Extent of resection and progression-free survival in vestibular schwannoma: a volumetric analysis.

OBJECTIVE: To preserve facial nerve function in vestibular schwannoma (VS) microsurgery, some have advocated subtotal resection (STR) if the tumor is densely adherent to a thinned facial nerve. The objective of this study was to determine if residual volume is associated with progression and whether there is a threshold residual volume that should be pursued during STR to prevent recurrence. A secondary objective of this study was to determine whether facial nerve function at last follow-up was associated with extent of resection (EOR). METHODS: Clinical and radiographic data were retrospectively collected from the records of 164 patients with VS who underwent resection. Tumor volumes were measured using Visage, and standard statistical methods were used. The House-Brackmann scale was used to assess changes in facial nerve function before surgery and at last follow-up. RESULTS: Sixty-one patients (37%) received gross-total resection (GTR) and 103 (63%) received STR. The median clinical and radiographic follow-ups were 49 and 48 months, respectively. The median residual volume was 0.5 cm3 after STR. Kaplan-Meier actuarial survival analysis revealed a 96.3% 5-year progression-free survival (PFS) rate after GTR, which was greater than that after STR (84.5%, p = 0.03). Recursive partitioning analysis of patients receiving STR revealed a residual volume of 0.60 cm3 as the optimal threshold for recurrence. Patients with residual volume ≥ 0.60 cm3 had a 76.0% 5-year PFS, regardless of adjuvant SRS, which was lower than that for patients undergoing GTR (96.3%) or STR (95.6%) with residual volumes < 0.60 cm3 (p < 0.01). On Cox regression analysis, residual volume ≥ 0.60 cm3 (HR 14.4, p = 0.01) was independently associated with progression, even when accounting for patient age, adjuvant radiosurgery, and preoperative tumor size. In 112 patients with at least 24 months of follow-up after their last treatment, tumor control was achieved in 111 (99.1%) patients at a median last follow-up of 71 months. Worse facial nerve function at the last follow-up was independently associated with prior treatment for VS (adjusted OR 3.7, p = 0.04), but not residual volume cohort or preoperative tumor volume. CONCLUSIONS: Residual volume > 0.60 cm3 after VS resection was independently associated with tumor progression, even accounting for adjuvant SRS. These data support maximizing the EOR during VS surgery, even if GTR cannot be safely achieved.

Hydrogel-Based Artificial Synapses for Sustainable Neuromorphic Electronics.

Hydrogels find widespread applications in biomedicine because of their outstanding biocompatibility, biodegradability, and tunable material properties. Hydrogels can be chemically functionalized or reinforced to respond to physical or chemical stimulation, which opens up new possibilities in the emerging field of intelligent bioelectronics. Here, the state-of-the-art in functional hydrogel-based transistors and memristors is reviewed as potential artificial synapses. Within these systems, hydrogels can serve as semisolid dielectric electrolytes in transistors and as switching layers in memristors. These synaptic devices with volatile and non-volatile resistive switching show good adaptability to external stimuli for short-term and long-term synaptic memory effects, some of which are integrated into synaptic arrays as artificial neurons; although, there are discrepancies in switching performance and efficacy. By comparing different hydrogels and their respective properties, an outlook is provided on a new range of biocompatible, environment-friendly, and sustainable neuromorphic hardware. How potential energy-efficient information storage and processing can be achieved using artificial neural networks with brain-inspired architecture for neuromorphic computing is described. The development of hydrogel-based artificial synapses can significantly impact the fields of neuromorphic bionics, biometrics, and biosensing.

Atherosclerosis quantification and cardiovascular risk: the ISCHEMIA trial.

BACKGROUND AND AIMS: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.

Gene Expression Changes Associated With Recurrence After Gross Total Resection of Newly Diagnosed World Health Organization Grade 1 Meningioma.

BACKGROUND AND OBJECTIVE: Patients who undergo gross total resection (GTR) of Central Nervous System World Health Organization (WHO) grade 1 meningioma constitute a "low-risk" group, but some low-risk meningiomas can recur despite reassuring clinical and histological features. In this study, gene expression values in newly diagnosed WHO grade 1 meningiomas that had undergone GTR were evaluated for their association with recurrence. METHODS: This was a retrospective, international, multicenter cohort study that included WHO grade 1 meningiomas that underwent GTR, as first treatment, based on postoperative magnetic resonance imaging. Normalized gene expression values from a previously validated 34-gene panel were evaluated for their association with recurrence. Kaplan-Meier, multivariable Cox proportional hazard analyses, and K-means clustering were performed to assess the association of genes of interest with recurrence and identify molecular subgroups among clinically and histologically low-risk meningiomas. RESULTS: In total, 442 patients with WHO grade 1 meningiomas that underwent GTR and had available gene expression profiling data were included in the study. The median follow-up was 5.0 years (interquartile range 2.6-7.7 years), local recurrence occurred in 36 patients (8.1%), 5-year local freedom from recurrence was 90.5%, and median time to recurrence was 2.9 years (range 0.5-10.7 years). Eleven genes were associated with local recurrence, including lower expression of ARID1B, ESR1, LINC02593, PGR, and TMEM30B and higher expression of CDK6, CDKN2C, CKS2, KIF20A, PGK1, and TAGLN. Of these genes, PGK1 had the largest effect size. K-means clustering based on these 11 genes distinguished 2 molecular groups of clinically and histologically low-risk meningiomas with significant differences in local freedom from recurrence (hazard ratio 2.5, 95% CI 1.2-5.1, P = .016). CONCLUSION: Gene expression profiling may help to identify newly diagnosed WHO grade 1 meningiomas that have an elevated risk of recurrence despite GTR.

Evaluation of Tibial Slope on Radiographs in Pediatric Patients With Tibial Spine Fractures: An Age- and Sex-Matched Study.

Background: A recent study has reported that the radiographic measurement of posterior tibial slope (PTS) is larger in male pediatric patients with tibial spine fractures (TSF) than in controls. However, they found no difference in PTS between female patients and controls. Purpose: (1) To identify whether PTS is larger in female pediatric patients with TSF than in female controls and (2) to validate the relationship between PTS and pediatric TSF in male patients. Study Design: Cross-sectional study; Level of evidence, 3. Methods: After an a priori power analysis, 84 pediatric patients with TSF (50 female patients and 34 male patients) and 84 age- and sex-matched controls were enrolled in this study. Demographic information, including sex, age, and race, was recorded. Skeletal maturity was determined based on the stage of epiphyseal union on knee radiographs. PTS was defined as the angle between a line perpendicular to the longitudinal axis of the tibia and the posterior inclination of the medial tibial plateau on standard knee lateral radiographs. Results: The mean age when the TSF occurred was 11.2 ± 2.7 years for female patients and 12.9 ± 2.5 years for male patients. There was no significant difference in skeletal maturity between female patients and female controls or between male patients and male controls. The mean PTS was not significantly different between female patients (8.8°± 2.8°) and female controls (8.3°± 3.1°) (P = .366) or between male patients (9.0°± 2.8°) and male controls (9.3°± 2.6°) (P = .675). Those with a PTS >1 SD (2.9°) above the mean (8.8°) had no greater odds (1.0 [95% CI, 0.4-2.5]; P≥ .999) of having a TSF than others. Conclusion: PTS was not found to be a risk factor for pediatric TSF in female or male patients in this study.

Clonal hematopoiesis of indeterminate potential is associated with reduced risk of cognitive impairment in patients with chronic kidney disease.

INTRODUCTION: Clonal hematopoiesis of indeterminate potential (CHIP) and dementia disproportionately burden patients with chronic kidney disease (CKD). The association between CHIP and cognitive impairment in CKD patients is unknown. METHODS: We conducted time-to-event analyses in up to 1452 older adults with CKD from the Chronic Renal Insufficiency Cohort who underwent CHIP gene sequencing. Cognition was assessed using four validated tests in up to 6 years mean follow-up time. Incident cognitive impairment was defined as a test score one standard deviation below the baseline mean. RESULTS: Compared to non-carriers, CHIP carriers were markedly less likely to experience impairment in attention (adjusted hazard ratio [HR] [95% confidence interval {CI}] = 0.44 [0.26, 0.76], p = 0.003) and executive function (adjusted HR [95% CI] = 0.60 [0.37, 0.97], p = 0.04). There were no significant associations between CHIP and impairment in global cognition or verbal memory. DISCUSSION: CHIP was associated with lower risks of impairment in attention and executive function among CKD patients. HIGHLIGHTS: Our study is the first to examine the role of CHIP in cognitive decline in CKD. CHIP markedly decreased the risk of impairment in attention and executive function. CHIP was not associated with impairment in global cognition or verbal memory.

Hepatocyte-independent PAR1-biased signaling controls liver pathology in experimental obesity.

BACKGROUND AND OBJECTIVE: Protease-activated receptor-1 (PAR1) has emerged as an important link between coagulation and the complications of obesity including metabolic dysfunction-associated steatotic liver disease (MASLD). PAR1 is expressed by various cells and cleaved by different proteases to generate unique tethered agonists that activate distinct signaling pathways. Mice expressing PAR1 with an R41Q mutation have disabled canonical thrombin-mediated signaling, whereas R46Q mice express PAR1 resistant to non-canonical signaling by activated protein C (APC). METHODS: Mice with whole body and hepatocyte-selective PAR1 deficiency, as well as PAR1 R41Q and R46Q mice were fed a high fat diet to induce MASLD. RESULTS AND CONCLUSIONS: High fat diet (HFD)-fed R41Q mice displayed reduced hepatic steatosis and liver/body weight ratio. In contrast, HFD-fed R46Q mice displayed increased relative liver weight and hepatic steatosis alongside increased serum ALT activity. Surprisingly, despite the distinct impact of PAR1 mutations on steatosis, selective deletion of PAR1 in hepatocytes had no impact. To evaluate a viable PAR1-targeted approach, mice with HFD-induced obesity were treated with the allosteric PAR1 modulator NRD-21, which inhibits canonical PAR1 inflammatory signaling but promotes PAR1 protective, non-canonical anti-inflammatory signaling. NRD-21 treatment reduced plasma TNFα, serum ALT activity, hepatic steatosis, and insulin resistance (HOMA-IR), but increased plasma active GLP-1. The results suggest non-hepatocellular canonical PAR1 cleavage drives MASLD in obese mice and provide translational proof-of-concept that selective pharmacological modulation of PAR1 yields multiple metabolic benefits in experimental obesity.

Measuring repeatability of dynamic contrast-enhanced MRI biomarkers improves evaluation of biological response to radiotherapy in lung cancer.

OBJECTIVES: To measure dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) biomarker repeatability in patients with non-small cell lung cancer (NSCLC). To use these statistics to identify which individual target lesions show early biological response. MATERIALS AND METHODS: A single-centre, prospective DCE-MRI study was performed between September 2015 and April 2017. Patients with NSCLC were scanned before standard-of-care radiotherapy to evaluate biomarker repeatability and two weeks into therapy to evaluate biological response. Volume transfer constant (Ktrans), extravascular extracellular space volume fraction (ve) and plasma volume fraction (vp) were measured at each timepoint along with tumour volume. Repeatability was assessed using a within-subject coefficient of variation (wCV) and repeatability coefficient (RC). Cohort treatment effects on biomarkers were estimated using mixed-effects models. RC limits of agreement revealed which individual target lesions changed beyond that expected with biomarker daily variation. RESULTS: Fourteen patients (mean age, 67 years +/- 12, 8 men) had 22 evaluable lesions (12 primary tumours, 8 nodal metastases, 2 distant metastases). The wCV (in 8/14 patients) was between 9.16% to 17.02% for all biomarkers except for vp, which was 42.44%. Cohort-level changes were significant for Ktrans and ve (p < 0.001) and tumour volume (p = 0.002). Ktrans and tumour volume consistently showed the greatest number of individual lesions showing biological response. In distinction, no individual lesions had a real change in ve despite the cohort-level change. CONCLUSION: Identifying individual early biological responders provided additional information to that derived from conventional cohort cohort-level statistics, helping to prioritise which parameters would be best taken forward into future studies. CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced magnetic resonance imaging biomarkers Ktrans and tumour volume are repeatable and detect early treatment-induced changes at both cohort and individual lesion levels, supporting their use in further evaluation of radiotherapy and targeted therapeutics. KEY POINTS: Few literature studies report quantitative imaging biomarker precision, by measuring repeatability or reproducibility. Several DCE-MRI biomarkers of lung cancer tumour microenvironment were highly repeatable. Repeatability coefficient measurements enabled lesion-specific evaluation of early biological response to therapy, improving conventional assessment.

Effectiveness of a Systems-Wide Initiative to Address Motivation and Expectations for Treatment on Initial Session Attendance to Outpatient Gambling Treatment.

This brief report expands the results of a prior efficacy study that examined the effect of a letter addressing prospective clients' motivation and expectations for outpatient gambling disorder treatment on initial session attendance. The results of that efficacy study indicated more clients attended the initial session when receiving the letter (77%) compared to receiving a reminder telephone call (51%). The present study examines the effectiveness of messages addressing prospective clients' motivation and expectations for outpatient gambling treatment across an entire treatment system. Messages were sent via letters, telephone, and in-person communication with all clinic staff. Participants were 54 clients with gambling disorder who were seeking outpatient psychological treatment. Results indicated that the percentage of clients attending the initial session was 85%, and no differences in attendance were found between in-person and telehealth sessions. These findings suggest that messages that address motivation and expectations persist under real-world conditions, and treatment systems can make meaningful changes that increase attendance to initial treatment sessions.

Reprint of: Implementation and perception of outpatient pharmacists prescribing hormonal contraceptives in North Carolina.

BACKGROUND: North Carolina (NC) House Bill 96, effective February 2022, enabled trained immunizing pharmacists across the state to prescribe hormonal contraceptives (HCs). However, the extent and barriers to deployment are unknown. The purpose of this study was to describe the uptake and challenges from outpatient pharmacists who trained to provide HCs in an outpatient practice to assist others in the implementation of this service. OBJECTIVES: The primary objective was to estimate the proportion of trained NC pharmacists who provided HCs in an outpatient setting. The secondary objective was to identify barriers during the implementation of this service. METHODS: This cross-sectional, anonymous, web-based survey was emailed on December 13, 2022, to NC-licensed pharmacists enrolled in the required training. A reminder email was sent on January 10, 2023, with all responses considered up to January 31, 2023. Pharmacists licensed in NC who performed at least 50% of their clinical practice in an outpatient setting were included. The primary endpoint was having prescribed HC (Y/N). All endpoints were analyzed using descriptive statistics. RESULTS: Of 1633 pharmacists eligible, 96 completed responses were included in the analysis (5.9%). Training was incomplete in 11 of 96 (11.5%), and 66 of 96 (68.8%) completed the training without implementing the service. Of the remaining 19 of 96 (19.8%) that developed a HC service, 15 of 96 (15.6%) had prescribed HCs. Among the 15 prescribing pharmacists, all reported positive patient feedback, while 7 reported improved job satisfaction. Among all 96 respondents, barriers reported included time constraints (49%) and a lack of appropriate reimbursement (43.8%). CONCLUSION: Few HC-trained NC outpatient pharmacists are prescribing HCs. Addressing prescribing barriers would potentially expand the scope of this service and further innovate the outpatient pharmacy setting.

Rates of Sudden Death After Myocardial Infarction-Insights From the VALIANT and PARADISE-MI Trials.

Importance: Sudden death is a leading cause of death after acute myocardial infarction (AMI). The Prospective ARNi vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI (PARADISE-MI) and Valsartan in Acute Myocardial Infarction (VALIANT) trials enrolled patients with pulmonary congestion and/or left ventricular dysfunction after AMI. Whether the prognosis in such patients has changed over time has not been examined. Objective: To compare the rate of sudden death/resuscitated cardiac arrest (RCA) after AMI in the PARADISE-MI and VALIANT trials. Design, Setting, and Participants: This was a secondary analysis of multicenter randomized clinical trials enrolling patients after AMI. In the primary analysis, the VALIANT cohort was restricted to patients with "PARADISE-MI-like" characteristics (eg, at least 1 augmenting risk factor and no history of heart failure). The baseline characteristics of people in both trials were compared. The VALIANT trial enrolled from December 1998 to June 2001, and the PARADISE-MI trial enrolled between December 2016, and March 2020. The median follow-up in the VALIANT and PARADISE-MI trials was 24.7 and 22 months, respectively. People with AMI, complicated by pulmonary congestion and/or left ventricular dysfunction, were included in the analysis. Exposure: Sudden death after AMI. Results: A total of 5661 patients were included in the PARADISE-MI cohort (mean [SD] age, 63.7 [11.5] years; 4298 male [75.9%]), 9617 were included in the VALIANT (PARADISE-MI-like) cohort (mean [SD] age, 66.1 [11.5] years; 6504 male [67.6%]), and 14 703 patients were included in the VALIANT (total) cohort (mean [SD] age, 64.8 [11.8] years; 10 133 male [68.9%]). In the PARADISE-MI-like cohort of the VALIANT trial, 707 of 9617 participants (7.4%) experienced sudden death/RCA. A total of 148 of 5661 people (2.6%) in the PARADISE-MI trial experienced sudden death/RCA. Sudden death rates were highest in the first month after infarction in both trials: 19.3 (95% CI, 16.4-22.6) per 100 person-years in the VALIANT trial and 9.5 (95% CI, 7.0-12.7) per 100 person-years in the PARADISE-MI trial, and these rates declined steadily thereafter. Compared with the VALIANT cohort, people in the PARADISE-MI trial were more often treated with percutaneous coronary intervention for their qualifying AMI and received a ß-blocker, statin, and mineralocorticoid receptor antagonist more frequently. Conclusions and Relevance: After AMI, the risk of sudden death/RCA was highest in the first month, declining rapidly thereafter. Results revealed that compared with counterparts from 20 years ago, the rate of sudden death/RCA in patients with a reduced left ventricular ejection fraction and/or pulmonary congestion was 2- to 3-fold lower in people receiving contemporary management. Interventions to further protect people in the highest risk first month after infarction are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT02924727.

The impacts of muscle-specific force-velocity properties on predictions of mouse muscle function during locomotion.

Introduction: The accuracy of musculoskeletal models and simulations as methods for predicting muscle functional outputs is always improving. However, even the most complex models contain various assumptions and simplifications in how muscle force generation is simulated. One common example is the application of a generalised ("generic") force-velocity relationship, derived from a limited data set to each muscle within a model, uniformly across all muscles irrespective of whether those muscles have "fast" or "slow" contractile properties. Methods: Using a previously built and validated musculoskeletal model and simulation of trotting in the mouse hindlimb, this work examines the predicted functional impact of applying muscle-specific force-velocity properties to typically fast (extensor digitorum longus; EDL) and slow-contracting (soleus; SOL) muscles. Results: Using "real" data led to EDL producing more positive work and acting significantly more spring-like, and soleus producing more negative work and acting more brake-like in function compared to muscles modelled using "generic" force-velocity data. Extrapolating these force-velocity properties to other muscles considered "fast" or "slow" also substantially impacted their predicted function. Importantly, this also further impacted EDL and SOL function beyond that seen when changing only their properties alone, to a point where they show an improved match to ex vivo experimental data. Discussion: These data suggest that further improvements to how musculoskeletal models and simulations predict muscle function should include the use of different values defining their force-velocity relationship depending on their fibre-type composition.

Crystal structure of 4-bromo-5,7-dimeth-oxy-2,3-di-hydro-1H-inden-1-one.

In the title mol-ecule, C11H11BrO3, the di-hydro-indene moiety is essentially planar but with a slight twist in the saturated portion of the five-membered ring. The meth-oxy groups lie close to the above plane. In the crystal, π-stacking inter-actions between six-membered rings form stacks of mol-ecules extending along the a-axis direction, which are linked by weak C-H⋯O and C-H⋯Br hydrogen bonds. A Hirshfeld surface analysis was performed showing H⋯H, O⋯H/H⋯O and Br⋯H/H⋯Br contacts make the largest contributions to inter-molecular inter-actions in the crystal.

Determining how oxygen legacy affects trajectories of soil denitrifier community dynamics and N2O emissions.

Denitrification - a key process in the global nitrogen cycle and main source of the greenhouse gas N2O - is intricately controlled by O2. While the transition from aerobic respiration to denitrification is well-studied, our understanding of denitrifier communities' responses to cyclic oxic/anoxic shifts, prevalent in natural and engineered systems, is limited. Here, agricultural soil is exposed to repeated cycles of long or short anoxic spells (LA; SA) or constant oxic conditions (Ox). Surprisingly, denitrification and N2O reduction rates are three times greater in Ox than in LA and SA during a final anoxic incubation, despite comparable bacterial biomass and denitrification gene abundances. Metatranscriptomics indicate that LA favors canonical denitrifiers carrying nosZ clade I. Ox instead favors nosZ clade II-carrying partial- or non-denitrifiers, suggesting efficient partnering of the reduction steps among organisms. SA has the slowest denitrification progression and highest accumulation of intermediates, indicating less functional coordination. The findings demonstrate how adaptations of denitrifier communities to varying O2 conditions are tightly linked to the duration of anoxic episodes, emphasizing the importance of knowing an environment's O2 legacy for accurately predicting N2O emissions originating from denitrification.

Cold atmospheric plasma deposition of antibacterial polypyrrole-silver nanocomposites on wearable electronics for prolonged performance.

Wearable electronics have become integral for monitoring physiological parameters in diverse applications, particularly in medical and military fields. e-Textiles, featuring integrated conductive threads or fabrics, offer seamless integration and comfort for prolonged contact with the body. Despite their potential, the biofouling of textile-based electrode systems by skin microbes remains a significant challenge, limiting their operational lifespan. Recent studies have highlighted the efficacy of conductive nanocomposites with antibacterial agents, such as silver nanoparticles (AgNPs), in addressing biofouling concerns. However, implementing such systems on 3D fibrous structures and textile surfaces often proves complex and inefficient. To overcome these challenges, we explored cold atmospheric plasma (CAP)-based in situ polymerization for the direct deposition of functional conductive polypyrrole-silver (PPy-Ag) nanocomposites onto conductive textile surfaces. For this process, a customized CAP deposition system was engineered, enabling precise material deposition through robotic control of the plasma jet. This process achieved direct, conformal attachment onto textile fibrous structures, ensuring uniform distribution of conductive polypyrrole and silver in the form of AgNPs throughout the polymer polypyrrole matrix without compromising fabric flexibility and breathability, which was validated through different surface electron microscopy and chemical analysis (e.g., EDX, FTIR, Raman, and XRD). Systematic studies with various precursor mixtures identified an optimized PPy-Ag composition that demonstrated stable antibacterial properties and biocompatibility against common skin microbes and epithelial cells. Systematic studies with various precursor mixtures identified an optimized PPy-Ag composition, with the precursor mixture containing 96 wt% pyrrole and 4 wt% AgNO3 weight ratios as the optimal surface coating process, demonstrating stable antibacterial properties and biocompatibility against common skin microbes and epithelial cells respectively. As a proof of concept, the nanocomposite coating was applied to conductive carbon fabric surfaces as dry electrodes in a wearable garment for continues electrocardiography (ECG) monitoring over 10 days. Results revealed a significantly longer performance of the dry electrodes as comparable to standard gel-based Ag/AgCl electrodes (1 day) while providing less noise in ECG signal measurements from the subject, showcasing the potential of this technology for practical wearable applications. Envisioned as a groundbreaking solution, this technology opens new avenues for the scalable and effective integration of functional conductive circuits and sensors into everyday garments, ensuring prolonged and efficient performance in wearable electronics.

ceas: an R package for Seahorse data analysis and visualization.

SUMMARY: Measuring cellular energetics is essential to understanding a matrix's (e.g. cell, tissue, or biofluid) metabolic state. The Agilent Seahorse machine is a common method to measure real-time cellular energetics, but existing analysis tools are highly manual or lack functionality. The Cellular Energetics Analysis Software (ceas) R package fills this analytical gap by providing modular and automated Seahorse data analysis and visualization. AVAILABILITY AND IMPLEMENTATION: ceas is available on CRAN (https://cran.r-project.org/package=ceas). Source code and installable tarballs are freely available for download at https://github.com/jamespeapen/ceas/releases/ under the MIT license. Package documentation may be found at https://jamespeapen.github.io/ceas/. ceas is implemented in R and is supported on macOS, Windows and Linux.

Effect of antihypertensive deprescribing on hospitalisation and mortality: long-term follow-up of the OPTiMISE randomised controlled trial.

BACKGROUND: Deprescribing of antihypertensive medications is recommended for some older patients with low blood pressure and frailty. The OPTiMISE trial showed that this deprescribing can be achieved with no differences in blood pressure control at 3 months compared with usual care. We aimed to examine effects of deprescribing on longer-term hospitalisation and mortality. METHODS: This randomised controlled trial enrolled participants from 69 general practices across central and southern England. Participants aged 80 years or older, with systolic blood pressure less than 150 mm Hg and who were receiving two or more antihypertensive medications, were randomly assigned (1:1) to antihypertensive medication reduction (removal of one antihypertensive) or usual care. General practitioners and participants were aware of the treatment allocation following randomisation but individuals responsible for analysing the data were masked to the treatment allocation throughout the study. Participants were followed up via their primary and secondary care electronic health records at least 3 years after randomisation. The primary outcome was time to all-cause hospitalisation or mortality. Intention-to-treat analyses were done using Cox regression modelling. A per-protocol analysis of the primary outcome was also done, excluding participants from the intervention group who did not reduce treatment or who had medication reinstated during the initial trial 12-week follow-up period. This study is registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT2016-004236-38) and the ISRCTN Registry (ISRCTN97503221). FINDINGS: Between March 20, 2017, and Sept 30, 2018, a total of 569 participants were randomly assigned. Of these, 564 (99%; intervention=280; control=284) were followed up for a median of 4·0 years (IQR 3·7-4·3). Participants had a mean age of 84·8 years (SD 3·4) at baseline and 273 (48%) were women. Medication reduction was sustained in 109 participants at follow-up (51% of the 213 participants alive in the intervention group). Participants in the intervention group had a larger reduction in antihypertensives than the control group (adjusted mean difference -0·35 drugs [95% CI -0·52 to -0·18]). Overall, 202 (72%) participants in the intervention group and 218 (77%) participants in the control group experienced hospitalisation or mortality during follow-up (adjusted hazard ratio [aHR] 0·93 [95% CI 0·76 to 1·12]). There was some evidence that the proportion of participants experiencing the primary outcome in the per-protocol population was lower in the intervention group (aHR 0·80 [0·64 to 1·00]). INTERPRETATION: Half of participants sustained medication reduction with no evidence of an increase in all-cause hospitalisation or mortality. These findings suggest that an antihypertensive deprescribing intervention might be safe for people aged 80 years or older with controlled blood pressure taking two or more antihypertensives. FUNDING: British Heart Foundation and National Institute for Health and Care Research.

Association of pediatric firearm injury with neighborhood social deprivation in Philadelphia.

Background: Firearm-related injury is the leading cause of death among children and adolescents. There is a need to clarify the association of neighborhood environment with gun violence affecting children. We evaluated the relative contribution of specific social determinants to observed rates of firearm-related injury in children of different ages. Methods: This was a population-based study of firearm injury in children (age <18 years) that occurred in Philadelphia census tracts (2015-2021). The exposure was neighborhood Social Deprivation Index (SDI) quintile. The outcome was the rate of pediatric firearm injury due to interpersonal violence stratified by age, sex, race, and year. Hierarchical negative binomial regression measured the risk-adjusted association between SDI quintile and pediatric firearm injury rate. The relative contribution of specific components of the SDI to neighborhood risk of pediatric firearm injury was estimated. Effect modification and the role of specific social determinants were evaluated in younger (<15 years old) versus older children. Results: 927 children were injured due to gun violence during the study period. Firearm-injured children were predominantly male (87%), of black race (89%), with a median age of 16 (IQR 15-17). Nearly one-half of all pediatric shootings (47%) occurred in the quintile of highest SDI (Q5). Younger children represented a larger proportion of children shot in neighborhoods within the highest (Q5), compared with the lowest (Q1), SDI quintile (25% vs 5%; p<0.007). After risk adjustment, pediatric firearm-related injury was strongly associated with increasing SDI (Q5 vs Q1; aRR 14; 95% CI 6 to 32). Specific measures of social deprivation (poverty, incomplete schooling, single-parent homes, and rented housing) were associated with significantly greater increases in firearm injury risk for younger, compared with older, children. Component measures of the SDI explained 58% of observed differences between neighborhoods. Conclusions: Neighborhood measures of social deprivation are strongly associated with firearm-related injury in children. Younger children appear to be disproportionately affected by specific adverse social determinants compared with older children. Root cause evaluation is required to clarify the interaction with other factors such as the availability of firearms and interpersonal conflict that place children at risk in neighborhoods where gun violence is common. Level of evidence: Level III - Observational Study.

Outcomes of Pro Re Nata versus Treat-and-Extend Anti-VEGF Injections for Myopic Macular Neovascularization in Multiethnic Patients in the United States.

PURPOSE: To compare visual outcomes and recurrence rates between pro re nata (PRN), treat-and-extend and stop (TES), and treat-and-extend with chronic maintenance dosing (TEM) regimens of anti-vascular endothelial growth factor (VEGF) injections for myopic macular neovascularization (MNV) in multiethnic patients. METHODS: This retrospective study included patients treated with PRN, TES, or TEM for myopic MNV using intravitreal bevacizumab or ranibizumab. The primary outcome measure was visual improvement at 12 months. RESULTS: We included 127 eyes of 117 patients (75 females and 42 males). The mean follow-up duration was 37.9 months. We compared the outcomes of PRN (47 eyes [37%]), TES (52 eyes [41%]), and TEM (28 eyes [22%]). All groups showed significant visual improvement at 12 months and at the final follow-up (all P<0.05). Visual outcomes did not differ significantly between the three groups at 12 months and final follow-up (all P>0.05). However, the number of eyes with recurrences was significantly higher in the PRN group and significantly lower in the TEM group during follow-up (38%, 21%, and 11% in the PRN, TES, and TEM groups, respectively; P=0.020). The PRN group received the fewest injections during follow-up (5.3, 10.9, and 19.9 injections in the PRN, TES, and TEM groups respectively; P<0.001). CONCLUSIONS: Anti-VEGF injections with PRN, TES, or TEM regimens are effective for myopic MNV and have comparable visual outcomes. Since PRN provides favorable outcomes with fewer injections, it should be the first-line approach. However, a treat-and-extend approach with TES and TEM may be an option given individual patient factors.