Miracle-dz/UniFAR-FTUs huggingface dataset:
A cohort study of cigarette smoking and risk of fibroadenoma.

BACKGROUND This cohort study examines the association between cigarette smoking and risk of fibroadenoma. METHODS The study was conducted among the 56,537 women in the Canadian National Breast Screening Study (NBSS) who completed self-administered lifestyle and dietary questionnaires. (The NBSS is a randomised, controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) Cases were the 222 women who were diagnosed with biopsy-confirmed incident fibroadenoma. For comparative purposes, a subcohort, consisting of a random sample of 5,681 women was selected from the full dietary cohort. After exclusions for various reasons, the analyses were based on 222 cases and 5,488 non-cases. Incidence rate ratios (IRR) and 95% confidence intervals (CI) were estimated using Poisson regression. RESULTS Cigarette smoking was associated with reduced risk of fibroadenoma, the IRR (95% CI) for more than 550 cigarette-years of exposure being 0.66 (0.40-1.10). Although the reduction in risk was evident for all smokers combined (ex-smokers and current smokers), it was indicative largely of an inverse association in current smokers, in whom the IRR (95% CI) for > 300 cigarette-years of exposure was 0.49 (0.24-0.98). The results were mostly the same when examined in strata defined by method of detection of fibroadenoma, menopausal status and history of previous breast disease. There was no evidence for a reduction in risk with time since last use of cigarettes. CONCLUSIONS The results of this study suggest that cigarette smoking is associated with reduced risk of fibroadenoma, especially in current smokers.
Association of canine obesity with reduced serum levels of C-reactive protein

The prevalence of obesity is increasing in dogs as well as in humans. C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. The objective of the present study was to determine if serum CRP levels are altered in obese dogs. Fifteen lean (control group) and 16 overweight (obese group) dogs were examined. Blood samples were collected under fasted conditions for serum determination of CRP, glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated that obese dogs were insulin resistant because serum insulin and insulin/glucose ratios were higher than in lean dogs (P ≤ 0.05). Serum CRP concentrations were lower in obese dogs than in controls (P ≤ 0.001). C-reactive protein was negatively correlated with insulin/glucose ratio (R = −0.42) and cholesterol (R = −0.39; P ≤ 0.05). Furthermore, levels of cholesterol, triglycerides, and fructosamine were increased in the obese group compared with the control group. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs.
The Dynamics of Firm Size Distribution

The shape and evolution of ﬁrm size distribution has been studied in industrial organization and labor economics. The standard hypothesis of Gibrat’s law of proportionate eﬀect posits that the rate of ﬁrm growth is size-independent. We test Gibrat’s law using a new empirical methodology and considering the underinvestigated Brazilian case. Quantile regression is used to estimate the evolution of ﬁrm size distribution and to investigate the validity of Gibrat’s law in some parts of the conditional distribution, unlike previous studies, which considered the conditional mean dynamics only. An interesting empirical issue is that usual IV/GMM methods are inappropriate under the null but consistent under the alternative hypothesis, while non-IV methods that impose exogeneity are consistent only under the null hypothesis. Results suggest that Gibrat’s law is rejected; that smaller ﬁrms grow faster; and that there seems to be a strong negative asymmetry in conditional distribution as ﬁrm size increases.
The Effect of Hyperbaric Oxygen on Ischemia–Reperfusion Injury: An Experimental Study in a Rat Musculocutaneous Flap

Abstarct The effect of hyperbaric oxygen is known to increase survival of ischemic tissue but its mechanism is not fully understood. The purpose of this study was to evaluate the effect of hyperbaric oxygen on a rat musculocutaneous flap versus ischemia–reperfusion injury, focusing on the mechanism involving the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD18 of neutrophils. A transverse rectus abdominis musculocutaneous (TRAM) flap (6 × 5 cm) supplied by a single superior epigastric vascular pedicle was elevated in 100 Sprague–Dawley rats. The rats were divided into 4 groups: group 0, sham (n = 10); group I, 4 hours of ischemia followed by reperfusion (n = 30); group II, 4 hours of ischemia and hyperbaric oxygen (100% oxygen, 2.5 atm absolute, during the last 90 minutes of ischemia before reperfusion) followed by reperfusion (n = 30); and group III, 4 hours of ischemia followed by reperfusion and hyperbaric oxygen (100% oxygen, 2.5 atm absolute, after reperfusion for 90 minutes; n = 30). The study consisted of gross examination for flap survival, histology, immunohistochemical staining, myeloperoxidase assay, flow cytometric study of CD18, and Northern blot analysis on ICAM-1 messenger ribonucleic acid expression. Gross measurement of the flap showed increased survival in groups II and III compared with group I (P < 0.05). The leukocytes adherent to the endothelium were counted at 24 hours and on day 5. Group I leukocytes were significantly increased compared with groups II and III (P < 0.05). The myeloperoxidase assay of TRAM flaps at 24 hours revealed a significant increase in group I compared with groups II and III (P < 0.05). The expression of CD18 was similar between groups I, II, and III. Immunohistochemical staining for ICAM-1 and Northern blot analysis on ICAM-1 messenger ribonucleic acid showed decreased expression in groups II and III compared with group I. Throughout the analysis, groups II and III did not show any significant differences. These results suggests that hyperbaric oxygen reduces the accumulation of leukocytes in the TRAM flap, but not enough to prevent adhesion of neutrophils on endothelial cells; ischemia–reperfusion injury increases the expression of CD18 and ICAM-1 and causes increased adhesion of leukocytes on the endothelium; hyperbaric oxygen does not alter the expression of CD18 but decreases the expression of ICAM-1; and the point of application for hyperbaric oxygen, whether applied before or after reperfusion, did not show any differences in outcome. In conclusion, the application of hyperbaric oxygen against ischemia–reperfusion injury increases flap survival and the beneficial effect may be explained by a protective mechanism involving downregulation of ICAM-1 on endothelial cells.
Identification of ChChd3 as a Novel Substrate of the cAMP-dependent Protein Kinase (PKA) Using an Analog-sensitive Catalytic Subunit*

Due to the numerous kinases in the cell, many with overlapping substrates, it is difficult to find novel substrates for a specific kinase. To identify novel substrates of cAMP-dependent protein kinase (PKA), the PKA catalytic subunit was engineered to accept bulky N6-substituted ATP analogs, using a chemical genetics approach initially pioneered with v-Src (1). Methionine 120 was mutated to glycine in the ATP-binding pocket of the catalytic subunit. To express the stable mutant C-subunit in Escherichia coli required co-expression with PDK1. This mutant protein was active and fully phosphorylated on Thr197 and Ser338. Based on its kinetic properties, the engineered C-subunit preferred N6(benzyl)-ATP and N6(phenethyl)-ATP over other ATP analogs, but still retained a 30 μm Km for ATP. This mutant recombinant C-subunit was used to identify three novel PKA substrates. One protein, a novel mitochondrial ChChd protein, ChChd3, was identified, suggesting that PKA may regulate mitochondria proteins.
Genetic variation of Tunisian Myrtus communis L. (Myrtaceae) populations assessed by isozymes and RAPDs

The genetic variation of six Tunisian Myrtus communis L. (Myrtaceae) populations was assessed using nine isozymes coding for 17 putative loci and 79 RAPD markers, amplified by five decamer random primers. The analysed populations belonged to three bioclimatic zones (lower humid, sub-humid and upper semi-arid). A high genetic diversity within populations was detected both by isozymes and RAPDs. The level of variation differed according to bioclimate. Populations collected from sub-humid bioclimate showed more polymorphism than those grown in the upper semi-arid zone. For all populations, the genetic diversity revealed by RAPDs was more pronounced than that detected with isozymes. A high differentiation among populations related to bioclimate and geographic distance was revealed by both methods. Population’s structure based on RAPD markers was more concordant with bioclimatic zones in comparison with isozymes. Differentiation between ecological groups was higher than that revealed within groups. Conservation programs should take into account the level of genetic diversity within population revealed by the two complementary classes of markers according to bioclimate. RésuméLa variabilité génétique de six populations tunisiennes de Myrtus communis L. (Myrtaceae) a été estimée à l’aide de neuf systèmes isoenzymatiques contrôlés par 17 loci et 79 marqueurs RAPD amplifiés par cinq amorces. Les populations analysées appartiennent à trois étages bioclimatiques différents : humide inférieur, sub-humide et semi-aride supérieur. Une diversité génétique intrapopulation importante a été détectée. Le niveau de polymorphisme varie selon le bioclimat. Les populations du sub-humide sont plus polymorphes. Pour l’ensemble des populations, la diversité génétique révélée par les RAPDs est plus importante que celle détectée par les isozymes. Une forte différenciation entre les populations, selon le bioclimat et l’éloignement géographique, a été révélée par les deux méthodes. La structuration des populations selon les marqueurs RAPD concorde mieux avec le bioclimat. La différenciation entre les populations appartenant à des groupes écologiques différents est plus importante que celle entre populations d’un même groupe. Les programmes de conservation de l’espèce doivent tenir compte aussi bien du degré de la diversité génétique intrapopulation révélé par les deux types de marqueurs que du bioclimat.
Interface Stress in Socket/Residual Limb with Transtibial Prosthetic Suspension Systems During Locomotion on Slopes and Stairs

ObjectiveThis study aimed to compare the effects of different suspension methods on the interface stress inside the prosthetic sockets of transtibial amputees when negotiating ramps and stairs. DesignThree transtibial prostheses, with a pin/lock system, a Seal-In system, and a magnetic suspension system, were created for the participants in a prospective study. Interface stress was measured as the peak pressure by using the F-socket transducers during stairs and ramp negotiation. ResultsTwelve individuals with transtibial amputation managed to complete the experiments. During the stair ascent and descent, the greatest peak pressure was observed in the prosthesis with the Seal-In system. The magnetic prosthetic suspension system caused significantly different peak pressure at the anterior proximal region compared with the pin/lock (P = 0.022) and Seal-In (P = 0.001) during the stair ascent. It was also observed during the stair descent and ramp negotiation. ConclusionsThe prostheses exhibited varying pressure profiles during the stair and ramp ascent. The prostheses with the pin/lock and magnetic suspension systems exhibited lower peak pressures compared with the Seal-In system. The intrasystem pressure distribution at the anterior and posterior regions of the residual limb was fairly homogenous during the stair and ramp ascent and descent. Nevertheless, the intrasystem pressure mapping revealed a significant difference among the suspension types, particularly at the anterior and posterior sensor sites.
All-Optical-Fiber Orbital Angular Momentum Mode Generator With a Helical Phase Disk Inserted Between Fibers

An all-optical-fiber orbital angular momentum (OAM) mode generator is designed based on the effective medium theory. The generator is formed by many coaxial vortex structures with the same height and gradually decreasing width following the azimuth angle, which causes the linear decrement of the effective refractive index with the azimuth angle. The different effective refractive index will cause the different optical path and the corresponding phase delay along the azimuthal angle. The OAM generation process is simulated using a finite-difference time-domain (FDTD) software package.
Anion efflux from cytotrophoblast cells derived from normal term human placenta is stimulated by hyposmotic challenge and extracellular A23187 but not by membrane‐soluble cAMP

The regulation of placental anion transport influences fetal accretion and placental homeostasis. We investigated whether efflux of 125I− or 36Cl− from multinucleated cytotrophoblast cells derived from human term placenta is regulated by one of three stimuli: (a) the calcium ionophore A23187, (b) a ‘cocktail’ of agents designed to raise intracellular levels of cAMP, (c) a hyposmotic solution. After loading with the appropriate isotope for 2 h and thorough washing, cells were exposed to sequential aliquots of buffer applied and removed each minute. Following an equilibration period of 5 min one of the stimuli was applied at room temperature At the end of the experiment the cells were lysed to give a lysate count which was used to express the count obtained from each aliquot as percentage efflux of that possible for that minute. The cAMP ‘cocktail’ and A23187 were applied for 5 min; the hyposmotic solution was applied for 10 min. The results for 125I− at 7 min showed that the mean efflux in the presence of hyposmotic shock was greater than control (5.7 ± 1.0% min−1 versus 2.2 ±0.1 % min−1, respectively; mean ± S.E.M., n = 4 placentas). Similarly mean efflux at 6 min in the presence of A23187 was also significantly greater than control (6.5 ±1.9 % min−1 versus 2.6 ± 1.0 % min−1, respectively, n = 3 placentas). The mean efflux in the presence of the cAMP cocktail was not different from control at any time point. The results were qualitatively the same if 38Cl− was used in the place of 125I− and when the experiment was performed with 36Cl− in a HCO3− buffer gassed with CO2. Mean 125I− efflux at 6 min in response to hyposmotic challenge was 33 % less (P < 0.01) in the presence of 1 mM 4,4′‐diisothiocyanatostilbene‐2,2′‐disulphonic acid (DIDS) and 37% less (P <0.005) in the presence of 10 μm tamoxifen but no different if the hyposmotic solution was nominally calcium free. We conclude that there are differential effects of second messengers on anion efflux from the differentiated cytotrophoblast cells.
Meta-analysis of local metronidazole in the treatment of chronic periodontitis.

BACKGROUND Meta-analysis was used to assess the effectiveness of local delivery of metronidazole alone or as an adjunct to mechanical therapy in patients with chronic periodontitis. METHODS Studies were identified using MEDLINE and other sources. Meta-analyses were performed on the basis of probing depth (PD) at baseline and experimental and control regimens studied (i.e., metronidazole plus scaling and root planing [SRP] versus SRP and metronidazole versus SRP); the effect of local metronidazole on PD and attachment level (AL) was evaluated for follow-up times of 4, 8, 12, 24, and 36 weeks. The DerSimonian & Laird random effects model was used. RESULTS Twelve studies that met inclusion criteria were entered into the meta-analysis. A significant mean reduction in PD for the combined metronidazole and SRP was observed in all comparisons with initial PD > or = 4 mm (0.38 mm at 8 weeks to 0.6 mm at 12 weeks); whereas, with initial PD > or = 5 mm a significant mean reduction was observed from 12 weeks (0.29 to 0.48 mm at 24 and 36 weeks, respectively). Meta-analysis could be performed for AL to test the effectiveness of metronidazole as an adjunct to SRP and a significant AL improvement was found in all analyses (0.2 mm at 4 weeks to 0.29 mm at 24 and 36 weeks). Meta-analyses were performed including two to four studies. CONCLUSION Our results demonstrated the effectiveness of metronidazole as an adjunct to SRP in the treatment of chronic adult periodontitis, but clinical significance and dissemination of antibiotics should be taken into account in the evaluation of metronidazole as an alternative to SRP.
EPISTASIS AND THE EVOLUTION OF ADDITIVE GENETIC VARIANCE IN POPULATIONS THAT PASS THROUGH A BOTTLENECK

Traditional models of genetic drift predict a linear decrease in additive genetic variance for populations passing through a bottleneck. This perceived lack of heritable variance limits the scope of founder‐effect models of speciation. We produced 55 replicate bottleneck populations maintained at two male‐female pairs through four generations of inbreeding (average F = 0.39). These populations were formed from an F2 intercross of the LG/J and SM/J inbred mouse strains. Two contemporaneous control strains maintained with more than 60 mating pairs per generation were formed from this same source population. The average level of within‐strain additive genetic variance for adult body weight was compared between the control and experimental lines. Additive genetic variance for adult body weight within experimental bottleneck strains was significantly higher than expected under an additive genetic model This enhancement of additive genetic variance under inbreeding is likely to be due to epistasis, which retards or reverses the loss of additive genetic variance under inbreeding for adult body weight in this population. Therefore, founder‐effect speciation processes may not be constrained by a loss of heritable variance due to population bottlenecks.
Effects of acute thermal stress on the immune system of the Northern Bobwhite (Colinus virginianus)

We tested the hypothesis that exposure of Northern Bobwhites (Colinus virgi- nianus) to acute temperature stressors impairs their immune-system function and resistance to disease. Birds were randomly assigned to either a thermoneutral (constant 21? C), cold- stress (cycled from 3.6 to -20? C over 24 h), or heat-stress (cycled from 30.8 to 39.0? C over 24 h) treatment for four consecutive days. Immunocompetence of each bird was evaluated on day 5 using a panel of assays, including a measure of resistance to a Pasteurella multocida Type 3 challenge. Neither thermal stressor had an influence on spleen mass or measures of cell- mediated and humoral immunity. Disease resistance of Northern Bobwhites to P. multocida was not influenced by heat stress but increased following cold stress. Cold stress may have increased the activity of phagocytic leukocytes, which are important in resistance of birds to bacterial pathogens. A concomitant decrease in lymphocyte numbers suggested that resistance to viral pathogens was compromised during cold stress. Received 20 February 1996, accepted 26 September 1996.
Antidepressant treatment and the risk of fatal and non-fatal self harm in first episode depression: nested case-control study

Abstract Objective To compare the risk of non-fatal self harm and suicide in patients taking selective serotonin reuptake inhibitors (SSRIs) with that of patients taking tricyclic antidepressants, as well as between different SSRIs and different tricyclic antidepressants. Design Nested case-control study. Setting Primary care in the United Kingdom. Participants 146 095 individuals with a first prescription of an antidepressant for depression. Main outcome measures Suicide and non-fatal self harm. Results 1968 cases of non-fatal self harm and 69 suicides occurred. The overall adjusted odds ratio of non-fatal self harm was 0.99 (95% confidence interval 0.86 to 1.14) and that of suicide 0.57 (0.26 to 1.25) in people prescribed SSRIs compared with those prescribed tricyclic antidepressants. We found little evidence that associations differed over time since starting or stopping treatment. We found some evidence that risks of non-fatal self harm in people prescribed SSRIs compared with those prescribed tricyclic antidepressants differed by age group (interaction P = 0.02). The adjusted odds ratio of non-fatal self harm for people prescribed SSRIs compared with users of tricylic antidepressants for those aged 18 or younger was 1.59 (1.01 to 2.50), but no association was apparent in other age groups. No suicides occurred in those aged 18 or younger currently or recently prescribed tricyclic antidepressants or SSRIs. Conclusion We found no evidence that the risk of suicide or non-fatal self harm in adults prescribed SSRIs was greater than in those prescribed tricyclic antidepressants. We found some weak evidence of an increased risk of non-fatal self harm for current SSRI use among those aged 18 or younger. However, preferential prescribing of SSRIs to patients at higher risk of suicidal behaviour cannot be ruled out.
Origin of Fatigue in Multiple Sclerosis: Review of the Literature

Fatigue is one of the most common and most disabling symptoms of multiple sclerosis (MS). Although numerous studies have tried to reveal it, no definite pathogenesis factor behind this fatigue has been identified. Fatigue may be directly related to the disease mechanisms (primary fatigue) or may be secondary to non—disease-specific factors. Primary fatigue may be the result of inflammation, demyelination, or axonal loss. A suggested functional cortical reorganization may result in a higher energy demand in certain brain areas, culminating in an increase of fatigue perception. Higher levels of some immune markers were found in patients with MS-related fatigue, whereas other studies rejected this hypothesis. There may be a disturbance in the neuroendocrine system related to fatigue, but it is not clear whether this is either the result of the interaction with immune activation or the trigger of this process. Fatigue may be secondary to sleep problems, which are frequently present in MS and in their turn result from urinary problems, spasms, pain, or anxiety. Pharmacologic treatment of MS (symptoms) may also provoke fatigue. The evidence for reduced activity as a cause of secondary fatigue in MS is inconsistent. Psychological functioning may at least play a role in the persistence of fatigue. Research did not reach consensus about the association of fatigue with clinical or demographic variables, such as age, gender, disability, type of MS, education level, and disease duration. In conclusion, it is more likely to explain fatigue from a multifactor perspective than to ascribe it to one mechanism. The current evidence on the pathogenesis of primary and secondary fatigue in MS is limited by inconsistency in defining specific aspects of the concept fatigue, by the lack of appropriate assessment tools, and by the use of heterogeneous samples. Future research should overcome these limitations and also include longitudinal designs.