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Knowledge tracing (KT) is the problem of predicting students' future performance based on their historical interactions with intelligent tutoring systems. Recent studies have applied multiple types of deep neural networks to solve the KT problem. However, there are two important factors in real-world educational data that are not well represented. First, most existing works augment input representations with the co-occurrence matrix of questions and knowledge components\footnote{\label{ft:kc}A KC is a generalization of everyday terms like concept, principle, fact, or skill.} (KCs) but fail to explicitly integrate such intrinsic relations into the final response prediction task. Second, the individualized historical performance of students has not been well captured. In this paper, we proposed \emph{AT-DKT} to improve the prediction performance of the original deep knowledge tracing model with two auxiliary learning tasks, i.e., \emph{question tagging (QT) prediction task} and \emph{individualized prior knowledge (IK) prediction task}. Specifically, the QT task helps learn better question representations by predicting whether questions contain specific KCs. The IK task captures students' global historical performance by progressively predicting student-level prior knowledge that is hidden in students' historical learning interactions. We conduct comprehensive experiments on three real-world educational datasets and compare the proposed approach to both deep sequential KT models and non-sequential models. Experimental results show that \emph{AT-DKT} outperforms all sequential models with more than 0.9\% improvements of AUC for all datasets, and is almost the second best compared to non-sequential models. Furthermore, we conduct both ablation studies and quantitative analysis to show the effectiveness of auxiliary tasks and the superior prediction outcomes of \emph{AT-DKT}., Accepted at WWW'23: The 2023 ACM Web Conference, 2023

The purpose of this study was to compare hospitalization outcomes among US inpatients with brain metastases who received stereotactic radiosurgery (SRS) and/or non-SRS radiation therapies without neurosurgical intervention. A cross-sectional study was conducted whereby existing data on 35,199 hospitalization records (non-SRS alone: 32,981; SRS alone: 1035; SRS + non-SRS: 1183) from 2005 to 2014 Nationwide Inpatient Sample were analyzed. Targeted maximum likelihood estimation and Super Learner algorithms were applied to estimate average treatment effects (ATE), marginal odds ratios (MOR) and causal risk ratio (CRR) for three distinct types of radiation therapy in relation to hospitalization outcomes, including length of stay (‘ ≥ 7 days’ vs. ‘

Acquiring high-fidelity 3D models from real-world scans is challenging. Existing shape completion-methods are incapable of generating details of objects or learning complex point distributions. To address this problem, we propose two transformer-based point-cloud-completion networks and a coarse-to-fine strategy to extract object shape features by way of self-attention (SA) and multi-resolution (MR), respectively. Specifically, in the first stage, the model extracts incomplete point-cloud features based on self-attention and multi-resolution encoders and predicts the missing partial with a set of parametric surface elements. Then, in the second stage, it merges the coarse-grained prediction with the input point cloud by iterative furthest point sampling (IFPS), to obtain a complete but coarse-grained point cloud. Finally, in the third stage, the complete but coarse point-cloud distribution is improved by a point-refiner network based on a point-cloud transformer (PCT). The results from comparison to state-of-the-art methods and ablation experiments on the ShapeNet-Part dataset both verified the effectiveness of our method.

Objective This study aimed to examine patterns of sleep disorders among hospitalized adults 65 years and older as related to Parkinson's disease (PD) status and to evaluate sex differences in the associations between PD with sleep disorders. Methods A cross-sectional study was conducted using 19,075,169 hospital discharge records (8,169,503 men and 10,905,666 women) from the 2004-2014 Nationwide Inpatient Sample databases. PD and sleep disorder diagnoses were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification coding. Logistic regression models were constructed for each sleep disorder as a correlate of PD status; adjusted odds ratios (aOR) with their 95% confidence intervals (CIs) were calculated taking into account patient and hospital characteristics. Results Period prevalences of PD and sleep disorder were estimated to be 2.1% and 8.1%, respectively. Most sleep disorder types, with the exception of sleep-related breathing disorders, were positively associated with PD diagnosis. Statistically significant interactions by sex were noted for associations of insomnia (men: aOR = 1.29, 95% CI = 1.24-1.36; women: aOR = 1.17, 95% CI = 1.12-1.22), parasomnia (men: aOR = 3.74, 95% CI = 3.44-4.07; women: aOR = 2.69, 95% CI = 2.44-2.96), sleep-related movement disorder (men: aOR = 1.09, 95% CI = 1.07-1.11; women: aOR = 1.22, 95% CI = 1.20-1.25), and any sleep disorder (men: aOR = 1.06, 95% CI = 1.05-1.08; women: aOR = 1.15, 95% CI = 1.13-1.17) with PD status. Conclusions Overall, hospitalized men are more likely to experience PD with insomnia or parasomnia, whereas hospitalized women are more likely to experience PD with sleep-related movement disorder or any sleep disorder. Prospective cohort studies are needed to replicate these cross-sectional findings.

Background: The 2010 Affordable Care Act aimed at reducing healthcare costs, improving healthcare quality and expanding health insurance coverage among uninsured individuals in the United States. We examined trends in utilization of radiation therapies and stereotactic radiosurgery before and after its implementation among U.S. adults hospitalized with brain metastasis.Methods: Interrupted time-series analyses of data on 383934 2005-2014 Nationwide Inpatient Sample hospitalizations were performed, whereby yearly and quarterly cross-sectional data were evaluated and Affordable Care Act implementation was considered the main exposure variable, stratifying by patient and hospital characteristics. Results: We observed consistently declining trends in radiation therapy over time and post-Affordable Care Act status with variability in level of utilization among specific sub-groups. Stereotactic radiosurgery prevalence increased over time among Hispanics, elective admissions, Midwestern hospitals, non-teaching hospitals and hospitals with medium bed size. Post-Affordable Care Act was associated with increased stereotactic radiosurgery prevalence among African-Americans, non-elective and weekend admissions, with changes in slope in the context of weekend admissions and hospitals with large bed size. Conclusions: Whereas hospitalized adults in the United States utilized less radiation therapy and slightly more stereotactic radiosurgery over the ten-year period, utilization levels and trends were not consistent among distinct sub-groups defined by patient and hospital characteristics, with some traditionally underserved populations more likely to receive healthcare services post-Affordable Care Act implementation. The Affordable Care Act may be helpful at reducing the need for radiation therapy and closing the gap in access to technological advances such as stereotactic radiosurgery for treating brain metastases.

The ventral tegmental area (VTA) is the origin of dopaminergic neurons and the dopamine (DA) reward pathway. This pathway has been widely studied in addiction and drug reinforcement studies and is believed to be the central processing component of the reward circuit. In this study, we used a well-established rat model to expose mother dams to alcohol, nicotine-alcohol, and saline perinatally. DA and non-DA neurons collected from the VTA of the rat pups were used to study expression profiles of miRNAs and mRNAs. miRNA pathway interactions, putative miRNA-mRNA target pairs, and downstream modulated biological pathways were analyzed. In the DA neurons, 4607 genes were differentially upregulated and 4682 were differentially downregulated following nicotine-alcohol exposure. However, in the non-DA neurons, only 543 genes were differentially upregulated and 506 were differentially downregulated. Cell proliferation, differentiation, and survival pathways were enriched after the treatments. Specifically, in the PI3K/AKT signaling pathway, there were 41 miRNAs and 136 mRNAs differentially expressed in the DA neurons while only 16 miRNAs and 20 mRNAs were differentially expressed in the non-DA neurons after the nicotine-alcohol exposure. These results depicted that chronic nicotine and alcohol exposures during pregnancy differentially affect both miRNA and gene expression profiles more in DA than the non-DA neurons in the VTA. Understanding how the expression signatures representing specific neuronal subpopulations become enriched in the VTA after addictive substance administration helps us to identify how neuronal functions may be altered in the brain.

Nicotine and alcohol are two of the most commonly used and abused recreational drugs, are often used simultaneously, and have been linked to significant health hazards. Furthermore, patients diagnosed with dependence on one drug are highly likely to be dependent on the other. Several studies have shown the effects of each drug independently on gene expression within many brain regions, including the ventral tegmental area (VTA). Dopaminergic (DA) neurons of the dopamine reward pathway originate from the VTA, which is believed to be central to the mechanism of addiction and drug reinforcement. Using a well-established rat model for both nicotine and alcohol perinatal exposure, we investigated miRNA and mRNA expression of dopaminergic (DA) neurons of the VTA in rat pups following perinatal alcohol and joint nicotine–alcohol exposure. Microarray analysis was then used to profile the differential expression of both miRNAs and mRNAs from DA neurons of each treatment group to further explore the altered genes and related biological pathways modulated. Predicted and validated miRNA-gene target pairs were analyzed to further understand the roles of miRNAs within these networks following each treatment, along with their post transcription regulation points affecting gene expression throughout development. This study suggested that glutamatergic synapse and axon guidance pathways were specifically enriched and many miRNAs and genes were significantly altered following alcohol or nicotine–alcohol perinatal exposure when compared to saline control. These results provide more detailed insight into the cell proliferation, neuronal migration, neuronal axon guidance during the infancy in rats in response to perinatal alcohol/ or nicotine–alcohol exposure.

The mesoporous Co/KIT-6 catalysts with 10 wt% Co loading were prepared at different reduction temperatures. The physicochemical properties of the Co/KIT-6 catalysts were characterized by TEM, BET, XRD, XPS, and CO2-TPD, and the effect of reduction temperature on CO2 hydrogenation catalytic performance of Co/KIT-6 catalysts was studied. The results show that reduction temperature has a significant impact on the specific surface area, crystallinity and content of Co0 species, and CO2 adsorption performance of the prepared Co/KIT-6 catalysts. The low reduction temperature is not conduct to the reduction of CoOx, while the high reduction temperature lead to the increase of Co0 species crystallinity and the formation of Co2SiO4 and/or CosbndOsbndSi species which are unfavorable to the form Co0 species. The RT400 catalyst exhibits the highest Co0 species content and the best CO2 adsorption performance. Both the CO2 hydrogenation catalytic activity and CH4 selectivity of the Co/KIT-6 catalysts follow the order: RT400 > RT350 > RT450 > RT500 > RT550, with a small amount of by-product CO. At the reaction temperature of 340 °C, the CO2 reaction rate (CO2 conversion) of the RT400 catalyst can reach 2.98 × 10−5 mol/gcat/s (40%), the CH4 and CO selectivity are 86.7% and 13.3%, respectively.

In this study, we design and present a five-fold digital slit-lamp microscope (DSLM) with built-in photographic lens and CCD. The initial structures of the front objective, Galilean telescope system, and photographic lens are systematically investigated and discussed in the design. A progressive optimization process is employed in the non-coaxial system design after the coaxial system achieves high performance. The analysis of spot diagrams and the modulation transfer function (MTF) show that this DSLM optical system achieves quasi-diffraction-limited performance and enables high-quality imaging for ophthalmic examination. Furthermore, tolerance analysis of this optical system is also performed, which provides a theoretical basis for machining and assembly. This design provides an idea for the design of a digital-zoom microscope in biomedical imaging instruments.

Nonviral methods have been explored as the replacement of viral systems for their low toxicity and immunogenicity. However, they have yet to reach levels competitive to their viral counterparts. In this paper, we combined physical and chemical methods to improve the performance of polyplex delivery of DNA and small interfering RNA. Specifically, gold nanoparticles (AuNPs) were used to carry polyplex (a chemical approach) while electroporation (a physical approach) was applied for fast and direct cytosolic delivery. In this hybrid approach, cationic polymer molecules condense and/or protect genetic probes as usual while AuNPs help fix polycations to reduce their cytotoxicity and promote the transfection efficiency of electroporation. AuNPs of various sizes were first coated with polyethylenimine, which were further conjugated with DNA plasmids or small interfering RNA molecules to form AuNPs-polyplex. The hybrid nanoparticles were then mixed with cells and introduced into cell cytosol by electroporation. The delivery efficiency was evaluated with both model anchor cells (i.e., NIH/3T3) and suspension cells (i.e., K562), together with their impact on cell viability. We found that AuNP-polyplex showed 1.5∼2 folds improvement on the transfection efficiency with no significant increase of toxicity when compared to free plasmid delivery by electroporation alone. Such a combination of physical and chemical delivery concept may stimulate further exploration in the delivery of various therapeutic materials for both in vitro and in vivo applications.

Electroporation serves as a promising non-viral gene delivery approach, while its current configuration carries several drawbacks associated with high-voltage electrical pulses and heterogeneous treatment on individual cells. Here we developed a new micropillar array electroporation (MAE) platform to advance the electroporation-based delivery of DNA and RNA probes into mammalian cells. By introducing well-patterned micropillar array texture on the electrode surface, the number of pillars each cell faces varies with its plasma membrane surface area, despite their large population and random locations. In this way, cell size specific electroporation is conveniently carried out, contributing to a 2.5~3 fold increase on plasmid DNA transfection and an additional 10–55% transgene knockdown with siRNA probes, respectively. The delivery efficiency varies with the number and size of micropillars as well as their pattern density. As MAE works like many single cell electroporation are carried out in parallel, the electrophysiology response of individual cells is representative, which has potentials to facilitate the tedious, cell-specific protocol screening process in current bulk electroporation (i.e., electroporation to a large population of cells). Its success might promote the wide adoption of electroporation as a safe and effective non-viral gene delivery approach needed in many biological research and clinical treatments.

This secondary analysis of survey data examined mediating-moderating effects of allostatic load score (calculated using the Rodriquez method) on the association between nutrient-based Dietary Approaches to Stop Hypertension (DASH) diet score (Mellen Index) and the all-cause and cause-specific mortality risks among 11,630 adults &ge, 30 years of age from the 2001&ndash, 2010 National Health and Nutrition Examination Surveys with no history of cardiovascular disease or cancer at baseline, and who were followed-up for ~9.35 years. Multivariable models were adjusted for demographic, socioeconomic, lifestyle, and health characteristics. All-cause, cardiovascular disease, and cancer-specific mortality rates were estimated at 6.5%, 1.1%, and 1.9%, respectively. The median DASH total score was 3.0 (range: 1&ndash, 8) (with 78.3% scoring &lt, 4.5), whereas the median allostatic load score was 3 (range: 0&ndash, 9). The DASH diet, fiber, and magnesium were negatively correlated with allostatic load, whereas allostatic load predicted higher all-cause mortality, irrespective of the DASH diet. Whereas protein was protective, potassium increased all-cause mortality risk, irrespective of allostatic load. Potassium was protective against cardiovascular disease-specific mortality but was a risk factor for cancer-specific mortality. Although no moderating effects were observed, mediation by the allostatic load on cardiovascular disease-specific mortality was observed for DASH total score and selected component scores. Direct (but not indirect) effects of DASH through the allostatic load were observed for all-cause mortality, and no direct or indirect effects were observed for cancer-specific mortality. From a public health standpoint, the allostatic load may be a surrogate for the preventive effects of the DASH diet and its components on cardiovascular disease-specific mortality risk.

The DNA-damaging drug doxorubicin (Dox) induces cell senescence at concentrations significantly lower than those required for induction of apoptosis. At low Dox concentrations, tumor suppressor p53 is activated, which enhances the expression of p21(Waf1/Cip1) (p21). At high concentrations, Dox activates p53 leading to apoptosis without enhancing p21 expression. The underlying mechanisms and factors that govern the differential effects of Dox in inducing senescence and apoptosis are unclear. Here, we report that the DNA methyltransferase (DNMT) DNMT3a was upregulated by Dox especially at concentrations that induced apoptosis in HCT116 colorectal cancer cells, and this process was regulated by p53. Meanwhile, p21 expression was significantly upregulated at senescence-inducing concentrations and kept low on treatment with apoptosis-inducing concentrations of Dox. The differential expression of DNMT3a and p21 in response to Dox suggests that DNMT3a may be a key factor in switches between Dox-induced senescence and apoptosis. Moreover, when DNMT3a was silenced, treatment of HCT116 cells with apoptosis-inducing concentration of Dox increased the percentage of cells undergoing senescence, accompanied by upregulation of p21. Contrarily, senescence-inducing concentration of Dox promoted apoptosis rate, and p21 expression was repressed. Surprisingly, no changes in DNA methylation status at p21 promoter were detected at either ranges of Dox, although DNMT3a and HDAC1 were recruited to p21 promoter at apoptosis-inducing Dox concentration, where they were present in the same complex. Overall, these data demonstrate that DNMT3a impacts the expression of p21 and plays a role in determining the Dox-induced senescence and apoptosis in HCT116 cells.

Helicobacter pylori has a highly variable genome with ongoing diversification via inter- and intragenomic recombination and spontaneous mutation. DNA repair genes modulating mutation and recombination rates that influence diversification have not been well characterized for H. pylori . To examine the role of putative base excision repair ung and mutY glycosylase and xthA apurinic/apyrimidinic endonuclease genes in H. pylori , mutants of each were constructed in strain JP26 by allelic exchange. Spontaneous mutation frequencies of JP26 mutY mutants, assessed by rifampin resistance, were consistently higher (26-fold) than that of the wild type, whereas the ung and xthA mutants showed smaller increases. In trans complementation of the JP26 mutY mutant restored spontaneous mutation frequencies to wild-type levels. In cross-species studies, H. pylori mutY complemented an Escherichia coli mutY mutant and vice versa. In contrast, the ung and mutY mutants did not show higher frequencies of intergenomic recombination or greater sensitivity to UV-induced DNA damage than the wild type. The H. pylori mutY open reading frame contains an eight-adenine homonucleotide tract; we provide evidence that this is subject to slipped-strand mispairing, leading to frameshifts that eliminate gene function. Our findings indicate that H. pylori possesses phase-variable base excision repair, consistent with a tension between repair and mutation.

Electroporation figured prominently as an effective nonviral gene delivery approach for its balance on the transfection efficiency and cell viability, no restrictions of probe or cell type, and operation simplicity. The commercial electroporation systems have been widely adopted in the past two decades while still carry drawbacks associated with the high applied electric voltage, unsatisfied delivery efficiency, and/or low cell viability. By adding highly conductive gold nanoparticles (AuNPs) in electroporation solution, we demonstrated enhanced electroporation performance (i.e., better DNA delivery efficiency and higher cell viability) on mammalian cells from two different aspects: the free, naked AuNPs reduce the resistance of the electroporation solution so that the local pulse strength on cells was enhanced; targeting AuNPs (e.g., Tf-AuNPs) were brought to the cell membrane to work as virtual microelectrodes to porate cells with limited area from many different sites. The enhancement was confirmed with leukemia cells in both a commercial batch electroporation system and a home-made flow-through system using pWizGFP plasmid DNA probes. Such enhancement depends on the size, concentration, and the mixing ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs exhibited the best enhancement with the transfection efficiency increased 2-3 folds at minimum sacrifice of cell viability. This new delivery concept, the combination of nanoparticles and electroporation technologies, may stimulate various in vitro and in vivo biomedical applications which rely on the efficient delivery of nucleic acids, anticancer drugs, or other therapeutic materials.

Takotsubo cardiomyopathy (TC) is a transient left ventricular apical ballooning syndrome which results in an acute, reversible, left ventricular dysfunction. Unlike a myocardial ischemia, TC is not due to coronary artery stenosis. Initially the syndrome was described by a series of five Japanese patients in 1991 [1] and there have been multiple subsequent reports. The syndrome received its name from an octopus trap (tako-tsubo) which is a wide pot that has a narrow opening. This trap resembles the left ventricle of a patient with TC during systole as the apex is rounded and balloons out despite a hypercontractile and narrow base. TC has also been called “broken heart syndrome” because it is usually associated with a stressful event. Although recurrent cases of TC have been reported, this is the first presentation of a patient that experienced recurrent TC induced cardiac arrest in the same perioperative period.

Macrophage migration inhibitory factor (MIF) is an evolutionarily ancient and highly conserved cytokine with multiple functions. In the present study, a MIF-like gene was cloned from Zhikong scallop Chlamys farreri (designated as CfMIF) based on expressed sequence tag (EST) analysis and rapid amplification of cDNA ends (RACE) approach. The full-length cDNA of CfMIF was of 2296 bp, consisting of a 5' untranslated region (UTR) of 60 bp, a 3' UTR of 1903 bp with a poly(A) tail and an open reading frame (ORF) of 333 bp encoded 111 amino acid residues with a calculated molecular mass of 12.6 kDa and a theoretical iso-electric point of 5.63. The deduced amino acid sequence of CfMIF shared 27-50.5% similarity with those of other known MIFs. A conserved MIF domain was identified in the deduced amino acid sequence of CfMIF, and conserved proline(2) and lysine(33) were also found to be present in CfMIF. Phylogenetic analysis revealed that CfMIF is one of MIF members. The tissue distribution and temporal expression of CfMIF in hemocytes of scallop after lipopolysaccharide (LPS), peptidoglycan (PGN) and beta-glucan stimulation were detected by real-time RT-PCR. CfMIF gene was ubiquitously expressed in six selected tissues of healthy scallops, with the higher expression levels in hepatopancreas, mantle and gill. In comparison with the control group, the expression of CfMIF mRNA in hemocytes was up-regulated significantly at 6h, 24h and 48 h after LPS treatment, and at all time points after PGN and glucan treatment. The cDNA fragment encoding mature peptide of CfMIF was recombined and expressed in Escherichia coli BL21 (DE3) pLysS. The recombinant protein of CfMIF (rCfMIF) promoted sheep fibroblast migration into scraped spaces in vitro. These results generated from the present study encourage us to suggest that CfMIF was a novel member of MIF family, and it was involved in immune response and wound healing by promoting fibroblast migration. (C) 2010 Elsevier Ltd. All rights reserved.

AIM: To confirm the role of sex-determining region Y-box 7 (Sox7) in aspirin-mediated growth inhibition of COX-independent human colorectal cancer cells. METHODS: The cell survival percentage was examined by MTT (Moto-nuclear cell direc cytotoxicity) assay. SOX7 expression was assessed by using reverse transcription-polymerase chain reaction and Western blotting. SB203580 was used to inhibit the p38MAPK signal pathway. SOX7 promoter activity was detected by Luciferase reporter assay. RESULTS: SOX7 was upregulated by aspirin and was involved in aspirin-mediated growth inhibition of SW480 human colorectal cancer cells. The p38MAPK pathway played a role in aspirin-induced SOX7 expression, during which the AP1 transcription factors c-Jun and c-Fos upregulated SOX7 promoter activities. RESULTS: SOX7 is upregulated by aspirin and is involved in aspirin-mediated growth inhibition of human colorectal cancer SW480 cells.