Miracle-dz/UniFAR-FTUs huggingface dataset:
Self-Adaptive Systems in Organic Computing: Strategies for Self-Improvement

With the intensified use of intelligent things, the demands on the technological systems are increasing permanently. A possible approach to meet the continuously changing challenges is to shift the system integration from design to run-time by using adaptive systems. Diverse adaptivity properties, so-called self-* properties, form the basis of these systems and one of the properties is self-improvement. It describes the ability of a system not only to adapt to a changing environment according to a predefined model, but also the capability to adapt the adaptation logic of the whole system. In this paper, a closer look is taken at the structure of self-adaptive systems. Additionally, the systems' ability to improve themselves during run-time is described from the perspective of Organic Computing. Furthermore, four different strategies for self-improvement are presented, following the taxonomy of self-adaptation suggested by Christian Krupitzer et al.
Bioconversion of p-Tyrosol into Hydroxytyrosol under Bench-Scale Fermentation

Tyrosol hydroxylating Pseudomonas strain was previously isolated from olive mill wastewaters-irrigated soil. In the present work, experimental design was used to study the bioconversion of tyrosol in laboratory fermenters aiming at the recovery of the highest yields of hydroxytyrosol. The effects of biocatalyst loading and tyrosol concentration were studied. The bioconversion yield reached 86.9% (37.3 mM hydroxytyrosol) starting from a tyrosol concentration of 43 mM. Under these conditions, the specific productivity relative to the biocatalyst was 4.78 μM/min/g. The established model to predict bioconversion yield was validated in two bench-scale fermenters. At the downstream stage, the reaction product was recovered as a hydroxytyrosol rich solution after microfiltration and concentration under vacuum. Subsequent to this operation, hydroxytyrosol composition yielded 73.8% of the total dry matter.
A Hybrid Recommender System for Patient-Doctor Matchmaking in Primary Care

We partner with a leading European healthcare provider and design a mechanism to match patients with family doctors in primary care. We define the matchmaking process for several distinct use cases given different levels of available information about patients. Then, we adopt a hybrid recommender system to present each patient a list of family doctor recommendations. In particular, we model patient trust of family doctors using a large-scale dataset of consultation histories, while accounting for the temporal dynamics of their relationships. Our proposed approach shows higher predictive accuracy than both a heuristic baseline and a collaborative filtering approach, and the proposed trust measure further improves model performance.
Analysis of medication therapy discontinuation orders in new electronic prescriptions and opportunities for implementing CancelRx

Abstract Objective To illustrate the need for wider implementation of the CancelRx message by quantifying and characterizing the inappropriate usage of new electronic prescription (NewRx) messages for communicating discontinuation instructions to pharmacies. Materials and Methods A retrospective analysis on a nationally representative random sample of 1 400 000 NewRx messages transmitted over 7 days to identify e-prescriptions containing medication discontinuation instructions in NewRx text fields. A vocabulary of search terms signifying cancellation instructions was formulated and then iteratively refined. True-positives were subsequently identified programmatically and through manual reviews. Two independent reviewers identified incidences in which these instructions were associated with high-alert or look-alike-sound-like (LASA) medications. Results We identified 9735 (0.7% of the total) NewRx messages containing prescription cancellation instructions with 78.5% observed in the Notes field; 35.3% of identified NewRxs were associated with high-alert or LASA medications. The most prevalent cancellation instruction types were medication strength or dosage changes (39.3%) and alternative therapy replacement orders (39.0%). Discussion While the incidence of prescribers using the NewRx to transmit cancellation instructions was low, their transmission in NewRx fields not intended to accommodate such information can produce significant potential patient safety concerns, such as duplicate or inaccurate therapies. These findings reveal the need for wider industry adoption of the CancelRx message by electronic health record (EHR) and pharmacy systems, along with clearer guidance and improved end-user training, particularly as states increasingly mandate electronic prescribing of controlled substances. Conclusion Encouraging the use of CancelRx and reducing the misuse of NewRx fields would reduce workflow disruptions and unnecessary risks to patient safety.
Pancreatic cancer circulating tumor cells: applications for personalized oncology

ABSTRACT Introduction: Pancreatic cancer (PC) is a highly lethal disease, in part because of early metastasis, late diagnosis, and limited treatment options. Circulating tumor cells (CTCs) are cancer cells that have achieved the metastatic step of intravasation, and are thus a unique source of biomarkers with potential applications in the staging, prognostication, and treatment of PC. Areas covered: This review describes the use of CTCs in PC, including isolation methods, the significance of CTC enumeration, and studies examining phenotypic and molecular characteristics of CTCs. We also speculate on future directions for PC CTC research such as single-cell analysis and CTC culture. Expert commentary: CTCs represent a potential unique serial source of cancer tissue via a convenient and minimally invasive blood draw. Recent development of isolation methods that allow for the release of viable CTCs with unaltered molecular characteristics has set the stage for single-cell analysis and ex vivo culture. Although there is significant potential for CTCs as a biomarker to impact PC from diagnosis to therapy, there still remain a number of challenges to the routine implementation of CTCs in the clinical management of PC.
A polymorphism rs3746444 within the pre‐miR‐499 alters the maturation of miR‐499‐5p and its antiapoptotic function

microRNAs (miRNAs) are non‐coding RNAs that function as post‐transcriptional regulators of cardiac development and cardiovascular diseases. Single nucleotide polymorphisms (SNPs) in miRNA genes are a novel class of genetic variations in the human genome that confer the risk of cardiovascular diseases. Here, we identified a polymorphism A→G (rs3746444) in miR‐499 precursor (pre‐miR‐499) that affects the maturation of miR‐499‐5p and alters its antiapoptotic function by converting stable A‐U base pair to wobble G‐U base pair in pre‐miR‐499 secondary structure. Furthermore, our results showed that the concentrations of plasma miR‐499‐5p could be correlated with myocardial infarction (MI) and heart failure (HF) patients in comparison with control subjects and polymorphism rs3746444 in miR‐499 could influence its abundance in plasma. Finally, our results also showed that the variant of polymorphism in miR‐499 influenced the severity of the myocardial infarction significantly. This is the first report to highlight the biological significance of this polymorphism on the maturation of miR‐499‐5p and its antiapoptotic role during MI. These findings may pave a way to better understand the individual variability based on miRNA SNPs in heart diseases and may contribute to better treatment for disease severity on a personalized level.
Assessing Theory of Mind by Humor: The Humor Comprehension and Appreciation Test (ToM-HCAT)

Theory of Mind (ToM) may be defined as the ability to understand the mental states, such as beliefs, desires, intentions, and emotions, of others. Impairment of ToM ability leads to disorders with pathologies in social skills, such as autism spectrum disorder and schizophrenia. In addition to differences in ToM ability among patient populations, there is variation between neurotypical individuals. Unfortunately, ToM tasks are usually developed for children or patients with cognitive disorders and cannot detect variations in healthy adults. As an alternative tool, humor may be used. Humor plays a role in social communication and requires many different cognitive functions. Humor is believed to represent complex high-order cognitive processes. There are numerous types of humor; the most complex type is considered ToM humor, where an understanding of social/emotional content is necessary. Given the need for a ToM assessment test suitable for healthy adult populations, we developed a test for measuring humor comprehension and appreciation, with and without ToM content (ToM-HCAT). The present ToM-HCAT test is a performance test consisting of cartoons. The test measures perceived funniness, reaction time to perceived funniness decision, and meaning inference. Cartoons were selected after pilot studies involving 44 participants. Subscales were constituted according to expert views and confirmed by confirmatory factor analysis (N = 135). Goodness of fit values for the final 35-item test were acceptable to excellent: GFI = 0.97; AGFI = 0.97; NFI = 0.97; RFI = 0.97, and SRMR = 0.067. Both categories were internally consistent (α1 = 0.84, α2 = 0.94). External validity was assessed against autistic traits. One hundred and three participants completed the Autism Spectrum Quotient and were grouped by +0.5 standard deviations from the mean as high in autistic traits. The meaning-inference scores of the subscale with the ToM cartoons were significantly lower (p = 0.034) for the high autistic traits group, providing evidence of external validity. In conclusion, we developed and validated a test for assessment of ToM by humor comprehension and appreciation. We believe that the present test will be useful for the detection of variations in ToM ability in the healthy adult population.
Psychedelics as anti-inflammatory agents

Abstract Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged as promising new treatment options for a variety of disorders. The recent success of these agonists, also known as psychedelics, like psilocybin for the treatment of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has ushered in a renaissance in the way these compounds are perceived in the medical community and populace at large. One emerging therapeutic area that holds significant promise is their use as anti-inflammatory agents. Activation of 5-HT2A receptors produces potent anti-inflammatory effects in animal models of human inflammatory disorders at sub-behavioural levels. This review discusses the role of the 5-HT2A receptor in the inflammatory response, as well as highlight studies using the 5-HT2A agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to treat inflammation in cellular and animal models. It also examines potential mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall, psychedelics regulate inflammatory pathways via novel mechanisms, and may represent a new and exciting treatment strategy for several inflammatory disorders.
Comprehensive comparative analysis of methods and software for identifying viral integrations

Many viruses are capable of integrating in the human genome, particularly viruses involved in tumorigenesis. Viral integrations can be considered genetic markers for discovering virus-caused cancers and inferring cancer cell development. Next-generation sequencing (NGS) technologies have been widely used to screen for viral integrations in cancer genomes, and a number of bioinformatics tools have been developed to detect viral integrations using NGS data. However, there has been no systematic comparison of the methods or software. In this study, we performed a comprehensive comparative analysis of the designs, performance, functionality and limitations among the existing methods and software for detecting viral integrations. We further compared the sensitivity, precision and runtime of integration detection of four representative tools. Our analyses showed that each of the existing software had its own merits; however, none of them were sufficient for parallel or accurate virome-wide detection. After carefully evaluating the limitations shared by the existing methods, we proposed strategies and directions for developing virome-wide integration detection.
The social structure of mortgage discrimination

Abstract In the decade leading up to the US housing crisis, black and Latino borrowers disproportionately received high-cost, high-risk mortgages—a lending disparity well documented by prior quantitative studies. We analyse qualitative data from actors in the lending industry to identify the social structure though which this mortgage discrimination took place. Our data consist of 220 depositions, declarations and related exhibits submitted by borrowers, loan originators, investment banks and others in fair lending cases. Our analyses reveal specific mechanisms through which loan originators identified and gained the trust of black and Latino borrowers in order to place them into higher cost, higher risk loans than similarly situated white borrowers. Loan originators sought out lists of individuals already borrowing money to buy consumer goods in predominantly black and Latino neighbourhoods to find potential borrowers, and exploited intermediaries within local social networks, such as community or religious leaders, to gain those borrowers’ trust.
Linkage disequilibrium maps to guide contig ordering for genome assembly

Motivation: Efforts to establish reference genome sequences by de novo sequence assembly have to address the difficulty of linking relatively short sequence contigs to form much larger chromosome assemblies. Efficient strategies are required to span gaps and establish contig order and relative orientation. We consider here the use of linkage disequilibrium (LD) maps of sequenced contigs and the utility of LD for ordering, orienting and positioning linked sequences. LD maps are readily constructed from population data and have at least an order of magnitude higher resolution than linkage maps providing the potential to resolve difficult areas in assemblies. We empirically evaluate a linkage disequilibrium map‐based method using single nucleotide polymorphism genotype data in a 216 kilobase region of human 6p21.3 from which three shorter contigs are formed. Results: LD map length is most informative about the correct order and orientation and is suggested by the shortest LD map where the residual error variance is close to one. For regions in strong LD this method may be less informative for correcting inverted contigs than for identifying correct contig orders. For positioning two contigs in linkage disequilibrium with each other the inter‐contig distances may be roughly estimated by this method. Availability and implementation: The LDMAP program is written in C for a linux platform and is available at https://www.soton. ac.uk/genomicinformatics/research/ld.page. Supplementary information: Supplementary data are available at Bioinformatics online.
A comparison between the Supreme laryngeal mask airway and the laryngeal tube suction during spontaneous ventilation: A randomized prospective study

Background and Aims: The Supreme laryngeal mask airway (SLMA) and the laryngeal tube suction-disposable (LTS-D), both second-generation supraglottic airway devices, have a record of efficiency when used for airway management in mechanically ventilated patients, during general anesthesia. There is no published data comparing these two devices in patients breathing spontaneously during general anesthesia. Material and Methods: Eighty patients with normal airways undergoing elective general anesthesia with spontaneous ventilation were randomized to airway management with a SLMA or LTS-D. Efficacy and adequacy of oxygenation and ventilation were compared. Results: No cases of desaturation of oxygen saturation (SpO2) values of less than 95% occurred with either device. The mean difference for SpO2 between the two devices (0.7%) has no clinical significance. Slight hypercapnia was noted with both devices to acceptable values during spontaneous ventilation. Conclusions: Both SLMA and LTS-D are suitable and effective for airway management in patients breathing spontaneously during general anesthesia for minor surgery of short duration.
High prevalence of hypervirulent Klebsiella pneumoniae infection in the genetic background of elderly patients in two teaching hospitals in China

Purpose Aerobactin is a critical factor for hypervirulent Klebsiella pneumoniae (hvKp) in genetic backgrounds, but data based on the genotype for the elderly is limited. Materials and methods A retrospective study was conducted on elderly patients from June 2008 to July 2017 in 2 teaching hospitals. The clinical and microbiological data, including antimicrobial susceptibility testing, string test, extended-spectrum β-lactamase (ESBL) production, virulence gene, and multilocus sequence typing, of the hvKp group defined as aerobactin positive were compared with those of classic K. pneumoniae isolates. Results A total of 45.7% of 202 K. pneumoniae isolates were hvKp.ST23, which were predominant in 2 hospitals, but they were not highly associated with hvKp in different hospitals. Hypermucoviscosity, K1, K2, magA, and rmpA/A2 genes were highly related to hvKp (P=0.000). With regard to the host, invasive infections (P=0.000), liver abscess (P=0.000), abdominal infection (P=0.000), pneumonia (P=0.037), and septic shock (P=0.045) were significantly higher in the elderly with hvKp. In the hvKp group, patients with better nutritional status were associated with a more severe sequential organ failure assessment score and a more serious inflammation reaction. Patients with diabetes (odds ratio [OR]=2.566) are more likely to be infected with hvKp. Previous hvKp is associated with hypermucoviscosity (OR=15.249) are often paralleled with hvKp. Importantly, 26% of hvKp isolates produced ESBLs, and most of them showed a carbapenems-resistant (CR) phenotype. Multivariate analysis implied that patients with a history of surgery within the last 1 month (OR=15.999) is an independent risk factor for CR-hvKp infection. Conclusion The prevalence of hvKP is high in the elderly. ESBL-hvKp, especially CR-hvKp, is emerging, which is a sign that clinical awareness and infection monitoring needs to improve.
EGCG Nanoparticles Attenuate Aluminum Chloride Induced Neurobehavioral Deficits, Beta Amyloid and Tau Pathology in a Rat Model of Alzheimer’s Disease

Rational: Alzheimer’s disease (AD) is a neurodegenerative pathology characterized by the presence of neuritic plaques and neurofibrillary tangles. Aluminum has been reported to play an important role in the etiology and pathogenesis of this disease. Hence, the present study aimed to evaluate the neuroprotective role of epigallocatechin-gallate (EGCG) loaded nanoparticles (nanoEGCG) against aluminum chloride (AlCl3) induced neurobehavioral and pathological changes in AD induced rats. Method: 100 mg/kg body weight AlCl3 was administered orally for 60 days, which was followed by 10 mg/kg body weight free EGCG and nanoEGCG treatment for 30 days. Morris water maze, open field and novel object recognition tests were employed for neurobehavioral assessment of the rats. This was followed by histopathological assessment of the cortex and the hippocampus in the rat brain. For further validation biochemical, immunohistochemistry and western blot assays were carried out. Result: Aluminum exposure reduced the exploratory and locomotor activities in open field and significantly reduced the memory and learning curve of rats in Morris water maze and novel object recognition tests. These neurobehavioral impairments were significantly attenuated in nanoEGCG treated rats. Histopathological assessment of the cortex and hippocampus of AlCl3 induced rat brains showed the presence of both neuritic plaques and neurofibrillary tangles. In nanoEGCG treated rats this pathology was absent. Significant increase in biochemical, immunohistochemical and protein levels was noted in AlCl3 induced rats. While these levels were greatly reduced in nanoEGCG treated rats. Conclusion: In conclusion, this study strengthens the hypothesis that EGCG nanoparticles can reverse memory loss, neuritic plaque and neurofibrillary tangles formation.
Phase I dose‐escalation trial of Sym004, an anti‐EGFR antibody mixture, in Japanese patients with advanced solid tumors

Sym004 is a 1:1 mixture of two antibodies targeting non‐overlapping epitopes of the epidermal growth factor receptor that antagonizes ligand binding and induces receptor downregulation. In preclinical models, it has superior antitumor activity to cetuximab and panitumumab. Japanese adults aged ≥20 years with an Eastern Cooperative Oncology Group status of 0/1 and life expectancy ≥3 months were eligible. Patients in Part A (dose escalation) had refractory or recurrent late‐stage solid tumors and received Sym004 6 mg/kg/wk (n = 3), 9 mg/kg loading/6 mg/kg/wk (n = 6), 12 mg/kg/wk (n = 6), or 18 mg/kg biweekly (n = 6). Patients in expansion Part B (n = 30) had esophageal squamous cell carcinoma and received Sym004 at the dose recommended from Part A. Fifty‐one patients received Sym004. No dose‐limiting toxicities were observed in Part A. A dose of 12 mg/kg/wk was selected for Part B. All patients in Part B experienced treatment‐related adverse events, most commonly dermatitis acneiform (76.7%). Eighteen grade ≥3 treatment‐related adverse events and five serious adverse events occurred (cardiac arrest, lung infection, interstitial lung disease, toxic skin eruption, blood creatinine increase). Two patients had treatment‐related adverse events resulting in death (cardiac arrest and blood creatinine increase). Five patients in Part B had a best overall response of partial response, 12 stable diseases and 12 disease progression (1 not evaluable). The objective response rate was 16.7% (95% CI: 5.6%‐34.7%). Sym004 therapy was well tolerated with no dose‐limiting toxicities at any dose studied. Evidence of antitumor activity was seen in patients with esophageal squamous cell carcinoma. ClinicalTrials.gov Identifier: NCT01955473.
Efficacy and tolerability of rituximab and reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy for elderly patient with diffuse large B-cell lymphoma

ABSTRACT Objectives: Chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone combined with rituximab (R-CHOP) is currently the first-line therapy for diffuse large B-cell lymphoma (DLBCL). However, management of elderly patients is challenging and often requires dose reductions or prolonged treatment intervals. We investigated the proper dose of R-CHOP for them. Methods: At our institute, for DLBCL patients aged 65–79 and ≥80 years, we had reduced CHOP dose to 5/6 and 7/12, respectively, and retrospectively evaluated the reduced-dose R-CHOP. Results: Although the median age in the standard, 5/6, and 7/12-dose groups was 57, 73, and 84 years, respectively (p < 0.001), the 3-year event-free survival (EFS) rate did not differ between the standard and 5/6-dose groups (60.2 and 56.7%); however, 7/12-dose group had significantly inferior survival (25.9%). When patients aged 60–80 were evaluated, no difference in EFS was observed between the standard and 5/6-dose groups using the same international prognostic index. The neutrophil nadir and the frequency of infection were comparable among the three dose groups. Discussion and Conclusions: Reduced-dose R-CHOP chemotherapy is a promising treatment for elderly patients with DLBCL in terms of efficacy and toxicity.