Background and Purpose: Phosphodiesterase-5 inhibitors (PDE5i) are under investigation for repurposing as an intervention for colon cancer prevention. A drawback to conventional PDE5i are side-effects and drug-drug interactions that would be poorly tolerated when taken on a chronic basis for prevention. Experimental Approach: We designed an analog of the prototypical PDE5i sildenafil by replacing the methyl group on the piperazine ring with malonic acid to reduce lipophilicity and measured its entry into the circulation and effects on colon epithelium. Key Results: This modification did not affect pharmacology as malonyl-sildenafil had a similar IC50 to sildenafil (6.5 nM vs 7.5 nM respectively) but exhibited almost 100-fold reduced cell entry compared to sildenafil. Using an LC-MS/MS approach, doses of malonyl-sildenafil up to 36 mg/kg were barely detectable in mouse plasma after oral administration but was detected at high levels in the feces. This contrasted with sildenafil that was detected in the plasma but not in the feces. No bioactive metabolites of malonyl-sildenafil were detected in the circulation by measuring interactions with isosorbide mononitrate. Treatment of mice with malonyl-sildenafil in the drinking water for 8 days was well-tolerated and resulted in a suppression of proliferation in the colon epithelium that is consistent with results published previously for mice treated with PDE5i. Conclusion and Implications: A carboxylic acid-containing analog of sildenafil prohibits systemic delivery of the compound but maintains sufficient penetration into the colon epithelium to suppress proliferation. This highlights a novel approach to generate a first in class drug for colon cancer chemoprevention.

Department of Computer Engineering, Gujrat Technological College, Ahmedabad, IndiaEmail address:Shezi1131@gmail.comTo cite this article:Diptiben Ghelni. Deep Learning and Artificial Intelligence Framework to Improve the Cyber Security. American Journal of Artificial Intelligence . Vol. x, No. x, 2022, pp. x-x. Abstract: Deep learning derived from an artificial neural network (ANN), is one of the essential technologies for today’s intelligent cyber security systems or policies. The benefits and drawbacks of using artificial intelligence (AI) in cyber risk analytics to improve organizational resilience and better comprehend cyber risk. Multilayer perceptron, convolutional neural network, recurrent neural network or long short-term memory, self-organizing map, auto-encoder, restricted Boltzmann machine, deep belief networks, generative adversarial network, deep transfer learning, and deep reinforcement learning, as well as their ensembles and hybrid approaches, can be used to tackle the diverse cyber security issues intelligently. The backpropagation algorithm’s ultimate goal is to correctly maximize the network weights to translate the inputs to the intended outputs. During the training phase, several optimization approaches such as Stochastic Gradient Descent (SGD), Limited Memory BFGS (L-BFGS), and Adaptive Moment Estimation (Adam) are applied. These neural networks may be utilized to handle a variety of cybersecurity problems. MLP-based networks are used to construct an intrusion detection model, malware analysis, security threat analysis, identify malicious botnet traffic, and build trustworthy IoT systems. MLP is sensitive to feature scaling and requires tuning a variety of hyperparameters such as the number of hidden layers, neurons, and iterations, which might make solving a complicated security model computationally costly.Keywords: Cyber Security, Artificial Intelligence, Deep Learning, Internet of Things1. IntroductionIndustry 4.0, an IoT phrase coined in 1999, is built on the Internet of Things (IoT) technology, providing the first glimpse of what an IoT-based ecosystem would look like in the future. CPS refers to the interdisciplinary and complex characteristics of intelligent systems constructed and relies on the interplay of physical and computational components. CPS theory evolved from control theory and control systems engineering. It focuses on the connectivity of physical features and the utilization of sophisticated software entities to create new network and system capabilities. CPSs connect biological and engineering systems, bridging the cyber and physical worlds [1].On the other hand, IoT theory is based on computer science and Internet technologies, and it focuses primarily on the interconnection, interoperability, and integration of physical components on the Internet. This integration effort is expected to lead to advances such as IoT automation of CPSs as the IoT industry matures over the next decade. CPS systems and automated CPSs guide trained employees in production situations in real-time. In this context, we look at how such systems enable artificial intelligence (AI) breakthroughs in real-time processing, sensing, and actuation across these new systems and give cyber structure system analysis capabilities. As a result, we’ll concentrate on artificial intelligence, which is a notion that encompasses both the cyber-physical and social components of the hazards associated with new technology deployment [2].There are two research aims in this study. To begin, we provide an up-to-date summary of current and emerging cyber risk analytics breakthroughs. This incorporates current standards into a new risk analytics feedback loop by combining existing literature to generate shared core terminology and techniques. Second, by providing a novel understanding of cyber network risk and the role of AI in future CPS, we capture best practices and spark debate among practitioners and academia. Throughout the article, this architecture is explored and may be used as a best practice for designing and prototyping AI-enabled dynamic cyber risk analyses [3].2. Artificial intelligence, CPS, and predictive cyber risk analytics literature reviewThe IoT has been defined as a revolutionary technological augmentation that transforms the traditional living into a high-tech lifestyle in terms of data streams. CPSs and IoT generate massive amounts of data, necessitating powerful analytical tools for analysis. We almost likely need AI-assisted analytical tools to clean up the data’s noise and inconsistencies. On the other hand, CPS architectures cover a wide range of topics. These many notions must be integrated into a system [4].Furthermore, CPS mandates anti-counterfeiting and supply chain risk management to combat malicious supply chain components that have been altered from their original design to create disruption or perform illegal functions. Hyper-connectivity in the digital supply chain must be promoted in addition to design and process standardization. It is proposed that restricting source code access to critical and experienced employees can offer software assurance and application security and may be required to prevent the introduction of purposeful faults and vulnerabilities in CPSs. Forensics, prognostics, and recovery plans should be included in security measures for cyber-attack analysis and coordination with other CPSs and entities that detect external cyber-attack vectors [5]. An internal track and trace network procedure can help by recognizing or avoiding gaps in logistical security measures. To prevent the exploitation of CPS vulnerabilities discovered by reverse engineering assaults, a method for anti-malicious and anti-tamper system engineering is required. Taxonomic analysis was performed using the Smart literature review approach based on latent Dirichlet allocation. The resulting areas of concentration are organized into a taxonomy with acronyms to aid in the integration of artificial intelligence with the current CPS. Deep learning (DL) is a subset of machine learning (ML) and artificial intelligence (AI), and it is one of the primary technologies of the Fourth Industrial Revolution. It is derived from an artificial neural network (ANN) (Industry 4.0) [6]. ”Cyber security” and ”Deep learning” are becoming increasingly popular worldwide, as demonstrated in Figure 1.

Over winter freeze-thaw events are notoriously difficult to represent in hydrologic models and have serious implications for the hydrologic function of intermittently freezing regions. With changing climate leading to higher variability in observed weather patterns, it is anticipated that mid-winter thaw events may become more numerous at locales where intermittent thaw was previously rare. Midwinter thaw events are often the cause of flooding due to the combined impacts of snowmelt, precipitation, and limited soil infiltrability. A numerically efficient, semi-analytical coupled thermal and mass transport model is presented that is capable of representing the ice content of near-surface soil. This model allows for rapid and stable prediction of the ice content of frozen or partially frozen near-surface soil without having to solve a discrete form of the coupled partial differential equations describing the soil water and energy balance. The model tracks pore ice formation and mean soil temperature in terms of enthalpy. It is tested against data collected in Southern Saskatchewan and is shown to capably reproduce field observations. This model is efficient enough to be incorporated as a module into existing regional hydrologic models and is expected to improve predictions of soil ice content, which can later lead to improved estimates of over-winter streamflow and flood potential.

Cerebral ischemic stroke is attributed to paradoxical cerebral embolism (PCE). pulmonary arteriovenous fistula (PAVF) is a potential rare cause of cerebral ischemic stroke. Transient ischemic attack (TIA) induced by PAVF in children is rare, lacking typical clinical manifestations, which can not be ignored.

Depression was an affective disorder, and the incidence of depression was increasing, which was projected to be the first disease burden worldwide by 2030. Therefore, it is particularly urgent to find new anti-depressant curative. The renin-angiotensin system (RAS) was important for regulating blood pressure, water, and electrolyte balance. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) were commonly used as first-line antihypertensive agents. A large number of basic studies confirmed that RAS played a key role in hypertension, affective disorders, and neurological diseases. Recently, studies have found that RAS blockers (ACEI/ARB) acted on the classical ACE/AngII/AT1 receptor pathway and ACE2/Ang-(1-7)/Mas receptor pathway, which may have promising clinical value for the treatment of anxiety disorders and depression. Therefore, the modulation role of RAS in the nervous system has progressively come to light. This review addresses the overview of the RAS, the relationship between RAS and depression/anxiety, and the potential mechanisms of RAS blockers in the therapy of affective disorders, involving brain inflammation, HPA axis, oxidative stress, and BDNF. The evidence for positive effects of RAS blockers on depression and anxiety alone or comorbidity was reviewed, hoping to provide a reference for new clinical uses, which go beyond blood pressure management.

Spondylotic myelopathy involves chronic spinal cord compression from degenerative spine changes presenting a myriad of neurological and pain symptoms. We report a case of cervical myelopathy with transverse pancake-like gadolinium enhancement seen on MRI in a 42-year-old gentleman with progressive bilateral upper extremity numbness, tingling, and impaired gait.

Many long-term genetic monitoring programs began before next-generation sequencing became widely available. Older programs can now transition to new marker systems usually consisting of 1000s of SNP loci, but there are still important questions about comparability, precision, and accuracy of key metrics estimated using SNPs. Ideally, transitioned programs should capitalize on new information without sacrificing continuity of inference across the time series. We combined existing microsatellite-based genetic monitoring information with SNP-based microhaplotypes obtained from archived samples of Rio Grande silvery minnow (Hybognathus amarus) across a 20-year time series to evaluate point estimates and trajectories of key genetic metrics. Demographic and genetic monitoring bracketed multiple collapses of the wild population, and included cases where captive-born repatriates comprised the majority of spawners in the wild. Even with smaller sample sizes, microhaplotypes yielded comparable and in some cases more precise estimates of variance genetic effective population size, multilocus heterozygosity and inbreeding compared to microsatellites because many more microhaplotype loci were available. Microhaplotypes also recorded shifts in allele frequencies associated with population bottlenecks. Trends in microhaplotype-based inbreeding metrics were associated with the fraction of hatchery-reared repatriates to the wild, and should be incorporated into future genomic monitoring. Although differences in accuracy and precision of some metrics were observed between marker types, biological inferences and management recommendations were consistent.

Wolbachia are among the most prevalent and widespread endosymbiotic bacteria on earth. Wolbachia’s success in infecting an enormous number of arthropod species is attributed to two features: the range of phenotypes they induce in their hosts, and their ability to switch between host species. Whilst much progress has been made in elucidating their induced phenotypes, our understanding of Wolbachia host shifting is still very limited: we lack answers to even fundamental questions concerning Wolbachia’s routes of transfer and the importance of factors influencing host shifts. Here, we investigate the diversity and host-shift patterns of Wolbachia in scale insects, a group of arthropods with intimate associations with other insects that make them well-suited to studying host shifts. Using Illumina multi-target amplicon sequencing of Wolbachia-infected scale insects and their direct associates we determined the identity of all Wolbachia strains. We then fitted a Generalised Additive Mixed Model (GAMM) to our data to estimate the influence of host phylogeny and the geographic distribution on Wolbachia strain sharing among scale insect species. The model predicts no significant contribution of host geography but strong effects of host phylogeny, with high rates of Wolbachia sharing among closely related species and a sudden drop-off in sharing with increasing phylogenetic distance. We also detected the same Wolbachia strain in scale insects and several intimately associated species (ants, wasps, beetles, and flies). This indicates putative host shifts and potential routes of transfers via these associates and highlights the importance of ecological connectivity in Wolbachia host-shifting.

This paper firstly finishes off the exact solutions of Riemann-Liouville fractional differential time-delay oscillatory system of order ρ∈(1 ,2) by using two newly defined delayed perturbations of Mittag-Leffler matrix functions and constant variation method. In the light of the exact solutions, we explore the finite time stability of the nonhomogeneous fractional oscillatory differential equations with pure delay. Ultimately, an example is cited to verify the rationality of the results. Through our method, the public problems left by Mahmudov in 2022 were partially solved.

we reported a-24-year-old woman, who was a known case of Darier Disease (DD) since the age of 5 years old. She was presented with hemorrhagic macules, and vesicles on the dorsum aspects of her hands, fingers, and palmar area with no triggers like trauma, and with spontaneous recovery.

Background: Epistaxis management frequently includes the insertion of a non-absorbable nasal pack, and patients may often be admitted during this treatment. During the recent COVID-19 pandemic, UK guidance to discharge “suitable” patients, with pack in-situ, was published in order to minimise hospital admissions and viral nosocomial transmission. Evidence which defines patient suitability for discharge, however, is lacking. Method: The medical records of 100 patients admitted for idiopathic epistaxis in our trust, managed with non-absorbable packing, were analysed. We sought to determine whether risk factors for re-bleeding through packs, or for haemorrhage-related complications, for which inpatient admission would allow more timely treatment, could be identified. Patient factors and outcomes were correlated using binomial logistic regression. Results: 13 patients re-bled through nasal packing. Statistically significant (1 tailed, P<0.05) predictors of bleeding despite packing were male sex, hypertension diagnosis, and aspirin use, with younger patients being at a modestly increased risk. Warfarin or direct oral anticoagulant (DOAC) use was not associated with increased bleeding risk. Conclusion: This study provides initial evidence of factors that affect the risk of bleeding through packs, and which patients may require inpatient care when packed. We recommend a future multicentre study with larger recruitment numbers to expand upon this pilot study’s results.

Multi-chamber soft pneumatic actuators (m-SPAs) have been widely used in soft robotic systems to achieve versatile grasping and locomotion. However, existing m-SPAs have slow actuation speed and are either limited by a finite air supply or require energy-consuming hardware to continuously supply compressed air. Here, we address these shortcomings by introducing an internal exhaust air recirculation (IEAR) mechanism for high-speed and low-energy actuation of m-SPAs. This mechanism recirculates the exhaust compressed air and recovers the energy by harnessing the rhythmic actuation of multiple chambers. We develop a theoretical model to guide the analysis of the IEAR mechanism, which agrees well with the experimental results. Comparative experimental results of several sets of m-SPAs show that our IEAR mechanism significantly improves the actuation speed by more than 82.4% and reduces the energy consumption per cycle by more than 47.7% under typical conditions. We further demonstrate the promising applications of the IEAR mechanism in various pneumatic soft machines and robots such as a robotic fin, fabric-based finger, and quadruped robot. Corresponding author(s) Email:    guguoying@sjtu.edu.cn

Species distribution patterns are essential for the conservation of biodiversity. The aim of this study was to evaluate the influence of multiple ecological hypotheses on the spatial patterns of rodent species richness in China. First, we divided the geographic region of China into 80 × 80 km2 grid cells and mapped the distribution ranges of the 237 rodent species. Rodent taxa were separated into three response variables based on their distribution: (a) all species, (b) non-endemic species, and (c) endemic species. The predictors were divided into four factor sets: (a) energy-water, (b) climatic seasonality, (c) habitat heterogeneity, and (d) human factors, which were used to represent four different ecological hypotheses. We then performed multiple regression analysis (OLS), spatial autoregressive models (SAR), and variation partitioning analyses to determine the effects of predictors on the spatial patterns of rodent species. The Hengduan Mountains and surrounding mountains in southwest China showed the highest species richness and endemism. Habitat heterogeneity is the most important factor explaining the species richness distribution patterns across all species and non-endemic species. Endemic species richness patterns are most susceptible to seasonal changes in climate and least affected by human factors. The effects of energy and water on the three response variables showed consistent levels of importance.

The eastern tree hyrax is thought to be a solitarily living arboreal species of the forests of East Africa. However, in the coast of Kenya, indigenous forests have been almost entirely cleared, and some of the last tree hyrax populations live in limestone rocky formations and caves. Interestingly, they seem to be living in social groups. Here, we describe and document photographically these unique tree hyrax populations. We also describe their acoustical communication and their calling activity in three different habitats. Based on these animals' physical appearance and acoustic analyses of their calls, they represent the species eastern tree hyrax, Dendrohyrax validus. Due to immence pressure from humans, the future of these small and isolated, cave-living tree hyrax populations does not seem bright.

Superior mesenteric artery syndrome-induced pancreatitis is rarely reported .We report a case which can be explained by an occlusive post-papillary syndrome, which produces retrograde reflux of bile into the pancreatic duct, activating inflammation responsible for pancreatitis.

Here, we present the first case of hypersensitivity pneumonitis to Yeasts (Trichosporon asahii and Candida parapsilosis) and associated with humidifier fever linked to exposure to gram negative bacteria and endotoxins. The association of HP and humidifier fever is rarely reported.

Pitfall trapping is one of the widely used methods in ecological studies to assess epigean arthropods' diversity and density. Our work is the first study to evaluate the capture efficiency of different pitfall traps for collecting scorpions. We examined the impact of trap diameter, trap cover, and use of funnels, and designed eight different trap types by combining these factors. A total of 64 traps were tested in an arid plain in Khuzestan Province, southwest Iran, during winter and spring over a 24-day period, and a total of 772 scorpions were trapped. The results indicate that pitfall traps are most productive for capturing burrowing scorpions. In addition, most scorpions were captured with covered traps, which can be explained by the cryptic lifestyle of scorpions, which tend to use spaces under rocks and other objects for shelter or to search for their prey. It is also noted that larger traps catch more scorpions, and the use of funnels does not significantly affect the number of scorpions caught. However, using funnels is recommended because it can reduce the number of unwanted bycatch samples. Based on our results, an optimized trap design for collecting scorpions is proposed, namely a funnel trap with an opening diameter of ca. 15 cm equipped with a plastic cover.

Objectives Otitis media with effusion (OME) is a common pathology in children. Effusions contain Metalloproteinases (MMPs), which can lead to atrophy of the tympanic membrane (TM) due to destructive effect on the lamina propria. Not all cases of OME are complicated with atrophy, maybe explained by an inter-individual variation of MMP concentration in effusions. The purpose of this study was to determine the correlation between concentration of MMPs and existence of TM atrophy in children. Participants - Main outcome measures The effusion from thirty middle ears were collected during insertion of VT in children aged 15 months to 10 years, including 11 eardrums with tympanic atrophy and 19 without tympanic atrophy. ELISA tests were used to measure concentrations of MMP-2, MMP-7, MMP-9 and TIMP-2 in the effusions. Correlations between MMP levels and atrophy of eardrum was investigated, as well as correlation with age, gender, number of previous ventilation tube insertion, and viscosity of the glue. Results The mean concentration of MMP-2 was higher in the atrophic group than in effusions without TM atrophy (0.6 ng/mg versus 0.5 ng/mg total protein respectively), while the TIMP-2 concentration was lower in this group. The level of MMP-2 decreased with the age. Finally, a significantly higher concentration of MMP-9 and TIMP-2 was found in high-viscosity effusions. Conclusion This study suggests that MMP-2 activity could play an important role in destruction of the eardrum during OME in infancy. MMP-2 level assessment could be interesting for determining children with risk of lamina propria destruction.

Five succinct key points: -Otolaryngologists are at high risk for ergonomic injury, particularly in the neck and cervical spine region. - There is a need to use validated ergonomic assessment tools to quantify the amount of risk in specific otolaryngology procedures and identify alternative methods to decrease that risk. -The physical positioning of the senior author was studied using the RULA score during two different operative approaches to tonsillectomy: one using an endoscope and one using direct visualization without the aid of an endoscope. - The RULA score for the traditional, non-endoscopic approach was 5, with a Neck, Trunk, and Leg Score of 6 and a Wrist/Arm score of 1, demonstrating a high risk and suggesting a need for further investigation and change. The RULA score for the endoscopic-assisted approach was 3, with a Neck, Trunk, and Leg score of 4 and a Wrist/Arm score of 1. -An endoscopic-assisted approach to tonsillectomy allowed for a lower RULA score than traditional tonsillectomy. This study suggests that an endoscopic approach may decrease the potential for musculoskeletal strain and reduce occupational-related pain and injury seen in practicing otolaryngologists.

Background: Catheter ablation for atrial fibrillation (AF) is a common therapeutic strategy for patients with either paroxysmal or persistent AF, but long-term ablation success rates are imperfect. Maintenance of sinus rhythm immediately prior to ablation with anti-arrhythmic drug (AAD) therapy has been associated with improved outcomes in patients undergoing ablation. Amiodarone has superior efficacy relative to other AADs. Whether failure of amiodarone to maintain sinus rhythm prior to ablation for either paroxysmal or persistent AF is associated with poor outcomes is unknown. Methods: A total of 307 patients who received amiodarone in a one-year window before undergoing catheter ablation for AF were included. Patients were divided into amiodarone success (n=183) and amiodarone failure (n=124) groups based on the response to pre-ablation amiodarone treatment. Analysis of procedural outcomes as a function of response to amiodarone therapy was performed. Patients were followed for at least 12 months post-ablation to assess outcomes (adverse events and arrhythmia recurrence). Procedural success was defined by the absence of documented arrhythmia (>30s) without any anti-arrhythmic agents beyond a 90d blanking period. Results: Following ablation for either paroxysmal or persistent AF, freedom from any recurrent atrial arrhythmia at 1y was 57.7% for the entire cohort. One-year freedom from recurrent arrhythmia in the amiodarone success group was comparable to that in the amiodarone failure group (55.7% vs 60.5%; p=0.54). Success rates following ablation did not vary by the response to amiodarone when analyzed for paroxysmal or persistent AF subgroups. Conclusion: Failure to restore and maintain sinus rhythm with amiodarone prior to ablation for either paroxysmal or persistent AF is not a predictor of ablation procedural failure. Amiodarone failure alone should not deter practitioners from considering ablation therapy for patients with AF.

Aims A multipolar pulsed-field ablation (PFA) catheter was recently introduced for pulmonary vein isolation and shows great promise with respect to procedural efficacy and safety. We describe our initial experience using this multipolar PFA catheter for the treatment of left atrial (LA) reentry tachycardia. Methods We included all patients with LA reentry tachycardia treated with PFA at our institution between September 2021 and March 2022. The tachycardia mechanism was identified using 3D electro-anatomical mapping (3D-EAM). Subsequently, a roof line, anterior line, or mitral isthmus line was ablated as appropriate. Roof line ablation was always combined with LA posterior wall (LAPW) isolation. Supplementary ablation of a roof- or anterior line was added in patients with extensive low-voltage areas to avoid future arrhythmias. Positioning of the PFA catheter was guided by a 3D-EAM system, and by fluoroscopy. Bidirectional block across lines was verified using standard criteria. Additional focal radiofrequency ablation (RFA) was used to achieve bidirectional block as necessary. Results Among 22 patients (median age 70 (59-75) years; 9 females), we identified 27 LA reentry tachycardia: Seven roof dependent macro-reentries, one micro-reentry located on the posterior wall, twelve peri-mitral macro-reentries, and seven micro-reentries located on the anterior wall. We ablated a total of 20 roof lines, 13 anterior lines and 6 mitral isthmus lines. Additional RFA was necessary for two anterior lines (15%) and three mitral isthmus lines (50%). Bidirectional block was achieved across all roof lines, 92% of anterior lines and 83% of mitral isthmus lines. We observed no acute procedural complications. Conclusion Ablation of a roof line and LAPW isolation is feasible, effective and safe using this multipolar PFA catheter. However, the catheter is less suited for ablation of the mitral isthmus and the anterior line. A focal pulsed-field ablation catheter may be more effective for ablation of these lines.

Quantifying genetic structure and levels of genetic variation are fundamentally important to predicting the ability of populations to persist in human-altered landscapes and adapt to future environmental changes. Genetic structure reflects the dispersal of individuals over generations, which can be mediated by species-level traits or environmental factors. Dispersal distances are commonly positively associated with body size and negatively associated with the amount of degraded habitat between sites, motivating investigation of these potential drivers of dispersal concomitantly. We quantified genetic structure and genetic variability within populations of ten bee species in the tribe Euglossini across fragmented landscapes. We genotyped bees at thousands of SNP loci and tested the following predictions: (1) larger species disperse farther; (2) species with greater resource specialization disperse farther; (3) deforested areas restrict dispersal; and (4) sites surrounded by more intact habitat have higher genetic diversity. Body size was a strong predictor of genetic structure, but, surprisingly, larger species showed higher genetic structure than smaller species. The way that deforestation affected dispersal varied with body size, such that larger species dispersed less far in areas with more forest. There was no effect of geographic distance on dispersal, and sites with more intact habitat had higher genetic diversity. These results challenge the dominant paradigm that individuals of larger species disperse farther, motivating further work into ecological drivers of dispersal for bees.

Introduction Oral sotalol initiation requires a multiple-day, inpatient admission to monitor for QT prolongation during loading. A one-day intravenous (IV) sotalol loading protocol was approved by the FDA in March 2020, but limited data on clinical use and administration currently exists. This study describes implementation of an IV sotalol protocol within an integrated health system, provides initial efficacy and safety outcomes, and examines length of stay compared to oral sotalol initiation. Methods IV sotalol was administered according to a pre-specified initiation protocol to adult patients with refractory atrial or ventricular arrhythmias. Baseline characteristics, safety and feasibility outcomes, and length of stay (LOS) were compared to patients receiving oral sotalol over a similar time period. Results From January 2021 to June 2022, a total of 29 patients (average age 66.0 ± 8.6 years, 27.6% women) underwent IV sotalol load and 20 patients (average age 60.4 ± 13.9 years, 65.0% women) underwent PO sotalol load. The load was successfully completed in 22/29 (75.9%) patients receiving IV sotalol and 20/20 (100%) of patients receiving oral sotalol, although 7/20 of the oral sotalol patients (35.0%) required dose reduction. Adverse events interrupting IV sotalol infusion included bradycardia (7 patients, 24.1%) and QT prolongation (3 patients, 10.3%). No patients receiving IV or oral sotalol developed sustained ventricular arrhythmias prior to discharge. LOS for patients completing IV load was 2.6 days shorter (mean 1.0 vs 3.6, p < 0.001) compared to LOS with oral load. Conclusion Intravenous sotalol loading has a safety profile that is similar to oral sotalol. It significantly shortens hospital LOS, potentially leading to large cost savings.

End stage renal disease (ESRD), characterized by cessation in kidney function, has been linked to severe metabolic disturbances, caused by buildup of toxic solutes in blood. To remove these solutes, ESRD patients undergo dialysis. As a proof of concept, we tested whether ESRD-related metabolic signatures can be detected in perspiration samples using a combined methodology. Our rapid methodology involves swabbing a glass slide across the patient’s forehead, detecting the metabolites in the imprint using desorption electrospray ionization mass spectrometry, and identifying the key differences using machine learning methods. Based on collecting 42 healthy and 27 ESRD samples, we find saturated fatty acids are consistently suppressed in ESRD patients, with little change after dialysis. Also, our method enables the detection of uremic solutes, where we find elevated levels of uric acid (6.7 fold higher on average) that sharply decrease after dialysis. Beyond the study of individual metabolites, we find that a lasso model, which selects for 8 m/z fragments from 24,602 detected analytes, achieves area under the curve performance of 0.85 and 0.87 on training (n=52) and validation sets (n=17) respectively. Together, these results suggest that this methodology is promising for detecting signatures relevant for Precision Health.