Miracle-dz/UniFAR-FTUs huggingface dataset:
Antibodies against polyethylene glycol in healthy subjects and in patients treated with PEG-conjugated agents

In contrast to the accepted general assumption that polyethylene glycol (PEG) is non-immunogenic and non-antigenic, animal studies clearly showed that uricase, ovalbumin and some other PEGylated agents can elicit antibody formation against PEG (anti-PEG). In humans, anti-PEG may limit therapeutic efficacy and/or reduce tolerance of PEG-asparaginase (PEG-ASNase) in patients with acute lymphoblastic leukemia and of pegloticase in patients with chronic gout, but did not impair hyposensitization of allergic patients with mPEG-modified ragweed extract or honeybee venom or the response to PEG-IFN in patients with hepatitis C. Of major importance is the recent finding of a 22 – 25% occurrence of anti-PEG in healthy blood donors, compared with a very low 0.2% occurrence two decades earlier. This increase may be due to an improvement of the limit of detection of antibodies during the years and to greater exposure to PEG and PEG-containing compounds in cosmetics, pharmaceuticals and processed food products. These results raise obvious concerns regarding the efficacy of PEG-conjugated drugs for a subset of patients. To address these concerns, the immunogenicity and antigenicity of approved PEGylated compounds should be carefully examined in humans. With all these data in hand, patients should be pre-screened and monitored for anti-PEG prior to and throughout a course of treatment with a PEGylated compound. Finally, protein conjugates with the poorly immunogenic hydroxy-PEG sequence or other hydrophilic polymers are in early phases of development and may represent an alternative to immunogenic PEGylated proteins.
Effects of metronidazole plus amoxicillin as the only therapy on the microbiological and clinical parameters of untreated chronic periodontitis.

AIM To determine the effect of metronidazole plus amoxicillin (M+A) as the sole therapy, on the subgingival microbiota of chronic periodontitis. MATERIAL AND METHODS Twenty-two patients with untreated chronic periodontitis were randomly assigned to a group that received M+A for 7 days, or to a group receiving scaling and root planing (SRP) and two placebos. Clinical measurements including sites with plaque, bleeding on probing (BOP), probing depth (PD) and attachment level (AL) were made at baseline, 3, 6, 9 and 12 months. Subgingival plaque samples were taken from all teeth at baseline 3, 6, 9 and 12 months for the counts of 40 subgingival species using checkerboard DNA-DNA hybridization. RESULTS Mean PD was reduced from 2.80+/-0.45 at baseline to 1.95+/-0.05 at 12 months (P<0.001) and from 2.39+/-0.41 to 1.95+/-0.10 (P<0.001) in the M+A- and SRP-treated patients, respectively. Corresponding values for relative mean AL were 10.07+/-1.30-9.77+/-0.34 (P<0.001) and 9.94+/-0.28-9.77+/-0.26 (P<0.001). Percentage of sites exhibiting BOP were 40.6+/-18.3-14.0+/-1.4 (P<0.001), and 38.5+/-5.1-19.0+/-2.8 (P<0.001) in the M+A and SRP groups, respectively. Mean total DNA probe counts and counts of the majority of the 40 test species were significantly reduced over time in both groups, with no significant differences detected at any time point between groups. At 12 months many of the species were still present at significantly lowered levels compared with their baseline counts in both groups. CONCLUSIONS Changes in clinical and microbiological parameters were similar after receiving systemically administered M+A as the sole therapy or after receiving SRP only.
Low Long-Term Interest Rates as a Global Phenomenon

International linkages between interest rates in different currencies are strong, and ultra-low rates have become a global phenomenon. This paper compares how interest rates in advanced economies and in emerging economies are conditioned by two global benchmarks - the Federal funds rate at the short end and the "world" real interest rate at the long end. Real equilibrium policy rates (the natural rate) have fallen in many countries, and short-term rates worldwide have been further depressed by many years of the US policy rate close to zero. Nevertheless, changes in the Federal funds rate have less effect on longer-term rates, and thus on financing conditions, than is often supposed. The decline in the world long-term rate since 2008 has been driven almost entirely by a fall in the world term premium (negative in nominal terms since mid-2014). The world short-term rate expected over the long run has fallen only modestly over the past seven years or so, and is now just over 2% (compared with around 4% pre-Lehman).
Cell cycle specific radiosensitisation by the disulfiram and copper complex

The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Treatment with 0.1 and 0.3 μM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c) and UVW cells, respectively. The increased potency of ionising radiation treatment induced by DSF:Cu and/or gemcitabine was determined by clonogenic assay. Treatment with 0.3 μM DSF:Cu resulted in greater radiation kill, exemplified by dose enhancement factor values of 2.64 and 2.84 in SK-N-BE(2c) and UVW cells, respectively. Although DSF:Cu failed to sensitise S phase cells to irradiation, we observed that DSF:Cu radiosensitisation was potentiated by the S phase-specific cytotoxic drug gemcitabine. The efficacy of the combination treatment consisting of DSF:Cu, gemcitabine and ionising radiation was schedule-dependent. Together, these results describe cell cycle specific radiosensitisation by DSF:Cu. The well-established toxicity profiles of DSF and gemcitabine should facilitate their evaluation as a combination treatment in patients undergoing radiotherapy.
Comparisons between the structures of HCV and Rep helicases reveal structural similarities between SF1 and SF2 super‐families of helicases

Three helicase structures have been determined recently: that of the DNA helicase PcrA, that of the hepatitis C virus RNA helicase, and that of the Escherichia coli DNA helicase Rep. PcrA and Rep belong to the same super‐family of helicases (SF1) and are structurally very similar. In contrast, the HCV helicase belongs to a different super‐family of helicases, SF2, and shows little sequence homology with the PcrA/Rep helicases. Yet, the HCV helicase is structurally similar to Rep/PcrA, suggesting preservation of structural scaffolds and relationships between helicase motifs across these two super‐families. The comparison study presented here also reveals the existence of a new helicase motif in the SF1 family of helicases.
Factors Influencing The Outcome Of Kidney Transplants

This study is a multifactorial analysis of 389 transplants performed from June 1977 to December 1981. Analyis of the effects of transfusions antilymphocyte serum (ALS), histocom-patibility testing, gender, and patient risk factors (presence of concomitant disease, greater than 50 years of age, etc.) was done. Two-hundred fifty-three patients received cadaver kidneys and 136 patients obtained kidneys from a relative. Two-hundred eighty-three (73%) patients received blood transfusions prior to transplantation. Our data showed that recipients receiving transfusions prior to transplantation had a significantly higher graft survival than those who were not transfused in both cadaveric and related graft recipients. Two-hundred twenty-one (56%) patients received ALS following the transplant. This group had a 15% higher graft survival than a comparable group. Analysis of histocompatibility testing data shows approximately 5% higher functional graft survival between each match grade. Surprisingly, female patients receiving kidneys from living related donors had a 16% higher graft survival than male patients. In cadaver recipients female patients had a 10% higher patient survival as compared to male patients. The risk factor status of recipients affected not only graft survival but patient survival, which probably is due to the consequences of immunotherapy. The authors' conclusion is that the above mentioned factors may be additive in nature. Further, multivariable analysis is necessary in order to correctly transplant data.
Past and current gene flow in the selfing, wind‐dispersed species Mycelis muralis in western Europe

The distribution of genetic diversity in Mycelis muralis, or wall lettuce, was investigated at a European scale using 12 microsatellite markers to infer historical and contemporary forces from genetic patterns. Mycelis muralis has the potential for long‐distance seed dispersal by wind, is mainly self‐pollinated, and has patchily distributed populations, some of which may show metapopulation dynamics. A total of 359 individuals were sampled from 17 populations located in three regions, designated southern Europe (Spain and France), the Netherlands, and Sweden. At this within‐region scale, contemporary evolutionary forces (selfing and metapopulation dynamics) are responsible for high differentiation between populations (0.34 < FST < 0.60) but, contrary to expectation, levels of within‐population diversity, estimated by Nei's unbiased expected heterozygosity (HE) (0.24 < HE < 0.68) or analyses of molecular variance (50% of the variation found within‐populations), were not low. We suggest that the latter results, which are unusual in selfing species, arise from efficient seed dispersal that counteracts population turnover and thus maintains genetic diversity within populations. At the European scale, northern regions showed lower allelic richness (A = 2.38) than populations from southern Europe (A = 3.34). In light of postglacial colonization hypotheses, these results suggest that rare alleles may have been lost during recolonization northwards. Our results further suggest that mutation has contributed to genetic differentiation between southern and northern Europe, and that Sweden may have been colonized by dispersers originating from at least two different refugia.
The Mei5-Sae3 Protein Complex Mediates Dmc1 Activity in Saccharomyces cerevisiae*

During homologous recombination, a number of proteins cooperate to catalyze the loading of recombinases onto single-stranded DNA. Single-stranded DNA-binding proteins stimulate recombination by coating single-stranded DNA and keeping it free of secondary structure; however, in order for recombinases to load on single-stranded-DNA-binding protein-coated DNA, the activity of a class of proteins known as recombination mediators is required. Mediator proteins coordinate the handoff of single-stranded DNA from single-stranded DNA-binding protein to recombinase. Here we show that a complex of Mei5 and Sae3 from Saccharomyces cerevisiae preferentially binds single-stranded DNA and relieves the inhibition of the strand assimilation and DNA binding abilities of the meiotic recombinase Dmc1 imposed by the single-stranded DNA-binding protein replication protein A. Additionally, we demonstrate the physical interaction of Mei5-Sae3 with replication protein A. Our results, together with previous in vivo studies, indicate that Mei5-Sae3 is a mediator of Dmc1 assembly during meiotic recombination in S. cerevisiae.
An Inhibitory Role for the Transcription Factor Stat3 in Controlling IL-4 and Bcl6 Expression in Follicular Helper T Cells

The transcription factor Bcl6 is required for development of follicular helper T (TFH) cells. Cytokines that activate Stat3 promote Bcl6 expression and TFH cell differentiation. Previous studies with an acute virus infection model showed that TFH cell differentiation was decreased but not blocked in the absence of Stat3. In this study, we further analyzed the role of Stat3 in TFH cells. In Peyer’s patches, we found that compared with wild-type, Stat3-deficient TFH cells developed at a 25% lower rate and expressed increased IFN-γ and IL-4. Whereas Peyer’s patch germinal center B cells developed at normal numbers with Stat3-deficient TFH cells, IgG1 class switching was greatly increased. Following immunization with sheep RBCs, splenic Stat3-deficient TFH cells developed at a slower rate than in control mice, and splenic germinal center B cells were markedly decreased. Stat3-deficient TFH cells developed poorly in a competitive bone marrow chimera environment. Under all conditions tested, Stat3-deficient TFH cells overexpressed both IL-4 and Bcl6, a pattern specific for the TFH cell population. Finally, we found in vitro that repression of IL-4 expression in CD4 T cells by Bcl6 required Stat3 function. Our data indicate that Stat3 can repress the expression of Bcl6 and IL-4 in TFH cells, and that Stat3 regulates the ability of Bcl6 to repress target genes. Overall, we conclude that Stat3 is required to fine-tune the expression of multiple key genes in TFH cells, and that the specific immune environment determines the function of Stat3 in TFH cells.
The Randomised Heston Model

We propose a randomised version of the Heston model -- a widely used stochastic volatility model in mathematical finance -- assuming that the starting point of the variance process is a random variable. In such a system, we study the small- and large-time behaviours of the implied volatility, and show that the proposed randomisation generates a short-maturity smile much steeper ('with explosion') than in the standard Heston model, thereby palliating the deficiency of classical stochastic volatility models in short time. We precisely quantify the speed of explosion of the smile for short maturities in terms of the right tail of the initial distribution, and in particular show that an explosion rate of t^r (r in [0,1/2]) for the squared implied volatility -- as observed on market data -- can be obtained by a suitable choice of randomisation. The proofs are based on large deviations techniques and the theory of regular variations.
Interfacial ultramorphology evaluation of resin luting cements to dentin: A correlative scanning electron microscopy and transmission electron microscopy analysis

The objective of this study was to analyze the dentin‐resin cements interfacial ultramorphologies using two different methods: scanning (SEM) and transmission electron microscopy (TEM). Four commercial products were evaluated: two conventional cementing system (RelyX ARC/Adper™ Scotchbond™ Multi‐Purpose Plus, 3M ESPE and Clearfil Esthetic Cement/DC Bond, Kuraray) and two self‐adhesive resin cements (RelyX Unicem, 3M ESPE and Clearfil SA Cement, Kuraray). Prepolymerized resin disks (Sinfony, 3M ESPE) were cemented on oclusal dentin surfaces of 24 third human molars, simulating the indirect restorations. After 24 h, teeth were sectioned into 0.9‐mm thick slabs and processed for microscopy analyses (SEM or TEM/ n = 3). Qualitative characterization of dentin‐resin cement interface was performed. Hybrid layer formation with long and dense resin tags was observed only for RelyX ARC cementing system. Clearfil Esthetic Cement/DC Bond system revealed few and short resin tags formation, whereas no hybridization and resin tags were detected for self‐adhesive resin cements. Some interfacial regions exhibited that the self‐adhesive resin cements were not bonded to dentin, presenting bubbles or voids at the interfaces. In conclusion, TEM and SEM bonding interface analyses showed ultramorphological variations among resin cements, which are directly related to dental bonding strategies used for each resin cement tested. Microsc. Res. Tech. 76:1234–1239, 2013. © 2013 Wiley Periodicals, Inc.
Prospective Follow-up Study of Borderline Personality Disorder: Prognosis, Prediction of Outcome, and Axis II Comorbidity

Objective: To examine the rate of persistence of borderline personality disorder (BPD), the existence of concomitant personality disorders on follow-up, and the predictors of outcome in patients who met criteria for BPD compared with patients with borderline features who failed to meet all of the criteria. Method: This prospective cohort study reassessed subjects for BPD diagnosis and cooccurring personality pathology at 7 years follow-up. Initial measures of borderline and comorbid personality psychopathology were used to predict levels of borderline or other personality disorder psychopathology at follow-up. Results: Of the 5 7 subjects who initially met the criteria for BPD, 30 (52.6%) were found to have remitted BPD, and 27 (47.4%) were characterized as having persistent BPD. The remitted group met significantly fewer comorbid personality disorder diagnoses than the persistent group (mean = 0.8, mean = 3.5 respectively; P < 0.05). Results also indicated that the initial level of borderline psychopathology was predictive of borderline psychopathology at follow-up, which explained 17% of the variance. Conclusions: This prospective follow-up study found that almost 50% of former inpatients with BPD continue to test positive for BPD at 7 years follow-up, and these persistent BPD patients also had significantly more comorbid personality psychopathology. Borderline psychopathology at follow-up was primarily predicted by the level of borderline psychopathology recorded at the initial assessment.
CaV3.2 T-type channels mediate Ca2+ entry during oocyte maturation and following fertilization

ABSTRACT Initiation of mouse embryonic development depends upon a series of fertilization-induced rises in intracellular Ca2+. Complete egg activation requires influx of extracellular Ca2+; however, the channels that mediate this influx remain unknown. Here, we tested whether the α1 subunit of the T-type channel CaV3.2, encoded by Cacna1h, mediates Ca2+ entry into oocytes. We show that mouse eggs express a robust voltage-activated Ca2+ current that is completely absent in Cacna1h−/− eggs. Cacna1h−/− females have reduced litter sizes, and careful analysis of Ca2+ oscillation patterns in Cacna1h−/− eggs following in vitro fertilization (IVF) revealed reductions in first transient length and oscillation persistence. Total and endoplasmic reticulum (ER) Ca2+ stores were also reduced in Cacna1h−/− eggs. Pharmacological inhibition of CaV3.2 in wild-type CF-1 strain eggs using mibefradil or pimozide reduced Ca2+ store accumulation during oocyte maturation and reduced Ca2+ oscillation persistence, frequency and number following IVF. Overall, these data show that CaV3.2 T-type channels have prev8iously unrecognized roles in supporting the meiotic-maturation-associated increase in ER Ca2+ stores and mediating Ca2+ influx required for the activation of development. Summary: In mouse oocytes, CaV3.2 T-type channels have previously unrecognized roles in supporting accrual of Ca2+ stores during oocyte maturation and in mediating Ca2+ influx following fertilization.
Acaricidal activity of Metarhizium anisopliae isolated from paddocks in the Mexican tropics against two populations of the cattle tick Rhipicephalus microplus

The acaricidal effects of 55 strains of Metarhizium anisopliae (Metschnikoff) Sorokin, 1883 (Hypocreales: Clavicipitaceae) isolated from paddocks of cattle farms were evaluated in two Rhipicephalus microplus (Canestrini 1887) (Ixodida: Ixodidae) populations, of which one was multi‐resistant and one was susceptible to chemical acaricides. Percentage mortality and reproductive efficiency indices in R. microplus were evaluated by adult immersion tests at a dose of 1 × 108 conidia/mL for each fungal strain. Some strains were selected to calculate lethal concentrations to kill 50% (LC50) and 99% (LC99) of engorged ticks. Strains MaV22, MaV26 and MaV55 induced 100% mortality in R. microplus on day 14. Strains MaV05, MaV09 and MaV22 caused mortality of >90% from day 12 onward in both tick populations. The most effective acaricidal fungal strain, MaV55, inhibited egg laying by 54.86 and 55.86% in acaricide‐resistant and ‐susceptible R. microplus populations, respectively. None of the fungal strains had statistically significant effects on larval hatching. In conclusion, nine strains of M. anisopliae demonstrated high acaricidal effects against R. microplus and reduced its egg laying. No differences in acaricidal effects were observed between the two populations of ticks tested.
Vertical niche partitioning between cryptic sibling species of a cosmopolitan marine planktonic protist

A large portion of the surface‐ocean biomass is represented by microscopic unicellular plankton. These organisms are functionally and morphologically diverse, but it remains unclear how their diversity is generated. Species of marine microplankton are widely distributed because of passive transport and lack of barriers in the ocean. How does speciation occur in a system with a seemingly unlimited dispersal potential? Recent studies using planktonic foraminifera as a model showed that even among the cryptic genetic diversity within morphological species, many genetic types are cosmopolitan, lending limited support for speciation by geographical isolation. Here we show that the current two‐dimensional view on the biogeography and potential speciation mechanisms in the microplankton may be misleading. By depth‐stratified sampling, we present evidence that sibling genetic types in a cosmopolitan species of marine microplankton, the planktonic foraminifer Hastigerina pelagica, are consistently separated by depth throughout their global range. Such strong separation between genetically closely related and morphologically inseparable genetic types indicates that niche partitioning in marine heterotrophic microplankton can be maintained in the vertical dimension on a global scale. These observations indicate that speciation along depth (depth‐parapatric speciation) can occur in vertically structured microplankton populations, facilitating diversification without the need for spatial isolation.
Value of rapid assessment cytology in the surgical management of head and neck tumors in a Nigerian mission hospital

Fine‐needle aspiration (FNA) or touch preparation with rapid assessment is a valuable diagnostic tool with a reported accuracy of diagnosis similar to intraoperative frozen section consultation. The Nigeria Christian Hospital partners with health care professionals from the United States to provide surgical care for rural residents of Aba, Nigeria. Frozen section diagnosis is impractical in this setting because of very limited resources. Therefore, intraoperative rapid assessment FNA or touch preparation to guide surgical management was performed on all mass lesions, and the results were evaluated.