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Background BCMA-directed CAR T-cell therapy (CAR-T) has altered the treatment landscape of relapsed/refractory (r/r) multiple myeloma, but is hampered by unique side effects that can lengthen hospital stays and increase morbidity. Hematological toxicity (e.g. profound and prolonged cytopenias) represents the most common grade ≥ 3 toxicity and can predispose for severe infectious complications. Here, we examined the utility of the CAR-HEMATOTOX (HT) score to predict toxicity and survival outcomes in patients receiving standard-of-care idecabtagene vicleucel and ciltacabtagene autoleucel. Methods Data were retrospectively collected from 113 r/r multiple myeloma patients treated between April 2021 and July 2022 across six international CAR-T centers. The HT score—composed of factors related to hematopoietic reserve and baseline inflammatory state—was determined prior to lymphodepleting chemotherapy. Results At lymphodepletion, 63 patients were HT low (score 0–1) and 50 patients were HT high (score ≥ 2). Compared to their HT low counterparts, HT high patients displayed prolonged severe neutropenia (median 9 vs. 3 days, p < 0.001), an increased severe infection rate (40% vs. 5%, p < 0.001), and more severe ICANS (grade ≥ 3: 16% vs. 0%, p < 0.001). One-year non-relapse mortality was higher in the HT high group (13% vs. 2%, p = 0.019) and was predominantly attributable to fatal infections. Response rates according to IMWG criteria were higher in HT low patients (≥ VGPR: 70% vs. 44%, p = 0.01). Conversely, HT high patients exhibited inferior progression-free (median 5 vs. 15 months, p < 0.001) and overall survival (median 10.5 months vs. not reached, p < 0.001). Conclusions These data highlight the prognostic utility of the CAR-HEMATOTOX score for both toxicity and treatment response in multiple myeloma patients receiving BCMA-directed CAR-T. The score may guide toxicity management (e.g. anti-infective prophylaxis, early G-CSF, stem cell boost) and help to identify suitable CAR-T candidates.

This cohort study analyzed persistent symptoms among adults with coronavirus disease 2019 up to 9 months after illness onset.

Many SARS-CoV-2 variants have mutations at key sites targeted by antibodies. However, it is unknown if antibodies elicited by infection with these variants target the same or different regions of the viral spike as antibodies elicited by earlier viral isolates. Here we compare the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y.V2), which contains mutations in multiple key spike epitopes. The serum neutralizing activity of antibodies elicited by infection with both early 2020 viruses and B.1.351 is heavily focused on the spike receptor-binding domain (RBD). However, within the RBD, B.1.351-elicited antibodies are more focused on the “class 3” epitope spanning sites 443 to 452, and neutralization by these antibodies is notably less affected by mutations at residue 484. Our results show that SARS-CoV-2 variants can elicit polyclonal antibodies with different immunodominance hierarchies.

Exposure histories to SARS-CoV-2 variants and vaccinations will shape the specificity of antibody responses. To understand the specificity of Delta-elicited antibody immunity, we characterize the polyclonal antibody response elicited by primary or mRNA vaccine-breakthrough Delta infections. Both types of infection elicit a neutralizing antibody response focused heavily on the receptor-binding domain (RBD). We use deep mutational scanning to show that mutations to the RBD’s class 1 and class 2 epitopes, including sites 417, 478, and 484–486 often reduce binding of these Delta-elicited antibodies. The anti-Delta antibody response is more similar to that elicited by early 2020 viruses than the Beta variant, with mutations to the class 1 and 2, but not class 3 epitopes, having the largest effects on polyclonal antibody binding. In addition, mutations to the class 1 epitope (e.g., K417N) tend to have larger effects on antibody binding and neutralization in the Delta spike than in the D614G spike, both for vaccine- and Delta-infection-elicited antibodies. These results help elucidate how the antigenic impacts of SARS-CoV-2 mutations depend on exposure history.

BackgroundGastrointestinal (GI) symptoms are recognized sequelae of acute respiratory illness (ARI), but their prevalence is not well documented. Our study aim was to assess the incidence of GI symptoms in community ARI cases for persons of all ages and their association with clinical outcomes.MethodsWe collected mid-nasal swabs, clinical, and symptom data from Seattle-area individuals during the 2018–2019 winter season as part of a large-scale prospective community surveillance study. Swabs were tested by polymerase chain reaction (PCR) for 26 respiratory pathogens. Likelihood of GI symptoms given demographic, clinical, and microbiological covariates were analyzed with Fisher’s exact, Wilcoxon-rank-sum, and t-tests and multivariable logistic regression.ResultsIn 3183 ARI episodes, 29.4% had GI symptoms (n = 937). GI symptoms were significantly associated with pathogen detection, illness interfering with daily life, seeking care for the illness, and greater symptom burden (all p < 0.05). Controlling for age, > 3 symptoms, and month, influenza (p < 0.001), human metapneumovirus (p = 0.004), and enterovirus D68 (p = 0.05) were significantly more likely to be associated with GI symptoms than episodes with no pathogen detected. Seasonal coronaviruses (p = 0.005) and rhinovirus (p = 0.04) were significantly less likely to be associated with GI symptoms.ConclusionIn this community-surveillance study of ARI, GI symptoms were common and associated with illness severity and respiratory pathogen detection. GI symptoms did not track with known GI tropism, suggesting GI symptoms may be nonspecific rather than pathogen-mediated. Patients presenting with GI and respiratory symptoms should have respiratory virus testing, even if the respiratory symptom is not the primary concern.

Background: Indoor air pollutants (IAPs) cause multiple health impacts. Prioritizing mitigation options that differentially affect individual pollutants and comparing IAPs with other environmental health hazards require a common metric of harm. Objectives: Our objective was to demonstrate a methodology to quantify and compare health impacts from IAPs. The methodology is needed to assess population health impacts of large-scale initiatives— including energy efficiency upgrades and ventilation standards— that affect indoor air quality (IAQ). Methods: Available disease incidence and disease impact models for specific pollutant-disease combinations were synthesized with data on measured concentrations to estimate the chronic heath impact, in disability-adjusted life-years (DALYs) lost, due to inhalation of a subset of IAPs in U.S. residences. Model results were compared with independent estimates of DALYs lost due to disease. Results: Particulate matter ≤ 2.5 μM in aerodynamic diameter (PM2.5), acrolein, and formaldehyde accounted for the vast majority of DALY losses caused by IAPs considered in this analysis, with impacts on par or greater than estimates for secondhand tobacco smoke and radon. Confidence intervals of DALYs lost derived from epidemiology-based response functions are tighter than those derived from toxicology-based, interspecies extrapolations. Statistics on disease incidence in the United States indicate that the upper-bound confidence interval for aggregate LAP harm is implausibly high. Conclusions: The approach demonstrated in this study may be used to assess regional and national initiatives that affect IAQ at the population level. Cumulative health impacts from inhalation in U.S. residences of the IAPs assessed in this study are estimated at 400-1,100 DALYs lost annually per 100,000 persons.

Online behavioral weight management programs offer a scalable solution to address overweight and obesity but often face high dropout rates and variable success. Understanding the barriers and facilitators experienced by participants who achieve weight loss targets versus those who do not is critical for optimizing programs. This study compared the barriers and facilitators reported by participants achieving ≥5% weight loss with those achieving <5%, using a social–ecological framework to capture influences across individual, interpersonal, and environmental levels. The framework was chosen to reflect the complex, interacting factors beyond the individual that shape behavior. Forty-eight participants completed semi-structured telephone interviews exploring factors affecting their weight loss journey. Interviews were analyzed using a thematic framework approach. Across both groups, key facilitators included willpower, knowledge, social support, and perceived safety in the local environment, with their absence acting as barriers. Food availability at home and in the workplace was also reported as a barrier due to temptation. Social roles could challenge behavior change, though perceiving themselves as role models provided motivation. Program-specific factors, such as group dynamics and difficulty using the platform, were barriers for both groups. Notable differences emerged between groups in responding to challenges. The ≥ 5% weight loss group proactively addressed stressors and sought solutions, while the < 5% weight loss group reported greater difficulty overcoming barriers, more interpersonal stressors, and dissatisfaction with their weight targets. This is the first study to compare qualitative experiences across social–ecological domains between participants achieving ≥5% and <5% weight loss during program participation. Findings highlight the need to address environmental infrastructure, interpersonal skills, and communication of weight targets to improve program effectiveness. Future research should examine how these factors can identify individuals at risk of not achieving 5% weight loss and inform tailored interventions.

Residential natural gas cooking burners (NGCBs) can emit substantial quantities of pollutants, and they are typically used without venting range hoods. We quantified pollutant concentrations and occupant exposures resulting from NGCB use in California homes. A mass-balance model was applied to estimate time-dependent pollutant concentrations throughout homes in Southern California and the exposure concentrations experienced by individual occupants. We estimated nitrogen dioxide (NO2), carbon monoxide (CO), and formaldehyde (HCHO) concentrations for 1 week each in summer and winter for a representative sample of Southern California homes. The model simulated pollutant emissions from NGCBs as well as NO2 and CO entry from outdoors, dilution throughout the home, and removal by ventilation and deposition. Residence characteristics and outdoor concentrations of NO2 and CO were obtained from available databases. We inferred ventilation rates, occupancy patterns, and burner use from household characteristics. We also explored proximity to the burner(s) and the benefits of using venting range hoods. Replicate model executions using independently generated sets of stochastic variable values yielded estimated pollutant concentration distributions with geometric means varying by <10%. The simulation model estimated that-in homes using NGCBs without coincident use of venting range hoods-62%, 9%, and 53% of occupants are routinely exposed to NO2, CO, and HCHO levels that exceed acute health-based standards and guidelines. NGCB use increased the sample median of the highest simulated 1-hr indoor concentrations by 100, 3,000, and 20 ppb for NO2, CO, and HCHO, respectively. Reducing pollutant exposures from NGCBs should be a public health priority. Simulation results suggest that regular use of even moderately effective venting range hoods would dramatically reduce the percentage of homes in which concentrations exceed health-based standards.

Europe imports large amounts of soybean that are predominantly used for livestock feed, mainly sourced from Brazil, USA and Argentina. In addition, the demand for GM-free soybean for human consumption is project to increase. Soybean has higher protein quality and digestibility than other legumes, along with high concentrations of isoflavones, phytosterols and minerals that enhance the nutritional value as a human food ingredient. Here, we examine the potential to increase soybean production across Europe for livestock feed and direct human consumption, and review possible effects on the environment and human health. Simulations and field data indicate rainfed soybean yields of 3.1 ± 1.2 t ha −1 from southern UK through to southern Europe (compared to a 3.5 t ha −1 average from North America). Drought-prone southern regions and cooler northern regions require breeding to incorporate stress-tolerance traits. Literature synthesized in this work evidenced soybean properties important to human nutrition, health, and traits related to food processing compared to alternative protein sources. While acknowledging the uncertainties inherent in any modelling exercise, our findings suggest that further integrating soybean into European agriculture could reduce GHG emissions by 37–291 Mt CO 2e year −1 and fertiliser N use by 0.6–1.2 Mt year −1 , concurrently improving human health and nutrition.

Macaques are a commonly used model for studying immunity to human viruses, including for studies of SARS-CoV-2 infection and vaccination. However, it is unknown whether macaque antibody responses resemble the response in humans. To answer this question, we employed a phage-based deep mutational scanning approach (Phage-DMS) to compare which linear epitopes are targeted on the SARS-CoV-2 Spike protein in convalescent humans, convalescent (re-infected) rhesus macaques, mRNA-vaccinated humans, and repRNA-vaccinated pigtail macaques. We also used Phage-DMS to determine antibody escape pathways within each epitope, enabling a granular comparison of antibody binding specificities at the locus level. Overall, we identified some common epitope targets in both macaques and humans, including in the fusion peptide (FP) and stem helix-heptad repeat 2 (SH-H) regions. Differences between groups included a response to epitopes in the N-terminal domain (NTD) and C-terminal domain (CTD) in vaccinated humans but not vaccinated macaques, as well as recognition of a CTD epitope and epitopes flanking the FP in convalescent macaques but not convalescent humans. There was also considerable variability in the escape pathways among individuals within each group. Sera from convalescent macaques showed the least variability in escape overall and converged on a common response with vaccinated humans in the SH-H epitope region, suggesting highly similar antibodies were elicited. Collectively, these findings suggest that the antibody response to SARS-CoV-2 in macaques shares many features with humans, but with substantial differences in the recognition of certain epitopes and considerable individual variability in antibody escape profiles, suggesting a diverse repertoire of antibodies that can respond to major epitopes in both humans and macaques. Differences in macaque species and exposure type may also contribute to these findings.