Parallelization with Dual-Trap Single-Column Configuration Maximizes Throughput of Proteomic Analysis.

Proteomic analysis on the scale that captures population and biological heterogeneity over hundreds to thousands of samples requires rapid mass spectrometry methods, which maximize instrument utilization (IU) and proteome coverage while maintaining precise and reproducible quantification. To achieve this, a short liquid chromatography gradient paired to rapid mass spectrometry data acquisition can be used to reproducibly quantify a moderate set of analytes. High-throughput profiling at a limited depth is becoming an increasingly utilized strategy for tackling large sample sets but the time spent on loading the sample, flushing the column(s), and re-equilibrating the system reduces the ratio of meaningful data acquired to total operation time and IU. The dual-trap single-column configuration (DTSC) presented here maximizes IU in rapid analysis (15 min per sample) of blood and cell lysates by parallelizing trap column cleaning and sample loading and desalting with the analysis of the previous sample. We achieved 90% IU in low microflow (9.5 µL/min) analysis of blood while reproducibly quantifying 300-400 proteins and over 6000 precursor ions. The same IU was achieved for cell lysates and over 4000 proteins (3000 at CV below 20%) and 40,000 precursor ions were quantified at a rate of 15 min/sample. Thus, DTSC enables high-throughput epidemiological blood-based biomarker cohort studies and cell-based perturbation screening.

Standardized Workflow for Precise Mid- and High-Throughput Proteomics of Blood Biofluids.

BACKGROUND: Accurate discovery assay workflows are critical for identifying authentic circulating protein biomarkers in diverse blood matrices. Maximizing the commonalities in the proteomic workflows between different biofluids simplifies the approach and increases the likelihood for reproducibility. We developed a workflow that can accommodate 3 blood-based proteomes: naive plasma, depleted plasma and dried blood. METHODS: Optimal conditions for sample preparation and data independent acquisition-mass spectrometry analysis were established in plasma then automated for depleted plasma and dried blood. The mass spectrometry workflow was modified to facilitate sensitive high-throughput analysis or deeper profiling with mid-throughput analysis. Analytical performance was evaluated by the linear response of peptides and proteins to a 6- or 7-point dilution curve and the reproducibility of the relative peptide and protein intensity for 5 digestion replicates per day on 3 different days for each biofluid. RESULTS: Using the high-throughput workflow, 74% (plasma), 93% (depleted), and 87% (dried blood) displayed an inter-day CV <30%. The mid-throughput workflow had 67% (plasma), 90% (depleted), and 78% (dried blood) of peptides display an inter-day CV <30%. Lower limits of detection and quantification were determined for peptides and proteins observed in each biofluid and workflow. Based on each protein and peptide's analytical performance, we could describe the observable, reliable, reproducible, and quantifiable proteomes for each biofluid and workflow. CONCLUSION: The standardized workflows established here allows for reproducible and quantifiable detection of proteins covering a broad dynamic range. We envisage that implementation of this standard workflow should simplify discovery approaches and facilitate the translation of candidate markers into clinical use.

Discovery Proteomics for COVID-19: Where We Are Now.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible coronavirus responsible for the pandemic coronavirus disease 2019 (COVID-19), which has had a devastating impact on society. Here, we summarize proteomic research that has helped elucidate hallmark proteins associated with the disease with respect to both short- and long-term diagnosis and prognosis. Additionally, we review the highly variable humoral response associated with COVID-19 and the increased risk of autoimmunity.

Absent pyramidal eminence and stapedial tendon associated with congenital stapes footplate fixation: Intraoperative and radiographic findings.

OBJECTIVE: Report an association between congenital stapes footplate fixation (CSFF) and radiological absence of the pyramidal eminence and stapedial tendon. PATIENTS: Children and adults with intraoperatively confirmed CSFF and an absent stapedial tendon. INTERVENTIONS: Computed tomography (CT); exploratory tympanotomy with stapedotomy. MAIN OUTCOME MEASURES: Absence of a pyramidal eminence and stapedial tendon aperture identified on preoperative CT that was confirmed intraoperatively. RESULTS: Eight patients with intraoperative confirmation of CSFF and absent stapedial tendon were retrospectively identified. The average preoperative bone conduction and air conduction pure tone averages were 19.6 dB (SD 15.6 dB) and 55.9 dB (SD 23.6 dB), respectively. The average air-bone gap was 36.3 dB (SD 17.9 dB) preoperatively. In the seven patients who underwent preoperative CT, all were consistently identified to have an absent or hypoplastic pyramidal eminence and absent stapedial tendon aperture at the pyramidal eminence. In six cases, the stapedial footplate appeared normal, while in one case the footplate appeared abnormal which correlated with severe facial nerve prolapse observed intraoperatively. All eight cases underwent exploratory tympanotomy and demonstrated intraoperative stapes footplate fixation, absent stapedial tendon and either absent or hypoplastic pyramidal eminence, which correlated with preoperative CT findings. CONCLUSIONS: This study identifies a clinically pragmatic association between an absent pyramidal eminence identified on high-resolution CT and the diagnosis of CSFF. In a condition that otherwise generally lacks distinctive radiological features, the absence of a pyramidal eminence on CT in a patient with nonprogressive, congenital conductive hearing loss may strengthen clinical suspicion for CSFF.

Healthcare providers and community perspectives on expedited partner therapy (EPT) for use with gay, bisexual and other men who have sex with men.

OBJECTIVES: Expedited partner therapy (EPT) is an effective strategy to reduce rates of chlamydia and gonorrhoea infection and ensure sexual partners are treated. Currently, EPT is provided to heterosexual patients; however, EPT is not routinely recommended for use with gay, bisexual and other men who have sex with men (GBMSM) because of concerns about HIV coinfection. The objective of the qualitative study was to understand provider and community views on the use of EPT with GBMSM. METHODS: Using convenience sampling methods, we recruited a sample of 18 healthcare providers and 21 GBMSM to participate in in-depth, semistructured interviews. Interviews were conducted over the phone and included questions about knowledge, experiences and potential barriers and facilitators to the use of EPT with GBMSM. RESULTS: Most providers wanted to provide EPT to GBMSM and believed that the potential barriers and concerns to EPT use were not unique to a patient's sexual orientation. Several providers noted that they were currently providing EPT to GBMSM as part of HIV prevention services. Community members were generally unaware of EPT as a service and most indicated that they would only use EPT if they were in a committed relationship. Barriers included partner allergies and resistance, pharmacy protocols, structural concerns (eg, insurance coverage, pharmacists onsite and transportation) and potential disclosure issues. Facilitators included cultural humility and telemedicine with patients' partners to overcome these barriers. CONCLUSIONS: Acceptability of EPT use for both chlamydia and gonorrhoea was high among providers and community members. Barriers to EPT use, including concerns about patients' partners' allergies and resistance, disclosure concerns and linkage to HIV prevention services can be overcome through cultural humility trainings and telemedicine. Changing EPT recommendations at the national level to be inclusive of GBMSM is critical to curtail the rising STI and HIV epidemic.

Development and Preliminary Findings of the Dizziness Symptom Profile.

OBJECTIVES: Dizziness, vertigo, and unsteadiness are common complaints of patients who present to primary care providers. These patients often are referred to otology for assessment and management. Unfortunately, there are a small number of specialists to manage these patients. However, there are several dizziness disorders that can be successfully managed by primary care providers if the disorder is properly identified. To assist in the identification of several of the most common dizziness disorders, we developed the dizziness symptom profile (DSP). The DSP is a self-report questionnaire designed to generate one or more differential diagnoses that can be combined with the patient's case history and physical examination. DESIGN: This report describes three investigations. Investigations 1 and 2 (i.e., exploratory and confirmatory investigations, N = 514) describe the development of the DSP. Investigation 3 (N = 195) is a validation study that describes the level of agreement between the DSP completed by the patient, and, the differential diagnosis of the otologist. RESULTS: The final version of the DSP consists of 31 items. Preliminary findings suggest that the DSP is in agreement with the differential diagnoses of ear specialists for Meniere's disease (100% agreement), vestibular migraine (95% agreement), and benign paroxysmal positional vertigo (82% agreement). CONCLUSIONS: Early results suggest that DSP may be useful in the creation of differential diagnoses for dizzy patients that can be evaluated and managed locally. This has the potential to reduce the burden on primary care providers and reduce delays in the diagnosis of common dizziness and vertigo disorders.

Anterior Canal benign paroxysmal positional Vertigo following surgical Management of superior canal dehiscence.

OBJECTIVE: Benign paroxysmal positional vertigo (BPPV) is a common post-surgical finding in patients managed for superior semicircular canal dehiscence (SSCD). The posterior semicircular canal has been reported as the involved canal in the majority of cases of post-surgical BPPV, with only two cases reported of lateral canal involvement. The objective of this report is to present a case in which an anterior semicircular canal BPPV response was identified in a patient following surgical management for SSCD. METHOD: This case report presents an adult with residual dizziness following surgical management of SSCD and vestibular rehabilitation therapy (VRT). During subsequent evaluation of vestibular function, a transient and torsional, down-beating nystagmus was provoked along with vertigo during Dix-Hallpike positioning to the right. This was consistent with BPPV affecting the left superior (anterior) semicircular canal. RESULTS: The patient was treated with a repositioning maneuver to manage anterior semicircular canal BPPV and no nystagmus response was recorded with post-repositioning Dix-Hallpike test. Review of radiographic images, obtained prior to vestibular function testing, showed a hyperintensity in the area of the left anterior semicircular canal ampulla. It was felt this was likely a bone chip from the SSCD repair that was pushing against the ampulla with further mobile debris within the canal. CONCLUSION: It is reported that BPPV is a common complication in patients surgically managed for SSCD. Posterior semicircular canal BPPV is reported most often, with a couple of cases of lateral semicircular canal BPPV also reported. As far as we are aware, the current case represents the first report of anterior semicircular canal BPPV in this type of patient.

Cochleostomy and facial recess packing alter cochlear implant electrode location in a human cochlea model.

PURPOSE: Determine the effect of cochleostomy and facial recess packing on cochlear implant electrode distance from the modiolus. MATERIALS AND METHODS: Two otolaryngology residents (PGY5 and PGY6) and one attending ear surgeon performed electrode insertions on a human cochlea model using perimodiolar (Cochlear® Slim Modiolar 532™, CI532) and lateral wall electrodes (Cochlear® Slim Straight 522™, CI522) via a cochleostomy. Packing material was simulated using cotton and placed in the cochleostomy and facial recess under the following conditions: 1) inferior to the electrode, 2) superior, 3) both inferior and superior, and 4) no packing. Distance of the electrode from the modiolus at the proximal, middle, and distal basal turn of the cochlea were measured by photomicrograph analysis. RESULTS: Packing superior to the CI532 resulted in a significant decrease in distance from the modiolus at the middle and distal basal turn compared to the inferior condition, with the largest effect in the middle basal turn (0.25 mm vs. 1.92 mm, respectively, p < 0.001). For the CI522, packing superior similarly resulted in decreased distance to the modiolus when compared to the inferior packing condition at the middle and distal basal turn regions, with the largest effect in the middle basal turn (1.25 mm vs. 1.75 mm, respectively, p = 0.002). CONCLUSIONS: Packing of the cochleostomy site and facial recess has a significant effect on electrode distance from the modiolus in the middle and distal basal turn using a model of a human cochlea. Effects were more pronounced when using the perimodiolar (CI532) electrode.

Multiple cranial neuropathies following etanercept administration.

There have been recent reports of sarcoid-like granulomatosis development following the administration of tumor necrosis factor (TNF) inhibitors. To date, only four cases of neurosarcoidosis have been reported in association with TNF inhibitors, two of which were attributed to etanercept. We present the first case of etanercept-induced neurosarcoidosis involving multiple cranial neuropathies, including the trigeminal, facial, and vestibulocochlear nerves, while also highlighting the differential diagnoses of multiple cranial neuropathies and the association of TNF inhibitors and neurosarcoidosis.

Factors associated with recurrence of squamous cell carcinoma involving the temporal bone.

OBJECTIVE: This study aimed to better identify factors associated with recurrence of squamous cell carcinoma (SCC) involving the temporal bone. METHODS: A retrospective study was conducted at a tertiary hospital. Sixty patients who were diagnosed over a 10-year period with SCC involving the temporal bone and underwent surgical resection were analyzed. All patients were staged based on the University of Pittsburgh staging system. Demographic, intraoperative, and pathologic data were analyzed with respect to recurrence. RESULTS: Thirteen (21.7%) patients were T1, 8 (13.3%) T2, 7 (11.7%) T3, and 32 (53.3%) T4. Eighteen patients (30.0%) recurred in the study period. The mean time to recurrence was 5.8 months. Tumors originating in the skin overlying the parotid gland and the external auditory canal had higher recurrence rates than those from the auricle/postauricular skin and temporal bone (P = .05). Direct parotid and perineural spread accounted for 15.0% of all routes of temporal invasion but resulted in 22.2% of all recurrences (P = .04). Increased N stage was statistically associated with increased risk of recurrence (P = .01). Cervical, as compared to perifacial and parotid, lymph node involvement was associated with increased risk of recurrence (odds ratio = 6.91; 95% confidence interval, 1.11-42.87). CONCLUSION: We have identified multiple factors that are associated with increased recurrence of SCC involving the temporal bone.

Concordance and discordance in patient and provider perceptions of dizziness.

PURPOSE: The purpose of the present investigation was to determine whether there are significant differences in patient/healthcare provider perceptions of patient's dizziness severity, dizziness disability/handicap, anxiety, and signs of autonomic system activation. MATERIALS AND METHODS: This was a prospective investigation of 30 patient-provider dyads drawn as a sample of convenience from an otology clinic in a large, tertiary care, medical center. Patients completed both the Dizziness Handicap Inventory (DHI) and the Vestibular Symptom Scale (VSS) prior to vestibular function testing. Providers were instructed to complete the same measures following the patient's clinic visit from what they estimated was the patient's point of view. The two measures were analyzed for concordance and discordance. RESULTS: Patient/provider differences in DHI and VSS vertigo subscale scores were not significantly different. However, difference scores on the VSS anxiety/autonomic subscale indicated that providers significantly under-estimated patient anxiety and symptoms of autonomic system activation. CONCLUSIONS: The results suggest that providers may be missing information pertinent to the role anxiety and autonomic system activation may play in patient visits for complaints of dizziness. We suggest that this problem can be mitigated by administrating to patients prior to their clinic visit a standardized measure that quantifies patient self-report dizziness, vertigo, anxiety and autonomic system arousal. Patterns of response by patients on these measures can enable providers to diagnose correctly dizziness disorders that are rooted in clinically significant anxiety either related to, or unrelated to, a history of vestibular system impairment.

The limitations of computed tomography in adult cochlear implant evaluation.

OBJECTIVE: To demonstrate the added value of magnetic resonance imaging (MRI) over computed tomography (CT) during adult cochlear implant evaluation. PATIENTS: Two adult patients are discussed in whom MRI studies diagnosed bilateral vestibular schwannomas during cochlear implant candidacy evaluation. INTERVENTIONS: Temporal bone CT and MRI. MAIN OUTCOME MEASURE: Diagnosis of NF2. RESULTS: Two adult patients, ages 67 and 68 years, were evaluated for cochlear implant candidacy. Both patients experienced slowly progressive, bilateral hearing loss without complaints of vertigo, and neither patient had a family history of hearing loss or neurogenic tumors. Both patients had near-symmetric pure tone thresholds on audiometric testing. An MRI and a CT scan were performed on both patients, and bilateral vestibular schwannomas were identified on MRI. CONCLUSIONS: Though MRI is not routinely utilized in adult cochlear implant evaluation, it may be of greater clinical value than CT in the setting of adult-onset hearing loss. MRI allows for sensitive evaluation of cochlear patency and architecture, and cochlear nerve status. As demonstrated in the two index cases, MRI also provides the added benefit of evaluating for causes of retrocochlear hearing loss. These two patients would have likely experienced a significant delay in diagnosis of NF2 without preoperative MRI, particularly given the limitations of scanning following CI magnet placement.

Does radiation dose to the vestibule predict change in balance function and patient perceived dizziness following stereotactic radiotherapy for vestibular schwannoma?

OBJECTIVE: To date, the majority of the vestibular schwannoma (VS) literature has focused on tumor control rates, facial nerve function and hearing preservation. Other factors that have been shown to significantly affect quality-of-life (QOL), such as dizziness, remain understudied. The primary objective of the current study is to investigate the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported dizziness handicap. MATERIALS AND METHODS: This is a prospective observational pilot study at a tertiary academic referral center including all subjects that underwent linear accelerator-based stereotactic radiotherapy (SRS) for sporadic VS and completed pre-treatment and post-treatment vestibular testing and Dizziness Handicap Inventory (DHI) questionnaires. Associations between objective vestibular test results, patient-reported DHI scores and radiation dose parameters were investigated. RESULTS: Ten patients met inclusion criteria. Tumor control was achieved in all individuals. There were no statistically significant associations or identifiable trends between radiation dose and change in vestibular function or DHI scores. Notably, the four ears receiving the highest vestibular dose had minimal changes in vestibular function tests and DHI scores. CONCLUSIONS: To the best of our knowledge, no previous reports have described the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported DHI. Based on these preliminary data, radiation dose to the vestibule does not reliably predict change in objective or subjective vestibular outcome measures.

Impedance testing on cochlear implants after electroconvulsive therapy.

OBJECTIVE: Cochlear implants (CI) are neural prostheses that restore hearing to individuals with profound sensorineural hearing loss. The surgically implanted component consists of an electrode array, which is threaded into the cochlea, and an electronic processor, which is buried under the skin behind the ear. The Food and Drug Administration and CI manufacturers contend that electroconvulsive therapy (ECT) is contraindicated in CI recipients owing to risk of damage to the implant and/or the patient. We hypothesized that ECT does no electrical damage to CIs. METHODS: Ten functional CIs were implanted in 5 fresh cadaveric human heads. Each head then received a consecutive series of 12 unilateral ECT sessions applying maximum full pulse-width energy settings. Electroconvulsive therapy was delivered contralaterally to 5 CIs and ipsilaterally to 5 CIs. Electrical integrity testing (impedance testing) of the electrode array was performed before and after CI insertion, and after the first, third, fifth, seventh, ninth, and 12th ECT sessions. Electroconvulsive therapy was performed by a staff psychiatrist experienced with the technique. Explanted CIs were sent back to the manufacturer for further integrity testing. RESULTS: No electrical damage was identified during impedance testing. Overall, there were statistically significant decreases in impedances (consistent with no electrical damage) when comparing pre-ECT impedance values to those after 12 sessions. There was no statistically significant difference (P > 0.05) in impedance values comparing ipsilateral to contralateral ECT. Manufacturer testing revealed no other electrical damage to the CIs. CONCLUSION: Electroconvulsive therapy does not seem to cause any detectable electrical injury to CIs.

Clinical characteristics associated with isolated unilateral utricular dysfunction.

PURPOSE: The ocular vestibular evoked myogenic potential (oVEMP) represents the sound-induced activation of extraocular muscles and is believed to originate from the utricle and superior vestibular nerve. Isolated unilateral oVEMP abnormalities with otherwise normal balance function test (BFT) results have not yet been characterized in a large patient series, and their clinical significance remains unclear. MATERIALS AND METHODS: Retrospective review of adult patients with vestibular complaints at a tertiary academic neurotologic referral center was performed. Patients with isolated unilateral oVEMP abnormalities were identified. The prevalence of vestibular symptoms and results of the Dizziness Handicap Inventory (DHI) and Hospital Anxiety and Depression Scale (HADS) were compared between these patients and those with normal BFT results. RESULTS: Thirty-one adult patients with isolated unilateral oVEMP abnormalities were identified (71% female, mean age 48 ± 14 years). Presenting complaints included vertigo in 53%, non-vertiginous dizziness in 68%, postural instability in 52%, and swaying/rocking sensation in 13%. Significant differences were observed in the percentage of patients with postural instability (p=0.046) and swaying/rocking sensation (p=0.04) when comparing the abnormal oVEMP group to patients with a normal BFT battery. No differences were observed when comparing other symptoms, age, gender, diagnoses, and DHI/HADS scores between groups. CONCLUSION: This is the largest series to date reporting on patients with isolated unilateral oVEMP abnormalities. Our results suggest this population may demonstrate an increased prevalence of postural instability and swaying/rocking sensation. Other measures of postural stability may further characterize the vestibular impairments associated with isolated unilateral utricular dysfunction.

Quantum Lyapunov exponent in dissipative systems.

The out-of-time order correlator (OTOC) has been widely studied in closed quantum systems. However, there are very few studies for open systems and they are mainly focused on isolating the effects of scrambling from those of decoherence. Adopting a different point of view, we study the interplay between these two processes. This proves crucial in order to explain the OTOC behavior when a phase space contracting dissipation is present, ubiquitous not only in real life quantum devices but in the dynamical systems area. The OTOC decay rate is closely related to the classical Lyapunov exponent-with some differences-and more sensitive in order to distinguish the chaotic from the regular behavior than other measures. On the other hand, it is revealed as a generally simple function of the longest lived eigenvalues of the quantum evolution operator. We find no simple connection with the Ruelle-Pollicott resonances, but by adding Gaussian noise of ℏ_{eff} size to the classical system we recover the OTOC decay rate, which is a consequence of the correspondence principle put forward in Phys. Rev. Lett. 108, 210605 (2012)10.1103/PhysRevLett.108.210605 and Phys. Rev. E 99, 042214 (2019)10.1103/PhysRevE.99.042214.

Sustainable Castor Bean Biodiesel Through Ricinus communis L. Lipase Extract Catalysis.

The rise in oil prices, global warming, and the depletion of nonrenewable resources have led researchers to study sustainable alternatives to increasing energy demand. The autocatalysis from castor oil and castor lipases to produce biodiesel can be an excellent alternative to reduce the production costs and avoid the drawbacks of chemical transesterification. This study aimed to evaluate the catalytic activity of castor bean lipase extract (CBLE) on three vegetable oils hydrolysis, to obtain and enhance biodiesel yield by an autocatalysis from castor oil and CBLE. Furthermore, the enzymatic biodiesel physicochemical quality was analyzed. The enzymatic activity for olive oil was 76.12 U, 90.06 U for commercial castor oil, and 75.60 U in raw castor oil. The hydrolysis percentages were high at 25 °C, pH 4.5, for 4 h with 97.18% for olive oil, 98.86%, and 96.19% for commercial and raw castor oil, respectively. The CBLE catalyzed the transesterification reaction on castor oil to obtain 82.91% biodiesel yield under the selected conditions of 20% lipase loading, 1:6 oil/methanol molar ratio, and 10% buffer pH 4.5, 37 °C for 8 h. The castor biodiesel quality satisfied the ASTM-D6751 (USA) and EN-14214 (European Union) values, except for the density, viscosity, and moisture, as expected for this kind of biodiesel.

Immobilization of Natural Antimicrobial Compounds on Food-Grade Supports as a New Strategy to Preserve Fruit-Derived Foods.

The use of natural antimicrobials in the food industry is being proposed as an eco-friendly postharvest technology to preserve fruit-derived foods. In this context, this systematic review aims to describe and discuss the application of naturally occurring antimicrobial compounds in the processing of fruit-derived foods by the PRISMA methodology. In a first step, the use of free natural antimicrobials was investigated as an approach to identify the main families of bioactive compounds employed as food preservatives and the current limitations of this dosage form. Then, the use of immobilized antimicrobials, in an innovative dosage form, was studied by distinguishing two main applications: addition to the food matrix as preservatives or use during processing as technological aids. Having identified the different examples of the immobilization of natural antimicrobial compounds on food-grade supports, the mechanisms of immobilization were studied in detail to provide synthesis and characterization guidelines for future developments. Finally, the contribution of this new technology to decarbonization and energy efficiency of the fruit-derived processing sector and circular economy is discussed in this review.

Protein biomarkers of disease progression in patients with systemic sclerosis associated interstitial lung disease.

Systemic sclerosis is a rare connective tissue disease; and interstitial lung disease (SSc-ILD) is associated with significant morbidity and mortality. There are no clinical, radiologic features, nor biomarkers that identify the specific time when patients are at risk for progression at which the benefits from treatment outweigh the risks. Our study aimed to identify blood protein biomarkers associated with progression of interstitial lung disease in patients with SSc-ILD using an unbiased, high-throughput approach. We classified SSc-ILD as progressive or stable based on change in forced vital capacity over 12 months or less. We profiled serum proteins by quantitative mass spectrometry and analyzed the association between protein levels and progression of SSc-ILD via logistic regression. The proteins associated with at a p value of < 0.1 were queried in the ingenuity pathway analysis (IPA) software to identify interaction networks, signaling, and metabolic pathways. Through principal component analysis, the relationship between the top 10 principal components and progression was evaluated. Unsupervised hierarchical clustering with heatmapping was done to define unique groups. The cohort consisted of 72 patients, 32 with progressive SSc-ILD and 40 with stable disease with similar baseline characteristics. Of a total of 794 proteins, 29 were associated with disease progression. After adjusting for multiple testing, these associations did not remain significant. IPA identified five upstream regulators that targeted proteins associated with progression, as well as a canonical pathway with a higher signal in the progression group. Principal component analysis showed that the ten components with the highest Eigenvalues represented 41% of the variability of the sample. Unsupervised clustering analysis revealed no significant heterogeneity between the subjects. We identified 29 proteins associated with progressive SSc-ILD. While these associations did not remain significant after accounting for multiple testing, some of these proteins are part of pathways relevant to autoimmunity and fibrogenesis. Limitations included a small sample size and a proportion of immunosuppressant use in the cohort, which could have altered the expression of inflammatory and immunologic proteins. Future directions include a targeted evaluation of these proteins in another SSc-ILD cohort or application of this study design to a treatment naïve population.

Computational study of a novel catheter for liver radioembolization.

Radioembolization (RE) is a medical treatment for primary and secondary liver cancer that involves the transcatheter intraarterial delivery of micron-sized and radiation-emitting microspheres, with the goal of improving microsphere deposition in the tumoral bed while sparing healthy tissue. An increasing number of in vitro and in silico studies on RE in the literature suggest that the particle injection velocity, spatial location of the catheter tip and catheter type are important parameters in particle distribution. The present in silico study assesses the performance of a novel catheter design that promotes particle dispersion near the injection point, with the goal of generating a particle distribution that mimics the flow split to facilitate tumour targeting. The design is based on two factors: the direction and the velocity at which particles are released from the catheter. A series of simulations was performed with the catheter inserted at an idealised hepatic artery tree with physiologically realistic boundary conditions. Two longitudinal microcatheter positions in the first generation of the tree were studied by analysing the performance of the catheter in terms of the outlet-to-outlet particle distribution and split flow matching. The results show that the catheter with the best performance is one with side holes on the catheter wall and a closed frontal tip. This catheter promotes a flow-split-matching particle distribution, which improves as the injection crossflow increases.