Invasive Route Research Articles

ANGI-05. UNSUPERVISED DECONVOLUTION OF SPATIOTEMPORAL HETEROGENEITY REVEALS HIGH-RESOLUTION INVASION STATES IN GLIOBLASTOMA

Abstract Diffuse invasion of glioblastoma cells through normal brain tissue is a key contributor to tumor aggressiveness, resistance to conventional therapies, and dismal prognosis in patients. A deeper understanding of how components of the tumor microenvironment (TME) contribute to overall tumor organization and to programs of invasion may reveal opportunities for improved therapeutic strategies. Towards this goal, we applied a novel computational workflow to a spatiotemporally profiled GBM xenograft cohort, leveraging the ability to distinguish human tumor from mouse TME to overcome previous limitations in analysis of diffuse invasion. Our analytic approach, based on unsupervised deconvolution, performs reference-free discovery of cell types and cell activities within the complete GBM ecosystem. We present a comprehensive catalogue of 15 tumor cell programs set within the spatiotemporal context of 90 mouse brain and TME cell types, cell activities, and anatomic structures. Distinct tumor programs related to invasion were aligned with routes of perivascular, white matter, and parenchymal invasion. Furthermore, sub-modules of genes serving as program network hubs were highly prognostic in GBM patients. The compendium of programs presented here provides a basis for rational targeting of tumor and/or TME components. We anticipate that our approach will facilitate an ecosystem-level understanding of immediate and long-term consequences of such perturbations, including identification of compensatory programs that will inform improved combinatorial therapies.

11848 Comparative Perioperative Outcomes of vNOTES Versus Other Minimally Invasive Hysterectomy Routes: A National Study

11848 Comparative Perioperative Outcomes of vNOTES Versus Other Minimally Invasive Hysterectomy Routes: A National Study

Nano-Biomechanical Investigation of Phosphatidylserine-Mediated Ebola Viral Attachment via Human Gas6 and Axl

The Ebola virus is a deadly pathogen that has been threatening public health for decades. Recent studies have revealed alternative viral invasion routes where Ebola virus approaches cells via interactions among phosphatidylserine (PS), PS binding ligands such as Gas6, and TAM family receptors such as Axl. In this study, we investigate the interactions among phosphatidylserine on the Ebola viral-like particle (VLP) membrane, human Gas6, and human Axl using atomic force microscope-based single molecule force spectroscopy to compare their binding strength and affinity from a biomechanical perspective. The impact of calcium ions on their interactions is also studied and quantified to provide more details on the calcium-dependent phosphatidylserine-Gas6 binding mechanism. Our results indicate that, in the presence of calcium ions, the binding strengths of VLP-Gas6 and VLP-Gas6-Axl increase but are still weaker than that of Gas6-Axl, and the binding affinity of VLP-Gas6 and VLP-Gas6-Axl is largely improved. The binding strength and affinity of Gas6-Axl basically remain the same, indicating no impact in the presence of calcium ions. Together, our study suggests that, under physiological conditions with calcium present, the Ebola virus can utilize its membrane phosphatidylserine to dock on cell surface via Gas6-Axl bound complex.

Insulin Stabilization Designs for Enhanced Therapeutic Efficacy and Accessibility.

ConspectusInsulin has remained indispensable in the treatment of diabetes since it was first discovered in 1921. Unlike small molecular drugs, insulin and other protein drugs are prone to degradation when exposed to elevated temperatures, mechanical agitation during transportation, and prolonged storage periods. Therefore, strict cold-chain management is crucial for the insulin supply, requiring significant resources, which can limit the access to insulin, particularly in low-income areas. Moreover, although insulin formulations have advanced tremendously in the last century, insulin treatment still imposes a challenging regimen and provides suboptimal outcomes for the majority of patients. There is an increasing focus on pursuing improved pharmacology, specifically on safer, more user-friendly insulin therapies that minimize the self-management burden. These challenges underscore the need for developing novel insulin formulations with improved stability that are compatible with advanced insulin therapy.Insulin stabilization can be achieved through either chemical modification of insulin or formulation component design. Inspired by insulin-like peptides from invertebrates, we have developed novel stable insulin analogs based on a fundamental understanding of the insulin receptor engagement for insulin bioactivity. We created a novel four-disulfide insulin analog with high aggregation stability and potency by introducing a fourth disulfide bond between a C-terminal extended insulin A-chain and residues near the C-terminus of the B-chain. In an effort to stabilize insulin in its monomeric state to develop ultrafast-acting insulin with rapid absorption upon injection, we have developed a series of structurally miniaturized yet fully active insulin analogs that do not form dimers due to the lack of the canonical B-chain C-terminal octapeptide. Additionally, our study provided strategies for expanding the scope of cucurbit[7]uril (CB[7])-assisted insulin stabilization by engineering safe and biodegradable CB[7]-zwitterionic polypeptide excipients. We also explored insulin N-terminal substitution methods to achieve pH-dependent insulin stabilization without prolonging the duration of action.This Account describes our exploration of engineering stable insulin analogs and formulation design strategies for stabilizing insulin in aqueous solutions. Beyond conventional stabilization strategies for insulin injections, the unmet challenges and recent innovations in insulin stabilization are discussed, addressing the growing demand for alternative, less invasive routes of insulin administration. Additionally, we aim to provide a thorough overview of insulin stabilization from the perspective of commercially available insulin drugs and common pharmaceutical engineering practices in the industry. We also highlight unresolved insulin stabilization challenges and ongoing research strategies. We anticipate that further emphasis on collective efforts of protein engineering, pharmaceutical formulation design, and drug delivery will inform the development of stable and advanced insulin therapy.

Strategies for transportation of peptides across the skin for treatment of multiple diseases.

An established view in genetic engineering dictates an increase in the discovery of therapeutic peptides to enable the treatment of multiple diseases. The use of hypodermic needle for delivery of proteins and peptides occurs due to the hydrophilic nature, sensitivity toward proteolytic enzymes and high molecular weight. The non-invasive nature of the transdermal delivery technique offers multiple advantages over the invasive route to release drugs directly into the systemic circulation to enhance bioavailability, better patient compliance, reduced toxicity and local irritability. The transdermal route seems highly desirable from the pharmaco-therapeutic and patient compliance point of view, however, the lipophilic barrier of skin restricts the application. The use of several techniques like electrical methods (iontophoresis, sonophoresis etc.), chemical penetration enhancers (e.g. protease inhibitors, penetration enhancers, etc.) and nanocarriers (dendrimers, lipid nanocapsules, etc.) are utilized to improve the passage of drug molecules across the biomembranes. Additionally, such clinical interventions facilitate the physicochemical characteristics of peptides, to enable effective preservation, conveyance and release of therapeutic agents. Moreover, strategies ensure the attainment of the intended targets and enhance treatment outcomes for multiple diseases. This review article focuses on the techniques of peptide transportation across the skin to advance the delivery approaches and therapeutic efficiency.

Searching Method for Three-Dimensional Puncture Route to Support Computed Tomography-Guided Percutaneous Puncture.

In CT-guided percutaneous punctures-an image-guided puncture method using CT images-physicians treat targets such as lung tumors, liver tumors, renal tumors, and intervertebral abscesses by inserting a puncture needle into the body from the exterior while viewing images. By recognizing two-dimensional CT images prior to a procedure, a physician determines the least invasive puncture route for the patient. Therefore, the candidate puncture route is limited to a two-dimensional region along the cross section of the human body. In this paper, we aim to construct a three-dimensional puncture space based on multiple two-dimensional CT images to search for a safer and shorter puncture route for a given patient. If all puncture routes starting from a target in the three-dimensional space were examined from all directions (the brute-force method), the processing time to derive the puncture route would be very long. We propose a more efficient method for three-dimensional puncture route selection in CT-guided percutaneous punctures. The proposed method extends the ray-tracing method, which quickly derives a line segment from a given start point to an end point on a two-dimensional plane, and applies it to three-dimensional space. During actual puncture route selection, a physician can use CT images to derive a three-dimensional puncture route that is safe for the patient and minimizes the puncture time. The main novelty is that we propose a method for deriving a three-dimensional puncture route within the allowed time in an actual puncture. The main goal is for physicians to select the puncture route they will use in the actual surgery from among the multiple three-dimensional puncture route candidates derived using the proposed method. The proposed method derives a three-dimensional puncture route within the allowed time in an actual puncture. Physicians can use the proposed method to derive a new puncture route, reducing the burden on patients and improving physician skills. In the evaluation results of a computer simulation, for a 3D CT image created by combining 170 two-dimensional CT images, the processing time for deriving the puncture route using the proposed method was approximately 59.4 s. The shortest length of the puncture route from the starting point to the target was between 20 mm and 22 mm. The search time for a three-dimensional human body consisting of 15 CT images was 4.77 s for the proposed method and 2599.0 s for a brute-force method. In a questionnaire, physicians who actually perform puncture treatments evaluated the candidate puncture routes derived by the proposed method. We confirmed that physicians could actually use these candidates as a puncture route.

Global Invasion History and Genomic Signatures of Adaptation of the Highly Invasive Sycamore Lace Bug.

Invasive species cause massive economic and ecological damage. Climate change has resulted in an unprecedented increase in the number and impact of invasive species; however, the mechanisms underlying these invasions are unclear. The sycamore lace bug, Corythucha ciliata, is a highly invasive species originating from North America and has expanded across the Northern Hemisphere since the 1960s. In this study, we assembled the C. ciliata genome using high-coverage Pacific Biosciences (PacBio), Illumina, and high-throughput chromosome conformation capture (Hi-C) sequencing. A total of 15,278 protein-coding genes were identified, and expansions of gene families with oxidoreductase and metabolic activities were observed. In-depth resequencing of 402 samples from native and nine invaded countries across three continents revealed 2.74 million single nucleotide polymorphisms. Two major invasion routes of C. ciliata were identified from North America to Europe and Japan, with a contact zone forming in East Asia. Genomic signatures of selection associated with invasion and long-term balancing selection in native ranges were identified. These genomic signatures overlapped with expanded genes, suggesting improvements in the oxidative stress and thermal tolerance of C. ciliata. These findings offer valuable insights into the genomic architecture and adaptive evolution underlying the invasive capabilities of species during rapid environmental changes.

The Asian Citrus Psyllid (<i>Diaphorina citri</i>) in Africa: using MaxEnt to predict current and future climatic suitability, with a focus on potential invasion routes

The Asian Citrus Psyllid (ACP) (Diaphorina citri Kuwayama, 1908) (Hemiptera: Psyllidae) is a major citrus pest. The species has been introduced to West and East Africa, but has not yet spread to southern Africa, where it could have a devastating impact on citrus farming and livelihoods. A proactive response is key to mitigating the species’ impacts, particularly the ongoing monitoring of potential invasion routes and entry points into South Africa. Species distribution models (SDMs) were developed under current and future climates for ACP in Africa, and these models were used to (1) determine where the species likely poses a threat, (2) identify potential invasion routes into South Africa, and (3) assess how these factors will be affected under climate change. The SDMs indicated that there is an almost contiguous band of suitable climate along the east coast of Africa that joins the species’ current range in East Africa to South Africa, and under aggressive climate change a potential route of invasion through Namibia and Botswana. Much of South Africa is climatically suitable for the species, but under climate change, climatically suitable areas are likely to shift further inland. The spread of ACP into South Africa is unlikely to be prevented, but the outputs of the present models will inform monitoring activities and assist with preparations to respond to this predicted biological invasion.

The Asian Citrus Psyllid (<i>Diaphorina citri</i>) in Africa: using MaxEnt to predict current and future climatic suitability, with a focus on potential invasion routes

The Asian Citrus Psyllid (ACP) (Diaphorina citri Kuwayama, 1908) (Hemiptera: Psyllidae) is a major citrus pest. The species has been introduced to West and East Africa, but has not yet spread to southern Africa, where it could have a devastating impact on citrus farming and livelihoods. A proactive response is key to mitigating the species’ impacts, particularly the ongoing monitoring of potential invasion routes and entry points into South Africa. Species distribution models (SDMs) were developed under current and future climates for ACP in Africa, and these models were used to (1) determine where the species likely poses a threat, (2) identify potential invasion routes into South Africa, and (3) assess how these factors will be affected under climate change. The SDMs indicated that there is an almost contiguous band of suitable climate along the east coast of Africa that joins the species’ current range in East Africa to South Africa, and under aggressive climate change a potential route of invasion through Namibia and Botswana. Much of South Africa is climatically suitable for the species, but under climate change, climatically suitable areas are likely to shift further inland. The spread of ACP into South Africa is unlikely to be prevented, but the outputs of the present models will inform monitoring activities and assist with preparations to respond to this predicted biological invasion.

Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma

BackgroundDiffuse invasion of glioblastoma cells through normal brain tissue is a key contributor to tumor aggressiveness, resistance to conventional therapies, and dismal prognosis in patients. A deeper understanding of how components of the tumor microenvironment (TME) contribute to overall tumor organization and to programs of invasion may reveal opportunities for improved therapeutic strategies.ResultsTowards this goal, we apply a novel computational workflow to a spatiotemporally profiled GBM xenograft cohort, leveraging the ability to distinguish human tumor from mouse TME to overcome previous limitations in the analysis of diffuse invasion. Our analytic approach, based on unsupervised deconvolution, performs reference-free discovery of cell types and cell activities within the complete GBM ecosystem. We present a comprehensive catalogue of 15 tumor cell programs set within the spatiotemporal context of 90 mouse brain and TME cell types, cell activities, and anatomic structures. Distinct tumor programs related to invasion align with routes of perivascular, white matter, and parenchymal invasion. Furthermore, sub-modules of genes serving as program network hubs are highly prognostic in GBM patients.ConclusionThe compendium of programs presented here provides a basis for rational targeting of tumor and/or TME components. We anticipate that our approach will facilitate an ecosystem-level understanding of the immediate and long-term consequences of such perturbations, including the identification of compensatory programs that will inform improved combinatorial therapies.

Language-Based Disparities in Route of Hysterectomy for Benign Disease

Study ObjectiveTo assess the association between patient primary language and route of hysterectomy. DesignA retrospective cohort study was conducted using the Healthcare Cost and Utilization Project's State Inpatient Database (SID) and State Ambulatory Surgery and Services Database (SASD). SettingAll inpatient and outpatient hysterectomies from the most recent year of available data (2020–2021) from the six states that record patient primary language in the SID and SASD (Indiana, Iowa, Maryland, Michigan, Minnesota, and New Jersey) were queried. Patients or ParticipantsPatients aged 18 and over undergoing an inpatient or ambulatory hysterectomy for benign indication. InterventionsMinimally invasive hysterectomy compared to abdominal hysterectomy. Measurement and Main ResultsThe association between patient primary language (English vs. non-English) and route of hysterectomy (abdominal vs minimally invasive) was evaluated. The cohort included 52,226 patients who met inclusion criteria. The majority of patients were non-Hispanic White (71%), with a median age of 46 years (IQR 40.0–53.0). 91.4% of patients spoke English as their primary language, 3.6% spoke Spanish, and 5.0% spoke another non-English language. Patients with a non-English primary language were significantly less likely to undergo minimally invasive hysterectomy compared to patients who spoke English (OR 0.60, 95% CI 0.56–0.64, p <.001). This association remained significant following adjustments for age, race, insurance, median income, state, and fibroid, abnormal uterine bleeding, prolapse or endometriosis diagnosis (aOR 0.77, 95% CI 0.71–0.84). In a sensitivity analysis of English vs Spanish vs other non-English language, the association remained significant for other non-English languages (aOR 0.67, 95% CI 0.60–0.75) but not for Spanish (aOR 0.95, 95% CI 0.83–1.09). ConclusionPatients who are non-English speaking are significantly less likely to receive a minimally invasive hysterectomy. Addressing language disparities may improve access to a minimally invasive route of surgery, a possible surrogate for improved surgical outcomes, for our gynecologic patients.

Deep intravital brain tumor imaging enabled by tailored three-photon microscopy and analysis

Intravital 2P-microscopy enables the longitudinal study of brain tumor biology in superficial mouse cortex layers. Intravital microscopy of the white matter, an important route of glioblastoma invasion and recurrence, has not been feasible, due to low signal-to-noise ratios and insufficient spatiotemporal resolution. Here, we present an intravital microscopy and artificial intelligence-based analysis workflow (Deep3P) that enables longitudinal deep imaging of glioblastoma up to a depth of 1.2 mm. We find that perivascular invasion is the preferred invasion route into the corpus callosum and uncover two vascular mechanisms of glioblastoma migration in the white matter. Furthermore, we observe morphological changes after white matter infiltration, a potential basis of an imaging biomarker during early glioblastoma colonization. Taken together, Deep3P allows for a non-invasive intravital investigation of brain tumor biology and its tumor microenvironment at subcortical depths explored, opening up opportunities for studying the neuroscience of brain tumors and other model systems.

Uncoupling the CRMP2-CaV2.2 Interaction Reduces Pain-Like Behavior in a Preclinical Joint-Pain Model

Osteoarthritis (OA) represents a significant pain challenge globally, as current treatments are limited and come with substantial and adverse side effects. Voltage-gated calcium channels have proved to be pharmacologically effective targets, with multiple Food and Drug Administration-approved CaV2.2 modulators available for the treatment of pain. Although effective, drugs targeting CaV2.2 are complicated by the same obstacles facing other pain therapeutics—invasive routes of administration, narrow therapeutic windows, side effects, and addiction potential. We have identified a key regulator of CaV2.2 channels, collapsin response mediator protein 2, that allows us to indirectly regulate CaV2.2 expression and function. We previously developed a peptidomimetic modulator of collapsin response mediator protein 2, CBD3063, that effectively reverses neuropathic and inflammatory pain without negative side effects by reducing membrane expression of CaV2.2. The potent analgesic properties of CBD3063, combined with the lack of negative side effects, prompted us to assess the efficacy of CBD3063 in a rodent model of OA pain. Here, we demonstrate the intraperitoneal administration of CBD3063 alleviates both evoked and nonevoked behavioral hallmarks of OA pain. Further, we reveal that CBD3063 reduces OA-induced increased neural activity in the parabrachial nucleus, a key supraspinal site modulating the pain experience. Together, these studies suggest that CBD3063 is an effective analgesic for OA pain. PerspectiveDespite the high prevalence of OA pain worldwide, current treatment options remain limited. We demonstrate that CBD3063-mediated disruption of the CaV2.2-collapsin response mediator protein 2 interaction alleviates pain in a preclinical joint pain model, providing a promising basis for the development of new OA pain treatments.

Dissecting the invasion history of Spotted-Wing Drosophila (Drosophila suzukii) in Portugal using genomic data

BackgroundThe invasive pest Spotted-Wing Drosophila, Drosophila suzukii (Matsumura), causes extensive damage and production losses of soft-skinned fruits. Native to Asia, the species has now spread worldwide, with first reports in Portugal in 2012. In this study, we focus on the genomic signatures of the recent Portuguese invasion, in the context of worldwide patterns established in previous works. We analyzed whole genome pool sequencing data from three Portuguese populations (N = 240) sampled in 2019 and 2021.ResultsThe correlation of allele frequencies suggested that Portuguese populations are related to South European ones, indicating a Mediterranean invasion route. While two populations exhibited levels of genetic variation comparable to others in the invasive range, a third showed low levels of genetic diversity, which may result from a recent colonization of the region. Genome-wide analyses of natural selection identified ten genes previously associated with D. suzukii’s invasive capacity, which may have contributed to the species’ success in Portugal. Additionally, we pinpointed six genes evolving under positive selection across Portuguese populations but not in European ones, which is indicative of local adaptation. One of these genes, nAChRalpha7, encodes a nicotinic acetylcholine receptor, which are known targets for insecticides widely used for D. suzukii control, such as neonicotinoids and spinosyns. Although spinosyn resistance has been associated with mutations in the nAChRalpha6 in other Drosophila species, the putative role of nAChRalpha7 in insecticide resistance and local adaptation in Portuguese D. suzukii populations encourages future investigation.ConclusionsOur results highlight the complex nature of rapid species invasions and the role of rapid local adaptation in determining the invasive capacity of these species.

Making cups and rings: the 'stalled-wave' model for macropinocytosis.

Macropinocytosis is a broadly conserved endocytic process discovered nearly 100 years ago, yet still poorly understood. It is prominent in cancer cell feeding, immune surveillance, uptake of RNA vaccines and as an invasion route for pathogens. Macropinocytic cells extend large cups or flaps from their plasma membrane to engulf droplets of medium and trap them in micron-sized vesicles. Here they are digested and the products absorbed. A major problem - discussed here - is to understand how cups are shaped and closed. Recently, lattice light-sheet microscopy has given a detailed description of this process in Dictyostelium amoebae, leading to the 'stalled-wave' model for cup formation and closure. This is based on membrane domains of PIP3 and active Ras and Rac that occupy the inner face of macropinocytic cups and are readily visible with suitable reporters. These domains attract activators of dendritic actin polymerization to their periphery, creating a ring of protrusive F-actin around themselves, thus shaping the walls of the cup. As domains grow, they drive a wave of actin polymerization across the plasma membrane that expands the cup. When domains stall, continued actin polymerization under the membrane, combined with increasing membrane tension in the cup, drives closure at lip or base. Modelling supports the feasibility of this scheme. No specialist coat proteins or contractile activities are required to shape and close cups: rings of actin polymerization formed around PIP3 domains that expand and stall seem sufficient. This scheme may be widely applicable and begs many biochemical questions.

Is It Time for a Paradigm Shift in the Surgical Management of Trigeminal Schwannomas? Evaluating the Role of the Transorbital Approach: An Anatomo-Clinical Study and Systematic Literature Review

BackgroundEndoscopic transorbital approach emerged in recent years as an effective, minimally invasive route to access Meckel’s cave area. Several case series proved its effectiveness in the surgical treatment of trigeminal schwannomas. Nonetheless, this route provides the advantages of a minimally invasive approach associated with low morbidity rates. In this anatomo-clinical study we illustrate the usefulness of the superior eyelid transorbital approach for the surgical treatment of trigeminal schwannoma guiding the clinical applicability of the anatomical findings into the real surgical practice. MethodsSuperior eyelid transorbital endoscopic approach was performed on eight cadaveric specimens, and the surgical results were confirmed in a retrospective review of all the surgical cases of transorbital surgery performed by the senior authors providing an illustrative case. Finally, we performed a literature review of all the case series of trigeminal schwannomas operated through an endoscopic transorbital approach. ResultsStepwise dissection was divided in 3 phases: skin, endo-orbital and endocranial. The illustrative case provided demonstrate gross total resection of a cavernous sinus type trigeminal schwannomas treated through this route. Literature review revealed 68 cases of trigeminal schwannomas that were successfully treated using the transorbital approach. ConclusionsThe endoscopic transorbital approach may offer a valuable alternative for the surgical treatment of trigeminal schwannomas. This technique provides a minimally invasive, direct and natural “interdural” route to the lateral wall of the cavernous sinus and Meckel's cave.

Introduction of a snake trematode of the genus Ochetosoma in eastern Japan

In Japan, trematodes of the family Ochetosomatidae are not naturally distributed. However, the introduced ochetosomatid Ochetosoma kansense (Crow, 1913) has been reported from the oral cavity of native snakes in western Japan since 2010s. In this study, trematodes were isolated from the oral cavities of the native Japanese snakes, Elaphe quadrivirgata (Boie, 1826), E. climacophora (Boie, 1826), and Rhabdophis tigrinus (Boie, 1826), in the central Kanto region of eastern Japan. Morphological and molecular analyses of the isolated trematodes revealed that all trematodes were identifiable to a newly introduced ochetosomatid species to Japan, O. elongatum (Pratt, 1903), which originated from North America; Lechriorchis tygarti Talbot, 1933 was synonymized with O. elongatum based on identical molecular data and morphological similarity. To identify first intermediate hosts of O. elongatum, seven freshwater snail species were examined in eastern Japan. Molecular analysis was used to identify O. elongatum sporocysts in the freshwater snail Physella acuta (Draparnaud, 1805), which also originated from North America. The other six species did not host O. elongatum, suggesting that Ph. acuta is the only first intermediate host of O. elongatum in Japan. Although O. elongatum has been detected in Japan, its invasion route and period of introduction are unclear. Frequent imports of freshwater snails and wild snakes from North America, after the 1990s and 2005, respectively, presumably introduced O. elongatum in Japan.

A National Database Study on Racial Disparities in Route of Hysterectomy With a Surrogate Control for Uterine Size: A Proposed Quality Metric for Benign Indications

Study ObjectiveTo investigate the association between race and route of hysterectomy among patients undergoing hysterectomy for abnormal uterine bleeding in the absence of uterine fibroid disease and excluding malignancy. DesignA cross-sectional cohort study utilizing the Healthcare Cost and Utilization Project Nationwide Inpatient Sample and National Ambulatory Surgical databases to compare abdominal to minimally invasive route of hysterectomy. SettingHospitals and hospital-affiliated ambulatory surgical centers participating in the Healthcare Cost and Utilization Project in 2019 Patients75,838 patients who had undergone hysterectomy for abnormal uterine bleeding excluding uterine fibroids and malignancy. Interventionsn/a Measurements and Main ResultsOf the 75,838 hysterectomies performed for abnormal uterine bleeding in the absence of uterine fibroids and malignancy, 10.1% were performed abdominally and 89.9% minimally invasively. After adjusting for confounders, Black patients were 38% more likely to undergo abdominal hysterectomy compared to White patients (OR 1.38, CI 1.12-1.70 p=0.002). Black race thus is independently associated with open surgery. ConclusionDespite excluding uterine fibroids as a risk factor for an abdominal route of hysterectomy, Black race remained an independent predictor for abdominal versus minimally invasive hysterectomy and Black patients were found to undergo a disproportionately higher rate of abdominal hysterectomy compared to White patients.

Bakanae Disease Resistance in Rice: Current Status and Future Considerations

Bakanae disease is mainly caused by Fusarium fujikuroi and is a significant fungal disease with a number of disastrous consequences. It causes great losses in rice production. However, few studies have focused on the details of bakanae disease resistance in rice. Here, we summarize and discuss the progress of bakanae disease resistance in rice. Besides rice germplasm screening and resistance-related gene/quantitative trait locus (QTL) exploration, the route of pathogen invasion in rice plants was determined. We further discussed the regulation of phytohormone-related genes and changes in endogenous phytohormones in rice plants that are induced by the pathogen. To achieve better control of bakanae disease, the use of natural fungicides was assessed in this review. During rice—F. fujikuroi interactions, the infection processes and spatial distribution of F. fujikuroi in infected seedlings and adult plants exhibit different trends. Fungal growth normally occurs both in resistant and susceptible cultivars, with less abundance in the former. Generally, bakanae disease is seed-borne, and seed disinfection using effective fungicides should always be the first and main option to better control the disease. Besides the friendly and effective measure of using natural fungicides, breeding and utilization of resistant rice cultivars is also an effective control method. To some extent, rice cultivars with low grain quality, indica subspecies, and some dwarf or semi-dwarf rice germplasms are more resistant to bakanae disease. Although no highly resistant germplasms were obtained, 37 QTLs were located, with almost half of the QTLs being located on chromosome 1. Using omics methods, WRKYs and MAPKs were usually found to be regulated during rice—F. fujikuroi interactions. The regulation of certain phytohormone-related genes and changes in some endogenous phytohormones induced by the pathogen were clear, i.e., it downregulated gibberellin-related genes and repressed endogenous gibberellins in resistant genotypes, but the opposite results were noted in susceptible rice genotypes. Overall, exploring resistant germplasms or resistance-related genes/QTLs for the breeding of rice with bakanae disease resistance, expanding research on the complex mechanism of rice—F. fujikuroi interactions, and using cost-effective and eco-friendly innovative control methods against the disease are necessary for present and future bakanae disease management.

High-Volume Surgeons and Reducing Racial Disparities in Route of Hysterectomy

Study ObjectiveTo examine racial disparities in route of hysterectomy and perioperative outcomes before and after expansion of high-volume minimally invasive surgeons (>10 minimally invasive hysterectomies (MIH)/year) DesignRetrospective cohort study SettingMulti-center academic teaching institution PatientsAll patients who underwent a scheduled hysterectomy for benign indications during 2018 (pre-intervention) and 2022 (post-intervention) InterventionsRecruitment of Fellowship in Minimally Invasive Gynecologic Surgery (FMIGS)- trained faculty and increased surgical training for academic specialists in obstetrics and gynecology occurred in 2020. Measurements and Main ResultsPatients in the pre-intervention cohort (n=171) were older (median age 45 years vs. 43 years, p=0.003) while patients in the post-intervention cohort (n=234) had a higher burden of comorbidities (26% ASA class III vs. 19%, p=0.03). Uterine weight was not significantly different between cohorts (p=0.328). Between the pre-intervention and post-intervention cohorts, high-volume minimally invasive surgeons increased from 27% (n=4) to 44% (n=7) of those performing hysterectomies within the division and percentage of hysterectomies performed via minimally invasive route increased (63% vs. 82%, p<0.001). In the pre-intervention cohort, Black patients had a lower percentage of hysterectomies performed via minimally invasive route compared to White patients (Black = 56% MIH vs. White = 76% MIH, p=0.014). In the post-intervention cohort, differences by race were no longer significant (Black = 78% MIH vs. White = 87% MIH, p= 0.127). There was a significant increase (22%) in MIH for Black patients between cohorts (p<0.001). After adjusting for age, BMI, ASA class, prior surgery, and uterine weight, disparities by race were no longer present in the post-intervention cohort. Perioperative outcomes including length of stay (p<0.001), infection rates (p=0.002) and blood loss (p=0.01) improved post-intervention. ConclusionIncreasing FMIGs-trained gynecologic surgeons and providing more opportunities in robotic/laparoscopic training for academic specialists may improve access to MIH for Black patients and reduce disparities.