Miracle-dz/UniFAR-FTUs huggingface dataset:
Human papillomavirus infections in a group of renal transplant recipients

One hundred and twenty renal transplant recipients were investigated. Fifty‐eight (48%) were found to have warts, 13(11%) keratoses and six (5%) to have, or recently to have had cancers. The longer the time of immunosuppression, the greater the prevalence of warts; of those patients who had had their transplant for at least 5 years, 87% had warts. Those with a graft survival time of 10 years or more are at special risk of warts, keratoses and malignancy. Five (10%) of 50 women had genital warts, four of whom had internal lesions (vaginal, cervical or anal) and one developed a carcinoma of the vulva. These findings indicate the advisability of colposcopy for all female renal transplant recipients, a high risk group. Eighty‐eight specimens from 42 patients were examined by DNA restriction enzyme analysis and cross hybridization for the presence and type of human papillomavirus (HPV). HPV DNA was detected in 66% of the warts examined, HPV2 and HPV4 occurring most often and HPV1 and HPV3 only infrequently. In sequential specimens from common hand warts of one individual, an HPV was found which could not be precisely identified but was related to HPV4. HPV16 was detected in a vaginal wart from one patient and an HPV6‐related virus in a vulval wart of another. HPV DNA of an unknown type was demonstrated in one of 11 keratoses examined. With the probes used to examine the few samples of skin cancers available, HPV 16 was found in a squamous cell carcinoma of the vulva, and faint bands from an unidentified type of HPV were detected in two squamous cell carcinomata from a patient's hand. One woman had plaque lesions morphologically and histologically resembling those found in epidermodysplasia verruciformis (EV). HPV5 was identified in these lesions. This is only the third reported case of HPV5, previously thought to be unique to EV, in a renal transplant recipient.
Optimization of Meropenem Minimum Concentration/MIC Ratio To Suppress In Vitro Resistance of Pseudomonas aeruginosa

ABSTRACT Suppression of resistance in a dense Pseudomonas aeruginosa population has previously been shown with optimized quinolone exposures. However, the relevance to β-lactams is unknown. We investigated the bactericidal activity of meropenem and its propensity to suppress P. aeruginosa resistance in an in vitro hollow-fiber infection model (HFIM). Two isogenic strains of P. aeruginosa (wild type and an AmpC stably derepressed mutant [MIC = 1 mg/liter]) were used. An HFIM inoculated with approximately 1 × 108 CFU/ml of bacteria was subjected to various meropenem exposures. Maintenance doses were given every 8 h to simulate the maximum concentration achieved after a 1-g dose in all regimens, but escalating unbound minimum concentrations (Cmins) were simulated with different clearances. Serial samples were obtained over 5 days to quantify the meropenem concentrations, the total bacterial population, and subpopulations with reduced susceptibilities to meropenem (>3× the MIC). For both strains, a significant bacterial burden reduction was seen with all regimens at 24 h. Regrowth was apparent after 3 days, with the Cmin/MIC ratio being ≤1.7 (time above the MIC, 100%). Selective amplification of subpopulations with reduced susceptibilities to meropenem was suppressed with a Cmin/MIC of ≥6.2 or by adding tobramycin to meropenem (Cmin/MIC = 1.7). Investigations that were longer than 24 h and that used high inocula may be necessary to fully evaluate the relationship between drug exposures and the likelihood of resistance suppression. These results suggest that the Cmin/MIC of meropenem can be optimized to suppress the emergence of non-plasmid-mediated P. aeruginosa resistance. Our in vitro data support the use of an extended duration of meropenem infusion for the treatment of severe nosocomial infections in combination with an aminoglycoside.
Spatial influence on breast muscle morphological structure, myofiber size, and gene expression associated with the wooden breast myopathy in broilers.

The wooden breast (WB) myopathy is identified by the palpation of a rigid pectoralis major (p. major) muscle and is characterized as a fibrotic, necrotic p. major disorder in broilers. The objective of the current study was to determine spatial morphological and gene expression differences at 4 locations within WB affected muscle from different genetic lines. Morphology was evaluated in 2 broiler lines expressing the WB myopathy (Lines A and B) and a line without WB (Line C) at 3 ventral locations and one anterodorsal location in the p. major muscle. In WB affected muscle of Line A, fibrosis was greatest in the anterior locations of WB affected muscle. In Line B muscle, fibrosis was greatest in the anteroventral region and minimal in the anterodorsal or posterior regions. Average p. major myofiber diameter was 30% larger in Lines A and B compared to Line C. However, in Line A there were no differences between the percentage of large fibers (diameter >70 μm) in unaffected and WB affected muscles at any sampling region. The percentage of small fibers (diameter <10 μm), likely small regenerating fibers, and expression of myogenic determination factor 1 (MYOD1) and myogenin were increased in Line A WB affected muscle compared to unaffected muscle. In Line B, the percentage of small fibers and MYOD1 expression in WB affected muscle was not different from unaffected muscle. Connective tissue organization within WB affected muscle was also different in Lines A and B, which may be attributed to decorin, a proteoglycan that mediates collagen crosslinking, growth factor signaling, and cell growth. Decorin expression was increased at all locations within Line A. However, in Line B decorin was increased only in the fibrotic regions of the p. major. The compiled results provide evidence that the WB myopathy is not uniform throughout the entire p. major muscle and the anterior end of the p. major muscle was more affected by the condition.
Cidofovir gel as treatment of follicular spicules in multiple myeloma.

IMPORTANCE The cause of follicular spicules in multiple myeloma (MM) is not known. OBSERVATIONS We present a case of follicular spicules in a patient with MM, which is very reminiscent of trichodysplasia spinulosa caused by a polyomavirus. No trichodysplasia spinulosa-associated polyomavirus could be isolated from the skin lesions; however, the spicules were positive for Merkel cell carcinoma virus, which is also a polyomavirus. CONCLUSIONS AND RELEVANCE Follicular spicules in MM are probably not caused by the trichodysplasia spinulosa-associated virus. Merkel cell polyomavirus could contribute to the origin of this dermatosis.
Predicting In Vitro Antibacterial Efficacy across Experimental Designs with a Semimechanistic Pharmacokinetic-Pharmacodynamic Model

ABSTRACT We have previously described a general semimechanistic pharmacokinetic-pharmacodynamic (PKPD) model that successfully characterized the time course of antibacterial effects seen in bacterial cultures when exposed to static concentrations of five antibacterial agents of different classes. In this PKPD model, the total bacterial population was divided into two subpopulations, one growing drug-susceptible population and one resting drug-insensitive population. The drug effect was included as an increase in the killing rate of the drug-susceptible bacteria with a maximum-effect (E max) model. The aim of the present study was to evaluate the ability of this PKPD model to describe and predict data from in vitro experiments with dynamic concentration-time profiles. Dynamic time-kill curve experiments were performed by using an in vitro kinetic system, where cultures of Streptococcus pyogenes were exposed to benzylpenicillin, cefuroxime, erythromycin, moxifloxacin, or vancomycin using different starting concentrations (2 and 16 times the MIC) and elimination conditions (human half-life, reduced half-life, and constant concentrations). The PKPD model was applied, and the observations for the static as well as dynamic experiments were compared to model predictions based on parameter estimation using (i) static data, (ii) dynamic data, and (iii) combined static and dynamic data. Differences in experimental settings between static and dynamic experiments did not affect the growth kinetics of the bacteria significantly. With parameter reestimation, the structure of our previously proposed PKPD model could well characterize the bacterial growth and killing kinetics when exposed to dynamic concentrations with different elimination rates of all five investigated antibiotics. Furthermore, the model with parameter estimates based on data from only the static time-kill curve experiments could predict the majority of the time-kill curves from the dynamic experiments reasonably well. Adding data from dynamic experiments in the estimation improved the model fit for cefuroxime and vancomycin, indicating some differences in sensitivity to experimental conditions among the antibiotics studied.
IGF-I increases forearm blood flow without increasing forearm glucose uptake.

Decreased insulin-mediated muscle glucose uptake is a characteristic feature of non-insulin-dependent diabetes mellitus and other insulin-resistant states. It has been suggested that an impairment in the ability of insulin to augment limb blood flow, resulting in diminished glucose delivery to muscle, may contribute to this abnormality. In this study, we used human insulin-like growth factor (IGF) I in conjunction with the forearm balance technique to determine whether forearm glucose uptake could be stimulated by increasing blood flow without directly stimulating the intrinsic ability of the muscle to extract glucose. IGF-I was infused intra-arterially in healthy controls at a rate of either 0.4 microg . kg-1 . min-1 (high IGF) or 0.04 microg . kg-1 . min-1 (low IGF) for 140 min. With high IGF, forearm blood flow increased approximately twofold (34 +/- 3 vs. 64 +/- 8 ml . min-1 . l forearm volume-1, P < 0.01), and arteriovenous glucose concentration difference (a-v difference) increased modestly (0.19 +/- 0.05 vs. 0.31 +/- 0.08 mM, P = 0.32), resulting in an increased forearm glucose uptake (6.4 +/- 1.7 vs. 21.7 +/- 7.4 micromol . min-1 . l forearm volume-1, P = 0.09 vs. basal). With low IGF, forearm blood flow increased by 59% (29 +/- 4 vs. 46 +/- 9 ml . min-1 . l forearm volume-1, P < 0.05) and was associated with a proportional decrease in the a-v difference (0. 29 +/- 0.04 vs. 0.18 +/- 0.05 mM, P < 0.05). Forearm glucose uptake therefore was not significantly different from basal values (7.6 +/- 0.6 vs. 6.9 +/- 1.8 micromol . min-1 . kg-1). These data demonstrate that increasing blood flow without increasing the intrinsic ability of the muscle to extract glucose does not increase forearm muscle glucose uptake.
Bergmann and Converse Bergmann Latitudinal Clines in Arthropods: Two Ends of a Continuum?1

Abstract Two seemingly opposite evolutionary patterns of clinal variation in body size and associated life history traits exist in nature. According to Bergmann's rule, body size increases with latitude, a temperature effect. According to the converse Bergmann rule, body size decreases with latitude, a season length effect. A third pattern causally related to the latter is countergradient variation, whereby populations of a given species compensate seasonal limitations at higher latitudes by evolving faster growth and larger body sizes compared to their low latitude conspecifics. We discuss these patterns and argue that they are not mutually exclusive because they are driven by different environmental causes and proximate mechanisms; they therefore can act in conjunction, resulting in any intermediate pattern. Alternatively, Bergmann and converse Bergmann clines can be interpreted as over- and undercompensating countergradient variation, respectively. We illustrate this with data for the wide-spread yellow dung fly, Scathophaga stercoraria (Diptera: Scathophagidae), which in Europe shows a Bergmann cline for size and a converse Bergmann cline (i.e., countergradient variation) for development time. A literature review of the available evidence on arthropod latitudinal clines further shows a patterned continuum of responses. Converse Bergmann clines due to end-of-season time limitations are more common in larger species with longer development times. Our study thus provides a synthesis to the controversy about the importance of Bergmann's rule and the converse Bergmann rule in nature.
What Are We Fighting For?: The Effects of Framing on Ingroup Identification and Allegiance

ABSTRACT Two studies were conducted examining the impact of framing on ingroup identification and allegiance in the context of international conflicts. The first study was carried out among British students at the beginning of the war in Afghanistan (N = 69). Perceptions of the war were manipulated by varying the frame that determined whether the war was perceived as positive and just or negative. Participants provided with a positive frame on the war identified more with their ingroup (Britain), and displayed higher allegiance to the United States than when given a negative frame. These findings were replicated in a second study conducted in the context of the second Iraq war (N = 51). Discussion focuses on the way in which framing affects perceptions of intergroup relations and the relationship between self, ingroup and out-group(s).
Absence of lipopolysaccharide-induced inhibition of neutrophil apoptosis in patients with diabetes.

BACKGROUND Patients with diabetes mellitus are considered to be at increased risk for infections and often experience more serious and prolonged infections. Defects in neutrophil microbicidal function have been identified in diabetic patients and are believed to contribute to this problem. Neutrophil apoptosis or programmed cell death regulates functional longevity, and is an integral component of inflammation and its resolution. It remains unknown whether neutrophils from diabetic patients demonstrate defects in apoptosis. HYPOTHESIS Neutrophils from diabetic patients have defects in spontaneous and/or endotoxin (lipopolysaccharide [LPS])-induced apoptosis. DESIGN Peripheral venous blood samples were collected from healthy volunteers and insulin-dependent diabetic patients to harvest neutrophils for in vitro study. INTERVENTIONS AND MAIN OUTCOME MEASURES Neutrophils were cultured for 0 and 24 hours in the absence and presence of LPS. Normal neutrophils were also cultured under conditions of normal or high glucose concentration. Percentage of apoptotic cells was determined by flow cytometry. RESULTS Normal neutrophils undergo significant apoptosis after 24 hours, and the percentage of apoptotic cells is reduced in the presence of LPS. Diabetic neutrophils undergo normal spontaneous apoptosis, but do not demonstrate LPS-induced inhibition of apoptosis. The LPS-induced inhibition of apoptosis in normal neutrophils is prevented under high-glucose conditions. CONCLUSIONS Neutrophils from diabetic patients demonstrated defects in LPS-induced apoptosis. High-glucose environment may mediate these findings. The inability of diabetic neutrophils to reduce apoptosis following LPS exposure resulted in relatively increased apoptosis. This would cause decreased functional longevity of neutrophils and increased neutrophil clearance from infectious sites, possibly contributing to the increased susceptibility and severity of infections in diabetic patients.
Epidermal Growth Factor Receptor Test Performed on Liquid-Based Cytology Lung Samples: Experience of an Academic Referral Center

Objectives: In this study we reviewed our practice of lung cancer epidermal growth factor receptor (EGFR) mutational testing in an academic centralized laboratory setting, where direct smears and liquid-based cytology (LBC) slides represent the most frequent cytological specimens received. The aim was to assess the differences, if any, between these sample types in terms of DNA yield, adequacy rates and overall EGFR testing performance. Study Design: A total of 362 cases were retrieved - received from January 2012 to January 2014 for EGFR testing - including 204 LBC specimens and 158 smears. Exon 19 deletions and the L858R point mutation in exon 21, detected by fragment assay and TaqMan assay, respectively, were confirmed by direct sequencing or by high-resolution melting. Results: Although the direct smears showed a higher DNA yield (60.94 vs. 23.07 ng/µl) and were more frequently cell-rich (54%) than the LBC slides (31.4%), the differences in adequacy (direct smears: 97.4%; LBCs: 94.1%) and in mutant rate (direct smears: 10.3%; LBCs: 14.0%) between the two sample types did not reach statistical significance. Conclusions: Not only direct smears but also LBC slides represent an effective preparation and storage medium for cytological material to be used for EGFR molecular testing.
The Effect of Cu on Ultrastructure of Wheat

Transmission electron microscope (TEM) was used to investigate the damage of wheat seedlings by copper and the distribution of Cu2+ in different parts of wheat seedlings was discussed. Experiment showed that Cu is more susceptible to migration than other metals in wheat cells. Needle dark electron dense particles were existed in leaves cells with 5 mg/L Cu stressed. Swollen cristae in mitochondria were existed in cells with 50 mg/L stressed, while mitochondria were almost disappear with 100 mg/L stressed. Chloroplast increased in wheat leaves under low concentration Cu2+ stressed while swollen chloroplast and disrupted chloroplast membrane and cascade structure damaged of chloroplast stroma were existed under high concentration. The inference of Cu2+ on wheat root nucleolus was serious. Disruption of nuclear membrane, multi-vesicle nucleoplasm and agglutination of nucleus chromatin were appeared at root cells under 50 mg/L Cu2+ and more serious damage were appeared under 100 mg/L Cu2+.
Mode of delivery at periviable gestational ages: impact on subsequent reproductive outcomes

Abstract Aim: The aim of this study was to assess the risk of subsequent delivery complications after extremely preterm deliveries by initial (index) pregnancy mode of delivery (MOD): cesarean (CD) versus vaginal (VD). Methods: This is a retrospective, longitudinal cohort study using Washington State birth certificate data and International Classification of Diseases, Ninth Revision codes, 1989–2008, identifying women with deliveries 20–26 weeks’ gestation and linked subsequent deliveries. Index MOD was considered as a predictor of adverse subsequent maternal and neonatal outcomes, using t-test, χ2-test or Fisher’s exact test, and regression analysis. Results: Of 2472 women with periviable delivery and subsequent birth, index CD (n=386) and index VD (n=2086) showed similar risks of composite morbidity (16.1% vs. 15.4%, P=0.76) and subsequent hemorrhage (9.6% vs. 11.1%, P=0.39). Women with index CD were more likely than index VD to experience uterine rupture (1.8% vs. 0.1%, P<0.001), to deliver earlier (35.9 vs. 36.9 weeks, P<0.001), and to have lower birth weight (2736 vs. 3014 g, P<0.001) subsequently. Neonatal hospital charges and lengths of stay were also higher after index CD. Conclusions: MOD at extreme prematurity did not impact subsequent maternal hemorrhage or overall morbidity. However, CD was associated with substantial uterine rupture risk despite evidence of practice to avoid labor (lower birth weight and earlier delivery) in the subsequent pregnancy.
Glycogen synthase kinase‐3 negatively regulates tissue factor expression in monocytes interacting with activated platelets

Summary. Background: At the site of vascular injury, monocytes (MN) interacting with activated platelets (PLT) synthesize tissue factor (TF) and promote thrombus formation. Intracellular signals necessary for the expression of TF in MN, in the context of a developing thrombus, remain unknown. Objective: The study was designed to investigate the role of the glycogen synthase kinase 3 (GSK3, a serine‐threonine kinase) downstream insulin receptor pathway, in PLT‐induced TF expression in MN. Methods: To this purpose we used a well‐characterized in vitro model of human MN‐PLT interactions that allows detailed analysis of TF activity, TF protein and gene expression.Results: The results demonstrated that, in MN interacting with activated PLT: (i) TF activity, antigen and mRNA were low until 8–10 h and dramatically increased thereafter, up to 24 h; (ii) according to the kinetics of TF expression in MN, GSK3β undergoes phosphorylation on serine 9, a process associated with down‐regulation of enzyme activity; (iii) pharmacological blockade of GSK3 further increased TF expression and was accompanied by increased accumulation of NF‐kB, in the nucleus; (iv) blockade of phosphoinositide‐3 kinase (PI(3)K) by wortmannin inhibited PLT‐induced TF expression; and (v) according to the established role of the GSK3 downstream insulin receptor, insulin increased PLT‐induced TF expression in a PI(3)K‐dependent manner. Conclusion: GSK3 acts as a molecular brake on the signaling pathway, leading to TF expression in MN interacting with activated PLT. PI(3)K, through Akt‐dependent phosphorylation of GSK3, relieves this brake and allows TF gene expression. This study identifies a novel molecular link between thrombotic risk and metabolic disorders.
Hormone replacement therapy: prevalence, compliance and the 'healthy women' notion.

BACKGROUND The objective of this study was to assess the current trends of hormone replacement therapy (HRT) use, including rates of use, length of use, continuation rates and characteristics of users and non-users and to examine the hypothesis that 'healthy women' are more likely to be users of HRT. METHODS Analysis was carried out of three representative South Australian population studies in 1991, 1993 and 1995 comprising 3019, 3004 and 3016 personal interviews, respectively. RESULTS Current use (and ever-use) of HRT in all women aged 50 years and over rose from 13.2% (26.7%) in 1991, to 21.2% (31.9%) in 1993 and 26.0% (40.5%) in 1995. Highest use is now in the 55-59-year age group where, in 1995, current use was 50.9% and ever use was 69.0%. Median compliance rates with HRT rose from 24 months in 1991 to 60 months in 1995 for current users aged 50 years of age or above. The pattern of increasing use of HRT is not consistent across age groups. Analyses of the 1995 data show that, in contrast with increasing rates of current use in women over 55 years, there was no overall change in rates for women below this age. There were no statistically significant differences in health indicators, e.g. blood pressure, smoking, cholesterol levels or body mass index between users and non-users of HRT. However, users reported significantly higher rates of previous osteoporosis and hysterectomy. CONCLUSIONS Prevalence rates of HRT use are increasing together with compliance rates and this may reflect increased confidence with HRT therapy. Users of HRT have an increased rate of mammography compared to non-users and this may contribute to earlier detection and, therefore, increased estimates of breast cancer in HRT users. There was no support from the 1995 data for a 'healthy women' hypothesis among HRT users.
Support Mechanisms for Early, Medium and Longer-Term Use of Technologies

In this paper we examine the support mechanisms that encourage and support early, medium and longer-term use of technologies. In two longitudinal studies, we examine use of a Learning Management System and the software application EndNote in an educational setting. Our findings suggest that providing classroom-based training for users may be a good mechanism encouraging adoption and early use. However, in the medium and longer-term, access to a variety of support mechanisms are necessary to encourage and support the appropriation process. Findings from these studies reveal that, in the medium and longer-term, localized oneon- one support, peer-support and availability of advanced training in the form of one-on-one contact with the trainer at critical time periods are key factors in encouraging productive use and avoiding rejection of the technology in the longer-term.