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It is estimated that nearly five billion people do not have access to surgical care. Approximately 94% of individuals in low- and middle-income countries (LMICs) lack access to surgery in comparison to 14.9% in high-income countries (HICs). There are several urologic conditions requiring surgical intervention that are not treated because of the limited number of expert urologists in LMICs. Telesurgery is a concept that connects patients and surgeons in different locations through the use of a robotic surgery system. In this review, we explain the origins of telesurgery as well as the benefits and obstacles to its global implementation. Telesurgery can reduce travel times and the dangers associated with traveling for surgical care in LMICs. Additionally, telesurgery allows patients in LMICs to gain access to expert urologists while also providing effective training to upcoming surgeons. However, LMICs require substantial investment to improve digital infrastructure that will support urologic telesurgery. There will also be ethical, legal, and policy considerations that will need to be resolved for safe and equitable urologic telesurgery to occur. There have been multiple successful applications of urologic telesurgery, suggesting that the technology for this to become routine is already available. The time for international collaboration must begin now to reduce global disparities in access to urologic surgery.

Activating the expression of host susceptibility (S) genes is one of the strategies plant pathogens employed to promote infection of their host. Here, the authors show that targeted methylation at the TAL20 effector binding element of the cassava SWEET10a gene lead to resistance to Xanthomonas phaseoli.

Cassava mosaic disease is caused by geminiviruses and suppresses cassava yields throughout the tropics. Here, the authors show that mutations in MePOLD1, encoding DNA polymerase δ subunit 1, co-segregate with CMD2, the major source of genetic resistance for this disease.

Abstract Background Methods to accurately quantify disease severity are fundamental to plant pathogen interaction studies. Commonly used methods include visual scoring of disease symptoms, tracking pathogen growth in planta over time, and various assays that detect plant defense responses. Several image-based methods for phenotyping of plant disease symptoms have also been developed. Each of these methods has different advantages and limitations which should be carefully considered when choosing an approach and interpreting the results. Results In this paper, we developed two image analysis methods and tested their ability to quantify different aspects of disease lesions in the cassava-Xanthomonas pathosystem. The first method uses ImageJ, an open-source platform widely used in the biological sciences. The second method is a few-shot support vector machine learning tool that uses a classifier file trained with five representative infected leaf images for lesion recognition. Cassava leaves were syringe infiltrated with wildtype Xanthomonas, a Xanthomonas mutant with decreased virulence, and mock treatments. Digital images of infected leaves were captured overtime using a Raspberry Pi camera. The image analysis methods were analyzed and compared for the ability to segment the lesion from the background and accurately capture and measure differences between the treatment types. Conclusions Both image analysis methods presented in this paper allow for accurate segmentation of disease lesions from the non-infected plant. Specifically, at 4-, 6-, and 9-days post inoculation (DPI), both methods provided quantitative differences in disease symptoms between different treatment types. Thus, either method could be applied to extract information about disease severity. Strengths and weaknesses of each approach are discussed.

Environmental variability poses a major challenge to any field study. Researchers attempt to mitigate this challenge through replication. Thus, the ability to detect experimental signals is determined by the degree of replication and the amount of environmental variation, noise, within the experimental system. A major source of noise in field studies comes from the natural heterogeneity of soil properties which create microtreatments throughout the field. In addition, the variation within different soil properties is often nonrandomly distributed across a field. We explore this challenge through a sorghum field trial dataset with accompanying plant, microbiome, and soil property data. Diverse sorghum genotypes and two watering regimes were applied in a split-plot design. We describe a process of identifying, estimating, and controlling for the effects of spatially distributed soil properties on plant traits and microbial communities using minimal degrees of freedom. Importantly, this process provides a method with which sources of environmental variation in field data can be identified and adjusted, improving our ability to resolve effects of interest and to quantify subtle phenotypes.

Size‐based selectivity for metal ions based on highly preorganized five‐membered chelate rings is discussed. Metal ion complexation by the tetra‐pyridyl ligand EBIP ((8,9‐dihydro‐diquino[8,7‐b:7′,8′‐j][1,10]phenanthroline) is investigated, Formation constants (log K1) are reported for EBIP with 28 metal ions in 50 % CH3OH/H2O (v/v). The shift in size‐selectivity toward large metal ions and against small metal is demonstrated. Log K1 for the EBIP complexes shows a steady increase from La(III) to Lu(III), with a strong local maximum at Sm(III), and strong local minimum at Gd(III). This difference in log K1 between Sm(III) and Gd(III) for the tetra‐pyridyls is shown to depend largely on the level of preorganization of the ligand, being at a maximum for EBIP and a minimum for quaterpyridine. Log K1 for the Y(III) complex is invariably lower than for the similarly‐sized Ho(III) for all ligands that contain any nitrogen donors. Lower log K values for Y(III) are due to stabilization of the Ln(III) complexes with nitrogen donors by participation of the 5d orbitals, and to a lesser extent the 4 f orbitals, of the Ln(III) ions in M−L bonding. A DFT analysis of selectivity of tetra‐pyridyls for metal ions shows that Y(III) complexes should be less stable than similarly‐sized Ho(III) complexes. [ABSTRACT FROM AUTHOR]

Background: Stuttering priapism is characterized by recurrent, self-limited episodes of penile erection lasting from a few minutes to a maximum of three hours, often resolving spontaneously. These episodes can occur with or without sexual stimulation. If not treated promptly and effectively, stuttering priapism can severely impact a patient's quality of life, leading to significant psychological distress and anxiety related to sexual performance. Although it has been associated with various hematological disorders and pharmacological treatments, many cases of stuttering priapism remain idiopathic, meaning they have no identifiable cause. Currently, no conclusive randomized clinical trials exist on the management of idiopathic stuttering priapism. This study aims to review the existing literature on the pathophysiology and management of idiopathic stuttering priapism and propose an algorithm to assist physicians in its evaluation and treatment., Results: A systematic literature review was conducted using the PubMed database, focusing on the terms "idiopathic," "stuttering," "ischemic," and "priapism." The search identified 23 relevant references published between 1991 and 2022. The selection and analysis of these studies adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, and results were described qualitatively. Recent research into the effectiveness, sustainability, tolerability, and side effects of various treatments for idiopathic stuttering priapism has enhanced the understanding of its underlying molecular mechanisms. Various treatments, targeting different mechanisms, have been identified that can potentially reduce the frequency and severity of episodes and improve patient outcomes., Conclusion: Current research predominantly addresses the acute treatment of idiopathic stuttering priapism rather than strategies to alter the disease's overall course. The limited number of treatment reviews, case reports, and the low level of evidence available, combined with the absence of randomized clinical trials, prevent the establishment of a consensus on treatment protocols. As a result, idiopathic stuttering priapism remains under-recognized and under-treated. This review proposes a management framework to help clinicians access and apply the available literature effectively, minimizing the reliance on extensive case reports and review articles., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Ad26.RSV.preF is an adenovirus serotype 26 vector-based respiratory syncytial virus (RSV) vaccine encoding a prefusion conformation-stabilized RSV fusion protein (preF) that demonstrated robust humoral and cellular immunogenicity and showed promising efficacy in a human challenge study in younger adults. Addition of recombinant RSV preF protein might enhance RSV-specific humoral immune responses, especially in older populations., Methods: This randomized, double-blind, placebo-controlled, phase 1/2a study compared the safety and immunogenicity of Ad26.RSV.preF alone and varying doses of Ad26.RSV.preF-RSV preF protein combinations in adults aged ≥60 years. This report includes data from cohort 1 (initial safety, n = 64) and cohort 2 (regimen selection, n = 288). Primary immunogenicity and safety analyses were performed 28 days postvaccination (cohort 2) for regimen selection., Results: All vaccine regimens were well tolerated, with similar reactogenicity profiles among them. Combination regimens induced greater humoral immune responses (virus-neutralizing and preF-specific binding antibodies) and similar cellular ones (RSV-F-specific T cells) as compared with Ad26.RSV.preF alone. Vaccine-induced immune responses remained above baseline up to 1.5 years postvaccination., Conclusions: All Ad26.RSV.preF-based regimens were well tolerated. A combination regimen comprising Ad26.RSV.preF, which elicits strong humoral and cellular responses, and RSV preF protein, which increases humoral responses, was selected for further development. Clinical Trials Registration. NCT03502707., Competing Interests: Potential conflicts of interests. C. A. C and E. H. are former employees of Janssen Vaccines & Prevention B.V. A. R. B., L.v. d. F., R. v. H., B. C., and J. S. are employees of Janssen Vaccines & Prevention B.V. V. K. is an employee of Janssen Infectious Diseases. E. D. P. and E. O. are former employees of Janssen Infectious Diseases. S. B. reports no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Family members of autistic individuals often provide support for their autistic relative throughout the lifespan which can lead to massive burden themselves. Reduced health-related Quality of Life (HRQoL) in family caregivers is assumed; however, only a handful studies on the HRQoL of family caregivers providing care to adult relatives exist as opposed to autistic children. Thus, the current study aimed to (i) investigate the current state of physical and mental HRQoL of family caregivers of autistic adults compared to the general population, and (ii) examine caregiver-related (e.g., age, subjective caregiver burden) and care recipient-related variables (e.g., symptom severity, utilization of formal services) explaining variance in the caregivers' HRQoL., Methods: N = 149 family caregivers completed a nationwide online survey, including the Short-Form Health Survey (SF-8) in order to assess the HRQoL. T-tests were used to compare the HRQoL of family caregivers with the general population. Bivariate correlational and multiple linear regression analyses were conducted in order to identify predictors explaining variance in family caregivers' HRQoL., Results: Family caregivers of autistic adults reported significantly lower physical ( M = 46.71, SD = 8.72, Cohen's d = 0.42) and mental HRQoL ( M = 40.15, SD = 11.28, Cohen's d = 1.35) compared to the general population. Multiple linear regression with the mental HRQoL as the outcome showed a significant model ( F (11, 95) = 5.53, p < .001, adj. R 2 = .32) with increased subjective burden explaining most of the variance in mental HRQoL ( ß = .32, GDW = .141, p < .001). Multiple linear regression analysis with the outcome physical HRQoL did not reveal a statistically significant model ( F (11,95) = 1.09, p = .38). However, bivariate analyses also showed a positive correlation with the subjective caregiver burden ( r = .20, p < .05)., Discussion: Findings highlight the need to consider HRQoL (and caregiver burden) of family caregivers of autistic adults in several healthcare settings to monitor a potential comprised health status in early stages, with the long-term goal to improve family caregivers' HRQoL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dückert, Bart, Gewohn, König, Schöttle, Konnopka, Rahlff, Erik, Vogeley, Schulz, David and Peth.)

Background: Chikungunya, a mosquito-borne viral disease caused by the chikungunya virus (CHIKV), causes a significant global health burden, and there is currently no approved vaccine to prevent chikungunya disease. In this study, the safety and immunogenicity of a CHIKV mRNA vaccine candidate (mRNA-1388) were evaluated in healthy participants in a CHIKV-nonendemic region., Methods: This phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study enrolled healthy adults (ages 18-49 years) between July 2017 and March 2019 in the United States. Participants were randomly assigned (3:1) to receive 2 intramuscular injections 28 days apart with mRNA-1388 in 3 dose-level groups (25 μg, 50 μg, and 100 μg) or placebo and were followed for up to 1 year. Safety (unsolicited adverse events [AEs]), tolerability (local and systemic reactogenicity; solicited AEs), and immunogenicity (geometric mean titers [GMTs] of CHIKV neutralizing and binding antibodies) of mRNA-1388 versus placebo were evaluated., Results: Sixty participants were randomized and received ≥ 1 vaccination; 54 (90 %) completed the study. mRNA-1388 demonstrated favorable safety and reactogenicity profiles at all dose levels. Immunization with mRNA-1388 induced substantial and persistent humoral responses. Dose-dependent increases in neutralizing antibody titers were observed; GMTs (95 % confidence intervals [CIs]) at 28 days after dose 2 were 6.2 (5.1-7.6) for mRNA-1388 25 μg, 53.8 (26.8-108.1) for mRNA-1388 50 μg, 92.8 (43.6-197.6) for mRNA-1388 100 μg, and 5.0 (not estimable) for placebo. Persistent humoral responses were observed up to 1 year after vaccination and remained higher than placebo in the 2 higher mRNA-1388 dose groups. The development of CHIKV-binding antibodies followed a similar trend as that observed with neutralizing antibodies., Conclusions: mRNA-1388, the first mRNA vaccine against CHIKV, was well tolerated and elicited substantial and long-lasting neutralizing antibody responses in healthy adult participants in a nonendemic region., Clinicaltrials: gov: NCT03325075., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A.A., C.A.S., C.K., H.Z., and L.P. are employees of Moderna, Inc., and may hold stock/stock options in the company. S.B., P.-G.J.B., T.B., and S.W. have no relevant or material financial interests that relate to the research described in this article., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity., Methods: We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3)., Results: Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively)., Conclusions: In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.)., (Copyright © 2023 Massachusetts Medical Society.)

Hypertriglyceridemia (HTG) is a prevalent medical condition in patients with cardiometabolic risk factors and is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), if left undiagnosed and undertreated. Current guidelines identify HTG as a risk-enhancing factor and, as a result, recommend clinical evaluation and lifestyle-based interventions to address potential secondary causes of elevated triglyceride (TG) levels. For individuals with mild to moderate HTG at risk of ASCVD, statin therapy alone or in combination with other lipid-lowering medications known to decrease ASCVD risk are guideline-endorsed. In addition to lifestyle modifications, patients with severe HTG at risk of acute pancreatitis may benefit from fibrates, mixed formulation omega-3 fatty acids, and niacin; however, evidence does not support their use for ASCVD risk reduction in the contemporary statin era. Novel therapeutics including those that target apoC-III and ANGPTL3 have shown to be safe, well-tolerated, and effective for lowering TG levels. Given the growing burden of cardiometabolic disease and risk factors, public health and health policy strategies are urgently needed to enhance access to effective pharmacotherapies, affordable and nutritious food options, and timely health care services.

Lepidopteran species can be both pests and also beneficial pollinators for agricultural crops. However, despite these important roles, the effects of pesticides on this diverse taxa are relatively understudied. To facilitate the assessment of pesticides and other chemical hazards on this taxa, we present a novel bioassay capable of testing chemical sensitivity to lepidopteran larvae through dietary exposure. We used Mamestra brassicae caterpillars as a model lepidopteran and tested their sensitivity for the organophosphate insecticide chlorpyrifos. We exposed larvae to an artificial diet spiked with chlorpyrifos and monitored survival over time, as well as weight change over a 96-hour exposure period. To test the repeatability and reliability of the developed bioassay, the experiment was repeated three times. The survival in time data collected enabled analysis with the General Unified Threshold of Survival (GUTS) model, recently recognized by EFSA as a ready-to-use tool for regulatory purposes. The GUTS modelling was used to derive a set of relevant toxicokinetic and toxicodynamic parameters relating to the larval response to exposure over time. We found that across the three repeats studies there was no more than a threefold difference in LC₅₀ values (13.1, 18.7 and 8.1 mg/Kg) at 48 h and fourfold difference at 96 h, highlighting the repeatability of the bioassay. We also highlighted the potential of the method to observe sub-lethal effects such as changes in weight. Finally, we discuss the applications of this new bioassay method to chemical risk assessments and its potential for use in other scenarios, such as mixture or pulsed exposure testing., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:David Spurgeon reports financial support was provided by UK Research and Innovation. Claire Badder reports financial support was provided by UKRI., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The Dynamic Energy Budget theory (DEB) enables ecotoxicologists to model the effects of chemical stressors on organism life cycles through the coupling of toxicokinetic-toxicodynamic (TK-TD) models. While good progress has been made in the application of DEB-TKTD models for aquatic organisms, applications for soil fauna are scarce, due to the lack of dedicated experimental designs suitable for collecting the required time series effect data. Enchytraeids (Annelida: Clitellata) are model organisms in soil ecology and ecotoxicology. They are recognised as indicators of biological activity in soil, and chemical stress in terrestrial ecosystems. Despite this, the application of DEB-TKTD models to investigate the impact of chemicals has not yet been tested on this family. Here we assessed the impact of the pyrethroid insecticide cypermethrin on the life cycle of Enchytraeus crypticus. We developed an original experimental design to collect the data required for the calibration of a DEB-TKTD model for this species. E. crypticus presented a slow initial growth phase that has been successfully simulated with the addition of a size-dependent food limitation for juveniles in the DEB model. The DEB-TKTD model simulations successfully agreed with the data for all endpoints and treatments over time. The highlighted physiological mode of action (pMoA) for cypermethrin was an increase of the growth energy cost. The threshold for effects on survival was estimated at 73.14 mg kg - 1 , and the threshold for effects on energy budget (i.e., sublethal effects) at 19.21 mg kg - 1 . This study demonstrates that DEB-TKTD models can be successfully applied to E. crypticus as a representative soil species, and may improve the ecological risk assessment for terrestrial ecosystems, and our mechanistic understanding of chemical effects on non-target species., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roman Ashauer reports a relationship with Syngenta Crop Protection AG that includes: employment., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: In 2018, the French High Authority of Health (HAS) included a "time-out" phase in the latest version of the checklist for the operating room in order to improve the safety of operated patients. The aim of this study is to evaluate the practice of French urologists concerning the check list (CL) of the operating room., Material and Methods: A survey of 30 items was developed by the committee of accreditation of the French Association of Urology (AFU) and other contributors. It was centered on the characteristics of the urologists, the details of application of the CL, and the evaluation of the current version. After validation, the questionnaire was emailed as an online form in July 2021 for all the members of the AFU and AFUF., Results: Overall, 369 form the 1700 contacted urologists responded to the survey. The majority were more than 40 years old (70.11%) and less than 20 year of experience (54.49%). The engagement in individual or team accreditation was observed in 222 (60.7%) and 145 (39.84%) urologists, respectively. Almost half of them were present at the beginning of the CL (47.18%), and prescribed postoperative medication with the anesthesiologist (55.56%). The CL has modified the practice in 47.54%, however, with greater administrative burden, and 80% preferred that the AFU adapts the CL to the urology field., Conclusion: The practice of CL between urologists is variable. On multivariate analysis, the engagement in team accreditation was the only variable to influence the practice of time out., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Before plant protection product (PPP) marketing authorization, a risk assessment for nontarget soil organisms (e.g., earthworms) is required as part of Regulation (EC) No. 1107/2009. Following a stepwise approach, higher tier earthworm field studies are needed if they cannot demonstrate low long-term risk based on laboratory studies. The European guidance for terrestrial ecotoxicology refers to ISO guideline 11268-3 as a standard to conduct earthworm field studies. Assessment of such studies may be challenging, as no European harmonized guidance is available to properly analyze the accuracy, representativeness, and appropriateness of experimental designs, as well as the statistical analysis robustness of results and their scientific reliability. Following the ISO guideline 11268-3, a field study was performed in 2016-2017 (Versailles, France). An assessment of the first year of this field study was performed in agreement with the quality criteria provided in 2006 in the guidance document published by de Jong and collaborators and recommendations by Kula and collaborators that allows describing the protocol and results of earthworm field studies. Not only did we underline the importance of a detailed analysis of raw data on the effects of pesticides on earthworms in field situations, but we also provided recommendations to harmonize protocols for assessing higher tier field studies devoted to earthworms to advance a better assessment of PPP fate and ecotoxicity. In particular, we provided practical field observations related to the study design, pesticide applications, and earthworm sampling. Concurrently, in addition to the conventional earthworm community study, we propose carrying out an assessment of soil function (i.e., organic matter decomposition, soil structuration, etc.) and calculating diversity indices to obtain information about earthworm community dynamics after the application of PPPs. Finally, through field observations, any relevant observation of external and/or internal recovery should be reported. Integr Environ Assess Manag 2023;19:254-271. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

The first part of this article deals with accreditation of the quality of the professional practice of urologists and medical teams working in public or private health care institutions. This is a voluntary national risk management process based on the reporting and analysis of medical risk events and the development and implementation of recommendations. The fundamental objective of the system is to reduce the frequency and severity of adverse events associated with care for the patient. The second part aims to describe the mechanisms and management of surgical complications. The perception of complications by the urologist is discussed, as it may be distorted by cognitive biases leading to inappropriate actions. Two important points were also emphasized: communication with the patient following an injury, therapeutic hazard or complication following an error, and proper maintenance of the medical record. A joint effort to cultivate a culture of safety and quality in urological surgical practice should be encouraged. Collective actions by urologists in the future should help to maintain a proactive attitude: - generalization of quality accreditation of urologic physicians' professional practice; - national registry: which has demonstrated its advantages in the world of aeronautics; - creation of a specific module "Management of complications in urology" in teaching (ECU) and continuing education (SUC, website); - creation of an AFU "Complications" Committee; - management of social networks., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

The assessment of chemical mixture toxicity is one of the major challenges in ecotoxicology. Chemicals can interact, leading to more or less effects than expected, commonly named synergism and antagonism respectively. The classic ad hoc approach for the assessment of mixture effects is based on dose-response curves at a single time point, and is limited to identifying a mixture interaction but cannot provide predictions for untested exposure durations, nor for scenarios where exposure varies in time. We here propose a new approach using toxicokinetic-toxicodynamic modelling: The General Unified Threshold model of Survival (GUTS) framework, recently extended for mixture toxicity assessment. We designed a dedicated mechanistic interaction module coupled with the GUTS mixture model to i) identify interactions, ii) test hypotheses to identify which chemical is likely responsible for the interaction, and finally iii) simulate and predict the effect of synergistic and antagonistic mixtures. We tested the modelling approach experimentally with two species (Enchytraeus crypticus and Mamestra brassicae) exposed to different potentially synergistic mixtures (composed of: prochloraz, imidacloprid, cypermethrin, azoxystrobin, chlorothalonil, and chlorpyrifos). Furthermore, we also tested the model with previously published experimental data on two other species (Bombus terrestris and Daphnia magna) exposed to pesticide mixtures (clothianidin, propiconazole, dimethoate, imidacloprid and thiacloprid) found to be synergistic or antagonistic with the classic approach. The results showed an accurate simulation of synergistic and antagonistic effects for the different tested species and mixtures. This modelling approach can identify interactions accounting for the entire time of exposure, and not only at one time point as in the classic approach, and provides predictions of the mixture effect for untested mixture exposure scenarios, including those with time-variable mixture composition., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Roman Ashauer reports a relationship with Syngenta Crop Protection AG that includes: employment., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To describe our new endoscopic approach in treating iatrogenic ureteral stenosis using the "cut-to-The-light" technique., Methods: Case of a 54 year-old female patient who underwent a right percutaneous nephrolithotomy to treat a staghorn calculus with two subsequent complimentary ureteroscopies complicated by a severe proximal ureteral obstruction. An antegrade flexible uretereroscope and a retrograde rigid ureteroscope were used to locate the stenosis. With the aid of a 365-µm Ho: YAG laser fiber (settings 0.4 J, 12 Hz), we managed to successfully create a small incision in the stenotic lesion, the rigid ureterscopy light was clearly seen by the antegrade flexible ureteroscope and a through-and-through guidewire was then placed, securing the ureter. Ureteral dilatation was then performed followed by a full thickness incision of the ureteral stenosis. A single 8Fr, 28 cm double J ureteral stent was finally placed after stone fragmentation., Results: The operating time was 200 mins. No blood loss. No fever or signs of UTI were seen shortly after the operation. The Foley catheter was successfully removed at day one post-op. The hospital stay was short of only 2 days., Conclusion: The "cut-to-the-light" technique is a new application in the arsenal of ureteral stricture treatment that has been scarcely described in the literature before. The use of this method seems to offer excellent outcomes thus demonstrating the importance of this minimally invasive technique as an alternative to conventional invasive methods used. We believe that studies with larger samples and longer follow up are needed in order to fully determine the benefits of this method and to assess and reveal its suitable application and its drawbacks., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Yarak et al.)

Background: Though clinically similar, Ebola virus disease and Marburg virus disease are caused by different viruses. Of the 30 documented outbreaks of these diseases in sub-Saharan Africa, eight were major outbreaks (≥200 cases; five caused by Zaire ebolavirus [EBOV], two by Sudan ebolavirus [SUDV], and one by Marburg virus [MARV]). Our purpose is to develop a multivalent vaccine regimen protecting against each of these filoviruses. This first-in-human study assessed the safety and immunogenicity of several multivalent two-dose vaccine regimens that contain Ad26.Filo and MVA-BN-Filo., Methods: Ad26.Filo combines three vaccines encoding the glycoprotein (GP) of EBOV, SUDV, and MARV. MVA-BN-Filo is a multivalent vector encoding EBOV, SUDV, and MARV GPs, and Taï Forest nucleoprotein. This Phase 1, randomized, double-blind, placebo-controlled study enrolled healthy adults (18-50 years) into four groups, randomized 5:1 (active:placebo), to assess different Ad26.Filo and MVA-BN-Filo vaccine directionality and administration intervals. The primary endpoint was safety; immune responses against EBOV, SUDV, and MARV GPs were also assessed., Results: Seventy-two participants were randomized, and 60 (83.3%) completed the study. All regimens were well tolerated with no deaths or vaccine-related serious adverse events (AEs). The most frequently reported solicited local AE was injection site pain/tenderness. Solicited systemic AEs most frequently reported were headache, fatigue, chills, and myalgia; most solicited AEs were Grade 1-2. Solicited/unsolicited AE profiles were similar between regimens. Twenty-one days post-dose 2, 100% of participants on active regimen responded to vaccination and exhibited binding antibodies against EBOV, SUDV, and MARV GPs; neutralizing antibody responses were robust against EBOV (85.7-100%), but lower against SUDV (35.7-100%) and MARV (0-57.1%) GPs. An Ad26.Filo booster induced a rapid further increase in humoral responses., Conclusion: This study demonstrates that heterologous two-dose vaccine regimens with Ad26.Filo and MVA-BN-Filo are well tolerated and immunogenic in healthy adults., Clinicaltrials.gov: NCT02860650., Competing Interests: Viki Bockstal, Neil Goldstein, and Cynthia Robinson were full-time employees of Janssen Vaccines and Prevention, B.V. at the time of the study and may hold shares of Johnson & Johnson. Georgi Shukarev, Chelsea McLean, Auguste Gaddah, Dickson Anumenden, Jeroen N. Stoop, Anne Marit de Groot, Maria G. Pau, Jenny Hendriks, Benoit Callendret, Kerstin Luhn, and Macaya Douoguih are full-time employees of Janssen Vaccines and Prevention, B.V., and may hold shares of Johnson & Johnson. Stephan Bart, Stephen C. De Rosa, Kristen W. Cohen, and M. Juliana McElrath report grants from Janssen during the conduct of the study paid to their institutions. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Janssen has an agreement with the Yale Open Data Access (YODA) Project to serve as the independent review panel for the evaluation of requests for clinical study reports and participant-level data from investigators and physicians for scientific research that will advance medical knowledge and public health. Data will be made available following publication and approval by YODA of any formal requests with a defined analysis plan. For more information on this process or to make a request, please visit the Yoda Project site at http://yoda.yale.edu. The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency.

Background: The clinical utility of radiomics is hampered by a high correlation between the large number of features analysed which may result in the "bouncing beta" phenomenon which could in part explain why in a similar patient population texture features identified and/or cut-off values of prognostic significance differ from one study to another. Principal component analysis (PCA) is a technique for reducing the dimensionality of large datasets containing highly correlated variables, such as texture feature datasets derived from FDG PET images, increasing data interpretability whilst at the same time minimizing information loss by creating new uncorrelated variables that successively maximize variance. Here, we report on PCA of a texture feature dataset derived from 123 malignant melanoma lesions with a significant range in lesion size using the freely available LIFEx software., Results: Thirty-eight features were derived from all lesions. All features were standardized. The statistical assumptions for carrying out PCA analysis were met. Seven principal components with an eigenvalue > 1 were identified. Based on the "elbow sign" of the Scree plot, only the first five were retained. The contribution to the total variance of these components derived using Varimax rotation was, respectively, 30.6%, 23.6%, 16.1%, 7.4% and 4.1%. The components provided summarized information on the locoregional FDG distribution with an emphasis on high FDG uptake regions, contrast in FDG uptake values (steepness), tumour volume, locoregional FDG distribution with an emphasis on low FDG uptake regions and on the rapidity of changes in SUV intensity between different regions., Conclusions: PCA allowed to reduce the dataset of 38 features to a set of 5 uncorrelated new variables explaining approximately 82% of the total variance contained within the dataset. These principal components may prove more useful for multiple regression analysis considering the relatively low numbers of patients usually included in clinical trials on FDG PET texture analysis. Studies assessing the superior differential diagnostic, predictive or prognostic value of principal components derived using PCA as opposed to the initial texture features in clinical relevant settings are warranted., (© 2022. The Author(s).)

Background: This phase 1 placebo-controlled study assessed the safety and immunogenicity of 2-dose regimens of Ad26.ZEBOV (adenovirus serotype 26 [Ad26]) and MVA-BN-Filo (modified vaccinia Ankara [MVA]) vaccines with booster vaccination at day 360., Methods: Healthy US adults (N = 164) randomized into 10 groups received saline placebo or standard or high doses of Ad26 or MVA in 2-dose regimens at 7-, 14-, 28-, or 56-day intervals; 8 groups received booster Ad26 or MVA vaccinations on day 360. Participants reported solicited and unsolicited reactogenicity; we measured immunoglobulin G binding, neutralizing antibodies and cellular immune responses to Ebola virus glycoprotein., Results: All regimens were well tolerated with no serious vaccine-related adverse events. Heterologous (Ad26,MVA [dose 1, dose 2] or MVA,Ad26) and homologous (Ad26,Ad26) regimens induced humoral and cellular immune responses 21 days after dose 2; responses were higher after heterologous regimens. Booster vaccination elicited anamnestic responses in all participants., Conclusions: Both heterologous and homologous Ad26,MVA Ebola vaccine regimens are well tolerated in healthy adults, regardless of interval or dose level. Heterologous 2-dose Ad26,MVA regimens containing an Ebola virus insert induce strong, durable humoral and cellular immune responses. Immunological memory was rapidly recalled by booster vaccination, suggesting that Ad26 booster doses could be considered for individuals at risk of Ebola infection, who previously received the 2-dose regimen., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

On December 2, 2021, the Minnesota Department of Health (MDH) notified CDC of a COVID-19 case caused by sequence-confirmed SARS-CoV-2 B.1.1.529 (Omicron) variant in a Minnesota resident (patient A), the first such case identified in the state and one of the earliest identified in the United States. Patient A had attended a large indoor convention in New York, New York with approximately 53,000 attendees from 52 U.S jurisdictions and 30 foreign countries during November 19-21, 2021, and had close contact † during 5 days with 29 fellow attendees. The convention required attendees to have received ≥1 COVID-19 vaccine dose and enforced mask-use while indoors. On November 22, these close contact attendees were directly and immediately notified by patient A of their exposure to SARS-CoV-2, and they sought testing over the next few days while quarantined or isolated. As part of the larger investigation into SARS-CoV-2 transmission at the convention, a subinvestigation was conducted during December by CDC, MDH, and respective state and local health departments to characterize the epidemiology of Omicron variant infection among this group of close contacts and determine the extent of secondary household transmission. Among 30 convention attendees that included patient A (the index patient) and the 29 other close contacts, 23 were interviewed, among whom all were fully vaccinated, including 11 (48%) who had received a booster dose; all 23 sought testing, and 16 (70%) received a positive SARS-CoV-2 test result. Fewer attendees who had received a booster dose before the convention received a positive test result (six of 11) compared with those who had not received a booster dose (10 of 12). The 16 attendees with positive test results had a total of 20 household contacts, 18 of whom sought testing after exposure; six received a positive test result for SARS-CoV-2. None of the persons with positive test results was hospitalized or died. There was limited convention-associated transmission identified outside of this cluster; the larger investigation included cases of both SARS-CoV-2 B.1.617.2 (Delta) and Omicron, and all Omicron cases were associated with this group (1). Data from this investigation reinforces the importance of COVID-19 booster doses in combination with early notification and other multicomponent prevention measures to limit transmission and prevent severe illness from Omicron and other SARS-CoV-2 variants., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

In this article, a [Formula: see text] piezoelectric micromachined ultrasonic transducer (PMUT) array is designed and driven with one cycle of a 5-MHz sinusoid at 10 [Formula: see text] for radial artery motion tracking. The transmit and receive performance figure of merit (FOM) of an individual PMUT over operating frequency is modeled and validated using laser Doppler vibrometer (LDV) measurements. Given a fixed cross section, the FOM inversely scales with frequency. The array aperture size is selected to obtain enough pressure and received signal to measure the radial artery wall reflection at a 5-mm depth in tissue. The 2-mm acoustic beamwidth provides enough lateral resolution for radial artery wall motion tracking. Single-line ultrasonic pulse-echo measurements with high time resolution, also called M-mode ultrasound imaging, are demonstrated to reproduce a known target motion profile with a precision of around 0.5 [Formula: see text]. In vivo radial artery dynamics are measured by placing the sensor on the wrist of a volunteer. The measured diameter change waveform of the radial artery is consistent with reports in the literature and captures key arterial pulse waveform features, including systolic upstroke, systolic decline, dicrotic notch, and diastolic runoff. The system has sufficient accuracy and precision to measure both the 50 [Formula: see text] overall diameter change and the 5- [Formula: see text] diameter change due to the dicrotic notch. A heart rate of 70 beats/min is also derived. This demonstrates the great potential of custom PMUT arrays for continuous cardiovascular system monitoring.