Mapping dynamic molecular changes in hippocampal subregions after traumatic brain injury through spatial proteomics.

BACKGROUND: Traumatic brain injury (TBI) often results in diverse molecular responses, challenging traditional proteomic studies that measure average changes at tissue levels and fail to capture the complexity and heterogeneity of the affected tissues. Spatial proteomics offers a solution by providing insights into sub-region-specific alterations within tissues. This study focuses on the hippocampal sub-regions, analyzing proteomic expression profiles in mice at the acute (1 day) and subacute (7 days) phases of post-TBI to understand subregion-specific vulnerabilities and long-term consequences. METHODS: Three mice brains were collected from each group, including Sham, 1-day post-TBI and 7-day post-TBI. Hippocampal subregions were extracted using Laser Microdissection (LMD) and subsequently analyzed by label-free quantitative proteomics. RESULTS: The spatial analysis reveals region-specific protein abundance changes, highlighting the elevation of FN1, LGALS3BP, HP, and MUG-1 in the stratum moleculare (SM), suggesting potential immune cell enrichment post-TBI. Notably, established markers of chronic traumatic encephalopathy, IGHM and B2M, exhibit specific upregulation in the dentate gyrus bottom (DG2) independent of direct mechanical injury. Metabolic pathway analysis identifies disturbances in glucose and lipid metabolism, coupled with activated cholesterol synthesis pathways enriched in SM at 7-Day post-TBI and subsequently in deeper DG1 and DG2 suggesting a role in neurogenesis and the onset of recovery. Coordinated activation of neuroglia and microtubule dynamics in DG2 suggest recovery mechanisms in less affected regions. Cluster analysis revealed spatial variations post-TBI, indicative of dysregulated neuronal plasticity and neurogenesis and further predisposition to neurological disorders. TBI-induced protein upregulation (MUG-1, PZP, GFAP, TJP, STAT-1, and CD44) across hippocampal sub-regions indicates shared molecular responses and links to neurological disorders. Spatial variations were demonstrated by proteins dysregulated in both or either of the time-points exclusively in each subregion (ELAVL2, CLIC1 in PL, CD44 and MUG-1 in SM, and SHOC2, LGALS3 in DG). CONCLUSIONS: Utilizing advanced spatial proteomics techniques, the study unveils the dynamic molecular responses in distinct hippocampal subregions post-TBI. It uncovers region-specific vulnerabilities and dysregulated neuronal processes, and potential recovery-related pathways that contribute to our understanding of TBI's neurological consequences and provides valuable insights for biomarker discovery and therapeutic targets.

Association Between Diagnosis-to-Limb Revascularization Time and Clinical Outcomes in Outpatients With Chronic Limb-Threatening Ischemia: Insights From the CLIPPER Cohort.

BACKGROUND: The extent and consequences of ischemia in patients with chronic limb-threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis-to-limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. METHODS AND RESULTS: In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk-adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time <30 days, there was no association between D2L time and all-cause death or major lower extremity amputation. However, among patients with D2L time >30 days, each additional 10-day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014-1.036]). There was no association between D2L time and all-cause death. CONCLUSIONS: A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

The Role of IVC Filters in the Management of Acute Pulmonary Embolism.

Venous thromboembolism (VTE), comprising deep venous thrombosis (DVT) and pulmonary embolism (PE), is a prevalent cardiovascular condition, ranking third globally after myocardial infarction and stroke. The risk of VTE rises with age, posing a growing concern in aging populations. Acute PE, with its high morbidity and mortality, emphasizes the need for early diagnosis and intervention. This review explores prognostic factors for acute PE, categorizing it into low-risk, intermediate-risk, and high-risk based on hemodynamic stability and right ventricular strain. Timely classification is crucial for triage and treatment decisions. In the contemporary landscape, low-risk PE patients are often treated with Direct Oral Anticoagulants (DOACS) and rapidly discharged for outpatient follow-up. Intermediate- and high-risk patients may require advanced therapies, such as systemic thrombolysis, catheter-directed thrombolysis, mechanical thrombectomy, and IVC filter placement. The latter, particularly IVC filters, has witnessed increased usage, with evolving types like retrievable and convertible filters. However, concerns arise regarding complications and the need for timely retrieval. This review delves into the role of IVC filters in acute PE management, addressing their indications, types, complications, and retrieval considerations. The ongoing debate surrounding IVC filter use, especially in patients with less conventional indications, reflects the need for further research and data. Despite complications, recent studies suggest that clinically significant issues are rare, sparking discussions on the appropriate and safe utilization of IVC filters in select PE cases. The review concludes by highlighting current trends, gaps in knowledge, and potential avenues for advancing the role of IVC filters in future acute PE management.

Implementation of a Clinical Vessel Wall MR Imaging Program at an Academic Medical Center.

BACKGROUND AND PURPOSE: The slow adoption of new advanced imaging techniques into clinical practice has been a long-standing challenge. Principles of implementation science and the reach, effectiveness, adoption, implementation, maintenance (RE-AIM) framework were used to build a clinical vessel wall imaging program at an academic medical center. MATERIALS AND METHODS: Six phases for implementing a clinical vessel wall MR imaging program were contextualized to the RE-AIM framework. Surveys were designed and distributed to MR imaging technologists and clinicians. Effectiveness was measured by surveying the perceived diagnostic value of vessel wall imaging among MR imaging technologists and clinicians, trends in case volumes in the clinical vessel wall imaging examination, and the number of coauthored vessel wall imaging-focused publications and abstracts. Adoption and implementation were measured by surveying stakeholders about workflow. Maintenance was measured by surveying MR imaging technologists on the value of teaching materials and online tip sheets. The Integration dimension was measured by the number of submitted research grants incorporating vessel wall imaging protocols. Feedback during the implementation phases and solicited through the survey is qualitatively summarized. Quantitative results are reported using descriptive statistics. RESULTS: Six phases of the RE-AIM framework focused on the following: 1) determining patient and disease representation, 2) matching resource availability and patient access, 3) establishing vessel MR wall imaging (VWI) expertise, 4) forming interdisciplinary teams, 5) iteratively refining workflow, and 6) integrating for maintenance and scale. Survey response rates were 48.3% (MR imaging technologists) and 71.4% (clinicians). Survey results showed that 90% of the MR imaging technologists agreed that they understood how vessel wall MR imaging adds diagnostic value to patient care. Most clinicians (91.3%) reported that vessel wall MR imaging results changed their diagnostic confidence or patient management. Case volumes of clinical vessel wall MR imaging performed from 2019 to 2022 rose from 22 to 205 examinations. Workflow challenges reported by MR imaging technologists included protocoling examinations and scan length. Feedback from ordering clinicians included the need for education about VWI indications, limitations, and availability. During the 3-year implementation period of the program, the interdisciplinary teams coauthored 27 publications and abstracts and submitted 13 research grants. CONCLUSIONS: Implementation of a clinical imaging program can be successful using the principles of the RE-AIM framework. Through iterative processes and the support of interdisciplinary teams, a vessel wall MR imaging program can be integrated through a dedicated clinical pipeline, add diagnostic value, support educational and research missions at an academic medical center, and become a center for excellence.

Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease.

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.

Functionally mediated cranial allometry evidenced in a genus of rock-wallabies.

In assessments of skeletal variation, allometry (disproportionate change of shape with size) is often corrected to examine size-independent variation for hypotheses relating to function. However, size-related trade-offs in functional demands may themselves be an underestimated driver of mammalian cranial diversity. Here, we use geometric morphometrics alongside dental measurements to assess craniodental allometry in the rock-wallaby genus Petrogale (all 17 species, 370 individuals). We identified functional aspects of evolutionary allometry that can be both extensions of, and correlated negatively with, static or ontogenetic allometric patterns. Regarding constraints, larger species tended to have relatively smaller braincases and more posterior orbits, the former of which might represent a constraint on jaw muscle anatomy. However, they also tended to have more anterior dentition and smaller posterior zygomatic arches, both of which support the hypothesis of relaxed bite force demands and accommodation of different selective pressures that favour facial elongation. By contrast, two dwarf species had stouter crania with divergent dental adaptations that together suggest increased relative bite force capacity. This likely allows them to feed on forage that is mechanically similar to that consumed by larger relatives. Our results highlight a need for nuanced considerations of allometric patterns in future research of mammalian cranial diversity.

Menstrual cup use and intrauterine device expulsion in a copper intrauterine device randomized trial.

OBJECTIVE: To evaluate menstrual cup use and intrauterine device (IUD) expulsion. STUDY DESIGN: We performed a secondary analysis of a 3-year contraceptive efficacy trial comparing two copper 380 mm2 IUDs. Investigators randomized participants approximately 1:4 to the TCu380A or NTCu380-Mini IUD. Approximately 12 months after enrollment began, we advised participants against menstrual cup use due to observed IUD expulsions in cup users. We evaluated IUD expulsion (including spontaneous partial and complete expulsion and accidental self-removal) at 12 and 36 months. We used multivariable logistic regression to evaluate IUD expulsion by age, baseline menstrual volume, body mass index, IUD type, menstrual cup use, parity, and uterine length. RESULTS: This analysis included 1046 participants (203 TCu380A and 843 NTCu380-Mini), with 879 (84.0%) nulliparas. Through 12 and 36 months, expulsion occurred in 74 (7.1%, 95% CI 5.5-8.6%) and 133 (12.7%, 95% CI 10.7-14.7%) participants, respectively. Overall, 250 (23.9%) reported menstrual cup use. More menstrual cup users than non-users experienced expulsion through 12 months (32/203 [15.8%] vs. 42/843 [5.0%]) and 36 months (58/250 [23.2%] vs. 75/796 [9.4%]). Through 36 months, NTCu380-Mini menstrual cup users had higher expulsion odds, while TCu380A cup users did not. Menstrual cup users more frequently experienced accidental self-removal than non-users in participants using the TCu380A (3/53 [5.7%] vs. 0/150 [0.0%]) and the NTCu380-Mini (20/197 [10.2%] vs. 7/646 [1.1%]). In multivariable regression, we found increased odds of expulsion through 36 months in participants using menstrual cups with the NTCu380-Mini (aOR 3.13, 95% CI 1.16-8.46) and <25 years (aOR 1.59, 95% CI 1.07-2.34). CONCLUSIONS: We found higher odds of IUD expulsion with menstrual cup and concurrent NTCu380-Mini IUD use over 36 months of use, but not with concurrent TCu380A IUD use. Menstrual cup users experienced higher likelihood of accidental self-removal regardless of IUD type. IMPLICATIONS: Menstrual cup and NTCu380-Mini use may increase IUD expulsion risk and may increase accidental self-removal risk with TCu380A and NTCu380-Mini use. Clinicians should advise patients of these risks and consider warning patients using an IUD shaped like the NTCu380-Mini (Nova-T frames) of expulsion risk with menstrual cup use.

Tracing the path of disruption: 13C isotope applications in traumatic brain injury-induced metabolic dysfunction.

Cerebral metabolic dysfunction is a critical pathological hallmark observed in the aftermath of traumatic brain injury (TBI), as extensively documented in clinical investigations and experimental models. An in-depth understanding of the bioenergetic disturbances that occur following TBI promises to reveal novel therapeutic targets, paving the way for the timely development of interventions to improve patient outcomes. The 13C isotope tracing technique represents a robust methodological advance, harnessing biochemical quantification to delineate the metabolic trajectories of isotopically labeled substrates. This nuanced approach enables real-time mapping of metabolic fluxes, providing a window into the cellular energetic state and elucidating the perturbations in key metabolic circuits. By applying this sophisticated tool, researchers can dissect the complexities of bioenergetic networks within the central nervous system, offering insights into the metabolic derangements specific to TBI pathology. Embraced by both animal studies and clinical research, 13C isotope tracing has bolstered our understanding of TBI-induced metabolic dysregulation. This review synthesizes current applications of isotope tracing and its transformative potential in evaluating and addressing the metabolic sequelae of TBI.

Biochemical and Structural Studies of the Carminomycin 4-O-Methyltransferase DnrK.

Structural and functional studies of the carminomycin 4-O-methyltransferase DnrK are described, with an emphasis on interrogating the acceptor substrate scope of DnrK. Specifically, the evaluation of 100 structurally and functionally diverse natural products and natural product mimetics revealed an array of pharmacophores as productive DnrK substrates. Representative newly identified DnrK substrates from this study included anthracyclines, angucyclines, anthraquinone-fused enediynes, flavonoids, pyranonaphthoquinones, and polyketides. The ligand-bound structure of DnrK bound to a non-native fluorescent hydroxycoumarin acceptor, 4-methylumbelliferone, along with corresponding DnrK kinetic parameters for 4-methylumbelliferone and native acceptor carminomycin are also reported for the first time. The demonstrated unique permissivity of DnrK highlights the potential for DnrK as a new tool in future biocatalytic and/or strain engineering applications. In addition, the comparative bioactivity assessment (cancer cell line cytotoxicity, 4E-BP1 phosphorylation, and axolotl embryo tail regeneration) of a select set of DnrK substrates/products highlights the ability of anthracycline 4-O-methylation to dictate diverse functional outcomes.

Nearshore wave buoy data from southeastern Australia for coastal research and management.

Wind wave observations in shallow coastal waters are essential for calibrating, validating, and improving numerical wave models to predict sediment transport, shoreline change, and coastal hazards such as beach erosion and oceanic inundation. Although ocean buoys and satellites provide near-global coverage of deep-water wave conditions, shallow-water wave observations remain sparse and often inaccessible. Nearshore wave conditions may vary considerably alongshore due to coastline orientation and shape, bathymetry and islands. We present a growing dataset of in-situ wave buoy observations from shallow waters (<35 m) in southeast Australia that comprises over 7,000 days of measurements at 20 locations. The moored buoys measured wave conditions continuously for several months to multiple years, capturing ambient and storm conditions in diverse settings, including coastal hazard risk sites. The dataset includes tabulated time series of spectral and time-domain parameters describing wave height, period and direction at half-hourly temporal resolution. Buoy displacement and wave spectra data are also available for advanced applications. Summary plots and tables describing wave conditions measured at each location are provided.

Telemedicine and Depression Screening After the Start of the COVID-19 Pandemic.

This cohort study investigates the probability of depression screening by visit type and by patient demographic characteristics in a large health system during the early COVID-19 pandemic.

Understanding the mechanical behavior of intrauterine devices during simulated removal.

OBJECTIVE: To evaluate differences based on intrauterine device (IUD) frame geometry in force, and stress, and strain at the stem/arms junction during simulated IUD removal. STUDY DESIGN: We manufactured injection-molded frame models for three Nova-T IUDs (Mirena [model M]; Liletta [model L]; Kyleena [model K]) and a Tatum-T IUD (Paragard [model P]) at two-times scaling. We created a custom fixture to simulate the uterus and used a screw-driven machine to pull models at various displacement rates through the 10 cm fixture cavity to measure force and strain and calculate stress at the IUD stem/arms junction. We tested models at 30 mm/min and higher displacement rates for exploratory analyses. We used Mann-Whitney U test for statistical testing. RESULTS: We completed testing at 30 mm/min using five of each Nova-T model and nine model P samples. Resistance against the cavity walls created significantly more force on model P (11.83, interquartile range [IQR] 11.61-12.31) than any Nova-T model samples (p < 0.001). The smaller model K created slightly more median stress (MPa) than the larger model M (0.36 [IQR 0.33-0.38] and 0.79 [IQR 0.76-0.80], respectively, p = 0.008); model P samples generated significantly more median stress than other models (1.70 [IQR 1.67-1.77], p < 0.001). Strain plots demonstrated permanent deformation for some samples during IUD removal simulation. We tested 20 samples at various higher displacement rates up to 2500 mm/min, with stress notably increasing for model P samples with increasing rates. No fractures occurred. CONCLUSIONS: Force and stress at the stem/arms junction are higher with Tatum-T-shaped compared to Nova-T-shaped IUD models under the same testing conditions, and a higher speed of extraction causes more stress. IMPLICATIONS: Sharp corners create vulnerability under static and fatigue loading in structural components due to increased local stresses. Our findings suggest that IUDs with Tatum-T frames should be removed slowly to minimize the stress at the stem/arms junction. Future studies can provide more information if performed with commercially available products.

Oral iron therapy: Current concepts and future prospects for improving efficacy and outcomes.

Iron deficiency (ID) and iron-deficiency anaemia (IDA) are global public health concerns, most commonly afflicting children, pregnant women and women of childbearing age. Pathological outcomes of ID include delayed cognitive development in children, adverse pregnancy outcomes and decreased work capacity in adults. IDA is usually treated by oral iron supplementation, typically using iron salts (e.g. FeSO4 ); however, dosing at several-fold above the RDA may be required due to less efficient absorption. Excess enteral iron causes adverse gastrointestinal side effects, thus reducing compliance, and negatively impacts the gut microbiome. Recent research has sought to identify new iron formulations with better absorption so that lower effective dosing can be utilized. This article outlines emerging research on oral iron supplementation and focuses on molecular mechanisms by which different supplemental forms of iron are transported across the intestinal epithelium and whether these transport pathways are subject to regulation by the iron-regulatory hormone hepcidin.

Systematic Implementation of Effective Quality Assurance Processes for the Assessment of Radiation Target Volumes in Head and Neck Cancer.

PURPOSE: Significant heterogeneity exists in clinical quality assurance (QA) practices within radiation oncology departments, with most chart rounds lacking prospective peer-reviewed contour evaluation. This has the potential to significantly affect patient outcomes, particularly for head and neck cancers (HNC) given the large variance in target volume delineation. With this understanding, we incorporated a prospective systematic peer contour-review process into our workflow for all patients with HNC. This study aims to assess the effectiveness of implementing prospective peer review into practice for our National Cancer Institute Designated Cancer Center and to report factors associated with contour modifications. METHODS AND MATERIALS: Starting in November 2020, our department adopted a systematic QA process with real-time metrics, in which contours for all patients with HNC treated with radiation therapy were prospectively peer reviewed and graded. Contours were graded with green (unnecessary), yellow (minor), or red (major) colors based on the degree of peer-recommended modifications. Contours from November 2020 through September 2021 were included for analysis. RESULTS: Three hundred sixty contours were included. Contour grades were made up of 89.7% green, 8.9% yellow, and 1.4% red grades. Physicians with >12 months of clinical experience were less likely to have contour changes requested than those with <12 months (8.3% vs 40.9%; P < .001). Contour grades were significantly associated with physician case load, with physicians presenting more than the median number of 50 cases having significantly less modifications requested than those presenting <50 (6.7% vs 13.3%; P = .013). Physicians working with a resident or fellow were less likely to have contour changes requested than those without a trainee (5.2% vs 12.6%; P = .039). Frequency of major modification requests significantly decreased over time after adoption of prospective peer contour review, with no red grades occurring >6 months after adoption. CONCLUSIONS: This study highlights the importance of prospective peer contour-review implementation into systematic clinical QA processes for HNC. Physician experience proved to be the highest predictor of approved contours. A growth curve was demonstrated, with major modifications declining after prospective contour review implementation. Even within a high-volume academic practice with subspecialist attendings, >10% of patients had contour changes made as a direct result of prospective peer review.

Clinical correlates of CT imaging-derived phenotypes among lean and overweight patients with hepatic steatosis.

The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ - 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients-lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p < 0.0001). Ten phenotypes were significant in the PheWAS, including chronic kidney disease, renal failure, and cardiovascular disease. Hepatic steatosis was found to be associated with cardiovascular, kidney, and metabolic conditions, separate from overweight BMI.

Effects of Drug Conjugation on the Biological Activity of Single-Chain Nanoparticles.

The field of single-chain nanoparticles (SCNPs) continues to mature, and an increasing range of reports have emerged that explore the application of these small nanoparticles. A key application for SCNPs is in the field of drug delivery, and recent work suggests that SCNPs can be readily internalized by cells. However, limited attention has been directed to the delivery of small-molecule drugs using SCNPs. Moreover, studies on the physicochemical effects of drug loading on SCNP performance is so far missing, despite the accepted view that such small nanoparticles should be significantly affected by the drug loading content. To address this gap, we prepared a library of SCNPs bearing different amounts of a covalently conjugated therapeutic drug-sulfasalazine (SSZ). We evaluated the impact of the conjugated drug loading on both the synthesis and biological activity of SCNPs on pancreatic cancer cells (AsPC-1). Our results reveal that covalent drug conjugation to the side chains of the SCNP polymer precursor interferes with chain collapse and cross-linking, which demands optimization of reaction conditions to reach high degrees of cross-linking efficiencies. Small-angle neutron scattering and diffusion-ordered spectroscopy nuclear magnetic resonance (DOSY NMR) analyses reveal that SCNPs with a higher drug loading display larger sizes and looser structures, as well as increased hydrophobicity associated with a higher SSZ content. Increased SSZ loading led to reduced cellular uptake when assessed in vitro, whereby SCNP aggregation on the surface of AsPC-1 cells led to reduced toxicity. This work highlights the effects of drug loading on the drug delivery efficiency and biological behavior of SCNPs.

Does Sponsorship Promote Equity in Career Advancement in Academic Medicine? A Scoping Review.

Sponsorship describes a set of actions wherein an influential champion (sponsor) uses their position to actively support a colleague's career by helping them gain visibility, recognition, and/or positions. There is growing awareness of the importance of sponsorship for career advancement in academic medicine, particularly for women and those who are historically underrepresented and excluded in medicine (UIM). This scoping review examines the current landscape of evidence, and knowledge gaps, on sponsorship as it relates to career advancement in academic medicine for women and UIM faculty. We searched peer-reviewed literature in PubMed, Embase, and Web of Science (WoS) over the past 50 years (from 1973 through July 2023). Sixteen studies were included in the final review. We found relative consensus on sponsorship definition and value to career advancement. Heterogeneity in study design limited our ability to directly compare study outcomes. All included studies focused on gender differences in sponsorship: two of four quantitative studies found men were more likely to receive sponsorship, one reported no gender differences, and one was insufficiently powered. All but one of the qualitative studies reported gender differences, with women less likely to access or be identified for sponsorship. The mixed-methods studies suggested sponsorship may vary by career stage. Only two studies analyzed sponsorship for UIM populations. The existing data are inconclusive regarding best ways to measure and assess sponsorship, what institutional support (e.g., structured programs, formal recognition, or incentives for sponsorship) should look like, and at what career stage sponsorship is most important. Addressing this knowledge gap will be critically important for understanding what sponsorship best practices, if any, should be used to promote equity in career advancement in academic medicine. We advocate for commitment at the institutional and national levels to develop new infrastructure for transparently and equitably supporting women and UIM in career advancement.

Machine learning of dissection photographs and surface scanning for quantitative 3D neuropathology.

We present open-source tools for 3D analysis of photographs of dissected slices of human brains, which are routinely acquired in brain banks but seldom used for quantitative analysis. Our tools can: (i) 3D reconstruct a volume from the photographs and, optionally, a surface scan; and (ii) produce a high-resolution 3D segmentation into 11 brain regions per hemisphere (22 in total), independently of the slice thickness. Our tools can be used as a substitute for ex vivo magnetic resonance imaging (MRI), which requires access to an MRI scanner, ex vivo scanning expertise, and considerable financial resources. We tested our tools on synthetic and real data from two NIH Alzheimer's Disease Research Centers. The results show that our methodology yields accurate 3D reconstructions, segmentations, and volumetric measurements that are highly correlated to those from MRI. Our method also detects expected differences between post mortem confirmed Alzheimer's disease cases and controls. The tools are available in our widespread neuroimaging suite "FreeSurfer" ( https://surfer.nmr.mgh.harvard.edu/fswiki/PhotoTools ).