Research Program Research Articles

Changes in S100 calcium-binding protein β (S100β) and cognitive function from pre- to post-chemotherapy among women with breast cancer

Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function. A total of 505 women with breast cancer (mean (sd) age; 53.4 (53.6)) and 336 age-matched controls without cancer (52.8 (10.3)) were included from a nationwide study as part of the National Cancer Institute Community Oncology Research Program (NCORP). Both groups provided blood samples and completed neurocognitive assessments within 7 days before the patients with breast cancer received their first chemotherapy dose (pre-chemotherapy; T1) and within 1 month of their last chemotherapy administration (post-chemotherapy; T2). Utilizing a linear mixed model, multivariate linear regressions, and Spearman rank correlations (rs), we investigated longitudinal changes in serum S100β concentrations and their relationships to changes in neurocognitive outcomes over time. We observed an increase in S100β for patients with breast cancer (p = 0.002), but not for controls without cancer over time (p = 0.683). Additionally, we identified subtle relationships between increases in serum S100β and worsening in cognitive performance on the Backward Counting test (rs = 0.11, p = 0.041) and self-reported FACT-Cog Perceived Cognitive Abilities (rs = −0.10, p = 0.025). Regression analyses adjusted for age, race, body-mass index (BMI), education, menopausal status, anxiety, and depression revealed a trend remained for the relationship of S100β with Backward Counting. In conclusion, we found that patients with breast cancer experience a significant increase in concentration of serum S100β over the course of chemotherapy. This increase is correlated with worsening in some neurocognitive outcomes from pre-to post-chemotherapy, with trending results remaining following adjustment for covariates.

Association between alcohol consumption and incidence of dementia in current drinkers: linear and non-linear mendelian randomization analysis

Previous conventional epidemiological studies found a J-shape relationship between alcohol consumption and dementia, but this result was subject to confounding biases and reverse causation. Therefore, we aimed to investigate the potential linear or non-linear causal association between alcohol consumption and the incident risk of dementia in current drinkers. This study used data from the UK Biobank to investigate the relationship between alcohol consumption and dementia risk. 313,958 White British current drinkers, who were free of dementia during 2006-2010, were followed up until 2021. Alcohol consumption was self-reported and calculated according to the National Health Service guideline. The primary outcome was all-cause dementia identified through hospital and mortality records. We used multivariable Cox models with restricted cubic splines for conventional analysis and both non-linear and linear Mendelian Randomization (MR) analyses to assess causal relationships, employing a genetic score based on 95 SNPs identified from a meta-genome-wide association study of 941,280 people from Europe. 313,958 current drinkers consumed an average of 13.6 [IQR: 7.1-25.2] units/week alcohol (men averaged 20.2 [11.1-33.9] units/week and women 9.5 [5.3-16.7] units/week). During a mean follow-up of 13.2 years, 5394 (1.7%) developed dementia. Multivariable Cox model with restricted cubic spline functions identified a J-shaped relationship between alcohol consumption and dementia risk, with the lowest risk at 12.2 units/week. The non-linear MR failed to identify a significant non-linear causal relationship (p=0.45). Both individual-level (HR: 2.22 95%CI [1.06-4.66]) and summary-level (1.89 [1.53-2.32]) linear MR analyses indicated that higher genetically predicted alcohol consumption increased dementia risk. This study identified a positive linear causal relationship between alcohol consumption and dementia among current drinkers. The J-shaped association found in conventional epidemiological analysis was not supported by non-linear MR analyses. Our findings suggested that there was no safe level of alcohol consumption for dementia. The Shenzhen Science and Technology Program and the Strategic Priority Research Program of Chinese Academy of Sciences.

Phenome-Wide Association of APOE Alleles in the All of Us Research Program.

Genetic variation in APOE is associated with altered lipid metabolism, as well as cardiovascular and neurodegenerative disease risk. However, prior studies are largely limited to European ancestry populations and differential risk by sex and ancestry has not been widely evaluated. We utilized a phenome-wide association study (PheWAS) approach to explore APOE-associated phenotypes in the All of Us Research Program. We determined APOE alleles for 181,880 All of Us participants with whole genome sequencing and electronic health record (EHR) data, representing seven gnomAD ancestry groups. We tested association of APOE variants, ordered based on Alzheimer's disease risk hierarchy (ε2/ε2<ε2/ε3<ε3/ε3<ε2/ε4<ε3/ε4<ε4/ε4), with 2,318 EHR-derived phenotypes. Bonferroni-adjusted analyses were performed overall, by ancestry, by sex, and with adjustment for social determinants of health (SDOH). In the overall cohort, PheWAS identified 17 significant associations, including an increased odds of hyperlipidemia (OR 1.15 [1.14-1.16] per APOE genotype group; P=1.8×10-129), dementia, and Alzheimer's disease (OR 1.55 [1.40-1.70]; P=5×10-19), and a reduced odds of fatty liver disease (OR 0.93 [0.90-0.95]; P=1.6×10-9) and chronic liver disease. ORs were similar after SDOH adjustment and by sex, except for an increased number of cardiovascular associations in males, and decreased odds of noninflammatory disorders of vulva and perineum in females (OR 0.89 [0.84-0.94]; P=1.1×10-5). Significant heterogeneity was observed for hyperlipidemia and mild cognitive impairment across ancestry. Unique associations by ancestry included transient retinal arterial occlusion in the European ancestry group, and first-degree atrioventricular block in the American Admixed/Latino ancestry group. We replicate extensive phenotypic associations with APOE alleles in a large, diverse cohort, despite limitations in accuracy for EHR-derived phenotypes. We provide a comprehensive catalog of APOE-associated phenotypes and present evidence of unique phenotypic associations by sex and ancestry, as well as heterogeneity in effect size across ancestry.

Coassembly and binning of a twenty-year metagenomic time-series from Lake Mendota

The North Temperate Lakes Long-Term Ecological Research (NTL-LTER) program has been extensively used to improve understanding of how aquatic ecosystems respond to environmental stressors, climate fluctuations, and human activities. Here, we report on the metagenomes of samples collected between 2000 and 2019 from Lake Mendota, a freshwater eutrophic lake within the NTL-LTER site. We utilized the distributed metagenome assembler MetaHipMer to coassemble over 10 terabases (Tbp) of data from 471 individual Illumina-sequenced metagenomes. A total of 95,523,664 contigs were assembled and binned to generate 1,894 non-redundant metagenome-assembled genomes (MAGs) with ≥50% completeness and ≤10% contamination. Phylogenomic analysis revealed that the MAGs were nearly exclusively bacterial, dominated by Pseudomonadota (Proteobacteria, N = 623) and Bacteroidota (N = 321). Nine eukaryotic MAGs were identified by eukCC with six assigned to the phylum Chlorophyta. Additionally, 6,350 high-quality viral sequences were identified by geNomad with the majority classified in the phylum Uroviricota. This expansive coassembled metagenomic dataset provides an unprecedented foundation to advance understanding of microbial communities in freshwater ecosystems and explore temporal ecosystem dynamics.

Counselling for patients with a temporomandibular disorder: A scoping review and concept analysis.

An integral component of comprehensive temporomandibular disorder (TMD) treatment involves what is commonly referred to in literature as patient counselling or patient education. Despite its importance, a clear definition of the concept is lacking. To describe the concept of counselling (i.e. what is it, what should it consist of, and when should it be given) through a concept analysis of the literature. All papers that include a description of counselling or education for TMD are included. Literature searches were performed in the electronic databases PubMed, Cinahl, and PsycInfo. A qualitative analysis was done using the principle-based concept analysis approach, where descriptions of counselling from the included papers were analysed by the researchers. A total of 71 articles were included. Based on the qualitative analysis of the included articles and descriptions of counselling, the following content themes were identified: (1) general information on TMD; (2) overuse of the masticatory system; (3) posture education; (4) lifestyle and psychosocial factors; (5) exercise- and thermotherapy; and (6) additional information and therapies. A definition and framework of counselling for TMD has been provided, which can be used in the clinic, research, and educational programs.

Investigating Published Research towards a Fossil-Energy-Free Agriculture Transformation

The defossilisation of the agricultural sector is driven by intense worldwide academic research on non-fossil, renewable and energy-efficient agriculture, and the acknowledgment of the need for sustainable farming practices. For this purpose, not only technical transformations but also socio-technical system changes towards sustainability need to take place in a co-evolutionary manner. This paper investigates structural and qualitative characteristics of the knowledge produced by research on fossil-energy-free agriculture. We provide evidence on the worldwide research directions, as well as investigate whether academic research and publicly funded research projects foster knowledge creation for the desired transformation. Bibliographic maps are constructed using a query-based methodology as social networks to investigate the efficiency of the EU-funded research to achieve the goals set for the 2050 EU Green Deal. The H2020-funded papers are further analysed with dictionary-based text analysis to quantify the relative emphasis of different types of knowledge in the text. This approach is eventually used to relate transformational capacity to project profiles in the European Union, to evaluate past funding schemes and to improve the shape of future research programs on renewable and sustainable agriculture.

Cellular, Molecular, and Genetic Mechanisms of Avian Beak Development and Evolution.

Diverse research programs employing complementary strategies have been uncovering cellular, molecular, and genetic mechanisms essential to avian beak development and evolution. In reviewing these discoveries, I offer an interdisciplinary perspective on bird beaks that spans their derivation from jaws of dinosaurian reptiles, their anatomical and ecological diversification across major taxonomic groups, their common embryonic origins, their intrinsic patterning processes, and their structural integration. I describe how descriptive and experimental approaches, including gene expression and cell lineage analyses, tissue recombinations, surgical transplants, gain- and loss-of-function methods, geometric morphometrics, comparative genomics, and genome-wide association studies, have identified key constituent parts and putative genes regulating beak morphogenesis and evolution. I focus throughout on neural crest mesenchyme, which generates the beak skeleton and other components, and describe how these embryonic progenitor cells mediate species-specific pattern and link form and function as revealed by 20 years of research using chimeras between quail and duck embryos.

NCI's Proteomic Data Commons: A Cloud-Based Proteomics Repository Empowering Comprehensive Cancer Analysis Through Cross-Referencing with Genomic and Imaging Data.

Proteomics has emerged as a powerful tool for studying cancer biology, developing diagnostics, and therapies. With the continuous improvement and widespread availability of high-throughput proteomic technologies, the generation of large-scale proteomic data has become more common in cancer research, and there is a growing need for resources that support the sharing and integration of multi-omics datasets. Such datasets require extensive metadata including clinical, biospecimen and experimental and workflow annotations that are crucial for data interpretation and reanalysis. The need to integrate, analyze, and share these data has led to the development of National Cancer Institute's (NCI) Proteomic Data Commons (PDC), accessible at https://pdc.cancer.gov. As a specialized repository within the NCI Cancer Research Data Commons (CRDC), PDC enables researchers to locate and analyze proteomic data from various cancer types and connect with genomic and imaging data available for the same samples in other CRDC nodes. Presently, PDC houses annotated data from nearly 140 datasets across 19 cancer types, generated by several large-scale cancer research programs with cohort sizes exceeding 100 samples (tumor and associated normal when available). In this paper, we review the current state of PDC in cancer research, discuss the opportunities and challenges associated with data sharing in proteomics, and propose future directions for the resource.

EXPERIMENTAL STUDY OF HYDRATE FORMATION PECULIARITIES FOR CONDITIONS OF THE TURNO AND CENOMANIAN DEPOSITS: Part II

This paper is the second part of the research devoted to the study of hydrate formation features for the conditions of Turonian and Cenomanian deposits. The launch of new gas projects at the Turon and Senoman production facilities in Western Siberia provided a good opportunity to critically analyze the known methods of protecting production, gathering and transportation facilities of the gas field from the formation of solid gas hydrates. The paper presents the experience of implementing a program of laboratory studies of conditions of gas hydrate formation with their subsequent processing and in-depth analysis. The research program covered the area of thermobaric parameters typical for the conditions of Turon-Senoman deposits exploitation with localization of hydrate-hazardous areas in the conditions of Technological Regimes for full development. The description of laboratory studies is given, in which two gas compositions of Senoman and Turon objects, different variants of mineralization and ionic composition corresponding to formation and condensation water, as well as hydrate formation conditions under changing dosages of basic inhibitor on the basis of methanol were considered. The details of the experiment based on the method of swinging cells and the subsequent analysis of the results of the completed experiments to determine the thermobaric conditions of formation and decomposition of hydrates are given. The main features of the experiment are specified, estimates of the rate of change of the influencing parameters of the experiment on its quality are given. In the process of implementation of the experimental program, the optimal values of these parameters were selected, which allowed us to significantly reduce the variation of experimental results to determine the thermobaric conditions of hydrate formation. It is experimentally established that the temperature of hydrate decomposition is higher than the temperature of its formation at all investigated gas compositions and water mineralization.

Ab initio study of Z(N) = 6 magicity* *This work is partially supported by the National Natural Science Foundation of China (Grant Nos. 12175280, 12250610193, 12375143, 11975282, 11705240, 11435014), the Natural Science Foundation of Gansu Province, China (Grant Nos. 20JR10RA067, 23JRRA675), the Chinese Academy of Sciences "Light of West China" Program, the Key Research Program of the Chinese Academy of

The existence of magic numbers of protons and neutrons in nuclei is essential for understanding the nuclear structure and fundamental nuclear forces. Over decades, researchers have conducted theoretical and experimental studies on a new magic number, Z(N)=6, focusing on observables such as radii, binding energy, electromagnetic transition, and nucleon separation energies. We performed ab initio no-core shell model calculations for the occupation numbers of the lowest single particle states in the ground states of Z(N)=6 and Z(N)=8 isotopes (isotones). The results of our calculations do not support Z(N)=6 as a magic number over a range of atomic numbers. However, 14C and 14O exhibit the characteristics of double-magic nuclei.

EXPRESS: The Scientific Value of Medical Student Research: The Experience at the Arrow Program for Medical Research Education.

This study presents a comparative analysis of the publications of students participating in the Arrow Research Program in comparison to those of attending physicians and researchers at the same tertiary medical center in order to assess the impact of the Arrow Research Program on the students' scientific achievements. The study encompassed 90 Arrow Research Program students that were involved in the program at the Sheba Medical Center between 2019 and 2021. As a comparison group, 2082 attending physicians and researchers affiliated with the same center during the same period of time were considered. Publications were collected from the Web of Science Database, and the publication data parameters of each group were compared to assess scientific outcomes. The Arrow Research Program students collectively published 67 articles, and the 2082 physicians and researchers in the comparison group produced 4283 papers during the study timeframe. Similarly, the average impact factor of the journals in which the Arrow Research Program papers were published was 4.16 ± 2.68, similar to the average impact factor of 4.74 ± 6.26 in the comparison group (p = 0.388). Likewise, the average quartile of the journals in which the Arrow Research Program articles were published was 1.39 ± 0.59, which is similar to the comparison group's average quartile of 1.39 ± 0.63 (p = 0.997). In conclusion, the Arrow Research Program demonstrates its effectiveness in empowering young students to execute successful research projects. This study may help develop educational programs worldwide.

Socioeconomic disparities in kidney transplant access for patients with end-stage kidney disease within the All of Us Research Program.

Disparity in kidney transplant access has been demonstrated by a disproportionately low rate of kidney transplantation in socioeconomically disadvantaged patients. However, the information is not from national representative populations with end-stage kidney disease (ESKD). We aim to examine whether socioeconomic disparity for kidney transplant access exists by utilizing data from the All of Us Research Program. We analyzed data of adult ESKD patients using the All of Us Researcher Workbench. The association of socioeconomic data including types of health insurance, levels of education, and household incomes with kidney transplant access was evaluated by multivariable logistic regression analysis adjusted by baseline demographic, medical comorbidities, and behavioral information. Among 4078 adults with ESKD, mean diagnosis age was 54 and 51.64% were male. The majority had Medicare (39.6%), were non-graduate college (75.79%), and earned $10000-24999 annual income (20.16%). After adjusting for potential confounders, insurance status emerged as a significant predictor of kidney transplant access. Individuals covered by Medicaid (adjusted odds ratio [AOR] 0.45; 95% confidence interval [CI], 0.35-0.58; P-value < .001) or uninsured (AOR 0.21; 95% CI, 0.12-0.37; P-value < .001) exhibited lower odds of transplantation compared to those with private insurance. Our findings reveal the influence of insurance status and socioeconomic factors on access to kidney transplantation among ESKD patients. Addressing these disparities through expanded insurance coverage and improved healthcare access is vital for promoting equitable treatment and enhancing health outcomes in vulnerable populations.

Impact of Social Determinants of Health on Health-Related Quality of Life Among Cancer Survivors in the United States.

Purpose : Health-related quality of life (HRQoL) is a critical aspect of cancer survivorship, influenced by various social determinants of health (SDoH) such as economic stability, education access, and healthcare coverage. Understanding the impact of these determinants is essential for developing interventions that improve the well-being of cancer survivors. Methods : Cross-sectional analyses were conducted using data from 20,534 adults with cancer, including 15,754 from the All of Us (AOU) Research Program (2015-2024) and 4,780 from the National Health and Nutrition Examination Survey (NHANES) (2001-2018). HRQoL outcomes were assessed across multiple dimensions: physical health, mental health, emotional well-being, social support, functional ability, and physical activity. Results : Higher economic stability, education access, and healthcare coverage were significantly associated with better HRQoL outcomes in both cohorts. In the AOU cohort, those with higher family income were more likely to report very good (OR: 20.24; CI: 12.86-31.87) or excellent (OR: 33.06; CI: 20.01-54.64) quality of life. Similar trends were observed for physical and mental health. The NHANES cohort showed consistent findings. Participants with no negative SDoH factors were significantly more likely to report excellent outcomes across all HRQoL dimensions. Conclusions and Implications for Cancer Survivors : These findings highlight the significant impact of SDoH on cancer survivors' HRQoL and support the need for targeted interventions and policies to mitigate the adverse effects of negative SDoH factors. Addressing economic, educational, and healthcare disparities is crucial for improving the long-term health and quality of life of cancer survivors.

Capacity building for road safety in LMICs: the need for a sustainable local knowledge and research infrastructure

Road crashes continue to be a major cause of death and serious injury for low- and middle-income countries (LMICs). At the global level, 90% of traffic fatalities occur in these countries with a dramatic daily amount of 3 260 road deaths, many of whom are children. The first UN Decade of Action for Road Safety 2011–2020 was designed to develop a massive movement towards a decrease of these numbers. This resulted in many initiatives to introduce the safe system approach in LMICs, i.e. to implement road safety management, make roads, road users, and vehicles safer, and improve post-crash health care. International organisations together with NGOs and universities prepared road safety guides and manuals, gave courses and webinars, introduced auditing and inspection systems, with the overall intention to build capacity in LMICs. Together these actions contributed to a variety of road safety developments in LMICs but the overall results were still modest. At the third Global Ministerial Conference on Road Safety in Stockholm, 2020, and in the Global Status report by the World Health Organization, 2023, the results of all efforts were presented and evaluated. Many countries made progress through road safety management and better legislation addressing risk factors such as speeding, drinking and driving, failing to use seatbelts, and poor infrastructure design. However, the reduction in road deaths strongly lagged behind the original goals. Continued implementation of programs and development of new approaches are needed to make a breakthrough, and to reach the goals of the 2nd Decade of Action, i.e. a 50% reduction in fatalities by 2030, and the same percentage reduction in injuries. The present position paper argues that despite the enormous amount of road safety information, which has been and is ‘sent’ to LMICs, and despite the quality and robustness of international organisations behind these programs, there is a shortfall in the scale of the knowledge and research infrastructure currently existing in LMICs, which is needed to ‘receive and transfer’ this knowledge. In order to develop evidence-based policy, LMICs need research programs that are able to transfer safe system principles to the local context and culture. Several literature overviews illustrate the lack of such research in LMICs, i.e. the limited number of programs at local universities and research institutes. Although recently initiatives have been taken in some countries, the implementation of such programs is urgently needed. Based on this observation we call on international organisations to establish a special program for the development of a sustainable road safety knowledge and research infrastructure in LMICs. Such structural local capacity is a prerequisite to translate international road safety knowledge into local guidelines and to develop an evidence-based road safety policy. Most importantly, this local infrastructure will give countries a national knowledge bank, thus providing them with an urgently needed sustainable road safety memory.

Introduction to the Special Issue on Wars and Disasters: Advancing Care during Times of Crisis

Civilian mass-casualty disasters and armed conflict share many features, including the fact that both maximally challenge multidisciplinary burn teams. Rigorous training is required to build teams and systems that can respond effectively. One of the critical but potentially overlooked components of readiness for crisis care is a robust clinical research program. Rather than stalling progress, disasters and conflict over the last 100 years consistently energized advances in care. This was made possible by the hard work of our predecessors to learn from the crisis in the midst of the crisis, and resulted in significant reductions in postburn mortality. Now, further work is needed not only to maintain these improvements in mortality, but also to understand the long-term functional outcomes and to improve the quality of life of burn survivors. Clinical research programs to address these issues must be established now, so that we are optimally prepared for the next conflict or disaster.

Reconceptualizing and Defining Exposomics within Environmental Health: Expanding the Scope of Health Research.

Exposomics, the study of the exposome, is flourishing, but the field is not well defined. The term "exposome" refers to all environmental influences and associated biological responses throughout the lifespan. However, this definition is very similar to that of the term "environment"-the external elements and conditions that surround and affect the life and development of an organism. Consequently, the exposome seems to be nothing more than a synonym for the environment, and exposomics a synonym for environmental research. As a result, some have rebranded their "standard" environmental health research with the neologistic exposome term, whereas others ignore or seek to abandon the seemingly redundant concept of the exposome. We argue that exposomics needs to sharpen its mission focus to counteract this apparent redundancy. Exposomics should be defined as a research program in environmental health aimed at enabling a comprehensive and discovery-driven approach to identifying environmental determinants of human health. Similar to the aim of the Human Genome Project, exposomics aims to analyze the complete complexity of exposures and their corresponding biological responses. Exposomics' primary premise is that the existence of undiscovered, potentially interconnected, nongenetic (environmental) risk factors for health necessitates a comprehensive discovery-driven analysis approach. We argue that exposomics researchers should adopt our reconceptualization of exposomics and focus on the productiveness and integrity of their research program: its purpose and principles. We suggest that exposomics researchers should coordinate the writing of reviews that assess the program's productiveness and integrity, as well as provide a platform for exposomics researchers to define their vision for the field. https://doi.org/10.1289/EHP14509.

53914 Association between Atopic Dermatitis and Peripheral Vascular Disease: A Cross-Sectional Study in the All of Us Research Program

53914 Association between Atopic Dermatitis and Peripheral Vascular Disease: A Cross-Sectional Study in the All of Us Research Program

54311 Autoimmune co-morbidities associated with vitiligo: A United States population-based case-control analysis using the All of Us research program

54311 Autoimmune co-morbidities associated with vitiligo: A United States population-based case-control analysis using the All of Us research program

50836 Obstructive sleep apnea in psoriasis and hidradenitis suppurativa: a case-control analysis of the All of Us Research Program

50836 Obstructive sleep apnea in psoriasis and hidradenitis suppurativa: a case-control analysis of the All of Us Research Program

Multiancestry transferability of a polygenic risk score for diverticulitis

ObjectivePolygenic risk scores (PRS) for diverticular disease must be evaluated in diverse cohorts. We sought to explore shared genetic predisposition across the phenome and to assess risk stratification in individuals...