Live-cell imaging unveils distinct R-loop populations with heterogeneous dynamics.

We have developed RHINO, a genetically encoded sensor that selectively binds RNA:DNA hybrids enabling live-cell imaging of cellular R-loops. RHINO comprises a tandem array of three copies of the RNA:DNA hybrid binding domain of human RNase H1 connected by optimized linker segments and fused to a fluorescent protein. This tool allows the measurement of R-loop abundance and dynamics in live cells with high specificity and sensitivity. Using RHINO, we provide a kinetic framework for R-loops at nucleoli, telomeres and protein-coding genes. Our findings demonstrate that R-loop dynamics vary significantly across these regions, potentially reflecting the distinct roles R-loops play in different chromosomal contexts. RHINO is a powerful tool for investigating the role of R-loops in cellular processes and their contribution to disease development and progression.

Racial and Ethnic Disparities in Operative Experience Among General Surgery Residents: A Multi-Institutional Study from the US ROPE Consortium.

OBJECTIVE: To determine the relationship between race/ethnicity and case volume among graduating surgical residents. BACKGROUND: Racial/ethnic minority individuals face barriers to entry and advancement in surgery; however, no large-scale investigations of the operative experience of racial/ethnic minority residents have been performed. METHODS: A multi-institutional retrospective analysis of the Accreditation Council for Graduate Medical Education case logs of categorical general surgery residents at 20 programs in the US Resident OPerative Experience Consortium database was performed. All residents graduating between 2010 and 2020 were included. The total, surgeon chief, surgeon junior, and teaching assistant case volumes were compared between racial/ethnic groups. RESULTS: The cohort included 1343 residents. There were 211 (15.7%) Asian, 65 (4.8%) Black, 73 (5.4%) Hispanic, 71 (5.3%) "Other" (Native American or Multiple Race), and 923 (68.7%) White residents. On adjusted analysis, Black residents performed 76 fewer total cases (95% CI, -109 to -43, P <0.001) and 69 fewer surgeon junior cases (-98 to -40, P <0.001) than White residents. Comparing adjusted total case volume by graduation year, both Black residents and White residents performed more cases over time; however, there was no difference in the rates of annual increase (10 versus 12 cases per year increase, respectively, P =0.769). Thus, differences in total case volume persisted over the study period. CONCLUSIONS: In this multi-institutional study, Black residents graduated with lower case volume than non-minority residents throughout the previous decade. Reduced operative learning opportunities may negatively impact professional advancement. Systemic interventions are needed to promote equitable operative experience and positive culture change.

BELB: a biomedical entity linking benchmark.

MOTIVATION: Biomedical entity linking (BEL) is the task of grounding entity mentions to a knowledge base (KB). It plays a vital role in information extraction pipelines for the life sciences literature. We review recent work in the field and find that, as the task is absent from existing benchmarks for biomedical text mining, different studies adopt different experimental setups making comparisons based on published numbers problematic. Furthermore, neural systems are tested primarily on instances linked to the broad coverage KB UMLS, leaving their performance to more specialized ones, e.g. genes or variants, understudied. RESULTS: We therefore developed BELB, a biomedical entity linking benchmark, providing access in a unified format to 11 corpora linked to 7 KBs and spanning six entity types: gene, disease, chemical, species, cell line, and variant. BELB greatly reduces preprocessing overhead in testing BEL systems on multiple corpora offering a standardized testbed for reproducible experiments. Using BELB, we perform an extensive evaluation of six rule-based entity-specific systems and three recent neural approaches leveraging pre-trained language models. Our results reveal a mixed picture showing that neural approaches fail to perform consistently across entity types, highlighting the need of further studies towards entity-agnostic models. AVAILABILITY AND IMPLEMENTATION: The source code of BELB is available at: https://github.com/sg-wbi/belb. The code to reproduce our experiments can be found at: https://github.com/sg-wbi/belb-exp.

Interval Sentinel Lymph Nodes With the Use of Routine Lymphoscintigraphy in Extremity Melanoma.

INTRODUCTION: Lymphoscintigraphy (LS) helps identify drainage to interval (epitrochlear or popliteal) lymph node basins for extremity melanomas. This study evaluated how often routine LS evaluation identified an interval sentinel lymph node (SLN) and how often that node was found to have metastasis. METHODS: A single institution, retrospective study identified patients with an extremity melanoma who underwent routine LS and SLN biopsy over a 25-y period. Comparisons of factors associated with the identification of interval node drainage and tumor status were made. RESULTS: In 634 patients reviewed, 5.7% of patients drained to an interval SLN. Of those biopsied, 29.2% were positive for micrometastases. Among patients with biopsies of both the traditional and interval nodal basins, nearly 20% had positive interval nodes with negative SLNs in the traditional basin. Sex, age, thickness, ulceration, and the presence of mitotic figures were not predictive of identifying an interval node on LS, nor for having disease in an interval node. Anatomic location of the primary melanoma was the only identifiable risk factor, as no interval nodes were identified in melanomas of the thigh or upper arm (P ≤ 0.001). CONCLUSIONS: Distal extremity melanomas have a moderate risk of mapping to an interval SLN. Routine LS should be considered in these patients, especially as these may be the only tumor-positive nodes. However, primary extremity melanomas proximal to the epitrochlear or popliteal nodal basins do not map to interval nodes, and improved savings and workflow could be realized by selectively omitting routine LS in such patients.

Barriers to resection following neoadjuvant chemotherapy for resectable pancreatic adenocarcinoma: A national and local perspective.

BACKGROUND: Neoadjuvant chemotherapy (NAC) use for pancreatic ductal adenocarcinoma (PDAC) has increased, but some patients never get resection following NAC. METHODS: Data from January 2012 to December 2019 for all clinically resectable patients across two health networks were utilized, as well as data from the ACS NCDB registry. Univariate testing, multivariable logistic regression, and survival analyses were employed to evaluate failure to resection after neo-adjuvant chemotherapy. RESULTS: Of the 10 007 registry patients eligible for resection, the resected group was younger (64.6 vs. 69.5 years; p < 0.001) and had a slightly lower mean comorbidity index (0.41 vs. 0.45; p < 0.001) than the nonsurgical group. The nonsurgical group was composed of a higher percentage of Black and Hispanic patients (17.5 vs. 13.1%; p < 0.001). After adjusting for age and comorbidities, the factors associated with decreased probability of resection after NAC were evaluation at a community hospital (OR 2.4), Black or Hispanic race (OR 1.6), areas of increased high school drop-out rates (OR 1.4), and lack of private health insurance (OR 1.3). The median overall survival for nonsurgery was markedly worse than the surgical cohort (10.6 vs. 26.6 months; p < 0.001). The most frequent reasons for a lack of definitive resection were operative upstaging to unresectable (39.6%), patient preference (14.5%), progression on NAC (13.2%), deconditioning or comorbidity severity (12.5%), and nonreferral to a surgeon (8.8%). CONCLUSIONS: Racial, economic, and educational disparities have a considerable influence on the successful completion of a neoadjuvant approach for resectable PDAC. A comprehensive closed or highly collaborative/communicative multidisciplinary neoadjuvant program is optimal for treatment success and completion.

Complete genome sequence of vaccinium-associated virus C, a new member of the family Totiviridae from Vaccinium floribundum.

Blueberries (Vaccinium sp.) are a major crop grown in the Pacific Northwest region. Currently, there are at least 17 known viruses that infect blueberry plants, and some of them cause a wide range of symptoms and economic losses. A new virus, vaccinium-associated virus C (VaVC) (family Totiviridae, genus Totivirus) was identified in an imported blueberry accession from the USDA-ARS National Clonal Germplasm Repository in Corvallis, Oregon. The complete genomic sequence of VaVC was determined, but the biological significance of VaVC is unknown and requires further study. Additional Vaccinium sp. accessions should be screened to investigate the incidence of this new virus.

Simultaneous mapping of cathodoluminescence spectra and backscatter diffraction patterns in a scanning electron microscope.

Electron backscatter diffraction and cathodoluminescence are complementary scanning electron microscopy modes widely used in the characterisation of semiconductor films, respectively revealing the strain state of a crystalline material and the effect of this strain on the light emission from the sample. Conflicting beam, sample and detector geometries have meant it is not generally possible to acquire the two signals together during the same scan. Here, we present a method of achieving this simultaneous acquisition, by collecting the light emission through a transparent sample substrate. We apply this combination of techniques to investigate the strain field and resultant emission wavelength variation in a deep-ultraviolet micro-LED. For such compatible samples, this approach has the benefits of avoiding image alignment issues and minimising beam damage effects.

Combined pre-operative risk score predicts pancreatic leak after pancreatic resection.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a major complication following pancreatectomy and is currently difficult to predict pre-operatively. This study aims to validate pre-operative risk factors and develop a novel combined score for the prediction of POPF in the pre-operative setting. METHODS: Data were collected from 2016 to 2021 for radiologic main pancreatic duct diameter (MPD), body mass index (BMI), physical status classified by American Society of Anesthesiologists (ASA), polypharmacy, mean platelet ratio (MPR), comorbidity-polypharmacy score (CPS), and a novel Combined Pancreatic Leak Prediction Score (CPLPS) (derived from MPD diameter, BMI, and CPS) were obtained from pre-operative data and analyzed for their independent association with POPF occurrence. RESULTS: In total, 166 patients who underwent pancreatectomy with pancreatic leak (Grade A, B, and C) occurring in 51(30.7%) of patients. Pre-operative radiologic MPD diameter < 4 mm (p < 0.001), < 5 mm (p < 0.001), < 6 mm (p = 0.001), BMI ≥ 25 (p = 0.009), and ≥ 30 (p = 0.017) were independently associated with the occurrence of pancreatic leak. CPLPS was also predictive of pancreatic leak following pancreatectomy on univariate (p = 0.005) and multivariate analysis (p = 0.036). CONCLUSION: MPD and BMI were independent risk factors predictive for the development of pancreatic leak. CPLPS, was an independent predictor of pancreatic leak following pancreatectomy and could be used to help guide surgical decision making and patient counseling.

Childcare needs as a barrier to healthcare among women in a safety-net health system.

BACKGROUND: Childcare needs are an understudied social determinant of health. The effect of childcare needs on access to healthcare must be understood to inform health system interventions and policy reform. This study sought to characterize childcare needs, access to childcare, and prior experience with navigating childcare needs in healthcare settings among women in a safety-net population. METHODS: We conducted a cross-sectional study of patient-reported survey data collected in-person between April and October 2019. Surveys were administered in waiting rooms of ambulatory services in a large, urban safety-net health system in Dallas, Texas. Survey respondents were derived from a random convenience sample of women waiting for outpatient appointments. Participants were screened for having children under the age of 13 and/or childcare responsibilities for inclusion in the sample. Outcomes of interest included self-reported delayed or missed care, reasons for delayed or missed care, perceived difficulty in accessing childcare, prior methods for managing childcare during healthcare appointments, and prior experience with childcare centers. RESULTS: Among the 336 respondents (96.7% response rate), 121 (36.0%) reported delaying or missing a mean 3.7 appointments/year. Among women with delayed or missed care, 54.5% reported childcare barriers as the primary reason for deferral of care, greater than transportation (33%) or insurance (25%) barriers. Respondents rated childcare access as more difficult than healthcare access. Delayed or missed care due to childcare was more common among White (68.8%) and Black (55.0%) women compared to Hispanic women (34.3%). Common methods of navigating childcare needs during scheduled appointments included bringing children to appointments (69.1%) and re-scheduling or missing the scheduled appointment (43.0%). 40.6% of patients reported leaving an appointment before completion due to childcare needs. CONCLUSIONS: Childcare needs are a leading barrier to healthcare among women accessing care in safety-net settings. Unmet childcare needs result in deferral of care, which may impact health outcomes. Childcare access is perceived as more challenging than healthcare access itself. Health system and policy interventions are needed to address childcare as a social determinant of health.

Core-Shell Nanorods as Ultraviolet Light-Emitting Diodes.

Existing barriers to efficient deep ultraviolet (UV) light-emitting diodes (LEDs) may be reduced or overcome by moving away from conventional planar growth and toward three-dimensional nanostructuring. Nanorods have the potential for enhanced doping, reduced dislocation densities, improved light extraction efficiency, and quantum wells free from the quantum-confined Stark effect. Here, we demonstrate a hybrid top-down/bottom-up approach to creating highly uniform AlGaN core-shell nanorods on sapphire repeatable on wafer scales. Our GaN-free design avoids self-absorption of the quantum well emission while preserving electrical functionality. The effective junctions formed by doping of both the n-type cores and p-type caps were studied using nanoprobing experiments, where we find low turn-on voltages, strongly rectifying behaviors and significant electron-beam-induced currents. Time-resolved cathodoluminescence measurements find short carrier liftetimes consistent with reduced polarization fields. Our results show nanostructuring to be a promising route to deep-UV-emitting LEDs, achievable using commercially compatible methods.

Selective 1,2-Hydroarylation(Alkenylation) of gem-Difluoroalkenes to Access (-CF2 H) Motifs.

An emerging class of C-C coupling transformations that furnish drug-like building blocks involves catalytic hydrocarbonation of alkenes. However, despite notable advances in the field, hydrocarbon addition to gem-difluoroalkenes without additional electronic activation remains largely unsuccessful. This owes partly to poor reactivity and the propensity of difluoroalkenes to undergo defluorinative side reactions. Here, we report a nickel catalytic system that promotes efficient 1,2-selective hydroarylation and hydroalkenylation, suppressing defluorination and providing straightforward access to a diverse assortment of prized organofluorides bearing difluoromethyl-substituted carbon centers. In contrast to radical-based pathways and reactions triggered by hydrometallation via a nickel-hydride complex, our experimental and computational studies support a mechanism in which a catalytically active nickel-bromide species promotes selective carbonickelation with difluoroalkenes followed by alkoxide exchange and hydride transfer, effectively overcoming the difluoroalkene's intrinsic electronic bias.

Cyclopropenimine-Mediated CO2 Activation for the Synthesis of Polyurethanes and Small-Molecule Carbonates and Carbamates.

Carbon dioxide (CO2) is an abundant C1 feedstock with tremendous potential to produce versatile building blocks in synthetic applications. Given the adverse impact of CO2 on the atmosphere, it is of paramount importance to devise strategies for upcycling it into useful materials, such as polymers and fine chemicals. To activate such stable molecule, superbases offer viable modes of binding to CO2. In this study, a superbase cyclopropenimine derivative was found to exhibit exceptional proficiency in activating CO2 and mediating its polymerization at ambient temperature and pressure for the synthesis of polyurethanes. The versatility of this reaction can be extended to monofunctional amines and alcohols, yielding a variety of functional carbonates and carbamates.

Disparities in the Operative Experience Between Female and Male General Surgery Residents: A Multi-institutional Study From the US ROPE Consortium.

OBJECTIVE: To examine differences in resident operative experience between male and female general surgery residents. BACKGROUND: Despite increasing female representation in surgery, sex and gender disparities in residency experience continue to exist. The operative volume of male and female general surgery residents has not been compared on a multi-institutional level. METHODS: Demographic characteristics and case logs were obtained for categorical general surgery graduates between 2010 and 2020 from the US Resident OPerative Experience Consortium database. Univariable, multivariable, and linear regression analyses were performed to compare differences in operative experience between male and female residents. RESULTS: There were 1343 graduates from 20 Accreditation Council for Graduate Medical Education-accredited programs, and 476 (35%) were females. There were no differences in age, race/ethnicity, or proportion pursuing fellowship between groups. Female graduates were less likely to be high-volume residents (27% vs 36%, P < 0.01). On univariable analysis, female graduates performed fewer total cases than male graduates (1140 vs 1177, P < 0.01), largely due to a diminished surgeon junior experience (829 vs 863, P < 0.01). On adjusted multivariable analysis, female sex was negatively associated with being a high-volume resident (OR = 0.74, 95% CI: 0.56 to 0.98, P = 0.03). Over the 11-year study period, the annual total number of cases increased significantly for both groups, but female graduates (+16 cases/year) outpaced male graduates (+13 cases/year, P = 0.02). CONCLUSIONS: Female general surgery graduates performed significantly fewer cases than male graduates. Reassuringly, this gap in operative experience may be narrowing. Further interventions are warranted to promote equitable training opportunities that support and engage female residents.

Infection reporting in patients undergoing irreversible electroporation of locally advanced pancreatic cancer.

BACKGROUND: Intraoperative bile cultures (IOBCs) taken during pancreatic surgery are commonly performed and there has been limited evidence that a positive IOBC could aid in perioperative adverse event (AE) management. Therefore, this study aims to describe infection management in patients undergoing irreversible electroporation (IRE). METHODS: An Institutional Review Board (IRB)-approved prospective database was utilized from 8/2016 to 6/2022, with 127 pancreatic adenocarcinoma patients included. RESULTS: A total of 28 patients that underwent IRE also had a simultaneous positive IOBC and the remaining 99 patients that underwent IRE had negative IOBC. A total of 11(39%) of the patients with a positive IOBC had AE's, and 38 (38%) of the patients with negative IOBC had AE's. Both groups had similar rates of AEs leading to new hospitalization and prolonged hospitalizations. Overall, there was no correlation between a positive IOBC and a patient developing an AE. CONCLUSIONS: The findings of this study provide insights that improve the infectious management of patients undergoing IRE.

Imaging of Suspected Stroke in Children, From the AJR Special Series on Emergency Radiology.

Pediatric stroke encompasses different causes, clinical presentations, and associated conditions across ages. Although it is relatively uncommon, pediatric stroke presents with poor short- and long-term outcomes in many cases. Because of a wide range of overlapping presenting symptoms between pediatric stroke and other more common conditions, such as migraine and seizures, stroke diagnosis can be challenging or delayed in children. When combined with a comprehensive medical history and physical examination, neuroimaging plays a crucial role in diagnosing stroke and differentiating stroke mimics. This review highlights the current neuroimaging workup for diagnosing pediatric stroke in the emergency department, describes advantages and disadvantages of different imaging modalities, highlights disorders that predispose children to infarct or hemorrhage, and presents an overview of stroke mimics. Key differences in the initial approach to suspected stroke between children and adults are also discussed.

Biofuel blending reduces particle emissions from aircraft engines at cruise conditions.

Aviation-related aerosol emissions contribute to the formation of contrail cirrus clouds that can alter upper tropospheric radiation and water budgets, and therefore climate. The magnitude of air-traffic-related aerosol-cloud interactions and the ways in which these interactions might change in the future remain uncertain. Modelling studies of the present and future effects of aviation on climate require detailed information about the number of aerosol particles emitted per kilogram of fuel burned and the microphysical properties of those aerosols that are relevant for cloud formation. However, previous observational data at cruise altitudes are sparse for engines burning conventional fuels, and no data have previously been reported for biofuel use in-flight. Here we report observations from research aircraft that sampled the exhaust of engines onboard a NASA DC-8 aircraft as they burned conventional Jet A fuel and a 50:50 (by volume) blend of Jet A fuel and a biofuel derived from Camelina oil. We show that, compared to using conventional fuels, biofuel blending reduces particle number and mass emissions immediately behind the aircraft by 50 to 70 per cent. Our observations quantify the impact of biofuel blending on aerosol emissions at cruise conditions and provide key microphysical parameters, which will be useful to assess the potential of biofuel use in aviation as a viable strategy to mitigate climate change.

A meta-analysis and systematic review of the comparison of laparoscopic ablation to percutaneous ablation for hepatic malignancies.

BACKGROUND: The optimal access for thermal ablation of the liver has not been evaluated in the literature for the laparoscopic versus percutaneous techniques. The aim of this manuscript was to determine the optimal ablation technique and patient selection for hepatic malignancies by comparing the efficacy and recurrence-free survival of laparoscopic and percutaneous thermal ablation. METHODS: A detailed literature search was made in PubMed, Web of Science, Google scholar, and EMBASE for related research publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, and Odds Ratio (OR) or Hazard Ratio (HR) with corresponding confidence intervals (CIs) was calculated and summarized respectively. RESULTS: A total of 10 articles were included with 1916 ablation patients. Laparoscopic ablation success (Median 100%) was found to be higher than percutaneous ablation success (median 89.4%) (p = ns). There was a higher percentage of both local and non-local hepatic recurrence in the patients treated with percutaneous ablation versus laparoscopic ablation. Meta-analysis indicated no difference in the adjusted hazard rate of recurrence by procedure type (p = 0.94). Laparoscopic ablation had a higher percentage of complications compared to percutaneous ablation (median lap 14.5% vs. perc 3.3%). CONCLUSIONS: While laparoscopic and percutaneous ablation are both effective interventions for hepatic malignancies, laparoscopic ablation was found to have improved ablation success and less local and non-local hepatic recurrence compared to percutaneous ablation.

Trustworthiness as information: Satisfying the understanding condition of valid consent.

Within medical ethics, there is widespread agreement that morally valid consent includes an understanding condition. Disagreement centers on what is meant by that understanding condition. Tom Dougherty proposed that this understanding condition should be divided into the two mutually exclusive categories of descriptive information and contextual information. Further, Dougherty argues that each type of information is necessary to satisfy the understanding condition. In contrast, I argue that when the deontic aspect of valid consent is in view, each type of information can be sufficient to satisfy the understanding condition on its own. Moreover, by analyzing delegation, which is conceptually related to consent since both are morally transformative actions, I show that delegation often depends not on descriptive or contextual information but on trust. So, I argue that trustworthiness can also be a type of information that does the same work as descriptive and contextual information in satisfying the understanding condition for valid consent.

A Prospective Study of Social Needs Associated with Mental Health among Postpartum Patients Living in Underserved Communities.

OBJECTIVE: Given the rising rates of maternal morbidity and mortality in the United States and the contribution of mental illness, especially among individuals living in underresourced communities, the objective was to evaluate the prevalence of unmet health-related social needs and their impact on perinatal mental health outcomes. STUDY DESIGN: This was a prospective observational study of postpartum patients residing within regions with increased rates of poor perinatal outcomes and sociodemographic disparities. Patients were enrolled in a multidisciplinary public health initiative "extending Maternal Care After Pregnancy (eMCAP)" between October 1, 2020 and October 31, 2021. Unmet health-related social needs were assessed at delivery. Symptoms of postpartum depression and anxiety were evaluated at 1 month postpartum utilizing the Edinburgh Postnatal Depression Scale (EPDS) and Generalized Anxiety Disorder-7 (GAD7) screening tools, respectively. Mean EPDS and GAD7 scores and odds of screening positive (scoring ≥ 10) were compared among individuals with and without unmet health-related social needs with p < 0.05 considered significant. RESULTS: Of participants enrolled in eMCAP, 603 completed at least one EPDS or GAD7 at 1 month. Most had at least one social need, most commonly dependence on social programs for food (n = 413/603; 68%). Individuals lacking transportation to medical (odds ratio [OR]: 4.0, 95% confidence interval [CI]: 1.2-13.32) and nonmedical appointments (OR: 4.17, 95% CI: 1.08-16.03) had significantly higher odds of screening positive on EPDS while participants lacking transportation to medical appointments (OR: 2.73, 95% CI: 0.97-7.70) had significantly higher odds of screening positive on GAD7. CONCLUSION: Among postpartum individuals in underserved communities, social needs correlate with higher depression and anxiety screening scores. This highlights the need to address social needs to improve maternal mental health. KEY POINTS: · Social needs are prevalent among underserved patients.. · Needs can be assessed in a structured or freeform manner.. · Unmet needs correlate with poor mental health outcomes.. · Similar needs correlate with depression and anxiety..

Learning dynamics on invariant measures using PDE-constrained optimization.

We extend the methodology in Yang et al. [SIAM J. Appl. Dyn. Syst. 22, 269-310 (2023)] to learn autonomous continuous-time dynamical systems from invariant measures. The highlight of our approach is to reformulate the inverse problem of learning ODEs or SDEs from data as a PDE-constrained optimization problem. This shift in perspective allows us to learn from slowly sampled inference trajectories and perform uncertainty quantification for the forecasted dynamics. Our approach also yields a forward model with better stability than direct trajectory simulation in certain situations. We present numerical results for the Van der Pol oscillator and the Lorenz-63 system, together with real-world applications to Hall-effect thruster dynamics and temperature prediction, to demonstrate the effectiveness of the proposed approach.