Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of Human Papillomavirus Type Replacement Postvaccination Must Account for Diagnostic Artifacts: Masking of HPV52 by HPV16 in Anogenital Specimens

It has been hypothesized that, following a reduction in human papillomavirus (HPV) vaccine–targeted genotypes, an increase in prevalence of other HPV types may occur due to reduced competition during natural infection. Any apparent postvaccination increase must be distinguished from diagnostic artifacts consequent to consensus PCR assays failing to detect HPV types present in low copy numbers in coinfected specimens (under the assumption that with a drop in vaccine-preventable types there may be increased detection of previously “masked” types). We reanalyzed anogenital specimens to evaluate unmasking of HPV52 that may be caused by elimination of HPV16. Using highly sensitive type-specific real-time HPV52 PCR, we retested 1,200 anogenital specimens (all HPV52 negative according to consensus PCR assays) from six epidemiologic studies (200 specimens/study; 100 HPV16+/study). Multivariate logistic regression, with adjustment for age and number of sexual partners, was used to evaluate the association between HPV16 positivity and detection of HPV52. In our pooled analysis (n = 1,196), the presence of HPV16 was positively associated with HPV52 detection [adjusted OR, 1.47; 95% confidence interval (CI), 0.76–2.82]. In our separate (study specific) analyses, a statistically significant association was observed in one study that included HIV-infected males (HIPVIRG study; adjusted OR, 3.82; 95% CI, 1.19–12.26). We observed a positive association between HPV16 viral load (tertiles) and detection of HPV52 (P for trend = 0.003). These results indicate that diagnostic artifacts, resulting from unmasking of HPV52, may occur in some settings in the evaluation of HPV type replacement. Additional studies exploring the extent and severity of unmasking are needed. Cancer Epidemiol Biomarkers Prev; 24(1); 286–90. ©2014 AACR.
Purification and Characterization of a Glucuronyltransferase Involved in the Biosynthesis of the HNK-1 Epitope on Glycoproteins from Rat Brain*

The glucuronyltransferase involved in the biosynthesis of the HNK-1 epitope on glycoproteins was purified to an apparent homogeneity from the Nonidet P-40 extract of 2-week postnatal rat forebrain by sequential chromatographies on CM-Sepharose CL-6B, UDP-GlcA-Sepharose 4B, asialo-orosomucoid-Sepharose 4B, Matrex gel Blue A, Mono Q, HiTrap chelating, and HiTrap heparin columns. The purified enzyme migrated as a 45-kDa protein upon SDS-polyacrylamide gel electrophoresis under reducing conditions, but eluted as a 90-kDa protein upon Superose gel filtration in the presence of Nonidet P-40, suggesting that the enzyme forms homodimers under non-denatured conditions. The enzyme transferred glucuronic acid to various glycoprotein acceptors bearing terminal N-acetyllactosamine structure such as asialo-orosomucoid, asialo-fetuin, and asialo-neural cell adhesion molecule, whereas little activity was detected to paragloboside, a precursor glycolipid of the HNK-1 epitope on glycolipids. These results suggested that the enzyme is specifically associated with the biosynthesis of the HNK-1 epitope on glycoproteins. Sphingomyelin was specifically required for expression of the enzyme activity. Stearoyl-sphingomyelin (18:0) was the most effective, followed by palmitoyl-sphingomyelin (16:0) and lignoceroyl-sphingomyelin (24:0). Interestingly, activity was demonstrated only for sphingomyelin with a saturated fatty acid,i.e. not for that with an unsaturated fatty acid, regardless of the length of the acyl group .
Lurasidone compared to other atypical antipsychotic monotherapies for bipolar depression: A systematic review and network meta-analysis

Abstract Objectives: To assess the efficacy and tolerability of lurasidone versus other atypical antipsychotic monotherapy agents in patients with bipolar depression, using a Bayesian network meta-analysis. Methods: Fourteen randomised clinical trials (6221 patients) of lurasidone, quetiapine (extended release and immediate release), aripiprazole, olanzapine, and ziprasidone for bipolar depression were included. Efficacy assessments included change in the Montgomery–Åsberg Depression Rating Scale (MADRS), rates of response (≥50% improvement in MADRS) and remission (MADRS ≤12 at study endpoint), and change in the Clinical Global Impressions–Bipolar Disorder–Severity (CGI-BP-S) scale. Tolerability outcomes included weight, somnolence, extrapyramidal symptoms (EPS), and all-cause discontinuation. Changes from baseline or odds ratios (OR) with 95% credible intervals (CrI) were evaluated. Results: Improvement in the MADRS associated with lurasidone treatment was significantly greater than placebo (–4.70, 95%CrI: –7.20, –2.21), aripiprazole (–3.62, 95%CrI: –7.04, –0.20), and ziprasidone (–3.38, 95%CrI: –6.68, –0.11), but not olanzapine (–0.15, 95%CrI: –3.12, 2.74) or quetiapine (0.10, 95%CrI: –2.68, 2.84). Results for improvement in the CGI-BP-S, and for response and remission were similar. Lurasidone was associated with less weight gain than olanzapine (–2.54 kg, 95%CrI: –3.42, –1.67) and quetiapine (–0.83kg, 95%CrI: –1.59, –0.08); and with lower rates of somnolence than quetiapine (OR: 0.33, 95%CrI: 0.11, 0.82) and ziprasidone (OR: 0.34, 95%CrI: 0.09, 0.93). No significant differences among atypical antipsychotic agents were observed in rates of discontinuation or in rates of EPS. Conclusions: In this network meta-analysis, lurasidone was found to be more efficacious than aripiprazole and ziprasidone, and was associated with less weight gain than quetiapine and olanzapine and less somnolence than quetiapine and ziprasidone.
Maternal Drug Use and Infant Cleft Lip/Palate with Special Reference to Corticoids

Objective To study the association between maternal drug use in early pregnancy and orofacial cleft in the infant. Design Register analysis based on prospectively collected information. Patients All delivered women in Sweden July 1, 1995, through December 31, 2001. Main outcome measure Presence of orofacial cleft in infant. Results Prospective information on maternal drug use during the first trimester, as reported in early pregnancy, was studied in 1142 infants with orofacial clefts, isolated or with other malformations, excluding chromosome anomalies. Any drug use was not associated with clefts (odds ratio [OR] = 0.98, 95% confidence interval [95% CI] = 0.85 to 1.13), with isolated clefts (OR = 0.92) with isolated median cleft palate (OR = 1.03, 95% CI = 0.79 to 1.36) or with isolated cleft lip with or without cleft palate (OR = 0.86, 95% CI = 0.71 to 1.05). Reported use of multivitamins, folic acid, or B12 was not associated with a decrease in orofacial cleft risk (OR = 1.00, 95% CI = 0.63 to 1.52). ORs above 2 were seen for some drugs: sulfasalazine, naproxen, and anticonvulsants, but only a few exposed cases occurred. An association between glucocorticoid use and infant cleft was indicated and seemed to be strongest for median cleft palate. Conclusion Maternal drug use seems to play only a small role for the origin of orofacial clefts, at least in Sweden.
Specialized Pheromone and Lure Application Technology as an Alternative Male Annihilation Technique to Manage Bactrocera tryoni (Diptera: Tephritidae)

Abstract The results of this study suggest that a novel male annihilation technique (specialized pheromone and lure application technology [SPLAT] incorporating cue-lure [CL] plus spinosad) is as effective as industry standard male annihilation controls, and is worth exploring further to manage Bactrocera tryoni (Froggatt) populations. Three lures were evaluated in a contact and feeding bioassay and a cage attractancy trial: 1) SPLAT-CL + spinosad; 2) SPLAT-CL without spinosad; and 3) wick-CL + malathion. In a field attraction trial, lures (1) and (3) were evaluated with a third treatment, caneite blocks-CL + malathion. Lures were weathered for 0, 1, 2, 4, or 8 wk, with an additional weathering treatment of 12 wk included in the field trial. In the contact and feeding bioassay, lures with SPLAT-CL + spinosad were >97% effective at 48 h for up to 2 wk weathering; however, wicks-CL + malathion killed B. tryoni within 2 h of exposure under all weathering periods. In the cage attractancy trial, SPLAT-CL + spinosad was as effective as, or performed better than, wicks-CL + malathion under all weathering treatments. The field study trap catches were similar for SPLAT-CL + spinosad and blocks-CL + malathion, and both had higher trap catches than wicks-CL + malathion at all weathering periods, except week 12. Overall, SPLAT-CL + spinosad compared favorably with current standard techniques for male annihilation and warrants further research. SPLAT-CL + spinosad may be a reduced-risk alternative for wicks-CL + malathion or blocks-CL + malathion for B. tryoni and other CL-responding fruit flies, such as Bactrocera cucurbitae Coquillett, because it contains a reduced-risk insecticide that poses a lower risk to humans and the environment and does not require labor-intensive handling and placement.
Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high‐responding inhibitors

Summary. Background: Immune tolerance induction (ITI) is the only therapeutic approach that can eradicate factor VIII (FVIII) inhibitors in patients with hemophilia A. Predictors of ITI outcome are still debated, and the role of F8 gene mutations in this is not well established. Objectives: To investigate the relationship between F8 genotype and ITI outcome in patients with severe hemophilia A and high‐responding inhibitors. Patients and Methods:F8 mutations were identified in 86 patients recruited as part of the Italian ITI registry (the PROFIT study). ITI outcome was centrally reviewed according to the following definitions: success (undetectable inhibitor and normal FVIII pharmacokinetics), partial success (inhibitor titer < 5 BU mL−1 and/or abnormal FVIII pharmacokinetics), and failure. Results:F8 mutations known to be associated with a high risk of inhibitor development (large deletions, inversions, nonsense mutations and splice site mutations) were found in 70 patients (81%); among these, the intron 22 inversion was present in 49 patients (57%). In 16 patients (19%) lower‐risk F8 defects (small insertions/deletions and missense mutations) were identified. The latter group of patients showed a significantly higher ITI success rate than those carrying high‐risk mutations [13/16 (81%) vs. 33/70 (47%); risk ratio 1.7, 95% confidence interval (CI) 1.1–2.1, P = 0.01]. On multivariate analysis, the mutation risk class remained a significant predictor of success [adjusted odds ratio (OR) 6.2, 95% CI 1.1–36.0, P = 0.04], as were inhibitor titer at ITI start (< 5 BU mL−1, OR 11.8, 95% CI 3.5–40.2, P < 0.001), and peak titer during ITI (< 100 BU mL−1, OR 11.4, 95% CI 3.2–40.8, P < 0.001). Conclusions: ITI success is influenced by F8 genotype. This knowledge should contribute to the stratification of prognosis, and to the clinical choices made for ITI in patients with high‐responding inhibitors.
Challenges of mobile-phone money transfer services' market penetration and expansion in Singida District, Tanzania

This study examined the challenges facing mobile money transfer services and their expansion in Singida, Tanzania. It adopted cross-sectional survey to collect quantitative data from users of mobile money services. It also included agents and service providers’ representatives from Aitel Money, Tigo-Pesa and Vodacom M-Pesa in Singida district, Tanzania. It found out that there are significant challenges affecting market penetration and expansion and regular use of mobile money. Lack of financial capital problems for agents, unavailability of network coverage and regulatory barriers to mobile money payment systems were leading to low penetration level in Singida and Tanzania. Reduction of transaction charges, ensuring widespread availability of agents in rural areas, stability of network, regular supply of electricity, training and information to users are necessary measures to increase usage, penetration and expansion of mobile phone money services. Keywords-mobile-phone money transfer; market penetration; value-added services; transaction charges and stability of network
The role of monoclonal antibodies in neurological disorders.

mulTiple sClerosis In multiple sclerosis, autoreactive T cells cross the blood-brain barrier under the influence of proinflammatory cytokines and cellular adhesion molecules, resulting in an attack on myelin, with resulting inflammation, degeneration and demyelination. Given the multitude of interactions involved in the immunopathogenesis of multiple sclerosis, several immunological pathways may be targeted with highly specific and selective antibodies.
Peribulbar anesthesia and sub-Tenon injection for vitreoretinal surgery: 300 cases.

BACKGROUND AND OBJECTIVES We carried out a prospective study in order to evaluate the efficacy and safety of peribulbar anaesthesia supplemented by a sub-Tenon injection in case of inadequate analgesia during vitreoretinal surgery. METHODS We performed 300 consecutive vitreoretinal procedures. Patients received a mean volume of 17+/-4.5 ml of a mixture of etidocaine 1%, bupivacaine 0.50% and hyaluronidase (25 UI/ml). Supplementation was represented by a sub-Tenon infiltration of lidocaine 2% (2 or 3 ml). This volume was not included in the mean volume. RESULTS Analgesia was adequate throughout surgery without any supplementation in 85% of cases and with a sub-Tenon infiltration in 99%. Akinesia was complete in 82%, mild in 15% and absent in 3% of cases. The sub-Tenon injection was performed immediately before starting the procedure in 58% of cases and during the surgery with a delay of 80+/-21 min in 42%. Eleven patients (3.66%) were agitated during surgery and two of them needed a general anaesthesia to allow for the procedure. Generalised epilepsy was encountered in two patients (0.66%) immediately after the peribulbar injection in one patient and 15 min later in the other. The systolic blood pressure severely decreased between 60 to 70 mm Hg 40 min after the accomplishment of the peribulbar in 2 patients and at 90 min in 2 others. CONCLUSION Our results demonstrate that peribulbar anaesthesia alone offers excellent analgesia in 85% of patients and supplemented by a sub-Tenon injection in 99%.
Impact of High Temperatures on Mortality: Is There an Added Heat Wave Effect?

Background: Mortality during sustained periods of hot weather is generally regarded as being in excess of what would be predicted from smooth temperature-mortality gradients estimated using standard time-series regression models. However, the evidence for an effect of continuous days of exceptional heat (“heat wave effect”) is indirect. In addition, because some interventions may be triggered only during forecasted heat waves, it would be helpful to know what fraction of all heat-related deaths falls during these specific periods and what fraction occurs throughout the remainder of the summer. Methods: Extended time-series data sets of daily mortality counts in 3 major European cities (London, 28 years of data; Budapest, 31 years; Milan, 18 years) were examined in relation to hot weather using a generalized estimating equations approach. We modeled temperature and specific heat wave terms using a variety of specifications. Results: With a linear effect of same-day temperature above an identified threshold, an additional “heat wave” effect of 5.5% was observed in London (95% confidence interval = 2.2 to 8.9), 9.3% in Budapest (5.8 to 13.0), and 15.2% in Milan (5.7 to 22.5). Heat wave effects were reduced slightly when we relaxed the linear assumption and these effects were reduced substantially when temperature was modeled as an average value of lags 0 to 2 days. In London, fewer than half of all heat-related deaths could be attributed to identified heat wave periods. In Milan and Budapest, the fraction was less than one fifth. Conclusions: Heat wave effects were apparent in simple time-series models but were reduced in multilag nonlinear models and small when compared with the overall summertime mortality burden of heat. Reduction of the overall heat burden requires preventive measures in addition to those that target warnings and responses uniquely to heat waves.
Rapamycin improves motor function, reduces 4-hydroxynonenal adducted protein in brain, and attenuates synaptic injury in a mouse model of synucleinopathy

Background Synucleinopathy is any of a group of age-related neurodegenerative disorders including Parkinson's disease, multiple system atrophy, and dementia with Lewy Bodies, which is characterized by α-synuclein inclusions and parkinsonian motor deficits affecting millions of patients worldwide. But there is no cure at present for synucleinopathy. Rapamycin has been shown to be neuroprotective in several in vitro and in vivo synucleinopathy models. However, there are no reports on the long-term effects of RAPA on motor function or measures of neurodegeneration in models of synucleinopathy. Methods We determined whether long-term feeding a rapamycin diet (14 ppm in diet; 2.25 mg/kg body weight/day) improves motor function in neuronal A53T α-synuclein transgenic mice (TG) and explored underlying mechanisms using a variety of behavioral and biochemical approaches. Results After 24 weeks of treatment, rapamycin improved performance on the forepaw stepping adjustment test, accelerating rotarod and pole test. Rapamycin did not alter A53T α-synuclein content. There was no effect of rapamycin treatment on midbrain or striatal monoamines or their metabolites. Proteins adducted to the lipid peroxidation product 4-hydroxynonenal were decreased in brain regions of both wild-type and TG mice treated with rapamycin. Reduced levels of the presynaptic marker synaptophysin were found in several brain regions of TG mice. Rapamycin attenuated the loss of synaptophysin protein in the affected brain regions. Rapamycin also attenuated the loss of synaptophysin protein and prevented the decrease of neurite length in SH-SY5Y cells treated with 4-hydroxynonenal. Conclusion Taken together, these data suggest that rapamycin, an FDA approved drug, may prove useful in the treatment of synucleinopathy.
Trends in Inter‐Birth Intervals in Developing Countries 1965–2014

The temporal character of cohort fertility is strictly and perfectly a function of three components: the timing of the onset of childbearing the length of intervals between births and the timing of the termination of childbearing (at age and/or parity). These three components comprise the “starting spacing and stopping” familiar to demographers. Despite the abundance of appropriate data—in particular the national demographic surveys conducted regularly from the 1970s to the present (WFS DHS etc.) which contain complete birth histories—we are not aware of any recent rigorous effort to assess the relative contributions of these three components to fertility decline since 1960. Toward such an assessment we examine the spacing of births the component that has received the least attention of the three in the recent research literature. While population change is first and foremost a function of change in total fertility commonly represented by indicators such as the period TFR and cohort completed fertility the tempo of childbearing is itself consequential including effects on maternal and child health kinship configuration and population age structure.
The permease homologue Ssy1p controls the expression of amino acid and peptide transporter genes in Saccharomyces cerevisiae

Amino acid transporters of the yeast plasma membrane (permeases) belong to a family of integral membrane proteins with pronounced structural similarity. We present evidence that a member of this family, encoded by the open reading frame (ORF) YDR160w (SSY1), is required for the expression of a set of transporter genes. Thus, deletion of the SSY1 gene causes loss of leucine‐inducible transcription of the amino acid permease genes BAP2, TAT1 and BAP3 (ORF YDR046c) and the peptide transporter, PTR2. D‐leucine can generate the signal without entering the cell. We propose that Ssy1p is situated in the plasma membrane and is involved in sensing leucine in the medium.
Sustained reduction in the carriage of Neisseria meningitidis as a result of a community meningococcal disease control programme

The effect of a community intervention programme of antibiotics and meningitis vaccine on pharyngeal carriage of Neisseria meningitidis was investigated. Carriage rates were determined in pupils at both secondary schools (ages 11–18 years) included in the community intervention programme and compared with two schools outside the area matched for socio-economic status. A total of 1869 pupils were studied 6 months after the programmes, and 2457 pupils after 11 months. Six months after the programme was completed there was a 72% reduction in pharyngeal carriage of Neisseria meningitidis in pupils attending the schools in the intervention area compared with pupils in the control schools. After 11 months this difference persisted in the 11–14 age group but not in the 15–18 age group. No resistance to the antibiotics used in the programme was found. A community intervention programme of antibiotics and vaccine for the control of meningococcal disease led to a long-term reduction in Neisseria meningitidis carriage in some age groups.
Significant nonsurgical risk factors for endophthalmitis after cataract surgery: EPSWA fourth report.

PURPOSE Endophthalmitis remains a devastating complication of cataract surgery, despite improved methods of prophylaxis and surgical technique. The current study was conducted to identify sociodemographic, environmental, and clinical risk factors for the development of postoperative endophthalmitis, using population-based administrative data from Western Australia. METHODS The Western Australian Data Linkage System identified all patients who underwent cataract surgery, along with those in whom postoperative endophthalmitis subsequently developed, from 1980 to 2000 inclusive. Cases of endophthalmitis were cross-referenced with other sources and validated by medical record review. After selection and preliminary analysis of potential risk factors, multivariate logistic regression modeling was used to estimate odds ratios for the selected variables. RESULTS Over the 21 years, 210 cases of endophthalmitis occurred after 117,083 cataract procedures, yielding a cumulative incidence rate of 1.79 per 1000 procedures. The incidence of endophthalmitis decreased for extracapsular extraction over the whole period, but not for phacoemulsification over the recent 12 years. There was no risk-adjusted difference in the incidence rate of endophthalmitis for the various cataract surgery procedure types. However, a significantly higher risk was found in patients aged over 80 years, in having surgery in private hospitals, and to a lesser degree in having same-day surgery and surgery in winter. Cataract surgery with lacrimal or eyelid procedures dramatically increased the risk of endophthalmitis. CONCLUSIONS It may be possible to reduce the incidence rate of postoperative endophthalmitis by almost 80% with a systematic approach to the management of elderly patients, hospital stay, and clinical protocols.