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The efficacy of antibody responses is inherently linked to paratope diversity, as generated through V(D)J recombination and somatic hypermutation. Despite this, it is unclear how genetic diversification mechanisms evolved alongside codon optimality and affect antibody expression. Here, we analyze germline immunoglobulin (IG) genes, natural V(D)J repertoires, serum IgG, and monoclonal antibody (mAb) expression through the lens of codon optimality. Germline variable genes (IGVs) exhibit diverse optimality that is inversely related to mutability. Hypermutation deoptimizes heavy-chain (IGH) VDJ repertoires within human tonsils, bone marrow, lymph nodes (including SARS-CoV-2-specific clones), blood (HIV-1-specific clones), mice, and zebrafish. Analyses of mutation-affected codons show that targeting to complementarity-determining regions constrains deoptimization. Germline IGHV optimality correlates with serum variable fragment (VH) usage after influenza vaccination, while synonymous deoptimization attenuated mAb yield. These findings provide unanticipated insights into an antagonistic relationship between diversification mechanisms and codon optimality. Ultimately, the need for diversity takes precedence over that for the most optimal codon usage., Competing Interests: Declaration of interests A patent application was filed 11/11/2021 relating to anti-SARS-CoV-2 antibodies with P.C.W./S.C. as inventors (application number PCT/US22/79916)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Punishment serves as a balancing force that dissuades people from acting selfishly, which complements cooperation as an essential characteristic for the prosperity of human societies. Past studies using economic games with two options (cooperation and defection) reported that cooperation decisions are generally faster than defection decisions and that time pressure possibly induces human players to be more intuitive and thus cooperative. However, it is unclear where punishment decisions sit on this time spectrum. Therefore, we recruited human players and implemented two series of online network games with cooperation, defection, and punishment options. First, we find that punishment decisions are slower than cooperation or defection decisions across both game series. Second, we find that imposing experimental time pressure on in-game decisions neither reduces nor increases the frequency of punishment decisions, suggesting that time pressure may not directly interact with the mechanisms that drive players to choose to punish., (© 2024. The Author(s).)

The rapid evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identified S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) that was derived from an individual previously infected with WT SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrated broad cross-neutralization of all dominant variants, including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1/XBB). Furthermore, S728-1157 protected hamsters against in vivo challenges with WT, Delta, and BA.1 viruses. Structural analysis showed that this antibody targets a class 1/RBS-A epitope in the receptor binding domain via multiple hydrophobic and polar interactions with its heavy chain complementarity determining region 3 (CDR-H3), in addition to common motifs in CDR-H1/CDR-H2 of class 1/RBS-A antibodies. Importantly, this epitope was more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared with diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential and may inform target-driven vaccine designs against future SARS-CoV-2 variants.

Introduction: Molecular pathological epidemiology (MPE) is an integrative transdisciplinary area examining the relationships between various exposures and pathogenic signatures of diseases. In line with the accelerating advancements in MPE, social science and its health-related interdisciplinary areas have also developed rapidly. Accumulating evidence indicates the pathological role of social-demographic factors. We therefore initially proposed social MPE in 2015, which aims to elucidate etiological roles of social-demographic factors and address health inequalities globally. With the ubiquity of molecular diagnosis, there are ample opportunities for researchers to utilize and develop the social MPE framework., Areas Covered: Molecular subtypes of breast cancer have been investigated rigorously for understanding its etiologies rooted from social factors. Emerging evidence indicates pathogenic heterogeneity of neurological disorders such as Alzheimer's disease. Presenting specific patterns of social-demographic factors across different molecular subtypes should be promising for advancing the screening, prevention, and treatment strategies of those heterogeneous diseases. This article rigorously reviewed literatures investigating differences of race/ethnicity and socioeconomic status across molecular subtypes of breast cancer and Alzheimer's disease to date., Expert Opinion: With advancements of the multi-omics technologies, we foresee a blooming of social MPE studies, which can address health disparities, advance personalized molecular medicine, and enhance public health.

Sustaining economic activities while curbing the number of new coronavirus disease 2019 (COVID-19) cases until effective vaccines or treatments become available is a major public health and policy challenge. In this paper, we use agent-based simulations of a network-based susceptible-exposed-infectious-recovered (SEIR) model to investigate two network intervention strategies for mitigating the spread of transmission while maintaining economic activities. In the simulations, we assume that people engage in group activities in multiple sectors (e.g., going to work, going to a local grocery store), where they interact with others in the same group and potentially become infected. In the first strategy, each group is divided into two subgroups (e.g., a group of customers can only go to the grocery store in the morning, while another separate group of customers can only go in the afternoon). In the second strategy, we balance the number of group members across different groups within the same sector (e.g., every grocery store has the same number of customers). The simulation results show that the dividing groups strategy substantially reduces transmission, and the joint implementation of the two strategies could effectively bring the spread of transmission under control (i.e., effective reproduction number ≈ 1.0)., Competing Interests: Competing interest statement: A.N. is a consultant to Urbanic & Associates. A.E. received a research grant from Taisho Pharmaceutical Co., Ltd., (Copyright © 2020 the Author(s). Published by PNAS.)

Context: Healthy vending machine policies are viewed as a promising strategy for combating the growing obesity epidemic in the United States. Few studies have evaluated the short- and intermediate-term outcomes of healthy vending policies, especially for interventions that require 100% healthy products to be stocked., Objective: To evaluate the potential impact of a 100% healthy vending machine nutrition policy., Design: The vendor's quarterly revenue, product sales records, and nutritional information data from 359 unique vending machines were used to conduct a baseline and follow-up policy analysis., Setting: County of Los Angeles facilities, 2013-2015., Participants: Vending machines in facilities located across Los Angeles County., Intervention: A healthy vending machine policy executed in 2013 that required 100% of all products sold in contracted machines meet specified nutrition standards., Outcome Measures: Policy adherence; average number of calories, sugar, and sodium in food products sold; revenue change., Results: Policy adherence increased for snacks and beverages sold by the vending machines by 89% and 98%, respectively. Average snack and beverage revenues decreased by 37% and 34%, respectively, during the sampled period., Conclusions: Although a 100% healthy vending policy represents a promising strategy for encouraging purchases of healthier foods, steps should be taken to counteract potential revenue changes when planning its implementation.

Introduction: In 2010, the Los Angeles County Department of Public Health launched a local sodium-reduction initiative to address the rising prevalence of high blood pressure (hypertension) and related cardiovascular conditions in the population. To inform this effort, we evaluated self-reported knowledge and health behaviors related to sodium intake among Los Angeles County residents., Methods: We administered 3 cross-sectional Internet panel surveys on knowledge about dietary sodium to a sample of Los Angeles County adults, at intervals from December 2014 through August 2016. Multinomial and logistic regression models were constructed to describe associations between sodium knowledge and self-reported health behaviors., Results: A total of 7,067 panel subjects clicked into the online survey, and 2,862 completed the survey (adjusted response rate = 40.5%). Only 102 respondents (3.6%) were able to accurately report the recommended milligrams of sodium that an average adult should consume daily (1,500 mg to 2300 mg). Knowing about daily sodium intake recommendations was associated with increased odds of using Nutrition Facts labels to make food purchase decisions (adjusted odds ratio [AOR], 3.48; 95% confidence interval [CI], 1.59-7.60) and with decreased odds of taking measures to prevent hypertension (AOR, 0.38; 95% CI, 0.19-0.74)., Conclusions: Los Angeles County residents had a limited knowledge of recommended daily sodium intake. Efforts to increase understanding of these recommendations may encourage wider engagement in healthy behaviors. Health agencies should integrate sodium reduction messages in their diet and nutrition educational efforts.

Purpose: Evidence of the transmission of disease via donor ocular tissue has been demonstrated for adenocarcinoma, rabies, hepatitis B virus, cytomegalovirus, herpes simplex virus, Creutzfeldt-Jakob disease, and a variety of bacterial and fungal infections., Methods: Although there is no evidence to date of disease transmission for HIV infection, syphilis, hepatitis C, hepatitis A, tuberculosis, HTLV-1 and -2 infection, active leprosy, active typhoid, smallpox, and active malaria, these entities remain contraindications for transplantation for all eye banks nationally and internationally. The potential sources of contamination include infected donors, during the process of removing tissue from cadaveric donors, the processing environment, and contaminated supplies and reagents used during processing. The transmissions of Herpes simplex virus and HSV via corneal graft have been shown to be responsible for primary graft failure. HSV-1 may also be an important cause of PFG., Results: The long latency period of some diseases, the emergence of new infectious disease, and the reemergence of others emphasize the need for long-term record maintenance and effective tracing capabilities., Conclusions: The standardization of definitions for adverse events and reactions will be necessary to support the prevention and transmission of disease. International classification of a unique identification system for donors will be increasingly important for vigilance and traceability in cross-national exportation of human cells, tissues, and cellular- and tissue-based products. Opportunities for continuous improvement exist as does the need for constant vigilance and surveillance.