bluuebunny/crossref_metadata_2025 huggingface dataset:
Learning
Authors: Nordell Shawn E. , Valone Thomas J.
Published: August 2024

This chapter discusses the broad array of ways that animals learn, ranging from simple habituation to complex problem-solving. The chapter also examines the physical changes in the brain that are associated with learning and goes on to discuss individual and social learning and looks in particular at how the latter can lead to the development of animal traditions and even culture.
Mating Behavior
Authors: Nordell Shawn E. , Valone Thomas J.
Published: August 2024

This chapter examines the mating behavior of animals. It also uses the Parker model to expound on the evolution of anisogamy. On the other hand, parental investment theory predicts that the sex investing more time and energy on the offspring can benefit by being selective in its choice of mates. On the other hand, sexual selection can happen after mating via sperm competition and mate guarding of animals. The chapter also notes mate choice copying wherein the choice is impacted by the decision of other animals' mating decisions. Additionally, mating choice can evolve as an indirect benefit to offspring.
Urban Environments, Air Pollution, and Human Health
Authors: Sturman Andrew , Quénol Hervé
Published: August 2024

This chapter explores the interplay of urban environments, air pollution, and human health. Intensive urbanization and related commercial and industrial activity have caused significant reductions in air quality. Essentially, the spatio-temporal variability of urban climate is the result of very strong heterogeneity of urbanized space. Urban air pollution refers to the atmospheric constituents in urban areas that are modified, which have detrimental impacts on human health and the environment. The chapter considers the impact of climate change on the urban environment, such as a rise in the sea level and the effect of climate change on public health. The chapter cites that the urban adaptation strategy should include several components, such as improvements in the efficiency of urban infrastructure.
Natural Ecosystems
Authors: Sturman Andrew , Quénol Hervé
Published: August 2024

This chapter tackles the complex relationship between climate change and natural ecosystems. It explains that climate has a fundamental control on the distribution of natural ecosystems through its influence on key environmental processes. However, climate change is the only factor currently having a detrimental effect on natural ecosystems. The chapter also considers the methods for assessing climate change's effects on natural ecosystems. It shows that adaptation strategies need to be developed at the regional and local scales based on an improved understanding of how ecosystems work in specific areas. This is especially the case as the resilience of ecosystems in different areas varies considerably.
Pharmaceutical mathematical terminology
Authors: Langley Chris , Perrie Yvonne
Published: August 2024

This chapter outlines and explains in detail all the key terminologies relating to pharmaceutical calculations. It introduces the range of mathematical terminology used within the fields of pharmaceutical compounding and medication supply. Owing to the risk caused by incorrect calculation of a pharmaceutical dose as a result of unfamiliarity with one or more pharmaceutical terms, it is vital to be confident in the ability to interpret pharmaceutical terminology without error. The chapter details two basic types of conversion between standard units: conversion between units within the same system at a differing magnitude and conversion between units of different systems. Calculations involving conversions between units within the same system involve alteration of a particular value from one magnitude to another.
Maths supporting the science of pharmacy
Authors: Langley Chris , Perrie Yvonne
Published: August 2024

This chapter reviews calculations relating to the core pharmaceutical sciences and covers displacement, freezing points, molarity, and molecular concentration. It outlines key factors that influence the formulation of medicines, which need to be considered in the preparation of a range of products including dry powder antibiotics, injections for reconstitution, suppositories, and pessaries. It also examines the clinical impact of isotonicity and serum osmolality, including the ways to prepare isotonic solutions. The chapter looks at the impact of adding solids to liquids in terms of final volumes and concentrations. It discusses solutions and suspensions that are prepared by reconstituting solids with a diluent prior to be given to the patient.
Quantities to dispense: accuracy within supply
Authors: Langley Chris , Perrie Yvonne
Published: August 2024

This chapter covers all aspects of pharmaceutical calculations relating to the quantities of medicines for dispensing in relation to different medication orders. It discusses aspects of dispensing relating to special containers and the supply of medication affected by expiry of the medicinal product during the period of supply. It also reviews problems with medication supply, especially repeating supply of medication for chronic illnesses, as there needs to be a range of pack sizes of pre-packed medication to cover different month lengths. The chapter highlights confusion that can occur when the number of dosage units to be taken at each administration varies. It considers how the supply of solid dosage forms is relatively straightforward from a calculation perspective.
Biotechnology and Food and Drink Production
Authors: Yeoman Kay , Fahnert Beatrix , Lea-Smith David , Clarke Tom
Published: August 2024

This chapter details the interplay of biotechnology with food and drink production. Humans have had a long and rich history of using microbes for food and beverage production. The technique of preservation allows microbial growth, which helps with pH changes, gas production, gastronomic value, shelf life, and the texture of the food. The chapter also explains that microbes can be used to make components for food production, including amino acids, enzymes, oils, and polysaccharides. Moreover, microorganisms also play a role in the production of food supplements, such as vitamins and pigments. Essentially, different microbes can be used to make biomass for consumption. However, there are issues with safety and acceptability.
Clinical immunology
Authors: Blann Andrew
Published: August 2024

This chapter looks into key concepts in the study of clinical immunology. It defines immunodeficiency as a state in which the immune system fails to protect the body as it should. Moreover, a number of aspects of immunodeficiency are characterized by quantitative and qualitative changes in leukocytes and the antibodies and complement of the humoral immune response. The chapter describes the key features of hypersensitivity, the aetiology of autoimmune disease, and the basis of inflammatory connective tissue diseases. It also provides an overview of the processes of transplantation of organs, which is an increasingly successful therapy for end-stage disease that is dependent on human leukocyte antigen (HLA) matching and immunosuppressive drugs.
Diseases of malnutrition and the digestive system
Authors: Blann Andrew
Published: August 2024

This chapter considers diseases of the digestive system which, as one single area of disease, was the seventh most common cause of death in England and Wales in 2021. The chapter starts with the parts of the digestive system and its respective diseases, pathology, and treatment. The upper digestive tract mainly consists of digestive organs above the diaphragm and the middle digestive tract refers to the stomach, liver, biliary system, and pancreas, while the lower digestive tract refers to small and large intestines. Next, the chapter looks at cases of undernutrition and obesity, which constitute the polar extremes of calorific intakes. The chapter highlights the importance of a good diet and nutrition before elaborating on the pathologies associated with a poor diet.
How and why do cells talk to each other?
Authors: Paxson Julia
Published: August 2024

Associate Professor
Epidemiology and the causes of cancer
Authors: Divan Aysha , Royds Janice
Published: August 2024

This chapter discusses epidemiology and the causes of cancer. Cancer is a multifactorial disease that results from the combined effects of genetic, environmental, and lifestyle factors. Epidemiology plays a key role in the identification of the influences and risk factors of cancer. The chapter then explains that cancer incidence and mortality rates for different cancers vary by geographical location, sex, gender, and ethnicity for some cancer types. Meanwhile, sporadic cancers arise due to exposure to lifestyle and environmental risks that act in combination with an individual's genetic profile. The chapter identifies effective vaccination and screening programmes to prevent some infection-related cancers.
Sustainable Communities, Cities, and Regions
Authors: Niesenbaum Richard
Published: August 2024

This chapter explores the sustainability enacted in communities, cities, and regions. Sustainable communities are made more liveable through economic development, job creation, and improved quality of life. Additionally, the development of a sustainable community also depends on transparent governance and decision-making. The chapter then discusses community sustainability within the context of broader regions in correlation to the barriers to community and regional sustainability, such as subsidies, taxes, policies, corruption, and hidden costs that favour sprawl instead of smart growth. It considers the instances where the barriers were overcome through visionary leadership and planning, participatory processes, and programs that promote sustainability.
Communication systems in the body: neural
Authors: Henney Neil , Penson Peter
Published: August 2024

This chapter details the role, structure and function of the peripheral nervous system. It cites that when things go wrong with the peripheral nervous system, the result is often severe movement disorders. Drugs that act on the somatic part of the peripheral nervous system can be useful in preventing pain or relaxing muscles during surgery. The chapter provides an overview of drugs that affect neurotransmission. Neurotransmission occurs from cell to cell across narrow gaps called synapses. Drugs that effect the peripheral nervous system include local anaesthetics and muscle relaxants. The chapter also looks into pain and sensory neurotransmission.
The autonomic nervous system
Authors: Lane Emma , Ford William
Published: August 2024

This chapter explores the autonomic nervous system (ANS). It looks into the basic physiology of the ANS in addition to the functions it provides to different organs and neurochemical transmission. Essentially, specific brain regions supervise and influence the functions of the ANS. The chapter then provides an overview of how therapeutic molecules may interfere with synaptic transmission. It also discusses non-adrenergic non-cholinergic control (NANC). It looks at the effect of the ANS on several body systems, such as the cardiovascular system, respiratory system, oculomotor system, and digestive system, by considering the context of physiology, pharmacology, and therapeutics.
Introduction to pharmaceutics
Authors: Denton Philip
Published: August 2024

This chapter introduces the key concepts surrounding pharmaceutics. It explains that medicine come in a range of forms, but all are composed of an active pharmaceutical ingredient (API). All pharmaceutical products begin as a chemical compound which interacts with a target in the body. This compound acts like a drug when it exhibits a desirable pharmacology. The chapter highlights that all pharmacists have good knowledge of medicine, the formulation of drugs, and dosage. It considers the understanding of the physicochemical properties of compounds, such as the behavior of dosage forms before their administration and in vitro and the fate of dosage forms in vivo as they make their way to the biological target.
Intrinsic link between PGRN and Gba1 D409V mutation dosage in potentiating Gaucher disease
Authors: Lin Yi , Zhao Xiangli , Liou Benjamin , Fannin Venette , Zhang Wujuan , Setchell Kenneth D R , Wang Xiaohong , Pan Dao , Grabowski Gregory A , Liu Chuan-ju , Sun Ying
Published: August 2024

Gaucher disease (GD) is caused by biallelic GBA1/Gba1 mutations that encode defective glucocerebrosidase (GCase). Progranulin (PGRN, encoded by GRN/Grn) is a modifier of GCase, but the interplay between PGRN and GCase, specifically GBA1/Gba1 mutations, contributing to GD severity is unclear. Mouse models were developed with various dosages of Gba1 D409V mutation against the PGRN deficiency (Grn−/−) [Grn−/−;Gba1D409V/WT (PG9Vwt), Grn−/−;Gba1D409V/D409V (PG9V), Grn−/−;Gba1D409V/Null (PG9VN)]. Disease progression in those mouse models was characterized by biochemical, pathological, transcriptomic, and neurobehavioral analyses. Compared to PG9Vwt, Grn−/−;Gba1WT/Null and Grn−/− mice that had a higher level of GCase activity and undetectable pathologies, homozygous or hemizygous D409V in PG9V or PG9VN, respectively, resulted in profound inflammation and neurodegeneration. PG9VN mice exhibited much earlier onset, shorter life span, tissue fibrosis, and more severe phenotypes than PG9V mice. Glycosphingolipid accumulation, inflammatory responses, lysosomal-autophagy dysfunction, microgliosis, retinal gliosis, as well as α-Synuclein increases were much more pronounced in PG9VN mice. Neurodegeneration in PG9VN was characterized by activated microglial phagocytosis of impaired neurons and programmed cell death due to necrosis and, possibly, pyroptosis. Brain transcriptomic analyses revealed the intrinsic relationship between D409V dosage, and the degree of altered gene expression related to lysosome dysfunction, microgliosis, and neurodegeneration in GD, suggesting the disease severity is dependent on a GCase activity threshold related to Gba1 D409V dosage and loss of PGRN. These findings contribute to a deeper understanding of GD pathogenesis by elucidating additional underlying mechanisms of interplay between PGRN and Gba1 mutation dosage in modulating GCase function and disease severity in GD and GBA1-associated neurodegenerative diseases.
Lifestyle Intervention Modulates the CD4+ T Cell Profile in the Blood of Crohn’s Disease Patients
Authors: Mekes-Adamczyk Alexandra , Gausmann Nadine , Öznur Özlem , Pfuhlmann Katrin , Dziobaka Jan , Buer Jan , Langhorst Jost , Westendorf Astrid M
Published: August 2024

Background

Crohn’s disease (CD) significantly affects patients’ well-being and is influenced by stress and lifestyle factors, highlighting the importance of improving quality of life in CD management. An imbalance between pro- and anti-inflammatory CD4+ T cell responses is a key factor in CD, and stress has been shown to alter the function of CD4+ T cells. Therefore, this study aimed to evaluate the effect of a mind-body medicine stress management and lifestyle modification (MBM) program on the CD4+ T cell profile in CD patients.

Methods

Circulating CD4+ T cells from CD patients were analyzed by flow cytometry following the MBM program. Patients were randomly assigned to either a guided intervention group (IG) or a self-guided waitlist control group (CG) over a 9-month trial and compared with healthy blood donors.

Results

Lifestyle intervention reduced regulatory T cell (Treg) frequencies in the blood of CD patients. Notably, we observed a significant correlation between the quality of life improvement and Treg frequencies in the IG but not in the CG. Furthermore, differential activation and expression of the gut-homing molecules G protein–coupled receptor 15 and CCR9 on circulating Tregs and CD4+ effector T cells were detected in both the IG and CG.

Conclusions

The MBM program, whether guided or self-directed, has the potential to restore the CD4+ T cell profile of CD patients to levels comparable to healthy blood donors. Lifestyle interventions may benefit CD progression, symptoms, and immunological status, but further analysis is needed to substantiate these findings and to fully understand their clinical implications. (ClinicalTrials.gov: NCT05182645).
Habitat-specific response of fish assemblages in a small fully protected urban MPA
Authors: Ventura Patrícia , Gautier-Debernardi Jacqueline , Di Franco Eugenio , Francour Patrice , Di Franco Antonio , Pey Alexis
Published: August 2024

This study aims at assessing the reserve effect on fish assemblage in a small urban fully protected and highly enforced Marine Protected Area (MPA), Larvotto MPA (Monaco, Mediterranean Sea). The data about fish density, size, and biomass was collected by underwater visual census in the MPA and unprotected areas in two habitats, artificial rocky substrates and Posidonia oceanica meadows. On artificial rocky substrates, we recorded significantly higher fish biomass within the MPA compared to unprotected areas, while no significant difference was detected on Posidonia, with this suggesting the habitat-specific responses of fish assemblages to protection. Here we highlight the potential effectiveness of highly enforced small-sized urban MPAs, such as the Larvotto MPA, in generating ecological benefits, and speculate about their potential role in supporting networks of MPAs. This study supports increased attention to urban MPAs in conservation efforts, emphasizing the need for efficient management strategies in the face of ongoing coastal expansion.
Identification of Phosphodiesterase-7A (PDE7A) as a Novel Target for Reducing Ethanol Consumption in Mice
Authors: Wei Ran , Zong Fangjiao , Dong Jiahao , Zhao Wei , Zhang Fangfang , Wang Wei , Zhao Shuang , Wang Ziqi , Zhang Fang , Zhang Han-Ting
Published: August 2024

Background

Ethanol elicits a rapid stimulatory effect and a subsequent, prolonged sedative response, which are potential predictors of EtOH consumption by decreasing adenosine signaling; this phenomenon also reflects the obvious sex difference. cAMP (cyclic Adenosine Monophosphate)-PKA (Protein Kinase A) signaling pathway modulation can influence the stimulatory and sedative effects induced by EtOH in mice. This study’s objective is to clarify the role of phosphodiesterase (PDE) in mediating the observed sex differences in EtOH responsiveness between male and female animals.

Methods

EtOH was administered i.p. for 7 days to identify the changes in PDE isoforms in response to EtOH treatment. Additionally, EtOH consumption and preference of male and female C57BL/6J mice were assessed using the drinking-in-the-dark and 2-bottle choice tests. Further, pharmacological inhibition of PDE7A heterozygote knockout mice was performed to investigate its effects on EtOH-induced stimulation and sedation in both male and female mice. Finally, Western blotting analysis was performed to evaluate the alterations in cAMP-PKA/Epac2 pathways.

Results

EtOH administration resulted in an immediate upregulation in PDE7A expression in female mice, indicating a strong association between PDE7A and EtOH stimulation. Through the pharmacological inhibition of PDE7A KD mice, we have demonstrated for the first time, to our knowledge, that PDE7A selectively attenuates EtOH responsiveness and consumption exclusively in female mice, whichmay be associated with the cAMP-PKA/Epac2 pathway and downstream phosphorylation of CREB and ERK1/2.

Conclusions

Inhibition or knockdown of PDE7A attenuates EtOH responsivenessand consumption exclusively in female mice, which is associated with alterations in the cAMP-PKA/Epac2 signaling pathways, thereby highlighting its potential as a novel therapeutic target for alcohol use disorder.
On adversarial robustness and the use of Wasserstein ascent-descent dynamics to enforce it
Authors: García Trillos Camilo Andrés , García Trillos Nicolás
Published: August 2024

We propose iterative algorithms to solve adversarial training problems in a variety of supervised learning settings of interest. Our algorithms, which can be interpreted as suitable ascent-descent dynamics in Wasserstein spaces, take the form of a system of interacting particles. These interacting particle dynamics are shown to converge toward appropriate mean-field limit equations in certain large number of particles regimes. In turn, we prove that, under certain regularity assumptions, these mean-field equations converge, in the large time limit, toward approximate Nash equilibria of the original adversarial learning problems. We present results for non-convex non-concave settings, as well as for non-convex concave ones. Numerical experiments illustrate our results.
Biological invasions and epidemics with nonlocal diffusion along a line
Authors: Berestycki Henri , Roquejoffre Jean-Michel , Rossi Luca
Published: August 2024

To James D. Murray, with our admiration.

The goal of this work is to understand and quantify how a line with nonlocal diffusion given by an integral enhances a reaction-diffusion process occurring in the surrounding plane. This is part of a long-term programme where we aim at modelling, in a mathematically rigorous way, the effect of transportation networks on the speed of biological invasions or propagation of epidemics.

We prove the existence of a global propagation speed and characterize in terms of the parameters of the system the situations where such a speed is boosted by the presence of the line. In the course of the study we also uncover unexpected regularity properties of the model. On the quantitative side, the two main parameters are the intensity of the diffusion kernel and the characteristic size of its support. One outcome of this work is that the propagation speed will significantly be enhanced even if only one of the two is large, thus broadening the picture that we have already drawn in our previous works on the subject, with local diffusion modelled by a standard Laplacian.

We further investigate the role of the other parameters, enlightening some subtle effects due to the interplay between the diffusion in the half plane and that on the line. Lastly, in the context of propagation of epidemics, we also discuss the model where, instead of a diffusion, displacement on the line comes from a pure transport term.
Copy Number Variations of Plasmodium vivax DBP1, EBP/DBP2, and RBP2b in Ethiopians Who Are Duffy Positive and Duffy Negative
Authors: Pestana Kareen , Ford Anthony , Rama Rei , Abagero Beka , Kepple Daniel , Tomida Junya , Popovici Jean , Yewhalaw Delenasaw , Lo Eugenia
Published: August 2024

Recent evidence challenges the belief that individuals who are Duffy-negative are resistant to Plasmodium vivax due to lacking the Duffy antigen receptor for chemokines. Erythrocyte-binding protein (EBP/DBP2) has shown moderate binding to Duffy-negative erythrocytes in vitro. Reticulocyte-binding protein 2b (RBP2b) interactions with transferrin receptor 1 suggest involvement in Duffy-negative infections. Gene copy number variations in PvDBP1, PvEBP/DBP2, and PvRBP2b were investigated in Duffy-positive and Duffy-negative P vivax infections from Ethiopia. Among Duffy-positive samples, 34% displayed PvDBP1 duplications (Cambodian type). In Duffy-negative infections, 30% showed duplications, mostly Cambodian type. For PvEBP/DBP2 and PvRBP2b, Duffy-positive samples exhibited higher duplication rates (1–8 copies for PvEBP/DBP2, 46%; 1–5 copies for PvRBP2b, 43%) as compared with Duffy-negative samples (20.8% and 26%, respectively). The range of copy number variations was lower in Duffy-negative infections. Demographic and clinical factors associated with gene multiplications in both Duffy types were explored, enhancing understanding of P vivax evolution in Africans who are Duffy negative.
The active form of vitamin D (calcitriol) promotes CXCR5 expression during follicular helper T cell differentiation
Authors: Iwata Makoto , Takada Ayumi , Sakamoto Rei , Song Si-Young , Ito Etsuro
Published: August 2024

Follicular helper T (Tfh) cells promote B cell differentiation and antibody production in the B cell follicles of secondary lymphoid organs. Tfh cells express their signature transcription factor BCL6, interleukin (IL)-21, and surface molecules including inducible T cell costimulator (ICOS), programmed cell death-1 (PD-1), and C-X-C motif chemokine receptor 5 (CXCR5). Migration of Tfh cells to B cell follicles largely depends on the CXCR5 expression induced by interactions with antigen-presenting dendritic cells in the T cell area. How Tfh cells acquire sufficient levels of CXCR5 expression, however, has remained unclear. Using our in vitro culture system to generate CXCR5low Tfh-like cells from naive CD4+ T cells with IL-6 in the absence of other cell types, we found that the active form of vitamin D, calcitriol, markedly enhanced CXCR5 expression after the release from persistent T cell receptor (TCR) stimulation. CH-223191, an aryl hydrocarbon receptor antagonist, further enhanced CXCR5 expression. IL-12 but not IL-4, in place of IL-6, also supported calcitriol to enhance CXCR5 expression even before the release from TCR stimulation, whereas the cell viability sharply decreased after the release. The Tfh-like cells generated with IL-6 and calcitriol exhibited chemotaxis toward C-X-C motif chemokine ligand 13 (CXCL13), expressed IL-21, and helped B cells to produce IgG antibodies in vitro more efficiently than Tfh-like cells generated without added calcitriol. Calcitriol injections into antigen-primed mice increased the proportion of CXCR5+PD-1+CD4+ cells in their lymphoid organs, and enhanced T cell entry into B cell follicles. These results suggest that calcitriol promotes CXCR5 expression in developing Tfh cells and regulates their functional differentiation.
How far do forest container mosquitoes (Diptera: Culicidae) invade rural and urban areas in Japan? — Simple landscape ecology with comparison of the invasiveAedesecology between native and invasive ranges
Authors: Mogi Motoyoshi , Armbruster Peter A , Eritja Roger , Sunahara Toshihiko , Tuno Nobuko
Published: August 2024

The distribution of container mosquitoes in relation to distances from forests was studied in temperate Japan. Mosquito larvae were collected between May and September in 4 years from tree holes, bamboo stumps, riverine rock pools, and artificial containers; sampling ranged spatially from the mountain forest across the deforested plain developed as agriculture and urban areas to the seacoast. Although tree holes, bamboo stumps, and artificial containers existed throughout the deforested plain area, 10 container species of 6 genera were found virtually only within 5 km from the nearest forest edge. Worldwide invasive Aedes albopictus (Skuse) and Aedes japonicus (Theobald) of Asian origin showed unique occurrence patterns different from other container species and from each other. Ae. japonicus was dominant in artificial containers in and near the forest but minor in forest natural containers and only occurred within 5 km from the forest. Ae. albopictus was minor in the forest irrespective of container types but not bound to the forest and dominant in natural and artificial containers throughout rural and urban areas. The 5-km range was designated as the circum-forest zone for container mosquitoes (except Ae. albopictus) in Japan, and an expanded concept, circum-boundary zone, is proposed. The widths of these zones primarily depend on the dispersal traits of mosquitoes. Whether the relation of Ae. albopictus and Ae. japonicus to forests we observed are common in the native and invasive ranges is discussed. The study of across-ecosystem dispersal is important for mosquito management under anthropogenically changing environments due to either deforestation or green restoration.
Virtual Pooled Registry-Cancer Linkage System: an improved method for ascertaining cancer diagnoses
Authors: Deapen Dennis , Clerkin Castine , Howe William , Green Don , Johnson Christopher J , Kohler Betsy A , Landgren Annelie M , Preda Anca , Elena Joanne , Penberthy Lynne
Published: August 2024

Background

The National Cancer Institute funds many large cohort studies that rely on self-reported cancer data requiring medical record validation. This is labor intensive, costly, and prone to underreporting or misreporting of cancer and disparity-related differential response. US population-based central cancer registries identify incident cancer within their catchment area, yielding all malignant neoplasms and benign brain and central nervous system tumors with standardized data fields. This manuscript describes the development, implementation, and features of a system to facilitate linkage between cohort studies and cancer registries and the release of cancer registry data for matched cohort participants.

Methods

The Virtual Pooled Registry-Cancer Linkage System (VPR-CLS) provides an online system to link cohorts with multiple state cancer registries by 1) securely transmitting a study file to registries, 2) providing an optimized linkage algorithm to generate preliminary match counts, and 3) providing a streamlined process and templated forms for submitting and tracking data requests for cohort participants who matched with registries.

Results

In 2022, the VPR-CLS launched with 45 registries, covering 95% of the US state populations and Puerto Rico. Registries have linked with 15 studies having 14 273-10.9 million participants. Except in 1 study, linkage sensitivity ranged from 87.0% to 99.9%. Numerous registries have adopted the VPR-CLS templated institutional review board–registry application (n = 39), templated data use agreement (n = 25), and central institutional review board (n = 16).

Conclusions

The VPR-CLS markedly improves ascertainment of cancer outcomes and is the preferred approach for determination of outcomes from cohort studies, postmarketing surveillance, and clinical trials.
Reporting tumor genomic test results to SEER registries via linkages
Authors: Petkov Valentina I , Byun Jung S , Ward Kevin C , Schussler Nicola C , Archer Natalie P , Bentler Suzanne , Doherty Jennifer A , Durbin Eric B , Gershman Susan T , Cheng Iona , Insaf Tabassum , Gonsalves Lou , Hernandez Brenda Y , Koch Lori , Liu Lihua , Monnereau Alain , Morawski Bozena M , Schwartz Stephen M , Stroup Antoinette , Wiggins Charles , Wu Xiao-Cheng , Bonds Sarah , Negoita Serban , Penberthy Lynne
Published: August 2024

Background

Precision medicine has become a mainstay of cancer care in recent years. The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program has been an authoritative source of cancer statistics and data since 1973. However, tumor genomic information has not been adequately captured in the cancer surveillance data, which impedes population-based research on molecular subtypes. To address this, the SEER Program has developed and implemented a centralized process to link SEER registries’ tumor cases with genomic test results that are provided by molecular laboratories to the registries.

Methods

Data linkages were carried out following operating procedures for centralized linkages established by the SEER Program. The linkages used Match*Pro, a probabilistic linkage software, and were facilitated by the registries’ trusted third party (an honest broker). The SEER registries provide to NCI limited datasets that undergo preliminary evaluation prior to their release to the research community.

Results

Recently conducted genomic linkages included OncotypeDX Breast Recurrence Score, OncotypeDX Breast Ductal Carcinoma in Situ, OncotypeDX Genomic Prostate Score, Decipher Prostate Genomic Classifier, DecisionDX Uveal Melanoma, DecisionDX Preferentially Expressed Antigen in Melanoma, DecisionDX Melanoma, and germline tests results in Georgia and California SEER registries.

Conclusions

The linkages of cancer cases from SEER registries with genomic test results obtained from molecular laboratories offer an effective approach for data collection in cancer surveillance. By providing de-identified data to the research community, the NCI’s SEER Program enables scientists to investigate numerous research inquiries.
Toward real-time reporting of cancer incidence: methodology, pilot study, and SEER Program implementation
Authors: Chen Huann-Sheng , Negoita Serban , Schwartz Steve , Hsu Elizabeth , Hafterson Jennifer , Coyle Linda , Stevens Jennifer , Fernandez Anna , Potts Mary , Feuer Eric J
Published: August 2024

Background

A lag time between cancer case diagnosis and incidence reporting impedes the ability to monitor the impact of recent events on cancer incidence. Currently, the data submission standard is 22 months after a diagnosis year ends, and the reporting standard is 27.5 months after a diagnosis year ends. This paper presents the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) Program’s efforts to minimize the lag and achieve “real-time” reporting, operationalized as submission within 2 months from the end of a diagnosis year.

Methods

Technology for rapidly creating a consolidated tumor case (CTC) from electronic pathology (e-path) reports is described. Statistical methods are extended to adjust for biases in incidence rates due to reporting delays for the most recent diagnosis years.

Results

A registry pilot study demonstrated that real-time submissions can approximate rates obtained from 22-month submissions after adjusting for reporting delays. A plan to be implemented across the SEER Program rapidly ascertains unstructured e-path reports and uses machine learning algorithms to translate the reports into the core data items that comprise a CTC for incidence reporting. Across the program, cases were submitted 2 months after the end of the calendar year. Registries with the most promising baseline values and a willingness to modify registry operations have joined a program to become certified as real-time reporting.

Conclusion

Advances in electronic reporting, natural language processing, registry operations, and statistical methodology, energized by the SEER Program’s mobilization and coordination of these efforts, will make real-time reporting an achievable goal.
The SEER Program’s longstanding commitment to making cancer resources available
Authors: Murphy Patricia K , Sellers Mark E , Bonds Sarah H , Scott Susan
Published: August 2024

The Surveillance, Epidemiology, and End Results (SEER) Program, an authoritative source of cancer statistics in the United States, has been funded by the National Cancer Institute (NCI) since 1973. The goals of SEER include measuring the cancer burden in the United States, making the results available, and supporting cancer research. These goals render products that serve as resources for different audiences, such as cancer registrars, researchers, and the public. Cancer registrars have access to a dedicated tab on the SEER website for questions, assistance with cancer coding, and training and technical resources such as SEER*Rx and SEER Data Management System (SEER*DMS). For researchers, SEER provides access to databases and software such as SEER*Stat and other linked databases such as SEER-Medicare that may offer answers to emerging issues in the field of cancer outcomes, cancer burden, health disparities, healthcare access, diagnosis, and prevention. The public can access cancer materials such as the SEER Cancer Stat Facts sheets, SEER*Explorer, and Did You Know? video series to learn more about cancer. SEER continues to update its resources with and ahead of legislation such as the Plain Writing Act and 21st Century Integrated Digital Experience Act (IDEA) to improve both clarity and user experience. Moving forward, SEER continues to promote awareness of SEER resources, remains accessible and understandable across all audiences, and standardizes how new resources are shared with these groups. The longstanding commitment to making cancer resources available is fundamental to the value of SEER, as evidenced by testimonials from members of various audience types.
Pre-implementation determinants for digital mental health integration in Chicago pediatric primary care
Authors: Stiles-Shields Colleen , Gustafson Erika L , Lim Paulina S , Bobadilla Gabriella , Thorpe Dillon , Summersett Williams Faith C , Donenberg Geri R , Julion Wrenetha A , Karnik Niranjan S
Published: August 2024

Objective

Pediatric primary care (PPC) is a common treatment site for pediatric mental health, but it is currently unable to meet the needs of all teen patients, particularly those with minoritized identities and/or marginalized experiences. Digital mental health (DMH) low-intensity treatments (LITs) can increase mental health screening and care capacity in PPC, but how this is done successfully without burdening providers, patients, or families is unclear. This paper presents a pre-implementation study aimed at understanding the implementation context (PPCs in Chicago, IL) for a specific DMH LIT.

Method

Using a mixed-methods design, quantitative data from an online survey of providers assessed current DMH practices in PPC, and qualitative interviews with Pediatricians and Pediatric Psychologists examined implementation determinants for a specific DMH LIT. Quantitative data were analyzed using descriptive statistics, and interviews were analyzed using rapid qualitative assessment.

Results

Survey reports (n = 105) and interviews (n = 6) indicated low current use of DMH. Providers in PPC clinics voiced multiple reasons for low usage and low perceived feasibility, including: Consolidated Framework for Implementation Research (CFIR) Inner Setting Domain (PPC clinic workflow, responsibility and ethical considerations, patient privacy and confidentiality), CFIR Outer Setting Domain (hospital and healthcare system factors), CFIR Innovation Domain (DMH design), and a cross-cutting theme of safety.

Conclusions

Provider-reported low feasibility for integrating DMH in PPC is a call to action to partner with interdisciplinary colleagues and identify how such settings can ethically and seamlessly deliver digital evidence-based and accessible screening and care prior to implementation.
Embrace the noise: it is ok to ignore measurement error in a covariate, sometimes
Authors: Dong Hao , Millimet Daniel L
Published: August 2024

In linear regression models, measurement error in a covariate causes ordinary least squares (OLS) to be biased and inconsistent. Instrumental variables (IV) is a common solution. While IV is also biased, it is consistent. Here, we undertake an asymptotic comparison of OLS and IV in the case where a covariate is mismeasured for ⌊Nδ⌋ of N observations with δ∈[0,1]. We show that OLS is consistent for δ<1 and is asymptotically normal and more efficient than IV for δ<0.5. Simulations and an application to the impact of body mass index on family income demonstrate the practical usefulness of this result.
Extended fiducial inference: toward an automated process of statistical inference
Authors: Liang Faming , Kim Sehwan , Sun Yan
Published: August 2024

While fiducial inference was widely considered a big blunder by R.A. Fisher, the goal he initially set—‘inferring the uncertainty of model parameters on the basis of observations’—has been continually pursued by many statisticians. To this end, we develop a new statistical inference method called extended Fiducial inference (EFI). The new method achieves the goal of fiducial inference by leveraging advanced statistical computing techniques while remaining scalable for big data. Extended Fiducial inference involves jointly imputing random errors realized in observations using stochastic gradient Markov chain Monte Carlo and estimating the inverse function using a sparse deep neural network (DNN). The consistency of the sparse DNN estimator ensures that the uncertainty embedded in observations is properly propagated to model parameters through the estimated inverse function, thereby validating downstream statistical inference. Compared to frequentist and Bayesian methods, EFI offers significant advantages in parameter estimation and hypothesis testing. Specifically, EFI provides higher fidelity in parameter estimation, especially when outliers are present in the observations; and eliminates the need for theoretical reference distributions in hypothesis testing, thereby automating the statistical inference process. Extended Fiducial inference also provides an innovative framework for semisupervised learning.
Politeness and Authority in 3 John: Epistolary Phraseology and Rhetoric Reconsidered
Authors: Kim Kyu Seop
Published: August 2024

This paper examines the phraseology of three epistolary formulae—namely, the formula valetudinis initialis (opening health wish formula), the formula of joy, and the καλῶς ποιήσεις formula, in Greco-Egyptian private letters written between the first century bce and third century ce. In particular, we observe that the letter writers make an opening health wish customarily when the letter recipients’ position/status is higher or at least equal to the writers—but rarely when the recipients’ position/status is lower than the writers. Furthermore, when the opening health wishes were made in expanded and reconfigured forms, they signal intensified courtesy to the recipients. The formula of joy also reinforced the favourable atmosphere when persuasion or request was intended. In this vein, the expanded and reconfigured formula valetudinis initialis used together with the formula of joy in 3 John 2–4 shows that the Elder does not intend to write his letter from the position of a higher authority. Furthermore, in requesting hospitality, he uses the καλῶς ποιήσεις formula, indicating his intention to persuade Gaius, whom he also includes in ‘us’ (3 John 12). Thus, the epistolary rhetoric of 3 John fits better with a correspondence between partners rather than an exhortation in an institutionalised hierarchy, unlike the case of the Ignatian letters.
Stellar flares are far-ultraviolet luminous
Authors: Berger Vera L , Hinkle Jason T , Tucker Michael A , Shappee Benjamin J , van Saders Jennifer L , Huber Daniel , Reep Jeffrey W , Sun Xudong , Yang Kai E
Published: August 2024

We identify 182 flares on 158 stars within 100 pc of the Sun in both the near-ultraviolet (NUV; $1750\!-\!2750$ Å) and far-ultraviolet (FUV; $1350\!-\!1750$ Å) using high-cadence light curves from the Galaxy Evolution Explorer. Ultraviolet (UV) emission from stellar flares plays a crucial role in determining the habitability of exoplanetary systems. However, whether such UV emission promotes or threatens such life depends strongly on the energetics of these flares. Most studies assessing the effect of flares on planetary habitability assume a 9000 K blackbody spectral energy distribution that produces more NUV flux than FUV flux ($\mathcal {R} \equiv F_{\rm FUV} / F_{\rm NUV} \approx \frac{1}{6}$). Instead, we observe the opposite with the excess FUV reaching $\mathcal {R} \approx \frac{1}{2}\!-\!2$, roughly $3\!-\!12$ times the expectation of a 9000 K blackbody. The ratio of FUV to NUV time-integrated flare energies is 3.0 times higher on average than would be predicted by a constant 9000 K blackbody during the flare. Finally, we find that the FUV/NUV ratio at peak tentatively correlates (${\sim} 2 \sigma$ significance) both with total UV flare energy and with the G − RP colour of the host star. On average, we observe higher FUV/NUV ratios at peak in $E_{\text{UV}}\gt 10^{32}$ erg flares and in flares on fully convective stars.
The Possible Earliest Allopolyploidization in Tracheophytes Revealed by Phylotranscriptomics and Morphology of Selaginellaceae
Authors: Kang Jong-Soo , Yu Ji-Gao , Xiang Qiao-Ping , Zhang Xian-Chun
Published: August 2024

Selaginellaceae, originated in the Carboniferous and survived the Permian–Triassic mass extinction, is the largest family of lycophyte, which is sister to other tracheophytes. It stands out from tracheophytes by exhibiting extraordinary habitat diversity and lacking polyploidization. The organelle genome-based phylogenies confirmed the monophyly of Selaginella, with six or seven subgenera grouped into two superclades, but the phylogenetic positions of the enigmatic Selaginella sanguinolenta clade remained problematic. Here, we conducted a phylogenomic study on Selaginellaceae utilizing large-scale nuclear gene data from RNA-seq to elucidate the phylogeny and explore the causes of the phylogenetic incongruence of the S. sanguinolenta clade. Our phylogenetic analyses resolved three different positions of the S. sanguinolenta clade, which were supported by the sorted three nuclear gene sets, respectively. The results from the gene flow test, species network inference, and plastome-based phylogeny congruently suggested a probable hybrid origin of the S. sanguinolenta clade involving each common ancestor of the two superclades in Selaginellaceae. The hybrid hypothesis is corroborated by the evidence from rhizophore morphology and spore micromorphology. The chromosome observation and Ks distributions further suggested hybridization accompanied by polyploidization. Divergence time estimation based on independent datasets from nuclear gene sets and plastid genome data congruently inferred that allopolyploidization occurred in the Early Triassic. To our best knowledge, the allopolyploidization in the Mesozoic reported here represents the earliest record of tracheophytes. Our study revealed a unique triad of phylogenetic positions for a hybrid-originated group with comprehensive evidence and proposed a hypothesis for retaining both parental alleles through gene conversion.
Invasion and Amplification of Endogenous Retroviruses in Dasyuridae Marsupial Genomes
Authors: Harding Emma F , Mercer Lewis K , Yan Grace J H , Waters Paul D , White Peter A
Published: August 2024

Retroviruses are an ancient viral family that have globally coevolved with vertebrates and impacted their evolution. In Australia, a continent that has been geographically isolated for millions of years, little is known about retroviruses in wildlife, despite the devastating impacts of a retrovirus on endangered koala populations. We therefore sought to identify and characterize Australian retroviruses through reconstruction of endogenous retroviruses from marsupial genomes, in particular the Tasmanian devil due to its high cancer incidence. We screened 19 marsupial genomes and identified over 80,000 endogenous retrovirus fragments which we classified into eight retrovirus clades. The retroviruses were similar to either Betaretrovirus (5/8) or Gammaretrovirus (3/8) retroviruses, but formed distinct phylogenetic clades compared to extant retroviruses. One of the clades (MEBrv 3) lost an envelope but retained retrotranspositional activity, subsequently amplifying throughout all Dasyuridae genomes. Overall, we provide insights into Australian retrovirus evolution and identify a highly active endogenous retrovirus within Dasyuridae genomes.
Varying Selection Pressure for a Na+ Sensing Site in Epithelial Na+ Channel Subunits Reflect Divergent Roles in Na+ Homeostasis
Authors: Wang Xue-Ping , Srinivasan Priyanka , El Hamdaoui Mustapha , Blobner Brandon M , Grytz Rafael , Kashlan Ossama B
Published: August 2024

The epithelial Na+ channel (ENaC) emerged early in vertebrates and has played a role in Na+ and fluid homeostasis throughout vertebrate evolution. We previously showed that proteolytic activation of the channel evolved at the water-to-land transition of vertebrates. Sensitivity to extracellular Na+, known as Na+ self-inhibition, reduces ENaC function when Na+ concentrations are high and is a distinctive feature of the channel. A fourth ENaC subunit, δ, emerged in jawed fishes from an α subunit gene duplication. Here, we analyzed 849 α and δ subunit sequences and found that a key Asp in a postulated Na+ binding site was nearly always present in the α subunit, but frequently lost in the δ subunit (e.g. human). Analysis of site evolution and codon substitution rates provide evidence that the ancestral α subunit had the site and that purifying selection for the site relaxed in the δ subunit after its divergence from the α subunit, coinciding with a loss of δ subunit expression in renal tissues. We also show that the proposed Na+ binding site in the α subunit is a bona fide site by conferring novel function to channels comprising human δ subunits. Together, our findings provide evidence that ENaC Na+ self-inhibition improves fitness through its role in Na+ homeostasis in vertebrates.