Stem that could engage FcγR2a and FcγR3a were also present at higher levels after one dose of WPV compared to SV and remained elevated after the second dose. Furthermore, WPV-enhanced antibody responses were associated with higher frequencies of HA-specific B-cells and IFN-γ-producing CD4+ T-cell responses. Our data additionally demonstrate stronger boosting of HI titres by WPV following prior infection and support WPV administered as a priming dose irrespective of the follow up vaccine for the second dose. Our findings thus show that compared to SV vaccination, WPV-induced humoral responses are significantly increased in scope and magnitude, advocating WPV vaccination regimens for priming immunologically-naïve individuals and also in the event of a pandemic outbreak.

The assessment of microgaps at the implant–abutment interface is an important factor that may influence clinical success. Thus, the aim of this study was to evaluate the size of microgaps between prefabricated and customised abutments (Astra Tech, Dentsply, York, PA, USA; Apollo Implants Components, Pabianice, Poland) mounted on a standard implant. The measurement of the microgap was performed using micro-computed tomography (MCT). Due to 15-degree rotation of samples, 24 microsections were obtained. Scans were performed at four levels established at the interface between the abutment and the implant neck. Moreover, the volume of the microgap was evaluated. The size of the microgap at all measured levels varied from 0.1 to 3.7 µm for Astra and from 0.1 to 4.9 µm for Apollo (p > 0.05). Moreover, 90% of the Astra specimens and 70% of the Apollo specimens did not exhibit any microgaps. The highest mean values of microgap size for both groups were detected at the lowest portion of the abutment (p > 0.05). Additionally, the average microgap volume was greater for Apollo than for Astra (p > 0.05). It can be concluded that most samples did not exhibit any microgaps. Furthermore, the linear and volumetric dimensions of microgaps observed at the interface between Apollo or Astra abutments and Astra implants were comparable. Additionally, all tested components presented microgaps (if any) that were clinically acceptable. However, the microgap size of the Apollo abutment was higher and more variable than that of the Astra one.

Background: Late relapse (LR) of nonseminomatous germ cell tumour (NSGCT) is uncommon, with limited data published. LR is defined as relapse occurring after a disease-free interval of 2 yr. Objective: To review features of NSGCT LR in a UK tertiary centre. Design, setting, and participants: A total of 3064 patients were referred from January 2005 to December 2017. We identified patients who experienced LR after initial pathology demonstrated NSGCT and reviewed data for their original and LR presentation and management. Outcome measurements and statistical analysis: Outcomes included time to LR measured from the date of diagnosis, and overall survival. This was assessed using Cox proportional Hazards modelling, with stratification or adjustment for potential confounders. Results and limitations: We identified 101 patients with LR; the median time to LR was 96 mo. Forty-three patients (42.6%) experienced relapse after 10 yr. Univariable log-rank testing revealed that the median time to LR was significantly shorter for patients who had not received induction chemotherapy (iCTx; 54 mo, 95% confidence interval [CI] 48–108) than for those who did (112 mo, 95% CI 84–186; p = 0.04). Patients who had received iCTx were less likely to have elevated tumour markers (36% vs 46%) and more likely to undergo initial surgical resection at LR compared to CTx-naïve patients. Postpubertal teratoma (PPT), yolk sac, and dedifferentiated elements predominated for patients with iCTx exposure, whereas active GCT or fibrosis predominated in postchemotherapy resections for CTx-naïve patients at LR. Forty-one men underwent postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) as part of their initial treatment for metastatic disease. Of these, 20 experienced LR in the retroperitoneum, with 18 undergoing repeat RPLND as part of their LR management. Fifteen of the repeat RPLND histopathology specimens had a PPT component. There have been 23 deaths overall; survival was worse for patients presenting with symptoms (13/36, 33%) and those receiving CTx and no surgery (10/17, 59%) at LR. Conclusions: When LR of NSGCT occurs, it is frequently after an extended interval and is later among patients with prior iCTx, with PPT predominating. The high frequency of LR within the retroperitoneum following PC-RPLND reinforces the need for good-quality PC-RPLND. Patient summary: We reviewed data for patients who had a late relapse of testicular cancer. We found that patients who did not receive chemotherapy as the first treatment for their initial diagnosis had a shorter time to relapse. Our results highlight the importance of long-term follow-up for testicular cancer.

Abstract Background To identify the association between inpatient postpartum opioid consumption, race, and amount of opioids prescribed at discharge after vaginal or cesarean delivery. Methods A total of 416 women who were prescribed an oral opioid following vaginal or cesarean delivery at a single tertiary academic institution between July 2018 and October 2018 were identified. Women with postoperative wound complications, third and fourth degree lacerations, cesarean hysterectomy, or a history of opioid abuse were excluded. The primary outcome was the number of oxycodone 5 mg tablets prescribed at discharge, stratified by race and mode of delivery. Only “Black” and “White” women were included in analyses due to low absolute numbers of other identities. Black women were compared to white women using multivariable logistic regression. Multiple sensitivity analyses were performed. Results The median number of oxycodone tablets consumed during hospitalization following cesarean delivery was seven (IQR: 2.5–12 tablets) and following vaginal delivery was one (IQR: 0–3). White women were more likely to be older at delivery regardless of route (median 32 vs. 30 years for cesarean delivery, and 29 vs. 27 years for vaginal delivery; p

Abstract Changes in brain resting-state functional connectivity (rsFC) were investigated using a longitudinal design by following a 2-month focused attention meditation (FAM) practice and analyzing their association with FAM practice time. Ten novice meditators were recruited from a university meditation course. Participants were scanned with a resting-state fMRI sequence with multi-echo EPI acquisition at baseline and at the 2-month follow-up. Total FAM practice time was calculated from the daily log of the participants. We observed significantly increased rsFC between the posterior cingulate cortex (PCC) and dorsal attention network (DAN), the right middle temporal (RMT) region and default mode network (DMN), the left and right superior parietal lobules (LSPL/RSPL) and DMN, and the LSPL/RSPL and DAN. Furthermore, the rsFC between the LSPL and medial prefrontal cortex was significantly associated with the FAM practice time. These results demonstrate increased connectivity within the DAN, between the DMN and DAN, and between the DMN and visual cortex. These findings demonstrate that FAM can enhance the brain connection among and within brain networks, especially DMN and DAN, indicating potential effect of FAM on fast switching between mind wandering and focused attention and maintaining attention once in the attentive state.

The immunological parameters that define severe influenza disease are not clear within human real time infections. Here the authors compare a severe influenza infection cohort with an influenza vaccinated cohort to understand correlates of severe influenza disease.

Joining a function-enhanced Fc-portion of human IgG to the SARS-CoV-2 entry receptor ACE2 produces an antiviral decoy with strain transcending virus neutralizing activity. SARS-CoV-2 neutralization and Fc-effector functions of ACE2-Fc decoy proteins, formatted with or without the ACE2 collectrin domain, were optimized by Fc-modification. The different Fc-modifications resulted in distinct effects on neutralization and effector functions. H429Y, a point mutation outside the binding sites for FcγRs or complement caused non-covalent oligomerization of the ACE2-Fc decoy proteins, abrogated FcγR interaction and enhanced SARS-CoV-2 neutralization. Another Fc mutation, H429F did not improve virus neutralization but resulted in increased C5b-C9 fixation and transformed ACE2-Fc to a potent mediator of complement-dependent cytotoxicity (CDC) against SARS-CoV-2 spike (S) expressing cells. Furthermore, modification of the Fc-glycan enhanced cell activation via FcγRIIIa. These different immune profiles demonstrate the capacity of Fc-based agents to be engineered to optimize different mechanisms of protection for SARS-CoV-2 and potentially other viral pathogens.

Plasma samples taken at different time points from donors who received either AstraZeneca (Vaxzevria) or Pfizer (Comirnaty) or Moderna (Spikevax) coronavirus disease-19 (COVID-19) vaccine were assessed in virus neutralization assays against Delta and Omicron variants of concern and a reference isolate (VIC31). With the Pfizer vaccine there was 6-8-fold reduction in 50% neutralizing antibody titres (NT50) against Delta and VIC31 at 6 months compared to 2 weeks after the second dose; followed by 25-fold increase at 2 weeks after the third dose. Neutralisation of Omicron was only consistently observed 2 weeks after the third dose, with most samples having titres below the limit of detection at earlier timepoints. Moderna results were similar to Pfizer at 2 weeks after the second dose, while the titres for AstraZeneca samples derived from older donors were 7-fold lower against VIC31 and below the limit of detection against Delta and Omicron. Age and gender were not found to significantly impact our results. These findings indicate that vaccine matching may be needed, and that at least a third dose of these vaccines is necessary to generate sufficient neutralising antibodies against emerging variants of concern, especially Omicron, amidst the challenges of ensuring vaccine equity worldwide.

Disruption of circadian rhythms occurs in rotating shift-work, jetlag, and in individuals with irregular sleep schedules. Circadian disruption is known to alter inflammatory responses and impair immune function. However, there is limited understanding of how circadian disruption modulates cancer-induced inflammation. Inflammation is a hallmark of cancer and is linked to worse prognosis and impaired brain function in cancer patients. Here, we investigated the effect of circadian disruption on cancer-induced inflammation in an orthotopic breast cancer model. Using a validated chronic jetlag protocol that advances the light-cycle by 8 ​h every 2 days to disrupt circadian rhythms, we found that circadian disruption alters cancer-induced inflammation in a tissue-specific manner, increasing inflammation in the body and brain while decreasing inflammation within the tumor tissue. Circadian disruption did not affect inflammation in mice without tumors, suggesting that the impact of circadian disruption may be particularly detrimental in the context of underlying inflammatory conditions, such as cancer. Importantly, circadian disruption did not affect tumor burden, suggesting that increased inflammation was not a result of increased cancer progression. Overall, these findings identify the importance of healthy circadian rhythms for limiting cancer-induced inflammation.

Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

Current vaccine strategies for SARS-CoV-2 focus on eliciting neutralising antibodies to the spike protein (S), but differences in immunogenicity of full-length S versus receptor binding domain (RBD) only aren’t fully understood. Here, the authors show immunogenicity of different prime-boost strategies with S and/or RBD in mice and macaques.

Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course of ~5 months, showing that although neutralizing antibody responses drop off after ~4 months, B cell immune responses strengthen.

The vertical propagation of wave energy into a planet’s exosphere, a process that affects atmospheric evolution, is calculated here using 1D molecular kinetic simulations. Effects sensitive to molecular interactions are examined by comparing simulation results to solutions of linear fluid models for steady wave activity using parameters associated with Mars’ upper atmosphere. In addition to correctly describing the wave behavior in the exobase region, these simulations directly yield nonlinear effects such as atmospheric heating. They also readily include the transient behavior due to the onset and decay of waves propagating into the rarefied region of a planet’s atmosphere. This is a first step in understanding the effects of variable wave activity in the region where the atmosphere evolves from collisional to collisionless.

Abstract The ferret is a key animal model for investigating the pathogenicity and transmissibility of important human viruses, and for the pre‐clinical assessment of vaccines. However, relatively little is known about the ferret immune system, due in part to a paucity of ferret‐reactive reagents. In particular, T follicular helper (Tfh) cells are critical in the generation of effective humoral responses in humans, mice and other animal models but to date it has not been possible to identify Tfh in ferrets. Here, we describe the screening and development of ferret-reactive BCL6, CXCR5 and PD-1 monoclonal antibodies. We found two commercial anti-BCL6 antibodies (clone K112-91 and clone IG191E/A8) had cross-reactivity with lymph node cells from influenza-infected ferrets. We next developed two murine monoclonal antibodies against ferret CXCR5 (clone feX5-C05) and PD-1 (clone fePD-CL1) using a single B cell PCR-based method. We were able to clearly identify Tfh cells in lymph nodes from influenza infected ferrets using these antibodies. The development of ferret Tfh marker antibodies and the identification of ferret Tfh cells will assist the evaluation of vaccine-induced Tfh responses in the ferret model and the design of novel vaccines against the infection of influenza and other viruses, including SARS-CoV2.

ABSTRACT Shared bacteria between maternal breast milk and infant stool, infers that transfer of maternal breast milk microbiota through breastfeeding seeds the establishment of the infant gut microbiome. Whether combination antiretroviral therapy (cART) impacts the breast milk microbiota in women living with HIV is unknown. Since current standard of care for people living with HIV includes cART, it has been difficult to evaluate the impact of cART on the microbiome. Here, we performed a next-generation sequencing retrospective study from pre-ART era clinical trials in Nairobi, Kenya (between 2003–2006 before cART was standard of care) that tested the effects of ART regimens to prevent mother-to-child HIV transmission. Kenyan women living with HIV were randomized to receive either no ART during breastfeeding (n = 24) or cART (zidovudine, nevirapine, lamivudine; n = 25) postpartum. Using linear mixed-effects models, we found that alpha diversity and beta diversity of the breast milk bacterial microbiome changed significantly over time during the first 4 weeks postpartum (alpha diversity P

We discuss the phenomenology of no-scale supergravity (SUGRA), in which the universal scalar mass is zero at the high scale, focussing on the recently updated muon g-2 measurement, and including dark matter and the correct Higgs boson mass. Such no-scale supergravity scenarios arise naturally from string theory and are also inspired by the successful Starobinsky inflation, with a class of minimal models leading to a strict upper bound on the gravitino mass m3/2