Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of Adverse Events in Cancer Patients Receiving Nivolumab With Ipilimumab: A Meta-Analysis

Background Combining two immune checkpoint inhibitors (ICIs) instead of using one can effectively improve the prognosis of advanced malignant tumors. At present, ipilimumab alongside nivolumab is the most widely used combinatorial regimen of ICIs. However, the risk of treatment-related adverse events is higher in combinatorial regimens than in single-drug regimens. Thus, this study aimed to evaluate the risks of common adverse events associated with the combinatorial regimen of ipilimumab and nivolumab by using meta-analysis. Methods We searched Pubmed, Medline, EMBASE, and Cochrane Library for reports published by 30 September 2021. A randomized controlled study was developed and analyzed using the statistical software R to determine the efficacy of the combinatorial treatment. Risk estimates (hazard ratios, RR) and 95% confidence intervals for various common serious adverse events were used. Results A total of 23 randomized control trials (n = 3970 patients) were included. Our meta-analysis indicated the risks of adverse events of any grade and grade ≥ 3 as 90.42% (95%CI: 85.91% ~ 94.18%) and 46.46% (95%CI: 39.37% ~ 53.69%), respectively; the risks of treatment-related death and adverse events leading to discontinuation were estimated at 0.42% (95% CI, 0.18% ~ 0.72%) and 19.11% (95% CI, 14.99% ~ 24.38%), respectively. Classification of 19 common adverse events. The top 5 grade 1-2 adverse events were found to be fatigue (30.92%, 95% CI: 24.59% ~ 37.62%), pruritus (26.05%, 95%CI: 22.29%~29.99%), diarrhea (23.58%, 95% CI: 20.62% ~ 26.96%), rash (19.90%, 95%CI: 15.75% ~ 25.15%), and nausea (17.19%, 95% CI:13.7% ~ 21.57%). The top 5 grade ≥ 3 adverse events were identified as increased alanine aminotransferase(8.12%, 95% CI: 5.90%~10.65%), increased lipase(7.62%, 95% CI: 4.88% ~ 10.89%), and colitis (6.39%, 95%CI: 3.98% ~ 10.25%), increased aspartate aminotransferase (6.30%, 95% CI: 4.61% ~ 8.22%), and diarrhea(5.72%, 95%CI: 3.50% ~ 8.44%). Subgroup analysis revealed some differences in the adverse events between the N1-I3 and N3-I1 subgroups and between subgroups of different cancer types. Conclusion This study summarized the risks of common adverse events in the co-treatment of malignant-tumor patients with ipilimumab and nivolumab and identified the impacts of various initial administration schemes on the risks of such events, thereby providing an important reference for the toxicity of co-treatment with ipilimumab and nivolumab. Systematic Review Registration https://www.crd. york.ac. uk/prospero/, identifier: CRD42020181350.
Decline in Traffic Congestion Increased Crash Severity in the Wake of COVID-19

Highway fatalities are a leading cause of death in the U.S. and other industrialized countries. Using highly detailed crash, speed, and flow data, we show highway travel and motor vehicle crashes fell substantially in California during the response to the COVID-19 pandemic. However, we also show the frequency of severe crashes increased owing to lower traffic congestion and higher highway speeds. This “speed effect” is largest in counties with high pre-existing levels of congestion, and we show it partially or completely offsets the “VMT effect” of reduced vehicle miles traveled on total fatalities. During the first eleven weeks of the COVID-19 response, highway driving decreased by approximately 22% and total crashes decreased by 49%. While average speeds increased by a modest 2 to 3 mph across the state, they increased between 10 and 15 mph in several counties. The proportion of severe crashes increased nearly 5 percentage points, or 25%. While fatalities decreased initially following restrictions, increased speeds mitigated the effect of lower vehicle miles traveled on fatalities, yielding little to no reduction in fatalities later in the COVID period.
The The Changing Role of Textbooks in Primary Education in the Digital Era: What Can We Learn from Reading Research?

Textbooks have been the primary teaching tool since the 19th century. By their nature, they contained a comprehensive compilation of the content of a particular subject with the intention of explaining it; this knowledge, in turn, was usually filtered to conform to a particular society’s expectations of elementary knowledge about the natural and social environments. There has been a great deal of research on how the content of textbooks has changed in line with changing values in different societies and over different periods. However, little research has been done on how textbook reading substrates and design have changed and how these changes have affected learning and comprehension: studies that systematically examined the effects of different reading substrates and different layouts on reading and learning comprehension did not appear until the late 20th century and early 21st century. We examine such studies and PISA 2021 results to draw five conclusions for future textbook research. These conclusions indicate that screens are worse than printed texts for some types of reading, while interactivity and dynamic design are not values per se but require coherent design to improve reading performance and higher-level thinking skills.
The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence

Cellular senescence is an irreversible state of cell cycle arrest occurring in response to stressful stimuli, such as telomere attrition, DNA damage, reactive oxygen species, and oncogenic proteins. Although beneficial and protective in several physiological processes, an excessive senescent cell burden has been involved in various pathological conditions including aging, tissue dysfunction and chronic diseases. Oxidative stress (OS) can drive senescence due to a loss of balance between pro-oxidant stimuli and antioxidant defences. Therefore, the identification and characterization of antioxidant compounds capable of preventing or counteracting the senescent phenotype is of major interest. However, despite the considerable number of studies, a comprehensive overview of the main antioxidant molecules capable of counteracting OS-induced senescence is still lacking. Here, besides a brief description of the molecular mechanisms implicated in OS-mediated aging, we review and discuss the role of enzymes, mitochondria-targeting compounds, vitamins, carotenoids, organosulfur compounds, nitrogen non-protein molecules, minerals, flavonoids, and non-flavonoids as antioxidant compounds with an anti-aging potential, therefore offering insights into innovative lifespan-extending approaches.
Do Native STEM Graduates Increase Innovation? Evidence from U.S. Metropolitan Areas

This paper examines the effects of college graduates educated in STEM fields on patenting intensity in U.S. metropolitan areas. Some prior research suggests a positive effect on urban innovation from foreign-born STEM workers, but little is known about the effects of native STEM graduates on innovation. My preferred results use time-differenced 2SLS regressions, and I introduce a novel approach to instrumenting for the growth in native STEM graduates. I find positive effects of foreign STEM on innovation, roughly consistent with previous literature. However, my preferred approach yields a negative coefficient estimate for native STEM graduates on innovation that is not statistically significant but suggests that a meaningfully large positive effect is unlikely during the 2009-2015 time-period. I discuss possible explanations and implications.
Impaired Oxygenation of the Prefrontal Cortex During Verbal Fluency Task in Young Adults With Major Depressive Disorder and Suicidality: A Functional Near-Infrared Spectroscopy Study

Background Few previous studies have focused on prefrontal activation in young adults diagnosed with major depressive disorder (MDD) and suicidality via functional near-infrared spectroscopy (fNIRS). Materials and Methods A total of 59 healthy controls (HCs), 35 patients with MDD but without suicidality, and 25 patients with MDD and suicidality, between the ages of 18–34 years, were enrolled. Changes in oxygenated hemoglobin (oxy-Hb) levels of the prefrontal cortex at baseline, 4 weeks, and 8 weeks, were evaluated using a protocol consisting of three consecutively repeated trials of rest, speech, and verbal fluency test (VFT) via fNIRS. MDD was diagnosed and suicidality was evaluated based on Mini International Neuropsychiatric Interview (MINI). Results Oxy-Hb levels were impaired in patients with MDD compared with HCs (p = 0.018 for left prefrontal cortex; p = 0.021 for right ventromedial prefrontal cortex; p = 0.002 for left frontopolar cortex). Among the three groups including HCs, MDD without suicidality, and MDD with suicidality, prefrontal oxygenation was most decreased in MDD patients with suicidality. A significantly impaired prefrontal oxygenation in the right ventrolateral prefrontal cortex (VLPFC) was detected after adjusting for covariates in MDD patients with suicidality, compared to those without suicidality. Conclusion Impaired prefrontal oxygenation during cognitive execution may serve as a diagnostic biomarker for suicidality in young adult patients with MDD.
Broadly Applicable, Virus-Free Dual Reporter Assay to Identify Compounds Interfering with Membrane Fusion: Performance for HSV-1 and SARS-CoV-2

Membrane fusion constitutes an essential step in the replication cycle of numerous viral pathogens, hence it represents an important druggable target. In the present study, we established a virus-free, stable reporter fusion inhibition assay (SRFIA) specifically designed to identify compounds interfering with virus-induced membrane fusion. The dual reporter assay is based on two stable Vero cell lines harboring the third-generation tetracycline (Tet3G) transactivator and a bicistronic reporter gene cassette under the control of the tetracycline responsive element (TRE3G), respectively. Cell–cell fusion by the transient transfection of viral fusogens in the presence of doxycycline results in the expression of the reporter enzyme secreted alkaline phosphatase (SEAP) and the fluorescent nuclear localization marker EYFPNuc. A constitutively expressed, secreted form of nanoluciferase (secNLuc) functioned as the internal control. The performance of the SRFIA was tested for the quantification of SARS-CoV-2- and HSV-1-induced cell–cell fusion, respectively, showing high sensitivity and specificity, as well as the reliable identification of known fusion inhibitors. Parallel quantification of secNLuc enabled the detection of cytotoxic compounds or insufficient transfection efficacy. In conclusion, the SRFIA reported here is well suited for high-throughput screening for new antiviral agents and essentially will be applicable to all viral fusogens causing cell–cell fusion in Vero cells.
Polyurethane dispersions prepared from vegetable oil and their application as textile finishes

One of the major challenges facing the polymer industry now is finding sustainable and renewable alternatives to petroleum-based raw materials. To overcome such challenges, these novel water-borne polyurethane dispersions were prepared from bioresources (vegetable oil). Vegetable oil-based polyol is synthesized by epoxidation and hydroxylation methods from vegetable oil. Consequently, polyurethane dispersions are prepared by reacting the vegetable oil-based polyol with isophorone diisocyanate and dimethylol propionic acid to form the polyurethane prepolymer, which further reacts with 1,4-butanediol, and the final product is obtained by the addition of water. Fourier transform infrared analysis is used for the structural confirmation of the prepared vegetable oil-based polyol and polyurethane dispersions. A number of textile tests, including mechanical (tear strength (ASTM 1424) and tensile strength (ASTM D-5034)) and antibacterial, were conducted on poly/cotton plain weave fabrics after applying the synthesized dispersions by pad dry-cure methods. The hemolytic test method was used to check the biocompatibility of the synthesized dispersions. Results reveal that these finishes effectively increase the tensile strength of the treated fabric samples, such as white fabric samples, which show tensile strength values of (248, 255, 268 and 325 N from untreated 240 N) in the warp direction. The biological outcomes show the antibacterial and hemolytic activity of the dispersions are influenced by the presence of natural polyols in the dispersions. These results indicate that covering poly/cotton fabrics with vegetable oil-based polyurethane dispersions improve their tensile strength and antibacterial properties and they can replace petroleum-based polyurethane finishes.
KECAKAPAN GENERIK DAN PENGEMBANGANNYA DI SEKOLAH MENENGAH KEJURUAN

Kecakapan generik merupakan kecakapan nonteknikal yang sangat menen-tukan terhadap keberhasilan seseorang untuk mendapatkan pekerjaan, eksis dalam pe-kerjaan, dan berkembang secara maksimal dalam pekerjaannya. Istilah kecakapan ge-nerik (generic skills) memiliki banyak sinonim, yaitu soft skills, empoyability skills, key skills, common skills, essential skills, basic skills, necessary skills, competencies skills, dan transferable skills. Pengembangan kecakapan tersebut di SMK dapat dila-kukan melalui dua pendekatan, yaitu secara kurikuler melalui kegiatan pembelajaran di kelas dan laboratorium/bengkel/studio dan secara nonkurikuler melalui berbagai kegiatan ekstrakurikuler yang diselenggaran sekolah.
Multi-Timepoint Metabolic Fingerprinting of a Post-Episode Period of Hypoglycemia and Ketoacidosis Among Children With Type 1 Diabetes

Background: Acute complications of type 1 diabetes mellitus such as diabetes ketoacidosis (DKA) and hypoglycemia (HG) are detrimental in a short- and long-term perspective. Restoration of normoglycemia and correction of pH do not mean that all metabolic disturbances caused by HG or DKA are immediately reversed. Aim: This study aimed to identify serum metabolic changes caused by an episode of DKA and HG that may indicate the mechanisms contributing to long-term consequences of DKA/HG. Materials and methods: Four groups of children with type 1 diabetes were recruited. The first two study groups included patients after an episode of DKA or HG, respectively. Additionally, two comparative groups were recruited—children with established type 1 diabetes (EDM) and patients with newly diagnosed diabetes without diabetes ketoacidosis (NDM). Serum samples were collected in three group-specific time points (since the hospital admission): HG 0h-12h–48h; DKA or NDM 0h-24h–72 h; and one random fasting sample from patients with EDM. Two batches of 100 samples each were created: for DKA batch 20 × 3 DKA patients, 10 × 3 NDM and 10 EDM; for HG batch: 10 × 3 HG patients, 25 EDM and 15 × 3 NDM. All patients within the batches were age and sex matched. Metabolic fingerprinting was performed with LC-QTOF-MS. Results: Four metabolites were associated with a DKA episode occurring in the preceding 72 h: three were found higher after the DKA episode versus comparative groups: lysophosphatidylcholine (LPC) (18:1), sphingomyelins (SM) (34:0 and d18:0/15:0), and one was found lower: LPC (18:0). Similarly, four metabolites were identified for the HG episode in the last 48 h: three were found higher after the HG episode versus comparative groups: two lysophosphatidylethanolamines (LPE) (18:2 and 20:3) and one LPC (18:2); and one was found lower after the HG episode: oxy-phosphatidylocholine (PC O-34:4). Conclusions: We found eight metabolites whose levels may be traced in the serum, indicating the DKA or HG episode for up to 72 h and 48 h, respectively. Acute complications of diabetes may cause persistent metabolic disturbances long after pH and glucose level normalization.
Seventy-Two-Hour LRRK2 Kinase Activity Inhibition Increases Lysosomal GBA Expression in H4, a Human Neuroglioma Cell Line

Mutations in LRRK2 and GBA1 are key contributors to genetic risk of developing Parkinson’s disease (PD). To investigate how LRRK2 kinase activity interacts with GBA and contributes to lysosomal dysfunctions associated with the pathology of PD. The activity of the lysosomal enzyme β-Glucocerebrosidase (GCase) was assessed in a human neuroglioma cell model treated with two selective inhibitors of LRKK2 kinase activity (LRRK2-in-1 and MLi-2) and a GCase irreversible inhibitor, condutirol-beta-epoxide (CBE), under 24 and 72 h experimental conditions. We observed levels of GCase activity comparable to controls in response to 24 and 72 h treatments with LRRK2-in-1 and MLi-2. However, GBA protein levels increased upon 72 h treatment with LRRK2-in-1. Moreover, LC3-II protein levels were increased after both 24 and 72 h treatments with LRRK2-in-1, suggesting an activation of the autophagic pathway. These results highlight a possible regulation of lysosomal function through the LRRK2 kinase domain and suggest an interplay between LRRK2 kinase activity and GBA. Although further investigations are needed, the enhancement of GCase activity might restore the defective protein metabolism seen in PD.
Efficient Load Forecasting Model Assessment for Embedded Building Energy Management Systems

Growing urbanization tendencies have increased the role that buildings play in future energy systems. We present a comparative study of load forecasting methods for large commercial buildings’ energy traces. Forecasts can be used to improve control algorithms at the local and grid level and to devise practical anomaly detection algorithms. The main approaches for classical modeling, machine learning, and deep learning methods are illustrated with considerations for statistical relevance and contextual information. Model parameter design is achieved using heuristics or systematic parameter space searches for robustness. For the available building consumption datasets, two short-term prediction methods are deployed: Seasonal AutoRegressive Integrated Moving Average (SARIMA) and Recurrent Neural Networks (RNN). An extensive evaluation of prediction performance was conducted based on several metrics. The daily load energy forecast for the 7 considered buildings showed higher precision when using RNN methods compared to the SARIMA auto-regressive algorithm. Implementation of the proposed embedded online building management system can be replicated for other buildings.
Binary-Input Ternary-Output Turbo Codes for Ternary PSK Transmission

Ternary phase shift keying (TPSK) is one of the potential transmission schemes with spectral efficiency higher than $\pi / 2$ -shift BPSK adopted by the fifth generation (5G) mobile communications for long-distance communications, while retaining lower peak-to-average power ratio (PAPR) signal property compared to QPSK. However, its application to practical systems is challenging as the conventional coding and modulation schemes are not designed for ternary signaling. In this work, we first introduce a phase shifting approach for TPSK in order to effectively reduce the PAPR in the framework of OFDM with DFT-precoding. We then propose a design of binary-input ternary-output (BITO) turbo codes that match with TPSK signaling. Through computer simulations, we demonstrate its superior error rate performance, and elucidate its advantages over the conventional PSK systems.
An Empirical Analysis of Monetary Policy Transmission Instruments and Non-oil Real Sector Private Investment in Nigeria

In recent times, the performance of Non-oil real Private investment in Nigeria has remained suboptimal. This has been generally attributed to ineffective monetary policy, among others. This study therefore examines the impact of selected Monetary Policy transmission instruments namely: Monetary Policy Rate (MPR), Cash Reserve Ratio, (CRR) Liquidity Ratio, (LR) and Foreign Exchange Rate (NFXR), on Non-oil Real Sector Private Investment (NRSPI). The time series data is sourced from CBN, spanning through a period of 1981 to 2020. Johansen Co-integration and Error correction model (ECM) econometric analysis was employed.The empirical findings established that in the long run, inverse and significant relationships exist between (NRSPI) and MPR, LR, and CRR while FXR is positively and significantly related. The coefficient of the ECM (-1.16) which measures NRSPI’s speed of equilibrium adjustment to changes in the selected policy instruments, is significant and correctly signed. It suggests that in the long run, NRSPI adjusts slowly to short-run disequilibrium in the selected policy instruments; indicating a lag effect. Overall, the policy instruments do not contribute effectively to NRSPI growth in Nigeria. Therefore, the monetary authorities should lay emphasis on aligning their policy contractionary measures, to reduce adverse effect of these selected instruments, They should maintain optimal lending rate that reflects the overall internal rate of return on investment, with due attention to market fundamentals. Lastly, Policy makers should take into consideration the lag effect, and design policies in line with the magnitude of expected changes.
Internal audit function is a global governance pursuit: What could be done in emerging markets?

This paper investigates the internal and the external auditors’ perceptions of how compliance with the Institute of Internal Auditors (IIA) International Standards for the Professional Practices of Internal Auditing (Standards) enhances the implementation of internal audit function (IAF) as a corporate governance mechanism in the listed companies in an emerging economy. Based on the Common Body of Knowledge (CBOK) database questionnaires were sent to internal auditors (IAs) and external auditors (EAs) of listed firms, and interviews were made with individuals involved in the IAF. The results reveal that IAF in an emerging economy faces difficulties related to objectivity, qualifications, and the roles of the internal audit staff reducing its role in corporate governance (CG). Significant positive correlations between compliance with Attribute Standards of independence, objectivity, proficiency, and free of interference and performance standards enhanced the organizational status of the internal audit. But there is a weak correlation between audit documentation and the organizational status of the internal audit. Quality assurance and improvement program, ongoing monitoring, and self-assessment by other personnel inside the organization having enough knowledge of the internal audit practices are needed for IAF to fulfill its CG responsibilities. This study is considered among the first that surveyed the status of the use of the professional IIA Standards in the listed firms in one of the emerging economies characterized by having good corporate governance practices from the perspectives of both IAs and EAs of the same companies under study.
Discovering Service Variations through Service Prototyping

Abstract Designing services require embracing the variability that makes it unique. This paper investigates how the use of a service prototyping technique enables participants to explore the variations inherent in services. The video data are analyzed using qualitative content analysis and the articulated variations are abstracted as categories. The resulting categories are then mapped across the service logic framework and the corresponding provider, joint and patient spheres. This paper aims to contribute to research on service prototyping by augmenting the use of prototyping methods to gain an understanding of the sources and possibly types of variations in a particular service. It clarifies how prototyping a service allows people untrained in design to diagnose variations that may occur in a future service and the decision-making process in accommodating variation. Further, the knowledge gained enables improved value co-creation opportunities in a service.