Dietary plasticity and broad North Atlantic origins inferred from bulk and amino acid-specific δ15N and δ13C favour killer whale range expansions into Arctic waters.

Killer whales (Orcinus orca) occur seasonally in the eastern Canadian Arctic (ECA), where their range expansion associated with declining sea ice have raised questions about the impacts of increasing killer whale predation pressure on Arctic-endemic prey. We assessed diet and distribution of ECA killer whales using bulk and compound-specific stable isotope analysis (CSIA) of amino acids (AA) of 54 skin biopsies collected from 2009 to 2020 around Baffin Island, Canada. Bulk ECA killer whale skin δ15N and δ13C values did not overlap with potential Arctic prey after adjustment for trophic discrimination, and instead reflected foraging history in the North Atlantic prior to their arrival in the ECA. Adjusted killer whale stable isotope (SI) values primarily overlapped with several species of North Atlantic baleen whales or tuna. Amino acid (AA)-specific δ15N values indicated the ECA killer whales fed primarily on marine mammals, having similar glutamic acid δ15N-phenylalanine δ15N (δ15NGlx-Phe) and threonine δ15N (δ15NThr) as mammal-eating killer whales from the eastern North Pacific (ENP) that served as a comparative framework. However, one ECA whale grouped with the fish-eating ENP ecotype based δ15NThr. Distinctive essential AA δ13C of ECA killer whale groups, along with bulk SI similarity to killer whales from different regions of the North Atlantic, indicates different populations converge in Arctic waters from a broad source area. Generalist diet and long-distance dispersal capacity favour range expansions, and integration of these insights will be critical for assessing ecological impacts of increasing killer whale predation pressure on Arctic-endemic species.

Neurological outcomes for patients meeting radiographic criteria for DEFUSE 3 and SELECT2.

BACKGROUND: The DEFUSE 3 and SELECT2 thrombectomy trials included some patients with similar radiographic profiles, although the rates of good functional outcomes differed widely between the studies. OBJECTIVE: To report neurological outcomes for patients who meet CT and CT perfusion (CTP) inclusion criteria common to both DEFUSE 3 and SELECT2. METHODS: Retrospective study of thrombectomy patients, presenting between November 2016 and December 2023 to a large health system, with Alberta Stroke Program Early CT score ≥6, core infarction 50-69 mL, mismatch ratio ≥1.8, and mismatch volume ≥15 mL. The primary outcome was 90-day modified Rankin Scale score 0-2. A logistic regression analysis was performed to identify independent predictors of the primary outcome. RESULTS: 85 patients, with mean age 64.6 (16.6) years and median National Institutes of Health Stroke Scale score 18 (15-23), were included. Thirty-eight of 85 patients (44.7%) were functionally independent at 90 days. Predictors of functional independence included age (OR=0.943, 95% CI 0.908 to 0.980; P=0.003), initial glucose (OR=0.989, 95% CI 0.978 to 1.000; P=0.044), and time last known well to skin puncture (OR=0.997, 95% CI 0.994 to 1.000; P=0.028). The area under the curve for the multivariable model predicting the primary outcome was 0.82 (95% CI 0.73 to 0.92). CONCLUSION: Nearly half of patients meeting radiographic criteria common to DEFUSE 3 and SELECT2 are functionally independent at 90 days, similar to rates reported for the treated DEFUSE 3 cohort. This might be due to their moderate core volumes and large ischemic penumbra.

Staging Extramitral Cardiac Damage in Mitral Annular Calcification With Mitral Valve Dysfunction.

BACKGROUND: Mitral annular calcification (MAC) is a progressive degenerative process associated with comorbidities and increased mortality. A staging system that considers extramitral cardiac damage in MAC may help improve patient selection for mitral valve interventions. OBJECTIVES: This study sought to develop a transthoracic echocardiogram (TTE)-based cardiac staging system in patients with MAC and significant mitral valve dysfunction and assess its prognostic utility. METHODS: We retrospectively evaluated all adults who underwent TTE over 1 year at Mayo Clinic with MAC and significant mitral valve dysfunction defined as mitral stenosis and/or at least moderate mitral regurgitation. Patients were categorized into 5 stages according to extramitral cardiac damage by TTE. All-cause mortality and heart failure hospitalization were assessed. RESULTS: For the 953 included patients, the mean age was 76.2 ± 10.7 years, and 54.0% were women. Twenty-eight (2.9%) patients were classified in stages 0 to 1, 499 (52.4%) in stage 2, 115 (12.1%) in stage 3, and 311 (32.6%) in stage 4. At the 3.8-year follow-up, mortality was significantly higher in patients in stages 2 to 4 compared to stages 0 to 1 and increased with each stage. Survival differences were maintained after adjustment for age, diabetes mellitus, and glomerular filtration rate. The rate of heart failure hospitalization was significantly higher in stages 3 and 4 compared to stages 0 to 1. Similar results were observed in subgroup analysis in patients with moderate or severe MAC, predominant mitral stenosis, or predominant mitral regurgitation. CONCLUSIONS: Using the proposed extramitral cardiac damage staging system in patients with MAC and significant mitral valve dysfunction, more advanced stages are associated with higher mortality.

Cumulative asparagine to aspartate deamidation fails to perturb γD-crystallin structure and stability.

Deamidation frequently is invoked as an important driver of crystallin aggregation and cataract formation. Here, we characterized the structural and biophysical consequences of cumulative Asn to Asp changes in γD-crystallin. Using NMR spectroscopy, we demonstrate that N- or C-terminal domain-confined or fully Asn to Asp changed γD-crystallin exhibits essentially the same 1H-15N HSQC spectrum as the wild-type protein, implying that the overall structure is retained. Only a very small thermodynamic destabilization for the overall Asn to Asp γD-crystallin variants was noted by chaotropic unfolding, and assessment of the colloidal stability, by measuring diffusion interaction parameters, yielded no substantive differences in association propensities. Furthermore, using molecular dynamics simulations, no significant changes in dynamics for proteins with Asn to Asp or iso-Asp changes were detected. Our combined results demonstrate that substitution of all Asn by Asp residues, reflecting an extreme case of deamidation, did not affect the structure and biophysical properties of γD-crystallin. This suggests that these changes alone cannot be the major determinant in driving cataract formation.

TIN-X version 3: update with expanded dataset and modernized architecture for enhanced illumination of understudied targets.

TIN-X (Target Importance and Novelty eXplorer) is an interactive visualization tool for illuminating associations between diseases and potential drug targets and is publicly available at newdrugtargets.org. TIN-X uses natural language processing to identify disease and protein mentions within PubMed content using previously published tools for named entity recognition (NER) of gene/protein and disease names. Target data is obtained from the Target Central Resource Database (TCRD). Two important metrics, novelty and importance, are computed from this data and when plotted as log(importance) vs. log(novelty), aid the user in visually exploring the novelty of drug targets and their associated importance to diseases. TIN-X Version 3.0 has been significantly improved with an expanded dataset, modernized architecture including a REST API, and an improved user interface (UI). The dataset has been expanded to include not only PubMed publication titles and abstracts, but also full-text articles when available. This results in approximately 9-fold more target/disease associations compared to previous versions of TIN-X. Additionally, the TIN-X database containing this expanded dataset is now hosted in the cloud via Amazon RDS. Recent enhancements to the UI focuses on making it more intuitive for users to find diseases or drug targets of interest while providing a new, sortable table-view mode to accompany the existing plot-view mode. UI improvements also help the user browse the associated PubMed publications to explore and understand the basis of TIN-X's predicted association between a specific disease and a target of interest. While implementing these upgrades, computational resources are balanced between the webserver and the user's web browser to achieve adequate performance while accommodating the expanded dataset. Together, these advances aim to extend the duration that users can benefit from TIN-X while providing both an expanded dataset and new features that researchers can use to better illuminate understudied proteins.

Reelin marks cocaine-activated striatal ensembles, promotes neuronal excitability, and regulates cocaine reward.

Drugs of abuse activate defined neuronal ensembles in brain reward structures such as the nucleus accumbens (NAc), which are thought to promote the enduring synaptic, circuit, and behavioral consequences of drug exposure. While the molecular and cellular effects arising from experience with drugs like cocaine are increasingly well understood, the mechanisms that sculpt NAc ensemble participation are largely unknown. Here, we leveraged unbiased single-nucleus transcriptional profiling to identify expression of the secreted glycoprotein Reelin (encoded by the Reln gene) as a marker of cocaine-activated neuronal ensembles within the rat NAc. Multiplexed in situ detection confirmed selective expression of the immediate early gene Fos in Reln+ neurons after cocaine experience, and also revealed enrichment of Reln mRNA in Drd1 + medium spiny neurons (MSNs) in both the rat and human brain. Using a novel CRISPR interference strategy enabling selective Reln knockdown in the adult NAc, we observed altered expression of genes linked to calcium signaling, emergence of a transcriptional trajectory consistent with loss of cocaine sensitivity, and a striking decrease in MSN intrinsic excitability. At the behavioral level, loss of Reln prevented cocaine locomotor sensitization, abolished cocaine place preference memory, and decreased cocaine self-administration behavior. Together, these results identify Reelin as a critical mechanistic link between ensemble participation and cocaine-induced behavioral adaptations.

Investigation of setmelanotide, an MC4R agonist, for obesity in individuals with Smith-Magenis syndrome.

BACKGROUND: Smith Magenis Syndrome (SMS) is a rare genetic disorder caused by RAI1 haploinsufficiency. Obesity in people with SMS is believed partially due to dysfunction of the proximal melanocortin 4 receptor (MC4R) pathway. We therefore studied effects of treatment with the MC4R agonist setmelanotide on obesity and hunger, as well as metabolic, cardiac and safety, in individuals with SMS. METHODS: People with SMS received once-daily setmelanotide injections, with the dose titrated bi-weekly to a maximum of 3 mg over ∼1 month; and a full-dose treatment duration of 3mo. The primary outcome was percent change in body weight. Secondary outcomes included hunger, waist circumference, body composition, and safety. RESULTS: 12 individuals, ages 11-39 y, enrolled and 10 completed the full-dose treatment phase. Mean percent change in body weight at end-treatment was - 0.28 % [(95 % CI, -2.1 % to 1.5 %; n = 12; P = 0.66]. Participants experienced a significant decrease in total cholesterol associated with a significant decrease in HDL-cholesterol and a trend for lower LDL-cholesterol. Self-reported hunger was reduced at end-treatment (p = 0.011). All participants reported adverse events (AEs), most commonly injection-site reactions and skin hyperpigmentation. No AEs led to withdrawal or death. CONCLUSIONS: In this trial, setmelanotide did not significantly reduce body weight in participants with SMS. Participants reported significant differences in hunger, but such self-reports are difficult to interpret without a placebo-treated group. The changes in lipid profiles require further investigation. Results of this study do not suggest that dysfunction of the proximal MC4R pathway is the main etiology for obesity in people with SMS.

Multicenter evaluation of mechanical thrombectomy for distal medium vessel occlusions with National Institute of Health Stroke Scale Scores ≥ 6 and ≤ 6.

BACKGROUND: While mechanical thrombectomy is considered standard of care for large vessel occlusions, scientific evidence to support treatment for distal and medium vessel occlusions remains scarce. PURPOSE: To evaluate feasibility, safety, and outcomes in patients with low National Institute of Health Stroke Scale scores undergoing mechanical thrombectomy for treatment of distal medium vessel occlusions. MATERIALS AND METHODS: Retrospective data review and analysis of prospectively maintained databases at 41 academic centers in North America, Asia, and Europe between January 2017 and January 2022. Characteristics and outcomes were compared between groups with low stroke scale score (≤ 6) versus and higher stroke scale scores (> 6). Propensity score matching using the optimal pair matching method and 1:1 ratio was performed. RESULTS: Data were collected on a total of 1068 patients. After propensity score matching, there were a total of 676 patients included in the final analysis, with 338 patients in each group. High successful reperfusion rates were seen in both groups, 90.2% in ≤ 6 and 88.7% in the > 6 stroke scale groups. The frequency of excellent and good functional outcome was seen more common in low versus higher stroke scale score patients (64.5% and 81.1% versus 39.3% and 58.6%, respectively). The 90-day mortality rate observed in the ≤ 6 stroke scale group was 5.3% versus 13.3% in the > 6 stroke scale group. CONCLUSION: Mechanical thrombectomy in distal and medium vessel occlusions, specifically in patients with low stroke scale scores is feasible, though it may not necessarily improve outcomes over IVT.

Advancing diagnostic precision of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage: The potential for a vasospasm index score on perfusion imaging to detect vasospasm.

BACKGROUND: The occurrence of delayed cerebral ischemia and vasospasm following aneurysmal subarachnoid hemorrhage (aSAH) results in high morbidity and mortality, but the diagnosis remains challenging. This study aimed to identify neuroimaging perfusion parameters indicative of delayed cerebral ischemia in patients with suspected vasospasm. METHODS: This is a case-control study. Cases were adult aSAH patients who underwent magnetic resonance perfusion or computed tomography perfusion (CTP) imaging ≤ 24 h before digital subtraction angiography performed for vasospasm diagnosis and treatment. Controls were patients without aSAH who underwent CTP. Quantitative perfusion parameters at different thresholds, including Tmax 4-6-8-10 s delay, cerebral blood flow and cerebral blood volume were measured and compared between cases and controls. The Vasospasm Index Score was calculated as the ratio of brain volume with time-to-max (Tmax) delay > 6 s over volume with Tmax > 4 s. RESULTS: 54 patients with aSAH and 119 controls without aSAH were included. Perfusion parameters with the strongest prediction of vasospasm on cerebral angiography were the combination of the Vasospasm Index Score (Tmax6/Tmax4) + CBV ≤ 48 % (area under the curve value of 0.85 [95 % CI 0.78-0.91]) with a sensitivity of 63 % and specificity of 95 %. CONCLUSION: The Vasospasm Index Score in combination with CBV ≤ 48 % on cerebral perfusion imaging reliably identified vasospasm as the cause of DCI on perfusion imaging.

Forecasting daily total pollen concentrations on a global scale.

BACKGROUND: There is evidence that global anthropogenic climate change may be impacting floral phenology and the temporal and spatial characteristics of aero-allergenic pollen. Given the extent of current and future climate uncertainty, there is a need to strengthen predictive pollen forecasts. METHODS: The study aims to use CatBoost (CB) and deep learning (DL) models for predicting the daily total pollen concentration up to 14 days in advance for 23 cities, covering all five continents. The model includes the projected environmental parameters, recent concentrations (1, 2 and 4 weeks), and the past environmental explanatory variables, and their future values. RESULTS: The best pollen forecasts include Mexico City (R2(DL_7) ≈ .7), and Santiago (R2(DL_7) ≈ .8) for the 7th forecast day, respectively; while the weakest pollen forecasts are made for Brisbane (R2(DL_7) ≈ .4) and Seoul (R2(DL_7) ≈ .1) for the 7th forecast day. The global order of the five most important environmental variables in determining the daily total pollen concentrations is, in decreasing order: the past daily total pollen concentration, future 2 m temperature, past 2 m temperature, past soil temperature in 28-100 cm depth, and past soil temperature in 0-7 cm depth. City-related clusters of the most similar distribution of feature importance values of the environmental variables only slightly change on consecutive forecast days for Caxias do Sul, Cape Town, Brisbane, and Mexico City, while they often change for Sydney, Santiago, and Busan. CONCLUSIONS: This new knowledge of the ecological relationships of the most remarkable variables importance for pollen forecast models according to clusters, cities and forecast days is important for developing and improving the accuracy of airborne pollen forecasts.

Chst9 marks a spatially and transcriptionally unique population of Oprm1-expressing neurons in the nucleus accumbens.

Opioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (µORs). The µOR is encoded by the Oprm1 gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc). Oprm1 expression in NAc medium spiny neurons (MSNs) mediates opioid place preference, seeking, and consumption. However, recent single nucleus RNA sequencing (snRNA-seq) studies have revealed that multiple subpopulations of NAc neurons express Oprm1 mRNA, making it unclear which populations mediate diverse behaviors resulting from µOR activation. Using published snRNA-seq datasets from the rat NAc, we identified a novel population of MSNs that express the highest levels of Oprm1 of any NAc cell type. Here, we show that this population is selectively marked by expression of Chst9, a gene encoding a carbohydrate sulfotransferase. Notably, Chst9+ neurons exhibited more abundant expression of Oprm1 as compared to other cell types, and formed discrete cellular clusters along the medial and ventral borders of the NAc shell subregion. Moreover, CHST9 mRNA was also found to mark specific MSN populations in published human and primate snRNA-seq studies, indicating that this unique population may be conserved across species. Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression of Chst9. The abundant expression of Oprm1 in this population and the conservation of these cells across species suggests that they may play a key functional role in opioid response and identify this subpopulation as a target for further investigation.

Advancing Animal Models of Human Type 1 Diabetes.

Multiple rodent models have been developed to study the basis of type 1 diabetes (T1D). However, nonobese diabetic (NOD) mice and derivative strains still provide the gold standard for dissecting the basis of the autoimmune responses underlying T1D. Here, we review the developmental origins of NOD mice, and how they and derivative strains have been used over the past several decades to dissect the genetic and immunopathogenic basis of T1D. Also discussed are ways in which the immunopathogenic basis of T1D in NOD mice and humans are similar or differ. Additionally reviewed are efforts to "humanize" NOD mice and derivative strains to provide improved models to study autoimmune responses contributing to T1D in human patients.

Predictors of Futile Recanalization in Ischemic Stroke Patients with low baseline NIHSS.

BACKGROUND: There is yet no randomized controlled evidence that mechanical thrombectomy (MT) is superior to best medical treatment in patients with large vessel occlusion but minor stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] <6). Prior studies of patients with admission NIHSS scores >6 observed unfavorable functional outcomes despite successful recanalization, commonly termed as futile recanalization (FR), in up to 50% of cases. AIM: The aim of this study is to determine the prevalence of FR in patients with minor stroke and identify associated patient-specific risk factors. METHODS: Our multicenter cohort study screened all patients prospectively enrolled in the German Stroke Registry Endovascular Treatment from 2015 to 2021 (n=13082). Included were patients who underwent MT for anterior circulation vessel occlusion with a baseline NIHSS score of <6 and successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] score of 2b-3). FR was defined by a modified Rankin Scale (mRS) score of 2-6 at 90 days. Multivariable logistic regression analysis was conducted to explore factors associated with FR. RESULTS: A total of 674 patients met the inclusion criteria. FR occurred in 268 (40%) patients. Multivariable logistic regression analysis indicates that higher age (adjusted odds ratio: 1.04 [95% confidence interval: 1.02-1.06]), pre-stroke mRS 1 (aOR: 2.70 [1.51-4.84]), transfer from admission hospital to comprehensive stroke center (aOR: 1.67 [1.08-2.56]), longer time from symptom onset/last seen well to admission (aOR: 1.02 [1.00-1.04]), MT under general anesthesia (aOR: 1.78 [1.13-2.82]), higher NIHSS after 24 hours (aOR: 1.09 [1.05-1.14]), and symptomatic intracranial hemorrhage (aOR: 16.88 [2.03-140.14]) increased the odds of FR. There was no significant difference in primary outcome between achieving mTICI 2b or 3. CONCLUSIONS: Unfavorable functional outcomes despite successful vessel recanalization were frequent in acute ischemic stroke patients with low NIHSS scores on admission. We provide patient-specific risk factors that indicate an increased risk of FR and should be considered when treating patients with minor stroke. DATA ACCESS STATEMENT: The data that support the findings of our study are available on reasonable request after approval of the GSR steering committee.

Better Guidelines and Policies: AAP's Partnership for Policy Implementation.

OBJECTIVES: In 2005, the American Academy of Pediatrics founded the Partnership for Policy Implementation (PPI). The PPI has collaborated with authors to improve the quality of clinical guidelines, technical reports, and policies that standardize care delivery, improve care quality and patient outcomes, and reduce variation and costs. METHODS: In this article, we describe how the PPI trained informaticians apply a variety of tools and techniques to these guidance documents, eliminating ambiguity in clinical recommendations and allowing guideline recommendations to be implemented by practicing clinicians and electronic health record (EHR) developers more easily. RESULTS: Since its inception, the PPI has participated in the development of 45 published and 27 in-progress clinical practice guidelines, policy statements, technical and clinical reports, and other projects endorsed by the American Academy of Pediatrics. The partnership has trained informaticians to apply a variety of tools and techniques to eliminate ambiguity or lack of decidability and can be implemented by practicing clinicians and EHR developers. CONCLUSIONS: With the increasing use of EHRs in pediatrics, the need for medical societies to improve the clarity, decidability, and actionability of their guidelines has become more important than ever.

Strain to shine: stretching-induced three-dimensional symmetries in nanoparticle-assembled photonic crystals.

Stretching elastic materials containing nanoparticle lattices is common in research and industrial settings, yet our knowledge of the deformation process remains limited. Understanding how such lattices reconfigure is critically important, as changes in microstructure lead to significant alterations in their performance. This understanding has been extremely difficult to achieve due to a lack of fundamental rules governing the rearrangements. Our study elucidates the physical processes and underlying mechanisms of three-dimensional lattice transformations in a polymeric photonic crystal from 0% to over 200% strain during uniaxial stretching. Corroborated by comprehensive experimental characterizations, we present analytical models that precisely predict both the three-dimensional lattice structures and the macroscale deformations throughout the stretching process. These models reveal how the nanoparticle lattice and matrix polymer jointly determine the resultant structures, which breaks the original structural symmetry and profoundly changes the dispersion of photonic bandgaps. Stretching induces shifting of the main pseudogap structure out from the 1st Brillouin zone and the merging of different symmetry points. Evolutions of multiple photonic bandgaps reveal potential optical singularities shifting with strain. This work sets a new benchmark for the reconfiguration of soft material structures and may lay the groundwork for the study of stretchable three-dimensional topological photonic crystals.

Using mobile health to expedite access to specialty care for youth presenting to the emergency department with concussion at highest risk of developing persisting symptoms: a protocol paper for a non-randomised hybrid implementation-effectiveness trial.

INTRODUCTION: Paediatric concussion is a common injury. Approximately 30% of youth with concussion will experience persisting postconcussion symptoms (PPCS) extending at least 1 month following injury. Recently, studies have shown the benefit of early, active, targeted therapeutic strategies. However, these are primarily prescribed from the specialty setting. Early access to concussion specialty care has been shown to improve recovery times for those at risk for persisting symptoms, but there are disparities in which youth are able to access such care. Mobile health (mHealth) technology has the potential to improve access to concussion specialists. This trial will evaluate the feasibility of a mHealth remote patient monitoring (RPM)-based care handoff model to facilitate access to specialty care, and the effectiveness of the handoff model in reducing the incidence of PPCS. METHODS AND ANALYSIS: This study is a non-randomised type I, hybrid implementation-effectiveness trial. Youth with concussion ages 13-18 will be enrolled from the emergency department of a large paediatric healthcare network. Patients deemed a moderate-to-high risk for PPCS using the predicting and preventing postconcussive problems in paediatrics (5P) stratification tool will be registered for a web-based chat platform that uses RPM to collect information on symptoms and activity. Those patients with escalating or plateauing symptoms will be contacted for a specialty visit using data collected from RPM to guide management. The primary effectiveness outcome will be the incidence of PPCS, defined as at least three concussion-related symptoms above baseline at 28 days following injury. Secondary effectiveness outcomes will include the number of days until return to preinjury symptom score, clearance for full activity and return to school without accommodations. The primary implementation outcome will be fidelity, defined as the per cent of patients meeting specialty care referral criteria who are ultimately seen in concussion specialty care. Secondary implementation outcomes will include patient-defined and clinician-defined appropriateness and acceptability. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Children's Hospital of Philadelphia (IRB 22-019755). Study findings will be published in peer-reviewed journals and disseminated at national and international meetings. TRIAL REGISTRATION NUMBER: NCT05741411.

Solvent concentration at 50% protein unfolding may reform enzyme stability ranking and process window identification.

As water miscible organic co-solvents are often required for enzyme reactions to improve e.g., the solubility of the substrate in the aqueous medium, an enzyme is required which displays high stability in the presence of this co-solvent. Consequently, it is of utmost importance to identify the most suitable enzyme or the appropriate reaction conditions. Until now, the melting temperature is used in general as a measure for stability of enzymes. The experiments here show, that the melting temperature does not correlate to the activity observed in the presence of the solvent. As an alternative parameter, the concentration of the co-solvent at the point of 50% protein unfolding at a specific temperature T in short c U 50 T is introduced. Analyzing a set of ene reductases, c U 50 T is shown to indicate the concentration of the co-solvent where also the activity of the enzyme drops fastest. Comparing possible rankings of enzymes according to melting temperature and c U 50 T reveals a clearly diverging outcome also depending on the specific solvent used. Additionally, plots of c U 50 versus temperature enable a fast identification of possible reaction windows to deduce tolerated solvent concentrations and temperature.

Studying interactions among anthropogenic stressors in freshwater ecosystems: A systematic review of 2396 multiple-stressor experiments.

Understanding the interactions among anthropogenic stressors is critical for effective conservation and management of ecosystems. Freshwater scientists have invested considerable resources in conducting factorial experiments to disentangle stressor interactions by testing their individual and combined effects. However, the diversity of stressors and systems studied has hindered previous syntheses of this body of research. To overcome this challenge, we used a novel machine learning framework to identify relevant studies from over 235,000 publications. Our synthesis resulted in a new dataset of 2396 multiple-stressor experiments in freshwater systems. By summarizing the methods used in these studies, quantifying trends in the popularity of the investigated stressors, and performing co-occurrence analysis, we produce the most comprehensive overview of this diverse field of research to date. We provide both a taxonomy grouping the 909 investigated stressors into 31 classes and an open-source and interactive version of the dataset (https://jamesaorr.shinyapps.io/freshwater-multiple-stressors/). Inspired by our results, we provide a framework to help clarify whether statistical interactions detected by factorial experiments align with stressor interactions of interest, and we outline general guidelines for the design of multiple-stressor experiments relevant to any system. We conclude by highlighting the research directions required to better understand freshwater ecosystems facing multiple stressors.

"It's another gay disease": an intersectional qualitative approach contextualizing the lived experiences of young gay, bisexual, and other sexual minoritized men in the United States during the mpox outbreak.

BACKGROUND: The U.S. mpox outbreak in 2022 introduced new and exacerbated existing challenges that disproportionately stigmatize gay, bisexual, and other sexual minoritized men (GBSMM). This study contextualizes the perceptions, susceptibility, and lived experiences of the mpox outbreak among GBSMM in the U.S. using an intersectional framework. METHODS: Between September 2022 to February 2023, we conducted 33 semi-structured qualitative interviews with purposively sampled GBSMM in the Northeast and the South region of the United States on various aspects related to their experience during the mpox outbreak. RESULTS: We identified four themes: (1) understanding and conceptualizations of mpox, (2) mpox vaccine availability and accessibility, (3) mpox vaccine hesitancy and mistrust, and (4) call to action and recommendations. GBSMM collectively discussed the elevated mpox stigmatization and homophobic discourse from mainstream social media and news outlets. GBSMM also discussed the lack of availability of mpox vaccines, unclear procedures to receive the vaccine, and continued mistrust in government, non-government, and other institutions of health that were complicit in anti-LGBTQ + narratives related to mpox. However, they expressed that these challenges may be addressed through more LGTBQ + representation and leveraging ways to empower these communities. CONCLUSION: GBSMM have mpox experiences that are distinct and multifaceted. Effectively addressing mpox and mitigating public health emergencies for GBSMM requires prioritizing destigmatizing communication channels and vaccine distribution strategies by centering their stories and lived experiences to advance health equity.