International Medical Graduates Matching Into U.S. General Surgery Residency: 30-Year Match Trends.

INTRODUCTION: International medical graduates (IMGs) make up a small but important percentage of the U.S. surgical workforce. Detailed and contemporary studies on IMGs matching into U.S. general surgery residency positions are lacking. Our objective was to study these trends over a 30-y period. METHODS: We utilized the National Resident Matching Program reports from 1994 to 2023 to analyze the trends of U.S. M.D. seniors, D.O. seniors, and U.S. citizen and non-U.S. citizen IMGs matching into first-year categorical and preliminary general surgery residency positions. The percent of positions filled were calculated and trended over time using linear regression, where ß coefficient estimated the percentage of annual change in matched positions, and the R2 coefficient measured the amount of variance explained (perfect regression R2 = 1.0). RESULTS: Over the last 30 y, IMG match percentages have increased for both categorical (ß = 0.218%, R2 = 0.49, P < 0.001) and preliminary (ß = 0.705%, R2 = 0.76, P < 0.001) general surgery positions, with a greater increase in preliminary positions (ß = 0.705%). The percentage of positions filled by M.D. U.S. seniors in categorical positions has steadily decreased over the 30-y period (ß = -0.625%, R2 = 0.79, P < 0.001), and this decrease has largely occurred with a concurrent greater increase in U.S. D.O. seniors match percentage rates (ß = 0.430%, R2 = 0.64, P < 0.001), rather than IMGs (ß = 0.218%). Allopathic M.D. U.S. seniors preliminary match percentages have steadily decreased at the steepest rate (ß = -0.927%, R2 = 0.80, P < 0.001). In categorical positions, non-U.S. citizen IMGs' match percentages (ß = 0.069%, R2 = 0.204, P = 0.012) increased at a slightly slower rate than U.S. citizen IMGs (ß = 0.149%, R2 = 0.607, P < 0.001). In preliminary positions, non-U.S. citizen IMGs' match percentages (ß = 0.33%, R2 = 0.478, P < 0.001) increased at a similar rate as U.S. citizen IMGs (ß = 0.375%, R2 = 0.823, P < 0.0.001). In the 2023 National Resident Matching Program match, U.S. citizen and non-U.S. citizen IMGs together made up 10.3% of the categorical and 44.5% of the preliminary general surgery positions that were filled. For categorical positions in 2023, there was no major difference between positions matched by U.S. citizen IMGs (4.62%) and non-U.S. citizen IMGs (5.72%); on the other hand, for preliminary positions in 2023, non-U.S. citizen IMGs (31.96%) filled 2.5× times the number of positions as U.S. citizen IMGs (12.54%). CONCLUSIONS: Over the last 30 y, U.S. allopathic M.D. seniors matching into categorical general surgery positions have steadily decreased, while both U.S. osteopathic D.O. seniors and IMGs matching have increased. These data have important implications for the future U.S. surgical workforce.

Comparison of academic productivity and funding support between United States and international medical graduate vascular surgeons.

OBJECTIVE: The demand for vascular surgeons in the United States stands to far exceed the current supply. International medical graduates (IMGs) are not only vital to meeting the country's growing health care needs, but also help to advance clinical research and medical education in the field of vascular surgery. Nearly 17% of practicing vascular surgeons in the United States are IMGs, yet little is known about their relative contributions to academic vascular surgery. Our study aims to compare the academic profiles and funding support for IMG vascular surgeons to that of their US medical graduate (USMG) counterparts. METHODS: A cross-sectional study was performed on all IMG and USMG academic vascular surgeons practicing in US-based hospitals with vascular surgery residency and/or fellowship programs. In addition to the baseline surgeon characteristics, academic profiles and research output were also collected. Furthermore, the National Institutes of Health (NIH) research reporting tool and open payments database were queried for any funding/payments to surgeons in both groups. Matching for year of vascular surgery training program graduation was performed where appropriate. RESULTS: A total of 908 academic vascular surgeons were included; 759 (83.6%) were USMGs and 149 (16.4%) were IMGs. The median year of graduation was comparable between the two groups, but USMGs had a significantly higher proportion of female surgeons (23.6% vs 10.7%; P = .0003). There were no significant differences in the academic profiles and leadership positions between the two groups. Although research productivity is similar between the two groups, IMG surgeons were more likely to have first or senior-authorship papers (47.1% vs 37.5%; P < .001). Additionally, faculty departments chaired/cheifed by a USMG were less likely to be staffed with IMG vascular surgeons (1.6 surgeons vs 3.1 surgeons; P < .0001). Following grant analysis, USMG surgeons received more NIH R01 grants (5.7% vs 1.3%; P = .026). R01-funded surgeons had significantly greater research output by number of publications (121.0 vs 47.5), citations (3872 vs 938), H-index (32.0 vs 17.5), and average journal impact factor (>10: 86.7% vs 33.3%) (all P < .001). CONCLUSIONS: The efforts to further diversify vascular surgery are vital to better serving an increasingly diverse US population, amid growing disparities in health care. Although IMGs account for a minority of academic vascular surgeons, and contribute significantly to their published research, they had less NIH R01 funding, warranting further investigation.

Characterization of IMG Microglial Cell Line as a Valuable In Vitro Tool for NLRP3 Inflammasome Studies.

Microglial cells constantly surveil the cerebral microenvironment and become activated following injury and disease to mediate inflammatory responses. The nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) inflammasome, which is abundantly expressed in microglial cells, plays a key role in these responses as well as in the development of many neurological disorders. Microglial cell lines are a valuable tool to study the causes and possible treatments for neurological diseases which are linked to inflammation. Here, we investigated whether the mouse microglial cell line IMG is suitable to study NLRP3 inflammasome by incubating cells with different concentrations of NLRP3 inflammasome priming and activating agents lipopolysaccharide (LPS) and ATP, respectively, and applying short (4 h) or long (24 h) LPS incubation times. After short LPS incubation, the mRNA levels of most pro-inflammatory and NLRP3 inflammasome-associated genes were more upregulated than after long incubation. Moreover, the combination of higher LPS and ATP concentrations with short incubation time resulted in greater levels of active forms of caspase-1 and interleukin-1 beta (IL-1ß) proteins than low LPS and ATP concentrations or long incubation time. We also demonstrated that treatment with NLRP3 inflammasome inhibitor glibenclamide suppressed NLRP3 inflammasome activation in IMG cells, as illustrated by the downregulation of gasdermin D N-fragment and mature caspase-1 and IL-1ß protein levels. In addition, we conducted similar experiments with primary microglial cells and BV-2 cell line to determine the similarities and differences in their responses. Overall, our results indicate that IMG cell line could be a valuable tool for NLRP3 inflammasome studies. In IMG cells, 4-h incubation with lipopolysaccharide (LPS) induces a stronger upregulation of NLRP3 inflammasome-associated pro-inflammatory genes compared to 24-h incubation. NLRP3 inflammasome is robustly activated only after the addition of 3 mM of ATP following short LPS incubation time.

Regenerative Potential of Granulocyte Colony-Stimulating Factor Immobilized by Using Electron-Beam Synthesis Nanotechnology in an Experimental Model of Ovarian Reserve Depletion.

The pharmacological activity of granulocyte CSF (G-CSF) immobilized using electron-beam synthesis nanotechnology (imG-CSF) was evaluated in an experimental model of ovarian reserve depletion. The effectiveness of the drug was compared with that of its unmodified form. Depletion of the ovarian follicular pool in female Sprague-Dawley rats was caused by a single intravenous injection of the antitumor drug etoposide in the maximum tolerated dose. The effectiveness of the studied drugs was assessed by serum concentration of anti-Mullerian hormone (AMH) measured by ELISA and by the number of primordial, two-layer, multilayer, and atretic follicles counted on serial sections of the ovaries (5-µm thick; through the entire organ) stained with hematoxylin and eosin. It was found that imG-CSF prevents depletion of the ovarian reserve in the model used, which was confirmed by high AMH concentration and higher numbers of primordial, two- and multilayer follicles in comparison with the corresponding parameters in the control (etoposide), and by a decrease in the severity of atretic processes. Unmodified form of the drug demonstrated lower efficiency.

Bone marrow-derived inducible microglia-like cells ameliorate motor function and survival in a mouse model of amyotrophic lateral sclerosis.

BACKGROUND AIMS: Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease. Neuroinflammation in the spinal cord plays a pivotal role in the pathogenesis of ALS, and microglia are involved in neuroinflammation. Microglia mainly have two opposite phenotypes involving cytotoxic and neuroprotective properties, and neuroprotective microglia are expected to be a novel application for the treatment of ALS. Therefore, to establish a clinically applicable therapeutic method using neuroprotective microglia, the authors investigated the effect of inducing neuroprotective microglia-like cells from bone marrow for transplantation into ALS model mice. METHODS: Bone marrow-derived mononuclear cells were isolated from green fluorescent protein mice and cultured using different protocols of cytokine treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. Cells with a high potency of proliferation and differentiation into microglia were evaluated by gene analysis, flow cytometry and direct neuroprotective effects in vitro. These cells were named bone marrow-derived inducible microglia-like (BM-iMG) cells and transplanted into the spinal cords of ALS model mice, and behavioral tests, immunohistochemistry and gene expression profiling were performed. RESULTS: Three-day GM-CSF and 4-day GM-CSF + IL-4 stimulations were most effective in inducing BM-iMG cells from the bone marrow. Transplantation of BM-iMG cells improved motor function, prolonged survival and suppressed neuronal cell death, astrogliosis and microgliosis in the spinal cords of ALS mice. Moreover, neuroprotective genes such as Arg1 and Mrc1 were upregulated, whereas pro-inflammatory genes such as Nos2 and Il6 were downregulated. CONCLUSIONS: Intraspinal transplantation of BM-iMG cells demonstrated therapeutic effects in a mouse model of ALS. Further studies and clinical applications in patients with ALS are expected in the future.

Doctors on the move 2: a qualitative study on the social integration of middle eastern physicians following their migration to Germany.

BACKGROUND: The integration of immigrating physicians has become a challenge for many societies and health care systems worldwide. Facilitating the integration process may benefit both the uptaking country and the immigrating physicians. Previous studies have approached this problem from a system integration perspective. The present study explores the degree of social integration of an exemplary group of Middle Eastern physicians following their migration to Germany from an individual perspective. METHODS: Based on social constructivist epistemology, a series of fifteen interviews and two focus groups with immigrated Middle Eastern physicians (n = 23, purposively sampled) were conducted between 2017 and 2020 in Germany. The audio recordings were transcribed, translated into English and analysed deductively based on Esser's model of social integration, consisting of four dimensions: acculturation, positioning, interaction and identification. RESULTS: The social integration of the participants showed a multifaceted picture. The early phase was characterized by disorientation and trial and error. Cultural differences were of major importance. Acculturation was facilitated by German language acquisition and increased over time, although some cultural difficulties remained. Professional positioning was facilitated by the need for physicians and a relatively low-hurdle relicensing procedure. Interaction and identification depended on the efforts of the individual physicians. CONCLUSIONS: This study provides a comprehensive picture of the individual social integration of Middle Eastern physicians in Germany. Language and cultural adaptation are identified as being of primary importance. Social integration can be facilitated through orientation programmes or cross-cultural training that benefits the uptaking countries as well as the immigrating physicians.

Iron potentiates microglial interleukin-1ß secretion induced by amyloid-ß.

Alzheimer's disease (AD) is characterized by accumulation of amyloid-beta (Aß) senile plaques in patients' brain tissues. Elevated levels of interleukin-1beta (IL-1ß) have been identified in cerebrospinal fluid of living AD patients and in animal models of AD. Increased expression of IL-1ß and iron accumulation have been identified in microglial cells that cluster around amyloid plaques in AD mouse models and post-mortem brain tissues of AD patients. The goals of this study were to determine the effects of Aß on the secretion of IL-1ß by microglial cells and whether iron status influences this pro-inflammatory signaling cue. Immortalized microglial (IMG) cells were incubated with Aß with or without iron. qRT-PCR and western blot analyses showed that Aß induces biosynthesis of IL-1ß by IMG cells. IMG cells secrete the mature form of IL-1ß in a caspase 1-dependent manner. Incubation with iron provoked a greater pro-inflammatory response. Inhibition of the iron transporter divalent metal transporter 1 protected IMG cells against Aß-induced inflammation. Potentiation of Aß-elicited IL-1ß induction by iron was also antagonized by ROS inhibitors, supporting the model that divalent metal transporter 1-mediated iron loading and subsequent increase in ROS contribute to the inflammatory effects of Aß in microglia. Immunoblotting and immunofluorescence microscopy indicate that iron enhances Aß activation of NF-κB signaling to promote IL-1ß synthesis. These results support the hypothesis that Aß stimulates IL-1ß expression by activating NF-κB signaling in microglia cells. Most importantly, iron appears to exacerbate the pro-inflammatory effects of Aß to increase IL-1ß levels.

Improved Methodology for Sensitive and Rapid Quantitative Proteomic Analysis of Adult-Derived Mouse Microglia: Application to a Novel In Vitro Mouse Microglial Cell Model.

Microglia, as the resident brain immune cells, can exhibit a broad range of activation phenotypes, which have been implicated in a multitude of central nervous system disorders. Current widely studied microglial cell lines are mainly derived from neonatal rodent brain that can limit their relevance to homeostatic function and disease-related neuroimmune responses in the adult brain. Recently, an adult mouse brain-derived microglial cell line has been established; however, a comprehensive proteome dataset remains lacking. Here, an optimization method for sensitive and rapid quantitative proteomic analysis of microglia is described that involves suspension trapping (S-Trap) for efficient and reproducible protein extraction from a limited number of microglial cells expected from an adult mouse brain (≈300 000). Using a 2-h gradient on a 75-cm UPLC column with a modified data dependent acquisition method on a hybrid quadrupole-Orbitrap mass spectrometer, 4855 total proteins have been identified where 4698 of which are quantifiable by label-free quantitation with a median and average coefficient of variation (CV) of 6.7% and 10.6%, respectively. This dataset highlights the high depth of proteome coverage and related quantitation precision of the adult-derived microglial proteome including proteins associated with several key pathways related to immune response. Data are available via ProteomeXchange with identifier PXD012006.

Are You Applying to More Than One Specialty?

Although the majority of U.S. medical students predominantly apply to only one specialty, some apply to more than one. When it comes to emergency medicine (EM), applicants may apply to additional specialties due to several reasons: being international medical graduates as well as their inability to make a decision regarding the choice of specialty, fear from the growing competitiveness of EM, or the desire to stay in a specific geographic area. Accordingly, in this article we aim to guide medical students through the process of applying to more than one specialty, including using the Electronic Residency Application Service application, writing a personal statement, getting letters of recommendation, and an Early Match. Moreover, we elaborate on the effect of applying to more than one specialty on a student's application to a residency in EM.

American Cleft-Palate Craniofacial Association Annual Meeting: International Medical Graduate's Perspective as a First-Time Attendee.

In the United States, plastic surgery continues to be one of the most competitive fields to match into for medical graduates. However, the process is even more difficult for international medical graduates (IMGs) mostly due to their unknown academic backgrounds and unfamiliarity with US health-care system. While many IMGs pursue of research to publish articles in peer-reviewed journals and obtain letters of recommendations as a means to prove one's potential, networking with well-known plastic surgeons in US plastic surgery programs via national meetings is of utmost importance. These conferences provide the perfect opportunity to learn about the multidisciplinary US health-care system, expand one's network of mentors and colleagues, and demonstrate one's research experience. This article describes my experience as a first-time attendee in the American Cleft-Palate Craniofacial Association 76th Annual Meeting, with the aim to encourage other IMGs interested in applying to plastic surgery residency programs to actively pursue and attend national plastic surgery society meetings.

International Medical Graduates in Nephrology: Roles, Rules, and Future Risks.

International medical graduates (IMGs) have become an increasingly essential part of many residency and fellowship programs in the United States. IMGs, who may be of either US or non-US citizenship, contribute significantly to the physician workforce across this country, particularly in underserved areas, as well as in their home countries on their return after training. Approximately 65% of nephrology fellows are IMGs, with most of these being non-US citizens. Non-US IMG applications for nephrology fellowship have been declining, exacerbating an ongoing shortage of nephrology trainees. IMGs face visa status restrictions and immigration policy concerns, limitations on federally funded research support, and difficulty finding desirable jobs in both private practices and academia after fellowship. We review training, examination, and licensure requirements, as well as visa status rules for IMGs. We also discuss the potential negative impact of recent immigration policies limiting the entry of non-US IMGs on the medical community in general and in nephrology in particular.

Internationally educated nurses' and medical graduates' experiences of getting a license and practicing in Sweden - a qualitative interview study.

BACKGROUND: The Swedish healthcare system has an increased need for nurses and physicians, and the number of International Educated Nurses (IENs) and International Medical Graduates (IMGs) seeking job opportunities and a license to practice in Sweden is rising. This study explored how IENs and IMGs describe their experience of getting a license to practice, their perceptions of working in Sweden and of how their intercultural competence is utilized. METHOD: A qualitative study based on semi-structured interviews with 11 IENs and 11 IMGs. The interviews were conducted between 2015 and 2017. The data were analyzed using qualitative content analysis. RESULTS: Three main themes were identified: 'Getting a license - a different story,' 'The work is familiar, yet a lot is new,' 'Trying to master a new language.' The time to obtain a license to practice and finding a job was shorter for IENs and IMGs coming from European countries than for those from non-European countries. Some of the experiences of getting a license to practice and of entering a new workplace in another country were the same for nurses and physicians. In general, both IENs and IMGs felt welcomed and used their intercultural competence at work. Lack of language skills was regarded as the main problem for both professions, while workplace introduction was shorter for IMGs than for IENs. CONCLUSIONS: Problems related to language and culture are often underestimated, therefore organizations and managers employing IENs and IMGs should provide longer workplace introduction to facilitate the acculturation process. More time-efficient language courses specifically adapted to IENs and IMGs could make the transition easier and shorten the time to obtain a license to practice for both professions.

Supporting community annotation and user collaboration in the integrated microbial genomes (IMG) system.

BACKGROUND: The exponential growth of genomic data from next generation technologies renders traditional manual expert curation effort unsustainable. Many genomic systems have included community annotation tools to address the problem. Most of these systems adopted a "Wiki-based" approach to take advantage of existing wiki technologies, but encountered obstacles in issues such as usability, authorship recognition, information reliability and incentive for community participation. RESULTS: Here, we present a different approach, relying on tightly integrated method rather than "Wiki-based" method, to support community annotation and user collaboration in the Integrated Microbial Genomes (IMG) system. The IMG approach allows users to use existing IMG data warehouse and analysis tools to add gene, pathway and biosynthetic cluster annotations, to analyze/reorganize contigs, genes and functions using workspace datasets, and to share private user annotations and workspace datasets with collaborators. We show that the annotation effort using IMG can be part of the research process to overcome the user incentive and authorship recognition problems thus fostering collaboration among domain experts. The usability and reliability issues are addressed by the integration of curated information and analysis tools in IMG, together with DOE Joint Genome Institute (JGI) expert review. CONCLUSION: By incorporating annotation operations into IMG, we provide an integrated environment for users to perform deeper and extended data analysis and annotation in a single system that can lead to publications and community knowledge sharing as shown in the case studies.

In the minds of OSCE examiners: uncovering hidden assumptions.

The Objective Structured Clinical Exam (OSCE) is a widely used method of assessment in medical education. Rater cognition has become an important area of inquiry in the medical education assessment literature generally, and in the OSCE literature specifically, because of concerns about potential compromises of validity. In this study, a novel approach to mixed methods that combined Ordinal Logistic Hierarchical Linear Modeling and cognitive interviews was used to gain insights about what examiners were thinking during an OSCE. This study is based on data from the 2010 to 2014 administrations of the Clinician Assessment for Practice Program OSCE for International Medical Graduates (IMGs) in Nova Scotia. An IMG is a physician trained outside of Canada who was a licensed practitioner in a different country. The quantitative data were examined alongside four follow-up cognitive interviews of examiners conducted after the 2014 administration. The quantitative results show that competencies of (1) Investigation and Management and (2) Counseling were highly predictive of the Overall Global score. These competencies were also described in the cognitive interviews as the most salient parts of OSCE. Examiners also found Communication Skills and Professional Behavior to be relevant but the quantitative results revealed these to be less predictive of the Overall Global score. The interviews also reveal that there is a tacit sequence by which IMGs are expected to proceed in an OSCE, starting with more basic competencies such as History Taking and building up to Investigation Management and Counseling. The combined results confirm that a hidden pattern exists with respect to how examiners rate candidates. This study has potential implications for research into rater cognition, and the design and scoring of practice-ready OSCEs.

Exploring cultural and linguistic influences on clinical communication skills: a qualitative study of International Medical Graduates.

BACKGROUND: International Medical Graduates (IMGs) are known to perform less well in many postgraduate medical examinations when compared to their UK trained counterparts. This "differential attainment" is observed in both knowledge-based and clinical skills assessments. This study explored the influence of culture and language on IMGs clinical communication skills, in particular, their ability to seek, detect and acknowledge patients' concerns in a high stakes postgraduate clinical skills examination. Hofstede's cultural dimensions framework was used to look at the impact of culture on examination performance. METHODS: This was a qualitative, interpretative study using thematic content analysis of video-recorded doctor-simulated patient consultations of candidates sitting the MRCP(UK) PACES examination, at a single examination centre in November 2012. The research utilised Hofstede's cultural dimension theory, a framework for comparing cultural factors amongst different nations, to help understand the reasons for failure. RESULTS: Five key themes accounted for the majority of communication failures in station 2, "history taking" and station 4, "communication skills and ethics" of the MRCP(UK) PACES examination. Two themes, the ability to detect clues and the ability to address concerns, related directly to the overall construct managing patients' concerns. Three other themes were found to impact the whole consultation. These were building relationships, providing structure and explanation and planning. CONCLUSION: Hofstede's cultural dimensions may help to contextualise some of these observations. In some cultures doctor and patient roles are relatively inflexible: the doctor may convey less information to the patient (higher power distance societies) and give less attention to building rapport (high uncertainty avoidance societies.) This may explain why cues and concerns presented by patients were overlooked in this setting. Understanding cultural differences through Hofstede's cultural dimensions theory can inform the preparation of candidates for high stakes bedside clinical skills examinations and for professional practice.

International Medical Graduates in US Orthopedic Residency Programs: A Comprehensive Analysis.

BACKGROUND: This study aims to provide insight regarding the different qualities of international medical graduates (IMGs) involved in US orthopedic residency programs. METHODS: Orthopedic residency programs accredited by the ACGME and listed in the AMA database were screened. Data on program size and location, IMG year of training, the geographic region of IMG's medical schools, their research experiences and number of gap years were included. RESULTS: A total of 167(80.3%) orthopedic residency programs were included. A total of 3838 residents were identified, of which 44 (1.15%) were IMGs. The United Kingdom and Ireland had the highest number of matched IMGs with four (9.1%) each. Massachusetts was the state with the highest number of enrolled IMGs. On average, IMGs had 26.3 publications and joined US orthopedic residency 4.66 years following medical school graduation. CONCLUSION: Despite the many hurdles experienced by IMGs, a decent number succeeds in matching into US orthopedic residency programs each year.

Extended Half-life Antibodies: A Narrative Review of a New Approach in the Management of Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by intense pruritus and eczematous lesions, significantly impacting physical health and quality of life. The pathogenesis of AD involves genetic predisposition, immune dysregulation, and environmental factors, with a defective skin barrier playing a crucial role. Treatment options for AD include both topical and systemic therapies, with advanced treatments like Janus kinase inhibitors and biologics offering significant improvements but facing limitations in safety and dosing frequency. Extended half-life antibodies represent a promising advancement for the management of immune-mediated inflammatory diseases, including AD. These antibodies, engineered for prolonged circulation and reduced dosing frequency, target key cytokines and immune pathways known to be involved in the pathogenesis of AD, offering potential for less frequent administration while maintaining efficacy. Currently, two such agents are in phase 2 trials. APG777, targeting interleukin-13 (IL-13), and IMG-007, targeting OX40 receptor, have shown promising preclinical and early clinical results. They demonstrated prolonged half-lives and the potential for less frequent dosage regimen, along with significant improvements in AD symptoms. These therapies could enhance patient adherence and reduce healthcare burdens by decreasing injection frequencies and clinic visits. As research continues, extended half-life antibodies could significantly improve AD management and patient quality of life. Further studies will determine the long-term safety and efficacy of extended half-life antibodies, with ongoing innovations in antibody engineering likely to broaden their applications and benefits.

An integrated toolkit for human microglia functional genomics.

BACKGROUND: Microglia, the brain's resident immune cells, play vital roles in brain development, and disorders like Alzheimer's disease (AD). Human iPSC-derived microglia (iMG) provide a promising model to study these processes. However, existing iMG generation protocols face challenges, such as prolonged differentiation time, lack of detailed characterization, and limited gene function investigation via CRISPR-Cas9. METHODS: Our integrated toolkit for in-vitro microglia functional genomics optimizes iPSC differentiation into iMG through a streamlined two-step, 20-day process, producing iMG with a normal karyotype. We confirmed the iMG's authenticity and quality through single-cell RNA sequencing, chromatin accessibility profiles (ATAC-Seq), proteomics and functional tests. The toolkit also incorporates a drug-dependent CRISPR-ON/OFF system for temporally controlled gene expression. Further, we facilitate the use of multi-omic data by providing online searchable platform that compares new iMG profiles to human primary microglia: https://sherlab.shinyapps.io/IPSC-derived-Microglia/ . RESULTS: Our method generates iMG that closely align with human primary microglia in terms of transcriptomic, proteomic, and chromatin accessibility profiles. Functionally, these iMG exhibit Ca2 + transients, cytokine driven migration, immune responses to inflammatory signals, and active phagocytosis of CNS related substrates including synaptosomes, amyloid beta and myelin. Significantly, the toolkit facilitates repeated iMG harvesting, essential for large-scale experiments like CRISPR-Cas9 screens. The standalone ATAC-Seq profiles of our iMG closely resemble primary microglia, positioning them as ideal tools to study AD-associated single nucleotide variants (SNV) especially in the genome regulatory regions. CONCLUSIONS: Our advanced two-step protocol rapidly and efficiently produces authentic iMG. With features like the CRISPR-ON/OFF system and a comprehensive multi-omic data platform, our toolkit equips researchers for robust microglial functional genomic studies. By facilitating detailed SNV investigation and offering a sustainable cell harvest mechanism, the toolkit heralds significant progress in neurodegenerative disease drug research and therapeutic advancement.

Experimental results of a 330 GW impedance-matched Marx generator.

Impedance-matched Marx generators (IMGs) are considered next generation pulsed-power drivers because of their long lifetime (> 10,000 shots), repetition rate (> 0.1-Hz), fast rise time (~ 100-ns), and high-energy-delivery efficiency (~ 90%). "TITAN" is a 14-stage IMG designed to deliver 1-TW to a 2-Ω matched load. In this paper, design, simulation, and experimental results for six stages of TITAN including its triggering system, air delivery system, and pulse shaping are presented. To achieve efficiency over 85% and maximize the capability of an IMG, synchronized triggering, reduced pre-fire rate, and pulse shaping ability are crucial. In this paper, novel engineering solutions are introduced, tested, and proven to overcome those challenges. 6-stage TITAN, powered by 102 identical bricks and 102 field-distortion-triggered gas switches, could generate ~ 600-kA and ~ 700-kV across a ~ 0.9-Ω matched load when fully charged to ± 100-kV. In these experiments, 6-stage TITAN is tested up to ± 70-kV charge voltage which delivers a peak power of 330-GW to a 1.2-Ω resistive load.

Bibliometric Analysis of International Medical Graduates and Professorship Promotion in Neurosurgery.

BACKGROUND: International medical graduates (IMGs) comprise ∼25% of physicians in the United States. Differences in promotion rates from assistant to associate to full professorship based on medical school location have been understudied. We aim to stratify odds of professional advancement by 3 categories: IMG with U.S. residency, IMG with international residency, and U.S. medical with U.S. residency training. METHODS: We created and queried a database after exclusions of 1334 neurosurgeons including multiple demographic factors: academic productivity and promotion rates. Stratified logistic regression modeled odds of promotion including the variables: decades out of training, Scopus h-index, gender, and training location. Odds ratios (ORs) and 95% confidence intervals (CIs) for each variable were calculated. RESULTS: Significant predictors of increased associate versus assistant professorship included decades out of training (OR = 2.519 [95% CI: 2.07-3.093], P < 0.0001) and Scopus h-index (OR = 1.085 [95% CI: 1.064-1.108], P < 0.0001) while international medical school with U.S. residency (OR = 0.471 [95% CI: 0.231-0.914], P = 0.0352) was associated with decreased promotion. Significant predictors of associate versus full professorship were decades out of training (OR = 2.781 [95% CI: 2.268-3.444], P < 0.0001) and Scopus h-index (OR = 1.064 [95% CI: 1.049-1.080], P < 0.0001). Attending medical school or residency internationally was not associated with odds of full professorship. CONCLUSIONS: Time out of residency and Scopus h-index were associated with higher academic rank regardless of career level. Attending medical school internationally with U.S. residency was associated with lower odds of associate professorship promotion over 10 years. There was no relationship between IMG and full professorship promotion. IMGs who attended residency internationally did not have lower promotion rates. These findings suggest it may be harder for IMGs to earn promotion from assistant to associate professor in neurosurgery.