Miracle-dz/UniFAR-FTUs huggingface dataset:
An Immunosuppressive Effect of Melanoma-derived Exosomes on NY-ESO-1 Antigen-specific Human CD8+ T Cells is Dependent on IL-10 and Independent of BRAFV600E Mutation in Melanoma Cell Lines

ABSTRACT Exosomes, including human melanoma-derived exosomes (HMEX), are known to suppress the function of immune effector cells, which for HMEX has been associated with the surface presence of the immune checkpoint ligand PD-L1. This study investigated the relationship between the BRAF mutational status of melanoma cells and the inhibition of secreted HMEX exosomes on antigen-specific human T cells. Exosomes were isolated from two melanoma cell lines, 2183-Her4 and 888-mel, which are genetically wild-type BRAFWT and BRAFV600E, respectively. HMEX were isolated using a modified, size-exclusion chromatography (SEC) method shown to reduce co-isolation of non-exosome-associated cytokines compared to ultracentrifugation isolation. The immunoinhibitory effect of the exosomes was tested in vitro on patient-derived NY-ESO-1-specific CD8+ T cells challenged with NY-ESO-1 antigen. HMEX from both cell lines inhibited the immune response of antigen-specific T cells comparably, as evidenced by the reduction of IFN-γ and TNF-α in NY-ESO-1 tetramer-positive cells. This inhibition could be partially reversed by the presence of anti-PD-L1 and anti-IL-10 antibodies. IL-10 has been demonstrated to be a critical pathway for sustaining enhanced tumorigenesis in BRAFV600E mutant cells compared to BRAFWT melanoma cells. Thus, we demonstrate that HMEX inhibit antigen-specific T cell responses independent of the BRAF mutational status of the parent cells. In addition, PD-L1 and IL-10 contribute to the HMEX-mediated immunosuppression of antigen-specific human T cells. The inhibitory capacity of exosomes should be taken into consideration when developing therapies that are reliant upon the potency of customized, antigen-specific effector T cells.
Interoceptive signaling in alcohol cognitive biases: Role of family history and alliesthetic components

The role of interoceptive signals in the development of cognitive biases for drug‐related cues has been hypothesized in the past; however, experimental evidence is lacking. This report examined the relationship between physiological responses and memories for alcohol cues. Participants (n = 158) were categorized as having either a positive or negative family history of alcohol use disorder (AUD). They were assigned to an alcohol, placebo, or control beverage condition to which they were blinded. All participants were presented with alcohol, neutral, and emotional cues. Heart rate variability (HRV) at 0.1 Hz, as an index of viscero‐afferent reactivity, and in the high‐frequency range was measured during picture‐cue exposure. Participants then completed free recall and repetition priming tasks to assess memories for previously presented stimuli. Participants with a positive family history (FHP) for AUD who received an alcohol beverage displayed a positive relationship between 0.1 Hz HRV and free recall. This effect was specific to alcohol cues, highlighting the relevance of physiological signals in the development of alcohol cognitive biases. These results support the hypothesis of a coordinated brain‐body interaction in the development of drug‐related behaviors. FHP as an AUD risk factor may increase the mapping of physiological responses onto cognitive biases for alcohol cues. Increased ratings of subjective intoxication dampened this relationship, suggesting that perceived bodily states may modulate incentive salience processes. This report provides novel evidence for the involvement of interoceptive signals in addictive processes, setting a precedent for the exploration of brain‐body interactions in the study of alcohol cognitive biases.
THE ROLE OF ALDOSTERONE INHIBITORS ON CARDIAC ISCHEMIA/REPERFUSION INJURY.

Myocardial ischaemia-reperfusion (I/R) injury is well known term for paradoxal exacerbation of cellular destruction and dysfunction, after the restoration of blood flow to previously ischaemic heart. A vast number of studies that has demonstrated the role of mineralocorticoids in cardiovascular diseases is based on the use of pharmacological mineralocorticoid receptor antagonists (MRA) such as spironolactone and eplerenone. This review paper aimed to summarize current knowledge on the effects of MR antagonists on myocardial I/R injury, as well as post-infarction remodeling. Animal models, predominantly Langendorff technique and left anterior descending coronary artery occlusion (LAD) have confirmed the potency of MRA as preconditioning and postconditioning agents in limiting infarct size and postinfarction remodeling. Several preclinical studies in rodents have established and proved possible mechanisms of cardioprotection by MRA, such as reduction of oxidative stress, reduction of inflammation and apoptosis, therefore limiting infarct zone. However, the results of some clinical trials are inconsistent with these results since they reported no benefit of MRA in acute myocardial infarction. Due to this, further studies and the results of on-going clinical trials regarding MRA administration in patients with acute myocardial infarction are being awaited with great interest.
Insights into Friedman stage II and III OSA patients through drug-induced sleep endoscopy

Background The Friedman staging is a classic system to predict outcomes of obstructive sleep apnea (OSA) surgery. Increasing stage indicates more severe upper airway (UA) obstruction and worse surgical successful rate. In previous studies, the UA obstruction between stages were usually assessed based on awake examination. Drug-induced sleep endoscopy (DISE) is a new method that can evaluate airway collapse characteristics during sleep. Therefore, we planned to compare Friedman staging and DISE findings and fulfill the knowledge gap on the correlation between awake and sedated UA examination. Methods Retrospective case series study that assessed patients with OSA who underwent DISE. Subjects were classified to stage II and stage III groups based on Friedman staging system. UA collapse characteristics based on velum, oropharynx, tongue base, epiglottis (VOTE) classification, including single/multiple obstruction sites, single/combined upper and lower obstruction levels, collapse degree and patterns in different sites, and surgical results among the groups were analyzed. Results A total of 175 cases were analyzed. No significant differences were found in baseline measurements between groups. Stage III patients (n=102) had a higher proportion (74.5%) with 3 or 4 obstruction sites than stage II (57.5%, n=73). Velum (V) + oropharynx (O) + tongue base (T) was the most common multi-sites combined obstruction pattern with 33% in stage II and 37% in stage III, isolated lower level obstruction was the least with 6% and 4%, respectively. No significant differences were found in obstruction sites and levels. 106 patients underwent surgeries and 33 had post-surgical sleep study, 73.7% and 63.6% response rate were found in stage II and III with no significant difference. Conclusions Upper and lower combined obstruction was the main pattern of collapse in both, Friedman stage II and III patients. Patients with OSA and Friedman stage III had more than 2 sites of obstruction than stage II patients.
Acute loss of smell and taste among patients with symptoms compatible with COVID-19.

INTRODUCTION The aim of this study was to describe the clinical symptoms, including affection of sense of smell and taste, among participants in a party held in Copenhagen after which many participants reported symptoms compatible with coronavirus disease 2019 (COVID-19). METHODS A 37-item questionnaire was sent electronically to all 95 participants seven weeks after the party. The questionnaire included questions about the type, timing and duration of COVID-19 symptoms. RESULTS In total, 65 of 95 (68%) participants responded, among whom 51/65 (78%) had symptoms compatible with COVID-19; 53% (27/51) had affection of their sense of smell and taste; 70% (19/27) reported a total loss of taste. These symptoms continued for 1-3 weeks for 78% and 3-6 weeks for 22% (6/27). Interestingly, 11/27 (41%) reported that they had not fully regained their sense of taste and 3/27(11%) were still very affected by this symptom. Moreover, 44% of the respondents who had lost their sense of taste perceived this symptom as moderate to severe. Eighty-one percent (22/27) reported a total loss of smell. This symptom continued for 1-3 and > 3 weeks in 74% and 26%, respectively. At the time of the investigation, 48% had not fully regained their sense of smell and 7% were still very affected. More than half of the respondents who lost their sense of smell perceived this symptom as moderate to severe. CONCLUSIONS Many patients with clinically diagnosed COVID-19 report an affected sense of smell and taste. The duration of these symptoms currently remains unknown. FUNDING none. TRIAL REGISTRATION not relevant.
Impact of Proinflammatory Cytokine Gene Polymorphisms and Circulating CD3 on Long-Term Renal Allograft Outcome in Egyptian Patients

ABSTRACT The extant study aimed to explore the influence of two cytokines TNF-α − 308 and IFN-γ + 874 gene polymorphism on development of renal transplant rejection and to investigate the feasibility of Th1 cytotoxic immune reaction (CD3). It includes 152 kidney recipients were divided into two subgroups: 76 stable graft functions (SGF) and 76 allograft dysfunctions (AD) compared with 56 healthy individuals as control group. TNF-α − 308 G > A and IFN-γ + 874 A > T genetic polymorphisms were characterized using ARMS-PCR technique. CD3 protein expression was measured using ELISA Kit. The effect on transplant outcome was analyzed where, statistically significant differences of TNF-a-308 G/A were observed between AD group when compared to SGF group (OR = 0.296, 95% CI = 0.091–0.965, p = .031) in AG genotype (intermediate producer genotype). Also, AD group displayed a statistically significant increase of IFN-γ + 874 TT (high producer genotype) when compared to SGF group (OR = 0.290, 95% CI = 0.127–0.665, p = .003). The expression of CD3+ T lymphocytes in recipients with allograft dysfunction was statistically higher than that with stable allograft function and control groups (732 ± 76, 235 ± 51 and 442 ± 50) respectively and (p ≤ 0.001). In conclusion, IFN-γ + 874 T and TNF-α − 308 A alleles are risk alleles for renal transplant rejection and these two single nucleotide polymorphisms (SNPs) may be implicated in the tendency of rejection after renal transplantation. CD3 may be used as non-invasive biomarker in monitoring of rejection and avoid exposing patients for biopsy risks and sampling error.
A Study on Wild Rats and Their endoparasite fauna From the Endau Rompin National Park, Johor

A survey of the Endau Rompin National Park's wild terrestrial rats and related helminth parasites was carried out to determine the current population and biodiversity. A total of 128 rats were trapped, identified and examined for endoparasites. Prevalence and mean abundance of different parasites were calculated. A total of eight rat species were identified, namely, Leopoldamys sabanus, Maxomys rajah, Maxomys surifer, Maxomys whiteheadii, Rattus exulans, Rattus rattus diardii, Rattus tiomanicus and Sundamys muelleri. Endoparasite fauna recovered from all rats consists of 23 nematode species (Angiostrongylus malaysiensis, Capillaria hepatica, Cyclodonstomum purvisii, Filarioidea fam. gen. sp., Globocephalus connorfilii, Gongylonema neoplasticum, Heligmonoides bulbosus, Heterakis spumosa, Mastopharus muris, Macrostrongylus ratti, Malaystrongylus odontospicularis, Maxomystrongylus sp., Nippostrongylus brasiliensis, Orientostrongylus sp., Paraheligmonelloides sp., Physalopteridae gen. sp., Rattustrongylus odontoconus, Rattustrongylus rotundoconus, Reticularia tanii, Strongyloides ratti, Strongyloides venezuelensis, Subulara andersoni, and Syphacia muris), three cestode species (Hymenolepis diminuta, Rodentolepis nana and Taenia taeniaformis), two trematode species (Fibricola ramachandrani and Zonorchis sp.) and one pentastomide species (Armillifer moniliformis). Overall prevalence was 90.63% with Heligmonellidae parasites being the dominant helminth. New rat hosts of several parasites were also identified. Changes in the types of parasites between the present survey and an earlier study of the same area are believed to have been caused by the intrusion of commensal rats, particularly Rattus tiomanicus, into the park. The current qualitative composition of rats and related endoparasites can be attributed to the ongoing human activities at the park. Therefore it is the aim of the present study to provide the much needed baseline data to design an appropriate programme for environmental monitoring and biomedical research within the park.
Determinants of Discretionary and Non-Discretionary Service Utilization among Caregivers of People with Dementia: Focusing on the Race/Ethnic Differences

ABSTRACT Using Andersen’s behavioral model of service utilization, this study aimed to understand how predisposing, enabling, and need factors were associated with two types of service utilization among caregivers of people with dementia. Caregiver participants (N = 637) were from the Resources for Enhancing Alzheimer’s Caregivers Health (REACH II) study. Binary logistic and linear regression analyses were conducted to predict whether participants used services and the frequency of such service utilization. Results showed that some enabling and need factors were significantly associated with both discretionary and non-discretionary service utilization. Results also indicated some need factors were significant factors of the frequency of use for both discretionary and non-discretionary services. In addition, being Hispanic or African American moderated the association between some enabling or needs factors and service utilization. Practice attention needs to be paid on several enabling and needs factors among Hispanic and African American caregivers of people with dementia.
Comparing Biclustering Algorithms: A Simulation Study

— Biclustering is a data mining technique that simultaneously apply clustering to both of rows and columns of a matrix that represents a data set to detect local patterns in the data. Biclustering methods are developed originally to analyze gene expression data or any data that can be presented as a matrix. For this purpose, many biclustering algorithms have been introduced in the literature. However, efforts to compare the performance of these algorithms are limited. The purpose of this work is to compare the performance of biclustering algorithms. FLOC, Qubic, CTWC, SAMBA and Bimax algorithms were chosen in our work. The data contains four biclusters generated randomly with four different normal distributions. Algorithms showed varies performance with the simulated data type. To obtain the full information from the data more than one algorithm must be used. In addition, the chosen algorithm must be repeated many times with different parameters to have the best results.
Civil Service Reform in U.S. States: Structural Causes and Impacts on Delegation∗

This paper studies the causes and consequences of civil service reforms creating an independent bureaucracy – that is, moving from a spoils system (where the civil service is controlled by politicians) to a merit system (where bureaucrats are more independent). We first demonstrate theoretically that divided government is a key trigger of civil service reform: legislators have a stronger incentive to establish an independent bureaucracy when their interests diverge from the governor’s. Taking this idea to comprehensive civil service reforms in U.S. states in the second half of the 20th century, we find that states tended to introduce stronger merit systems when there was divided government. Next, we examine the impact of these reforms on legislation using new methods from computational linguistics. We find that after civil service reform, legislators start writing more detailed statutes that contain more legal provisions. This is consistent with an agency cost model where a more independent bureaucracy requires more specific instructions to avoid bureaucratic drift, rather than an expertise model where a more professionalized bureaucracy should be given more discretion.
Publication agreement

We design an experiment to examine the causal effect of legal institutional quality on informal norms of cooperation, and study the interaction of institutions and culture in sustaining economic exchange. 346 subjects in Italy and Kosovo play a market game under different and randomly allocated institutional treatments, which generate different incentives to behave honestly, preceded and followed by a non-contractible and non-enforceable trust game. Significant increases in individual trust and trustworthiness follow exposure to ‘better’ institutions. A reduction by one percentage point in the probability of facing a dishonest partner in the market game, which is induced by the quality of legal institutions, increases trust by 7 to 11%, and trustworthiness by 13 to 19%. This suggests that moral norms of cooperative behavior can follow improvements in formal institutional quality. Cultural origin, initial trust and trustworthiness influence opportunistic behavior in markets, but only in the absence of strong formal institutions.
Wetland development and paleoclimate reconstruction based on two Late Holocene sequences from Sani Valley, Lesotho highlands, Drakensberg

Wetland development and paleoclimate reconstruction based on two Late Holocene sequences from Sani Valley, Lesotho highlands, Drakensberg The study of wetlands in a paleoclimatological context has increased in the last years, because of its potential to preserve climate signals and as the understanding of its importance in short term climate change has grown. Here, several chemical and physical proxies have been used to determine changes in detrital input (Si/Ti, Zr/Ti, bulkdensitet), redox conditions (Fe/Ti, Mn/Ti) and biological productivity (Ca/Ti, C/N, diatoms) at two wetland sites in Lesotho: Ladybird (LB) and Frog Springs (FS). Four units of similar character have been identified at both sites and represent the development of these wetlands since the initiation of organic accumulation around 2 800 cal yr BP (FS) and 1 300 cal yr BP (LB). The proposed development path is that alpine pans, formed from aeolian and fluvial erosion, have been the basis for the development of ponds and puddles that have later been infilled with mineral and organic matter, which in time have led to the transition into a wetland stage, as there is today. This development has been linked to other studies in Lesotho and other parts of southern Africa.
Numerical simulation of a laboratory experiment testing hydraulic fracture initiation monitored by acoustic emission

Hydraulic fracturing and stimulation practices are key for the successful development of enhanced geothermal and unconventional oil and gas projects involving ultra-low permeability reservoirs. However, the injection of large volumes of fluids and triggering of induced seismicity with these practices has raised public and regulatory concerns. Understanding the mechanisms of fault slip and influence of fault characteristics on susceptibility is critical for properly mitigating this potential hazard.
Newmark sliding displacements of slopes

Estimation of Newmark sliding displacement plays an important role for 4 evaluating seismic stability of slopes. Current empirical models generally utilize predefined 5 functional forms and relatively large model uncertainty is involved. On the other hand, 6 machine learning method has superior capacity in processing comprehensive datasets in a 7 non-parametric way. In this study, a machine learning framework is proposed to predict 8 Newmark sliding displacements using the extreme gradient boosting model (XGBoost) and 9 the Next Generation Attenuation (NGA)-West2 database, where the subset simulation (SS) is 10 coupled with K-fold cross validation (CV) technique for the first time to tune 11 hyper-parameters of the XGBoost model. The framework can achieve excellent 12 generalization capability in predicting displacements and prevent data overfitting by using 13 1 Ph.D. Student, State Key Laboratory of Water Resources and Hydropower Engineering Science, Institute of Engineering Risk and Disaster Prevention, Wuhan University, 299 Bayi Road, Wuhan 430072, China 2 Associate Professor, Department of Hydraulic Engineering, Tsinghua University, Beijing 100084, China. Corresponding Author (huangduruo@tsinghua.edu.cn) 3 Associate Professor, Department of Civil and Environmental Engineering, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong 4 Professor, State Key Laboratory of Water Resources and Hydropower Engineering Science, Institute of Engineering Risk and Disaster Prevention, Wuhan University, 299 Bayi Road, Wuhan 430072, China Accepted by Journal of Geotechnical and Geoenvironmental Engineering, ASCE, March 2020
DAS05377 Personal Investment Theory and Japanese University Students’ Achievement on the Test of English as a Foreign Language

Researchers and theorists in the area of Second Language Acquisition (e.g., Ellis, 1994; Gass & Selinker, 1994; Larsen-Freeman & Long, 1991; Spolsky, 1989) consider there to be a wide variety of factors that contribute to language proficiency and achievement. These include motivation, language aptitude, the learning environment, learning styles and strategies, age, and personality factors. This paper focuses on motivational and sense-of-self characteristics, and their contribution to achievement on an academic English test. Data were collected from 500 female, Japanese, first-year university students using the Inventory of University Motivation, based on Maehr’s multiple goal model of Personal Investment (Maehr, 1984; Maehr & Braskamp, 1986). Results from multiple regression analyses showed that half of the components of the scales were effective in predicting academic English proficiency as measured by Test of English as a Foreign Language (TOEFL) scores. Three scales, Sense of competence at English, Competition in English, and Social Concern in English, had the highest predictive utility.
The Dorsal Root Ganglion as a Novel Neuromodulatory Target to Evoke Strong and Reproducible Motor Responses in Chronic Motor Complete Spinal Cord Injury: A Case Series of Five Patients

Current strategies for motor recovery after spinal cord injury (SCI) aim to facilitate motor performance through modulation of afferent input to the spinal cord using epidural electrical stimulation (EES). The dorsal root ganglion (DRG) itself, the first relay station of these afferent inputs, has not yet been targeted for this purpose. The current study aimed to determine whether DRG stimulation can facilitate clinically relevant motor response in motor complete SCI.
Effect of Visualization of Pedestrian Intention Recognition on Trust and Cognitive Load

Autonomous vehicles carry the potential to greatly improve mobility and safety in traffic. However, this technology has to be accepted and of value for the intended users. One challenge on this way is the detection and recognition of pedestrians and their intentions. While there are technological solutions to this problem, there seems to be no research on how to make this information transparent to the user in order to calibrate the user’s trust. Our work presents a comparative study of 5 visualization techniques with Augmented Reality or tablet-based visualization technology and two or three information clarity states of pedestrian intention in the context of highly automated driving. We investigated these in a user study in Virtual Reality (N=15). We found that such a visualization was rated reasonable, necessary, and that especially the Augmented Reality-based version with three clarity states was preferred.