Miracle-dz/UniFAR-FTUs huggingface dataset:
A new model for non-typeable Haemophilus influenzae middle ear infection in the Junbo mutant mouse

ABSTRACT Acute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and, as a consequence, is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used. We have established a robust model of middle ear infection by NTHi in the Junbo mouse, a mutant mouse line that spontaneously develops chronic middle ear inflammation in specific pathogen-free conditions. The heterozygote Junbo mouse (Jbo/+) bears a mutation in a gene (Evi1, also known as Mecom) that plays a role in host innate immune regulation; pre-existing middle ear inflammation promotes NTHi middle ear infection. A single intranasal inoculation with NTHi produces high rates (up to 90%) of middle ear infection and bacterial titres (104-105 colony-forming units/µl) in bulla fluids. Bacteria are cleared from the majority of middle ears between day 21 and 35 post-inoculation but remain in approximately 20% of middle ears at least up to day 56 post-infection. The expression of Toll-like receptor-dependent response cytokine genes is elevated in the middle ear of the Jbo/+ mouse following NTHi infection. The translational potential of the Junbo model for studying antimicrobial intervention regimens was shown using a 3 day course of azithromycin to clear NTHi infection, and its potential use in vaccine development studies was shown by demonstrating protection in mice immunized with killed homologous, but not heterologous, NTHi bacteria. Summary: Acute otitis media is an important disease in children. We describe a new infection model for translational research that uses the Junbo mouse mutant intranasally inoculated with non-typeable Haemophilus influenzae.
Alterations of Mast Cells in the Esophageal Mucosa of the Patients With Non-Erosive Reflux Disease

Background Mast cells (MCs) are widely distributed in the gastrointestinal tract, which could be involved in visceral hypersensitivity and gut dysmotility. Whether esophageal MCs play a role in non-erosive reflux disease (NERD) has yet to be determined. The aim of this study was to characterize esophageal MCs distribution, degranulation, and ultrastructure. Methods The esophageal mucosa at 5 cm above the end of esophagus was obtained from 26 NERD and 14 healthy volunteers (control) by gastroscopy. Immunohistochemistry was performed and average MC counts per high-power field (HPF) and the percentage of degranulated MCs were obtained. The ultrastructure of MCs was observed by transmission electron microscope (TEM). Results More MCs were observed in NERD (7.23 ± 2.41 cells/HPF) as compared with controls (3.79 ± 1.67 cells/HPF) (P < 0.01) and the percentage of degranulated MCs in NERD was also significantly higher than controls (26.85 ± 8.79% vs 11.5 ± 4.18%, P < 0.01). Under TEM, more Golgi apparatus, mitochondria and endoplasmic reticulum were found in MCs in patients with NERD. Special secreting particles were also found in cytoplasm, more vacuoles were left after MCs degranulation in patients with NERD. Conclusions Our results indicate that increased numbers of MCs and MCs activation may be involved in the pathogenesis of NERD.
Cell cycle regulation of an exogenous human poly(ADP‐ribose) polymerase cDNA introduced into murine cells

We have evaluated the regulation of expression of the poly(ADP‐ribose) polymerase gene during cell growth and replication. In a synchronized population of HeLa cells or in serum‐stimulated WI‐38 cells, steady‐state levels of the polymerase mRNA were highest at late S and S‐G2 phases and negligible in early S phase. Transcription did not solely account for the significant increase in the mRNA levels observed in late S phase by Northern analysis. The stability of the mRNA was dependent upon the percent proliferating cells in the culture. Accordingly, polymerase mRNA from cells in early exponential phase was significantly more stable than from cells in stationary phase of asynchronous growth. To clarify these observations, we utilized a novel heterologous expression system that involved murine 3T3 cells transfected with a human poly(ADP‐ribose) polymerase cDNA under the control of a non‐cell cycle‐specific promoter. Cells were synchronized, and a comparison was made of the endogenous (murine) and exogenous (human) polymerase mRNA levels. Both the endogenous and the exogenous mRNA were specifically stabilized by the same mechanisms and only during late S phase; therefore, we concluded that mRNA pools for the polymerase are regulated at the post‐transcriptional level. The heterologous expression system confirmed that the post‐transcriptional regulation system in the mouse cells can recognize and faithfully regulate the human cDNA in response to the murine cell cycle signals. More importantly, the presence of extra copies (human) of the polymerase gene did not provide an increased amount of the total polymerase mRNA or protein and, in fact, the sum of the endogenous and exogenous mRNA in the transfected cells was approximately the same as the level of endogenous transcript in the control cells. This suggested that there might be a limit to the amount of polymerase protein accumulating in the cellular pool and thus levels of poly(ADP‐ribose) polymerase may be autoregulated.
Pilot study with pegylated liposomal doxorubicin for advanced or unresectable hepatocellular carcinoma

We performed a pilot-study on pegylated liposomal doxorubicin (PLD) for advanced hepatocellular carcinoma. Seventeen patients received 40 mg/m2 PLD intravenously every 4 weeks. A clinical benefit response was achieved in 50% (complete remission 7%, minor remission 7%, stable disease 36%). Toxicities were moderate. In view of these encouraging findings, further studies appear warranted. © 2001 Cancer Research Campaign
Sialylation of Prion Protein Controls the Rate of Prion Amplification, the Cross-Species Barrier, the Ratio of PrPSc Glycoform and Prion Infectivity

The central event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrPC) into the disease-associated, transmissible form (PrPSc). PrPC is a sialoglycoprotein that contains two conserved N-glycosylation sites. Among the key parameters that control prion replication identified over the years are amino acid sequence of host PrPC and the strain-specific structure of PrPSc. The current work highlights the previously unappreciated role of sialylation of PrPC glycans in prion pathogenesis, including its role in controlling prion replication rate, infectivity, cross-species barrier and PrPSc glycoform ratio. The current study demonstrates that undersialylated PrPC is selected during prion amplification in Protein Misfolding Cyclic Amplification (PMCAb) at the expense of oversialylated PrPC. As a result, PMCAb-derived PrPSc was less sialylated than brain-derived PrPSc. A decrease in PrPSc sialylation correlated with a drop in infectivity of PMCAb-derived material. Nevertheless, enzymatic de-sialylation of PrPC using sialidase was found to increase the rate of PrPSc amplification in PMCAb from 10- to 10,000-fold in a strain-dependent manner. Moreover, de-sialylation of PrPC reduced or eliminated a species barrier of for prion amplification in PMCAb. These results suggest that the negative charge of sialic acid controls the energy barrier of homologous and heterologous prion replication. Surprisingly, the sialylation status of PrPC was also found to control PrPSc glycoform ratio. A decrease in PrPC sialylation levels resulted in a higher percentage of the diglycosylated glycoform in PrPSc. 2D analysis of charge distribution revealed that the sialylation status of brain-derived PrPC differed from that of spleen-derived PrPC. Knocking out lysosomal sialidase Neu1 did not change the sialylation status of brain-derived PrPC, suggesting that Neu1 is not responsible for desialylation of PrPC. The current work highlights previously unappreciated role of PrPC sialylation in prion diseases and opens multiple new research directions, including development of new therapeutic approaches.
Synchronized gas and partial liquid ventilation in lung‐injured animals: Improved gas exchange with decreased effort

We hypothesized that partial liquid ventilation (PLV) with perflubron in spontaneously breathing lung‐injured animals would increase respiratory workload compared to animals treated with gas ventilation (GV), and that a fully synchronized mode, assist‐control ventilation (AC), would reduce the piglets' effort when compared to intermittent mandatory ventilation (IMV) or synchronized IMV (SIMV) during both GV and PLV. Newborn piglets with saline lavage‐induced lung injury were randomized to sequential 30‐min periods of IMV → SIMV → AC (n = 5), or AC → SIMV → IMV (n = 5) during GV followed by PLV. Pulmonary mechanics measurements and an esophageal patient effort index (PEI, defined as the product of the area below baseline of the esophageal pressure‐time curve and respiratory rate [RR]) were determined to estimate the patient's nonmechanical work of breathing, using a computer‐assisted lung mechanics analyzer.
Exploring the Bag-of-Words method for 3D shape retrieval

This paper investigates the capabilities of the Bag-of-Words (BW) method in the 3D shape retrieval field. The contributions of this paper are: 1) the 3D shape retrieval task is categorized from different points of view: specific vs. generic, partial-to-global (PG) vs. global-to-global (GG) retrieval, and articulated vs. non-articulated; 2) The spatial information, which is represented as concentric spheres, is integrated into the framework to improve the discriminative capability; 3) the analysis of the experimental results on Purdue Engineering Benchmark (PEB) [4] reveals that some properties of the BW approach make it perform better on the PG task than the GG task. 4) The BW approach is evaluated on non-articulated database PEB [4] and articulated database McGill Shape Benchmark (MSB) [17] and compared to other methods.
Global Seabird Response to Forage Fish Depletion—One-Third for the Birds

One-third of maximum fish biomass must be available for seabirds to sustain high breeding success. Determining the form of key predator-prey relationships is critical for understanding marine ecosystem dynamics. Using a comprehensive global database, we quantified the effect of fluctuations in food abundance on seabird breeding success. We identified a threshold in prey (fish and krill, termed “forage fish”) abundance below which seabirds experience consistently reduced and more variable productivity. This response was common to all seven ecosystems and 14 bird species examined within the Atlantic, Pacific, and Southern Oceans. The threshold approximated one-third of the maximum prey biomass observed in long-term studies. This provides an indicator of the minimal forage fish biomass needed to sustain seabird productivity over the long term.
Catatonia and alcohol withdrawal: a complex and underestimated syndrome.

AIMS Catatonia is a neuropsychiatric syndrome characterized by alterations in motor behavior, vigilance, thought and mood. Catatonia syndrome occurs in many neuropsychiatric and medical conditions, but it is very rarely mentioned as occurring during alcohol withdrawal. We think that this co-occurrence could be underestimated in clinics because alcohol withdrawal symptoms may distract from its identification. METHODS We report the case of a patient presenting with catatonia during the benzodiazepine reduction period of alcohol detoxification. RESULTS A 65-year-old woman presented with a 15-year history of alcohol dependence and developed catatonic episodes several times during alcohol withdrawal treatment. Misdiagnosis delayed specific treatment. Symptoms of episodes dramatically improved 48 h after treatment with diazepam and revealed an anxiety disorder. CONCLUSION This report confirms that catatonia is a non-specific response to psychological, physical and psychosocial stress factors. Recent alcohol withdrawal may sensitize the patient to benzodiazepine withdrawal catatonia, and this phenomenon is probably underestimated. Catatonia Rating Scales can be useful when diagnosis is complicated as in alcohol and benzodiazepine withdrawal. In that situation, misdiagnosis is common and may delay specific treatment.
A crucial role for interleukin (IL)-1 in the induction of IL-17–producing T cells that mediate autoimmune encephalomyelitis

It was recently demonstrated that interleukin (IL)-23–driven IL-17–producing (ThIL-17) T cells mediate inflammatory pathology in certain autoimmune diseases. We show that the induction of antigen-specific ThIL-17 cells, but not T helper (Th)1 or Th2 cells, by immunization with antigens and adjuvants is abrogated in IL-1 receptor type I–deficient (IL-1RI−/−) mice. Furthermore, the incidence of experimental autoimmune encephalomyelitis (EAE) was significantly lower in IL-1RI−/− compared with wild-type mice, and this correlated with a failure to induce autoantigen-specific ThIL-17 cells, whereas induction of Th1 and Th2 responses was not substantially different. However, EAE was induced in IL-1RI−/− mice by adoptive transfer of autoantigen-specific cells from wild-type mice with EAE. IL-23 alone did not induce IL-17 production by T cells from IL-1RI−/− mice, and IL-23–induced IL-17 production was substantially enhanced by IL-1α or IL-1β, even in the absence of T cell receptor stimulation. We demonstrate essential roles for phosphatidylinositol 3-kinase, nuclear factor κB, and novel protein kinase C isoforms in IL-1– and IL-23–mediated IL-17 production. Tumor necrosis factor α also synergized with IL-23 to enhance IL-17 production, and this was IL-1 dependent. Our findings demonstrate that IL-1 functions upstream of IL-17 to promote pathogenic ThIL-17 cells in EAE.
What do people think about when they answer the Brief Illness Perception Questionnaire? A 'think-aloud' study.

OBJECTIVES The Brief Illness Perception Questionnaire (Brief IPQ) is a commonly used questionnaire that aims to assess patients' illness beliefs. There is, however, no direct information on how people interpret and respond to this questionnaire, nor on the nature and extent of problems people have when completing it. The present study describes the problems that patients encounter when completing the Brief IPQ. DESIGN Cross-sectional observational study. METHODS A 'think-aloud' method was employed with two samples: 6 patients attending a preoperative exercise programme in secondary care, and 11 patients receiving physiotherapy in primary care. RESULTS In total, 88 problems were identified, mostly (N= 45) consisted of participants re-reading a question or stumbling in reading it. In 8 cases, participants misinterpreted a question. The pattern of findings was striking similar across the two samples. The questions about identity, personal control, illness coherence, and causal attributions yielded most difficulties (18, 16, 16, and 11 problems, respectively). CONCLUSIONS Given that the Brief IPQ assesses each construct with a single item, the number of problems people have with completing it is particularly problematic, and calls into question the content validity of this measure. Further developmental work with this questionnaire may be needed to better quantify and resolve the problems identified.
Lessons from a double‐transgenic neutrophil approach to induce antiproteinase 3 antibody–mediated vasculitis in mice

ANCA to either PR3 or MPO are found in patients with necrotizing vasculitis and glomerulonephritis. ANCA binding to their target antigens on neutrophils and subsequent neutrophil activation are pivotal disease mechanisms that lead to vascular inflammation and necrosis. ANCA interaction with PR3 is more complex than with MPO as the neutrophil‐specific CD177 receptor is involved in PR3 surface expression and PR3‐ANCA–induced neutrophil activation. Modeling human disease is important to clinical research. Highly successful mouse models of MPO‐ANCA vasculitis exist; however, recapitulating PR3‐ANCA vasculitis has not been successful. We generated double‐transgenic (DT) mice that expressed human PR3 and CD177 under a myeloid‐specific huMRP8 promoter in an attempt to model PR3‐ANCA vasculitis. DT mice strongly expressed the human transgenes in and on murine neutrophils and bound murine and human anti‐PR3 antibodies. Nevertheless, passive transfer of these antibodies into LPS‐primed DT mice or immunization of C57BL/6 mice with human PR3 followed by irradiation and transplantation of DT bone marrow failed to induce glomerulonephritis. Further analyses revealed that anti‐PR3 antibodies did not activate DT neutrophils as shown by superoxide generation. Moreover, we found that mice did not properly process human pro‐PR3 into mature PR3 and, consequently, the signaling complex between PR3, CD177, and CD11b, which promotes neutrophil activation by anti‐PR3 antibodies, failed to form. We conclude that important species differences in PR3 and CD177 exist between men and mice that prevented successful generation of a murine anti‐PR3 antibody model.
Predictors of Outcomes in Autism Early Intervention: Why Don’t We Know More?

Response to early intervention programs in autism is variable. However, the factors associated with positive versus poor treatment outcomes remain unknown. Hence the issue of which intervention/s should be chosen for an individual child remains a common dilemma. We argue that lack of knowledge on “what works for whom and why” in autism reflects a number of issues in current approaches to outcomes research, and we provide recommendations to address these limitations. These include: a theory-driven selection of putative predictors; the inclusion of proximal measures that are directly relevant to the learning mechanisms demanded by the specific educational strategies; the consideration of family characteristics. Moreover, all data on associations between predictor and outcome variables should be reported in treatment studies.
Variation Between Strains of Hamsters in the Lethality of Pichinde Virus Infections

Infection by Pichinde virus, a member of the arenavirus group, was studied in Golden Syrian hamsters (Mesocricetus auratus) with regard to possible mechanisms of resistance to virus infection in adult hamsters. Two hamster strains were found to differ in their susceptibility to lethal Pichinde virus infection. LVG/Lak randomly bred hamsters were found to be 100% susceptible to low doses of Pichinde virus during the first 6 days of life, but after 8 days of life, mortality was uncommon. Peak virus titers in the serum of animals infected at 3 days of life were 4 logs greater than in animals infected at 12 days. MHA/Lak inbred hamsters, in contrast, were found to be susceptible to lethal virus infection both as newborns and as adults. Peak virus titers of greater than 108 plaque-forming units/ml were observed in serum 8 days after infection of adult MHA hamsters as compared with less than 103 plaque-forming units/ml in the serum of adult LVG hamsters. Cultured primary kidney cells and peritoneal macrophages from either hamster strain supported Pichinde virus replication equally well in vitro. Antibodies to the complement-fixing antigens and to antigens at the surface of virus-infected cells were produced by both strains of hamsters. Cyclophosphamide immunosuppression rendered adult LVG animals susceptible to lethal infections, and virus grew to high titers in the treated animals. These findings suggest that immunological factors that appear early in life in LVG hamsters and are deficient in MHA hamsters limit Pichinde virus infection. Unlike previously reported arenavirus diseases, the observations suggest that death is produced by a direct viral effect and not through immunopathological mechanisms.
Unfiltered Aluminium Vacuum Arc Plasma Application for High-Frequency Short-Pulse Plasma Immersion Ion Implantation

This paper is devoted to the studying of the dynamical changes in the density of aluminium microparticles (MPs) on the substrate surface made of stainless steel, immersed in vacuum arc plasma, at high-frequency short-pulse negative bias potential. It is shown experimentally that the density of aluminium MPs on the substrate surface is decreased dynamically by 3 orders when the treatment time is increased from 15 s to 3 min at the bias potential –2 kV. A possibility of the application of MPs unfiltered vacuum arc plasma for high-frequency short-pulse plasma immersion ion implantation to form the intermetallic layers is discussed.
Possible Involvement of Angiotensin-Converting Enzyme 2 and Mas Activation in Inhibitory Effects of Angiotensin II Type 1 Receptor Blockade on Vascular Remodeling

We explored the roles of angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7), and Mas activation in angiotensin II type 1 receptor blockade-mediated attenuation of vascular remodeling. Vascular injury was induced by polyethylene-cuff placement around the mouse femoral artery. After cuff placement, the mRNA level of both ACE2 and Mas was markedly decreased in wild-type mice, whereas ACE mRNA was not changed. Immunostaining of ACE2 and Mas was observed mainly in the media and was reduced in the injured artery. Administration of angiotensin-(1-7) decreased neointimal formation after cuff placement, whereas administration of [D-Ala(7)] angiotensin-(1-7), a Mas antagonist, increased it. Consistent with these results, we also demonstrated that neointimal formation induced by cuff placement was further increased in ACE2 knockout mice. In angiotensin II type 1a receptor knockout mice, mRNA expression and immunostaining of ACE2 and Mas in the injured artery were greater, with less neointimal formation than in wild-type mice. Increased ACE2 expression in the injured artery was also observed by treatment of wild-type mice with an angiotensin II type 1 receptor blocker, olmesartan. These results suggested that activation of the ACE2-angiotensin-(1-7)-Mas axis is at least partly involved in the beneficial effects of angiotensin II type 1 receptor blockade on vascular remodeling.
Temperature sensor based on frequency upconversion in Er/sup 3+/-doped fluoroindate glass

We describe the characterization of a temperature sensor based on the infrared-to-visible frequency upconversion process excited in a sample of Er/sup 3+/-doped fluoroindate glass. The present results demonstrate the feasibility of constructing a compact practical device using a low-power CW 1.48-/spl mu/m diode laser as the excitation source.
Implicit and Explicit Memory for Spatial Information in Alzheimer’s Disease

There is abundant evidence that memory impairment in dementia in patients with Alzheimer’s disease (AD) is related to explicit, conscious forms of memory, whereas implicit, unconscious forms of memory function remain relatively intact or are less severely affected. Only a few studies have been performed on spatial memory function in AD, showing that AD patients’ explicit spatial memory is impaired, possibly related to hippocampal dysfunction. However, studies on implicit spatial memory in AD are lacking. The current study set out to investigate implicit and explicit spatial memory in AD patients (n = 18) using an ecologically valid computer task, in which participants had to remember the locations of various objects in common rooms. The contribution of implicit and explicit memory functions was estimated by means of the process dissociation procedure. The results show that explicit spatial memory is impaired in AD patients compared with a control group (n = 21). However, no group difference was found on implicit spatial function. This indicates that spared implicit memory in AD extends to the spatial domain, while the explicit spatial memory function deteriorates. Clinically, this finding might be relevant, in that an intact implicit memory function might be helpful in overcoming problems in explicit processing.