bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometric distortion caused by metallic femoral head prosthesis in prostate cancer imaging on an MR Linac: in-vivo measurements of spatial deformation
Authors: McDaid Lisa , Clough Abigael , Benson Rebecca K , Nelder Claire , McMahon John , Jackson Steven , Aznar Marianne , Choudhury Ananya C , van Herk Marcel , Eccles Cynthia L
Published: February 2024

Objectives

Metallic implants cause artefacts and distortion on MRI. To ensure accurate dose delivery and plan adaptation on an MR Linac, there is a need to evaluate distortion caused.

Methods

Participants were imaged on an MR Linac (Elekta Unity, Elekta AB Stockholm). Three sequences were evaluated. Two vendor supplied (T2W TSE 3D), and one T2W TSE 3D optimized to reduce metal artefact distortions. Images were rigidly registered to CT images by a single observer, using bony anatomy. Three coronal and three axial images were selected, and six paired, adjacent, bony landmarks were identified on each slice. Images bisecting treatment isocentre were included. Difference between landmark coordinates was taken to be measure of distortion.

Results

Five observers participated. Thirty six pairs of bony landmarks were identified. Median difference in position of landmarks was ≤3 mm (range 0.3-4.4 mm). One-way analysis of variance (ANOVA) between observer means showed no significant variation between sequences or patients (P = 1.26 in plane, P = 0.11 through plane). Interobserver intra class correlation (ICC) was 0.70 in-plane and 0.78 through-plane. Intra-observer ICC for three observers was 0.76, 0.81, 0.83, showing moderate to good reliability on this small cohort.

Conclusions

This in-vivo feasibility study suggests distortion due to metallic hip prosthesis is not an obstacle for pelvic radiotherapy on an MR Linac. Research on the impact on plan quality is warranted.

Advances in knowledge

This work supports feasibility of treating patients with metallic hip prosthesis on an MR Linac.
Management of malignant ureteric obstruction with ureteric stenting or percutaneous nephrostomy
Authors: Blackmur James ,   Scottish Malignant Ureteric Obstruction Study Group, Blackmur J P , Llewellyn O , Laird A , Teahan S , McLennan R , McNeill S A , Mariappan P , Kerr L , Aning J J , Young N J , Marzoug A , Hamilton D , Ng A , Fernando D , Drummond L , Holt P , Boyle C , Shin J S , Carrera A , Lee X W , Anderson J , Dreyer B , Krishnan J , Rodger F , Singh J , McCollum C , Boyle C , Zycinski C , Nandwani G M , Nabi G , Brush J , Taylor J , Keanie J , Granitsiotis P , Hayward L , McLaren D , Law A , Kata S G , Thomas B G , Al Jaafari F
Published: February 2024

Lay summary

Malignant ureteric obstruction (MUO) is frequently encountered in patients with advanced cancers. In the largest study to date, assessing 852 patients from across Scotland, the authors demonstrated the presence of MUO as a marker of advanced disease across cancer types, with poor survival for many patients, even with intervention. There is uncertainty in optimal management of this condition, with marked differences in management between hospitals. Treatment to relieve the obstruction does not guarantee either improvement in kidney function or progression to further oncological treatment. The authors have developed a prognostic tool to estimate outcomes after intervention for MUO, and advocate its use for clinicians along with other data presented for patient counselling.
One-dimensional Fe7S8 nanorods encapsulated in N, S co-doped carbon shells accelerate lithium storage kinetics for lithium-ion capacitors
Authors: Liu Xinyu
Published: February 2024

The slow kinetics of battery-type anode materials for lithium-ion capacitors (LICs) hinder their matching with capacitive-type cathodes. Designing anode materials with greater capacity and improved rate performance is a key to solving this challenge. Here, we fabricated one-dimensional N, S co-doped carbon encapsulated Fe7S8 nanorods to realize fast lithium storage kinetics and stable cycling performance. The matched Fe7S8@C//AC LICs achieved an extraordinary energy density of 101 Wh kg−1 and a power density of 3927 W kg−1.
Causal Association Analysis of Periodontitis and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization Study
Authors: Qing Xiangli , Zhang Chenhui , Zhong Zhuotai , Zhang Tao , Wang Lin , Fang Shuangshuang , Jiang Tianyuan , Luo Xiaoying , Yang Yang , Song Gengqing , Wei Wei
Published: February 2024

Background

Periodontitis has been reported to be associated with inflammatory bowel disease (IBD), including ulcerative colitis (UC), and Crohn’s disease (CD). However, the causality of these 2 diseases remains unclear. We conducted bidirectional Mendelian randomization (MR) to investigate the causal relationship between periodontitis and IBD.

Methods

We obtained the genome-wide association study (GWAS) summary data of European populations from FinnGen database (for IBD) and a published article (for periodontitis), from which independent single nucleotide polymorphisms were selected as instrumental variables. Inverse variance–weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for MR analysis. Heterogeneity or pleiotropy was detected through Cochran’s Q test and MR-Egger intercept, respectively. Outlier was identified with MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) and leave-one-out analysis. All statistical analyses were performed with R 4.2.1 and the packages of TwoSampleMR version 0.5.6.

Results

Genetic prediction showed that periodontitis was the risk factor of UC (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.01-1.26; P = .027), rather than of CD (OR, 0.92; 95% CI, 0.74-1.15; P = .456) and IBD (OR, 0.96; 95% CI, 0.81-1.13; P = .619). To the contrary, CD, not UC or IBD, resulted in exacerbating periodontitis in terms of the results of the IVW (OR, 1.09; 95% CI, 1.01-1.17; P = .021) and WM (OR, 1.10; 95% CI, 1.01-1.20; P = .030) methods. Heterogeneity or pleiotropy was acceptable.

Conclusions

Our results indicated that CD was the risk factor for periodontitis; conversely, periodontitis was responsible for the exacerbation of UC, enhancing the existence of mouth-gut axis. Patients with UC should pay more attention to periodontal health, while patients with periodontitis should actively pay close heed to intestinal health.
Judicial self-empowerment and unconstitutional constitutional amendments
Authors: Tommasini Nicola
Published: February 2024

In the context of global judicial aggrandizement, many courts have developed and accepted the unconstitutional constitutional amendments doctrine. However, with the exception of some case studies, there is little comparative scholarship on the causes of judicial expansion in this area. This article addresses this gap by examining the development of the power to review amendments in three constitutional systems: Colombia, India, and Malaysia. The article argues that in all three cases, one of the important elements that contributed to the consolidation of this power is the strategic behavior of courts. To understand the importance of strategy, the article suggests a rational choice theory of judicial empowerment, according to which judges estimate the costs of potential backlashes and act in certain moments and in certain ways so as to make political reaction unlikely. It further suggests three different types of strategies utilized by these courts that helped curb political backlash. First, courts engaged in timing strategies: they decided the scope of their own power when political competition was high and the likelihood of backlash was low. Second, courts engaged in outcome strategies: they expanded their own power while simultaneously giving the dominant political coalition a “win.” Third, courts employed case selection strategies: they picked mundane and low-stake cases in order to decrease the incentives for political reaction. The article concludes with some considerations on the limits of judicial strategy.
Dosage optimization for reducing tumor burden using a phenotype-structured population model with a drug-resistance continuum
Authors: Han Lifeng , Yogurtcu Osman N , Rodriguez Messan Marisabel , Valega-Mackenzie Wencel , Nukala Ujwani , Yang Hong
Published: February 2024

Drug resistance is a significant obstacle to effective cancer treatment. To gain insights into how drug resistance develops, we adopted a concept called fitness landscape and employed a phenotype-structured population model by fitting to a set of experimental data on a drug used for ovarian cancer, olaparib. Our modeling approach allowed us to understand how a drug affects the fitness landscape and track the evolution of a population of cancer cells structured with a spectrum of drug resistance. We also incorporated pharmacokinetic (PK) modeling to identify the optimal dosages of the drug that could lead to long-term tumor reduction. We derived a formula that indicates that maximizing variation in plasma drug concentration over a dosing interval could be important in reducing drug resistance. Our findings suggest that it may be possible to achieve better treatment outcomes with a drug dose lower than the levels recommended by the drug label. Acknowledging the current limitations of our work, we believe that our approach, which combines modeling of both PK and drug resistance evolution, could contribute to a new direction for better designing drug treatment regimens to improve cancer treatment.
Simple Unbalanced Optimal Transport
Authors: Khesin Boris , Modin Klas , Volk Luke
Published: February 2024

We introduce and study a simple model capturing the main features of unbalanced optimal transport. It is based on equipping the conical extension of the group of all diffeomorphisms with a natural metric, which allows a Riemannian submersion to the space of volume forms of arbitrary total mass. We describe its finite-dimensional version and present a concise comparison study of the geometry, Hamiltonian features, and geodesics for this and other extensions. One of the corollaries of this approach is that along any geodesic the total mass evolves with constant acceleration, as an object’s height in a constant buoyancy field.
Will the United States pass on telemedicine progress?
Authors: Cummins Mollie R , Ivanova Julia , Ong Triton , Soni Hiral , Barrera Janelle F , Wilczewski Hattie , Welch Brandon M , Bunnell Brian E
Published: February 2024

Background

During the COVID-19 pandemic, federal and state health policies allowed temporary flexibilities for Medicare and Medicaid beneficiaries, leading to a sharp increase in telemedicine use. However, many of the flexibilities that enabled innovation and growth in telemedicine continue temporarily since the federal emergency declaration ended in May 2023, and the United States has not made permanent decisions about telemedicine policy. Analysts have raised concerns about increased spending, program integrity, safety, and equity, and recommend strengthening oversight.

Methods

Here, we argue that we must continue the flexibilities to better understand telemedicine’s quality, safety, and outcomes, and until the United States can develop an evidence-based digital health strategy. A premature regression to pre-pandemic telemedicine policies risks unintended consequences.

Conclusion

We must continue the current policy flexibilities, safeguard against fraud and abuse, and immediately prioritize research and evaluation of telemedicine’s quality, safety, and outcomes, to avoid unintended consequences and support more permanent policy decision-making.
Cutting-edge skin ageing research on tissue stem cell
Authors: Ichijo Ryo
Published: February 2024

In developed economies, the growing number of older individuals is a pressing issue. As a result, research progress into ageing has emphasized the significance of staying healthy in one’s later years. Stem cells have a fundamental role to play in fostering diverse cell types and necessary processes for tissue repair and regeneration. Stem cells experience the effects of ageing over time, which is caused by their functional deterioration. Changes to stem cells, their niches and signals from other tissues they interact with are crucial factors in the ageing of stem cells. Progress in single-cell RNA sequencing (scRNA-seq) technology has greatly advanced stem cell research. This review examines the mechanisms of stem cell ageing, its impact on health and investigates the potential of stem cell therapy, with a special emphasis on the skin.
Psychiatric Risk Factors and Burn Severity in Self-immolation
Authors: Mannekote Thippaiah Srinagesh , Ayub Ibraheim , Challita Youssef P , Ramos Gilbert , Richey Karen J , Foster Kevin N
Published: February 2024

Self-immolation, a form of self-harm involving setting oneself on fire, is associated with high mortality, morbidity, and healthcare burden. This study aimed to characterize potential clinical correlates and predisposing factors for self-immolation based on burn severity using TBSA percentage scoring. Additional objectives included identifying motivational elements, associated risk factors, and clinical characteristics to optimize patient care and reduce future self-immolation incidents. A retrospective review of admissions to the Arizona Burn Center from July 2015 to August 2022 identified 103 self-immolation patients for the study. Burn severity was categorized as mild to moderate (TBSA < 20%) or severe (TBSA ≥ 20%) based on TBSA. This study population had a mortality rate of 21%. Positive urine drug screens were found in 44% of subjects, and 63% having chronic substance use, with methamphetamine (37%) and alcohol (30%), being the most prevalent. Underlying psychiatric illnesses were present in 83% of patients. Suicidal intent strongly predicted severe burns (P < .001) among the 68 severe burn cases identified. In conclusion, this study emphasizes that the presence of suicidal intent among self-immolation patients significantly correlates with burn severity. These findings highlight the importance of involving psychiatric services early in patient care to improve outcomes and reduce the recurrence of self-immolation acts.
Biology and management of Coleophora deauratella (Lepidoptera: Coleophoridae) in red clover seed-growing regions in North America and New Zealand
Authors: Kaur Navneet , Anderson Nicole P , Dorman Seth J , Walenta Darrin L , Donovan Brain C , Tanner Christy , Mori Boyd A , Otani Jennifer , Sim Richard E , Rolston Phil , Faulkner Joel
Published: February 2024

Red clover (Trifolium pratense L.), a perennial forage legume belonging to the Fabaceae family, is grown for seed in many temperate regions of the world. Coleophora deauratella Leinig and Zeller (Lepidoptera: Coleophoridae) is a significant insect pest occurring globally in several primary red clover seed-producing regions. Coleophora deauratella inflicts crop damage by larval feeding on developing seed within individual florets, thus reducing seed yield. The first detection of C. deauratella and seed yield losses up to 90% were reported in the Peace River region of Alberta, in western Canada, in 2006, signifying its damage and potential threat to other red clover seed-producing areas of the world as an invasive insect pest species. As a result, crop stand age was reduced to 1 yr to mitigate seed yield loss caused by this pest in second-year fields in Alberta. Coleophora deauratella was first discovered in western Oregon in 2011, but the resulting economic damage remains unknown after more than a decade of its discovery. The first confirmed case of C. deauratella and tremendous seed yield devastation in red clover seed crops in the mid-Cantebury region of New Zealand occurred in 2016. Continued monitoring efforts in Oregon and New Zealand revealed that pest populations started receding after 2018, and the presence of unknown biocontrol agents, climatic, or genetic factors was speculated for its lower establishment rate. In this article, we discuss C. deauratella biology, ecology, and pest status in North America and New Zealand, along with the key research highlights to control C. deauratella.
Morphological changes of larvae and pupae of Lucilia sericata (Diptera: Calliphoridae) reared at two temperatures and on three food types
Authors: Bambaradeniya Tharindu Bandara , Magni Paola Annarosa , Dadour Ian Robert
Published: February 2024

Determining the minimum postmortem interval (minPMI) from an entomological perspective relies mainly on development data recorded for various species of flies collected from a crime scene or suspicious death. This study focused on the larval and pupal development of Lucilia sericata (Meigen), with an emphasis on the changes of the external morphology of the puparium and its pupal content throughout the duration of metamorphosis. Colonies of L. sericata were reared on 3 types of swine tissue (skeletal muscle, liver tissue, and heart tissue) at 2 different temperature regimes; 24 ± 1 °C and 30 ± 1 °C. The overall developmental time, larval width and length, and inner and outer pupal morphology changes were observed and recorded. The results show that: (i) temperature significantly influenced overall development time, as well as changes in larval width and length, but this effect was not dependent on tissue type; (ii) larval development duration was longest on heart tissue, and shortest on skeletal muscle for both temperatures; and (iii) pupation was longest for larvae reared on skeletal muscle at 24 ± 1 °C, and on liver tissue at 30 ± 1 °C, while those larvae reared on liver tissue at 24 ± 1 °C and heart tissue at 30 ± 1 °C had the shortest pupation period. A seven-character checklist plus 4 landmark stages were developed comprising the external morphology of the puparium and pupal content changes of L. sericata. In conclusion, the study provides larval and pupal development timetables, as well as checklists and photo guides for pupal character development that may be useful for future postmortem determinations.
G-quadruplex-mediated genomic instability drives SNVs in cancer
Authors: Richl Tilmann , Kuper Jochen , Kisker Caroline
Published: February 2024

G-quadruplex (G4s) DNA structures have been implicated in inducing genomic instability and contributing to cancer development. However, the relationship between G4s and cancer-related single nucleotide variants (cSNVs) in clinical settings remains unclear. In this large-scale study, we integrated experimentally validated G4s with genomic cSNVs from 13480 cancer patients to investigate the spatial association of G4s with the cellular cSNV landscape. Our findings demonstrate an increase in local genomic instability with increasing local G4 content in cancer patients, suggesting a potential role for G4s in driving cSNVs. Notably, we observed distinct spatial patterns of cSNVs and common single nucleotide variants (dbSNVs) in relation to G4s, implying different mechanisms for their generation and accumulation. We further demonstrate large, cancer-specific differences in the relationship of G4s and cSNVs, which could have important implications for a new class of G4-stabilizing cancer therapeutics. Moreover, we show that high G4-content can serve as a prognostic marker for local cSNV density and patient survival rates. Our findings underscore the importance of considering G4s in cancer research and highlight the need for further investigation into the underlying molecular mechanisms of G4-mediated genomic instability, especially in the context of cancer.
DNA-PK controls Apollo’s access to leading-end telomeres
Authors: Sonmez Ceylan , Toia Beatrice , Eickhoff Patrik , Matei Andreea Medeea , El Beyrouthy Michael , Wallner Björn , Douglas Max E , de Lange Titia , Lottersberger Francisca
Published: February 2024

The complex formed by Ku70/80 and DNA-PKcs (DNA-PK) promotes the synapsis and the joining of double strand breaks (DSBs) during canonical non-homologous end joining (c-NHEJ). In c-NHEJ during V(D)J recombination, DNA-PK promotes the processing of the ends and the opening of the DNA hairpins by recruiting and/or activating the nuclease Artemis/DCLRE1C/SNM1C. Paradoxically, DNA-PK is also required to prevent the fusions of newly replicated leading-end telomeres. Here, we describe the role for DNA-PK in controlling Apollo/DCLRE1B/SNM1B, the nuclease that resects leading-end telomeres. We show that the telomeric function of Apollo requires DNA-PKcs’s kinase activity and the binding of Apollo to DNA-PK. Furthermore, AlphaFold-Multimer predicts that Apollo’s nuclease domain has extensive additional interactions with DNA-PKcs, and comparison to the cryo-EM structure of Artemis bound to DNA-PK phosphorylated on the ABCDE/Thr2609 cluster suggests that DNA-PK can similarly grant Apollo access to the DNA end. In agreement, the telomeric function of DNA-PK requires the ABCDE/Thr2609 cluster. These data reveal that resection of leading-end telomeres is regulated by DNA-PK through its binding to Apollo and its (auto)phosphorylation-dependent positioning of Apollo at the DNA end, analogous but not identical to DNA-PK dependent regulation of Artemis at hairpins.
Processivity and specificity of histone acetylation by the male-specific lethal complex
Authors: Kiss Anna E , Venkatasubramani Anuroop V , Pathirana Dilan , Krause Silke , Sparr Aline Campos , Hasenauer Jan , Imhof Axel , Müller Marisa , Becker Peter B
Published: February 2024

Acetylation of lysine 16 of histone H4 (H4K16ac) stands out among the histone modifications, because it decompacts the chromatin fiber. The metazoan acetyltransferase MOF (KAT8) regulates transcription through H4K16 acetylation. Antibody-based studies had yielded inconclusive results about the selectivity of MOF to acetylate the H4 N-terminus. We used targeted mass spectrometry to examine the activity of MOF in the male-specific lethal core (4-MSL) complex on nucleosome array substrates. This complex is part of the Dosage Compensation Complex (DCC) that activates X-chromosomal genes in male Drosophila. During short reaction times, MOF acetylated H4K16 efficiently and with excellent selectivity. Upon longer incubation, the enzyme progressively acetylated lysines 12, 8 and 5, leading to a mixture of oligo-acetylated H4. Mathematical modeling suggests that MOF recognizes and acetylates H4K16 with high selectivity, but remains substrate-bound and continues to acetylate more N-terminal H4 lysines in a processive manner. The 4-MSL complex lacks non-coding roX RNA, a critical component of the DCC. Remarkably, addition of RNA to the reaction non-specifically suppressed H4 oligo-acetylation in favor of specific H4K16 acetylation. Because RNA destabilizes the MSL-nucleosome interaction in vitro we speculate that RNA accelerates enzyme-substrate turn-over in vivo, thus limiting the processivity of MOF, thereby increasing specific H4K16 acetylation.
Novel mechanisms of diversity generation in Acinetobacter baumannii resistance islands driven by Tn7-like elements
Authors: Correa Alberto , Shehreen Saadlee , Machado Laura Chacon , Thesier Jordan , Cunic Lille M , Petassi Michael T , Chu Joshua , Kapili Bennett J , Jia Yu , England Kevin A , Peters Joseph E
Published: February 2024

Mobile genetic elements play an important role in the acquisition of antibiotic and biocide resistance, especially through the formation of resistance islands in bacterial chromosomes. We analyzed the contribution of Tn7-like transposons to island formation and diversification in the nosocomial pathogen Acinetobacter baumannii and identified four separate families that recognize different integration sites. One integration site is within the comM gene and coincides with the previously described Tn6022 elements suggested to account for the AbaR resistance island. We established Tn6022 in a heterologous E. coli host and confirmed basic features of transposition into the comM attachment site and the use of a novel transposition protein. By analyzing population features within Tn6022 elements we identified two potential novel transposon-encoded diversification mechanisms with this dynamic genetic island. The activities of these diversification features were confirmed in E. coli. One was a novel natural gain-of-activity allele that could function to broaden transposition targeting. The second was a transposon-encoded hybrid dif-like site that parasitizes the host dimer chromosome resolution system to function with its own tyrosine recombinase. This work establishes a highly active Tn7-like transposon that harnesses novel features allowing the spread and diversification of genetic islands in pathogenic bacteria.
Reactions to a Hypothetical Ban of Open-System Electronic Cigarettes Among People Who Currently Use Electronic Cigarettes
Authors: Soule Eric K , Mayne Shannon , Snipes William , Guy Mignonne C , Breland Alison , Fagan Pebbles
Published: February 2024

Introduction

Policies limiting electronic cigarette (ECIG) device and liquid characteristics have been considered to prevent dependence potential and youth product appeal. “Open-system” ECIGs allow people to adjust device and liquid characteristics, which may undermine these policies. This study examined anticipated reactions to a policy prohibiting the sale of open-system ECIG devices in the United States using concept mapping.

Methods

In 2020, adults who reported ECIG use in the past 30 days (n = 70; 45.1% women; mean age = 33.0, SD = 10.6) recruited from a research registry of individuals from across the United States provided statements into a shared list that completed a prompt: “If open-system vaping devices were no longer sold in the US and only closed-system vaping devices were available, what is a specific reaction or response you would have?” at a study website. Participants rated statements (1–7) on how true the statements were for them. Multidimensional scaling and hierarchical cluster analyses were used to identify thematic clusters. Mean ratings of statements were calculated and compared based on the type of ECIG used and current cigarette smoking status.

Results

Participants generated 85 unique statements. The analysis identified eight themes that were organized into two broad groups. The first group of five clusters described behavioral responses to the hypothetical policy (Loopholes, Switch to Closed-System ECIGs, Legal Approaches to Use Open-System ECIGs, ECIG Use Cessation, Switch to non-ECIG Products). The second group of three clusters described psychological responses to the hypothetical policy (Closed-System ECIG Cons, Psychological Responses, Policy Outcome Concerns).

Conclusions

While a ban on open-system ECIG devices may have positive impacts on public health, policy loopholes, and consumer behaviors may undermine the policy. Efforts to support policy enforcement could increase policy effectiveness.

Implications

Open-system electronic cigarettes (ECIGs) that allow people who use ECIGs to modify ECIG device and liquid characteristics may limit the effectiveness of policies that establish product standards which attempt to limit nicotine delivery and flavor content in ECIG liquids. This study identified predicted reactions to a hypothetical policy prohibiting the sale of open-system ECIGs in the United States. Results suggest that people who use ECIGs may view a policy prohibiting open-system ECIGs unfavorably, but would be willing to use closed-system ECIGs. However, many ECIG users may attempt to find loopholes in the policy or alternative sources to purchase open-system ECIGs if open-systems were banned. Future research should identify strategies for tobacco regulatory policy enforcement to increase effectiveness.
Why Study Logic?
Authors: Migotti Mark
Published: February 2024

This chapter expounds and defends a Peircean thesis that has yet to receive the attention it deserves: the thesis that there is a distinctly and illuminatingly intimate connection between the question what is logic? and the questions why and when is it worth studying? The first half of the chapter deals mainly with the bearing on this topic of the relationship between logic and experience, and on the scope of logic, including a discussion of the status of the Pragmatic maxim as a principle of logic. The second half examines the bearing on the topic of Peirce’s universal categories and the relationship between logic and mathematics.
Peirce’s Theories of Generalized Propositions
Authors: Stjernfelt Frederik
Published: February 2024

The chapter will cover the mature theories of propositions that Peirce develops in his intense theoretical thrust of 1902–1906, with a brief introduction about propositions through his earlier development. The chapter’s focus will be on the generalizations that the notion of proposition undergoes in the period mentioned, and the resulting prelinguistic, multimodal theory of propositions with a conclusion about its current relevance.
Diagrammatic Thinking, Diagrammatic Representations, and the Moral Economy of Nineteenth-Century Science
Authors: Ambrosio Chiara
Published: February 2024

This chapter examines Peirce’s work on and with diagrams and places it in a historical and historiographical context. The chapter shows that Peirce’s philosophical reflections on diagrammatic representations and diagrammatic thinking are greatly enriched when placed explicitly in dialogue with the scientific practice of the time and considered from the perspective of what historians of science have characterized as its “moral economy.” It argues that diagrams and diagrammatic practices, as they emerged and consolidated throughout Peirce’s lifetime, were the shared common ground over which an ever-expanding community of scientists negotiated their reasonings and that debates over validity, rigor, perspicuity, and communicability were as much about issues of reliable representation as they were about the reliability and standing of scientists themselves. Peirce was right at the center of these debates, and his philosophical writings on diagrams, as well as his ambitious program for an innovative system of diagrammatic logic, reflect his active participation in them.
Diagrams, Semiosis, and Peirce’s Metaphor
Authors: Jappy Tony
Published: February 2024

Peirce’s concept of the icon provides an innovative theoretical background to the understanding of metaphor, of the media it is communicated through, and of the intentionalities determining it. However, his evolving conception of signs threatened to cancel advances he had made in 1903, when he introduced a highly original definition of metaphor as one of three hypoicons, or subclasses of the icon. Developments in the semiotics potentially undermining this new approach were the redefinition of the subclass of the icon previously identified as metaphor and the ineligibility of the icon–index–symbol division to function as a stage in the very process of sign-production, namely, semiosis. The chapter first contextualizes and illustrates the definition of metaphor of 1903; it then reviews significant developments in the semiotics in the 1905–1906 period; finally, it proposes a form of mediatization as one means of reconciling two seemingly distinct conceptions of the sign.
Peirce on Biology
Authors: Kull Kalevi
Published: February 2024

This chapter provides (1) a brief account of Peirce’s own statements on biological issues; (2) a short account of the usage of Peirce’s ideas in semiotic biology, (a) before 1990 and (b) after 1990; and (3) a brief review of points that have appeared in biosemiotic literature as critical on applications of some of Peirce’s concepts in biosemiotics. Selecting only the statements in which Peirce explicitly speaks about biology, the chapter observes a more emergentist take than can be concluded from canonical readings of Peirce.
Pragmatic Clarification
Authors: Bergman Mats
Published: February 2024

Although the principal aim of Peirce’s pragmatism seems self-evident—that is, “to render ideas clear”—a closer look at his various articulations and uses of the maxim of pragmatism reveals a more nuanced picture, with several objectives in play. To back up this claim, this chapter sets out from a brief discussion of the provenance of pragmatic elucidation in Peirce’s thought, drawing attention to the significance of the context of inquiry in the work of clarification. Turning to the question of what the Peircean method is supposed to make clear, it is argued that it primarily targets the conceptual constituent of signs. Then, three aims of conceptual clarification, labeled elimination, definition, and development, are identified. These considerations bear upon the largely neglected question of whether Peirce’s method of pragmatism is best construed as a form of “Socratic midwifery,” a tool for clearing the way for inquiry proper, or the kind of investigation that is fueled by genuine doubt and aims at settlement of belief or habit-change. Qualifying Peirce’s assertion that “the maxim of Pragmatism does not bestow a single smile upon beauty, upon moral virtue, or upon abstract truth,” the chief conclusion of the chapter is that at least some uses of the maxim of pragmatism can plausibly be construed as forms of melioristic inquiry.
Peirce on Kant’s Refutation of Idealism
Authors: Gava Gabriele
Published: February 2024

This chapter analyzes two short texts in which Peirce sketches out an anti-skeptical argument inspired by Kant’s refutation of idealism. The chapter will first consider why Peirce found Kant’s argument interesting and promising, given that it is often regarded as problematic and unsuccessful. It will then briefly reconstruct Kant’s refutation, highlighting its most problematic passages. Moreover, since Peirce’s own version of the argument relies on Kant’s views regarding the temporal structure of consciousness, the chapter will explain how Peirce tackles this issue in “The Law of Mind.” Finally, the chapter considers Peirce’s own anti-skeptical argument and examines whether and how it can be seen as appropriating Kant’s strategy.
Charles S. Peirce and the Feeling of Understanding
Authors: de Regt Herman C. D. G.
Published: February 2024

In two early and classic papers, “The Fixation of Belief” and “How to Make Our Ideas Clear,” Peirce draws attention to the evolutionary biology of humans and how it might have repercussions for the way our beliefs and feelings relate to the results of inquiry, even if that inquiry is scientific. We find relevant pragmatist ideas suggesting that the feeling of understanding generated by scientific explanations is not a reliable indicator for thinking our beliefs are true. This offers a new way to criticize the currently widely supported contextual theory of scientific understanding. Surprisingly, the feeling of understanding might be an evolutionary bias leading to pseudoscientific beliefs. Peirce’s two classic papers continue to be valuable resources to help us grasp the way humans manage their beliefs and feelings.
A Science Like Any Other
Authors: Dea Shannon
Published: February 2024

This chapter argues that a Peircean philosophy of sex offers a nonreductionist approach to sex as a biological category. The chapter surveys traditional biological accounts of sex categories and several social constructivist accounts of sex. It then provides an overview of Peirce’s scholastic realism and his ethics of inquiry. While Peirce regarded the distinction between the sexes as a rare “polar distinction,” the chapter works to recover the nuanced view of sex that Peirce ought to have adopted had he extended his scholastic realism to reproductive biology. Ultimately, the Peircean account offered treats sex differences as norms expressed as bimodal distributions. The chapter concludes by illustrating some applications of this Peircean philosophy of sex and gesturing to those that we can yet barely imagine.
Scientific Pride and Metaphysical Prejudice
Authors: Mayorga Rosa
Published: February 2024

Metaphysicians and physicists both share the proud desire to understand the world and all the things in it, to fully comprehend the nature of reality. Almost one hundred years after it was proposed, quantum theory has radically transformed the science of physics, inviting a conception of reality that is drastically at odds with our most rooted metaphysical convictions. A scientist and metaphysician extraordinaire, Charles Peirce (1839–1914) was singularly poised to recognize some of the “metaphysical prejudices” about the world that quantum theory, developed years later, has revealed. This chapter proposes to trace how Peirce’s realism, inspired by the thirteenth-century Franciscan monk John Duns Scotus (c. 1266–1308) and adapted for a reconceived scientific metaphysics, parallels some of the familiar enigmas posed by quantum physics in the early twenty-first century.
The Philosophical Relevance of Peirce’s Historical Studies
Authors: Viola Tullio
Published: February 2024

The chapter explores the different uses of history that emerge from Peirce’s writings and asks to what extent history, from a Peircean perspective, is relevant to philosophy. It starts by looking at the emergence of Peirce’s interest in history as part and parcel of his polymathic profile. It goes on to analyze history’s role in the development of Peirce’s evolutionary account of the human mind. Finally, it explores the relationship between history and logic. Peirce was interested both in exploring history’s bearing on the investigation of logical questions and in employing his logical theories to elaborate a methodology of historical inquiry.
Peirce’s Thwarted Career
Authors: Misak Cheryl
Published: February 2024

This chapter traces the sad history of Peirce’s career in academia. This brilliant philosopher and logician struggled to get a job and then didn’t manage to hold onto it. I show that there was considerable self-harm involved but also suggest that, nonetheless, history must judge America’s great early institutions of higher education—Harvard and Johns Hopkins—as failing to nurture one of the finest talents of American thought.
Peirce’s Formal and Material Categories in Phenomenology
Authors: Atkins Richard Kenneth
Published: February 2024

Peirce’s preferred name for the science of phenomenology is phaneroscopy. He regards phaneroscopy as primarily an observational and classificatory science. Its aim is to analyze the phaneron (whatsoever may come before the mind howsoever) and to classify its constituents. Peirce recognizes at least two different sets of categories according to which the phaneron’s constituents may be classified. These are the formal, quantitative categories and the material, qualitative categories. He devotes most of his energies to pursuing the hypothesis that the formal categories by which we classify the phaneron’s constituents are to be based on the basic forms of predicates. This chapter explains what phaneroscopy is, why it is of importance, and Peirce’s work on the formal and material categories.
The Vicissitudes of Experience
Authors: Houser Nathan
Published: February 2024

Peirce’s conception of experience is framed by his doctrine of categories and is inextricably linked with his related conceptions of consciousness, perception, and semiosis. The aim of this chapter is to consider experience from these different perspectives and to contribute toward a more integrated general Peircean theory of experience. It is suggested that Peirce’s analysis of semiosis and his classification of signs is an analysis and classification of possible experiential links between world and mind or, more strictly, between sensation and perception. Peirce viewed himself as an empiricist, but his empiricism is framed in a realist ontology and epistemology that distinguishes it from more usual nominalist approaches.
Charles S. Peirce on the Inquiry into the Discovery of Ideals, Norms, and Values
Authors: da Costa e Silva Tiago
Published: February 2024

The present chapter studies the first two normative sciences, that is, esthetics and ethics, focusing upon the exposition of the systemic structuring of these sciences as well as their specific mode of operation. We show how these normative sciences function within the sciences of discovery. The chapter focuses, furthermore, on the examination of the specific objects of inquiry of esthetics and ethics and the role they play in the development of Peirce’s theory of inquiry. The chapter analyzes the specific results that esthetics and ethics arrive at in investigating the highest ideals attainable and the ideals of conduct and how these results can be employed by logic and by other sciences that receive these results as norms, values, and principles. The chapter concludes with a brief exposition of the pragmatistic adequacy of normative esthetics and ethics as well as their role in the advancement of inquiry.
Changes in opioid prescribing and prescription drug monitoring program utilization following electronic health record integration—Massachusetts, 2018
Authors: Corry Brian , Cremer Laura J , Donnelly Christopher , Sargent Wesley M , Mells Jamie , Kelly Rodd , Reynolds Joshua , Young Leonard D
Published: February 2024

Objective

In this study, we explored key prescription drug monitoring program-related outcomes among clinicians from a broad cohort of Massachusetts healthcare facilities following prescription drug monitoring program (PDMP) and electronic health record (EHR) data integration.

Methods

Outcomes included seven-day rolling averages of opioids prescribed, morphine milligram equivalents (MMEs) prescribed, and PDMP queries. We employed a longitudinal study design to analyze PDMP data over a 15-month study period which allowed for six and a half months of pre- and post-integration observations surrounding a two-month integration period. We used longitudinal mixed effects models to examine the effect of EHR integration on each of the key outcomes.

Results

Following EHR integration, PDMP queries increased both through the web-based portal and in total (0.037, [95% CI = 0.017, 0.057] and 0.056, [95% CI = 0.035, 0.077]). Both measures of clinician opioid prescribing declined throughout the study period; however, no significant effect following EHR integration was observed. These results were consistent when our analysis was applied to a subset consisting only of continuous PDMP users.

Conclusions

Our results support EHR integration contributing to PDMP utilization by clinicians but do not support changes in opioid prescribing behavior.
Effects of Maize Chlorotic Mottle Virus and Potyvirus Resistance on Maize Lethal Necrosis Disease
Authors: Gentzel Irene N. , Paul Pierce , Wang Guo-Liang , Ohlson Erik W.
Published: February 2024

Maize lethal necrosis (MLN) is a viral disease caused by host co-infection by maize chlorotic mottle virus (MCMV) and a potyvirus, such as sugarcane mosaic virus (SCMV). The disease is most effectively managed by growing MLN-resistant varieties. However, the relative importance of MCMV and potyvirus resistance in managing this synergistic disease is poorly characterized. In this study, we evaluated the effects of SCMV and/or MCMV resistance on disease, virus titers, and synergism and explored expression patterns of known potyvirus resistance genes TrxH and ABP1. MLN disease was significantly lower in both the MCMV-resistant and SCMV-resistant inbred lines compared with the susceptible control Oh28. Prior to 14 days postinoculation (dpi), MCMV titers in resistant lines N211 and KS23-6 were more than 100,000-fold lower than found in the susceptible Oh28. However, despite no visible symptoms, titer differences between MCMV-resistant and -susceptible lines were negligible by 14 dpi. In contrast, systemic SCMV titers in the potyvirus-resistant line, Pa405, ranged from 130,000-fold to 2 million-fold lower than susceptible Oh28 as disease progressed. Initial TrxH expression was up to 49,000-fold lower in Oh28 compared with other genotypes, whereas expression of ABP1 was up to 4.5-fold lower. Measures of virus synergy indicate that whereas MCMV resistance is effective in early infection, strong potyvirus resistance is critical for reducing synergist effects of co-infection on MCMV titer. These results emphasize the importance of both potyvirus resistance and MCMV resistance in an effective breeding program for MLN management.
A synthetic, closed‐looped gene circuit for the autonomous regulation of RUNX2 activity during chondrogenesis
Authors: Kaur Gurcharan , Wu Biming , Murali Sanjana , Lanigan Thomas , Coleman Rhima M.
Published: February 2024

The transcription factor RUNX2 is a key regulator of chondrocyte phenotype during development, making it an ideal target for prevention of undesirable chondrocyte maturation in cartilage tissue‐engineering strategies. Here, we engineered an autoregulatory gene circuit (cisCXp‐shRunx2) that negatively controls RUNX2 activity in chondrogenic cells via RNA interference initiated by a tunable synthetic Col10a1‐like promoter (cisCXp). The cisCXp‐shRunx2 gene circuit is designed based on the observation that induced RUNX2 silencing after early chondrogenesis enhances the accumulation of cartilaginous matrix in ATDC5 cells. We show that the cisCXp‐shRunx2 initiates RNAi of RUNX2 in maturing chondrocytes in response to the increasing intracellular RUNX2 activity without interfering with early chondrogenesis. The induced loss of RUNX2 activity in turn negatively regulates the gene circuit itself. Moreover, the efficacy of RUNX2 suppression from cisCXp‐shRunx2 can be controlled by modifying the sensitivity of cisCXp promoter. Finally, we show the efficacy of inhibiting RUNX2 in preventing matrix loss in human mesenchymal stem cell‐derived (hMSC‐derived) cartilage under conditions that induce chondrocyte hypertrophic differentiation, including inflammation. Overall, our results demonstrated that the negative modulation of RUNX2 activity with our autoregulatory gene circuit enhanced matrix synthesis and resisted ECM degradation by reprogrammed MSC‐derived chondrocytes in response to the microenvironment of the degenerative joint.
Long-Term Quality of Life After Obstetric Intensive Care Unit Admission: A Cross-Sectional Cohort Study
Authors: Ramlakhan K.P. , van der Zande J.A. , Roos-Hesselink J.W. , Franx A. , Cornette J.
Published: February 2024

(BJOG. 2024;130(7):813–822)

Women admitted to the intensive care unit (ICU) during pregnancy or postpartum have altered their physical and psychological quality of life (QoL). Maternal and perinatal mortality and morbidity are distressing issues impacting many facilities. The long-term impact of peripartum ICU admission is unknown. Two prior studies on QoL after obstetric ICU admissions have found it important to record the physical and emotional impact on the patient and their family.
Stalled Progress in Reducing Maternal Mortality Globally: What Next?
Authors: Moyer C.A. , Lawrence E.R. , Beyuo T.K. , Tuuli M.G. , Oppong S.A.
Published: February 2024

(Lancet. 2023;401(10382):1060–1062. PMID: 36924780)

According to a report published by the World Health Organization (WHO) in February 2023, the global maternal mortality rate (MMR) improved considerably from 2000 to 2015 (the Millennium Development Goal era). However, from 2016 to 2020, the first 5 years of the Sustainable Development Goal (SDG) era, MMR stagnated or worsened in most regions of the world. During this period, only 2 regions, Australia and New Zealand and Central and Southern Asia, saw reductions in MMR (34.6% and 15.7%, respectively). The highest MMR was in Sub-Saharan Africa, accounting for ~70% of all maternal deaths in 2020.
Cracking the Environmental Problem of Nitrous Oxide in Obstetrics
Authors: Lucas D.N. , Wong R. , Kearsley R.
Published: February 2024

(Anaesthesia. 2023; 78:288–293)

Global warming and climate change are the most concerning crises that our world currently faces. The National Health Service (NHS) has worked to reduce its overall carbon footprint as a primary health care company. There are growing concerns about the effects that nitrous oxide has on the environment. It is estimated that 40% of all nitrous oxide emissions are due to human impact, and nitrous oxide use for labor analgesia increases those emissions. Catalytic cracking has been introduced to improve the impact that nitrous oxide has on our environment.