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mRNA technology has been successfully deployed to rapidly develop and mass-manufacture vaccines. Beyond vaccines, RNA-based therapeutics have potential for treatments for infectious diseases, cancer, metabolic disorders, cardiovascular conditions and autoimmune diseases. mRNA based vaccines and therapeutics work by translating exogenous mRNA into the target protein. Analytical methods for mRNA characterisation, lot release and stability testing of mRNA drug substance and drug product must be developed and performed to monitor critical quality attributes (CQAs). mRNA is a highly polar molecule due to its extensive negatively charged phosphodiester backbone. Its single stranded nature forms dynamic alternative secondary structures that can generate potential sample heterogeneity, creating challenges for the analysis and characterisation of this large biomolecule. In this review, we describe current analytical methods, focussing on high performance liquid chromatography in conjunction with both UV detection and mass spectrometry for the analysis and characterisation of mRNA. In particular, we describe recent developments covering a wide range of methods centred on liquid chromatography for the analysis of important CQAs including mRNA identity, mRNA integrity, 5' capping efficiency and poly(A) tail length and heterogeneity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier B.V.)

Objectives: To describe and assess, via simulation, a constraint-based spline approach to implement smooth hazard ratio (HR) waning in time-to-event analyses., Methods: A common consideration when extrapolating survival functions to evaluate the long-term performance of a novel intervention is scenarios where the beneficial effect of an intervention eventually disappears (treatment effect waning). One approach to relaxing the proportional hazards assumption for a treatment effect is to model it as a function of the timescale, with a spline function offering a flexible approach. We consider the constraint of coefficients of spline variables to 0 during estimation, leading to log-treatment effects that are constrained to 0 (HR = 1) from a given time-point: enforcing treatment efficacy waning. An example is reported. Datasets were simulated under a variety of scenarios and analyzed with treatment effect waning assumptions under various modeling choices. Bias in mean survival time difference, given fully observed waning or fully censored waning, was assessed and constrained HR estimates were visualized., Results: Given full waning, biases were small unless constraints directly contradicted truths. When waning was extrapolated, akin to real-life practice, biases over observed periods were minimized through the inclusion of a knot at the 95th percentile. The rate at which the HR waned slowed as the upper boundary knot/constraint was placed later, inducing less conservative treatment effect waning assumptions., Conclusion: An alternative approach to modeling smooth treatment efficacy waning is demonstrated, enabling HR conditioning and marginal RMST calculation in a single framework, along with applications of the method beyond this use., (© 2025 The Author(s). Statistics in Medicine published by John Wiley & Sons Ltd.)

This study aimed to develop exposure-response relationships (ERRs) between road, rail, and air traffic noise and high noise annoyance (HNA) and to assess the HNA disease burden. In 2023, 4640 adults were cross-sectionally sampled from the five largest cities in Bulgaria. Participants' road, rail/tram, and air traffic HNA was defined as the top two categories (60% cut-off point) of a 5-point scale. A 72% cut-off approximation was also used. European Noise Directive maps were used to assign day-evening-night equivalent sound levels (L den ) to residences. ERRs were derived and used, together with the new WHO disability weight for HNA, to calculate disability-adjusted life years (DALYs). DALYs were monetised based on Bulgaria's gross domestic product (GDP) per capita and the value of a life year (VOLY). In fully adjusted models, L den was non-linearly associated with HNA. Road traffic L den [range 42.5-77.5 dB] was positively associated with HNA only above 62.5 dB, whereas the upward trend for rail [range 37.5-72.5 dB] and air traffic L den [range 37.5-57.5 dB] started at 40-45 dB. Using this study's ERRs, the burden among people exposed to ≥40 dB was 3476 (1896-5056) DALYs, $ 39 138 953 (21 348 520-56 929 386) based on GDP, and € 243 310 984 (94 796 487-505 581 266) based on VOLY. Using the WHO's curves, the burden was 4312 (2352-6273) DALYs, $ 48 559 330 (26 486 907-70 631 753), and € 301 873 648 (117 613 110-627 269 918). In conclusion, we could only derive a plausible ERR for railway noise annoyance. Until better ERRs are derived for the Bulgarian population, we recommend using the WHO curves for road traffic and aircraft noise annoyance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with ST-segment elevation myocardial infarction (STEMI) frequently present with multivessel coronary artery disease (CAD) during primary percutaneous coronary intervention, and the optimal timing of complete revascularization (CR) in these cases remains uncertain. This study aims to assess major adverse cardiovascular events (MACEs) and procedural complications in patients with STEMI with multivessel CAD who underwent immediate (index procedure) versus staged CR. We conducted a systematic review and meta-analysis of randomized controlled trials comparing immediate to staged CR in STEMI and multivessel CAD. Trials were identified by way of a systematic search of MEDLINE, Embase, and Cochrane Libraries from database inception to March 6, 2024. The data were analyzed using the RevMan software. A total of 5 randomized controlled trials (n = 1,415) were included in our study, which showed no significant differences in MACEs (13.3% vs 9.8%, relative risk [RR] 1.07, 95% confidence interval [CI] 0.62 to 1.83), all-cause mortality (3% vs 4.55%, RR 0.70, 95% CI 0.41 to 1.21), or myocardial infarction (4.5% vs 2.6%, RR 1.43, 95% CI 0.58 to 3.55) at a weighted mean follow-up duration of 16 months. However, the staged group had a higher rate of unplanned revascularization (8.6% vs 4.4%, RR 1.92, 95% CI 1.21 to 3.04). In conclusion, in patients with STEMI with multivessel CAD, at a mean follow-up of approximately 1.3 years, there is no significant difference in immediate versus staged revascularization (SR) for MACEs; however, SR was associated with a significantly higher incidence of unplanned ischemia-driven revascularization. SR within the index hospitalization may be as effective as immediate CR; further trials are needed to confirm this. Condensed Abstract We conducted a meta-analysis of 5 randomized controlled trials comparing immediate to staged complete revascularization in patients with ST-segment elevation myocardial infarction with multivessel coronary artery disease. There was no significant difference in major adverse cardiovascular events, all-cause mortality, and myocardial infarction rates between immediate and staged complete revascularization. However, staged revascularization was associated with a higher incidence of unplanned ischemia-driven revascularization., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to compare the clinical outcomes 2 years following surgery between robotic-arm assisted bi-unicompartmental knee arthroplasty (bi-UKA) compared with conventional mechanically aligned total knee arthroplasty (TKA)., Methods: This is a single-centre, double-blinded, randomised controlled trial comparing bi-UKA and TKA. Patient-reported outcome measures (PROMs) were collected from 60 patients (27 bi-UKA and 33 TKA patients) 2 years following surgery, including Oxford Knee Score (OKS), New Knee Society Score (NKSS), Forgotten Joint Score, EQ-5D-3L, UCLA activity scale, Hospital Anxiety and Depression Scale, Pain and Stiffness Visual Analogue Scales, Satisfaction and Range of Motion. Complications were also recorded at each visit., Results: TKA and bi-UKA continue to offer comparable PROMs. The clinical NKSS demonstrated a significant difference between the two interventions, TKA 59.5 (37-65) versus bi-UKA 26.0 (22-40) (p < 0.001). There were no significant differences shown between the interventions across all time points and remaining outcome measures (OKS at 2-year follow-up; TKA-42.0 [34.0-45.5] vs. bi-UKA-41.0 [28.0-45.0]) or the proportion of participant achieving bi-phasic gait at 2 years following surgery (p = 0.429). There was no difference in complication rates following surgery at 2 years., Conclusion: Robotic arm-assisted, cruciate-sparing bi-UKA and mechanically aligned TKA offer similar clinical outcomes 2 years following surgery with no difference in complication rates. Further, follow-up is required to monitor patients as they enter mid/long-term follow-up and determine whether patients will gain long-term benefits from the cruciate-sparing bi-UKA approach., Level of Evidence: Level I., (© 2025 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

We report the effect of a minimal ( i , i + 4) staple on the dynamic interconversion between right-handed ( P ) and left-handed ( M ) forms of an optically inactive α-helical peptide composed only of helicogenic achiral amino acids, such as 1-amino-cyclohexanecarboxylic acid (Ac 6 c) and 4-aminopiperidine-4-carboxylic acid (Api) residues. The P / M interconversion rate of the peptide with a flexible hydrocarbon-based staple was estimated to be 0.41 s -1 at 298 K through variable temperature 1 H NMR measurements in 1,1,2,2-tetrachloroethane- d 2 . A combined analysis using 1 H NMR spectroscopy, single-crystal X-ray crystallography, and density functional theory (DFT) calculations revealed that the present flexible stapling does not effectively constrain the conformational freedom of the helical peptide. DFT calculations revealed that Ac 6 c residues exhibit a stronger propensity for α-helical conformation over the 3 10 -helix than α-aminoisobutyric acid (Aib) residues, with their influence being highly dependent on position and sequence within the oligopeptides.

This study examined the moderating effect of self-compassion on the relationship between post-traumatic symptoms (PTS) and post-traumatic growth (PTG) among adults with trauma exposure. A sample of 413 participants (254 women, 155 men) aged 18 to 81 years (M = 33.8; SD = 12.9) completed questionnaires assessing trauma exposure, PTS, PTG, and self-compassion. The results indicated that women reported significantly higher PTS and lower self-compassion than men, while no significant gender differences were found for PTG. Correlational analyses revealed a significant positive association between PTS and PTG, and a significant negative association between PTS and self-compassion. Moderation analysis demonstrated that self-compassion significantly moderated the relationship between PTS and PTG, with higher levels of self-compassion linked to greater PTG, even at elevated levels of PTS. These findings underscore the importance of self-compassion as a protective factor in trauma recovery, promoting positive psychological transformation despite the presence of distress., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical standards: The study was reviewed by the University of Nicosia Research Ethics Committee. Informed consent: Informed consent was obtained from all participants in this study., (© 2025. The Author(s).)

Frontopolar cortex (FPC), for a long time elusive to functional description, is now associated with a wide range of cognitive processes. Prominent accounts of FPC function emerged from studies of memory (e.g., episodic and prospective memory; EM and PM, respectively) and of executive function (e.g., planning, multi-tasking, relational reasoning, cognitive branching, etc). In recent years, FPC function has begun to be described within the context of value-based decision making in terms of monitoring the value of alternatives and optimizing cognitive resources to balance the explore/exploit dilemma in the face of volatile environments. In this perspective, we propose that the broad counterfactual inference and behavioural flexibility account can help re-interpret findings from EM and PM studies and offer an explanatory bridge between the memory and executive function accounts. More specifically, we propose that counterfactual value monitoring in FPC modulates the reallocation of cognitive resources between present and past information and contributes to efficient episodic and prospective retrieval by concurrently assessing the value of competing memories in relation to the decision at hand and proactively evaluating future potential scenarios to anticipate optimal engagement of intentions., (Copyright © 2025. Published by Elsevier Ltd.)

Sterile acute kidney injury (AKI) is common in the clinic and frequently associated with unexplained hypoxemia that does not improve with dialysis. AKI induces remote lung inflammation with neutrophil recruitment in mice and humans, but which cellular cues establish neutrophilic inflammation and how it contributes to hypoxemia is not known. Here we report that AKI induces rapid intravascular neutrophil retention in lung alveolar capillaries without extravasation into tissue or alveoli, causing hypoxemia by reducing lung capillary blood flow in the absence of substantial lung interstitial or alveolar edema. In contrast to direct ischemic lung injury, lung neutrophil recruitment during remote lung inflammation did not require cues from intravascular non-classical monocytes or tissue-resident alveolar macrophages. Instead, lung neutrophil retention depended on neutrophil chemoattractant CXCL2 released by activated classical monocytes. Comparative single-cell RNA-sequencing analysis of direct and remote lung inflammation revealed that alveolar macrophages are highly activated and produce CXCL2 only in direct lung inflammation. Establishing a CXCL2 gradient into the alveolus by intratracheal CXCL2 administration during AKI-induced remote lung inflammation enabled neutrophils to extravasate. We thus discovered important differences in lung neutrophil recruitment in direct versus remote lung inflammation and identified lung capillary neutrophil retention that negatively affects oxygenation by causing a ventilation-perfusion mismatch as a driver of AKI-induced hypoxemia.

Conservation genomics is a rapidly growing subdiscipline of conservation biology that uses genome-wide information to inform management of biodiversity at all levels. Such efforts typically focus on species or systems of conservation interest, but rarely consider associated microbes. At least three major approaches have been used to study how microorganisms broadly contribute to conservation areas: (1) diversity surveys map out microbial species distribution patterns in a variety of hosts, natural environments or regions; (2) functional surveys associate microbial communities with factors of interest, such as host health, symbiotic interactions, environmental characteristics, ecosystem processes, and biological invasions; and (3) manipulative experiments examine the response of changes to microbial communities or determine the functional roles of specific microbes within hosts or communities by adding, removing, or genetically modifying microbes. In practice, multiple approaches are often applied simultaneously. The results from all three conservation genomics approaches can be used to help design practical interventions and improve management actions, some of which we highlight below. However, experimental manipulations allow for more robust causal inferences and should be the ultimate goal of future work. Here we discuss how further integration of microbial research of a host's microbiome and of free living microbes into conservation biology will be an essential advancement for conservation of charismatic organisms and ecosystem functions in light of ongoing global environmental change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Disease-causing genetic variants often disrupt mRNA splicing, an intricate process that is incompletely understood. Thus, accurate inference of which genetic variants will affect splicing and what their functional consequences will be is challenging, particularly for variants outside of the essential splice sites. Here, we describe a set of data-driven heuristics that inform the interpretation of human splice-altering variants (SAVs) based on the analysis of annotated exons, experimentally validated SAVs, and the currently understood principles of splicing biology. We defined requisite splicing criteria by examining around 202,000 canonical protein-coding exons and 19,000 experimentally validated splicing branchpoints. This analysis defined the sequence, spacing, and motif strength required for splicing, with 95.9% of the exons examined meeting these criteria. By considering over 12,000 experimentally validated variants from the SpliceVarDB, we defined a set of heuristics that inform the evaluation of putative SAVs. To ensure the applicability of each heuristic, only those supported by at least 10 experimentally validated variants were considered. This allowed us to establish a measure of spliceogenicity: the proportion of variants at a location (or motif site) that affected splicing in a given context. This study makes considerable advances toward bridging the gap between computational predictions and the biological process of splicing, offering an evidence-based approach to identifying SAVs and evaluating their impact. Our splicing heuristics enhance the current framework for genetic variant evaluation with a robust, detailed, and comprehensible analysis by adding valuable context over traditional binary prediction tools., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

An 82-year-old man developed acute breathlessness and cyanosis, exacerbated while upright and improved on lying flat (platypnea-orthodeoxia syndrome). Echocardiography revealed acute torrential tricuspid regurgitation due to a flail posterior leaflet leading to right-to-left shunting through a patent foramen ovale (PFO). The patient's symptoms resolved after transcatheter PFO closure and tricuspid valve edge-to-edge repair., Competing Interests: Funding Support and Author Disclosures Dr Dawkins has received grants/research support from Edwards Lifesciences; and honoraria and consultation fees from Abbott and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

De novo protein design provides a framework to test our understanding of protein function and build proteins with cofactors and functions not found in nature. Here, we report the design of proteins designed to bind powerful photooxidants and the evaluation of the use of these proteins to generate diffusible small-molecule reactive species. Because excited-state dynamics are influenced by the dynamics and hydration of a photooxidant's environment, it was important to not only design a binding site but also to evaluate its dynamic properties. Thus, we used computational design in conjunction with molecular dynamics (MD) simulations to design a protein, designated NBP ( N DI B inding P rotein), that held a naphthalenediimide (NDI), a powerful photooxidant, in a programmable molecular environment. Solution NMR confirmed the structure of the complex. We evaluated two NDI cofactors in this de novo protein using ultrafast pump-probe spectroscopy to evaluate light-triggered intra- and intermolecular electron transfer function. Moreover, we demonstrated the utility of this platform to activate multiple molecular probes for protein labeling.

The composition of viral communities (i.e. viromes) can be dynamic and complex. Co-evolution may lead to virome host-specificity. However, eco-evolutionary factors may influence virome dynamics in wild host communities, potentially leading to disease emergence. Social bees are relevant models to address the drivers of virome composition: these important pollinators form multi-species assemblages, with high niche overlap and strong seasonality in their biotic interactions. We applied a microbial community approach to disentangle the role of host phylogeny and host ecology in shaping bee viromes, combining plant-pollinator networks with meta-transcriptomics, and small interfering RNAs as proxies for viral replication in pollinators and pollen. We identified over a hundred insect and plant viral sequences from ca. 4500 insect pollinator samples across three time points in one year. While host genetic distance drives the distribution of bee viruses, we find that plant-pollinator interactions and phenology drive plant virus communities collected by bees. This reveals the opportunities for virus spread in the bee assemblage. However, we show that transmission to multiple hosts is only realized for a fraction of insect viruses, with even fewer found to be actively replicating in multiple species, including the particularly virulent multi-host acute bee paralysis virus., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Oomycete pathogens cause large economic losses in agriculture through diseases such as late blight ( Phytophthora infestans ), and stem and root rot of soybean ( Phytophthora sojae ). The effector protein AVR3a, from P. infestans , and its homologue AVR3a11 from Phytophthora capsici , are host-translocated effectors that interact with plant proteins to evade defense mechanisms and enable infection. Both proteins belong to the family of RXLR effectors and contain an N-terminal secretion signal, an RXLR motif for translocation into the host cell, and a C-terminal effector domain. Within this family, many proteins have been predicted to contain one or more WY domains as their effector domain, which is proposed to encompass a conserved minimal core fold containing three helices, further stabilized by additional helices or dimerization. In AVR3a11, a helical N-terminal extension to the core fold forms a four-helix bundle, as determined by X-ray crystallography. For a complete picture of the dynamics of AVR3a11, we have determined the solution structure of AVR3a11, and studied its dynamics in the fast time scale (ns-ps, from NMR relaxation parameters) and in the slow time scale (seconds to minutes, from hydrogen/deuterium exchange experiments). Hydrogen/deuterium exchange showed that the N-terminal helix is less stable than the other three helices, confirming the core fold originally proposed. Relaxation measurements confirm that AVR3a11 undergoes extensive conformational exchange, despite the uniform presence of fast motions in the spectral density function throughout most of its sequence. As functional residues are in the more mobile regions, flexibility in the slow/intermediate time scale may be functionally important.

A 13-year-old male neutered Labradoodle presented with a 1-year history of gagging, retching, coughing, and stridor. Physical examination revealed large pedunculated tonsillar masses, confirmed by CT imaging to be obstructing the upper airway, and concurrent laryngeal paralysis. The larger mass, originating from the left tonsillar crypt, extended into the nasopharynx, while a smaller mass was identified on the right. A bilateral tonsillectomy was performed, histopathology confirmed the diagnosis of tonsillar polyps and postoperative recovery was uneventful. Based on our literature research, this is the first reported case of bilateral tonsillar polyps in a dog described on CT., (© 2025 American College of Veterinary Radiology.)

This study aims to evaluate the implementation of concomitant CAD assessment on pre-TAVI (transcatheter aortic valve implantation) planning CTA (CT angiography) aided by CT-FFR (CT-fractional flow reserve) [The CT2TAVI protocol] and investigates the incremental value of CT-FFR to coronary CT angiography (CCTA) alone in the evaluation of patients undergoing CT2TAVI. This is a prospective observational real-world cohort study at an academic health system on consecutive patients who underwent CTA for TAVI planning from 1/2021 to 6/2022. This represented a transition period in our health system, from not formally reporting CAD on pre-TAVI planning CTA (Group A) to routinely reporting CAD on pre-TAVI CTA (Group B; CT2TAVI protocol). All CTAs were retrospective ECG-gated using a dual source 192 slice CT scanner without nitrate or intravenous beta blocker premedication. We assessed downstream ICA and revascularization pre-TAVI and clinical outcomes 30 days and 1 year post-TAVI in both groups. 307 patients were included with 199 patients in Group A and 108 patients in Group B. In Group B, ICA was performed pre-TAVI in only 40.7% of patients. The use of CT-FFR, which was primarily aimed at identifying hemodynamically significant proximal vessel disease, helped avoid downstream invasive testing for 60.5% (23/38) of patients who were deemed to have obstructive proximal vessel disease using CCTA alone or had one or more uninterpretable proximal segments using CCTA. All-cause mortality, cardiovascular mortality, myocardial infarction and need for revascularization at 1-year post-TAVI were comparable between groups with a higher trend toward heart failure hospitalizations in Group A. Routine ICA can safely be deferred pre-TAVI, with the CT2TAVI strategy using modern CT scanners aided by CT-FFR analysis., Competing Interests: Declarations. Competing interests: Dr. Amit Pursnani has received speaker honorarium from Heartflow Inc. All remaining authors have no relevant financial or non-financial interests to disclose., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Injured patients have high rates of uninsurance, which is associated with worse outcomes. Insurance linkage programs that connect patients to Medicaid coverage can prevent catastrophic costs for patients. Less is known about the long-term impact of insurance enrollment. We examined health care utilization for previously uninsured patients, hypothesizing that newly insured patients postinjury would use health care more than those remaining uninsured., Methods: We linked institutional trauma registry data to the electronic medical record to identify injured patients aged 18 to 64 years from 2017 to 2021. Patients admitted without insurance and then retroactively insured (RI) during hospitalization were compared with patients with preestablished Medicaid (Medicaid insured [MI]) and those remaining uninsured. We compared demographic and injury characteristics and future health care utilization, including hospitalizations, emergency department (ED) visits, and clinic visits, among groups at 30 days and 12 months postinjury. Patient-reported outcomes (PROs) 6 months after injury were compared by group for a subset of patients participating in an ongoing study of long-term PROs., Results: We compared 494 RI patients with 1,706 MI and 148 uninsured patients. Retroactively insured patients were younger, more likely to have penetrating injuries, and longer hospitalization than other groups. There was a significant increase in ED and clinic visits and hospital admissions at 30 days and 12 months between RI and uninsured patients ( p < 0.001). Using multivariable logistic regression, RI was associated with higher future ED utilization, hospital admissions, and specialist visits at 30 days and 12 months compared with uninsured patients. Of the 265 patients with 6-month PROs, Medicaid coverage was not associated with any significant difference in physical function or anxiety., Conclusion: Patients enrolled in insurance postinjury are more likely to use health care in the future than patients without insurance, but the downstream effects are less clear. Health insurance is a necessary step but not independently sufficient to optimize care and improve health outcomes., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cholangiocarcinoma (CCA) has rising incidence and mortality rates. Outcomes from combination systemic, loco-regional therapy (LRT) and liver transplantation (LT) are improving, but more granular data are needed to inform evidence-based management, including patient selection and immunosuppression., Methods: Patients with peri-hilar (PH) and intrahepatic (IH) CCA who underwent LT at a single center between January 2008 and February 2023 were reviewed retrospectively. Primary outcomes were overall survival (OS) and recurrence-free survival (RFS) with significance determined by Cox proportional hazards model., Results: During the study period, 53 patients underwent LT for either PH (n = 27), or IH (26). Cohort had mean age 58.5 years old (IQR, 47.0-63.0), body mass index (BMI) 25.9 (IQR, 22.9-30.0) kg/m 2 , and mean biologic MELD 9 (IQR, 7-17). Most frequent etiology was PSC (n = 12, 22.6%). Forty-nine patients (92.5%) received neoadjuvant therapy, including systemic (n = 48, 90.6%) and locoregional therapy (LRT) (n = 22, 41.5%), to which PH tumors were both most and least responsive (P = .03). On explant pathology, tumor were a median size of 3.5 cm and lympho-vascular invasion (LVI) was present in 13 (24.5%) cases. Median follow-up post-transplant was 910 days (IQR, 407-1509). Probabilities of OS and RFS at 3-years post-LT were 69.2% (95% CI, 56.9%-84.2%) and 57.4% (95% CI, 43.7%-75.4%). In multivariable analysis, OS was associated with tumor type and LVI, and RFS with age, BMI, PSC and LRT. After a median post-LT period of 38 days (IQR, 27-79.5), 39 (71.7%) patients started mTOR inhibition with lowered tacrolimus goal. Cox proportional hazard model showed significant association of OS with mTOR inhibition, though this was not validated by a time-dependent co-variate approach., Conclusions: In this single center cohort of CCA, post-LT outcomes were significantly greater for patients with IH tumors and no LVI. Immunosuppression with mTOR inhibition was not consistently associated with outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Background: The Eaton-Littler ligament reconstruction is widely used for thumb carpometacarpal instability, yet the existing literature lacks a thorough analysis of the outcomes for nontraumatic instability. This study aimed to assess the outcomes of the Eaton-Littler ligament reconstruction and to identify prognostic factors associated with postoperative pain., Methods: Patients with nontraumatic carpometacarpal joint instability, unresponsive to conservative treatment, were included in this prospective study. The visual analog scale (range 0 to 100) for pain and the Michigan Hand Outcome Questionnaire (MHQ; range 0 to 100) total score were measured at intake and 3 and 12 months postoperatively. Multivariable linear regression was used to analyze the association between preoperative variables and the 12-month MHQ pain score., Results: Seventy-four patients undergoing Eaton-Littler ligament reconstruction were included. The median visual analog scale pain score improved significantly ( P < 0.001) from intake (70 [interquartile range, 63 to 78]) to 12 months postoperatively (27 [interquartile range, 7 to 56]). The mean MHQ total score also improved significantly ( P < 0.001) from intake (52; SD, 13) to 12 months (74; SD, 17). All thumbs were stable at follow-up with preserved range of motion. Grip and pinch strength also improved significantly after surgery. Undergoing a concurrent surgery during ligament reconstruction and a better MHQ pain score at intake were found to be predictors of a favorable postoperative MHQ pain score., Conclusions: Patient- and clinician-reported outcomes improved significantly at 3 and 12 months after Eaton-Littler ligament reconstruction. The authors advise concurrent hand pathologies resulting from instability (eg, tendinitis, synovitis) to be treated simultaneously during ligament reconstruction., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Acute-on-chronic liver failure (ACLF) is a syndrome that develops in approximately 30% of patients hospitalised with cirrhosis and is characterised by an acute decompensation of liver function associated with extra-hepatic organ failures and a high short-term mortality. At present, no specific therapies are available for ACLF, and current management is limited to treatment of the precipitating event and organ support. Given the high prevalence and high mortality of this severe liver disease, there is an urgent need for targeted treatments. There is increasing evidence of the important role played by systemic inflammation and immune dysfunction in the pathophysiology of ACLF and a better understanding of these immune processes is resulting in new therapeutic targets. The aim of this review is to present an overview of ongoing studies of potentially promising therapies and how they could be utilised in the management of ACLF., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

OBJECTIVE: To compare return-to-sport outcomes between females/women/girls and males/men/boys undergoing hip arthroscopy and explore social and structural determinants of health that may influence return to sport. DESIGN: Systematic review with meta-analysis. LITERATURE SEARCH: CINAHL, Cochrane Central Register of Controlled Trials, Embase, Medline, SPORTDiscus, and Web of Science from inception to February 2024. STUDY SELECTION CRITERIA: Studies were included if they assessed return to sport after hip arthroscopy and analyzed the influence of sex/gender on return-to-sport outcomes, or reported sex- or gender-stratified return-to-sport rates. DATA SYNTHESIS: We used a random effects model to calculate pooled odds ratios and conducted meta-regressions to compare return-to-sport outcomes between females/women/girls and males/men/boys. RESULTS: Forty-five studies were included, with all pooled results deemed as very low-certainty evidence. Compared to males/men/boys, females/women/girls had inferior return to sport at the same or higher level between 1 and 3 years postoperatively (pooled OR = 0.53; 95% CI: 0.34, 0.81; P = .004), and at any level of sport at >3 years postoperatively (pooled OR = 0.46; 95% CI: 0.25, 0.86; P = .014). Sports participation decreased over time, with ~5.5% to 10% lower proportions observed in females/women/girls compared to males/men/boys. The reporting of determinants of returning to sport was minimal, precluding further exploration of their effects. CONCLUSION : Females/women/girls had lower odds of return to sport, especially during longer follow-up periods, than males/men/boys. The lack of reporting of social and structural determinants of health influencing return-to-sport outcomes makes the reasons for this disparity unclear. J Orthop Sports Phys Ther 2025;55(3):1-13. Epub 10 February 2025. doi:10.2519/jospt.2025.12813 .

Adolescence is a developmental period marked by significant alterations to brain neurobiology and behavior. Adolescent nicotine use disrupts developmental trajectories and increases vulnerability to maladaptive drug-taking in adulthood. The mesolimbic dopamine (DA) system, including the nucleus accumbens core (NAc), mediates the reinforcing effects of nicotine. While dopaminergic reorganization is necessary for the transition into adulthood, how adolescent nicotine exposure affects cholinergic modulation of adult NAc DA dynamics is less understood. Here, we use 12 days of intravenous self-administration (SA) and ex vivo fast-scan cyclic voltammetry (FSCV) to explore the effects of adolescent (P31-42) versus adult (P63-75) nicotine (0.03mg/kg/infusion) intake on DA dynamics following three weeks of forced abstinence in adult male rats. This three-week abstinence period ensured that all neurochemical measurements were performed in adulthood. Consistent with the literature, we show that adolescent and adult male rats self-administer similar amounts of nicotine. While adult nicotine exposure + forced abstinence decreased NAc DA release relative to adult saline exposure, we found no difference in adult NAc DA release after adolescent nicotine or saline exposure. Investigating α6-versus non-α6-containing nicotinic acetylcholine receptors (nAChRs) revealed differential modulatory effects in adults and adolescents self-administering nicotine relative to respective saline controls. Both α6- and non-α6β2-containing nAChRs facilitation of NAc DA release was increased across frequencies only after adolescent nicotine versus saline SA. These data provide a foundation for understanding the long-term effects of nicotine in adolescence on cholinergic modulation of NAc DA dynamics in adulthood., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2025. Published by Elsevier B.V.)

Competing Interests: Disclosure The following authors disclosed financial relationships: P. Hosseini-Carroll: Advisory board and speaker for Janssen. R. B. Issaka: Consultant for Guardant Health, Inc. F. P. May: Consultant for Exact Sciences, Medtronic, Geneoscopy, Freenome, Guardant, and Natura. D. K. Rex: Research support from Boston Scientific and Olympus America Corp; consultant for Olympus America and Exact Sciences; honoraria from Sebela Pharmaceuticals, Boston Scientific, and Laborie Medical Technologies. J. A. Christie: Consultant for Olympus America; advisory board for Takeda Pharmaceuticals and Neurogastrx Inc. All other authors disclosed no financial relationships. Research support for this study was provided by an unrestricted grant from Exact Sciences, with additional support from Ironwood Pharmaceuticals and Braintree, A Part of Sebela Pharmaceuticals.

Background: Characteristics of parent-child interaction (PCI) early in life have been associated with later development in the child. Twin studies can help to disentangle child contributions to parent-child interaction, for example, by assessing the influence of the child's genetics on his/her social environment, which includes parental behaviour., Methods: Infant twins from a community sample [354 monozygotic (MZ), 268 same-sex dizygotic (DZ)] were assessed in terms of PCI at age 5 months. We used the classical twin design to map the aetiology of several parent and child PCI scales and their covariation. We investigated the relations between PCI and later parent-rated child's social communication, language, and autistic traits at ages 2 and 3., Results: Heritability was below 20% for all the included PCI traits. Unique (nonshared) environmental influences substantially overlapped across several PCI scales, suggesting that idiosyncrasies linked to each session shaped the scoring of several traits in a systematic way. Factor analysis revealed three uncorrelated latent factors, which were conceptualized as 'child negative affect', 'positive affective interaction', and 'parent's supportive strategies'. Parents who were rated highly on 'sensitive responsiveness' at 5 months tended to rate their offspring higher in terms of socio-communicative and language development and lower in terms of autistic traits in the second and third years of life., Conclusions: This study maps the phenotypic and aetiological structure of PCI in early infancy and supports the view that parents' sensitive responsiveness towards their infant is associated with later developmental gains in several domains. We did not find strong evidence of any so-called evocative genetic effects on parents' behaviour. We discuss the results considering the general challenge for lab-based observational PCI measures to capture the richness of parent-child interaction., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objectives: Physiotherapy is considered part of first line treatment for functional motor disorder (FMD) although not all patients benefit. Predictors of treatment outcome may help to inform triage decisions. We aimed to determine which baseline variables predicted treatment outcome in the pragmatic multicentre Physio4FMD randomised controlled trial of specialist physiotherapy for FMD., Methods: Participants randomised to the specialist physiotherapy arm of the trial were included in the analysis. Treatment outcome was dichotomised into improvement vs no improvement, based on two measures, Short Form 36 Physical Functioning (SF36 PF) and participant-rated Clinical Global Impression Scale of Improvement (CGI-I). Predictors of outcome were selected from baseline variables. Univariate logistic regression was used to calculate the odds ratio of improvement for each variable. Variables associated with improvement at p < 0.1 were considered for inclusion in a multiple logistic regression model., Results: A greater perception of having control over recovery predicted improvement on the CGI-I (OR 1.18, 95 % CI 1.07, 1.31). Predictors of lack of improvement were an increased perception of the permanence of symptoms, predicting lack of improvement on the SF36 PF (OR 0.91, 95 % CI 0.84, 0.99) and older age, predicting lack of improvement on the CGI-I (OR 0.97, 95 % CI 0.95, 0.998)., Conclusions: Age and perceptions of symptom control were weak predictors of outcome from specialist physiotherapy. In contrast, a number of factors commonly believed to predict poorer treatment response, including illness duration and levels of pain and fatigue, were not related to the outcomes measured in this study., Competing Interests: Declaration of competing interest GN, LM & IN receive research funding from the NIHR. MJE does medical expert reporting in personal injury and clinical negligence cases, including in cases of functional neurological disorder (FND). MJE has shares in Brain & Mind, which provides neuropsychiatric and neurological rehabilitation in the independent medical sector, including in people with functional neurological disorder. MJE has received financial support for lectures from the International Parkinson's and Movement Disorders Society and the FND Society (FNDS). MJE receives royalties from Oxford University Press for his book The Oxford Specialist Handbook of Parkinson's Disease and Other Movement Disorder. M.J.E has received honoraria for medical advice to Teva Pharmaceuticals. MJE receives grant funding, including for studies related to FND, from the National Institute for Health and Care Research (NIHR) and the Medical Research Council (MRC). MJE is an associate editor of the European Journal of Neurology. MJE is a member of the international executive committee of the International Parkinson's and Movement Disorders Society and a board member of the FNDS. MJE is on the medical advisory boards of the charities FND Hope UK and Dystonia UK. MR receives a salary from Elsevier as Editor-in-Chief of Seizure – European Journal of Epilepsy, honoraria from UptoDate, and payments from IqVIA for his role on a data management board. He has received speakers fees from UCB Pharma, Jazz Pharma and Angellini and an unrestricted research grant from UCP Pharma. He receives royalties from Oxford University Press and JKP for books on seizures and FND-related subjects. JS reports honoraria from UptoDate, personal fees from Expert Witness Work and grants from National Research Scotland. He runs a free self-help website, www.neurosymptoms.org, for patients with Functional Neurological Disorder. He is secretary of the FND Society and on the medical advisory boards of the charities FND Hope UK and FND Action. AC gives expert testimony in court on a range of neuropsychiatric topics, including FND. He is Past-President of the FND Society and Associate Editor of JNNP. JM has undertaken commercial research for Roche-Hoffmann Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Surgery remains an important treatment for low-risk patients with severe symptomatic aortic stenosis (AS). This study evaluated 5-year outcomes in low-risk patients undergoing isolated surgical aortic valve replacement (SAVR) or SAVR with concomitant procedures within the randomized Placement of Aortic Transcatheter Valves (PARTNER) 3 trial., Methods: In the PARTNER 3 trial, 454 patients underwent surgery for severe, symptomatic, trileaflet AS and were followed up for 5 years. Patients were stratified into those undergoing isolated SAVR (n = 334; 73.6%) vs concomitant SAVR (n = 120; 26.4%). Short- and long-term morbidity was adjudicated by a Clinical Events Committee. Hemodynamic valve performance was evaluated by an echocardiographic core laboratory. Patient-reported health status was measured with the Kansas City Cardiomyopathy Questionnaire (KCCQ)., Results: The mean age of participants was 73.6 ± 6.1 years; 71.1% of these patients were male. The median SAVR implant size was 23 mm overall. Five-year all-cause mortality (with vital status sweep) was 9.0% for all patients (8.5% isolated SAVR; 10.2% concomitant SAVR; P = .58), comparable to a recent analysis of low-risk isolated SAVR-treated patients in the STS database (overall mortality, 7.1%). The average 5-year mean gradient was 11.7 ± 5.6 mm Hg overall. Reintervention rates were low in both groups (isolated SAVR, 2.3% vs concomitant SAVR, 5.0%; P = .21), and most patients (isolated SAVR, 87.9%; concomitant SAVR, 86.1%) were alive with no evidence of bioprosthetic valve failure at 5 years., Conclusions: SAVR in low-risk patients in the PARTNER 3 trial demonstrated excellent 5-year outcomes. Five-year mortality was similar in patients undergoing isolated SAVR vs concomitant SAVR. This result was comparable to recently published national SAVR outcomes, thus demonstrating the generalizability of these findings., Competing Interests: Disclosures Vinod H. Thourani reports a relationship with Abbott Vascular that includes: consulting or advisory; with AtriCure that includes: consulting or advisory; with Artivion that includes: consulting or advisory; with Boston Scientific that includes: consulting or advisory; with Edwards Lifesciences that includes: consulting or advisory; with Medtronic that includes: consulting or advisory; with JenaValve Technology that includes: consulting or advisory; with Highlife that includes: consulting or advisory; with Croivalve that includes: consulting or advisory; and with Dasi Simulations that includes: equity or stocks. Martin B. Leon reports a relationship with W.L. Gore & Associates Medical Products Division that includes: consulting or advisory; with Meril Life Sciences that includes: consulting or advisory; with Medtronic that includes: consulting or advisory; with Boston Scientific that includes: consulting or advisory; and with Abbott that includes: consulting or advisory. Raj Makkar reports a relationship with Cordis that includes: consulting or advisory; and with Medtronic that includes: consulting or advisory. Wilson Y. Szeto reports a relationship with Terumo Interventional Systems that includes: consulting or advisory; with MicroInterventional Devices that includes: consulting or advisory; and with Cardiac Dimensions that includes: consulting or advisory. Susheel K. Kodali reports a relationship with Philips that includes: consulting or advisory; with Admedus that includes: consulting or advisory and equity or stocks; with TriCares that includes: consulting or advisory; with Dura Biotech that includes: consulting or advisory and equity or stocks; with Thubrikar Aortic Valve that includes: equity or stocks; with MicroInterventional Devices that includes: equity or stocks; with Supira that includes: equity or stocks; with TriFlo that includes: equity or stocks; with Adona that includes: equity or stocks; and with Tioga that includes: equity or stocks. Rebecca T. Hahn reports a relationship with Abbott that includes: speaking and lecture fees; with Baylis Medical Company that includes: speaking and lecture fees; with Edwards Lifesciences that includes: speaking and lecture fees; with Medtronic that includes: speaking and lecture fees; with Philips that includes: speaking and lecture fees; and with Siemens that includes: speaking and lecture fees. S. Chris Malaisrie reports a relationship with Medtronic that includes: funding grants; with Edwards Lifesciences that includes: consulting or advisory; with Terumo Interventional Systems that includes: consulting or advisory; and with Artivion that includes: consulting or advisory. Howard C. Herrmann reports a relationship with Abbott that includes: consulting or advisory; with Edwards Lifesciences that includes: consulting or advisory; with Medtronic that includes: consulting or advisory; with Johnson & Johnson that includes: consulting or advisory; with Prolifagen that includes: consulting or advisory; and with MicroInterventional Devices that includes: equity or stocks. Vasilis Babaliaros reports a relationship with Edwards Lifesciences that includes: consulting or advisory; and with Transmural Systems that includes: equity or stocks. Philippe Genereux reports a relationship with Abbott that includes: consulting or advisory; with AbioMed that includes: consulting or advisory; with Boston Scientific that includes: consulting or advisory; with Caranx Medical that includes: consulting or advisory; with Cardiovascular Systems that includes: consulting or advisory; with Edwards Lifesciences that includes: consulting or advisory; with Egnite that includes: consulting or advisory; with GE Healthcare that includes: consulting or advisory; with iRhythm Technologies that includes: consulting or advisory; with Medtronic that includes: consulting or advisory; with Shockwave Medical that includes: consulting or advisory; with Siemens that includes: consulting or advisory; with Teleflex that includes: consulting or advisory; with 4C Medical Technologies that includes: consulting or advisory; with Pi-Cardia that includes: equity or stocks; with Puzzle Medical that includes: equity or stocks; with Soundbite Medical that includes: equity or stocks; and with Saranas that includes: equity or stocks. David J. Cohen reports a relationship with Abbott that includes: consulting or advisory; with Boston Scientific that includes: consulting or advisory; and with Edwards Lifesciences that includes: consulting or advisory; and with Elixir Medical that includes: consulting or advisory. Molly Szerlip reports a relationship with Edwards Lifesciences that includes: consulting or advisory; with Boston Scientific that includes: consulting or advisory; and with Abbott that includes: consulting or advisory. Julien Ternacle reports a relationship with Edwards Lifesciences that includes: consulting or advisory; with Abbott that includes: consulting or advisory; with GE Medical that includes: consulting or advisory; and with Philips that includes: consulting or advisory. Jonathon Leipsic reports a relationship with HeartFlow Inc that includes: consulting or advisory; and with Circle CVI that includes: consulting or advisory. Philipp Blanke reports a relationship with Edwards Lifesciences that includes: consulting or advisory; and with Laralab that includes: consulting or advisory. John G. Webb reports a relationship with Edwards Lifesciences that includes: consulting or advisory., (Copyright © 2025 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Vitamin D deficiency (VDD) in children can cause hypocalcaemia and rickets, but the prevalence of these complications and the 25-hydroxyvitamin D (25OHD) concentrations below which they arise is uncertain. We investigated this in children (< 18 years) with 25OHD measurements., Design, Measurement and Patients: We obtained 25OHD results from the regional laboratory database, alongside albumin-adjusted serum calcium (aCa), parathyroid hormone (PTH) and alkaline phosphatase (ALP) within 6 months of the index 25OHD. We defined confirmed VDD with biochemical abnormalities (VDDba) as all of low aCa, elevated PTH and elevated ALP. Possible/potential VDDba were defined as 2/3 VDDba criteria with the third test missing (possible), or in the normal range (potential). Clinical records of identified cases were reviewed, and a consensus diagnosis was reached., Results: A total of 30,663 25OHD measurements were identified over 11.5 years (1 January 2009 to 15 June 2020); mean age 8 y, 47% female. After excluding ineligible results, 12,858 25OHD measurements from 9516 individuals with ≥ 2 aCa, PTH and ALP were analysed. Median 25OHD was 61 nmol/L; 36% < 50 nmol/L, 10% < 25 nmol/L. In total, 152 index 25OHD measurements were categorised as VDDba (30 confirmed, 23 possible and 99 potential). Following record review, 118 individuals (111 < 3 years) had 120 clinically confirmed VDDba episodes (62 clinical rickets, 15 biochemical rickets, 16 hypocalcaemia, 23 secondary hyperparathyroidism and 4 partially treated rickets). Fifty-six had undetectable 25OHD, and 104 < 25 nmol/L. The proportion of clinically confirmed VDDba was 0.9% for all eligible 25OHD measurements, and 8% for 25OHD < 25 nmol/L., Conclusion: VDDba is uncommon in children undergoing 25OHD testing, and occurs almost entirely in children < 3 years., (© 2024 John Wiley & Sons Ltd.)

A recently introduced quantitative susceptibility mapping (QSM) technique, χ-separation, offers the capability to separate paramagnetic (χ para ) and diamagnetic (χ dia ) susceptibility distribution within the brain. In-vivo high-resolution mapping of iron and myelin distribution, estimated by χ-separation, could provide a deeper understanding of brain substructures, assisting the investigation of their functions and alterations. This can be achieved using 7T MRI, which benefits from a high signal-to-noise ratio and susceptibility effects. However, applying χ-separation at 7T presents difficulties due to the requirement of an R 2 map, coupled with issues such as high specific absorption rate (SAR), large B 1 transmit field inhomogeneities, and prolonged scan time. To address these challenges, we developed a novel deep neural network, R2PRIMEnet 7T , designed to convert a 7T R 2 * map into a 3T R 2 ' map. Building on this development, we present a new pipeline for χ-separation at 7T, enabling us to generate high-resolution χ-separation maps from multi-echo gradient-echo data. The proposed method is compared with alternative pipelines, such as an end-to-end network and linearly-scaled R 2 ', and is validated against χ-separation maps at 3T, demonstrating its accuracy. The 7T χ-separation maps generated by the proposed method exhibit similar contrasts to those from 3T, while 7T high-resolution maps offer enhanced clarity and detail. Quantitative analysis confirms that the proposed method surpasses the alternative pipelines. The proposed method results well delineate the detailed brain structures associated with iron and myelin. This new pipeline holds promise for analyzing iron and myelin concentration changes in various neurodegenerative diseases through precise structural examination., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2025. Published by Elsevier Inc.)

Objectives: (i) Investigate if lower-limb running biomechanics differ between women and men with femoroacetabular impingement syndrome, and (ii) explore whether sex-specific relationships between lower-limb running biomechanics and symptom severity and sport-related concerns exist., Design: Cross-sectional., Setting: Gait laboratory., Participants: Twenty women and 22 men enrolled in a clinical trial of physiotherapist-led treatments for femoroacetabular impingement syndrome., Main Outcome Measures: Kinematics and kinetics of hip, knee, and ankle joints during the stance phase (calculated from three-dimensional biomechanics data) were compared using statistical parametric mapping. The International Hip Outcome Tool-33 and Copenhagen Hip and Groin Outcomes Score quantified hip-related symptom severity and sport-related concerns., Results: Women had larger hip adduction angles (34%-44% of stance,p = 0.045) than men. For kinetics, women displayed larger external hip extension moments (77%-100%,p = 0.001), smaller knee extension moments (80%-100%,p = 0.007), and smaller ankle dorsiflexion moments (26%-67%,p < 0.001) than men. Worse sport-related concern was associated with a larger peak hip extension angle (0.18, 95%CI 0.05,0.31) and smaller hip flexion moment impulse (0.14∗10 -2 , 95% CI 0.02∗10 -2 ,0.25∗10 -2 ) in women, and smaller hip external rotation moment impulse in men (0.06∗10 -2 , 95% CI 0.01∗10 -2 ,0.11∗10 -2 )., Conclusions: Women and men with FAI syndrome display differences in lower-limb running biomechanics and relationships between symptom severity and running biomechanics are sex-dependent, warranting consideration in future analyses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To review the spectrum of clinical and imaging features of glomus tumor involving the musculoskeletal system including the typically solitary forms as well as the rarer multifocal forms (glomuvenous malformation and glomangiomatosis)., Materials and Methods: A retrospective review of our institutional pathology database from 1996 to 2023 identified 176 patients with 218 confirmed glomus tumors. Primary imaging studies included MRI (125), radiographs (100), clinical/intraoperative photos (77), and ultrasound (36). Lesions were divided into two groups: those that are typically solitary involving specific anatomic areas (finger, toe, soft tissue, coccyx, and bone), and those that are multifocal (glomuvenous malformation and glomangiomatosis)., Results: The finger was the most frequently involved anatomic location for the classic (sporadic) glomus tumor occurring in 51% of patients, 77% of which were women, with the nail plate involved in more of the 75% of cases. Sporadic lesions involving the skin, subcutaneous adipose tissue, and deep soft tissue were termed "soft tissue," and were identified in 39% of patients, 90% of which were in the extremities and in men in 81% of cases. The multifocal syndromic forms of glomus disease occurred in younger individuals and involved less than 6% of the study group. Patients with glomuvenous malformation presented early with predominantly cutaneous involvement, while those with glomangiomatosis present later, often with both superficial and deep involvement, and a high rate of local tumor recurrence., Conclusion: While glomus tumor is generally uncommon, it frequently involves the musculoskeletal extremities. Knowledge of the spectrum of characteristic locations and appearances will facilitate definitive diagnosis., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Background: Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry posttrauma in humans. Neuroimaging markers may be particularly useful because they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. In this study, we aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure., Methods: Participants were recruited from U.S. emergency departments for the AURORA study (n = 286; 178 female). Trauma-related change in alcohol use at 8 weeks posttrauma relative to pretrauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency measure. Reward-related neurocircuitry activation and functional connectivity were assessed 2 weeks posttrauma using functional magnetic resonance imaging during a monetary reward task using region of interest and whole-brain voxelwise analyses., Results: Greater increase in alcohol use from pretrauma to 8 weeks posttrauma was predicted by 1) greater ventral tegmental area, 2) greater cerebellum activation during gain > loss trials measured 2 weeks posttrauma, and 3) greater seed-based functional connectivity between the ventral tegmental area and lateral occipital cortex and precuneus., Conclusions: Altered ventral tegmental area activation and functional connectivity early posttrauma may be associated with reward seeking and processing, thereby contributing to greater alcohol use posttrauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early posttrauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

This study investigated the associations between residential environmental characteristics and the prevalence of cardiometabolic diseases in the five largest Bulgarian cities. Representative cross-sectional survey data (N = 4640 adults) was collected in Sofia, Plovdiv, Varna, Burgas, and Ruse. Participants self-reported diagnosis or medication intake for hypertension, ischemic heart disease (IHD), stroke, and diabetes mellitus, as well as domestic burning of solid fuel and having a domestic garden. Residential addresses were linked to greenspace (overall vegetation level, tree cover, urban greenspace), bluespace, walkability, air pollution (NO 2 ), and traffic noise (L den ). In the 300 m buffer, bluespace presence was inversely associated with hypertension (odds ratio [OR] = 0.67; 95% CI: 0.45, 1.00), IHD (OR = 0.45; 95% CI: 0.21, 0.99), and diabetes (OR = 0.51; 95% CI: 0.25, 1.04). Higher walkability and tree cover were inversely associated with hypertension (OR per 2 units  = 0.85; 95% CI: 0.75, 0.96) and diabetes (OR per 10%  = 0.77; 95% CI: 0.62, 0.97), respectively. These associations were stronger in larger buffers. Solid fuel burning was associated with IHD (OR = 1.63; 95% CI: 1.07, 2.50). There was an indication of a positive association between aircraft L den and both stroke and IHD. The direction of the associations for domestic gardens, NO 2 , road traffic and railway L den was counterintuitive. We detected some nonlinear associations. In conclusion, people living in urban neighborhoods that were more walkable, closer to bluespace, and greener had lower prevalence of cardiometabolic diseases, while solid fuel burning was associated with higher odds of cardiovascular diseases. Unexpected associations with some exposures may be due to unaccounted for urban fabric characteristics. This study is among the first assessing an understudied region in Southeastern Europe. Its findings have the potential to inform public discourse and provide evidence to support the implementation of urban design conducive to cardiometabolic health., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Lack of insurance after traumatic injury is associated with decreased use of postacute care and poor outcomes. Insurance linkage programs enroll eligible patients in Medicaid at the time of an unplanned admission. We hypothesized that Medicaid enrollment would be associated with increased use of postacute care, but also with prolonged hospital length of stay (LOS) while awaiting insurance authorization., Methods: We linked trauma registry and EMR data to identify patients ages 18 years to 64 years admitted from 2017 to 2021 to a Level I trauma center. Patients admitted without insurance and retroactively insured (RI) during hospitalization were compared with patients with established Medicaid (MI) and those remaining uninsured (UI). We measured postacute care use including home health care, rehabilitation, and skilled nursing facilities. We tested the association between insurance status and discharge disposition and LOS (primary outcome) using multivariable negative binomial regression. Direct costs were compared between groups., Results: We compared 494 RI patients to 1706 MI and 148 UI patients. Retroactively insured patients had longer hospitalization (median LOS [interquartile range], 4 days [2-9 days]) than other groups (MI, 4 [2-8] and UI 2 [1-3]), p < 0.001). Retroactively insured patients were more likely to be discharged with home health care and to inpatient rehabilitation than UI patients ( p < 0.001). After adjusting for injury and management characteristics, RI was associated with longer LOS compared with MI for patients discharged to inpatient facilities ( p < 0.001). Median costs for RI patients discharged to a facility were $10,284 higher than MI patients, ranging from $8,582 for Injury Severity Score <9 to $51,883 for Injury Severity Score ≥25., Conclusion: Enrollment in Medicaid after traumatic injury is associated with postacute care use, but the current enrollment process may delay discharge. Streamlining insurance enrollment and permitting discharge with pending application status could reduce unnecessary hospital days, saving costs and improving improve patient experience., Level of Evidence: Prognostic and Epidemiological; Level IV., (Copyright © 2025 American Association for the Surgery of Trauma.)

Cardiovascular disease is the leading cause of mortality in the United States. Studies suggest a role for environmental exposures in the etiology of cardiovascular disease, including exposure to arsenic through drinking water. Arsenic exposure during pregnancy has been shown to have effects on offspring, but few studies have examined impacts on maternal cardiovascular health. Although our prior work documented the detrimental effect of arsenic on the maternal heart during pregnancy, our current study examines the effect of gestational arsenic exposure on the maternal heart postpartum. Timed-pregnant wild-type (C57BL/6J) mice were exposed to 0, 100, or 1,000 µg/L sodium arsenite (NaAsO 2 ) via drinking water from embryonic day 2.5 until parturition. Postpartum heart structure and function was assessed via transthoracic echocardiography and gravimetric measurement. Hypertrophic markers were probed via qRT-PCR and Western blot. Isolated cardiomyocyte Ca 2+ -handling and contraction were also assessed, along with the expression of with Ca 2+ -handling and contractile proteins. Interestingly, we found that exposure to either 100 or 1,000 µg/L sodium arsenite increased postpartum heart size at postpartum day 12 vs. nonexposed postpartum controls. At the cellular level, we found altered cardiomyocyte Ca 2+ -handling and contraction, along with expression changes of key contractile proteins, including α-actin and cardiac myosin binding protein C (cMyBP-c). Together, these findings suggest that gestational arsenic exposure impacts the postpartum maternal heart, possibly inducing long-term cardiovascular changes. Furthermore, these findings highlight the importance of reducing arsenic exposure during pregnancy, and the need for more research on the impact of arsenic on maternal heart health and adverse pregnancy events. NEW & NOTEWORTHY Gestational exposure to sodium arsenite at environmentally relevant doses (100 and 1,000 µg/L) increases postpartum heart size, and induces dysregulated Ca 2+ homeostasis and impaired shortening in isolated cardiomyocytes. This is the first study to demonstrate that gestational arsenic exposure impacts postpartum heart structure and function beyond the exposure period.

Lasso peptides are a diverse class of naturally occurring, highly stable molecules kinetically trapped in a distinctive [1]rotaxane conformation. How the ATP-dependent lasso cyclase constrains a relatively unstructured substrate peptide into a low entropy product has remained a mystery owing to poor enzyme stability and activity in vitro. In this study, we combined substrate tolerance data with structural predictions, bioinformatic analysis, molecular dynamics simulations and mutational scanning to construct a model for the three-dimensional orientation of the substrate peptide in the lasso cyclase active site. Predicted peptide cyclase molecular contacts were validated by rationally engineering multiple, phylogenetically diverse lasso cyclases to accept substrates rejected by the wild-type enzymes. Finally, we demonstrate the utility of lasso cyclase engineering by robustly producing previously inaccessible variants that tightly bind to integrin αvβ8, which is a primary activator of transforming growth factor β and, thus, an important anti-cancer target., Competing Interests: Competing interests: M.J.B. and D.A.M. are co-founders of and own stock in Lassogen, Inc. S.E.B. and D.A.M. are inventors on a provisional patent application filed by the University of Illinois at Urbana-Champaign covering lasso cyclase engineering (US Provisional Application Ser. No. 63/673,853). M.J.B., P.A.J. and G.C.M.d.C. are inventors on a provisional patent application filed by Lassogen, Inc. for the design of lasso peptide integrin binders (US Provisional Application No. 63/612,957). The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Regulation of myocardial mass is key for maintaining cardiovascular health. This review highlights the complex and regulatory relationship between mechanosignaling and myocardial mass, influenced by many internal and external factors including hemodynamic and microgravity, respectively. The heart is a dynamic organ constantly adapting to changes in workload (preload and afterload) and mechanical stress exerted on the myocardium, influencing both physiological adaptations and pathological remodeling. Mechanosignaling pathways, such as the mitogen-activated protein kinases (MAPKs) and the phosphoinositide 3-kinases and serine/threonine kinase (PI3K/Akt) pathways, mediate downstream effects on gene expression and play key roles in transducing mechanical cues into biochemical signals, thereby modulating cellular processes, including control of myocardial mass. Dysregulation of these processes can lead to pathological cardiac remodeling, such as hypertrophic cardiomyopathy. Furthermore, recent studies have highlighted the importance of protein quality control mechanisms, such as the ubiquitin-proteasome system, in settings of extreme physiological conditions that alter the heart workload such as pregnancy and microgravity. Overall, this review provides a thorough insight into how mechanical signals are converted into chemical signals to regulate myocardial mass in both healthy and diseased conditions.

Background & Aims: The virulence and severity of SARS-CoV-2 infections have decreased over time in the general population due to vaccinations and improved antiviral treatments. Whether a similar trend has occurred in patients with cirrhosis is unclear. We used the National COVID Cohort Collaborative (N3C) to describe the outcomes over time., Methods: We utilized the N3C level 3 data set with uncensored dates to identify all patients with chronic liver disease (CLD) with and without cirrhosis who had SARS-CoV-2 infection as of November 2023. We described the observed 30-day case fatality rate (CFR) by month of infection. We used adjusted survival analyses to calculate relative hazard of death by month of infection compared with infection at the onset of the COVID-19 pandemic., Results: We identified 117,811 total patients with CLD infected with SARS-CoV-2 between March 2020 and November 2023: 27,428 (23%) with cirrhosis and 90,383 (77%) without cirrhosis. The observed 30-day CFRs during the entire study period were 1.1% (1016) for patients with CLD without cirrhosis and 6.3% (1732) with cirrhosis. Observed 30-day CFRs by month of infection varied throughout the pandemic and showed a sustained downward trend since 2022. Compared with infection in Quarter 2 of 2020 (at the beginning of the pandemic), the adjusted hazards of death at 30 days for infection in Quarter 3 of 2023 were 0.20 (95% confidence interval [CI], 0.08-0.50) for patients with CLD without cirrhosis and 0.35 (95% CI, 0.18-0.69) for patients with CLD with cirrhosis., Conclusions: In this N3C study, we found that the observed 30-day CFR decreased progressively for patients with CLD both with and without cirrhosis, consistent with broader trends seen in the general population., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Diabetic foot ulcers (DFUs) are one of the most serious chronic diabetes-related complications. Since medial arterial calcification (MAC) can be present in patients with a DFU, toe pressure (TP) measurements are advised to grade potential ischemia. However, the value of TP to predict clinical outcomes in this group of patients is poorly understood. Therefore, the primary aim of this study was to investigate the relationship between TP values and ulcer healing in patients with DFU and concomitant MAC., Methods: A single-center retrospective cohort study was conducted. Patients were included if they were 18 years or older, presented with a DFU, had a TP measurement and concomitant MAC in the same limb. MAC was defined as an ankle-brachial index (ABI) above 1.30, or incompressible arteries during ABI measurement. Multistate models were fitted to analyze the outcomes of interest (ulcer healing, revascularization, amputation, and mortality)., Results: In total, 148 patients were included. During the 180 days follow-up, the cumulative incidence of a healed ulcer was 34% (95% confidence interval [CI]: 27-42%), whereas 32% (95% CI: 26-41%) of patients had a persisting open wound. An approximately positive linear correlation was observed between TP values and the probability of ulcer healing, regardless of whether patients had undergone a revascularization procedure. However, the absolute healing rate was low, and no clear distinction could be made for intermediate TP values (between 30 and 80 mm Hg)., Conclusion: Lower TP values are correlated with nonhealing of a DFU in patients with MAC, but clear absolute differences in healing are only seen between very low (below 30 mm Hg) and high (above 80 mm Hg) measurements. For intermediate TP values, the predictive strength of ulcer healing is weak. This should be of particular importance when grading ischemia in this subgroup of patients in wound classification systems., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Autistic individuals often receive psychiatric diagnoses prior to their autism diagnosis. It remains unclear to what extent autistic females and males differ in their likelihood of receiving psychiatric diagnoses prior to their autism diagnosis and continue seeking care for them after an autism diagnosis., Methods: In a nationwide cohort of all individuals born in Sweden 1990-2015 with a clinical autism diagnosis (N = 72,331, n females  = 24,110), we used linear and logistic regression to estimate the association between sex and (a) psychiatric diagnoses before autism diagnosis, including time trends by autism diagnosis year (2010-2020), (b) autism diagnosis age in those with preceding diagnoses, (c) stability of preceding diagnoses (defined as continued care utilization indicated through diagnosis or medication in the 5 years following autism diagnosis)., Results: In total 54.2% of autistic females and 40.9% of autistic males received at least one preceding psychiatric diagnosis (most common: ADHD, anxiety, depression). Autistic females showed higher odds than males for most preceding psychiatric diagnoses (OR range  = 1.29 [1.18, 1.41]-10.69 [8.06, 14.17]), except psychotic disorders (OR = 0.91 [0.78, 1.06]) and ADHD (OR = 0.69 [0.66, 0.71]). Sex differences in preceding diagnoses were persistent across different autism diagnosis years (2010-2020). For most conditions, females with a preceding diagnosis were diagnosed with autism later than males with the same condition. For both sexes, the stability of preceding diagnoses varied considerably (23.1%-88.9%) and was less than 50% for most diagnoses. Females showed a higher stability for anxiety, sleep disorders and self-harm (OR range  = 1.45 [1.30, 1.62]-2.37 [1.93, 2.90]), and males for psychotic disorders (OR = 0.60 [0.44, 0.81])., Conclusions: Autistic females are more likely to be diagnosed with psychiatric conditions prior to an autism diagnosis and receive care for them post autism diagnosis. Our findings emphasize the variability of clinical presentation and importance of disentangling persistent support needs from overlapping diagnostic presentations, particularly in autistic females, to provide appropriate and timely care., (© 2025 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Cas9 must be localized to the nucleus to access the genome of mammalian cells. For most proteins, adding a single nuclear localization signal (NLS) is sufficient to promote nuclear entry. However, Cas9 nuclear entry appears to be inefficient as multiple NLSs are typically added to Cas9. Here, we found that three different Cas9 variants interact with the ribosome in HEK293T cells, and that this interaction is RNA mediated. Following immunoprecipitation-mass spectrometry of cytoplasmic-localized Cas9-0NLS and nuclear-localized Cas9-4NLS constructs, we identified novel Cas9 interactors in postmitotic neurons, including KEAP1 and additional ribosomal subunits, the latter were enriched in Cas9-0NLS samples. Collectively, our results suggest that Cas9 is sequestered in the cytoplasm of mammalian cells, in part, via interaction with the ribosome. Increasing the number of NLSs on Cas9 and/or increasing the amount of cytoplasmic guide RNA has the potential to outcompete ribosomal RNA binding and promote efficient nuclear localization of CRISPR-Cas9 variants.

The photovoltaic-alkaline water (PV-AW) electrolysis system offers an appealing approach for large-scale green hydrogen generation. However, current PV-AW systems suffer from low solar-to-hydrogen (STH) conversion efficiencies (e.g., <20%) at practical current densities (e.g., >100 mA cm -2 ), rendering the produced H 2 not economical. Here, we designed and developed a highly efficient PV-AW system that mainly consists of a customized, state-of-the-art AW electrolyzer and concentrator photovoltaic (CPV) receiver. The highly efficient anodic oxygen evolving catalyst, consisting of an iron oxide/nickel (oxy)hydroxide (Fe 2 O 3 -NiO x H y ) composite, enables the customized AW electrolyzer with unprecedented catalytic performance (e.g., 1 A cm -2 at 1.8 V and 0.37 kgH 2 /m -2 hour -1 at 48 kWh/kgH 2 ). Benefiting from the superior water electrolysis performance, the integrated CPV-AW electrolyzer system reaches a very high STH efficiency of up to 29.1% (refer to 30.3% if the lead resistance losses are excluded) at large current densities, surpassing all previously reported PV-electrolysis systems.

Atomic force microscopy (AFM) allows direct imaging of atomic- or molecular-scale surface structures in liquid. However, such subnanoscale measurements are often sensitive to the AFM tip properties. To overcome this problem, 30 nm Si-sputter coating was proposed, and its effectiveness in improving stability and reproducibility has been demonstrated in atomic-scale imaging of various materials. However, this method involves tip blunting, enhancing the tip-induced dilation effect. As an alternative method, here we investigate atomic layer deposition (ALD) Al2O3-coating, where the film thickness is atomically well-controlled. Our transmission electron microscopy, contact angle and force curve measurements consistently suggest that as-purchased tips are covered with organic contaminants, and the initial 20 cycles gradually remove them, reducing the tip radius (Rt) and hydrophobicity. Further deposition increases Rt and hydrophilicity and forms an intact Al2O3 film over 50 cycles. We compared 50-cycle ALD-coated tips with 30 nm Si-sputter-coated tips in imaging mica and chitin nanocrystals (NCs). On mica, ALD coating gives slightly less stability and reproducibility in hydration force measurements than the Si sputter coating, yet they are sufficient in atomic-scale imaging. In imaging chitin NCs, ALD-coated tips give a less tip-induced dilation effect while maintaining molecular-scale imaging capability. We also found that 10-cycle-ALD coated tips covered with carbon give a better resolution and reproducibility in observing subnanoscale features at chitin NC surfaces. This result and our experience empirically suggest carbon-coated tips' effectiveness in observing carbon-based materials., (© The Author(s) 2025. Published by Oxford University Press on behalf of The Japanese Society of Microscopy.)

Severe tricuspid regurgitation (TR) is associated with significant morbidity and mortality. Management of severe TR includes treatment of the underlying cause(s), medical therapy and less commonly surgical tricuspid valve repair. Newer transcatheter tricuspid valve repair devices show promise for those patients who remain symptomatic with severe TR despite such efforts. The presence of a Cardiac Implantable Electronic Device (CIED) with leads across the tricuspid valve poses a significant challenge from both diagnostic and therapeutic standpoints. In this paper, we propose an algorithm to manage patients with CIED leads across the tricuspid valve and symptomatic TR. We include case studies to illustrate implementation of the algorithm in clinical care. Key takeaway messages: (1) CIED leads across the tricuspid valve (TV) in the setting of TR are often innocent but may be causal and/or interfere with valve imaging. (2) CIED lead extraction often does not reduce TR and is reserved for select patients. (3)Transcatheter TV interventions can be performed in the presence of CIED leads. (4) An algorithm-driven interventional cardiology, electrophysiology and advanced imaging team approach is needed to best manage TR in the setting of CIED leads., (© 2025 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Cerebral arteriovenous malformations (AVMs) are congenital vascular anomalies that can lead to severe complications, including hemorrhage and neurological deficits. This study compares the outcomes of microsurgical resection and stereotactic radiosurgery (SRS) for SM grade I and II AVMs. Out of a large multicenter registry, we identified 180 matched patients with SM grade I and II AVMs treated with either microsurgical resection or SRS between 2010 and 2023. The primary outcomes were AVM obliteration rates and complications; secondary outcomes included neurological status and functional outcomes measured by the modified Rankin Scale (mRS). Propensity score matching (PSM) was utilized to ensure comparability between treatment groups. After PSM, 90 patients were allocated to each treatment group. Significant differences were observed in complete obliteration rates, with resection achieving higher rates compared to SRS in overall cases (97.8% vs. 60.0%, p < 0.001), unruptured AVMs (100% vs. 58.3%, p < 0.001), and ruptured AVMs (95.2% vs. 61.9%, p < 0.001). Functional improvement rates were similar between the groups for overall cases (67.2% in resection vs. 66.7% in SRS, p = 0.95), unruptured AVMs (55.2% in resection vs. 55.6% in SRS, p > 0.9), and ruptured AVMs (78.1% in resection vs. 74.1% in SRS, p = 0.7). Symptomatic complication rates were identical between the groups (11.1% each, p > 0.9), while permanent complication rates were comparable (6.7% in resection vs. 5.6% in SRS, p = 0.8). Resection demonstrated significantly higher complete obliteration rates compared to SRS across all cases, including unruptured and ruptured AVMs. Functional improvement rates were similar between the two treatment groups, with no significant differences in symptomatic or permanent complication rates., Competing Interests: Declarations. Ethical approval: This retrospective multicenter clinical cohort study was conducted in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study protocol was reviewed and approved by the Institutional Review Board (IRB) of University of Virginia Hospital. Due to the retrospective nature of the study, the requirement for informed consent was waived by the IRB. All patient data were anonymized and de-identified prior to analysis to ensure patient confidentiality. Conflict of interest: The researchers reported that there was no conflict of interest Disclosure: Dr. Griessenauer reported personal fees from MicroVention and Stryker, proctoring for Medtronic, and grants from Penumbra and Baxter outside the submitted work. Dr. Tjoumakaris reported being a consultant for MicroVention. Dr. Burkhardt reported being a consultant for MicroVention, Stryker, Q’Apel, Cerenovos, and Longeviti Neuro Solutions outside the submitted work. Dr. Möhlenbruch reported grants from Balt, MicroVention, Medtronic, and Stryker outside the submitted work. A. B. Patel reported personal fees from MicroVention, Medtronic, and Penumbra outside the submitted work.Dr. Cuellar reported being a consultant for MicroVention. The rest of authors declared no personal, financial, or institutional interests related to the drugs, materials, or devices discussed in the article. Consent to participate: The study was approved by institutional review boards, with waived informed consent due to its retrospective design. Data was de-identified for confidentiality. Clinical trial number: Not applicable., (© 2025. The Author(s).)

Circadian rhythms are a mechanism by which species adapt to environmental variability and fundamental to understanding species behavior. However, we lack data and a standardized framework to accurately assess and compare temporal activity for species during rapid ecological change. Through a global network representing 38 countries, we leveraged 8.9 million mammalian observations to create a library of 14,587 standardized diel activity estimates for 445 species. We found that less than half the species' estimates were in agreement with diel classifications from the reference literature and that species commonly used more than one diel classification. Species diel activity was highly plastic when exposed to anthropogenic change. Furthermore, body size and distributional extent were strongly associated with whether a species is diurnal or nocturnal. Our findings provide essential knowledge of species behavior in an era of rapid global change and suggest the need for a new, quantitative framework that defines diel activity logically and consistently while capturing species plasticity.

A 16-mo-old, pregnant, Nigerian Dwarf doe was presented to the veterinary hospital after being struck by a farm truck. A piece of tissue was found on the ground next to the goat after impact. The doe was painful on abdominal and perineal palpation, but abdominal radiographs and ultrasound did not reveal fractures or soft tissue herniations. The accompanying piece of tissue was a blind-ended sac covered with fecal material, most suggestive of the cecal apex. The goat declined to lateral recumbency, and due to the poor prognosis, the owners elected euthanasia. Postmortem examination identified free feces throughout the abdominal cavity, a complete, circumferential laceration through the mid-body of the cecum with an absent apex, and a full-thickness rectal tear at the anal orifice. Histologic examination of the accompanying piece of tissue was confirmatory of the cecal apex, and the anorectal tear had acute hemorrhage most consistent with trauma. Our report highlights the unique case presentation of traumatic cecal transection with transanal evisceration through an anorectal tear, a combination of injuries not previously reported in people or animals, to our knowledge. Pregnancy is a predisposing factor to rectal injuries in humans and veterinary species., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.