Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular Senescence Markers p16INK4a and p21CIP1/WAF Are Predictors of Hodgkin Lymphoma Outcome

Purpose: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of cellular senescence (CS). We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21CIP1/WAF1 and p16INK4a by HRS cells might be predictive of the probability of event-free survival (EFS). Experimental Design: The study analyzed a retrospective cohort of 147 patients and the results were validated on a cohort of 91 patients independently diagnosed and treated in a different institution. p16INK4a and p21CIP1/WAF1 were categorized as dichotomous variables (< or ≥ 30% of HRS cells at diagnosis) and evaluated in univariate and multivariate analysis. Results: Both molecules were independent prognostic factors. A positive staining of one of the two molecules in more than 30% HRS cells predicted a better EFS (P < 0.01). p16INK4a/p21CIP1/WAF1 together as a unique categorical variable (both <30%, either <30%, both ≥ 30%) sorted out three prognostic groups with better, intermediate, or worse outcome either overall or within I–II, bulky and advanced stages. The presence or the lack of the robust expression of p21CIP1/WAF1 and/or p16INK4a defined the prognosis in our series. Conclusions: These findings point to (i) the relevance of CS-related mechanisms in cHL, and to (ii) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16INK4a and p21CIP1/WAF1 expression. Clin Cancer Res; 21(22); 5164–72. ©2015 AACR.
Visual Outcome after Nd:YAG Laser Capsulotomy

A longitudinal study was carried out in the laser unit of the Combined Military Hospital (CMH), Dhaka on 500 eyes of 500 patients who were treated with Neodymium-yttrium-aluminium-garnet (Nd:YAG) laser capsulotomy over a period of two and a half years. The aim of this study was to evaluate the visual acuity following Nd:YAG laser capsulotomy. The main entry criteria for this study were posterior capsular opacification (PCO) following Extracapsular Cataract Extraction (ECCE). The patients with corneal opacity, glaucoma, vitreous opacity, macular diseases, optic nerve diseases and any other retinopathies causing visual impairment were excluded from this study. Thirty six percent patients had pre-capsulotomy visual acuity 6/36 to 6/60, 32% patients had 6/18 to 6/24, 18% patients had <6/60 and 14% patients had 6/12. After seven days of capsulotomy 76% patients gained 6/12 or better vision. Eighty percent patients gained visual acuity of 6/12 with optical correction after thirty days. On the other hand, 64% patients had pre-capsulotomy near vision < N10 and 16% patients had N8. After capsulotomy near vision improved considerably. Four percent of the patients failed to improve vision following laser capsulotomy. It can be concluded that Nd:YAG laser capsulotomy in PCO can improve both distant and near vision, which can be augmented with optical correction after one month of laser surgery. Key words: Laser capsulotomy, Nd:YAG laser, visual acuity. DOI: 10.3329/jafmc.v5i2. 4580 JAFMC Bangladesh Vol.5(2) (December) 2009, pp.29-31
Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial

Objectives To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). Design Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months ’ follow-up. 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. Conclusions Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributabletovaccineHPVtypes(6,11,16,and18)anda substantial reduction in the burden of these diseases through 42 months of follow-up. NCT00092534.
Radiolabeled oligonucleotides targeting the RNA subunit of telomerase inhibit telomerase and induce DNA damage in telomerase-positive cancer cells.

Telomerase is expressed in the majority (>85%) of tumours, but has restricted expression in normal tissues. Long-term telomerase inhibition in malignant cells results in progressive telomere shortening and reduction in cell proliferation. Here we report the synthesis and characterisation of radiolabeled oligonucleotides that target the RNA subunit of telomerase, hTR, simultaneously inhibiting enzymatic activity and delivering radiation intracellularly. Oligonucleotides complementary (match) and non-complementary (scramble or mismatch) to hTR were conjugated to diethylenetriaminepentaacetic dianhydride (DTPA), allowing radiolabeling with the Auger electron-emitting radionuclide indium-111 (111In). Match oligonucleotides inhibited telomerase activity with high potency which was not observed with scramble or mismatch oligonucleotides. DTPA-conjugation and 111In-labeling did not change telomerase inhibition. In telomerase-positive cancer cells, unlabeled match oligonucleotides had no effect on survival, however, 111In-labeled match oligonucleotides significantly reduced clonogenic survival and upregulated the DNA damage marker γH2AX. Minimal radiotoxicity and DNA damage was observed in telomerase-negative cells exposed to 111In-match oligonucleotides. Match oligonucleotides localised in close proximity to nuclear Cajal bodies in telomerase-positive cells. In comparison to match oligonucleotides, 111In-scramble or 111In-mismatch oligonucleotides demonstrated reduced retention and negligible impact on cell survival. This study indicates the therapeutic activity of radiolabeled oligonucleotides that specifically target hTR through potent telomerase inhibition and DNA damage induction in telomerase-expressing cancer cells, and paves way for the development of novel oligonucleotide radiotherapeutics targeting telomerase-positive cancers.
Diminazene attenuates pulmonary hypertension and improves angiogenic progenitor cell functions in experimental models.

RATIONALE Studies have demonstrated that angiotensin-converting enzyme 2 (ACE2) plays a protective role against lung diseases, including pulmonary hypertension (PH). Recently, an antitrypanosomal drug, diminazene aceturate (DIZE), was shown to exert an "off-target" effect of enhancing the enzymatic activity of ACE2 in vitro. OBJECTIVES To evaluate the pharmacological actions of DIZE in experimental models of PH. METHODS PH was induced in male Sprague Dawley rats by monocrotaline, hypoxia, or bleomycin challenge. Subsets of animals were simultaneously treated with DIZE. In a separate set of experiments, DIZE was administered after 3 weeks of PH induction to determine whether the drug could reverse PH. MEASUREMENTS AND MAIN RESULTS DIZE treatment significantly prevented the development of PH in all of the animal models studied. The protective effects were associated with an increase in the vasoprotective axis of the lung renin-angiotensin system, decreased inflammatory cytokines, improved pulmonary vasoreactivity, and enhanced cardiac function. These beneficial effects were abolished by C-16, an ACE2 inhibitor. Initiation of DIZE treatment after the induction of PH arrested disease progression. Endothelial dysfunction represents a hallmark of PH pathophysiology, and growing evidence suggests that bone marrow-derived angiogenic progenitor cells contribute to endothelial homeostasis. We observed that angiogenic progenitor cells derived from the bone marrow of monocrotaline-challenged rats were dysfunctional and were repaired by DIZE treatment. Likewise, angiogenic progenitor cells isolated from patients with PH exhibited diminished migratory capacity toward the key chemoattractant stromal-derived factor 1α, which was corrected by in vitro DIZE treatment. CONCLUSIONS Our results identify a therapeutic potential of DIZE in PH therapy.
Diagnostic Value of Salivary Gland Ultrasonographic Scoring System in Primary Sjögren’s Syndrome: A Comparison with Scintigraphy and Biopsy

Objective. To compare an ultrasonographic (US) scoring system of salivary glands with scintigraphy and salivary gland biopsy, in order to evaluate its diagnostic value in primary Sjögren’s syndrome (SS). Methods. In 135 patients with suspected SS, the grades of 5 US measures of both parotid and submandibular salivary glands were scored (0–48 scale). Diagnosis of primary SS was established following the American-European Consensus Group criteria of 2002. The patients’ total scintigraphic score (0–12 scale) was determined and the histopathological changes of minor salivary glands graded. Area under the receiver-operating characteristic (ROC) curve was employed to evaluate the diagnostic value of the US scoring system. Results. Primary SS was diagnosed in 107 (79.2%) patients and the remaining 28 subjects (20.8%) constituted the control group. US changes of salivary glands were established in 98/107 patients with SS and in 14/28 controls. Mean US score was 26 in SS patients and 6 in controls. Through ROC curves, US arose as the best performer (0.95 ± 0.01), followed by scintigraphy (0.86 ± 0.31). Setting the cutoff score for US at 19 resulted in the best ratio of specificity (90.8%) to sensitivity (87.1%), while setting the cutoff scintigraphic score at 6 resulted in specificity of 86.1% and sensitivity of 67.1%. Among 70 patients with US score ≥ 19, a scintigraphic score > 6 was recorded in 54/70 (77.1%) and positive biopsy findings in 62/70 (88.5%) patients. Conclusion. We show high diagnostic accuracy of a novel US scoring system of salivary glands (0–48) in patients with primary SS comparable to invasive methods, i.e., scintigraphy and salivary gland biopsy.
Effects of Parental Hypertension on Longitudinal Trends in Blood Pressure and Plasma Metabolic Profile: Mixed-Effects Model Analysis

The mechanism underlying the association of parental hypertension with cardiovascular events in offspring remains unclear. In this study, the effects of parental hypertension on longitudinal trends of blood pressure and metabolic parameters were examined by mixed-effects model analysis. From 1977 to 2006, 5198 subjects participated in the Tanno-Sobetsu Study, and we selected 2607 subjects (1095 men and 1512 women) for whom data on parental history of hypertension were available. In both men and women with and without parental hypertension, systolic blood pressure and fasting blood glucose levels consistently increased from the third to eighth decades of life, whereas diastolic blood pressure and serum triglyceride levels followed biphasic (inverted U shape) time courses during that period. However, the relationships between the parameters and age were significantly shifted upward (by ≈5.3 mm Hg in systolic blood pressure, 2.8 mm Hg in diastolic blood pressure, 0.30 mmol/L in blood glucose, and 0.09 mmol/L in triglyceride) in the group with parental hypertension compared with those in the group without parental hypertension. Both paternal and maternal histories of hypertension were determinants of systolic blood pressure and diastolic blood pressure, and there was no significant interaction between the sides of parental history. There were no significant effects of parental hypertension on age-dependent or body mass index-dependent changes in serum low-density lipoprotein cholesterol or high-density lipoprotein cholesterol level. The present results indicate that parental hypertension has an age-independent impact on elevation of blood pressure, plasma glucose, and triglyceride levels, which may underlie the reported increase in cardiovascular events by family history of hypertension.
Protective effect of luteolin on cigarette smoke extract-induced cellular toxicity and apoptosis in normal human bronchial epithelial cells via the Nrf2 pathway.

UNLABELLED Luteolin, one of the most common abundant flavonoids in vegetables and herbs, has antitumor effects on various tumors by inducing apoptosis, antioxidant effects and inhibition of angiogenesis. However, the potential chemoprevention of luteolin on lung cell damage and its related mechanism(s) are not fully known. The present study evaluated the protective effects of luteolin on cigarette smoke extract (CSE)-induced toxicity and apoptosis in normal human bronchial epithelial (NHBE) cells and explored its underlying mechanism(s). MTT assay showed that pretreatment with luteolin increased CSE-decreased cell viability (p<0.05). Luteolin increased cellular glutathione (GSH) levels but decreased reactive oxygen species (ROS) generation (p<0.05). Cytometry assay and western blot analysis showed that luteolin attenuated CSE-induced apoptosis and apoptosis‑related protein activation, including caspase‑3, -8 and -9 (p<0.05). The expression of CSE-induced NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were decreased significantly by luteolin (p<0.05). Furthermore, luteolin attenuated CSE-induced apoptosis, noticeably reduced CSE-induced expression of NF-E2-related factor 2 (Nrf2), NQO1 and HO-1 using a small interfering RNA (siRNA) transfection assay. The data demonstrated that CSE-induced oxidative damage and apoptosis through the Nrf2 pathway was inhibited by luteolin and it may serve as a chemopreventive agent for the prevention and treatment of lung cancer.
A Parametric Approach to the Phonetics of Postvocalic /r/ in Dutch

Abstract This paper describes the phonetic exponents of rhoticity in postvocalic position in the speech of 4 young adult speakers of Standard Dutch. In addition to describing aspects of the segmental realisation of /r/, the paper focusses on parametric differences between rhymes with and without postvocalic /r/ in the material under consideration, presenting both impressionistic observations and instrumental measurements. Results of the investigation suggest that parametric analysis is a crucial complement to segmental classification, in providing insights into the relation between segmental realisations and ‘contextual effects’ of /r/, the phonetics of /r/ deletion and similarities and differences between rhotics cross-linguistically.
A Study on L2-Loss (Squared Hinge-Loss) Multiclass SVM

Crammer and Singer's method is one of the most popular multiclass support vector machines (SVMs). It considers L1 loss (hinge loss) in a complicated optimization problem. In SVM, squared hinge loss (L2 loss) is a common alternative to L1 loss, but surprisingly we have not seen any paper studying the details of Crammer and Singer's method using L2 loss. In this letter, we conduct a thorough investigation. We show that the derivation is not trivial and has some subtle differences from the L1 case. Details provided in this work can be a useful reference for those who intend to use Crammer and Singer's method with L2 loss. They do not need a tedious process to derive everything by themselves. Furthermore, we present some new results on and discussion of both L1- and L2-loss formulations.
New reference values for the neonatal cerebral ventricles.

PURPOSE To establish new cross-sectional reference values for the size of the lateral ventricles in a large cohort of neonates between 24 and 42 weeks' gestational age (GA) as well as longitudinal reference values for the follow-up of very preterm infants born at less than 30 weeks' gestation. MATERIALS AND METHODS Institutional review board approval and parental written informed consent were obtained for this prospective cohort study of 625 neonates (58% male patients) with a median GA of 33.4 weeks (range, 24.7-42.6 weeks). All infants underwent cranial ultrasonography (US) within 4 days after birth to evaluate the size of the lateral ventricles. Scanning was repeated in 301 preterm and term neonates within the 1st week of life to assess the presence of ventricular reopening. Seventy-nine very preterm infants (GA, <30 weeks) were prospectively included for cranial US at term-equivalent age (TEA). US measurements were performed of the ventricular index (VI), anterior horn width (AHW), and thalamo-occipital distance (TOD). Statistical analysis was conducted by using a paired t test, multilevel analysis, and analysis of covariance. RESULTS Cross-sectional reference values for the VI and TOD increased with maturity, whereas the AHW remained constant. Vaginal birth was independently associated with a slightly smaller AHW following birth and with an increase in AHW within the 1st week of life (P < .05). Preterm-born infants showed a larger ventricular size at TEA compared with term infants (P < .001). CONCLUSION New cross-sectional and longitudinal reference curves were established for the size of the neonatal lateral ventricles, which may allow for early identification and quantification of ventriculomegaly due to either posthemorrhagic ventricular dilation or periventricular white matter loss.
Interventional oncology research in the United States: slowing growth, limited focus, and a low level of funding.

PURPOSE To establish the characteristics of published interventional oncology (IO) research, including the volume, growth, geographic distribution, type of research, and funding patterns, and to determine how IO research compares with overall radiology research. MATERIALS AND METHODS This retrospective bibliometric analysis of public data was exempt from Institutional Review Board approval. IO articles published between 1996 and 2008 were identified in the National Library of Medicine MEDLINE database. Country of origin, article methodology, study topic, and source of funding were recorded. Growth was analyzed by using linear and nonlinear regression. RESULTS Total journal articles numbered 3801, including 847 (22.3%) from the United States, 722 (19.0%) from Japan, and 390 (10.3%) from China. World publications grew with a sigmoid (logistic) pattern (predicted maximum of 586.8 articles per year, P < .001). The United States and China also had logistic and slowing growth (maximums of 111.0 and 48.1 articles per year, respectively; both P < .001). Growth was linear in Japan (growth of 3.0 articles per year, P < .001) and exponential and accelerating in Germany, Italy, South Korea, France, and the United Kingdom. The United States produced 187 (36.9%) review articles but only 52 (13.1%) clinical trials. Japan (75, 18.8%) and China (71, 17.8%) both produced more clinical trials than other countries. U.S. IO articles were less likely than general radiology articles to receive funding from government (12.5% vs 23.7%) and nongovernment (15.0% vs 17.0%) sources. Liver cancer articles constituted 2388 (62.8%) of all IO articles. CONCLUSION IO research is slowing in the United States but growing elsewhere. Japan and China are leaders in clinical trial research. U.S. IO research receives less funding than does overall radiology research. IO research focuses primarily on liver cancer.
Occurrence and Predictors of Falls in People With Stroke: Six-Year Prospective Study

Background and Purpose— The purpose was to investigate the occurrence of self-reported falls in people with stroke at 3, 6, and 12 months and 6 years post stroke and predictors for falls during 6 years. Methods— A prospective study involving 121 people with stroke. Data were obtained through structured interviews and assessments. Generalized estimating equation modeling using proportional odds was used to explore the predictive value of fall history, functioning/disability, and personal factors during 6 years. Results— The proportion of fallers constituted of 35%, 26%, 33%, and 35% of the sample at 3, 6, and 12 months and 6 years of follow-up, respectively. Higher perceived effect of stroke on activities of daily living (odds ratio, 1.37; 95% confidence interval, 1.04–1.80), falls at 3 months (odds ratio, 1.0; 95% confidence interval, 1.01–3.94), and no gait/balance disability at baseline (odds ratio, 7.29; 95% confidence interval, 1.99–26.73) were predictors for future falls. During the 6 years, the odds for a fall decreased for participants with gait/balance disability at baseline but increased for those with no gait/balance disability. Conclusions— Results highlight the importance of performing fall risk evaluations over time among people with stroke, even when gait and balance functioning initially post stroke is good.
Recent advances of TNF-α antagonists in rheumatoid arthritis and chronic heart failure

Tumor necrosis factor (TNF)-α has been thoroughly investigated and established as a pivotal component of the inflammatory cascade. This review encompasses the safety and efficacy of TNF antagonists in rheumatoid arthritis, the interplay between rheumatoid arthritis and heart failure, as well as presentation of the available preclinical and clinical data discussing the use of anti-TNF therapy in patients with chronic heart failure. There is well-documented evidence for the role of anti-TNF-α in rheumatoid arthritis, in contrast to the controversial role of anti-TNF-α in heart failure. In animal models and small-scale clinical trials, anti-TNF therapy showed some promise in treating chronic heart failure, whereas larger, multicenter, randomized, placebo-controlled clinical trials (i.e., RECOVER [Research into Etanercept Cytokine Antagonism in Ventricular Dysfunction] and RENAISSANCE [Randomized Etanercept North American Strategy to Study Antagonism of Cytokines]) failed to show a statistically significant difference in composite clinical function score for anti-TNF therapy versus placebo. Future investigation is needed to determine if individualized dosing of anti-TNF therapy is necessary and whether or not treating patients with earlier-stage disease will show a benefit.
Acute stroke management: an online course

This article will explore the development and evaluation of an online course tailored specifically for emergency health professionals. Methods: a literature search was undertaken to inform the development of the course. Included studies related to stroke and positioning, oxygen therapy, blood pressure, body temperature and blood glucose. Following development and roll out of the course, all participants were invited to complete an online evaluation of the course, which consisted of eight closed and four open questions. Results: between February 2006 and July 2009, 1446 emergency health professionals completed the RESPONSE course. Of these, 570 (39%) completed the online evaluation. 555 (97.2%) participants reported that they were either very satisfied or satisfied with the course and 546 (95.6%) reported an increased knowledge in the management of acute stroke. Conclusion: the positive aspects of this web-based course have been identified as its usability, interactive nature, and flexibility. This online .