Biological Challenge Research Articles

Embracing mortality: psychological preparation on death in the guidance of stoic philosophy

Humanity's greatest fear is the inevitability of death, the ultimate fate that all strive to evade. This collective dread of mortality stems from its perceived malevolence. Across the ages, from religious rituals promising salvation to scientific efforts to delay death, human attempts to confront mortality vary widely. Yet death remains inescapable, a natural consequence of life. While religious doctrines offer comfort through ideas of an afterlife, and science views death as a biological challenge to be postponed. Conversely, philosophy advocates for an intellectual acceptance of death's inevitability. The Stoic Philosophy, in particular, advocate for the joyful acceptance of death as an integral part of life. This philosophical stance fosters a positive perspective on death, encouraging individuals to live life to its fullest potential. Embracing death with joy entails psychological reassurance and preparatory measures for life's inevitable end. This qualitative study explores psychological preparation for death using primary and secondary data sources. Primary sources include the philosophical texts by Seneca and Marcus Aurelius, specifically "Letters to Lucilius," "On the Shortness of Life," and "Meditations." Secondary data is collected from peer-reviewed journals, books, and reports that contextualize these works within modern psychological frameworks. The primary audience includes individuals preparing for death due to age or illness and those grieving loved ones, offering a pathway to peace and understanding through Stoic wisdom. Moreover, this will be a guidance to those who work with the terminally ill people to get psychological resilience. By embracing death, Stoicism encourages both the dying and the bereaved to find psychological reassurance and encourage all to live a meaningful life in the given time frame.

Comprehensive double-mutant analysis of the Bacillus subtilis envelope using double-CRISPRi.

Understanding bacterial gene function remains a major biological challenge. Double-mutant genetic interaction (GI) analysis addresses this challenge by uncovering the functional partners of targeted genes, allowing us to associate genes of unknown function with novel pathways and unravel connections between well-studied pathways, but is difficult to implement at the genome-scale. Here, we develop and use double-CRISPRi to systematically quantify genetic interactions at scale in the Bacillus subtilis envelope, including essential genes. We discover > 1000 known and novel genetic interactions. Our analysis pipeline and experimental follow-ups reveal the distinct roles of paralogous genes such as the mreB and mbl actin homologs, and identify new genes involved in the well-studied process of cell division. Overall, our study provides valuable insights into gene function and demonstrates the utility of double-CRISPRi for high-throughput dissection of bacterial gene networks, providing a blueprint for future studies in diverse bacterial species.

Biopsychosocial well-being of nursing home residents during the COVID-19 pandemic: A 3-year longitudinal study.

The COVID-19 pandemic was not only a biological challenge, but it also took a toll on the psychological and social well-being of older adults, especially those in nursing homes. This study aims to uncover the impact of the pandemic on the biopsychosocial well-being of nursing home residents, including the role of COVID-19 positivity and social contacts. Using a sample of 247 individuals in two Northern Italian nursing homes over 3 years (2018-2021), the study analyzed a broad range of biopsychosocial variables and traced the frequency of social contacts during the lockdown. The results showed a concerning trend of worsening well-being over time during the pandemic, irrespective of COVID-19 positivity. Surprisingly, the frequency of contacts with family caregivers did not seem to have a protective role, and worsening conditions were associated with an increase in subsequent social contacts. These findings shed light on the dynamics of the biopsychosocial well-being of institutionalized individuals, and they have significant public health implications. By disentangling the roles of the pandemic period, COVID-19 positivity, and social contacts, this study provides insights into the worsening of neuropsychiatric symptoms, as well as functional and clinical indicators, in nursing home residents. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Programmed Cell Death Reversal: Polyamines, Effectors of the U-Turn from the Program of Death in Helianthus tuberosus L.

This review describes a 50-year-long research study on the characteristics of Helianthus tuberosus L. tuber dormancy, its natural release and programmed cell death (PCD), as well as on the ability to change the PCD so as to return the tuber to a life program. The experimentation on the tuber over the years is due to its particular properties of being naturally deficient in polyamines (PAs) during dormancy and of immediately reacting to transplants by growing and synthesizing PAs. This review summarizes the research conducted in a unicum body. As in nature, the tuber tissue has to furnish its storage substances to grow vegetative buds, whereby its destiny is PCD. The review's main objective concerns data on PCD, the link with free and conjugated PAs and their capacity to switch the destiny of the tuber from a program of death to one of new life. PCD reversibility is an important biological challenge that is verified here but not reported in other experimental models. Important aspects of PA features are their capacity to change the cell functions from storage to meristematic ones and their involvement in amitosis and differentiation. Other roles reported here have also been confirmed in other plants. PAs exert multiple diverse roles, suggesting that they are not simply growth substances, as also further described in other plants.

Calling the question: what is mammalian transgenerational epigenetic inheritance?

ABSTRACT While transgenerational epigenetic inheritance has been extensively documented in plants, nematodes, and fruit flies, its existence in mammals remains controversial. Several factors have contributed to this debate, including the lack of a clear distinction between intergenerational and transgenerational epigenetic inheritance (TEI), the inconsistency of some studies, the potential confounding effects of in-utero vs. epigenetic factors, and, most importantly, the biological challenge of epigenetic reprogramming. Two waves of epigenetic reprogramming occur: in the primordial germ cells and the developing embryo after fertilization, characterized by global erasure of DNA methylation and remodelling of histone modifications. Consequently, TEI can only occur if specific genetic regions evade this reprogramming and persist through embryonic development. These challenges have revived the long-standing debate about the possibility of inheriting acquired traits, which has been strongly contested since the Lamarckian and Darwinian eras. As a result, coupled with the absence of universally accepted criteria for transgenerational epigenetic studies, a vast body of literature has emerged claiming evidence of TEI. Therefore, the goal of this study is to advocate for establishing fundamental criteria that must be met for a study to qualify as evidence of TEI. We identified five criteria based on the consensus of studies that critically evaluated TEI. To assess whether published original research papers adhere to these criteria, we examined 80 studies that either claimed or were cited as supporting TEI. The findings of this analysis underscore the widespread confusion in this field and highlight the urgent need for a unified scientific consensus on TEI requirements.

Study on the prediction method of grasshopper occurrence risk in Inner Mongolia based on the maximum entropy model during the growing period.

Grasshoppers represent a significant biological challenge in Inner Mongolia's grasslands, severely affecting the region's animal husbandry. Thus, dynamic monitoring of grasshopper infestation risk is crucial for sustainable livestock farming. This study employed the Maxent model, along with remote sensing data, to forecast Oedaleus decorus asiaticus occurrence during the growing season, using grasshopper suitability habitats as a base. The Maxent model's predictive accuracy was high, with an AUC of 0.966. The most influential environmental variables for grasshopper distribution were suitable habitat data (34.27%), the temperature-vegetation dryness index during the spawning period (18.81%), and various other meteorological and vegetation factors. The risk index model was applied to calculate the grasshopper distribution across different risk levels for the years 2019-2022. The data indicated that the level 1 risk area primarily spans central, eastern, and southwestern Inner Mongolia. By examining the variable weights, the primary drivers of risk level fluctuation from 2019 to 2022 were identified as accumulated precipitation and land surface temperature anomalies during the overwintering period. This study offers valuable insights for future O. decorus asiaticus monitoring in Inner Mongolia.

Developmental hourglass: Verification by numerical evolution and elucidation by dynamical-systems theory.

Determining the general laws between evolution and development is a fundamental biological challenge. Developmental hourglasses have attracted increased attention as candidates for such laws, but the necessity of their emergence remains elusive. We conducted evolutionary simulations of developmental processes to confirm the emergence of the developmental hourglass and unveiled its establishment. We considered organisms consisting of cells containing identical gene networks that control morphogenesis and evolved them under selection pressure to induce more cell types. By computing the similarity between the spatial patterns of gene expression of two species that evolved from a common ancestor, a developmental hourglass was observed, that is, there was a correlation peak in the intermediate stage of development. The fraction of pleiotropic genes increased, whereas the variance in individuals decreased, consistent with previous experimental reports. Reduction of the unavoidable variance by initial or developmental noise, essential for survival, was achieved up to the hourglass bottleneck stage, followed by diversification in developmental processes, whose timing is controlled by the slow expression dynamics conserved among organisms sharing the hourglass. This study suggests why developmental hourglasses are observed within a certain phylogenetic range of species.

Abstract 16746: Novel Role of Endothelial CD45 in Regulating Endothelial-to-Mesenchymal Transition (EndMT) in Atherosclerosis

Introduction: Atherosclerosis is the leading cause of mortality in the United States and most other developed countries. Endothelial cell (EC) activation is a hallmark of the initiation and progression of atherosclerosis; identification of molecular markers of dysfunctional endothelium represents a biological challenge to developing new therapeutic targets. CD45 is a marker of hematopoietic cells, which is rarely expressed in ECs. However, recent studies indicated that CD45 is indispensable in driving the endothelial-to-mesenchymal transition (EndMT) following myocardial infarction. EndMT has also been implicated in the pathogenesis of atheroma progression. Thus, we aim to investigate whether endothelial CD45 contributes to the progression of atherosclerosis by facilitating the EndMT. Methods and results: In vitro , we used CRISPR/inactive Cas9 transcriptional activation system to express CD45 in human endothelial colony-forming cells (ECFCs). Using FACS analyses, we found that CD45+ECFCs upregulate transforming growth factors (TGFβ 1-3 ) that implicate EndMT but downregulate FGFR1 expression, which exacerbates EndMT. qRT-PCR and WB showed that CD45+ECFCs downregulate transcription factors KLFs. In vivo , we generated a tamoxifen-inducible EC-specific CD45 deficient mouse strain (EC-CD45iKO) in ApoE-deficient (ApoE-/-) background and fed with a Western diet (C57BL/6) for atherosclerosis and molecular analyses. We found that ApoE-/- / EC-iCD45KO mice reduced plaque macrophages, foam cells, expression of adhesion molecule, and lesion development compared to ApoE-/- controls. Interestingly, ApoE-/- / EC-iCD45KO mice showed the reduction of α-smooth muscle actin, which is typical of EndMT, in the aortic plaque. Single-cell RNA-seq analyses have been performed to characterize that endothelial CD45 regulates the expression of pro-inflammatory, EndMT, and endothelial cell markers genes on the aortic ECs. Conclusion: These findings demonstrate that endothelial CD45 potentiates atherosclerosis by inducing TGF signaling and mesenchymal phenotype, causing FGFR1 downregulation and attenuating KLFs expression to drive EndMT, highlighting endothelial CD45 may be a new drug target for the treatment of atherosclerosis.

Spatial proteomics enables identification of prognostic biomarkers in papillary renal cell carcinoma

Abstract Background Papillary renal cell carcinoma (PRCC) is the second most common adult kidney cancer histology, constituting 15-20% of cases. While some patients may have indolent PRCC tumors that grow slowly, other tumors rapidly metastasize. Some PRCC tumors respond to immune checkpoint inhibitors. Thus, understanding the immune tumor microenvironment and how it correlates with patient outcomes in this relatively rare disease is a critical need. Spatial interrogation of patient samples has the potential to offer novel insights into the tumor-immune axis and provide avenues for enhanced diagnosis and treatment. Addressing questions of spatial arrangement within tumors has remained a technical and biological challenge, but emerging spatial biology technologies provide molecular data at single cell resolution. We hypothesized that the spatial interaction of immune, stromal and tumor cells would be prognostic for PRCC patients. Methods A tissue microarray was assembled from an archive of ~100 patients presenting with PRCC. This dataset was assayed with PhenoCycler/CODEX (Akoya Biosciences) using a 31-antibody panel with immune- and cancer-related proteins. We have developed methodology and novel algorithms to perform signal normalization, cell segmentation, and cell typing. We computed neighborhoods for each of 2.5 million cells and performed network analysis to identify spatial clusters. This method allowed us to identify clusters consistently present across multiple TMA spots from the same patient and across multiple patients. Results Using spatial neighborhood analysis, we have identified diverse spatial clusters of potential clinical relevance, including five distinct M2 macrophage spatial clusters. We have described one of the clusters as being physically associated with helper T cells, which is visualized on a PRCC spot and shows co-occurence of M2-macrophages (CD163) and helper T cells (CD4). This pattern was replicated in additional TMA spots from the same patient. In contrast, other clusters of M2-macrophages (M2-M2 spatial cluster and M2-M1 macrophages) are visualized to show vastly different cellular neighborhoods. Clinical associations show that the patients with presence of the M2-T helper cluster have a poor cancer-associated survival (p=0.005). In comparison, the total proportion of M2 macrophages is not associated with survival (p=0.4), highlighting the importance of characterizing spatial interactions beyond cell type quantitation. Conclusions In summary, we highlight the utility of spatial biology to explain the heterogeneity in patients’ tumors and to uncover novel correlates of clinical phenotypes, establishing a platform for future discovery in this field and the identification of additional spatial correlates of patient outcome and clinical response. CDMRP DOD Funding: yes

Microbial Gene Ontology informed deep neural network for microbe functionality discovery in human diseases.

The human microbiome plays a crucial role in human health and is associated with a number of human diseases. Determining microbiome functional roles in human diseases remains a biological challenge due to the high dimensionality of metagenome gene features. However, existing models were limited in providing biological interpretability, where the functional role of microbes in human diseases is unexplored. Here we propose to utilize a neural network-based model incorporating Gene Ontology (GO) relationship network to discover the microbe functionality in human diseases. We use four benchmark datasets, including diabetes, liver cirrhosis, inflammatory bowel disease, and colorectal cancer, to explore the microbe functionality in the human diseases. Our model discovered and visualized the novel candidates' important microbiome genes and their functions by calculating the important score of each gene and GO term in the network. Furthermore, we demonstrate that our model achieves a competitive performance in predicting the disease by comparison with other non-Gene Ontology informed models. The discovered candidates' important microbiome genes and their functions provide novel insights into microbe functional contribution.

The good and the bad of T cell cross-reactivity: challenges and opportunities for novel therapeutics in autoimmunity and cancer.

T cells are main actors of the immune system with an essential role in protection against pathogens and cancer. The molecular key event involved in this absolutely central task is the interaction of membrane-bound specific T cell receptors with peptide-MHC complexes which initiates T cell priming, activation and recall, and thus controls a range of downstream functions. While textbooks teach us that the repertoire of mature T cells is highly diverse, it is clear that this diversity cannot possibly cover all potential foreign peptides that might be encountered during life. TCR cross-reactivity, i.e. the ability of a single TCR to recognise different peptides, offers the best solution to this biological challenge. Reports have shown that indeed, TCR cross-reactivity is surprisingly high. Hence, the T cell dilemma is the following: be as specific as possible to target foreign danger and spare self, while being able to react to a large spectrum of body-threatening situations. This has major consequences for both autoimmune diseases and cancer, and significant implications for the development of T cell-based therapies. In this review, we will present essential experimental evidence of T cell cross-reactivity, implications for two opposite immune conditions, i.e. autoimmunity vs cancer, and how this can be differently exploited for immunotherapy approaches. Finally, we will discuss the tools available for predicting cross-reactivity and how improvements in this field might boost translational approaches.

0770 The Effect of In-Home Sleep Extension on Insulin Sensitivity for Habitually Short-Sleeping Adolescents

Abstract Introduction The interplay of physiological and behavioral factors of adolescence that result in dramatically insufficient sleep may confer a notable cardiometabolic risk. Increasing sleep duration reverses the negative metabolic consequences of insufficient sleep in adults, but this has not been examined in youth. Thus, the current study aimed to evaluate the impact of in-home sleep extension on insulin sensitivity (Si) in habitually short-sleeping adolescents. Methods Twenty-six healthy adolescents obtaining ≤7h sleep on school nights (age=16.6±1.1, 69% female, 73% non-Hispanic White) completed a randomized crossover trial consisting of one week each of Typical Sleep (usual school schedule) and Sleep Extension (≥1h additional time in bed) during the academic year. Sleep was estimated via actigraphy, and an intravenous glucose tolerance test (IVGTT) measured Si following each condition. Spearman and Kendall correlations assessed associations and paired samples t-tests and Wilcoxon signed-rank tests examined change in variables from Typical Sleep to Sleep Extension. Results A significant association between sleep and insulin sensitivity was observed during Typical Sleep, with poorer Si associated with longer sleep onset latency (rho=-0.29, p=0.04), and greater variability in waketime (rho=-0.44, p=0.02) and sleep duration (rho=-0.43, p=0.03). During Sleep Extension, participants significantly increased sleep duration by 1.4±0.7h (Typical Sleep=5.59±0.82, Sleep Extension=6.95±0.83 h; p< 0.001) by shifting bedtimes to an earlier clock hour (Typical Sleep=00:34±01:12; Sleep Extension=23:10±00:57; p< 0.001). Si did not significantly change between conditions (p=0.52). However, a trend was observed for a decrease in fasting glucose during Sleep Extension compared to Typical Sleep (Typical Sleep=92.5±8.87; Sleep Extension=88.48±12.06 mg/dL; p=0.055). Conclusion Habitually short-sleeping adolescents were successful at increasing sleep duration during an in-home intervention, but Si did not change compared to Typical Sleep. Notably, sleep duration during Sleep Extension was still less than the 8-10 h of sleep per night recommended for adolescents. A sufficiently early bedtime that supports adequate sleep is a biological challenge for adolescents when wake times are fixed due to early school start times. Future research is recommended examining whether combining sleep extension with a circadian health intervention can have a larger impact on sleep and cardiometabolic outcomes in adolescents. Support (if any) NIH NIDDK K23DK117021; NIH BIRCWH 2K12HD057022; CTSA UL1TR002535

Nanomaterials based on chitosan for skin regeneration: an update.

Nanomaterials based on chitosan for skin regeneration: an update.

SCENARIOS OF BUSINESS ENTITIES SOCIO-ECONOMIC INTERACTION IN THE CONTEXT OF GLOBAL CHALLENGES

Abstract. The coronavirus pandemic has become one of the greatest global challenges of our time, posing a significant threat to socio-political processes and requiring both government institutions and businesses to find ways to respond quickly and effectively. In the context of global challenges, the issue of forming scenarios of socio-economic interaction of business entities, research on changes in these scenarios due to the acceleration of digitalization and robotization of business and the transition to a remote format of work is especially relevant. The aim of the article is formation scenarios of business entities socio-economic interaction in the context of global challenges. The following methods were used to achieve the goal: abstract and logical, synergetic, statistical, comparative, horizontal, vertical, tabular, graphic, scenario methods. Results. The article defines the concept of scenario and scenario approach. It is noted that the scenarios for the development of the pandemic itself as a biological global challenge should be distinguished; scenarios of the impact of the COVID-19 pandemic on various spheres of social development; scenarios of doing business in a pandemic. Characteristics that can determine pandemic scenarios are considered. The pandemic impact scenarios provided by various international and national organizations and bodies and the change of these scenarios over time are analyzed. The forecast of GDP provided by different organizations is presented and in order to analyze the actual implementation of the forecast, a comparison of forecast values and real values of GDP, which was in 2020 and 2021 in fact. Macro indicators of economic and social development of Ukraine according to the main and alternative scenarios are analyzed. In developing scenarios of socio-economic cooperation in order to increase their effectiveness, it is proposed to take into account environmental factors (ecosystems), external and internal environments of the enterprise, in particular, take into account the scope of activities, size of the enterprise, regional location and regional differences, financial condition of entities during global challenges, flexibility of management, its ability to adapt and dynamism in response to challenges, the level of interaction of the business entity with public authorities and local governments (public-partnership relations), the level of corporate social responsibility, the desire to cooperate with employees, the public, to preserve the ecosystem, maintain employee health, charity, employee loyalty, etc. The practical significance of the research lies in the possibility of establishing effective interaction between business entities in the implementation of different scenarios in the context of global challenges. The development of scenarios and relevant strategies will make possible to renew the business in the long run after the crisis caused by such a global challenge as the COVID-19 pandemic, while maintaining control over the current situation, taking into account the requirements of rapid response. As part of further research, it is planned to develop scenarios for business entities socio-economic development and scenarios for their interaction within the implementation of existing business processes at the enterprise.

Biological knowledge graph-guided investigation of immune therapy response in cancer with graph neural network.

The determination of transcriptome profiles that mediate immune therapy in cancer remains a major clinical and biological challenge. Despite responses induced by immune-check points inhibitors (ICIs) in diverse tumor types and all the big breakthroughs in cancer immunotherapy, most patients with solid tumors do not respond to ICI therapies. It still remains a big challenge to predict the ICI treatment response. Here, we propose a framework with multiple prior knowledge networks guided for immune checkpoints inhibitors prediction-DeepOmix-ICI (or ICInet for short). ICInet can predict the immune therapy response by leveraging geometric deep learning and prior biological knowledge graphs of gene-gene interactions. Here, we demonstrate more than 600 ICI-treated patients with ICI response data and gene expression profile to apply on ICInet. ICInet was used for ICI therapy responses prediciton across different cancer types-melanoma, gastric cancer and bladder cancer, which includes 7 cohorts from different data sources. ICInet is able to robustly generalize into multiple cancer types. Moreover, the performance of ICInet in those cancer types can outperform other ICI biomarkers in the clinic. Our model [area under the curve (AUC = 0.85)] generally outperformed other measures, including tumor mutational burden (AUC = 0.62) and programmed cell death ligand-1 score (AUC = 0.74). Therefore, our study presents a prior-knowledge guided deep learning method to effectively select immunotherapy-response-associated biomarkers, thereby improving the prediction of immunotherapy response for precision oncology.

Подходы к разработке информационного ресурса для управления потоками пациентов в медицинской организации в период глобального биовызова (на примере COVID‑19)

Patient flow management in medical organizations and rational use of human, material, medical and technical resources during the period of global biological challenge are the key to the effective functioning of the health care system. The formation of a set of indicators and criteria that allow the organization, planning and management of hospitalizations should be carried out with using of modern information aggregators integrated with medical information systems both at the level of a single hospital and in general across a network of medical organizations in the region that provide specialized medical care in hospitals. Purpose of the study is to develop an information system architecture that allows assessing the level of use of the resources of a medical organization during a global biological challenge (on the example of COVID-19) and distributing patient flows depending on its current capabilities. Materials and methods. Based on the data on the results of hospitalization of 7576 patients with COVID-19 in the Noginsk Central District Hospital, 6 consecutive stages of developing an information system were formed, including user stratification and determining roles and levels of access to information for them, classifying the resources of a medical organization, developing digital models of databases data, standardization and mapping of work processes in the structural divisions of the hospital, compiling a list of input (accounting) and output (reporting) indicators correlated with each other through the use of directories and registers, as well as on the basis of logical links. Results. Digital layouts of 4 registration cards were developed (data of medical workers; data of patients, medical services provided to them and the time for their implementation; use of medical equipment and time spent on research; registration of hospitalizations in hospital departments), 10 reporting forms (on the activities of medical workers and medical services rendered by them; on the structure of hospitalized and diagnostic tests carried out by them; on the use of medical equipment; on hospitalizations and the use of hospital beds) and templates of analytical reports for making management decisions based on the data of reporting forms for 6 categories of users (for medical workers of the relevant structural units of the hospital heads of structural subdivisions, deputy heads of a medical organization and head of a medical organization, a specialist of a public authority of a constituent entity of the Russian Federation in the field of health protection). Conclusion: The information resource proposed for development makes it possible to carry out a current assessment of the workload of medical workers and medical equipment, the employment of the bed fund, compliance with time parameters when performing standard operating procedures in the structural divisions of the hospital and ensure operational management of patient flows.

Biological role of the major AP (abasic site) endonuclease of an archaeon from geothermal environments.

Archaea and bacteria in geothermal environments are predicted to suffer DNA depurination in vivo at high rates, which raises questions regarding the biological roles of their abasic-site-repair enzymes. Gene deletion and enzymatic assay demonstrated that the saci_0015 gene of Sulfolobus acidocaldarius encodes an AP endonuclease (Apn) accounting for as much as 95% of the assayable activity in cell extracts and is not essential for viability. To identify genetic functions of this enzyme, deletion (ΔApn) strains were examined with respect to growth, spontaneous mutation, transformation by ssDNA containing an abasic site, and conjugation. Relative to its isogenic control, the ΔApn strain did not exhibit any change in growth rate or final cell density, rate or spectrum of spontaneous mutation, transformation by DNA containing an abasic site, or efficiency of DNA transfer and recombination. The apparent lack of genetic impact of removing the major AP endonuclease was unexpected and indicated that abasic sites are rarely bypassed directly by DNA polymerases in S. acidocaldarius. AP endonuclease deficiency had no obvious effect on survival of S. acidocaldarius under several test conditions, but it accelerated the death of cells at 4º C under illumination. Our results suggest that the normal level of AP endonuclease in S. acidocaldarius is well above the minimum required for growth and cell division but not for recovery from prolonged exposure to certain low-temperature conditions. This situation illustrates a biological challenge that has not been emphasized in experimental studies of extremophiles, i.e., the problem of long-term survival under "non-extreme" conditions.

Abstract IA016: The DCIS: A biological challenge and clinical dilemma

Abstract Currently, one of the most challenging problems in oncology is predicting more precisely whether lesions that are detected by sensitive screening tests are indolent (hence, not requiring extensive treatment) or progressive and potentially life-threatening. For example, the increase in breast cancer “incidence” observed over the last 20 years is largely attributable to increased detection of ductal carcinoma in situ (DCIS) and stage I disease by imaging. Despite the increase in early-stage disease, the rates of advanced stage disease have changed only minimally, and the rate of metastatic disease has been virtually unchanged. Conversely, all screening tests miss some life-threatening cancers, known as “interval cancers,” that are diagnosed between scheduled screening tests. Breast cancer best illustrates the problem of interval cancers. It is known that more-aggressive types of breast cancer are more likely to be missed by screening; the cancer grows so quickly it becomes symptomatic after a normal screening test. For example, interval-detected breast cancers are 1.8 to 2.6-fold more likely to be estrogen receptor (ER) negative compared to screen-detected tumors, are likely to be diagnosed at a more advanced stage and are faster growing on average than screen-detected cancers. Relatively little is known about the molecular and cellular differences between screen- detected lesions and interval tumors which might be used to distinguish among the two types of lesions and potentially point to more effective strategies and targets for intervention. The National Cancer Institute has established programs to identify cellular and molecular characteristics that distinguish progressive from non-progressive lesions. Recent progress in this direction will be discussed by the speaker. Citation Format: Sudhir Srivastava. The DCIS: A biological challenge and clinical dilemma [abstract]. In: Proceedings of the AACR Special Conference on Rethinking DCIS: An Opportunity for Prevention?; 2022 Sep 8-11; Philadelphia, PA. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_1): Abstract nr IA016.

Anxiety Sensitivity Social Concerns Predicts Electrodermal Activity during the Niacin Biological Challenge Paradigm

Anxiety sensitivity social concerns (ASSC), or the fear of observable anxiety symptoms, is a risk factor for social anxiety. ASSC predicts anxiety following the niacin biological challenge, a paradigm in which niacin is used to manipulate facial flushing during a speech task. However, it remains unclear if ASSC predicts physiological arousal during this task. The current study was designed to examine the effects of ASSC on self-reported distress and electrodermal activity (EDA) during the niacin biological challenge in a sample of undergraduates (N = 36; M age = 18.9, SD = 0.84; 69.4% female). Participants were randomly assigned to one of four conditions in a 2 (100 mg niacin vs. 100 mg sugar) × 2 (instructional set) design. Participants completed a speech task in a virtual reality environment. Participants rated their distress halfway through the speech and EDA was averaged over four intervals. There was a main effect for ASSC on subjective distress. There was a significant ASSC by condition interaction predicting EDA, in that ASSC was related to EDA only in the niacin condition. ASSC also was more strongly related to EDA anticipating the speech. These findings highlight the role of ASSC in predicting anxiety and physiological arousal.

Meta-analysis of the incidence of pregnancy losses in dairy cows at different stages to 90 days of gestation

Pregnancy losses are a biological challenge and economically important in dairy herds. A meta-analysis was conducted to quantify losses in 4 periods from 19 to 90 d of pregnancy corresponding to the physiological development of gestation in dairy cows. A total of 19,723 diagnostic records from 46 studies were included. Pregnancy losses averaged 27%, 13%, 7%, and 2% in the early embryonic (19 to 32 d), late embryonic (30 to 45 d), early fetal (45 to 60 d), and later fetal (60 to 90 d) stages. These results provide a formal synthesis of the incidence of pregnancy losses in dairy cows.