Miracle-dz/UniFAR-FTUs huggingface dataset:
A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival.

BACKGROUND Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients. METHODS After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan-Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes. RESULTS We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025). CONCLUSIONS Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses.
Advanced Wound Care Therapies for Nonhealing Diabetic, Venous, and Arterial Ulcers

BACKGROUND Nonhealing ulcers affect patient quality of life and impose a substantial financial burden on the health care system. PURPOSE To systematically evaluate benefits and harms of advanced wound care therapies for nonhealing diabetic, venous, and arterial ulcers. DATA SOURCES MEDLINE (1995 to June 2013), the Cochrane Library, and reference lists. STUDY SELECTION English-language randomized trials reporting ulcer healing or time to complete healing in adults with nonhealing ulcers treated with advanced therapies. DATA EXTRACTION Study characteristics, outcomes, adverse events, study quality, and strength of evidence were extracted by trained researchers and confirmed by the principal investigator. DATA SYNTHESIS For diabetic ulcers, 35 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with a biological skin equivalent (relative risk [RR], 1.58 [95% CI, 1.20 to 2.08]) and negative pressure wound therapy (RR, 1.49 [CI, 1.11 to 2.01]) compared with standard care and low-strength evidence for platelet-derived growth factors and silver cream compared with standard care. For venous ulcers, 20 trials (9 therapies) met eligibility criteria. There was moderate-strength evidence for improved healing with keratinocyte therapy (RR, 1.57 [CI, 1.16 to 2.11]) compared with standard care and low-strength evidence for biological dressing and a biological skin equivalent compared with standard care. One small trial of arterial ulcers reported improved healing with a biological skin equivalent compared with standard care. Overall, strength of evidence was low for ulcer healing and low or insufficient for time to complete healing. LIMITATIONS Only studies of products approved by the U.S. Food and Drug Administration were reviewed. Studies were predominantly of fair or poor quality. Few trials compared 2 advanced therapies. CONCLUSION Compared with standard care, some advanced wound care therapies may improve the proportion of ulcers healed and reduce time to healing, although evidence is limited. PRIMARY FUNDING SOURCE Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.
An efficient 3D NoC synthesis by using genetic algorithms

The application of 3D Network on Chip (NoC) provides an effective way for tackling the performance bottleneck for high-performance Systems on Chips (SoCs). How to design an efficient 3D Network on Chip which is satisfied with the communication requirement of 3D system and simultaneously enables significant performance enhancements has encouraged a lot of attention. In this paper, we focus on the automatic design for custom based NoC architecture by use of a novel approach. The synthesis idea is proposed to develop a minimum cost topology and an optimized floorplan to decrease the power consumption, under the hardware and software constraints. Different algorithms are used to solve the sub-problems. In the core to switch connectivity stage, we firstly use Tarjan Algorithm to find the strong connectivity part in the core communication graph, and then use the Min-cut Algorithm to partition the core communication graph into sub-graphs. To establish the switch to switch connection, we apply Genetic Algorithm (GA) to do the path computation and flow control. Finally, we use Genetic Algorithm to solve the switch position problem. Optimized positions of switches in the floorplan for minimizing the power consumption are obtained while meeting the non-overlapping constraints. The experimental results show that our proposed synthesis approach is efficient and much power saving in the application of NoC design work.
Variability of routine pulmonary function tests1

Hruby, J. and Butler, J. (1975). Thorax, 30, 548-553. Variability of routine pulmonary functon tests. Pulmonary function tests sometimes indicate a progressive deterioration and at other times a 'stepwise' worsening which may be followed by improvement. Interpretation depends on the extent of random or diurnal variations in function. Routine pulmonary function tests (VC, FEV,, FRC, and airway resistance (Raw)) were repeatedly measured in normal subjects, patients with stable irreversible airways obstruction, and patients with stable restrictive disease. In all groups there was a significant (P<0 001) diurnal variation in Raw, with high values in the morning, low values at noon, and rising values in the evening. The midday Raw values were about 80% of the highest daily values. The considerable random and diurnal variability seen in all tests is reflected in the range of high and low values (% of mean individual response) in individuals. The largest variation in an individual between measurements taken at two different times was 81% in Raw (range: 40% above to 41% below the mean). There was less variation in FEV, (29%), FRC (62%), and VC (30%). Thus the finding of a stepwise change in function could reflect its natural variability. When repeated studies are done to assess progress or the effects of therapy on disease, there are many factors, including the time of day at which the tests are performed, which should be standardized as far as possible.
ANTIBODIES TO BRUCELLA SPP. AMONG BLUE WILDEBEEST AND AFRICAN BUFFALO IN KENYA

A serologic survey of blue wildebeest (Connochaetes taurinus Burchell) and African buffalo (Syncerus caffer Sparrman) in the Masai Mara area was conducted. Antibodies to Brucella spp. were found in 18% of the blue wildebeest and 30% of the African buffalo examined. There were titers in all age groups and in both sexes. Hygromata were seen in both species. The increase in numbers of blue wildebeest and African buffalo which share grazing and watering areas with cattle of the Masai people, makes the presence of infections by Brucella spp. in wildlife an important consideration in any program for control of brucellosis.
Selenium-containing histone deacetylase inhibitors for melanoma management

Melanoma incidence and mortality rates continue to increase each year. Lack of clinically viable agents, drug combinations, effective targeted delivery approaches and success inhibiting targets in tumor tissue have made this disease one of the most difficult to treat, which makes prevention an important option for decreasing disease incidence and mortality rates. Inhibiting histone deacetylases (HDAC) is an approach currently being explored to more effectively treat melanoma but use for prevention has not been explored. In this study, novel selenium containing derivatives of the FDA approved HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) called 5-phenylcarbamoylpentyl selenocyanide (PCP-SeCN) and Bis{5-phenylcarbamoylpentyl} diselenide (B(PCP)-2Se) were created and efficacy tested for preventing early melanocytic lesion development in skin. Topical application of PCP-SeCN and B(PCP)-2Se inhibited melanocytic lesion development in laboratory-generated skin by up to 87% with negligible toxicological effect. Mechanistically, PCP-SeCN and B(PCP)-2Se inhibited HDAC activity and had new inhibitory properties by moderating Akt activity to induce cellular apoptosis as demonstrated by an increase in the sub-G0-G1 cell population, and cleaved caspase-3 as well as PARP levels. Furthermore, PCP-SeCN and B(PCP)-2Se inhibited cell proliferation by inhibiting cyclin D1 expression and increasing p21 levels. Thus, PCP-SeCN and B(PCP)-2Se are potential melanoma chemopreventive agents with enhanced efficacy compared with SAHA due to new PI3 kinase pathway inhibitory properties.
Prediction of Decreased Susceptibility to Penicillin of Neisseria meningitidis Strains by Real-Time PCR

ABSTRACT Sequence analysis of the penA gene, encoding penicillin-binding protein 2 (PBP2), in 30 penicillin-intermediate (PenI) Neisseria meningitidis strains showed altered gene sequences due to the translocation of exogenous DNA blocks derived from commensal neisseriae, which are known to have PBP2 proteins with decreased affinity for the antibiotic. In order to obtain a rapid and reproducible method for predicting the PenI phenotype, a real-time PCR assay was set up with primers and probes designed on the basis of the penA gene. The A→G mutation at codon 566, in the transpeptidase domain of the penA gene (which is present in the whole sample of 30 PenI strains and in all the 41 sequences of PenI meningococci isolated worldwide and has been deposited in the sequence databank), was chosen as a marker of penA translocations. Two hybridization probes were designed to distinguish the wild-type penA gene in penicillin-susceptible (PenS) meningococci from the mutated penA gene at codon 566 in PenI strains. Thermal analysis of probe hybridization revealed a melting temperature difference of at least 6°C between PenI and PenS strains. This real-time PCR protocol characterizes the penicillin phenotype of N. meningitidis in a few hours without DNA sequencing and is useful for rapid screening of the penicillin-intermediate genotype among meningococcal isolates.
VSIE-Based Scattering Parameter Analysis for a Tunable Bandpass Filter With a PET-Controlled Magnetodielectric Perturber

Electromagnetic analysis with $S$ -parameter characteristic is carried out for a tunable bandpass filter with a magnetodielectric perturber controlled by a piezoelectric transducer. The filter consists of a hairpin-like microstrip resonator and a perturber as a superstrate, which is composed of thin ferrite film with a high permeability and Rogers dielectric material with a high permittivity in a sandwich style. The structure is of multiscale feature because the thickness of the thin film is very small but cannot be ignored and also of multimaterial property because there are three strongly different materials. The problem can be governed through surface integral equations in the integral equation approach, but we use volume-surface integral equations to formulate it so that the conditioning of impedance matrix can be improved in the method of moments (MoM) solution. In addition, the dyadic Green's function is kept in its original form in the implementation of MoM and thus the problems in the traditional MoM can be overcome. Numerical examples are presented to illustrate the approach and good results can be observed.
The Influence of Cervical Muscle Characteristics on Head Impact Biomechanics in Football

Background: An athlete is thought to reduce head acceleration after impact by contracting the cervical musculature, which increases the effective mass of the head. Purpose: To compare the odds of sustaining higher magnitude in-season head impacts between athletes with higher and lower preseason performance on cervical muscle characteristics. Study Design: Cohort study; Level of evidence, 2. Methods: Forty-nine high school and collegiate American football players completed a preseason cervical testing protocol that included measures of cervical isometric strength, muscle size, and response to cervical perturbation. Head impact biomechanics were captured for each player using the Head Impact Telemetry System. A median split was used to categorize players as either high or low performers for each of the following outcome measures: isometric strength (peak torque, rate of torque development), muscle size (cross-sectional area), and response to cervical perturbation (stiffness, angular displacement, muscle onset latency). The odds of sustaining moderate and severe head impacts were computed against the reference odds of sustaining mild head impacts across cervical characteristic categorizations. Results: Linemen with stronger lateral flexors and composite cervical strength had about 1.75 times’ increased odds of sustaining moderate linear head impacts rather than mild impacts compared with weaker linemen. Players who developed extensor torque more quickly had 2 times the increased odds of sustaining severe linear head impacts (odds ratio [OR], 2.10; 95% CI, 1.08-4.05) rather than mild head impacts. However, players with greater cervical stiffness had reduced odds of sustaining both moderate (OR, 0.77; 95% CI, 0.61-0.96) and severe (OR, 0.64; 95% CI, 0.46-0.89) head impacts compared with players with less cervical stiffness. Conclusion: The study findings showed that greater cervical stiffness and less angular displacement after perturbation reduced the odds of sustaining higher magnitude head impacts; however, the findings did not show that players with stronger and larger neck muscles mitigate head impact severity.
Impaired Immune Function in a Homeless Population with Stress-Related Disorders

Objective: Homeless people suffer high levels of psychological distress. The aim of the present work was to study the immune function in a group of homeless people with stress-related disorders and compare it with that of healthy non-homeless controls. Methods: We included in the study 40 homeless persons and 40 housed controls recruited from the population of Madrid and matched for age and gender. Samples from peripheral blood were collected and we studied several leukocyte functions previously described as good health and survival markers [adherence, chemotaxis, phagocytosis, superoxide anion levels, lymphocyte proliferation in response to phytohemagglutinin, NK activity and cytokine (IL-2, TNF-α) levels], as well as other related parameters, such as plasma cortisol levels and total antioxidant capacity. Results: There was a strongly suppressed immune response in the homeless group, with decreased adherence, chemotaxis, phagocytosis, superoxide levels, lymphoproliferation and NK activity. IL-2 and plasma antioxidant levels were also impaired. Conclusions: These findings suggest an altered immune function in the homeless population that might be responsible for the higher morbidity and mortality of homeless people. In addition, the present work points out directions for future research attempting to increase the quality of life and health status of homeless individuals, since it shows that oxidative stress seems to play a key role in this immune function impairment.
Elevation of cortical serotonin transporter activity upon peripheral immune challenge is regulated independently of p38 mitogen‐activated protein kinase activation and transporter phosphorylation

The serotonin transporter (SERT) is responsible for high‐affinity serotonin (5‐HT) uptake from extracellular fluid and is a prominent pharmacological target in the treatment of depression. In recent years, depression has also been linked to immune system activation. Inflammatory conditions can cause sickness behaviour and depression‐like symptoms in both animals and humans. Since SERT has been proposed as one of the molecular targets in inflammation‐induced depression, we applied the widely used lipopolysaccharides (LPS) model to study the effects of peripheral inflammation on SERT activity in the brain. We show that 24 h after intraperitoneal LPS administration, SERT‐mediated 5‐HT uptake is significantly enhanced in the frontal cortex. Analysis of uptake kinetics revealed that the transport capacity (Vmax) of cortical SERT was increased in LPS‐injected animals, while the Km value remained unchanged. The increase in Vmax was neither due to increased SERT protein expression nor increased synaptic surface exposure. The suppression of SERT activity upon inhibition of p38 MAPK was not selective for LPS‐induced enhancement of SERT function. In addition, SERT activity changes in LPS‐treated rats are unaffected by nitric oxide synthase and protein kinase G inhibitors. Using the Phos‐Tag method, we identified five SERT‐specific protein bands representing distinct phosphorylation states of SERT. However, the enhancement of SERT activity in LPS‐treated rats was not correlated with altered transporter phosphorylation. Together with previous studies by others, our results suggest that SERT is regulated by multiple mechanisms in response to peripheral immune system activation.
Heterogeneity of Depressive Symptom Trajectories through Adolescence: Predicting Outcomes in Young Adulthood.

OBJECTIVE This study describes developmental trajectories of depressive symptoms in adolescents and examines the association between trajectory group and mental health outcomes in young adulthood. METHODS Depressive symptoms were self-reported every three months from grade seven through grade 11 by 1293 adolescents in the Nicotine Dependence in Teens (NDIT) study and followed in young adulthood (average age 20.4, SD=0.7, n=865). Semi-parametric growth modeling was used to identify sex-specific trajectories of depressive symptoms. RESULTS THREE DISTINCT TRAJECTORY GROUPS WERE IDENTIFIED: 50% of boys and 29% of girls exhibited low, decreasing levels of depressive symptoms; 14% of boys and 28% of girls exhibited high and increasing levels; and 36% of boys and 43% of girls exhibited moderate levels with linear increase. Trajectory group was a statistically significant independent predictor of depression, stress, and self-rated mental health in young adulthood in boys and girls. Boys, but not girls, in the high trajectory group had a statistically significant increase in the likelihood of seeking psychiatric care. CONCLUSIONS Substantial heterogeneity in changes in depressive symptoms over time was found. Because early depressive symptoms predict mental health problems in young adulthood, monitoring adolescents for depressive symptoms may help identify those most at risk and in need of intervention.
The effect of somatic symptom attribution on the prevalence rate of depression and anxiety among nursing home patients

The validity of diagnostic psychiatric instruments for depression and anxiety disorders may be compromised among patients with complex physical illness and disability. The objective of this study was to determine the effect on the prevalence rate of depression and anxiety in a nursing home population of attributing somatic symptoms of depression and anxiety to either somatic or psychiatric disorder. Symptoms of major depression (MD), generalized anxiety disorder (GAD) and panic disorder (PD) were measured using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Somatic symptoms of MD, GAD and PD were attributed to somatic causes when the interviewer was not sure about a psychiatric cause. To analyse the effect of this attribution on the prevalence rate of MD, GAD and PD, a sensitivity analysis was undertaken in which symptoms that were attributed to somatic causes were recoded as symptoms attributed to psychiatric disorder. Prevalence rates of MD, GAD and PD were calculated before and after recoding.
Evidence for Multiple-Antibiotic Resistance in Campylobacter jejuni Not Mediated by CmeB or CmeF

ABSTRACT An efflux system, CmeABC, in Campylobacter jejuni was previously described, and a second efflux system, CmeDEF, has now been identified. The substrates of CmeDEF include ampicillin, ethidium bromide, acridine, sodium dodecyl sulfate (SDS), deoxycholate, triclosan, and cetrimide, but not ciprofloxacin or erythromycin. C. jejuni NCTC11168 and two efflux pump knockout strains, cmeB::Kanr and cmeF::Kanr, were exposed to 0.5 to 1 μg of ciprofloxacin/ml in agar plates. All mutants arising from NCTC11168 were resistant to ciprofloxacin but not to other agents and contained a mutation resulting in the replacement of threonine 86 with isoleucine in the quinolone resistance-determining region of GyrA. Mutants with two distinct phenotypes were selected from the efflux pump knockout strains. Mutants with the first phenotype were resistant to ciprofloxacin only and had the same substitution within GyrA as the NCTC11168-derived mutants. Irrespective of the parent strain, mutants with the second phenotype were resistant to ciprofloxacin, chloramphenicol, tetracycline, ethidium bromide, acridine orange, and SDS and had no mutation in gyrA. These mutants expressed levels of the efflux pump genes cmeB and cmeF and the major outer membrane protein gene porA similar to those expressed by the respective parent strains. No mutations were detected in cmeF or cmeB. Accumulation assays revealed that the mutants accumulated lower concentrations of drug. These data suggest the involvement of a non-CmeB or -CmeF efflux pump or reduced uptake conferring multiple-antibiotic resistance, which can be selected after exposure to a fluoroquinolone.
Folate, homocysteine, vitamin B12, and polymorphisms of genes participating in one-carbon metabolism in late-onset Alzheimer's disease patients and healthy controls.

AIMS We screened 378 late-onset Alzheimer's disease (LOAD) patients and 308 matched controls for the presence of the common MTHFR 677C>T, MTRR 66A>G, MTR 2756 A>G, and TYMS 28 bp repeat polymorphisms, searching for association with disease risk and age at onset. Moreover, we searched for correlation between each of the studied polymorphisms and available data on plasma homocysteine (Hcy), serum folate, and vitamin B12 values. RESULTS We observed a significant increased frequency of the MTHFR 677T allele (0.48 vs. 0.42; p=0.019) and of MTHFR 677CT (OR=1.46; 95%CI=1.03-2.06) and TT genotypes (OR=1.62; 95%CI=1.05-2.49) in LOAD subjects with respect to controls. We also observed a significant increased frequency of the MTRR 66G allele (0.49 vs. 0.43; p=0.044) and of the MTRR 66GG genotype (OR=1.57; 95%CI=1.01-2.46) in the LOAD group. Significantly increased mean plasma Hcy levels (22.7±1.7 vs 14.5±1.7 μmol/L; p=0.037) and decreased serum folate values (5.7±0.5 vs. 7.8±0.8 ng/mL; p=0.005) were observed in LOAD subjects with respect to controls, whilst the difference in serum vitamin B12 values did not reach statistical significance. Several interactions between the studied polymorphisms and biochemical biomarkers were observed. None of the studied polymorphisms was associated with disease age at onset. INNOVATION The present study suggests that the MTRR 66G allele might contribute to LOAD risk and confirms an increased frequency of the MTHFR 677T allele in LOAD. CONCLUSION Overall, present results support a contribution for one-carbon metabolism to LOAD pathogenesis.