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Abstract Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.25, p = 0.005), especially tumors with isocitrate dehydrogenase (IDH) mutations (OR = 1.38, p = 0.007) and IDHmut 1p/19q intact (IDHmut-intact OR = 1.53, p = 0.004) tumors. Genetically inferred increased counts of lymphocytes (IDHmut-intact OR = 0.70, p = 0.004) and neutrophils (IDHmut OR = 0.69, p = 0.019; IDHmut-intact OR = 0.60, p = 0.009) show inverse associations with risk, which may reflect enhanced immune-surveillance. Considering survival, we observe higher mortality risk in patients with IDHmut 1p/19q with genetically predicted increased counts of lymphocytes (hazard ratio (HR) = 1.65, 95% CI: 1.24–2.20), neutrophils (HR = 1.49, 1.13–1.97), and eosinophils (HR = 1.59, 1.18–2.14). Polygenic scores for blood cell traits are also differentially associated with 17 tumor immune microenvironment features in a subtype-specific manner, including signatures related to interferon signaling, PD-1 expression, and T-cell/Cytotoxic responses. Our findings highlight immune-mediated susceptibility mechanisms with potential disease management implications.

Background Worldwide, lung cancer (LC) is the second most frequent cancer and the leading cause of cancer related mortality. Low-dose CT (LDCT) screening reduced LC mortality by 20–24% in randomised trials of high-risk populations. A significant proportion of those screened have nodules detected that are found to be benign. Consequently, many individuals receive extra imaging and/or unnecessary procedures, which can have a negative physical and psychological impact, as well as placing a financial burden on health systems. Therefore, there is a need to identify individuals who need no interval CT between screening rounds.Methods and analysis The aim of this study is to identify risk factors predictive of LC, which are known at the time of the scan, in patients with LDCT screen-detected lung nodules. The MEDLINE and EMBASE databases will be searched and articles that are on cohorts or mention cohorts of screenees with nodules will be identified. A data extraction framework will ensure consistent extraction across studies. Individual participant data (IPD) will be collected to perform a one-stage IPD meta-analysis using hierarchical univariate models. Clustering will be accounted for by having separate intercept terms for each cohort. Where IPD is not available, the effects of risk factors will be extracted from publications, if possible. Effects from IPD cohorts and aggregate data will be reported and compared. The PROBAST (Prediction model Risk Of Bias ASsessment Tool) will be used for assessment of quality of the studies.Ethics and dissemination Ethical approval was not required as this study is a secondary analysis. The results will be disseminated through publication in peer-reviewed journals and presentations at relevant conferences.PROSPERO registration number CRD42022309515

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles. We discuss the importance of antigen identification by emphasizing the identification of tumor-specific and tumor-associated antigens and the development of CAR T therapies targeting these antigens. Furthermore, we highlight key structural innovations, including cytokine-armored CARs, protease-regulated CARs, and CARs engineered with chemokine receptors, to enhance tumor infiltration and activity within the immunosuppressive microenvironment. Additionally, novel manufacturing approaches, such as the Sleeping Beauty transposon system, mRNA-based CAR transfection, and in vivo CAR T cell production, are discussed as scalable solution to improve the accessibility of CAR T cell therapies. Finally, we address critical therapeutic limitations, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and suboptimal persistence of CAR T cells. An examination of emerging strategies for countering these limitations reveals that CRISPR-Cas9-mediated genetic modifications and combination therapies utilizing checkpoint inhibitors can improve CAR T cell functionality and durability. By integrating insights from preclinical models, clinical trials, and innovative engineering approaches, this review addresses advances in CAR T cell therapies and their performance in solid tumors.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of hematologic malignancies, achieving remarkable clinical success with FDA-approved therapies targeting CD19 and BCMA. However, the extension of these successes to solid tumors remains limited due to several intrinsic challenges, including antigen heterogeneity and immunosuppressive tumor microenvironments. In this review, we provide a comprehensive overview of recent advances in CAR T cell therapy aimed at overcoming these obstacles. We discuss the importance of antigen identification by emphasizing the identification of tumor-specific and tumor-associated antigens and the development of CAR T therapies targeting these antigens. Furthermore, we highlight key structural innovations, including cytokine-armored CARs, protease-regulated CARs, and CARs engineered with chemokine receptors, to enhance tumor infiltration and activity within the immunosuppressive microenvironment. Additionally, novel manufacturing approaches, such as the Sleeping Beauty transposon system, mRNA-based CAR transfection, and in vivo CAR T cell production, are discussed as scalable solution to improve the accessibility of CAR T cell therapies. Finally, we address critical therapeutic limitations, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and suboptimal persistence of CAR T cells. An examination of emerging strategies for countering these limitations reveals that CRISPR-Cas9-mediated genetic modifications and combination therapies utilizing checkpoint inhibitors can improve CAR T cell functionality and durability. By integrating insights from preclinical models, clinical trials, and innovative engineering approaches, this review addresses advances in CAR T cell therapies and their performance in solid tumors. [ABSTRACT FROM AUTHOR]

Photosynthetic eukaryotic microalgae are key primary producers in the Antarctic sea ice environment. Anticipated changes in sea ice thickness and snow load due to climate change may cause substantial shifts in available light to these ice-associated organisms. This study used a laboratory-based experiment to investigate how light levels, simulating different sea ice and snow thicknesses, affect fatty acid (FA) composition in two ice associated microalgae species, the pennate diatom Nitzschia cf. biundulata and the dinoflagellate Polarella glacialis. FA profiling and transcriptomic analyses were used to compare the impact of three light levels: High (baseline culturing conditions 90 ± 1 μmol photons m−2 s−1), mid (10 ± 1 μmol photons m−2 s−1); and low (1.5 ± 1 μmol photons m−2 s−1) on each isolate. Both microalgal isolates had altered growth rates and shifts in FA composition under different light conditions. Nitzschia cf. biundulata exhibited significant changes in specific saturated and monounsaturated FAs, with a notable increase in energy storage-related FAs under conditions emulating thinner ice or reduced snow cover. Polarella glacialis significantly increased production of polyunsaturated FAs (PUFAs) in mid light conditions, particularly octadecapentaenoic acid (C18:5N-3), indicating enhanced membrane fluidity and synthesis of longer-chain PUFAs. Notably, C18:5N-3 has been identified as an ichthyotoxic molecule, with fish mortalities associated with other high producing marine taxa. High light levels caused down regulation of photosynthetic genes in N. cf. biundulata isolates and up-regulation in P. glacialis isolates. This and the FA composition changes show the variability of acclimation strategies for different taxonomic groups, providing insights into the responses of microalgae to light stress. This variability could impact polar food webs under climate change, particularly through changes in macronutrient availability to higher trophic levels due to species specific acclimation responses. Further research on the broader microalgal community is needed to clarify the extent of these effects. [ABSTRACT FROM AUTHOR]

Glioma is a highly fatal and heterogeneous brain tumor with few known risk factors. Our study examines genetically predicted variability in blood cell indices in relation to glioma risk and survival in 3418 cases and 8156 controls. We find that increased platelet to lymphocyte ratio (PLR) confers an increased risk of glioma (odds ratio (OR) = 1.25, p = 0.005), especially tumors with isocitrate dehydrogenase (IDH) mutations (OR = 1.38, p = 0.007) and IDHmut 1p/19q intact (IDHmut-intact OR = 1.53, p = 0.004) tumors. Genetically inferred increased counts of lymphocytes (IDHmut-intact OR = 0.70, p = 0.004) and neutrophils (IDHmut OR = 0.69, p = 0.019; IDHmut-intact OR = 0.60, p = 0.009) show inverse associations with risk, which may reflect enhanced immune-surveillance. Considering survival, we observe higher mortality risk in patients with IDHmut 1p/19q with genetically predicted increased counts of lymphocytes (hazard ratio (HR) = 1.65, 95% CI: 1.24–2.20), neutrophils (HR = 1.49, 1.13–1.97), and eosinophils (HR = 1.59, 1.18–2.14). Polygenic scores for blood cell traits are also differentially associated with 17 tumor immune microenvironment features in a subtype-specific manner, including signatures related to interferon signaling, PD-1 expression, and T-cell/Cytotoxic responses. Our findings highlight immune-mediated susceptibility mechanisms with potential disease management implications. Glioma is an aggressive brain tumor subtype with few known risk factors. Here, the authors utilise Mendelian Randomisation to investigate correlation of immune cell counts with subtype-specific risk and mortality in glioma patients. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Suicide attempts and deaths among children are increasing in the United States, yet suicide in this preadolescent population remains understudied. A clearer understanding of which youth experience early onset of suicidal behavior is crucial for predicting risk and identifying youth best suited to early intervention. This paper examines how intersectional marginalized identities may predict the onset of suicidal behaviors among preadolescent youth.The Adolescent Brain and Cognitive Development (ABCD) Study is a prospective cohort study with annual assessments of youth ages 9 and 10 and their caregivers. Lifetime suicide attempts and preparatory suicidal behaviors were assessed annually. Survival models examined overall trends and demographic differences in the onset of suicidal behaviors.The final sample included 11,223 participants (mean age = 9.9 years old, SD = 7.5 months). 5,280 (47%) reported a minoritized racial/ethnic identity, and 1,410 (12.6%) were categorized as sexual or gender minorities. 208 suicide attempts and 143 instances of preparatory suicidal behaviors were reported across the study period. An interaction effect was found such that youth who hold multiple minoritized identities (i.e., sexual and gender minority youth from minoritized racial/ethnic backgrounds) were at elevated risk for onset of both suicide attempts (HR = 2.97, 95% CI = 1.59–5.56, p = .001) and preparatory suicidal behaviors (b = 3.09, 95% CI = 1.38–6.93, p = .006).Intersectional marginalized identities were associated with earlier onset of suicide attempts and preparatory suicidal behaviors. Findings suggest that early interventions for minoritized youth may be important to reduce the rapidly increasing suicide rate among preadolescent youth. [ABSTRACT FROM AUTHOR]

Chronic ingestion of foods containing elevated levels of beta carotene, a common dietary staple endemic in West Africa, may promote the development of yellow to orange hyperpigmentation of the oral mucosa and skin. This benign condition, known as carotenemia or hypercarotenemia, has received little attention in the general dental literature. The aim of this case report is to increase awareness of this phenomenon by describing the clinical presentation of a patient from Nigeria with conspicuous yellow discoloration of the floor of the mouth and soft palatal mucosa. Attending clinicians should seek clinicopathologic correlations of yellow mucocutaneous discoloration, most notably jaundice associated with hepatitis. In this case, the patient's normal liver biomarkers, absence of dermal manifestations, and high intake of beta carotene-rich foods led to a diagnosis of carotenemia. [ABSTRACT FROM AUTHOR]

Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders. We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores, urinary fractional excretion of lactulose-to-mannitol ratio, fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset. There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (P =.026) but not with baseline CD-polygenic risk scores or the lactulose-to-mannitol ratio. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio, 3.65; 95% confidence interval, 2.18–6.11, P <.001). Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families. In families with multiple cases of Crohn's disease, unaffected members are 3 times more likely to develop the disease, possibly due to environmental factors rather than genetics. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic sleeve gastrectomy (SG) is a commonly performed bariatric procedure. At our institution, two vessel sealing devices, Thunderbeat® (Olympus) and Maryland LigaSure™ (Covidien) are utilized for intraoperative dissection. Methods: A retrospective review of all patients who underwent primary SG from July 2013 through August 2022 was performed to evaluate postoperative bleeding (POB) rates between the two devices. The primary outcome measured was POB as defined by the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), with secondary outcomes including reoperation, source of bleed, and overall safety. Results: A total of 8157 underwent SG. Average BMI and age were 43.2 kg/m2 and 37.1 years, respectively. A total of 6600 (80.9%) were female. Thunderbeat® was utilized in 5143 (63%) cases and Maryland LigaSure™ was used in 3014 (37%) cases. There was no significant difference in overall bleeding between the Thunderbeat® (18/5143,.35%) and the Maryland LigaSure™ (19/3014,.63%; P =.0689). However, there was a difference noted when comparing reoperation for bleeding between Thunderbeat® (9/5143,.17%) and Maryland LigaSure™ (13/3014,.43%; P =.0291). Furthermore, the location of bleeding in the reoperations was more common from the cut edge of the mesentery compared to the staple line with the Maryland LigaSure™ versus the Thunderbeat® (P =.038). Conclusions: The Thunderbeat® device is comparatively more hemostatic than the Maryland LigaSure™ for SG. The location of postoperative bleed may be related to vessel sealing devices used. [ABSTRACT FROM AUTHOR]

Study Design: Observational Study. Objectives: This study aimed to investigate the most searched types of questions and online resources implicated in the operative and nonoperative management of scoliosis. Methods: Six terms related to operative and nonoperative scoliosis treatment were searched on Google's People Also Ask section on October 12, 2023. The Rothwell classification was used to sort questions into fact, policy, or value categories, and associated websites were classified by type. Fischer's exact tests compared question type and websites encountered between operative and nonoperative questions. Statistical significance was set at the.05 level. Results: The most common questions concerning operative and nonoperative management were fact (53.4%) and value (35.5%) questions, respectively. The most common subcategory pertaining to operative and nonoperative questions were specific activities/restrictions (21.7%) and evaluation of treatment (33.3%), respectively. Questions on indications/management (13.2% vs 31.2%, P <.001) and evaluation of treatment (10.1% vs 33.3%, P <.001) were associated with nonoperative scoliosis management. Medical practice websites were the most common website to which questions concerning operative (31.9%) and nonoperative (51.4%) management were directed to. Operative questions were more likely to be directed to academic websites (21.7% vs 10.0%, P =.037) and less likely to be directed to medical practice websites (31.9% vs 51.4%, P =.007) than nonoperative questions. Conclusions: During scoliosis consultations, spine surgeons should emphasize the postoperative recovery process and efficacy of conservative treatment modalities for the operative and nonoperative management of scoliosis, respectively. Future research should assess the impact of website encounters on patients' decision-making. [ABSTRACT FROM AUTHOR]

Purpose: Olecranon osteotomy has been associated with loss of reduction, nonunion, implant failure, and migration of wires. We aim to evaluate quality of reduction of the osteotomy site as a predictor of olecranon osteotomy nonunion. Methods: One hundred and twenty-five distal humerus fractures that underwent open reduction internal fixation (ORIF) were reviewed. Amount of dorsal step-off was measured from the lateral radiograph from the second postoperative visit. A receiver operating curve (ROC) analysis was used to assess the predictability of nonunion based on dorsal displacement of the olecranon osteotomy. Results: Between 2014 and 2022, 36 patients underwent a chevron olecranon osteotomy (29%). Of the 36 patients, 7 (19%) failed to successfully unite at the osteotomy site. Two experienced aseptic nonunion, 2 were malreduced leading to nonunion, 2 malunited, and 1 had persistent fracture lines following poor osteotomy cut. Patients that developed nonunion had a mean dorsal displacement of 3.87 mm versus 1.15 mm (p < 0.001). The ROC demonstrated excellent prediction for nonunion based on displacement (AUC = 0.896, p = 0.002). Youden’s index was determined at a sensitivity of 86% and a specificity of 73% corresponding to a dorsal step-off of 2.07 mm. This finding was confirmed on multivariate logistic regression showing a step-off over 2.07 mm is an independent predictor of olecranon osteotomy nonunion (p = 0.021). Conclusion: A malreduction resulting in a dorsal step-off larger than 2.07 mm is predictive of olecranon osteotomy nonunion or malreduction. Therefore, the success of the olecranon osteotomy approach is directly dependent on quality of anatomic reduction. Level of Evidence: III; Retrospective Cohort Study. [ABSTRACT FROM AUTHOR]

Scholars often disagree about how to interpret the narrative description of Christ as a proclaimer of peace in Ephesians 2.17. Most understand Ephesians to be either referring to the earthly ministry of Jesus or attributing to him the work of later apostolic preaching. This article argues that none of the existing interpretations is adequate, and instead maintains that Ephesians is advancing a metaphorical depiction of Christ as a diplomatic peace herald (caduceator) commissioned to call for the cessation of hostilities between God and humanity, and consequently between Jews and Gentiles. The article explores the purposes and practices of Greco-Roman diplomacy, paying special attention to the contribution of peace heralds in times of interstate conflict and how they came to signify the entire peacemaking process. The article then analyzes how Ephesians 2.11–22 deploys terminology commonly used to convey sociopolitical rivalry as a way to portray the Jew-Gentile relationship as one of figurative warfare. It is in within this symbolic world of ethnic conflict and diplomacy that Ephesians casts Christ in the image of a peace herald, whose metaphorical proclamation of peace to those far and near signifies the totality and finality of Christ’s conciliatory work. [ABSTRACT FROM AUTHOR]

This study aimed to examine the sleep parameters and sleep/wake regularity of a cohort of student-athletes who start training between 06:30 and 07:00. Twenty-one male Rugby Union players, aged 21 ± 2 years and competing at a national level, were assessed using actigraphy over two weeks, and the Athlete Sleep Screening Questionnaire (ASSQ). Sleep/wake regularity was calculated using the Sleep Regularity Index (SRI). Wilcoxon signed-rank tests showed that nocturnal sleep preceding morning training had a significantly shorter sleep duration (1.8 hr, r = .67), and advanced sleep onset (0.9 hr, r = .50) and sleep offset times (3.2 hr, r = .85) compared to nocturnal sleep preceding free days. The variability of training demands resulted in an inconsistent sleep pattern between consecutive days, resulting in a median SRI score of 67.0 (interquartile range: 17.0). Pearson correlations revealed that lower SRI was significantly associated with a higher daily sleep duration including naps (r = -.62), delayed sleep onset (r = -.50) and sleep offset (r = -.60), and a later chronotype assessed using the ASSQ (r = .52). These findings indicate that early morning training is a factor contributing to irregular sleep/wake patterns in student-athletes, and where feasible should be scheduled at an alternative time. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction/Aims Methods Results Discussion Glucocorticoid (GC)‐related adverse reactions and risks are commonly seen during the treatment of immune‐mediated and inflammatory neuromuscular disorders. There is wide variation in the management of associated complications. The aim of this study is to develop international consensus guidance on the management of GC‐related complications in neuromuscular disorders.Through the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM), an international task force of 15 experts was convened to develop clinical guidance for the management of GC‐related complications in neuromuscular patients. The RAND/UCLA appropriateness method (RAM) was used to develop consensus guidance statements. Initial guidance statements were crafted after a thorough literature review and were modified after anonymous panel input, with up to three rounds of voting via email to achieve consensus.Statements were developed and achieved consensus for general care, monitoring of patients while on GC, osteoporosis prevention, vaccinations, infection screening, and Pneumocystis jiroveci pneumonia prophylaxis. A multidisciplinary approach to the management of GC‐related complications was emphasized.These formal consensus statements provide guidance to clinicians who use GC in the treatment of neuromuscular diseases regarding prevention and management of the more common associated adverse events and risks that arise with long and short‐term GC use and serve as a springboard for investigation and updates. [ABSTRACT FROM AUTHOR]

Purpose: To improve the current method for MRI turbulence quantification which is the intravoxel phase dispersion (IVPD) method. Turbulence is commonly characterized by the Reynolds stress tensor (RST) which describes the velocity covariance matrix. A major source for systematic errors in MRI is the sequence's sensitivity to the variance of the derivatives of velocity, such as the acceleration variance, which can lead to a substantial measurement bias., Methods: We developed a Cartesian phase contrast sequence with fast velocity encoding and two separately measured partial echoes with opposite readout directions. This design aims to reduce the high-order gradient moments that are responsible for the described measurement error. Velocity encoding directions follow the ICOSA6 scheme to capture the full RST. Turbulence data is reconstructed using the intra-voxel phase dispersion (IVPD) technique. We validated this sequence in vitro using a periodic hill flow benchmark with highly anisotropic turbulence. MRI data underwent extensive averaging, with multiple velocity encoding values employed to reduce noise and isolate systematic effects., Results: The RST data obtained from the new sequence agree well with the ground truth. Compared to a state-of-the-art sequence, the maximum errors were reduced by factor five., Conclusion: Simple adjustments to current MRI protocols can greatly enhance turbulence measurement accuracy through the reduction of high-order gradient moments. The proposed measures include applying fast velocity encoding, high readout bandwidth, and a highly asymmetric readout. Ringing artifacts due to the asymmetric readout can be removed via a second, inverted readout., (Copyright © 2025. Published by Elsevier Inc.)

Toxic shock syndrome toxin-1 (TSST-1) is a superantigen produced by Staphylococcus aureus and is the determinant of menstrual toxic shock syndrome (mTSS); however, the impact of TSST-1 on the vaginal environment beyond mTSS is not understood. Herein, we assessed how TSST-1 affects vaginal colonization by S. aureus , host inflammatory responses, and changes in microbial communities within the murine vagina. We demonstrated that TSST-1 induced a CD8 + T-cell-dependent inflammatory response in 24 h that correlated with S. aureus persistence within the vaginal tract. This increase was due to superantigen-dependent T-cell activation that triggered a change in microbial composition within the vaginal tract. Altogether, this study demonstrates that within the vaginal tract, TSST-1 modulates the vaginal microbiota to favor the survival of S. aureus in the absence of mTSS.IMPORTANCEToxic shock syndrome toxin-1 (TSST-1) is a superantigen toxin produced from Staphylococcus aureus that causes the menstrual form of toxic shock syndrome. This research demonstrates that TSST-1 also has a wider function within the vaginal tract than previously expected. We show that TSST-1, by activating CD8 + T cells, induces an inflammatory environment that modifies the vaginal microbiota to favor colonization by S. aureus . These are important findings as S. aureus can colonize the human vaginal tract efficiently and subsequently trigger dysbiosis within the microbial communities leading to several adverse outcomes such as decreased fertility, increased risks for sexually transmitted diseases, and issues related to pregnancy and birth.

Background/objectives: There is currently no consensus regarding the optimal strategy for reversal of anticoagulation in life-threatening hemorrhage associated with factor XIa (FXIa) inhibitors., Methods: For this clinical case report, informed consent was obtained from surrogate., Results and Discussion: Here, we present the case of an 82-year-old female who sustained a large subdural hematoma after a fall. Her aPTT on admission was elevated at 90.4 s and remained persistently prolonged at 90.9 s 12-hour after receiving an adequate dose of 4-factor prothrombin complex concentrate (PCC). She was found to have received a factor XIa inhibitor in a clinical trial, and subsequently received recombinant activated factor VII (rFVIIa) 2 mg (45 mcg/kg) as a one-time dose, and tranexamic acid (TXA) 1 g intravenously for reversal given her intracranial bleeding in the setting of trauma complicated by recent factor XIa inhibitor use. However, given her clinical decline and high surgical risk, the patient's family elected to withdraw care and she expired three days later. Reversal of FXIa inhibitors is challenging but may best be achieved using a combination of rFVIIa and TXA., Practical Implications: Clinicians should consider administration of low dose recombinant activated factor VII (rFVIIa) in conjunction with an anti-fibrinolytic inhibitor such as tranexamic acid (TXA) for reversal of life-threatening hemorrhage in bleeding patients with exposure to novel factor XIa inhibitors that are currently in clinical trials., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Effective conservation of rare species necessitates the identification of critical habitats and their specific features that influence species occurrence. This study focused on smalltooth sawfish ( Pristis pectinata ), a critically endangered elasmobranch, to explore how predictive spatial modeling can enhance conservation efforts. By leveraging long-term occurrence and relative abundance data from scientific gillnet surveys, along with in situ environmental data, we used boosted regression trees (BRT) to pinpoint key habitat features essential for juvenile sawfish. Our analysis revealed strong correlations between sawfish presence and environmental variables, with a preferential selection of very shallow, warm, and saline waters fringed with mangroves, particularly those with high pneumatophore density. High relative abundances were observed in warmer months, and predictions of presence were consistent around discrete mangrove-lined areas in Everglades National Park throughout all seasons. This study emphasizes the importance of high-quality environmental data in predictive modeling and informs management strategies aimed at protecting the critical habitats necessary for the recovery of this species. Preventing the loss of mangroves in vulnerable regions of the smalltooth sawfish's range-especially near anthropogenic influences such as the Charlotte Harbor Estuary-is crucial for recovery. We also highlight the need for improved data access to facilitate global abundance predictions, thereby enhancing spatial management and conservation efforts for rare species., Competing Interests: The authors declare no conflicts of interest., (Published 2025. This article is a U.S. Government work and is in the public domain in the USA. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Middle meningeal artery embolization (MMAE) emerges as an alternative to conventional surgical drainage (CSD) for chronic subdural hematomas (cSDH). Several studies have suggested that MMAE improves the cost efficacy of cSDH treatment. However, further comprehensive analyses of the outcomes and healthcare costs of MMAE are necessary., Methods: Merative MarketScan Research Database from 2017-2022 was used to compare demographics, reoperation rates, complications, healthcare utilization, and payments of patients being treated with CSD, CSD and adjunctive MMAE, or standalone MMAE for cSDH or nontraumatic subdural hemorrhage., Results: From 2017-2022, there were 2108 patients who underwent CSD ( n  = 2015), or CSD+MMAE ( n  = 23) or MMAE only ( n  = 70). The median age of the surgical group was 61 years (IQR 53-73 years), the surgery plus MMAE was 67 years (56-77 years) and the MMAE group was 65 years (55-77 years). Median hospital days were significantly longer for the CSD (6 (IQR 5-7) days) and CSD + MMAE (7 (IQR 6-7) days) groups compared to MMAE only (0 days(IQR 0-1)( p  < 0.0001). Median index hospitalization payments were significantly higher for the CSD+MMAE group ($74,568) compared to both CSD ($39,658) ( p  = 0.003) and MMAE groups ($22,286) ( p  < 0.0001). The total median payments at six-month follow-up for the CSD group were higher compared to CSD+MMAE ($11494 vs $7300, p  = 0.0017) but not compared to MMAE only ($10,680, p  = 0.08)., Conclusions: The reduced complications, infection rate, hospital utilization, and costs observed in this study support MMAE as a promising treatment option in the arsenal for cSDH management., 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.

Respiratory and encephalitic virus infections represent a significant risk to public health globally. Detailed investigations of immunological responses and disease outcomes during sequential virus infections are rare. Here, we define the impact of influenza virus infection on a subsequent virus encephalitis. We used a model system in which mice were given influenza A virus (IAV) infection 8 days prior to Semliki Forest virus (SFV) infection (IAV→SFV). IAV infection clearly attenuated the subsequent SFV infection with reduced titers of infectious SFV and lower levels of cytokines and chemokines in the central nervous system (CNS). In contrast, the SFV viremia in both IAV→SFV and SFV-only mice was comparable. Increased type I interferon (IFN) levels in the CNS after IAV infection might have contributed to some level of protection towards SFV infection in the CNS, suggesting that early control of SFV replication in the CNS during IAV→SFV infection led to reduced adaptive response, given the lower number of CD8 + T cells recruited to the brain in IAV→SFV infection. In lungs, however, prior IAV infection elicited effector CD8 + T cells with highly activated CD38 and/or CD25 phenotypes, while SFV-only infection elicited distinct effector CD8 + T cells with increased frequencies of KLRG1 expression, a hallmark of short-lived effector T cells. Taken together, our findings demonstrate that prior IAV infection can confer protective immunity toward secondary SFV infection, confirmed by reduced disease severity and inflammatory immune responses in the brain. Our work provides important insights into therapies and vaccine regimens directed against unrelated pathogens., Importance: Influenza viruses are medically important human pathogens that caused epidemics and pandemics throughout history. Conversely, encephalitic arthropod-borne virus (arboviral) diseases affect both humans and domestic animals, creating massive public health issues. Influenza viruses circulate globally while arboviruses dominate tropical regions. Given both influenza virus and encephalitic arboviruses, such as alphaviruses, circulate in many regions globally, co-infections are likely to occur. In addition, arthropod-borne neurotropic infections are generally mild or asymptomatic, hence are likely to be unnoticed as a risk factor during influenza infection. However, the consequences of such co-infections are unclear. Our recent study showed that alphavirus infection preceding Influenza A virus (IAV) infection negatively impacted immune responses to the influenza virus in mice. Here, we aim to investigate the immune responses when the order of sequential infection with IAV and alphavirus are swapped. Altogether, our findings will provide key insights to improved diagnostics, preventative vaccines, and antiviral therapies.