The Space Omics and Medical Atlas (SOMA) and international astronaut biobank.

Spaceflight induces molecular, cellular, and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space1-6. Yet, current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools, and protocols. Here, we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular, and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study7, JAXA CFE study8,9, SpaceX Inspiration4 crew10-12, plus Axiom and Polaris. The SOMA resource represents a >10-fold increase in publicly available human space omics data, with matched samples available from the Cornell Aerospace Medicine Biobank. The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome data sets, which reveal some consistent features across missions, including cytokine shifts, telomere elongation, and gene expression changes, as well as mission-specific molecular responses and links to orthologous, tissue-specific murine data sets. Leveraging the datasets, tools, and resources in SOMA can help accelerate precision aerospace medicine, bringing needed health monitoring, risk mitigation, and countermeasures data for upcoming lunar, Mars, and exploration-class missions.

Collection of biospecimens from the inspiration4 mission establishes the standards for the space omics and medical atlas (SOMA).

The SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies. Venous whole blood was further processed to obtain aliquots of serum, plasma, extracellular vesicles and particles, and peripheral blood mononuclear cells. In total, 2,911 sample aliquots were shipped to our central lab at Weill Cornell Medicine for downstream assays and biobanking. This paper provides an overview of the extensive biospecimen collection and highlights their processing procedures and long-term biobanking techniques, facilitating future molecular tests and evaluations.As such, this study details a robust framework for obtaining and preserving high-quality human, microbial, and environmental samples for aerospace medicine in the Space Omics and Medical Atlas (SOMA) initiative, which can aid future human spaceflight and space biology experiments.

Single-cell multi-ome and immune profiles of the Inspiration4 crew reveal conserved, cell-type, and sex-specific responses to spaceflight.

Spaceflight induces an immune response in astronauts. To better characterize this effect, we generated single-cell, multi-ome, cell-free RNA (cfRNA), biochemical, and hematology data for the SpaceX Inspiration4 (I4) mission crew. We found that 18 cytokines/chemokines related to inflammation, aging, and muscle homeostasis changed after spaceflight. In I4 single-cell multi-omics data, we identified a "spaceflight signature" of gene expression characterized by enrichment in oxidative phosphorylation, UV response, immune function, and TCF21 pathways. We confirmed the presence of this signature in independent datasets, including the NASA Twins Study, the I4 skin spatial transcriptomics, and 817 NASA GeneLab mouse transcriptomes. Finally, we observed that (1) T cells showed an up-regulation of FOXP3, (2) MHC class I genes exhibited long-term suppression, and (3) infection-related immune pathways were associated with microbiome shifts. In summary, this study reveals conserved and distinct immune disruptions occurring and details a roadmap for potential countermeasures to preserve astronaut health.

Dissemination of antimicrobial resistance in agricultural ecosystems following irrigation with treated municipal wastewater.

The spread of antimicrobial resistance (AMR) in agricultural systems via irrigation water is a serious public health issue as it can be transmitted to humans through the food chain. Therefore, understanding the dissemination routes of antibiotic resistance genes (ARGs) in agricultural systems is crucial for the assessment of health risks associated with eating fresh vegetables such as spinach and radish irrigated with treated municipal wastewater (TMW). In this study, we investigated the bacterial community structure and resistome in the soil-plant-earthworm continuum after irrigation of spinach and radish with TMW containing the antibiotics trimethoprim (TMP), sulfamethoxazole (SMZ), and sulfapyridine (SPD) using 16S rRNA gene sequencing and high throughput quantitative PCR (HT-qPCR). The study was conducted in two phases: Phase I involved eight weeks of spinach and radish production using TMW for irrigation, whereas Phase II entailed three weeks of earthworm exposure to contaminated plant material obtained in Phase I. The 16S data indicated that the rhizosphere bacterial community composition and structure were more resilient to antibiotic residuals in the irrigated water, with radish showing less susceptibility than spinach than those of bulk soils. The HT-qPCR analysis revealed that a total of 271 ARGs (out of 285) and 9 mobile genetic elements (MGEs) (out of 10) were detected in all samples. Higher diversity and abundance of ARGs were observed for samples irrigated with higher concentrations of antibiotics in both spinach and radish treatments. However, compared to spinach, radish ARG dynamics in the soil biome were more stable due to the change of antibiotic introduction to the soil. At the class level, multi-drug resistance (MDR) class was altered significantly by the presence of antibiotics in irrigation water. Compared to earthworm fecal samples, their corresponding soil environments showed a higher number of detected ARGs, suggesting that earthworms could play a role in reducing ARG dissemination in the soil environments. These findings will not only provide insight into the dissemination of ARGs in agricultural environments due to antibiotic residuals in irrigated water but could help understand the potential human health risks associated with ARGs.

Virtual fitness buddy ecosystem: a mixed reality precision health physical activity intervention for children.

6-11-year-old children provide a critical window for physical activity (PA) interventions. The Virtual Fitness Buddy ecosystem is a precision health PA intervention for children integrating mixed reality technology to connect people and devices. A cluster randomized, controlled trial was conducted across 19 afterschool sites over two 6-month cohorts to test its efficacy in increasing PA and decreasing sedentary behavior. In the treatment group, a custom virtual dog via a mixed reality kiosk helped children set PA goals while sharing progress with parents to receive feedback and support. Children in the control group set PA goals using a computer without support from the virtual dog or parents. 303 children had 8+ hours of PA data on at least one day of each of the 3 intervention time intervals. Conversion of sedentary time was primarily to light-intensity PA and was strongest for children with low baseline moderate-to-vigorous PA than children above 45 min of baseline moderate-to-vigorous PA. Findings suggest that the VFB ecosystem can promote sustainable PA in children and may be rapidly diffused for widespread public health impact.

Proteomic profiling of antibiotic-resistant Escherichia coli GW-AmxH19 isolated from hospital wastewater treated with physical plasma.

Microorganisms which are resistant to antibiotics are a global threat to the health of humans and animals. Wastewater treatment plants are known hotspots for the dissemination of antibiotic resistances. Therefore, novel methods for the inactivation of pathogens, and in particular antibiotic-resistant microorganisms (ARM), are of increasing interest. An especially promising method could be a water treatment by physical plasma which provides charged particles, electric fields, UV-radiation, and reactive species. The latter are foremost responsible for the antimicrobial properties of plasma. Thus, with plasma it might be possible to reduce the amount of ARM and to establish this technology as additional treatment stage for wastewater remediation. However, the impact of plasma on microorganisms beyond a mere inactivation was analyzed in more detail by a proteomic approach. Therefore, Escherichia coli GW-AmxH19, isolated from hospital wastewater in Germany, was used. The bacterial solution was treated by a plasma discharge ignited between each of four pins and the liquid surface. The growth of E. coli and the pH-value decreased during plasma treatment in comparison with the untreated control. Proteome and antibiotic resistance profile were analyzed. Concentrations of nitrite and nitrate were determined as long-lived indicative products of a transient chemistry associated with reactive nitrogen species (RNS). Conversely, hydrogen peroxide served as indicator for reactive oxygen species (ROS). Proteome analyses revealed an oxidative stress response as a result of plasma-generated RNS and ROS as well as a pH-balancing reaction as key responses to plasma treatment. Both, the generation of reactive species and a decreased pH-value is characteristic for plasma-treated solutions. The plasma-mediated changes of the proteome are discussed also in comparison with the Gram-positive bacterium Bacillus subtilis. Furthermore, no effect of the plasma treatment, on the antibiotic resistance of E. coli, was determined under the chosen conditions. The knowledge about the physiological changes of ARM in response to plasma is of fundamental interest to understand the molecular basis for the inactivation. This will be important for the further development and implementation of plasma in wastewater remediation.

West Nile Virus Emergence in Germany 2019: Looking for Hidden Human West Nile Virus Infections.

Background: Autochthonous human West Nile virus (WNV) infections were notified in the infectious disease surveillance system in Germany in 2018 for the first time and every year since then. Since clinically apparent infections are infrequent, we conducted two studies to investigate subclinical infections of this emerging disease in Germany in 2019 to detect infections not visible to surveillance based on symptomatic infections: limited-scope blood donor testing and a serosurvey among employees at two Berlin zoos with a history of demonstrated WNV infections in animals. Methods: For the zoo study, employees of the two zoos in Berlin were invited to participate in the study in late 2019. Blood samples were drawn and tested for the presence of antibodies (immunoglobulin M [IgM] and immunoglobulin G [IgG]) against WNV, and two other flaviviruses present in Germany: Usutu virus and Tick-borne encephalitis virus (TBEV). For the study in blood donors, four blood establishments with collection sites in regions with documented WNV-infected animals in 2018 and 2019 participated in the study. All donations in these regions were tested for WNV genome from July to November 2019. Results: In the enzyme-linked immunosorbent assay, none of the 70 tested zoo employees were WNV IgM-positive, 8 were WNV IgG-positive, additional 2 participants had equivocal results. All 10 were negative in the virus neutralization test (VNT) for WNV, but positive in the VNT for TBEV. None of the 4273 samples from blood donors tested in areas with WNV-infected animals was positive for WNV-RNA. Conclusion: Our results indicate that WNV circulation in Germany, though clearly documented in animals in 2019, apparently affected very few humans. Still areas with WNV-positive animals remain risk areas for human infection as well.

Genome and clonal hematopoiesis stability contrasts with immune, cfDNA, mitochondrial, and telomere length changes during short duration spaceflight.

Background: The Inspiration4 (I4) mission, the first all-civilian orbital flight mission, investigated the physiological effects of short-duration spaceflight through a multi-omic approach. Despite advances, there remains much to learn about human adaptation to spaceflight's unique challenges, including microgravity, immune system perturbations, and radiation exposure. Methods: To provide a detailed genetics analysis of the mission, we collected dried blood spots pre-, during, and post-flight for DNA extraction. Telomere length was measured by quantitative PCR, while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations. A robust bioinformatic pipeline was used for data analysis, including variant calling to assess mutational burden. Result: Telomere elongation occurred during spaceflight and shortened after return to Earth. Cell-free DNA analysis revealed increased immune cell signatures post-flight. No significant clonal hematopoiesis of indeterminate potential (CHIP) or whole-genome instability was observed. The long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months post-flight. Conclusion: Our findings provide valuable insights into the physiological consequences of short-duration spaceflight, with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to Earth. CHIP sequencing data will serve as a reference point for studying the early development of CHIP in astronauts, an understudied phenomenon as previous studies have focused on career astronauts. This study will serve as a reference point for future commercial and non-commercial spaceflight, low Earth orbit (LEO) missions, and deep-space exploration.

The Obese Taste Bud study: Objectives and study design.

AIMS: Taste modifies eating behaviour, impacting body weight and potentially obesity development. The Obese Taste Bud (OTB) Study is a prospective cohort study launched in 2020 at the University of Leipzig Obesity Centre in cooperation with the HI-MAG Institute. OTB will test the hypothesis that taste cell homeostasis and taste perception are linked to obesity. Here, we provide the study design, data collection process and baseline characteristics. MATERIALS AND METHODS: Participants presenting overweight, obesity or normal weight undergo taste and smell tests, anthropometric, and taste bud density (TBD) assessment on Day 1. Information on physical and mental health, eating behaviour, physical activity, and dental hygiene are obtained, while biomaterial (saliva, tongue swap, blood) is collected in the fasted state. Further blood samples are taken during a glucose tolerance test. A stool sample is collected at home prior to Day 2, on which a taste bud biopsy follows dental examination. A subsample undergoes functional magnetic resonance imaging while exposed to eating-related cognitive tasks. Follow-up investigations after conventional weight loss interventions and bariatric surgery will be included. RESULTS: Initial results show that glycated haemoglobin levels and age are negatively associated with TBD, while an unfavourable metabolic profile, current dieting, and vegan diet are related to taste perception. Olfactory function negatively correlates with age and high-density lipoprotein cholesterol. CONCLUSION: Initial findings suggest that metabolic alterations are relevant for taste and smell function and TBD. By combining omics data from collected biomaterial with physiological, metabolic and psychological data related to taste perception and eating behaviour, the OTB study aims to strengthen our understanding of taste perception in obesity.

Ventral Hernia Reconstruction with GORE ENFORM Biomaterial.

Introduction: Ventral hernia repair (VHR) is one of the most common surgeries performed in the United States. Degradable mesh is the recommended choice for patients presenting with high-risk co-morbidities or increased risk for infection. GORE® ENFORM BiomaterialTM is a biosynthetic degradable mesh that has recently been approved for use in ventral hernia reconstruction with no reports of its clinical outcomes. Methods: This study was a single surgeon case series. Patients were included in the study if they underwent VHR with GORE® ENFORM BiomaterialTM. The decision to use GORE® ENFORM BiomaterialTM was the senior surgeon's decision based on the patient's center for disease control classification. Patient comorbidities, hernia characteristics, postoperative hernia recurrence, and surgical site occurrences (SSOs) were collected at in-patient follow-up appointments and chart review. Patients were asked to complete preoperative and postoperative patient-reported outcomes (PROs) using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Intensity short form 3a and the hernia-specific quality of life (HerQLes) survey. Results: A total of 15 patients were included in this study. The average length of follow-up was 315 days. Postoperatively, 26.7% of patients had an SSO with 4 surgical site infections. Two patients required an operative washout with mesh removal. One patient experienced hernia recurrence. Eight of the 15 patients completed preoperative and postoperative PROs. Conclusion: This is the first clinical study to report the outcomes of ventral hernia repair using ENFORM mesh. These results show that Enform mesh is an option to consider in complex ventral hernia reconstruction.

Introduction: La réparation d'une hernie ventrale (RHV) est l'une des opérations les plus fréquentes aux États-Unis. Le treillis dégradable est le choix recommandé pour les patients ayant des affections connexes à haut risque ou qui sont vulnérables aux infections. Le biomatériau GORE® ENFORM est un treillis biosynthétique dégradable qui a récemment été approuvé pour la reconstruction des hernies ventrales et dont les résultats cliniques n'ont fait l'objet d'aucun rapport. Méthodologie : La présente étude était constituée d'une série de cas réalisée par un seul chirurgien. Les patients étaient inclus dans l'étude s'ils avaient subi une RHV à l'aide de biomatériau GORE® ENFORM. Le chirurgien en chef prenait la décision d'utiliser ce biomatériau d'après la classification du contrôle des maladies au centre du patient. Les chercheurs ont colligé les affections connexes du patient, les caractéristiques de la hernie, les récurrences de hernie postopératoire et les occurrences au foyer de l'opération (OFO) lors des rendez-vous de suivi et de l'examen des dossiers. Les patients ont été invités à préciser leurs résultats préopératoires et postopératoires (RPP) au moyen du formulaire court 3a sur l'intensité de la douleur tiré du système d'information des mesures de résultats déclarés par le patient (PROMIS) et du sondage sur la qualité de vie propre à la hernie (HerQLes). Résultats : Au total, 15 patients ont participé à l'étude et ont été suivis pendant une durée moyenne de 315 jours. Après l'opération, 26,7% des patients ont présenté une OFO ainsi que quatre infections au foyer de l'opération. Deux patients ont eu besoin d'un lessivage opératoire et du retrait du treillis. Un patient a subi une récurrence de la hernie. Huit des 15 patients ont rempli les RDP avant et après l'opération. Conclusion : Il s'agit de la première étude clinique à déclarer les résultats cliniques de la réparation d'une hernie ventrale à l'aide du treillis ENFORM. Ces résultats démontrent que le treillis Enform peut être envisagé pour la reconstruction d'une hernie ventrale complexe.

Critical evaluation of the reliability of DNA methylation probes on the Illumina MethylationEPIC v1.0 BeadChip microarrays.

DNA methylation (DNAm) plays a crucial role in a number of complex diseases. However, the reliability of DNAm levels measured using Illumina arrays varies across different probes. Previous research primarily assessed probe reliability by comparing duplicate samples between the 450k-450k or 450k-EPIC platforms, with limited investigations on Illumina EPIC v1.0 arrays. We conducted a comprehensive assessment of the EPIC v1.0 array probe reliability using 69 blood DNA samples, each measured twice, generated by the Alzheimer's Disease Neuroimaging Initiative study. We observed higher reliability in probes with average methylation beta values of 0.2 to 0.8, and lower reliability in type I probes or those within the promoter and CpG island regions. Importantly, we found that probe reliability has significant implications in the analyses of Epigenome-wide Association Studies (EWAS). Higher reliability is associated with more consistent effect sizes in different studies, the identification of differentially methylated regions (DMRs) and methylation quantitative trait locus (mQTLs), and significant correlations with downstream gene expression. Moreover, blood DNAm measurements obtained from probes with higher reliability are more likely to show concordance with brain DNAm measurements. Our findings, which provide crucial reliability information for probes on the EPIC v1.0 array, will serve as a valuable resource for future DNAm studies.

Evaluation of the National Cancer Institute (NCI) Pathway to Independence Award (K99/R00) Program.

The National Cancer Institute (NCI) K99/R00 award is intended to help postdoctoral scholars transition in a timely manner to research independence and to foster their development of an impactful cancer research program that is competitive for subsequent independent funding. Here we analyzed factors that impact peer review outcomes and evaluated whether NCI K99/R00 awardees have achieved the goals of the K99/R00 funding mechanism. Our analysis of the K99/R00 review criterion scores demonstrates that while all review criterion scores are positively correlated with the overall impact score, the Research Plan criterion is the strongest predictor of the overall impact score and funding outcomes. In addition, our analysis shows the NCI K99/R00 award facilitated the successful transition of postdoctoral scholars to research independence and enhanced the likelihood of K99/R00 awardees to secure subsequent R01-equivalent NIH grant support although not in an accelerated fashion as originally intended. An NCI K99/R00 award was not determined to be a prerequisite to obtain a faculty position, but for some awardees, it was an asset in that transition. Our results suggest that the NCI K99/R00 award is an important component for training and retention of the next generation of independent cancer researchers and to increasing the percentage of women and promoting the diversity of the cancer research workforce.

Biaxial Flexural Strength of Printed Splint Materials.

One therapeutical alternative in the treatment of functional disorders is the use of printed oral splints. The mechanical properties of these materials are highly essential to their clinical effectiveness, and their performance may vary depending on factors such as cleaning, post-polymerization, or their orientation during construction. The objective of this in vitro investigation is to evaluate the effectiveness of the selected materials in terms of their biaxial flexural strength in relation to the criteria listed above. Splint materials were used in the printing of 720 discs. The printing process was carried out in different orientations in relation to the building platform. Either an automatic or manual cleaning process was performed on the samples. For post-polymerization, either an LED or Xenon light was utilized. A piston-on-three-ball test was used to measure the biaxial flexural strength (BFS) of the materials after they were stored in water for either 24 h or 60 days. The homogeneity of the data was controlled by employing the Levene method, and the differences between the groups were analyzed using the ANOVA and Bonferroni methods. After being stored for twenty-four hours, the mean BFS ranged anywhere from 79 MPa to 157 MPa. Following a period of sixty hours, the BFS exhibited a substantial drop and revealed values that ranged from 72 to 127 MPa. There was no significant difference that could be identified between the materials or between the various cleaning processes. The results of post-polymerization showed that the LED light produced higher means than the Xenon light did. In terms of position, the mean values varied greatly, with 0°'s mean value being 101 MPa, 45°'s mean value being 102 MPa, and 90°'s mean value being 115 MPa. The use of a build orientation of 90° and post-polymerization with LED light resulted in significantly increased biaxial flexural strength. According to this study, this design should be implemented in order to ensure that splint materials have the highest possible strength.

Harmonization of three different accelerometers to classify the 24 h activity cycle.

Increasing interest in measuring key components of the 24 h activity cycle (24-HAC) [sleep, sedentary behavior (SED), light physical activity (LPA), and moderate to vigorous physical activity (MVPA)] has led to a need for better methods. Single wrist-worn accelerometers and different self-report instruments can assess the 24-HAC but may not accurately classify time spent in the different components or be subject to recall errors.Objective. To overcome these limitations, the current study harmonized output from multiple complimentary research grade accelerometers and assessed the feasibility and logistical challenges of this approach.Approach. Participants (n= 108) wore an: (a) ActiGraph GT9X on the wrist, (b) activPAL3 on the thigh, and (c) ActiGraph GT3X+ on the hip for 7-10 d to capture the 24-HAC. Participant compliance with the measurement protocol was compared across devices and an algorithm was developed to harmonize data from the accelerometers. The resulting 24-HAC estimates were described within and across days.Main results. Usable data for each device was obtained from 94.3% to 96.7% of participants and 89.4% provided usable data from all three devices. Compliance with wear instructions ranged from 70.7% of days for the GT3X+ to 93.2% of days for the activPAL3. Harmonized estimates indicated that, on average, university students spent 34% of the 24 h day sleeping, 41% sedentary, 21% in LPA, and 4% in MVPA. These behaviors varied substantially by time of day and day of the week.Significance. It is feasible to use three accelerometers in combination to derive a harmonized estimate the 24-HAC. The use of multiple accelerometers can minimize gaps in 24-HAC data however, factors such as additional research costs, and higher participant and investigator burden, should also be considered.

Room-Temperature Copper-Catalyzed Etherification of Aryl Bromides.

We disclose the development of a Cu-catalyzed C-O coupling method utilizing a new N1,N2-diarylbenzene-1,2-diamine ligand, L8. Under optimized reaction conditions, structurally diverse aryl and heteroaryl bromides underwent efficient coupling with a variety of alcohols at room temperature using an L8-based catalyst. Notably, the L8-derived catalyst exhibited enhanced activity when compared to the L4-based system previously disclosed for C-N coupling, namely the ability to functionalize aryl bromides containing acidic functional groups. Mechanistic studies demonstrate that C-O coupling utilizing L8 ⋅ Cu involves rate-limiting alkoxide transmetallation, resulting in a mechanism of C-O bond formation that is distinct from previously described Pd-, Cu-, or Ni-based systems. This lower energy pathway leads to rapid C-O bond formation; a 7-fold increase relative to what is seen with other ligands. The results presented in this report overcome limitations in previously described C-O coupling methods and introduce a new ligand that we anticipate may be useful in other Cu-catalyzed C-heteroatom bond-forming reactions.

Building consensus on a set of ENDS-specific pictorial health warnings: a Delphi study among a tobacco control expert panel.

BACKGROUND: This study reports on the development of pictorial health warning labels for electronic nicotine delivery system (ENDS) using the Delphi approach with a panel of tobacco control experts. Twenty-four evidence-based ENDS-specific warnings corresponding to three themes (toxicity, health risks and specific harm) were developed and used in the Delphi study. METHODS: We conducted a three-round online Delphi study among 60 experts (55% female) between June 2022 and April 2023. We balanced the panel in areas of expertise and positions relevant to ENDS (risks, benefits). In round 1, participants rated the warnings on attention, relevance to evidence and perceived effectiveness (harm perception, motivation to quit) and provided suggestions for improvement. In rounds 2 and 3, participants ranked the revised warnings based on importance in each theme. We assessed levels of agreement between participants using interquartile deviations and medians. RESULTS: Warnings in theme 1, toxicity, received the highest ratings for perceived effectiveness on harm perception and encouraging quitting ENDS (p<0.05). Experts recommended using clear and affirmative text paired with emotion-provoking pictures and avoiding the rare side effects of ENDS. Most of the top-ranked warnings were from theme 3, ENDS-specific harm, pertained to lung damage, dual use of ENDS and cigarettes, nicotine addiction among youth, anti-ENDS industry sentiment and toxicity. DISCUSSION: This study developed 24 evidence-based ENDS health warning labels using a systematic process that included several rounds of expert panel feedback. These warnings can be used to advance ENDS prevention and tobacco control policies and further target different populations.

Application of fucosylation inhibitors for production of afucosylated antibody.

Fucosylation is an important quality attribute for therapeutic antibodies. Afucosylated antibodies exhibit higher therapeutic efficacies than their fucosylated counterparts through antibody-dependent cellular cytotoxicity (ADCC) mechanism. Since higher potency is beneficial in reducing dose or duration of the treatment, afucosylated antibodies have attracted a great deal of interest in biotherapeutics development. In this study, novel small molecules GDP-D-Rhamnose and its derivatives (Ac-GDP-D-Rhamnose and rhamnose sodium phosphate) were synthesized to inhibit the enzyme in the GDP-fucose synthesis pathway. Addition of these compounds into cell culture increased antibody afucosylation levels in a dose-dependent manner and had no significant impact on other protein quality attributes. A novel and effective mechanism to generate afucosylated antibody is demonstrated for biologics discovery, analytical method development, process development, and other applications.