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OBJECTIVES/GOALS: A growing number of older adults in the United States have multiple social determinants of health (SDoH) that are barriers to effective medical care. We used generalizable machine learning methods to identify and visualize subtypes based on participant-reported SDoH profiles, and their association with delayed medical care (self-reported yes/no). METHODS/STUDY POPULATION: Data. All participants aged >=65 in All of Us with complete data on 18 SDoH self-reported variables, selected through consensus by 2 experienced health services researchers, and guided by Andersen’s behavioral model. Covariates included demographics, and the outcome was delayed medical care . Cases (n=4090) consisted of participants with at least one of the 18 SDoH variables, and controls (n=7414) consisted of participants with none of them. Method. (1) Used bipartite network analysis and modularity maximization to identify participant-SDoH biclusters, and visualize them through ExplodeLayout. (2) Used multivariable logistic regression (adjusted for demographics and corrected through Bonferroni) to measure the odds ratio (OR) of each participant bicluster to the outcome, compared with the controls. RESULTS/ANTICIPATED RESULTS: The analysis identified 7 SDoH subtypes (https://postimg.cc/Vd7Pg4xZ) with statistically significant modularity compared with 100 random permutations of the data (All of Us=.51, Random Mean=.38, z=20, P DISCUSSION/SIGNIFICANCE: The results identified 7 distinct subtypes based on SDoH profiles and their risk for delayed medical care, highlighting the importance of addressing specific combinations of barriers, with affordability having the highest risk. Furthermore, the analytical methods used are generalizable and have been made publicly available on CRAN and All of Us.

OBJECTIVES/GOALS: While disease subtypes are critical for precision medicine, most projects use unipartite clustering methods such as k-means which are not fully automated, do not provide statistical significance, and are difficult to interpret. These gaps were addressed through bipartite networks and tested for generalizability on three national databases. METHODS/STUDY POPULATION: Data. All participants with self-reported stroke from the 2010 Health and Retirement Study (HRS), with cases (n=798) having one or more 8 depressive symptoms measured by the Centers for the Epidemiological Study–Depression 8 scale, and controls (n=389) with none of those symptoms. The replication data set consisted of independent identically-defined participants (cases=725, controls=190) from 1998 HRS. Method. (1) Bipartite network analysis and modularity maximization to automatically identify patient-symptom biclusters with significance. (2) Rand Index to measure the replicability of symptom co-occurrences in the replication data. (3) ExplodeLayout to visualize and interpret the subtypes. (4) R libraries to generalize the methods, upload them to CRAN, and then tested on the N3C and All of Us platforms. RESULTS/ANTICIPATED RESULTS: The analysis identified 4 depressive symptom subtypes (https://postimg.cc/Ny8YwXJW) which had significant modularity (Q=0.26, z=3.03, P DISCUSSION/SIGNIFICANCE: We developed generalizable methods to automatically identify biclusters, measure the clustering significance, and visualize the results for interpretation. These methods were successfully tested on three national level data bases. Such generalizable methods should accelerate the analysis of subtypes, and the design of targeted interventions.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder associated with significant morbidity. Current treatment approaches consist of a mixture of pharmacological and psychological approaches. The emergence of digital technology, and mobile gaming applications, represents a promising novel method in potentially augmenting existing interventions for ADHD. In this review, we will map out the use of mobile gaming applications in the management of ADHD and evaluate the effectiveness of these technologies and any areas for future research. Four electronic databases were searched for relevant articles. All articles were screened for abstract and full text by two independent reviewers, and data extracted onto a common data extraction sheet. The data was narratively synthesized and reported in line with the PRISMA-ScR guidelines. A total of 19 studies were included. Studies mostly evaluated the effectiveness of games on male children with ADHD. Most games were focused on the treatment of ADHD, while a minority were focused on the diagnosis and monitoring of ADHD. Some of the common gaming mechanisms employed in games included having participants responding to cures, remembering details, and making associations between different entities. The studies generally showed an improvement in performance of children as they played the games, but evidence for the effectiveness of these modalities remains scarce and mixed. While it is exciting that there is such a wide variety of games available currently in the diagnosis, treatment, and monitoring of ADHD, many of the games lack clinical evidence to prove their effectiveness. Furthermore, most studies contain several limitations including small sample size, limited ages of participants, lack of control group, and lack of comprehensive outcomes. To promote the application of these games to clinical practice, robust clinical trials, collaboration between stakeholders and using a comprehensive set of outcome measurements is essential.

ObjectiveTo establish a predictive nomogram to distinguish combined hepatocellular-cholangiocarcinoma (CHC) from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) based on preoperative clinical and ultrasound findings.MethodsA total of 261 patients with pathologically confirmed primary liver cancers (PLCs) were enrolled in this retrospective study, comprising 87 CHCs, 87 HCCs, and 87 ICCs matched by propensity score matching. Patients were randomly assigned to a training cohort and a validation one at the ratio of 7:3. A nomogram integrating ultrasound imaging characteristics and clinical features was established based on the independent risk factors selected by least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was evaluated in the training and validation cohorts in terms of discrimination, calibration, and clinical usefulness.ResultsThe nomogram, consisting of ultrasound imaging features (shape and margin on B-mode ultrasound, enhanced pattern on contrast-enhanced ultrasound) and clinical information [elevated alpha fetoprotein (AFP) level and serum protein electrophoresis (SPE) α1 level], showed promising performance in differentiating CHC from HCC and ICC, with the concordance index (C-index) of 0.8275 and 0.8530 in the training cohort and the validation cohort, respectively. Hosmer–Lemeshow test and the calibration curves suggested good consistency between predictions and observations. High clinical practicability was confirmed by the decision curve analysis.ConclusionsThe nomogram based on clinical and ultrasound imaging characteristics showed good performance in the discrimination of CHC from other subtypes of PLC and would be valuable in clinical decision-making.

Formamidinium lead triiodide (FAPbI3) perovskite has received great attention because of its distinct optoelectronic property, smaller band gap (~1.5 eV), and higher thermal stability than methylammonium lead triiodide (MAPbI3). However, the efficient synthesis of such perovskite materials on a large scale at a low cost remains a challenge. In this work, mixed-cation FA1−xCsxPbI3 thin films were directly prepared in an atmospheric environment with a high film formation rate, low material loss, low cost, and low requirements for experimental instruments and environment. The as-obtained FAPbI3 films exhibited excellent optoelectronic properties, showing promising applications in the photodetection field.

Based on first-principles calculations, variations in the stability as well as the electronic and optical properties of fluorinated MoSi2N4 (MoSi2N4-Fx, x = 0–16) were investigated. Analyses of the adsorption energy and phonon band dispersions proved that the fluorinated MoSi2N4 formed a stable structure. The band gap of MoSi2N4 was 1.92 eV. When the F number increased to x = 16, the band gap of MoSi2N4-F16 decreased to 0 eV, indicating that the fully fluorinated monolayer showed a metallic nature. At the same time, the work function of MoSi2N4-Fx increased from 4.72 (x = 0) to 6.17 eV (x = 16). Based on dielectric function spectra, MoSi2N4-Fx (x = 0–16) showed significant optical anisotropy. The light absorption range and intensity in the visible-light range were obviously enhanced after the fluorination process. The transmittance of the 10-nm-thick MoSi2N4 film (10 layers of MoSi2N4) was larger than 80%, indicating that this material had a good optical transmission ability. After the fluorination process, the optical transmittance of MoSi2N4 showed a significant decrease. Therefore, the properties of MoSi2N4 could be adjusted through the facile fluorination process, which could largely expand the applications of MoSi2N4 in electronic/optoelectronic devices and photocatalysts.

Objective: To investigate the impact of the severity of age-related hearing loss (ARHL) and tinnitus, presence of ARHL and/or tinnitus, and physical frailty on the health-related quality of life (HRQoL) and domain-specific HRQoL in Chinese community-dwelling older adults.Design: This was a cross-sectional study of a community-based cohort.Participants: We evaluated Chinese older adults (n = 429, 183 men and 246 women) aged ≥ 58years.Measurements: The severity of HL and tinnitus were measured using pure-tone audiometry and the Tinnitus Handicap Inventory (THI), respectively. Physical frailty was measured using the five-item Fried scale. HRQoL was assessed using the Assessment of Quality of Life-8-Dimension (AQoL-8D) multi-attribute utility instrument (35 HRQoL items and eight domain-specific HRQoL subcategories). Low HRQoL (HRQoL score or subscores in the highest quintile) was used as a dependent variable in logistic regression analyses adjusted for demographic (Model 1) and health-related (Model 2) and psychosocial (Model 3) confounders.Results: Age-related hearing loss severity was an independent determinant of senses in the physical dimension of HRQoL after adjusting for all covariates. Tinnitus severity was significantly associated with HRQoL and with independent living, senses, and pain in the physical dimension after adjusting for demographic and health-related covariates and was still associated with independent living and senses after adjusting for all covariates. The presence of ARHL and/or tinnitus was significantly associated with independent living and senses in the physical dimension after adjusting for all the covariates. Physical frailty was an independent determinant of HRQoL, independent living, and pain in the physical dimension and with mental health, happiness, and coping in the psychosocial dimension after adjusting for demographic and health-related covariates. The association with HRQoL, independent living, and pain in the physical dimension, and with happiness and coping in the psychosocial dimension remained significant after adjusting for the covariates. Depressive symptoms, social dysfunction, and a number of comorbidities were critical determinants of psychosocial HRQoL.Conclusion: Physical frailty has a stronger and more profound effect on HRQoL, particularly on independent living and pain in the physical dimension and on happiness and coping in the psychosocial dimension. Domain-specific HRQoL should be considered in the management of patients with ARHL with tinnitus and physical frailty.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT2017K020.

A comprehensive understanding on the phototransformation of antibiotics in aqueous environments requires consideration of particulate matters contained in natural waters. However, relevant studies on this issue are still limited. Considering the wide distribution of natural sands in natural waters, especially in rainy seasons, the photolysis of CIP in water containing natural sands was investigated, and the influence of natural sands on photolysis was evaluated. The photolytic kinetics showed that the natural sands suspended in water notably accelerated the photodegradation of CIP, and the affecting degree depended on their compositions. The scavenger experiments combined with electron paramagnetic resonance (EPR) experiments showed that 1O2, O2−•, and ·OH generated in the natural sand systems under irradiation, and responsible for the enhanced photodegradation of CIP. The H2O2 and HCl treatment experiments, together with deoxygenation experiments, confirmed that the production of reactive radicals was mainly ascribed to the photoactive oxides and natural organic matter (NOM) in natural sands. The photoproducts of CIP in the presence of natural sands were identified by LC-MS, and the possible degradation pathways were proposed. This study suggested that particulate matters contained in natural waters was a important factor influencing the phototransformation of pollutants, and should be considered in assessing their fate in aqueous environments.

Due to the fast response characteristics of battery storage, many renewable energy power stations equip battery storage to participate in auxiliary frequency regulation services of the grid, especially primary frequency regulation (PFR). In order to make full use of the battery capacity and improve the overall revenue of the renewable energy station, a two-level optimal scheduling strategy for battery storage is proposed to provide primary frequency regulation and simultaneously arbitrage, according to the peak-valley electricity price. The energy storage output is composed of the droop-based primary frequency regulation output and the economic output, according to the electricity price. First, day-ahead optimization defines the economic output profile and an appropriate droop coefficient, considering regulation needs, with the goal of maximizing the overall return. The scheduling result is then adjusted for hour-ahead optimization based on the updated regulation information to ensure more durable and reliable performance. Simulation results show that the proposed scheduling strategy can fully utilize the battery capacity, realize peak-valley arbitrage while assuming the obligation of primary frequency regulation of the renewable energy power station, and then improve the overall income of the power station. [ABSTRACT FROM AUTHOR]

Using first-principles calculations, this work investigated the structural, electronic, thermal and optical properties of ScAl3C3 and UAl3C3 under high pressure. Through the calculation of elastic constant, the mechanical stability of these two ceramics at high pressures were discussed. Then, by comparing the density of states of ScAl3C3 and UAl3C3 under different pressures, the pressure effect on electronic properties were discussed. What’s more, by calculating longitudinal, transverse sound, mean sound velocities, and the Debye temperatures at different pressures, the effect of high pressure on thermal properties of ScAl3C3 and UAl3C3 were explored. At the end of this work, the dielectric function ε(ω) and reflectivity R(ω) of ScAl3C3 and UAl3C3 were calculated to discuss change of their optical properties under high pressure. Keywords: Mn+1AXn (MAX), Thermal property, Optical property, High pressure

Aiming at safe stairs climbing and efficient locomotion on the ground for aged or physical disabled people, a planetary wheeled electric powered wheelchair (EPW) is designed and the composition of the wheelchair mechanism, control system scheme and its functional characteristics are introduced in detail. Through establishing the dynamic model of the planetary wheel clusters based on the Lagrange equation, the angle acceleration curves with various given equivalent torques are studied, the stability margin of the EPW is analyzed in detail in the process of a single step climbing which has demonstrated that the anti-tip-over bracket can effectively enhance the stability. The planetary wheeled stair-climbing wheelchair can effectively help those who are in need and meet the actual needs of daily travel and climbing stairs.

Isolated hepatic malignant melanoma with undetermined origin is relatively rare and the imaging findings vary significantly in published studies. In this report, we described an elderly male patient with pulmonary tuberculosis who was diagnosed with isolated hepatic malignant melanoma with undetermined origin by ultrasound-guided percutaneous coarse needle biopsy (US-CNB). The hepatic melanoma was detected accidentally on chest CT. On contrast-enhanced ultrasound (CEUS), it presented an enhancement pattern of fast washin and slow washout. However, on magnetic resonance imaging (CEMRI), it showed non-rim hyperenhancement in the arterial phase but hypointensity in the late phase, mimicking hepatocellular carcinoma. With inconsistent results, the patient underwent fluorine-18-fluro-2-deoxy-D-glucose-positron emission tomography/computed tomography (18F-FDG-PET/CT). The mass showed mild 18F-FDG uptake with SUVmax of 4.7, and hypermetabolic nodules were observed in the lung, chest wall, thoracic vertebra, and pelvis. Due to the advanced stage of the tumor, US-CNB was performed to acquire a pathological diagnosis. The immunohistochemical staining suggested malignant melanoma. Of note, no primary tumor was revealed. Finally, the patient refused systemic therapy and died from tumor progression seven months later. Hence, CEUS and CEMRI is fundamental in the diagnosis of hepatic melanoma, and PET-CT is helpful in clinical staging. For controversial results, US-CNB is required to establish the pathological diagnosis.

Disc pumps with radial straight blade are unconventional designs that have been developed for hard-to-pump mixtures for many industrial applications. They are frequently used in chemical industries, sub-sea petroleum pumping systems with multi-phase media and so on. Due to the radial straight blade arrangement, they may suffer from cavitation onsets when being used under different pressure conditions. To study the influence of cavitation characteristic inside the present disc pump flow passages, experimental data analysis on a radial blade disc pump for a wide flow rate range (0 to 110 m3/h) is obtained. In addition, the Reynolds averaged (RANS) approach using the RNG k-ε turbulence model, is carried out under different working conditions with and without cavitation modelling. Two different pump meshing models are also implemented: the first one without hub and shroud side channels between the discs and the volute casing, the second one with both side channels corresponding to the complete real case geometry. The comparisons between experimental and numerical results reveal first that the complete geometry meshing must be used to recover the experimental performance curve especially at low flow rates whatever the rotational speed. Secondly, the cavitation effect is found to take place in precise locations (straight blade and connection column) inside the impeller at high rotational speed and high flow rates. Their effects correspond to the unexpected performance curve deterioration found for the highest rotational speed and high flow rates. Moreover, with the decrease of the inlet absolute pressure, the cavitation degree becomes serious, and the coupling phenomenon of straight blade cavitation and connection column cavitation is formed, which enlarges the scope and enhances the degree of cavitation. The present study proposes a data reduction procedure when open loop experimental testing procedure is used for specific disc pump design and the importance of the impeller-side channels interactions on head pump decrease at low flow coefficients.

Hepcidin is widely present in many kinds of fish and is an important innate immune factor. A variety of HAMP2-type hepcidins have strong antimicrobial activity and immunomodulatory functions and are expected to be developed as substitutes for antibiotics. In this study, the antimicrobial activity of Hepc2 from Japanese seabass (Lateolabrax japonicus) (designated as LJ-hep2) was investigated using its recombinant precursor protein (rLJ-hep2) expressed in Pichia pastoris and a chemically synthesized mature peptide (LJ-hep2(66–86)). The results showed that both rLJ-hep2 and synthetic LJ-hep2(66–86) displayed broad antimicrobial spectrum with potent activity against gram-negative and gram-positive bacteria, and fungi. Especially, LJ-hep2(66–86) had stronger antimicrobial activity and exhibited potent activity against several clinically isolated multidrug-resistant bacteria, including Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Enterococcus faecium. Moreover, LJ-hep2(66–86) exerted rapid bactericidal kinetic (killed tested bacteria within 2 h), induced significant morphological changes and promoted agglutination of E. coli, P. aeruginosa and Aeromonas hydrophila. The activity of LJ-hep2(66–86) against E. coli, P. aeruginosa and A. hydrophila was stable and remained active when heated for 30 min. In addition, LJ-hep2(66–86) exhibited no cytotoxicity to the mammalian cell line HEK293T and fish cell lines (EPC and ZF4). In vivo study showed that LJ-hep2(66–86) could improve the survival rate of marine medaka (Oryzias melastigma) by about 40% under the challenge of A. hydrophila, indicating its immunoprotective function. Taken together, both rLJ-hep2 and LJ-hep2(66–86) have good prospects to be used as potential antimicrobial agents in aquaculture and medicine in the future.

ABSTRACT Biomarkers for prognosis-based detection of Trypanosoma cruzi-infected patients presenting no clinical symptoms to cardiac Chagas disease (CD) are not available. In this study, we examined the performance of seven biomarkers in prognosis and risk of symptomatic CD development. T. cruzi-infected patients clinically asymptomatic (C/A; n = 30) or clinically symptomatic (C/S; n = 30) for cardiac disease and humans who were noninfected and healthy (N/H; n = 24) were enrolled (1 − β = 80%, α = 0.05). Serum, plasma, and peripheral blood mononuclear cells (PBMCs) were analyzed for heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), vimentin, poly(ADP-ribose) polymerase (PARP1), 8-hydroxy-2-deoxyguanosine (8-OHdG), copeptin, endostatin, and myostatin biomarkers by enzyme-linked immunosorbent assay (ELISA) and Western blotting. Secreted hnRNPA1, vimentin, PARP1, 8-OHdG, copeptin, and endostatin were increased by 1.4- to 7.0-fold in CD subjects versus N/H subjects (P < 0.001) and showed excellent predictive value in identifying the occurrence of infection (area under the receiver operating characteristic [ROC] curve [AUC], 0.935 to 0.999). Of these, vimentin, 8-OHdG, and copeptin exhibited the best performance in prognosis of C/S (versus C/A) CD, determined by binary logistic regression analysis with the Cox and Snell test (R2C&S = 0.492 to 0.688). A decline in myostatin and increase in hnRNPA1 also exhibited good predictive value in identifying C/S and C/A CD status, respectively. Furthermore, circulatory 8-OHdG (Wald χ2 = 15.065), vimentin (Wald χ2 = 14.587), and endostatin (Wald χ2 = 17.902) levels exhibited a strong association with changes in left ventricular ejection fraction and diastolic diameter (P = 0.001) and predicted the risk of cardiomyopathy development in CD patients. We have identified four biomarkers (vimentin, 8-OHdG, copeptin, and endostatin) that offer excellent value in prognosis and risk of symptomatic CD development. Decline in these four biomarkers and increase in hnRNPA1 would be useful in monitoring the efficacy of therapies and vaccines in halting CD. IMPORTANCE There is a lack of validated biomarkers for diagnosis of T. cruzi-infected individuals at risk of developing heart disease. Of the seven potential biomarkers that were screened, vimentin, 8-OHdG, copeptin, and endostatin exhibited excellent performance in distinguishing the clinical severity of Chagas disease. A decline in these four biomarkers can also be used for monitoring the therapeutic responses of infected patients to established or newly developed drugs and vaccines and precisely inform the patients about their progress. These biomarkers can easily be screened using the readily available plasma/serum samples in the clinical setting by an ELISA that is inexpensive, fast, and requires low-tech resources at the facility, equipment, and personnel levels.

Four prospective trials have reported apatinib-related efficacy in osteosarcoma, with a high response rate of 43.2%. Currently, Adverse Events (AEs) have increasingly gained attention, as treatment with multiple tyrosine kinase inhibitors (TKIs) is potentially lifelong. For this reason, a consensus meeting of the Chinese Sarcoma Study Group (CSSG), which is a multidisciplinary panel composed of pediatric, medical and surgical oncologists specializing in sarcoma, nurse specialists, oncological senior pharmacists and gastroenterologists, was held to develop comprehensive guidelines on AEs emerging due to apatinib treatment to better assist in the prevention, management, and understanding of AE development. We summarized all AEs that arose in ≥10% of the participants as well as rare AEs that required extra caution to prevent that were observed in these four published prospective trials and arranged these AEs into 14 disorder systems according to CTCAE 5.0. In this review, we discuss strategies for the management of AEs in patients with advanced osteosarcoma, with the aim of maximizing treatment benefits and minimizing the need for apatinib treatment discontinuation. We also focus on providing recommendations for the prophylaxis and treatment of advanced osteosarcoma using apatinib to achieve optimal outcomes.

Soft-tissue sarcoma (STS) is represented by a heterogeneous group of rare malignancies with various molecular oncogenesis. Therapies targeting DNA repair pathways in STS have achieved minimal progress, potentially due to the lack of molecular biomarker(s) beyond the histology subtype. In this report, we comprehensively analyzed the expression profiles of 100 liposarcomas (LPSs), the most common STS subtype, in comparison with 21 adipose tissues from multiple GEO datasets to identify the potential prognostic and therapeutic biomarker for LPS. Furthermore, we investigated TCGA database, our archived tumor samples, and patient-derived tumor cell cultures (PTCCs) as a validation. We identified a total of 69 common differentially expressed genes (DEGs) among public datasets, with mini-chromosome maintenance protein 4 (MCM4) identified as a novel biomarker correlated with patients’ clinical staging and survival outcome. MCM4-high expression LPS was characterized by MCM4 copy number increase, genomic instability, and BRCAness phenotype compared with the MCM4-low expression counterpart. In contrast, the mutational and the immune landscape were minimally different between the two groups. Interestingly, the association of MCM4-high expression with genomic instability and BRCAness were not only validated in LPS samples from our institution (n = 66) but also could be expanded to the pan-sarcoma cohort from TCGA database (n = 263). Surprisingly, based on four sarcoma cell lines and eight PTCCs (three LPS and five other sarcoma), we demonstrated that MCM4 overexpression tumors were therapeutically sensitive to PARP inhibitor (PARPi) and platinum chemotherapy, independent of the histology subtypes. Our study, for the first time, suggested that MCM4 might be a novel prognostic biomarker, associated with dysregulated DNA repair pathways and potential therapeutic vulnerability in STS.

Epithelial tissues are primed to respond to insults by activating epithelial cell motility and rapid inflammation. Such responses are also elicited upon overexpression of the membrane-bound protease, Matriptase, or mutation of its inhibitor, Hai1. Unrestricted Matriptase activity also predisposes to carcinoma. How Matriptase leads to these cellular outcomes is unknown. We demonstrate that zebrafish hai1a mutants show increased H2O2, NfκB signalling, and IP3R -mediated calcium flashes, and that these promote inflammation, but do not generate epithelial cell motility. In contrast, inhibition of the Gq subunit in hai1a mutants rescues both the inflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demonstrate that hai1a has elevated MAPK pathway activity, inhibition of which rescues the epidermal defects. Finally, we identify RSK kinases as MAPK targets disrupting adherens junctions in hai1a mutants. Our work maps novel signalling cascades mediating the potent effects of Matriptase on epithelia, with implications for tissue damage response and carcinoma progression.

BackgroundCognitive frailty (CF) includes reversible and potentially reversible subtypes; the former is known as concurrent physical frailty (PF) and pre-mild cognitive impairment subjective cognitive decline (pre-MCI SCD), whereas the latter is known as concurrent PF and MCI. The diagnoses of pre-MCI SCD and MCI are based on clinical criteria and various subjective cognitive decline questionnaires. Heterogeneous assessment of cognitive impairment (CI) results in significant variability of CI, CF, and their subtype prevalence in various population-based studies.ObjectiveThis study aimed to compare the classification differences in CI and CF subtypes from PF and normal cognition by applying clinical and objective cognitive criteria. Clinical criteria comprised Fried PF and clinical MCI criteria combined with the SCD questionnaire, whereas objective criteria comprised Fried PF and objective cognitive criteria based on the norm-adjusted six neuropsychological test scores.MethodsOf the 335 volunteers (age ≥ 60 years) in this study, 191 were diagnosed with CI based on clinical cognitive diagnosis criteria, and 144 were identified as robust normal based on objective cognitive assessment from the community-dwelling older adult cohort. Individuals with clinical CI, including 94 with MCI and 97 with pre-MCI SCD, were reclassified into different z-score-derived MCI, pre-MCI SCD, and normal subgroups based on objective cognitive criteria. The classification diagnostic accuracy of normal cognition, PF, pre-MCI, MCI, CF, and CF subtypes based on clinical and objective criteria was compared before and after adjusting for age, sex, and education level.ResultsThe reclassification of objective assessments indicated better performance than that of clinical assessments in terms of discerning CI severity among different subgroups before adjusting for demographic factors. After covariate adjustment, clinical assessments significantly improved the ability to cognitively discriminate normal individuals from those with pre-MCI SCD and MCI but not the z-score-derived pre-MCI SCD and MCI groups from the robust normal group. Furthermore, the adjustment did not improve the ability to discriminate among individuals with reversible CF from those with potentially reversible CF and pre-MCI only SCD from MCI only SCD.ConclusionsObjective criteria showed better performance than clinical criteria in the diagnosis of individuals with CI or CF subtypes. Rapid clinical cognitive screening in combination with normative z-scores criteria is cost effective and sustainable in clinical practice.

The development of effective vaccines and delivery systems in aquaculture is a long-term challenge for controlling emerging and reemerging infections. Cost-efficient and advanced nanoparticle vaccines are of tremendous applicability in prevention of infectious diseases of fish. In this study, dihydrolipoamide dehydrogenase (DLDH) antigens of Vibrio alginolyticus were loaded into mesoporous silica nanoparticles (MSN) to compose the vaccine delivery system. Hydroxypropyl methylcellulose phthalate (HP55) was coated to provide protection of immunogen. The morphology, loading capacity, acid-base triggered release were characterized and the toxicity of nanoparticle vaccine was determined in vitro. Further, the vaccine immune effects were evaluated in large yellow croaker via oral administration. In vitro studies confirmed that the antigen could be stable in enzymes-rich artificial gastric fluid and released under artificial intestinal fluid environment. In vitro cytotoxicity assessment demonstrated the vaccines within 120 μg/ml have good biocompatibility for large yellow croaker kidney cells. Our data confirmed that the nanoparticle vaccine in vivo could elicit innate and adaptive immune response, and provide good protection against Vibrio alginolyticus challenge. The MSN delivery system prepared may be a potential candidate carrier for fish vaccine via oral administration feeding. Further, we provide theoretical basis for developing convenient, high-performance, and cost-efficient vaccine against infectious diseases in aquaculture.

Using cetyltrimethylammonium bromide (CTAB) as the surfactant from the precursors of SnCl2·2H2O, the flower-shaped nano composite of tin oxide (SnO2) is prepared by the simple eco-friendly hydrothermal method. We can see that the as-prepared SnO2 sample has a rutile phase crystal structure with regular-shaped nanosheets, and the nanosheets were cross-assembled to form nanoflowers. The band gap of the as-prepared SnO2 sample is 2.26 eV, which is close to the calculated energy gap of 2.58 eV based on density functional theory. The sample is used to degrade the organic dye, and this preliminary application study indicates that the as-prepared SnO2 sample has good stability and reusability in the visible light assisted degradation of methyl orange. Through capture experiments, it is determined that electrons and holes play a major role in the degradation process. The reaction mechanism is also analyzed to indicate the internal relationship between the as-prepared SnO2 samples and its photocatalytic properties.

The electronic structure, elastic, optical and thermodynamic properties of cubic perovskite NaBaF3 under high pressure were investigated using the ab initio calculations. The calculated lattice constant (a0) and bulk modulus (B0) at 0 GPa were determined to be 4.278 Å and 53.555 GPa, respectively, which are consistent with previous reports. The elastic constants and bulk modulus at high pressure were calculated. According to Pugh’s crystal mechanical stability conditions, the phase transition point of NaBaF3 is found to be 68.8 GPa, which has not been reported by any previous paper. The band structure calculations reveal that cubic perovskite NaBaF3 is a direct band-gap material in the pressure range from 0 GPa to 60 GPa. The dielectric function ɛ(ω), absorption coefficient α(ω), reflectivity R(ω), transmittance T(ω), absorbance A(ω) and complex refractive index N(ω) at 0 GPa, 20 GPa, 40 GPa and 60 GPa were studied. It is found that the band gap increases with the increasing pressure, and the absorption spectra show blue shift. The Debye temperature at 300 K and the values of the relative volume, heat capacity, bulk modulus, thermal expansion coefficient, heat capacities, and relative Debye temperature with pressures and temperatures effect were investigated. Our results will provide theoretical guidance for the experimental investigations and industrial applications of NaBaF3 in future.

BackgroundIncreasing evidence has shown that hypoxia microenvironment relates to tumor initiation and progression. However, no studies focus on the application of hypoxia-associated genes in predicting osteosarcoma patients’ prognosis. This research aims to identify the hypoxia-associated genes related to osteosarcoma metastasis and construct a gene signature to predict osteosarcoma prognosis.MethodsThe differentially expressed messenger RNAs (DEmRNAs) related to osteosarcoma metastasis were identified from Therapeutically Applicable Research to Generate Effective Treatments (Target) database. Univariate and multivariate cox regression analyses were performed to develop the hypoxia-associated prognostic signature. The Kaplan–Meier (KM) survival analyses of patients with high and low hypoxia risk scores were conducted. The nomogram was constructed and the gene signature was validated in the external Gene Expression Omnibus (GEO) cohort. Single-sample gene set enrichment analysis (ssGSEA) was conducted to investigate the relationships between immune infiltration and gene signature.ResultsTwo genes, including decorin (DCN) and prolyl 4-hydroxylase subunit alpha 1 (P4HA1), were involved in the hypoxia-associated gene signature. In training and testing datasets, patients with high-risk scores showed lower survival rates and the gene signature was identified as the independent prognostic factor. Receiver operating characteristic (ROC) curves demonstrated the robustness of signature. Functional analyses of DEmRNAs among high- and low-risk groups revealed that immune-associated functions and pathways were significantly enriched. Furthermore, ssGSEA showed that five immune cells (DCs, macrophages, neutrophils, pDCs, and TIL) and three immune features (CCR, APC co inhibition, and Check-point) were down-regulated in the high-risk group.ConclusionThe current study established and validated a novel hypoxia-associated gene signature in osteosarcoma. It could act as a prognostic biomarker and serve as therapeutic guidance in clinical applications.

The electronic and optical properties before and after Au decoration on (1 0 1¯ 4) surface of dolomite were investigated based on first principles calculations. The electronic structure analysis indicates that the band gap decreases from 4.25 eV (pristine) to 0.81 eV (1 Au decorated case), and the work functions increase from 2.41 eV to 3.53 eV. The density of states analysis revealed that the band gap decrease is mainly attributed to the Au 5d doping states in the forbidden band gap. Moreover, an additional peak located at 310 nm of polarization direction on E//c appears after Au decoration, resulting in the increased absorption intensity in the ultraviolet and visible range. By comparing the redox potential with that of different kinds of pollution gas, it can be found that the Au decorated dolomite might be a good photocatalyst for NO removal. The above results indicate that the Au decorated dolomite could be used in visible light photocatalysis or photovoltaic applications due to its semiconductor characteristics and suitable redox potentials.

BackgroundFried physical frailty, with mobility frailty and non-motor frailty phenotypes, is a heterogeneous syndrome. The coexistence of the two phenotypes and cognitive impairment is referred to as cognitive frailty (CF). It remains unknown whether frailty phenotype has a different association with hearing loss (HL) and tinnitus.MethodsOf the 5,328 community-dwelling older adults, 429 participants aged ≥58 years were enrolled in the study. The participants were divided into robust, mobility, and non-mobility frailty, mobility and non-mobility CF (subdivided into reversible and potentially reversible CF, RCF, and PRCF), and cognitive decline [subdivided into mild cognitive impairment (MCI) and pre-MCI] groups. The severity and presentations of HL and/or tinnitus were used as dependent variables in the multivariate logistic or nominal regression analyses with forward elimination adjusted for frailty phenotype stratifications and other covariates.ResultsPatients with physical frailty (mobility frailty) or who are robust were found to have lower probability of developing severe HL and tinnitus, and presented HL and/or tinnitus than those with only cognitive decline, or CF. Patients with RCF and non-mobility RCF had higher probability with less HL and tinnitus, and the presentation of HL and/or tinnitus than those with PRCF and mobility RCF. Other confounders, age, cognitive and social function, cardiovascular disease, depression, and body mass index, independently mediated the severity of HL and tinnitus, and presented HL and/or tinnitus.ConclusionFrailty phenotypes have divergent association with HL and tinnitus. Further research is required to understand the differential mechanisms and the personalized intervention of HL and tinnitus.Clinical Trial RegistrationClinicalTrials.gov identifier, NCT2017K020.

As a sustainable transportation system, car-sharing schemes have been attracting increasing attention. A large amount of research and practice has proved that the application and promotion of car sharing can help reduce the number of private cars purchased, increase the utilization rate of automobiles, effectively alleviate traffic congestion, save energy, and reduce emissions. Therefore, research on car sharing is imperative. The logit model is widely used in studies on car sharing and is an effective tool for analyzing traffic problems. This study first introduces the status of research into car sharing and analyzes the potential users and market prospects for shared cars. The study then provides the results from a questionnaire survey in Nanjing, China, to obtain sample data. Finally, a mixed logit model is established to analyze the influencing factors of car-sharing selection behavior. The results show that factors such as an individual’s housing situation and income significantly affect car-sharing decisions and that respondents who choose to use shared cars are relatively similar to commuters. The main contribution of this study is to use empirical analysis to determine the key influencing factors of car-sharing behavior in China and to provide practical insights for commercial practitioners and traffic planners.

Skilled sensorimotor deficit is an unsolved problem of peripheral nerve injury (PNI) led by limb trauma or malignancies, despite the improvements in surgical techniques of peripheral nerve anastomosis. It is now accepted that successful functional recovery of PNI relies tremendously on the multilevel neural plasticity from the muscle to the brain. However, animal models that recapitulate these processes are still lacking. In this report, we developed a rat model of PNI to longitudinally assess peripheral muscle reinnervation and brain functional reorganization using noninvasive imaging technology. Based on such model, we compared the longitudinal changes of the rat forepaw intrinsic muscle volume and the seed-based functional connectivity of the sensorimotor cortex after nerve repair. We found that the improvement of skilled limb function and the recovery of paw intrinsic muscle following nerve regeneration are incomplete, which correlated with the functional connectivity between the primary motor cortex and dorsal striatum. Our results were highly relevant to the clinical observations and provided a framework for future investigations that aim to study the peripheral central sensorimotor circuitry underlying skilled limb function recovery after PNI.

The electronic and optical properties of Ni-doped Bi4O5I2 systems were investigated via first-principle calculations. For the pristine Bi4O5I2, the band gap was calculated to be 2.17 eV, which was close to the experimental report. When the concentration of Ni increased, the band gap obviously decreased, which was ascribed to the introduction of Ni 3d doping states in the forbidden band gap. Based on the dielectric function analysis, the variations of the optical properties mainly took place in the visible light range, and the additional peak in the visible light range originated from the electron transition between the Ni 3d and Bi 6p states. Accordingly, the light absorption in the visible light range obviously increased, which was favorable for photocatalytic applications.

Objective This study was performed to explore the relationship between various clinical factors and the prognosis of limb osteosarcoma. Methods We retrospectively analyzed the clinical data of 336 patients with limb osteosarcoma treated from June 2000 to August 2016 at 7 Chinese cancer centers. Data on the patients’ clinical condition, treatment method, complications, recurrences, metastasis, and prognosis were collected and analyzed. Kaplan–Meier analysis and Cox regression models were used to analyze the data. Results The patients comprised 204 males and 132 females ranging in age from 6 to 74 years (average, 21.1 years). The overall 3- and 5-year survival rates were 65.0% and 55.0%, respectively. The 5-year overall survival rate was 64.0% with standard chemotherapy and 45.6% with non-standard chemotherapy. Cox regression analysis demonstrated that standard chemotherapy, surgery, recurrence, and metastasis were independent factors associated with the prognosis of limb osteosarcoma. Conclusion The survival of patients with limb osteosarcoma can be significantly improved by combining standard chemotherapy and surgery. The overall survival rate can also be improved by adding methotrexate to doxorubicin–cisplatin–ifosfamide triple chemotherapy.

Abstract Background Cysteine-rich intestinal protein 1 (CRIP1) is highly expressed in human intestine and aberrantly expressed in several types of tumor. However, studies on CRIP1 are limited and its role on tumor development and progression remains controversial and elusive. Methods Immunohistochemistry was performed to evaluate the expression of CRIP1 in paired normal and colorectal tumor specimens, as well as colorectal cell lines. Functional assays, such as CCK8, TUNEL assay and in vivo tumor growth assay, were used to detect the proliferation, apoptosis and response to 5-FU of CRIP1. Western blot was used to analyze Fas-mediated pathway induced by CRIP1. Rescue experiments were performed to evaluate the essential role of CRIP1 for Fas-mediated apoptosis. Results We demonstrated that CRIP1 is overexpressed in CRC tissues compared with adjacent normal mucosa. CRIP1 could dramatically recover the 5-Fluorouracil (5-FU) inhibited CRC cell proliferation in vitro and stimulate the tumor formation of CRC in vivo, probably through inhibiting CRC cell apoptosis. Moreover, CRIP1 also dramatically recovered the 5-Fluorouracil (5-FU) induced tumor cell apoptosis in vitro. Further study demonstrated that CRIP1 down-regulated the expression of Fas protein and proteins related to Fas-mediated apoptosis. CRIP1 could interact with Fas protein and stimulate its ubiquitination and degradation. In addition, a negative correlation was detected between the expression of CRIP1 and Fas protein in most of the clinical human CRC samples. Conclusion The current research reveals a vital role of CRIP1 in CRC progression, which provide a novel target for clinical drug resistance of colorectal cancer and undoubtedly contributing to the therapeutic strategies in CRC.

To study instability in the unsteady cavitating flow in a liquid rocket engine inducer, visualization experiments of non-cavitating and cavitating flows inside a model inducer were carried out at different flow conditions. Visual experiments were carried out to capture the evolution of non-cavitating and cavitating flows in a three-bladed inducer by using a high-speed camera. The external characteristic performance, cavitation performance, and pressure pulsation were analyzed based on the observation of non-cavitation and cavitation development and their instabilities. Under non-cavitation conditions, the change of flow rate has a significant impact on the pressure pulsation characteristics in the inducer. The occurrence of cavitation aggravated the instability of the flow and caused the intensity of pressure pulsation at each measuring point to increase. This cavitation structure has strong instability, and the tail region is often accompanied by shedding cavitation clouds perpendicular to the blade surface.

OBJECTIVES/GOALS: Approximately 10% of COVID-19 patients experience multiple symptoms weeks and months after the acute phase of infection. Our goal was to use advanced machine learning methods to identify PASC phenotypes based on their symptom profiles, and their association with critical adverse outcomes, with the goal of designing future targeted interventions. METHODS/STUDY POPULATION: Data. All COVID-19 outpatients from 12 University of Minnesota hospitals and 60 clinics. Independent variables consisted of 20 CDC-defined PASC symptoms extracted from clinical notes using NLP. Covariates included demographics, and outcomes included New Psychological Diagnostic Evaluation, and Number of PASC Hospital Visits (>=5). Cases (n=3235) consisted of patients with at least one symptom, and controls (n=3034) consisted of patients with no symptoms. Method. (1) Used bipartite network analysis and modularity maximization to identify patient-symptom biclusters. (2) Used multivariable logistic regression (adjusted for demographics and corrected through Bonferroni) to measure the odds ratio of each patient bicluster to adverse outcomes, compared to controls, and to each of the other biclusters. RESULTS/ANTICIPATED RESULTS: The analysis identified 6 PASC phenotypes (http://www.skbhavnani.com/DIVA/Images/Fig-1-PASC-Network.jpg), which was statistically significant compared to 1000 random permutations of the data (PASC=.31, Random Median=.27, z=11, P

Abstract Background Cell-based therapy by transplantation of nucleus pulposus (NP) progenitor/notochordal cells has been proposed as a promising way to halt and reverse the progression of disc degeneration. Although some studies have provided a broad panel of potential markers associated with the phenotype of notochordal cells, suitability of these markers for isolation of notochordal cells for the treatment of disc degeneration is unclear. Results Here, we found that the number of CD24-positive NP cells significantly decreased with increasing severity of disc degeneration. In addition, CD24-positive NP cells were shown to maintain their multipotent differentiation and self-renewal potential in vitro and to abundantly express brachyury, SHH, and GLUT-1, suggesting that CD24-positive NP cells are the progenitor/notochordal cells in the NP. Moreover, our in vivo experiments revealed that transplantation of CD24-positive NP cells enables the recovery of degenerate discs, as evidenced by increased disc height, restored magnetic resonance imaging T2-weighted signal intensity, and NP structure. In terms of the mechanism, HIF-1α–Notch1 pathway activation was essential for the maintenance of CD24-positive NP cells. Conclusion Our studies identify that CD24-positive NP cells are the resident progenitor/notochordal cells in disc regeneration and elucidate a crucial role of HIF-1α–Notch1 pathway in the phenotypic maintenance of CD24-positive NP cells.

Objective: To explore the imaging features of local recurrences (LRs) based on magnetic resonance imaging (MRI) after oncological orthopaedic surgery with prosthesis reconstruction. Methods: A total of 78 cases totalling 157 scans were retrospectively reviewed. Patients with nodule/mass-like signals were retrospectively classified into LR, infectious pseudotumour, and asymptomatic pseudotumour according to clinicopathological data. LRs were histologically confirmed, and the patients without recurrences were followed up for at least 2 years. Mass size distribution and radiological characteristics were analysed for differential diagnosis of the LR versus pseudotumour. Results: Thirty-three of 78 cases were positive with nodule/mass-like signal findings on the post-operative MRI images. By analysing the size distribution, we found that masses >2.1 cm (14) were almost attributable (98% specificity) to LRs and mostly (84.6%) timely treated. Contrarily, masses ≤2.1 cm (19) are challenging for differential diagnosis of LRs versus pseudotumour and were undertreated in five of the nine LR cases. MRI characteristics of masses ≤2.1 cm were found to be highly heterogeneous, with solid appearance, adjacent infiltration, and less peritumour oedema being significant indicators for LRs (P＜0.05). Receiver operating characteristic curve showed area under curve of 0.93 for this predictive model. Conclusions: For the post-operative MRI surveillance of oncological orthopaedic surgery with prosthesis reconstruction, a mass larger than 2.1 cm was highly specific for recurrence. When a mass was smaller than 2.1 cm, more solid property, more adjacent tissue infiltration, and less muscular oedema indicated recurrence rather than a benign mass. The translational potential of this article: There has been very little data associated with the post-operative magnetic resonance imaging features indicating recurrence in patients with malignant bone sarcoma after prosthesis replacement. This study could help develop diagnostic features of magnetic resonance imaging for differentiating recurrence from benign changes in these patients after prosthesis replacement. Keywords: Magnetic resonance imaging, Post-operative, Prosthesis, Recurrence

Disc pumps rely on the shear force generated by a co-rotating disc to transport the fluid, the interaction between the fluid and impeller is weak, providing such pumps advantages when handling multi-phase flow. In the present study, a loss analysis is presented on a different kind of disc pump that combines both shear and pressure forces using a co-rotating disc pump and radial blades and that is often applied in marine petroleum engineering for mud-lifting. Experimental measurements on the overall pump performance were performed, and the subsequent hydraulic efficiency analysis shows that similarity laws can be applied for this pump. A particular analysis was specifically performed on the impeller and shows that the resulting loss analysis indicates that the increase in the static pressure is small and that the total pressure increase is mainly contributed to by the dynamic pressure change from the inlet to the outlet impeller sections. In addition, an evaluation of the individual loss levels is proposed in the impeller that is based on one-dimensional assumptions. This type of evaluation has never been proposed for present specific TBD pump designs in the available literature. The obtained results showed that the most important loss levels are roughly equally distributed between the incidence effects, inter-blade leakage, and bolts losses in the impeller, and that all together, they can reach 80% of the total impeller losses, while the blade-loading and friction losses are relatively small. The losses downstream of the impeller are significant; thus, a specific volute design that has been adapted for a disc impeller outlet flow pattern must be considered in order to achieve better performance. The present loss analysis was able to predict the corresponding disc pump performance well, achieving a maximum error rate of ±5% for a rather wide flow coefficient range. The proposed method can be considered to be a useful approach for research or for industrial teams who are working on the same kind of geometry by adopting the same data reduction analysis, allowing them to compare their own results with the present ones.

Leaves of Camellia sinensis plants are used to produce tea, one of the most consumed beverages worldwide, containing a wide variety of bioactive compounds that help to promote human health. Tea cultivation is economically important, and its sustainable production can have significant consequences in providing agricultural opportunities and lowering extreme poverty. Soil parameters are well known to affect the quality of the resultant leaves and consequently, the understanding of the diversity and functions of soil microorganisms in tea gardens will provide insight to harnessing soil microbial communities to improve tea yield and quality. Current analyses indicate that tea garden soils possess a rich composition of diverse microorganisms (bacteria and fungi) of which the bacterial Proteobacteria, Actinobacteria, Acidobacteria, Firmicutes and Chloroflexi and fungal Ascomycota, Basidiomycota, Glomeromycota are the prominent groups. When optimized, these microbes' function in keeping garden soil ecosystems balanced by acting on nutrient cycling processes, biofertilizers, biocontrol of pests and pathogens, and bioremediation of persistent organic chemicals. Here, we summarize research on the activities of (tea garden) soil microorganisms as biofertilizers, biological control agents and as bioremediators to improve soil health and consequently, tea yield and quality, focusing mainly on bacterial and fungal members. Recent advances in molecular techniques that characterize the diverse microorganisms in tea gardens are examined. In terms of viruses there is a paucity of information regarding any beneficial functions of soil viruses in tea gardens, although in some instances insect pathogenic viruses have been used to control tea pests. The potential of soil microorganisms is reported here, as well as recent techniques used to study microbial diversity and their genetic manipulation, aimed at improving the yield and quality of tea plants for sustainable production. [ABSTRACT FROM AUTHOR]