Miracle-dz/UniFAR-FTUs huggingface dataset:
Risk of Malignant Transformation of Congenital Melanocytic Nevi in Blacks

Abstract: The risk of small congenital melanocytic nevi (CMN) developing into melanoma is not known, but Is highly controversial. The frequency of small CMN is, paradoxically, slightly higher in some populations, such as blacks, who are at a lower risk of developing melanoma than whites. An estimate of the risk of malignant transformation of CMN in such a low‐risk population could help In the management of congenital nevi in these patients and might also shed light on the inherent malignant fisk of small CMN. We used a national population‐based cancer registry, the Surveillance, Epidemiology, and End Results program (SEER), and the incidence of CMN in blacks taken from published newborn surveys to calculate a risk of malignant transformation. We calculated a maximum risk using a model based on a worst‐case scenario, assuming that all melanomas on glabrous skin arise in CMN. We also calculated a modified risk based on the known historical association of nevi and melanomas in blacks, and estimates of the histologic association of the two. The cumulative maximum risk of malignant transformation in blacks to age 75 years was 1 in 164. It was strongly age dependent, with the majority occurring in persons over age 45. The estimated maximum risk before age 15 was less than 1 in 10,000 CMN, and in blacks age 15 to 35 less than 1 in 3700 CMN. The modified risk suggests that the worst‐case scenario overestimates the risk by at least a factor of 12, making the actual risk in blacks up to age 75 approximately 1 In 2000. Both the worst‐case scenario model and the modified risk suggest a small to extremely small risk of malignant transformation, particularly before age 45. Although the specific morphology and circumstances of a particular CMN must be considered In decision making, we believe that routine prophylactic removal of small CMN in blacks is probably not warranted.
Acceptance of tamoxifen chemoprevention by physicians and women at risk

Tchou et al. recently published a retrospective chart review of women choosing to receive tamoxifen for chemoprevention of breast carcinoma. One hundred thirty-seven women seeking risk counseling for breast carcinoma were offered tamoxifen for chemoprevention, and 57 (42%) chose to receive this agent. The authors found that a history of atypical hyperplasia or lobular carcinoma in situ (LCIS) and older age were significant predictors of being offered and accepting treatment with tamoxifen. The figures reported by Tchou et al. are in sharp contrast to the results reported by Port et al, who found that 43 women with a 5-year risk of developing breast carcinoma 1.7% (as predicted by the Gail model) were given information regarding the benefits and risks of tamoxifen and that only 2 of these women (4.7%) chose to receive tamoxifen therapy. These discrepancies in terms of acceptance rates may be attributable to the way in which information was provided. Despite the best intentions of physicians, it may be impossible to present information to patients in a truly unbiased fashion. A physician’s description of a treatment and the strength of the recommendation, in addition to the framing of information, may influence patients. Although in these two previous studies, the authors state that they provided ‘neutral risk counseling’ or ‘neutral education sessions and literature’, this neutrality was not explicit, and some bias in favor or against tamoxifen use may have been present. The Tchou et al. study did not include the physician as a variable having a possible effect on the offering or acceptance of tamoxifen therapy. In our own prospective study, which attempted to remove physician-related biases through the use of a standardized decision guide, only 6 of 41 women (14.6%) who had high-risk status (mean 5-year Gail risk, 3.4%; atypia rate, 61%) were willing to receive tamoxifen for chemoprevention, a figure that was intermediate relative to the Tchou et al. and Port et al. studies. Although information cannot be tailored specifically to the patient using the decision guide, generic information can be conveyed to introduce the concept of chemoprevention, and the issue can be explored further at the request of the patient. We commend Tchou et al. for offering more insight into the proportion of women expressing an interest in tamoxifen chemoprevention. There remain several challenges related to how to best identify and approach women who have an elevated risk of developing breast carcinoma (as routine screening using the Gail model is not recommended) and how to best provide information on the small absolute benefits and the small but significant risks associated with tamoxifen use. The balance between the benefits and harms of tamoxifen use is a delicate one, and decisions regarding tamoxifen use are best made by informed patients who are free from the influence 209
Attachment, Social Support, and Responses following the Death of a Companion Animal

This research tested hypotheses concerning attachment, social support, and grief responses to the loss of animal companionship. Participants whose companion cat or dog had recently died (N = 429) completed the Attachment Style Questionnaire, the Inventory of Complicated Grief, and the Multidimensional Health Profile-Psychosocial Functioning questionnaires. Both attachment anxiety and attachment avoidance were found to be positively associated with respondents' grief, depression, anxiety, and somatic symptoms. Social support was found to be negatively associated with these outcomes as well as with attachment anxiety and attachment avoidance. In multiple regression analyses, attachment anxiety incrementally predicted grief, anxiety and somatic symptoms, attachment avoidance incrementally predicted grief and depression, and social support incrementally predicted all outcomes. Interaction effects of attachment and social support in relation to outcomes were not found. The present study's implications and limitations are discussed, as are directions for future research.
Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5

MAP kinase phosphatases (MKPs) have crucial roles in regulating the signaling activity of MAP kinases and are potential targets for drug discovery against human diseases. These enzymes contain a catalytic domain (CD) as well as a binding domain (BD) that help recognize the target MAP kinase. We report here the crystal structures at up to 2.2 Å resolution of the BD and CD of human MKP5 and compare them to the known structures from other MKPs. Dramatic structural differences are observed between the BD of MKP5 and that of MKP3 determined previously by NMR. In particular, the cluster of positively charged residues that is important for MAP kinase binding is located in completely different positions in the two structures, with a distance of 25 Å between them. Moreover, this cluster is α‐helical in MKP5, while it forms a loop followed by a β‐strand in MKP3. These large structural differences could be associated with the distinct substrate preferences of these phosphatases, but further studies are needed to confirm this. The CD of MKP5 is observed in an active conformation, and two loops in the active site have backbone shifts of up to 5 Å relative to the inactive CDs from other MKPs.
Time Course of Cortical Plasticity After Facial Nerve Palsy

Background. Functional connectivity is defined as the temporal correlation between spatially remote neurophysiological events. This method has become particularly useful for studying neuroplasticity to detect changes in the collaboration of brain areas during cortical reorganization. Methods. In this article, the authors longitudinally studied voxel-based morphometry and resting state functional magnetic resonance imaging 10 times in 1 patient during the course of Bell palsy (idiopathic facial nerve palsy) up to complete clinical recovery. Results. Morphometric analysis revealed a significant alteration in the face area of the primary motor cortex (M1) contralateral to the paretic face, with an initial increase in gray matter concentration. Functional connectivity analysis between the M1 and other parts of the facial motor network revealed acutely disrupted intrahemispheric connectivity but unaltered interhemispheric connectivity. The disrupted functional connectivity was most pronounced on the day of the onset of symptoms, with a subsequent return toward normal during the course of recovery. This time course was found to differ between the selected parts of the facial motor network. However, the increase in functional connectivity strength preceded clinical recovery in all areas and reached a stable level before the patient fully recovered. Conclusion. These results demonstrate that recovery from facial nerve palsy is complemented by cortical reorganization, with pronounced changes of functional connectivity that precede clinical recovery.
Neuromagnetic evidence for early access to cognitive representations

How do physical and cognitive properties of stimulus words influence the neuromagnetic response of the human brain? Are the physiological correlates of these properties dissociable and at which latencies can they be observed? Short and long words, as well as rare and common words, were repeatedly presented in a memory task while neuromagnetic brain responses were recorded using MEG. Word length and frequency were reflected by brain responses at overlapping but distinct intervals. The influence of the physical factor, length, started at ∼100 ms after onset of written words, immediately followed by a physiological manifestation of the non-physical cognitive stimulus property, word frequency, which was first apparent at 120–160 ms. There was a differential frequency effect: neurophysiological correlates of short words showed the frequency influence much earlier than did longer words. These data indicate that non-physical cognitive aspects of word stimuli can be reflected in early neuromagnetic responses, and that the latency of these physiological correlates of cognitive stimulus properties may depend on the physical stimulus make-up.
The reproductive response of female ostriches to dietary protein

Abstract A study was conducted with breeding ostriches over two consecutive breeding seasons to determine their response to different concentrations of a well-balanced dietary protein. Five concentrations of protein were fed to both females and males at an intake of 2.5 kg/bird d. The respective diets contained 75, 91, 108, 123 and 140 g protein/kg feed with energy held constant at 9.2 MJ metabolisable energy/kg feed. Egg production (mean ± SE, 39.1 ± 3.6 eggs/female/season) was unaffected by dietary protein concentration. Similarly, no significant trends were found for the number of unfertilised eggs (9.1 ± 1.8), dead-in-shell chicks (8.2 ± 1.3), the number of chicks hatched (19.5 ± 2.5) and change in the mass of females (−16.3 ± 10.2 kg). Egg weight decreased linearly as dietary protein content increased. Age of the ostrich female had a highly significant effect on the number of eggs laid, the number of chicks hatched, the number of dead-in-shell and infertile eggs produced per hen, as well as the mass change of female breeding birds, but did not affect the response of any of these variables to dietary protein content. It was concluded that ostriches do not benefit from dietary protein contents greater than about 75 g/kg when this is fed at a daily total feed intake rate of 2.5 kg/bird during the breeding season.
Insufficient Ascorbic Acid Uptake from the Diet and the Tendency for Suicide

The dietary habits of 12 women who attempted or committed suicide were studied. The result shows their ascorbic acid intake was significantly lower compared with the subjects in the control group. A conceivable explanation is that these women had somehow raised tissue levels of vanadium, and their ascorbic acid intake was not adequate enough to deal with depression due to excessive vanadium, resulting in attempted or committed suicide.
Factors associated with viremia and elevated transaminase levels in asymptomatic hepatitis D virus‐infected risk groups

To detect hepatitis D virus (HDV) RNA in asymptomatic HDV‐infected risk groups, Northern blot hybridization was carried out using a strand‐specific riboprobe. Univariate and multivariate analyses were carried out to evaluate factors associated with HDV viremia and elevated transaminase levels in these subjects. Two (15%) of 13 antibody to HDV (anti‐HDV) ‐positive intravenous drug addicts, 15 (33%) of 45 anti‐HDV positive prostitutes, and 6 (40%) of 15 anti‐HDV positive brothel goers had detectable serum HDV RNA. Older age (>31 years old) was negatively associated with HDV RNA (P < 0.04), while hepatitis B e antigen (HBeAg) was positively associated with it (P < 0.002) in univariate analysis. Only HBeAg was still significant in multivariate analysis (P < .05). Of the 76 asymptomatic anti‐HDV positive case, 28 (37%) had mildly elevated serum ALT levels and only 5 (7%) had ALT levels more than twice normal (>80 U/L). HBeAg (P < .05) and HDV RNA (P < .02) were two factors associated with ALT elevation in univariate analysis, and HDV RNA was the only significant factor in multivariate analysis (P < .005). In summary, active replication of HBV seemed to be of help for the assembly of HDV and viremia. However, active replication of HDV was associated mostly with mildly elevated ALT levels in these subjects. These cases may represent a particular group in the disease spectrum of HDV infection. © 1994 Wiiey‐Liss, Inc.
Effect of treatment on the outcome of very early rheumatoid arthritis.

OBJECTIVE To evaluate the effect of treatment on the outcome of very early RA. METHODS In a 3-year prospective study of 27 patients with very early RA (VERA) (symptoms <4 months before diagnosis) and 122 patients with early RA (symptoms between 4-24 months) the effect of active treatment on the clinical picture, functional capacity, and radiological progression was evaluated. RESULTS Initially VERA patients had a more active clinical picture and worse functional capacity. Despite a higher number of DMARDs used in VERA patients, C-reactive protein and Ritchie index remained significantly higher in these patients (although significant improvement occurred). They also had a more rapidly progressive disease (higher Larsen score/month of symptoms) during pre-treatment period, the progression of which was retarded with early, active DMARD therapy. By the end of 3 years, the rate of progression ran parallel in both groups. CONCLUSION Active treatment had an impact on the rate of radiological progression and clinical activity but not on the functional outcome in patients with initially active RA of short duration.
Beta-3 adrenoceptor-mediated increase in cutaneous blood flow in the dog.

Beta-3 adrenergic agonist administration decreases arterial blood pressure in the dog as previously shown. The putative presence of beta-3 adrenoceptors in peripheral microvascular muscle was studied in dogs through measurement of cutaneous blood flow and skin temperature changes. Experiments were carried out in normal and sinoaortic denervated dogs (i.e., animals deprived of baroreceptor pathways). In normal dogs, the infusion of 0.4 nmol/kg/min of 4-[-[(2-hydroxy-(3-chlorophenyl)ethyl)-amino]propyl] phenoxyacetate (BRL 37344) or (R,R-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3- benzodioxole-2,2-dicarboxylate (CL 316243) (two selective beta-3 adrenoceptor agonists), or 8 nmol/kg/min of 4-[3-t-butylamino-2-hydroxypropoxy]benzimidazol-2-one (CGP 12177) (a beta-1/beta-2 adrenergic antagonist also reported to act as an agonist for the beta-3 adrenoceptor) induced an increase in heart rate and cutaneous blood flow (evaluated in the internal part of the ear) and a decrease in blood pressure. The skin and the buccal mucous membrane became purplish. The infusion of (-)-isoproterenol (0.4 nmol/g/min), a dose known to stimulate preferentially beta-1/beta-2 adrenoceptors, or sodium nitroprusside (12 micrograms/kg/min) increased heart rate and decreased blood pressure, but reduced cutaneous blood flow. In sinoaortic denervated dogs, similar effects on cutaneous blood flow and blood pressure were observed. However, in these animals, heart rate remained unchanged whatever the infused drug. BRL 37344 (but not isoproterenol) increased cutaneous temperature in normal dogs. This study suggests that beta-3 adrenoceptors exist in canine cutaneous vascular smooth muscles and that their stimulation induces vasodilatation.
Modular Organization of Exploratory Force Development Under Isometric Conditions in the Human Arm

ABSTRACT Muscle coordination of isometric force production can be explained by a smaller number of modules. Variability in force output, however, is higher during exploratory/transient force development phases than force maintenance phase, and it is not clear whether the same modular structure underlies both phases. In this study, eight neurologically-intact adults isometrically performed target force matches in 54 directions at hands, and electromyographic (EMG) data from eight muscles were parsed into four sequential phases. Despite the varying degree of motor complexity across phases (significant between-phase differences in EMG-force correlation, angular errors, and between-force correlations), the number/composition of motor modules were found equivalent across phases, suggesting that the CNS systematically modulated activation of the same set of motor modules throughout sequential force development.
Epithelial Cholesterol Deficiency Attenuates Human Antigen R-linked Pro-inflammatory Stimulation via an SREBP2-linked Circuit*

Patients with chronic intestinal ulcerative diseases, such as inflammatory bowel disease, tend to exhibit abnormal lipid profiles, which may affect the gut epithelial integrity. We hypothesized that epithelial cholesterol depletion may trigger inflammation-checking machinery via cholesterol sentinel signaling molecules whose disruption in patients may aggravate inflammation and disease progression. In the present study, sterol regulatory element-binding protein 2 (SREBP2) as the cholesterol sentinel was assessed for its involvement in the epithelial inflammatory responses in cholesterol-depleted enterocytes. Patients and experimental animals with intestinal ulcerative injuries showed suppression in epithelial SREBP2. Moreover, SREBP2-deficient enterocytes showed enhanced pro-inflammatory signals in response to inflammatory insults, indicating regulatory roles of SREBP2 in gut epithelial inflammation. However, epithelial cholesterol depletion transiently induced pro-inflammatory chemokine expression regardless of the well known pro-inflammatory nuclear factor-κB signals. In contrast, cholesterol depletion also exerts regulatory actions to maintain epithelial homeostasis against excessive inflammation via SREBP2-associated signals in a negative feedback loop. Mechanistically, SREBP2 and its induced target EGR-1 were positively involved in induction of peroxisome proliferator-activated receptor γ (PPARγ), a representative anti-inflammatory transcription factor. As a crucial target of the SREBP2-EGR-1-PPARγ-associated signaling pathways, the mRNA stabilizer, human antigen R (HuR) was retained in nuclei, leading to reduced stability of pro-inflammatory chemokine transcripts. This mechanistic investigation provides clinical insights into protective roles of the epithelial cholesterol deficiency against excessive inflammatory responses via the SREBP2-HuR circuit, although the deficiency triggers transient pro-inflammatory signals.
Arcobacter species in diarrhoeal faeces from humans in New Zealand.

AIM To determine the prevalence, genetic diversity and antimicrobial susceptibility of Arcobacter spp in faecal samples from humans with diarrhoea in New Zealand. METHODS An enrichment method was used to isolate Arcobacter spp from diarrhoeal human faeces submitted to a community laboratory in Hawke's Bay. The identity of isolates was confirmed by PCR and their diversity was determined by pulsed field gel electrophoresis (PFGE). Antibiotic susceptibility was established with E test strips. RESULTS Arcobacter spp were isolated from 12 of 1380 diarrhoeal faecal samples examined (0.9%), including 7 A. butzleri and 5 A. cryaerophilus. Additional enteric pathogens were detected in four of these diarrhoeal faecal samples. All the Arcobacter isolates were genetically distinct and susceptible to ciprofloxacin. Most were also susceptible to erythromycin (92%) but fewer to tetracycline (67%) and ampicillin(50%). CONCLUSION A. butzleri and A. cryaerophilus cause a small proportion of cases of diarrhoea in humans resident in New Zealand.
Visfatin genotype may modify the insulin resistance and lipid profile in type 2 diabetes patients.

AIM We investigated the role of the -4689G/T promoter variant of the visfatin gene on serum visfatin concentration and biochemical markers in T2DM patient. METHODS In a cross-sectional study we recruited 93 patients with type 2 diabetes. Laboratory and anthropometric measurements were included FBG, OGTT, HbA1C, lipid Profile, fasting serum visfatin, fasting serum insulin, weight, height, Body Mass Index (BMI) and waist hip ratio (WHR). Genotyping for visfatin gene was performed by using the PCR-RFLP method. RESULTS Our findings showed significant differences in levels of low density lipoprotein (LDL) cholesterol, total cholesterol, high density lipoprotein (HDL) cholesterol and fasting serum insulin among various types of visfatin genotype (TT, GG, and GT). This study showed a significant correlation between circulating levels of visfatin and weight, BMI, hs-CRP and fasting insulin in TT genotype. But regarding GG genotype only fasting insulin had a significant correlation with circulating visfatin. CONCLUSIONS Visfatin genotypes may account for insulin resistance and levels of lipid profile that may cause by different visfatin expression between genotypes.