Miracle-dz/UniFAR-FTUs huggingface dataset:
Phase I clinical trial of cilengitide in children with refractory brain tumors: Pediatric Brain Tumor Consortium Study PBTC-012.

PURPOSE A phase I trial of the antiangiogenesis agent cilengitide (EMD 121974), an alpha v beta 3,5 integrin antagonist, was performed to estimate the maximum-tolerated dose (MTD) and describe dose-limiting toxicities (DLTs) and the incidence and severity of other toxicities when administered to children with refractory brain tumors. PATIENTS AND METHODS Thirty-one assessable patients received intravenous cilengitide over 1 hour twice a week for up to 52 weeks at dosages from 120 to 2,400 mg/m(2). Serial blood and urine samples for clinical pharmacology studies were obtained in a subset of consenting patients. RESULTS No DLTs were observed, and thus, the MTD was not estimated. Three of 13 patients at the dosage level of 2,400 mg/m(2) experienced grade 3 or 4 intratumoral hemorrhage (ITH) possibly related to the study drug; however, two of the ITH events were asymptomatic and, by the current toxicity criteria, would be classified as grade 1. For patients treated at cilengitide 2,400 mg/m(2), the 6-month cumulative incidence estimate of ITH is 23% (SE = 13%). No ITH was observed at 1,800 mg/m(2). Three patients completed 1 year of protocol therapy; one patient with glioblastoma multiforme demonstrated complete response, and two patients had stable disease (SD). An additional patient had SD for more than 5 months. CONCLUSION The phase II dosage of intravenous cilengitide in children with refractory brain tumors is 1,800 mg/m(2). A phase II trial to assess the efficacy of cilengitide therapy for children with refractory brain tumors is being developed by the Children's Oncology Group.
DIETARY POLYUNSATURATED FATS AND MALIGNANT MELANOMA

The consumption of polyunsaturated fat of a group of patients with malignant melanoma was compared to that of various groups of control subjects to determine whether such dietary fats predispose to the development of malignant melanoma. The results are tabulated with reference to various associated factors, and a statistical assessment of their significance is presented. The writers were unable to agree on the interpretation of the results, and present two opposing views on whether the ingestion of polyunsaturated fat is associated with the incidence of malignant melanoma.
Failure of neuronal protection by inhibition of glial activation in a rat model of striatonigral degeneration

Previous studies in rodent models of neurodegenerative disorders have demonstrated that minocycline exerts neuroprotective effects unrelated to its antimicrobial action. The purpose of the present study was to analyze whether minocycline exhibits neuroprotective activity in a rat model of striatonigral degeneration (SND), the core pathology underlying levodopa‐unresponsive parkinsonism associated with multiple system atrophy (MSA). We observed no significant effect of minocycline on locomotor impairment in double‐lesioned SND rats. Minocycline significantly suppressed astroglial and microglial activation (P < 0.01); however, 3′5′‐monophosphate‐regulated phosphoprotein (DARPP 32) immunohistochemistry revealed no significant differences in striatal lesion volume of minocycline‐treated versus untreated control SND rats. Furthermore, there was no protection of nigral dopaminergic neurons in the double‐lesion model. We conclude that despite its astrocytic and microglial suppression, minocycline failed to attenuate lesion‐induced neuronal damage in the SND rat model. © 2004 Wiley‐Liss, Inc.
Differences in time course of ACh and GABA modulation of excitatory synaptic potentials in slices of rat hippocampus.

Activation of muscarinic receptors and GABA(B) receptors causes presynaptic inhibition of glutamatergic synaptic potentials at excitatory feedback connections in cortical structures. These effects may regulate dynamics in cortical structures, with presynaptic inhibition allowing extrinsic afferent input to dominate during encoding, while the absence of presynaptic inhibition allows stronger excitatory feedback during retrieval or consolidation. However, proposals for a functional role of such modulatory effects strongly depend on the time course of these modulatory effects; how rapidly can they turn off and on? In brain slice preparations of hippocampal region CA1, we have explored the time course of suppression of extracellularly recorded synaptic potentials after pressure pulse application of acetylcholine and GABA. Acetylcholine causes suppression of extracellular potentials with onset time constants between 1 and 2 s, and decay constants ranging between 10 and 20 s, even with very brief injection pulses. GABA causes suppression of extracellular potentials with onset time constants between 0.2 and 0.7 s, and decay time constants that decrease to values shorter than 2 s for very brief injection pulses. These techniques do not give an exact measure of the physiological time course in vivo, but they give a notion of the relative time course of the two modulators. The slow changes due to activation of muscarinic acetylcholine receptors may alter the dynamics of cortical circuits over longer intervals (e.g., between different stages of waking and sleep), setting dynamics appropriate for encoding versus consolidation processes. The faster changes in synaptic potentials caused by GABA could cause changes within each cycle of the theta rhythm, rapidly switching between encoding and retrieval dynamics during exploration.
EffEct of SwinE RESiduE RatES on coRn, common BEan, SoyBEan and whEat yiEld

SummaRy Swine residue (SR) applied as nutrient source of crops such as corn, bean, soybean and wheat, besides representing an environmental-friendly way of disposing of organic waste resulting from swine production, may significantly increase grain yields, replacing mineral fertilizer. the objective was to evaluate the effect of SR rates on corn, common bean, soybean and wheat yields from 2002 to 2007, in comparison with mineral fertilizer. the experiment was carried out at the instituto agronomico do Parana – iaPaR, Pato Branco, PR and consisted of increasing SR rates (0, 15, 30, 45, and 60 m 3 ha -1 ) and one treatment with mineral fertilizer (nPK 4-30-10), using 250 kg ha -1 for bean and 300 kg ha -1 for corn, soybean and wheat. also, in the treatment with mineral fertilizer, 60, 120 and 90 kg ha -1 n was applied as topdressing to bean, corn and wheat, respectively. there were significant increases of grain yield in all evaluated years and crops with increasing SR rates, especially in the grass species under study. also, with increasing SR rates applied every six months, K, P, c a and m g were accumulated in the soil and the ph increased. the application of 60 m³ ha-1 SR increased yields and exceeded the yield obtained with the recommended mineral fertilizer, indicating this amount as adequate for these crops.
Comparison of the changes of alveolar bone thickness in maxillary incisor area in extraction and non-extraction cases: computerized tomography evaluation.

OBJECTIVE To compare, through computed tomography, alveolar bone thickness changes at the maxillary incisors area during orthodontic treatment with and without tooth extraction. METHODS Twelve patients were evaluated. They were divided into 2 groups: G1--6 patients treated with extraction of right and left maxillary first premolars, with mean initial age of 15.83 years and mean treatment length of 2.53 years; G2--6 patients treated without extraction, with mean initial age of 18.26 years and mean treatment length of 2.39 years. Computed tomographies, lateral cephalograms and periapical radiographs were used at the beginning of the treatment (T1) and 18 months after the treatment had started (T2). Extraction space closure occurred in the extraction cases. Intragroup and intergroup comparisons were performed by dependent and independent t test, respectively. RESULTS In G1, the central incisor was retracted and uprighted, while in G2 this tooth showed vestibularization. Additionally, G1 presented a higher increase of labial alveolar bone thickness at the cervical third in comparison with G2. The incidence of root resorption did not present significant differences between groups. CONCLUSION There were no changes in alveolar bone thickness when extraction and nonextraction cases were compared, except for the labial alveolar bone thickness at the cervical third of maxillary incisors.
Environmental and human influence on the ecology of Trichinella spiralis and Trichinella britovi in Western Europe

SUMMARY Surveys on Trichinella parasites in domestic and sylvatic animals collected in France, Italy, and in the Extremadura region of Spain showed that the distribution of Trichinella spiralis and Trichinella britovi is influenced by both environmental and human behaviour factors. In France, both Trichinella species are prevalent in the fox population from mountain areas and natural parks but are infrequent in wild boars (< 0·001%). In Italy, only T. britovi is present in sylvatic animals (foxes, wolves, and mustelids) living 500 m above sea level. This species is rare in wild boars ( < 0·001%) in that area. Sylvatic trichinellosis is found in only 24% and 34% of French and Italian territory, respectively, while lowland areas may generally be considered Trichinella-free, because the domestic cycle is absent. The ecology of T. spiralis and T. britovi in the Extremadura shows a different picture from that observed in France and Italy because of the presence of both domestic and sylvatic cycles. The domestic cycle not only allows the maintenance of T. spiralis in the domestic environment, but it also has a great impact on the prevalence in wild boar populations. It does not influence the prevalence in vulpine populations. These data suggest (1) that domestic trichinellosis occurs only in rural areas of Western Europe in association with traditional swine-rearing practices, but not in industrialized pig farms; (2) that sylvatic trichinellosis occurs only in natural habitats which, in Western Europe, are widespread in mountain areas; (3) that the fox is the primary reservoir in the sylvatic cycle, where the parasite is maintained in a closed circuit and (4) that among sylvatic animals T. spiralis is present at lower altitude than is T. britovi.
Cyst fluid carcinoembryonic antigen level is not predictive of invasive cancer in patients with intraductal papillary mucinous neoplasm of the pancreas.

CONTEXT Cyst fluid CEA concentration>192 ng/mL has proven accurate to differentiate mucinous from non-mucinous pancreatic cystic neoplasms. It is unclear whether the degree of cyst fluid CEA elevation is predictive of malignant behavior in IPMNs. OBJECTIVES To determine whether elevated cyst fluid CEA concentrations were predictive of invasive cancer. DESIGN Cross sectional study. SETTING Single National Cancer Institute comprehensive cancer care center experience. PATIENTS 47 patients underwent preoperative EUS-FNA with cyst fluid analysis and surgical resection of an IPMN over a 9 year period. MAIN OUTCOME MEASUREMENTS Cyst fluid CEA concentrations among the four grades associated with IPMN (low grade dysplasia, moderate dysplasia, high grade dysplasia, and invasive cancer). RESULTS The mean±standard deviation cyst fluid CEA concentration increased as the pathology progressed from low grade dysplasia (1,261±1,679 ng/mL) to moderate dysplasia (7,171±22,210 ng/mL) to high grade dysplasia (10,807±36,203 ng/mL). However, the mean CEA level decreased (462±631 ng/mL) once invasive cancer developed (P=0.869). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a cyst fluid CEA concentration greater than 200 ng/mL for the diagnosis of malignant IPMN (cases of high grade dysplasia and invasive IPMN) was 52.4%, 42.3%, 42.3%, 52.4% and 46.8%, respectively. LIMITATIONS Single center experience, small patient numbers, retrospective data collection. CONCLUSION The degree of cyst fluid CEA elevation is a poor predictor of malignant degeneration within IPMNs. Clinical management decisions regarding surgical resection should not be based upon degree of cyst fluid CEA elevation.
Mnev's Universality Theorem revisited

This article presents a complete proof of Mnëv’s Universality Theorem and and a first complete proof of Mnëv’s Universal Partition Theorem for oriented matroids. The Universality Theorem states that, for every primary semialgebraic set V there is an oriented matroid M, whose realization space is stably equivalent to V . The Universal Partition Theorem states that, for every partition V of IR induced by m polynomial functions f1, . , fm with integer coefficients there is a corresponding family of oriented matroids (Mσ)σ∈{−1,0,+1}m such that the collection of their realization spaces is stably equivalent to the family V.
The remediation challenge: theoretical and methodological insights from a systematic review

Objectives Remediation is usually offered to medical students and doctors in training who underperform on written or clinical examinations. However, there is uncertainty and conflicting evidence about the effectiveness of remediation. The aim of this systematic review was to synthesise the available evidence to clarify how and why remediation interventions may have worked in order to progress knowledge on this topic.
Patient-reported prevalence and symptomatic burden of uterine fibroids among women in the United States: findings from a cross-sectional survey analysis

Purpose To estimate the prevalence of women diagnosed with uterine fibroids and the associated symptom burden in the US. Patients and methods Responses of women aged 18–54 years, who completed an online survey, were analyzed. Data were weighted based on age, education, race, geographic region, income, and propensity score to derive national estimates of the prevalence of women diagnosed with uterine fibroids and associated symptom burden. Weighted means and percentages were reported. Prevalence across age and ethnic groups was examined. Symptom burden among women with and without uterine fibroids was compared using weighted logistic regressions. Results Of 59,411 respondents who met study inclusion criteria, 7.7% reported receiving a diagnosis of uterine fibroids. Of these, 5,670 women (1,402 in the uterine fibroid group and 4,268 in the control group) were excluded from analysis because they had a hysterectomy. Among the non-hysterectomized study participants, 3,031 self-reported a diagnosis of uterine fibroids (prevalence: 5.8%, 95% confidence interval [CI]: 5.5%–6.1%); prevalence increased as women aged and was greatest in the 50–54 age group (11.4%; 95% CI: 10.4%–12.4%). In addition, prevalence was greater in black vs white women (9.8%; 95% CI: 8.7%–11.0% vs 5.4%; 95% CI: 5.1%–5.7%). A greater percentage of women with uterine fibroids (vs those without) experienced severe heavy menstrual bleeding (16.7% vs 7.7%), severe constipation/bloating/diarrhea (7.7% vs 4.7%), severe passage of clots (6.7% vs 2.4%), severe spotting/bleeding between periods (1.7% vs 1.0%), and severe pelvic pressure (1.6% vs 0.6%). Among uterine fibroid patients with these typical uterine fibroid-related symptoms, 56.4%, 32.3%, 26.4%, 25.8%, and 20.4% reported heavy menstrual bleeding, passage of clots, spotting/bleeding between periods, constipation/bloating/diarrhea, and pelvic pressure, respectively, as extremely bothersome. Conclusion Uterine fibroids impose a heavy burden on women aged 18–54 years in the US.
Evaluation of the effect of sildenafil on the microvascular blood flow in patients with systemic sclerosis: a randomised, double-blind, placebo-controlled study.

OBJECTIVES To evaluate the effect of sildenafil as add-on therapy on the microvascular blood flow in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). METHODS In this double-blind, placebo-controlled study, 41 patients with RP secondary to SSc were randomly assigned to receive oral sildenafil 100 mg/day (21 patients, mean age 47.2 years) or placebo (20 patients, mean age 41.6 years) for 8 weeks. Patients were evaluated at baseline, 8 weeks after treatment, and 2 weeks after the end of the treatment. The primary outcome measures were the mean changes in finger blood flow (FBF) measured using laser Doppler imaging before and after cold stimulus at 8 weeks of treatment. Secondary endpoints included frequency and duration of RP attacks, Visual Analog Scale (VAS) score for RP severity, Raynaud's condition score, and serum levels of VEGF and endothelial progenitor cells (EPCs). RESULTS After 8 weeks of treatment, the sildenafil group presented a significantly higher mean percentage change from baseline in FBF before cold stimulus (p=0.026), and in FBF after cold stimulus (p=0.028) compared with the placebo group. There was a significant improvement in the duration of RP and in the percentage change from baseline to week 8 in the RP VAS score in sildenafil compared with placebo. There were no changes in EPCs and VEGF levels after treatment in either group. CONCLUSIONS Sildenafil improved digital blood flow and RP symptoms in SSc patients after 8 weeks of treatment, and might be a good therapeutic option for secondary RP.
Treatment as prevention: will it work?

In the past two years, rapidly emerging new trial results have provided the scientific community and people living with human immunodeficiency virus (HIV) or acquired immune deficiency syndrome (AIDS) or at risk of infection, with welcome news. Interesting scientific evidence is accumulating for the effectiveness of biomedical interventions to prevent the transmission of HIV. Infected people may become less contagious when the viral load is suppressed by antiretroviral therapy (ART). In 2010, results from the Pre-Exposure Prophylaxis Initiative (iPreX) randomised controlled trial provided the first evidence that antiretroviral preexposure prophylaxis can reduce HIV incidence. In their study, Grant et al showed, that that daily oral antiretroviral medication reduced HIV incidence in HIV negative men who have sex with men (MSM) by 44% [1]. In July 2011, two studies from the United States, the TDF2 (tenofovir disoproxil fumarate and emtricitabine (TDF)) study and the Partners Pre-exposure study provided evidence that a daily oral dose of antiretroviral medication can reduce HIV acquisition among uninfected individuals exposed to the virus through heterosexual sex by at least 60% [2-3]. The randomised controlled HIV Prevention Trials Network study (HPTN 052) by Cohen et al demonstrated that earlier treatment (time of enrolment in study compared with CD4 cell counts within or below 200-250 cells/mm3 or developing an AIDS defining illness) of HIV-infected persons with ART had both a clinical benefit for the infected individual and resulted in a 96% reduction in transmission to the uninfected sexual partner [4].
Longitudinal Relationship Between Cerebral Small-Vessel Disease and Cerebral Blood Flow: The Second Manifestations of Arterial Disease-Magnetic Resonance Study

Background and Purpose— Cerebral small-vessel disease and cerebral blood flow (CBF) are interrelated. However, the direction of the relationship is unknown, and longitudinal studies are scarce. We investigated the longitudinal relationship between CBF and white matter hyperintensities (WMHs) and lacunes, as representatives of cerebral small-vessel disease, in patients with manifest arterial disease. Methods— Within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study, 1.5T brain magnetic resonance imaging, including an MR angiography, was obtained at baseline and after on ≈3.9 years of follow-up in 575 patients with manifest arterial disease (mean age, 57±10 years). Longitudinal associations of WMHs and lacunes with parenchymal CBF (pCBF; per 100-mL brain volume) were estimated using regression analyses, adjusted for age, sex, follow-up time, and baseline brain measures. Results— Baseline pCBF was not associated with progression of WMHs and lacunes over time. However, periventricular and deep WMHs at baseline were associated with decline in pCBF; mean (95% confidence interval) decline in pCBF per % intracranial volume increase in periventricular and deep WMH volume was −0.70 (−1.40 to −0.00) and −1.01 (−1.64 to −0.38) mL/min per 100-mL brain volume, respectively. These associations were partly explained by cardiovascular risk factors but remained significant for deep WMHs (mean decline [95% confidence interval] in pCBF per % intracranial volume increase in deep WMH volume was −0.92 [−1.56 to −0.28] mL/min per 100-mL brain volume). Lacunes were not associated with change in pCBF. Conclusions— In patients with manifest arterial disease, baseline periventricular and deep WMH volumes were associated with decline in pCBF over time, but baseline pCBF was not associated with progression of WMHs and lacunes over time.
Modeling the interaction between aldolase and the thrombospondin‐related anonymous protein, a key connection of the malaria parasite invasion machinery

A complex molecular motor empowers substrate‐dependent motility and host cell invasion in malaria parasites. The interaction between aldolase and the transmembrane adhesin thrombospondin‐related anonymous protein (TRAP) transduces the motor force across the parasite surface. Here, we analyzed this interaction by using state‐of‐the‐art flexible docking. Besides algorithms to account for induced fit in the side‐chains of the Plasmodium falciparum aldolase (PfAldo) structure, we used additional in silico receptors modeled upon crystallographic structures of evolutionarily related aldolases to incorporate enzyme backbone flexibility, and to overcome structure inaccuracies due to the relatively low resolution (3.0 Å) of the genuine PfAldo structure. Our results indicate that, in spite of multiple intermolecular contacts, only the six C‐terminal residues of the TRAP cytoplasmic tail bind in an ordered manner to PfAldo. This portion of TRAP targets the PfAldo active site, with its n‐1 Trp residue, which is essential for this interaction, buried within the PfAldo catalytic pocket. Docking of a TRAP peptide bearing a Trp to Ala mutation rendered the lower energy configurations either bound weakly outside the active site or not bound to PfAldo at all. The position of the bound TRAP peptide, and particularly the close proximity between the carbonyl of its n‐2 Asp residue and the experimentally determined position of the phosphate‐6 group of fructose 1,6‐phosphate bound to mammalian aldolases, predicts an inhibitory effect of TRAP on catalysis. Enzymatic and TRAP‐binding assays using mutant PfAldo molecules strongly support the overall structural model. These results might provide the initial framework for the identification of novel antiparasitic compounds. Proteins 2007. © 2006 Wiley‐Liss, Inc.