Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of 6-18F-Fluoro-l-Dopa PET Uptake with Proliferation and Tumor Grade in Newly Diagnosed and Recurrent Gliomas

6-18F-fluoro-l-dopa (18F-FDOPA) measured with PET as a biomarker of amino acid uptake has been investigated in brain tumor imaging. The aims of the current study were to determine whether the degree of 18F-FDOPA uptake in brain tumors predicted tumor grade and was associated with tumor proliferative activity in newly diagnosed and recurrent gliomas. Methods: Fifty-nine patients (40 men, 19 women; mean age ± SD, 44.4 ± 12.3 y) with newly diagnosed (n = 22) or recurrent (n = 37) gliomas underwent 18F-FDOPA PET perioperatively. Tumor tissue was obtained by resection or biopsy in all patients. The tumor grade and Ki-67 proliferation index were obtained by standard pathology assays. Tumor 18F-FDOPA uptake was quantified by determining various standardized uptake value (SUV) parameters (mean SUV, maximum SUV [SUVmax], mean values of voxels with top 20% SUVs, and tumor–to–normal-brain tissue ratios) that were then correlated with histopathologic grade and Ki-67 proliferation index. Results: Fifty-nine lesions in 59 patients were analyzed. 18F-FDOPA uptake was significantly higher in high-grade than in low-grade tumors for newly diagnosed tumors (SUVmax, 4.22 ± 1.30 vs. 2.34 ± 1.35, P = 0.005) but not for recurrent tumors that had gone through treatment previously (SUVmax, 3.36 ± 1.26 vs. 2.67 ± 1.18, P = 0.22). An SUVmax threshold of 2.72 differentiated low-grade from high-grade tumors, with a sensitivity and specificity of 85% and 89%, respectively, using receiver-operating-characteristic curve analysis (area under the curve, 0.86). 18F-FDOPA PET uptake correlated significantly with Ki-67 tumor proliferation index in newly diagnosed tumors (r = 0.66, P = 0.001) but not in recurrent tumors (r = 0.14, P = 0.41). Conclusion: 18F-FDOPA uptake is significantly higher in high-grade than in low-grade tumors in newly diagnosed but not recurrent tumors that had been treated previously. A significant correlation between 18F-FDOPA uptake and tumor proliferation in newly diagnosed tumors was observed, whereas this correlation was not identified for recurrent tumors. Thus, 18F-FDOPA PET might serve as a noninvasive marker of tumor grading and might provide a useful surrogate of tumor proliferative activity in newly diagnosed gliomas.
Confusing placebo effect with natural history in epilepsy: A big data approach

For unknown reasons, placebos reduce seizures in clinical trials in many patients. It is also unclear why some drugs showing statistical superiority to placebo in one trial may fail to do so in another. Using Seizuretracker.com, a patient‐centered database of 684,825 seizures, we simulated “placebo” and “drug” trials. These simulations were employed to clarify the sources of placebo effects in epilepsy, and to identify methods of diminishing placebo effects. Simulation 1 included 9 trials with a 6‐week baseline and 6‐week test period, starting at time 0, 3, 6…24 months. Here, “placebo” reduced seizures regardless of study start time. Regression‐to‐the‐mean persisted only for 3 to 6 months. Simulation 2 comprised a 6‐week baseline and then 2 years of follow‐up. Seizure frequencies continued to improve throughout follow‐up. Although the group improved, individuals switched from improvement to worsening and back. Simulation 3 involved a placebo‐controlled “drug” trial, to explore methods of placebo response reduction. An efficacious “drug” failed to demonstrate a significant effect compared with “placebo” (p = 0.12), although modifications either in study start time (p = 0.025) or baseline population reduction (p = 0.0028) allowed the drug to achieve a statistically significant effect compared with placebo. In epilepsy clinical trials, some seizure reduction traditionally attributed to placebo effect may reflect the natural course of the disease itself. Understanding these dynamics will allow future investigations into optimal clinical trial design and may lead to identification of more effective therapies. Ann Neurol 2015;78:329–336
Poor compliance with the antibiotic policy in the intensive care unit (ICU) of a tertiary care hospital in India.

INTRODUCTION Most developing countries are adopting antibiotic policies to contain the acute problem of drug resistance; however, several obstacles prevent their fulfillment. This study was undertaken to prospectively determine the compliance with the antibiotic policy in the intensive care unit (ICU) of a tertiary care hospital and possible reasons for non-compliance. METHODOLOGY Compliance with the newly introduced antibiotic policy was studied for a period of six months. A total of 170 cases from the ICU were included. Relevant information regarding patient characteristics, treatment details, infection control, and antibiotic prescribing practices in the ICU with reference to the antibiotic policy was collected. Reasons for non-compliance were studied. RESULTS The rate of compliance with the antibiotic policy was 21.18%. Heavy use of antibiotics prior to the time of admission in the ICU was the major cause of non-compliance. Microbiological investigation had been sent in only 51.17% of the cases and change in treatment protocol based on culture report was done in 53.3%. The rate of use of third-generation cephalosporins was 76.78%. CONCLUSIONS We found non-compliance with the antibiotic policy in the ICU mainly due to improper and inappropriate antibiotic usage in other indoor units of the hospital. In our case, a policy covering the entire hospital is required to meet the goals of antibiotic usage restriction. An effective surveillance, review, and evaluation process should be an integral part of the policy, even in developing countries, to measure the effects of such policies.
Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact of recipient/donor factors, transplant conditions and myelotoxic drugs

Background Secondary cytopenias are serious complications following hematopoietic cell transplantation. Etiologies include myelotoxic agents, viral infections, and possibly transplant-related factors such as the intensity of the conditioning regimen and the source of stem cells. Design and Methods We retrospectively analyzed data from 2162 hematopoietic cell transplant recipients to examine the effect of these factors on overall cytopenias occurring after 28 days in hematopoietic cell transplantation. Results Advanced age of the patient, recipient cytomegalovirus seropositivity, unrelated donor status, human leukocyte antigen mismatch and lower doses of transplanted CD34+ cells (≤ 6.4×106/kg) significantly increased the risk of cytopenias after day 28. Non-myeloablative hematopoietic cell transplantation had protective effects on anemia and thrombocytopenia after day 28 (adjusted odds ratio 0.76, probability value of 0.05 and adjusted odds ratio 0.31, probability value of <0.0001, respectively) but not on overall or ganciclovir-related neutropenia. This lack of protection appeared to be due to the use of mycophenolate mofetil in the majority of recipients of non-myeloablative hematopoietic cell transplants. Peripheral blood stem cells did not confer protection from cytopenias when compared to bone marrow. Conclusions Elderly patients appear to be more prone to cumulative toxicities of post-transplant drug regimens, but non-myeloablative conditioning, optimized human leukocyte antigen matching, and higher doses of CD34+ cell infusions may reduce the risk of cytopenia after day 28.
Tocopherols in the Prevention and Treatment of Atherosclerosis and Related Cardiovascular Disease

Oxidants/antioxidants play an important role in cellular homeostasis. The human body has endogenous molecules that work as antioxidants, such as glutathione, superoxide dismutase, peroxidases, and catalase. Exogenous substances in the diet, such as β‐carotene, ascorbate, and vitamin E, are vital antioxidants. Of these, vitamin E is likely the most important antioxidant in the human diet, and many studies have been performed to elucidate its role in health and disease. Vitamin E is a family of several compounds, of which α‐tocopherol is the most widely known analog. α‐Tocopherol exhibits antioxidative property in vitro and inhibits oxidation of low‐density lipoprotein cholesterol. In addition, α‐tocopherol shows anti‐inflammatory activity and modulates expression of proteins involved in the uptake, transport, and degradation of atherogenic lipids. Though α‐tocopherol exhibits important antioxidant, anti‐inflammatory, and antiatherogenic features in vitro, α‐tocopherol supplements have failed to consistently reduce atherosclerosis‐related events in human trials. The conflicting results have led to reconsideration of the importance previously given to α‐tocopherol and led to interest in other members of vitamin E family, especially γ‐tocopherol, which exerts a much more potent antioxidant, anti‐inflammatory, and cardioprotective effect than α‐tocopherol. This reconsideration has been backed by solid laboratory and clinical research. We suggest that the absence of γ‐tocopherol in traditional preparations may be one reason for the lack of consistent salutary effects of vitamin E preparations in clinical trials. This review summarizes our current understanding of tocopherols as antioxidant molecules and emerging evidence of an important role of γ‐tocopherol in the pathophysiology of atherosclerosis‐related cardiovascular disease.
Apoptosis and increased expression of Fas ligand after uniocular anterior chamber (AC) inoculation of HSV-1

Purpose. To determine if apoptosis occurs in the eyes and brain following uniocular anterior chamber (AC) inoculation of HSV-1 and if expression of Fas ligand (FasL) or Fas is altered by virus infection. Methods. After inoculation of HSV-1 via the AC route, apoptotic cells in the eyes and brain were identified by TUNEL assay, and TUNEL results indicating DNA fragmentation in the brain were confirmed by DNA laddering assays. Expression of FasL and Fas in the eyes and brain was determined by immunohistochemistry and Western blotting and confirmed by RT-PCR, Southern blotting of RT-PCR products, and sequencing. Results. After AC inoculation of HSV-1, HSV-1 positive cells and apoptotic cells were observed in the eyes and brain. Immunofluorescent staining revealed that although both FasL and Fas were expressed in the cornea, retinal pigment epithelium cells (RPE), and photoreceptor cells of normal and virus infected mice, Fas and FasL were expressed at different locations in these cells. On day 8 p.i. , more FasL DNA expression was observed in HSV-infected mice compared with uninfected mice. Conclusions. HSV-1 infection following AC inoculation of virus induced apoptosis in the eyes and brain. Although FasL expression was upregulated by HSV-1 infection, these results suggest there are likely to be factors in addition to FasL and Fas, such as Bcl-2 and caspases, that are involved in apoptosis observed in the eyes and brain of HSV-1- infected mice.
‘Waiting at the dinner table for scraps’: a qualitative study of the help-seeking experiences of heterosexual men living with HIV infection

Objectives To characterise the help-seeking experiences of heterosexual men living with HIV infection and explain these experiences in relation to the broader social relations and discourses in which they are embedded. Design Qualitative study using focus groups and theoretically informed constructionist grounded theory. Setting With one exception, focus groups were conducted in the offices of community-based AIDS service organisations across Ontario, Canada. Participants 40 HIV-infected heterosexual men aged 18 years or older. Results Heterosexual men living with HIV perceive themselves to be relegated to the margins of a health care and service field that was developed historically within a context that privileges the priorities of gay men and heterosexual women living with the virus. Specifically, gay men are better positioned than heterosexual men when vying for the services and recognition of AIDS service organisations due to their social capital within these agencies, thereby benefiting by virtue of their membership with the group perceived to control the decision-making apparatuses when resource allocation and programme development are at stake. Relative to women, heterosexual men are poorly positioned due to their negative symbolic capital, derived from being perceived as the ‘guilty’ parties in the context of heterosexual HIV transmission. As a result, the material and support needs of women have been prioritised, while those of heterosexual men living with HIV remain largely unaddressed. Conclusions Heterosexual men living with HIV are operating within a health and service field that has not kept pace with their increased representation among the population of persons living with the virus. Researchers, clinicians and policy makers should strive to integrate heterosexual men living with HIV in decision making and community-based research initiatives that build capacity among this group while simultaneously generating a research and policy agenda specific to the concerns of this growing demographic.
Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization

Building Better Vaccines In the past few years, several highly potent, broadly neutralizing antibodies (bNAbs) specific for the gp120 envelope protein of HIV-1 have been discovered. The goal of this work is to use this information to inform the design of vaccines that are able to induce such antibodies (see the Perspective by Crowe). However, because of extensive somatic hypermutation, the epitope bound by these antibodies often does not bind to the germline sequence. Jardine et al. (p. 711, published online 28 March; see the cover) used computational analysis and in vitro screening to design an immunogen that could bind to VRC01-class bNAbs and to their germline precursors. Georgiev et al. (p. 751) took advantage of the fact that only four sites on the HIV viral envelope protein seem to bind bNAbs, and sera that contain particular bNAbs show characteristic patterns of neutralization. An algorithm was developed that could successfully delineate the neutralization specificity of antibodies present in polyclonal sera from HIV-infected patients. An algorithm predicts the neutralization specificity of sera from HIV-infected individuals. [Also see Perspective by Crowe] Serum characterization and antibody isolation are transforming our understanding of the humoral immune response to viral infection. Here, we show that epitope specificities of HIV-1–neutralizing antibodies in serum can be elucidated from the serum pattern of neutralization against a diverse panel of HIV-1 isolates. We determined “neutralization fingerprints” for 30 neutralizing antibodies on a panel of 34 diverse HIV-1 strains and showed that similarity in neutralization fingerprint correlated with similarity in epitope. We used these fingerprints to delineate specificities of polyclonal sera from 24 HIV-1–infected donors and a chimeric siman-human immunodeficiency virus–infected macaque. Delineated specificities matched published specificities and were further confirmed by antibody isolation for two sera. Patterns of virus-isolate neutralization can thus afford a detailed epitope-specific understanding of neutralizing-antibody responses to viral infection.
Left ventricular dilatation and the risk of congestive heart failure in people without myocardial infarction.

BACKGROUND Left ventricular dilatation is a well-recognized precursor of ventricular dysfunction and congestive heart failure after myocardial infarction. The effect of left ventricular dilatation on the risk of heart failure in people initially free of myocardial infarction is not known. METHODS We examined the relation of the left ventricular end-diastolic and end-systolic internal dimensions, as measured by M-mode echocardiography, to the risk of congestive heart failure in 4744 subjects (2083 men and 2661 women) who had not sustained a myocardial infarction and who were free of congestive heart failure. We used sex-stratified proportional-hazards regression to assess the association between base-line left ventricular internal dimensions and the subsequent risk of congestive heart failure, after adjusting for age, blood pressure, hypertension treatment, body-mass index, diabetes, valve disease, and interim myocardial infarction. RESULTS Over an 11-year follow-up period, congestive heart failure developed in 74 subjects (38 men and 36 women). The risk-factor-adjusted hazard ratio for congestive heart failure was 1.47 (95 percent confidence interval, 1.25 to 1.73) for an increment of 1 SD in the left ventricular end-diastolic dimension, indexed for height. We obtained similar results using the left ventricular end-systolic dimension (hazard ratio, 1.43; 95 percent confidence interval, 1.24 to 1.65). CONCLUSIONS An increase in left ventricular internal dimension is a risk factor for congestive heart failure in men and women who have not had a myocardial infarction. Knowledge of the left ventricular dimension improves predictions of the risk of congestive heart failure made on the basis of traditional risk factors, perhaps by aiding in the identification of subjects with subclinical left ventricular dysfunction.
The Murine Model for Hantaan Virus-Induced Lethal Disease Shows Two Distinct Paths in Viral Evolutionary Trajectory with and without Ribavirin Treatment

ABSTRACT In vitro, ribavirin acts as a lethal mutagen in Hantaan virus (HTNV)-infected Vero E6 cells, resulting in an increased mutation load and viral population extinction. In this study, we asked whether ribavirin treatment in the lethal, suckling mouse model of HTNV infection would act similarly. The HTNV genomic RNA (vRNA) copy number and infectious virus were measured in lungs of untreated and ribavirin-treated mice. In untreated, HTNV-infected mice, the vRNA copy number increased for 10 days postinfection (dpi) and thereafter remained constant through 26 dpi. Surprisingly, in ribavirin-treated, HTNV-infected mice, vRNA levels were similar to those in untreated mice between 10 and 26 dpi. Infectious virus levels, however, were different: in ribavirin-treated mice, the amount of infectious HTNV was significantly decreased relative to that in untreated mice, suggesting that ribavirin reduced the specific infectivity of the virus (amount of infectious virus produced per vRNA copy). Mutational analysis revealed a ribavirin-associated elevation in mutation frequency in HTNV vRNA similar to that previously reported in vitro. Codon-based analyses of rates of nonsynonymous (dN) and synonymous (dS) substitutions in the S segment revealed a positive selection for codons within the HTNV N protein gene in the ribavirin-treated vRNA population. In contrast, the vRNA population in untreated, HTNV-infected mice showed a lower level of diversity, reflecting purifying selection for the wild-type genome. In summary, these experiments show two different evolutionary paths that Hantavirus may take during infection in a lethal murine model of disease, as well as the importance of the in vivo host environment in the evolution of the virus, which was not apparent in our prior in vitro model system.
Chronic Alcoholism Increases the Induction Dose of Propofol in Humans

The doses of propofol that produce loss of consciousness were investigated in 26 patients with chronic alcoholism and in 20 patients with a history of small alcoholic intake undergoing ear, nose, and throat surgery under general anesthesia. Last ethanol consumption by the alcoholics was 24 h preoperatively, as they had no access to alcohol when admitted to the hospital. Propofol was infused at a rate of 1200 mL/h (200 mg/min). The doses required to produce (a) loss of verbal contact and (b) loss of ability to grasp a 20-mL syringe filled with water were recorded. At this time a 2-mL venous blood sample was collected to detect propofol blood concentrations. A painful stimulus was applied to the abdomen, and a positive or negative response was noted. The mean ± SD dose of propofol required for loss of verbal contact was 2.7 ± 0.42 mg/kg in the alcoholic group and 2.2 ± 0.43 mg/kg in the control group (P < 0.001). The dose of propofol required for dropping the syringe was significantly higher in the alcoholic group, 4.2 ± 1.02 mg/kg versus 3.2 ± 0.75 mg/kg in the control group (P < 0.01). The two groups did not differ significantly regarding the propofol blood concentrations at loss of consciousness, or the frequency of response or no response to painful stimulus. These findings suggest that the doses of propofol required to induce anesthesia in chronic alcoholic patients are more than in patients who drink socially.
Assessment of maternal anxiety levels before and after amniocentesis.

INTRODUCTION To assess anxiety levels in mothers before and after undergoing amniocentesis. The secondary aim was to see how counselling by nurse-counsellors affected maternal anxiety levels. METHODS A prospective study was carried out from February 2000 to August 2000 at the Kandang Kerbau Women's and Children's Hospital in Singapore. We used standard statistical analysis and Spielberger's state-trait anxiety inventory (STAI), that consisted of 40 items, to assess anxiety levels. Anxiety levels were assessed at different stages: before and after counselling; before amniocentesis and after amniocentesis; when results were disclosed; and after the routine 20-week screening ultrasound scan was acknowledged four to six weeks later. English-speaking women were recruited for the study as the STAI questionnaire has only been validated for an English-speaking population. 195 at-risk mothers (advanced maternal age, abnormal nuchal translucency on ultrasound scan, previous abnormal baby and high-risk maternal serum screening results) and patients requesting for amniocentesis between 15 to 20 weeks gestation were recruited. RESULTS 156 mothers agreed to amniocentesis. 38 mothers declined amniocentesis. S-anxiety levels declined significantly after counselling by trained nurse-counsellors in all mothers counselled. S-anxiety levels were highest and significantly higher compared to all other times just prior to amniocentesis despite counselling. Anxiety levels were the lowest and significantly lower compared to all other times at the last assessment stage. CONCLUSION High level of anxiety prior to amniocentesis despite counselling is understandable due to the invasive nature of the procedure. There is no long-lasting post-procedural anxiety to the mother.