Miracle-dz/UniFAR-FTUs huggingface dataset:
In pursuit of a moving target: nanotherapeutics for the treatment of non-Hodgkin B-cell lymphoma

Introduction: Non-Hodgkin lymphoma (NHL) is diagnosed in 70,000 Americans annually. Chemotherapy was the standard course of treatment until the addition of the monoclonal antibody (mAb) drug, rituximab, to therapy regimens in 1997. Although disease prognosis has improved dramatically since that time, nearly 20,000 patients succumb annually to the disease, with an average life expectancy beyond diagnosis of only 12 years. The advent of nanomedicine may fulfill the remaining need for novel therapy capable of eradicating solid tumor and disseminated B-cell lymphomas. Areas covered: This review details the current landscape of B-cell NHL and nanoparticles now being developed for its treatment. Specifically, we discuss lipid, polymer and metal nanoparticles that deliver an array of drugs, including toxins, chemotherapeutic agents and nucleic acids. Expert opinion: Because B-cell malignancies have responded quite well to new components in multi-drug regimens, nanomedicines that are mechanistically distinct from existing therapies hold significant promise. In our opinion, advancement of these technologies into the clinic will likely require significantly more effective targeting systems coupled with a better understanding of lymphoma biology. Furthermore, it is important for researchers to recognize the genetic and phenotypic heterogeneity of NHL and to develop therapeutic strategies for distinct subsets of NHL before attempting to generalize approaches.
Organizing Business Leaders To Impact the Democratic Policy-Making Process.

This paper presents findings of a study that examined the formation and development of a coalition of business leaders and its impact on state education policy. The coalition, called the Corporations for the Improvement of Educational Quality (CIEQ) , was developed in a large midwestern state. The paper uses and assesses the efficacy of five interest group theories: Truman's (1951) order and disturbance theory, Olson's (1965) byproduct theory; Salisbury's (1969) exchange theory; Sabatier's (1992) commitment theory; and MacFarland's (1987, 1992) countervailing power theory. The study asked the following research questions: (1) How and why has this group of business leaders joined together to form CIEQ? (2) How did CIEQ select and get its agenda? (3) How has CIEQ maintaihed and supplemented its members'aip and agenda? and (4) Who has benefitted from the efforts of CIEQ and what benefits did they receive? Data were obtained through participant observation, document analysis, and interviews with 28 key members, 8 state legislators, and 12 other individuals involved in state education policy. The study found limited support for each of the five theories, but found particularly strong support for order and disturbance, commitment, and countervailing power theories. Individuals joined, set their agenda, and maintained their membership through a combination of interests and needs. Such actions are contingent upon a number of issues--the presence of a significant societal disturbance, a strong personal interest in a specific issues, and participants' recognition that their voices are absent from the current debate. One table is included. (Contains 25 references.) (LMI) Reproductions supplied by EDRS are the best that can be made from the original document. ***********************************************************************
Multimodal imaging evidence of pathology-mediated disease distribution in corticobasal syndrome

Objective: To use multimodal neuroimaging to evaluate the influence of heterogeneous underlying pathology in corticobasal syndrome (CBS) on the neuroanatomical distribution of disease. Methods: We performed a retrospective evaluation of 35 patients with CBS with T1-weighted MRI, diffusion tensor imaging, and neuropathologic, genetic, or CSF evidence of underlying pathology. Patients were assigned to 2 groups: those with evidence of Alzheimer pathology (CBS-AD) and those without Alzheimer pathology (CBS–non-AD). Group comparisons of CBS-AD and CBS–non-AD assessed clinical features, gray matter (GM) cortical thickness, and white matter (WM) fractional anisotropy. Results: CBS-AD was found in 34% (n = 12) and CBS–non-AD in 66% (n = 23) of CBS patients. Clinical evaluations revealed that CBS–non-AD had a higher frequency of asymmetric rigidity compared to CBS-AD, but groups otherwise did not differ in dementia severity, impairments in cognition, or rates of extrapyramidal symptoms. We found frontoparietal GM and WM disease in each group compared to healthy, demographically comparable controls, as well as multimodal neuroimaging evidence of a double dissociation: CBS–non-AD had WM disease in the corpus callosum, corticospinal tract, and superior longitudinal fasciculus relative to CBS-AD, and CBS-AD had reduced temporoparietal GM relative to CBS–non-AD, including the precuneus and posterior cingulate. Conclusions: Patients with CBS have a pathology-mediated dissociation of GM and WM disease. Multimodality neuroimaging may be useful for improving in vivo pathologic diagnosis of CBS.
Extensive white matter abnormalities and clinical symptoms in drug-naive patients with first-episode schizophrenia: a voxel-based diffusion tensor imaging study.

BACKGROUND Increasing evidence shows that disruption of connectivity has been implicated as a central abnormality in schizophrenia, and the alterations in white matter may be the core basis for this disconnection. Diffusion tensor imaging (DTI) has shown white matter abnormalities in first-episode schizophrenia. However, few studies have examined the correlation between clinical symptoms and white matter abnormalities in drug-naive patients with first-episode schizophrenia. METHOD The white matter fractional anisotropy (FA) values of the whole-brain were determined by using voxel-based DTI in 39 drug-naive patients with first-episode schizophrenia (diagnosed according to DSM-IV) and 30 healthy controls matched for age and gender. The psychopathology of schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). The study was conducted from April 2009 to March 2010. RESULTS The patients showed widespread FA reduction in several brain regions, including corpus callosum, brainstem, internal capsule, cingulate, and cerebellum in patients with first-episode schizophrenia when compared to healthy controls (all P values < .01 after adjusting for gender, age, and education). The correlation analysis showed a significant negative correlation between the FA value in the left cerebellum and positive symptoms (r38 = -0.32, P < .05) and a significant positive correlation between the FA values in the corpus callosum and both the PANSS general psychopathology subscore (r38 = 0.39, P < .01) and the PANSS total score (r38 = 0.33, P < .05). CONCLUSIONS Our results indicate that widespread disruption of white matter integrity occurs in an early stage of schizophrenic onset, suggesting an important role in pathogenesis and symptomatology of schizophrenia.
Nutrient Risk Assessment: Setting Upper Levels and an Opportunity for Harmonization

Upper levels are estimates of the quantity of a nutrient that can be ingested daily over a lifetime without appreciable risk to health. The approach to establishing upper levels for nutrients, nutrient risk assessment, has derived from the risk assessment of foreign chemicals that are deliberately added to foods, or are in food as contaminants. This process of risk assessment is rigorous and transparent, particularly in dealing with the uncertainty arising from the data available and their assessment and extrapolation to human populations. Hazard identification and characterization, i.e., a dose—response pattern, as applied to xenobiotics, are discussed first, and then the difficulties of applying this approach to nutrients are reviewed. Nutrients, in contrast to foreign chemicals, have specific and selective metabolic pathways and homeostasis, as well as specific functions. This is the source of differences in the nutrient risk assessments produced by various national and international advisory bodies. Although the same data are used in such exercises, different judgments are made about identifying adverse effects, the nature of uncertainties in the assessment, and in matching the upper levels with exposure assessments and dietary reference values. The establishment of different upper levels for different national and international communities is a source of confusion in public health policy and practice and a barrier to trade. It is proposed that a basis for harmonizing the existing approaches used in nutrient risk assessment would be the collaborative development of the model for establishing upper levels of intake for nutrients and related substances that has been recently described by a Joint Task Force of the World Health Organization and the Food and Agriculture Organization.
Adjunctive clinical effect of a water-cooled Nd:YAG laser in a periodontal maintenance care programme: a randomized controlled trial.

BACKGROUND Various laser systems are currently available for intra-oral use. Neodymium:Yttrium-Aluminium Garnet lasers(Nd:YAG) have been approved by the US Food and Drug Administration for soft tissue treatment in the oral cavity. OBJECTIVES The aim of this study was to test whether the use of a water-cooled Nd:YAG laser during a maintenance care programme as an adjunct to supragingival and subgingival debridement (scaling and root planing, SRP) with hand and ultrasonic instruments results in clinical improvement compared with SRP alone. MATERIAL AND METHODS This study was an examiner-blind, randomized and controlled clinical trial using a split-mouth design. Thirty subjects were selected, originally diagnosed with moderate to severe generalized periodontitis, following a periodontal maintenance care programme (PMC). Immediately after SRP in two randomly assigned contra-lateral quadrants, all pockets ≥5 mm were additionally treated with a Nd:YAG laser (1064 nm, 4W, 250-μsec pulse). Clinical assessments [probing pocket depth PPD, bleeding on pocket probing (BOPP)] were performed pre-treatment and at 6 months. Based on these assessments, the periodontal inflamed surface area (PISA) was calculated. RESULTS At 6 months, the clinical parameters had significantly improved for both regimens. No statistically significant differences between treatment modalities were observed for PPD and BOPP scores at any time. PISA scores supported these findings. CONCLUSIONS In residual pockets ≥5 mm, treated in a PMC, the adjunctive use of an Nd:YAG laser does not provide a clinically significant additional advantage.
Clinical features and prognostic factors of ten patients with renal failure caused by IgG4-related retroperitoneal fibrosis

IgG4-related retroperitoneal fibrosis (IgG4-RPF) is a newly recognized entity which often mimics cancer. We aimed to investigate the clinical features and the causes of renal failure, as well as to explore the factors affecting the prognosis of renal function by analysis of the clinical data of patients with IgG4-RPF. We reviewed clinical features of 10 patients with renal failure caused by IgG4-RPF, which was confirmed by pathology review and clinic-pathologic correlations. All patients were male, and the mean age at onset was 64.2 ± 10.0 years. Five patients were revealed with acute renal failure (ARF), while the other five ones with ARF on chronic kidney disease (CKD) (A on C) at diagnosis. Initial favorable responses obtained in 90% of the patients who underwent steroid therapy. The serum creatinine (SCr) level returned to normal in six patients including five with ARF and one with A on C, while those of the rest four patients with A on C restored to baseline levels (GFR remained below 60 ml/min/1.73 m2 however) after therapy. These four unrecovered patients had a history of CKD, a longer period of persistently elevated SCr, a thinner total renal parenchyma thickness, and continuous elevated serum IgG4 levels after steroid therapy, compared with those recovered patients (P < 0.05). We concluded that recovery and long-term prognosis of the disease were primarily associated with timely diagnosis and proper treatment.
Physical fitness, respiratory symptoms and lung function.

Lung volumes (FVC1, FEV1.0 and peak flow) were measured in 403 men and 561 women volunteers for fitness testing, using the SRL automated spirometer system. Average scores for this population were 5--10% higher than predicted from age, height and sex using either the formulae inherent in the SRL computer or standards proposed by Anderson et al. [1968] for the Toronto population; existing standards may thus underestimate respiratory potential. Lung function data showed a dose-dependent decrease within the category of cigarette smokers, but there was no significant difference between average results for smokers and non-smokers. Multivariate analysis showed significant contributions of lean mass and obesity to the overall description of lung volumes; however, effects were not large enough to justify incorporation of such variables into routine prediction equations. Positive responses to the respiratory section of the Cornell Medical Index were in several instances associated with below expected lung volumes. The most consistent response was to the question 'do you suffer from asthma? ' Although the average effect was significant, the magnitude of response (10--20%) would have been overlooked in individual testing; this suggests that there may be more scope for pulmonary screening through the improvement of questionnaires than through the purchase of expensive electronic spirometers.
Maturity choice of private mortgage borrowers

This paper asks what factors influence the maturity choice of private mortgage borrowers and if the choice is rational. Using a unique data set from the German market with more than 50,000 financed projects, we find a significant influence of personal and macroeconomic factors. A high income, a low loan value, and a low value to income ratio lead to short maturities; so do economically good times with high GDP growth and low unemployment. In addition, we show that the importance of pricing variables is age dependent and declining for older borrowers. Moreover, we demonstrate that borrowers behave irrational and not according to the recommendations of models on optimal mortgage choice when choosing the maturity of their mortgage.
Prediagnostic Intake of Dairy Products and Dietary Calcium and Colorectal Cancer Survival—Results from the EPIC Cohort Study

Background: We investigated whether prediagnostic reported intake of dairy products and dietary calcium is associated with colorectal cancer survival. Methods: Data from 3,859 subjects with colorectal cancer (42.1% male; mean age at diagnosis, 64.2 ± 8.1 years) in the European Investigation into Cancer and Nutrition cohort were analyzed. Intake of dairy products and dietary calcium was assessed at baseline (1992–2000) using validated, country-specific dietary questionnaires. Multivariable Cox regression models were used to calculate HR and corresponding 95% confidence intervals (CI) for colorectal cancer–specific death (n = 1,028) and all-cause death (n = 1,525) for different quartiles of intake. Results: The consumption of total dairy products was not statistically significantly associated with risk of colorectal cancer–specific death (adjusted HR Q4 vs. Q1, 1.17; 95% CI, 0.97–1.43) nor that of all-cause death (Q4 vs. Q1, 1.16; 95% CI, 0.98–1.36). Multivariable-adjusted HRs for colorectal cancer–specific death (Q4 vs. Q1) were 1.21 (95% CI, 0.99–1.48) for milk, 1.09 (95% CI, 0.88–1.34) for yoghurt, and 0.93 (95% CI, 0.76–1.14) for cheese. The intake of dietary calcium was not associated with the risk of colorectal cancer–specific death (adjusted HR Q4 vs. Q1, 1.01; 95% CI, 0.81–1.26) nor that of all-cause death (Q4 vs. Q1, 1.01; 95% CI, 0.84–1.21). Conclusions: The prediagnostic reported intake of dairy products and dietary calcium is not associated with disease-specific or all-cause risk of death in patients diagnosed with colorectal cancer. Impact: The impact of diet on cancer survival is largely unknown. This study shows that despite its inverse association with colorectal cancer risk, the prediagnostic intake of dairy and dietary calcium does not affect colorectal cancer survival. Cancer Epidemiol Biomarkers Prev; 23(9); 1813–23. ©2014 AACR.
Effect of selenium and vitamin E content of the maternal diet on the antioxidant system of the yolk and the developing chick

1. The effects of selenium and vitamin E supplementation of the maternal diet on their transfer to the egg yolk and tissues of the newly hatched chick and on the development of the antioxidant system in the chick liver in early postnatal life were investigated. 2. One hundred Cobb broiler breeder hens were divided into 10 equal groups and housed in pens at 25 weeks of age. Each hen received 1 of the treatment diets which included 0.2 or 0.4 mg/kg selenium, 40, 100, 200 mg/kg vitamin E or their combination. After 6 weeks, the hens were artificially inseminated once per week. From week 8, eggs were collected and placed in an incubator. After hatching, chicks from each group were reared (under standard commercial conditions) to 10 d of age. The chicks were fed on a standard starter commercial broiler diet. At the time of hatching, and at 5 and 10 days old, 4 chicks from each group were sacrificed and blood, liver and brain were collected for the subsequent biochemical analyses. 3. The inclusion of organic selenium or vitamin E in the commercial diet significantly increased their concentration in the egg and in the liver of 1-d-old chicks obtained from the eggs enriched with these substances. A positive effect of such dietary supplementation was seen at d 5 and d 10 of postnatal development. 4. There was a positive effect of selenium supplementation of the maternal diet on glutathione concentration in the liver of 1-d-old and 5-d-old chicks. A combination of a dietary selenium supplementation with high vitamin E doses further increased glutathione concentration in the liver. Dietary selenium supplementation significantly increased selenium-dependent glutathione peroxidase (Se-GSH-Px) activity in the liver of the 1-d-old and 5-d-old chicks and decreased liver susceptibility to peroxidation. 6. It is concluded that the nutritional status of the laying hen determines the efficiency of the antioxidant system throughout embryonic and early postnatal development of the offspring.
Epidemiology of infection due to Escherichia coli O157: a 3-year prospective study

SUMMARY A 3-year study of Escherichia coli infections in Grampian Region was conducted to ascertain the incidence, document clinical sequelae and identify at-risk groups. Approximately 30000 stools from patients with acute diarrhoea were screened for E. coli O157, and an epidemiological questionnaire filled in for each patient whose stool was positive. Eighty-three patients were studied. The annual incidence was 6 per 100000. Proportionately more infections occurred in people involved in agriculture. Evidence was seen of case-to-case transmission, and contamination of a water supply. Eight cases developed haemolytic uraemic syndrome (HUS). There were 2 deaths due to HUS and 2 due to haemorrhagic colitis (HC). Symptomatic E. coli infection is relatively common in the Grampian Region, more common in the agricultural community, and is the main cause of HUS in this Region.
Use of Viral Load Measured After 4 Weeks of Highly Active Antiretroviral Therapy to Predict Virologic Outcome at 24 Weeks for HIV-1–Positive Individuals

SummaryEarly prediction of suboptimal viral response to highly active antiretroviral therapy (HAART) is vital to prevent early development of drug resistance. We used logistic regression to predict the odds of achieving virologic suppression (<50 copies/mL) after 24 weeks of HAART in 656 antiretroviral-naive patients starting HAART at the J.W. Goethe University, Chelsea and Westminster, and Royal Free Hospitals according to their week 4 viral load. Therapy changes involving the switch of a single antiretroviral were assumed to have occurred for toxicity reasons and ignored. Because complete regimen changes or additions of new antiretrovirals could be due to virologic failure, patients were counted as virological failures at week 24. Three hundred sixty (84%) of 430 patients with viral loads of <1000 copies/mL, 106 (61%) of 175 with viral loads between 1001 and 10,000 copies/mL, 11 (37%) of 30 with viral loads between 10,001 and 100,000 copies/mL, and 5 (24%) of 21 with viral loads of >100,000 copies/mL at week 4 subsequently attained virologic suppression at 24 weeks. The odds of attaining virologic suppression at 24 weeks was 65% lower for every 1-log higher viral load at week 4 (odds ratio, 0.35; 95% confidence interval, 0.27–0.45). The proportion of patients with an undetectable viral load at 24 weeks among those who have not attained a viral load of <1000 copies/mL by 4 weeks is quite low. We suggest that this group of patients should be particularly closely monitored.
In Vivo Bioluminescent Monitoring of Therapeutic Efficacy and Pharmacodynamic Target Assessment of Antofloxacin against Escherichia coli in a Neutropenic Murine Thigh Infection Model

ABSTRACT Antimicrobial resistance among uropathogens has increased the rates of infection-related morbidity and mortality. Antofloxacin is a novel fluoroquinolone with broad-spectrum antibacterial activity against urinary Gram-negative bacilli, such as Escherichia coli. This study monitored the in vivo efficacy of antofloxacin using bioluminescent imaging and determined pharmacokinetic (PK)/pharmacodynamic (PD) targets against E. coli isolates in a neutropenic murine thigh infection model. The PK properties were determined after subcutaneous administration of antofloxacin at 2.5, 10, 40, and 160 mg/kg of body weight. Following thigh infection, the mice were treated with 2-fold-increasing doses of antofloxacin from 2.5 to 80 mg/kg administered every 12 h. Efficacy was assessed by quantitative determination of the bacterial burdens in thigh homogenates and was compared with the bioluminescent density. Antofloxacin demonstrated both static and killing endpoints in relation to the initial burden against all study strains. The PK/PD index area under the concentration-time curve (AUC)/MIC correlated well with efficacy (R2 = 0.92), and the dose-response relationship was relatively steep, as observed with escalating doses of antofloxacin. The mean free drug AUC/MIC targets necessary to produce net bacterial stasis and 1-log10 and 2-log10 kill for each isolate were 38.7, 66.1, and 147.0 h, respectively. In vivo bioluminescent imaging showed a rapid decrease in the bioluminescent density at free drug AUC/MIC exposures that exceeded the stasis targets. The integration of these PD targets combined with the results of PK studies with humans will be useful in setting optimal dosing regimens for the treatment of urinary tract infections due to E. coli.