Search

STUDY DESIGN: Retrospective analysis at a tertiary care center. OBJECTIVE: This study describes a method of analyzing postoperative results using lateral view clinical photographs to create normalized projection ratios of the glabella and radix. METHODS: We reviewed preoperative and postoperative photographs of 15 patients. All photographs were in the lateral view Frankfort horizontal plane. We calculated the distances between the (a) tragus and cornea, (b) cornea and radix, (c) cornea and glabella, and the (θ) nasofrontal angle. RESULTS: Fifteen sets of patient photographs were analyzed and found that there was a favorable 14% reduction at the radix and an even greater reduction (78.9%) at the glabella. The nasofrontal angle was improved to a more feminine range from 131.84° preoperatively to 145.86° postoperatively. CONCLUSIONS: Normalized projection ratios of the glabella and radix, along with the nasofrontal angle, can be used to objectively measure outcomes of frontal feminizing cranioplasty.

ObjectiveWomen represent an increasing proportion of the otolaryngology workforce. Work-related musculoskeletal disorders (WRMSD) are a little-studied yet important impediment to career completion. Scant attention has been directed to study the impact of pregnancy on surgeon posture and ergonomics. We piloted the use of a pregnancy simulation suit (Empathy Belly) to assess the risk of ergonomic compromise when performing open septorhinoplasty.Study designSurgical simulation.SettingSingle session, training simulation lab at academic medical center.MethodsMedical students and surgical residents performed the initial steps of a rhinoplasty procedure without and with a pregnancy simulation suit and were filmed with an artificial intelligence-based video analysis app from Kinetica Labs that calculates joint angles and categorizes the ergonomic risk factors. Still images from videos were taken and analyzed using validated posture-based analysis rubrics. Participants were asked to complete a qualitative questionnaire after the session.ResultsTwelve medical students and surgical residents participated in the study. Posture-based analysis indicated increased ergonomics risk factors among trainees when performing a rhinoplasty while wearing the pregnancy suit. Video analysis indicated trends of worsening back angle and shoulder postures. Trainees reported experiencing pain in the neck, suprapubic area, and lower back. They acknowledged the importance of ergonomics in otolaryngology and desired further education about workplace injury risk mitigation.ConclusionPregnancy impacts the ergonomics of performing septorhinoplasty and further investigation is required into interventions to reduce risk of WRMSDs.

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities. We present CasPEDIA (http://caspedia.org), the Cas Protein Effector Database of Information and Assessment, a curated encyclopedia that integrates enzymatic classification for hundreds of different Cas enzymes across 27 phylogenetic groups spanning the Cas9, Cas12 and Cas13 families, as well as evolutionarily related IscB and TnpB proteins. All enzymes in CasPEDIA were annotated with a standard workflow based on their primary nuclease activity, target requirements and guide-RNA design constraints. Our functional classification scheme, CasID, is described alongside current phylogenetic classification, allowing users to search related orthologs by enzymatic function and sequence similarity. CasPEDIA is a comprehensive data portal that summarizes and contextualizes enzymatic properties of widely used Cas enzymes, equipping users with valuable resources to foster biotechnological development. CasPEDIA complements phylogenetic Cas nomenclature and enables researchers to leverage the multi-faceted nucleic-acid targeting rules of diverse Class 2 Cas enzymes.

Abstract Background Pantoea spp., a non-encapsulated, non-spore-forming Gram-negative rod bacterium that belongs to the Erwiniaceae family, can be found as a colonizer in humans, plants, and the environment, such as water and soil. Although it has the pathogenic potential to cause disease in humans, patients infected with this pathogen generally experience favorable outcomes. In this article, we present two cases of peritoneal dialysis (PD)-associated peritonitis caused by Pantoea spp. along with literature review. Case presentation The first case is a 66-year-old male patient with end-stage kidney disease (ESKD) on PD, admitted for P. dispersa peritonitis. He presented with abdominal pain and cloudy dialysis effluent, responding well to intraperitoneal vancomycin and cefepime. Antibiotics were deescalated to ceftazidime monotherapy on the basis of antibiotic susceptibility testing. Despite initial recovery with a 3-week course of antibiotics, he developed recurrent peritonitis with P. dispersa, necessitating PD catheter removal and transition to hemodialysis. The second case is a 42-year-old male patient with ESKD on PD who was admitted after 6 days of bloody PD fluid without trauma or associated symptoms. With elevated PD fluid cell counts and positive PD fluid culture showing Streptococcus mitis and P. agglomerans, he was empirically treated for PD-associated peritonitis with intraperitoneal vancomycin and cefepime. Due to a suboptimal response in repeat PD fluid cell counts at day 5, the PD catheter was removed, and he was switched to hemodialysis, followed by a 3-week course of intravenous ceftriaxone. Conclusions We described two unique cases of Pantoea peritonitis in PD, recurrent P. dispersa peritonitis and refractory P. agglomerans peritonitis, both of which resulted in PD catheter removal. Our cases indicate the formation of bacterial biofilm as a potential reason for recurrence of infection and underscores the importance of vigilant monitoring and need for PD catheter removal in Pantoea peritonitis.

Abstract Recent single-cell transcriptomes revealed spatiotemporal programmes of liver function on the sublobular scale. However, how sexual dimorphism affected this space-time logic remained poorly understood. We addressed this by performing scRNA-seq in the mouse liver, which revealed that sex, space and time together markedly influence xenobiotic detoxification and lipoprotein metabolism. The very low density lipoprotein receptor (VLDLR) exhibits a pericentral expression pattern, with significantly higher mRNA and protein levels in female mice. Conversely, VLDL assembly is periportally biased, suggesting a sexually dimorphic hepatic cycle of periportal formation and pericentral uptake of VLDL. In humans, VLDLR expression is also pericentral, with higher mRNA and protein levels in premenopausal women compared to similarly aged men. Individuals with low hepatic VLDLR expression show a high prevalence of atherosis in the coronary artery already at an early age and an increased incidence of heart attack.

An atraumatic approach to the inner ear is an important goal in the future development of cochlear implant surgery, as the current surgical procedure for electrode insertion is highly invasive. To reduce invasiveness, minimally invasive surgical options are being explored, such as the insertion of one or more drill channels. Due to the proximity to critical structures, a temperature sensor is incorporated into the medical drill for process parallel temperature monitoring to prevent thermal damage. The temperature data is sent to the analysis hardware via Bluetooth BLE. This requires a power supply for the electronics on the drill. There are a number of limitations to the design of such a power supply. For one, the drill is rotating. Therefore, the energy generation must be contactless. Secondly, the energy generation should not depend on the rotation of the drill, so that the temperature can be measured even without the drill rotating and the rotational speed of the drill is not limited. In this paper, we propose a solution for a contactless energy transmission system (ETS) based on inductive coupling. Considering the dimensional limitations of attaching the electronics to the drill shaft, a multilayer PCB coil with multiple contacts for different number of turns is developed. The electrical circuit is simulated and the best settings are identified. The power supply is validated according to the predefined requirements. In the future, the medical drill will be built with the newly developed ETS. Sterilization and wear tests are performed to confirm the suitability of the drill with integrated temperature sensor for the operating room.

Abstract Background Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision. Methods We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach. Discussion This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments. Systematic review registration PROSPERO CRD42023402365.

Abstract Background Endovascular thrombectomy (EVT) has been proven effective in anterior circulation stroke due to large vessel occlusion (LVO). However, translation from randomized clinical trials (RCTs) with highly selected patients to real-world requires confirmation, particularly to identify associations outside of strict selection criteria. Aims This study aims to compare functional outcomes after EVT in real-world with those reported in RCTs, and to identify associations with functional outcome after EVT outside RCT-criteria. Methods This study analyzed longitudinal German real-world data from the Stroke Research Consortium in Northern Bavaria (STAMINA) cohort from January, 2015 to June, 2019. We conducted a trial emulation, comparing patients with anterior circulation stroke and LVO meeting selection criteria for RCTs investigating EVT (1) predominantly within 6 hours with those from HERMES meta-analysis, and (2) within 6-24 hours with those from AURORA meta-analysis. We (3) analyzed treatment effects of EVT and association with functional outcome in patients treated outside RCT criteria. Results Of 598 patients, 281 (47.0%) met RCT-criteria for treatment within 6 hours (hereinafter STAMINA-HERMES), 74 (12.4%) met RCT-criteria for treatment within 6–24 hours (STAMINA-AURORA), and 277 (46.3%) patients received EVT outside RCT-criteria. We observed no difference in rates of functional independence or mortality, comparing STAMINA-HERMES with HERMES meta-analysis (mRS 0-1: n=120/281 [43%] vs. 291/633 [46%], p=0.36; mortality: n=34/281 [12%] vs. 97/633 [15%], p=0.20), and STAMINA-AURORA with AURORA meta-analysis (mRS 0-1: n=26/74 [35%] vs. 122/266 [46%], p=0.10, mortality: n=10/74 [14%] vs. 45/266 [17%], p=0.48). Patients treated outside RCT-criteria had worse outcome (mRS 0-1: n=38/277 [14%], mortality: n=90/277 [32%], both p

Background: Pediatric studies have shown associations between hepatic steatosis and total body fat, visceral fat, and lean mass. However, these associations have not been assessed simultaneously, leaving their relative importance unknown. Objective: To evaluate associations between hepatic steatosis and total-body adiposity, visceral adiposity, and lean mass in children. Method: In children at risk for fatty liver, hepatic steatosis, adipose, and lean mass were estimated with magnetic resonance imaging and dual-energy X-ray absorptiometry. Results: Two hundred twenty-seven children with mean age 12.1 years had mean percent body fat of 38.9% and mean liver fat of 8.4%. Liver fat was positively associated with total-body adiposity, visceral adiposity, and lean mass (P

Globally, key predators such as lobsters are thought to control urchins. In south-eastern Australia, the role of Sagmariasus verreauxi (eastern rock lobster) as a key predator of the native urchin Centrostephanus rodgersii (long-spined urchin) has been questioned while the sympatric Heliocidaris erythrogramma (short-spined urchin) may be eaten more frequently. To test this, we tethered and filmed 100 urchins (50 C. rodgersii and 50 H. erythrogramma) outside of a lobster den over 25 nights to identify predators and quantify predation rates, time to feeding onset and handling time. Sagmariasus verreauxi exhibited very low predation rates (4%), despite being filmed walking past urchins repeatedly whereas Heterodontus galeatus (crested horn shark) was the main predator (45%). Predation rates by all predators (lobsters and sharks) were influenced primarily by tethering night but not urchin size or species. Predation increased throughout the study and while H. erythrogramma and C. rodgersii were eaten at similar rates, there was a trend for lobsters to eat H. erythrogramma and sharks to eat C. rodgersii. Feeding onset had no significant predictors though large C. rodgersii took longer to handle during feeding for both predators. Importantly, sharks readily consumed 25 C. rodgersii up to 121 mm Test Diameter (TD) while lobsters only ate one C. rodgersii (58 mm TD). These findings, although from only one test location, provide important insights into the species eating urchins and highlight the potential significance of overlooked predators such as H. galeatus.

Abstract Worldwide, lobsters are considered key predators that control urchin populations. It has been widely reported that lobster size plays a significant role in the size of urchins they feed on, as does the size of the urchin. Generally, it is thought that small palinurid “spiny” lobsters measuring less than 120 mm carapace length (CL) are morphologically incapable of eating urchins, while large lobsters are voracious predators. Urchin size is expected to affect predation with larger urchins of greater than 90 mm test diameter (TD) presenting the most difficult prey. These generalities, however, have not been quantitatively tested for the eastern spiny lobster Sagmariasus verreauxi and recently the accepted size paradigm for lobsters eating urchins has come into question. The aim of this study was to assess whether lobster predation on urchins would differ with urchin size or species, or the size of lobster. Our results indicate that S. verreauxi does not fit the common lobster patterns regarding urchin predation. There were generally low rates of predation and a significant negative relationship between feeding and both lobster size and urchin size. We found that small lobsters were capable urchin predators with a higher likelihood of eating urchins than larger lobsters, which were more reluctant predators. While we did find the expected effect of smaller urchins being significantly more vulnerable prey, there was none of the expected size limitations for small lobsters eating large urchins and predation did not differ between urchin species, indicating that this was a general pattern. Overall, we observed low rates of predation, suggesting that either S. verreauxi may not be a key urchin predator like other lobster species elsewhere, or that small lobsters are underestimated as urchin predators in temperate marine ecosystems.

Estrogen and progesterone have been extensively studied in the mammary gland, but the molecular effects of androgen remain largely unexplored. Transgender men are recorded as female at birth but identify as male and may undergo gender-affirming androgen therapy to align their physical characteristics and gender identity. Here we perform single-cell-resolution transcriptome, chromatin, and spatial profiling of breast tissues from transgender men following androgen therapy. We find canonical androgen receptor gene targets are upregulated in cells expressing the androgen receptor and that paracrine signaling likely drives sex-relevant androgenic effects in other cell types. We also observe involution of the epithelium and a spatial reconfiguration of immune, fibroblast, and vascular cells, and identify a gene regulatory network associated with androgen-induced fat loss. This work elucidates the molecular consequences of androgen activity in the human breast at single-cell resolution.

Abstract This paper illustrates an interferometric inverse synthetic aperture radar based on three‐dimensional imaging and rotational velocity estimation from a multistatic setup with three ground‐based radars with non‐orthogonal baselines. The radar backscattering along the orbit is simulated based on physical optics approximation. The paper illustrates a novel shape‐dependent and rotation‐invariant feature called normalised eigenvalues for classification. A database of interferometric point clouds is generated using radar back scattering at different aspect angles and classified using various classification algorithms. The classification accuracy at varying SNR levels was evaluated using Monte Carlo simulations.

Abstract Polyethylene terephthalate (PET), the most abundantly produced polyester plastic, can be depolymerized by the Ideonella sakaiensis PETase enzyme. Based on multiple PETase crystal structures, the reaction has been proposed to proceed via a two-step serine hydrolase mechanism mediated by a serine-histidine-aspartate catalytic triad. To elucidate the multi-step PETase catalytic mechanism, we use transition path sampling and likelihood maximization to identify optimal reaction coordinates for the PETase enzyme. We predict that deacylation is likely rate-limiting, and the reaction coordinates for both steps include elements describing nucleophilic attack, ester bond cleavage, and the “moving-histidine” mechanism. We find that the flexibility of Trp185 promotes the reaction, providing an explanation for decreased activity observed in mutations that restrict Trp185 motion. Overall, this study uses unbiased computational approaches to reveal the detailed reaction mechanism necessary for further engineering of an important class of enzymes for plastics bioconversion.

ABSTRACTTo date, thousands of SARS-CoV-2 samples from many vaccine developers have been tested within the CEPI-Centralized Laboratory Network. To convert data from each clinical assay to international standard units, the WHO international standard and the CEPI standard generated by the Medicines and Healthcare products Regulatory Agency were run in multiple facilities to determine the conversion factor for each assay. Reporting results in international units advances global understanding of SARS-CoV-2 immunity and vaccine efficacy, enhancing the quality, reliability, and utility of clinical assay data.

The factors that contribute to postoperative trismus after mandibulectomy and fibula free flap reconstruction (FFFR) are undefined. We retrospectively assessed postoperative trismus (defined as a maximum interincisal opening ≤35 mm) in 106 patients undergoing mandibulectomy with FFFR, employing logistic regression to identify risk factors associated with this sequela. The surgical indication was primary ablation in 64%, salvage for recurrence in 24%, and osteonecrosis in 12%. Forty-five percent of patients had existing preoperative trismus, and 58% of patients received adjuvant radiation/chemoradiation following surgery. The overall rates of postoperative trismus were 76% in the early postoperative period (≤3 months after surgery) and 67% in the late postoperative period (>6 months after surgery). Late postoperative trismus occurred more frequently in patients with ramus-involving vs. ramus-preserving posterior mandibulotomies (82% vs. 46%, p = 0.004). A ramus-involving mandibulotomy was the only variable significantly associated with trismus >6 months postoperatively on multivariable logistic regression (OR, 7.94; 95% CI, 1.85−33.97; p = 0.005). This work demonstrates that trismus is common after mandibulectomy and FFFR, and suggests that posterior mandibulotomies that involve or remove the ramus may predispose to a higher risk of persistent postoperative trismus.

Focal radiation therapy (RT) has attracted considerable attention as a combinatorial partner for immunotherapy (IT), largely reflecting a well-defined, predictable safety profile and at least some potential for immunostimulation. However, only a few RT-IT combinations have been tested successfully in patients with cancer, highlighting the urgent need for an improved understanding of the interaction between RT and IT in both preclinical and clinical scenarios. Every year since 2016, ImmunoRad gathers experts working at the interface between RT and IT to provide a forum for education and discussion, with the ultimate goal of fostering progress in the field at both preclinical and clinical levels. Here, we summarize the key concepts and findings presented at the Sixth Annual ImmunoRad conference.

Group A Streptococcus (GAS) is a strict human pathogen possessing a unique pathogenic trait that utilizes the cooperative activity of NAD+-glycohydrolase (NADase) and Streptolysin O (SLO) to enhance its virulence. How NADase interacts with SLO to synergistically promote GAS cytotoxicity and intracellular survival is a long-standing question. Here, the structure and dynamic nature of the NADase/SLO complex are elucidated by X-ray crystallography and small-angle scattering, illustrating atomic details of the complex interface and functionally relevant conformations. Structure-guided studies reveal a salt-bridge interaction between NADase and SLO is important to cytotoxicity and resistance to phagocytic killing during GAS infection. Furthermore, the biological significance of the NADase/SLO complex in GAS virulence is demonstrated in a murine infection model. Overall, this work delivers the structure-functional relationship of the NADase/SLO complex and pinpoints the key interacting residues that are central to the coordinated actions of NADase and SLO in the pathogenesis of GAS infection.