Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Analysis of CREB3 and CREB3L2 Protein Expression in HEK293 Cells

We performed a comparative analysis of two ER-resident CREB3 family proteins, CREB3 and CREB3L2, in HEK293 cells using pharmacological and genome editing approaches and identified several differences between the two. Treatment with brefeldin A (BFA) and monensin induced the cleavage of full-length CREB3 and CREB3L2; however, the level of the full-length CREB3 protein, but not CREB3L2 protein, was not noticeably reduced by the monensin treatment. On the other hand, treatment with tunicamycin (Tm) shifted the molecular weight of the full-length CREB3L2 protein downward but abolished CREB3 protein expression. Thapsigargin (Tg) significantly increased the expression of only full-length CREB3L2 protein concomitant with a slight increase in the level of its cleaved form. Treatment with cycloheximide and MG132 revealed that both endogenous CREB3 and CREB3L2 are proteasome substrates. In addition, kifunensine, an α-mannosidase inhibitor, significantly increased the levels of both full-length forms. Consistent with these findings, cells lacking SEL1L, a crucial ER-associated protein degradation (ERAD) component, showed increased expression of both full-length CREB3 and CREB3L2; however, cycloheximide treatment downregulated full-length CREB3L2 protein expression more rapidly in SEL1L-deficient cells than the full-length CREB3 protein. Finally, we investigated the induction of the expression of several CREB3 and CREB3L2 target genes by Tg and BFA treatments and SEL1L deficiency. In conclusion, this study suggests that both endogenous full-length CREB3 and CREB3L2 are substrates for ER-associated protein degradation but are partially regulated by distinct mechanisms, each of which contributes to unique cellular responses that are distinct from canonical ER signals.
Network Pharmacology-Based Study on the Molecular Biological Mechanism of Action for Qingdu Decoction against Chronic Liver Injury

Background Qingdu Decoction (QDD) is a traditional Chinese medicine formula for treating chronic liver injury (CLI). Materials and methods. A network pharmacology combining experimental validation was used to investigate potential mechanisms of QDD against CLI. We firstly screened the bioactive compounds with pharmacology analysis platform of the Chinese medicine system (TCMSP) and gathered the targets of QDD and CLI. Then, we constructed a compound-target network and a protein-protein interaction (PPI) network and enriched core targets in Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. At last, we used a CLI rat model to confirm the effect and mechanism of QDD against CLI. Enzyme-linked immunosorbent assay (ELISA), western blot (WB), and real-time quantitative polymerase chain reaction (RT-qPCR) were used. Results 48 bioactive compounds of QDD passed the virtual screening criteria, and 53 overlapping targets were identified as core targets of QDD against CLI. A compound-CLI related target network containing 94 nodes and 263 edges was constructed. KEGG enrichment of core targets contained some pathways related to CLI, such as hepatitis B, tumor necrosis factor (TNF) signaling pathway, apoptosis, hepatitis C, interleukin-17 (IL-17) signaling pathway, and hypoxia-inducible factor (HIF)-1 signaling pathway. Three PPI clusters were identified and enriched in hepatitis B and tumor necrosis factor (TNF) signaling pathway, apoptosis and hepatitis B pathway, and peroxisome pathway, respectively. Animal experiment indicated that QDD decreased serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), endotoxin (ET), and IL-17 and increased prothrombin time activity (PTA) level. WB and RT-qPCR analyses indicated that, compared with the model group, the expression of cysteinyl aspartate specific proteinase-9 (caspase-9) protein, caspase-3 protein, B-cell lymphoma-2 associated X protein (Bax) mRNA, and cytochrome c (Cyt c) mRNA was inhibited and the expression of B-cell lymphoma-2 (Bcl-2) mRNA was enhanced in the QDD group. Conclusions QDD has protective effect against CLI, which may be related to the regulation of hepatocyte apoptosis. This study provides novel insights into exploring potential biological basis and mechanisms of clinically effective formula systematically.
Incidence of Hip Dysplasia Diagnosis in Young Patients With Hip Pain: A Geographic Population Cohort Analysis

Background: Hip dysplasia is a common source of hip pain and a known cause of early osteoarthritis of the hip. Purpose: To (1) define the population-based incidence of hip dysplasia diagnosis in young patients presenting with hip pain in a large geographically defined cohort, (2) analyze trends regarding presentation and diagnosis of hip dysplasia, and (3) report the rate and type of surgical interventions used to treat this population. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A geographic epidemiological database was queried to identify patients aged 14 to 50 years with hip pain between the years 2000 and 2016. Patient medical records were analyzed, and demographic, imaging, clinical, and treatment history were recorded. Incidence trends were examined by use of linear regression with confidence intervals for age and calendar year. Results: Overall, 1893 patients were included. Of these, 156 patients (196 hips) had a diagnosis of hip dysplasia. The incidence of hip dysplasia diagnosis in patients who reported hip pain was 12.7 per 100,000 person-years. Patients with dysplasia had a mean age of 26.7 ± 9.8 years, while the highest age-adjusted incidence occurred at age 14 to 18 years in both male and female patients. Female patients had double the age-adjusted incidence of male patients (cases per 100,000 person-years: 16.8 [95% CI, 13.9-19.7] vs 8.7 [95% CI, 6.6-10.8]; P < .01). Of the patients who underwent magnetic resonance imaging, 77% had imaging consistent with labral pathology. Patients were treated with physical therapy (67%), intra-articular steroid injection (29%), hip arthroscopy (10%), and periacetabular osteotomy (9%). The use of hip arthroscopy significantly increased over time (P < .01), whereas the use of steroid injection and periacetabular osteotomy did not (P < .28 and P < .08, respectively). Conclusion: The incidence of hip dysplasia diagnosis in patients presenting with hip pain was 12.7 per 100,000 person-years. Female patients had twice the age-adjusted incidence of male patients, and the highest age-adjusted incidence occurred in the age range of 14 to 18 years in both sexes. The use of hip arthroscopy to treat patients with hip dysplasia significantly increased over time.
Value of the Lung Immune Prognostic Index in Patients with Non-Small Cell Lung Cancer Initiating First-Line Atezolizumab Combination Therapy: Subgroup Analysis of the IMPOWER150 Trial

Simple Summary The lung immune prognostic index (LIPI) is proposed as a simple risk scoring tool to differentiate differences in survival from immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC). The tool has not been evaluated for performance in a NSCLC cohort initiating first-line, combination ICI approaches. In a large cohort of participants with chemotherapy-naïve, metastatic non-squamous NSCLC, we independently validated, for the first time, that LIPI discriminates a clear subgroup of patients likely to achieve reduced survival following the initiation of combination therapies including the ICI atezolizumab. Abstract The lung immune prognostic index (LIPI) is proposed to differentiate prognosis and treatment benefit from immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC). There is minimal information on the predictive importance with first-line, combination ICI approaches. In post-hoc analysis of IMpower150, Cox-proportional hazard analysis assessed the association between LIPI groups and overall survival (OS)/progression free survival (PFS). IMpower150 involved chemotherapy-naïve, metastatic non-squamous NSCLC participants randomized atezolizumab-carboplatin-paclitaxel (ACP), bevacizumab-carboplatin-paclitaxel (BCP), or atezolizumab-BCP (ABCP). Good (0 factors), intermediate (1 factor), and poor LIPI (2 factors) were defined via derived neutrophil-to-lymphocyte ratio >3, and lactate dehydrogenase >upper limit of normal. Of 1148 participants, 548 had good, 479 intermediate, and 121 poor LIPI. In 385 participants randomised ABCP, a significant association between LIPI and OS (HR (95%CI): intermediate LIPI = 2.16 (1.47–3.18), poor LIPI = 5.28 (3.20–8.69), p < 0.001) and PFS (HR (95%CI): intermediate LIPI = 1.47 (1.11–1.95), poor LIPI = 3.02 (2.03–4.50), p < 0.001) was identified. Median OS was 24, 16, and 7 months for good, intermediate, and poor LIPI, respectively. ACP associations were similar. Relative OS treatment effect (HR 95%CI) of ABCP vs. BCP was 0.78 (0.53–1.15), 0.67 (0.49–0.91), and 0.87 (0.51–1.47) for the good, intermediate, and poor LIPI groups, respectively (P(interaction) = 0.66), with no benefit in median OS observed in the poor LIPI group. LIPI identified subgroups with significantly different survival following ABCP and ACP initiation for chemotherapy-naïve, metastatic non-squamous NSCLC. There was insufficient evidence that LIPI identifies patients unlikely to benefit from ABCP treatment.
CTLA-4 (+49A/G) Polymorphism in Type 1 Diabetes Children of Sudanese Population

Abstract Background Type 1 diabetes mellitus (T1DM) is an organ-specific T cell-mediated autoimmune disease, characterized by destruction of pancreatic islets. Cytotoxic lymphocyte antigen-4 (CTLA-4) is a negative regulator of T cell proliferation, thus conferring susceptibility to autoimmunity. Aims This study aimed to investigate the association of CTLA-4 +49A/G (rs231775) polymorphism with a risk of T1DM in Sudanese children. Methods This a case–control study included 100 children with T1DM, referred to the pediatric clinic at referral pediatric teaching hospital in Gezira State-Sudan. Hundred unrelated healthy controls were recruited from departments in the same hospital. Genomic deoxyribonucleic acid (DNA) was extracted from Ethylenediaminetetraacetic Acid (EDTA)-preserved blood using QIAamp DNA Blood Mini Kit (QIAamp Blood) (QIAGEN; Valencia, CA). The polymerase chain reaction PCR restriction fragment length polymorphism (PCR-RFLP) and sequencing were applied for the CTLA-4 (+49A/G) genotyping. The changes accompanied the polymorphism were evaluated using relevant bioinformatics tools. Results The genotype and allele frequencies of the CTLA-4 (+49A/G) polymorphism were significantly different between the patients and controls (p = 0.00013 and 0.0002, respectively). In particular, the frequency of the G allele, GG homozygous genotype, and AG heterozygous genotype were significantly increased in patients than in controls ([28% versus 7%, odds ratio (OR) = 5.16, 95% confidence interval [CI] = 2.77–9.65, p = 0.00] [12% versus 2%, OR = 6.68, CI = 1.46–30.69, p = 0.01] [32% versus 10%, OR = 4.24, CI = 1.95–9.21, p = 0.00], respectively). The presence of the G allele (homozygous) showed an influence on the signal peptide polarity, hydrophobicity, and α-helix propensity of the CTLA-protein. Conclusion The results further support the association of CTLA-4 (+49A/G) polymorphism and the risk of T1DM in our study population.
Mandoline: Dynamic Slicing of Android Applications with Trace-Based Alias Analysis

Dynamic program slicing is used in a variety of tasks, including program debugging and security analysis. Building an efficient and effective dynamic slicing tool is a challenging task, especially in an Android environment, where programs are event-driven, asynchronous, and interleave code written by a developer with the code of the underlying Android platform. The user-facing nature of Android applications further complicates matters as the slicing solution has to maintain a low overhead to avoid substantial application slowdown.In this paper, we propose an accurate and efficient dynamic slicing technique for Android applications and implement it in a tool named Mandoline. The core idea behind our technique is to use minimal, low-overhead instrumentation followed by sophisticated, on-demand execution trace analysis for constructing a dynamic slice. We also contribute a benchmark suite of Android applications with manually constructed dynamic slices that use a faulty line of code as a slicing criterion. We evaluate Mandoline on that benchmark suite and show that it is substantially more accurate and efficient than the state-of-the-art dynamic slicing technique named AndroidSlicer.
Atomic structure of metallic interfaces

The atomic structure of the (310) symmetric tilt grain boundary in Nb and of an interface between Mo and Re is calculated. The calculations are done within the tight binding (TB) approximation to quantum mechanics and are checked carefully against some accurate first-principles calculations in the local density approximation to density functional theory. A non-orthogonal spd electron TB model is tested, but is found to be no improvement on the much simpler orthogonal d-electron model; in particular there is no improvement in the volume dependence of the total energy. The structure of the Nb grain boundary is compared to that obtained by other authors using high resolution electron microscopy. The comparison enables some statements to be made about the nature of the interatomic interactions and especially about the opposing forces that are balanced at the equilibrium grain boundary expansion. The paper includes the first quantum mechanical calculation of a dissimilar metal interface with a view to obtaining the structure of a misfit dislocation and a value for the theoretical strength of the interface. It is concluded that the misfit dislocation in this case has a widely spread core and that the theoretical strength is considerably reduced relative to the bulk crystal.
A Relational Approach to the Design for Peer Support

Peer-support services enhance mental wellbeing and increase the knowledge and capabilities of self-help groups in various settings. To ensure that these services foster peer-support relationships as intended, it is necessary to design and assess them from a relational perspective. This study presents a relational framework for peer-support design and its application to two existing peer-support services for solitary seniors in Seoul and Ulsan. The framework aims to support the analysis and conception of peer-support services. It incorporates network analysis and codesigning to understand multi-faceted peer-support relationships and to develop strategies for creating relational values, respectively. Case studies used observation and interviews to understand the multi-faceted issue of social support. Relational data for fourteen solitary seniors were collected and analyzed in terms of the qualities, quantities, and structure of peer-support relationships. Analysis results demonstrate an increased level of perceived peer support through relationship forming, as well as the factors that suppress peer-support building such as network fragmentation and the discrepancy of needs. Analysis results were fed into codesigning interventions with stakeholders. Based on these findings, we discuss the preconditions for building peer-support relationships and outline the relational approach to the design for peer support in a wider context.
An Assessment of Ergonomics Climate and Its Association with Self-Reported Pain, Organizational Performance and Employee Well-Being

Previous studies have demonstrated that a positive ergonomics climate with an equal focus on improving operational performance and employee well-being is beneficial to both employee health and organizational performance. This study aimed to assess the ergonomics climate at two power plants and examine its association with self-reported pain, performance, and well-being. At two power plants in Iran, survey responses from 109 and 110 employees were obtained. The questionnaires contained data on ergonomics climate, organizational performance, employee health, and self-reported pain. Results showed that the mean ergonomics climate scores between the Besat and Rey power plants were significantly different (p < 0.001). The overall ergonomics climate score, and all subscales scores, were positively associated with organizational performance (p < 0.001). The overall ergonomics climate score, and some of its subscales, were significantly associated with employees’ general health (p < 0.001). The ergonomics climate score was significantly higher in the group of employees who reported musculoskeletal pain than those who did not report musculoskeletal pain (p < 0.05). Investigation of ergonomics climate can provide organizations with a baseline for prioritizing their values and finding areas for improving organizational performance and employee health.
The magnetic contribution to the driving force for crystal nucleation in undercooled Co–Pd melts

To account for the dependence of the crystal nucleation temperature in Co–Pd melts over the entire range from 50 to 100 at. % Co it is necessary to incorporate a contribution to the driving free energy that derives from the difference in magnetic free energies between liquid and melt. A simple molecular-field model provides a satisfactory fit of the earlier data.
Effect of the Information Support Robot on the Daily Activity of Older People Living Alone in Actual Living Environment

Information support robots (ISRs) have the potential to assist older people living alone to have an independent life. However, the effects of ISRs on the daily activity, especially the sleep patterns, of older people have not been clarified; moreover, it is unclear whether the effects of ISRs depend on the levels of cognitive function. To investigate these effects, we introduced an ISR into the actual living environment and then quantified induced changes according to the levels of cognitive function. Older people who maintained their cognitive function demonstrated the following behavioral changes after using the ISR: faster wake-up times, reduced sleep duration, and increased amount of activity in the daytime (p < 0.05, r = 0.77; p < 0.05, r = 0.89, and p < 0.1, r = 0.70, respectively). The results suggest that the ISR is beneficial in supporting the independence of older people living alone since living alone is associated with disturbed sleep patterns and low physical activity. The impact of the ISR on daily activity was more remarkable in the subjects with high cognitive function than in those with low cognitive function. These findings suggest that cognitive function is useful information in the ISR adaptation process. The present study has more solid external validity than that of a controlled environment study since it was done in a personal residential space.
Segregated brain state during hypnosis

Abstract Can the brain be shifted into a different state using a simple social cue, as tests on highly hypnotizable subjects would suggest? Demonstrating an altered global brain state is difficult. Brain activation varies greatly during wakefulness and can be voluntarily influenced. We measured the complexity of electrophysiological response to transcranial magnetic stimulation in one ‘hypnotic virtuoso’. Such a measure produces a response arguably outside the subject’s voluntary control and has been proven adequate for discriminating conscious from unconscious brain states. We show that a single-word hypnotic induction robustly shifted global neural connectivity into a state where activity remained sustained but failed to ignite strong, coherent activity in frontoparietal cortices. Changes in perturbational complexity indicate a similar move towards a more segregated state. We interpret these findings to suggest a shift in the underlying state of the brain, likely moderating subsequent hypnotic responding.
Training Design, Performance Analysis, and Talent Identification—A Systematic Review about the Most Relevant Variables through the Principal Component Analysis in Soccer, Basketball, and Rugby

Since the accelerating development of technology applied to team sports and its subsequent high amount of information available, the need for data mining leads to the use of data reduction techniques such as Principal Component Analysis (PCA). This systematic review aims to identify determinant variables in soccer, basketball and rugby using exploratory factor analysis for, training design, performance analysis and talent identification. Three electronic databases (PubMed, Web of Science, SPORTDiscus) were systematically searched and 34 studies were finally included in the qualitative synthesis. Through PCA, data sets were reduced by 75.07%, and 3.9 ± 2.53 factors were retained that explained 80 ± 0.14% of the total variance. All team sports should be analyzed or trained based on the high level of aerobic capacity combined with adequate levels of power and strength to perform repeated high-intensity actions in a very short time, which differ between team sports. Accelerations and decelerations are mainly significant in soccer, jumps and landings are crucial in basketball, and impacts are primarily identified in rugby. Besides, from these team sports, primary information about different technical/tactical variables was extracted such as (a) soccer: occupied space, ball controls, passes, and shots; (b) basketball: throws, rebounds, and turnovers; or (c) rugby: possession game pace and team formation. Regarding talent identification, both anthropometrics and some physical capacity measures are relevant in soccer and basketball. Although overall, since these variables have been identified in different investigations, further studies should perform PCA on data sets that involve variables from different dimensions (technical, tactical, conditional).
Multi-Drug Featurization and Deep Learning Improve Patient-Specific Predictions of Adverse Events

While the clinical approval process is able to filter out medications whose utility does not offset their adverse drug reaction profile in humans, it is not well suited to characterizing lower frequency issues and idiosyncratic multi-drug interactions that can happen in real world diverse patient populations. With a growing abundance of real-world evidence databases containing hundreds of thousands of patient records, it is now feasible to build machine learning models that incorporate individual patient information to provide personalized adverse event predictions. In this study, we build models that integrate patient specific demographic, clinical, and genetic features (when available) with drug structure to predict adverse drug reactions. We develop an extensible graph convolutional approach to be able to integrate molecular effects from the variable number of medications a typical patient may be taking. Our model outperforms standard machine learning methods at the tasks of predicting hospitalization and death in the UK Biobank dataset yielding an R2 of 0.37 and an AUC of 0.90, respectively. We believe our model has potential for evaluating new therapeutic compounds for individualized toxicities in real world diverse populations. It can also be used to prioritize medications when there are multiple options being considered for treatment.
‘Single-laboratory’ validation of a method of quantitative analysis of alachlor, chlorpyriphos-methyl, fenthion, and trifluralin

A simple, new gas-chromatography method was developed and validated by a single-laboratory for quantitative determination of four active ingredients (alachlor, chlorpyriphos-methyl, fenthion, and trifluralin) in their commercially available emulsifiable concentrate formulations, widely used in Greece. This method enables the analysis of a number of pesticides with the same chromatographic conditions and internal standard. A capillary gas-chromatographic system equipped with a flame ionization detector and a split injector was used. The linearity of response, specificity, repeatability and other performance characteristics of the method are presented. As a result, the method is validated.