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Abstract Ballots are the core records of elections. Electronic records of actual ballots cast (cast vote records) are available to the public in some jurisdictions. However, they have been released in a variety of formats and have not been independently evaluated. Here we introduce a database of cast vote records from the 2020 U.S. general election. We downloaded publicly available unstandardized cast vote records, standardized them into a multi-state database, and extensively compared their totals to certified election results. Our release includes vote records for President, Governor, U.S. Senate and House, and state upper and lower chambers, covering 42.7 million voters in 20 states who voted for more than 2,200 candidates. This database serves as a uniquely granular administrative dataset for studying voting behavior and election administration. Using this data, we show that in battleground states, 1.9 percent of solid Republicans (as defined by their congressional and state legislative voting) in our database split their ticket for Joe Biden, while 1.2 percent of solid Democrats split their ticket for Donald Trump.

Abstract Drug discovery often involves targeting specific members within a family of similar proteins. For example, pyruvate dehydrogenase kinase (PDHK) exists as four isozymes, which exhibit varying expression patterns across multiple tissues. Different PDHK isozymes have been implicated in conditions such as cancer, heart failure, and diabetes, suggesting that targeting them with inhibitors may offer therapeutic benefits. However, simultaneous inhibition of all four PDHK isozymes has the potential to be counterproductive, or poorly tolerated, highlighting a need for isoform-selective PDHK inhibitors. Despite multiple prior reports of PDHK inhibitors, identifying isoform-specific inhibitors for each PDHK isozyme has proven elusive. In this work, we propose a comprehensive framework that combines a machine learning-based prediction method and biochemical testing to screen a library of novel and previously reported compounds, thereby identifying selective inhibitors for PDHK isozymes. Initially, a coupled tensor matrix completion (CTMC) approach is employed to predict compound-target interaction (CTI) and pinpoint target-specific inhibitors. Subsequently, biochemical testing is performed to validate the predicted CTIs. Utilizing this approach, we successfully identified five novel PDHK1-specific inhibitors, underscoring the reliability of this approach as a screening method in the early stages of drug discovery and hit identification.

Abstract Tessellations (surface architectures of arrays of hard tiles) are common in natural and man-made designs. Boxfishes (Ostracioidea) are almost completely encased in a tessellated armor and have evolved a plethora of cross-sectional carapace shapes, yet whether the scutes constructing these exhibit comparable variation is unknown. Using high-resolution microCT and semi-automatic segmentation algorithms, we quantitatively examined thousands of scutes from 13 species of diverse body form. A cluster analysis revealed that certain scute types are associated with specific carapace regions independent of carapace shape. Scute types differentiate between carapace edges and flat regions, as well as between the head region with many carapace openings and the more consistently closed abdominal region, pointing at a constructional commonality or constraint shared by all boxfish species. However, the dimensions of edge scutes varied systematically with carapace shape (e.g., scute aspect ratio tended to increase with decreasing carapace height). This suggests that protection is maintained across body forms by managing scute- and carapace-level mechanisms for increasing bending resistance. Future studies on other taxa are necessary to understand whether these architectural principles are specific evolutionary solutions for building a boxfish carapace or whether they are shared by other biological systems that serve a similar protective function.

Abstract Partial-thickness rotator cuff tears are a common cause of pain and disability and are central to developing full-thickness rotator cuff tears. However, limited knowledge exists regarding the alterations to the mechanical environment due to these lesions. Computational models that study the alterations to the mechanical environment of the supraspinatus tendon can help advance clinical management to avoid tear progression and provide a basis for surgical intervention. In this study, we use three-dimensional validated finite element models from six intact specimens to study the effects of low- and high-grade tears originating on the articular and bursal surfaces of the supraspinatus tendon. Bursal-sided tears generally had a lower failure load, modulus, and strain than articular-sided tears. Thus, caution should be taken when managing bursal-sided tears as they may be more susceptible to tear progression.

In recent years, the tobacco- and/or nicotine-containing product (TNP) portfolio has expanded to include products such as e-vapor products, heated tobacco products, and nicotine pouches. Although scientific papers and regulatory requirements/recommendations related to the assessment of product use behavior and exposure to product use have been published for these novel TNPs, there is great diversity in the terminology used to characterize and assess these types of products. The aim of this paper is to define the terms and methods used for assessing product use behavior and exposure, with the objective to suggest a uniform application of terms used by scientists working in this field of research. This publication is the work product of a cross-industry work item commissioned by the Cooperation Centre for Scientific Research Relative to Tobacco (CORESTA) Product Use Behaviour and Biomarkers Subgroups.

Abstract We examined how resistance exercise (RE), cycling exercise and disuse atrophy affect myosin heavy chain (MyHC) protein fragmentation. The 1boutRE study involved younger men (n = 8; 5 ± 2 years of RE experience) performing a lower body RE bout with vastus lateralis (VL) biopsies being obtained prior to and acutely following exercise. With the 10weekRT study, VL biopsies were obtained in 36 younger adults before and 24 h after their first/naïve RE bout. Participants also engaged in 10 weeks of resistance training and donated VL biopsies before and 24 h after their last RE bout. VL biopsies were also examined in an acute cycling study (n = 7) and a study involving 2 weeks of leg immobilization (n = 20). In the 1boutRE study, fragmentation of all MyHC isoforms (MyHCTotal) increased 3 h post‐RE (∼200%, P = 0.018) and returned to pre‐exercise levels by 6 h post‐RE. Interestingly, a greater magnitude increase in MyHC type IIa versus I isoform fragmentation occurred 3 h post‐RE (8.6 ± 6.3‐fold vs. 2.1 ± 0.7‐fold, P = 0.018). In 10weekRT participants, the first/naïve and last RE bouts increased MyHCTotal fragmentation 24 h post‐RE (+65% and +36%, P

Abstract Active gate driving (AGD) is a promising concept for achieving high‐performance power transistor switching. This is particularly crucial for Silicon Carbide (SiC) MOSFETs since their inherently fast switching characteristics give rise to severe overshoots and oscillations which translate into increased levels of electromagnetic interference (EMI) emissions. In this paper, an AGD strategy using a single‐pulse applied during the switching transient is considered for a 1200 V 400 A SiC MOSFET module. The effect of single‐pulse timing, load current, and temperature on the switching performance is analyzed in detail. The radiated EMI reduction benefits are quantified by H‐field and E‐field probes. A conceptual closed‐loop AGD approach is presented and compared to open‐loop operation. For the transistor turn‐off case under full load current of 400 A, experimental results show that it is possible to reduce voltage overshoot by 43.3%, voltage and current oscillations by 69.7% and 52.2% respectively, and EMI by 76.6%, with a trade‐off in the switching energy by a relatively minor increase of 18.2%, compared to the conventional gate driving case. For the turn‐on case, current overshoot was reduced by 32.7%, EMI by 52%, voltage and current oscillations by 54.6% and 52.8%, respectively, with a penalty of 50.9% increase in the switching loss.

Abstract Alcohol use is an independent risk factor for the development of bacterial pneumonia due, in part, to impaired mucus-facilitated clearance, macrophage phagocytosis, and recruitment of neutrophils. Alcohol consumption is also known to reduce peripheral natural killer (NK) cell numbers and compromise NK cell cytolytic activity, especially NK cells with a mature phenotype. However, the role of innate lymphocytes, such as NK cells during host defense against alcohol-associated bacterial pneumonia is essentially unknown. We have previously shown that indole supplementation mitigates increases in pulmonary bacterial burden and improves pulmonary NK cell recruitment in alcohol-fed mice, which were dependent on aryl hydrocarbon receptor (AhR) signaling. Employing a binge-on-chronic alcohol-feeding model we sought to define the role and interaction of indole and NK cells during pulmonary host defense against alcohol-associated pneumonia. We demonstrate that alcohol dysregulates NK cell effector function and pulmonary recruitment via alterations in two key signaling pathways. We found that alcohol increases transforming growth factor beta (TGF-β) signaling while suppressing AhR signaling. We further demonstrated that NK cells isolated from alcohol-fed mice have a reduced ability to kill Klebsiella pneumoniae. NK cell migratory capacity to chemokines was also significantly altered by alcohol, as NK cells isolated from alcohol-fed mice exhibited preferential migration in response to CXCR3 chemokines but exhibited reduced migration in response to CCR2, CXCR4, and CX3CR1 chemokines. Together this data suggests that alcohol disrupts NK cell-specific TGF-β and AhR signaling pathways leading to decreased pulmonary recruitment and cytolytic activity thereby increasing susceptibility to alcohol-associated bacterial pneumonia.

Abstract Gut microbiomes are widely hypothesised to influence host fitness and have been experimentally shown to affect host health and phenotypes under laboratory conditions. However, the extent to which they do so in free-living animal populations and the proximate mechanisms involved remain open questions. In this study, using long-term, individual-based life history and shallow shotgun metagenomic sequencing data (2394 fecal samples from 794 individuals collected between 2013–2019), we quantify relationships between gut microbiome variation and survival in a feral population of horses under natural food limitation (Sable Island, Canada), and test metagenome-derived predictions using short-chain fatty acid data. We report detailed evidence that variation in the gut microbiome is associated with a host fitness proxy in nature and outline hypotheses of pathogenesis and methanogenesis as key causal mechanisms which may underlie such patterns in feral horses, and perhaps, wild herbivores more generally.

Abstract Human iPSC-derived cardiomyocytes (hiPSC-CMs) have proven invaluable for cardiac disease modeling and regeneration. Challenges with quality, inter-batch consistency, cryopreservation and scale remain, reducing experimental reproducibility and clinical translation. Here, we report a robust stirred suspension cardiac differentiation protocol, and we perform extensive morphological and functional characterization of the resulting bioreactor-differentiated iPSC-CMs (bCMs). Across multiple different iPSC lines, the protocol produces 1.2E6/mL bCMs with ~94% purity. bCMs have high viability after cryo-recovery (>90%) and predominantly ventricular identity. Compared to standard monolayer-differentiated CMs, bCMs are more reproducible across batches and have more mature functional properties. The protocol also works with magnetically stirred spinner flasks, which are more economical and scalable than bioreactors. Minor protocol modifications generate cardiac organoids fully in suspension culture. These reproducible, scalable, and resource-efficient approaches to generate iPSC-CMs and organoids will expand their applications, and our benchmark data will enable comparison to cells produced by other cardiac differentiation protocols.

Mucopolysaccharidosis type I (MPS I) is a rare metabolic disorder caused by deficiency of α-L-iduronidase (IDUA), resulting in glycosaminoglycan (GAG) accumulation and multisystemic disease. Current treatments include hematopoietic stem cell transplantation and enzyme replacement therapy, but these do not address all manifestations of the disease. We infused MPS I mice with an adeno-associated virus 9 (AAV9)-IDUA vector (RGX-111) at doses from 107 to 1010 vector genomes (vg) via intrathecal (IT), intravenous (IV), and intrathecal+intravenous (IT+IV) routes of administration. In mice administered doses ≤109 vg IT or ≤108 vg IV, there was no therapeutic benefit, while in mice administered 109 vg IV, there was a variable increase in IDUA activity with inconclusive neurocognitive and cardiac assessments. However, at the 1010 vg dose, we observed substantial metabolic correction, with restored IDUA levels and normalized tissue GAGs for all treatment groups. Aortic insufficiency was mostly normalized, neurologic deficit was prevented, and microcomputed tomography (micro-CT) analysis showed normalization of skeletal parameters. Histologic analysis showed minimal GAG storage and lysosomal pathology. We thus report a minimal effective dose of 1010 vg (5 × 1011 per kg) RGX-111 for IV and IT routes of administration in MPS I mice, which prevented neurocognitive deficit, cardiac insufficiency, and skeletal manifestations, as a model for genetic therapy of human MPS I.

Background:. While rotator cuff tears are prevalent in the general population, the natural history of this disease is unclear. Understanding rotator cuff tear progression is crucial for refining surgical indications and evaluating the necessity of early interventions. This study presents an in-depth analysis of the existing literature on the definitions and progression rates of rotator cuff tears, aiming to enhance clinical decision making and patient outcomes. Methods:. A systematic literature search was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using Medline (PubMed), Embase (Elsevier), and Web of Science databases on January 12, 2023. Articles were identified as relevant to the natural history and progression of asymptomatic and symptomatic partial-thickness (PT) and full-thickness (FT) rotator cuff tears. Those written in English reporting rotator cuff progression rates of tears in adults, based on magnetic resonance imaging (MRI) or ultrasound, were included. After reviewing the articles, the data on the rates of tear progression and associated risk factors were extracted, compiled, and analyzed. The risk of bias was determined using the Newcastle-Ottawa Scale. Results:. Twenty-one articles met the inclusion criteria, with 1,831 tears included. The progression rate for all partial thickness tears was 26.7% ± 12.8% at an average follow-up of 2.2 ± 0.9 years, with 5 definitions for tear progression. For FT tears, the progression rate was 54.9% ± 18.6% at a follow-up time of 3.0 ± 2.0 years, with 8 definitions for tear enlargement. A significant difference (p < 0.0001) was found between the progression rates of PT and FT tears. Patients who were initially asymptomatic and became symptomatic had higher progression rates (33%–63%) than those who remained asymptomatic (4%–38%). Conclusion:. Further research would benefit by identifying a clinically relevant and standardized definition of rotator cuff tear progression, to describe the natural history of rotator cuff disease, making results more comparable and optimizing treatment planning. Level of Evidence:. Level II. See Instructions for Authors for a complete description of levels of evidence.

Background: The prognosis of pancreatic ductal adenocarcinomas (PDAC) remains very poor, emphasizing the critical importance of early detection, where biomarkers offer unique potential. Although growth differentiation factor 15 (GDF15) and Lipocalin 2 (LCN2) have been linked to PDAC, their precise roles as biomarkers are uncertain. Methods: Circulating levels of GDF15 and LCN2 were examined in human PDAC patients, heathy controls, and individuals with benign pancreatic diseases. Circulating levels of IL-6, CA19-9, and neutrophil-to-lymphocyte ratio (NLR) were measured for comparisons. Correlations between PDAC progression and overall survival were assessed. A mouse PDAC model was employed for comprehensive analyses, complementing the human studies by exploring associations with various metabolic and inflammatory parameters. Sensitivity and specificity of the biomarkers were evaluated. Findings: Our results demonstrated elevated levels of circulating GDF15 and LCN2 in PDAC patients compared to both healthy controls and individuals with benign pancreatic diseases, with higher GDF15 levels associated with disease progression and increased mortality. In PDAC mice, circulating GDF15 and LCN2 progressively increased, correlating with tumor growth, behavioral manifestations, tissue and molecular pathology, and cachexia development. GDF15 exhibited highly sensitive and specific for PDAC patients compared to CA19-9, IL-6, or NLR, while LCN2 showed even greater sensitivity and specificity in PDAC mice. Combining GDF15 and LCN2, or GDF15 and CA19-9, enhanced sensitivity and specificity. Interpretation: Our findings indicate that GDF15 holds promise as a biomarker for early detection and prognosis of PDAC, while LCN2 could strengthen diagnostic panels.

ABSTRACTObjective The purpose of this study was to examine the acute effects of a multi-ingredient, low calorie dietary supplement (MIDS, XTEND® Healthy Hydration) on 5-kilometer (5-km) time trial performance and blood electrolyte concentrations compared to a carbohydrate-electrolyte beverage (CE, GATORADE® Thirst Quencher) and distilled water (W).Methods During visit 1 (V1), participants (10 men and 10 women, 20–35 years old, BMI ≤ 29 kg/m2, recreationally active) reported to the laboratory whereby the following tests were performed: i) height and weight measurements, ii) body composition analysis, iii) treadmill testing to measure maximal aerobic capacity, and iv) 5-km time trial familiarization. The second visit (V2) was one week after V1 in the morning (0600 – 0900) and participants arrived 12–14 h fasted (no food or drink). The first battery of assessments (V2-T1) included nude body mass, urine specific gravity (USG), a profile of mood states (POMS) questionnaire, and the completion of a visual analogue scale (VAS) questionnaire to quantify cramping. Then heart rate (HR), blood pressure (BP), total body hydration (via bioelectrical impedance spectroscopy [BIS]) were examined. Finally, a measurement of blood markers via finger stick was performed. Participants consumed a randomized beverage (16 fl. oz. of MIDS, 16 fl. oz. of W, or 16 fl. oz. of CE) within 3 min followed by a 45-min rest. Following the rest period, a second battery (V2-T2) was performed whereby participants’ USG was assessed and they completed the POMS and VAS questionnaires, and HR, BP, and blood markers were measured. The participants then performed a 5-km treadmill time trial. Immediately following the 5-km time trial, participants completed a third testing battery (V2-T3) that began with blood markers, HR and BP assessments, followed by nude body weight assessment, and the POMS and VAS questionnaires. After 60 min, a fourth battery (V2-T4) was performed that included HR, BP, and blood markers. After sitting quietly for another 60 min a fifth battery assessment was performed (V2-T5) that included participants’ USG, POMS and VAS questionnaires, HR, BP, blood markers, and total body hydration. Visits 3 (V3) and 4 (V4) followed the same protocol except a different randomized drink (16 oz. of CE, MIDS, or W) was consumed; all of which were separated by approximately one week.Results No differences occurred between conditions for 5-km time trial completion, indirect calorimetry outcomes during 5-km time trials, USG, or nude mass measurements (p > 0.05 for all relevant statistical tests). However, blood potassium and the sodium/potassium ratio displayed significant interactions (p

Objective To examine the feasibility of implementing remote atrial fibrillation (AF) self-screening among older people supported by a remote central monitoring system.Design Process evaluation of the Mass AF randomised clinical trial (ACTRN12621000184875) with one-to-one semistructured interviews using interview guides underpinned by the Critical Realism approach and coded using the UK Medical Research Council Guidance of Process Evaluation Framework.Setting and participants Community-dwelling people aged ≥75 years from both genders (ratio 1:1) and urban/rural (ratio 2:1) in Australia.Interventions Participants were provided handheld single-lead electrocardiogram (ECG) devices and trained to self-record ECGs once daily on weekdays for at least 6 months. A remote central team notified participants and general practitioners (GPs) of AF.Primary feasibility outcomes The strengths, weaknesses, opportunities and threats (SWOT) analysis examined enablers (ie, strengths and opportunities) and barriers (ie, weaknesses and threats).Results Overall, 200 participants; 98.5% completed the 6-month programme, 96% reported being satisfied with screening and 48 were interviewed: mean age 79 years, 54% male and 71% urban. 11 GPs were interviewed: 55% female and 64% urban. Programme participants trusted the remote monitoring system that supported the screening programme and provided follow-up pathways where required. GPs saw opportunities to introduce this self-screening programme to at-risk patients and improve patients’ risk profiles. Programme participants reported that after being trained to use the device, they felt empowered to do self-screening and found it convenient. GPs saw empowerment could enhance the doctor–patient relationship. Programme participants and GPs valued screening in diagnosing AF that would otherwise be missed in usual care, but the uncertainty of effective screening duration could be a barrier.Conclusions This screening programme was feasible with the reinforcement of the underpinning enablers. Several implementation strategies were identified using SWOT analysis, including leveraging the opportunity for GPs to introduce this screening programme to at-risk patients.Trial registration number ACTRN12621000184875.

ABSTRACT Wildlife abundance and movement are strongly impacted by landscape heterogeneity, especially in cities which are among the world's most heterogeneous landscapes. Nonetheless, current global land cover maps, which are used as a basis for large‐scale spatial ecological modeling, represent urban areas as a single, homogeneous, class. This often requires urban ecologists to rely on geographic resources from local governments, which are not comparable between cities and are not available in underserved countries, limiting the spatial scale at which urban conservation issues can be tackled. The recent expansion of community‐based geographic databases, for example, OpenStreetMap (OSM), represents an opportunity for ecologists to generate large‐scale maps geared toward their specific research needs. However, computational differences in language and format, and the high diversity of information within, limit the access to these data. We provide a framework, using R, to extract geographic features from the OSM database, classify, and integrate them into global land cover maps. The framework includes an exhaustive list of OSM features describing urban and peri‐urban landscapes and is validated by quantifying the completeness of the OSM features characterized, and the accuracy of its final output in 34 cities in North America. We portray its application as the basis for generating landscape variables for ecological analysis by using the OSM‐enhanced map to generate an urbanization index, and subsequently analyze the spatial occupancy of six mammals throughout Chicago, Illinois, USA. The OSM features characterized had high completeness values for impervious land cover classes (50%–100%). The final output, the OSM‐enhance map, provided an 89% accurate representation of the landscape at 30m resolution. The OSM‐derived urbanization index outperformed other global spatial data layers in the spatial occupancy analysis and concurred with previously seen local response trends, whereby lagomorphs and squirrels responded positively to urbanization, while skunks, raccoons, opossums, and deer responded negatively. This study provides a roadmap for ecologists to leverage the fine resolution of open‐source geographic databases and apply it to spatial modeling by generating research‐specific landscape variables. As our occupancy results show, using context‐specific maps can improve modeling outputs and reduce uncertainty, especially when trying to understand anthropogenic impacts on wildlife populations.

Background It is unclear whether chronically training close to volitional failure influences motor unit recruitment strategies during fatigue. Purpose We compared resistance training to near volitional failure vs. non-failure on individual motor unit action potential amplitude (MUAP) and surface electromyographic excitation (sEMG) during fatiguing contractions. Methods Nineteen resistance-trained adults (11 males, 8 females) underwent 5 weeks (3×/week) of either low repetitions-in-reserve (RIR; 0–1 RIR) or high RIR training (4–6 RIR). Before and after the intervention, participants performed isometric contractions of the knee extensors at 30% of maximal peak torque until exhaustion while vastus lateralis sEMG signals were recorded and later decomposed. MUAP and sEMG excitation for the vastus lateralis were quantified at the beginning, middle, and end of the fatigue assessment. Results Both training groups improved time-to-task failure (mean change = 43.3 s, 24.0%), with no significant differences between low and high RIR training groups (low RIR = 28.7%, high RIR = 19.4%). Our fatigue assessment revealed reduced isometric torque steadiness and increased MUAP amplitude and sEMG excitation during the fatiguing task, but these changes were consistent between groups. Conclusion Both low and high RIR training improved time-to-task failure, but resulted in comparable motor unit recruitment during fatiguing contractions. Our findings indicate that both low and high RIR training can be used to enhance fatiguability among previously resistance-trained adults.

Data were collected from four plant materials courses over the span of 20 years. Two classes were at the undergraduate level, Trees and Shrubs for Sustainable Built Environments (HORT 306) and Plants for Sustainable Landscapes (HORT 308), and two classes were at the graduate level, Plants for Landscape Design (HORT 608) and Plants for Landscape Design II (HORT 609). Data from these courses were analyzed to determine trends in student performance and benchmarks that might be associated with student success. Data included student enrollment, midterm course grades, final course grades, number of unexcused absences, student-reported study times for various activities, student major, student experience (class rank), whether the courses were required, and perceived difficulty levels of the courses. Trends in grade distributions were fairly stable until the last 3 to 4 years before COVID-19, when mean final grades and the frequencies of A or B grades increased. Midterm grades were strongly positively correlated with final course grades across majors in all four courses before COVID-19 (R2 = 0.90, 0.74, 0.72, and 0.54 for HORT 306, HORT 308, HORT 608, and HORT 609, respectively; P ≤ 0.001) and continued to be positively correlated after COVID-19. The number of unexcused absences was negatively significantly correlated with final course grades across majors (R2 = −0.69, −0.63, −0.21, and −0.45 for HORT 306, HORT 308, HORT 608, and HORT 609, respectively) before COVID-19 (P ≤ 0.001) and continued to be similarly correlated after COVID-19. Fewer reductions from midterm to final grades were observed for fall courses than for spring courses, particularly for seniors. Self-reported time spent studying all aspects of the courses was either not significantly correlated (P ≤ 0.05) or surprisingly slightly negatively correlated with the final course grades for all four courses. Perceptions of courses as moderately difficult (range, 7.0–8.0 out of 10.0) were remarkably stable overall but varied considerably by major (range, 5.0–8.3) and experience (range, 7.5 for seniors to 8.1 for freshman). More than 96% of enrollment in the graduate courses both before and after COVID-19 comprised Horticulture and Landscape Architecture majors, whereas undergraduate enrollment included a wide diversity of majors; however, the majority of those students were horticulture or landscape architecture majors. Biological science students or students who were architectural design majors were the top-performing students in both undergraduate courses, whereas undeclared majors, social science majors, and those in probationary major categories were among the lower-performing students in both undergraduate courses.

Background Although current guidelines recommend implantable cardioverter‐defibrillator (ICD) placement in survivors of out‐of‐hospital cardiac arrest, contemporary data on secondary‐prevention ICDs in survivors of out‐of‐hospital cardiac arrest remain limited. Methods and Results Using 2013 to 2019 CARES (Cardiac Arrest Registry to Enhance Survival) linked to Medicare, we identified 3226 patients aged ≥65 years with an initial shockable rhythm who survived to discharge without severe neurological disability. Multivariable hierarchical regression models were used to examine the association between patient variables and ICD placement and quantify hospital variation in ICD implantation. The mean age was 72.2 years, 23.5% were women, 10% were Black individuals, and 4% were Hispanic individuals. Overall, 997 (30.9%) patients received an ICD before discharge, 1266 (39.2%) at 90 days, and 1287 (39.9%) within 6 months. Older age (≥85 years), female sex, history of diabetes, calendar year, and presentation with acute myocardial infarction were associated with lower odds of ICD implantation, but race or ethnicity was not associated with ICD implantation. Among 297 hospitals, the median proportion of survivors receiving ICD at discharge was 28.6% (interquartile range, 20%–50%). The relative odds of ICD implantation varied by 62% across hospitals (median odds ratio, 1.62 [95% CI, 1.38–1.82]) after adjusting for case mix. Conclusions Fewer than 1 in 3 survivors of out‐of‐hospital cardiac arrest due to a shockable rhythm received a secondary‐prevention ICD before discharge. Although patient variables were associated with ICD implantation, there was no difference by race or ethnicity. Even after adjusting for patient case mix, ICD implantation varied markedly across hospitals.

Abstract Although patients benefit from immune checkpoint inhibition (ICI) therapy in a broad variety of tumors, resistance may arise from immune suppressive tumor microenvironments (TME), which is particularly true of hepatocellular carcinoma (HCC). Since oncolytic viruses (OV) can generate a highly immune-infiltrated, inflammatory TME, OVs could potentially restore ICI responsiveness via recruitment, priming, and activation of anti-tumor T cells. Here we find that on the contrary, an oncolytic vesicular stomatitis virus, expressing interferon-ß (VSV-IFNß), antagonizes the effect of anti-PD-L1 therapy in a partially anti-PD-L1-responsive model of HCC. Cytometry by Time of Flight shows that VSV-IFNß expands dominant anti-viral effector CD8 T cells with concomitant relative disappearance of anti-tumor T cell populations, which are the target of anti-PD-L1. However, by expressing a range of HCC tumor antigens within VSV, combination OV and anti-PD-L1 therapeutic benefit could be restored. Our data provide a cautionary message for the use of highly immunogenic viruses as tumor-specific immune-therapeutics by showing that dominant anti-viral T cell responses can inhibit sub-dominant anti-tumor T cell responses. However, through encoding tumor antigens within the virus, oncolytic virotherapy can generate anti-tumor T cell populations upon which immune checkpoint blockade can effectively work.

Abstract During the early development of quantum chromodynamics, it was proposed that baryon number could be carried by a non-perturbative Y-shaped topology of gluon fields, called the gluon junction, rather than by the valence quarks as in the QCD standard model. A puzzling feature of ultra-relativistic nucleus-nucleus collisions is the apparent substantial baryon excess in the mid-rapidity region that could not be adequately accounted for in most conventional models of quark and diquark transport. The transport of baryonic gluon junctions is predicted to lead to a characteristic exponential distribution of net-baryon density with rapidity and could resolve the puzzle. In this context we point out that the rapidity density of net-baryons near mid-rapidity indeed follows an exponential distribution with a slope of $$-0.61\pm 0.03$$ - 0.61 ± 0.03 as a function of beam rapidity in the existing global data from A+A collisions at AGS, SPS and RHIC energies. To further test if quarks or gluon junctions carry the baryon quantum number, we propose to study the absolute magnitude of the baryon vs. charge stopping in isobar collisions at RHIC. We also argue that semi-inclusive photon-induced processes ( $$\gamma +p$$ γ + p /A) at RHIC kinematics provide an opportunity to search for the signatures of the baryon junction and to shed light onto the mechanisms of observed baryon excess in the mid-rapidity region in ultra-relativistic nucleus-nucleus collisions. Such measurements can be further validated in A+A collisions at the LHC and $$e+p$$ e + p /A collisions at the EIC.

Abstract The intestinal extracellular matrix (ECM) helps maintain appropriate tissue barrier function and regulate host-microbial interactions. Chondroitin sulfate- and dermatan sulfate-glycosaminoglycans (CS/DS-GAGs) are integral components of the intestinal ECM, and alterations in CS/DS-GAGs have been shown to significantly influence biological functions. Although pathologic ECM remodeling is implicated in inflammatory bowel disease (IBD), it is unknown whether changes in the intestinal CS/DS-GAG composition are also linked to IBD in humans. Our aim was to characterize changes in the intestinal ECM CS/DS-GAG composition in intestinal biopsy samples from patients with IBD using mass spectrometry. We characterized intestinal CS/DS-GAGs in 69 pediatric and young adult patients (n = 13 control, n = 32 active IBD, n = 24 IBD in remission) and 6 adult patients. Here, we report that patients with active IBD exhibit a significant decrease in the relative abundance of CS/DS isomers associated with matrix stability (CS-A and DS) compared to controls, while isomers implicated in matrix instability and inflammation (CS-C and CS-E) were significantly increased. This imbalance of intestinal CS/DS isomers was restored among patients in clinical remission. Moreover, the abundance of pro-stabilizing CS/DS isomers negatively correlated with clinical disease activity scores, whereas both pro-inflammatory CS-C and CS-E content positively correlated with disease activity scores. Thus, pediatric patients with active IBD exhibited increased pro-inflammatory and decreased pro-stabilizing CS/DS isomer composition, and future studies are needed to determine whether changes in the CS/DS-GAG composition play a pathogenic role in IBD.

Abstract For the last century, the source of sulfur in Earth’s very first organisms has remained a fundamental, unsolved enigma. While sulfates and their organic derivatives with sulfur in the S(+VI) oxidation state represent core nutrients in contemporary biochemistry, the limited bioavailability of sulfates during Earth’s early Archean period proposed that more soluble S(+IV) compounds served as the initial source of sulfur for the first terrestrial microorganisms. Here, we reveal via laboratory simulation experiments that the three simplest alkylsulfonic acids—water soluble organic S(+IV) compounds—can be efficiently produced in interstellar, sulfur-doped ices through interaction with galactic cosmic rays. This discovery opens a previously elusive path into the synthesis of vital astrobiological significance and untangles fundamental mechanisms of a facile preparation of sulfur-containing, biorelevant organics in extraterrestrial ices; these molecules can be eventually incorporated into comets and asteroids before their delivery and detection on Earth such as in the Murchison, Tagish Lake, and Allende meteorites along with the carbonaceous asteroid Ryugu.

Abstract Why do some songs and musicians become successful while others do not? We show that one of the reasons may be the “first-mover advantage”: artists that stand at the foundation of new music genres tend to be more successful than those who join these genres later on. To test this hypothesis, we have analyzed a massive dataset of over 920,000 songs, including 110 music genres: 10 chosen intentionally and preregistered, and 100 chosen randomly. For this, we collected the data from two music services: Spotify, which provides detailed information about songs’ success (the precise number of times each song was listened to), and Every Noise at Once, which provides detailed genre tags for musicians. 91 genres, out of 110, show the first-mover advantage—clearly suggesting that it is an important mechanism in music success and evolution.

Abstract SPI1 was recently reported as a genetic risk factor for Alzheimer’s disease (AD) in large-scale genome-wide association studies. However, it is unknown whether SPI1 should be downregulated or increased to have therapeutic benefits. To investigate the effect of modulating SPI1 levels on AD pathogenesis, we performed extensive biochemical, histological, and transcriptomic analyses using both Spi1-knockdown and Spi1-overexpression mouse models. Here, we show that the knockdown of Spi1 expression significantly exacerbates insoluble amyloid-β (Aβ) levels, amyloid plaque deposition, and gliosis. Conversely, overexpression of Spi1 significantly ameliorates these phenotypes and dystrophic neurites. Further mechanistic studies using targeted and single-cell transcriptomics approaches demonstrate that altered Spi1 expression modulates several pathways, such as immune response pathways and complement system. Our data suggest that transcriptional reprogramming by targeting transcription factors, like Spi1, might hold promise as a therapeutic strategy. This approach could potentially expand the current landscape of druggable targets for AD.

Abstract Solid-state spin qubits within silicon crystals at mK temperatures show great promise in the realisation of a fully scalable quantum computation platform. Qubit coherence times are limited in natural silicon owing to coupling to the 29Si isotope which has a non-zero nuclear spin. This work presents a method for the depletion of 29Si in localised volumes of natural silicon wafers by irradiation using a 45 keV 28Si focused ion beam with fluences above 1 × 1019 ions cm−2. Nanoscale secondary ion mass spectrometry analysis of the irradiated volumes shows residual 29Si concentration down to 2.3 ± 0.7 ppm and with residual C and O comparable to the background concentration in the unimplanted wafer. After annealing, transmission electron microscopy lattice images confirm the solid phase epitaxial re-crystallization of the as-implanted amorphous enriched volume extending over 200 nm in depth.

Abstract: Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system. The prognosis of GBM is grim, with a median overall survival of 14.6 months and only 6.9% of patients surviving 5 years after the initial diagnosis. Despite poor outcomes, standard therapy of surgical resection, radiotherapy, chemotherapy, and tumor-treating fields has remained largely unchanged. The introduction of immune checkpoint inhibitors (ICI) has been a paradigm shift in oncology, with efficacy across a broad spectrum of cancer types. Nonetheless, investigations of ICIs in both newly diagnosed and recurrent GBM have thus far been disappointing. This lack of clinical benefit has been largely attributed to the highly immunosuppressive nature of GBM. However, immunotherapy still holds promise for the treatment of GBM, with combinatorial strategies offering hope for potentially overcoming these current limitations. In this review, we discuss the outcomes of clinical trials employing ICIs in patients with GBM. Afterward, we review ICI combination strategies and how these combinations may overcome the immunosuppressive microenvironment of GBM in the context of preclinical/clinical evidence and ongoing clinical trials.

Abstract The TTG2 transcription factor of Arabidopsis regulates a set of epidermal traits, including the differentiation of leaf trichomes, flavonoid pigment production in cells of the inner testa (or seed coat) layer and mucilage production in specialized cells of the outer testa layer. Despite the fact that TTG2 has been known for over twenty years as an important regulator of multiple developmental pathways, little has been discovered about the downstream mechanisms by which TTG2 co-regulates these epidermal features. In this study, we present evidence of phosphoinositide lipid signaling as a mechanism for the regulation of TTG2-dependent epidermal pathways. Overexpression of the AtPLC1 gene rescues the trichome and seed coat phenotypes of the ttg2-1 mutant plant. Moreover, in the case of seed coat color rescue, AtPLC1 overexpression restored expression of the TTG2 flavonoid pathway target genes, TT12 and TT13/AHA10. Consistent with these observations, a dominant AtPLC1 T-DNA insertion allele (plc1-1D) promotes trichome development in both wild-type and ttg2-3 plants. Also, AtPLC1 promoter:GUS analysis shows expression in trichomes and this expression appears dependent on TTG2. Taken together, the discovery of a genetic interaction between TTG2 and AtPLC1 suggests a role for phosphoinositide signaling in the regulation of trichome development, flavonoid pigment biosynthesis and the differentiation of mucilage-producing cells of the seed coat. This finding provides new avenues for future research at the intersection of the TTG2-dependent developmental pathways and the numerous molecular and cellular phenomena influenced by phospholipid signaling.

Janice Du Mont,1,2 Frances Montemurro,1 Rhonelle Bruder,1,2 C Emma Kelly,1 Frances Recknor,1 Robin Mason1,2 1Women’s College Research Institute, Women’s College Hospital, Toronto, ON, M5S 1B2, Canada; 2Dalla Lana School of Public Health, University of Toronto, Toronto, ON, M5T 3M7, CanadaCorrespondence: Janice Du Mont, Women’s College Research Institute, Women’s College Hospital, 76 Grenville St, Toronto, ON, M5S 1B2, Canada, Email janice.dumont@wchospital.caAbstract: Health care providers are highly likely to encounter persons who have been domestically sex trafficked and, therefore, possess valuable insights that could be useful in understanding and improving existing services and supports. In-depth interviews were conducted with 31 health care providers residing and working in Canada’s largest province, Ontario. Results were analyzed using Braun and Clarke’s analytical framework. Across providers, a key theme was identified: “Facilitators to improve care”, which was comprised of two sub-themes, “Address needs in service provision” and “Center unique needs of survivors”. From these results, eight wide-ranging recommendations to improve services and supports were developed (eg, Jointly mobilize an intersectoral, collaborative, and coordinated approach to sex trafficking service provision; Employ a survivor-driven approach to designing and delivering sex trafficking services). These recommendations hold the potential to enhance services in Canada and beyond by reducing barriers to access and care, facilitating disclosure, aiding in recovery, and empowering those who have been domestically sex trafficked.Keywords: domestic, human trafficking, health care, recommendations, sex trafficking, social services

Abstract Resource distribution, habitat structure, and predators greatly influence spatial and temporal landscape use by prey species. The “risky places” hypothesis establishes prey will proactively respond to predators' presence based on habitat cues, whereas the “risky times” hypothesis predicts prey will reactively respond by increasing vigilance in the presence of predators regardless of habitat cues. We fit a multiscale, Bayesian species interaction occupancy model with detection/non‐detection data to evaluate black‐tailed jackrabbit (Lepus californicus) and eastern cottontail rabbit (Sylvilagus floridanus) habitat use in the presence and absence of coyotes (Canis latrans), American badgers (Taxidea taxus), and swift foxes (Vulpes velox). We also evaluated how species‐specific predator presence modified temporal activity patterns of prey. Jackrabbits decreased habitat use in areas with greater forage and opted to use areas with greater visibility when coyotes or swift foxes were present. However, cottontails used habitat in open areas with greater visibility when American badgers were present and all other predators absent, suggesting dissimilar habitat‐use patterns dictated by predator‐specific risks. Both lagomorph species are nocturnal with segregated peaks of activity compared with predators, suggesting fine‐scale temporal use partitioning. Our results provide insights into predator–prey dynamics across heterogenous landscapes in a multi‐predator system.

Abstract Small populations of imperiled species are susceptible to the negative consequences of skewed sex‐ratios. In imperiled species with environmental sex determination such as sea turtles, examining sex ratios across a range of environments and population abundance levels can provide insight into factors that influence population resilience, which can then be the foci of management plans for these species. Breeding sex ratios (the ratio of actively breeding males to females during a reproductive season; BSRs) extrapolated from genetic parentage analyses are a common approach for enumerating sex ratios in sea turtles. Such analyses also allow for the characterization of multiple paternity within sea turtle clutches, which should reflect BSRs and breeding behaviors. We characterized the first BSR for a breeding assemblage of loggerhead sea turtles (Caretta caretta) belonging to the temperate, low‐abundance Northern Gulf of Mexico Recovery Unit using genotypes of 16 microsatellite loci from nesting females and hatchlings. Unlike prior studies at both more‐tropical and more‐temperate, and higher‐abundance, Recovery Units in this region, we found a balanced BSR of 1.3:1 males:female and a low incidence (~17%) of multiple paternity. This suggests that there are relatively few males breeding at this assemblage and within this Recovery Unit. Beaches in this region are expected to produce substantial numbers of male hatchlings based on sand temperature data. The relative dearth of mature males may then be due to hydrologic disturbances that disproportionately affect the fitness and survival of male hatchlings, or due to demographic stochasticity. More work is needed to study the factors that might influence male hatchling production and fitness in this region, particularly as climate change is predicted to lead to feminization in global sea turtle populations. Our work demonstrates the broad utility of characterizing BSRs and other sex ratios across a range of populations in imperiled, environmentally sensitive species.

Abstract Introduction Controlled ankle motion (CAM) boots are a below‐knee orthotic device prescribed for the management of foot and ankle injuries to reduce ankle range of motion (RoM) and offload the foot and ankle whilst allowing continued ambulation during recovery. There is a lack of clarity within the current literature surrounding the biomechanical understanding and effectiveness of CAM boots. Aims To summarise the biomechanical effects of CAM boot wear as an orthotic for restricting ankle RoM and offloading the foot. Methods A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. All papers were independently screened by two authors for inclusion. Methodological quality was appraised using Joanna Briggs Critical Appraisal checklists. A narrative synthesis of all eligible papers was produced. Results Thirteen studies involving 197 participants (113 male and 84 female) were included. All studies were quasi‐randomised and employed a within‐study design, of which 12 studies included a control group and a range of CAM boots were investigated. CAM boots can be seen to restrict ankle RoM, however, neighboring joints such as the knee and hip do have kinetic and kinematic compensatory alterations. Plantar pressure of the forefoot is effectively redistributed to the hindfoot by CAM boots. Conclusion The compensatory mechanisms at the hip and knee joint during CAM boot wear could explain the secondary site pain often reported in patients, specifically at the ipsilateral knee and contralateral hip. Although CAM boots can be used to restrict ankle motion, this review has highlighted a lack of in‐boot kinematic analyses during CAM boot use, where tracking markers are placed on the anatomical structure rather than on the boot, or through video fluoroscopy, urging the need for a more robust methodological approach to achieve this. There is a need for studies to assess the biomechanical alterations caused by CAM boots in populations living with foot and ankle pathologies. Future research, adopting a longitudinal study design, is required to fully understand the effectiveness of CAM boots for rehabilitation.

Aminergic nuclei in mammals are generally composed of relatively small numbers of cells with broad projection patterns. Despite the gross similarity of many individual neurons, recent transcriptomic, anatomic and behavioral studies suggest previously unsuspected diversity. Smaller clusters of aminergic neurons in the model organism Drosophila melanogaster provide an opportunity to explore the ramifications of neuronal diversity at the level of individual cells. A group of approximately 10 tyraminergic/octopaminergic neurons innervates the female reproductive tract in flies and has been proposed to regulate multiple activities required for fertility. The projection patterns of individual neurons within the cluster are not known and it remains unclear whether they are functionally heterogenous. Using a single cell labeling technique, we show that each region of the reproductive tract is innervated by a distinct subset of tyraminergic/octopaminergic cells. Optogenetic activation of one subset stimulates oviduct contractions, indicating that the cluster as a whole is not required for this activity, and underscoring the potential for functional diversity across individual cells. Using whole cell patch clamp, we show that two adjacent and morphologically similar cells are tonically inhibited, but each responds differently to injection of current or activation of the inhibitory GluCl receptor. GluCl appears to be expressed at relatively low levels in tyraminergic/octopaminergic neurons within the cluster, suggesting that it may regulate their excitability via indirect pathways. Together, our data indicate that specific tyraminergic/octopaminergic cells within a relatively homogenous cluster have heterogenous properties and provide a platform for further studies to determine the function of each cell.

# Background The modified Thomas test (MTT) is commonly used to assess the flexibility of hip musculature, including the iliopsoas, rectus femoris, and tensor fascia latae. This measurement is important to include in a comprehensive musculoskeletal examination. However, existing research shows conflicting results regarding its reliability, particularly due to variations in controlling pelvic tilt during testing, which may lead to inaccurate measurements of hip extension when quantifying the test outcomes. # Purpose/Hypothesis This study aimed to evaluate the intra- and inter-rater reliability of the Modified Thomas Test (MTT) in assessing hip flexor length using a goniometer. It was hypothesized that controlling for pelvic tilt would enhance the reliability of these measurements. # Study Design Intra- and inter-rater reliability study # Methods Sixty-four healthy individuals were recruited to participate in this study. The MTT was performed twice on each leg by both an experienced and a student physical therapist. Blinded goniometric measurements for hip extension range of motion (ROM) in the MTT position were taken with neutral pelvic tilt being enforced via palpation. A double-blind protocol was used where both examiners were unaware of each other's measurements and the goniometer was covered to blind the measuring therapist to the values as well. ROM values were entered into a Microsoft Excel spreadsheet and quantified using SPSS software. Statistical analysis included calculating Intraclass Correlation Coefficients (ICCs) and Standard Errors of Measurement (SEMs) using SPSS software. # Results The study included 64 participants (mean age = 23.7 ± 4.34 years). The MTT demonstrated high intra-rater reliability (ICC = 0.911) and inter-rater reliability (ICC = 0.851). The SEMs indicated minimal variability around the mean scores. The average hip extension ROM measured was 5.43± 9.73 degrees. # Conclusion These results suggest that the MTT is a reliable tool for assessing hip flexor length in clinical practice, particularly when pelvic tilt is controlled. These results have important implications for accurately testing orthopedic limitations that can contribute to low back, hip, and knee pain. # Level of Evidence 3

ABSTRACT The annual meeting for the Intermountain Branch was held in April 2024 on the campus of Brigham Young University. There were 127 branch members from Utah, Idaho, and Nevada who attended the meeting and were composed of undergraduate students, graduate or medical students, and faculty. This report highlights the diversity of, and the emerging trends in, the research conducted by American Society for Microbiology members in the Intermountain Branch.

Cancer initiates as a consequence of genomic mutations and its subsequent progression relies in part on increased production of ribosomes to maintain high levels of protein synthesis for unchecked cell growth. Recently, cytidine deaminases have been uncovered as sources of mutagenesis in cancer. In an attempt to form a connection between these 2 cancer driving processes, we interrogated the cytidine deaminase family of proteins for potential roles in human ribosome biogenesis. We identified and validated APOBEC3A and APOBEC4 as novel ribosome biogenesis factors through our laboratory's established screening platform for the discovery of regulators of nucleolar function in MCF10A cells. Through siRNA depletion experiments, we highlight APOBEC3A's requirement in making ribosomes and specific role within the processing and maturation steps that form the large subunit 5.8S and 28S ribosomal (r)RNAs. We demonstrate that a subset of APOBEC3A resides within the nucleolus and associates with critical ribosome biogenesis factors. Mechanistic insight was revealed by transient overexpression of both wild-type and a catalytically dead mutated APOBEC3A, which both increase cell growth and protein synthesis. Through an innovative nuclear RNA sequencing methodology, we identify only modest predicted APOBEC3A C-to-U target sites on the pre-rRNA and pre-mRNAs. Our work reveals a potential direct role for APOBEC3A in ribosome biogenesis likely independent of its editing function. More broadly, we found an additional function of APOBEC3A in cancer pathology through its function in ribosome biogenesis, expanding its relevance as a target for cancer therapeutics.

In animals, pigments but also nanostructures determine skin coloration, and many shades are produced by combining both mechanisms. Recently, we discovered a new mechanism for blue coloration in the ribbontail stingray Taeniura lymma, a species with electric blue spots on its yellow-brown skin. Here, we characterize finescale differences in cell composition and architecture distinguishing blue from non-blue regions, the first description of elasmobranch chromatophores and the nanostructures responsible for the stingray’s novel structural blue, contrasting with other known mechanisms for making nature’s rarest color. In blue regions, the upper dermis comprised a layer of chromatophore units —iridophores and melanophores entwined in compact clusters framed by collagen bundles— this structural stability perhaps the root of the skin color’s robustness. Stingray iridophores were notably different from other vertebrate light-reflecting cells in having numerous fingerlike processes, which surrounded nearby melanophores like fists clenching a black stone. Iridophores contained spherical iridosomes enclosing guanine nanocrystals, suspended in a 3D quasi-order, linked by a cytoskeleton of intermediate filaments. We argue that intermediate filaments form a structural scaffold with a distinct optical role, providing the iridosome spacing critical to produce the blue color. In contrast, black-pigmented melanosomes within melanophores showed space-efficient packing, consistent with their hypothesized role as broadband-absorbers for enhancing blue color saturation. The chromatophore layer’s ultrastructure was similar in juvenile and adult animals, indicating that skin color and perhaps its ecological role are likely consistent through ontogeny. In non-blue areas, iridophores were replaced by pale cells, resembling iridophores in some morphological and nanoscale features, but lacking guanine crystals, suggesting that the cell types arise from a common progenitor cell. The particular cellular associations and structural interactions we demonstrate in stingray skin suggest that pigment cells induce differentiation in the progenitor cells of iridophores, and that some features driving color production may be shared with bony fishes, although the lineages diverged hundreds of millions of years ago and the iridophores themselves differ drastically.

The Devonian-Carboniferous (D-C; 359 Ma) boundary is marked by widespread deposition of organic-matter-rich black shales associated with the Hangenberg mass extinction event. The Exshaw Formation spans the D-C boundary in the Western Canada Sedimentary Basin (WCSB) and includes the basal Exshaw Shale deposited under broadly anoxic waters. The sediments at the base of the Exshaw Shale were deposited synchronously during a transgressive event across the WCSB, spanning the geographic variability of the basin. The variable Corg content of the shale was affected by local nutrient upwelling and paleotectonic features impacting water depth and circulation. To characterize the link between paleogeography and nutrient cycling, geographic (N = 20 locations) and stratigraphic (N = 6 locations) trends of δ13Corg and δ15Nbulk were examined throughout the WCSB, representing a range of depositional settings. The δ15Nbulk values range between 0.0 and 6.3‰ and δ13Corg from −29.5 to −26.8‰. Phytoplankton production in focused upwelling zones acquired a relatively 15N-depleted signature through isotopic fractionation during nutrient assimilation, and the residual nutrient pool was 15N-enriched. The advection of surface waters away from the location of upwelling supported additional phytoplankton growth and the deposition of sediments with higher δ15N values. The stratigraphic sections include black laminated and burrowed mudrock sequences that record changes in paleoredox conditions, water depth, and tectonism over time. Up-core from the base of the Exshaw, the Corg content decreases and simultaneously δ15Nbulk increases, suggesting a decrease in eutrophic conditions. Variable δ13Corg and δ15Nbulk trends demonstrate that there is no “type” isotopic profile spanning the D-C boundary in the WCSB.