Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition by mitoxantrone of in vitro migration of immunocompetent cells: a possible mechanism for therapeutic efficacy in the treatment of multiple sclerosis.

BACKGROUND Damage of the blood-brain barrier and invasion of immunocompetent cells into the central nervous system represent key events in the immunopathogenesis of multiple sclerosis. Mitoxantrone hydrochloride reduces progression of disability and clinical exacerbations in patients with multiple sclerosis. Its precise mode of action is unclear. OBJECTIVE To investigate the effects of mitoxantrone on the migratory capacity of immunocompetent cells ex vivo and in vitro. DESIGN Case-control study. SETTING Department of Neurology, Heinrich Heine University, Düsseldorf, Germany. PARTICIPANTS Peripheral blood mononuclear cells (PBMCs) were obtained from 11 patients with multiple sclerosis before and after intravenous mitoxantrone treatment; PBMCs from 5 healthy control donors were treated with mitoxantrone in vitro. MAIN OUTCOME MEASURES The migratory capacity was studied in an in vitro Boyden chamber assay; cells and their rates of migration were analyzed by light microscopy and flow cytometry. To determine the specificity of our findings, PBMCs were treated with perfosfamide in vitro. RESULTS Mitoxantrone decreased the migratory capacity of CD14(+) monocytes and (to a lesser degree) of CD4(+) and CD8(+) T lymphocytes. These observations were confirmed when control PBMCs were treated with an equivalent dose of mitoxantrone in vitro. Similar effects were seen when PBMCs were preincubated with perfosfamide. The inhibitory effects of mitoxantrone on the migratory capacity of PBMCs were mediated by reduced matrix metalloproteinase 9 activity, as demonstrated by zymography, polymerase chain reaction, and inhibitory studies. CONCLUSION Mitoxantrone may inhibit the migration of inflammatory cells into and within the central nervous system.
Regulators of Autophagosome Formation in Drosophila Muscles

Given the diversity of autophagy targets and regulation, it is important to characterize autophagy in various cell types and conditions. We used a primary myocyte cell culture system to assay the role of putative autophagy regulators in the specific context of skeletal muscle. By treating the cultures with rapamycin (Rap) and chloroquine (CQ) we induced an autophagic response, fully suppressible by knockdown of core ATG genes. We screened D. melanogaster orthologs of a previously reported mammalian autophagy protein-protein interaction network, identifying several proteins required for autophagosome formation in muscle cells, including orthologs of the Rab regulators RabGap1 and Rab3Gap1. The screen also highlighted the critical roles of the proteasome and glycogen metabolism in regulating autophagy. Specifically, sustained proteasome inhibition inhibited autophagosome formation both in primary culture and larval skeletal muscle, even though autophagy normally acts to suppress ubiquitin aggregate formation in these tissues. In addition, analyses of glycogen metabolic genes in both primary cultured and larval muscles indicated that glycogen storage enhances the autophagic response to starvation, an important insight given the link between glycogen storage disorders, autophagy, and muscle function.
Cellular Neurothekeoma: Detailed Characterization in a Series of 133 Cases

Cellular neurothekeomas are distinctive benign cutaneous tumors of uncertain histogenesis. As relatively few cases have been reported, their clinical features and morphologic spectrum remain incompletely defined, and the significance of atypical histologic features is uncertain. This study examined the clinicopathologic and immunohistochemical features of 133 cellular neurothekeomas received between 1987 and 2003. There was a 1.8:1 female predominance, with a mean age of 25 years (84% <40 y). Mean tumor size was 1.1 cm (range: 0.3 to 6 cm; 90% <2 cm). The tumors arose most often on the upper limb (35%) or head and neck (33%). Fifty-two percent of the tumors were limited to the dermis, and 48% also involved superficial subcutaneous tissue. In 30% of cases, neurothekeoma was suggested by the referring pathologist; the most common other diagnoses offered were plexiform fibrohistiocytic tumor, benign fibrous histiocytoma, and a low-grade sarcoma. Histologically, most cases were poorly marginated; 33 (25%) infiltrated fat, and 10 (8%) entrapped skeletal muscle (all but 1 situated on the face). Nearly all tumors had a lobulated or micronodular architecture and were composed of nests and bundles of epithelioid to spindled cells with palely eosinophilic cytoplasm, often separated by dense hyaline collagen; 17 (13%) showed focally sheetlike areas, and 5 (4%) were notably plexiform. Myxoid stroma was observed in 38 (29%) tumors; 11 (8%) were predominantly myxoid. Five (4%) showed marked stromal hyalinization. Osteoclastic giant cells were seen in 20 (15%) cases. The mean mitotic rate was 3 per 10 high power fields; 28 (21%) had ≥5 per 10 high power fields. Most tumors showed mild cytologic atypia in the form of nuclear variability and small nucleoli; 33 (25%) contained notably pleomorphic cells. All tumors were reactive for NKI-C3, 110/123 (89%) expressed neuron-specific enolase, 73/127 (57%) showed at least focal staining for smooth muscle actin, and only 1 was focally desmin positive. All tumors were negative for S-100 protein. Follow-up ranged from 5 to 146 months (mean 44 mo). Ten tumors recurred locally (7 situated on the face), after a mean of 18 months; tumor had been marginally excised or had involved excision margins in all cases with available information. No other clinical or pathologic features correlated with recurrence. Cellular neurothekeomas have a predilection for the upper limbs and head and neck of pediatric and young adult females and rarely recur following incomplete excision. There is no good evidence that these lesions show nerve sheath differentiation and the nomenclature will likely change when the tumor cell lineage is better defined. Atypical histologic features (including pleomorphism, infiltration of subcutis, and a high mitotic rate) seem to have no clinical significance.
Expression of Alpha 7 Nicotinic Acetylcholine Receptors by Bipolar, Amacrine, and Ganglion Cells of the Rabbit Retina

Cholinergic agents affect the light responses of many ganglion cells (GCs) in the mammalian retina by activating nicotinic acetylcholine receptors (nAChRs). Whereas retinal neurons that express β2 subunit-containing nAChRs have been characterized in the rabbit retina, expression patterns of other nAChR subtypes remain unclear. Therefore, we evaluated the expression of α7 nAChRs in retinal neurons by means of single-, double-, and triple-label immunohistochemistry. Our data demonstrate that, in the rabbit retina, several types of bipolar cells, amacrine cells, and cells in the GC layer express α7 nAChRs. At least three different populations of cone bipolar cells exhibited α7 labeling, whereas glycine-immunoreactive amacrine cells comprised the majority of α7-positive amacrine cells. Some GABAergic amacrine cells also displayed α7 immunoreactivity; α7 labeling was never detected in rod bipolar cells or rod amacrine cells (All amacrine cells). Our data suggest that activation of α7 nAChRs by acetylcholine (ACh) or choline may affect glutamate release from several types of cone bipolar cells, modulating GC responses. ACh-induced excitation of inhibitory amacrine cells might cause either inhibition or disinhibition of other amacrine and GC circuits. Finally, ACh may act on α7 nAChRs expressed by GCs themselves.
The Plasmid of Escherichia coli Strain S88 (O45:K1:H7) That Causes Neonatal Meningitis Is Closely Related to Avian Pathogenic E. coli Plasmids and Is Associated with High-Level Bacteremia in a Neonatal Rat Meningitis Model

ABSTRACT A new Escherichia coli virulent clonal group, O45:K1, belonging to the highly virulent subgroup B21 was recently identified in France, where it accounts for one-third of E. coli neonatal meningitis cases. Here we describe the sequence, epidemiology and function of the large plasmid harbored by strain S88, which is representative of the O45:K1 clonal group. Plasmid pS88 is 133,853 bp long and contains 144 protein-coding genes. It harbors three different iron uptake systems (aerobactin, salmochelin, and the sitABCD genes) and other putative virulence genes (iss, etsABC, ompTP, and hlyF). The pS88 sequence is composed of several gene blocks homologous to avian pathogenic E. coli plasmids pAPEC-O2-ColV and pAPEC-O1-ColBM. PCR amplification of 11 open reading frames scattered throughout the plasmid was used to investigate the distribution of pS88 and showed that a pS88-like plasmid is present in other meningitis clonal groups such as O18:K1, O1:K1, and O83:K1. A pS88-like plasmid was also found in avian pathogenic strains and human urosepsis strains belonging to subgroup B21. A variant of S88 cured of its plasmid displayed a marked loss of virulence relative to the wild-type strain in a neonatal rat model, with bacteremia more than 2 log CFU/ml lower. The salmochelin siderophore, a known meningovirulence factor, could not alone explain the plasmid's contribution to virulence, as a salmochelin mutant displayed only a minor fall in bacteremia (0.9 log CFU/ml). Thus, pS88 is a major virulence determinant related to avian pathogenic plasmids that has spread not only through meningitis clonal groups but also human urosepsis and avian pathogenic strains.
ULTRASONIC INVESTIGATION OF CONCRETE WITH DISTRIBUTED DAMAGE

Bridge decks deteriorate due to many causes including low level fatigue cycling, thermal loading, chemical attack, and reinforcing steel corrosion. This deterioration takes the form of distributed microscopic damage that may evolve into large defects such as cracks, delaminations, spalling, and scaling. An experimental program was conducted to evaluate ultrasonic techniques for measuring distributed cracking in concrete structures. Distributed cracking refers primarily to microcracking and other high porosity regions that generally precede large cracks. An investigation of distributed cracking yields information on weaknesses in the materials that may ultimately lead to major cracking and failure, but also can be used to evaluate distress mechanisms that do not necessarily result in large cracks. Distributed cracking in concrete was induced by freeze-thaw cycling and salt-scaling. Ultrasonic tests were used to measure changes in attenuation, pulse velocity, and peak frequency of the ultrasonic waves due to the distributed damage. The ultrasonic measurements were correlated with damage observed using optical microscopy. It was found that ultrasonic pulse velocity was not very sensitive to changes caused by distributed microcracking. The change in signal amplitude (a measure of ultrasonic attenuation) was quite sensitive to changes caused by microcracking, although the measurements showed considerable scatter. The peak frequency of the ultrasonic signal was also quite sensitive to the condition of the concrete. These results must be considered in the development field tests for evaluation of concrete structures.
Temporal changes in the rate of progression to death among Italians with known date of HIV seroconversion: estimates of the population effect of treatment. Italian HIV Seroconversion Study (ISS).

OBJECTIVE To evaluate changes in survival among HIV-positive individuals with known date of seroconversion (SC). DESIGN Prospective cohort study. METHODS Follow-up lasted from SC to death or to the end of 1997. A multivariate Cox model was applied to estimate relative hazards (RH) of death. The year of SC (as a categoric fixed variable) and calendar year (as a time-dependent variable) were considered to evaluate, respectively, cohort and prevalent changes in the rate of death. A separate Cox model was used to assess the association between survival and new combination therapies, using an "intention to treat" approach. RESULTS The study included 1535 individuals (53.9% injecting drug users, 25.3% homosexuals, 19.5% heterosexuals); 75.8% seroconverted between 1980 and 1991, and 24.2% seroconverted between 1992 and 1997. When adjusting for year of SC, the RH of death (and that of AIDS) was significantly lower in 1997, compared with before 1991 (RH = 0.54; 95% confidence interval, 0.30-0.98). Adjusted RHs of death were significantly lower for combination antiretroviral therapy, compared with no therapy. When combining the two Cox models, the 1997 reduction in risk of death was largely due to antiretroviral therapies; similar results were obtained when the endpoint was AIDS. CONCLUSIONS A reduction in the risk of death, probably due to combination antiretroviral therapy, was observed in 1997 after having adjusted for age at SC and year of SC.
Using a composite morbidity score and cultural survey to explore characteristics of high proficiency neonatal intensive care units

Background Continuous quality improvement (CQI) collaboration has not eliminated the morbidity variability seen among neonatal intensive care units (NICUs). Factors other than inconstant application of potentially better practices (PBPs) might explain divergent proficiency. Objective Measure a composite morbidity score and determine whether cultural, environmental and cognitive factors distinguish high proficiency from lower proficiency NICUs. Design/methods Retrospective analysis using a risk-adjusted composite morbidity score (Benefit Metric) and cultural survey focusing on very low birth weight (VLBW) infants from 39 NICUs, years 2000–2014. The Benefit Metric and yearly variance from the group mean was rank-ordered by NICU. A comprehensive survey was completed by each NICU exploring whether morbidity variance correlated with CQI methodology, cultural, environmental and/or cognitive characteristics. Results 58 272 VLBW infants were included, mean (SD) age 28.2 (3.0) weeks, birth weight 1031 (301) g. The 39 NICU groups’ Benefit Metric improved 40%, from 80 in 2000 to 112 in 2014 (P<0.001). 14 NICUs had composite morbidity scores significantly better than the group, 16 did not differ and 9 scored below the group mean. The 14 highest performing NICUs were characterised by more effective team work, superior morale, greater problem-solving expectations of providers, enhanced learning opportunities, knowledge of CQI fundamentals and more generous staffing. Conclusion Cultural, environmental and cognitive characteristics vary among NICUs perhaps more than traditional CQI methodology and PBPs, possibly explaining the inconstancy of VLBW infant morbidity reduction efforts. High proficiency NICUs foster spirited team work and camaraderie, sustained learning opportunities and support of favourable staffing that allows problem solving and widespread involvement in CQI activities.
Section Ii-exercise Physiology & Sports Medicine the Relationship between the Yo-yo Tests, Anaerobic Performance and Aerobic Performance in Young Soccer Players

Authors submitted their contribution of the article to the editorial board. The purposes of this study were to determine the relationship between performance in the Yo-Yo intermittent recovery test level 1 (YIRT1), the Yo-Yo intermittent recovery test level 2 (YIRT2) and the Yo-Yo endurance test (continuous) (YET) with maximal oxygen uptake (VO2max) and Wingate anaerobic performance (WaNT) test results in young soccer players (age 15.00 ± 0.0 years, body height 176.3 ± 4.2 cm and body mass 68.1 ± 3.6 kg). An ergospirometry device was used during the treadmill test (TRT) to determine VO2max. At the end of the study, significant differences were found between the Yo-Yo tests and TRT in terms of HRmax (TRT = 195,92, YIRT1 = 197,83, YIRT2 = 198,5 YET = 198) (p > 0.05). While there were moderate correlations between VO2max and YIRT 1-2 performances (respectively, r = 0.56, r = 0.53), there was only a weak relationship between VO2max and YET performance (r = 0.43) (distance covered). There were also moderate significant negative correlations between performance in the YIRT2 and peak power measured in the WaNT (r =-0.55), although there were no significant correlations between performance in the three tests and average power. A moderate negative correlation was found between performance in the YIRT2 and Fatigue index (FI) (r =-0,66). In conclusion, the YIRT2 may be a more suitable field test for determining both aerobic and anaerobic performance in soccer players.
A Transformerless Energy Storage System Based on a Cascade Multilevel PWM Converter With Star Configuration

This paper describes a transformerless energy storage system based on a cascade multilevel pulsewidth modulation converter with star configuration. The system is intended for power leveling of renewable energy sources, as well as for improving power quality and reliability of a power distribution system. This paper pays attention to active-power control and voltage-balancing control that are indispensable for proper operation of the energy storage system. A 200-V 10-kW 8.8-kJ downscaled laboratory system is designed, constructed, and tested, replacing electric double-layer capacitors with large-capacity electrolytic capacitors. Experimental results obtained from the laboratory system verify the viability and effectiveness of the 6.6-kV energy storage system.
A practical critique of antifungal treatment guidelines for haemato-oncologists

The management of invasive fungal disease (IFD) in the haemato-oncology setting remains a challenge. This article reviews recent guidelines relating to IFD for their similarities and differences, as well as applying the Appraisal of Guidelines Research and Evaluation (AGREE) criteria. The guidelines’ recommendations on antifungal prophylaxis, empirical and definitive treatment of candidiasis and aspergillosis are summarized; also, minimum standards for diagnosis and follow-up are discussed. This critique of the reviewed guidelines is a practical guide to physicians and commissioners in making local policies for IFD management.
Gait Difficulty, Postural Instability, and Muscle Weakness Are Associated with Fear of Falling in People with Parkinson's Disease

The present study aimed to examine the contribution of gait impairment, postural stability and muscle weakness to the level of fear of falling in people with Parkinson's disease (PD). Fifty-seven community-dwelling individuals with PD completed the study. Fear of falling was assessed by the Activities-specific Balance Confidence (ABC) scale. Postural stability and gait difficulty were determined by the posture and gait subscores of the Unified Parkinson's Disease Rating Scale (UPDRS-PG). A Cybex dynamometer was used to measure isokinetic knee muscle strength. Individuals with PD achieved a mean ABC score of 73.6 ± 19.3. In the multiple regression analysis, after accounting for basic demographics, fall history and disease severity, the UPDRS-PG score remained independently associated with the ABC score, accounting for 13.4% of the variance (P < 0.001). The addition of knee muscle strength significantly improved the prediction model and accounted for an additional 7.3% of the variance in the ABC score (P < 0.05). This is the first study to demonstrate that the UPDRS-PG score and knee muscle strength are important and independent determinants of the level of fear of falling in individuals with PD. Improving balance, gait stability and knee muscle strength could be crucial in promoting balance confidence in the appropriately targeted PD population.
A Waitlist-Controlled Trial of Behavioral Parent Training for Fathers of Children with ADHD

Fathers, in general, have been underrepresented in studies of parent training outcome for children with attention deficit hyperactivity disorder (ADHD), and the present study aimed to investigate the efficacy of a behavioral parent training program developed expressly for fathers. The present investigation randomly assigned 55 fathers of children ages 6 to 12 with ADHD to the Coaching Our Acting-out Children: Heightening Essential Skills (COACHES) program or a waitlist control group. Outcomes for the study included objective observations of parent behaviors and parent ratings of child behavior. Results indicated that fathers in the COACHES group reduced their rates of negative talk and increased rates of praise as measured in parent–child observations, and father ratings of the intensity of problem behaviors were reduced, relative to the waitlist condition. Groups did not differ on observations of use of commands or father ratings of child behavior problems. Untreated mothers did not significantly improve on observational measures or behavioral ratings. This study provides preliminary evidence for the efficacy of the COACHES parenting program for fathers of children with ADHD. Results are cast in light of the larger literature on behavioral parent training for ADHD as well as how to best work with fathers of children with ADHD in treatment contexts.
Several PATCHED1 Missense Mutations Display Activity in patched1-Deficient Fibroblasts*

Mutations in mouse and human patched1(ptc1) genes are associated with birth defects and cancer. Ptc1 is a receptor for Hedgehog (Hh) signaling proteins. Hh proteins activate transcription of target genes, including ptc1, and Ptc1 represses those genes, both by regulating the activity of Gli transcription factors. We have established mammalian cell lines with reduced Ptc1 function and a lacZ reporter to investigate Hh signal transduction. Embryonic fibroblasts were derived from mice, heterozygous or homozygous for a ptc1 mutation that insertslacZ under the control of the ptc1 promoter (ptc1-lacZ). In heterozygous ptc1 cells,ptc1-lacZ was expressed at low levels but could be induced by Sonic Hedgehog (Shh) and Gli-1. Homozygous ptc1 cells expressed high levels of ptc1-lacZ without Hh stimulation.ptc1-lacZ expression was dependent on cell density inptc1 homozygotes and Hh-stimulated heterozygotes but was independent of density when Gli1 was used to activateptc1-lacZ. A wild-type ptc1 transgene introduced into homozygous ptc1 cells greatly reducedptc1-lacZ expression. Expression of either half of Ptc1 alone resulted in improper maturation of the protein and a failure to complement the ptc1 −/− cells. When co-expressed, both Ptc1 halves matured and had an activity similar to that of the intact protein. Three missense PTCH1 mutations exhibited significant functions in homozygous ptc1 cells. The missense mutants retained activity when expressed at about 10-fold lower levels and appeared as stable as wild-type Ptc1. These studies suggest that some tumors and disease phenotypes may arise from small reductions in PTCH1 activity.
Rate-dependent Perception of Aspiration and Pre-aspiration in Icelandic

Speech segments are highly context-dependent and acoustically variable. One factor that contributes heavily to the variability of speech is speaking rate. Some speech cues are temporal in nature—that is, the distinctions that they signify are defined over time. How can temporal speech cues keep their distinctiveness in the face of extrinsic transformations, such as those wrought by different speaking rates? This issue is explored with respect to the perception, in Icelandic, of Voice Onset Time as a cue for word-initial stop voicing, wordinitial aspiration as a cue for [h], and Voice Offset Time as a cue for pre-aspiration. All the speech cues show rate-dependent perception though to different degrees, with Voice Offset Time being most sensitive to rate changes and Voice Onset Time least sensitive. The differences in the behaviour of these speech cues are related to their different positions in the syllable.