Miracle-dz/UniFAR-FTUs huggingface dataset:
Down-Regulation of Secretory Leukocyte Protease Inhibitor Expression in Gastric Mucosa Is a General Phenomenon in Helicobacter pylori-Related Gastroduodenal Diseases

Background: Secretory leukocyte protease inhibitor (SLPI) represents a multifunctional protein of the gastric mucosa exerting anti-microbial and anti-inflammatory effects. Recently, a local down-regulation of antral SLPI expression in Helicobacter pylori (Hp)-infected healthy volunteers was demonstrated. Aim: To analyze mucosal SLPI expression in patients with various gastroduodenal disorders. Methods: The prospective study included 90 patients with following gastroduodenal disorders diagnosed: gastric cancer (GC, n = 22), duodenal ulcer (DU, n = 17), Hp-positive dyspeptic patients (NUD, n = 31) and Hp-negative NUD (n = 20). During esophagogastroduodenoscopy, biopsies were taken each from antrum, corpus and tumor. SLPI expression was analyzed by quantitative RT-PCR and ELISA. Results: Antral SLPI levels were reduced in all Hp-infected patients (NUD, DU, GC) by about 75% (1,494–1,826 pg/50 µg protein) compared to Hp-negative NUD (6,563 pg/50 µg protein, p < 0.001, ANOVA). Tumor tissue had twofold higher SLPI levels than surrounding tumor-free gastric mucosa (3,900 vs. 1,826 pg/50 µg protein, p = 0.013), but revealed reduced SLPI levels compared to Hp-negative NUD patients (p = 0.067). No differences were found between SLPI expression of intestinal and diffuse GC. SLPI transcript levels were unchanged throughout all groups and locations implying that transcriptional regulation of SLPI is not involved. Conclusion: Local down-regulation of SLPI in antral mucosa is a general phenomenon of Hp-related diseases.
The Progression of Alzheimer’s Disease from Limbic Regions to the Neocortex: Clinical, Radiological and Pathological Relationships

Alzheimer’s disease (AD) is characterised by the gradual accumulation of neurofibrillary pathology in selected regions of the brain. Earlier studies indicate that the accumulation of neurofibrillary tangles is associated both with decline in patient’s cognitive performance as well as with medial temporal lobe atrophy on CT scans. There are also indications that progression through the pathological stages of AD is associated with decline in cognitive functions. The results of this study indicate that progression of disease, especially beyond the boundaries of the limbic regions, is associated with marked decline in the cognitive performance of patients suffering from AD. However the clinical manifestations of early pathological stages are not so well defined. We also found that the atrophy of the medial temporal lobe on CT scans is related to the progression of pathology. Atrophy is most apparent when the disease reaches its isocortical stages and is not marked in the limbic stages of the disease. The additive effect of pathologies co-existing with AD is apparent in reduced cognitive scores, while the atrophy of limbic structures, as measured on CT scans, seems to be mainly attributable to AD-related pathology.
Second Tumor Induction Risk in IMRT for Prostate Cancer: An Unbalanced Comparison Between Surgery and Radiotherapy?

AbstractThe aim of this study was to evaluate the risk of second tumor induction for prostate patients treated with volumetric modulated arc therapy in age classes 50–70. Based on both age-dependent models and doses to critical organs, the risk of second tumor induction was evaluated simulating the small field (prostate and seminal vesicles) and large field (whole pelvis) for Helical Tomotherapy and Rapid Arc. The doses to the organs closest to the treatment volume were derived from treatment planning system data. Whereas, due to the lack of calculation algorithms where leakage and internal radiation scattering are unreliable at a large distance from target, the doses to the organs outside the treatment volume were measured in an anthropomorphic phantom. Doses from Image Guided Radiotherapy (IGRT) were also assessed on phantom measurements. The Lifetime Attributable Risk (LAR) for second tumor induction increases from 2.2 to 13.7% as irradiated volume increases and age decreases. IGRT could add a non-negligible factor to the risk when daily set-up verification with high-resolution modality is included. As prostate cancer is detected earlier, the probability of an increase in early stage patients rises, and life expectancy thus increases. Radiotherapy has improved its capability in the tailoring of the dose around the target at the cost of a greater dose to surrounding organs, thus increasing the risk of second tumor induction, especially for those patients expected to survive 15 y or more.
The sleeper effect: Artifact or phenomenon-A brief comment on Bell et al. (2013).

OBJECTIVE Bell, Marcus, and Goodlad (2013) recently conducted a meta-analysis of randomized controlled additive trials and found that adding an additional component to an existing treatment vis-à-vis the existing treatment produced larger effect sizes on targeted outcomes at 6-months follow-up than at termination, an effect they labeled as a sleeper effect. One of the limitations with Bell et al.'s detection of the sleeper effect was that they did not conduct a statistical test of the size of the effect at follow-up versus termination. METHOD To statistically test if the differences of effect sizes between the additive conditions and the control conditions at follow-up differed from those at termination, we used a restricted maximum-likelihood random-effect model with known variances to conduct a multilevel longitudinal meta-analysis (k = 30). RESULTS Although the small effects at termination detected by Bell et al. were replicated (ds = 0.17-0.23), none of the analyses of growth from termination to follow-up produced statistically significant effects (ds < 0.08; p > .20), and when asymmetry was considered using trim-and-fill procedure or the studies after 2000 were analyzed, magnitude of the sleeper effect was negligible (d = 0.00). CONCLUSION There is no empirical evidence to support the sleeper effect. (PsycINFO Database Record
Effect of hypertonic saline and alcohol on viability of daughter cysts in hepatic hydatid disease.

OBJECTIVE To test the efficacy of hypertonic saline (20%) and absolute alcohol on the integrity of daughter cysts and the viability of the protoscoleces contained in these cysts. DESIGN Experimental study. SETTING Teaching hospital, Turkey. MATERIAL 80 daughter cysts obtained from two patients with Gharbi type III hydatid cysts of the liver. INTERVENTIONS The cysts were divided into two groups, in the first of which cysts were placed into hypertonic saline and in the second into absolute alcohol; they were kept there for 5, 15, 30 or 60 minutes. MAIN OUTCOME MEASURES Integrity of the cyst wall and viability of the contents were evaluated using a vital staining technique with 0.1% eosin. RESULTS Neither hypertonic saline nor absolute alcohol solution had any effect on the integrity of the daughter cysts or the viability of the protoscoleces. CONCLUSION Percutaneous drainage of type III hydatid cysts can lead to high recurrence rates.
Asthma in adults and its association with chronic rhinosinusitis: The GA2LEN survey in Europe

To cite this article: Jarvis D, Newson R, Lotvall J, Hastan D, Tomassen P, Keil T, Gjomarkaj M, Forsberg B, Gunnbjornsdottir M, Minov J, Brozek G, Dahlen SE, Toskala E, Kowalski ML, Olze H, Howarth P, Krämer U, Baelum J, Loureiro C, Kasper L, Bousquet PJ, Bousquet J, Bachert C, Fokkens W, Burney P. Asthma in adults and its association with chronic rhinosinusitis: The GA2LEN survey in Europe. Allergy 2012; 67: 91–98.
CANDiS: Coupled & Attention-Driven Neural Distant Supervision

Distant Supervision for Relation Extraction uses heuristically aligned text data with an existing knowledge base as training data. The unsupervised nature of this technique allows it to scale to web-scale relation extraction tasks, at the expense of noise in the training data. Previous work has explored relationships among instances of the same entity-pair to reduce this noise, but relationships among instances across entity-pairs have not been fully exploited. We explore the use of inter-instance couplings based on verb-phrase and entity type similarities. We propose a novel technique, CANDiS, which casts distant supervision using inter-instance coupling into an end-to-end neural network model. CANDiS incorporates an attention module at the instance-level to model the multi-instance nature of this problem. CANDiS outperforms existing state-of-the-art techniques on a standard benchmark dataset.
Time-Varying Formation Tracking for Linear Multiagent Systems With Multiple Leaders

Time-varying formation tracking problems for linear multiagent systems with multiple leaders are studied, where the states of followers form a predefined time-varying formation while tracking the convex combination of the states of multiple leaders. Followers are classified into well-informed ones and uninformed ones, where the neighbor set of the former contains all the leaders, whereas the latter contains no leaders. A formation tracking protocol is constructed using only neighboring relative information. Necessary and sufficient conditions for multiagent systems with multiple leaders to achieve time-varying formation tracking are proposed by utilizing the properties of the Laplacian matrix, where the formation tracking feasibility constraints are also given. An approach to design the formation tracking protocol is presented by solving an algebraic Riccati equation. The obtained results can be applied to deal with time-varying formation tracking problems, target enclosing problems, and consensus tracking problems for linear multiagent systems with one or multiple targets/leaders. Numerical simulations are provided to demonstrate the effectiveness of the theoretical results.
Analysis of the antitumoral mechanisms of lipopolysaccharide against glioblastoma multiforme

Our objective was to analyze the lipopolysaccharide (LPS) antitumoral effect upon glioblastoma, including whether the lipid A subunit alone can elicit glioblastoma regression, whether dexamethasone suppresses this response to LPS, whether B and T lymphocytes factor in this response, and whether this antitumoral effect of LPS provides resistance against subsequent challenge with glioblastoma. Mice (BALB/c, nude or SCID) implanted with s.c. DBT glioblastomas were treated with LPS (with or without dexamethasone) or with lipid A. A subset of BALB/c mice in which s.c. DBT glioblastomas had previously been eradicated using LPS were re-implanted with s.c. or intracranial (i.c.) DBT cells. For mice with s.c. tumors, mean tumor masses (MTM) were compared between groups. Survival was compared for mice with i.c. tumors. Lipid A caused near complete tumor regression of DBT glioblastomas in BALB/c mice (p<0.0001). Dexamethasone did not alter the antitumoral effect of LPS (p=0.48). LPS reduced the MTM of s.c. glioblastomas in T lymphocyte-deficient nude mice, but not as effectively as in immunocompetent mice. The antitumoral response to LPS for T and B lymphocyte-deficient SCID mice bearing DBT glioblastomas was similar to that for nude mice. Eradication of s.c. DBT glioblastoma in BALB/c provided partial resistance to subsequent challenge with s.c. or i.c. glioblastoma. We conclude that the LPS-mediated antitumoral response against glioblastoma is dependent upon the lipid A subunit of LPS, partially dependent upon T lymphocytes, independent of B lymphocytes, unaffected by dexamethasone and provides partial protection against subsequent challenges with glioblastoma.
Discovery and Validation of Pyridoxic Acid and Homovanillic Acid as Novel Endogenous Plasma Biomarkers of Organic Anion Transporter (OAT) 1 and OAT3 in Cynomolgus Monkeys

Perturbation of organic anion transporter (OAT) 1- and OAT3-mediated transport can alter the exposure, efficacy, and safety of drugs. Although there have been reports of the endogenous biomarkers for OAT1/3, none of these have all of the characteristics required for a clinical useful biomarker. Cynomolgus monkeys were treated with intravenous probenecid (PROB) at a dose of 40 mg/kg in this study. As expected, PROB increased the area under the plasma concentration-time curve (AUC) of coadministered furosemide, a known substrate of OAT1 and OAT3, by 4.1-fold, consistent with the values reported in humans (3.1- to 3.7-fold). Of the 233 plasma metabolites analyzed using a liquid chromatography–tandem mass spectrometry (LC-MS/MS)–based metabolomics method, 29 metabolites, including pyridoxic acid (PDA) and homovanillic acid (HVA), were significantly increased after either 1 or 3 hours in plasma from the monkeys pretreated with PROB compared with the treated animals. The plasma of animals was then subjected to targeted LC-MS/MS analysis, which confirmed that the PDA and HVA AUCs increased by approximately 2- to 3-fold by PROB pretreatments. PROB also increased the plasma concentrations of hexadecanedioic acid (HDA) and tetradecanedioic acid (TDA), although the increases were not statistically significant. Moreover, transporter profiling assessed using stable cell lines constitutively expressing transporters demonstrated that PDA and HVA are substrates for human OAT1, OAT3, OAT2 (HVA), and OAT4 (PDA), but not OCT2, MATE1, MATE2K, OATP1B1, OATP1B3, and sodium taurocholate cotransporting polypeptide. Collectively, these findings suggest that PDA and HVA might serve as blood-based endogenous probes of cynomolgus monkey OAT1 and OAT3, and investigation of PDA and HVA as circulating endogenous biomarkers of human OAT1 and OAT3 function is warranted.
Ribosomal Protein S6 Associates with Alphavirus Nonstructural Protein 2 and Mediates Expression from Alphavirus Messages

ABSTRACT Although alphaviruses dramatically alter cellular function within hours of infection, interactions between alphaviruses and specific host cellular proteins are poorly understood. Although the alphavirus nonstructural protein 2 (nsP2) is an essential component of the viral replication complex, it also has critical auxiliary functions that determine the outcome of infection in the host. To gain a better understanding of nsP2 function, we sought to identify cellular proteins with which Venezuelan equine encephalitis virus nsP2 interacted. We demonstrate here that nsP2 associates with ribosomal protein S6 (RpS6) and that nsP2 is present in the ribosome-containing fractions of a polysome gradient, suggesting that nsP2 associates with RpS6 in the context of the whole ribosome. This result was noteworthy, since viral replicase proteins have seldom been described in direct association with components of the ribosome. The association of RpS6 with nsP2 was detected throughout the course of infection, and neither the synthesis of the viral structural proteins nor the presence of the other nonstructural proteins was required for RpS6 interaction with nsP2. nsP1 also was associated with RpS6, but other nonstructural proteins were not. RpS6 phosphorylation was dramatically diminished within hours after infection with alphaviruses. Furthermore, a reduction in the level of RpS6 protein expression led to diminished expression from alphavirus subgenomic messages, whereas no dramatic diminution in cellular translation was observed. Taken together, these data suggest that alphaviruses alter the ribosome during infection and that this alteration may contribute to differential translation of host and viral messages.
Molecular targeted therapies for diffuse large B‐cell lymphoma based on apoptosis profiles

Diffuse large B‐cell lymphoma (DLBCL) is the most common type of adult non‐Hodgkin lymphoma and is treated with chemotherapy in combination with rituximab. Despite this aggressive therapy, the disease is fatal in 30–40% of patients. Inhibition of the apoptosis signalling pathways is strongly related to response to chemotherapy and eventual clinical outcome. In order to survive, lymphoma cells depend on disruption of the apoptosis pathway by mutations in apoptosis inducing genes or by continuous expression of anti‐apoptotic proteins. The development of molecules targeting these apoptosis inhibitors provides a very promising opportunity to specifically target tumour cells without toxicity to non‐malignant cells in DLBCL patients. Sensitivity for most of these antagonists can be predicted based on biological markers, suggesting the possibility of pre‐defining patients who will most likely benefit from these targeted therapies. Experimental therapies aimed at restoring the upstream apoptosis pathway or targeting apoptosis inhibitors are currently being tested in clinical trials and are expected to be effective particularly in chemotherapy‐refractory DLBCL, providing hope for patients who are refractory to current therapies. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
HFE genotype and transferrin saturation in the United States

Purpose: Examine the penetrance (defined by high transferrin saturation [TS]) of C282Y and H63D in the U.S. population.Methods: 5171 participants from the Third National Health and Nutrition Examination Survey, 1992 to 1994.Results: 77.1% (95% confidence interval [CI], 2.3, 95.1) of men and 51.9% (95% CI, 0, 84.2) of women with C282Y homozygosity had high TS. The associations of H63D homozygosity with high TS were stronger in people aged 50 years or older than in younger persons. Among Mexican-Americans, simple H63D heterozygosity was associated with high TS.Conclusions: The associations between HFE genotype and high TS may vary by sex, age, and ethnic group.
Use of statins and risk of haematological malignancies: a meta-analysis of six randomized clinical trials and eight observational studies.

AIMS Statins have been suggested to prevent haematological malignancies. Several epidemiological studies have evaluated this association, while randomized controlled trials (RCTs) on cardiovascular outcomes have provided relevant data as secondary end-points. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published in peer-reviewed literature. METHODS A comprehensive search for articles published up to December 2006 was performed, reviews of each study were conducted and data abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates and 95% confidence intervals (CIs) were calculated using the random effects model. RESULTS Fourteen studies (six RCTs, seven case-control and one cohort study) contributed to the analysis. Studies were grouped on the basis of study design, and two separate meta-analyses were conducted. There was no evidence of an association between statin use and haematological malignancies among either RCTs (RR = 0.92, 95% CI 0.72, 1.16) or the observational studies (RR = 0.83, 95% CI 0.53, 1.29). Similarly, we found no evidence of publication bias. However, high heterogeneity was detected among the observational studies. CONCLUSION Our meta-analysis findings do not support a potential role of statins in the prevention of haematological malignancies.
Be Clear: A New Intensive Speech Treatment for Adults With Nonprogressive Dysarthria.

PURPOSE This article describes the effects of a new intensive dysarthria treatment program (Be Clear) on speech intelligibility in adults with dysarthria secondary to stroke and traumatic brain injury. METHOD A small group-repeated measures research design was used to examine the effects of treatment on the speech of 8 participants with nonprogressive dysarthria. Treatment consisted of a 1-hr prepractice session followed by 1-hr therapy sessions, 4 times per week, for 4 weeks (16 sessions). Paired-comparison ratings of speech intelligibility served as the primary outcome measure for the study. Perceptual data, quality of life, and communication partner opinion were obtained at 3 time intervals: (a) prior to treatment, (b) immediately posttreatment, and (c) 1-3 months posttreatment. RESULTS Following treatment, group data demonstrated substantial improvements in speech intelligibility as perceived by naive listeners on a paired-comparison rating task. Word intelligibility was clinically significantly improved posttreatment and sentence intelligibility demonstrated statistically significant improvement. Communication partner ratings of speech intelligibility and overall communicative function were statistically significantly improved posttreatment. CONCLUSIONS The results of this study suggest that this new intensive treatment may have potential as an effective intervention for nonprogressive dysarthria. However, controlled studies are required to establish treatment efficacy.
An oral cancer information leaflet for smokers in primary care: results from two randomised controlled trials.

OBJECTIVES To investigate whether primary care patients who claim to smoke tobacco gain greater benefit of a patient information leaflet (PIL) on oral cancer than nonsmokers. METHODS Two studies were conducted. Study 1 examined the research question initially, and Study 2 acted as a replication and inclusion of additional secondary outcome measures. The leaflet was designed and tested in an earlier study. Knowledge of oral cancer was assessed by a previously validated 36-dichotomous-item scale. A single-item question ascertained self-reported smoking status (kappa = 0.94). Study 1 participants were drawn from 14 practices (6 medical, 8 dental). A randomised control group design was adopted. The experimental group received the leaflet on attendance to the practice and then completed the questionnaire. The control group received the questionnaire only. Complete data were collected from 739 respondents. The design of Study 2 was identical; 786 new respondents from 16 practices (7 medical, 9 dental) were collected. RESULTS Both studies confirmed that smokers knew less about oral cancer than nonsmokers (P < 0.05) when access to the leaflet had been denied. On receipt of the leaflet, there was no distinction in oral cancer knowledge between the smoking status categories of respondents. Evidence of reassurance about screening from leaflet exposure was supported by the second study. CONCLUSION This programmed research has demonstrated an effect of a brief PIL to offset the decrement in oral cancer knowledge observed in primary care patients who use tobacco in comparison to their nonsmoking counterparts. The leaflet reduced anxiety about oral health screening in smokers.
Specific attention disorders in drivers with traumatic brain injury

Objective: To highlight the impact of the increasing attentional load on performance of both normal drivers and drivers with traumatic brain injury. Background: Patients with brain injury have a higher accident risk than people with no brain injury [1], probably as a result of persistent attention disorders. Method: Ten patients and 10 paired controls took part in a computerized selective attention task involving specific attentional processes. They were asked to monitor a speedometer and to ignore sudden changes in the surrounding environment in three separate experimental situations involving different attentional load. Results: Although, in the control situation, patients’ results were equivalent to controls’, they displayed specific disorders in more complex situations where the attentional load increased. Conclusion: These difficulties may have a negative impact on real driving situations.