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ABSTRACT Callus and cell suspension culture techniques are valuable tools in plant biotechnology and are widely used in fundamental and applied research. For studies in callus and cell suspension cultures to be relevant, it is essential to know if the underlying biochemistry is similar to intact plants. This study examined the expression of core circadian genes in Arabidopsis callus from the cell suspension named AT2 and found that the circadian rhythms were impaired. The circadian waveforms were like intact plants in the light/dark cycles, but the circadian expression in the AT2 callus became weaker in the free‐running, constant light conditions. Temperature cycles could drive the rhythmic expression in constant conditions, but there were novel peaks at the point of temperature transitions unique to each clock gene. We found that callus freshly induced from seedlings had normal oscillations, like intact plants, suggesting that the loss of the circadian oscillation in the AT2 callus was specific to this callus. We determined that neither the media composition nor the source of the AT2 callus caused this disruption. We observed that ELF3 expression was not differentially expressed between dawn and dusk in both entrained, light–dark cycles and constant light conditions. Overexpression of AtELF3 in the AT2 callus partially recovers the circadian oscillation in the AT2 callus. This work shows that while callus and cell suspension cultures can be valuable tools for investigating plant responses, careful evaluation of their phenotype is important. Moreover, the altered circadian rhythms under constant light and temperature cycles in the AT2 callus could be useful backgrounds to understand the connections driving circadian oscillators and light and temperature sensing at the cellular level.

Abstract Background Feline blood transfusion is required for the treatment of various illnesses in cats, and the safety of donor cats is vital. Donor adverse reactions can include cardiorespiratory, venepuncture‐related, and behavioral abnormalities. Hypothesis/Objectives To describe a large number of feline blood donation events and document use of sedation and anxiolysis, record volume of blood collected and describe the frequency, type, and risk factors for, adverse reactions. Animals The study included 7812 individual cats and 29 201 donation events at a blood banking center over 5 years. Methods Retrospective analysis of donation event records with signalment, donation volume, sedation status, donation number, and adverse reactions (acute and caregiver reported) recorded. Risk factors for adverse reactions were examined by stratifying data according to groups exposed to relevant predictors and calculating odds ratios with 95% and 99% confidence intervals (CIs). Results Adverse reactions were uncommon (0.29%, 2.88/1000 donor events) and most commonly were cardiorespiratory (0.08%, 0.75/1000 donor events) or behavioral (0.06%, 0.62/1000 donor events). The only risk factor significantly associated with adverse reactions was conscious donation, with conscious donors 4.4 times more likely to have an adverse reaction (95% CI, 2.5‐7.9, P ≤ .0001). Conclusions and Clinical Importance Feline blood donation is associated with a low rate of adverse reactions. Sedation should be considered to reduce adverse reactions, and the environment and interactions optimized to reduce donor stress. Caregiver education on care postdonation could reduce behavioral adverse reactions.

Abstract Background Noninvasive ventilation (NIV) provides effective respiratory support in foals, but face masks are poorly tolerated and associated with hypercapnia. Bi‐nasal prongs might be a more effective device interface in foals. Objectives To compare bi‐nasal prongs and masks for NIV in foals with pharmacologically induced respiratory insufficiency. Animals Six healthy foals. Methods In a randomized cross‐over study, sedated foals received NIV delivered by mask or bi‐nasal prongs, with the treatment repeated using the alternative device interface after a 3‐day rest period. After periods of spontaneous ventilation through the allocated interface, with and without supplementary O2 (T2‐T3), foals were subject to 10‐minute treatment periods of NIV at different pressure support (5 or 10 cmH2O) and end‐expiratory pressure settings (5 or 10 cmH2O), with and without supplementary O2 (T4‐T7). Vital signs, arterial blood gases, spirometry, and gas exchange data were measured in the final 2 minutes of each treatment window. Results Bi‐nasal prongs were well tolerated and required less manual positioning or monitoring compared to the mask. Partial pressure of carbon dioxide did not increase during NIV with bi‐nasal prongs and was lower than observed with masks (mean difference, 8.2 mmHg [95% confidence interval, 4.1‐12.2 mmHg] at T6). Oxygenation and respiratory mechanics were improved in all foals and not different between device interfaces. Conclusions and Clinical Importance Nasal prongs were well tolerated, had similar effects on respiratory function, and appeared to ameliorate hypercapnia observed previously during NIV in foals.

Abstract Background Milk fever (MF), a metabolic disorder in dairy cows characterized by low blood calcium concentrations postpartum, is well‐recognized clinically. However, comprehensive data on the alteration of metabolites associated with this condition remains sparse. Hypothesis Delineate serum metabolite profiles and metabolic pathways preceding, coinciding with, and after the onset of MF. Animals Twenty‐six cows, including 20 healthy cows and 6 cows initially affected by MF. Because of culling, the number of MF‐affected cows decreased to 4 at MF week, +4 weeks, and +8 weeks postpartum. Methods A nested case‐control longitudinal study was conducted, with blood samples collected at −8 and −4 weeks prepartum, MF week, and +4 and +8 weeks postpartum. Serum analysis utilized direct injection/liquid chromatography/tandem mass spectrometry (DI/LC/MS/MS) techniques. Results Key findings included the identification of diverse metabolites such as hexose, amino acids, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelin, which varied between studied groups (P

Abstract Background Reference intervals for simple body weight‐independent measurements of right heart size and function are limited. Objectives Generate reference intervals for measurements of right heart size indexed to the long‐axis aortic valve diameter (AoD) or corresponding left heart structure (right heart ratios) and describe the reproducibility of these indices. Animals Ninety healthy adult dogs of variable body weight. Methods Prospective study. All dogs underwent an echocardiogram performed by the same operator. Numerous linear 2‐dimensional measurements of right heart size and function from different imaging planes were performed. Eight dogs underwent repeated echocardiograms by the same operator on 3 different days, and 3 different operators performed repeated echocardiograms on the same day. Reference intervals were generated using the Clinical Laboratory Standards Institute method. Reproducibility was quantitated using coefficients of variation (CVs) and reproducibility coefficients. Results Reference intervals for right heart ratios were generated and allow simple assessments of right heart size and function that do not require a scaling exponent or body weight table. Right heart ratios did not show clinically relevant associations with body weight. All CVs were

Abstract Background Reliability of echocardiographic calculations for stroke volume and mitral regurgitant fraction (RFMR) are affected by observer variability and lack of a gold standard. Variability is used to calculate critical change values (CCVs) that are thresholds representing real change in a measure not associated with observer variability. Hypothesis Observed intra‐ and interobserver accuracy and variability in healthy dogs help model CCV for RFMR. Animals Reliability cohort of 34 healthy dogs; allometric scaling cohort of 99 dogs with heart disease and 25 healthy dogs. Methods Accuracy, variability, and CCV of 2 observers using geometric and flow‐based echocardiography were prospectively compared against a standard of RFMR = 0% and extrapolated across a range of expected RFMR values in the reliability cohort partly derived from cardiac dimensions predicted by the allometric cohort. Results Accuracy of methods to determine RFMR in descending order was 4‐chamber bullet (Bullet4CH), mitral inflow, cube formula, and Simpson's method of disks. Intraobserver variability was relatively high. The CCV for RFMR ranged from 28% to 88% and was inversely related to RFMR when extrapolated for use in affected dogs. For both observers, the Bullet4CH method had the lowest intraobserver CCV (Operator 1:28%, Operator 2:41%). Interobserver strength of agreement was low with intraclass correlation coefficients ranging from 0.210 to 0.413. Conclusions and Clinical Importance Echocardiographic volumetric methods used to calculate stroke volume and RFMR have low accuracy and high variability in healthy dogs. Extrapolation of observed CCV to a range of expected RFMR suggests observers and methods are not interchangeable and variability might hinder routine clinical usage. Individual observers should be aware of their own variability and CCV.

Abstract Background Enteral nutrition (EN) is essential for management of hepatic lipidosis (HL) in cats. Objectives To determine if time to start of EN and other clinicopathologic variables are associated with outcome in cats with HL. Animals Forty‐eight cats with HL. Methods Retrospective study. Information retrieved from medical records and client communications included clinicopathologic findings, time to start of EN, initial % of resting energy requirements provided, type of feeding tube, duration of hospitalization, and 3‐month survival. Variables were compared between surviving and nonsurviving cats and between cats fed ≤12 hours and >12 hours after hospital admission. Multivariable statistical testing was performed to further investigate variables of interest. Results Seventeen of 25 (68%) cats fed ≤12 hours and 13 of 23 (57%) of cats fed >12 hours after hospital admission survived (P = .55). Only increasing age (odds ratio [OR], 1.313; 95% confidence interval [CI], 1.032‐1.671; P = .03) and the presence of ascites (OR, 6.415; 95% CI, 1.354‐30.395; P = .02) were associated with death in multivariable analysis. Hospitalization duration (median, interquartile range [IQR]) was shorter in cats fed >12 hours (2.8 days; IQR, 2.1‐3.8 days) as compared with cats fed ≤12 hours (4.8 days; IQR, 3.6‐6.2 days) after hospital admission (P

Abstract Background The proportion of cats with hypertrophic cardiomyopathy (HCM) that lose systolic anterior motion of the mitral valve (SAM) in the long term is unknown. Hypothesis/Objectives Cats with HCM will lose SAM in the long term. Loss of SAM will be associated with greater age, longer scan‐interval, and altered left ventricular (LV) dimensions. Animals Sixty unsedated cats with HCM, not receiving beta blockers or pimobendan. Methods A retrospective cohort study from 2 referral centers. Cats were eligible if they had been diagnosed with HCM and had a repeat echocardiogram ≥1 year later. Clinical and echocardiographic data of the left heart variables were collected. Results Thirty‐eight cats had SAM at the initial scan. After a median follow‐up time of 2.1 years (range: 1.0‐5.9), 7 cats had lost SAM (18%) and 5 cats (23%) gained SAM. On follow‐up, cats with SAM at the initial scan had a larger left atrium (P = .037), lower left atrial fractional shortening (P = .014), greater LV internal diameter in end‐systole (P = .002), and lower LV fractional shortening (P

Abstract This proposed study aims to characterize and utilize the biogas (BG) derived from the anaerobic co‐digestion of university hostel food waste and Vinasse (waste from the sugarcane industry) in a digester and to run an agricultural diesel engine with BG and Jatropha Curcas methyl ester (JCMS) on a dual fuel (DF) mode. In DF mode, BG from food waste was the main fuel, and JCMS100 was the pilot (secondary) fuel. The engine was run at different BG flow rates as 4, 8, and 12 liters per minute (LPM) with JCMS100 as injected fuel. As per the author's earlier experimental findings, the fuel injection pressure for the JCMS100 was elevated to 240 bar from the base range of 200 bar to enhance the engine performance. The experimental findings for the JCMS, and BG operation were compared with diesel in all aspects. It was revealed that the NOx emission of JCMS100 + 12 LPM of BG was about 7.5% lower than the D100 fuel at full load. Increasing BG intake up to 8 LPM, the BTE increased, however, afterward it started to decline. In a similar consequence, the brake specific fuel consumption (BSFC) declined up to 8 LPM of BG, however, when the engine was fed with 12 LPM of BG the BSFC started to elevate. The carbon monoxide and hydrocarbon also elevated with higher induction of BG. However, interestingly a NOx‐smoke compromised tradeoff was observed for JCME‐BG operation.

Abstract The Mariana Trough is the youngest back‐arc basin in a series of basins and arcs that developed behind the Mariana subduction zone in the western Pacific. Active seafloor spreading is ongoing at a spreading axis close to the Mariana Arc, resulting in a pronounced asymmetric configuration (double rate to the west 2:1) at 17°N. The formation of back‐arc basins is controlled by the subducting slab, which regulates the temporal development of mantle flow, entrainment of fluids, and hydrous melts together with the magma generation. To better understand the formation process of back‐arc basin asymmetry in the central Mariana Trough, we combined 2‐D P‐wave traveltime tomography results with high‐resolution bathymetric data. Here, we show that the crust in the central Mariana Trough is 6.5–9.5 km thick, which is unusually thick for oceanic crust. While the lower crust exhibits average seismic velocities of 6.5–7.2 km/s, high‐velocity anomalies occur at the margins of the Mariana Trough, indicating that magmatic accretion was affected by hydrous melting during rifting. While the Mariana Trough developed from a rather symmetric rifting (0.89:1) to a strongly asymmetric seafloor spreading stage (5.33:1), the contribution of hydrous melts declined and the opening direction changed at ∼5 Ma. Asymmetric basin opening is potentially driven by the far‐field stress effect of the subduction zones on the western boundary of the Philippine Sea Plate.

Abstract In this study we analyse projections of future changes to the El Niño Southern Oscillation (ENSO), Indian Ocean Dipole (IOD), and Southern Annular Mode (SAM) using the latest generation of climate models. Multiple future scenarios are considered. We quantify the fraction of models that project future increases or decreases in the frequency and amplitude of ENSO, IOD, and SAM events in the late 21st century. Changes to the frequency of co‐occurring and consecutive driver phases are also examined. We find that while there is large inter‐model spread, the most common pathways correspond to more frequent ENSO events; weaker, less frequent IOD events; and stronger, but less frequent austral spring SAM events. There is no clear consensus on the change to the frequency of concurrent events, though we find a significant increase in La Niña‐ and El Niño‐only events occurring with neutral IOD and SAM. We also find a significant increase to the frequency of consecutive positive IOD events under a high emissions scenario, but no significant change to the frequency of consecutive ENSO or negative IOD events. In most models, the correlation between drivers, that is, ENSO and IOD, and ENSO and SAM, does not significantly change between the late 20th and late 21st century. These results indicate a high degree of internal variability in the models.

ABSTRACT Background Mothers of high‐risk neonates experience tremendous stress during neonatal intensive care unit (NICU) admission. This stress has a negative impact on mothers' participation in neonatal care activities, psychological health and coping skills in the NICU. Objective To determine the impact of interventional strategies to reduce maternal stress and enhance coping skills during neonatal admission to the NICU. Design A scoping review was carried out following the methodological framework outlined by Arksey and O'Malley. Methods This scoping review was conducted as per the Joanna Briggs Institute guidelines, including a quality appraisal checklist for randomised and nonrandomised controlled trials. Patterns, advances, gaps, evidence for practice and research recommendations from the review (PAGER framework) were used to report the results. The following international databases were used to search for primary articles: Medline via PubMed, EBSCOhost via CINAHL, Scopus, Web of Science and the ProQuest Medical Library. Original studies published in English between January 2011 and January 2023 from low‐ and middle‐income countries (LMICs) that assessed maternal stress and coping skills during neonatal NICU admission were included in the review. Results The review included 15 articles from LMICs, of which 60% were from middle‐income, 25% were from lower‐middle‐income and 15% were from low‐income countries. Interventional strategies were described under five categories. Maternal stress decreased significantly across all three subscales of the PSPS: ‘sight and sound’, ‘baby looks and behavior’ and ‘parental relationship with baby and role alteration’ during neonatal NICU admission. Interventional strategies involving family‐centred care and emotional and psychological supportive care have been reported to have a consistently positive impact on alleviating maternal stress and enhancing coping skills in the NICU. Conclusion Healthcare professionals, especially nurses, are pivotal in promptly recognising maternal stress and NICU stressors. The participation of mothers in neonatal care, such as through family‐centred care and emotional support interventions, significantly reduces maternal stress and enhances coping skills.

ABSTRACT Introduction MGRS are new rare clinical entities, whose recognition and optimal management is evolving. Methods To implement real‐life data, we retrospectively analysed a multicentre cohort of 60 patients with renal biopsy‐proven MGRS receiving mainly novel treatments (between 2006 and 2021) in eight Italian centres. Based on renal biopsy, patients were divided into two subgroups: AL amyloidosis (70%, n = 42) and other‐MGRS (30%, n = 18). Results Baseline characteristics follow typical manifestations of MGRS disorders in terms of small clonal burden, laboratory and clinical features. More patients with AL amyloidosis had monotypic lambda light‐chain disease, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min and nephrotic proteinuria than other‐MGRS group. The most widely used drug was bortezomib, and about one‐third of patients underwent ASCT. Overall response rate was 86% with no differences in the two subgroups. However, high‐quality hematologic responses ≥very good partial response (VGPR) were greater in AL amyloidosis than in other‐MGRS group (67% vs 28%, p = 0.015). The depth of haematological response influenced renal response, obtained in 32 (59%) of evaluable patients, similarly in the subgroups. Indeed, 75% patients with ≥ VGPR (p = 0.049) and none with stable disease (p ≤ 0.001) obtained a renal response. No association between renal response and histotypes (p = 0.9) or type of first‐line therapy (p = 0.3) was found. At a median follow‐up of 54.4 months (IQR 24.8–102.8), median progression‐free survival (PFS) was 100.1 months (95% CI 34.9–NR), and median overall survival not reached (95% CI 129.8–NR). No significant difference emerged between the two groups in terms of survival outcomes. Achieving ≥ VGPR was confirmed as the main independent predictor of prolonged PFS in the general population (HR = 0.29, p = 0.023) and AL amyloidosis group (HR 0.23; p = 0.023). Preserved renal function at diagnosis was predictive of improved PFS in the AL amyloidosis group (eGFR ≥ 60 mL/min: HR = 0.003; p = 0.018; eGFR 30–60 mL/min: HR = 0.04, p = 0.046). Conclusion Further research is warranted to develop standardised response criteria and treatment strategies to improve MGRS management.

ABSTRACT Background & Aims Studies using eye‐tracking methodology have made important contributions to the study of language disorders such as aphasia. Nevertheless, in clinical groups especially, eye‐tracking studies often include small sample sizes, limiting the generalizability of reported findings. Online, webcam‐based tracking offers a potential solution to this issue, but web‐based tracking has not been compared with in‐lab tracking in past studies and has never been attempted in groups with language impairments. Materials & Methods Patients with post‐stroke aphasia (n = 16) and age‐matched controls (n = 16) completed identical sentence‐picture matching tasks in the lab (using an EyeLink system) and on the web (using WebGazer.js), with the order of sessions counterbalanced. We examined whether web‐based eye tracking is as sensitive as in‐lab eye tracking in detecting group differences in sentence processing. Results Patients were less accurate and slower to respond to all sentence types than controls. Proportions of gazes to the target and foil picture were computed in 100 ms increments, which showed that the two modes of tracking were comparably sensitive to overall group differences across different sentence types. Web tracking showed comparable fluctuations in gaze proportions to target pictures to lab tracking in most analyses, whereas a delay of approximately 500–800 ms appeared in web compared to lab data. Discussion & Conclusions Web‐based eye tracking is feasible to study impaired language processing in aphasia and is sensitive enough to detect most group differences between controls and patients. Given that validations of webcam‐based tracking are in their infancy and how transformative this method could be to several disciplines, much more testing is warranted.

ABSTRACT Introduction There is a high prevalence of attention‐deficit/hyperactivity disorder (ADHD) in prison populations compared to the general population, and ADHD has also been shown to be associated with criminality and antisocial behavior. This systematic review examines the effect of pharmacological ADHD treatment on criminal recidivism, ADHD symptoms, and rehabilitation in inmates with ADHD. Methods Adhering to PRISMA 2020 and AMSTAR guidelines, we conducted a structured search on September 6, 2023 using PubMed. We focused on original research published in peer‐reviewed scientific journals, following the IMRaD format, written in English, containing the established search terms, based on participants who met the criteria for ADHD diagnosis (any edition of DSM), and who were incarcerated at the start of pharmacological treatment for ADHD. The primary outcome was criminal recidivism, the secondary outcomes were ADHD symptoms, and rehabilitation‐related factors such as global function, norm‐breaking/antisocial behavior, adaptation to society/institutional behavior, cognitive function, and well‐being. Results Five studies, based on three patient cohorts, were included in this systematic review. Surprisingly, only one study investigated criminal recidivism. That study indicated that self‐reported criminal recidivism was lower than expected among inmates who had received pharmacological ADHD treatment. The five studies showed varying results in the effectiveness of pharmacological ADHD treatment on ADHD symptoms and other rehabilitation‐related factors. The included studies also varied regarding participant characteristics, study design, dosage, adherence to treatment, treatment regimes, and measured outcomes. All studies reported using osmotic‐release oral system (OROS) methylphenidate as their drug of choice. Conclusion We conclude that there is limited empirical evidence to support the efficacy of pharmacological ADHD treatment on criminal recidivism in inmates diagnosed with ADHD. Still, evidence suggests that these treatments can reduce ADHD symptoms and enhance rehabilitation outcomes, which may, in turn, lower the rate of reoffending. We point to the need for more targeted research in this area.

ABSTRACT Introduction Subanesthetic doses of ketamine are a promising novel treatment for suicidality; however, the evidence for predictive biomarkers is sparse. Recently, measures of complexity, including Lempel–Ziv complexity (LZC) and multiscale entropy (MSE), have been implicated in ketamine's therapeutic action. We evaluated electroencephalogram (EEG)‐derived LZC and MSE differences between responders and nonresponders to oral ketamine treatment. Methods A total of 31 participants received six single, weekly (titrated) doses of oral racemic ketamine (0.5–3 mg/kg) and underwent EEG scans at baseline (Week 0), post‐treatment (Week 6), and follow‐up (Week 10). Resting‐state (eyes closed and open) recordings were processed in EEGLAB, and complexity metrics were extracted using the Neurokit2 package. Participants were designated responders or nonresponders by clinical response (Beck Suicide Scale [BSS] score reduction of ≥ 50% from baseline to the respective timepoint or score ≤ 6) and then compared in terms of complexity across resting‐state conditions and time. Results Employing a Bayesian mixed effects model, we found strong evidence that LZC was higher in the eyes‐open compared to eyes‐closed condition, as were MSE scales 1–3. At a global level, responders displayed elevated eyes‐open baseline complexity compared to nonresponders, with these values decreasing from baseline to post‐treatment (Week 6) in responders only. Exploratory analyses revealed that the elevated baseline eyes‐open LZC in responders was spatially localized to the left frontal lobe (F1, AF3, FC1, and F3). Conclusion EEG‐complexity metrics may be sensitive biomarkers for evaluating and predicting oral ketamine treatment response, with the left prefrontal cortex bein a possible treatment response region.

ABSTRACT Translocation of species is a common practice used in endangered species management and conservation plans, which can have the purpose of establishing new populations which are at risk of being wiped out, increase a species chance of survival or recovery, and to preserve genetic diversity. The present study details the rescue and relocation process of Hispaniola Hutia (Plagiodontia aedium) in the municipality of Cotuí, Dominican Republic. Data are presented for eight individuals, belonging to two different families, detailing capture methods, handling, reintroduction method, and behavior, as well as data on post‐release monitoring for both families. It was found that the most efficient capture method was active capture by hand (6/8). The family groups were heterogeneous, although both families had in common the presence of a single adult male. The average weight of the individuals was 1.19 kg. Blood tests were carried out on the animals before being taken to the holding pens and compared with the values of other rodents, showing that hematic values for P. aedium were like those of another hutia species, Cynomys ludovicianus. During the period animals were held in pens before reintroduction, hutias showed trophic preferences for Clusia rosea and Guarea guidonea. The only supplementary food they consumed was Daucus carota. A fight was observed between members of different families during the acclimation period in the holding pen, between a subadult male and another dominant one, evidencing territorial behavior. Post‐release monitoring of the families showed that the selection of habitat for relocation, based on the characterization of active burrows in the area, was successful in one of the two families relocated. One of the families abandoned the selected area for translocation during the monitoring. It is important to note that accurate population data of the targeted population, such as abundance and density, are necessary to guarantee the survival of the translocated animals in the new environment. The reintroduction method used in this study may serve as a baseline for future translocation projects for the species.

ABSTRACT Recent developments in microscopic and molecular tools have allowed the implementation of new approaches for assessing parasitic infections in wildlife populations. This is particularly important for the noninvasive detection and quantification of endoparasites in live animals. Here, we combined copromicroscopic (Mini‐FLOTAC) and molecular (qPCR) techniques to detect the infection of the macroparasite Ligula intestinalis (Cestoda, Pseudophyllidea) in fresh droppings of Gull‐billed Terns Gelochelidon nilotica (Charadriiformes, Laridae) breeding in southwestern Spain. Additionally, we sequenced the cytochrome b gene in parasite isolates from Gull‐billed Terns (definitive host) and Common Bleak Alburnus alburnus (second intermediate host) sampled around tern colonies to explore potential genetic differences between the isolates. The qPCR test showed a higher prevalence (18%; in 13/73 samples) than Mini‐FLOTAC (9%; in 8/88 samples), indicating that qPCR was more sensitive for diagnostic purposes than fecal flotation alone. Although the agreement between both techniques was substantial (84.2%) mainly due to the large number of uninfected samples, only Mini‐FLOTAC allowed us to quantify parasite shedding. When combining techniques, the prevalence of infection did not differ between adults and chicks, suggesting frequent trophic transmission from parents to their offspring via food provisioning. Phylogenetic analyses identified four haplotypes in the isolates from Gull‐billed Terns and Bleak, all of which were placed within a European clade composed of tapeworms recovered exclusively from phylogenetically derived cyprinid fish. This, combined with the short lifespan of mature tapeworms, suggests that Gull‐billed Terns became infected after consuming infected fish around their breeding colonies rather than on their West African wintering grounds. Altogether, our results represent the first record of L. intestinalis in Gull‐billed Terns and the first molecular characterization of the parasite in the Iberian Peninsula. This integrative coprodiagnostic protocol can be applied to other host–parasite systems, allowing researchers to study helminth infections in wild populations using a noninvasive approach.

ABSTRACT Fucoid forests are areas dominated by marine brown seaweed in the taxonomic order Fucales that, like the better‐known marine foundation species—corals, kelps, seagrasses, salt marshes, and mangroves—are threatened by anthropogenic stressors. Fucoid forests are fabulous and important because they, like the better‐known marine foundation species (i) span large areas, bioregions, and ecosystems, (ii) provide ecological functions such as high productivity, biodiversity, and habitat for iconic and endemic species, and (iii) support a variety of ecosystem services, like commercial fisheries, regulation of nutrients and carbon, and cultural values. Fucoid forests are, based on a new citation analysis, forgotten worldwide, because they are described orders of magnitude less than the better‐known marine foundation species, in ecology and marine biology textbooks, in Google Scholar and Scopus databases over scientific literature, and in recent reports and reviews about seaweed forests. Fucoid forests would be less forgotten if more people acknowledge their biological importance and societal value more often and equate their importance to that of the better‐known marine foundation species. To decrease the knowledge gap between fucoids and the better‐known foundation species, researchers and science communicators could join forces under a broad “fucoid umbrella,” establish stronger online presences, coordinate and collaborate on publications, and produce free eye‐catching non‐technical materials for teachers, managers, politicians, grass‐root organizations, philanthropists, and funding agencies.

ABSTRACT The role of biotic interactions, such as interspecific competition, in driving geographical range evolution is still poorly understood. For instance, lineages distributed across regions with a large number of potential competitors might experience some level of geographical packing of their range limits, so that changes in their geographical distributions are hampered. Conversely, a large number of competitors could instead lead to accelerated rates of geographical range evolution, with lineages shifting their ranges to avoid competition. We recently introduced the concept of clade density (CD; the sum of the areas of overlap between a species and other members of its higher taxon, weighted by their phylogenetic distance) as a proxy of the potential for interspecific competition across the geographical distribution of a given species. In this study, we used a large dataset with 5936 terrestrial vertebrate species to test whether CD is significantly associated with variation in the rate of geographical range evolution using two alternative approaches. First, we tested if there is a significant relationship between CD and the geographical distance between sister species. In addition, we estimated tip rates of geographical range evolution and tested if they were consistently associated with variation in CD. We found no evidence for an effect of CD on geographical range evolution in either of the tested approaches, even after accounting for phylogenetic uncertainty. These results are inconsistent with equilibrial models of species diversification and suggest that interspecific competition might not play a pervasive role in geographical range evolution of terrestrial vertebrates.

ABSTRACT Precise mosquito identification is integral to effective arbovirus surveillance. Nonetheless, the conventional morphological approach to identifying mosquito species is laborious, demands expertise and presents challenges when specimens are damaged. DNA barcoding offers a promising alternative, surmounting challenges inherent in morphological identification. To integrate DNA barcoding into arbovirus surveillance effectively, a robust dataset of mosquito barcode sequences is required. This study established a comprehensive repository of Cytochrome Oxidase I (COI) barcodes, encompassing 177 samples representing 45 mosquito species from southern and northern Western Australia (WA), including 16 species which have not been previously barcoded. The average intraspecific and interspecific genetic distances were 1% and 6.8%, respectively. Anopheles annulipes sensu lato had the highest intraspecific distance at 9.1%, signifying a genetically diverse species. While validating the potential of COI barcodes to accurately differentiate mosquito species, we identified that some species pairs have low COI divergence. This includes Aedes clelandi and Ae. hesperonotius, Tripteroides atripes and Tp. punctolaeralis and Ae. turneri and Ae. stricklandi. In addition, we observed ambiguity in identification of the members of Culex sitiens subgroup (Cx. annulirostris, Cx. palpalis and Cx. sitiens) and three members of Cx. pipiens complex (Cx. australicus, Cx. globocoxitus, Cx. quinquefasciatus). In summary, despite presenting challenges in the identification of some mosquito species, the COI barcode accurately identified most of the species and generated a valuable resource that will support the WA arbovirus surveillance program and enhance public health intervention strategies for mosquito‐borne disease control.

ABSTRACT The gut microbiome has a well‐documented relationship with host fitness, physiology, and behavior. However, most of what is known comes from captive animals where diets and environments are more homogeneous or controlled. Studies in wild populations that experience dynamic environments and have natural life history variation are less common but are key to understanding the drivers of variation in the gut microbiome. Here we examine a wild population of yellow‐bellied marmots (Marmota flaviventer), an obligate winter hibernator, to quantify multivariate associations between host‐associated factors (e.g., age, sex, environmental harshness, and social behavior) and gut microbial composition. Across 5 years and 143 individuals, we found that males had a higher relative abundance of microbes associated with mass gain and cellulose digestion, which suggests a metabolic investment in mass gain (such as phylum Firmicutes and family Lachnospiraceae). By contrast, females had higher relative abundances of microbes associated with inflammation and metabolism (from microbial groups such as Tenericutes and Ruminococcus), possibly reflecting the importance of lactation and offspring investment. Post hoc analyses of lactating females showed a negative relationship with the abundance of microbes associated with mass gain but a positive relationship with microbes associated with metabolic energy, suggesting a trade‐off between investment in pups and maternal mass gain. Older animals also had reduced Proteobacteria relative abundance, a phylum associated with reduced inflammation. Results demonstrate that sex and age‐based traits, not sociality or environmental harshness, are associated with microbe‐mediated metabolism and inflammation in a wild, hibernating mammal.

ABSTRACT Labile traits, such as behavioural, physiological traits or body mass, vary within an individual either over time or across environments. Such changes within an individual can be linked across traits, forming within‐individual trait correlations. These correlations are particularly expected when ageing causes changes in the expression of multiple traits. Moreover, the direction of these correlations depends on mechanisms that explain age‐related changes in each trait, such as physiological deterioration or changes in future fitness expectations. Therefore, assessing within‐individual trait correlations offers insights into trait‐specific ageing patterns, their integration and age‐related reproductive strategies. Here, we tracked individual male cicadas (Tettigetta isshikii) in their natural habitat, repeatedly assessing their plant use (narrow‐leafed vs. large‐leafed plants), calling activity and body mass. The results revealed that male cicadas lost mass, increased calling activity and a preference for narrow‐leafed plants as they aged. This integration of age‐related plasticity led to negative within‐individual correlations between body mass and behaviours. Considering that adult cicadas consume nutritionally poor xylem sap, the negative within‐individual correlations between body mass and risk‐taking behaviour suggest that T. isshikii males follow a capital breeding strategy rather than an income breeding strategy. As adult cicadas may use up the energy stored during the nymph stage, an age‐related increase in energetically demanding calling activity could cause an age‐related decrease in body mass. The terminal investment hypothesis could also explain the age‐related increase in calling activity and the preference for narrow‐leafed plants. Therefore, we emphasise the importance of individual‐level tracking studies in the wild to achieve a comprehensive understanding of the life‐history strategies and behavioural ecology of a study animal.

ABSTRACT Benthic macrofauna are important and widely used biological indicators of marine ecosystems as they have limited mobility and therefore integrate the effects of local environmental stressors over time. Recently, environmental DNA (eDNA) analysis has provided a potentially more resource‐efficient approach for benthic biomonitoring than traditional morphology‐based methods. Several studies have compared eDNA with morphology‐based monitoring, but few have compared the two approaches using the exact same sediment cores. In addition, the meiofauna and pelagic organisms obtained as ‘bycatch’ using eDNA have largely been disregarded from comparisons. Here, we address these shortcomings through comparative invertebrate analyses of six sediment sample replicates from each of four stations in Denmark, using eDNA metabarcoding and morphological identification. Our results revealed large variation between the six replicates for both methods and little overlap in taxon compositions between methods. While the morphological dataset was dominated by molluscs and annelids, the eDNA dataset was dominated by arthropods and annelids. Using community composition data, we found that sampling stations could be distinguished both with eDNA and morphology. Finally, we inferred expected total richness from extrapolated accumulation curves of detected taxa from each method. This indicated that eDNA metabarcoding requires less replication than morphology for maximum coverage of diversity to be reached. However, both methods required high levels of replication, and our results on taxonomic composition add to the evidence that morphological and eDNA‐based methods should preferably be used as complimentary tools for marine bioassessment.

ABSTRACT Incidental mortality in fisheries is a major driver of population declines for albatrosses and petrels globally. However, accurate identification of species can be difficult due to the poor condition of bycaught birds and/or visual similarities between closely related species. We assessed three genetic markers for their ability to distinguish the 36 albatross and petrel species listed in Annex 1 to the Agreement on the Conservation of Albatrosses and Petrels (ACAP) and in Australia's Threat Abatement Plan (TAP) for the bycatch of seabirds during oceanic longline fishing operations. We generated 275 new sequences, from 29 species, to improve the coverage of reference databases for these listed species. The combined use of the selected Cytochrome b and Control Region markers enabled the identification of 31 of 36 listed seabirds to species level and four to sister species. One petrel species could not be evaluated as no reference sequences were available. We tested these markers on 59 feathers from bycaught seabirds and compared these to onboard visual identification. We successfully assigned all procellariiforms to species (n = 58), whereas only two seabirds were correctly identified to species visually onboard, highlighting the difficulty of visual species assignment and the need for alternative methods. We assessed the utility of our two chosen markers for the assignment of all procellariiform species, with 74% of species with reference sequences identified to species or sister species level. However, a precautionary approach is needed for application beyond our listed species due to unvalidated reference sequences. The approach described here provides a streamlined framework for the molecular identification of seabird bycatch. This approach is recommended for use in fisheries within and outside Australian waters to improve the resolution of bycatch reporting and to corroborate logbook entries, observer reports and audits of images captured by electronic monitoring systems as well as help inform conservation efforts.

ABSTRACT Hybrid populations of Africanized honey bees (scutellata‐hybrids), notable for their defensive behaviour, have spread rapidly throughout South and North America since their unintentional introduction. Although their migration has slowed, the large‐scale trade and movement of honey bee queens and colonies raise concern over the accidental importation of scutellata‐hybrids to previously unoccupied areas. Therefore, developing an accurate and robust assay to detect scutellata‐hybrids is an important first step toward mitigating risk. Here, we used an extensive population genomic dataset to assess the genomic composition of Apis mellifera native populations and patterns of genetic admixture in North and South American commercial honey bees. We used this dataset to develop a SNP assay, where 80 markers, combined with machine learning classification, can accurately differentiate between scutellata‐hybrids and non‐scutellata‐hybrid commercial colonies. The assay was validated on 1263 individuals from colonies located in Canada, the United States, Australia and Brazil. Notably, we demonstrate that using a reduced SNP set of as few as 10 loci can still provide accurate results.

Abstract Simultaneously recording network activity and ultrastructural changes of the synapse is essential for advancing understanding of the basis of neuronal functions. However, the rapid millisecond‐scale fluctuations in neuronal activity and the subtle sub‐diffraction resolution changes of synaptic morphology pose significant challenges to this endeavor. Here, specially designed graphene microelectrode arrays (G‐MEAs) are used, which are compatible with high spatial resolution imaging across various scales as well as permit high temporal resolution electrophysiological recordings to address these challenges. Furthermore, alongside G‐MEAs, an easy‐to‐implement machine learning algorithm is developed to efficiently process the large datasets collected from MEA recordings. It is demonstrated that the combined use of G‐MEAs, machine learning (ML) spike analysis, and 4D structured illumination microscopy (SIM) enables monitoring the impact of disease progression on hippocampal neurons which are treated with an intracellular cholesterol transport inhibitor mimicking Niemann–Pick disease type C (NPC), and show that synaptic boutons, compared to untreated controls, significantly increase in size, leading to a loss in neuronal signaling capacity.

ABSTRACT Yeast extract (YE) is a complex nutritional source associated with high performance on microbial production processes. However, its inherent compositional variability challenges its scalability. While prior efforts have focused on growth‐associated products, the dynamics of growth‐uncoupled production, which leads to higher production rates and conversion yields, still need to be explored. This production scenario is common in large‐scale applications. This study presents a systematic approach to replace YE for the production of the terpene amorpha‐4,11‐diene in Escherichia coli. Sequential processing was successfully applied to identify glutamic acid, alanine, leucine, valine, isoleucine and glycine as the key amino acids (AAs) under slow‐growth conditions. Thoroughly applying biomass retention as part of sequential processing increased production capacity by 45% using these AAs instead of YE. Further studies, including flux balance analyses, targeted pyruvate as the common AA precursor. The optimized fed‐batch process feeding pyruvate with 0.09 gPyr h−1 enhanced amorpha‐4,11‐diene production by 37%, although adding only 1% carbon via pyruvate. Flux balance analysis revealed the criteria for optimum pyruvate feeding, for example, to prevent succinate secretion and maintain the NADH/NAD+ balance. These findings illustrate the interplay between media composition and metabolic activity and provide a successful guideline for identifying lean, best‐performing media for industrial applications.

ABSTRACT Pseudomonas putida is widely used in industrial applications, including the recombinant proteins production, because of its natural advantageous properties. In this study, the gene encoding FleQ, the primary regulator of flagellar synthesis, was deleted to construct a new non‐motile P. putida KT2440‐derived strain (ΔfleQ). The non‐motile cells showed reduced biofilm formation and enhanced expression of a heterologous gene in nutrient‐rich media compared with the wild‐type (WT) strain, attributed to the reallocation of cellular resources from flagellar synthesis and cellular motility. Additionally, the ΔfleQ strain exhibited enhanced tolerance to chloramphenicol, indicating higher ribosome production, confirmed by a higher RNA/protein ratio relative to the WT. While the WT strain showed decreased growth and a three‐fold increase in reporter gene activity in minimal media, the ΔfleQ strain maintained consistent reporter gene expression and exhibited a relatively higher growth rate. This suggests that the FleQ is involved in modulating proteome allocation based on nutrient quality. The removal of FleQ allows for more flexible resource allocation, creating a chassis strain with nutrient quality‐independent gene expression capacity, which could be valuable in industrial applications where consistent output is essential.

Abstract Solid Earth CO2 outgassing, driven by plate tectonic processes, is a key driver of carbon cycle models. However, the magnitudes and variations in outgassing are poorly constrained in deep‐time. We assess plate tectonic carbon emissions and sequestration by coupling a plate tectonic model with reconstructions of oceanic plate carbon reservoirs and a thermodynamic model to quantify outfluxes from slabs and continental arcs over 1 billion years. In the early Neoproterozoic, our model predicts a peak in crustal production and net outgassing from 840 to 780 Ma that corresponds to a contemporaneous pulse in large igneous province eruptions. The Sturtian and Marinoan glaciations (717–635 Ma) correspond to a low in mid‐ocean ridge outgassing, while the following Ediacaran global warming coincides with a rise in net atmospheric carbon influx, driven by an increase in plate boundary and rift length. The Cambrian, Silurian/Devonian and Triassic Jurassic hothouse climates are synchronous with a reduction in carbon sequestration flux into oceanic plates, increasing net outgassing. In contrast, the Early Cretaceous hothouse climate is accompanied by a pronounced increase in mid‐ocean ridge outgassing. Both the Early Ordovician cooling and the late Paleozoic ice ages coincide with a significant decrease in net atmospheric outgassing, driven by an increase in carbon sequestration. The late Cenozoic glaciation is associated with a long‐term decrease in mid‐ocean ridge and rift degassing, and a pronounced increase in carbon flux into pelagic carbonate sediments. Our tectono‐thermodynamic carbon cycle model provides a new foundation for future long‐term climate and geochemical cycling models.

Abstract Marine shells incorporate oxygen isotope signatures during growth, creating valuable records of seawater temperature and marine oxygen isotopic compositions. Secondary ion mass spectrometry (SIMS) measures these compositions in situ at finer length‐scales than traditional stable isotope analyses. However, determining oxygen isotope ratios in aragonite, the most common shell mineral, is hampered by a lack of ideal reference materials, limiting the accuracy of SIMS‐based seawater temperature reconstructions. Here, we tested the capability of SIMS to produce seawater temperature reconstructions despite the matrix calibration challenges associated with aragonite. We cultured Anadara trapezia bivalves at four controlled seawater temperatures (13–28°C) and used strontium labeling to mark the start of the temperature‐controlled shell increment, allowing for more spatially precise SIMS analysis. An improved matrix calibration was developed to ensure more accurate bio‐aragonite analyses that addressed matrix differences between the pure abiotic reference materials and the bio‐aragonite samples with intricate mineral‐organic architectures and distinct minor and trace element compositions. We regressed SIMS‐IRMS biases of abiotic and biogenic aragonites that account for their systematic differences in major, minor, and trace elements, allowing for more accurate SIMS analyses of the temperature‐controlled shell increment. The thorough matrix calibration allowed us to provide a SIMS‐based seawater‐corrected oxygen isotope thermometer of T(°C) = 23.05 ± 0.36 − 4.48 · (δ18Oaragonite [‰ VPDB] − δ18Oseawater [‰ VSMOW] ± 0.25) and 103lnαaragonite‐seawater = (17.78 ± 0.88) · 103/T (K) − (29.44 ± 2.40) that agrees with existing aragonitic IRMS‐based thermometer relationships and improves the applicability of SIMS‐based paleo‐environmental reconstructions of marine bio‐aragonites.

Abstract The McDonald Islands, together with Heard Island and the Kerguelen Archipelago, are volcanic islands on the mostly submerged Kerguelen Plateau, and the products of the long‐lived Kerguelen mantle plume (at least 130 Myr; Coffin et al., 2002, https://doi.org/10.25919/jw5f‐ad35). The first multibeam bathymetry data acquired around the Heard and McDonald islands reveal > 70 sea knolls surrounding the McDonald Islands and three sea knolls north of Heard Island. Rocks dredged from McDonald Islands sea knolls include fresh vesicular phonolitic lavas, phonolitic obsidian, phonolitic pillow fragments, and one basanite. These are the first phonolites sampled from the seafloor on the Kerguelen Plateau. Dredging of one sea knoll north of Heard Island recovered basaltic lavas. Lavas from the sea knolls are young, returning 40Ar/39Ar plateau ages of 73.7 ± 15.1 ka to 7.0 ± 2.7 ka for McDonald Islands sea knoll phonolites and 9.0 ± 1.3 ka for the Heard Island sea knoll. We define a new magma series, the McDonald Series, characterized by low εHf (−3.9 to −4.4) and lower Δ207Pb/204Pb (4.5–4.8) and Δ208Pb/204Pb (79–85) than all other lavas on the Kerguelen Plateau. This newly defined series is the product of a relatively young (Pleistocene‐Holocene) phase of volcanism produced by a distinct component of the Kerguelen mantle plume. We propose that McDonald Series phonolites together with 53.4 Ma lavas previously dredged from Ninetyeast Ridge provide evidence for zonation of the Kerguelen mantle plume.

Abstract Anthropogenic climate change will drive extensive mass loss across both the Antarctic (AIS) and Greenland Ice Sheets (GrIS), with the potential for global climate system feedbacks, especially in polar regions. Historically, the high‐latitude North Atlantic and Southern Ocean have been critical regions for anthropogenic heat and carbon uptake, but our understanding of how this uptake will be altered by future freshwater discharge is incomplete. We assess each ice sheet's impact on global ocean anthropogenic heat and carbon storage for a high‐emission scenario over the 21st‐century using a coupled Earth system model. We explore the impact of contemporaneous mass loss from both ice sheets on anthropogenic heat and carbon storage and quantify their linear and nonlinear contributions. Notably, added freshwater reduces ocean heat and carbon storage by 2,100, and the sum of individual freshwater effects differ from those induced by simultaneous freshwater discharge from both ice sheets. Combined AIS and GrIS freshwater engenders distinct anthropogenic storage anomalies—particularly in the high‐latitude Southern Ocean and North Atlantic. From 2080 to 2100, GrIS freshwater exerts primary control on the temporal evolution of global ocean heat storage, while global ocean carbon storage is modulated by the linear AIS and GrIS freshwater impacts. Nonlinear impacts of simultaneous ice sheet discharge have a non‐negligible contribution to the evolution of global ocean heat storage. Further, anthropogenic heat changes are realized more quickly in response to ice sheet discharge than anthropogenic carbon. Our results highlight the need to incorporate both ice sheets actively in climate models to accurately project future global climate.

Abstract Land reclamations influence the morphodynamic evolution of estuaries and tidal basins, because an altered planform changes tidal dynamics and associated residual sediment transport. The morphodynamic response time to land reclamation is long, impacting the system for decades to centuries. Other human interventions (e.g., deepening of fairways or port construction) will add more morphodynamic adaptation timescales. Our understanding of the cumulative effects of anthropogenic interference with estuaries is limited because observations usually do not cover the complete morphological adaptation period. We aim to assess the impact of land reclamation works and other human interventions on an estuarine system by means of digital reconstructions of historical morphologies of the Ems Estuary over the past 500 years. Our analysis demonstrates that the intertidal‐subtidal area ratio altered due to land reclamation works and that the ratio partly restored after land reclamation ended. The land reclamation works have led to the degeneration of an ebb and flood channel system, transitioning the estuary from a multichannel to a single channel system. We infer that the 20th‐century intensification of channel dredging and re‐alignment works accelerated rather than caused this development. The centennial‐scale observations show that the Ems estuary evolution corresponds to a land reclamation response following tidal asymmetry‐based stability theory as it moves toward a new equilibrium configuration with modified tidal flats and channels. Considering the long history of land reclamation in the Ems Estuary, it provides an analogy for expected developments in comparable tidal systems where land reclamations were recently carried out.

Abstract Many water markets in the western United States (U.S.) have the ability to reallocate water temporarily during drought, often as short‐term water rights leases from lower value irrigated activities to higher value urban uses. Regulatory approval of water transfers, however, typically takes time and involves high transaction costs that arise from technical and legal analyses, discouraging short‐term leasing. This leads municipalities to protect against drought‐related shortfalls by purchasing large volumes of infrequently used permanent water rights. High transaction costs also result in municipal water rights rarely being leased back to irrigators in wet or normal years, reducing agricultural productivity. This research explores the development of a multi‐year two‐way option (TWO) contract that facilitates leasing from agricultural‐to‐urban users during drought and leasing from urban‐to agricultural users during wet periods. The modeling framework developed to assess performance of the TWO contracts includes consideration of the hydrologic, engineered, and institutional systems governing the South Platte River Basin in Colorado where there is growing competition for water between municipalities (e.g., the city of Boulder) and irrigators. The modeling framework is built around StateMod, a network‐based water allocation model used by state regulators to evaluate water rights allocations and potential rights transfers. Results suggest that the TWO contracts could allow municipalities to maintain supply reliability with significantly reduced rights holdings at lower cost, while increasing agricultural productivity in wet and normal years. Additionally, the TWO contracts provide irrigators with additional revenues via net payments of option fees from municipalities.

Abstract The state of Colorado's West Slope Basins are critical headwaters of the Colorado River and play a vital role in supporting Colorado's local economy and natural environment. However, balancing the multi‐sectoral water demands in the West Slope Basins while maintaining crucial downstream deliveries to Lake Powell is an increasing challenge for water managers. Internal variability of the hydroclimatic system and climate change complicate future vulnerability assessments. This work contributes a detailed accounting of multi‐sectoral drought vulnerability in the West Slope Basins and the impacts of drought on downstream deliveries. We first introduce a novel multi‐site Hidden Markov Model (HMM)‐based synthetic streamflow generator to create an ensemble of streamflows for all West Slope basins that better characterizes the region's drought extremes. We capture the effects of climate change by perturbing the HMM to generate an ensemble of streamflows reflecting plausible changes in climate. We then route both ensembles through StateMod, Colorado's water allocation model, to evaluate spatially compounding drought impacts across the West Slope Basins. Our results illustrate how drought events emerging from the system's stationary internal variability in the absence of climate change can significantly impact local water uses and deliveries to Lake Powell, exceeding extreme conditions in the historical record. Further, we find that even modest climate change can cause a regime shift where historically low downstream delivery volumes and extreme drought impacts become routine. These results can inform future Colorado River planning efforts, and our methodology can be expanded to other snow‐dominated regions that face persistent droughts.

Abstract Course‐based undergraduate research experiences (CUREs) can be a powerful tool in broadening participation in undergraduate research. In this paper, we review the benefits of and barriers to undergraduate research experiences and explore how CUREs can mitigate some of those issues. As a part of the NSF‐supported Biological Collections in Ecology and Evolution Network (BCEENET) activities, a series of network meetings produced a set of recommendations to increase the accessibility of CUREs for all students at all institution types. We use BCEENET CUREs that focus on digitized natural history collections data to illustrate how leveraging adaptable open educational resources that use freely available data and analysis tools can increase accessibility of undergraduate research. We also discuss how inclusive networks of educators and research collaborators can support broadening CURE implementation.

Abstract Lianas are key components of tropical forests, particularly at sites with more severe dry seasons. In contrast, trees are more abundant and speciose in wetter areas. The seasonal growth advantage (SGA) hypothesis postulates that such contrasting distributions are produced by higher liana growth relative to trees during seasonal droughts. The SGA has been investigated for larger size classes (e.g., ≥5 cm diameter at 1.3 m, dbh), but rarely for seedlings. Using eight annual censuses of >12,000 seedlings of 483 tree and liana species conducted at eight 1‐ha plots spanning a strong rainfall gradient in central Panama, we evaluated whether liana seedlings had higher growth and/or survival rates than tree seedlings at sites with stronger droughts. We also tested whether an extreme El Niño drought during the study period had a more negative effect on tree compared to liana seedlings. The absolute density of liana seedlings was similar across the rainfall gradient, ranging from 0.32 individuals/m2 (0.20–0.49, 95% credible interval [CI]) at the driest end of the gradient and 0.27 individuals/m2 (0.13–0.51 95% CI) at the wettest end of the gradient. The relative density of liana seedlings compared to tree seedlings was higher at sites with stronger dry seasons (0.27, 0.21–0.33, 95% CI), compared to wetter sites (0.12, 0.04–0.20 95% CI), due to lower tree seedling densities at drier sites. However, liana seedlings did not grow or survive better than tree seedlings in drier sites compared to wetter sites. Tree seedlings were more negatively impacted in terms of mortality by the extreme El Niño drought than liana seedlings, with an increase in annual mortality rate of 0.013 (0.003–0.025 95% CI) compared to lianas of −0.009 (−0.028 to 0.008 95% CI), but not growth. Our results indicate that lianas do not have a SGA over trees at the seedling stage. Instead, higher survival of liana versus tree seedlings during severe droughts or differences in liana versus tree fecundity or germination across the rainfall gradient likely explain why liana seedlings have higher relative densities at drier sites.

Abstract Cognitive decline in Parkinson's disease (PD) varies widely. While models to predict cognitive progression exist, comparing traditional probabilistic models to deep learning methods remains understudied. This study compares sequential modeling techniques to identify cognitive progression in individuals with and without PD. Using data from the Parkinson's Progression Marker Initiative, shallow Markov, deep recurrent (long short‐term memory [LSTM]), and nonrecurrent (temporal fusion transformer [TFT]) models were compared to predict cognitive status over time. Cognitive status was categorized into normal cognition (NC), mild cognitive impairment (MCI), and dementia. Predictions were made annually for up to 3 years using clinical data, including demographics, cognitive assessments, PD severity, and medical history. Each approach was evaluated using inverse probability weighted (IPW‐) F1 scores. An ensemble method combined outputs from the Markov, LSTM, and TFT models. The dataset included 917 individuals (53% PD; 30% at risk for PD; 17% Healthy Controls). The TFT model outperformed others across all annual periods (IPW‐F1 = 0.468) compared to the Markov (IPW‐F1 = 0.349) and LSTM (IPW‐F1 = 0.414) models, with improved performance using an ensemble approach (IPW‐F1 = 0.502). For MCI and dementia predictions, which were rarer occurrences compared to NC status (ratios: 50:8:1), the TFT model consistently outperformed competing models, achieving IPW‐F1 scores of 0.496 and 0.533 for MCI and dementia, respectively. In conclusion, sequential deep learning models like TFT, which mitigate long‐term memory loss and can interpret complex, high‐dimensional data, perform best overall in predicting clinically important cognitive transitions. These methods should be further explored for predicting degenerative conditions.

Abstract The increased use of sensor‐based digital health technologies (DHTs) in clinical trials brought to light concerns about implementation practices that might introduce burden on trial participants, resulting in suboptimal compliance and become an additional complicating factor in clinical trial conduct. These concerns may contribute to the lower‐than‐anticipated uptake of DHT deployment and data use for regulatory decision‐making, despite well‐articulated benefits. The Electronic Clinical Outcome Assessment (eCOA) Consortium gathered collective experience on deploying sensor‐based DHTs and supplemented this with relevant literature focusing on mechanisms that may enhance participant compliance. The process for DHT implementation starts with identifying a clinical concept of interest followed by a digital measure selection, defining active or passive data capture and their sources, the number of sensors with respective body location, plus the duration and frequency of use in the context of perceived participant burden. Roundtable discussions among patient groups, physicians, and technology providers prior to protocol development can be very impactful for optimizing trial design. While diversity and inclusion are essential for any clinical trial, patient populations should be considered carefully in the context of trial‐specific aims, requirements, and anticipated patient burden. Minimizing site burden includes assessment of training, research engagement, and logistical burden which needs to be triaged differently for early and late‐stage clinical trials. Additional considerations include sharing trial results with study participants and leveraging publicly available data for compliance modeling. To the best of our knowledge, this report provides holistic considerations for sensor‐based DHT implementation that may optimize participant compliance.

Abstract Despite increasing interest in using Artificial Intelligence (AI) and Machine Learning (ML) models for drug development, effectively interpreting their predictions remains a challenge, which limits their impact on clinical decisions. We address this issue by providing a practical guide to SHapley Additive exPlanations (SHAP), a popular feature‐based interpretability method, which can be seamlessly integrated into supervised ML models to gain a deeper understanding of their predictions, thereby enhancing their transparency and trustworthiness. This tutorial focuses on the application of SHAP analysis to standard ML black‐box models for regression and classification problems. We provide an overview of various visualization plots and their interpretation, available software for implementing SHAP, and highlight best practices, as well as special considerations, when dealing with binary endpoints and time‐series models. To enhance the reader's understanding for the method, we also apply it to inherently explainable regression models. Finally, we discuss the limitations and ongoing advancements aimed at tackling the current drawbacks of the method.

Abstract Introduction Perspectives on long‐acting injectable cabotegravir/rilpivirine (CAB/RPV‐LA) from HIV health disparity populations are under‐represented in current literature yet crucial to optimize delivery. Methods Between August 2022 and May 2023, we conducted in‐depth interviews with people with HIV (PWH) at four HIV clinics in Atlanta, Chicago and San Francisco. Eligibility criteria were current CAB/RPV‐LA use with receipt of ≥3 injections or CAB/RPV‐LA discontinuation. We purposefully sampled for PWH who initiated with viraemia (plasma HIV RNA >50 copies/ml) due to adherence challenges, discontinuers, and cis and trans women. Interviews were coded and analysed using thematic methods grounded in descriptive phenomenology. Clinical data were abstracted from the medical record. Results The sample (San Francisco n = 25, Atlanta n = 20, Chicago n = 14 for total n = 59, median number of injections = 6) consisted of 48 PWH using CAB/RPV‐LA and 11 who had discontinued. The median age was 50 (range 25–73) and 40 (68%) identified as racial/ethnic minorities, 19 (32%) cis or trans women, 16 (29%) were experiencing homelessness/unstable housing, 12 (20%) had recently used methamphetamine or opioids and 11 (19%) initiated with viraemia. All participants except one (who discontinued) had evidence of viral suppression at interview. Typical benefits of CAB/RPV‐LA included increased convenience, privacy and freedom from being reminded of HIV and reduced anxiety about forgetting pills. However, PWH who became virally suppressed through CAB/RPV‐LA use also experienced an amelioration of feelings of shame and negative self‐worth related to oral adherence challenges. Regardless of baseline viral suppression status, successful use of CAB/RPV‐LA amplified positive provider/clinic relationships, and CAB/RPV‐LA was often viewed as less “work” than oral antiretroviral therapy, which created space to attend to other aspects of health and wellness. For some participants, CAB/RPV‐LA remained “work,” particularly with regard to injection site pain and visit frequency. At times, these burdens outweighed the aforementioned benefits, resulting in discontinuation. Conclusions CAB/RPV‐LA offers a range of logistical, psychosocial and care engagement benefits, which are experienced maximally by PWH initiating with viraemia due to adherence challenges; however, benefits do not always outweigh treatment burdens and can result in discontinuation. Our findings on rationales for persistence versus discontinuation can inform both initial and follow‐up patient counselling.

Abstract Introduction There are no longitudinal HIV incidence data among men who have sex with men (MSM) and transgender women (TGW) in Indonesia. We aimed to estimate HIV prevalence and incidence and identify associated factors among clinic attendees in Jakarta and Bali. Methods We conducted a retrospective cohort study using medical records from five clinics. We reviewed HIV tests among MSM/TGW aged ≥18 years who attended the clinics between 1 January 2018 to 31 December 2020 in Jakarta and 1 January 2017 to 31 December 2019 in Bali. HIV prevalence was measured at the first test. Those with an HIV‐negative test and ≥1 follow‐up test/s were included in the person‐years (PY) at risk to determine HIV incidence. The PY at risk calculation started at the first negative test until the last recorded negative test or seroconversion. Multivariate Poisson regression was used to determine factors associated with HIV acquisition. Results Among 5203 and 2815 individuals with an HIV test result in Jakarta and Bali, respectively, at the first HIV test, 1205 and 616 were HIV positive (HIV prevalence 23.2% and 21.9%). The longitudinal sample included 1418 and 873 individuals, respectively. The median number of tests among repeat testers was 3 in Jakarta (interquartile range [IQR] = 2–4) and 3 in Bali (IQR = 2–5). At baseline, about one‐quarter were aged 90% were MSM and >35% had been tested for HIV previously. In Jakarta, there were 127 HIV seroconversions in 1353 PY (incidence 9.39/100 PY, 95% CI = 7.89–11.17), and in Bali, 71 seroconversions in 982 PY (incidence 7.24/100 PY, 95% CI = 5.73–9.13). Compared to those aged 18–24 years, the incidence rate was lower in older patients (Jakarta—30–39 years: aRR = 0.56, 95% CI = 0.34–0.92; 40+ years: aRR = 0.34, 95% CI = 0.14–0.81; Bali—25–29 years: aRR = 0.44, 95% CI = 0.25–0.79; 30–39 years: aRR = 0.33, 95% CI = 0.18–0.61; 40+ years: aRR = 0.06, 95% CI = 0.01–0.48). In Jakarta, incidence was lower in those with university education than in those without (aRR = 0.66, 95% CI = 0.45–0.96). In Bali, those who had been referred by outreach workers had a higher incidence than those who self‐presented for testing (aRR = 1.85, 95% CI = 1.12–3.07). Conclusions We observed very high HIV prevalence and incidence rate estimates. Measures to encourage regular testing and effective use of HIV prevention, including pre‐exposure prophylaxis scale‐up and demand creation, are needed.

Abstract Despite significant progress in the treatment of multiple myeloma (MM), relapsed/refractory patients urgently require more effective therapies. We here describe the discovery, mechanism of action, and preclinical anti‐MM activity of engineered toxin body MT‐0169, a next‐generation immunotoxin comprising a CD38‐specific antibody fragment linked to a de‐immunized Shiga‐like toxin A subunit (SLTA) payload. We show that specific binding of MT‐0169 to CD38 on MM cell lines triggers rapid internalization of SLTA, causing cell death via irreversible ribosome inhibition, protein synthesis blockade, and caspase 3/7 activation. In co‐culture experiments, bone marrow mesenchymal stromal cells did not induce drug resistance against MT‐0169. In the preclinical setting, MT‐0169 effectively lysed primary MM cells from newly diagnosed and heavily pretreated MM patients, including those refractory to daratumumab, with minimal toxicity against nonmalignant hematopoietic cells. MM cell lysis showed a significant correlation with their CD38 expression levels but not with cytogenetic risk, tumor load, or number of prior lines of therapy. Finally, MT‐0169 showed efficient in vivo anti‐MM activity in various mouse xenograft models, including one in which MM cells are grown in a humanized bone marrow‐like niche. These findings support clinical investigation of MT‐0169 in relapsed/refractory MM patients, including those refractory to CD38‐targeting immunotherapies.

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is the precursor of multiple myeloma (MM) and related disorders. MGUS is characterized by asymptomatic paraproteinemia. In some cases, multiple paraproteins can be identified but the clinical implications of this phenomenon are poorly understood. In this study, we aim to inform the approach to this challenging MGUS subgroup by utilizing data from iStopMM, a population‐based screening study and randomized trial of follow‐up strategies. In total, 75,422 Icelanders over the age of 40 were screened for MGUS with 3389 (4.4%) having at least one paraprotein of whom 303 (9%) had multiple paraproteins. IgM paraproteins were more common in those with multiple paraproteins (49% vs. 27% of paraproteins, p

Abstract Preliminary evidence suggests perturbations of the kynurenine pathway (KP) of tryptophan metabolism in infants with single ventricle heart disease (SVHD). In 72 infants with SVHD undergoing stage 2 palliation (S2P) and 41 controls, we quantified serum KP metabolite concentrations via tandem mass spectroscopy pre‐S2P and post‐S2P at 2, 24, and 48 h and assessed metabolite relationships with post‐S2P outcomes (length of stay, hypoxemia burden, and intubation duration). Pre‐S2P, SVHD infants had lower tryptophan and serotonin levels and higher kynurenic acid, 3‐hydroxykynurenine, and picolinic acid levels than controls. Post‐S2P, metabolites peaked at 2 h, with return to baseline by 48 h for all except kynurenic acid, which remained elevated. Metabolite concentrations pre‐S2P were poorly associated with outcomes. A lower serotonin peak 2 h post‐S2P was associated with longer length of stay and intubation duration. Multiple metabolites at 24 and 48 h correlated with outcomes; notably, elevated kynurenic acid was associated with worse results for all three outcomes. Our results confirm that interstage SVHD infants have altered KP activity compared to controls. Further, the link between outcomes and KP metabolites post‐S2P—but not at baseline—demonstrates that acute, perioperative changes in tryptophan catabolism may be more important to tolerating S2P physiology than chronic interstage changes.

Abstract This study investigates hemoglobin (Hb)‐induced kidney injury and the protective role of the ApoHemoglobin‐Haptoglobin (ApoHb‐Hp) complex against heme and Hb damage. Hb facilitates oxygen (O2) delivery but poses challenges outside red blood cells (RBCs) due to toxic Hb and heme mechanisms. These are managed by binding to serum proteins like Haptoglobin (Hp) and Hemopexin (Hpx). During hemolysis, depletion of Hp and Hpx leaves tissues vulnerable to Hb and heme. To address this, we developed the ApoHb‐Hp complex, based on Apohemoglobin, which is produced by removing heme from Hb, conjugated with Hp. This complex acts as a dual scavenger for Hb and heme, preventing tissue damage. Our findings demonstrate that ApoHb‐Hp significantly protects MPC5 podocytes from Hb‐induced damage. Fluorescent staining showed a higher percentage of nephrin‐positive cells in the ApoHb‐Hp group, and MTT assays revealed enhanced cell viability compared to Hb alone. Additionally, ApoHb‐Hp reduced reactive oxygen species (ROS) production, with the Hb group exhibiting significantly elevated ROS levels. The ApoHb‐Hp complex mitigated the depletion of protective mechanisms, as shown by significant increases in superoxide dismutase (SOD) and glutathione (GSH). Moreover, ApoHb‐Hp treatment reduced the activation of the NLRP3 inflammasome signaling pathway and inflammatory cytokines IL‐1β and IL‐18. These findings underscore the therapeutic potential of ApoHb‐Hp in mitigating Hb‐induced renal damage by preserving podocyte viability and reducing oxidative stress. Overall, ApoHb‐Hp maintained protective mechanisms depleted otherwise by Hb. These findings highlight ApoHb‐Hp's potential as a therapeutic agent against Hb‐induced renal damage, offering insights into its mechanisms and implications for treating conditions involving hemolysis.

ABSTRACT Background Detection of cancer at the early stage currently offers the only viable strategy for reducing disease‐related morbidity and mortality. Various approaches for multi‐cancer early detection are being explored, which largely rely on capturing signals from circulating analytes shed by tumors into the blood. The fact that biomarker concentrations are limiting in the early stages of cancer, however, compromises the accuracy of these tests. We, therefore, adopted an alternate approach that involved interrogation of the serum metabolome with machine learning‐based data analytics. Here, we monitored for modulations in metabolite patterns that correlated with the presence or absence of cancer. Results obtained confirmed the efficacy of this approach by demonstrating that it could detect a total of 15 cancers in women with an average accuracy of about 99%. Aims To further increase the scope of our test, we conducted an investigator‐initiated clinical trial involving a total of 6445 study participants, which included both cancer patients and non‐cancer volunteers. Our goal here was to maximize the number of cancers that could be detected, while also covering cancers in both females and males. Methods and Results Metabolites extracted from individual serum samples were profiled by ultra‐performance liquid chromatography coupled to a high‐resolution mass spectrometer using an untargeted protocol. After processing, the data were analyzed by our cancer detection machine‐learning algorithm to differentiate cancer from non‐cancer samples. Results revealed that our test platform could indeed detect a total of 30 cancers, covering both females and males, with an average accuracy of ~98%. Importantly, the high detection accuracy remained invariant across all four stages of the cancers. Conclusion Thus, our approach of integrating untargeted metabolomics with machine learning‐powered data analytics offers a powerful strategy for early‐stage multi‐cancer detection with high accuracy. Trial Registration: Registration No: CTRI/2023/03/050316

ABSTRACT Background and Aims Previous studies describe the occurrence of unacceptable behaviors reported by students pursuing health professional education in Aotearoa, New Zealand and across the globe. These include, but are not limited to, experiences of verbal abuse, sexual harassment, and discrimination based on race/ethnicity, religious beliefs, gender, and sexual orientation. University of Otago teaching staff across the various health professional programs often receive anecdotal reports of these phenomena from their clinical students. Our study will investigate the extent and sources of unacceptable behaviors, whether students report those events, and possible institutional responses to these behaviors. Methods A student codesign panel was formed alongside the research team to guide study design and data collection. This study will use a sequential two‐phase mixed methods design. The first phase will include a cross‐sectional survey using a modified version of a validated online questionnaire administered to all clinical students across the seven health professional programs at the University of Otago. The second phase will recruit students to participate in semi‐structured interviews. Descriptive and thematic analysis will be applied. Conclusion This novel mixed‐method study may offer valuable insights into the prevalence and impact of unacceptable behaviors on health professional students at the University of Otago, while ensuring student perspectives are incorporated into both the research design and the university's response strategies.