Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification by High-Throughput Real-Time PCR of 30 Major Circulating Listeria monocytogenes Clonal Complexes in Europe

Multilocus sequence typing (MLST) is the reference method for Listeria monocytogenes typing but is expensive and takes time to perform, from 3 to 5 days for laboratories that outsource sequencing. Thirty major MLST clonal complexes (CCs) are circulating in the food chain and are currently identifiable only by sequencing. ABSTRACT Listeria monocytogenes is a ubiquitous bacterium that causes a foodborne illness, listeriosis. Most strains can be classified into major clonal complexes (CCs) that account for the majority of outbreaks and sporadic cases in Europe. In addition to the 20 CCs known to account for the majority of human and animal clinical cases, 10 CCs are frequently reported in food production, thereby posing a serious challenge for the agrifood industry. Therefore, there is a need for a rapid and reliable method to identify these 30 major CCs. The high-throughput real-time PCR assay presented here provides accurate identification of these 30 CCs and eight genetic subdivisions within four CCs, splitting each CC into two distinct subpopulations, along with the molecular serogroup of a strain. Based on the BioMark high-throughput real-time PCR system, our assay analyzes 46 strains against 40 real-time PCR arrays in a single experiment. This European study (i) designed the assay from a broad panel of 3,342 L. monocytogenes genomes, (ii) tested its sensitivity and specificity on 597 sequenced strains collected from 24 European countries, and (iii) evaluated its performance in the typing of 526 strains collected during surveillance activities. The assay was then optimized for conventional multiplex real-time PCR for easy implementation in food laboratories. It has already been used for outbreak investigations. It represents a key tool for assisting food laboratories to establish strain relatedness with human clinical strains during outbreak investigations and for helping food business operators by improving their microbiological management plans. IMPORTANCE Multilocus sequence typing (MLST) is the reference method for Listeria monocytogenes typing but is expensive and takes time to perform, from 3 to 5 days for laboratories that outsource sequencing. Thirty major MLST clonal complexes (CCs) are circulating in the food chain and are currently identifiable only by sequencing. Therefore, there is a need for a rapid and reliable method to identify these CCs. The method presented here enables the rapid identification, by real-time PCR, of 30 CCs and eight genetic subdivisions within four CCs, splitting each CC into two distinct subpopulations. The assay was then optimized on different conventional multiplex real-time PCR systems for easy implementation in food laboratories. The two assays will be used for frontline identification of L. monocytogenes isolates prior to whole-genome sequencing. Such assays are of great interest for all food industry stakeholders and public agencies for tracking L. monocytogenes food contamination.
How does a family history of psychosis influence the risk of methamphetamine‐related psychotic symptoms: Evidence from longitudinal panel data

Abstract Aims To determine whether the risk of psychotic symptoms during weeks of methamphetamine use was dependent on, increased by, or independent of having a family history of psychosis. Design Secondary analysis of 13 contiguous 1‐week periods of data (1370 weeks). A risk modification framework was used to test each scenario. Setting Geelong, Wollongong and Melbourne, Australia. Participants Participants in a randomized controlled trial of treatment for methamphetamine dependence (n = 148) who did not have a primary psychotic disorder on enrolment. Measurements Psychotic symptoms in the previous week were defined as a score of 3+ on any of the Brief Psychiatric Rating Scale items of hallucinations, unusual thought content or suspiciousness. Any (vs no) methamphetamine use in the previous week was assessed using the Timeline Followback method. Self‐reported family history of psychosis was assessed using the Diagnostic Interview for Psychosis. Findings The risk of psychotic symptoms in the past week was independently associated with methamphetamine use in that week (relative risk [RR] = 2.3, 95% CI = 1.3–4.3) and with having a family history of psychosis (RR = 2.4, 95% CI = 0.9–7.0); the joint risk among participants with a family history of psychosis during weeks when they were using methamphetamine was large (RR = 4.0, 95% CI = 2.0–7.9). There was no significant interaction between a family history of psychosis and methamphetamine use in predicting psychotic symptoms (interaction RR = 0.7 95% CI = 0.3–1.8), but there was a small non‐significant excess risk due to the interaction (0.20 95% CI = −1.63 to 2.03). Conclusions Among people dependent on methamphetamine, the relative risk of psychotic symptoms during weeks of methamphetamine use does not appear to be dependent on, or increased by, having a family history of psychosis. However, a family history of psychosis does appear to be an independent risk factor that contributes to the absolute risk of psychotic symptoms in this population.
Artificial intelligence in medical device software and high-risk medical devices – a review of definitions, expert recommendations and regulatory initiatives

ABSTRACT Introduction Artificial intelligence (AI) encompasses a wide range of algorithms with risks when used to support decisions about diagnosis or treatment, so professional and regulatory bodies are recommending how they should be managed. Areas covered AI systems may qualify as standalone medical device software (MDSW) or be embedded within a medical device. Within the European Union (EU) AI software must undergo a conformity assessment procedure to be approved as a medical device. The draft EU Regulation on AI proposes rules that will apply across industry sectors, while for devices the Medical Device Regulation also applies. In the CORE-MD project (Coordinating Research and Evidence for Medical Devices), we have surveyed definitions and summarize initiatives made by professional consensus groups, regulators, and standardization bodies. Expert opinion The level of clinical evidence required should be determined according to each application and to legal and methodological factors that contribute to risk, including accountability, transparency, and interpretability. EU guidance for MDSW based on international recommendations does not yet describe the clinical evidence needed for medical AI software. Regulators, notified bodies, manufacturers, clinicians and patients would all benefit from common standards for the clinical evaluation of high-risk AI applications and transparency of their evidence and performance.
TRSRD: a database for research on risky substances in tea using natural language processing and knowledge graph-based techniques

Abstract During the production and processing of tea, harmful substances are often introduced. However, they have never been systematically integrated, and it is impossible to understand the harmful substances that may be introduced during tea production and their related relationships when searching for papers. To address these issues, a database on tea risk substances and their research relationships was constructed. These data were correlated by knowledge mapping techniques, and a Neo4j graph database centered on tea risk substance research was constructed, containing 4189 nodes and 9400 correlations (e.g. research category-PMID, risk substance category-PMID, and risk substance-PMID). This is the first knowledge-based graph database that is specifically designed for integrating and analyzing risk substances in tea and related research, containing nine main types of tea risk substances (including a comprehensive discussion of inclusion pollutants, heavy metals, pesticides, environmental pollutants, mycotoxins, microorganisms, radioactive isotopes, plant growth regulators, and others) and six types of tea research papers (including reviews, safety evaluations/risk assessments, prevention and control measures, detection methods, residual/pollution situations, and data analysis/data measurement). It is an essential reference for exploring the causes of the formation of risk substances in tea and the safety standards of tea in the future. Database URL http://trsrd.wpengxs. cn
Universal lab-on-a-chip platform for complex, perfused 3D cell cultures

The miniaturization, rapid prototyping and automation of lab-on-a-chip technology play nowadays a very important role. Lab-on-a-chip technology is successfully implemented not only for environmental analysis and medical diagnostics, but also as replacement of animals used for the testing of substances in the pharmaceutical and cosmetics industries. For that purpose the Fraunhofer IWS and partners developed a lab-on-a-chip platform for perfused cell-based assays in the last years, which includes different micropumps, valves, channels, reservoirs and customized cell culture modules. This technology is already implemented for the characterization of different human cell cultures and organoids, like skin, liver, endothelium, hair follicle and nephron. The advanced universal lab-on-a-chip platform for complex, perfused 3D cell cultures is divided into a multilayer basic chip with integrated micropump and application-specific 3D printed cell culture modules. Moreover a technology for surface modification of the printed cell culture modules by laser micro structuring and a complex and flexibly programmable controlling device based on an embedded Linux system was developed. A universal lab-on-a-chip platform with an optional oxygenator and a cell culture module for cubic scaffolds as well as first cell culture experiments within the cell culture device will be presented. The module is designed for direct interaction with robotic dispenser systems. This offers the opportunity to combine direct organ printing of cells and scaffolds with the microfluidic cell culture module. The characterization of the developed system was done by means of Micro-Particle Image Velocimetry (μPIV) and an optical oxygen measuring system.
Dynamacophore model for breast cancer estrogen receptor alpha as an effective lead generation screening technique

Abstract Regardless to overwhelming quantum of cancer research worldwide, there are few drugs on the market to treat disease conditions. This is owing to multiple process inferences of drug targets in integrated pathways for invasion, growth, and metastasis. Over the past years, the death rate due to breast cancer has been increasing, that set the stage for improved better treatment. Therefore, there is a persistent and vital demand for innovative development of drugs to treat breast cancer. Many studies have reported that more than 60% of breast cancers are Estrogen receptor-α (ERα)-positive tumours and a key transcription factor, Estrogen receptor-α (ERα) was believed to promote proliferation of breast cancer cells. In this study, 150 ns of molecular dynamics was performed for protein-ligand complex to retrieve the potential stable conformations. The most populated dynamics cluster of 4-Hydroxytamoxifen intact with active site amino acid was selected to generate dynamacophore model (dynamic pharmacophore). Further, internal model validation with AU-ROC values ∼0.93 indicate the best model to screen library. The refined hits are funnelled in pharmacokinetics/dynamics, CDOCKER molecular docking, MM-GBSA and density functional theory to identify the promising ERα ligand candidates. Communicated by Ramaswamy H. Sarma
Comparison of the accuracy of the Friedewald, Martin, and Sampson formulas to estimate very low levels of low-density lipoprotein cholesterol.

INTRODUCTION The Martin (MF) and Sampson (SF) formulas have shown greater accuracy for low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL compared to the Friedewald formula (FF); however, some disagreement is maintained. Non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) are alternatives to assessing cardiovascular risk in patients with very low LDL-C. The objective was to evaluate the accuracy of FF, MF, and SF formulas to estimate LDL-C < 70 mg/dL vs. directly measured LDL-C (LDLd-C) and to compare non-HDL-C and Apo-B levels between the groups of patients with concordant vs. discordant LDL-C. MATERIAL AND METHODS This was a prospective clinical study with measurements of lipid profile and LDLd-C in 214 patients with triglycerides < 400 mg/dL. For each formula, the estimated LDL-C was compared with the LDLd-C, and the correlation, the median difference, and the discordance rate were evaluated. Non-HDL-C and Apo-B levels were compared between the groups with concordant and discordant LDL-C. RESULTS The estimated LDL-C was < 70 mg/dL in 130 (60.7%) patients by FF, 109 (50.9%) by MF, and 113 (52.8%) by SF. The strongest correlation was found between LDLd-C and Sampson estimated LDL-C (LDLs-C) (R2 = 0.778), followed by Friedewald-estimated LDL-C (LDLf-C) (R2 = 0.680) and Martin estimated LDL-C (LDLm-C) (R2 = 0.652). Estimated LDL-C < 70 mg/dL was lower than LDLd-C, with the largest median absolute difference (25-75th) of -15 (-19 to -10) with FF. For estimated LDL-C < 70 mg/dL, the discordant rate was 43.8%, 38.1%, and 35.1%, reaching for 62.3%, 50.9%, and 50% when LDL-C < 55 mg/dL by FF, SF, and MF, respectively. Patients in the discordant group presented significantly higher levels of non-HDL-C and ApoB for all 3 formulas (p < 0.001). CONCLUSION FF was the most inaccurate formula to estimate very low LDL-C. Despite MF and SF showing better results, their frequency in underestimating LDL-C was still considerable. In patients with falsely low estimated LDL-C, apoB and non-HDL-C were significantly higher, reflecting its true high atherogenic burden.
Translational methods used for rendering special characteristics of Hebrew interrogatives in Karaim Bible translations

A szerző a cikkben a karaim bibliaforditasokban azt vizsgalja, milyen metodusokat hasznaltak a karaimok a heber Bibliaban levő, kulonleges funkcioval biro kerdőalakok forditasara.
Tradeoffs explain scaling, sex differences, and seasonal oscillations in the remarkable weapons of snapping shrimp (Alpheus spp.)

Evolutionary theory suggests that individuals should express costly traits at a magnitude that optimizes the trait bearer’s cost-benefit difference. Trait expression varies across a species because costs and benefits vary among individuals. For example, if large individuals pay lower costs than small individuals, then larger individuals should reach optimal cost-benefit differences at greater trait magnitudes. Using the cavitation-shooting weapons found in the big claws of male and female snapping shrimp, we test whether size- and sex-dependent expenditures explain scaling and sex differences in weapon size. We found that males and females from three snapping shrimp species (Alpheus heterochaelis, Alpheus angulosus, and Alpheus estuariensis) show patterns consistent with tradeoffs between weapon and abdomen size. For male A. heterochaelis, the species for which we had the greatest statistical power, smaller individuals showed steeper tradeoffs. Our extensive dataset in A. heterochaelis also included data about pairing, breeding season, and egg clutch size. Therefore, we could test for reproductive tradeoffs and benefits in this species. Female A. heterochaelis exhibited tradeoffs between weapon size and egg count, average egg volume, and total egg mass volume. For average egg volume, smaller females exhibited steeper tradeoffs. Furthermore, in males but not females, large weapons were positively correlated with the probability of being paired and the relative size of their pair mates. In conclusion, we identified size-dependent tradeoffs that could underlie reliable scaling of costly traits. Furthermore, weapons are especially beneficial to males and burdensome to females, which could explain why males have larger weapons than females.
Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival

Significance Gastric cancer is a clinically challenging disease with poor prognosis. Heparan sulfate proteoglycans (HSPGs) have emerged as key molecules in tumor progression and communication. However, the functional relevance of HSPGs during gastric cancer development remains poorly known. Here, we demonstrate that Syndecan 4 (SDC4) is highly expressed in intestinal subtype gastric tumors and associates with higher invasion and patient poor survival. We provide evidence that glycosylated-SDC4 is packed on extracellular vesicles (EVs) and impacts EV protein cargo, uptake by recipient cells and, importantly, defines the tropism of cancer EVs to the common metastatic sites of gastric cancer. Thus, our data uncover SDC4 potential as a therapeutic target in precision oncology for limiting gastric cancer invasion and communication routes.
Azole derivatives inhibit wildtype butyrylcholinesterase and its common mutants

Azoles, which have been used for antifungal chemotherapy for decades, have recently been of interest for their efficacy against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). There is little known about the potential of azoles against BChE, however there is none regarding their inhibitory effects against mutants of BChE. In the current study, an azole library of 1‐aryl‐2‐(1H‐imidazol‐1‐yl)ethanol/ethanone oxime esters were tested against AChE and BChE, which yielded derivates more potent than the positive control, galantamine, against both isoforms. Kinetic analyses were performed for wildtype and mutant (A328F and A328Y) inhibition for the two most potent BChE inhibitors, pivalic and 3‐bezoylpropanoic acid esters of 2‐(1H‐imidazol‐1‐yl)‐1‐(2‐naphthyl)ethanol, which were found to have great affinity to the wildtype and mutant BChE types with Ki values as low as 0.173 ± 0.012 µM. The compounds were identified to show linear competitive or mixed type inhibition. Molecular modeling confirmed these kinetic data and provided further insights regarding molecular basis of BChE inhibition by the active derivatives. Thus, current study suggests new azole derivatives with promising cholinesterase inhibitory effects and reveals the first set of information to promote our understanding for the inhibitory behavior of this class against the mutant BChE forms.
Ketamine for depression: a potential role in requests for Medical Aid in Dying?

Medical Aid in Dying (MAiD) is the act of a healthcare provider ending a patient’s life, at their request, due to unbearable suffering from a grievous and incurable disease. Access to MAiD has expanded in the last decade and, more recently, it has been made available for psychiatric illnesses in a few countries. Recent studies have found that such psychiatric requests are rapidly increasing and primarily involve mood disorders as the primary condition. Nevertheless, MAiD for psychiatric disorders is associated with significant controversy and debate, especially regarding the definition and determination of irremediability – that a given patient lacks any reasonable prospect for recovery. In this article, we report the case of a Canadian patient who was actively requesting Medical Assistance in Dying for severe and prolonged treatment-resistant depression until she experienced remarkable benefits from a course of intravenous ketamine infusions. To our knowledge, this is the first report of ketamine or any other intervention yielding remission in a patient who would have otherwise likely been eligible for MAiD for depression. We discuss implications for the evaluation of similar requests and, more specifically, why a trial of ketamine warrants consideration.
The prognostic impact of IKZF1 deletions and UKALL genetic classifiers in paediatric B‐cell precursor acute lymphoblastic leukaemia treated according to NOPHO 2008 protocols

We investigated 390 paediatric B‐cell precursor acute lymphoblastic leukaemia (BCP‐ALL) patients treated according to NOPHO ALL 2008, regarding copy number alterations (CNA) of eight loci associated with adverse prognosis, including IKZF1. The impact on outcome was investigated for each locus individually, combined as CNA profiles and together with cytogenetic information. The presence of IKZF1 deletion or a poor‐risk CNA profile was associated with poor outcome in the whole cohort. In the standard‐risk group, IKZF1‐deleted cases had an inferior probability of relapse‐free survival (pRFS) (p ≤ 0.001) and overall survival (pOS) (p ≤ 0.001). Additionally, among B‐other patients, IKZF1 deletion correlated with poor pRFS (60% vs. 90%) and pOS (65% vs. 89%). Both IKZF1 deletion and a poor‐risk CNA profile were independent factors for relapse and death in multivariable analyses adjusting for known risk factors including measurable residual disease. Our data indicate that BCP‐ALL patients with high‐risk CNA or IKZF1 deletion have worse prognosis despite otherwise low‐risk features. Conversely, patients with both a good CNA and cytogenetic profile had a superior relapse‐free (p ≤ 0.001) and overall survival (p ≤ 0.001) in the cohort, across all risk groups. Taken together, our findings highlight the potential of CNA assessment to refine stratification in ALL.
Recombinant production of a diffusible signal factor inhibits Salmonella invasion and animal carriage

ABSTRACT The complex chemical environment of the intestine is defined largely by the metabolic products of the resident microbiota. Enteric pathogens, elegantly evolved to thrive in the gut, use these chemical products as signals to recognize specific niches and to promote their survival and virulence. Our previous work has shown that a specific class of quorum-sensing molecules found within the gut, termed diffusible signal factors (DSF), signals the repression of Salmonella tissue invasion, thus defining a means by which this pathogen recognizes its location and modulates virulence to optimize its survival. Here, we determined whether the recombinant production of a DSF could reduce Salmonella virulence in vitro and in vivo. We found that the most potent repressor of Salmonella invasion, cis-2-hexadecenoic acid (c2-HDA), could be recombinantly produced in E. coli by the addition of a single exogenous gene encoding a fatty acid enoyl-CoA dehydratase/thioesterase and that co-culture of the recombinant strain with Salmonella potently inhibited tissue invasion by repressing Salmonella genes required for this essential virulence function. Using the well characterized E. coli Nissle 1917 strain and a chicken infection model, we found that the recombinant DSF-producing strain could be stably maintained in the large intestine. Further, challenge studies demonstrated that this recombinant organism could significantly reduce Salmonella colonization of the cecum, the site of carriage in this animal species. These findings thus describe a plausible means by which Salmonella virulence may be affected in animals by in situ chemical manipulation of functions essential for colonization and virulence. Plain Language Summary Despite our best efforts, infections of agricultural animals with Salmonella persist, posing threats to food safety. Few, if any, measures have proven effective in reducing Salmonella carriage in animals used for food, a major source of this pathogen. Antibiotics are ineffective at curtailing infection and have served only to exacerbate the global crisis of antimicrobial resistance. The alternative then is to seek novel means to reduce Salmonella disease and carriage by preventing its colonization of livestock and poultry. Here we describe an approach targeting invasion, a function essential for Salmonella carriage and disease in animals. We show that a potent chemical inhibitor of invasion, the diffusible signal factor cis-2 hexadecenoic acid, can be produced by recombinant E. coli strains capable of stably colonizing the animal intestine, providing a means to directly affect the virulence of Salmonella within an animal host. These studies may thus provide a route to reduce the carriage of this pathogen in production animals and thus the spread of disease to humans.