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Conventional methods for intraoperative histopathologic diagnosis are labour- and time-intensive, and may delay decision-making during brain-tumour surgery. Stimulated Raman scattering (SRS) microscopy, a label-free optical process, has been shown to rapidly detect brain-tumour infiltration in fresh, unprocessed human tissues. Here, we demonstrate the first application of SRS microscopy in the operating room using a portable fibre-laser-based microscope and unprocessed specimens from 101 neurosurgical patients. We also introduce an image-processing method—stimulated Raman histology (SRH)—that leverages SRS images to create virtual haematoxylin-and-eosin-stained slides, revealing essential diagnostic features. In a simulation of intraoperative pathologic consultation in 30 patients, we found a remarkable concordance of SRH and conventional histology for predicting diagnosis (Cohen’s kappa, κ  > 0.89), with accuracy exceeding 92%. We also built and validated a multilayer perceptron based on quantified SRH image attributes that predicts brain-tumour subtype with 90% accuracy. Our findings provide insight into how SRH can now be used to improve the surgical care of brain-tumour patients. By taking advantage of stimulated Raman spectroscopy and fibre-laser technology, virtual histology images can be obtained in real time in the operating room, with diagnostic quality comparable with that achieved via conventional histopathology.

Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis. The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.

Background and AimsThe presentation of virus derived peptides on HLA class I molecules is crucial for mounting antiviral immune responses. TAPBPR is a recently identified peptide editor involved in optimizing antigen selection on MHC class I molecules. Here, we present novel data on the impact of TAPBPR on the hepatitis B (HBV) immunopeptidome presented on HLA class I by using a mass spectrometry approach.MethodHeLa cells (HLA-A*68:02, -B*15:03 and -Cw12) and TAPBPR knock-out HeLa cells (TAPBPRKO) overexpressing individual HBV proteins HBsAg, Pol, HBcAg and HBx were generated. These cells were expanded to 5x108 cells, lysed and peptides were eluted using a pan HLA class I antibody (W6/32). Analysis was performed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Mass spectra data were then searched against a database of possible peptides that could be derived from the host and/or pathogen proteomes, to identify HBV derived peptides presented on HLA class I. The HBV immunopeptidome in TAPBPRKO cells was compared to HeLa cells expressing wild type TAPBPR and individual HBV proteins.ResultsA greater number of HBV peptides were presented in TAPBPRKO cell lines compared to wild type cell lines, which was consistently observed between cells expressing different HBV proteins. This was despite the fact that no substantial change in the total cellular peptide count was observed between wild type and TAPBPRKO cells. Amino acids positions 2 and 9 were clearly preferred for binding in both wild type and TAPBPRKO cells, and a greater number of peptides were assigned to HLA-B*15:03 than HLA-A*68:02. Furthermore, semi quantitative analysis revealed that depletion of TAPBPR resulted in up-modulation of almost all HBV-derived peptides identified. In addition, changes in the hierarchy of the abundance of HBV peptides presented were observed in TAPBPRKO cells. Of the up-modulated peptides, only four have been identified previously and are catalogued on IEDB. A total of 26 HBV-derived peptides were identified, 22 (84.62%) of which were novel. Of the novel peptides 7 were only identified in the TAPBPRKO cell lines. ConclusionThese findings strongly support a role of TAPBPR in HBV-derived peptide selection for presentation on HLA class I. However, it is still unclear whether this is advantageous for individuals with HBV expressing HLA alleles where TAPBPR mediates peptide exchange.

Purpose: To estimate the risk of hospital-acquired COVID-19 transmission in a population of orthopaedic trauma patients during the first wave of the pandemic. Patients and Methods: This is a retrospective cohort study of 109 patients who underwent an emergent orthopedic procedure by a single orthopedic traumatologist between March 1, 2020 and May 15, 2020 during the first peak of the pandemic. After applying inclusion and exclusion criteria, a total of 82 patients (67 inpatients and 15 ambulatory) were identified for final analysis. The primary outcome measured was postoperative Coronavirus (COVID-19) status. Secondary outcome measures included length of stay and discharge disposition. Results: The mean age and length of stay in the hospital group was 59.5 years ([+ or -] 21.7) and 4.3 days ([+ or -] 4.6), respectively, versus 47.9 years ([+ or -] 9.8) in the ambulatory group. 7.3% (6/82) of the inpatients subsequently tested or screened positive for COVID-19 at 2 weeks post-operatively, compared to 0/15 ambulatory patients (P=0.58). Of the 6 inpatients who tested positive, 4 (66.7%) were discharged to a rehabilitation center. Diabetes (P=0.05), hypertension (P=0.02), and congestive heart failure (P=0.005) were associated with transmission. Conclusion: In this analysis, there was a nosocomial transmission rate of 7% compared to zero in the ambulatory surgery center, however this was not found to be statistically significant. This data supports the use of precautions such as frequent screening, hand washing, and masks to reduce transmission when COVID-19 rates are high. There is a lower risk of nosocomial COVID-19 transmission for patients treated as an outpatient and elective surgical procedures may be safer in this setting. Keywords: coronavirus, pandemic, infection, hospital transmission

Disaster telehealth can be used to provide rapid access to remote specialty expertise and virtual surge capacity for overwhelmed local clinicians. The Regional Disaster Health Response System (RDHRS) is developing a disaster teleconsultation system for cross-jurisdictional care in the United States. In 2020, the Region 1 RDHRS provided Massachusetts hospitals access to disaster teleconsultation services with out-of-state critical care experts during the first wave of the COVID-19 pandemic response. We aimed to field-test (1) the acceptability and feasibility of using a prototype, web-based disaster teleconsultation platform with minimal-to-no user training and (2) the feasibility of deploying a national volunteer expert pool to access out-of-state expertise. This was a prospective, mixed methods, observational study. We recruited field clinicians from Massachusetts hospitals and out-of-state critical-care physicians as experts for a 2-week pilot (June 2020). Experts were trained to use a prototype platform, while field clinicians received a just-in-time tool. Field clinicians requested teleconsultations for hospitalized patients with COVID-19 (clinical call) or simulated patients (test call). We collected demographics, call performance data, and Telehealth Usability Questionnaire (TUQ) ratings to measure acceptability (primary outcome; total usability score ≥6 of 7) and feasibility (secondary outcome; interface, interaction quality, and reliability items), and interviewed participants. We report descriptive statistics and key themes using the Technology Acceptance Model framework. Ten experts from 6 states and 17 field clinicians from 4 hospitals participated. All experts and 10 field clinicians completed postpilot questionnaires (74% response overall). Of these, 20% had previously used telemedicine in a disaster. In total, 50 test calls and no clinical calls were logged. Most (70%) made ≥1 call; 22% (95% CI 10%-34%) connected successfully. The median time to connect was 1.6 (IQR 3.2) minutes. Among field clinician respondents, 50% used smartphone devices, 40% hospital desktop computers, and 10% laptop computers to access RDHRS teleconsultation services. Calls failed due to platform routing errors (49%), hospital computers without cameras or microphones (10%), firewalls (8%), and expert notification failures (5%). The mean total usability score was 5.6 (SD 1.3). TUQ item scores were highest in usefulness (mean 6.0, SD 1.1) and ease-of-use (mean 6.0, SD 1.4), and lowest in reliability (mean 2.4, SD 1.4). Participants were comfortable using the platform. Those with difficulty identified discomfort with technology as the cause. All experts were willing to participate in a national expert registry and obtain emergency licensure, and most (80%) were willing to serve on a volunteer, unpaid basis. Clinicians found the prototype platform acceptable, but the workflow requires revision to reduce call failure and improve feasibility and reliability for future use with minimal-to-no training. Using familiar clinical workflows for emergency consultation and mobile devices with camera and microphone capabilities could improve call performance and reliability.

BackgroundEmerging studies suggest that endocrine disrupting chemicals (EDCs) in personal care and other consumer products are linked with various adverse health effects, including respiratory and reproductive effects. Despite Black persons using more personal care products than other demographic groups and having a high asthma burden, little is known regarding their consumer product use patterns and associated EDC exposures.ObjectiveTo examine the association between recent exposure to select EDCs with specific consumer products and behaviors in a cohort of 110 predominantly Black children with asthma, ages 8–17 years, living in Baltimore City, Maryland.MethodsWe quantified concentrations of bisphenol A (BPA), bisphenol S (BPS), bisphenol F, two dichlorophenols, four parabens, triclosan, benzophenone-3, and triclocarban in spot urine samples. Questionnaires were used to capture recent (last 24-h) consumer product use and behaviors. Associations between EDCs and consumer product uses/behaviors were assessed using multivariable linear regression, adjusting for age, gender, race/ethnicity, and caregiver income level. Effect estimates were expressed as geometric mean ratios of biomarker concentrations of product-users vs non-users.ResultsIncreased concentrations to select EDCs were associated with recent use of air freshener (ratios; BPA: 1.9, 95%CI 1.4–2; BPS 1.7, 95%CI 1–2.97; propyl paraben: 3.0, 95%CI 1.6–5.6), scented candles (methyl paraben: 2.6, 95%CI 1.1–6.1), and scented carpet powder (2,5-dichlorophenol: 2.8, 95%CI 1.2–6.3). Additionally, consuming canned food was associated with some increased biomarker concentrations (ratios: BPA: 1.7, 95%CI 1.2–2.4; BPS: 2.1, 95% CI: 1.2–3.6).SignificanceThese findings add to the body of evidence suggesting that recent use of select consumer products in Black children contributes to exposure of chemicals of concern and could potentially inform exposure mitigation interventions. Findings have broad potential health implications for pediatric populations and Black children who may face exposure and health disparities.ImpactLittle is known about how children’s personal care product use and consumer behaviors affect their exposures to endocrine disrupting chemicals (EDCs). This is particularly true for Black children who often experience a disparate exposure burden to many EDCs. This is a significant knowledge gap among children that are uniquely vulnerable to EDCs as they undergo critical windows of growth and development. Our findings show associations between consumer products and EDC exposures in predominantly Black children in low-income settings. Identifying EDC exposure determinants has broad health implications as many of these chemicals have been associated with adverse health risks.

The Acacia drepanolobium (also known as Vachellia drepanolobium) ant‐plant symbiosis is considered a classic case of species coexistence, in which four species of tree‐defending ants compete for nesting space in a single host tree species. Coexistence in this system has been explained by trade‐offs in the ability of the ant associates to compete with each other for occupied trees versus the ability to colonize unoccupied trees. We seek to understand the proximal reasons for how and why the ant species vary in competitive or colonizing abilities, which are largely unknown. In this study, we use RADseq‐derived SNPs to identify relatedness of workers in colonies to test the hypothesis that competitively dominant ants reach large colony sizes due to polygyny, that is, the presence of multiple egg‐laying queens in a single colony. We find that variation in polygyny is not associated with competitive ability; in fact, the most dominant species, unexpectedly, showed little evidence of polygyny. We also use these markers to investigate variation in mating behavior among the ant species and find that different species vary in the number of males fathering the offspring of each colony. Finally, we show that the nature of polygyny varies between the two commonly polygynous species, Crematogaster mimosae and Tetraponera penzigi: in C. mimosae, queens in the same colony are often related, while this is not the case for T. penzigi. These results shed light on factors influencing the evolution of species coexistence in an ant‐plant mutualism, as well as demonstrating the effectiveness of RADseq‐derived SNPs for parentage analysis. We used RADseq‐derived SNP markers to test whether ant associates of the Vachellia drepanolobium ant‐plant mutualism varied in their degree of polygyny and/or polyandry. We found interspecific variation in both traits among the four ant species, but no evidence to support the hypothesis that this variation permits coexistence of the four species.

ObjectiveThis study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial.Study designBayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed.ResultsPrimary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40).ConclusionsTreatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.

Anti-carbohydrate antibodies (Abs) play crucial roles in pathogen control, but their generation remains poorly understood. By studying responses to in humans, we reveal that the glycan-targeted response shifts from IgM towards IgG and IgA memory with age and antigen exposure across blood, spleen, and tonsils. Both natural colonization and controlled human infection with increased class-switched B cells, with evidence of within-clone switching. Glycan-specific B cells readily participated in germinal center (GC) responses and showed robust somatic hypermutation despite a molecular signature consistent with receiving reduced T cell help. We conclude that mucosal pathogen encounters elicit glycan responses that class-switch, evolve and diversify through the GC. These findings reveal how age and infection history can influence the quality, quantity, and isotype use of glycan-specific B cells, with implications for the design and schedule of glycan-containing vaccines.

Plasmodium falciparum malaria results in immunoregulatory responses across multiple cell subsets, which protects the individual from inflammatory mediated immunopathogenesis. However, these anti-inflammatory responses also hamper the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform the development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analysed the immune landscape with single cell RNA sequencing of peripheral blood mononuclear cells during falciparum malaria and at convalescence in children and adults from a low malaria transmission area in Malaysia. To understand malaria driven changes specific to each immune cell subset, we interrogated transcriptional changes in sub-clustered major immune cell types during infection. We found that malaria drove development of immunosuppressive monocytes, alongside NK and γδ T cells which regulated inflammatory function but maintained cytolytic capacity. IL10-producing CD4 T cells and IL10-producing regulatory B cells were also induced. Type I interferon responses were identified across all cell types, linking Type I interferon signalling with the induction of immunoregulatory networks during malaria. Together, these findings provide insights into cell-specific and shared immunoregulatory changes induced during malaria, and provides a data set resource for additional analysis of anti-parasitic immunity and disease pathogenesis.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217930* https://doi.org/10.5281/zenodo.6973241