Miracle-dz/UniFAR-FTUs huggingface dataset:
A sensitive, type-specific, fluorogenic probe assay for detection of human papillomavirus DNA

A simple method for the detection of a number of human papillomavirus (HPV) genotypes associated with cervical cancer has been developed. The assay exploits the 5'-->3' exonucleolytic activity of Taq DNA polymerase to increase the signal from fluorescent dyes by releasing them from genotype-specific probes during PCR. The probes are oligonucleotides with a 5' reporter dye (6-carboxyfluorescein), a quencher dye (6-carboxy-tetramethyl-rhodamine), and a phosphate-blocked 3' end. In the intact probe, the proximity of the reporter and the quencher results in suppression of reporter fluorescence by Förster-type energy transfer (V. T. Förster. Ann. Phys. 2:55-75, 1948). If the probe is bound downstream of either primer during PCR, the 5'-->3' exonucleolytic activity of Taq polymerase degrades it, allowing the reporter to diffuse away from the quencher, which results in an increase in reporter fluorescence. The increased fluorescence is directly related to the amount of target DNA and can be detected with an automated fluorometer. Probes for the L1 region of the cervical-cancer-associated HPV types 16, 18, 31, 33, and 35 were synthesized and the assays were optimized. The most sensitive assay can detect as few as two copies of HPV DNA in human cervical specimens.
Aryl hydrocarbon receptor regulates Stat1 activation and participates in the development of Th17 cells

IL-17-producing T helper cells (Th17) have been recently identified as a previously undescribed subset of helper T cells. Here, we demonstrate that aryl hydrocarbon receptor (Ahr) has an important regulatory function in the commitment of Th17 cells. Ahr was robustly induced under Th17-polarizing conditions. Ahr-deficient naïve T cells showed a considerable loss in the ability to differentiate into Th17 cells when induced by TGF-β plus IL-6. We were able to demonstrate that Ahr interacts with Stat1 and Stat5, which negatively regulate Th17 development. Whereas Stat1 activation returned to its basal level in Ahr wild type naïve T cells 24 h after stimulation with TGF-β plus IL-6, Stat1 remained activated in Ahr-deficient naïve T cells after stimulation. These results indicate that Ahr participates in Th17 cell differentiation through regulating Stat1 activation, a finding that constitutes additional mechanisms in the modulation of Th17 cell development.
The essential nutrient pyrroloquinoline quinone may act as a neuroprotectant by suppressing peroxynitrite formation

Pyrroloquinoline quinone (PQQ) is a redox active essential nutrient that can generate or scavenge superoxide depending on its microenvironment. PQQ has been shown previously to be neuroprotective in a rodent stroke model. Here we test whether PQQ interacts with reactive nitrogen species, known to be involved in the pathogenesis of stroke. Using rat forebrain neurons in culture, we determined that the toxicity of SIN‐1 was mediated by peroxynitrite and that PQQ could block this toxic action. However, PQQ could not block the toxicity of peroxynitrite itself. Both SIN‐1 and peroxynitrite caused ATP depletion, but only SIN‐1 evoked ATP depletion was blocked by PQQ. In a cell‐free system, PQQ blocked nitration of bovine serum albumin produced by SIN‐1, but potentiated peroxynitrite‐induced nitration. PQQ was unable to block ATP depletion and cell death induced by NO· donors (DEA/NO, DPT/NO and DETA/NO), indicating that it does not directly interact with nitric oxide, and suggesting that it acts as a superoxide scavenger. PQQ significantly potentiated cGMP accumulation evoked by SIN‐1, similar to the effect of superoxide dismutase (SOD). However, unlike SOD, which potentiated neurotoxicity induced by SIN‐1, PQQ blocked its toxicity, arguing against the possibility that PQQ functions simply as a SOD mimetic. Indeed, substantially less H2O2 was produced by the incubation of SIN‐1 with PQQ, when compared to SOD. These results suggest that PQQ scavenges superoxide without forming toxic levels of H2O2. Therefore, the protective effect of PQQ on stroke might be due, at least in part, to the suppression of peroxynitrite formation.
The effect of cryotherapy on eccentric plantar flexion peak torque and endurance.

OBJECTIVE The effects of cryotherapy on eccentric torque production and muscle endurance have been controversial. Our intent was to examine the effect of cryotherapy on isokinetic eccentric plantar flexion peak torque at 30 degrees /sec and 120 degrees /sec and on endurance at 120 degrees /sec. DESIGN AND SETTING SUBJECTS WERE TESTED ON AN ISOKINETIC DYNAMOMETER FOR PEAK TORQUE AND ENDURANCE AND WERE THEN RANDOMLY ASSIGNED TO ONE OF FOUR GROUPS: (a) peak torque measurements at 30 degrees /sec and 120 degrees /sec after a 30-minute 10 degrees C ice bath immersion, (b) peak torque measurements at 30 degrees /sec and 120 degrees /sec without ice bath immersion (control), (c) endurance measurement at 120 degrees /sec after a 30-minute 10 degrees C ice bath immersion, and (d) endurance measurement at 120 degrees /sec without ice bath immersion (control). Subjects completed each of the four experimental conditions with 7 to 14 days between conditions. SUBJECTS Eleven male and 11 female volunteers (mean age, 23.8 +/- 3.5 years) were screened for normal ankle range of motion, past history of lower extremity injury, and contraindications to cryotherapy. MEASUREMENTS Dependent t tests were used to analyze practice session data in order to establish reliable baseline measurements. A 2 x 2 analysis of variance (ANOVA) with repeated measures (p < .05) was used to analyze peak torque data. A one-way ANOVA (p < .05) was used to analyze endurance data in the form of total work. RESULTS Velocity significantly affected peak torque production, with eccentric peak torque values significantly higher at 120 degrees /sec than at 30 degrees /sec for both the control and the immersion conditions. Cryotherapy had no effect on eccentric peak torque at either 30 degrees /sec or 120 degrees /sec, but it increased eccentric total work (endurance) at 120 degrees /sec. CONCLUSIONS Cryotherapy has long been known to have beneficial therapeutic effects. In our study, cryotherapy did not significantly affect eccentric peak torque, but it did increase muscle endurance. An athlete can reap the beneficial effects of cryotherapy, such as pain reduction, vasoconstriction, and edema control, without compromising eccentric force production or endurance.
Prognostic impact of serum 25-hydroxivitamin D [25(OH)D] concentrations in patients with lymphoid malignancies

Abstract The incidence of lymphoid malignancies has been increasing rapidly. Despite growing evidence for a relationship between serum 25-hydroxivitamin D [25(OH)D] concentrations and solid tumor risk, far less is known about the relationship between 25(OH)D and the risk of hematologic malignancy. This study aimed to assess the prognostic relevance of serum 25(OH)D concentrations in patients with B chronic lymphocytic leukemia (B-CLL) and non Hodgkin's lymphoma (NHL). The study was carried out on 195 newly diagnosed patients (75 B-CLL and 120 NHL) as well as 30 normal healthy controls. For all patients and normal controls serum 25(OH)D concentrations were assayed by enzyme-linked immunosorbent assay. Serum 25(OH)D levels were significantly lower in B-CLL and NHL patients as compared with normal controls (P = 0.00 for both). Also, there are significant associations between serum 25(OH)D levels and positive CD 38, positive ZAP 70 as well as Binet stages (χ2 = 16.071, 16.644, 21.134 respectively; P = 0.00 for all) in the B-CLL patient group. Moreover, there are significant associations between serum 25(OH)D status and international prognostic index (IPI), performance status (χ2 = 6.994, 9.212, P = 0.02, 0.01 respectively), but not with clinical stages (χ2 = 3.115, P = 0.539) in NHL. Multivariate analysis revealed that 25(OH)D insufficiency is an independent poor prognostic factor in both B-CLL and NHL patient groups. In conclusion, 25(OH)D insufficiency is an independent poor prognostic factor in patients with B-CLL and NHL. 25(OH)D might be a therapeutic target in lymphoid malignancies.
Enhancement of peritoneal leukocyte function by granulocyte colony-stimulating factor in rats with abdominal sepsis.

OBJECTIVE To investigate the therapeutic effects of granulocyte colony-stimulating factor (G-CSF) on the functional activities of circulating and peritoneal neutrophils during intra-abdominal sepsis. DESIGN Placebo, controlled study, using a rat model of intra-abdominal sepsis. SETTING Animal research facility. SUBJECTS Male specific pathogen-free Sprague-Dawley rats. INTERVENTIONS Abdominal sepsis was produced in rats by cecal ligation and puncture. The control animals received a sham operation. G-CSF (subcutaneous injection at 50 microg/kg) or vehicle (100 microL of 5% dextrose) treatment was initiated at 1 hr after cecal ligation and puncture or sham operation and repeated at 12-hr intervals thereafter. MEASUREMENTS AND MAIN RESULTS Six hours after cecal ligation and puncture, CD11b/c and CD18 expression on circulating neutrophils was significantly up-regulated when compared with those in the sham operated control animals. Peritoneal neutrophils exhibited a further up-regulation of these adhesion molecules than did the circulating neutrophils. A sustained up-regulation of CD11b/c and CD18 was found in peritoneal neutrophils even at 24 hrs after cecal ligation and puncture. G-CSF treatment increased CD11b/c expression on circulating neutrophils in 6-hr sham-operated rats, but did not further up-regulate CD11b/c or CD18 expression on circulating or peritoneal neutrophils in cecal ligation and puncture rats. Phagocytic activities of circulating neutrophils assessed by uptake of fluorescent latex microspheres were lower in 24-hr cecal ligation and puncture rats when compared with the sham-operated controls. G-CSF treatment prevented this inhibition. Furthermore, G-CSF enhanced the phagocytic activities of peritoneal neutrophils in both 6- and 24-hr cecal ligation and puncture rats when compared with those of the vehicle-treated animals. Spontaneous hydrogen peroxide generation by circulating neutrophils was increased in 6-hr cecal ligation and puncture rats, but not in 24-hr cecal ligation and puncture rats. Peritoneal neutrophils exhibited an inhibition of phorbol myristate acetate-stimulated hydrogen peroxide generation. G-CSF treatment did not up-regulate neutrophil hydrogen peroxide generation. CONCLUSIONS Circulating and peritoneal neutrophils exhibit marked polymorphism in their functional activities during the host response to abdominal sepsis. G-CSF treatment significantly enhanced the phagocytic function of both circulating and peritoneal neutrophils which may be one mechanism underlying its protective effect in abdominal sepsis.
Hyperthermia exhibits anti-vascular activity in the s.c. BT 4 An rat glioma: lack of interaction with the angiogenesis inhibitor batimastat

We investigated the anti-vascular activity of local hyperthermia (44°C, 60 min) in s.c. BT 4 An rat gliomas, and the influence on tumour growth of hyperthermia and the anti-angiogenic compound batimastat (30mg/kg i.p.). Heat-induced vascular damage was assessed in small (82 mm 3 ) and large (171 mm 3 ) tumours using confocal microscopy and immunostaining for von Willebrand factor. The influence of hyperthermia on tumour blood flow was measured using the 86 RbCl method. The anti-tumour activity of hyperthermia (one or two fractions a week apart) and batimastat (7 or 14 daily injections) and various combination schedules were examined. Hyperthermia disrupted 25-50% of the vasculature in the BT 4 An tumours, and the vascular damage was most extensive in the central part of the large tumours. The heated tumours exhibited a 40-60% blood flow reduction, which persisted until the last measurement after 24h. One fraction of hyperthermia caused a significant growth delay of 4 days, compared with the control group ( p = 0.01), but no additional tumour response was produced by a second heating session. Batimastat had no influence on tumour growth and the combination of drug and local heating did not enhance the tumour response, compared with heating alone. It was concluded that hyperthermia at 44°C for 60 min exhibits anti-vascular activity and inhibits tumour growth in the BT 4 An tumour model. Batimastat had no effect on tumour growth.
The effectiveness of insurer-supported safety and health engineering controls in reducing workers' compensation claims and costs.

BACKGROUND This study evaluated the effectiveness of a program in which a workers' compensation (WC) insurer provided matching funds to insured employers to implement safety/health engineering controls. METHODS Pre- and post-intervention WC metrics were compiled for the employees designated as affected by the interventions within 468 employers for interventions occurring from 2003 to 2009. Poisson, two-part, and linear regression models with repeated measures were used to evaluate differences in pre- and post-data, controlling for time trends independent of the interventions. RESULTS For affected employees, total WC claim frequency rates (both medical-only and lost-time claims) decreased 66%, lost-time WC claim frequency rates decreased 78%, WC paid cost per employee decreased 81%, and WC geometric mean paid claim cost decreased 30% post-intervention. Reductions varied by employer size, specific industry, and intervention type. CONCLUSIONS The insurer-supported safety/health engineering control program was effective in reducing WC claims and costs for affected employees.
Is there a ‘weight neutral’ second-generation antipsychotic for bipolar disorder?

ABSTRACT Introduction: Antipsychotic-induced weight gain (WG) and metabolic abnormalities are major concerns. This review was untaken to answer if there is a weight-neutral second-generation antipsychotic for bipolar disorder (BPD). Areas covered: English-language literature in MEDLINE was searched with the keywords of antipsychotic/second-generation antipsychotic or generic/brand name of second-generation antipsychotic, and BPD/mania/depression or bipolar maintenance, and safety/tolerability or WG/weight increase, and randomized, placebo-controlled trial. Difference between an antipsychotic monotherapy and placebo in absolute weight gain (AWG) and/or ≥ 7% (WG in three phases of BPD was compared based on the data from original publications. The number needed to treat to harm was used for the comparison of ≥ 7% WG. Among antipsychotics with short-term (mania and/or bipolar depression) and long-term (maintenance) studies, olanzapine, asenapine, quetiapine, risperidone had significant WG compared to placebo in both short-term and long-term trials. Aripiprazole did not cause significant WG compared to placebo in short-term studies, but caused significant WG in long-term studies. Paliperidone-ER-induced WG was significant in a mania study as measured with AWG, and ziprasidone caused significant WG in a mania study measured with ≥ 7% WG. Expert commentary: These data suggest that it is unlikely there is a weight-neutral second-generation antipsychotic in BPD.
Assessing self-regulatory processes during clinical skill performance: A pilot study

Background: Self-regulated learning (SRL) is a cyclical process involving the proactive use of strategies and feedback to optimise performance. Previous research has used SRL microanalysis to assess and inform the training of athletic skills but there has been no previous research in clinical contexts. Aims: The aim of this pilot study was to evaluate the use SRL microanalysis to assess the regulatory profiles of students who were successful and unsuccessful in a venipuncture task. Method: A SRL microanalysis protocol was administered to seven 3rd-year undergraduate medical students whilst they performed a venipuncture on a simulation mannequin arm. Results: The use of SRL microanalytic questions had good inter-rater reliability. Students who were successful in venipuncture had high levels of strategic thinking before, during and after the clinical task, whereas the students who struggled on this task tended to focus on outcomes. Conclusions: The results shown in this study mirror the findings from previous research using SRL microanalysis. SRL microanalysis has strong potential as a structured assessment technique targeting the self-regulatory processes underlying clinical skill performance. Further research is recommended, especially on how the assessment of self-regulatory skills can be used to guide training for struggling students.
Generic/matrix evaluation of SV40 clearance by anion exchange chromatography in flow‐through mode

The potential of viral contamination is a regulatory concern for continuous cell line‐derived pharmaceutical proteins. Complementary and redundant safety steps, including an evaluation of the viral clearance capacity of unit operations in the purification process, are performed prior to registration and marketing of biotechnology pharmaceuticals. Because process refinement is frequently beneficial, CBER/FDA has published guidance facilitating process improvement by delineating specific instances where the bracketing and generic approaches are appropriate for virus removal validation. In this study, a generic/matrix study was performed using Q‐Sepharose Fast Flow (QSFF) chromatography to determine if bracketing and generic validation can be applied to anion exchange chromatography. Key operational parameters were varied to upper and lower extreme values and the impact on viral clearance was assessed using simian virus 40 (SV40) as the model virus. Operational ranges for key chromatography parameters were identified where an SV40 log10 reduction value (LRV) of ≥4.7 log10 is consistently achieved. On the basis of the apparent robustness of SV40 removal by Q‐anion exchange chromatography, we propose that the concept of “bracketed generic” validation can be applied to this and potentially other chromatography unit operations. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 84: 179–186, 2003.
Longer thaw seasons increase nitrogen availability for leaching during fall in tundra soils

Climate change has resulted in warmer soil temperatures, earlier spring thaw and later fall freeze-up, resulting in warmer soil temperatures and thawing of permafrost in tundra regions. While these changes in temperature metrics tend to lengthen the growing season for plants, light levels, especially in the fall, will continue to limit plant growth and nutrient uptake. We conducted a laboratory experiment using intact soil cores with and without vegetation from a tundra peatland to measure the effects of late freeze and early spring thaw on carbon dioxide (CO2) exchange, methane (CH4) emissions, dissolved organic carbon (DOC) and nitrogen (N) leaching from soils. We compared soil C exchange and N production with a 30 day longer seasonal thaw during a simulated annual cycle from spring thaw through freeze-up and thaw. Across all cores, fall N leaching accounted for ∼33% of total annual N loss despite significant increases in microbial biomass during this period. Nitrate ( NO 3 − ) leaching was highest during the fall (5.33 ± 1.45 mg N m−2 d−1) following plant senescence and lowest during the summer (0.43 ± 0.22 mg N m−2 d−1). In the late freeze and early thaw treatment, we found 25% higher total annual ecosystem respiration but no significant change in CH4 emissions or DOC loss due to high variability among samples. The late freeze period magnified N leaching and likely was derived from root turnover and microbial mineralization of soil organic matter coupled with little demand from plants or microbes. Large N leaching during the fall will affect N cycling in low-lying areas and streams and may alter terrestrial and aquatic ecosystem nitrogen budgets in the arctic.
WOMEN ENTREPRENEURS: REASONS AND DIFFICULTIES FOR STARTING IN BUSINESS

Purpose: The aim of this research is to describe the main reasons and difficulties for women to establish businesses and to identify possible differences between those that go into industry and those that establish commerce or service businesses. Originality/gap/relevance/implications: The establishment of business is highly important for Entrepreneurship and its understanding is relevant to pinpoint the reasons and identify the difficulties that entrepreneurs have to establish their companies. Key methodological aspects: A quantitative study of 102 industry women entrepreneurs and 96 commerce/services entrepreneurs was carried out. Data were collected by a structured questionnaire and by two Likert scales, which measured reasons and difficulties in the establishment of companies. A cluster analysis was undertaken to identify possible groups of attributes related to reasons and difficulties in the establishment of enterprises to group variables. The Mann-Whitney test was employed to compare reasons and difficulties in the establishment of enterprises between the two groups (industry and commerce/service) to identify statistically significant differences. Summary of key results: Results by the Mann-Whitney test revealed that the two groups assigned the same level of importance to the reasons for business establishment: improvement difficulty in the previous job; desire to financially help offspring; re-entry into the labor market; earning lot of money. The same test showed no significant difference in importance level assigned to eight difficulties for the establishment of business: I did not believe in my own capacity; I had never had any link with other companies; I did not have any access to industry information; People did not believe in my potential; I was afraid to quit my job; I was never acquainted with a business plan; I had no money for advertising my business; I found it difficult to choose the location of the company. Key considerations/conclusions: Results show that women entrepreneurs are not a homogenous group and that there is a need for public policies that would minimize difficulties in the setting up of companies to increase women´s participation as entrepreneurs.
Metal deposition in deep sediments from the Central and South Adriatic Sea

Geochemical analysis and trace element distribution were performed on the marine sediments from short cores (30 to 50 cm) from the Middle (Jabuka and Palagruža pits, depth 230 m and 170 m respectively) and South Adriatic Sea (depth 1030 m) and the Albanian offshore (50 m depth). The distribution and mineralogy of trace elements (As, Co, Cd, Cu Cr, Ni, Zn, Hg, and Pb) and major elements (Al, Ca and Mn) in the sediments is presented. Sediments are highly heterogeneous and consist of carbonate and detrital aluminosilicates. The main mineral phase is calcite, followed by quartz, feldspars, micas and clay minerals (smectite, chlorite, illite and kaolinite). The cores were dated using 137Cs. The cores from the South Adriatic Pit and Palagruža Sill gave estimated sedimentation rates of 1.8 mm y-1 and 3.1 mm y-1 in Jabuka Pit. Distributions of Ni and Cr showed that they can be used as tracers of sediment provenance along the southern part of the Eastern Adriatic Current. Calculated enrichment factors for Pb, Cd and Hg are highest in the top 2 cm of the cores. Mercury shows the highest degree of enrichment in 0-2 cm sediment intervals (the highest in the Albania core). Generally the estimated surface enrichment follows the order: Hg>Pb>Cd. No enrichment was found for Zn, Ni and Cr.