Miracle-dz/UniFAR-FTUs huggingface dataset:
Granulomatous Reaction to Pneumocystis jirovecii: Clinicopathologic Review of 20 Cases

To better characterize the clinical and pathologic features of granulomatous reaction to Pneumocystis jirovecii, we reviewed 20 cases of this uncommon response. Patients included 15 males and 5 females (mean age 52 y). The most common symptom was dyspnea (5 of 14). Primary medical diagnoses included human immunodeficiency virus/acquired immunodeficiency syndrome (7 of 20), hematopoietic (6 of 20), and solid malignancies (4 of 20). Radiology findings included nodular (8 of 16) and diffuse (5 of 16) infiltrates and solitary nodules (3 of 16). Diagnostic procedures with the highest yield were open lung biopsy (13 of 20) and autopsy (5 of 20); false-negative results were most common on bronchial washings/brushings, bronchoalveolar lavage, fine needle aspiration, and transbronchial biopsy. Follow-up showed resolution of disease (6 of 13), death from disease (6 of 13), and death from unknown cause (1 of 13). Histologically, clusters of Gomori methenamine silver-positive (20 of 20) Pneumocystis organisms were identified in all cases. Organisms were identified within well (16 of 20) and poorly (4 of 20) formed necrotizing (16 of 20) and non-necrotizing (4 of 20) granulomas ranging in size from 0.1 to 2.5 cm (mean 0.5 cm); granulomas were multiple (18 of 20) or single (2 of 20). Giant cells (11 of 20), a fibrous rim (8 of 20), and eosinophils (6 of 20) were seen. Foamy eosinophilic exudates were present centrally within some granulomas (5 of 20). Cystic spaces (1 of 20) and calcification (1 of 20) were rare. Only one case demonstrated classic intra-alveolar foamy exudates containing Pneumocystis. Granulomatous P. jirovecii pneumonia occurs most commonly in males with human immunodeficiency virus/acquired immunodeficiency syndrome, hematopoietic, and solid malignancies. The diagnosis may be overlooked as conventional radiologic and pathologic features are absent. When suspected, open lung biopsy is most likely to yield diagnostic material. Attention to organism morphology avoids misdiagnosis as Histoplasma.
A visitors’ experience model for mixed reality in the museum

ABSTRACT Although virtual and augmented reality are receiving increasing attention in tourism and cultural heritage, the effect of mixed reality on museum visitors’ experience has still not been fully answered, and research on this topic is still in its infancy. This paper aims to contribute to this debate proposing a novel model that measures the impact of mixed reality on museum visitors’ experience and satisfaction. ‘The Ara as It Was’, an innovative project enhancing the value of the Italian masterpiece, the Ara Pacis Museum, has been used to test this model. The discussion and conclusion open up new avenues of research.
The Evidence for Intraoperative Neurophysiological Monitoring in Spine Surgery: Does It Make a Difference?

Objective. The objective of this article was to undertake a systematic review of the literature to determine whether IOM is able to sensitively and specifically detect intraoperative neurologic injury during spine surgery and to assess whether IOM results in improved outcomes for patients during these procedures. Summary and Background Data. Although relatively uncommon, perioperative neurologic injury, in particular spinal cord injury, is one of the most feared complications of spinal surgery. Intraoperative neuromonitoring (IOM) has been proposed as a method which could reduce perioperative neurologic complications after spine surgery. Methods. A systematic review of the English language literature was undertaken for articles published between 1990 and March 2009. MEDLINE, EMBASE, and Cochrane Collaborative Library databases were searched, as were the reference lists of published articles examining the use of IOM in spine surgery. Two independent reviewers assessed the level of evidence quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria, and disagreements were resolved by consensus. Results. A total of 103 articles were initially screened and 32 ultimately met the predetermined inclusion criteria. We determined that there is a high level of evidence that multimodal IOM is sensitive and specific for detecting intraoperative neurologic injury during spine surgery. There is a low level of evidence that IOM reduces the rate of new or worsened perioperative neurologic deficits. There is very low evidence that an intraoperative response to a neuromonitoring alert reduces the rate of perioperative neurologic deterioration. Conclusion. Based on strong evidence that multimodality intraoperative neuromonitoring (MIOM) is sensitive and specific for detecting intraoperative neurologic injury during spine surgery, it is recommended that the use of MIOM be considered in spine surgery where the spinal cord or nerve roots are deemed to be at risk, including procedures involving deformity correction and procedures that require the placement of instrumentation. There is a need to develop evidence-based protocols to deal with intraoperative changes in MIOM and to validate these prospectively.
Association of the Multisubstrate Docking Protein Gab1 with the Hepatocyte Growth Factor Receptor Requires a Functional Grb2 Binding Site Involving Tyrosine 1356*

Hepatocyte growth factor/scatter factor is a multifunctional factor that induces mitogenesis, motility, invasion, and branching tubulogenesis of several epithelial and endothelial cell lines in culture. The receptor for hepatocyte growth factor has been identified as the Met-tyrosine kinase. Upon stimulation with hepatocyte growth factor, the Met β subunit becomes highly phosphorylated on tyrosine residues, one of which, tyrosine 1356 within the carboxyl terminus, is crucial for dissociation, motility, and branching tubule formation in Madin-Darby canine kidney epithelial cells. Tyrosine 1356 forms a multisubstrate binding site for the Grb2 and Shc adaptor proteins, the p85 subunit of phosphatidylinositol 3′-kinase, phospholipase Cγ, and a phosphatase, SHP2. To investigate additional signaling molecules that are activated by the Met receptor, we have identified hepatocyte growth factor-induced phosphoproteins in tubular epithelial cells. We have established that proteins of 100–130 kDa are highly phosphorylated following stimulation of epithelial cells and that one of these is the Grb2-associated binding protein Gab1, a possible insulin receptor substrate-1-like signal transducer. We show that Gab1 is the major substrate for the Met kinase in vitro and in vivo. Association of Gab1 with Met requires a functional Grb2 binding site involving tyrosine 1356 and to a lesser extent tyrosine 1349. Met receptor mutants that fail to induce branching tubulogenesis are impaired in their ability to interact with Gab1, suggesting that Gab1 may play a role in these processes.
Developmental differences in detection and disclosure of sexual abuse.

OBJECTIVE This study examined the role of developmental differences in the detection and disclosure of child sexual abuse. METHOD A random medical record review was conducted of 72 children and adolescents seen over a consecutive 3-year period for suspected sexual abuse in the emergency room of a pediatric hospital. The following data were gathered: (1) demographic information, (2) presenting symptomatology that initiated caregiver decision to seek evaluation, (3) type of disclosure (purposeful or accidental), and (4) precipitants to disclosure. RESULTS Preschool age children were significantly more likely than school age children and adolescents to exhibit behavioral or physical symptoms that prompted caregivers' suspicion of sexual abuse. Preschool age children made disclosures accidentally and typically with an immediate precipitating event unrelated to the abuse itself. In contrast, sexual abuse disclosures from school age children were purposeful and not associated with a precipitating event. CONCLUSIONS Practitioners need to be aware of the developmental differences in the detection of sexual abuse, including the forces that inhibit disclosure in older children.
The role of generalized pain and pain behavior in tender point scores in fibromyalgia.

OBJECTIVE To determine and assess the significance of the independent role of pain, pain behavior, depression, and weekly stress in tender point scores in objectively diagnosed fibromyalgia (FM) patients. METHODS One hundred eleven patients with FM recruited from the community and private and university based clinics participated in a comprehensive evaluation of their pain, psychological distress, and pain behavior. Tender point assessment was carried out across 18 discrete sites according to American College of Rheumatology criteria. Pain was assessed with a composite index of 4 pain measures; psychological distress consisted of measures of stress and depression, and pain behavior was measured by an objective index derived from a 10 minute videotaped sequence in which 5 pain behaviors were recorded. RESULTS Multiple regression analyses revealed that high pain, high pain behavior, and shorter illness duration were related independently to tender point scores. Measures of depression and weekly stress were not independently related to tender point scores. CONCLUSION Tender point scores are related to generalized pain and pain behavior tendencies in patients with FM, and do not independently reflect generalized psychological distress.
Modal parameter estimation in the presence of non-linearities

This paper investigates the use of time-frequency techniques to assist in the estimation of power system modes which are resolvable by a Digital Fourier Transform (DFT). The limitations of linear estimation techniques in the presence of large disturbances which excite system non-linearities, particularly the swing equation non-linearity are shown. Where a nonlinearity manifests itself as time varying modal frequencies the Wigner-Ville Distribution (WVD) is used to describe the variation in modal frequencies and construct a window over which standard linear estimation techniques can be used. The error obtained even in the presence of multiple resolvable modes is better than 2%.
Adiponectin Stimulates RANKL and Inhibits OPG Expression in Human Osteoblasts Through the MAPK Signaling Pathway

Our study indicates that recombinant adiponectin induced RANKL and inhibited OPG expression in human osteoblasts through the AdipoR1/p38 MAPK pathway, and these responses contributed to the adiponectin‐induced osteoclasts formation in the co‐culture of osteoblast and peripheral blood monocytes systems. These findings showed that adiponectin increased osteoclast formation indirectly through stimulating RANKL and inhibiting OPG production in osteoblasts. It also suggests the pharmacological nature of recombinant adiponectin that indirectly induces osteoclasts formation.
BCR/ABL confers growth factor independence upon a murine myeloid cell line.

The BCR/ABL oncogene in chronic myelogenous leukemia produces an activated tyrosine kinase fusion protein (p210). Like other tyrosine kinase oncogenes, BCR/ABL can abrogate the interleukin-3 (IL-3) dependence of lymphoid cell lines. To investigate the ability of BCR/ABL to generate growth factor independence in myeloid cells, the IL-3 dependent myeloid cell line NFS/N1.H7 (H7) was transfected with the p210BCR/ABL-containing plasmid, pGD210. Stable clones A54 and A74 were capable of IL-3 independent growth and tumor formation in syngeneic mice. Relief of growth factor dependence was not mediated by autocrine release of IL-3. The baseline proliferation rate of the BCR/ABL transformed cells was greater than that of the parental H7 cells maximally stimulated by IL-3. Abundant constitutive expression of c-myc, c-jun, and c-fos was observed in the p210BCR/ABL transfectants even in low serum conditions. In contrast, c-myc expression in H7 cells was dependent upon IL-3 stimulation, and neither c-jun nor c-fos was highly expressed following IL-3 stimulation in H7 cells. Thus, BCR/ABL transformation and relief of IL-3 dependence involve not only pathways that can substitute for IL-3 induced growth via tyrosine kinase mediated signals, but also pathways that recruit constitutive c-jun and c-fos expression.
Noise suppression of fluorescein angiogram sequences using bilateral filter

In this paper, a relatively flexible filter called extended bilateral filter is proposed, by which some particular filters can be designed via selecting an appropriate pixel of interest (POI) and defining a kernel for the filter according to some specified requirements. Based on the filter, a fluorescein-angiogram-oriented filter, high-intensity preserving (HIP) filter is introduced to solve the problems of high-intensity preservation when denoising. The results of the experiments show that the HIP filter has the ability of noise suppression, and the ability of high-intensity preservation, which can keep the intensities of bright pixels from degrading via distributing the weights adaptively according to the location and the intensity of each pixel.
c-Src Links a RANK/αvβ3 Integrin Complex to the Osteoclast Cytoskeleton

ABSTRACT RANK ligand (RANKL), by mechanisms unknown, directly activates osteoclasts to resorb bone. Because c-Src is key to organizing the cell's cytoskeleton, we asked if the tyrosine kinase also mediates RANKL-stimulated osteoclast activity. RANKL induces c-Src to associate with RANK369–373 in an αvβ3-dependent manner. Furthermore, RANK369–373 is the only one of six putative TRAF binding motifs sufficient to generate actin rings and activate the same cytoskeleton-organizing proteins as the integrin. While c-Src organizes the cell's cytoskeleton in response to the cytokine, it does not participate in RANKL-stimulated osteoclast formation. Attesting to their collaboration, αvβ3 and activated RANK coprecipitate, but only in the presence of c-Src. c-Src binds activated RANK via its Src homology 2 (SH2) domain and αvβ3 via its SH3 domain, suggesting the kinase links the two receptors. Supporting this hypothesis, deletion or inactivating point mutation of either the c-Src SH2 or SH3 domain obviates the RANK/αvβ3 association. Thus, activated RANK prompts two distinct signaling pathways; one promotes osteoclast formation, and the other, in collaboration with c-Src-mediated linkage to αvβ3, organizes the cell's cytoskeleton.
Intraoperative Infusion of Amino Acids Induces Anabolism Independent of the Type of Anesthesia

BACKGROUND:The infusion of dextrose in patients receiving epidural and light general anesthesia or general anesthesia alone failed to achieve a positive protein balance. We sought to verify the hypothesis that nutritional supplementation with IV amino acids induced a greater protein balance in patients receiving epidural blockade compared with those receiving general anesthesia. METHODS:Sixteen patients were randomly assigned to receive either general anesthesia with desflurane (control group) or general anesthesia combined with epidural analgesia (EDA group). A primed constant infusion of stable isotope tracers l-[1-13C]leucine and [6,6-2H2]glucose was started after a 32-h fast before surgery, (3 h of fasted state), and continued for 3 h during surgery during which amino acids were infused IV (fed state). RESULTS:Compared with the fasted state, the endogenous rate of appearance of leucine decreased to a similar extent in both groups, and protein synthesis increased, with no difference between the two groups. Leucine oxidation did not change in either group. After amino acids infusion, endogenous glucose production remained unchanged and glucose clearance decreased in both groups. Blood glucose, plasma cortisol, serum insulin, and glucagon concentrations increased to the same extent in both groups. CONCLUSIONS:Epidural anesthesia provided no additional benefit beyond the anabolism obtained with amino acids.
Independent Structural Domains in Paramyxovirus Polymerase Protein*

Background: RNA-dependent RNA polymerases of nonsegmented negative-strand RNA viruses (Mononegavirales) harbor multiple catalytic activities. Results: Domain screening and trans-complementation of Paramyxovirus polymerase fragments with dimerization tags identifies independent folding-competent domains. Conclusion: Paramyxovirus polymerases harbor at least two independent domains that lack high-affinity interfaces but require molecular compatibility for bioactivity. Significance: First demonstration of Mononegavirales polymerase trans-complementation sets the stage for structural analyses of folding domains. All enzymatic activities required for genomic replication and transcription of nonsegmented negative strand RNA viruses (or Mononegavirales) are believed to be concentrated in the viral polymerase (L) protein. However, our insight into the organization of these different enzymatic activities into a bioactive tertiary structure remains rudimentary. Fragments of Mononegavirales polymerases analyzed to date cannot restore bioactivity through trans-complementation, unlike the related L proteins of segmented NSVs. We investigated the domain organization of phylogenetically diverse Paramyxovirus L proteins derived from measles virus (MeV), Nipah virus (NiV), and respiratory syncytial virus (RSV). Through a comprehensive in silico and experimental analysis of domain intersections, we defined MeV L position 615 as an interdomain candidate in addition to the previously reported residue 1708. Only position 1708 of MeV and the homologous positions in NiV and RSV L also tolerated the insertion of epitope tags. Splitting of MeV L at residue 1708 created fragments that were unable to physically interact and trans-complement, but strikingly, these activities were reconstituted by the addition of dimerization tags to the fragments. Equivalently split fragments of NiV, RSV, and MeV L oligomerized with comparable efficiency in all homo- and heterotypic combinations, but only the homotypic pairs were able to trans-complement. These results demonstrate that synthesis as a single polypeptide is not required for the Mononegavirales polymerases to adopt a proper tertiary conformation. Paramyxovirus polymerases are composed of at least two truly independent folding domains that lack a traditional interface but require molecular compatibility for bioactivity. The functional probing of the L domain architecture through trans-complementation is anticipated to be applicable to all Mononegavirales polymerases.
Mechanisms for the hepatic uptake of organic cations. Studies with the muscle relaxant vecuronium in isolated rat hepatocytes.

In hepatobiliary transport of organic cations some remarkable differences have been reported between the monovalent compounds (prototype procainamidethobromide) and the potentially bivalent cations, containing a second quaternary ammonium group or a protonated tertiary amine function (prototype d-tubocurarine). In order to characterize the hepatic uptake mechanism for such bivalent cations in more detail, we studied the uptake of the steroidal muscle relaxant vecuronium in isolated rat hepatocytes. Uptake occurred by both a saturable (Vmax = 181 pmol/min x 10(6) cells, Km = 15 microM) and a nonsaturable process (rate constant = 1.10 pmol/min/10(6) cells/microM). The uptake of vecuronium was reduced by various metabolic inhibitors and by sulfhydryl-blocking agents. The transport system showed temperature dependency with an activation energy of 85 kJ/mol. Sodium replacement by lithium or choline in the extracellular medium had no effect on the uptake of vecuronium. Replacement of sodium chloride by sucrose led to a decrease of the uptake, whereas chloride replacement by bicarbonate or iodide stimulated the vecuronium uptake. These data point to a significant anion-dependency of the uptake system and indicate electroneutral uptake of vecuronium. The uptake of vecuronium was inhibited by a variety of hepatic transport model compounds, including bile acids, uncharged compounds and high molecular weight organic cations. Low molecular weight monovalent cations had no effect on the uptake of vecuronium. (ABSTRACT TRUNCATED AT 250 WORDS)
Adhesion modification of neural stem cells induced by nanoscale ripple patterns

We have studied the influence of anisotropic nanopatterns (ripples) on the adhesion and morphology of mouse neural stem cells (C17.2) on glass substrates using cell viability assay, optical microscopy and atomic force microscopy. The ripples were produced by defocused ion beam sputtering with inert Ar ions, which physically remove atoms from the surface at the energy of 800 eV. The ripple periodicity (∼200 nm) is comparable to the thickness of the cytoplasmatic microspikes (filopodia) which link the stem cells to the substrate. All methods show that the cell adhesion is significantly lowered compared to the same type of cells on flat glass surfaces. Furthermore, the AFM analysis reveals that the filopodia tend to be trapped parallel or perpendicular to the ripples, which limits the spreading of the stem cell on the rippled substrate. This opens the perspective of controlling the micro-adhesion of stem cells and the orientation of their filopodia by tuning the anisotropic substrate morphology without chemical reactions occurring at the surface.
Debridement, Antibiotics, Irrigation, and Retention (DAIR) of the Prosthesis after Hip Hemiarthroplasty Infections. Does it Work?

Purpose Debridement, antibiotic, and implant retention (DAIR) is an attractive treatment modality after hip hemiarthroplasty (HA) infections. Data about the success of the procedure after acute onset infections is lacking. The aim of this study was to analyze the clinical outcome and associated risk factors. Methods A multicenter, retrospective cohort study was designed, including 39 patients with acute onset prosthetic infection who had undergone debridement and irrigation with prosthesis retention. The primary outcome measure was infection eradication without prosthesis removal. We also analyzed how the success rate was influenced by the length of the interval between implantation of the prosthesis and the beginning of the treatment. Results The overall success rate was 41%. Sedimentation rate over 60 mm/h and the longer duration (2 weeks) after prosthesis implantation were found as factors negatively influencing the success rate. Conclusions Our results indicated limited success to DAIR- treated patients with infected HA. The high failure rate of DAIR treatment after 2 weeks from the implantation should be taken into consideration.
Examining customer perceptions of restaurant restroom cleanliness and their impact on satisfaction and intent to return

ABSTRACT Competition in the Canadian restaurant industry is unyielding. Restaurant cleanliness is one of the most important aspects when a customer evaluates restaurant quality and return intention. In particular, restaurant restroom cleanliness (RRC) is often considered the central factor that leads to overall perception of cleanliness. This study examined how RRC affects restaurant customers. Restroom appearance had the greatest impact on cleanliness followed by personal hygiene items. In addition, RRC impacted customer satisfaction and did not vary based on customer segmentation. However, older restaurant patrons were more likely to report RRC issues than younger patrons. The research demonstrates that RRC is an essential element to the success and viability of a food service operation and is an important aspect of academic research in foodservice operations. Future directions for both industry and academic research in this area are discussed.