Simple Incisionless Temporary Stabilization: An Adjunct to Lower Blepharoplasty.

Background: Lateral canthal tightening is indicated for patients undergoing lower eyelid blepharoplasty who have preexisting lower eyelid laxity or ectropion. A canthoplasty or canthopexy is indicated at the time of lower blepharoplasty to avoid postoperative complications, such as eyelid retraction or ectropion. Various surgical techniques are described to accomplish this goal, including canthopexy procedures, which usually access the lateral canthal tendon through an upper eyelid blepharoplasty or lateral canthal incision. Objectives: To describe an incisionless technique adjunctive to lower blepharoplasty, which stabilizes the lower eyelid in the week following blepharoplasty. Methods: This operative technique description and retrospective case series includes 15 patients who underwent a simple incisionless temporary stabilization (SITS) during lower eyelid blepharoplasty. The procedures were performed at the same outpatient office-based surgery center and were performed by the author surgeons. Patients were followed from 3 to 6 months postoperatively. Results: The SITS procedure during lower eyelid blepharoplasty successfully maintained a desirable functional and aesthetic eyelid position with minimal complications. One patient reported tearing postoperatively which was determined to be unrelated to the SITS and resolved by the 1-month follow-up visit. No patient had any other complications during the follow-up period. Conclusions: The SITS procedure was successfully utilized in patients with mild-to-moderate lower eyelid laxity and/or a negative vector to prevent postoperative ectropion and eyelid retraction. It is a more favorable alternative to temporary tarsorrhaphy, as it does not obstruct vision during healing and better secures the eyelid. It should not be used in patients with significant lower eyelid laxity that would place the patient at significant risk of ectropion and lower eyelid retraction related to swelling and inappropriate eyelid position during the early postoperative course.

Ancient and recent hybridization in the Oreochromis cichlid fishes.

Cichlid fishes of the genus Oreochromis (tilapia) are among the most important fish for inland capture fisheries and global aquaculture. Deliberate introductions of non-native species for fisheries improvement and accidental escapees from farms have resulted in admixture with indigenous species. Such hybridization may be detrimental to native biodiversity, potentially leading to genomic homogenization of populations and the loss of important genetic material associated with local adaptation. By contrast, introgression may fuel diversification when combined with ecological opportunity, by supplying novel genetic combinations. To date, the role of introgression in the evolutionary history of tilapia has not been explored. Here we studied both ancient and recent hybridization in tilapia, using whole genome resequencing of 575 individuals from 23 species. We focused on Tanzania, a natural hotspot of tilapia diversity, and a country where hybridization between exotic and native species in the natural environment has been previously reported. We reconstruct the first genome-scale phylogeny of the genus and reveal prevalent ancient gene flow across the Oreochromis phylogeny. This has likely resulted in hybrid speciation of one species, O. chungruruensis. We identify multiple cases of recent hybridization between native and introduced species in the wild, linked to the use of non-native species in both capture fisheries improvement and aquaculture. This has potential implications for both conservation of wild populations and the development of the global tilapia aquaculture industry.

Biomechanical Predictors of Sacroiliac Joint Uptake on SPECT/CT.

OBJECTIVE: Single Photon Emission Computed Tomography/ Computed Tomography (SPECT/CT) is an emerging imaging modality that identifies sites of heightened bone metabolism in response to increased stresses. The relationship between sacroiliac joint (SI) radiotracer uptake and anatomic biomechanical parameters is poorly understood. METHODS: Adult patients with SPECT/CT scans performed at our institution between 2021-2023 for the workup of low back pain were included. Patient charts were reviewed for demographic factors, including age, gender, and prior thoracolumbar fusion history. Biomechanical spinopelvic parameters were measured from standing scoliosis x-rays. SPECT/CT scans were reviewed for uptake at the SI joint. Patients were stratified into two cohorts; patients with SI uptake greater than iliac crest uptake were designated "hot," whereas those with less or equal uptake were labeled "cold." RESULTS: 160 patients met inclusion criteria. Patients were slightly more male (55%) with average age 55 ± 14.9 years. 68 patients (43%) had evidence of increased SI activity. Interrater reliability showed substantial agreement (kappa = 0.62). The hot cohort demonstrated greater pelvic incidence (54.8 ± 14.0° vs. 51.0 ± 11.0°, p = 0.031) and pelvic tilt (20.8 ± 9.5° vs. 18.4 ± 8.6°, p =0.047) compared to the cold cohort. Patients were otherwise similar between cohorts (p >0.05). CONCLUSIONS: Increased pelvic incidence and pelvic tilt angles are associated with SPECT/CT uptake at the SIJ, which may reflect altered biomechanics at the spinopelvic junction. SPECT/CT may be a valuable tool to assess SI degeneration. Future studies are warranted to better characterize the clinical applications of these findings.

Do sociodemographic risk profiles for adolescents engaging in weekly e-cigarette, cigarette, and dual product use differ?

BACKGROUND: E-cigarette use represents a contemporary mode of nicotine product use that may be changing the risk profile of participating adolescents. Understanding differences in sociodemographic characteristics of adolescents engaging in contemporary e-cigarette use and traditional cigarette use is important for effectively developing and targeting public health intervention programs. The objective of this study was to identify and compare sociodemographic risk profiles for exclusive e-cigarette use and dual-product use among a large sample of Canadian youth. METHODS: A survey of 46,666 secondary school students in the 2021-22 wave of the COMPASS study measured frequency of past month e-cigarette and cigarette use as well as age, sex, gender, racial or ethnic background, spending money, relative family affluence, and having one's own bedroom. Rates of cigarette-only, e-cigarette-only, and dual product use were calculated, and separate classification trees were run using the CART algorithm to identify sociodemographic risk profiles for weekly dual-product use and weekly e-cigarette-only use. RESULTS: Over 13% of adolescents used only e-cigarettes at least weekly, 3% engaged in weekly dual e-cigarette and cigarette use, and less than 0.5% used only cigarettes. Available spending money was a common predictor of dual-product and e-cigarette-only use. Gender diverse youth and youth with lower perceived family affluence were at higher risk for dual-product use, while white and multiethnic adolescents were at greater risk of e-cigarette-only use. Two high-risk profiles were identified for e-cigarette-only use and four high-risk profiles were identified for dual product use. CONCLUSIONS: This study used a novel modelling approach (CART) to identify combinations of sociodemographic characteristics that profile high-risk groups for exclusive e-cigarette and dual-product use. Unique risk profiles were identified, suggesting that e-cigarettes are attracting new demographics of adolescents who have not previously been considered as high-risk for traditional cigarette use.

Coronal Deformity is Associated With Uptake on Single Photon Emission Computed Tomography in Patients With Low Back Pain.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) is emerging as a valuable imaging test for identifying pain generators within the lumbar spine. The relationship between radiotracer uptake on SPECT/CT and anatomic biomechanical parameters has not been previously studied. METHODS: We performed a retrospective review of all patients seen at our institution between 2021-2023 who obtained SPECT/CT scans for workup of thoracolumbar back pain. Patient data including demographic, clinical symptoms, and surgical history were collected. Radiology reports were reviewed for evidence of pathologic degeneration and increased bone metabolism on SPECT/CT. Biomechanical parameters were measured from standing scoliosis plain radiographs. Patients were stratified into two cohorts by either presence or absence of asymmetric coronal uptake on SPECT/CT. RESULTS: 160 patients met inclusion criteria. Patients were primarily male (55%) with average age 55 ± 15 years. 87 (54%) patients demonstrated asymmetric uptake on SPECT/CT. These patients were older (P < 0.001), but with similar gender, prior fusion history, sacroiliitis, adjacent segment degeneration, and pseudoarthrosis (P > 0.05). This cohort had more disc disease, facet arthropathy, and greater degree of coronal scoliosis and coronal imbalance (P < 0.001). There were significantly more sites of uptake in the asymmetric cohort, and uptake was preferentially observed in the concavity of the lumbar curve (P < 0.001). There were no significant differences in sagittal balance or spinopelvic mismatch between cohorts (P > 0.05). CONCLUSION: Asymmetric uptake on SPECT/CT was associated with coronal deformity in patients with low back pain. Further prospective studies are warranted to assess the effect of coronal deformity on pain generation.

Target and non-target effects of insecticide use during ornamental milkweed production.

There are widespread public efforts to conserve wildlife in urbanized landscapes via the installation of nursery-grown plants that support Lepidoptera taxa. Insecticides are commonly used during nursery production to suppress key plant pests, and many products have extended periods of toxicity and affect a wide range of herbivore taxa. While there are plentiful toxicological data on bee species, predominantly the Western honey bee (Apis mellifera L.), little is known about how insecticides affect nonpest lepidopterans. Lepidoptera has different modes of exposure (e.g., leaf-feeding) and differences in susceptibility to insecticide target sites compared to bees. Consequently, many products compatible with bee conservation pose an uncertain risk to nonpest lepidopterans and thus may represent an under-recognized conflict with conservation efforts. Using the monarch butterfly (Danaus plexippus, L.), tropical milkweed (Asclepias curassavica, L.), and oleander aphid (Aphis nerii, Fonscolombe, 1841) system, we conducted leaf and whole-plant feeding assays to evaluate effects of acute and chronic monarch exposure to industry standard and alternative reduced-risk insecticides used during nursery production. We also evaluated the efficacy of these insecticides against their target pest, the oleander aphid. Our results indicate that insecticides used to control pests on ornamental milkweed can cause monarch larval mortality up to 4 wk after treatment application. Furthermore, the duration of aphid suppression is often shorter than the duration of adverse effects on monarchs. This study demonstrates a conflict between insect pest management and Lepidoptera conservation during ornamental plant production and has implications for the conservation value of ornamentals after retail sale.

Genome-wide association study reveals shared and distinct genetic architecture underlying fatty acid and bioactive oxylipin metabolites in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Bioactive fatty acid-derived oxylipin molecules play key roles in mediating inflammation and oxidative stress, which underlie many chronic diseases. Circulating levels of fatty acids and oxylipins are influenced by both environmental and genetic factors; characterizing the genetic architecture of bioactive lipids could yield new insights into underlying biological pathways. Thus, we performed a genome wide association study (GWAS) of n=81 fatty acids and oxylipins in n=11,584 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) participants with genetic and lipidomic data measured at study baseline (58.6% female, mean age = 46.1 years, standard deviation = 13.8 years). Additionally, given the effects of central obesity on inflammation, we examined interactions with waist circumference using two-degree-of-freedom joint tests. Heritability estimates ranged from 0% to 47.9%, and 48 of the 81oxylipins and fatty acids were significantly heritable. Moreover, 40 (49.4%) of the 81 oxylipins and fatty acids had at least one genome-wide significant (p< 6.94E-11) variant resulting in 19 independent genetic loci involved in fatty acid and oxylipin synthesis, as well as downstream pathways. Four loci (lead variant minor allele frequency [MAF] range: 0.08-0.50), including the desaturase-encoding FADS and the OATP1B1 transporter protein-encoding SLCO1B1, exhibited associations with four or more fatty acids and oxylipins. The majority of the 15 remaining loci (87.5%) (lead variant MAF range = 0.03-0.45, mean = 0.23) were only associated with one oxylipin or fatty acid, demonstrating evidence of distinct genetic effects. Finally, while most loci identified in two-degree-of-freedom tests were previously identified in our main effects analyses, we also identified an additional rare variant (MAF = 0.002) near CARS2, a locus previously implicated in inflammation. Our analyses revealed shared and distinct genetic architecture underlying fatty acids and oxylipins, providing insights into genetic factors and motivating future multi-omics work to characterize these compounds and elucidate their roles in disease pathways.

Distinguishing Mechanisms for Reactive Uptake at Liquid Surfaces via Angular Distributions of Inelastically Scattered Molecules.

Angular distributions of OH inelastically scattered from the surfaces of the reactive hydrocarbon liquids squalane (fully saturated) and squalene (partially unsaturated) have been measured. A pulsed, rotationally cold molecular beam (Ei = 35 kJ mol-1) of OH was scattered from refreshed liquid surfaces in a vacuum. Spatially and temporally resolved OH number densities were measured by pulsed, planar laser-induced fluorescence. Results are compared with those for the inert liquid perfluoropolyether. The clearly asymmetric distributions for 45° incidence add to the weight of evidence for predominantly impulsive scattering from all three liquids. However, we propose that significant differences in their shapes may be diagnostic of contrasting reaction mechanisms. Direct, near-specular trajectories survive preferentially on squalene, consistent with an addition mechanism removing those at more backward angles. This trend is reversed for squalane, as expected for direct abstraction. The results reinforce the need to consider the effects of composition-dependent contributions from different reaction mechanisms in the modeling of OH-aging of atmospheric aerosol particles.

Adjuvant Delivery Method and Nanoparticle Charge Influence Peptide Amphiphile Micelle Vaccine Bioactivity.

Vaccines are an indispensable public health measure that have enabled the eradication, near elimination, and prevention of a variety of pathogens. As research continues and our understanding of immunization strategies develops, subunit vaccines have emerged as exciting alternatives to existing whole vaccine approaches. Unfortunately, subunit vaccines often possess weak antigenicity, requiring delivery devices and adjuvant supplementation to improve their utility. Peptide amphiphile micelles have recently been shown to function as both delivery devices and self-adjuvanting systems that can be readily associated with molecular adjuvants to further improve vaccine-mediated host immunity. While promising, many "design rules" associated with the plethora of underlying adjustable parameters in the generation of a peptide amphiphile micelle vaccine have yet to be uncovered. This work explores the impact micellar adjuvant complexation method and incorporated antigen type have on their ability to activate dendritic cells and induce antigen specific responses. Interestingly, electrostatic complexation of CpG to micelles resulted in improved in vitro dendritic cell activation over hydrophobic association and antigen|adjuvant co-localization influenced cell-mediated, but not antibody-mediated immune responses. These exciting results complement those previously published to build the framework of a micelle vaccine toolbox that can be leveraged for future disease-specific formulations.

Longitudinal changes in adiposity following anterior cruciate ligament reconstruction and associations with knee symptoms and function.

Objective: To evaluate adiposity after anterior cruciate ligament reconstruction (ACLR): i) cross-sectionally (1-year post-ACLR) compared to uninjured controls; ii) longitudinally up to 5 years post-ACLR; and iii) associations with patient-reported symptoms and physical performance. Methods: In 107 individuals post-ACLR and 19 controls, we assessed global (BMI), peripheral (subcutaneous adipose tissue thickness on the posteromedial side of knee MRI), and central (waist circumference in ACLR group) adiposity. Patient-reported symptoms (Knee injury and Osteoarthritis Outcome Score) and physical performance (hop for distance) were evaluated at 1 and 5 years post-ACLR. Linear regression models evaluated adiposity between groups. Paired t-tests evaluated changes in adiposity from 1- to 5 years post-ACLR. Linear regression models analyzed adiposity's associations with patient-reported symptoms and physical performance at 1-year post-ACLR, changes in symptoms and performance over 4 years post-ACLR, and longitudinal changes in adiposity and symptoms and performance, controlling for age, sex, and activity level. Results: Individuals 1-year post-ACLR were associated with higher average global (3 â€‹kg/m2) and peripheral adiposity (2.3 â€‹mm). From 1- to 5 years post-ACLR, higher average global (0.58 â€‹kg/m2) and central (5 â€‹cm) adiposity, and lower average peripheral adiposity (1.3 â€‹mm) were observed. In general, adiposity at one-year post-ACLR was negatively associated with patient-reported symptoms and physical performance, and changes from 1 to 5 years post-ACLR. Increases in adiposity were negatively associated with changes in patient-reported symptoms and physical performance over four years post-ACLR. Conclusion: Greater global and central adiposity is a feature of young adults following ACLR and influences current and future patient-reported symptoms and physical performance.

Reproducible preclinical models of androgen receptor driven human prostate cancer bone metastasis.

BACKGROUND: Preclinical models recapitulating the metastatic phenotypes are essential for developing the next-generation therapies for metastatic prostate cancer (mPC). We aimed to establish a cohort of clinically relevant mPC models, particularly androgen receptor positive (AR+) bone metastasis models, from LuCaP patient-derived xenografts (PDX) that reflect the heterogeneity and complexity of mPC. METHODS: PDX tumors were dissociated into single cells, modified to express luciferase, and were inoculated into NSG mice via intracardiac injection. The progression of metastases was monitored by bioluminescent imaging. Histological phenotypes of metastases were characterized by immunohistochemistry and immunofluorescence staining. Castration responses were further investigated in two AR-positive models. RESULTS: Our PDX-derived metastasis (PDM) model collection comprises three AR+ adenocarcinomas (ARPC) and one AR- neuroendocrine carcinoma (NEPC). All ARPC models developed bone metastases with either an osteoblastic, osteolytic, or mixed phenotype, while the NEPC model mainly developed brain metastasis. Different mechanisms of castration resistance were observed in two AR+ PDM models with distinct genotypes, such as combined loss of TP53 and RB1 in one model and expression of AR splice variant 7 (AR-V7) expression in another model. Intriguingly, the castration-resistant tumors displayed inter- and intra-tumor as well as organ-specific heterogeneity in lineage specification. CONCLUSION: Genetically diverse PDM models provide a clinically relevant system for biomarker identification and personalized medicine in metastatic castration-resistant prostate cancer.

Genome size variation in Cape schoenoid sedges (Schoeneae) and its ecophysiological consequences.

PREMISE: Increases in genome size in plants-often associated with larger, low-density stomata and greater water-use efficiency (WUE)-could affect plant ecophysiological and hydraulic function. Variation in plant genome size is often due to polyploidy, having occurred repeatedly in the austral sedge genus Schoenus in the Cape Floristic Region (CFR), while species in the other major schoenoid genus in the region, Tetraria, have smaller genomes. Comparing these genera is useful as they co-occur at the landscape level, under broadly similar bioclimatic conditions. We hypothesized that CFR Schoenus have greater WUE, with lower maximum stomatal conductance (gwmax) imposed by larger, less-dense stomata. METHODS: We investigated relationships between genome size and stomatal parameters in a phylogenetic context, reconstructing a phylogeny of CFR-occurring Schoeneae (Cyperaceae). Species' stomatal and functional traits were measured from field-collected and herbarium specimens. Carbon stable isotopes were used as an index of WUE. Genome size was derived from flow-cytometric measurements of leafy shoots. RESULTS: Evolutionary regressions demonstrated that stomatal size and density covary with genome size, positively and negatively, respectively, with genome size explaining 72-75% of the variation in stomatal size. Larger-genomed species had lower gwmax and C:N ratios, particularly in culms. CONCLUSIONS: We interpret differences in vegetative physiology between the genera as evidence of more-conservative strategies in CFR Schoenus compared to the more-acquisitive Tetraria. Because Schoenus have smaller, reduced leaves, they likely rely more on culm photosynthesis than Tetraria. Across the CFR Schoeneae, ecophysiology correlates with genome size, but confounding sources of trait variation limit inferences about causal relationships between traits.

The Importance of Recovery in Resistance Training Microcycle Construction.

Systemic resistance training aims to enhance performance by balancing stress, fatigue and recovery. While fatigue is expected, insufficient recovery may temporarily impair performance. The aim of this review was to examine evidence regarding manipulation of resistance training variables on subsequent effects on recovery and performance. PubMed, Medline, SPORTDiscus, Scopus and CINAHL were searched. Only studies that investigated recovery between resistance training sessions were selected, with a total of 24 articles included for review. Training to failure may lengthen recovery times, potentially impairing performance; however, it may be suitable if implemented strategically ensuring adequate recovery between sessions of similar exercises or muscle groups. Higher volumes may increase recovery demands, especially when paired with training to failure, however, with wide variation in individual responses, it is suggested to start with lower volume, monitor recovery, and gradually increase training volume if appropriate. Exercises emphasising the lower body, multi-joint movements, greater muscle recruitment, eccentric contractions, and/or the lengthened position may require longer recovery times. Adjusting volume and frequency of these exercises can affect recovery demands depending on the goals and training logistics. Daily undulating programming may maximise performance on priority sessions while maintaining purposeful and productive easy days. For example, active recovery in the form of training opposing muscle groups, light aerobic cardio, or low-volume power-type training may improve recovery and potentially elicit a post activation potentiation priming effect compared to passive recovery. However, it is possible that training cessation may be adequate for allowing sufficient recovery prior to sessions of importance.

The Impact of Higher BMI on Wound Complications Following Adolescent Breast Reduction: A Retrospective Study of 1215 Cases.

BACKGROUND: Macromastia is a physically and psychologically distressing condition for adolescents. While reduction mammaplasty is often the best treatment, risk factors for adolescent wound complications remain unclear. This study aims to investigate the impact of obesity and other predictors of postoperative wound complications following adolescent reduction mammaplasty using a national database. METHODS: The 2012-2019 National Surgical Quality Improvement Program Pediatric (NSQIP-P) databases were reviewed to identify primary reduction mammaplasty encounters. World Health Organization Body Mass Index (BMI), alongside patient and case characteristics, were assessed for association for 30-day wound disruption or surgical site complications. Statistical analyses were performed to identify independent predictors for complications and determine a potential BMI cutoff for risk stratification. RESULTS: There were 1215 patients with an average age of 16.6 years. The average BMI was 30.7 kg/m2, and 593 (48.8%) patients were nonobese while 622 (51.2%) were obese. The incidence of complications was 5.27%. Independent predictors of complications included a BMI 35-39.9, BMI > 40, and an American Society of Anesthesiologists (ASA) Classification > 3. A receiver operating characteristic curve determined that a BMI of 34.6 can be a potential cutoff for increased complication risk. CONCLUSIONS: Higher obesity increases risk of wound complications; however, complication rates remain low. A BMI of 34.6 is a potential screening metric for counseling and monitoring patients. Reduction mammaplasty should remain a viable option as it can significantly improve quality of life. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Reliability and predictability of phenotype information from functional connectivity in large imaging datasets.

One of the central objectives of contemporary neuroimaging research is to create predictive models that can disentangle the connection between patterns of functional connectivity across the entire brain and various behavioral traits. Previous studies have shown that models trained to predict behavioral features from the individual's functional connectivity have modest to poor performance. In this study, we trained models that predict observable individual traits (phenotypes) and their corresponding singular value decomposition (SVD) representations - herein referred to as latent phenotypes from resting state functional connectivity. For this task, we predicted phenotypes in two large neuroimaging datasets: the Human Connectome Project (HCP) and the Philadelphia Neurodevelopmental Cohort (PNC). We illustrate the importance of regressing out confounds, which could significantly influence phenotype prediction. Our findings reveal that both phenotypes and their corresponding latent phenotypes yield similar predictive performance. Interestingly, only the first five latent phenotypes were reliably identified, and using just these reliable phenotypes for predicting phenotypes yielded a similar performance to using all latent phenotypes. This suggests that the predictable information is present in the first latent phenotypes, allowing the remainder to be filtered out without any harm in performance. This study sheds light on the intricate relationship between functional connectivity and the predictability and reliability of phenotypic information, with potential implications for enhancing predictive modeling in the realm of neuroimaging research.

Clear neuroimaging margin at the brain-tumor interface is associated with gross total resection and longer survival in non-enhancing diffuse gliomas.

BACKGROUND: This study aimed to determine whether the presence of distinct glioma margins on preoperative imaging is correlated with improved intraoperative identification of tumor-brain interfaces and overall improved surgical outcomes of non-enhancing gliomas. METHODS: This is a retrospective study of all primary glioma resections at our institution between 2000-2020. Tumors with contrast enhancement or with final pathology other than diffuse infiltrative glial neoplasm (WHO II or WHO III) were excluded. Tumors were stratified into two groups: those with distinct radiographical borders between tumor and brain, and those with ill-defined radiographical margins. Multivariate analysis was performed to determine the impact of clear preoperative margins on the primary outcome of gross-total resection. RESULTS: Within the study period, 59 patients met inclusion criteria, of which 31 (53%) had distinct margins. These patients were predominantly younger (37.6 vs. 48.1 years, P=0.007). Tumor and other patient characteristics were similar in both cohorts, including gender, laterality, size, location, tumor type, grade, and surgical adjuncts utilized (P>0.05). Multivariate regression identified that distinct preoperative margins correlated with increased rates of gross total resection (P=0.02). Distinct margins on preoperative neuroimaging also correlated positively with surgeon identification of intra-operative margins (P<0.0001), fewer deaths over the study period (P=0.01), and longer overall survival (P=0.03). CONCLUSIONS: Distinct glioma-parenchyma margins on preoperative imaging are associated with improved surgical resection for diffuse gliomas, as distinct margins may correlate with distinguishable glioma-brain interfaces intraoperatively. Further prospective studies may discover additional clinical uses for these findings.

Association of geographical disparities and segregation in regional treatment facilities for Black patients with aneurysmal subarachnoid hemorrhage in the United States.

Background and objectives: This study investigates geographic disparities in aneurysmal subarachnoid hemorrhage (aSAH) care for Black patients and aims to explore the association with segregation in treatment facilities. Understanding these dynamics can guide efforts to improve healthcare outcomes for marginalized populations. Methods: This cohort study evaluated regional differences in segregation for Black patients with aSAH and the association with geographic variations in disparities from 2016 to 2020. The National Inpatient Sample (NIS) database was queried for admission data on aSAH. Black patients were compared to White patients. Segregation in treatment facilities was calculated using the dissimilarity (D) index. Using multivariable logistic regression models, the regional disparities in aSAH treatment, functional outcomes, mortality, and end-of-life care between Black and White patients and the association of geographical segregation in treatment facilities was assessed. Results: 142,285 Black and White patients were diagnosed with aSAH from 2016 to 2020. The Pacific division (D index = 0.55) had the greatest degree of segregation in treatment facilities, while the South Atlantic (D index = 0.39) had the lowest. Compared to lower segregation, regions with higher levels of segregation (global F test p < 0.001) were associated a lower likelihood of mortality (OR 0.91, 95% CI 0.82-1.00, p = 0.044 vs. OR 0.75, 95% CI 0.68-0.83, p < 0. 001) (p = 0.049), greater likelihood of tracheostomy tube placement (OR 1.45, 95% CI 1.22-1.73, p < 0.001 vs. OR 1.87, 95% CI 1.59-2.21, p < 0.001) (p < 0. 001), and lower likelihood of receiving palliative care (OR 0.88, 95% CI 0.76-0.93, p < 0.001 vs. OR 0.67, 95% CI 0.59-0.77, p < 0.001) (p = 0.029). Conclusion: This study demonstrates regional differences in disparities for Black patients with aSAH, particularly in end-of-life care, with varying levels of segregation in regional treatment facilities playing an associated role. The findings underscore the need for targeted interventions and policy changes to address systemic healthcare inequities, reduce segregation, and ensure equitable access to high-quality care for all patients.

CCK+ Interneurons Contribute to Thalamus-Evoked Feed-Forward Inhibition in the Prelimbic Prefrontal Cortex.

Interneurons in the medial prefrontal cortex (PFC) regulate local neural activity to influence cognitive, motivated, and emotional behaviors. Parvalbumin-expressing (PV+) interneurons are the primary mediators of thalamus-evoked feed-forward inhibition across the mouse cortex, including the anterior cingulate cortex, where they are engaged by inputs from the mediodorsal (MD) thalamus. In contrast, in the adjacent prelimbic (PL) cortex, we find that PV+ interneurons are scarce in the principal thalamorecipient layer 3 (L3), suggesting distinct mechanisms of inhibition. To identify the interneurons that mediate MD-evoked inhibition in PL, we combine slice physiology, optogenetics, and intersectional genetic tools in mice of both sexes. We find interneurons expressing cholecystokinin (CCK+) are abundant in L3 of PL, with cells exhibiting fast-spiking (fs) or non-fast-spiking (nfs) properties. MD inputs make stronger connections onto fs-CCK+ interneurons, driving them to fire more readily than nearby L3 pyramidal cells and other interneurons. CCK+ interneurons in turn make inhibitory, perisomatic connections onto L3 pyramidal cells, where they exhibit cannabinoid 1 receptor (CB1R) mediated modulation. Moreover, MD-evoked feed-forward inhibition, but not direct excitation, is also sensitive to CB1R modulation. Our findings indicate that CCK+ interneurons contribute to MD-evoked inhibition in PL, revealing a mechanism by which cannabinoids can modulate MD-PFC communication.

UCHL1-dependent control of hypoxia-inducible factor transcriptional activity during liver fibrosis.

Liver fibrosis is the excessive accumulation of extracellular matrix proteins that occurs in most types of chronic liver disease. At the cellular level, liver fibrosis is associated with the activation of hepatic stellate cells (HSCs) which transdifferentiate into a myofibroblast-like phenotype that is contractile, proliferative and profibrogenic. HSC transdifferentiation induces genome-wide changes in gene expression that enable the cell to adopt its profibrogenic functions. We have previously identified that the deubiquitinase ubiquitin C-terminal hydrolase 1 (UCHL1) is highly induced following HSC activation; however, the cellular targets of its deubiquitinating activity are poorly defined. Here, we describe a role for UCHL1 in regulating the levels and activity of hypoxia-inducible factor 1 (HIF1), an oxygen-sensitive transcription factor, during HSC activation and liver fibrosis. HIF1 is elevated during HSC activation and promotes the expression of profibrotic mediator HIF target genes. Increased HIF1α expression correlated with induction of UCHL1 mRNA and protein with HSC activation. Genetic deletion or chemical inhibition of UCHL1 impaired HIF activity through reduction of HIF1α levels. Furthermore, our mechanistic studies have shown that UCHL1 elevates HIF activity through specific cleavage of degradative ubiquitin chains, elevates levels of pro-fibrotic gene expression and increases proliferation rates. As we also show that UCHL1 inhibition blunts fibrogenesis in a pre-clinical 3D human liver slice model of fibrosis, these results demonstrate how small molecule inhibitors of DUBs can exert therapeutic effects through modulation of HIF transcription factors in liver disease. Furthermore, inhibition of HIF activity using UCHL1 inhibitors may represent a therapeutic opportunity with other HIF-related pathologies.

A novel expectation-maximization approach to infer general diploid selection from time-series genetic data.

Detecting and quantifying the strength of selection is a main objective in population genetics. Since selection acts over multiple generations, many approaches have been developed to detect and quantify selection using genetic data sampled at multiple points in time. Such time series genetic data is commonly analyzed using Hidden Markov Models, but in most cases, under the assumption of additive selection. However, many examples of genetic variation exhibiting non-additive mechanisms exist, making it critical to develop methods that can characterize selection in more general scenarios. Thus, we extend a previously introduced expectation-maximization algorithm for the inference of additive selection coefficients to the case of general diploid selection, in which heterozygote and homozygote fitnesses are parameterized independently. We furthermore introduce a framework to identify bespoke modes of diploid selection from given data, as well as a procedure for aggregating data across linked loci to increase power and robustness. Using extensive simulation studies, we find that our method accurately and efficiently estimates selection coefficients for different modes of diploid selection across a wide range of scenarios; however, power to classify the mode of selection is low unless selection is very strong. We apply our method to ancient DNA samples from Great Britain in the last 4,450 years, and detect evidence for selection in six genomic regions, including the well-characterized LCT locus. Our work is the first genome-wide scan characterizing signals of general diploid selection.