Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the Digene Hybrid Capture II Assay with the Rapid Capture System for Detection of Chlamydia trachomatis and Neisseria gonorrhoeae

ABSTRACT Screening for chlamydial and gonococcal infection has been strongly recommended for all sexually active women under the age of 26. Advances in the ability to detect infection by nucleic acid detection techniques have improved access to screening methods in routine clinical practices. To meet the increasing demand for testing, a high-throughput system is desirable. We evaluated the performance of the Hybrid Capture 2 CT/GC (HC2) assay with the Digene Rapid Capture System (HC2-RCS). The results of HC2-RCS for endocervical samples from 330 women were compared to those of culture and the COBAS Amplicor PCR. For detection of chlamydial infection, HC2-RCS had a sensitivity and a specificity similar to those of PCR (P > 0.5) and an improved sensitivity compared to that of culture (P = 0.007). For identification of gonococcal infections, all assays performed similarly (P > 0.5). The performance of HC2-RCS was also compared to that of the manual HC2 format (HC2-M) with these samples and with 911 endocervical samples collected previously. The performance of HC2-RCS was equivalent to that of HC2-M; the overall concordance rates for the detection of chlamydia and gonorrhea were 99.7% (κ = 0.97) and 99.8% (κ = 0.97), respectively. When the HC2 assay was performed with a semiautomated system application designed for high throughput, it demonstrated high sensitivity and a high specificity for detection of both Chlamydia trachomatis and Neisseria gonorrhoeae.
Bovine papillomavirus type 1 E1 replication-defective mutants are altered in their transcriptional regulation

Bovine papillomavirus type 1 (BPV-1) is capable of replicating as a stable, high-copy-number plasmid in transformed rodent cells. The BPV-1 E1 open reading frame (ORF) encodes multiple functions involved in viral DNA replication. Mutations which disrupt the translational integrity of the E1 ORF disable the viral genome from replicating as a stable plasmid and result in the integration of the viral genome into the host chromosome generally at a low copy number. Despite the low copy number of the integrated genomes, BPV-1 E1 mutants transform rodent cells to anchorage independence very efficiently, at levels equal to or greater than that of wild-type (wt) BPV-1. Studies were performed to provide insight into why these low-copy-number, replication-defective mutants are capable of expressing an equal or greater transformation potential than wt BPV-1. Analysis of viral RNA revealed higher rates of transcription per viral genome in cells harboring E1 mutated BPV-1 DNA than in cells containing wt BPV-1 DNA. Furthermore, the levels of viral RNA mapping the P89 promoter were found to be 15- to 35-fold higher in cells transformed by E1 mutated DNAs compared with wt BPV-1 transformants. This promoter controls expression of the BPV-1 E6 transforming gene and is regulated by the viral E2 gene products. The studies presented in this report determined that the E1 mutants were perturbed in their E2 transcriptional regulation, suggesting a possible explanation for the observed P89 induction. Mutations throughout the E1 ORF, in either of the two regions previously identified as encoding distinct replication functions, were altered in viral transcription.
Language, memory, and aging: an electrophysiological exploration of the N400 during reading of memory-demanding sentences.

Twenty-four young and 24 middle-aged academics carried out a language recognition task in which sentences were presented that made either a high or a low demand on working memory (WM). The sentences ended either normally (i.e., congruent) or with an incongruous word. Middle-aged subjects had smaller WM scores, a marginally slowed down recognition performance, and a smaller and delayed N400 component. The event-related potential (ERP) difference between congruent and incongruent endings was smaller in the high-load condition for younger subjects and totally disappeared for the middle-aged subjects. ERPs for all subjects showed a WM-related positivity in the middle of the sentence and a WM-related negativity at the sentence ending. These shifts could be associated with either storage and retrieval processes or with clause wrap-up processes. Most ERP-effects were dependent on WM capacity. Age differences in sentence processing are not simply explained by age itself but depend to a large extent on individual memory capacity.
The Effect of Methadone Dose Regimen on Neonatal Abstinence Syndrome

Objectives:To evaluate the effects of a multiple daily dose methadone regimen in pregnancy on neonatal outcomes. Methods:Although methadone maintenance has been the standard for the treatment of opioid dependence in pregnancy, there is no consensus on proper dosing. Single daily dosing is the most common strategy. Because of accelerated metabolism of methadone in pregnancy, this regimen may expose mother and fetus to daily episodes of withdrawal and possibly contribute to more severe Neonatal Abstinence Syndrome (NAS). This study reports on a protocol that increased both methadone dose and dose frequency in response to maternal reports of withdrawal. Results:Treatment of NAS was needed in 29% of neonates, compared to a published rate of 60% to 80%. The mean methadone dose was 152 mg at delivery, divided into 2 to 6 doses per day. Ninety-two percent of mothers were free of illicit drug use at delivery. There was no relationship between methadone dose and treatment of NAS. Female babies had a treatment rate of 16% versus 38% for male babies. Beyond abstinence symptoms, cohort outcomes in terms of gestational age, birth weight, prematurity, Caesarian sections, and breastfeeding equaled or approximated US population norms. Conclusions:The protocol was associated with low rates of treatment of NAS and high rates of maternal recovery. High rates of treatment for NAS reported in methadone-exposed neonates might relate in part to iatrogenic factors and be reduced through the use of divided daily doses and protocols that minimize maternal withdrawal.
The Interaction of Eltanolone and Fentanyl with Special Reference to Logistic Regression Analysis

We investigated whether fentanyl decreases the serum concentrations of the steroid anesthetic eltanolone effective in producing loss of consciousness in 50% of patients (EC50induction) and in preventing movement at skin incision in 50% of patients (EC50incision). For anesthetic induction, patients received effect-site target concentrations of fentanyl 0.0, 1.5, 3.0, or 4.5 ng/mL and eltanolone 500, 750, 1000, or 1200 ng/mL. Loss of response to verbal command was assessed after 10 min. For incision, patients received effect-site target concentrations of fentanyl 0.5, 1.5, 3.0, or 4.5 ng/mL and eltanolone 547-2926 ng/mL. Movement at incision was assessed at least 10 min after new targets were entered. Probability of loss of consciousness and of movement versus arterial serum concentration combinations were analyzed by logistic regression. Dixon up-down analysis was used to estimate ET50incision effective target concentration combinations. In the absence of fentanyl, anesthesia was induced in only 1 of 12 patients, which suggests that the EC50induction is >1500 ng/mL at fentanyl 0.0 ng/mL. With fentanyl (38 patients), eltanolone EC (50induction) was independent of fentanyl concentration, calculated as 628 ng/mL. For the incision phase (52 patients), logistic regression failed to generate a valid model. Dixon analysis (43 patients) produced an eltanolone ET50incision of 2288 ng/mL at fentanyl targets of 0.5 ng/mL, 754 ng/mL at 1.5 ng/mL, 735 ng/mL at 3.0 ng/mL, and 645 ng/mL at 4.5 ng/mL. Fentanyl reduced the serum concentration of eltanolone required to produce loss of consciousness and the target concentration of eltanolone required to prevent movement to skin incision. Implications: Fentanyl reduced the serum concentration of eltanolone required to produce loss of consciousness and the target concentration of eltanolone required to prevent movement to skin incision. Future interaction studies of this nature using logistic regression should model responses to hypnotic alone separately from responses to hypnotic-analgesic combinations. (Anesth Analg 1998;87:967-72)
Dissecting the Roles of the 5′ Exoribonucleases Xrn1 and Xrn2 in Restricting Hepatitis C Virus Replication

ABSTRACT The replication of hepatitis C virus (HCV) is uniquely dependent on a host microRNA, miR-122. Previous studies using genotype 1a H77S.3 virus demonstrated that miR-122 acts in part by protecting the RNA genome from 5′ decay mediated by the cytoplasmic 5′ exoribonuclease, Xrn1. However, this finding has been challenged by a recent report suggesting that a predominantly nuclear exoribonuclease, Xrn2, mediates the degradation of genotype 2a JFH1 RNA. Here, we dissect the roles of these two 5′ exoribonucleases in restricting the replication of different HCV strains and mediating the decay of HCV RNA. Small interfering RNA (siRNA) depletion experiments indicated that Xrn1 restricts replication of all HCV strains tested: JFH1, H77S.3, H77D (a robustly replicating genotype 1a variant), and HJ3-5 (a genotype 1a/2a chimeric virus). In contrast, the antiviral effects of Xrn2 were limited to JFH1 and H77D viruses. Moreover, such effects were not apparent in cells infected with a JFH1 luciferase reporter virus. Whereas Xrn1 depletion significantly slowed decay of JFH1 and HJ3-5 RNAs, Xrn2 depletion marginally enhanced the JFH1 RNA half-life and had no effect on HJ3-5 RNA decay. The positive effects of Xrn1 depletion on JFH1 replication were largely redundant and nonadditive with those of exogenous miR-122 supplementation, whereas Xrn2 depletion acted additively and thus independently of miR-122. We conclude that Xrn1 is the dominant 5′ exoribonuclease mediating decay of HCV RNA and that miR-122 provides protection against it. The restriction of JFH1 and H77D replication by Xrn2 is likely indirect in nature and possibly linked to cytopathic effects of these robustly replicating viruses. IMPORTANCE HCV is a common cause of liver disease both within and outside the United States. Its replication is dependent upon a small, liver-specific noncoding RNA, miR-122. Although this requirement has been exploited for the development of an anti-miR-122 antagomir as a host-targeting antiviral, the molecular mechanisms underpinning the host factor activity of miR-122 remain incompletely defined. Conflicting reports suggest miR-122 protects the viral RNA against decay mediated by distinct cellular 5′ exoribonucleases, Xrn1 and Xrn2. Here, we compare the roles of these two exoribonucleases in HCV-infected cells and confirm that Xrn1, not Xrn2, is primarily responsible for decay of RNA in cells infected with multiple virus strains. Our results clarify previously published research and add to the current understanding of the host factor requirement for miR-122.
Births and Ectopic Pregnancies in a Large Cohort of Women Tested for Chlamydia trachomatis

Background: Recent studies show divergent results concerning the risk of ectopic pregnancy following Chlamydia trachomatis (CT) infection. Goal: Our goal was to investigate future reproductive health outcomes (births and ectopic pregnancies) among women tested for CT. Methods: Our cohort consisted of 20,762 women born during 1970–1984 who were tested for CT during 1990–2003. We linked CT data to data on ectopic pregnancies and births during 1990–2004. Cox regression with time-dependent covariates was used to assess the association between CT history and births/ectopic pregnancies adjusted for age at first test. Analyses with ectopic pregnancy as outcome were also adjusted for parity. Results: We observed 9.6 births per 100 person-years of observation among women with negative tests only and 10.2 per 100 person-years among women with at least 1 positive test (hazard ratio adjusted for age at first test, 1.07; 95% CI, 1.01–1.12). Ectopic pregnancy incidence rates were higher for women with positive test(s) compared with women with negative test only (0.24 vs. 0.13 per 100 person-years; hazard ratio adjusted for age at first test and parity, 1.82; 95% CI, 1.27–2.60). Among women with at least 1 registered pregnancy, the adjusted hazard ratio was 2.03; 95% CI, 1.28–3.22). Conclusion: Although women diagnosed with CT were at higher risk for ectopic pregnancy than women with negative test results only, our study suggest that their fertility prospects were better than they would have been had CT screening not been implemented in this population. Opportunistic CT screening is an appropriate method for maintaining female reproductive health.
Subdivisions of auditory cortex and ipsilateral cortical connections of the parabelt auditory cortex in macaque monkeys

Auditory cortex of macaque monkeys can be divided into a core of primary or primary‐like areas located on the lower bank of the lateral sulcus, a surrounding narrow belt of associated fields, and a parabelt region just lateral to the belt on the superior temporal gyrus. We determined patterns of ipsilateral cortical connections of the parabelt region by placing injections of four to seven distinguishable tracers in each of five monkeys. Results were related to architectonic subdivisions of auditory cortex in brain sections cut parallel to the surface of artificially flattened cortex (four cases) or cut in the coronal plane (one case). An auditory core was clearly apparent in these sections as a 16‐ to 20‐mm rostrocaudally elongated oval, several millimeters from the lip of the sulcus, that stained darkly for parvalbumin, myelin, and acetylcholinesterase. These features were most pronounced caudally in the cortex assigned to auditory area I, only slightly reduced in the rostral area, and most reduced in the narrower rostral extension we define as the rostrotemporal area. A narrow band of cortex surrounding the core stained more moderately for parvalbumin, acetylcholinesterase, and myelin. Two regions of the caudal belt, the caudomedial area, and the mediolateral area, stained more darkly, especially for parvalbumin. Rostromedial and medial rostrotemporal, regions of the medial belt stained more lightly for parvalbumin than the caudomedial area or the lateral belt. The parabelt region stained less darkly than the core and belt fields. Injections confined to the parabelt region labeled few neurons in the core, but large numbers in parts of the belt, the parabelt, and adjacent portions of the temporal lobe. Injections that encroached on the belt labeled large numbers of neurons in the core and helped define the width of the belt. Caudal injections in the parabelt labeled caudal portions of the belt, rostral injections labeled rostral portions, and both caudal and rostral injections labeled neurons in the rostromedial area of the medial belt. These observations support the concept of dividing the auditory cortex into core, belt, and parabelt; provide evidence for including the rostral area in the core; suggest the existence of as many as seven or eight belt fields; provide evidence for at least two subdivisions of the parabelt; and identify regions of the temporal lobe involved in auditory processing. J. Comp. Neurol. 394:475–495, 1998. © 1998 Wiley‐Liss, Inc.
Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer

Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit.
Mucin-type O-Glycosylation during Development*

Mucin-type O-glycosylation is an evolutionarily conserved protein modification present on membrane-bound and secreted proteins. Aberrations in O-glycosylation are responsible for certain human diseases and are associated with disease risk factors. Recent studies have demonstrated essential roles for mucin-type O-glycosylation in protein secretion, stability, processing, and function. Here, we summarize our current understanding of the diverse roles of mucin-type O-glycosylation during eukaryotic development. Appreciating how this conserved modification operates in developmental processes will provide insight into its roles in human disease and disease susceptibilities.
Cellular camouflage: fooling the immune system with polymers.

Immunological recognition of foreign cells is a primary concern in both transfusion and transplantation medicine. Our unique approach to this problem is to globally camouflage the surface of the foreign cell using nonimmunogenic, long chain polymers such as methoxypoly(ethylene glycol) [mPEG]. mPEG-modification of red blood cells effectively attenuates both antibody binding to surface epitopes and decreases the inherent immunogenicity of foreign, even xenogeneic red cells. These cells exhibit normal structural and functional characteristicsin vitro and exhibit normal in vivo survival in animal models. Pegylation of white blood cells (particularly antigen presenting cells and T lymphocytes) surprisingly prevents recognition of foreign class II molecules and prevents T cell proliferation in response to foreign MHC molecules. Potential applications for the covalent binding of nonimmunogenic, long chain polymers (e.g., PEG) to intact cells include, but are not limited to: 1) derivatized RBC to diminish transfusion reactions arising from sensitization to minor blood group antigens (allosensitization) in the chronically transfused (e.g., sickle and thalassemia patients); 2) use of mPEG modification of "passenger" lymphocytes to prevent immune recognition and graft versus host disease; and 3) derivatization of the vascular endothelium of donor tissues prior to transplantation to prevent/diminish acute tissue rejection. In contrast to highly specific blocking mechanisms (e.g., anti-CD4; proteolytic removal of RBC A/B antigens), the generation of globally camouflaged (i.e., stealth) cells may more effectively prevent the often complex and redundant events leading to immune recognition of foreign cells.
Variable Changes in Body Composition, Strength and Lower-Body Power During an International Rugby Sevens Season

Abstract Mitchell, JA, Pumpa, KL, Williams, KJ, and Pyne, DB. Variable changes in body composition, strength and lower-body power during an international rugby sevens season. J Strength Cond Res 30(4): 1127–1136, 2016—This study determined whether body composition, strength, and power changes that occur during preseason can be maintained during an international rugby sevens season. Fourteen male international rugby sevens players (age 21.4 ± 2.2 years; mean ± SD) were categorized as forward (n = 7) or back (n = 7), and assessed for height, mass (M), skinfolds (S) (∑7), upper-body (UB) strength, lower-body (LB) strength, and LB power. Bench press, back squat, and a countermovement jump were used to measure strength and power at 3 time points: initial, early season, and late season. Forwards were taller (185 ± 4 cm), heavier (95 ± 6 kg), and possessed a greater lean body mass (55.5 ± 4.0 M·S−0.14) than backs (181 ± 8 cm, 88.5 ± 5.5 kg, and 51.9 ± 3.4 M·S−0.14). Over the full season, small (∼5 ± 5%; mean ± 90% confidence limits) positive changes occurred in body composition. Lower-body strength gained during the preseason, decayed in-season, whereas UB strength increased moderately (∼10 ± 3%) across the season. Power showed inconsistencies between measured variables with a moderate positive change across the season in mean velocity and relative peak power. Forwards showed a small decrease in peak power (relative and absolute). Moderate changes were observed in mean power over the season, forwards decreasing (∼6 ± 6%) and backs increasing (∼8 ± 6%). Rugby sevens forwards in this study found it difficult to maintain and improve power qualities in-season. Training loads of forwards and backs should be differentiated to maximize strength and power in-season.
Does High Caregiver Stress Predict Nursing Home Entry?

This study estimates how informal care, paid formal care, and caregiver stress or burden relate to nursing home placement. Data came from the 1999 National Long Term Care Survey and were merged with administrative data. Results show that stress is a strong predictor of entry over follow-up periods of up to two years, and physical strain and financial hardship are important predictors of high levels of caregiver stress. The estimates indicate that reducing these stress factors would significantly reduce caregiver stress and, as a result, nursing home entry. We conclude that initiatives to reduce caregiver stress hold promise as a strategy to avoid or defer nursing home entry.
Monoubiquitination Promotes Calpain Cleavage of the Protein Phosphatase 2A (PP2A) Regulatory Subunit α4, Altering PP2A Stability and Microtubule-associated Protein Phosphorylation*

Background: α4 binds to the PP2A catalytic subunit and the microtubule-associated E3 ligase MID1. Results: MID1-dependent monoubiquitination promotes calpain-mediated cleavage of α4, altering its phosphatase regulatory function. Conclusion: Defects in this regulatory process may underlie the MAP hypophosphorylation and hyperphosphorylation seen in Opitz syndrome and Alzheimer disease. Significance: Pharmacological agents that interfere with α4 monoubiquitination or cleavage are potential therapeutics to treat Alzheimer disease. Multiple neurodegenerative disorders are linked to aberrant phosphorylation of microtubule-associated proteins (MAPs). Protein phosphatase 2A (PP2A) is the major MAP phosphatase; however, little is known about its regulation at microtubules. α4 binds the PP2A catalytic subunit (PP2Ac) and the microtubule-associated E3 ubiquitin ligase MID1, and through unknown mechanisms can both reduce and enhance PP2Ac stability. We show MID1-dependent monoubiquitination of α4 triggers calpain-mediated cleavage and switches α4's activity from protective to destructive, resulting in increased Tau phosphorylation. This regulatory mechanism appears important in MAP-dependent pathologies as levels of cleaved α4 are decreased in Opitz syndrome and increased in Alzheimer disease, disorders characterized by MAP hypophosphorylation and hyperphosphorylation, respectively. These findings indicate that regulated inter-domain cleavage controls the dual functions of α4, and dysregulation of α4 cleavage may contribute to Opitz syndrome and Alzheimer disease.