Miracle-dz/UniFAR-FTUs huggingface dataset:
Chronic Upregulation of Cleaved-Caspase-3 Associated with Chronic Myelin Pathology and Microvascular Reorganization in the Thalamus after Traumatic Brain Injury in Rats

Traumatic brain injury (TBI) is associated with long-term disabilities and devastating chronic neurological complications including problems with cognition, motor function, sensory processing, as well as behavioral deficits and mental health problems such as anxiety, depression, personality change and social unsuitability. Clinical data suggest that disruption of the thalamo-cortical system including anatomical and metabolic changes in the thalamus following TBI might be responsible for some chronic neurological deficits following brain trauma. Detailed mechanisms of these pathological processes are not completely understood. The goal of this study was to evaluate changes in the thalamus following TBI focusing on cleaved-caspase-3, a specific effector of caspase pathway activation and myelin and microvascular pathologies using immuno- and histochemistry at different time points from 24 h to 3 months after controlled cortical impact (CCI) in adult Sprague-Dawley rats. Significant increases in cleaved-caspase-3 immunoreactivity in the thalamus were observed starting one month and persisting for at least three months following experimental TBI. Further, the study demonstrated an association of cleaved-caspase-3 with the demyelination of neuronal processes and tissue degeneration in the gray matter in the thalamus, as reflected in alterations of myelinated fiber integrity (luxol fast blue) and decreases in myelin basic protein (MBP) immunoreactivity. The immunofluorescent counterstaining of cleaved-caspase-3 with endothelial barrier antigen (EBA), a marker of blood-brain barrier, revealed limited direct and indirect associations of cleaved caspase-3 with blood-brain barrier damage. These results demonstrate for the first time a significant chronic upregulation of cleaved-caspase-3 in selected thalamic regions associated with cortical regions directly affected by CCI injury. Further, our study is also the first to report that significant upregulation of cleaved-caspase-3 in selected ipsilateral thalamic regions is associated with microvascular reorganization reflected in the significant increases in the number of microvessels with blood-brain barrier alterations detected by EBA staining. These findings provide new insights into potential mechanisms of TBI cell death involving chronic activation of caspase-3 associated with disrupted cortico-thalamic and thalamo-cortical connectivity. Moreover, this study offers the initial evidence that this upregulation of activated caspase-3, delayed degeneration of myelinated nerve fibers and microvascular reorganization with impaired blood-brain barrier integrity in the thalamus might represent reciprocal pathological processes affecting neuronal networks and brain function at the chronic stages of TBI.
Impact of Antiretroviral Drugs on Fracture Risk in HIV-Infected Individuals: A Case–Control Study Nested Within the French Hospital Database on HIV (FHDH-ANRS CO4)

Background: HIV-infected patients have lower bone mineral density and a higher incidence of fractures than the general population of the same age and sex. To assess the impact of antiretroviral (ARV) drugs exposure on the risk of osteoporotic fractures, we conducted a nested case–control study. Methods: Cases were individuals enrolled while ARV-naive, with a first prospectively recorded fracture between 2000 and 2010. Controls were randomly selected after matching for sex, age (±3 years), period of HIV diagnosis (<1997/≥1997), and clinical center. The risk of fracture was analyzed with conditional logistic regression models, using different ways to model ARV exposure. All exposure variables and potential confounders were included in multivariable models. Results: Among 861 reviewed cases, 261 fractures were osteoporotic and 254 of cases were matched to at least one control (376 controls). The median year of fracture diagnosis was 2007 (interquartile range 2004–2009): 49% of patients had been exposed to tenofovir disoproxil fumarate (TDF) and 82% to protease inhibitors (PIs). After taking into account the transmission group, AIDS status, geographic origin, body mass index, current smoking status, alcohol consumption, exposure to systemic glucocorticoids, and the period of enrollment, there was no association between the risk of fracture and exposure to TDF [odds ratio for cumulative exposure: 1.04 (0.86–1.27), similar results for ever-exposed subjects], to nucleoside reverse transcriptase inhibitors, or to PIs [odds ratio for cumulative PI exposure: 1.02 (0.92–1.12)]. Conclusions: We found no evidence of an excess risk of fracture after exposure to TDF or PIs. This has important implications for the debate concerning tenofovir alafenamide versus generic TDF.
Better Outcomes Among HIV-Infected Rwandan Children 18–60 Months of Age After the Implementation of “Treat All”

Background: In 2012, Rwanda introduced a Treat All approach for HIV-infected children younger than 5 years. We compared antiretroviral therapy (ART) initiation, outcomes, and retention, before and after this change. Methods: We conducted a retrospective study of children enrolled into care between June 2009 and December 2011 [Before Treat All (BTA) cohort] and between July 2012 and April 2015 [Treat All (TA) cohort]. Setting: Medical records of a nationally representative sample were abstracted for all eligible aged 18–60 months from 100 Rwandan public health facilities. Results: We abstracted 374 medical records: 227 in the BTA and 147 in the TA cohorts. Mean (SD) age at enrollment was [3 years (1.1)]. Among BTA, 59% initiated ART within 1 year, vs. 89% in the TA cohort. Median time to ART initiation was 68 days (interquartile range 14–494) for BTA and 9 days (interquartile range 0–28) for TA (P < 0.0001), with 9 (5%) undergoing same-day initiation in BTA compared with 50 (37%) in TA (P < 0.0001). Before ART initiation, 59% in the BTA reported at least one health condition compared with 35% in the TA cohort (P < 0.0001). Although overall loss to follow-up was similar between cohorts (BTA: 13%, TA: 8%, P = 0.18), loss to follow-up before ART was significantly higher in the BTA (8%) compared with the TA cohort (2%) (P = 0.02). Conclusions: Nearly 90% of Rwandan children started on ART within 1 year of enrollment, most within 1 month, with greater than 90% retention after implementation of TA. TA was also associated with fewer morbidities.
Distributional Semantic Features as Semantic Primitives - Or Not

Copyright c © 2015, Association for the Advancement of Artificial Intelligence (www.aaai.org). All rights reserved. abandoned in AI, the problems that primitive-based knowledge representations were meant to address remain challenging. For that reason, we think it makes sense to use primitivebased approaches as a point of comparison to shed light on a currently popular approach to computationally representing word and phrase meaning: distributional semantics.
Dental Implant Placement in Patients on Bisphosphonate Therapy: a Systematic Review

ABSTRACT Objectives The review aims to study dental implant placement purposefulness for patients who have been treated or are on treatment with bisphosphonate medication. Material and Methods Structured search strategy was applied on electronic databases: MEDLINE, PubMed, PubMed Central and ResearchGate. Scientific publications in English between 2006 and 2017 were identified in accordance with inclusion, exclusion criteria. Publication screening, data extraction, and quality assessment were performed. Outcome measures included implant failure or implant-related osteonecrosis of the jaw. Results In total, 32 literature sources were reviewed, and 9 of the most relevant articles that are suitable to the criteria were selected. Heterogeneity between the studies was found and no meta-analysis could be done. Five studies analysed intraoral bisphosphonate medication in relation with implant placement, three studies investigated intravenous bisphosphonate medication in relation with implant placement and one study evaluated both types of medication given in relation with implant placement. Patients with intraoral therapy appeared to have a better implant survival (5 implants failed out of 423) rate at 98.8% vs. patients treated intravenously (6 implants failed out of 68) at 91%; the control group compared with intraoral bisphosphonate group appeared with 97% success implant survival rate (27 implants failed out of 842), showing no significant difference in terms of success in implant placement. Conclusions Patients treated with intravenous bisphosphonates seemed to have a higher chance of developing implant-related osteonecrosis of the jaw. The intraorally treated patient group appeared to have more successful results. Implant placement in patients treated intraorally could be considered safe with precautions.
Development of an Improved Carotenoid Extraction Method to Characterize the Carotenoid Composition under Oxidative Stress and Cold Temperature in the Rock Inhabiting Fungus Knufia petricola A95

Black yeasts are a highly specified group of fungi, which are characterized by a high resistance against stress factors. There are several factors enabling the cells to survive harsh environmental conditions. One aspect is the pigmentation, the melanin black yeasts often display a highly diverse carotenoid spectrum. Determination and characterization of carotenoids depend on an efficient extraction and separation, especially for black yeast, which is characterized by thick cell walls. Therefore, specific protocols are needed to ensure reliable analyses regarding stress responses in these fungi. Here we present both. First, we present a method to extract and analyze carotenoids and secondly we present the unusual carotenoid composition of the black yeast Knufia petricola A95. Mechanical treatment combined with an acetonitrile extraction gave us very good extraction rates with a high reproducibility. The presented extraction and elution protocol separates the main carotenoids (7) in K. petricola A95 and can be extended for the detection of additional carotenoids in other species. K. petricola A95 displays an unusual carotenoid composition, with mainly didehydrolycopene, torulene, and lycopene. The pigment composition varied in dependency to oxidative stress but remained relatively constant if the cells were cultivated under low temperature. Future experiments have to be carried out to determine if didehydrolycopene functions as a protective agent itself or if it serves as a precursor for antioxidative pigments like torulene and torularhodin, which could be produced after induction under stress conditions. Black yeasts are a promising source for carotenoid production and other substances. To unravel the potential of these fungi, new methods and studies are needed. The established protocol allows the determination of carotenoid composition in black yeasts.
Social Disadvantage, Maternal Psychological Distress, and Difficulties in Children’s Social-Emotional Well-Being

This study used data from wave four of the United Kingdom (U.K.) Millennium Cohort Study to examine whether there is an individual (i.e., maternal education) and area-level social disadvantage (i.e., neighborhood deprivation) gradient to difficulties in social-emotional well-being (SEW) in 7-year-old English children. We then investigated to what extent maternal psychological distress (Kessler 6 score) explains the relationship between social disadvantage indicators and boys’ and girls’ SEW difficulties. Subjects consisted of 3661 child–mother dyads (1804 boys and 1857 girls). Results discerned gender differences in the effect social disadvantage indicators have on child SEW difficulties. Maternal education had a comparable effect on boys’ and girls’ SEW difficulties, but a steeper neighborhood deprivation gradient was evident for boys’ SEW difficulties compared to girls’ SEW difficulties. The effect of each social disadvantage indicator on boys’ and girls’ SEW difficulties was for most part direct and strong (p ≤ 0.001) rather than through maternal psychological distress, suggesting that the theoretical framework was incomplete. Here we demonstrate that where children are positioned on the social disadvantage gradient matters greatly to their SEW. Improving the living conditions and health of mothers with psychological distress may offer a pathway to improve child SEW.
Update on global epidemiology of viral hepatitis and preventive strategies

Viral hepatitis is one of the major public health concerns around the world but until recently it has drawn little attention or funding from global health policymakers. Every year 1.4 million people die from viral hepatitis-related cirrhosis and liver cancer. However, the majority of the infected population are unaware of their condition. This population have significant obstacles to overcome such as lack of awareness, vulnerability, increased migration, disease stigma, discrimination, as well as poor health resources, conflict in policy development and program implementation. Despite implementing infection control measures over the last few decades eradication or significant disease reduction remains elusive. This study aims to present the current global prevalence status and examines potential elimination strategies. The information for this research were obtained through a systematic review, published scientific literatures, the official websites of various government organisations, international public health organisations and internationally recognised regulatory bodies over a period of 40 years between 1978 and 2018.
Anti-anthropomorphism and Its Limits

There is a diffuse sentiment that to anthropomorphize is a mild vice that people tend to do easily and pleasingly, but that an adult well educated person should avoid. In this paper it will be provided an elucidation of “anthropomorphism” in the field of common sense knowledge, the issue of animal rights, and about the use of humans as a model in the scientific explanation. It will be argued for a “constructive anthropomorphism,” i.e., the idea that anthropomorphism is a natural attitude to attribute human psychological features to other individuals, no matter they are actually rational agents, or not. If we know the “grammar” of this attitude, we can avoid the risks in overestimatinasg the environmental inputs toward anthropomor-phism and, at the same time, take the heuristic advantages of anthropomor-phism in the use of human mind as a model for both everyday circumstances and scientific enterprise.
A Recipe for State Dependent Distributed Delay Differential Equations

We use the McKendrick equation with variable ageing rate and randomly distributed maturation time to derive a state dependent distributed delay differential equation. We show that the resulting delay differential equation preserves non-negativity of initial conditions and we characterise local stability of equilibria. By specifying the distribution of maturation age, we recover state dependent discrete, uniform and gamma distributed delay differential equations. We show how to reduce the uniform case to a system of state dependent discrete delay equations and the gamma distributed case to a system of ordinary differential equations. To illustrate the benefits of these reductions, we convert previously published transit compartment models into equivalent distributed delay differential equations.
The Impact of the Opioid Antagonist Naloxone on Experimentally Induced Craving in Nicotine-Dependent Individuals

Objective: Preclinical and clinical findings suggest a substantial association of the endogenous opioid system in nicotine dependence. The present study investigates the possible dose-dependent influence of naloxone, an unspecific opioid-receptor-antagonist, combined with cue exposure on the physiological state, locomotor activity, craving and the hypothalamic-pituitary-adrenal axis in nicotine-dependent humans. Methods: Twenty nicotine-dependent, outpatient participants were deprived of nicotine for over 4 h, before receiving challenges with naloxone (1.6 mg or 3.2 mg q70 kg IV) or the placebo. Additionally, following drug administration, either smoking-related cues or neutral images were presented. Nicotine withdrawal was monitored by evaluating the following objective signs – skin conductance, heart rate, temperature, respiration, locomotor activity, cortisol, prolactin and ACTH levels as well as craving. Results: With respect to subjective effects, participants administered a higher dosage of naloxone and those who were shown smoking-related cues were significantly less pleased (p = 0.019), felt more depressed (p = 0.033) and thought smoking would make them feel better (p = 0.028) than participants given naloxone and shown neutral cues. Participants given no naloxone but with smoking-related cues felt a higher urge to smoke than participants given naloxone and shown neutral cues (p = 0.042). Naloxone – in both dosages – also decreased the desire and intention to smoke in comparison to placebo. Compared to the placebo group, significantly higher cortisol, prolactin and ACTH values were observed after administration of lower and higher dosage of naloxone followed by smoking-related cues. Conclusion: Naloxone influenced nicotine withdrawal and strengthened significantly by cue exposure, both on objective measurement and on craving scales. These findings suggest an involvement of the endogenous opioid system in the development and maintenance of nicotine dependence.
Multimodal imaging of the receptor for advanced glycation end-products with molecularly targeted nanoparticles

The receptor for advanced glycation end-products (RAGE) is central to multiple disease states, including diabetes-related conditions such as peripheral arterial disease (PAD). Despite RAGE's importance in these pathologies, there remains a need for a molecular imaging agent that can accurately assess RAGE levels in vivo. Therefore, we have developed a multimodal nanoparticle-based imaging agent targeted at RAGE with the well-characterized RAGE ligand, carboxymethyllysine (CML)-modified human serum albumin (HSA). Methods: A multimodal tracer (64Cu-Rho-G4-CML) was developed using a generation-4 (G4) polyamidoamine (PAMAM) dendrimer, conjugated with both rhodamine and copper-64 (64Cu) chelator (NOTA) for optical and PET imaging, respectively. First, 64Cu-Rho-G4-CML and its non-targeted analogue (64Cu-Rho-G4-HSA) were evaluated chemically using techniques such as dynamic light scattering (DLS), electron microscopy and nuclear magnetic resonance (NMR). The tracers' binding capabilities were examined at the cellular level and optimized using live and fixed HUVEC cells grown in 5.5-30 mM glucose, followed by in vivo PET-CT imaging, where the probes' kinetics, biodistribution, and RAGE targeting properties were examined in a murine model of hindlimb ischemia. Finally, histological assessment of RAGE levels in both ischemic and non-ischemic tissues was performed. Conclusions: Our RAGE-targeted probe demonstrated an average size of 450 nm, a Kd of 340-390 nM, rapid blood clearance, and a 3.4 times greater PET uptake in ischemic RAGE-expressing hindlimbs than their non-ischemic counterpart. We successfully demonstrated increased RAGE expression in a murine model of hindlimb ischemia and the feasibility for non-invasive examination of cellular, tissue, and whole-body RAGE levels with a molecularly targeted tracer.
RFID and the Internet of Things: Technology, Applications, and Security Challenges

Radio Frequency Identification (RFID) has started to exert a major influence on modern supply chain management. In manufacturing, RFID changes the way objects are tracked on the shop floor and how manufactured goods interact with the production environment. In logistics, RFID is used to track and trace pallets or individual objects on a global scale. In retail, RFID is used to identify objects, retrieve related information, and prevent theft. Sometimes the tags remain attached to the objects post-sale, thus facilitating additional services. Overall, enterprises have much more detailed information about the objects: the use and produce, their location, their trajectories, and their physical state.
High-Throughput Stability Screening of Neoantigen/HLA Complexes Improves Immunogenicity Predictions

Using a rapid, high-throughput method, peptide/HLA thermal stability was determined for a variety of peptides and peptide variants. This approach allows for predicting neoantigens that can best serve as targets for a robust T-cell response against cancer. Mutated peptides (neoantigens) from a patient's cancer genome can serve as targets for T-cell immunity, but identifying which peptides can be presented by an MHC molecule and elicit T cells has been difficult. Although algorithms that predict MHC binding exist, they are not yet able to distinguish experimental differences in half-lives of the complexes (an immunologically relevant parameter, referred to here as kinetic stability). Improvement in determining actual neoantigen peptide/MHC stability could be important, as only a small fraction of peptides in most current vaccines are capable of eliciting CD8+ T-cell responses. Here, we used a rapid, high-throughput method to experimentally determine peptide/HLA thermal stability on a scale that will be necessary for analysis of neoantigens from thousands of patients. The method combined the use of UV-cleavable peptide/HLA class I complexes and differential scanning fluorimetry to determine the Tm values of neoantigen complexes. Measured Tm values were accurate and reproducible and were directly proportional to the half-lives of the complexes. Analysis of known HLA-A2–restricted immunogenic peptides showed that Tm values better correlated with immunogenicity than algorithm-predicted binding affinities. We propose that temperature stability information can be used as a guide for the selection of neoantigens in cancer vaccines in order to focus attention on those mutated peptides with the highest probability of being expressed on the cell surface.
Automated Glycan Assembly of Plant Oligosaccharides and Their Application in Cell‐Wall Biology

The plant cell wall provides the richest available resource of fermentable carbohydrates and biobased materials. The main component of plant cell walls is cellulose, which is the most abundant biomolecule on earth. Apart from cellulose, which is constructed from relatively simple β‐1,4‐glucan chains, plant cell walls also contain structurally more complex heteropolysaccharides (hemicellulose and pectin), as well as lignin and cell‐wall proteins. A detailed understanding of the molecular structures, functions, and biosyntheses of cell‐wall components is required to further promote their industrial use. Plant cell‐wall research is, to a large degree, hampered by a lsack of available well‐defined oligosaccharide samples that represent the structural features of cell‐wall glycans. One technique to access these oligosaccharides is automated glycan assembly; a technique in which monosaccharide building blocks are, similarly to automated peptide and oligonucleotide chemistry, successively added to a linker‐functionalized resin in a fully automated manner. Herein, recent research into the automated glycan assembly of different classes of cell‐wall glycans used as molecular tools for cell‐wall biology is discussed. More than 60 synthetic oligosaccharides were prepared and printed as microarrays for screening monoclonal antibodies that recognize plant cell‐wall polysaccharides. The synthesized oligosaccharides have also been used to investigate glycosyltransferases and glycoside hydrolases, which are involved in synthesis and degradation of plant cell walls, as well as for the analysis of cell‐wall‐remodeling enzymes.