Miracle-dz/UniFAR-FTUs huggingface dataset:
Dead or alive? Autofluorescence distinguishes heat-fixed from viable cells

Purpose: A proof-of-concept study to evaluate a new autofluorescence method to differentiate necrotic thermally fixed cells from viable tissue following thermal ablation. Methods: A conductive interstitial thermal therapy (CITT) device was used to ablate swine mammary tissue and rabbit VX-2 carcinomas in vivo. The ablated regions and 10-mm margins were resected 24 h following treatment, embedded in HistOmer® and sectioned at 3 mm. The fresh sections were evaluated for gross viability with triphenyl tetrazolium chloride, 1 h post-resection. Representative non-viable and viable areas were then processed and embedded into paraffin, and sectioned at 5 µm. Standard H&E staining and proliferating cell nuclear antigen (PCNA) immunohistochemistry were compared against autofluorescence intensity, at 488-nm wavelength, for cellular viability. Results: Heat-fixed cells in non-viable regions exhibit increased autofluorescence intensity compared to viable tissue (area under receiver operating characteristics (ROC) curve = 0.96; Mann-Whitney P < 0.0001). An autofluorescence intensity-based classification rule achieved 92% sensitivity with 100% specificity for distinguishing non-viable from viable samples. In contrast, PCNA staining did not reliably distinguish heat-fixed, dead cells from viable cells. Conclusions: Examination of H&E-stained sections using autofluorescence intensity-based classification is a reliable and readily available method to accurately identify heat-fixed cells in ablated surgical margins.
Atherosclerotic occlusive extracranial vertebral artery disease: indications for intervention, endovascular techniques, short-term and long-term results.

BACKGROUND Atherosclerotic occlusive disease of the vertebral artery (VA) affects a significant proportion of patients with cerebrovascular disease and can cause significant morbidity and mortality despite maximal medical therapy. Careful selection of both symptomatic and asymptomatic patients for intervention based on neurological symptoms, as well as anatomical and hemodynamic considerations, is essential. METHODS To achieve proper results with angioplasty and stenting, standard endovascular techniques are modified for the unique anatomical considerations of the VA. Several technical nuances are described here to aid in the endoluminal revascularization of the VA. RESULTS Technical success (<50% residual diameter stenosis) rates ranging from 94 to 98% and low rates of periprocedural complications have been achieved with VA angioplasty and stenting in select series with angiographic follow-up. The long-term success in those series is limited by the high (10-43%) rate of recurrent stenosis. Proper placement of the stent can reduce the risk of periprocedural complications and restenosis. In-stent stenosis appears most commonly during the first 6-12 months after stent placement, but does not appear to correlate with return of neurological symptoms. We believe the high rate of recurrent stenosis makes follow-up angiography essential, especially in the first 12 months after the procedure. CONCLUSION Endovascular VA angioplasty with stent placement provides an innovative approach to treat a difficult clinical entity. Evolving therapies, including drug-eluting stents or bioresorbable stents, may prove to provide better long-term results.
Vasoconstrictor effects of various neuropeptide Y analogues on the rat tail artery in the presence of phenylephrine

1 The increase in perfusion pressure induced by neuropeptide Y (NPY), peptide YY (PYY) and related peptides were compared in the perfused rat tail artery precontracted by a submaximal concentration (1 μm) of the vasoconstrictor, phenylephrine. 2 NPY, PYY, [Leu31,Pro34]NPY, [Glu16, Ser18, Ala22, Leu28,31]NPY (ESALL‐NPY) and the centrally truncated and stabilized analogues [d‐Cys5, 8‐aminooctanoic acid7–20, Cys24]‐NPY (d‐Cys5‐NPY) and [d‐Cys7, 8‐aminooctanoic acid8–17, Cys20]‐NPY (d‐Cys7‐NPY) produced a concentration‐dependent enhancement of the vasoconstrictor response induced by 1 μm phenylephrine. PYY was two times more potent than NPY and [Leu31,Pro34]NPY while ESALL‐NPY, d‐Cys7‐NPY and d‐Cys5‐NPY were approximately 3, 5 and 16 times less potent than NPY respectively. NPY, d‐Cys5‐NPY and d‐Cys7‐NPY gave similar maximal responses whereas those observed for PYY, [Leu31,Pro34]NPY and ESALL‐NPY were much greater than that of NPY. 3 NPY 13–36 and [des‐Ser3,Lys4, Cys2, 8‐aminooctanoic acid3–24, d‐Cys27]‐NPY ([des‐Ser3,Lys4]Cys2‐NPY) were practically inactive at concentrations up to 3μm, whereas [des‐Ser3,Lys4, d‐Cys2, 8‐aminooctanoic acid3–24, Cys27]‐NPY ([des‐Ser3,Lys4]d‐Cys2‐NPY), which differs from [des‐Ser3,Lys4]Cys2‐NPY in the disulphide bridge (a d‐Cys in position 2 for [des‐Ser3,Lys4]d‐Cys2‐NPY instead of an l‐Cys for [des‐Ser3,Lys4]Cys2‐NPY) was a weak agonist the maximal effect of which could not be ascertained. 4 The contractile effects of [des‐Ser3,Lys4]d‐Cys2‐NPY were additive with those of NPY and [Leu31, Pro34]NPY demonstrating that it is not a partial agonist but may simply not interact competitively with the receptor binding site for NPY. NPY and PYY interacted in a manner expected of agonists competing for the same binding site. 5 PYY, NPY and [Leu31,Pro34]NPY were equipotent in displacing the I125‐labelled PYY from binding sites on membranes from Y1‐receptor expressing SK‐N‐MC cells, while the centrally truncated analogues were much less potent. The rank order of potencies for displacement of the I125‐PYY binding by these peptides in SK‐N‐MC cells correlated with their activity in enhancing the vasoconstrictor response of phenylephrine in the tail artery. For the [des‐Ser3,Lys4]d‐Cys2‐NPY analogue, the displacement pattern was more complex in that the displacement analysis revealed the presence of two binding sites. 6 In conclusion, these data provide no evidence for other than postjunctional Y1‐receptors mediating the enhancement of the contractile response elicited by phenylephrine in the perfused rat tail artery. The effects of [des‐Ser3,Lys4]d‐Cys2‐NPY indicate that the Y1‐receptor may possess an allosteric binding site.
Efficacy and Safety of a 10-Day Course of 400 or 600 Milligrams of Grepafloxacin Once Daily for Treatment of Acute Bacterial Exacerbations of Chronic Bronchitis: Comparison with a 10-Day Course of 500 Milligrams of Ciprofloxacin Twice Daily

ABSTRACT A randomized, prospective, double-blind, double-dummy, multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily, grepafloxacin at 600 mg once daily, or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bronchitis. At the end of treatment, clinical success (cure or improvement) was achieved for 93% (140 of 151), 88% (137 of 156), and 91% (145 of 160) of patients in the groups receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively (clinically evaluable population). At follow-up (14 to 28 days posttreatment), the clinical success rates were 87% (124 of 143), 81% (122 of 151), and 80% (123 of 154) in the groups receiving grepafloxacin at 400 mg and 600 mg and ciprofloxacin, respectively. A total of 379 pathogens were isolated from 290 patients, with the most common isolates being Moraxella catarrhalis(21%), Staphylococcus aureus (20%), Haemophilus influenzae (18%), and Streptococcus pneumoniae(7%). For the evaluable population, successful bacteriologic response was obtained at the end of treatment for 96% (92 of 96), 98% (87 of 89), and 92% (82 of 90) of patients receiving grepafloxacin at 400 mg, grepafloxacin at 600 mg, and ciprofloxacin, respectively, and was maintained in 86% (82 of 95), 88% (78 of 89), and 82% (69 of 84) of patients, respectively, at follow-up. All pretreatment S. pneumoniae isolates were susceptible to grepafloxacin, but two strains were resistant to ciprofloxacin. All treatments were well tolerated, with the most frequently reported drug-related adverse events being nausea, taste perversion, and headache. All drug-related adverse events in the grepafloxacin groups were mild or moderate in severity. This study demonstrates that 10-day courses of grepafloxacin given at 400 or 600 mg once daily were as effective, clinically and bacteriologically, as ciprofloxacin given at 500 mg twice daily for the treatment of acute bacterial exacerbations of chronic bronchitis.
Psychopathological and Behavior Impairments in Williams-Beuren Syndrome: The Influence of Gender, Chronological Age, and Cognition

The aim of this study was to explore psychopathological and behavior impairments in Williams-Beuren syndrome (WBS) by focusing on individual differences rather than group tendencies. Parent/Guardian ratings on the Child Behavior Checklist were analyzed in order to examine the influence of gender, chronological age, and cognitive abilities on psychopathological impairment within WBS. In line with predictions, and consistent with cognitive heterogeneity in WBS, psychopathological and behavioral abnormalities were variable, with gender and specific cognitive abilities making significant and independent contributions to this variance. For gender, females were significantly more likely than males with WBS to display difficulties with externalizing problems. For specific cognitive abilities, those cognitive functions characteristic of the classic WBS cognitive profile (a strength in verbal skills and a weakness in spatial skills) related to significantly greater internalizing difficulties. Future studies should explore underlying genetic and neurological differences in individuals with WBS in order to help explain the variability in psychopathological and cognitive functions.
Tunable Electromagnetic Band Gap slits for mutual coupling reduction

Novel tunable two-layer Electromagnetic Band - Gap (EBG) slit-patch structures are presented for reducing the electromagnetic coupling between closely spaced CPW-fed monopole antennas. Ultra wideband monopoles are employed in order to demonstrate the tuning range of the slit. The proposed slit is etched in the common ground between the monopoles and a conducting patch is printed on a 55 μm thick polyester dielectric sheet separating it from the slit and the ground. The tuning is achieved by means of a varactor diode placed in the middle of the patch, which is electrically isolated from the ground plane of the antennas since it lies on a different layer. A tunable transmission zero is produced in the S21 leading to a significant reduction of the mutual coupling between the antennas. The tuning range covers the wide operating frequency band of the monopoles. The proposed slit is linear and of sub-wavelength dimensions (~λ/12) and hence it occupies very little space on the ground. Multiple EBG slit-patch structures are considered for more broadband antenna isolation. Simulation results were obtained in 3D electromagnetic simulation software (CST Microwave studio) and are presented.
Vitamin D receptor-mediated gene regulation mechanisms and current concepts of vitamin D analog selectivity.

Lipophilic hormones of steroidal origin such as the sex hormones and 1,25-dihydroxy vitamin D(3) (1,25[OH](2)D(3)) function by regulating patterns of gene expression in cells. The mediators of such actions are nuclear receptors that recognize these ligands with high affinity and selectivity and function through several mechanisms as gene specific transcription factors. As a result of the mechanistic complexity of nuclear receptor action, recent studies have revealed that both synthetic analogs as well as novel mimetics of a receptor's natural hormonal ligand are capable of modulating functional responses in both cell- and gene-selective manners. These findings have given rise to the term selective receptor modulators, typified by such synthetic estrogen receptor ligands as tamoxifen and raloxifene. A number of vitamin D analogs have been prepared that appear to exhibit tissue-selective activity--most notable through their inability to induce levels of hypercalcemia typical of the activity of the natural hormone 1,25(OH)(2)D(3). Because this debilitating yet normal feature of the natural ligand limits its usefulness in a variety of clinical indications, including its application to prevent bone disease caused by secondary hyperparathyroidism, this feature of many of the new analogs is especially welcome. This article discusses what constitutes a selective receptor modulator and whether the current vitamin D analogs represent such entities.
The association between sleep disordered breathing, academic grades, and cognitive and behavioral functioning among overweight subjects during middle to late childhood.

STUDY OBJECTIVES (1) to determine the associations of sleep disordered breathing (SDB) with behavioral functioning, cognitive test scores, and school grades during middle- to late-childhood, an under-researched developmental period in the SDB literature, and (2) to clarify whether associations between SDB and school grades are mediated by deficits in cognitive or behavioral functioning. DESIGN cross-sectional correlative study. SETTING Office/hospital, plus reported functioning at home and at school. PARTICIPANTS 163 overweight subjects aged 10-16.9 years were divided into 4 groups based upon their obstructive apnea+hypopnea index (AHI) during overnight polysomnography and parent report of snoring: Moderate-Severe OSA (AHI > 5, n = 42), Mild OSA (AHI = 1-5, n = 58), Snorers (AHI < 1 + snoring, n = 26), and No SDB (AHI < 1 and nonsnoring, n = 37). MEASUREMENTS inpatient overnight polysomnography, parent- and self-report of school grades and sleep, parent- and teacher-report of daytime behaviors, and office-based neuropsychological testing. RESULTS The 4 groups significantly differed in academic grades and parent- and teacher-reported behaviors, particularly inattention and learning problems. These findings remained significant after adjusting for subject sex, race, socioeconomic status, and school night sleep duration. Associations with SDB were confined to reports of behavioral difficulties in real-world situations, and did not extend to office-based neuropsychological tests. Findings from secondary analyses were consistent with, but could not definitively confirm, a causal model in which SDB affects school grades via its impact on behavioral functioning. CONCLUSIONS SDB during middle- to late-childhood is related to important aspects of behavioral functioning, especially inattention and learning difficulties, that may result in significant functional impairment at school.
Towards an explicit account of implicit learning

Purpose of reviewThe human brain supports acquisition mechanisms that can extract structural regularities implicitly from experience without the induction of an explicit model. Reber defined the process by which an individual comes to respond appropriately to the statistical structure of the input ensemble as implicit learning. He argued that the capacity to generalize to new input is based on the acquisition of abstract representations that reflect underlying structural regularities in the acquisition input. We focus this review of the implicit learning literature on studies published during 2004 and 2005. We will not review studies of repetition priming (‘implicit memory’). Instead we focus on two commonly used experimental paradigms: the serial reaction time task and artificial grammar learning. Previous comprehensive reviews can be found in Seger's 1994 article and the Handbook of Implicit Learning. Recent findingsEmerging themes include the interaction between implicit and explicit processes, the role of the medial temporal lobe, developmental aspects of implicit learning, age-dependence, the role of sleep and consolidation. SummaryThe attempts to characterize the interaction between implicit and explicit learning are promising although not well understood. The same can be said about the role of sleep and consolidation. Despite the fact that lesion studies have relatively consistently suggested that the medial temporal lobe memory system is not necessary for implicit learning, a number of functional magnetic resonance studies have reported medial temporal lobe activation in implicit learning. This issue merits further research. Finally, the clinical relevance of implicit learning remains to be determined.
Effects of Atorvastatin on Coronary Flow Reserve in Patients with Slow Coronary Flow

Statins improve endothelial functioning in patients with coronary artery disease and hypercholesterolemia, while substantially little is known about induced changes in myocardial microcirculation. However, although previous studies have suggested that microvascular abnormalities and endothelial dysfunction is responsible for slow coronary flow (SCF), there is no study investigating possible effects of statins on coronary microvascular function in patients with SCF.
Reporting the Recruitment Process in Clinical Trials: Who Are These Patients and How Did They Get There?

What is the problem and what is known about it so far? When researchers perform clinical studies comparing one treatment with another, they often use an experimental design known as a randomized, controlled trial (RCT). This design ensures that patients are randomly assigned to treatment groups in a way that will not bias the results by putting many people who are likely to respond favorably into one group and many who are not likely to respond into another. Although RCTs are generally accepted as the strongest way to design a clinical study, the usefulness of the findings depends not only on the strength of random assignment but also on how well the experimental patients represent all patients with the particular disease being studied. Why did the researchers do this particular study? The researchers wanted to find out whether RCTs published in good medical journals provided enough information about the selection of study participants to allow readers to judge whether most people with a particular disease could be expected to have the same results as the participants in the experiment. What was studied? 172 RCTs involving humans that were published in four widely respected medical journals over a 1-year period beginning April 1, 1999. How was the study done? All RCTs published during that year were identified, and articles appropriate for evaluation were selected for review. The researchers then recorded how many articles provided information about the number of people screened for eligibility to participate in the study, how many described the number of people who were found to be eligible for participation, and how many people were actually enrolled. In addition, the researchers recorded the type of study being performed, where the money came from to perform the study, and the severity of the disease being studied. What did the researchers find? Only about half of the published RCTs reported the number of potential participants who were screened for eligibility. Forty-three percent reported how many people were eligible for participation, and 28% reported enough information to calculate what proportion of the screened population was found to be eligible for participation. The researchers also found that in order to recruit each participant for the study, more people needed to be screened if the disease being studied was more severe. Funding source did not appear to affect recruitment. What were the limitations of the study? Only four medical journals were included in the study, and RCTs they published may not be representative of all published RCTs. What are the implications of the study? More information needs to be provided about the people who take part in RCTs in order for clinicians to be able to judge whether the findings are applicable to all patients with a particular disease.
Risk of epithelial ovarian cancer recurrence in patients with rising serum CA-125 levels within the normal range.

PURPOSE To evaluate the risk of epithelial ovarian cancer (EOC) recurrence in patients with rising serum cancer antigen 125 (CA-125) levels that remain below the upper limit of normal (< 35 U/mL). PATIENTS AND METHODS All patients treated for EOC between September 1997 and March 2003 were identified and screened retrospectively for the following: (1) elevated serum CA-125 at time of diagnosis, (2) complete clinical and radiographic response (CR) to initial treatment with normalization of serum CA-125, (3) at least three serial serum CA-125 determinations that remained within the normal range, and (4) clinical and/or radiographic determination of disease status at the time of last follow-up or recurrence. For statistical analyses, univariate regression models were used to compare absolute and relative changes in CA-125 levels among patients with recurrent disease and those without EOC recurrence. RESULTS A total of 39 patients satisfied study inclusion criteria; 22 patients manifested EOC recurrence at a median interval from complete response of 11 months. The median follow-up time from complete response to last contact was 32 months for the 17 patients in the no recurrence group. A relative increase in CA-125 of 100% (odds ratio [OR] = 23.7; 95% CI, 2.9 to 192.5; P = .003) was significantly predictive of recurrence. From baseline CA-125 nadir levels, an absolute increase in CA-125 of 5 U/mL (OR = 8.4; 95% CI, 2.2 to 32.6; P = .002) and 10 U/mL (OR = 71.2; 95% CI, 4.8 to > 999.9; P = .002) were also significantly associated with the likelihood of concurrent disease recurrence. CONCLUSION Among patients with EOC in complete clinical remission, a progressive low-level increase in serum CA-125 levels is strongly predictive of disease recurrence.
Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women.

OBJECTIVE We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, and impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS A total of 2,964 elderly men and women (mean age 73.6 years) were recruited for cross-sectional comparisons of diabetes or glucose tolerance, generalized obesity with dual-energy X-ray absorptiometry, and regional body fat distribution with computed tomography. RESULTS-Approximately one-third of men with type 2 diabetes and less than half of women with type 2 diabetes were obese (BMI > or =30 kg/m(2)). Despite similar amounts of subcutaneous thigh fat, intermuscular fat was higher in subjects with type 2 diabetes and IGT than in subjects with normal glucose tolerance (NGT) (11.2 +/- 9.4, 10.3 +/- 5.8, and 9.2 +/- 5.9 cm(2) for men; 12.1 +/- 6.1, 10.9 +/- 6.5, and 9.4 +/- 5.3 cm(2) for women; both P < 0.0001). Visceral abdominal fat was also higher in men and women with type 2 diabetes and IGT than in subjects with NGT (172 +/- 79, 163 +/- 72, and 145 +/- 66 cm(2) for men; 162 +/- 66, 141 +/- 60, and 116 +/- 54 cm(2) for women; both P < 0.0001 across groups). Higher rates of intermuscular fat and visceral abdominal fat were associated with higher fasting insulin in normal-weight (BMI <25 kg/m(2)) men (r = 0.24 for intermuscular fat, r = 0.37 for visceral abdominal fat, both P < 0.0001) and women (r = 0.20 for intermuscular fat, r = 0.40 for visceral abdominal fat, both P < 0.0001). These associations were not found in obese subjects. CONCLUSIONS Elderly men and women with normal body weight may be at risk for metabolic abnormalities, including type 2 diabetes, if they possess an inordinate amount of muscle fat or visceral abdominal fat.