Miracle-dz/UniFAR-FTUs huggingface dataset:
Contemporaneous fluctuations in T cell responses to persistent herpes virus infections

The classical paradigm for T cell dynamics suggests that the resolution of a primary acute virus infection is followed by the generation of a long‐lived pool of memory T cells that is thought to be highly stable. Very limited alteration in this repertoire is expected until the immune system is re‐challenged by reactivation of latent viruses or by cross‐reactive pathogens. Contradicting this view, we show here that the T cell repertoire specific for two different latent herpes viruses in the peripheral blood displayed significant contemporaneous co‐fluctuations of virus‐specific CD8+ T cells. The coordinated responses to two different viruses suggest that the fluctuations within the T cell repertoire may be driven by sub‐clinical viral reactivation or a more generalized ‘bystander’ effect. The later contention was supported by the observation that, while absolute number of CD3+ T cells and their subsets and also the cell surface phenotype of antigen‐specific T cells remained relatively constant, a loss of CD62L expression in the total CD8+ T cell population was coincident with the expansion of tetramer‐positive virus‐specific T cells. This study demonstrates that the dynamic process of T cell expansion and contractions in persistent viral infections is not limited to the acute phase of infection, but also continues during the latent phase of infection.
Genetic diversity and differentiation of core vs. peripheral populations of eastern white cedar, Thuja occidentalis (Cupressaceae).

PREMISE OF THE STUDY Geographically peripheral (marginal) populations are expected to have lower genetic diversity and higher genetic differentiation than geographically core (central) populations as a result of supposedly lower effective population size (N(e)) and higher genetic drift, founder effect, fragmentation, and isolation in peripheral than in core populations. Here we address this issue for a long-lived plant species, eastern white cedar (Thuja occidentalis). METHODS Genetic diversity and population structure of 13 natural populations of eastern white cedar from its Canadian eastern peripheral and core natural ranges in New Brunswick, Nova Scotia, and Prince Edward Island were studied using six nuclear microsatellite DNA markers. KEY RESULTS The core populations of eastern white cedar had significantly higher allelic diversity (mean A = 8.83, A(r) = 8.13, A(e) = 4.03) and N(e) (428) than the peripheral populations (A = 6.64, A(r) = 6.15, A(e) = 3.12, N(e) = 198). However, expected heterozygosity was similar in the core (H(e) = 0.64) and peripheral (H(e) = 0.60) populations. Genetic differentiation was significantly higher among the peripheral (F(ST) = 0.089) than among the core (F(ST) = 0.032) populations. No genetic differentiation (F(ST)/Φ(RT) = 0.000) was detected between core and peripheral regions. CONCLUSIONS Peripheral populations have significantly lower N(e) and genetic diversity in terms of allelic diversity (richness) and significantly higher genetic differentiation than the core populations of eastern white cedar in its Canadian eastern range. However, core and peripheral populations have similar levels of expected heterozygosity. Implications for conservation of eastern white cedar genetic resources are discussed.
Elevated Serum miR-7, miR-9, miR-122, and miR-141 Are Noninvasive Biomarkers of Acute Pancreatitis

Background It has been reported that several microRNAs (miRNAs), such as miR-141, miR-9, and miR-122, are involved in the regulation of pancreatitis-related proteins or that their levels change in acute pancreatitis (AP) animal models. However, the serum levels, as well as the clinical diagnostic and prognostic values, of these miRNAs in AP patients remain unclear. Furthermore, as a pancreas- (islet) enriched miRNA, miR-7 was reported to be downregulated in AP patients, which requires further verification. Methods The levels of miR-7, miR-9, miR-122, and miR-141 were examined and compared using qRT-PCR among 80 severe AP patients, 80 mild AP patients, and 74 healthy controls. Results The serum levels of these four miRNAs were increased markedly in the AP patients compared with the controls, and these levels decreased significantly after effective therapy. Particularly, the level of miR-7 was higher in severe AP patients than in mild AP patients. ROC curve analysis demonstrated that four miRNAs could be used as potential biomarkers for AP. Moreover, these miRNAs showed strong positive correlations with CRP, which may be associated with inflammation. Conclusions The serum miR-7, miR-9, miR-122, and miR-141 levels were increased in AP patients. These 4 miRNAs may represent diagnostic and prognostic biomarkers for AP.
Age at Diagnosis, Extent of Disease and Breast Cancer Survival: A Population-Based Study in Florence, Italy

Background The effect of age at diagnosis on the prognosis of breast cancer is still controversial. The study described the variation by age at diagnosis of some clinical-pathologic features and evaluated the relationship between age and survival, taking into account the effect of extent of disease. Materials The study comprised a large population-based series of 1,182 invasive breast cancers, incident in the period 1985–1986 in the province of Florence. Results The proportion of cases without nodal involvement progressively lowered from 59% in the age group ≤39 years to 22% in the age group ≥80 years. The extent of disease was unknown in 14% of cases aged 70–79 years and in 43% of those aged ≥80 years (other age groups: 3%–5%). A lower rate of surgical treatment and axillary surgery were the main reasons for inadequate staging in the elderly. Ten-year observed survival progressively decreased from 71% for age ≤39 years to 12% for age ≥80 years. Ten-year relative survival showed less evident differences, dropping from 72% for age ≤39 years to 57% for age ≥80 years. In the relative survival analysis, the differences in relative risks of death among age groups were not significant, either in the univariate or multivariate analysis. Nevertheless, the model with adjustment for extension of disease showed a flattening of the estimated relative risks in age groups over 59 years. Conclusions Age at diagnosis was not significantly related to 10-year breast cancer relative survival, suggesting that the worse prognosis in the elderly was largely related to the risk of death from other causes, rather than to a different malignant potential of the tumor. The worse distribution by extent of disease in older women indirectly suggested that diagnostic delays also influenced the different prognosis observed among age groups.
Categorization and Concepts

Concepts are the building blocks of thought. They are critically involved when we reason, make inferences, and try to generalize our previous experiences to new situations. Behind every word in every language lies a concept, although there are concepts, like the small plastic tubes attached to the ends of shoelaces, that we are familiar with and can think about even if we do not know that they are called aglets. Concepts are indispensable to human cognition because they take the “blooming, buzzing confusion” (James, 1890, p. 488) of disorganized sensory experiences and establish order through mental categories. These mental categories allow us to make sense of the world and predict how worldly entities will behave. We see, hear, interpret, remember, understand, and talk about our world through our concepts, and so it is worthy of reflection time to establish where concepts come from, how they work, and how they can best be learned and deployed to suit our cognitive needs.
Metaplastic Breast Carcinoma: Analysis of Clinical and Pathologic Characteristics - A Case Series.

OBJECTIVE Metaplastic breast cancer (MBC) is a rare type of breast cancer that is considered to be clinically aggressive. The clinical significance and prognostic risk factors of MBC are limited. This study comprises a retrospective analysis of the clinical and pathologic findings of a series of patients treated for MBC. MATERIALS AND METHODS The files of 657 patients who underwent surgery because of breast cancer at our clinic were examined and the data found on 11 patients who were diagnosed as having MBC were analyzed. RESULTS With a median age of 56 years, all patients were postmenopausal and presented with a palpable mass on physical examination. Symptoms of ulceration and skin involvement were seen in only one patient. Eight patients were diagnosed as having squamous cell carcinoma (SCC), and 3 had both SCC and osseous differentiation. The median diameter was 3.8 cm (max. 14 cm; min. 1.5 cm). Lymph node metastasis was detected in 5 (45%) patients. Progesterone (PR) and estrogen (ER) were both negative in 11 (100%) patients and 10 (90.9%) patients, respectively, and CerbB2 was negative in 7 (63.6%) patients. Patients were followed up for a median period of 15 months (range, 6-40 months); at the end of which, 10 patients survived and one died of cardiac arrest at 7 months post-operatively. No instances of local recurrence or distant organ metastasis were found in any patients. The overall patient survival rate was 90%. CONCLUSION There is no consensus on the clinical significance or best treatment approach for metaplastic carcinoma. In our study, patients with MBC were of advanced age, had tumors with large margins, high negativity for hormone receptors, and moderate- to well-differentiated histology.
Implications of changing definitions of myocardial infarction on number of events and all-cause mortality: the WHO 1979, ESC/ACC 2000, AHA 2003, and Universal 2007 definitions revisited

Purpose To analyse the impact of four different definitions of acute myocardial infarction (AMI) on number of events and all-cause mortality after AMI. Methods We retrospectively examined number of AMI events and mortality according to four different definitions of AMI, among 1494 patients admitted to Haukeland University Hospital in Norway from March 2002 to February 2003. Eligible for analysis were 815 patients with a discharge diagnosis of an AMI, and 679 patients without any AMI discharge diagnosis but with elevated cardiac troponin I level during admission. Results Applying the WHO 1979 definition resulted in 566 definite AMIs among the 1494 patients and was used as reference. According to the other definitions, there were 455 (−20%) definite AMIs by the original troponin ‘rise and fall’ version of the ESC/ACC 2000 definition, 729 (+29%) by the troponin ‘rise or fall’ interpretation of the ESC/ACC 2000 definition, 761 (+34%) by the AHA 2003 definition, and 743 (+31%) by the Universal 2007 definition (all p < 0.001). The 28-day, 1-year, 5-year, and 8-year mortality for definite AMI applying the WHO 1979 definition was 12, 19, 32, and 40%, whereas applying the Universal 2007 definition resulted in a mortality of 14, 21, 35, and 43%, respectively. Conclusions The change of definitions of AMI during the last decades has had a significant impact on the number of AMI events and a moderate impact on the AMI mortality among hospitalized patients.
Tumour Necrosis Factor Alpha and Oxidative Stress in the Breath Condensate of Those with Non-Small Cell Lung Cancer

Background and Aims: Lung cancer is a leading cause of cancer mortality worldwide and is associated with the release of tumour necrosis factor-α (TNF-α), subsequent cellular apoptosis and the generation of oxidative stress. Exhaled breath condensate (EBC) analysis is a non-invasive method for sampling biofluids from the lower respiratory tract. This study aimed to evaluate possible biomarkers of lung cancer by measuring the levels of TNF-α and the oxidation of ascorbic acid in EBC. Patients with lung cancer were enrolled into the study prior to treatment, during treatment and post-treatment, and results compared with an age-matched control population. Material and Methods: Patients with Stage II-IV non small cell lung cancer (NSCLC) were recruited prior to and at stages of their treatment. EBC levels of TNF-α, and rate of ascorbic acid oxidation were measured. Results: A total of 19 patients with NSCLC (mean age 71.37 ± 7.77 yrs) and 25 age-matched control subjects were enrolled. Levels of EBC TNF-α were elevated in the EBC of patients with lung cancer compared with control subjects (1.02 ± 0.07 pg/ml vs. 0.51 ± 0.06 pg/ml, p < 0.0001). Moreover, the rate of ascorbic acid oxidation was significantly greater in the EBC of patients with lung cancer compared with control subjects (2.20% [0.4 – 11.0] vs. 1.00% [0.1 – 8.5], p = 0.0244). Conclusion: TNF-α and the rate of ascorbic acid oxidation was elevated in the EBC of patients with lung cancer regardless of treatment. Longitudinal studies in a larger population are required to evaluate these markers for the effect of treatment and prognosis.
Cholinoceptive and cholinergic properties of cardiomyocytes involving an amplification mechanism for vagal efferent effects in sparsely innervated ventricular myocardium

Our recent studies have shown that, as indicated by vagal stimulation, an acetylcholinesterase inhibitor donepezil, an anti‐Alzheimer’s disease drug, prevents progression of heart failure in rats with myocardial infarction, and activates a common cell survival signal shared by acetylcholine (ACh) in vitro. On the basis of this and evidence that vagal innervation is extremely poor in the left ventricle, we assessed the hypothesis that ACh is produced by cardiomyocytes, which promotes its synthesis via a positive feedback mechanism. Rat cardiomyocytes expressed choline acetyltransferase (ChAT) in the cytoplasm and vesicular acetylcholine transporter with the vesicular structure identified by immunogold electron microscopy, suggesting that cardiomyocytes possess components for ACh synthesis. Intracellular ACh in rat cardiomyocytes was identified with physostigmine or donepezil. However, with atropine, the basal ACh content was reduced. In response to exogenous ACh or pilocarpine, cardiomyocytes increased the transcriptional activity of the ChAT gene through a muscarinic receptor and ChAT protein expression, and, finally, the intracellular ACh level was upregulated by pilocarpine. Knockdown of ChAT by small interfering RNA accelerated cellular energy metabolism, which is suppressed by ACh. Although physostigmine had a minimal effect on the ChAT promoter activity by inhibiting acetylcholinesterase, donepezil resulted in elevation of the activity, protein expression and intracellular ACh level even in the presence of sufficient physostigmine. Orally administered donepezil in mice increased the ChAT promoter activity in a reporter gene‐transferred quadriceps femoris muscle and the amount of cardiac ChAT protein. These findings suggest that cardiomyocytes possess an ACh synthesis system, which is positively modulated by cholinergic stimuli. Such an amplification system in cardiomyocytes may contribute to the beneficial effects of vagal stimulation on the ventricles.
Are two antidepressant mechanisms better than one?

338 J Clin Psychiatry 58:8, August 1997 © Coyright 997 Phsicians Poraduate Pess, nc. ne pesonal opy ay be pinted New drugs with multiple mechanisms may not only be able to reduce side effects, they might even improve antidepressant efficacy. There is a troubling clinical notion, especially among some investigators, that the SSRIs are not as powerful as the TCAs for treating patients who have severe depression or who are resistant to prior trials of antidepressants. Looking at the pharmacology of the favorite Europe TCA clomipramine, we see that it is both a serotonin and a norepinephrine reuptake inhibitor. Is it possible that the SSRIs went too far by removing he classical antidepressants, namely tricyclic antidepressants (TCAs) and monoamIssue: A drug that combines two or more synergistic mechanisms of action may yield superior therapeutic efficacy or tolerability compared to a single therapeutic mechanism of highly selective agents. Are Two Antidepressant Mechanisms Better Than One?
Rorschach Comprehensive System Data for a Sample of 309 Adult Nonpatients From Portugal

Three hundred and nine nonpatient adults, evenly distributed according to sex, age, educational level, and residence, took part in the Rorschach test study carried out in Portugal. The sample was drawn from selected regions of the country and was balanced for population density in urban and rural areas. Test administration was controlled through the services of psychologists familiar with the Rorschach Comprehensive System (CS; Exner, 1993). Results indicate that, in Portugal (Pires, 2000), level of education is the variable that seems to have the largest effect on Rorschach responding.
The relationship between oral contraceptive use and functional outcome in women with recent-onset inflammatory polyarthritis: results from the Norfolk Arthritis Register.

OBJECTIVE Use of oral contraceptives (OCs) may prevent the development of rheumatoid arthritis, but the influence of OC use on disease outcome is unresolved. The purpose of this study was to examine functional outcome and OC use in women with inflammatory polyarthritis (IP). METHODS The Norfolk Arthritis Register (NOAR) is an inception cohort of patients with recent-onset IP. We studied patient-reported history of OC use in 663 women who were born after 1945 and who had not used OCs during followup. OC use during followup was additionally investigated in 265 women who were <50 years old and had not undergone menopause or hysterectomy during followup. All patients were recruited to the NOAR between 1990 and 2004. Functional ability was assessed using the Health Assessment Questionnaire (HAQ), with adjustment for age at symptom onset. RESULTS The median followup was 4.9 years. In the investigation analyzing OC use before symptom onset, patients who had used OCs before symptom onset had lower HAQ scores throughout followup than patients who had not taken OCs before symptom onset (difference in score at 5-year followup -0.35; 95% confidence interval [95% CI] -0.51, -0.19). Patients who were taking OCs at baseline had lower HAQ scores over time than women who were not taking OCs at baseline but had previously done so (mean difference -0.21; 95% CI -0.40, -0.02). In the investigation analyzing OC use during followup, OC use during followup was associated with lower HAQ scores over time than no OC use during followup (mean difference -0.06; 95% CI -0.16, 0.03); however, this was only significant for women with moderate or severe functional disability at the previous assessment (mean difference -0.23; 95% CI -0.40, -0.07). Further adjustment for potential confounders and exclusion of hormone replacement therapy users had little impact. CONCLUSION OC use is generally associated with a beneficial functional outcome in IP, and use before and at symptom onset appeared to have the most consistent benefit.
Evaluation of the primary effect of brefeldin A treatment upon herpes simplex virus assembly.

Addition of the drug brefeldin A (BFA) to cells infected by herpes simplex virus (HSV) type 1 is known to result in a complex pattern of defects in particle assembly. BFA-treated, infected cells accumulate perinuclear enveloped virions and non-enveloped ("naked") cytoplasmic capsids, and it has been difficult to interpret these data in terms of the assembly pathway of HSV and the known effects of BFA on the secretory apparatus. Since BFA is a cytotoxic drug, and earlier studies commonly examined the effects of long-term BFA incubations on infected cells, it was hypothesized that the drug could have pleiotropic and indirect effects on HSV assembly. To test this, use was made of an HSV synchronized assembly assay, in which cells are infected with the virus mutant tsProt.A and maintained at 39 degrees C to induce reversible accumulation of a population of procapsids. By first adding BFA and then shifting these cells to 31 degrees C for 3 h to allow the accumulated procapsids to mature, it was possible to test the effect of short-term BFA treatment on only those HSV assembly events that are downstream of procapsid maturation. Under these conditions, it was found that procapsids matured and packaged the viral genome normally, but remained non-enveloped and failed to exit the nucleus. It is concluded that the primary effect of BFA on HSV replication is to inhibit budding at the inner nuclear membrane.
Early and late calcium waves during wound healing in corneal endothelial cells

Immediately after wounding, bovine corneal endothelial cells develop a fast calcium wave that propagates from the wound border to the rest of the monolayer and extinguishes in approximately 5 minutes. One hour after wounding, a late, slow calcium wave (SCW) develops concomitantly to the depolarization of the plasma membrane potential of the border cells. The incorporation of inhibitors of the epithelial sodium channel and of the sodium‐calcium exchanger produces inhibition of the membrane depolarization and the SCW, and diminishes the rate of wound healing. The L‐type calcium channel blocker nimodipine does not have any effect on the SCW. The reversible inhibition of the fast calcium wave does not affect the SCW and only slightly decreases the velocity of healing. Our results suggest that the SCW is at least partially produced by the coupling of the epithelial sodium channel and the sodium‐calcium exchanger functioning in reverse mode. They also suggest that the SCW may play a role in the overall healing process.
Remediation Strategies for Historical Mining and Smelting Sites

The environmental, social and economic problems associated with abandoned mine sites are serious and global. Environmental damage arising from polluted waters and dispersal of contaminated waste is a feature characteristic of many old mines in North America, Australia, Europe and elsewhere. Today, because of the efficiency of mining operations and legal requirements in many countries for prevention of environmental damage from mining operations, the release of metals to the environment from modern mining is low. However, many mineralized areas that were extensively worked in the 18th and 19th centuries and left abandoned after mining had ceased, have left a legacy of metal contaminated land. Unlike organic chemicals and plastics, metals cannot be degraded chemically or biologically into non-toxic and environmentally neutral constituents. Thus sites contaminated with toxic metals present a particular challenge for remediation. Soil remediation has been the subject of a significant amount of research work in the past decade; this has resulted in a number of remediation options currently available or being developed. Remediation strategies for metal/metalloid contaminated historical mining sites are reviewed and summarized in this article. It focuses on the current applications of in situ remediation with the use of soil amendments (adsorption and precipitation based methods are discussed) and phytoremediation fin situ plant based technology for environmental clean up and restoration). These are promising alternative technologies to traditional options of excavation and ex situ treatment, offering an advantage of being non-invasive and low cost. In particular, they have been shown to be effective in remediation of mining and smelting contaminated sites, although the long-term durability of these treatments cannot be predicted.