Miracle-dz/UniFAR-FTUs huggingface dataset:
Sepsis: A Threat That Needs a Global Solution.

When Martin Luther King stated in 1966 that of all the forms of inequality, injustice in healthcare was the most shocking and inhumane, those in the incipient critical care field were not yet discussing the controversies surrounding the definition of sepsis, even though sepsis was already killing millions of people worldwide. He certainly did not perceive that his sentence fitted this deadly disease perfectly. Nonetheless, his quote remains lamentably contemporary, as sepsis is still killing millions. The reasons are profoundly entangled with the disparities not only in healthcare but also, more broadly speaking, in general health. Accordingly, an urgently needed global solution will require actions aiming to reduce inequalities, ranging from preventative measures to early recognition and the provision of fair treatment to all those who are at risk, in other words, everyone.
The management and treatment of acute leukemias in the elderly population

ABSTRACT Introduction: Treatment of elderly patients with acute leukemia is challenging. Older age is associated with increased risk of treatment-related toxicity. Currently, no consensus exists regarding optimal therapy in this patient population. Areas covered: The following review is a comprehensive summary of various therapeutic options reported over the past few years in elderly patients with acute leukemia. Expert commentary: While evidences can guide identification of frail older patients, sensitive assessment strategies are required to identify fit and vulnerable patients regardless of chronologic age. Individualized treatments may take into account not only an increase in survival, but also the maintenance or improvement in terms of quality of life, the management of symptoms, and a maximization of time outside of hospital care. In this setting, comprehensive geriatric assessments have been shown to improve routine assessment. Molecular abnormalities provide the genomic footprint for the development of targeted therapies. The addition of new monoclonal antibodies to conventional treatments also demonstrated promising primary results. Ongoing clinical trials testing the activity of these new agents may reshape treatment strategies in the elderly patient population.
Some simple but challenging Markov processes

In this note, we present few examples of Piecewise Deterministic Markov Processes and their long time behavior. They share two important features: they are related to concrete models (in biology, networks, chemistry,. . .) and they are mathematically rich. Their math-ematical study relies on coupling method, spectral decomposition, PDE technics, functional inequalities. We also relate these simple examples to recent and open problems.
Loss of RASGRP1 in humans impairs T‐cell expansion leading to Epstein‐Barr virus susceptibility

Inherited CTPS1, CD27, and CD70 deficiencies in humans have revealed key factors of T‐lymphocyte expansion, a critical prerequisite for an efficient immunity to Epstein–Barr virus (EBV) infection. RASGRP1 is a T‐lymphocyte‐specific nucleotide exchange factor known to activate the pathway of MAP kinases (MAPK). A deleterious homozygous mutation in RASGRP1 leading to the loss RASGRP1 expression was identified in two siblings who both developed a persistent EBV infection leading to Hodgkin lymphoma. RASGRP1‐deficient T cells exhibited defective MAPK activation and impaired proliferation that was restored by expression of wild‐type RASGRP1. Similar defects were observed in T cells from healthy individuals when RASGRP1 was downregulated. RASGRP1‐deficient T cells also exhibited decreased CD27‐dependent proliferation toward CD70‐expressing EBV‐transformed B cells, a crucial pathway required for expansion of antigen‐specific T cells during anti‐EBV immunity. Furthermore, RASGRP1‐deficient T cells failed to upregulate CTPS1, an important enzyme involved in DNA synthesis. These results show that RASGRP1 deficiency leads to susceptibility to EBV infection and demonstrate the key role of RASGRP1 at the crossroad of pathways required for the expansion of activated T lymphocytes.
Digital Presence of Norwegian Scholars on Academic Network Sites—Where and Who Are They?

The use of academic profiling sites is becoming more common, and emerging technologies boost researchers’ visibility and exchange of ideas. In our study we compared profiles at five different profiling sites. These five sites are ResearchGate, Academia.edu, Google Scholar Citations, ResearcherID and ORCID. The data set is enriched by demographic information including age, gender, position and affiliation, which are provided by the national CRIS-system in Norway. We find that approximately 37% of researchers at the University of Bergen have at least one profile, the prevalence being highest (> 40%) for members at the Faculty of Psychology and the Faculty of Social Sciences. Across all disciplines, ResearchGate is the most widely used platform. However, within Faculty of Humanities, Academia.edu is the preferred one. Researchers are reluctant to maintain multiple profiles, and there is little overlap between different services. Age turns out to be a poor indicator for presence in the investigated profiling sites, women are underrepresented and professors together with PhD students are the most likely profile holders. We next investigated the correlation between bibliometric measures, such as publications and citations, and user activities, such as downloads and followers. We find different bibliometric indicators to correlate strongly within individual platforms and across platforms. There is however less agreement between the traditional bibliometric and social activity indicators.
Korean Home Learning Environment and Parent Characteristics Influencing Children's Expressive and Receptive Language Abilities

This study analyzed data derived from ‘The Panel Study on Korean Children’ implemented by the Korea Institute of Child Care & Education (KICCE). Two scales, EC-HOME and REVT were used to investigate specific types of home environments and parent characteristics beneficial in the facilitation of children’s receptive and expressive language development. The Step-wise Multiple Regression Analysis identified four variables (Responsively, Physical Environment, Father Education, and Mother Habitation) that made a significant contribution to children’s receptive language development, and six different variables (Mother Education, Academic Stimulation, and Physical Environment, Acceptance, Mother’s Current Job Status, and Communicative Stimulation) for expressive language development. This study found that home learning environment is a more significant factor for children's receptive and expressive language development than parent demographic characteristics with the exception of the education level of parents, current job status of the mother, and habitation status of the mother.
Connexin43 recruits PTEN and Csk to inhibit c-Src activity in glioma cells and astrocytes

Connexin43 (Cx43), the major protein forming gap junctions in astrocytes, is reduced in high-grade gliomas, where its ectopic expression exerts important effects, including the inhibition of the proto-oncogene tyrosine-protein kinase Src (c-Src). In this work we aimed to investigate the mechanism responsible for this effect. The inhibition of c-Src requires phosphorylation at tyrosine 527 mediated by C-terminal Src kinase (Csk) and dephosphorylation at tyrosine 416 mediated by phosphatases, such as phosphatase and tensin homolog (PTEN). Our results showed that the antiproliferative effect of Cx43 is reduced when Csk and PTEN are silenced in glioma cells, suggesting the involvement of both enzymes. Confocal microscopy and immunoprecipitation assays confirmed that Cx43, in addition to c-Src, binds to PTEN and Csk in glioma cells transfected with Cx43 and in astrocytes. Pull-down assays showed that region 266–283 in Cx43 is sufficient to recruit c-Src, PTEN and Csk and to inhibit the oncogenic activity of c-Src. As a result of c-Src inhibition, PTEN was increased with subsequent inactivation of Akt and reduction of proliferation of human glioblastoma stem cells. We conclude that the recruitment of Csk and PTEN to the region between residues 266 and 283 within the C-terminus of Cx43 leads to c-Src inhibition.
Database Aggregation

Knowledge can be represented compactly in a multitude ways, from a set of propositional formulas, to a Kripke model, to a database. In this paper we study the aggregation of information coming from multiple sources, each source submitting a database modelled as a first-order relational structure. In the presence of an integrity constraint, we identify classes of aggregators that respect it in the aggregated database, provided all individual databases satisfy it. We also characterise languages for first-order queries on which the answer to queries on the aggregated database coincides with the aggregation of the answers to the query obtained on each individual database. This contribution is meant to be a first step on the application of techniques from rational choice theory to knowledge representation in databases.
Guarding Pain and Spontaneous Activity of Nociceptors after Skin versus Skin Plus Deep Tissue Incision

Background:Guarding pain after rat plantar incision is similar to pain at rest in postoperative patients. Spontaneous activity (SA) in nociceptive pathways quite likely transmits such ongoing pain. This study examined the extent of tissue injury by incision on pain behaviors and nociceptor SA. Methods:Rat pain behaviors were measured after a sham procedure, skin incision, or skin plus deep tissue incision. Separate groups of rats underwent in vivo single-fiber recording 1 day after a sham procedure, skin, or skin plus deep tissue incision or 7 days after skin plus deep tissue incision. Results:Compared with the control procedure, skin incision induced moderate guarding on the day of incision only, whereas skin plus deep tissue incision caused guarding for 5 days. Mechanical and heat hyperalgesia were similar in both incised groups, except that mechanical hyperalgesia lasted longer after skin plus deep tissue incision. On Postoperative Day 1, skin incision (18.2%) produced a similar prevalence of SA in nociceptors as in controls (13.0%), whereas skin plus deep tissue incision generated a greater prevalence of SA (61.0%); SA rate also tended to be greater (6.1 vs. 10.0 imp/s) after skin plus deep tissue incision. Seven days after skin plus deep tissue incision, the SA prevalence was similar (13.6%) as in controls. Conclusions:These data demonstrated that incised deep tissue rather than skin had a central role in the genesis of guarding behavior and nociceptor SA. Understanding the responses of deep tissue to incision and the mechanisms for deep tissue pain will improve postoperative pain management.
Impact of observation status on hospital use for patients with cancer.

PURPOSE For patients with cancer, the impact of observation status on hospital and patient outcomes is not well understood. Our objective was to assess the impact that an observation unit had on hospital use for patients with cancer who presented to the Urgent Care Center at a comprehensive cancer center. METHODS We assessed the proportion of Urgent Care Center visits that resulted in an admission to the hospital at a comprehensive cancer center, before (July 9, 2012-December 31, 2012) versus after (July 9, 2013-December 31, 2013) implementation of the observation unit. We also assessed differences in length of stay and stratified the data by presenting complaint. RESULTS During each 6-month study interval, there were more than 10,000 patient visits to the Urgent Care Center, representing approximately 6,000 unique patients. Fewer visits resulted in an inpatient admission postimplementation (47%) compared with preimplementation (50%). The duration of hospital stay for admitted patients was higher in the post period (median 108 hours) than in the pre period (median 96 hours). Alternatively, the proportion of hospital admissions with a length of stay less than 24 hours was lower in the post period (pre: 7%; post: 5%). Lower admission rates postimplementation were observed for patients who presented with fluid and electrolyte disorders, nausea and vomiting, syncope, and chest pain. CONCLUSION We observed reductions in hospital use for patients with cancer related to an observation unit in a comprehensive cancer center. Adoption of this approach for this patient population has the potential to reduce hospital use, which is of interest to hospitals, payers, and patients.
Surgically Induced Focal Retinal Detachment Does Not Cause Detectable SD-OCT Retinal Changes in Normal Human Retina

Purpose Induction of focal retinal detachment (RD) for subretinal delivery of stem cells and gene therapy is increasingly common. In order to determine if this procedure has an adverse impact on the retina, we use spectral-domain optical coherence tomography (SD-OCT) to evaluate the pre- and postoperative retinal anatomy of the incidentally detached normal retina surrounding large submacular hemorrhages (SMH) during surgical displacement procedures. Methods Retrospective, observational study of human subjects with monocular SMH evaluated before and after surgical displacement using clinical exam, fundus photography, and SD-OCT. Manual measurements of the inner retinal thickness (IRT), outer retinal thickness (ORT), and full retinal thickness (FRT) were made in regions involving the SMH and surrounding normal retina. Comparison of retinal thickness measurements was made using the Wilcoxon signed-rank test. Results Seven eyes were included in this study. All eyes successfully underwent surgical displacement of SMH. Visual acuity improved in 6/7 subjects and was unchanged in the remaining subject. Incidental RD of the normal retinal regions surrounding the SMH did not cause any significant change in IRT, ORT, or FRT that was detectable by SD-OCT. In contrast, mean FRT overlying regions with SMH was significantly greater before surgery compared to after displacement of SMH or normal adjacent retina. Conclusions Surgically induced focal RD does not cause detectable retinal changes in the incidentally detached normal retina surrounding large SMH. Therefore, surgical induction of focal RD should not be considered to have the same adverse impact on the retina as pathologic RD.
Morphological and functional analyses of skeletal muscles from an immunodeficient animal model of limb‐girdle muscular dystrophy type 2E

Introduction: Limb‐girdle muscular dystrophy type 2E (LGMD2E) is caused by mutations in the β‐sarcoglycan gene, which is expressed in skeletal, cardiac, and smooth muscles. β‐Sarcoglycan‐deficient (Sgcb‐null) mice develop severe muscular dystrophy and cardiomyopathy with focal areas of necrosis. Methods: In this study we performed morphological (histological and cellular characterization) and functional (isometric tetanic force and fatigue) analyses in dystrophic mice. Comparison studies were carried out in 1‐month‐old (clinical onset of the disease) and 7‐month‐old control mice (C57Bl/6J, Rag2/γc‐null) and immunocompetent and immunodeficient dystrophic mice (Sgcb‐null and Sgcb/Rag2/γc‐null, respectively). Results: We found that the lack of an immunological system resulted in an increase of calcification in striated muscles without impairing extensor digitorum longus muscle performance. Sgcb/Rag2/γc‐null muscles showed a significant reduction of alkaline phosphate‐positive mesoangioblasts. Discussion: The immunological system counteracts skeletal muscle degeneration in the murine model of LGMD2E. Muscle Nerve 58: 133–144, 2018
Role of surface modification in zinc oxide nanoparticles and its toxicity assessment toward human dermal fibroblast cells

The wide-scale applications of zinc oxide (ZnO) nanoparticles (NPs) in photocatalysts, gas sensors, and cosmetics may cause toxicity to humans and environments. Therefore, the aim of the present study was to reduce the toxicity of ZnO NPs by coating them with a silica (SiO2) layer, which could be used in human applications, such as cosmetic preparations. The sol–gel method was used to synthesize core ZnO with SiO2-shelled NPs (SiO2/ZnO NPs) with varying degrees of coating. Diverse studies were performed to analyze the toxicity of NPs against cells in a dose- and time-dependent manner. To ensure the decreased toxicity of the produced SiO2/ZnO NPs, cytotoxicity in membrane damage and/or intracellular reactive oxygen species (ROS) were assessed by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, lactate dehydrogenase, 2′,7′-dichlorofluorescin, and lipid peroxide estimations. The cores of ZnO NPs exhibited cytotoxicity over time, regardless of shell thickness. Nevertheless, the thicker SiO2/ZnO NPs revealed reduced enzyme leakage, decreased peroxide production, and less oxidative stress than their bare ZnO NPs or thinner SiO2/ZnO NPs. Therefore, thicker SiO2/ZnO NPs moderated the toxicity of ZnO NPs by restricting free radical formation and the release of zinc ions, and decreasing surface contact with cells.
Evaluation of Anti-Metastatic Potential of the Combination of Fisetin with Paclitaxel on A549 Non-Small Cell Lung Cancer Cells

The identification and development of new agents with a therapeutic potential as well as novel drug combinations are gaining the attention of scientists and clinicians as a plausible approach to improve therapeutic regimens for chemoresistant tumors. We have recently reported that the flavonoid fisetin (FIS), at physiologically attainable concentrations, acts synergistically with clinically achievable doses of paclitaxel (PTX) to produce growth inhibitory and pro-death effects on A549 human non-small cell lung cancer (NSCLC) cells. To further investigate a potential therapeutic efficacy of the combination of fisetin with paclitaxel, we decided to assess its impact on metastatic capability of A549 cells as well as its toxicity toward normal human lung fibroblast. Cell viability, cell migration, and invasion were measured by thiazolyl blue tetrazolium bromide (MTT) assay, wound healing assay, and Transwell chamber assay, respectively. The expression of metastasis-related genes was assessed with quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR). Actin and vimentin filaments were examined under the fluorescence microscope. The combination of FIS and PTX significantly reduced cancer cell migration and invasion, at least partially, through a marked rearrangement of actin and vimentin cytoskeleton and the modulation of metastasis-related genes. Most of these effects of the combination treatment were significantly greater than those of individual agents. Paclitaxel alone was even more toxic to normal cells than the combination of this drug with the flavonoid, suggesting that FIS may provide some protection against PTX-mediated cytotoxicity. The combination of FIS and PTX is expected to have a synergistic anticancer efficacy and a significant potential for the treatment of NSCLC, however, further in vitro and in vivo studies are required to confirm this preliminary evidence.
Identification of a Novel Serum Biomarker for Tuberculosis Infection in Chinese HIV Patients by iTRAQ-Based Quantitative Proteomics

Tuberculosis (TB) is a major comorbidity in HIV patients as well as a serious co-epidemic. Traditional detection methods are not effective or sensitive for the detection of Mycobacterium tuberculosis at the early stage. TB has become a major cause of lethal on HIV patients. We employed isobaric tags for relative and absolute quantitation (iTRAQ) technology to identify the different host responses in HIV-noTB and HIV-TB patients’ sera. Given the diversity of HIV subtypes, which results in a variety of host responses in different human populations, we focused on the Chinese patients. Of the 25 proteins identified, 7 were increased and 18 were decreased in HIV-TB co-infected patients. These proteins were found to be involved in host immune response processes. We identified a candidate protein, endoglin (ENG), which showed an 4.9 times increase by iTRAQ and 11.5 times increase by ELISA. ENG demonstrated the diagnostic efficacy and presented a novel molecular biomarker for TB in HIV-infected Chinese patients. This study provides new insight into the challenges in the diagnosis and effective management of patients with HIV-TB.
Certification, Reputation and Entry: An Empirical Analysis

Markets with asymmetric information will often employ third-party certification labels to distinguish between higher and lower quality transactions, yet little is known about the effects of certification policies on the evolution of markets. How does the stringency in quality certification affect the intensity and composition of entry, incumbents' reactions, and market outcomes? We use detailed administrative data and exploit a policy change on eBay to explore how a more selective certification policy affects entry and behavior across a rich set of online market segments. We find that after the policy change, entry increases and does so more intensely in markets where it is harder to become certified. The average quality of entrants also increases more in the more affected markets, while the quality distribution of entrants exhibits fatter tails ex post. Finally, some incumbents increase the quality of their service to maintain certification and deliver higher quality after the policy change. The results help inform the design of certification policies in electronic and other markets with asymmetric information.
Anatomically realistic ultrasound phantoms using gel wax with 3D printed moulds

Here we describe methods for creating tissue-mimicking ultrasound phantoms based on patient anatomy using a soft material called gel wax. To recreate acoustically realistic tissue properties, two additives to gel wax were considered: paraffin wax to increase acoustic attenuation, and solid glass spheres to increase backscattering. The frequency dependence of ultrasound attenuation was well described with a power law over the measured range of 3–10 MHz. With the addition of paraffin wax in concentrations of 0 to 8 w/w%, attenuation varied from 0.72 to 2.91 dB cm−1 at 3 MHz and from 6.84 to 26.63 dB cm−1 at 10 MHz. With solid glass sphere concentrations in the range of 0.025–0.9 w/w%, acoustic backscattering consistent with a wide range of ultrasonic appearances was achieved. Native gel wax maintained its integrity during compressive deformations up to 60%; its Young’s modulus was 17.4 ± 1.4 kPa. The gel wax with additives was shaped by melting and pouring it into 3D printed moulds. Three different phantoms were constructed: a nerve and vessel phantom for peripheral nerve blocks, a heart atrium phantom, and a placental phantom for minimally-invasive fetal interventions. In the first, nerves and vessels were represented as hyperechoic and hypoechoic tubular structures, respectively, in a homogeneous background. The second phantom comprised atria derived from an MRI scan of a patient with an intervening septum and adjoining vena cavae. The third comprised the chorionic surface of a placenta with superficial fetal vessels derived from an image of a post-partum human placenta. Gel wax is a material with widely tuneable ultrasound properties and mechanical characteristics that are well suited for creating patient-specific ultrasound phantoms in several clinical disciplines.