Miracle-dz/UniFAR-FTUs huggingface dataset:
Game Genres and High-Level Design Pattern Formations

In this paper, I argue for the need to recognize a higher level of abstraction above that of game design pattern. I propose the concept of “game architecture” defined as high-level, strongly synergistic formations of design patterns that efficiently implement a specific gameplay. I suggest that these game architectures form the design backbone of mechanics-centric game genres and constitute a significant factor in game evolution and innovation. They are reproduced in a number of individual games because they allow players to experience variety while remaining within the scope of a familiar and appreciated game experience for which they are already competent. A simple model is proposed to frame game architectures in relationship to other levels of abstraction in game design: form and content. Evidence for game architectures is discussed in a historical analysis of adventure games and trick-taking card games.
Early Detection of Opioid Over-Procurement: A Machine Learning Approach

Over the past three decades, the misuse of prescription opioids has been the leading cause of the decline in life expectancy in the United States. In this study, we present machine learning models to identify the illegal diversion of controlled substances across the prescription drug supply chain in the US. The models use a combination of state-of-the-art machine learning algorithms and a vast volume of administrative data to discover suspicious opioid purchasing behavior. We show that the algorithms can detect illicit opioid transactions with high accuracy, and are capable of early detection up to several years in advance. We estimate that the implementation of our machine learning models could have prevented the illegal distribution of as many as 600 million pills between 2006 and 2012. Our ﬁndings hold promise for using data-driven machine learning algorithms to detect, prevent, and investigate the diversion of prescription opioids.
Persuasive Advertising in a Vertically Differentiated Market

We study advertising content strategies in a vertically differentiated market when consumer valuation of quality is concave in quality. We consider two types of persuasive effects of the content of ads — shifting a consumer’s valuation of quality such that she values quality either more or less relative to price (valuation shifting), and shifting a consumer’s perception of quality by altering the reference point against which she evaluates quality (reference shifting). We find that a monopolist always and only prefers valuation-shifting advertising content. In a duopoly with firms selling vertically differentiated products, however, the choice is more nuanced. Specifically, the high-quality firm may not always prefer valuation-shifting content because this increases the proportion of high-valuation consumers in the market, which intensifies price competition. Furthermore, the high-quality firm may benefit from reference-shifting content, even though it reduces the perceived absolute valuation of its product, because it increases its valuation relative to the low-quality product. We also find that either the low-quality or the high-quality firm may choose not to advertise at all (under conditions that this firm would if it were a monopolist).
Using Global Vectors in Social Interaction Network for Song Recommendation

Much like speech, or written text, music is one of the cohesive forces that binds society together, and is arguably the oldest form of communication, even before language. Today music has become more globalized than ever, and social networks have a lot to contribute to it. The music industry today relies heavily on streaming services, like Apple Music, Spotify, Google Play Music, Pandora, and the like. A defining characteristic of these services is that they have either curated playlists, where a team of music experts compile lists of songs of the same genre, or recommended playlists, using the user’s listening history. However, a particular user can be the member of different streaming services, and can listen to various songs on different platforms at different points of time. Therefore, the auto-generated lists based on history for that particular user will vary across streaming services. Also, a limitation of history based recommendation strategies is that it depends a lot on the user’s history and globally trending songs. The first runs the risk of getting stuck in a filter bubble of the same songs again and again, while the second runs the risk of over-generalization, as in globally trending songs may not cater to the tastes of each user. Our proposed recommender is the best of both worlds, as it harnesses both the trend component and personalized reaction components in a social network, and is agnostic to the music service preferred by the user.
Study on Polystyrene/MWCNT Nanocomposite as a Temperature Sensor

The aim of this research is to fabricate a novel temperature sensor for any calorimetry system. A new mixed solution method was introduced to prepare polystyrene/multiwall carbon nanotube nanocomposite samples with different weight percentages as 0.05, 0.1, 0.28, 1, and 2 of MWCNTs. To demonstrate the dispersion state of the inclusion into the polymer matrix, the SEM analysis was applied. Also, XRD and Raman spectroscopy analyses were carried out. The electrical percolation threshold was investigated and achieved at about 0.28 weight percent of the inclusion. Finally, the electrical resistance of the samples was measured from room temperature up to ~100oC. Consequently, positive temperature coefficient and negative temperature coefficient effects were observed before and after Tg for the most nanocomposite samples, respectively. The best linear response of the resistance-temperature curve was achieved at 20-50oC, which using a second-order fitting curve it can be used up t0 ~70oC. Results show that the polystyrene/multiwall carbon nanotube nanocomposite near the percolation threshold can be used as a temperature sensor for calorimetric purposes.
A Theoretical Study of Highly Nitrated Azacubanes

The geometries of highly nitrated azacubanes have been fully optimized at the B3LYP/6-31 ++ G** theory level, and the gas phase enthalpies of formation have been obtained by designing the isodesmic reaction in which the azacubane cage skeleton is not destroyed. An efficient procedure for judging the driving force of detonation products of energetic compounds has been developed from the conservation of energy condition. The MP2/6-31 ++ G**//B3LYP/6-31 ++ G** atom-atom overlap-weighted NAO bond order shows that after the full nitration of 1,4-diazacubane and 1,3,5,7-tetraazacubane the weakest C–N bond on the 1,3,5,7-tetraazacubane cage skeleton strengthens slightly, but on the 1,4-diazacubane cage skeleton it weakens. For highly nitrated azacubanes, the introduction of –NH2 group results in the destabilization of the neighboring C–N bond on the cage skeleton. The shock stability of 2,4,6,8-tetranitro-1,3,5,7-tetraazacubane (TNTAzC) is superior to that of 2,3,5,6,7,8-hexanitro-1,4-diazacubane (HNDAzC). The detonation velocity and pressure for TNTAzC are predicted to reach 11.10 km/s and 101.7 GPa, respectively. The driving force of detonation products of HNDAzC is close to that of octanitrocubane, and the driving force of TNTAzC is about 4.0 times as large as that of the widely used high explosive HMX, showing that TNTAzC is a potential candidate of super high-energy compound.
Structural analysis of Sulfolobus solfataricus TF55β chaperonin in open and filamentous states

Chaperonins are biomolecular complexes that assist protein folding. Thermophilic Factor 55 (TF55) is a group II chaperonin found in the archaeal genus Sulfolobus that has α, β and γ subunits. Using cryo-electron microscopy, we have determined the structure of the β-only complex of S. solfataricus TF55 complexes to 3.6–4.2 Å resolution and a filamentous form to 5.2 Å resolution. The structures of the TF55β complexes formed in the presence of ADP or ATP highlighted an open state in which nucleotide exchange can occur before progressing in the refolding cycle. The structure of the filamentous state indicates how helical protrusions facilitate end-on-end interactions. Synopsis The isolated complex and filamentous forms of TF55β chaperonin from the thermophilic archaea Sulfolobus solfataricus are reported. Using cryo-EM, nucleotide-bound complexes of TF55β at 3.6–4.2 Å resolution reveal an open conformation, while a 5.2 Å reconstruction of the filamentous chaperonin reveals contacts at the apical domain similar to crystal-packed structures.
Short hydrogen bonds enhance nonaromatic protein-related fluorescence

Significance Intrinsic fluorescence of nonaromatic amino acids is a puzzling phenomenon with an enormous potential in biophotonic applications. The physical origins of this effect, however, remain elusive. Herein, we demonstrate how specific hydrogen bond networks can modulate fluorescence. We highlight the key role played by short hydrogen bonds, present in the protein structure, on the ensuing fluorescence. We provide detailed experimental and molecular evidence to explain these unusual nonaromatic optical properties. Our findings should benefit the design of novel optically active biomaterials for applications in biosensing and imaging. Fluorescence in biological systems is usually associated with the presence of aromatic groups. Here, by employing a combined experimental and computational approach, we show that specific hydrogen bond networks can significantly affect fluorescence. In particular, we reveal that the single amino acid L-glutamine, by undergoing a chemical transformation leading to the formation of a short hydrogen bond, displays optical properties that are significantly enhanced compared with L-glutamine itself. Ab initio molecular dynamics simulations highlight that these short hydrogen bonds prevent the appearance of a conical intersection between the excited and the ground states and thereby significantly decrease nonradiative transition probabilities. Our findings open the door to the design of new photoactive materials with biophotonic applications.
TITLE: Novel polygenic risk score links depression-related cortical transcriptomic changes to brain morphology and symptom severity

Our group developed a transcriptome-based polygenic risk score (T-PRS) that uses common genetic variants to capture ‘depression-like’ shifts in cortical gene expression. Here, we mapped T-PRS onto diagnosis and symptom severity in major depressive disorder (MDD) cases and controls from the Psychiatric Genomics Consortium (PGC). To evaluate potential mechanisms, we further mapped T-PRS onto discrete measures of brain morphology and broad depression risk in healthy young adults. Genetic, self-report, and/or neuroimaging data were available in 29,340 PGC participants (59% women; 12,923 MDD cases, 16,417 controls) and 482 participants in the Duke Neurogenetics Study (DNS: 53% women; aged 19.8±1.2 years). T-PRS was computed from SNP data using PrediXcan to impute cortical expression levels of MDD-related genes from a previous post-mortem transcriptome meta-analysis. Sex-specific regressions were used to test effects of T-PRS on depression diagnosis, symptom severity, and Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index in the PGC and DNS samples, respectively. T-PRS did not predict depression diagnosis (OR=1.007, 95%CI=[0.997-1.018]); however, it correlated with symptom severity in men (rho=0.175, p=7.957x10 -4 ) in one large PGC cohort (N=762, 48% men). In DNS, T-PRS was associated with smaller amygdala volume in women (β=-0.186, t=-3.478, p=.001) and less prefrontal gyrification (max≤-2.970, p≤.006) in both sexes. In men, prefrontal gyrification mediated an indirect effect of T-PRS on broad depression risk (b=.005, p=.029), indexed using self-reported family history of depression. Depression-like shifts in cortical gene expression predict symptom severity in
The Genetic Architecture of Alzheimers Disease Risk: A Genomic Structural Equation Modelling Study

Background: Targeting modifiable risk factors may have a role in the prevention of Alzheimers disease. However, the mechanisms by which these risk factors influence Alzheimers risk remain incompletely understood. Genomic structural equation modelling can reveal patterns of shared genetic architecture that provide insight into the pathophysiology of complex traits. Methods: We identified genome-wide association studies for Alzheimers disease and its major modifiable risk factors: less education, hearing loss, hypertension, high alcohol intake, obesity, smoking, depression, social isolation, physical inactivity, type 2 diabetes, sleep disturbance and socioeconomic deprivation. We performed linkage disequilibrium score regression among these traits, followed by exploratory factor analysis, confirmatory factor analysis and structural equation modelling. Results: We identified complex networks of linkage disequilibrium among Alzheimers disease risk factors. The data were best explained by a bi-factor model, incorporating a Common Factor for Alzheimers risk, and three orthogonal sub-clusters of risk factors, which were validated across the two halves of the autosome. The first sub-cluster was characterised by risk factors related to sedentary lifestyle behaviours, the second by traits associated with reduced life expectancy and the third by traits that are possible prodromes of Alzheimers disease. Alzheimers disease was more genetically distinct and displayed minimal shared genetic architecture with its risk factors, which was robust to the exclusion of APOE. Conclusion: Shared genetic architecture may contribute to epidemiological associations between Alzheimers disease and its risk factors. Understanding the biology reflected by this communality may provide novel mechanistic insights that could help to prioritise targets for dementia prevention.
The Efficacy of Isoniazid Prophylaxis in Renal Transplant Recipients in a High TB Burden Country

Introduction: Renal transplant recipients are at high risk of tuberculosis (TB). We have started Isoniazid (INH) prophylaxis of 1-year duration in all renal transplant recipients from April 2009. Our aim is to assess the incidence of TB on INH prophylaxis and its tolerability. Methods: This was a retrospective observational study. The files of renal transplant recipients from April 2009 to December 2011 were reviewed till June 2015. We noted the incidence of TB, INH tolerability and development of resistance. We compared the incidence of TB with the historical controls who never received the prophylaxis. Results: A total of 910 patients were reviewed and followed for 4.8 years. INH prophylaxis was completed by 825 (91%) patients. A total of 46 patients (5%) developed active TB as compared to 15% in the historical controls. The median time of TB diagnosis from transplantation was 2.8 years. In the first-year post transplant, out of total TB cases, 52% occurred in the historical controls whereas 13% occurred in study cohort. Around 67% had TB > 2 years after transplant. Overall 1.43% had hepatotoxicity. There was a significant reduction in TB among those who completed prophylaxis to those who did not (p=0.02). Out of 14 cultures one isolate was INH resistant (7%). Conclusion: INH prophylaxis is well tolerated. The incidence of TB has decreased during the first 2 years. However there was a surge in TB cases 1 year after stopping INH therapy. We should consider prolonging the duration of INH prophylaxis in high TB burden countries in renal transplant recipients.
CADA: phenotype-driven gene prioritization based on a case-enriched knowledge graph

Many rare syndromes can be well described and delineated from other disorders by a combination of characteristic symptoms. These phenotypic features are best documented with terms of the human phenotype ontology (HPO), which is increasingly used in electronic health records (EHRs), too. Many algorithms that perform HPO-based gene prioritization have also been developed, however, the performance of many such tools suffers from an overrepresentation of atypical cases in the medical literature. This is certainly the case if the algorithm cannot handle features that occur with reduced frequency in a disorder. With CADA we built a knowledge-graph that is based on case annotations and disorder annotations and show that CADA exhibits superior performance particularly for patients that present with the pathognomonic findings of a disease. Crucial in the design of our approach is the use of the growing amount of phenotypic information that diagnostic labs deposit in databases such as ClinVar. By this means CADA is an ideal reference tool for differential diagnostics in rare disorders that can also be updated regularly.
UDVA : uncorrected distance visual acuity

24 Purpose: To evaluate the outcome of a web‐based digital assessment of visual acuity and refractive 25 error, compared to a manifest refraction assessment, in keratoconus patients with complex 26 refractive errors. 27 Material and methods: Keratoconus patients, aged 18 to 40, with a refractive error between ‐6 and 28 +4 diopters were eligible. Each participant subsequently underwent an uncorrected visual acuity and 29 a refractive assessment. Refractive error was assessed with the web‐based tool (index test), an 30 autorefractor, and a manifest refraction (reference test) by an optometrist. Corrected visual acuity 31 was assessed with the web‐based and manifest refractive prescription. Non‐inferiority was defined 32 as the 95% limits‐of‐agreement (95%LoA) of the differences in spherical equivalent between the 33 index and reference test not exceeding +/‐ 0.5 diopters. Agreement was assessed by an intraclass 34 correlation coefficient and Bland‐Altman analyses. 35 Results: A total of 100 eyes of 50 patients were examined. The overall mean difference of the 36 uncorrected visual acuity measured ‐0.01 LogMAR (95%LoA:‐0.63–0.60). The variability decreased in 37 the high uncorrected visual acuity subgroup (mean difference: 0.15 LogMAR, 95%LoA:‐0.25–0.55). 38 The intraclass correlation coefficient of the three refractive assessments was 0.32. The overall mean 39 difference in spherical equivalent between the index and reference test measured ‐0.58 diopters 40 (95%LoA:‐4.49 – 3.33, P=0.008). The mean differences for myopic and hyperopic subjects were 0.09 41 diopters (P=0.675) and ‐2.06 diopters (P<0.001), respectively. 42 Conclusions: Our results show promising results in the ability of the web‐based tool to remotely 43 assess visual acuity in keratoconus patients. The agreement is better in higher visual acuity ranges 44 and could provide physicians with an objective measurement to enhance teleconsultations, 45 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted March 2, 2021. ; https://doi.org/10.1101/2021.03. 01.21252664 doi: medRxiv preprint
Subcutaneous, Paracardiac, and Epicardial Fat CT Density Before/After Contrast Injection: Any Correlation with CAD?

Adipose tissue, in particular epicardial adipose tissue, has been identified as a potential biomarker of cardiovascular pathologies such as coronary artery disease (CAD) in the light of its metabolic activity and close anatomic and pathophysiologic relationship to the heart. Our purpose was to evaluate epicardial adipose tissue density at both unenhanced and contrast-enhanced computed tomography (CT), along with CT densities of paracardiac and subcutaneous adipose tissue, as well as the relations of such densities with CAD. We retrospectively reviewed patients who underwent cardiac CT at our institution for CAD assessment. We segmented regions of interest on epicardial, paracardiac, and subcutaneous adipose tissue on unenhanced and contrast-enhanced scans. A total of 480 patients were included, 164 of them presenting with CAD. Median epicardial adipose tissue density measured on contrast-enhanced scans (−81.5 HU; interquartile range −84.9 to −78.0) was higher than that measured on unenhanced scans (−73.4 HU; −76.9 to −69.4) (p < 0.001), whereas paracardiac and subcutaneous adipose tissue densities were not (p ≥ 0.055). Patients with or without CAD, did not show significant differences in density of epicardial, paracardiac, and subcutaneous adipose tissue either on unenhanced or contrast-enhanced scans (p ≥ 0.092). CAD patients may experience different phenomena (inflammation, fibrosis, increase in adipose depots) leading to rises or drops in epicardial adipose tissue density, resulting in variations that are difficult to detect.
Toxic Blood Hydrogen Cyanide Concentration as a Vital Sign of a Deceased Room Fire Victim—Case Report

Carbon monoxide (CO) and hydrogen cyanide (HCN) are two common toxic products of combustion. HCN concentrations of fire victims are not routinely determined in most legal medicine services in Romania. We present the case of a room fire victim in which we evaluated the concentrations of HCN and carboxyhemoglobin (COHb), their contribution to the mechanism of death, and the possibility that HCN concentration can be interpreted as vital sign. COHb was determined by spectrophotometry. HCN was spectrophotometrically determined with ninhydrin in postmortem blood samples after its removal with 20% phosphoric acid and uptake into a solution of potassium carbonate. The presence of ethyl alcohol was determined by gas chromatography. The COHb concentration was 6.15%, while the blood HCN concentration was 1.043 µg × mL−1 and the total HCN was 1.904 µg × ml−1. A blood alcohol content of 4.36 g‰ and a urine alcohol content of 5.88 g‰ were also found. Although the fire produced a considerable amount of soot, and there were signs of inhalation of soot particles, the COHb level cannot be interpreted as a vital sign. Toxic concentrations of HCN and total HCN can be interpreted as a vital sign and indicates a contributive effect of HCN in the mechanism of death.
Crystal structure and NMR investigation of the serine proteinase inhibitor MR889, a cyclic thiolic compound

The serine proteinase inhibitor N-(2-oxo-2,3,4,5-tetrahydro-3-thienyl)-2-(2-thenoylthio)propion-amide (MR889) has been crystallised, and its three-dimensional structure studied by X-ray diffraction and by NMR techniques in solution and in the solid state. MR889 crystallises in the monoclinic space group P21/n with cell constants a= 10.539(2), b= 9.647(5), c= 14.654(1)A, β= 101.62(1)°; the asymmetric unit contains one molecule of MR889. The weighted crystallographic R factor for the refined structure is 0.044. The solution structure of MR889 has been elucidated through the measurement of proton–proton and proton–carbon nuclear Overhauser enhancements. Measurement of the 13C longitudinal relaxation times yields information about the dynamics of MR889 in dimethylsulfoxide solution. The comparison between solid and solution state 13C NMR spectra allows an understanding of the quite different structures in the two states.