Miracle-dz/UniFAR-FTUs huggingface dataset:
Progression of Parkinson's disease is associated with gut dysbiosis: Two-year follow-up study

Background We previously reported gut dysbiosis in patients with Parkinson’s disease (PD). Objective The aim of this study is to examine whether gut dysbiosis correlates with the progression of PD. Methods We examined changes in gut microbiota and demographic features in 2 years in 36 PD patients. Results A change of total UPDRS scores in 2 years was predicted by the counts of Bifidobacterium and Atopobium cluster at year 0 with a correlation coefficient of 0.52. Correlation analysis additionally revealed that low counts of Bifidobacterium and Bacteroides fragilis at year 0 were associated with worsening of UPDRS I scores in 2 years. In addition, low counts of Bifidobacterium at year 0 were associated with worsening of hallucinations/delusions in 2 years. Similarly, low counts of B. fragilis at year 0 were associated with worsening of motivation/initiative in 2 years. The patients were evenly divided into the deteriorated and stable groups based on the degree of worsening of total UPDRS scores. The deteriorated group had lower counts of Bifidobacterium, B. fragilis, and Clostridium leptium than the stable group at year 0 but not at year 2, suggesting that the deteriorated group may demonstrate accelerated lowering of these bacteria at year 0. Conclusions The total counts of intestinal bacterial decrease in the course of PD progression. Temporal profiles of lowering of bacterial counts are likely to be different from bacteria to bacteria, and also between the deteriorating and stable groups, which may be able to be exploited to differentiate patients with rapidly and slowly progressive PD pathology.
Hepatocyte growth factor activates quiescent skeletal muscle satellite cells in vitro

The effect of hepatocyte growth factor (HGF) on the activation of quiescent rat skeletal muscle satellite cells was evaluated in vitro. Satellite cells from 9‐month‐old adult rats are quiescent in vivo and when cultured, display a protracted lag phase prior to division that is not present in satellite cells from neonatal or regenerating muscle. Under normal growth conditions, satellite cells divide for the first time between 42 and 60 hr. Hepatocyte growth factor increased proliferation in a dose‐dependent fashion prior to 48 hr with half‐maximal stimulation at approximately 3 ng/ml; in addition, heparin enhanced this activity. The time course of cyclin‐D1 and proliferating cell nuclear antigen (PCNA) expression was accelerated in HGF‐treated satellite cells, indicating that cells entered the cell cycle earlier. No significant effects on muscle‐derived fibroblast proliferation was observed. The signalling receptor for HGF is the product of the c‐met protooncogene, and rtPCR analysis of satellite cells 0–72 hr in culture demonstrated the presence of this message throughout this time period. The presence of c‐met in quiescent satellite cells, the ability of HGF to stimulate precocious entry into the cell cycle, and the previously described localization of HGF message in regenerating muscle (Jennische et al., 1993) indicate that HGF could act as an activator of quiescent satellite cells in vivo. © 1995 Wiley‐Liss, Inc.
Attitudes of Staff Towards Patients With Personality Disorder in Community Mental Health Teams

Objective: The purpose of the present paper was to assess the attitudes of clinicians working with personality disordered patients. Methods: Secondary analysis of the Comorbidity of Substance Misuse and Mental Illness Collaborative (COSMIC) data set was undertaken using a priori hypothesis testing. The null hypothesis was that there would be no measurable difference between the attitudes of mental health professionals toward patients with a clinical diagnosis of personality disorder and those with an instrument-rated diagnosis of personality disorder. The potential confounders of global psychopathology, need, social functioning and documented aggression were assessed as possible reasons explaining a rejection of the null hypothesis. Results: Clinicians believed those with the clinical diagnostic label of personality disorder to be more difficult to manage than personality-disordered patients identified by a research tool who did not carry this label. These attitudes were not explained by the potential confounders of psychopathology, social morbidity or acts of aggression. Conclusions: An awareness of a personality disorder diagnosis is associated with a clinician belief that patients will be harder to manage. Objective measures of potential confounders do not explain why this group should be harder to manage. One explanation of this finding is that the label ‘personality disorder’ is stigmatizing. This may also explain the disparity between clinical and research assessments of personality disorder.
Expression patterns of the retinal development-related genes in the fetal and adult retina.

BACKGROUND Retina is important in converting light into neural signals, but little is known about the regulatory genes essential for the retinal morphological formation, development and functional differentiation. This study aimed to investigate the mRNA expression patterns and cellular or subcellular distribution of 33 differentially expressed genes in the retina belonging to the early and middle-late embryogenesis stages as well as the early adult stage during human development. METHODS In situ hybridization and real-time fluorescent quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) were used to assay 33 differentially expressed genes which were screened out using microarray analysis and were not present in the retinal cDNA or the Expressed Sequence Tags (EST) database of the National Eye Institute (NEI) Genebank. RESULTS Nine of the 33 genes belonged to EST or the unknown cDNA fragments, and the remaining belonged to the novel genes in the retina. During the human retinal development 17 genes were down-regulated, 6 were up-regulated and the remaining 10 were relatively unchanged. Most of the genes expressed in all layers of the retina at the gestation stage, and in the fully developed retina some genes examined did show higher expression level in certain specific cells and structures such as retinal ganglion cells or the outer segment of photoreceptor cells. CONCLUSION The gene expression profile during retinal development possesses temporal and spatial distribution features, which can provide experimental evidence for further research of the functions of those genes.
Microfluidic PCR Combined with Pyrosequencing for Identification of Allelic Variants with Phenotypic Associations among Targeted Salmonella Genes

ABSTRACT A novel targeted massive parallel sequencing approach identified genetic variation in eight known or predicted fimbrial adhesins for 46 Salmonella strains. The results highlight associations between specific adhesin alleles, host species, and antimicrobial resistance. The differentiation of allelic variants has potential applications for diagnostic microbiology and epidemiological investigations.
Multifaceted intervention to promote beta-blocker use in heart failure.

BACKGROUND Despite a survival benefit and guideline recommendation for beta-blockers in left ventricular systolic dysfunction, beta-blockers are underused in clinical practice. METHODS Medical practices with > or = 15 patients with heart failure (HF) in the Duke Databank for Cardiovascular Disease (DDCD) were identified for a prospective, randomized study using a multifaceted intervention to improve beta-blocker use. Intervention practices received provider education, patient education materials, feedback on beta-blocker use of their patients with HF, and access to telephone consultation with an HF expert. The primary outcome was a comparison between intervention and control practices of the proportion of patients with HF self-reporting beta-blocker use on their first routine DDCD follow-up in the postintervention year. A random effects model was used for the analysis. RESULTS Post intervention, 2631 patients (1701 in 23 intervention practices and 930 in 22 control practices) completed DDCD follow-up. No significant difference in the proportion of patients with HF reporting beta-blocker use was found in the intervention versus control groups (OR 1.16, 95% CI 0.94-1.43, P = .2), although more patients in the intervention group started a beta-blocker than stopped a beta-blocker during the study period (P = .02). CONCLUSIONS This multifaceted intervention did not significantly increase the mean proportion of patients taking beta-blockers within practices exposed to the intervention, although favorable trends were observed. Further studies are needed to identify and evaluate strategies for translating evidence into clinical practice to reduce the global health burden associated with HF.
Impaired Target Site Penetration of Vancomycin in Diabetic Patients following Cardiac Surgery

ABSTRACT Soft tissue infections constitute a serious complication following surgery in diabetic patients and frequently require the administration of vancomycin. However, despite antibiotic treatment, mortality of patients with postoperative infections remains high and might be related to an impaired penetration of anti-infective agents to target tissues. Therefore, the present study was designed to measure vancomycin tissue concentrations in six diabetic and six nondiabetic patients after cardiac surgery. Vancomycin was administered as a continuous intravenous infusion at an infusion rate of 80 to 120 mg/h. Vancomycin concentrations in soft tissues and plasma were measured in all patients during steady state as “therapeutic window” concentrations in plasma by microdialysis on day 8 ± 4 after initiation of vancomycin treatment. Vancomycin tissue concentrations in diabetic patients were significantly lower than in nondiabetics (3.7 mg/liter versus 11.9 mg/liter; P = 0.002). The median vancomycintissue/vancomycinplasma concentration ratio was 0.1 in diabetic patients and 0.3 in nondiabetics (P = 0.002). Our study demonstrated that vancomycin penetration into target tissues is substantially impaired in diabetic patients versus nondiabetics. Insufficient tissue concentrations could therefore possibly contribute to failure of antibiotic treatment and the development of antimicrobial resistance in diabetic patients.
Desipramine clearance in children and adolescents: absence of effect of development and gender.

OBJECTIVE To examine the influence of development and gender on the pharmacokinetics of desipramine (DMI) in the pediatric population. METHOD DMI pharmacokinetic parameters were calculated from 407 routinely drawn, dose- and weight-normalized serum concentrations in 173 youths receiving DMI (90 children, 83 adolescents; 29 were female, 144 were male). RESULTS Mean pharmacokinetic parameters for the entire population included dose (3.78 +/- 1.51 mg/kg), weight- and dose-normalized serum concentration (45.41 +/- 47.39 [micrograms/L]/[mg/kg]), and DMI clearance (0.68 +/- 1.51 [L/kg]/hr). No between-group differences for children and adolescents were detected in dose (child, adolescent) (3.73 +/- 1.40 mg/kg, 3.83 +/- 1.68 mg/kg), weight- and dose-normalized serum concentrations (44.52 +/- 39.6 [micrograms/L]/[mg/kg], 46.34 +/- 34.89 [micrograms/L]/[mg/kg]; p = .62), and clearance (0.680 +/- 0.890 [L/kg]/hr, 0.695 +/- 1.05 [L/kg]/hr; p = .103). No between-group gender differences were detected in dose (male, female) (3.83 +/- 1.55 mg, 3.39 +/- 1.84 mg), weight- and dose-normalized serum concentrations (45.15 +/- 37.76 [micrograms/L]/[mg/kg], 47.14 +/- 34.96 [micrograms/L]/mg/kg]; p = .720), and clearance (0.699 +/- 0.89 [L/kg]/hr, 0.606 +/- 0.535 [L/kg]/hr; p = .390). CONCLUSIONS These results suggest that age and gender do not significantly influence DMI clearance or dose-normalized serum concentrations in the pediatric population.
Reduced levels of Dusp3/Vhr phosphatase impair normal spindle bipolarity in an Erk1/2 activity‐dependent manner

Dual specificity phosphatase‐3 (Dusp3/Vhr) regulates cell cycle progression by counteracting the effects of mitogen‐activated protein kinases (Mapk) Erk1/2 and Jnk. Despite the known upregulation of Dusp3 at M phase in mammalian cells, its mitotic functions are poorly characterized. Here, we report that loss of Dusp3 by RNAi leads to the formation of multipolar spindles in human mitotic cancer cells in an Erk1/2‐dependent manner. In the phosphatase‐silenced cells, the normal bipolar spindle structure was restored by chemical inhibition of Erk1/2 and ectopic overexpression of Dusp3. We propose that at M phase Dusp3 keeps Erk1/2 activity in check to facilitate normal mitosis.
Insulin-like growth factor binding proteins in sera of pregnant nonhuman primates.

Insulin-like growth factors (IGFs) are mitogenic peptides that are important for fetal and maternal tissue growth during pregnancy. They circulate complexed primarily with a serum binding protein, IGFBP-3, which regulates the availability of the IGFs to their target tissues. We previously reported that in pregnant women, serum IGFBP-3 levels, assessed by Western ligand blotting, decline markedly beginning at 6 weeks gestation due to a circulating protease that cleaves IGFBP-3 into a 29-kilodalton (kDa) protein and lower mol wt (M(r)) fragments. In the current study, we compared IGFBP profiles, IGFBP-3 and IGFBP-1 levels, and IGFBP protease activities in sera from pregnant and nonpregnant women, baboons, and rhesus monkeys, using Western ligand blotting, IGFBP-specific immunoassays, IGFBP-3 protease assay, and zymographic gel electrophoresis. Serum IGFBP profiles in nonpregnant human and nonhuman primates were similar and were not cycle-dependent. IGFBP-3 (37-43 kDa), IGFBP-2 (31 kDa), and IGFBP-1 (28 kDa) were identified in all three species using IGFBP-specific human antisera. A 24-kDa IGFBP was also present and is believed to be IGFBP-4. Serum IGFBP-1 levels increased throughout gestation in human and nonhuman primates. Serum IGFBP-2 and putative IGFBP-4 were barely detectable in all three species from midgestation to term, but increased several days postpartum. In contrast, serum IGFBP-3 profiles differed markedly between species during gestation. Rather than the decrease seen in human pregnancy serum, there was an increase in circulating IGFBP-3 levels in nonhuman primates. Furthermore, for both baboon and rhesus monkey, the M(r) of serum IGFBP-3 was about 2 kDa greater in pregnant than in nonpregnant animals, and deglycosylation studies suggested that the higher M(r) forms may be alternatively glycosylated or may have a unique primary structure. As in nonpregnant women, serum IGFBP-3 protease activity was absent in nonpregnant and pregnant baboons. However, rhesus monkey serum contained a calcium-dependent protease that cleaved recombinant human IGFBP-3 into unique fragments, compared to the human pregnancy enzyme. Unlike human pregnancy serum, which proteolyzes IGFBP-3, in human nonpregnancy serum, rhesus serum incubated under similar conditions did not result in proteolysis of rhesus IGFBP-3, suggesting that the IGFBP-3 protease in human pregnancy serum is not present in the circulation of the rhesus monkey. To assess proteolytic activity in these sera, zymographic polyacrylamide gel analysis, using gelatin as a substrate, was performed. A minor band of proteolytic activity (72 kDa) was observed in all three species throughout gestation. (ABSTRACT TRUNCATED AT 400 WORDS)
AFR1 promotes polarized apical morphogenesis in Saccharomyces cerevisiae

The G protein-coupled alpha-factor receptor promotes polarized growth toward a mating partner. alpha-Factor induces the expression of AFR1, which acts together with the receptor C terminus to promote normal morphogenesis. The function of AFR1 was investigated by engineering cells to constitutively express AFR1 without alpha-factor. Constitutive AFR1 expression caused cells to form elongated buds that demonstrate that AFR1 can also interact with the morphogenesis components that promote bud formation. A similar elongated bud phenotype is caused by mutation of the CDC3, CDC10, CDC11, and CDC12 genes, which encode putative filament proteins that form a ring at the bud neck. AFR1 may act directly on the filament proteins, since immunolocalization detected AFR1 at the bud neck and interaction of AFR1 and CDC12 was detected in the two-hybrid protein assay. AFR1 localized to the base of pheromone-induced projections. These results suggest that AFR1 and the putative filament proteins act together with the receptor to facilitate proper localization of components during mating.
Impact of EGFR inhibitor in non-small cell lung cancer on progression-free and overall survival: a meta-analysis.

BACKGROUND The epidermal growth factor receptor (EGFR) signaling pathway is crucial for regulating tumorigenesis and cell survival and may be important in the development and progression of non-small cell lung cancer (NSCLC). We examined the impact of EGFR-tyrosine kinase inhibitors (TKIs) on progression-free survival (PFS) and overall survival (OS) in advanced NSCLC patients with and without EGFR mutations. METHODS Randomized trials that compared EGFR-TKIs monotherapy or combination EGFR-TKIs-chemotherapy with chemotherapy or placebo were included. We used published hazard ratios (HRs), if available, or derived treatment estimates from other survival data. Pooled estimates of treatment efficacy of EGFR-TKIs for the EGFR mutation-positive (EGFRmut(+)) and EGFR mutation-negative (EGFRmut(-)) subgroups were calculated with the fixed-effects inverse variance weighted method. All statistical tests were two-sided. RESULTS We included 23 eligible trials (13 front-line, 7 second-line, 3 maintenance; n = 14570). EGFR mutation status was known in 31% of patients. EGFR-TKIs treatment prolonged PFS in EGFRmut(+) patients, and EGFR mutation was predictive of PFS in all settings: The front-line hazard ratio for EGFRmut(+) was 0.43 (95% confidence interval [CI] = 0.38 to 0.49; P < .001), and the front-line hazard ratio for EGFRmut(-) was 1.06 (95% CI = 0.94 to 1.19; P = .35; P interaction < .001). The second-line hazard ratio for EGFRmut(+) was 0.34 (95% CI = 0.20 to 0.60; P < .001), and the second-line hazard ratio for EGFRmut(-) was 1.23 (95% CI = 1.05 to 1.46; P = .01; P interaction < .001). The maintenance hazard ratio for EGFRmut(+) was 0.15 (95% CI = 0.08 to 0.27; P < .001), and the maintenance hazard ratio for EGFRmut(-) was 0.81 (95% CI = 0.68 to 0.97; P = .02; P interaction < .001). EGFR-TKIs treatment had no impact on OS for EGFRmut(+) and EGFRmut(-) patients. CONCLUSIONS EGFR-TKIs therapy statistically significantly delays disease progression in EGFRmut(+) patients but has no demonstrable impact on OS. EGFR mutation is a predictive biomarker of PFS benefit with EGFR-TKIs treatment in all settings. These findings support EGFR mutation assessment before initiation of treatment. EGFR-TKIs should be considered as front-line therapy in EGFRmut(+) advanced NSCLC patients.
Relationship between ambulatory capacity and cardiorespiratory fitness in chronic stroke: influence of stroke-specific impairments.

STUDY OBJECTIVES To identify the following in individuals with chronic stroke: (1) the relationship between the maximal oxygen consumption (Vo(2)max) during cycle ergometry and the distance covered in the 6-min walk test (6MWT), and (2) the stroke-specific impairments that are important determinants for the 6MWT distance. DESIGN Cross-sectional study using a convenience sample. SETTING Exercise testing laboratory in a tertiary rehabilitation center. PARTICIPANTS Sixty-three older adults (mean age +/- SD, 65.3 +/- 8.7 years) with an average poststroke interval of 5.5 +/- 4.9 years. INTERVENTION Not applicable. MAIN OUTCOME MEASURES Each subject underwent a maximal cycle ergometer test and a 6MWT. Oxygen consumption (Vo(2)) was measured during both tests. Subjects were also evaluated for Berg balance scale, modified Ashworth scale of spasticity, isometric knee extension strength, and percentage of body fat. RESULTS The 6MWT distance had a low correlation with the Vo(2)max (r = 0.402). Balance, knee extension strength, and spasticity were all significant determinants for the 6MWT distance, with balance being the major contributor for the 6MWT distance, accounting for 66.5% of its variance. CONCLUSIONS Factors other than the cardiorespiratory status considerably influenced the ambulatory capacity as measured by the 6MWT. The 6MWT distance alone should not be used to indicate cardiorespiratory fitness in individuals with chronic stroke.
GPs' strategies in intercultural clinical encounters.

BACKGROUND In North America and Europe, patients and physicians are increasingly likely to come from non-Western cultural backgrounds. The expectations of these patients may not match those of physicians. OBJECTIVE To identify strategies used by GPs with patients from cultures other than their own. METHODS We conducted a qualitative inductive study based on 25 semi-structured interviews with family physicians practising in Montreal, Canada. We elicited physicians' strategies when dealing with patients from a cultural background different from their own. We began by asking physicians to describe an encounter they found difficult and one they found easy. RESULTS Physicians reported three types of strategies: (i) insistence on patient adaptation to local beliefs and behaviours; (ii) physician adaptation to what he or she assumed patients wanted; and (iii) negotiation of a mutually acceptable plan. Individual physicians did not adopt the same strategy in all situations. Their choice of strategy depended on the topic. When dealing with issues they felt deeply about, such as the autonomy of women, many physicians insisted on patient adaptation. Physicians used a patient-centred model of care, but had no framework to elicit information about patients' culture. CONCLUSIONS A patient-centred model of care enables physicians to consult effectively despite a wide range of cultural differences between themselves and their patients. However, their lack of a conceptual framework for addressing cultural difference prevents systematic data collection and consideration of challenges to respect for individual autonomy. Physician training should include the provision of an explicit conceptual framework for approaching patients from a different culture.
Improving efficiency of resource usage in two-hop full duplex relay systems based on resource sharing and interference cancellation

This letter presents a new full duplex relay (FDR) system that features more efficient use of time resource and antennas. The proposed FDR system is constructed based on time and antenna-sharing and elimination of underlying interference. The underlying interference caused by time- and antenna-sharing is eliminated using precoding. We propose a design for the precoder and decoder, and investigate the achievable rate of the proposed FDR system when the precoder and decoder are applied. Simulation results show improved achievable rate and BER performances with the proposed FDR system compared to half duplex and conventional full duplex relay systems.