Miracle-dz/UniFAR-FTUs huggingface dataset:
Could gastric histology be a useful marker for making decision on Helicobacter pylori eradication therapy in patients with dyspepsia?

CONTEXT It still remains an open debate whether Helicobacter pylori eradication is beneficial or not for the improvement of symptoms in functional dyspepsia. Differences in geographic distribution, the worldwide H. pylori genetic variability and the fact that the outcome of infection is strongly related to the virulence of the infecting strain are factors that might be driving ongoing controversies. OBJECTIVE To study the correlation between gastric histology and H. pylori serology status in patients with dyspepsia. METHODS This is a cross-sectional study where 40 consecutive dyspeptic patients (28 women and 12 men, mean age 48.5 years) with endoscopically normal stomachs were selected from the endoscopy unit at a university hospital in Recife, PE, Northeast of Brazil, between March 1998 and July 1999. Patients underwent gastric mucosal biopsy and serological tests (anti-Hp and anti-CagA antibodies). Gastric biopsies were examined using H-E and Giemsa stains and gastritis was classified and graded (mild, moderate or severe) according to 'the updated Sydney System-Houston, 1994'. RESULTS Among 40 patients with dyspepsia the gastric histology revealed that about (1/4) had moderate (25%) or severe (2.5%) gastritis. This subgroup of patients also had a greater positive frequency of anti-Hp (100% vs 41%; P = 0.0005) and anti-CagA (91% vs 58%; P = 0.09) antibodies when compared with those with normal histology (27.5%) or mild gastritis (45%). CONCLUSION Since upper gastrointestinal endoscopy is part of the functional dyspepsia investigation and serology for anti-CagA antibody is not available in daily clinical practice, by biopsying gastric mucosa we would only be able to selectively apply H. pylori eradication therapy for those with histology that best correlate with virulent infecting strains (moderate or severe gastritis)--around (1/4) of our study patients with dyspepsia.
Effects of Chronic Clonidine Administration on Sympathetic Nerve Traffic and Baroreflex Function in Heart Failure

Abstract—Congestive heart failure is characterized by a sympathetic activation that is coupled with a baroreflex impairment. Whether these alterations are affected by clonidine is unknown. In 26 normotensive patients age 58.0±1.1 years (mean±SEM) affected by congestive heart failure (New York Heart Association functional class II or III) and treated with furosemide and enalapril, we measured mean arterial pressure, heart rate, venous plasma norepinephrine, and muscle sympathetic nerve traffic (microneurography) at rest and during baroreceptor stimulation and deactivation caused by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Measurements were repeated after a 2-month administration of transdermal clonidine patch (14 patients) or placebo (12 patients) according to a double-blind, randomized sequence. Clonidine caused a slight, nonsignificant reduction in mean arterial pressure and heart rate without affecting exercise capacity and echocardiographically determined left ventricular ejection fraction. In contrast, both plasma norepinephrine and sympathetic nerve traffic were significantly reduced (−46.8% and −26.7%, respectively;P <0.01 for both). This reduction was coupled with no change in cardiac and sympathetic baroreflex responses. Transdermal placebo administration for a 2-month period did not affect any of the above-mentioned variables. Thus, in congestive heart failure patients who are undergoing conventional drug treatment, chronic clonidine administration exerts marked sympathoinhibitory effects without adversely affecting cardiac functions and clinical state. Whether this leads to further therapeutic benefits remains to be tested.
MyoD inhibits Fstl1 and Utrn expression by inducing transcription of miR-206

Terminal differentiation of distinct cell types requires the transcriptional activation of differentiation-specific genes and the suppression of genes associated with the precursor cell. For example, the expression of utrophin (Utrn) is suppressed during skeletal muscle differentiation, and it is replaced at the sarcolemma by the related dystrophin protein. The MyoD transcription factor directly activates the expression of a large number of skeletal muscle genes, but also suppresses the expression of many genes. To characterize a mechanism of MyoD-mediated suppression of gene expression, we investigated two genes that are suppressed in fibroblasts converted to skeletal muscle by MyoD, follistatin-like 1 (Fstl1) and Utrn. MyoD directly activates the expression of a muscle-specific microRNA (miRNA), miR-206, which targets sequences in the Fstl1 and Utrn RNA, and these sequences are sufficient to suppress gene expression in the presence of miR-206. These findings demonstrate that MyoD, in addition to activating muscle-specific genes, induces miRNAs that repress gene expression during skeletal muscle differentiation.
Cough threshold in patients with chronic obstructive pulmonary disease

BACKGROUND Cough is an important symptom of patients with chronic obstructive pulmonary disease (COPD). The cough threshold to citric acid and capsaicin in patients with COPD and in normal volunteers was measured, as well as bronchial hyperresponsiveness to methacholine. METHODS Nineteen patients with COPD and 22 controls were recruited. Subjects underwent a methacholine bronchoprovocation test and a cough challenge to citric acid and capsaicin. RESULTS The log citric acid cough threshold D2 (concentration causing two coughs) was significantly lower in patients with COPD (mean 2.17 versus 2.56, mean difference (95% CI) 0.39 (0.04 to 0.74), p = 0.02) but not for capsaicin cough D2 (0.66 versus 0.8, p = 0.41). Sixteen patients with COPD had bronchial hyperresponsiveness which was correlated with baseline FEV1 (r= 0.6, p = 0.01, 95% CI 0.15 to 0.84). CONCLUSIONS Patients with COPD have a lower cough threshold to citric acid, possibly due to a differential effect of cigarette smoke on citric acid sensitive cough receptors.
A New 3D Lip Model for Analysis and Synthesis of Lip Motion In Speech Production

This work presents a methodology for 3D modeling of lip motion in speech production and its application to lip tracking and visual speech animation. Firstly, a geometric modeling allows to create a 3D lip model from 30 control points for any lip shape. Secondly, a statistical analysis, performed on a set of 10 key shapes, generates a lip gesture coding with three articulatory-oriented parameters, specific to one speaker. The choice of the key shapes is based on general phonetic observations. Finally, the application for lip tracking of the 3D model controlled by the three parameters is presented and evaluated.
Clostridium difficile and its cytotoxin in feces of patients with antimicrobial agent-associated diarrhea and miscellaneous conditions

Fecal specimens from 223 subjects were evaluated for the presence of Clostridium difficile by use of a selective medium developed in our laboratory and for the presence of C. difficile cytotoxin. C. difficile and cytotoxin were detected in 89 and 83%, respectively, of patients with antimicrobial agent-associated pseudomembranous colitis (PMC). In patients in whom PMC was not documented, C. difficile and cytotoxin were present in only 37 and 21%, respectively. C. difficile and cytotoxin were also recovered from the feces of 6 and 3, respectively, of 13 antimicrobial recipients who did not have diarrhea. Although C. difficile appears to be a major cause of PMC, it is not responsible for at least some two-thirds of cases of antimicrobial agent-associated diarrhea in which PMC is not documented. Neither the recovery of C. difficile nor the detection of its cytotoxin should be considered diagnostic for C. difficile-induced disease.
Cardiovascular Mortality in Hypertensive Men According to Presence of Associated Risk Factors

Abstract—To evaluate the risk of cardiovascular disease (CVD) mortality in hypertensive men according to the presence of associated risk factors (ARFs). The population was composed of 29640 normotensive men without ARFs (reference group) and 60343 hypertensive men (with and without ARFs) who had a standard health checkup at the Centre d’Investigations Préventives et Cliniques between 1978 and 1988. Mortality data for a mean period of 14 years were analyzed. The following ARFs were considered: total cholesterol ≥2.5 g/L, personal history of diabetes, smoking (current smokers), body mass index >28 kg/m2, and heart rate >80 bpm. CVD risk related to the presence of isolated hypertension (assessed in hypertensive subjects without ARFs versus the reference group) increased linearly from 15% at the age of 30 years to 134% at the age of 80 years. In hypertensive subjects, one additional ARF increased CVD risk by 56% (47% to 65%, P <0.01) in younger subjects but only by 4% (−8% to 17%, P =NS) in older subjects. The role of hypercholesterolemia and tobacco smoking in CVD mortality was significantly higher in hypertensive subjects aged <55 years than in hypertensive subjects aged ≥55 years (P <0.01), whereas the roles of tachycardia and obesity were not affected by age. In younger hypertensive subjects, evaluation of CVD risk and therapeutic strategies should target ARFs. In older subjects, the presence of high blood pressure levels seems to be the major determinant of CVD risk.
Putting the safety of organic food into perspective

The demand for organic foods is constantly increasing mainly due to consumers' perception that they are healthier and safer than conventional foods. There is a need for information related to food safety to inform consumers of the health benefits and/or hazards of food products of both origins, in order to optimise the impact on health and minimise the risks. Several gaps and limitations in scientific knowledge with regard to food risk evaluation make it difficult to draw generalised conclusions. Still, some organic foods can be expected to contain fewer agrochemical residues and lower levels of nitrate than conventionally grown alternatives. On the other hand, environmental contaminants are equally present in foods of both origins. With regard to other food hazards, such as natural chemicals, microbial pathogens and mycotoxins, no clear conclusions can be drawn, although several interesting points can be highlighted. It is difficult, therefore, to weigh the risks, but what should be made clear to consumers is that ‘organic’ does not equal ‘safe’. If producers adopt proper agricultural practices and consumers maintain hygienic conditions, risks associated with food contaminants can be minimised, regardless of the food's organic or conventional origin.
A novel missense-mutation-related feature extraction scheme for 'driver' mutation identification

MOTIVATION It becomes widely accepted that human cancer is a disease involving dynamic changes in the genome and that the missense mutations constitute the bulk of human genetic variations. A multitude of computational algorithms, especially the machine learning-based ones, has consequently been proposed to distinguish missense changes that contribute to the cancer progression ('driver' mutation) from those that do not ('passenger' mutation). However, the existing methods have multifaceted shortcomings, in the sense that they either adopt incomplete feature space or depend on protein structural databases which are usually far from integrated. RESULTS In this article, we investigated multiple aspects of a missense mutation and identified a novel feature space that well distinguishes cancer-associated driver mutations from passenger ones. An index (DX score) was proposed to evaluate the discriminating capability of each feature, and a subset of these features which ranks top was selected to build the SVM classifier. Cross-validation showed that the classifier trained on our selected features significantly outperforms the existing ones both in precision and robustness. We applied our method to several datasets of missense mutations culled from published database and literature and obtained more reasonable results than previous studies. AVAILABILITY The software is available online at http://www.methodisthealth. com/software and https://sites.google. com/site/drivermutationidentification/. CONTACT xzhou@tmhs.org. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Dynamics and Effective Topology Underlying Synchronization in Networks of Cortical Neurons

Cognitive processes depend on synchronization and propagation of electrical activity within and between neuronal assemblies. In vivo measurements show that the size of individual assemblies depends on their function and varies considerably, but the timescale of assembly activation is in the range of 0.1–0.2 s and is primarily independent of assembly size. Here we use an in vitro experimental model of cortical assemblies to characterize the process underlying the timescale of synchronization, its relationship to the effective topology of connectivity within an assembly, and its impact on propagation of activity within and between assemblies. We show that the basic mode of assembly activation, “network spike,” is a threshold-governed, synchronized population event of 0.1–0.2 s duration and follows the logistics of neuronal recruitment in an effectively scale-free connected network. Accordingly, the sequence of neuronal activation within a network spike is nonrandom and hierarchical; a small subset of neurons is consistently recruited tens of milliseconds before others. Theory predicts that scale-free topology allows for synchronization time that does not increase markedly with network size; our experiments with networks of different densities support this prediction. The activity of early-to-fire neurons reliably forecasts an upcoming network spike and provides means for expedited propagation between assemblies. We demonstrate this capacity by observing the dynamics of two artificially coupled assemblies in vitro, using neuronal activity of one as a trigger for electrical stimulation of the other.
Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial

Objectives To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers. Design 6-month randomized, placebo-controlled trial. Participants Ninety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45). Intervention Daily calcium carbonate (1,200 mg) and cholecalciferol [2,000–6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months. Measurements Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin. Results Participants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed. Conclusions Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12609000043235
Studies of biomarker responses to intervention with vitamin B-12: a systematic review of randomized controlled trials.

BACKGROUND Mild vitamin B-12 deficiency is common among older adults, but evidence for setting dietary recommendations is limited because most studies have administered vitamin B-12 via nonoral routes or at doses several hundred times higher than current recommendations. Furthermore, different biomarkers of vitamin B-12 status have not been systematically reviewed. OBJECTIVE The aim was to assess the effectiveness of biomarkers of vitamin B-12 status through a systematic review of published randomized controlled trials of oral vitamin B-12 supplementation. DESIGN Methods included a structured search strategy on Ovid MEDLINE, EMBASE (Ovid), and Cochrane databases; formal inclusion and exclusion criteria; data extraction; validity assessment; and meta-analysis. RESULTS Eight randomized controlled trials were included, and all studies measured serum and plasma total vitamin B-12, 3 studies measured methylmalonic acid, and 6 studies measured total homocysteine response. All 3 biomarkers were found to be effective measures of altered vitamin B-12 intake in populations with low and borderline baseline vitamin B-12 status (P < 0.00001); however, in the case of total vitamin B-12, substantial heterogeneity that could not be fully explained by subgroup analysis was observed. Insufficient data were available to determine the effectiveness of plasma holotranscobalamin, which was measured in only one randomized controlled trial. CONCLUSIONS The available evidence suggests that plasma and serum concentrations of total vitamin B-12, methylmalonic acid, and total homocysteine are all effective biomarkers of a change in vitamin B-12 intake; however, because the available data were limited, it was not possible to examine fully the factors that could explain the substantial heterogeneity in total vitamin B-12. Future trials should include low-dose vitamin B-12 in adults across the entire age spectrum and measure the holotranscobalamin response to supplementation.
Leukocyte Telomere Dynamics: Longitudinal Findings Among Young Adults in the Bogalusa Heart Study

Leukocyte telomere length (LTL) is ostensibly a biomarker of human aging. Cross-sectional analyses have found that LTL is relatively short in a host of aging-related diseases. These studies have also provided indirect estimates of age-dependent LTL shortening. In this paper, the authors report findings of the first comprehensive longitudinal study of 450 whites and 185 African Americans in Louisiana (aged 31.4 and 37.4 years at baseline (1995–1996) and follow-up (2001–2006) examinations, respectively) participating in the Bogalusa Heart Study. Rate of change in LTL was highly variable among individuals, with some displaying a paradoxical gain in LTL during the follow-up period. The most striking observation was that age-dependent LTL shortening was proportional to LTL at baseline examination. At both baseline and follow-up examinations, African Americans had longer LTLs than whites, and smokers had shorter LTLs than nonsmokers. The longer LTL in African Americans than in whites explained in part the faster rate of LTL shortening observed among African Americans. These findings underscore the complexity of leukocyte telomere dynamics in vivo and suggest that determinants in addition to the “end-replication problem” contribute to telomere shortening in vivo.
Reduction of proliferation and induction of apoptosis are associated with shrinkage of head and neck squamous cell carcinoma due to neoadjuvant chemotherapy.

BACKGROUND Neoadjuvant chemotherapy (NACT) is a treatment modality whereby chemotherapy is used as the initial treatment of HNSCC in patients presenting with advanced cancer that cannot be treated by other means. It leads to shrinkage of tumours to an operable size without significant compromise to essential oro-facial organs of the patients. The molecular mechanisms behind shrinkage due to NACT is not well elucidated. MATERIALS AND METHODS Eleven pairs of primary HNSCCs and adjacent normal epithelium, before and after chemotherapy were screened for cell proliferation and apoptosis. This was followed by immunohistochemical analysis of some cell cycle (LIMD1, RBSP3, CDC25A, CCND1, cMYC, RB, pRB), DNA repair (MLH1, p53) and apoptosis (BAX, BCL2) associated proteins in the same set of samples. RESULTS Significant decrease in proliferation index and increase in apoptotic index was observed in post-therapy tumors compared to pre-therapy. Increase in the RB/ pRB ratio, along with higher expression of RBSP3 and LIMD1 and lower expression of cMYC were observed in post-therapy tumours, while CCND1 and CDC25A remained unchanged. While MLH1 remained unchanged, p53 showed higher expression in post-therapy tumors, indicating inhibition of cell proliferation and induction of apoptosis. Increase in the BAX/BCL2 ratio was observed in post-therapy tumours, indicating up-regulation of apoptosis in response to therapy. CONCLUSIONS Thus, modulation of the G1/S cell cycle regulatory proteins and apoptosis associated proteins might play an important role in tumour shrinkage due to NACT.
VEGF is a chemoattractant for FGF-2–stimulated neural progenitors

Mmigration of undifferentiated neural progenitors is critical for the development and repair of the nervous system. However, the mechanisms and factors that regulate migration are not well understood. Here, we show that vascular endothelial growth factor (VEGF)-A, a major angiogenic factor, guides the directed migration of neural progenitors that do not display antigenic markers for neuron- or glia-restricted precursor cells. We demonstrate that progenitor cells express both VEGF receptor (VEGFR) 1 and VEGFR2, but signaling through VEGFR2 specifically mediates the chemotactic effect of VEGF. The expression of VEGFRs and the chemotaxis of progenitors in response to VEGF require the presence of fibroblast growth factor 2. These results demonstrate that VEGF is an attractive guidance cue for the migration of undifferentiated neural progenitors and offer a mechanistic link between neurogenesis and angiogenesis in the nervous system.