Miracle-dz/UniFAR-FTUs huggingface dataset:
Chemistry and human exposure implications of secondary organic aerosol production from indoor terpene ozonolysis

Surface cleaning using commercial disinfectants, which has recently increased during the coronavirus disease 2019 pandemic, can generate secondary indoor pollutants both in gas and aerosol phases. It can also affect indoor air quality and health, especially for workers repeatedly exposed to disinfectants. Here, we cleaned the floor of a mechanically ventilated office room using a commercial cleaner while concurrently measuring gas-phase precursors, oxidants, radicals, secondary oxidation products, and aerosols in real-time; these were detected within minutes after cleaner application. During cleaning, indoor monoterpene concentrations exceeded outdoor concentrations by two orders of magnitude, increasing the rate of ozonolysis under low (<10 ppb) ozone levels. High number concentrations of freshly nucleated sub–10-nm particles (≥105 cm−3) resulted in respiratory tract deposited dose rates comparable to or exceeding that of inhalation of vehicle-associated aerosols.
Bayesian sample size determination in a three-arm non-inferiority trial with binary endpoints

ABSTRACT A three-arm non-inferiority trial including a test treatment, a reference treatment, and a placebo is recommended to assess the assay sensitivity and internal validity of a trial when applicable. Existing methods for designing and analyzing three-arm trials with binary endpoints are mainly developed from a frequentist viewpoint. However, these methods largely depend on large sample theories. To alleviate this problem, we propose two fully Bayesian approaches, the posterior variance approach and Bayes factor approach, to determine sample size required in a three-arm non-inferiority trial with binary endpoints. Simulation studies are conducted to investigate the performance of the proposed Bayesian methods. An example is illustrated by the proposed methodologies. Bayes factor method always leads to smaller sample sizes than the posterior variance method, utilizing the historical data can reduce the required sample size, simultaneous test requires more sample size to achieve the desired power than the non-inferiority test, the selection of the hyperparameters has a relatively large effect on the required sample size. When only controlling the posterior variance, the posterior variance criterion is a simple and effective option for obtaining a rough outcome. When conducting a previous clinical trial, it is recommended to use the Bayes factor criterion in practical applications.
Reconstructing the epidermal proteolytic cascades in health and disease

The epidermis is the outer stratified epithelium of the skin, forming the physical barrier that is indispensable for homeostasis. Epidermal proteolysis, mainly but not exclusively executed by kallikrein‐related peptidases (KLKs), is tightly regulated to ensure maintenance of physiological skin renewal and an intact skin barrier. Perturbation of epidermal proteolytic networks is implicated in a wide array of rare and common skin pathologies of diverse genetic backgrounds. Recent studies of monogenic human skin diseases and newly developed animal models have revealed new mechanisms of regulation of proteolytic pathways in epidermal physiology and in disease states. These new data have challenged some accepted views, for example the role of matriptase in epidermal desquamation, which turned out to be restricted to mouse skin. The significance of PAR2 signaling in skin inflammation should also be reconsidered in the face of recent findings. Cumulatively, recent studies necessitate a sophisticated redefinition of the proteolytic and signaling pathways that operate in human skin. We elaborate how epidermal proteolysis is finely regulated at multiple levels, and in a spatial manner that has not been taken into consideration so far, in which specific proteases are confined to distinct epidermal sublayers. Of interest, transglutaminases have emerged as regulators of epidermal proteolysis and desquamation by spatially fixing endogenous protease inhibitors, constituting regulatory factors that were not recognized before. Furthermore, new evidence suggests a link between proteolysis and lipid metabolism. By synthesis of established notions and recent discoveries, we provide an up‐to‐date critical evaluation and synthesis of current knowledge and the extended complexity of proteolysis regulation and signaling pathways in skin. © 2022 The Pathological Society of Great Britain and Ireland.
Muscle hypertrophic effect of inhaled beta2‐agonist is associated with augmented insulin‐stimulated whole‐body glucose disposal in young men

Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2‐agonist treatment. However, the doses administered to rodents are not comparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2‐agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin‐stimulated whole‐body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo‐controlled parallel‐group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg × day−1, n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects’ whole‐body insulin‐stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg × min−1, P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: −37 to 195 mg × min−1, P = 0.154). GLUT4 content in muscle or adipose tissue did not change, nor did hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2‐agonist treatment in close‐to‐therapeutic doses may augment whole‐body insulin‐stimulated glucose disposal in healthy young men and part of the change is likely to be explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2‐agonists for improving insulin sensitivity.
Implementing a Novel Interprofessional Clinical Informatics Curriculum

A novel interprofessional clinical informatics curriculum was developed, piloted, and implemented, using an academic medical record. Targeted learners included undergraduate, graduate, and professional students across five health science colleges. A team of educators and practitioners representing those five health science colleges was formed in 2016, to design, develop, and refine educational modules covering the essentials of clinical informatics. This innovative curriculum consists of 10 online learning modules and 18 unique imbedded exercises that use standardized patient charts and tailored user views. The exercises allow learners to adopt the role of various providers who document in EMRs. Students are exposed to the unique perspectives of an attending physician, nurse, radiological technician, and health information manager, with the goal of developing knowledge and skills necessary for efficient and effective interprofessional communication within the EMR. The campus-wide clinical informatics curriculum is online, flexible, asynchronous, and well-established within each college, allowing faculty to select and schedule content based on discipline-specific learner and course needs. Program modifications over the past 4 years have correlated with a positive impact on the students' experience.
Characterization of a convection‐based support microstructure through a flow resistance parameter

Modern convection‐based supports differ substantially in pore size, porosity, and microstructure topology. Due to such variability, it is challenging to evaluate the contribution of a particular microstructure topology on flow resistance. We demonstrated that the flow resistance parameter (ϕ) introduced decades ago can be used as a criterion to evaluate the effect of microstructure topology on a pressure drop when the pore size is used as a characteristic support dimension. Furthermore, the ϕ value of simple cubic packing was calculated over the entire range of open porosity and compared to the ϕ values determined for pressure drop models derived for particular convection‐based supports and experimental values of various convection‐based supports from the literature. It was shown that different convection‐based supports become clustered into distinct groups when plotted according to their ϕ and open porosity values, allowing their discrimination.
Reduction of Common Mode Voltage in Asymmetrical Dual Inverter Configuration Using Discontinuous Modulating Signal Based PWM Technique

Conventional space vector pulse width modulation based asymmetrical dual inverter configuration produces high common mode voltage (CMV) variations. This CMV causes the flow of common mode current, which adversely affects the motor bearings and electromagnetic interference of nearby electronic systems. In this study, a simple and generalized carrier based pulse width modulation (PWM) technique is proposed for dual inverter configuration. This simple approach generates various continuous and discontinuous modulating signals based PWM algorithms. With the application of the discontinuous modulating signal based PWM algorithm to the asymmetrical dual inverter configuration, the CMV can be reduced with a slightly improved quality of output voltage. The performance of the continuous and discontinuous modulating signals based PWM algorithms is explored through both theoretical and experimental studies. Results show that the discontinuous modulating signal based PWM algorithm efficiently reduces the CMV and switching losses.
Indirect influence in social networks as an induced percolation phenomenon

Significance Increasing empirical evidence in diverse social and ecological systems has shown that indirect interactions play a pivotal role in shaping systems’ dynamical behavior. Our empirical study on collaboration networks of scientists further reveals that an indirect effect can dominate over direct influence in behavioral spreading. However, almost all models in existence focus on direct interactions, and the general impact of indirect interactions has not been studied. We propose a new percolation process, termed induced percolation, to characterize indirect interactions and find that indirect interactions raise a plethora of new phenomena, including the wide range of possible phase transitions. Such an indirect mechanism leads to very different spreading outcomes from that of direct influences.
Prolonged Insertion Time Reduces Translocation Rate of a Precurved Electrode Array in Cochlear Implantation

Hypothesis: Insertion speed during cochlear implantation determines the risk of cochlear trauma. By slowing down insertion speed tactile feedback is improved. This is highly conducive to control the course of the electrode array along the cochlear contour and prevent translocation from the scala tympani to the scala vestibuli. Background: Limiting insertion trauma is a dedicated goal in cochlear implantation to maintain the most favorable situation for electrical stimulation of the remaining stimulable neural components of the cochlea. Surgical technique is one of the potential influencers on translocation behavior of the electrode array. Methods: The intrascalar position of 226 patients, all implanted with a precurved electrode array, aiming a mid-scalar position, was evaluated. One group (n = 113) represented implantation with an insertion time less than 25 seconds (fast insertion) and the other group (n = 113) was implanted in 25 or more seconds (slow insertion). A logistic regression analysis studied the effect of insertion speed on insertion trauma, controlled for surgical approach, cochlear size, and angular insertion depth. Furthermore, the effect of translocation on speech performance was evaluated using a linear mixed model. Results: The translocation rate within the fast and slow insertion groups were respectively 27 and 10%. A logistic regression analysis showed that the odds of dislocation increases by 2.527 times with a fast insertion, controlled for surgical approach, cochlear size, and angular insertion depth (95% CI = 1.135, 5.625). We failed to find a difference in speech recognition between patients with and without translocated electrode arrays. Conclusion: Slowing down insertion speed till 25 seconds or longer reduces the incidence of translocation.
The Costs and Benefits of Plant-Arbuscular Mycorrhizal Fungal Interactions.

The symbiotic interaction between plants and arbuscular mycorrhizal (AM) fungi is often perceived as beneficial for both partners, though a large ecological literature highlights the context dependency of this interaction. Changes in abiotic variables, such as nutrient availability, can drive the interaction along the mutualism-parasitism continuum with variable outcomes for plant growth and fitness. However, AM fungi can benefit plants in more ways than improved phosphorus nutrition and plant growth. For example, AM fungi can promote abiotic and biotic stress tolerance even when considered parasitic from a nutrient provision perspective. Other than being obligate biotrophs, very little is known about the benefits AM fungi gain from plants. In this review, we utilize both molecular biology and ecological approaches to expand our understanding of the plant-AM fungal interaction across disciplines. Expected final online publication date for the Annual Review of Plant Biology, Volume 73 is May 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Current Guidelines on Management of Amaurosis Fugax and Transient Ischemic Attacks

Abstract Transient ischemic attack (TIA) is defined as a transient episode of neurological dysfunction resulting from focal brain, spinal cord, or retinal ischemia, without associated infarction. Consequently, a TIA encompasses amaurosis fugax (AF) that is a term used to denote momentary visual loss from transient retinal ischemia. In this review, we use the word TIA to refer to both cerebral TIAs (occurring in the brain) and AF (occurring in the retina). We summarize the key components of a comprehensive evaluation and management of patients presenting with cerebral and retinal TIA. All TIAs should be treated as medical emergencies, as they may herald permanent disabling visual loss and devastating hemispheric or vertebrobasilar ischemic stroke. Patients with suspected TIA should be expeditiously evaluated in the same manner as those with an acute stroke. This should include a detailed history and examination followed by specific diagnostic studies. Imaging of the brain and extracranial and intracranial blood vessels forms the cornerstone of diagnostic workup of TIA. Cardiac investigations and serum studies to evaluate for etiological risk factors are also recommended. The management of all TIAs, whether cerebral or retinal, is similar and should focus on stroke prevention strategies, which we have categorized into general and specific measures. General measures include the initiation of appropriate antiplatelet therapy, encouraging a healthy lifestyle, and managing traditional risk factors, such as hypertension, dyslipidemia, and diabetes. Specific management measures require the identification of a specific TIA etiology, such as moderate-severe (greater than 50% of stenosis) symptomatic extracranial large vessel or intracranial steno-occlusive atherosclerotic disease, aortic arch atherosclerosis, and atrial fibrillation.
Effects of Dabigatran on Dementia Pathogenesis and Neuropsychological Function: A Review.

BACKGROUND Patients with atrial fibrillation (AF) carry higher risks of cognitive consequences and psychological burden. An optimal anticoagulant therapy would be expected to better preserve neuropsychological function in addition to effective prevention of stroke and systemic thromboembolism. OBJECTIVE The aim of this review is to explore the effects of the non-vitamin K antagonist oral anticoagulant (NOAC) dabigatran, a direct thrombin inhibitor, on cognitive and psychological function as well as dementia pathogenesis. METHODS We performed a comprehensive search of PubMed/Medline for all types of relevant articles using a combination of dabigatran and associated keywords updated to August 31, 2021. All titles and abstracts were screened for eligibility, and potentially relevant papers were collected for inclusion. RESULTS The pooled results demonstrated neutral to positive impacts of dabigatran on cognitive and psychological outcomes, including laboratory results in animal models of Alzheimer's disease, and reduced incidences of anxiety/depression and dementia for AF patients. Dabigatran also exhibited better therapeutic profiles than warfarin in preclinical and observational research. CONCLUSION Given limited strength of evidence from heterogeneous studies, our review proposed modest beneficial effects of dabigatran on neuropsychological function. Further clinical trials are warranted to affirm the pleiotropic protective effects of NOACs on dementia treatment.
Anatomical Variations of the Epitympanum and the Usable Space for Middle Ear Implants Analyzed With CT-assisted Imaging Using a Tablet-based Software

Objective: To evaluate interindividual anatomical variations of the epitympanum and the usable space for implantation of active middle ear implants (AMEI) as well as the usefulness of a tablet-based software to assess individual anatomy on computed tomography (CT) scans. Patients: CT scans of 126 patients, scheduled for cochlea implantation (50.8% men; 0.6–90.0 yr) without middle ear malformations or previous middle ear surgery and with slice thickness ≤0.7 mm were analyzed. Main Outcome Measures: Since no standardized measurements to assess the size of the epitympanum are available, relevant distances were defined according to anatomical landmarks. Three independent raters measured these distances using a tablet-based software. Interrater correlation was computed to evaluate the quality of the measurement process. Descriptive data were analyzed for validation and for evaluation of interindividual anatomical variations. Influence of age and sex on the taken measurements was assessed. Results: No relevant correlation between age or sex and the anatomy of the epitympanum was found. Interrater correlation ranged from Spearman's ρ = 0.3–0.9 and there were significant differences between individual rater results for various combinations. Descriptive data revealed high interindividual anatomical variance of the epitympanum, especially regarding the distance between incus and skull base. Conclusion: The reported descriptive data regarding the anatomy of the epitympanum emphasizes the importance of preoperative planning, especially since the height of the epitympanum showed great interindividual variance potentially limiting implantation of AMEIs. The herein used tablet-based software seems to be convenient for preoperative assessment of individual anatomy in the hand of otosurgeons.
Resting-State Electroencephalography and P300 Evidence: Age-Related Vestibular Loss as a Risk Factor Contributes to Cognitive Decline

Background: In recent years, there have been several meaningful advances in the understanding of the cognitive effects of vestibular loss. However, there has not yet been an investigation exploring the early biomarkers of preclinical cognitive decline in individuals with age-related vestibular loss. Objective: We aim to explore the “early biomarkers” of preclinical cognitive decline based on altered cortical activity (resting-state electroencephalography (EEG) and P300) with a multichannel EEG system in individuals with age-related vestibular loss. Method: This is a case-control study. A total of 21 patients with age-related vestibular loss (66.50±5.79 years, 13 [62% ] females), 19 patients with cognitive decline (68.42±5.82 years, 13 [68% ] females), and 21 age- and sex-matched healthy controls were recruited. All participants underwent a comprehensive battery of neuropsychological tests, audio-vestibular evaluations, resting-state EEG and P300 recordings. Results: Significant visuo-spatial, executive, and attention hypofunction were observed in the age-related vestibular group, reflected by decreased subscale scores. Reduced gamma functional connectivity between the right cuneus (Brodmann area 19, BA19) and the left superior parietal gyrus (BA7) was observed in both the age-related vestibular group and the cognitive impairment group. Smaller P300 amplitudes were observed in the age-related vestibular group (1.43±3.69μV) and cognitive impairment group (1.15±4.24μV) than in the healthy control group (3.97±2.38μV). Conclusion: Decreased P300 amplitude and functional connectivity between the right BA19 and the left BA7 were “early biomarkers” observed in individuals with age-related vestibular loss; these biomarkers may contribute to visuospatial, executive, and attention hypofunction.
Peptidic microarchitecture-trapped tumor vaccine combined with immune checkpoint inhibitor or PI3Kγ inhibitor can enhance immunogenicity and eradicate tumors

Background With the rapid development of immune checkpoint inhibitors and neoantigen (NeoV)-based personalized tumor vaccines, tumor immunotherapy has shown promising therapeutic results. However, the limited efficacy of available tumor vaccines impedes the development of personalized tumor immunotherapy. In this study, we developed a novel tumor vaccine system and proposed combined therapeutic strategies for improving treatment effects. Methods We developed a novel tumor vaccine system comprising a newly synthesized peptidic microarchitecture (PMA) with high assembly efficacy. The PMA-trapped neoantigen vaccine was developed to codeliver tumor neoantigen and the Toll-like receptor 9 agonist CpG (NeoV), abbreviated as PMA-NeoV. A microfluidic chip was used to produce PMA particles in a uniform and precise manner. Vaccine effectiveness was investigated both in vitro and in vivo. The combined immunotherapeutic effect of PMA-NeoV with anti-programmed cell death ligand 1 antibody (aPD-L1) or with the phosphatidylinositol 3‑kinase γ (PI3Kγ) inhibitor IPI-549 was further tested in MC38 mouse tumor model. Results PMA-NeoV not only promoted codelivery of the tumor vaccine but also potentiated vaccine immunogenicity. Moreover, compared with free NeoV, PMA-NeoV significantly increased the number of tumor-infiltrating lymphocytes, promoted the neoantigen-specific systemic immune response, and suppressed murine colon MC38 tumor growth. Furthermore, PMA-NeoV increased the expression of programmed cell death receptor-1 on T lymphocytes, and in combination with aPD-L1 eradicated seven of eight MC38 tumors by rescuing exhausted T lymphocytes. Moreover, we combined the PMA-NeoV with the IPI-549, a molecular switch that controls immune suppression, and found that this combination significantly suppressed tumor growth and eradicated five of eight inoculated tumors, by switching suppressive macrophages to their active state and activating T cells to prime a robust tumor immune microenvironment. Conclusions We developed a tumor vaccine delivery system and presented a promising personalized tumor vaccine-based therapeutic regimen in which a tumor vaccine delivery system is combined with an aPD-L1 or PI3Kγ inhibitor to improve tumor immunotherapy outcomes.