Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of activation induced cell death in human T blasts despite CD95L up‐regulation: protection from apoptosis by MEK signalling

The generation of effective immunity requires that antigen‐specific T cells are activated, clonally expanded and ultimately eliminated by apoptosis. The involvement of CD95‐mediated apoptosis in T‐cell elimination is well established, but the conditions which regulate the death pathway under normal circumstances are still emerging. Using superantigen‐activated human T cells, we found that whilst T‐cell receptor (TCR) signalling triggered up‐regulation of CD95 ligand (CD95L), the majority of T cells were resistant to apoptosis induction, despite co‐expressing high levels of CD95. Resistance was maintained following direct antibody‐mediated cross‐linking of CD95 and was not confined to early time periods following activation. Our data implicate TCR‐derived signals in protection from apoptosis and reveal a role for the mitogen‐activated protein (MAP) kinase pathway by use of a MAP kinase kinase (MEK) inhibitor. Collectively these data demonstrate that resistance to activation‐induced cell death in human T cells is prolonged rather than transient, is not attributable to a lack of CD95L up‐regulation and is due, at least in part, to signalling via the MEK pathway.
Pharmacokinetics of cefonicid, a new broad-spectrum cephalosporin

This study determined the pharmacokinetic disposition of cefonicid. A single dose of 7.5 mg/kg of body weight was administered to five healthy volunteers as a 5-min intravenous infusion. Multiple plasma and urine samples were collected for 48 h. Peak plasma concentrations ranged from 95 to 156 micrograms/ml and fell slowly (mean plasma half-life, 4.4 +/- 0.8 h), so that levels after 12 h were in the range of 6 to 12 micrograms/ml. Urinary concentrations were high but variable and ranged from 100 to 1,000 micrograms/ml for the first 12 h after the dose and averaged 84 micrograms/ml between 12 and 24 h. Plasma and renal clearances were 0.32 +/- 0.06 and 0.29 +/- 0.05 ml/min per kg, respectively. An average of 88 +/- 6% of the dose was excreted unchanged in the urine over 48 h. The mean steady-state volume of distribution was found to be 0.11 +/- 0.01 liters/kg.
Effects of Aldose Reductase Inhibitors on the Progression of Nerve Damage

Ever since nerve degeneration and demyelination were implicated in the development of diabetic neuropathy, much attention has been focused on the role of the polyol pathway, and in particular the enzyme aldose reductase, in the development of this devastating diabetic complication. In the nerve, the accumulation of sorbitol has been linked with depletion of myo-inositol, decreased sodium-potassium ATPase activity and energy utilization, and slowed motor nerve conduction velocity,' leading to characteristic morphometric changes such as axo-glial dysjunction.2 Therefore, the ability to inhibit this sorbitol accumulation pharmacologically could represent an opportunity to reverse the nerve damage associated with these metabolic alterations. Aldose reductase inhibitors have been shown to prevent or reverse the metabolic and even structural changes found in the nerves of diabetic rat model^. ^ However, their effectiveness in treating clinically overt human diabetic neuropathy has been questionable. Short-term trials of various aldose reductase inhibitors have been inconclusive at best. "6 However, three long-term trials have recently been completed for morphometric analysis and have yielded some meaningful insight into the best means to investigate the effects of aldose reductase inhibitors on nerve fiber morphology. The Sorbinil North American Neuropathy Trial was a 12-month, double-blind, randomized, controlled study testing the effectiveness of the Pfizer aldose reductase inhibitor sorbinil.2 At one centre in Toronto, Canada, a total of 16 diabetic patients with symptomatic peripheral neuropathy of at least 1 year duration underwent nerve biopsy at the start of study and after 1 year of treatment with either the active drug (250 mg day-', n = 10) or placebo (n = 6). Biochemical analysis of the nerves revealed a statistically significant decrease in sorbitol level in the treated patients versus no change in the placebo patients. Morphometric findings consisted of a partial correction of nerve fibre loss in the treated patients exhibited by an increase in fibre density accompanied by a four-fold increase in fibre regeneration. No such changes were observed in the placebo patients. A number of other lesions specific to nerve fibres, such as axoglial dysjunction, were increased at baseline in both groups and corrected towards normal in the sorbinil-
Prevalence of fibromyalgia in the Israeli population: a population-based study to estimate the prevalence of fibromyalgia in the Israeli population using the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ).

UNLABELLED Fibromyalgia represents the tip of the iceberg of chronic pain in the general population. We have attempted to estimate the prevalence of fibromyalgia in the Israeli population, using the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ), an instrument previously utilised in several European countries. METHODS The LFESSQ-4 screens for widespread pain, and the LFESSQ-6 for widespread pain and chronic fatigue. The LFESSQ was administered via telephone to a sample of 1019 individuals. To estimate the positive predictive value (PPV) of LFESSQ-4 and LFESSQ-6, this questionnaire was submitted to a sample of rheumatology outpatients (n=76), who were examined to confirm or exclude fibromyalgia according to the 1990 criteria. The prevalence of fibromyalgia in the general population was estimated by applying the PPV to community subjects. RESULTS In the community survey, 5.1% and 3.9% of individuals screened positive for the LFESSQ-4 and LFESSQ-6, respectively. The point prevalence of FMS in the Israeli general population was 2.6% (95%CI 1.7-3.4) when using LFESSQ-4 and 2.0% (95%CI 1.3-2.7) when using the LFESSQ-6 criteria. CONCLUSIONS The prevalence of the fibromyalgia syndrome in the Israeli population is considerable and constitutes a significant health care issue. The prevalence is similar to that observed in other western populations. Based on this tool, over 25% of fibromyalgia cases appear to be among males, a proportion higher than generally appreciated.
Invasive Group A Streptococcal Infections in Florida

Background Several previous studies of invasive Group A streptococcal (GAS) disease have been hindered by small sample sizes (≤ 100 patients) and limited generalizability. Methods We conducted a population-based study of invasive GAS disease. The objectives of the study were to describe the clinical features of individuals who were hospitalized for invasive GAS disease and to identify risk factors for hospital mortality. The cases were 257 patients who were hospitalized throughout Florida during a 4-year period and reported to the Florida Department of Health. Logistic regression was used to calculate adjusted odds ratios (OR) for mortality and 95% confidence intervals (CI). Results The overall mortality was 18% (41 of 228). Admission into an intensive care unit was a strong predictor of mortality (OR, 20.41; 95% CI, 6.41–64.96). Treatment with clindamycin reduced mortality in patients who had necrotizing fasciitis (OR, 0.11; 95% CI, 0.01–0.89) but not in patients who did not have necrotizing fasciitis (OR, 1.01; 95% CI, 0.31–3.33). Conclusion Clindamycin reduces mortality in patients with invasive GAS disease who have necrotizing fasciitis.
Topic-based inter-video structuring of a large-scale news video corpus

We propose a topic-based inter-video news video corpus structuring method and a visual interface to efficiently browse through the structured corpus. Such inter-video structuring was not deeply sought in previous works. The topic-based structure is analyzed by closed-caption text analysis; topic segmentation and tracking. The visual interface provides the ability to 1) search and select a topic by query terms and 2) track a topic thread interactively referring to the text analysis results. Although topic retrieval is somewhat similar to conventional video retrieval methods, the combination with topic tracking makes it remarkably easy to narrow down the results that match a user's interest and moreover reveal underlying content-based structures, where the structure itself contains rich information.
Thyroid Frozen Sections in Patients With Preoperative FNAs:  Review of Surgeons' Preoperative Rationale, Intraoperative Decisions, and Final Outcome.

OBJECTIVES We wished to discover (1) in what circumstances surgeons wished to request frozen sections (FSs) on thyroid nodules having a prior fine needle aspiration (FNA) and the preoperative plan in these cases; (2) what the surgeons did with the information provided by FS and (3) in what types of cases was value added with the FS. METHODS A retrospective chart review was performed of 121 consecutive patients receiving an intraoperative FS diagnosis on a thyroid nodule, all of which had been evaluated with a preoperative FNA. RESULTS The medical record documented rationale for the request in 83% of cases. The most common reason for a FS request of a nodule was whether a planned hemithyroidectomy should proceed to a total thyroidectomy (TT). This scenario led to a TT in 9% of patients with a FNA diagnosed as benign thyroid nodule, 16% diagnosed as follicular neoplasm/suspicious for follicular neoplasm and 69% diagnosed as suspicious for malignancy. CONCLUSIONS The stated rationale for FSs in patients with preoperative FNA was not supported by patient outcome in most cases. There may be some utility for FSs in lesions with a suspicious for malignancy preoperative FNA diagnosis.
Heparin Modulates the Binding of Insulin-like Growth Factor (IGF) Binding Protein-5 to a Membrane Protein in Osteoblastic Cells (*)

Osteoblast-like cells secrete insulin-like growth factor (IGF) binding protein-5 (IGFBP-5), which may act to enhance IGF-stimulated osteoblast function. We recently demonstrated that carboxyl-truncated IGFBP-5 (IGFBP-5) binds to the osteoblast surface and stimulates mitogenesis by a pathway that is independent of IGF action. The present study was conducted to determine the mechanism of osteoblast binding of IGFBP-5, beginning with the assumption that cell surface glycosaminoglycans may mediate the binding of this heparin binding protein. Intact I-IGFBP-5 and I-IGFBP-5 exhibited one-site binding to mouse osteoblast monolayers with dissociation constants of 28 and 6 nM for intact I-IGFBP-5 and I-IGFBP-5, respectively. Osteoblast binding of intact I-IGFBP-5 was inhibited by low heparin concentrations, while I-IGFBP-5 binding was stimulated by heparin. Treatment of cells with heparinase or chlorate to decrease surface glycosaminoglycan density failed to reduce the binding of either form of IGFBP-5. In contrast, pretreatment of cells with IGFBP-5 caused down-regulation of I-IGFBP-5 binding. Cross-linking studies revealed that both intact I-IGFBP-5 and I-IGFBP-5 bind to proteins in Triton extracts of osteoblast membranes, which were absent in osteoblast-derived matrix. Purification of membrane extracts by IGFBP-5 affinity chromatography revealed a 420-kDa band on reduced SDS-polyacrylamide gels. While the membrane protein internalized both forms of IGFBP-5, heparin treatment inhibited the internalization of intact I-IGFBP-5 but stimulated I-IGFBP-5 internalization. These data indicate that IGFBP-5 binds to and is internalized by an osteoblast membrane protein, which does not appear to be a proteoglycan. Glycosaminoglycans, however, modulate the binding and internalization of IGFBP-5 in a way that may preferentially favor the intracellular accumulation of the carboxyl-truncated form.
Rapid adjustments of sperm characteristics in relation to social status

Sperm competition models predict that males typically mating in disfavoured roles should be selected to compensate for their disadvantage by investing more into sperm. We studied the effect of rapid changes in social status on ejaculate investments during experimental trials with an externally fertilizing teleost—the Arctic charr (Salvelinus alpinus). We document that males becoming dominant produce less sperm with lower velocity, but have higher sex steroid concentrations than subordinate males. These differences in sperm characteristics seem mainly to result from a decreased investment in sperm among fish that become dominant compared to pre-trial levels. Moreover, these adjustments of sperm production and sperm velocity seem not to be traded against sperm longevity. Our results support theoretical models of sperm competition, as males forced to mate in disfavoured roles seem to invest more into ejaculate quality than males in favoured roles. Additionally, we are the first to report that males, in a species with status-dependent shifts in reproductive tactics, have evolved rapid tactic specific adjustments of sperm production and sperm velocity corresponding to what could be predicted from their reproductive roles.
Ischemia-Reperfusion Injury in Fatty Liver Is Mediated by Activated NADPH Oxidase 2 in Rats

Background Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery, and steatosis is a risk factor for liver damage. Reactive oxygen species generated by nicotinamide adenine dinucleotide phosphate oxidase (NOX) contribute to liver dysfunction. Here we examined the role of NOX in I/R injury of fatty livers. Methods Rats were fed a methionine and choline-deficient diet to induce a fatty liver. Rats then underwent surgically induced partial hepatic ischemia followed by reperfusion. Results The overall survival rate after I/R was lower in rats with fatty livers than with normal livers (P < 0.01). Necrotic area and the concentrations of 8-hydroxy-2′-deoxyguanosine (8-OHdG), TNF&agr;, and IL-6 were higher in fatty liver tissue than in normal liver tissue (P < 0.01). The number of p47phox-positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 24 hours after reperfusion. The number of TLR-4 positive cells was significantly higher in fatty liver tissue than in normal liver tissue after reperfusion and peaked 4 and 24 hours after reperfusion coupled with a decreased number of high-mobility group box 1–positive hepatocytes. Apocynin significantly improved the survival rate, necrotic area, and concentrations of 8-hydroxy-2′-deoxyguanosine, TNF&agr;, and IL-6 (P < 0.01). The protective effect of apocynin on fatty livers was greater than on normal livers. Conclusions Ischemia-reperfusion injury was associated with increased high-mobility group box 1, TLR4, and NOX2. Inhibition of NOX activity improved oxidative stress and may prevent I/R injury in fatty liver.
FACTORS INFLUENCING DEVELOPMENT OF TUMORS IN FROGS *

The f rog kidney has become a useful theater for the study of carcinogenesis. Its mesonephric character, small number of tubules, and large-size cells enhance the possibilities of experimentation. From LuckB’s pioneering observations’ and my own work on tumor filtrates dating back to 1954 and 1956, the viral nature of the disease transmission has been established. Nevertheless, many other problems concerned with development of tumors in amphibia have arisen. For example, i t is not yet clear whether the viral particles described by Fawcett’ and Lunger , and others in this monograph are really the causi t ive agents or merely passengers. A new question has arisen concerning the role of parasites, both in the kidney and in the lung. Finally, there a re important questions about other types of cancer in the f rog kidney and whether one agent or mechanism is responsible for all. The object of this paper is to present and discuss some of the other types of f rog cancers and their possible relationships to true renal adenocarcinoma. This form of malignant disease was shown to arise directly from transformations of proximal tubule cells. ’ Because there exist in the kidney fibrosarcomas, adrenal tumors, metastatic carcinoma from the lung, liposarcoma, lymphosarcoma, and possible mesothelioma, i t is dangerous to speak of the “Luck6 tumor” as an entity. In spite of the wish to honor Balduin Luck6 with the eponym, a plea is here made to use generic names for different cancer types. In view of the expanding world effort to link viruses to the origin of malignancy, and because of the growing importance of poikilotherms in these studies, certain basic considerations need to be restated. It is curious how often they a re avoided. (1) It must be shown by the experimentalist how a carcinogenic agent confers on the target cells a campet i t ive advantage in growth, i.e., in protein synthesis for cytoarchitecture of the sister cells. (2) I t must be shown how this carcinogenic agent alters the genes of target cells so tha t their progeny, or descendent cells, cmt inue to breed on as cancer cells. (3 ) It must be shown how this agent alters the target cells’ surface activity, so tha t the transforming cells can break away, and actually become invasive. These three criteria were directly applicable to the experiments reported here. By stimulation of nucleolar hypersecretion, the cytoplasm (ribc ,omal
The reason for having a code of pharmaceutical ethics: Spanish Pharmacists Code of Ethics.

The pharmacist profession needs its own code of conduct set out in writing to serve as a stimulus to pharmacists in their day-to-day work in the different areas of pharmacy, in conjunction always with each individual pharmacist´s personal commitment to their patients, to other healthcare professionals and to society. An overview is provided of the different codes of ethics for pharmacists on the national and international scale, the most up-to-date code for 2015 being presented as a set of principles which must guide a pharmacutical conduct from the standpoint of deliberative judgment. The difference between codes of ethics and codes of practice is discussed. In the era of massive-scale collaboration, this code is a project holding bright prospects for the future. Each individual pharmacutical attitude in practicing their profession must be identified with the pursuit of excellence in their own personal practice for the purpose of achieving the ethical and professional values above and beyond complying with regulations and code of practice.
The ionizing radiation-induced replication protein A phosphorylation response differs between ataxia telangiectasia and normal human cells

Replication protein A (RPA), the trimeric single-stranded DNA-binding protein complex of eukaryotic cells, is important to DNA replication and repair. Phosphorylation of the p34 subunit of RPA is modulated by the cell cycle, occurring during S and G2 but not during G1. The function of phosphorylated p34 remains unknown. We show that RPA p34 phosphorylation is significantly induced by ionizing radiation. The phosphorylated form, p36, is similar if not identical to the phosphorylated S/G2 form. gamma-Irradiation-induced phosphorylation occurs without new protein synthesis and in cells in G1. Mutation of cdc2-type protein kinase phosphorylation sites in p34 eliminates the ionizing radiation response. The gamma-irradiation-induced phosphorylation of RPA p34 is delayed in cells from ataxia telangiectasia, a human inherited disease conferring DNA repair defects and early-onset tumorigenesis. UV-induced phosphorylation of RPA p34 occurs less rapidly than gamma-irradiation-induced phosphorylation but is kinetically similar between ataxia telangiectasia and normal cells. This is the first time that modification of a repair protein, RPA, has been linked with a DNA damage response and suggests that phosphorylation may play a role in regulating DNA repair pathways.
Latency of evoked neuromagnetic M100 reflects perceptual and acoustic stimulus attributes

THE latency of components of the auditory evoked neuromagnetic field has been shown to reflect, or encode, stimulus attributes. In particular, the M100 component, occurring ∼100 ms post stimulus onset has a latency that depends on stimulus pitch, spectral complexity and presentation level. This study used magnetoencephalography to record neuromagnetic fields evoked by presentation of two-tone complexes consisting of various proportions of 100 Hz and 1 kHz energy. These are perceived categorically, as evidenced by classification and reaction time measurements. It is found that the M100 latency also varies categorically, that is, characterized by two plateau regions with a sharp interface. Thus, we find that not only does the M100 latency reflect acoustic attributes of a stimulus, but also such perceptual characteristics.
Women with past history of bone fracture have low spinal bone density before menopause.

AIMS Recent work from our laboratory has demonstrated that young girls with bone fractures have low spinal bone density more often than girls who have never fractured. This study was undertaken to determine whether adult women approaching menopause who have any past history of fracture have lower spinal density than women who have never fractured. METHODS A lifetime fracture history was taken from all premenopausal women (n = 59) enrolled in a clinical trial examining the effect of menopause on cardiac risk. Bone mineral density of the lumbar spine was measured at study entry by dual energy x-ray absorptiometry (Lunar DPX-L) and results from patients with and without fracture were compared. RESULTS Women with a previous history of fracture (n = 23) had significantly lower bone density (6% less) than the women who had never broken a bone (n = 36). CONCLUSIONS We conclude that women who report a previous history of fracture, either as young adults or in childhood, should be targeted for perimenopausal screening for osteoporosis since they are likely to have lower bone density and a greater risk of future fracture than women with no past history of fracture.
Targeting Improves the Efficacy of a DNA Vaccine against Corynebacterium pseudotuberculosis in Sheep

ABSTRACT A large-scale DNA vaccination trial was performed with sheep to investigate whether an antigen targeted by CTLA-4 enhanced and accelerated the humoral immune response. Vaccination with genetically detoxified phospholipase D (ΔPLD) has been shown to be effective, at least partially, against Corynebacterium pseudotuberculosis, the causal agent of caseous lymphadenitis in sheep. CTLA-4 binds to B7 on antigen-presenting cells and thus was used to direct the fusion antigens to sites of immune induction. Here we demonstrated that targeting ΔPLD as a CTLA-4 fusion protein significantly enhanced the speed, magnitude, and longevity of the antibody response compared to that obtained with DNA encoding ΔPLD. While all groups of sheep vaccinated with DNA encoding ΔPLD were afforded better protection against an experimental challenge withC. pseudotuberculosis than those immunized with an irrelevant plasmid or those left unimmunized, the best protection was provided by the targeted DNA vaccine. We propose that targeting antigens to antigen-presenting cells offers a generic strategy for enhancing the efficacy of DNA vaccines.
MEM: Mechanisms of Recollection

The MEM framework (Johnson, 1991a, b; Johnson & Hirst, 1992; Johnson & Multhaup, 1992) consists of a relatively small set of component cognitive processes configured into memory subsystems. Here MEM is used to discuss recollection, particularly the mechanisms by which aspects of experience become bound together to yield the phenomenal experience of contextually specific, event-like memories. I consider how central aspects of complex events are bound to each other and propose that these same cognitive activities operate to bind central and contextual elements into episodic memories. Attention is particularly focused on the role of reactivation in establishing complex memories and in strengthening or consolidating them over time.