Swirls and scoops: Ice base melt revealed by multibeam imagery of an Antarctic ice shelf.

Knowledge gaps about how the ocean melts Antarctica's ice shelves, borne from a lack of observations, lead to large uncertainties in sea level predictions. Using high-resolution maps of the underside of Dotson Ice Shelf, West Antarctica, we reveal the imprint that ice shelf basal melting leaves on the ice. Convection and intermittent warm water intrusions form widespread terraced features through slow melting in quiescent areas, while shear-driven turbulence rapidly melts smooth, eroded topographies in outflow areas, as well as enigmatic teardrop-shaped indentations that result from boundary-layer flow rotation. Full-thickness ice fractures, with bases modified by basal melting and convective processes, are observed throughout the area. This new wealth of processes, all active under a single ice shelf, must be considered to accurately predict future Antarctic ice shelf melt.

Evaluating the Compatibility of New Recombinant Protein Antigens (Trivalent NRRV) with a Mock Pentavalent Combination Vaccine Containing Whole-Cell Pertussis: Analytical and Formulation Challenges.

Introducing new recombinant protein antigens to existing pediatric combination vaccines is important in improving coverage and affordability, especially in low- and middle-income countries (LMICs). This case-study highlights the analytical and formulation challenges encountered with three recombinant non-replicating rotavirus vaccine (NRRV) antigens (t-NRRV formulated with Alhydrogel® adjuvant, AH) combined with a mock multidose formulation of a pediatric pentavalent vaccine used in LMICs. This complex formulation contained (1) vaccine antigens (i.e., whole-cell pertussis (wP), diphtheria (D), tetanus (T), Haemophilus influenza (Hib), and hepatitis B (HepB), (2) a mixture of aluminum-salt adjuvants (AH and Adju-Phos®, AP), and (3) a preservative (thimerosal, TH). Selective, stability-indicating competitive immunoassays were developed to monitor binding of specific mAbs to each antigen, except wP which required the setup of a mouse immunogenicity assay. Simple mixing led to the desorption of t-NRRV antigens from AH and increased degradation during storage. These deleterious effects were caused by specific antigens, AP, and TH. An AH-only pentavalent formulation mitigated t-NRRV antigen desorption; however, the Hib antigen displayed previously reported AH-induced instability. The same rank-ordering of t-NRRV antigen stability (P[8] > P[4] > P[6]) was observed in mock pentavalent formulations and with various preservatives. The lessons learned are discussed to enable future multidose, combination vaccine formulation development with new vaccine candidates.

Coronary artery fistula following surgical myectomy for hypertrophic obstructive cardiomyopathy: a case report.

Background: Coronary artery fistula is a rare, but recognized complication of surgical myectomy. Although most communicate with the right heart, a large fistula into the left ventricular cavity may result in a shunt haemodynamically analogous to aortic regurgitation. Understanding the variable presentation of iatrogenic coronary fistulae and the optimal evaluation strategy is critical to obtaining a timely diagnosis and instituting treatment. Case summary: We report the case of a 57-year-old renal transplant recipient admitted for evaluation of presyncope, one-year post-surgical myectomy for hypertrophic obstructive cardiomyopathy. An iatrogenic coronary artery fistula was suspected by transthoracic echocardiography, and later confirmed with both non-invasive and invasive coronary angiography. Discussion: We highlight various cardiac imaging modalities that confirmed the diagnosis of coronary artery fistula and helped to determine the clinical significance. We report the tailored approach often required to determine the anatomic and haemodynamic characteristics of coronary fistulae and outline potential management strategies.

Resonant Auger decay of iodobenzene below the I 4d edge.

New data are presented on the resonant Auger decay of iodobenzene (C6H5I) in the region of the I 4d-1 ionization threshold. The excited molecules decay by participator and spectator processes to populate single-hole valence states and two-hole, one-particle excited states of the cation, providing new information on the structure of C6H5I+. Excitation of dissociative C6H5I (I 4d5/2,3/2-1)σ* resonances can, in principle, result in ultrafast dissociation to C6H5 + I** and the subsequent autoionization of I**, but no evidence for this process is observed. The results are compared with our recent study of the resonant Auger decay of methyl iodide (CH3I).

Catheter Ablation for Atrial Fibrillation-Influence of Modifiable Risk Factors and Ablation Modality on Procedural Efficacy and Safety.

BACKGROUND: Modifiable lifestyle risk factors, in particular obesity and related conditions, are important drivers of atrial fibrillation (AF), impacting the severity of symptoms and influence the efficacy and safety of treatment. OBJECTIVE: The study aimed to assess the impact of modifiable lifestyle factors on the effectiveness and safety of AF ablation, and examine the procedural characteristics, efficacy, safety and cost outcomes of cryoballoon vs radiofrequency ablation, in a real-world clinical setting. METHOD: Patients undergoing catheter ablation for AF (June 2017 to December 2020) were included in this retrospective analysis. Efficacy and safety outcomes were obtained from electronic medical records and state-wide databases. The primary outcome was successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy at 12 months. RESULTS: The study included 141 patients (mean age 60±11 years, 57% male). The average body mass index (BMI) was 29.2±5.6 kg/m2. Ablation by cryoballoon was undertaken in 59% (radiofrequency 41%). Acutely successful pulmonary vein isolation was achieved in 92%, however, only 52% (n=74) met the primary outcome (successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy) at 12 months. Successful management of AF was more likely in patients with lower BMI (p=0.006; particularly with BMI <27 kg/m2; p=0.004) and weight (p=0.003), and in those without obstructive sleep apnoea (p=0.032). The only independent predictor of the primary outcome was BMI (ß=0.25, p=0.004). Over 75% of complications occurred in those with BMI ≥27 kg/m2. CONCLUSIONS: Catheter ablation for AF is more likely to be unsuccessful in patients with uncontrolled risk factors, particularly obesity. Risk factor optimisation may improve procedural success and reduce the risk of procedural complications.

Activity of the Ubiquitin-activating Enzyme Inhibitor TAK-243 in Adrenocortical Carcinoma Cell Lines, Patient-derived Organoids, and Murine Xenografts.

Current treatment options for metastatic adrenocortical carcinoma (ACC) have limited efficacy, despite the common use of mitotane and cytotoxic agents. This study aimed to identify novel therapeutic options for ACC. An extensive drug screen was conducted to identify compounds with potential activity against ACC cell lines. We further investigated the mechanism of action of the identified compound, TAK-243, its synergistic effects with current ACC therapeutics, and its efficacy in ACC models including patient-derived organoids and mouse xenografts. TAK-243, a clinical ubiquitin-activating enzyme (UAE) inhibitor, showed potent activity in ACC cell lines. TAK-243 inhibited protein ubiquitination in ACC cells, leading to the accumulation of free ubiquitin, activation of the unfolded protein response, and induction of apoptosis. TAK-243 was found to be effluxed out of cells by MDR1, a drug efflux pump, and did not require Schlafen 11 (SLFN11) expression for its activity. Combination of TAK-243 with current ACC therapies (e.g., mitotane, etoposide, cisplatin) produced synergistic or additive effects. In addition, TAK-243 was highly synergistic with BCL2 inhibitors (Navitoclax and Venetoclax) in preclinical ACC models including patient-derived organoids. The tumor suppressive effects of TAK-243 and its synergistic effects with Venetoclax were further confirmed in a mouse xenograft model. These findings provide preclinical evidence to support the initiation of a clinical trial of TAK-243 in patients with advanced-stage ACC. TAK-243 is a promising potential treatment option for ACC, either as monotherapy or in combination with existing therapies or BCL2 inhibitors. SIGNIFICANCE: ACC is a rare endocrine cancer with poor prognosis and limited therapeutic options. We report that TAK-243 is active alone and in combination with currently used therapies and with BCL2 and mTOR inhibitors in ACC preclinical models. Our results suggest implementation of TAK-243 in clinical trials for patients with advanced and metastatic ACC.

Deconvolution of the X-ray absorption spectrum of trans-1,3-butadiene with resonant Auger spectroscopy.

High-resolution carbon K-edge X-ray photoelectron, X-ray absorption, non-resonant and resonant Auger spectra are presented of gas phase trans-1,3-butadiene alongside a detailed theoretical analysis utilising nuclear ensemble approaches and vibronic models to simulate the spectroscopic observables. The resonant Auger spectra recorded across the first pre-edge band reveal a complex evolution of different electronic states which remain relatively well-localised on the edge or central carbon sites. The results demonstrate the sensitivity of the resonant Auger observables to the weighted contributions from multiple electronic states. The gradually evolving spectral features can be accurately and feasibly simulated within nuclear ensemble methods and interpreted with the population analysis.

Development of a Machine Learning Modelling Tool for Predicting HIV Incidence Using Public Health Data from a County in the Southern United States.

BACKGROUND: Recent advancements in Machine Learning (ML) have significantly improved the accuracy of models predicting HIV incidence. These models typically utilize electronic medical records and patient registries. This study aims to broaden the application of these tools by utilizing de-identified public health datasets for notifiable sexually transmitted infections (STIs) from a southern U.S. County known for high HIV incidence rates. The goal is to assess the feasibility and accuracy of ML in predicting HIV incidence, which could potentially inform and enhance public health interventions. METHODS: We analyzed two de-identified public health datasets, spanning January 2010 to December 2021, focusing on notifiable STIs. Our process involved data processing and feature extraction, including sociodemographic factors, STI cases, and social vulnerability index (SVI) metrics. Various ML algorithms were trained and evaluated for predicting HIV incidence, using metrics such as accuracy, precision, recall, and F1 score. RESULTS: The study included 85,224 individuals, with 2,027 (2.37%) newly diagnosed with HIV during the study period. The ML models demonstrated high performance in predicting HIV incidence among males and females. Influential predictive features for males included age at STI diagnosis, previous STI information, provider type, and SVI. For females, they included age, ethnicity, previous STIs information, overall SVI, and race. CONCLUSIONS: The high accuracy of our ML models in predicting HIV incidence highlights the potential of using public health datasets for public health interventions such as tailored HIV testing and prevention. While these findings are promising, further research is needed to translate these models into practical public health applications.

Valence shell electronically excited states of norbornadiene and quadricyclane.

The absolute photoabsorption cross sections of norbornadiene (NBD) and quadricyclane (QC), two isomers with chemical formula C7H8 that are attracting much interest for solar energy storage applications, have been measured from threshold up to 10.8 eV using the Fourier transform spectrometer at the SOLEIL synchrotron radiation facility. The absorption spectrum of NBD exhibits some sharp structure associated with transitions into Rydberg states, superimposed on several broad bands attributable to valence excitations. Sharp structure, although less pronounced, also appears in the absorption spectrum of QC. Assignments have been proposed for some of the absorption bands using calculated vertical transition energies and oscillator strengths for the electronically excited states of NBD and QC. Natural transition orbitals indicate that some of the electronically excited states in NBD have a mixed Rydberg/valence character, whereas the first ten excited singlet states in QC are all predominantly Rydberg in the vertical region. In NBD, a comparison between the vibrational structure observed in the experimental 11B1-11A1 (3sa1 ← 5b1) band and that predicted by Franck-Condon and Herzberg-Teller modeling has necessitated a revision of the band origin and of the vibrational assignments proposed previously. Similar comparisons have encouraged a revision of the adiabatic first ionization energy of NBD. Simulations of the vibrational structure due to excitation from the 5b2 orbital in QC into 3p and 3d Rydberg states have allowed tentative assignments to be proposed for the complex structure observed in the absorption bands between ∼5.4 and 7.0 eV.

Resonant Auger decay of dissociating CH3I near the I 4d threshold.

Resonant Auger processes provide a unique perspective on electronic interactions and excited vibrational and electronic states of molecular ions. Here, new data are presented on the resonant Auger decay of excited CH3I in the region just below the I 4d-1 ionization threshold. The resonances include the Rydberg series converging to the five spin-orbit and ligand-field split CH3I (I 4d-1) thresholds, as well as resonances corresponding to excitation from the I 4d5/2,3/2 orbitals into the σ* lowest unoccupied molecular orbital. This study focuses on participator decay that populates the lowest lying states of CH3I+, in particular, the X̃2E3/2 and 2E1/2 states, and on spectator decay that populates the lowest-lying (CH3I2+)σ* states of CH3I+. The CH3I (I 4d-1)σ* resonances are broad, and dissociation to CH3 + I competes with the autoionization of the core-excited states. Auger decay as the molecule dissociates produces a photoelectron spectrum with a long progression (up to v3+ ∼ 25) in the C-I stretching mode of the X̃2E3/2 and 2E1/2 states, providing insights into the shape of the dissociative core-excited surface. The observed spectator decay processes indicate that CH3I+ is formed on the repulsive wall of the lower-lying (CH3I2+)σ* potentials, and the photon-energy dependence of the processes provides insights into the relative slopes of the (4d-1)σ* and (CH3I2+)σ* potential surfaces. Data are also presented for the spectator decay of higher lying CH3I (I 4d-1)nl Rydberg resonances. Photoelectron angular distributions for the resonant Auger processes provide additional information that helps distinguish these processes from the direct ionization signal.

Monitoring the Evolution of Relative Product Populations at Early Times during a Photochemical Reaction.

Identifying multiple rival reaction products and transient species formed during ultrafast photochemical reactions and determining their time-evolving relative populations are key steps toward understanding and predicting photochemical outcomes. Yet, most contemporary ultrafast studies struggle with clearly identifying and quantifying competing molecular structures/species among the emerging reaction products. Here, we show that mega-electronvolt ultrafast electron diffraction in combination with ab initio molecular dynamics calculations offer a powerful route to determining time-resolved populations of the various isomeric products formed after UV (266 nm) excitation of the five-membered heterocyclic molecule 2(5H)-thiophenone. This strategy provides experimental validation of the predicted high (∼50%) yield of an episulfide isomer containing a strained three-membered ring within ∼1 ps of photoexcitation and highlights the rapidity of interconversion between the rival highly vibrationally excited photoproducts in their ground electronic state.

Improved mRNA affinity chromatography binding capacity and throughput using an oligo-dT immobilized electrospun polymer nanofiber adsorbent.

Increased demand for mRNA-based therapeutics and improved in vitro transcription (IVT) yields have challenged the mRNA purification platform. Hybridization-affinity chromatography with an immobilized oligo-deoxythymidilic acid (oligodT) ligand is often used to capture mRNA through base pairing with the polyadenylated tail. Commercially available oligodT matrices include perfusive cross-linked poly(styrene-divinylbenzene) 50 µm POROS™ chromatography resin beads and convective polymethacrylate CIMmultus® monolithic columns consisting of 2 µm interconnected channels. POROS™ columns may be limited by poor mass transfer for larger mRNAs and slow flowrates, while monoliths can operate at higher flowrates but are limited by modest binding capacity. To enable both high flowrates and binding capacity for mRNA of all lengths, prototype chromatography media was developed by Cytiva using oligodT immobilized electrospun cellulose nanofibers (Fibro™) with a 0.3-0.4 µm pore size. In this work, four polyadenylated mRNAs ranging from ∼1900-4300 nucleotides were used to compare the dynamic binding capacity (DBC) of Fibro™, POROS® and CIMmultus® columns as a function of residence time and binding buffer compositions. Fibro™ improved the DBC ∼2-4-fold higher than CIMmultus® and ∼2-13-fold higher than POROS™ across all residence times, mRNA length, and binding matrix compositions tested. CIMmultus® DBC was least dependent on residence time and mRNA size, while both Fibro™ and POROS™ DBC increased at slower flowrates and with shorter mRNA. Surprisingly, inverse size exclusion (ISE) experiments showed that POROS™ was not limited by diffusion and POROS™ along with CIMmultus® demonstrate higher mRNA permeation however the Fibro™ prototype is not in the final configuration. Lastly, IVT reaction products were subjected to purification and oligodT elution product yield, quality, and purity were consistent across the three matrices investigated. These results highlight the benefits of high DBC and equivalent product profiles offered by the oligodT Fibro™ prototype compared to commercially available oligodT media.

Ultrafast electronic relaxation pathways of the molecular photoswitch quadricyclane.

The light-induced ultrafast switching between molecular isomers norbornadiene and quadricyclane can reversibly store and release a substantial amount of chemical energy. Prior work observed signatures of ultrafast molecular dynamics in both isomers upon ultraviolet excitation but could not follow the electronic relaxation all the way back to the ground state experimentally. Here we study the electronic relaxation of quadricyclane after exciting in the ultraviolet (201 nanometres) using time-resolved gas-phase extreme ultraviolet photoelectron spectroscopy combined with non-adiabatic molecular dynamics simulations. We identify two competing pathways by which electronically excited quadricyclane molecules relax to the electronic ground state. The fast pathway (<100 femtoseconds) is distinguished by effective coupling to valence electronic states, while the slow pathway involves initial motions across Rydberg states and takes several hundred femtoseconds. Both pathways facilitate interconversion between the two isomers, albeit on different timescales, and we predict that the branching ratio of norbornadiene/quadricyclane products immediately after returning to the electronic ground state is approximately 3:2.

Is the Current Cut Point for Glycated Haemoglobin (HbA1c) Correct for Diagnosing Diabetes Mellitus in Premenopausal Women? Evidence to Inform Discussion.

INTRODUCTION: Women are on average diagnosed with diabetes mellitus at later age than men but have higher mortality. As the diagnosis of diabetes mellitus is primarily based on HbA1c, the use of a non-specific reference range and cut point for diabetes mellitus that does not account for gender differences in diabetes could potentially lead to underdiagnosis of diabetes mellitus in women and missed opportunities for intervention. We investigated whether a contributing factor to the later diagnosis in women may be a difference in distribution of HbA1c in premenopausal women versus men of the same age by comparing HbA1c values in men and women across multiple sites in the UK. METHODS: We analysed the HbA1c levels of 146,907 individuals who underwent single testing only and had HbA1c ≤ 50 mmol/mol between 2012 and 2019 in one laboratory (cohort 1). This was replicated in six laboratories with 938,678 individuals tested between 2019 and 2021 (cohort 2). RESULTS: In cohort 1, women < 50 years old had an HbA1c distribution markedly lower than that in men by a mean of 1.6 mmol/mol (p < 0.0001), while the difference in the distribution of HbA1c for individuals aged ≥ 50 years was less pronounced (mean difference 0.9 mmol/mol, p < 0.0001). For individuals under the age of 50, HbA1c in women lagged by up to 10 years compared to men. Similar findings were found in cohort 2. We estimated an additional 17% (n = 34,953) of undiagnosed women aged < 50 years in England and Wales could be reclassified to have diabetes mellitus, which may contribute to up to 64% of the difference in mortality rates between men/women with diabetes mellitus aged 16-50 years. CONCLUSION: The HbA1c cut point for diagnosis of diabetes mellitus may need to be re-evaluated in women under the age of 50 years. Early identification of diabetes mellitus in women has the potential to improve women's health outcomes in the longer term.

Methotrexate-based PROTACs as DHFR-specific chemical probes.

Methotrexate (MTX) is a tight-binding dihydrofolate reductase (DHFR) inhibitor, used as both an antineoplastic and immunosuppressant therapeutic. MTX, like folate undergoes folylpolyglutamate synthetase-mediated γ-glutamylation, which affects cellular retention and target specificity. Mechanisms of MTX resistance in cancers include a decrease in MTX poly-γ-glutamylation and an upregulation of DHFR. Here, we report a series of potent MTX-based proteolysis targeting chimeras (PROTACs) to investigate DHFR degradation pharmacology and one-carbon biochemistry. These on-target, cell-active PROTACs show proteasome- and E3 ligase-dependent activity, and selective degradation of DHFR in multiple cancer cell lines. By comparison, treatment with MTX increases cellular DHFR protein expression. Importantly, these PROTACs produced distinct, less-lethal phenotypes compared to MTX. The chemical probe set described here should complement conventional DHFR inhibitors and serve as useful tools for studying one-carbon biochemistry and dissecting complex polypharmacology of MTX and related drugs. Such compounds may also serve as leads for potential autoimmune and antineoplastic therapeutics.

Resonance between projected Tibetan Plateau surface darkening and Arctic climate change.

The Tibetan Plateau (TP) exerts a profound influence on global climate over million-year timescales due to its past uplift. However, whether the ongoing climate changes over the TP, particularly the persistent reduction in its local albedo (referred to as "TP surface darkening"), can exert global impacts remains elusive. In this study, a state-of-the-art coupled land-atmosphere global climate model has been employed to scrutinize the impact of TP darkening on polar climate changes. Results indicate that the projected TP darkening has the potential to generate a stationary Rossby wave train, thereby modulating the atmospheric circulation in the high-latitudes of the Northern Hemisphere and instigating a dipole-like surface air temperature anomaly pattern around the Arctic region. An additional experiment suggests that the projected Arctic warming may in return warm the TP, thus forming a bi-directional linkage between these two climate systems. Given their association with vast ice reservoirs, the elucidation of this mechanism in our study is crucial in advancing our comprehension of Earth system climate projections.

Barriers and Facilitators to HIV Service Access among Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex with Men in Metropolitan Atlanta-a Qualitative Analysis.

Hispanic/Latino persons are disproportionately impacted by HIV in the US, and HIV diagnoses among Hispanic/Latino men in Georgia have increased over the past decade, particularly in metropolitan Atlanta. In 2022, the Georgia Department of Public Health detected five clusters of rapid HIV transmission centered among Hispanic/Latino gay, bisexual, and other men who have sex with men (HLMSM) in metropolitan Atlanta. We conducted in-depth interviews with 65 service providers and 29 HLMSM to identify barriers and facilitators to HIV service access for HLMSM. Interviews were audio recorded, transcribed, and translated, if needed. Initial data analyses were conducted rapidly in the field to inform public health actions. We then conducted additional analyses including line-by-line coding of the interview transcripts using a thematic analytic approach. We identified four main themes. First, inequity in language access was a predominant barrier. Second, multiple social and structural barriers existed. Third, HLMSM encountered intersectional stigma. Finally, the HLMSM community is characterized by its diversity, and there is not a one-size-fits-all approach to providing appropriate care to this population. The collection of qualitative data during an HIV cluster investigation allowed us to quickly identity barriers experienced by HLMSM when accessing HIV and other medical care, to optimize public health response and action. Well-designed program evaluation and implementation research may help elucidate specific strategies and tools to reduce health disparities, ensure equitable service access for HLMSM, and reduce HIV transmission in this population.

Evaluating Stacked Methylation Markers for Blood-Based Multicancer Detection.

The ability to detect several types of cancer using a non-invasive, blood-based test holds the potential to revolutionize oncology screening. We mined tumor methylation array data from the Cancer Genome Atlas (TCGA) covering 14 cancer types and identified two novel, broadly-occurring methylation markers at TLX1 and GALR1. To evaluate their performance as a generalized blood-based screening approach, along with our previously reported methylation biomarker, ZNF154, we rigorously assessed each marker individually or combined. Utilizing TCGA methylation data and applying logistic regression models within each individual cancer type, we found that the three-marker combination significantly increased the average area under the ROC curve (AUC) across the 14 tumor types compared to single markers (p = 1.158 × 10-10; Friedman test). Furthermore, we simulated dilutions of tumor DNA into healthy blood cell DNA and demonstrated increased AUC of combined markers across all dilution levels. Finally, we evaluated assay performance in bisulfite sequenced DNA from patient tumors and plasma, including early-stage samples. When combining all three markers, the assay correctly identified nine out of nine lung cancer plasma samples. In patient plasma from hepatocellular carcinoma, ZNF154 alone yielded the highest combined sensitivity and specificity values averaging 68% and 72%, whereas multiple markers could achieve higher sensitivity or specificity, but not both. Altogether, this study presents a comprehensive pipeline for the identification, testing, and validation of multi-cancer methylation biomarkers with a considerable potential for detecting a broad range of cancer types in patient blood samples.

An evolutionarily distinct ringed seal in the Ilulissat Icefjord.

The Earth's polar regions are low rates of inter- and intraspecific diversification. An extreme mammalian example is the Arctic ringed seal (Pusa hispida hispida), which is assumed to be panmictic across its circumpolar Arctic range. Yet, local Inuit communities in Greenland and Canada recognize several regional variants; a finding supported by scientific studies of body size variation. It is however unclear whether this phenotypic variation reflects plasticity, morphs or distinct ecotypes. Here, we combine genomic, biologging and survey data, to document the existence of a unique ringed seal ecotype in the Ilulissat Icefjord (locally 'Kangia'), Greenland; a UNESCO World Heritage site, which is home to the most productive marine-terminating glacier in the Arctic. Genomic analyses reveal a divergence of Kangia ringed seals from other Arctic ringed seals about 240 kya, followed by secondary contact since the Last Glacial Maximum. Despite ongoing gene flow, multiple genomic regions appear under strong selection in Kangia ringed seals, including candidate genes associated with pelage coloration, growth and osmoregulation, potentially explaining the Kangia seal's phenotypic and behavioural uniqueness. The description of 'hidden' diversity and adaptations in yet another Arctic species merits a reassessment of the evolutionary processes that have shaped Arctic diversity and the traditional view of this region as an evolutionary freezer. Our study highlights the value of indigenous knowledge in guiding science and calls for efforts to identify distinct populations or ecotypes to understand how these might respond differently to environmental change.