Miracle-dz/UniFAR-FTUs huggingface dataset:
Localization of nucleic acid‐sensing toll‐like receptors in human and mouse pancreas

Nucleic acid‐sensing toll‐like receptors (TLRs) (3, 7, 8, 9) have a role both in antiviral innate immunity and in autoimmune disorders. We assessed the expression of TLR3, 7, 8 and 9 in human and mouse pancreas focusing on the subpopulations of cells in the Langerhans islets. We studied eight human samples with normal pancreatic islets and two samples from patients with type 1 diabetes. Additionally, 10 CD‐1 mouse pancreases were analysed. Immunohistochemical double‐stainings for the TLRs and insulin, glucagon or somatostatin, respectively, were performed along with appropriate controls. In human pancreas, strong immunoreaction of TLR7 and TLR8 was observed in the insulin‐positive beta cells, whereas glucagon‐ or somatostatin‐expressing cells of the islets were weakly stained or negative. In type 1 diabetes, the expression in islets was weak or lost (TLR7: p = 0.014, TLR8: p = 0.053), correlating with loss of beta cells. TLR3 and 9 were expressed only weakly with no correlation with specific cell types. In mouse pancreas, only TLR9 was detected. Intra‐pancreatic nerve ganglia strongly expressed TLR7. The strong expression of TLR7 and TLR8 in the beta cells of normal human islets could be an important piece in the puzzle of type 1 diabetes pathogenesis, and be linked with destruction of this particular subpopulation of the islet cells. In normal mice, only TLR9 can be constantly detected in the islets, highlighting differences between the species.
Developmental expression of poly(A) binding protein mRNAs during spermatogenesis in the mouse

The poly(A) binding protein (PABP), a conserved protein that binds to the 3′ poly(A) tail on mRNAs in eukaryotic cells, has been implicated in the regulation of mRNA stability and translation. Two PABP cDNAs with different sequences were isolated from mouse testis cDNA libraries. The predicted amino acid sequence of one, PABP1, is nearly identical (98.9%) to human liver PABP, while 80% of the amino acids of the second, PABPt, are identical to mouse and human PABPs. Northern blots reveal that there is one major PABP mRNA species in liver, muscle, kidney, and brain, two in spleen, and at least four in testis. The levels of PABP mRNA in testis are 5–10‐fold higher than in these somatic tissues, but surprisingly the vast majority of all PABP mRNA size variants sediment more slowly than single ribosome, indicating strong translational repression. Reverse transcriptase‐polymerase chain reaction assays demonstrate that PABPt mRNAs are abundant only in testis. Northern blots of RNAs purified from highly enriched spermatogenic cells show that the high levels, multiple sizes of PABP mRNAs, and the PABPt mRNA are present in meiotic and early haploid spermatogenic cells, and are sharply reduced in late haploid cells. Comparison of the binding of PABP1 and PABPt to poly(A) Sepharose in vitro revealed subtle differences, even though PABPt contains substitutions for highly conserved aromatic amino acids that are thought to be necessary for binding to poly(A). The existence of two PABP isoforms in mouse spermatogenic cells could influence cytoplasmic gene expression during spermatogenesis. © 1994 Wiley‐Liss, Inc.
First-in-Human Trial of MIV-150 and Zinc Acetate Coformulated in a Carrageenan Gel: Safety, Pharmacokinetics, Acceptability, Adherence, and Pharmacodynamics

Objective:To evaluate the safety and pharmacokinetics of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics were also explored. Design:A 3-day open-label safety run-in (n = 5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14 days. Methods:Assessments included physical examinations, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LC-MS/MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability, and adherence were analyzed descriptively. Pharmacokinetic parameters were calculated using noncompartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose–response inhibition analysis. Results:Participants (n = 20) ranged from 19–44 years old; 52% were black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. Seven of seven CVLs collected 4-hour postdose demonstrated antiviral (HIV, human papillomavirus) activity. High baseline CVL anti–herpes-simplex virus type-2 (HSV-2) activity precluded assessment of postdose activity. Conclusions:PC-1005 used vaginally for 14 days was well tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Postdose CVLs had anti-HIV and anti–human papillomavirus activity. These data warrant further development of PC-1005 for HIV and sexually transmitted infection prevention.
Density Dependence Slows Invader Spread in Fragmented Landscapes

Patchiness is a defining characteristic of most natural and anthropogenic habitats, yet much of our understanding of how invasions spread has come from models of spatially homogeneous environments. Except for populations with Allee effects, an invader’s growth rate when rare and dispersal determine its spread velocity; intraspecific competition has little to no influence. How this result might change with landscape patchiness, however, is poorly understood. We used simulation models and their analytical approximations to explore the effect of density dependence on the spread of annual plant invaders moving through heterogeneous landscapes with gaps in suitable habitat. We found that landscape patchiness and discrete invader population size interacted to generate a strong role for density dependence. Intraspecific competition greatly slowed the spread of invasions through patchy landscapes by regulating how rapidly a population could produce enough seeds to surpass habitat gaps. Populations with continuously varying density showed no such effect of density dependence. We adapted a stochastic dispersal model to approximate spread when gap sizes were small relative to the mean dispersal distance and a Markov chain approximation for landscapes with large gaps. Our work suggests that ecologists must consider reproduction at both low and high densities when predicting invader spread.
Applying Trigger Tools to Detect Adverse Events Associated With Outpatient Surgery

Objective: The objective of this study is to evaluate the performance of 5 triggers to detect adverse events (AEs) associated with outpatient surgery. Triggers use surveillance algorithms derived from clinical logic to flag cases where AEs have most likely occurred. Current efforts to detect AEs have focused primarily on the inpatient setting, despite the increase in outpatient surgery in all health care settings. Methods: Using trigger logic, we retrospectively evaluated data from 3 large health care systems' electronic medical records. Patients were eligible for inclusion if they had an outpatient (same-day) surgery in 2007 and at least 1 clinical note in the 6 months after the surgery. Two nurse abstractors reviewed a sample of trigger-flagged cases from each health care system. After reaching interrater reliability targets (&kgr; > 0.60), we calculated the positive predictive value (PPV) of each trigger and the confidence interval of the estimate. Results: The surgical triggers flagged between 1% and 22% of the outpatient surgery cases, with a wide range in PPVs (6.0%-62.0%). The pulmonary embolism and deep vein thrombosis and emergency department triggers had the lowest proportion of flagged cases along with the highest PPVs, showing the most promise for screening cases with a high probability of AE occurrence. Conclusions: Triggers may be useful in identifying a narrow set of surgeries for further review to determine if a surgical AE occurred, complementing existing tools and initiatives used to detect AEs. Improved detection of AEs in outpatient surgery should help target potential areas for quality improvement.
Role of Antigen-Processing Machinery in the In Vitro Resistance of Squamous Cell Carcinoma of the Head and Neck Cells to Recognition by CTL1

Squamous cell carcinoma of the head and neck (SCCHN) cells are poorly recognized in vitro by CTL despite expressing the restricting HLA class I allele and the targeted tumor Ag (TA). Several lines of evidence indicate that the lack of SCCHN cell recognition by CTL reflects defects in targeted TA peptide presentation by HLA class I Ag to CTL because of Ag-processing machinery (APM) dysfunction. First, lack of recognition of SCCHN cells by CTL is associated with marked down-regulation of the IFN-γ-inducible APM components low-m.w. protein 2, TAP1, TAP2, and tapasin. Second, SCCHN cell recognition by CTL is restored by pulsing cells with exogenous targeted TA peptide. Third, the restoration of CTL recognition following incubation of SCCHN cells with IFN-γ is associated with a significant (p = 0.001) up-regulation of the APM components TAP1, TAP2, and tapasin. Lastly, and most conclusively, SCCHN cell recognition by CTL is restored by transfection with wild-type TAP1 cDNA. Our findings may explain the association between APM component down-regulation and poor clinical course of the disease in SCCHN. Furthermore, the regulatory nature of the APM defects in SCCHN cells suggests that intralesional administration of IFN-γ may have a beneficial effect on the clinical course of the disease and on T cell-based immunotherapy of SCCHN by restoring SCCHN cell recognition by CTL.
A Brazilian Investigation of the 36- and 16-Item Difficulties in Emotion Regulation Scales.

OBJECTIVE About 10 years ago, Gratz and Roemer (2004) introduced the Difficulties in Emotion Regulation Scale (DERS), a 36-item self-report instrument measuring 6 areas of emotion regulation problems. Recently, Bjureberg et al. (2015) have introduced a new, briefer version of the DERS comprising only 16 of the 36 items included in the original version. Because no studies have yet cross-validated the recently introduced 16-item DERS and the 36-item DERS has never been tested in Brazil, we sought to inspect the psychometric properties of scores from both DERS versions with a nonclinical Brazilian sample. METHOD Participants were 725 adult volunteers aged 18-70 years (mean = 30.54, standard deviation = 10.59), 82.3% of whom were women. All were administered the DERS along with a number of other self-report and performance-based instruments. Data analyses inspected internal consistency, factor structure, and convergent as well as divergent validity of scores from both DERS versions. RESULTS Results show that scores from both DERS versions possess good psychometric properties. Interestingly, both versions correlated, in the expected direction, with psychopathology and showed no significant correlations with cognitive measures. Like in other studies, however, the Awareness factor of the 36-item DERS did not produce optimal validity and reliability indexes. CONCLUSION Taken together, our findings indicate that the 16-item DERS may be preferred over the 36-item version and provide additional support to the differentiation between emotion regulation and cognitive tasks of emotional perception and abstract and verbal reasoning.
[Inappropriate multiple medication and prescribing of drugs immobile elderly patients living in the community].

OBJECTIVES To ascertain and analyse the drug consumption of the immobile elderly, as well as the number of potentially inappropriate medications (PIM). DESIGN Cross-sectional study. SETTING Fourteen rural primary care centres. PARTICIPANTS Non-institutionalised immobile patients, older than 64 years were selected by systematic sampling. PRINCIPAL MEASUREMENTS Review of patients' medicine cabinets and noting the daily doses and current number of drugs, as well as the origin of the prescription. Identification of PIM (Beers criteria). RESULTS One-hundred forty-three homes visits were made. The mean age was 81.3+/-7.9 years, of whom 74.8% were women. The most common drugs were: analgesics (9.2%), antacids (7.1%), nitrites-calcium antagonists (6.5%), non-steroidal anti-inflammatories (5.0%), and angiotensin converting enzyme inhibitors (4.7%). The percentage of patients who took more than 4 drugs was 76.1%. A PIM was taken by 35% of the elderly. The most common were: long-acting tranquilisers (41.5%), hypnotics (13.8%), digoxin (13.8%), indomethacin (7.7%), and antispasmodics (6.1%). In the majority of cases, the prescribing of the PIM was made by the family doctor (77.7%). Women took significantly more inappropriate drugs than men (0.50+/-0.72 vs to 0.25+/-0.50; P=.001) and those on multiple medication more than those not on multiple medication (0.50+/-0.73 vs 0.31+/-0.52; P=.008). CONCLUSIONS The prevalence of inappropriate therapy in the immobile elderly is high, therefore an effort must be made to reduce it. Procedures directed towards increasing the quality of prescribing could improve the state of health and quality of life of these patients.
Genital Mycotic Infections in Patients With Diabetes

Abstract Patients with diabetes, especially those with poorly controlled glycemia, are prone to developing genital mycotic infections—vulvovaginal candidiasis in women and Candida balanitis in men—the latter almost exclusively in uncircumcised men. Candida albicans is the most common pathogen causing balanitis and is also the dominant cause of vulvovaginal candidiasis in women with diabetes, although Candida glabrata is a prominent pathogen in women with type 2 diabetes mellitus. Candida glabrata is less virulent but also less susceptible to conventional antifungal treatment. High blood glucose levels promote yeast attachment and growth, and also interfere with immune responses in the host. In uncircumcised men, the moist, warm space underneath the foreskin is thought to promote yeast growth, especially when hygiene is poor. Several other risk factors have been identified that predispose to genital mycotic infections, including antibiotic use, corticosteroid use, immunosuppression, atopy, and, in women only, genetics, pregnancy, estrogen/oral contraceptive use, and select sexual behaviors (eg, orogenital sex). In patients with hyperglycemia, risk is increased for not only incident infection but also for recurrence, underscoring the key role of establishing and maintaining euglycemia in the management of genital mycotic infections in patients with diabetes. In addition to blood glucose control, first-line treatment involves either an antifungal cream/ointment (or suppository for women only) that is applied intravaginally by women and directly to the affected area(s) by men, or oral treatment, which infrequently causes systemic side effects. Antifungal treatment should also be offered to sexual partners of patients with diabetes with a genital mycotic infection if the partner is similarly infected. Given high efficacy rates, follow-up test-of-cure after the completion of treatment is generally unnecessary.
Bipolar cell pathways for color vision in non-primate dichromats

Abstract Color vision in mammals is based on the expression of at least two cone opsins that are sensitive to different wavelengths of light. Furthermore, retinal pathways conveying color-opponent signals are required for color discrimination. Most of the primates are trichromats, and “color-coded channels” of their retinas are unveiled to a large extent. In contrast, knowledge of cone-selective pathways in nonprimate dichromats is only slowly emerging, although retinas of dichromats like mice or rats are extensively studied as model systems for retinal information processing. Here, we review recent progress of research on color-coded pathways in nonprimate dichromats to identify differences or similarities between di- and trichromatic mammals. In addition, we applied immunohistochemical methods and confocal microscopy to retinas of different species and present data on their neuronal properties, which are expected to contribute to color vision. Basic neuronal features such as the “blue cone bipolar cell” exist in every species investigated so far. Moreover, there is increasing evidence for chromatic OFF channels in dichromats and retinal ganglion cells that relay color-opponent signals to the brain. In conclusion, di- and trichromats share similar retinal pathways for color transmission and processing.
UV Exposure Alters Respiratory Allergic Responses in Mice¶

Abstract We have tested the hypothesis that exposure to ultraviolet light would inhibit T helper-1 (Th1) responses and stimulate T helper-2 (Th2) responses, and that thus in a mouse model of allergic (i.e. extrinsic) asthma (using ovalbumin [OVA] as the allergen) increased symptoms would be observed, while in a model of Th1-dependent occupational asthma (in which picryl chloride is the allergen) decreased symptoms would be observed. Whereas reduced interferon (IFN)-γ production, decreased inflammatory responses in the airways, and reduced airway reactivity to nonspecific stimuli were observed in UV-preexposed picryl chloride sensitized and challenged mice, the results in the OVA model were less clear. Increased interleukin (IL)-10 production as a result of UV exposure was observed, together with unchanged IL-4 and IFN-γ. In addition, decreased OVA-specific immunoglobin, IgG1 and IgE, titers were noted, as well as decreased nonspecific airway hyperreactivity. Eosinophilic inflammatory responses were not influenced. The results indicate that UV exposure can have systemic effects that influence ongoing immune responses in the respiratory tract. The effects are not only restricted to immune responses that are predominantly Th1 dependent (i.e. pulmonary delayed-type hypersensitivity and IFN-γ production in response to picryl chloride) but also to immune response that are predominantly Th2 dependent, i.e. decreased specific IgE titers.
Review: cytokines and the pathogenesis of multiple sclerosis

Perivascular accumulation of mononuclear cells (MNCs) in the central nervous system (CNS) and high levels of myelin autoantigen‐reactive T cells in blood and further enriched in cerebrospinal fluid (CSF) are characteristic for multiple sclerosis (MS) and suggest a role for immunoregulatory cytokines in MS pathogenesis. The difficulties inherent to measurements of cytokine concentrations in body fluids have been partly overcome by adopting techniques allowing cytokine determinations on cellular level. MS is associated with the parallel up‐regulation of proinflammatory [interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), lymphotoxin‐α, and interleukin (IL)‐12] and immune response‐down‐regulating [transforming growth factor‐β (TGF‐β), IL‐10] cytokines systemically. A preferential up‐modulation of TNF‐α and lymphotoxin‐α is observed in clinical exacerbations and of TGF‐β and IL‐10 in remissions. The B cell‐stimulating IL‐4 and IL‐6 are also up‐regulated in MS, as is the cytolysis‐promoting perforin. Cytokine production is elevated to an even higher degree in the CSF than systemically, underlining the autonomy of the immune responses in the CSF. All cytokine abnormalities are demonstrable already in very early MS, manifested by acute unilateral optic neuritis associated with more than two MS‐like lesions on brain magnetic resonance imaging and oligoclonal IgG bands in CSF. The cytokine abnormalities hitherto observed are not MS specific, because they can be found in other inflammatory CNS diseases, e.g., aseptic meningitis and even noninflammatory neurological diseases like stroke. The influence on cytokine profiles, e.g., suppressing proinflammatory cytokines and promoting TGF‐β and IL‐10, could be an important way to identify new and promising treatments of MS. © 1996 Wiley‐Liss, Inc.
A Simultaneous Localization and Mapping Algorithm in Complex Environments: SLASEM

In this paper we present an algorithm for the application of simultaneous localization and mapping in complex environments. Instead of building a grid map or building a feature map with a small number of the obstacles' geometric parameters, the proposed algorithm builds a sampled environment map (SEM) to represent a complex environment with a set of environment samples. To overcome the lack of one-toone correspondence between environment samples and raw observations, the signed orthogonal distance function is proposed to be used as the observation model. A method considering geometric constraints is presented to remove redundant environment samples from the SEM. We also present a method to improve the SEM's topological consistency by using corner constraints. The proposed algorithm has been verified in a simulation and an indoor experiment. The results show that the algorithm can localize the robot and build a complex map effectively.
Necrotizing cerebritis in an allogeneic bone marrow transplant recipient due to Cladophialophora bantiana

We describe a necrotizing cerebritis in an allogeneic bone marrow transplant recipient caused by the neurotropic, dematiaceous fungus Cladophialophora bantiana. The patient presented 7 months after bone marrow transplantation with fever and sudden onset of left-sided weakness, followed shortly by cranial nerve III and VI palsies. The patient had a lesion (3.0 by 2.0 by 2.0 cm) of the right midbrain with extension to the pons, the left brain stem, and the right superior and the middle cerebellar peduncles. The diagnosis was made by microscopic examination and culture of a brain biopsy.
Secretion of the baby hamster kidney 30-kDa galactose-binding lectin from polarized and nonpolarized cells: a pathway independent of the endoplasmic reticulum-Golgi complex.

A carbohydrate-binding protein of molecular weight 30 kDa (CBP30) isolated from baby hamster kidney (BHK) cells binds polylactosamine glycans present prominently on extracellular matrix glycoproteins of oncofetal origin, such as Engelbroth-Holm-Swarm (EHS) tumor laminin and amniotic fluid fibronectin, and inhibits attachment and spreading of BHK cells to EHS laminin substrata mediated by integrin(s) suggesting an extracellular function for the lectin (S. Sato and R. C. Hughes (1992) J. Biol. Chem. 267, 6983-6990). Here we show that CBP30 shares amino acid sequence homologies with other lectins of similar size, e.g., murine CBP35, Mac2 antigens, and rat IgE-binding protein. Unlike most secreted proteins these lectins contain no signal sequence and we report that drugs, such as brefeldin A and monensin, which inhibit the intracellular transport of classical secretory (glyco)proteins do not block secretion of CBP30 from BHK cells. Secretion is inhibited by methylamine and serum starvation and is increased by heat shock and calcium ionophore A23187, treatments known to block or stimulate exocytosis, respectively. Immunofluorescence and biochemical analysis shows that CBP30 is distributed throughout the cytoplasm of subconfluent BHK cells where it turns over with a half-life of about 30 h, and small amounts are also deposited on the cell surface and substratum. At confluency, the CBP30 assembles into patches that eventually appear to underlie the plasma membrane and extracellular deposits become more numerous. In filter-grown confluent monolayers of Madin-Darby canine kidney cells the lectin is secreted from and expressed at the apical domain of the polarized cells whereas laminin is secreted from the basal domain and becomes incorporated into the matrix between cells and substratum.