Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum cytokeratin-18 and its relation to liver fibrosis and steatosis diagnosed by FibroScan and controlled attenuation parameter in nonalcoholic fatty liver disease and hepatitis C virus patients

Background Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disease worldwide. Multiple diagnostic noninvasive methods for NAFLD were studied (both serological and imaging), either single or combined. Attention has been focused on cytokeratin-18 (CK18) as a novel serological marker for the diagnosis of steatosis/fibrosis in NAFLD and hepatitis C virus (HCV) patients. Aim The aim of this study was to evaluate serum CK18 in NAFLD and HCV fibrosis/steatosis and also to correlate its performance with the diagnostic accuracy of transient elastography (TE) and controlled attenuation parameter (CAP) in the diagnosis of fibrosis/steatosis in these patients. Patients and methods Three equal groups of participants were enrolled (n=135): group I included patients with chronic HCV, group II included NAFLD patients, and group III included control participants. For all groups, TE/CAP and labs including serum CK18 were performed. Liver biopsy was performed for the NAFLD group. Results Serum CK18 was significantly higher in the NAFLD group (19.01±3.49 ng/ml) versus the HCV group (8.95±1.06 ng/ml) and the control group (4.83±1.6 ng/ml) (P<0.001). The CK18 levels in biopsy stages (steatosis, ballooning, inflammation, and fibrosis) and FibroScan/CAP degrees showed that CK18 increased significantly with steatosis and fibrosis stages (biopsy or FibroScan/CAP), but did not reach significance with ballooning or inflammation grades. CK18 was significantly different in nonalcoholic steatohepatitis versus non-nonalcoholic steatohepatitis patients (P=0.041). The best CK18 cutoff to detect steatosis (S≥2) in NAFLD and HCV was 11.65 and 6.84 ng/ml, respectively with an overall sensitivity and specificity over 97%. The CK18 cutoff for significant fibrosis (F≥2) by FibroScan in the NAFLD/HCV groups was 9.115 ng/ml, with 62.5%/69.2% sensitivity/specificity (P=0.031). However, inflammation had a cutoff with a marginal P value (P=0.080), and a reliable cutoff for ballooning was not attained (P=0.386). There was a positive correlation between CK18 and fibrosis (by FibroScan) in the NAFLD and HCV groups (P<0.05). The correlation between CK18 and steatosis in CAP and the nonalcoholic fatty liver disease activity score was very good (P<0.001). Conclusion Serum CK18 is related strongly to the development/progression of NAFLD and HCV-related fibrosis/steatosis. TE was correlated highly with liver biopsy results. The combination of CK18 with other noninvasive modalities increases the diagnostic yield of these tests.
Long-term population spike-timing-dependent plasticity promotes synaptic tagging but not cross-tagging in rat hippocampal area CA1

Significance Deciphering the rules that shape neuronal connections is critical to our understanding of information processing in a neural network. Our study describes how the relative timing of the activities of afferents and their associated postsynaptic neurons determines synaptic strength at the hippocampal CA1 circuit, an area important for learning and memory. A low number of repeated, paired activities between afferents and their neurons differentially shapes the hippocampal CA3–CA1 synaptic pathway for hours and even affects how future information is processed in the neuronal ensemble. In spike-timing-dependent plasticity (STDP), the direction and degree of synaptic modification are determined by the coherence of pre- and postsynaptic activities within a neuron. However, in the adult rat hippocampus, it remains unclear whether STDP-like mechanisms in a neuronal population induce synaptic potentiation of a long duration. Thus, we asked whether the magnitude and maintenance of synaptic plasticity in a population of CA1 neurons differ as a function of the temporal order and interval between pre- and postsynaptic activities. Modulation of the relative timing of Schaffer collateral fibers (presynaptic component) and CA1 axons (postsynaptic component) stimulations resulted in an asymmetric population STDP (pSTDP). The resulting potentiation in response to 20 pairings at 1 Hz was largest in magnitude and most persistent (4 h) when presynaptic activity coincided with or preceded postsynaptic activity. Interestingly, when postsynaptic activation preceded presynaptic stimulation by 20 ms, an immediate increase in field excitatory postsynaptic potentials was observed, but it eventually transformed into a synaptic depression. Furthermore, pSTDP engaged in selective forms of late-associative activity: It facilitated the maintenance of tetanization-induced early long-term potentiation (LTP) in neighboring synapses but not early long-term depression, reflecting possible mechanistic differences with classical tetanization-induced LTP. The data demonstrate that a pairing of pre- and postsynaptic activities in a neuronal population can greatly reduce the required number of synaptic plasticity-evoking events and induce a potentiation of a degree and duration similar to that with repeated tetanization. Thus, pSTDP determines synaptic efficacy in the hippocampal CA3–CA1 circuit and could bias the CA1 neuronal population toward potentiation in future events.
Viewpoint: the road to room-temperature conventional superconductivity

It is a honor to write a contribution on this memorial for Sandro Massidda. For both of us, at different stages in our lives, Sandro was first and foremost a friend. We both admired his humble, playful and profound approach to life and physics. In this contribution we describe the route which permitted to meet a long-standing challenge in solid state physics, i.e. room temperature superconductivity. In less than 20 years the critical temperature of conventional superconductors, which in the last century had been widely believed to be limited to 25 K, was raised from 40 K in MgB2 to 265 K in LaH10. This discovery was enabled by the development and application of computational methods for superconductors, a field in which Sandro Massidda played a major role.
Myasthenic congenital myopathy from recessive mutations at a single residue in NaV1.4

Objective To identify the genetic and physiologic basis for recessive myasthenic congenital myopathy in 2 families, suggestive of a channelopathy involving the sodium channel gene, SCN4A. Methods A combination of whole exome sequencing and targeted mutation analysis, followed by voltage-clamp studies of mutant sodium channels expressed in fibroblasts (HEK cells) and Xenopus oocytes. Results Missense mutations of the same residue in the skeletal muscle sodium channel, R1460 of NaV1.4, were identified in a family and a single patient of Finnish origin (p.R1460Q) and a proband in the United States (p.R1460W). Congenital hypotonia, breathing difficulties, bulbar weakness, and fatigability had recessive inheritance (homozygous p.R1460W or compound heterozygous p.R1460Q and p.R1059X), whereas carriers were either asymptomatic (p.R1460W) or had myotonia (p.R1460Q). Sodium currents conducted by mutant channels showed unusual mixed defects with both loss-of-function (reduced amplitude, hyperpolarized shift of inactivation) and gain-of-function (slower entry and faster recovery from inactivation) changes. Conclusions Novel mutations in families with myasthenic congenital myopathy have been identified at p.R1460 of the sodium channel. Recessive inheritance, with experimentally established loss-of-function, is a consistent feature of sodium channel based myasthenia, whereas the mixed gain of function for p.R1460 may also cause susceptibility to myotonia.
A Systematic Literature Review

Background: Certification of nurses has been identified as a strategy to improve health care quality. However, the impact nursing certification has on clinical patient outcomes remains unclear. Purpose: The purpose was to examine the relationship between nursing certification and clinical outcomes. Methods: A systematic review of the literature was conducted through the search of relevant bibliographic databases (CINAHL Plus, PubMed, Medline, and Cochrane Collaboration). Results: Nursing certification was found to have a significant inverse relationship to patient falls and health care–associated infections. Significant correlations were not established in outcomes such as pressure injuries
Deletion of a flippase subunit Tmem30a in hematopoietic cells impairs mouse fetal liver erythropoiesis

Transmembrane protein 30A (Tmem30a) is the β-subunit of P4-ATPases which function as flippase that transports aminophospholipids such as phosphatidylserine from the outer to the inner leaflets of the plasma membrane to maintain asymmetric distribution of phospholipids. It has been documented that deficiency of Tmem30a led to exposure of phosphatidylserine. However, the role of Tmem30a in vivo remains largely unknown. Here we found that Vav-Cre-driven conditional deletion of Tmem30a in hematopoietic cells led to embryonic lethality due to severe anemia by embryonic day 16.5. The numbers of erythroid colonies and erythroid cells were decreased in the Tmem30a deficient fetal liver. This was accompanied by increased apoptosis of erythroid cells. Confocal microscopy analysis revealed an increase of localization of erythropoietin receptor to areas of membrane raft microdomains in response to erythropoietin stimulation in Ter119−erythroid progenitors, which was impaired in Tmem30a deficient cells. Moreover, erythropoietin receptor (EPOR)-mediated activation of the STAT5 pathway was significantly reduced in Tmem30a deficient fetal liver cells. Consistently, knockdown of TMEM30A in human CD34+ cells also impaired erythropoiesis. Our findings demonstrate that Tmem30a plays a critical role in erythropoiesis by regulating the EPOR signaling pathway through the formation of membrane rafts in erythroid cells.
Exploring Secondary Metabolite Profiles of Stachybotrys spp. by LC-MS/MS

The genus Stachybotrys produces a broad diversity of secondary metabolites, including macrocyclic trichothecenes, atranones, and phenylspirodrimanes. Although the class of the phenylspirodrimanes is the major one and consists of a multitude of metabolites bearing various structural modifications, few investigations have been carried out. Thus, the presented study deals with the quantitative determination of several secondary metabolites produced by distinct Stachybotrys species for comparison of their metabolite profiles. For that purpose, 15 of the primarily produced secondary metabolites were isolated from fungal cultures and structurally characterized in order to be used as analytical standards for the development of an LC-MS/MS multimethod. The developed method was applied to the analysis of micro-scale extracts from 5 different Stachybotrys strains, which were cultured on different media. In that process, spontaneous dialdehyde/lactone isomerization was observed for some of the isolated secondary metabolites, and novel stachybotrychromenes were quantitatively investigated for the first time. The metabolite profiles of Stachybotrys species are considerably influenced by time of growth and substrate availability, as well as the individual biosynthetic potential of the respective species. Regarding the reported adverse effects associated with Stachybotrys growth in building environments, combinatory effects of the investigated secondary metabolites should be addressed and the role of the phenylspirodrimanes re-evaluated in future research.
Validation of Baveno VI Criteria for Screening and Surveillance of Esophageal Varices in Patients With Compensated Cirrhosis and a Sustained Response to Antiviral Therapy.

BACKGROUND & AIMS Management of patients with cirrhosis includes endoscopic screening and surveillance to detect esophageal varices (EV) and prevent bleeding. However, the Baveno VI guidelines recommend avoiding endoscopies for patients with liver stiffness measurements below 20 kPa and platelet counts above 150,000 (favorable Baveno VI status) and endoscopic assessment of patients with higher levels of liver stiffness and platelet counts (unfavorable Baveno VI status). We aimed to validate the Baveno VI guidelines, evaluating outcomes of patients in the ANRS-CO12 CirVir cohort with compensated cirrhosis associated with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, with or without a sustained response to antiviral therapy. METHODS We performed an ancillary study using data from 891 patients in the ANRS CO12 CirVir cohort, treated at 35 centers in France, with HCV or HBV infection and biopsy-proven cirrhosis, Child-Pugh A scores, no previous complications, and no hepatocellular carcinoma who underwent an endoscopic procedure and had interpretable liver stiffness measurements and platelet counts. Progression of portal hypertension (PHT) was defined as the onset of varices needing treatment (VNT) or PHT-related bleeding. An sustained response to antiviral therapy was defined as undetectable level of HCV RNA by polymerase chain reaction assay (<50 IU/mL) 12 weeks after the end of treatment (SVR) or an undetectable level of HBV DNA. The primary aims were to validate the Baveno VI guidelines for screening and surveillance of EV in patients with compensated cirrhosis and to study the effects of an SVR on the progression of PHT. RESULTS A total of 200 patients achieved an SVR (22.4%) (94 patients with HCV infection, 98 patients with HBV infection, and 8 patients with both); 80 of these patients had favorable Baveno VI status and none had VNT. Progression of PHT was studied in 548 patients; during a follow-up period of 61.2 months (interquartile range, 39.5-80.6 months), 105 of these patients (19.1%) had progression of PHT. Lack of an SVR and grade 1 EV were independently associated with progression of PHT. At the time of PHT progression, all patients had unfavorable Baveno VI status. Achieving favorable Baveno VI status after an SVR was associated with the absence of PHT progression. Favorable Baveno VI status and SVR were independently associated with survival. CONCLUSIONS In an analysis of data from a large cohort of patients with HBV- or HCV-associated cirrhosis in France, we validated the Baveno VI guidelines on screening and surveillance of PHT, even for patients who achieved a sustained response to antiviral therapy.
EffFeu Project: Towards Mission-Guided Application of Drones in Safety and Security Environments

The number of unmanned aerial system (UAS) applications for supporting rescue forces is growing in recent years. Nevertheless, the analysis of sensed information and control of unmanned aerial vehicle (UAV) creates an enormous psychological and emotional load for the involved humans especially in critical and hectic situations. The introduced research project EffFeu (Efficient Operation of Unmanned Aerial Vehicle for Industrial Firefighters) especially focuses on a holistic integration of UAS in the daily work of industrial firefighters. This is done by enabling autonomous mission-guided control on top of the presented overall system architecture, goal-oriented high-level task control, comprehensive localisation process combining several approaches to enable the transition from and to GNSS-supported and GNSS-denied environments, as well as a deep-learning based object recognition of relevant entities. This work describes the concepts, current stage, and first evaluation results of the research project.
Patient-derived xenografts: a promising resource for preclinical cancer research

ABSTRACT Patient-derived xenograft tumors retain molecular and histopathological features of the originating tumor and are useful preclinical tools for drug discovery and assessment. We recently reported that ‘rapid’ engraftment of head and neck squamous cell carcinoma samples is highly prognostic and correlates with deregulation of the G1/S checkpoint. Tumors with genetic alterations in cyclinD1 (CCND1) and/or cyclin-dependent kinase inhibitor 2A (CDKN2A) are more likely to respond to abemaciclib.
Genomic correlates of extraintestinal infection are linked with changes in cell morphology in Campylobacter jejuni

Campylobacter jejuni is the most common cause of bacterial diarrheal disease in the world. Clinical outcomes of infection can range from asymptomatic infection to life-threatening extraintestinal infections. This variability in outcomes for infected patients has raised questions as to whether genetic differences between C. jejuni isolates contribute to their likelihood of causing severe disease. In this study, we compare the genomes of ten C. jejuni isolates that were implicated in extraintestinal infections with reference gastrointestinal isolates, in order to identify unusual patterns of sequence variation associated with infection outcome. We identified a collection of genes that display a higher burden of uncommon mutations in invasive isolates compared with gastrointestinal close relatives, including some that have been previously linked to virulence and invasiveness in C. jejuni. Among the top genes identified were mreB and pgp1, which are both involved in determining cell shape. Electron microscopy confirmed morphological differences in isolates carrying unusual sequence variants of these genes, indicating a possible relationship between extraintestinal infection and changes in cell morphology.
Associations between sleep disturbances and suicidal ideation, plans, and attempts in adolescents: a systematic review and meta-analysis.

STUDY OBJECTIVES To systematically review and meta-analyze the associations between sleep disturbances and suicidal ideation, plans, and attempts in adolescents and explore potential moderators of these associations. METHODS Embase, PubMed, ProQuest, and the China Knowledge Resource Integrated Database were searched from their inception dates to October 19, 2018. We selected cross-sectional, prospective, or retrospective studies without time or language restrictions. RESULTS Nine cross-sectional studies, four prospective studies, and one retrospective report that, respectively, involved 37 536, 9295, and 80 adolescents were included in the meta-analysis. Cross-sectional analyses revealed that adolescents with sleep disturbances were at higher risks of suicidal ideation, plans, and attempts (pooled odds ratios [ORs] = 2.35, 1.58, and 1.92) than those without sleep disturbances. Prospective reports indicated that sleep disturbances in adolescents significantly predicted the risk of suicidal ideation but not suicide attempts (pooled ORs = 1.79 and 1.98, 95% confidence intervals = 1.36-2.36 and 0.62-6.29, respectively). The retrospective study did not support the association between sleep disturbances and suicide attempts. Depression did not moderate the associations between sleep disturbances and suicidal ideation or attempts in adolescents. Adolescents with insomnia complaints had a higher risk of suicidal ideation than those with other sleep complaints. Age, the female percentage, and reliable sleep measures were significant moderators (all p < .05). CONCLUSIONS Sleep disturbances, particularly insomnia, should be considered an influencing factor when developing preventive strategies against adolescent suicidal ideation. Additional prospective studies are warranted to establish causality of sleep disturbances in youth suicide plans and attempts.
Cytocompatibility of Potential Bioactive Cerium-Doped Glasses based on 45S5

The cytocompatibility of potential bioactive cerium-containing (Ce3+/Ce4+) glasses is here investigated by preparing three different glasses with increasing amount of doping CeO2 (1.2, 3.6 and 5.3 mol% of CeO2, called BG_1.2, BG_3.6 and BG_5.3, respectively) based on 45S5 Bioglass® (called BG). These materials were characterized by Environmental Scanning Electron Microscopy (ESEM) and infrared spectroscopy (FTIR) after performing bioactivity tests in Dulbecco’s Modified Eagle Medium (DMEM) solution, and the ions released in solution were determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and Optical Emission Spectrometry (ICP-OES). The data obtained clearly show that the glass surfaces of BG, BG_1.2 and BG_3.6 were covered by hydroxyapatite (HA), while BG_5.3 favored the formation of a cerium phosphate crystal phase. The cytotoxicity tests were performed using both murine long bone osteocyte-like (MLO-Y4) and mouse embryonic fibroblast (NIH/3T3) cell lines. The cerium-containing bioactive glasses show an increment in cell viability with respect to BG, and at long times, no cell aggregation and deformation were observed. The proliferation of NIH/3T3 cells increased with the cerium content in the glasses; in particular, BG_3.6 and BG_5.3 showed a higher proliferation of cells than the negative control. These results highlight and enforce the proposal of cerium-doped bioactive glasses as a new class of biomaterials for hard-tissue applications.
FPGA Modeling and Optimization of a SIMON Lightweight Block Cipher

Security of sensitive data exchanged between devices is essential. Low-resource devices (LRDs), designed for constrained environments, are increasingly becoming ubiquitous. Lightweight block ciphers provide confidentiality for LRDs by balancing the required security with minimal resource overhead. SIMON is a lightweight block cipher targeted for hardware implementations. The objective of this research is to implement, optimize, and model SIMON cipher design for LRDs, with an emphasis on energy and power, which are critical metrics for LRDs. Various implementations use field-programmable gate array (FPGA) technology. Two types of design implementations are examined: scalar and pipelined. Results show that scalar implementations require 39% less resources and 45% less power consumption. The pipelined implementations demonstrate 12 times the throughput and consume 31% less energy. Moreover, the most energy-efficient and optimum design is a two-round pipelined implementation, which consumes 31% of the best scalar’s implementation energy. The scalar design that consumes the least energy is a four-round implementation. The scalar design that uses the least area and power is the one-round implementation. Balancing energy and area, the two-round pipelined implementation is optimal for a continuous stream of data. One-round and two-round scalar implementations are recommended for intermittent data applications.
Comparing memory group training and computerized cognitive training for improving memory function following stroke: A phase II randomized controlled trial.

OBJECTIVES Memory deficits are common after stroke, yet remain a high unmet need within the community. The aim of this phase II randomized controlled trial was to determine whether group compensatory or computerized cognitive training approaches were effective in rehabilitating memory following stroke. METHODS A parallel, 3-group, single-blind, randomized controlled trial was used to compare the effectiveness of a compensatory memory skills group with restorative computerized training on functional goal attainment. Secondary outcomes explored change in neuropsychological measures of memory, subjective ratings of prospective and everyday memory failures and ratings of internal and external strategy use. RESULTS A total of 65 community dwelling survivors of stroke were randomized (24: memory group, 22: computerized cognitive training, and 19: wait-list control). Participants allocated to the memory group reported significantly greater attainment of memory goals and internal strategy use at 6-week follow-up relative to participants in computerized training and wait-list control conditions. However, groups did not differ significantly on any subjective or objective secondary outcomes. CONCLUSION Preliminary evidence shows that memory skills groups, but not computerized training, may facilitate achievement of functional memory goals for community dwelling survivors of stroke. These findings require further replication, given the modest sample size, subjective nature of the outcomes and the absence of objective eligibility for inclusion.