Miracle-dz/UniFAR-FTUs huggingface dataset:
Dopaminergic responses in the Fischer 344 rat heart: preserved chronotropic and dromotropic responses with aging.

BACKGROUND Marked decreases in cardiac responses to beta-adrenergic stimuli have been found in cellular, animal, and human models of physiologic aging. As another probe of receptor-regulated cardiovascular changes with aging, responses to dopamine were studied. Responses were studied with and without depletion of myocardial catecholamines to eliminate effects secondary to myocardial catecholamine release. METHODS Responses of heart rate (A-A intervals), atrioventricular conduction (AV intervals and AV Wenckebach block cycle length) to 0-50 microM dopamine were studied in Langendorff perfused hearts from 10 mature (6.2 +/- 0.8 mo, mean +/- SD) and 9 senescent (23.6 +/- 0.7 mo) Fischer 344 rats and in hearts from 10 mature (5.3 +/- 0.4 mo) and 8 senescent (23.9 +/- 0.8) Fischer 344 rats after myocardial catecholamine depletion by reserpine (0.25 mg/kg i.p. x 5 days). RESULTS Dopamine decreased A-A (p < .0001) and AV conduction intervals (p < .0001) and increased peak developed pressure (p < .0001) and dP/dt (p < .001) in hearts from nonreserpine treated mature and senescent rats. Greater decreases in A-A intervals and AV conduction were seen in senescent compared to mature hearts (p < .0001). Contractile responses were greater in mature hearts (p < .001). After reserpine, A-A interval and paced AV conduction dose vs response relationships shifted rightward (p < .0001), but peak responses and age-related differences in responses were not significantly affected. In contrast, increases in peak developed pressure were greatly reduced in mature hearts (p < .0001) and age-related differences in contractile responses to dopamine were eliminated in hearts from reserpine-treated rats. CONCLUSIONS (a) A-A interval and AV conduction responses to dopamine were greater in senescent hearts even after catecholamine depletion, suggesting age-related differences in sinus and AV nodal responses to direct dopaminergic stimuli exist. (b) Age-related differences in contractile responses to dopamine were eliminated by reserpine suggesting basal age-related differences in response were secondary to age-related differences in responses to myocardial catecholamine release.
A Study Evaluating the Bidirectional Relationship Between Inflammatory Bowel Disease and Self-reported Non-celiac Gluten Sensitivity

Background:Non-celiac gluten sensitivity and the associated use of a gluten-free diet (GFD) are perceived to belong to the spectrum of irritable bowel syndrome (IBS). However, recent reports suggest substantial use of a GFD in inflammatory bowel disease (IBD). We assessed the bidirectional relationship between IBD and self-reported non-celiac gluten sensitivity (SR-NCGS). Methods:A cross-sectional questionnaire screened for SR-NCGS and the use of a GFD in 4 groups: ulcerative colitis (n = 75), Crohn's disease (n = 70), IBS (n = 59), and dyspeptic controls (n = 109). We also assessed diagnostic outcomes for IBD in 200 patients presenting with SR-NCGS. Results:The prevalence of SR-NCGS was 42.4% (n = 25/59) for IBS, followed by 27.6% (n = 40/145) for IBD, and least among dyspeptic controls at 17.4% (n = 19/109); P = 0.015. The current use of a GFD was 11.9% (n = 7/59) for IBS, 6.2% (n = 9/145) for IBD, and 0.9% (1/109) for dyspeptic controls; P = 0.02. No differences were established between ulcerative colitis and Crohn's disease. However, Crohn's disease patients with SR-NCGS were significantly more likely to have stricturing disease (40.9% versus 18.9%, P = 0.046), and higher mean Crohn's Disease Activity Index score (228.1 versus 133.3, P = 0.002), than those without SR-NCGS. Analysis of 200 cases presenting with SR-NCGS suggested that 98.5% (n = 197) could be dietary-related IBS. However, 1.5% (n = 3) were found to have IBD; such patients had associated alarm symptoms, and/or abnormal blood parameters, prompting colonic investigations. Conclusions:SR-NCGS is not only exclusive to IBS but also associated with IBD, where its presence may be reflecting severe or stricturing disease. Randomized studies are required to further delineate the nature of this relationship and clarify whether a GFD is a valuable dietetic intervention in selected IBD patients.
Effects of inulin on performance, egg quality, gut microflora and serum and yolk cholesterol in laying hens

1. The present study was conducted to investigate the effects of inulin on laying hens. A total of 360 Brown Nick laying hens were divided randomly into 6 groups of 60 with 6 replicates of 10 hens and fed on diets containing 0 (control), 0·1, 0·5, 1·0, 1·5 or 2·0% inulin during the 4-week trial. 2. Dietary supplementation of inulin reduced cholesterol concentration (mg/g yolk) and content (mg/egg) in eggs. Cholesterol content in eggs decreased linearly with increasing levels of dietary inulin level. 3. Supplementation of inulin in diets decreased coliform bacteria counts and pH in the caecum. The lowest coliform bacteria counts (6·30 ± 0·03 log10 cfu/g) and pH (6·47 ± 0·01) were obtained in the 2·0% inulin group, the two indices decreasing by 21·6% and 3·0% respectively, compared with the control group. Coliform bacteria count and pH were changed linearly in accordance with increasing levels of dietary inulin level. Caecal Bifidobacteria counts were increased in the 2·0%-inulin group. 4. Inulin supplementation of layer diets did not appear to have any adverse effects on laying rate, egg weight, feed intake, feed conversion efﬁciency, cracked-egg rate, eggshell thickness or Haugh unit compared with the control laying hens. 5. Therefore, dietary supplementation with inulin may lead to the development of low-cholesterol chicken eggs as demanded by health-conscious consumers.
Comparison of a low‐energy diet and a very low‐energy diet in sedentary obese individuals: a pragmatic randomized controlled trial

There is no consensus on whether ‘very low‐energy diets’ (VLED; <800 kcal d−1) cause greater weight loss in obese individuals than ‘low‐energy diets’ (LED; 800–1200 kcal d−1). The objective was to determine whether a very low‐energy formula diet would cause greater weight loss than a formula 810 kcal d−1 LED in older sedentary individuals. This is a pragmatic randomized controlled trial. Inclusion criteria: obesity (body mass index [BMI] > 30); age >50 years, with knee osteoarthritis. Participants were randomized to VLED (420–554 kcal d−1) or LED (810 kcal d−1) for 8 weeks, followed by a fixed‐energy (1200 kcal d−1) diet with food and two diet products daily for 8 weeks. In all, 192 participants were randomized. Mean age was 63 years (standard deviation: 6), mean weight 103.2 kg (15.0) and BMI of 37.3 kg m−2 (4.8) at baseline. Mean weight losses in VLED and LED groups were 11.4 kg (standard error: 0.5) and 10.7 kg (0.5) at week 8 and 13.3 kg (0.7) and 12.2 kg (0.6) at week 16. Mean differences between groups were 0.76 kg (95% confidence interval: −0.59 to 2.10; P = 0.27) and 1.08 kg (−0.66 to 2.81; P = 0.22) at 8 and 16 weeks, respectively. Loss of lean body mass was 2.1 kg (0.2) and 1.2 kg (0.4) (17% and 11% of the weight lost, respectively) at week 16 in the VLED and LED group with a mean difference of 0.85 kg (0.01 to 1.69; P = 0.047). Significant adverse effects comparing VLED and LED, were bad breath: 34 (35%) vs. 21 (22%), intolerance to cold: 39 (41%) vs. 17 (18%) and flatulence: 43 (45%) vs. 28 (29%) for VLED and LED at 8 weeks (P < 0.05 in all cases). The VLED and LED regimens were equally successful in inducing weight loss. The significantly lower loss of lean tissue in the LED group together with more frequently reported side effects in the VLED group, favours the choice of low‐energy diet (LED) for the treatment of obesity.
Serial measurement of interleukin-6, transforming growth factor-beta, and S-100 protein in patients with acute stroke.

BACKGROUND AND PURPOSE Cytokine changes in patients with acute stroke have been insufficiently studied. The purpose of this study was to delineate the characteristics of serial changes of serum interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) in patients with cerebral infarction and intracerebral hemorrhage. METHODS We serially (within 24 hours, at day 3, and at day 7) measured the serum levels of IL-6 and TGF-beta in 29 patients with acute stroke (10 with large cortical cerebral infarction, 9 with subcortical small infarction, and 10 with intracerebral hemorrhage). As an index of brain damage. S-100 protein was also measured. Twelve age-matched healthy subjects were tested as a control. RESULTS S-100 protein was detected in only 11 patients with large infarction or intracerebral hemorrhage. Its level peaked at day 3 in patients with infarction, whereas it peaked within 24 hours in those with intracerebral hemorrhage. The level of IL-6 was most markedly elevated at day 1, which tended to decrease thereafter. However, its level remained significantly elevated compared with that of the control group even at day 7. The level of TGF-beta was significantly decreased at day 1 and day 3 and tended to return toward the control value thereafter. The levels of both cytokines were not significantly different among the three different stroke subtypes and were not correlated with the number of blood leukocytes and platelets. CONCLUSIONS The alteration of IL-6 and TGF-beta levels, which occurs rapidly after acute stroke regardless of the subtype, may reflect the changing immunological-inflammatory status of these patients and does not appear to reflect merely the consequence of the brain damage.
On the Benzodiazepine Binding Pocket in GABAA Receptors*

Benzodiazepines are used for their sedative/hypnotic, anxiolytic, muscle relaxant, and anticonvulsive effects. They exert their actions through a specific high affinity binding site on the major inhibitory neurotransmitter receptor, the γ-aminobutyric acid, type A (GABAA) receptor channel, where they act as positive allosteric modulators. To start to elucidate the relative positioning of benzodiazepine binding site ligands in their binding pocket, GABAA receptor residues thought to reside in the site were individually mutated to cysteine and combined with benzodiazepine analogs carrying substituents reactive to cysteine. Direct apposition of such reactive partners is expected to lead to an irreversible site-directed reaction. We describe here the covalent interaction of α1H101C with a reactive group attached to the C-7 position of diazepam. This interaction was studied at the level of radioactive ligand binding and at the functional level using electrophysiological methods. Covalent reaction occurs concomitantly with occupancy of the binding pocket. It stabilizes the receptor in its allosterically stimulated conformation. Covalent modification is not observed in wild type receptors or when using mutated α1H101C-containing receptors in combination with the reactive ligand pre-reacted with a sulfhydryl group, and the modification rate is reduced by the binding site ligand Ro15-1788. We present in addition evidence that γ2Ala-79 is probably located in the access pathway of the ligand to its binding pocket.
Improved Spectral Clustering Using Adaptive Mahalanobis Distance

In this paper, we consider the manifold clustering problem. In manifold clustering, data are sampled from multiple manifolds and the goal is to partition the data accordingly. Spectral clustering algorithms have been developed to solve this problem, but they tend to fail when the underlying manifolds are very close to each other and/or they intersect. We propose an improvement to spectral clustering algorithms using adaptive neighborhoods computed using Mahalanobis distance. We show the effectiveness of this approach on some artificial data. We further incorporate the modification into recent related algorithms and compare the results on datasets in motion segmentation, handwritten digit recognition, and object rotation.
Activation of the Phosphatidylinositol 3-Kinase-Akt/Protein Kinase B Signaling Pathway in Arachidonic Acid-stimulated Human Myeloid and Endothelial Cells

Although arachidonic acid has been demonstrated to stimulate a wide variety of cellular functions, the responsible mechanisms remain poorly defined. We now report that arachidonic acid stimulated the activity of class Ia phosphatidylinositol 3-kinase (PI3K) in human umbilical vein endothelial cells, HL60 cells, and human neutrophils. Pretreatment of endothelial cells with AG-1478, an inhibitor of the ErbB receptor family, resulted in the suppression of PI3K activation by arachidonic acid. The fatty acid enhanced the tyrosine phosphorylation of ErbB4 but not of ErbB2 or ErbB3. The ability of arachidonic acid to stimulate PI3K activity in neutrophils was suppressed by indomethacin and nordihydroguaiaretic acid, inhibitors of the cyclooxygenases and lipoxygenases, respectively, but not by 17-octadecynoic acid, an inhibitor of ω-hydroxylation of arachidonic acid by cytochrome P450 monooxygenases. Consistent with this, the activity of PI3K in neutrophils was stimulated by 5-hydroxyeicosatetraenoic acid. Arachidonic acid also transiently stimulated the phosphorylation of Akt on Thr-308 and Ser-473. Although PI3K was not required for the activation of the mitogen-activated protein kinases, ERK1, ERK2, and p38, in arachidonic acid-stimulated neutrophils, the fatty acid acted via PI3K to stimulate the respiratory burst. These results not only define a novel mechanism through which some of the actions of arachidonic acid are mediated but also demonstrate that, in addition to ErbB1 (epidermal growth factor receptor), ErbB4 can also be transactivated by a non-epidermal growth factor-like ligand.
Analysis of Immune Responses against a Wide Range of Mycobacterium tuberculosis Antigens in Patients with Active Pulmonary Tuberculosis

ABSTRACT Characterizing host immune responses to molecular targets of Mycobacterium tuberculosis is essential to develop effective immunodiagnostics and better vaccines. We investigated the immune response against a large series of M. tuberculosis antigens, including 5 classical and 64 nonclassical (39 DosR regulon-encoded, 4 resuscitation-promoting factor [RPF], and 21 reactivation-associated) antigens in active-pulmonary-tuberculosis (TB) patients. Whole blood from TB patients (n = 34) was stimulated in vitro with M. tuberculosis antigens. Gamma interferon (IFN-γ) was measured after 7 days of stimulation, using an enzyme-linked immunosorbent assay (ELISA). The majority of the study participants responded to the classical M. tuberculosis antigens TB10.4 (84.8%), early secreted antigenic target-6 kDa (ESAT-6)/CFP-10 (70.6%), and purified protein derivative (PPD) (55.9%). However, only 26.5% and 24.2% responded to HSP65 and Ag85A/B, respectively. Of the 64 nonclassical antigens, 23 (33.3%) were immunogenic (IFN-γ levels, >62 pg/ml) and 8 were strong inducers of IFN-γ (IFN-γ levels, ≥100 pg/ml). The RPF antigens were the most immunogenic. In addition, we observed distinct cytokine expression profiles in response to several M. tuberculosis antigens by multiplex immunoassay. Tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), and IL-6 were commonly detected at high levels after stimulation with 4/15 latency antigens (Rv0081, Rv2006, Rv2629, and Rv1733c) and were found especially in supernatants of the three strong IFN-γ inducers (Rv2629, Rv1009, and Rv2389c). IL-8, IL-6, and IL-17 were exclusively detected after stimulation with Rv0574c, Rv2630, Rv1998, Rv054c, and Rv2028c. In conclusion, in active-pulmonary-TB patients, we identified 23 new immunogenic M. tuberculosis antigens. The distinct expression levels of IFN-γ, TNF-α, IL-6, and IL-10 in response to specific subsets of M. tuberculosis antigens may be promising for the development of immunodiagnostics.
Direct Sequencing and Characterization of a Clinical Isolate of Epstein-Barr Virus from Nasopharyngeal Carcinoma Tissue by Using Next-Generation Sequencing Technology

ABSTRACT Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting that EBV plays an important role in tumorigenesis. However, the nature of EBV with respect to genome width in vivo and whether EBV undergoes clonal expansion in the tumor tissues are still poorly understood. In this study, next-generation sequencing (NGS) was used to sequence DNA extracted directly from the tumor tissue of a patient with NPC. Apart from the human sequences, a clinically isolated EBV genome 164.7 kb in size was successfully assembled and named GD2 (GenBank accession number HQ020558). Sequence and phylogenetic analyses showed that GD2 was closely related to GD1, a previously assembled variant derived from a patient with NPC. GD2 contains the most prevalent EBV variants reported in Cantonese patients with NPC, suggesting that it might be the prevalent strain in this population. Furthermore, GD2 could be grouped into a single subtype according to common classification criteria and contains only 6 heterozygous point mutations, suggesting the monoclonal expansion of GD2 in NPC. This study represents the first genome-wide analysis of a clinical isolate of EBV directly extracted from NPC tissue. Our study reveals that NGS allows the characterization of genome-wide variations of EBV in clinical tumors and provides evidence of monoclonal expansion of EBV in vivo. The pipeline could also be applied to the study of other pathogen-related malignancies. With additional NGS studies of NPC, it might be possible to uncover the potential causative EBV variant involved in NPC.
Cervical cancer response to neoadjuvant therapy: MR imaging assessment.

PURPOSE To determine the accuracy of magnetic resonance (MR) imaging in evaluating the invasive cervical carcinoma response to concurrent chemotherapy and radiation therapy. MATERIALS AND METHODS MR imaging was performed before and after concurrent chemotherapy and radiation therapy in 18 patients with locally invasive cervical carcinoma. Surgery followed neoadjuvant therapy in all patients. The presence of a lesion, signal intensity, zonal anatomy integrity, vaginal and parametrial invasion, and lymph node enlargement was determined. Posttreatment MR and histopathologic findings were correlated. RESULTS Fourteen patients had histopathologic confirmation of MR findings: Twelve had true-negative and two had true-positive findings. (Two had microscopic neoplastic foci beyond the spatial resolution of MR images; these foci do not change surgical treatment planning and probably do not influence prognosis. Therefore, these two patients were considered to have complete response). Four patients had false-positive findings; the hyperintense lesion on posttreatment MR images was due to a tunnel cluster pattern (focal hyperplasia of the endocervical glands with inflammation) in three patients and necrosis in one patient, without any evidence of neoplastic tissue. Thirty-three of 36 parametrial halves and 67 of 72 vaginal fornices were correctly interpreted on posttreatment images. Involvement of three parametrial halves and five fornices was overestimated at MR, because edema or inflammation was not distinguishable from tumor. CONCLUSION MR imaging is 78% accurate in evaluation of tumor response; in 22% of patients, however, benign conditions were not distinguishable from tumor.
Effects of dietary phosphate restriction and phosphate binders on FGF23 levels in CKD.

BACKGROUND Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this 2×2 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline. RESULTS Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet × time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC × time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet × LC × time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end. CONCLUSION The combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 3-4 and normal serum phosphate levels.
Local Police Departments, 2013: Personnel, Policies, and Practices

A s of January 1, 2013, the more than 12,000 local police departments in the United States employed an estimated 605,000 persons on a full-time basis (figure 1). This total included about 477,000 sworn officers (those with general arrest powers) and about 128,000 nonsworn employees. Since 1987, the number of full-time local police employees has increased by about 156,000 (up 35%). The increase includes about 122,000 (up 34%) more local police officers. Findings are based on the 2013 Law Enforcement Management and Administrative Statistics (LEMAS) Survey sponsored by the Bureau of Justice Statistics (BJS). The LEMAS Survey, conducted periodically since 1987, collects data on a range of topics from a nationally representative sample of state and local law enforcement agencies. Prior to the 2013 survey, the most recent LEMAS Survey was conducted in 2007. This report uses selected variables from the 2013 LEMAS data to describe the personnel, policies, and practices of local police departments. Comparisons are made with prior years where appropriate and when data are available.
Disparities in women's health across a generation: a mother-daughter comparison.

BACKGROUND The U.S. Centers for Disease Control and Prevention has set national goals to eliminate health disparities by race, sex, and socioeconomic status. Progress in meeting these goals has been mixed. This paper provides a different view on the evolving health of U.S. women by examining a sample of daughters and their mothers. METHODS The aim was to determine if the health risk profiles of daughters (born 1975-1992) were different from their mothers (born 1957-1964) measured when both were between the ages of 17 and 24 years. The U.S.-based National Longitudinal Survey of Youth 1979 and associated Children and Young Adult Surveys were used. The sample was 2411 non-Hispanic white and African American girls born to 1701 mothers. Outcomes were height, weight, body mass index (BMI), age of menarche, and self-reported health. RESULTS In both races, daughters were taller but entered adulthood at greater risk for the development of chronic illness than their mothers. Racial differences were greater in the daughters' generation than in the mothers'. Whites in both generations experienced educational differences in health based upon the mother's educational level, with fewer years of maternal education associated with poorer health. African Americans of both generations experienced differences by maternal education in self-reported health. However, when African American daughters were compared with their mothers, daughters born to college educated women gained more weight and had higher BMI and earlier menarche than did daughters born to high school dropouts. CONCLUSION Health deterioration across generations in both races suggests that much work is needed to meet Healthy People 2020 goals of health equity.