Miracle-dz/UniFAR-FTUs huggingface dataset:
An overview of proteomic methods for the study of ‘cytokine storms’

ABSTRACT Introduction: The cytokine storm is a form of excessive systemic inflammatory reaction triggered by a myriad of factors that may lead to multi-organ failure, and finally to death. The cytokine storm can occur in a number of infectious and noninfectious diseases including COVID-19, sepsis, ebola, avian influenza, and graft versus host disease, or during the severe inflammatory response syndrome. Area covered: This review mainly focuses on the most common and well-known methods of protein studies (PAGE, SDS-PAGE, and high- performance liquid chromatography). It also discusses other modern technologies in proteomics like mass spectrometry, soft ionization techniques, cytometric bead assays, and the next generation of microarrays that have been used to get an in-depth understanding of the pathomechanisms involved during the cytokine storm. Expert opinion: Overactivation of leukocytes drives the production and secretion of inflammatory cytokines fueling the cytokine storm. These events lead to a systemic hyper-inflammation, circulatory collapse and shock, and finally to multiorgan failure. Therefore, monitoring the patient’s systemic cytokine levels with proteomic technologies that are redundant, economical, and require minimal sample volume for real-time assessment might help in a better clinical evaluation and management of critically ill patients.
An engineered neurovascular unit for modeling neuroinflammation

The neurovascular unit (NVU) comprises multiple types of brain cells, including brain endothelial cells, astrocytes, pericytes, neurons, microglia, and oligodendrocytes. Each cell type contributes to the maintenance of the molecular transport barrier and brain tissue homeostasis. Several disorders and diseases of the central nervous system, including neuroinflammation, Alzheimer’s disease, stroke, and multiple sclerosis, have been associated with dysfunction of the NVU. As a result, there has been increased demand for the development of NVU in vitro models. Here, we present a three-dimensional (3D) immortalized human cell-based NVU model generated by organizing the brain microvasculature in a collagen matrix embedded with six different types of cells that comprise the NVU. By surrounding a perfusable brain endothelium with six types of NVU-composing cells, we demonstrated a significant impact of the 3D co-culture on the maturation of barrier function, which is supported by cytokines secreted from NVU-composing cells. Furthermore, NVU-composing cells alleviated the inflammatory responses induced by lipopolysaccharides. Our human cell-based NVU in vitro model could enable elucidation of both physiological and pathological mechanisms in the human brain and evaluation of safety and efficacy in the context of high-content analysis during the process of drug development.
Fixed dexmedetomidine infusion versus fixed-dose midazolam bolus as primary sedative for maintaining intra-procedural sedation during endobronchial ultrasound-guided transbronchial needle aspiration: a double blind randomized controlled trial

ABSTRACT Objective: The utility and safety of fixed dexmedetomidine infusion was compared to fixed-dose midazolam bolus among patients undergoing EBUS-TBNA. Methods: In this randomized double-blind study, 197 patients were assigned to receive dexmedetomidine (Group D, 1 μg/kg before, and 0.6 μg/kg/hour during, procedure) or midazolam (Group M, 2 mg before procedure) sedation. The primary outcome was number of rescue midazolam boluses administered to achieve Ramsay Sedation Scale (RSS) score of two or more. We also studied sedation depth during procedure, adverse hemodynamic and hypoxemic events, bronchoscopist and patient satisfaction, and time-to-discharge from recovery room. Results: Rescue midazolam requirement was significantly lesser in 99 Group D (0.9 ± 1.2 boluses) than in 98 Group M (2.0 ± 2.4 boluses), subjects. Mean RSS score was significantly higher in Group D subjects (2.5 ± 0.7 vs. 2.3 ± 0.7). Significantly more subjects in Group D developed hypotension (46 vs. 27) or bradycardia (37 vs. 5), but none required specific intervention. Bronchoscopists reported significantly greater overall procedure satisfaction in Group D subjects. Conclusion: Fixed dexmedetomidine infusion reduced need for rescue sedation during EBUS-TBNA, and allowed slightly faster post-procedure recovery, as compared to fixed-dose midazolam bolus. However, it caused hypotension and bradycardia more frequently. Clinical trial registration: www.clinicaltrials. gov identifier is NCT02713191
Source Specific Cyto- and Genotoxicity of Atmospheric Aerosol Samples

Atmospheric aerosol samples were studied during wintry conditions at three Hungarian locations (rural background, urban background, traffic site). Ratio of biomass burning and fossil fuel related aerosol were highly different at the sampling points. Cyto- and genotoxicity of the samples were measured by using ＂Pseudomonas putida＂ growth inhibition test and Ames test, respectively. Dominant particle emission sources were apportioned through tracer heavy metal content measurement, optically and thermo-optically methods. According to the results, both ecotoxicity parameters are strongly emission source dependent; the higher the ratio of the biomass burning related carbonaceous aerosol the higher the cytotoxicity and the higher the ratio of the fossil fuel related carbonaceous aerosol the higher the genotoxicity. Cytotoxicity showed positive correlation with carbonaceous aerosol related to biomass burning (R^2=0.74) and negative with lead content of the samples (R^2=-0.56). Genotoxicity showed positive correlation with carbonaceous aerosol related to traffic (R^2=0.42) and cadmium content of the samples (R^2=0.74). At the same time, it showed negative correlation with organic/elemental carbon ratio of the samples (R^2=-0.43).
Remineralization of dentin induced by a compound of polyamide-amine and chlorhexidine in a resin dentin bonding microenvironment

Background The purpose of this study was to investigate the effect of a complex of polyamide-amine dendrimer (PAMAM) and chlorhexidine gluconate (CG) on remineralization of dentin in an artificial simulated resin dentin bonding microenvironment. Methods The structure of this complex was characterized by FT-IR. Twelve standard dentin samples were randomly divided into four treatment fluid groups namely a PAMAM group, CG group, PAMAM + CG group, and deionized water group. A microenvironmental mineralization model was established in vitro with 50 µm gap width between resin and dentin. The dentin surface was observed by a scanning electron microscope (SEM), and the chemical structure of the surface was analyzed by X-ray energy spectrum (EDS), X-ray diffraction (XRD), and laser Raman spectroscopy. Results SEM showed the density of dentinal tubules exposed in the PAMAM group decreased after a 14-day immersion, with corn rod-shaped crystal structures gathered around the tubules. In addition, visible mineralization occurred in partial areas of the CG group, rod-shaped crystals and in comparison, dentinal tubules in the PAMAM + CG group were almost completely covered by flaky crystal structures. Raman spectrum analysis showed that crystals formed by PAMAM, CG, and PAMAM + CG solution all had strong phosphate characteristic peaks, indicating the presence of hydroxyapatite (HA), that of the PAMAM + CG group was the strongest. The EDS results showed that the Ca and P levels of the PAMAM group and the CG group were slightly higher than those of the deionized water group, while PAMAM + CG group significantly higher than the others, Ca/P value approaching 1.67. The results of XRD showed the characteristic peaks of hydroxyapatite detected by the PAMAM + CG group at 2θ=26.0 (002), 2θ=32.0 (211), and 2θ=33.0 (112) were high and sharp, with a few diffraction line burrs indicating it had high crystallinity and purity. The Scherrer equation results showed that the appearance and size of the grains formed by the PAMAM + CG group were basically consistent with those of healthy dentin. Conclusions Altogether, the compound of polyamide-amine dendrimer and chlorhexidine could induce the remineralization of human dentin in a resin dentin bonding microenvironment with a gap of 50 µm to form a crystal structure similar to dentin hydroxyapatite.
Survey of Residency Directors’ Views on Entrepreneurship

Medical students enter the medicine field with fresh ideas that may make them great entrepreneurs. However, medical students are uncertain about how the program directors of their desired residency would view them if they pursued business opportunities. We surveyed residency directors to obtain their views on medical students’ entrepreneurship experiences. This viewpoint article aims to help American medical students who are interested in health innovations understand how their interests and entrepreneurial experiences may affect how they are viewed by residency program directors. Most program directors had favorable views of medical students with experience in entrepreneurship, and they believed that the innovative traits gained from such experiences would add to the program.
Stability of the Hydronium Cation in the Structure of Illite

Some aspects of the crystal structure of illite are not understood properly yet, in spite of its abundance and significance as a component of soils, sediments, and low-grade metamorphic rocks. The present study aimed to explore the role of hydronium cations in the interlayer space of illite in a theoreticalexperimental approach in order to clarify previous controversial reports. The infrared spectroscopy of this mineral has been studied experimentally and by means of atomistic calculations at the quantum mechanical level. The tetrahedral charge is critical for the stability of the hydronium cations, the presence of which has probably been underestimated in previous studies. In the present study, computational studies have shown that the hydronium cations in aqueous solutions are likely to be intercalated in the interlayer space of illite, exchanging for K cations. During the drying process these cations are stabilized by hydrogen bonds in the interlayer space of illite.
Inflammasome Genetic Variants, Macrophage Function, and Clinical Outcomes in Cystic Fibrosis.

Cystic fibrosis (CF) is characterized by chronic airway infection, inflammation, and tissue damage that lead to progressive respiratory failure. NLRP3 and NLRC4 are cytoplasmic pattern recognition receptors that activate the inflammasome, initiating a caspase-1 mediated response. We hypothesized that gain of function inflammasome responses are associated with worse outcomes in children with CF. We genotyped nonsynonymous variants in NLRP3 and the NLRC4 pathway from individuals in the Early Pseudomonas Infection Control (EPIC) Observational Study cohort and tested for association with CF outcomes. We generated knockouts of NLRP3 and NLRC4 in human macrophage-like cells and rescued knockouts with wild-type or variant forms of NLRP3 and NLRC4. We identified a SNP in NLRP3, p.(Q705K), that was associated with a higher rate of Pseudomonas aeruginosa colonization (N=609, p=0.01, HR=2.3, Cox model) and worsened lung function over time as measured by forced expiratory volume in 1 second (FEV1) (N=445, p=0.001, generalized estimating equation). We identified a SNP in NLRC4, p.(A929S), that was associated with a lower rate of P. aeruginosa colonization as part of a composite of rare variants (N=405, p=0.045, HR=0.68, Cox model) and that was individually associated with protection from lung function decline (p<0.001, generalized estimating equation). Rescue of the NLRP3 knockout with the p.(Q705K) variant produced significantly more IL-1β in response to NLRP3 stimulation than rescue with the wild-type (p=0.020, Student's t-test). We identified a subset of children with CF at higher risk of early lung disease progression. Knowledge of these genetic modifiers could guide therapies targeting inflammasome pathways.
Assessment of preparation time and 1-year Invisalign aligner attachment survival using flowable and packable composites.

OBJECTIVES To compare preparation time and 1-year Invisalign aligner attachment survival between a flowable composite (FC) and a packable composite (PC). MATERIALS AND METHODS Fifty-five participants (13 men and 42 women, mean age ± SD: 24.2 ± 5.9 years) were included in the study. Ipsilateral quadrants (ie, maxillary and mandibular right, or vice versa) of attachments were randomly assigned to the FC group (Filtek Z350XT Flowable Restorative) and the PC group (Filtek Z350XT Universal Restorative) by tossing a coin. The primary outcome was preparation time. The secondary outcome was time to the first damage of an attachment. Preparation times were compared using the paired t-test, and the survival data were analyzed by the Cox proportional hazards model with a shared frailty term, with α = . 05. RESULTS The preparation times were significantly shorter with the FC (6.22 ± 0.22 seconds per attachment) than with the PC (32.83 ± 2.16 seconds per attachment; P < .001). The attachment damage rates were 14.79% for the FC and 9.70% for the PC. According to the Cox models, attachment damage was not significantly affected by the attachment material, sex, arch, tooth location, attachment type, presence of overbite, or occurrence of tooth extraction. CONCLUSIONS The use of a FC may save time as compared with the use of a PC. With regard to attachment survival, there was no significant difference between the two composites. None of the covariates of attachment materials (sex, arch, tooth location, attachment type, presence of overbite, oir occurrence of tooth extraction) affected attachment damage.
Developing force field parameters for water interacting with graphene and graphene-like materials

Confined water can have properties dramatically different from bulk water, and these properties can be used to develop unique functionality at the nanoscale. For example, fast water transport, rotation-translation coupling, and fast rotational motion have been observed in graphitic carbon-based nano structures, which enables various applications like energy storage and seawater desalination. The explosive studies on graphene have sparked new interests towards graphene-analogous materials including hexagonal boron nitride (hBN) and molybdenum disulfide (MoS2). Compared to graphene, the graphene-analogous materials possess non-zero bandgap, chemical inertness, and biological compatibility. The graphene-analogous materials are promising materials, complementary to graphene, for high-temperature, biomedical and nanofluidic applications. We would like to understand and optimize graphene and graphene-analogous materials in these applications. The study of graphene and graphene-analogous materials at the atomic level requires accurate force field parameters to describe the water-surface interaction. We begin with benchmark quality first principles quantum Monte Carlo (QMC) calculations on the interaction energy between water and surface, which are used to validate random phase approximation (RPA) calculations. We then proceed with RPA to derive force field parameters, which are used to simulate properties like water contact angle on the surface, attaining a value within the experimental uncertainties. This work demonstrates that end-to-end multiscale modeling, starting at detailed many-body quantum mechanics, and ending with macroscopic properties, with the approximations controlled along the way, is feasible for these systems.
Trifecta outcomes of modified robot-assisted simple enucleation and standard robot-assisted partial nephrectomy for treating clinical T1b renal cell carcinoma

Background To compare perioperative outcomes and Trifecta achievement of modified robot-assisted simple enucleation (MRASE) with robot-assisted partial nephrectomy (RAPN) for treating clinical T1b renal tumors. Methods We analyzed 203 patients who underwent MRASE or RAPN for clinical T1b renal tumors at our institution from September 2014 to June 2018. The two groups were compared regarding perioperative outcome variables. Trifecta was defined as no perioperative complications, negative surgical margin, and ischemia time ≤25 minutes. Results In all, 139 patients underwent MRASE and 64 underwent RAPN respectively. Patients in the MRASE group had shorter operative time (197.7 vs. 215.6 min, P=0.039) and warm ischemic time (21.2 vs. 24.1 min, P=0.004) in comparison to the RAPN group. The groups were comparable in estimated blood loss (230.5 vs. 269.8 mL, P=0.259). Tumor bed suturing was performed with a significantly lower frequency in the MRASE group than in the RAPN group (11.5% vs. 90.6%, P<0.01). The incidence of perioperative complications was similar. The rate of positive surgical margins was similar in both groups (2.2% vs. 6.3%, P=0.284). Trifecta was achieved in 61.2% and 42.2% of MRASE and RAPN patients (P=0.012). On multivariable analysis, the type of procedure, RENAL score, estimated blood loss, and operative time were positive factors for the achievement of Trifecta. Conclusions In this series MRASE was superior to RAPN with regard to the achievement of Trifecta in treating T1b renal tumors. Besides, MRASE had better outcomes for shorter operative time, shorter warm ischemic time, and less need for tumor bed suturing as compared with RAPN.
Barriers and Facilitators to Substance Use Disorder Treatment in Low-and Middle-Income Countries: A Qualitative Review Synthesis

Abstract Background and aims One of the ways to address the treatment gap for substance use disorders is to understand the barriers and facilitators to treatment. This study aimed to synthesize the literature on barriers and facilitators of treatment in Low- and Middle-Income Countries (LMICs). Methods We search Medline electronic database to identify English language peer reviewed empirical studies, both qualitative and quantitative which reported barriers and/or facilitators of treatment of substance use disorders. Results Of 1389 titles, we selected 28 studies (14 were qualitative and 14 quantitative studies). The sample sizes of the qualitative studies ranged from 11 to 235. The majority of studies were from community or clinic settings. A wide range of barriers and facilitators were identified from the qualitative studies and were synthesized according to perceived susceptibility/seriousness, self-efficacy, perceived costs, perceived benefits, and cues to action. Most of the quantitative studies were community-based cross sectional-observational by design. Commonly identified barriers in these quantitative studies were perceived lack of problem or lack of need for treatment and low motivation whereas factors such as good family support and availability of effective treatment was found to facilitate substance use disorder treatment. Conclusion There are a wide range of barriers that hinder the substance use disorder treatment as well as certain factors that facilitate the treatment. Addressing them can help to minimize the treatment gap, which in turn can help in reducing the familial and social burden due to substance use disorders.
Protein Source and Quality for Skeletal Muscle Anabolism in Young and Older Adults: A Systematic Review and Meta-Analysis

ABSTRACT Background There is much debate regarding the source/quality of dietary proteins in supporting indices of skeletal muscle anabolism. Objective We performed a systematic review and meta-analysis to determine the effect of protein source/quality on acute muscle protein synthesis (MPS) and changes in lean body mass (LBM) and strength, when combined with resistance exercise (RE). Methods A systematic search of the literature was conducted to identify studies that compared the effects of ≥2 dose-matched, predominantly isolated protein sources of varying “quality. ” Three separate models were employed as follows: 1) protein feeding alone on MPS, 2) protein feeding combined with a bout of RE on MPS, and 3) protein feeding combined with longer-term resistance exercise training (RET) on LBM and strength. Further subgroup analyses were performed to compare the effects of protein source/quality between young and older adults. A total of 27 studies in young (18–35 y) and older (≥60 y) adults were included. Results Analysis revealed an effect favoring higher-quality protein for postprandial MPS at rest [mean difference (MD): 0.014%/h; 95% CI: 0.006, 0.021; P < 0.001] and following RE (MD: 0.022%/h; 95% CI: 0.014, 0.030; P < 0.00001) in young (model 1: 0.016%/h; 95% CI: −0.004, 0.036; P = 0.12; model 2: 0.030%/h; 95% CI: 0.015, 0.045; P < 0.0001) and older (model 1: 0.012%/h; 95% CI: 0.006, 0.018; P < 0.001; model 2: 0.014%/h; 95% CI: 0.007, 0.021; P < 0.001) adults. However, although higher protein quality was associated with superior strength gains with RET [standardized mean difference (SMD): 0.24 kg; 95% CI: 0.02, 0.45; P = 0.03)], no effect was observed on changes to LBM (SMD: 0.05 kg; 95% CI: −0.16, 0.25; P = 0.65). Conclusions The current review suggests that protein quality may provide a small but significant impact on indices of muscle protein anabolism in young and older adults. However, further research is warranted to elucidate the importance of protein source/quality on musculoskeletal aging, particularly in situations of low protein intake.
Interventions and Outcomes of Adult Patients with B-ALL Progressing After CD19 Chimeric Antigen Receptor T Cell Therapy.

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has become a breakthrough treatment for patients with relapsed/refractory B acute lymphoblastic leukemia (B-ALL). However, despite the high initial response rate, the majority of adult patients with B-ALL progress after CD19 CAR T therapy. Data on the natural history, management, and outcome of adult B-ALL progressing after CD19 CAR T cells have not been described in detail. Herein, we report comprehensive data of 38 adult B-ALL patients who progressed after CD19 CAR T therapy at our institution. The median time to progression after CAR T therapy was 5.5 months. Median survival after post-CAR T progression was 7.4 months. A high disease burden at the time of CAR T cell infusion was significantly associated with risk of post-CAR T progression. Thirty patients (79%) received salvage treatment for post-CAR T disease progression and 13 patients (43%) achieved complete remission (CR), but remission duration was short. Notably, 7 of 12 patients (58.3%) achieved CR after blinatumomab and/or inotuzumab administered after post-CAR T failure. Multivariate analysis demonstrated longer remission duration from CAR T cells was associated with superior survival after progression following CAR T therapy. In conclusion, overall prognosis of adult B-ALL patients progressing after CD19 CAR T cells was poor though a subset of patients achieved sustained remissions to salvage treatments including blinatumomab, inotuzumab and re-infusion of CAR T cells. Novel therapeutic strategies are needed to reduce risk of progression after CAR T therapy and improve outcomes of these patients.