Miracle-dz/UniFAR-FTUs huggingface dataset:
A kit formulated under good manufacturing practices for labeling human epidermal growth factor with 111In for radiotherapeutic applications.

UNLABELLED Our goal was to design and manufacture a kit under good manufacturing practices (GMP) for the preparation of (111)In-DTPA-hEGF Injection, a novel targeted radiotherapeutic agent for advanced epidermal growth factor receptor (EGFR)-positive breast cancer. METHODS Human EGF (hEGF) was derivatized with diethylenetriaminepentaacetic acid (DTPA) and then purified by size-exclusion chromatography and ultrafiltration. Kits were prepared by dispensing 0.25 mg (1 mL) of DTPA-hEGF in 1 mol/L sodium acetate buffer [pH 6.0] into single-dose glass vials. Raw materials were pharmacopoieal or reagent grade according to the American Chemical Society and were tested for identity and purity. Kits were tested for protein concentration, purity and homogeneity (sodium dodecyl sulfate polyacrylamide gel electrophoresis and size-exclusion high-performance liquid chromatography), pH, clarity and color, volume, DTPA substitution, labeling efficiency, receptor binding to MDA-MB-468 human breast cancer cells, and sterility and apyrogenicity. (111)In-DTPA-hEGF Injection was tested for pH, radionuclidic and radiochemical purity, clarity and color, and sterility and apyrogenicity. RESULTS Four lots of kits and 8 lots of (111)In-DTPA-hEGF Injection passed all quality specifications. The labeling efficiency was 94%-99% with 115-773 MBq (111)In chloride added to a single kit. (111)In-DTPA-hEGF exhibited preserved receptor binding against MDA-MB-468 cells (affinity constant [K(a)], 0.9-1.1 x 10(7) L/mol; maximum number of binding sites per cell [B(max)], 1.1-2.2 x 10(6) sites per cell). In addition, labeling of aliquots of the kit suggested that a single vial could be labeled with up to 3,083 MBq (111)In while maintaining a radiochemical purity of >90%. Kits were stable for >90 d and (111)In-DTPA-hEGF Injection was stable for >24 h stored at 4 degrees C. CONCLUSION The kit formulation is suitable for preparing (111)In-DTPA-hEGF Injection for a phase I clinical trial in patients with advanced EGFR-positive breast cancer. Establishment of the GMP processes for (111)In-DTPA-hEGF Injection provides a useful example of manufacturing biotechnology-based investigational radiopharmaceuticals in an academic environment for early phase I clinical trials.
DNA bar coding and pyrosequencing to analyze adverse events in therapeutic gene transfer

Gene transfer has been used to correct inherited immunodeficiencies, but in several patients integration of therapeutic retroviral vectors activated proto-oncogenes and caused leukemia. Here, we describe improved methods for characterizing integration site populations from gene transfer studies using DNA bar coding and pyrosequencing. We characterized 160 232 integration site sequences in 28 tissue samples from eight mice, where Rag1 or Artemis deficiencies were corrected by introducing the missing gene with gamma-retroviral or lentiviral vectors. The integration sites were characterized for their genomic distributions, including proximity to proto-oncogenes. Several mice harbored abnormal lymphoproliferations following therapy—in these cases, comparison of the location and frequency of isolation of integration sites across multiple tissues helped clarify the contribution of specific proviruses to the adverse events. We also took advantage of the large number of pyrosequencing reads to show that recovery of integration sites can be highly biased by the use of restriction enzyme cleavage of genomic DNA, which is a limitation in all widely used methods, but describe improved approaches that take advantage of the power of pyrosequencing to overcome this problem. The methods described here should allow integration site populations from human gene therapy to be deeply characterized with spatial and temporal resolution.
Reform said or done? The case of Emilia-Romagna within the Italian psychiatric context.

OBJECTIVE The authors sought to evaluate how the services required by the Italian Psychiatric Reform of 1978 were implemented in Emilia-Romagna, a region of 4 million inhabitants in Northern Italy. METHOD All psychiatric facilities were monitored from 1978 to 1994 to determine the number and rates of admissions, average duration of stay, average intake, and percent of beds occupied at inpatient facilities as well as the number of patients residing in former mental hospitals and the number and rates of first contacts with mental health community centers. RESULTS Three mental hospitals out of nine were closed during the period, and the number of patients who resided in mental hospitals declined from 4,798 to 655. By 1994, there were 145 community centers, 48 day treatment centers, 12 general hospital psychiatric wards, three university psychiatric clinics, seven private psychiatric clinics, 24 psychiatric residences, and 123 supervised apartments that were operating as alternatives to asylums. The overall rate of inpatient admissions remained stable, but compulsory admissions gradually decreased by 35% throughout the period. First contacts at outpatient centers increased by 17.9% from 1984 to 1991. CONCLUSIONS The shift from a hospital-based to a community-based psychiatric system of care, as foreseen by the Italian psychiatric reform, seems feasible. Some general political, administrative, and social backup conditions appear crucial to ensure the good outcome of this process.
Effect of Interferon and Interferon Inducers on Infections with a Nonviral Intracellular Microorganism, Chlamydia trachomatis

The effect of mouse interferon (IF) on the multiplication of Chlamydia trachomatis (strain MRC-1/G) in homologous (L-929) cell cultures and the effect of the IF inducers Newcastle disease virus (NDV) and polyriboinosinic acid-polyribocytidylic acid complex (poly I:C) on the experimental infection of mice with aerosolized C. trachomatis (strain MoPn) were investigated. Treatment of infected cell cultures with IF reduced the number of cells containing chlamydial inclusions and depressed the yield of chlamydiae as determined by titrations for infectivity. Growth of chlamydiae was reduced when cultures were exposed to IF 6 or 18 hr before infection, and slight reduction of the yield was also detectable in cell cultures treated with IF at early intervals (0 or 4 hr) after chlamydial infection. No effect of IF on penetration of chlamydiae into mouse cells was observed, whether phagocytic cells from peritoneal washings or L-929 cells were used, indicating that the inhibitory effect of IF occurs after chlamydiae enter the host cell. Additional evidence was obtained that a significant effect of IF occurs at an early stage in maturation of the intracellular chlamydiae. In mice exposed repeatedly to NDV aerosols and challenged with aerosolized MoPn 8 hr after the first exposure to NDV, mortality was delayed by 2 to 3 days and lung consolidation was slightly reduced at 3 days after infection. Yields of chlamydiae from lung pools of NDV-treated mice, taken at 3, 6, and 9 days after challenge, were not significantly different from those of controls. Similar results were obtained when mice were challenged with MoPn 8 hr after intranasal injection with 100 μg of poly I:C or 24 hr after intravenous injection with 200 μg of poly I:C. In contrast, administration of 0.2 ml of NDV (108.3 plaque-forming units) intravenously 10 hr before or 24 hr after challenge with MoPn accelerated mortality of mice by 2 to 3 days. In all experiments, detectable levels of IF in sera or 20% lung suspensions were found only up to 48 to 72 hr after exposure of mice to IF inducers.
Stent length is a contributing factor of suboptimal stent expansion in drug-eluting stents.

BACKGROUND Failure to achieve optimal stent expansion poses a risk of treatment failure in percutaneous coronary intervention (PCI). Although intravascular ultrasound provides useful information for suboptimal stent expansion, a substantial portion of PCIs are currently being performed under angiographic guidance only. AIM In order to evaluate the adequacy of stent expansion of four widely used drug-eluting stents in angiography-guided PCI, we performed a retrospective analysis of lesions undergoing PCI using quantitative coronary angiography. METHODS A total of 112 de novo lesions were analysed. Minimal lumen diameter (MLD) was measured at peak pressure during stent deployment (MLD1), after stent deployment (MLD2), and after postdilatation (MLD3). Stent underexpansion, stent elastic recoil, and stent deficit were calculated. Optimal stent deployment was defined as final MLD ≥ 90% of predicted diameter. RESULTS For deploying a stent balloon, higher than nominal pressure was used in 83% of cases (93/112). However, optimal deployment was observed in only 32% (36/112). Adjuvant post-dilatation was performed in 59% (45/76) of lesions with suboptimal expansion, which increased the optimal deployment rate by 60% (27/45). Final optimal stent deployment rate was achieved in 56% (63/112). We found that the MLD1 (p = 0.04), MLD3 (p = 0.02), final MLD (p = 0.04), and optimal stent deployment rate (p = 0.036) were significantly reduced in longer stent deployment lesions (≥ 20 mm) compared to shorter lesions (< 20 mm). CONCLUSIONS Stent length may be a contributing factor of suboptimal stent expansion in angiography-guided PCI.
Smoking, low formal level of education, alcohol consumption, and the risk of rheumatoid arthritis

Objective: Suggested predictors of rheumatoid arthritis (RA) include environmental exposure, such as smoking. Our purpose was to investigate potential predictors of RA in a nested case–control study based on a prospective cohort. Method: Between 1991 and 1996, 30 447 persons were included in the Malmö Diet and Cancer Study (MDCS). Individuals who developed RA after inclusion up to 31 December 2004 were identified by linking the database to different registers. Four controls were selected for every case. Data on lifestyle factors were collected in the MDCS. Results: We identified 172 incident cases of RA [36 men/136 women, mean age at diagnosis 63 years, 69% rheumatoid factor (RF) positive, median time from inclusion to diagnosis 5 (range 1–13) years]. In bivariate analyses, baseline smoking [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.31–3.12] and a low level of formal education (i.e. ≤ 8 years; OR 2.42, 95% CI 1.18–4.93 vs. University degree) predicted subsequent development of RA. Infrequent baseline alcohol consumption was a predictor of RA (OR 3.47, 95% CI 1.91–6.30) compared to recent use (within the past month), and individuals with moderate baseline alcohol consumption (3.5–15.2 g/day vs. < 3.5 g/day) tended to have a reduced risk of RA (OR 0.48, 95% CI 0.22–1.05) in multivariate analyses, adjusted for smoking and level of education. Conclusions: Smoking and a low level of formal education were found to be independent predictors of RA. Moderate alcohol consumption may also be associated with a reduced risk.
Pain-determined dissociation episodes.

OBJECTIVES Dissociation disorders are a group of conditions characterized by a disruption of integrated function of consciousness, memory, or perception. The purpose of this report is to describe the impact of increased pain levels on the genesis of two types of dissociation disorders, dissociative fugue ( DF) and dissociative identity disorder ( DID), in patients with chronic pain ( PWCP). DESIGN/PATIENTS/INTERVENTIONS/OUTCOME MEASURES: From November 1992 to July 2000, 2 DID and 4 DF patients were identified from 2,544 consecutive PWCP evaluated and/or treated at the University of Miami Comprehensive Pain and Rehabilitation Center. The salient features of these six dissociation PWCP are presented. All four DF PWCP completed a dissociation experience scale first at the time of identification of the dissociation disorder (with chronic pain) and one alleging their experiences with dissociation predevelopment of chronic pain. RESULTS Frequency percentage for dissociation for this population was 0.235%. For all four of the DF PWCP, dissociation episodes began after the onset of chronic pain. All six (100%) PWCP described or associated their episodes of dissociation to times when their pain would increase. Mean dissociation scale scores for the four DF PWCP were 1.4 +/- 1.11 pre-chronic pain and 20.53 +/- 16.82 at time of identification of the dissociative disorder (with chronic pain). CONCLUSIONS The frequency percentage for dissociation within PWCP is small compared with psychiatric populations. There may be an etiological association between the development of dissociation episodes and the development of chronic pain and/or increases in chronic pain.
Decision Making after Traumatic Brain Injury: A Temporal Discounting Paradigm

Abstract A temporal discounting paradigm was used to examine decision making for hypothetical monetary reward following traumatic brain injury (TBI). A case-control design compared individuals following moderate or severe TBI with a healthy control group matched for age and gender. The impact of intelligence, impulsivity, and mood on temporal discounting performance was examined. A within-subjects design for the TBI group determined the influence of a range of neuropsychological tests on temporal discounting performance. Both patients and controls demonstrated temporal discounting. However, the TBI group discounted more than controls, suggesting that their decision making was more impulsive, consistent with ratings on the impulsiveness questionnaire. Discounting performance was independent of neuropsychological measures of intelligence, memory, and executive function. There was no relationship between temporal discounting and ratings of everyday executive function made by patients' relatives. Low mood did not account for discounting performance. The results of this study suggest that temporal discounting may be a useful neuropsychological paradigm to assess decision making linked to monetary reward following TBI. Performance was relatively independent of intelligence, memory and standard tests of executive ability and may therefore assist when assessing a patient's mental capacity to manage their financial affairs. (JINS, 2013, 19, 1–8)
Striatal dopamine D2/D3 receptor availability correlates with individual response characteristics to pain

We studied in healthy humans the contribution of cerebral dopamine D2/D3 receptors to individual differences in response characteristics to painful stimulation. Positron emission tomography was used to measure the dopamine D2/D3 binding potential (D2/D3 BP) with [11C]raclopride in the striatum (n = 8) and with [11C]FLB 457 in the extrastriatal regions (n = 11). Sensitivity to cutaneous heat pain was assessed by a traditional threshold method and by an analysis based on the signal detection theory which allows the separation of an individual subject's discriminative capacity from the response criterion, i.e. the area under the receiver operating characteristic curve provides a measure of the sensory discriminability (sensory factor) and the response criterion gives an estimate of the subject's response bias or attitude (nonsensory factor). The pain threshold and response criterion were inversely correlated with the D2/D3 BP in the right putamen, whereas the discriminative capacity was not significantly correlated with the D2/D3 BP in any brain region. The correlation of the D2/D3 BP in the putamen with the pain threshold and the subject's response criterion may rather be explained by a dopaminergic effect on nonsensory factors determining the subject's attitude towards pain than by a dopaminergic effect on the subject's discriminative capacity. Alternatively, striatal dopamine D2/D3 receptors could control a modulatory pathway producing a parallel shift in the stimulus–response function for sensory signals, mimicking a change in the subject's response criterion.
The Metropolitan Atlanta Congenital Defects Program: 35 years of birth defects surveillance at the Centers for Disease Control and Prevention.

BACKGROUND The Metropolitan Atlanta Congenital Defects Program (MACDP) is a population-based birth defects surveillance program administered by the Centers for Disease Control and Prevention (CDC) that has been collecting, analyzing, and interpreting birth defects surveillance data since 1967. This paper presents an overview of MACDP current methods and accomplishments over the past 35 years. METHODS MACDP actively monitors major birth defects among infants born to residents of five counties of metropolitan Atlanta, an area with approximately 50,000 annual births. Cases are ascertained from multiple sources, coded using a modified British Pediatric Association six-digit code, and reviewed and classified by clinical geneticists. RESULTS MACDP has monitored trends in birth defects rates and has served as a case registry for descriptive, risk factor, and prognostic studies of birth defects, including studies of Agent Orange exposure among Vietnam War veterans, maternal use of multivitamins, diabetes, febrile illnesses, and survival of children with neural tube defects. MACDP has served as a data source for one of the centers participating in the National Birth Defects Prevention Study, and for developing and evaluating neural tube defects prevention strategies related to the periconceptional use of folic acid supplements. CONCLUSIONS Since its inception, MACDP has served as a resource for the development of uniform methods and approaches to birth defect surveillance across the United States and in many other countries, monitoring birth defects rates, and as a case registry for various descriptive, etiologic, and survival studies of birth defects. MACDP has also served as a training ground for a large number of professionals active in birth defects epidemiology.
Effects of energy density and protein source on diet digestibility and performance of calves after arrival at the feedlot.

Sixty Angus crossbred steers (initial BW, 237 kg) were used in a 2 x 2 factorial experiment to determine the effects of energy density and protein source in receiving diets on steers performance and total tract nutrient digestion. The factors compared were energy density (1.80 vs 1.48 Mcal/kg of NEm, referred to as high-energy and low-energy, respectively) and protein source (ring-dried blood meal [BM] vs soybean meal [SBM]). Diets containing BM resulted in a 10.6% greater (P < .09) ADG and a 7.6% improvement (P < .05) in efficiency of feed utilization compared with those containing SBM. High-energy diets resulted in an 8.7% improvement (P < .05) in feed efficiency vs low-energy diets. Dry matter digestibility (DMD), NDF digestibility (NDFD), and CP digestibility (CPD) were exceptionally high during wk 1, when DMI was approximately 1.5 kg/d. Nutrient digestibility declined during wk 2 and 3, as intake increased, before stabilizing between wk 4 and 6. Additionally, NDFD was not consistently lower (P > .10) during this study for high-energy diets than for low-energy diets. The results of the overall performance data indicate that, compared to SBM, feeding BM may improve ADG and feed efficiency during the receiving period when dietary CP is approximately 13%. Additionally, DMD, NDFD, and CPD were higher on d 7 than at any other time, indicating that by d 7 ruminal function was not adversely affected. Therefore, it seems that the reduced feed intake and growth rate normally seen during the first 2 wk in the feedlot is not caused by a reduction in diet digestibility.
Fixed implant-supported prostheses in elderly patients: a 5-year retrospective comparison between partially and completely edentulous patients aged 80 years or older at implant surgery.

BACKGROUND Knowledge on implant treatment in the partially edentulous patient is low for elderly patients aged 80 years or older at inclusion. PURPOSE The objective of this study was to report and compare the clinical and radiological performance of implant treatment in edentulous and partially edentulous elderly patients during 5 years in function. MATERIAL AND METHODS Altogether, 192 edentulous (control) and 72 partially edentulous (study) patients, consecutively treated and provided with 1,091 and 265 Brånemark implants, respectively, were included during a period between January 1986 and December 2003, and followed-up for 5 years. Clinical information was retrospectively retrieved from patient files and intraoral radiographs were analyzed for examinations at prosthesis placement and after 1 and 5 years in function. RESULTS Altogether, 92 (48%) control and 24 (33%) study patients were lost to follow-up during the 5-year period. In total, 13 (4.9%) and 26 (2.4%) implants were in the study and control groups, respectively, were lost during follow-up, resulting in a comparable 5-year implant cumulative survival rate ranging from 93.9% to 99.3% for upper and lower jaws for study and control groups, respectively. Comparable mean marginal bone loss during 5 years, ranging from 0.4 mm to 0.6 mm, was also observed in the groups. The most common complications for patients in both study and control group were soft tissue inflammation (mucositis). Patients included in the first years of the inclusion (1986-1991) period showed comparable results as patient included at the last part of the inclusion period (1998-2003). CONCLUSIONS Implant treatment in the partially edentulous elderly patients showed comparable clinical and radiographic results as elderly patients treated in the edentulous jaw.
Mosquito larvicidal and pupicidal activity of seaweed extracts against Aedes aegypti , Anopheles stephensi and Culex quinquefasciatus

Mosquito problem has become acute in recent years and many programmes have been launched to control these vectors. The use of biologically active plant materials with antilarval properties has attracted considerable interest of scientists all over the world. In this background, this study was undertaken to investigate the larvicidal and pupicidal potential of the seaweeds of Turbinaria conoides against the mosquito species Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. By using three different solvent seaweed extracts (aqueous, acetone and ethanol), LC50 and LC90 values were found out and the pupae mortality was also analyzed. The results showed that the aqueous extract of seaweed exhibited high degree of blocking the development by induction of great mortality of larvae and pupae. These findings may help in developing a prospective alternative source to control the mosquitoes
Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.