Miracle-dz/UniFAR-FTUs huggingface dataset:
Conservation genetics and population history of the threatened European mink Mustela lutreola, with an emphasis on the west European population

In species of great conservation concern, special attention must be paid to their phylogeography, in particular the origin of animals for captive breeding and reintroduction. The endangered European mink lives now in at least three well‐separated populations in northeast, southeast and west Europe. Our aim is to assess the genetic structure of these populations to identify ‘distinct population segments’ (DPS) and advise captive breeding programmes. First, the mtDNA control region was completely sequenced in 176 minks and 10 polecats. The analysis revealed that the western population is characterized by a single mtDNA haplotype that is closely related to those in eastern regions but nevertheless, not found there to date. The northeast European animals are much more variable (π = 0.012, h = 0.939), with the southeast samples intermediate (π = 0.0012, h = 0.469). Second, 155 European mink were genotyped using six microsatellites. The latter display the same trends of genetic diversity among regions as mtDNA [gene diversity and allelic richness highest in northeast Europe (HE = 0.539, RS = 3.76), lowest in west Europe (HE = 0.379, RS = 2.12)], and provide evidences that the southeast and possibly the west populations have undergone a recent bottleneck. Our results indicate that the western population derives from a few animals which recently colonized this region, possibly after a human introduction. Microsatellite data also reveal that isolation by distance occurs in the western population, causing some inbreeding because related individuals mate. As genetic data indicate that the three populations have not undergone independent evolutionary histories for long (no phylogeographical structure), they should not be considered as distinct DPS. In conclusion, the captive breeding programme should use animals from different parts of the species’ present distribution area.
Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging: Potential Role for Hypoxia-Inducible Transcription Factor-1–Regulated Pathways

Background and Purpose— Iron chelation therapy is emerging as a novel neuroprotective strategy. The mechanisms of neuroprotection are diverse and include both neuronal and vascular pathways. We sought to examine the effect of iron chelation on cerebrovascular function in healthy aging and to explore whether hypoxia-inducible transcription factor-1 activation may be temporally correlated with vascular changes. Methods— We assessed cerebrovascular function (autoregulation, vasoreactivity, and neurovascular coupling) and serum concentrations of vascular endothelial growth factor and erythropoietin, as representative measures of hypoxia-inducible transcription factor-1 activation, during 6 hours of deferoxamine infusion in 24 young and 24 older healthy volunteers in a randomized, blinded, placebo-controlled cross-over study design. Cerebrovascular function was assessed using the transcranial Doppler ultrasound. Vascular endothelial growth factor and erythropoietin serum protein assays were conducted using the Meso Scale Discovery platform. Results— Deferoxamine elicited a strong age- and time-dependent increase in the plasma concentrations of erythropoietin and vascular endothelial growth factor, which persisted ⩽3 hours post infusion (age effect P=0.04; treatment×time P<0.01). Deferoxamine infusion also resulted in a significant time- and age-dependent improvement in cerebral vasoreactivity (treatment×time P<0.01; age P<0.01) and cerebral autoregulation (gain: age×time×treatment P=0.04). Conclusions— Deferoxamine infusion improved cerebrovascular function, particularly in older individuals. The temporal association between improved cerebrovascular function and increased serum vascular endothelial growth factor and erythropoietin concentrations is supportive of shared hypoxia-inducible transcription factor-1–regulated pathways. Therefore, pharmacological activation of hypoxia-inducible transcription factor-1 to enhance cerebrovascular function may be a promising neuroprotective strategy in acute and chronic ischemic syndromes, especially in elderly patients. Clinical Trial Registration— URL: http://www.clinicaltrials. gov. Unique identifier: NCT013655104.
The creation of the client reflexivity scale: A measure of minute fluctuations in self-awareness and exploration.

Abstract Objective: to design and pilot a reliable observer-based scale of client reflexivity that can be used on short segments of time (“coding intervals”) across therapy sessions. Reflexivity was defined as the level of a client's awareness and exploration of his or her interiority. Interiority was defined as thoughts, feelings, sensations, intentions, and desires. Method: The Client Reflexivity Scale (CRS) was designed through the coding of public access therapy videos featuring demonstrations of therapy. Along with the Experiencing Scale, the CRS was then piloted on one good outcome and one poor outcome session of cognitive-behavioural therapy for anxiety. Each session of therapy featured the same therapist but different clients. Two raters coded the sessions. Results: Weighted kappas for inter-rater reliability ranged from 0.74 to 0.81. The level of reflexivity was significantly higher in the good outcome session than the poor outcome session, though the trajectory of reflexivity for both sessions was the same. The CRS was also compared to the Experiencing Scale in order to determine similarities and differences between the scales. Conclusions: the CRS reliably measured reflexivity within the therapy sessions, and in the future can be layered with other process measures in order to map interactions across therapy sessions.
State-of-the-art and good practice in the field of living labs

Living Labs are an emerging Public Private Partnership (PPP) concept in which firms, public authorities and citizens work together to create, prototype, validate and test new services, businesses, markets and technologies in real-life contexts, such as cities, city regions, rural areas and collaborative virtual networks between public and private players. The real-life and everyday life contexts will both stimulate and challenge research and development as public authorities and citizens will not only participate in, but also contribute to the whole innovation process. This paper examines the state-of-the art in involving the user and stakeholder organisations into the innovation process in various ongoing, embryonic Living Labs initiatives, examines the key practices that need to be in place for the maturation of the concept and gives examples on how those are currently being deployed. The paper concludes with a section dedicated to identifying areas in which future research is required.
Hidradenitis suppurativa ‐ characteristics and consequences

The general characteristics of patients with hidradenitis suppurativa have not been previously described in detail. Although rare complications of the disease have been described, little is known of the average impact of hidra‐denitis suppurativa. We have now aimed to describe the general characteristics of the disease and its impact on patients with an established diagnosis of hidradenitis (a= 68) and compare these with those of an unselected general population sample (n= 523).
Combined treatment of primary vitreoretinal lymphomas significantly prolongs the time to first relapse

Background Vitreoretinal lymphomas belong to the family of central nervous system (CNS) lymphomas. The optimal approach for the treatment of isolated primary vitreoretinal lymphoma is unclear because of the lack of large comparative clinical series. Combination of intravitreal and systemic chemotherapy is recommended in many reports. The aim of our retrospective study was to compare the survival rate and prognosis of patients with vitreoretinal lymphoma with and without CNS involvement. Methods Twenty patients with vitreoretinal lymphomas were observed between the years 2004and2016, 10 patients with primary vitreoretinal lymphoma and 10 with primary CNS lymphoma. To compare survival rates, we included 53 patients diagnosed with primary CNS lymphoma without vitreoretinal involvement between the years 2002and2011 from our haemato-oncology department. Results The 5-year survival rate was estimated 71% in patients with vitreoretinal lymphoma in our observation. Significantly longer 5-year overall survival (P˂0.01) was observed in patients with vitreoretinal lymphoma compared with patients with primary CNS lymphoma without vitreoretinal involvement. Progression-free survival was almost equal in both groups of patients with primary vitreoretinal lymphoma and primary CNS lymphoma (P=0.363). The relapse of lymphoma was frequent (50%–60%) with the median time to first relapse of 31 months. Combined treatment (local and systemic) in patients without CNS involvement significantly prolonged progression-free survival in our study (P˂0.05). Conclusion Combined treatment of primary vitreoretinal lymphoma significantly delays the relapse of lymphoma compared with local therapy alone. Intraocular involvement brings significant positive prognostic value when overall survival is compared.
Cognitive remediation therapy in schizophrenia: randomised controlled trial.

BACKGROUND Cognitive difficulties are prevalent in people with a diagnosis of schizophrenia and are associated with poor long-term functioning. AIMS To evaluate the effectiveness of cognitive remediation therapy on cognitive difficulties experienced by people with schizophrenia. METHOD Participants with a diagnosis of schizophrenia, a social behaviour problem and a cognitive difficulty (n=85) were randomised to 40 sessions of cognitive remediation or treatment as usual in a single-blind randomised controlled trial. Working memory, cognitive flexibility and planning, were measured at weeks 0,14 and 40. RESULTS There were durable improvements in working memory (advantage 1.33 points, 95% CI 0.43-2.16, standardised effect size 0.34) as well as an indication of improvement in cognitive flexibility. Memory improvement predicted improvement in social functioning. Costs were lower in the cognitive remediation group following therapy but rose at follow-up. However, cost-effectiveness analyses showed that improvements in memory were achieved at little additional cost. CONCLUSIONS Cognitive remediation therapy is associated with durable improvements in memory, which in turn are associated with social functioning improvements in people with severe mental illness.
Acquisition and generalization of fear conditioning are not modulated by the BDNF-val66met polymorphism in humans.

Few studies have investigated the role of the BDNF-val66met polymorphism in fear conditioning in humans, and previous results have been inconsistent. In the present study, we examined whether the BDNF-val66met was associated with differences in the acquisition and generalization of fear during a differential conditioning paradigm in a large sample of participants (N = 141). Using three different indexes of fear learning (fear-potentiated startle, skin conductance response, and online risk ratings) no effects of the BDNF-val66met were found either on the acquisition or the generalization of conditioned fear. Taken together with previous data, our study suggests that the BDNF-val66met polymorphism has no effect on the acquisition or generalization of fear.
of Nebraska - Lincoln DigitalCommons@University of Nebraska - Lincoln Measuring Tsunami Planning Capacity on U.S. Pacific Coast Measuring Tsunami Planning Capacity on U.S. Pacific Coast

: The U.S. Paciﬁc coastal states are at risk from both locally and distantly generated tsunamis. This vulnerability can be reduced by effective hazard management plans, but no studies have been conducted to determine how local jurisdictions have incorporated tsunami hazard management into their planning frameworks. This paper analyzes the quality of hazard management plans from 43 coastal counties in these states. Plan quality was measured by a plan evaluation protocol deﬁned by ﬁve components and 37 indicators. The results show that few Paciﬁc coastal counties have prepared well for tsunamis. Most plans have a weak factual basis, unclear goals and objectives, weak policies, and few coordination and implementation mechanisms. The average plan quality score is 12.25 out of 50 points and 10 counties never mention tsunami risks in their local plans at all. This evaluation suggests that these jurisdictions need to build a solid factual basis about tsunami hazards, set appropriate goals and practical objectives, expand the array of tools used by planners, enhance interdisciplinary and interorganizational coordination mechanisms, and improve their mechanisms for plan implementation.
Selenoprotein S expression in reactive astrocytes following brain injury

Selenoprotein S (SelS) is an endoplasmic reticulum (ER)‐resident protein involved in the unfolded protein response. Besides reducing ER‐stress, SelS attenuates inflammation by decreasing pro‐inflammatory cytokines. We have recently shown that SelS is responsive to ischemia in cultured astrocytes. To check the possible association of SelS with astrocyte activation, here we investigate the expression of SelS in two models of brain injury: kainic acid (KA) induced excitotoxicity and cortical mechanical lesion. The regulation of SelS and its functional consequences for neuroinflammation, ER‐stress, and cell survival were further analyzed using cultured astrocytes from mouse and human. According to our immunofluorescence analysis, SelS expression is prominent in neurons and hardly detectable in astrocytes from control mice. However, brain injury intensely upregulates SelS, specifically in reactive astrocytes. SelS induction by KA was evident at 12 h and faded out after reaching maximum levels at 3–4 days. Analysis of mRNA and protein expression in cultured astrocytes showed SelS upregulation by inflammatory stimuli as well as ER‐stress inducers. In turn, siRNA‐mediated SelS silencing combined with adenoviral overexpression assays demonstrated that SelS reduces ER‐stress markers CHOP and spliced XBP‐1, as well as inflammatory cytokines IL‐1β and IL‐6 in stimulated astrocytes. SelS overexpression increased astrocyte resistance to ER‐stress and inflammatory stimuli. Conversely, SelS suppression compromised astrocyte viability. In summary, our results reveal the upregulation of SelS expression in reactive astrocytes, as well as a new protective role for SelS against inflammation and ER‐stress that can be relevant to astrocyte function in the context of inflammatory neuropathologies. © 2011 Wiley‐Liss, Inc.
Opposing regulation of neutrophil apoptosis through the formyl peptide receptor‐like 1/lipoxin A4 receptor: implications for resolution of inflammation

Neutrophils have a central role in innate immunity, and their programmed cell death and removal are critical to the optimal expression as well as to efficient resolution of inflammation. Human neutrophils express the pleiotropic receptor formyl peptide receptor‐like 1/lipoxin A4 (LXA4) receptor that binds a variety of ligands, including the acute‐phase reactant serum amyloid A (SAA), the anti‐inflammatory lipids LXA4 and aspirin‐triggered 15‐epi‐LXA4 (ATL), and the glucocorticoid‐inducible protein annexin 1. In addition to regulation of neutrophil activation and recruitment, these ligands have a profound influence on neutrophil survival and apoptosis with contrasting actions, mediating aggravation or resolution of the inflammatory response. Thus, annexin 1 accelerates, whereas SAA rescues human neutrophils from constitutive apoptosis by preventing mitochondrial dysfunction and subsequent activation of caspase‐3. Furthermore, ATL overcomes the antiapoptosis signal from SAA and redirects neutrophils to caspase‐mediated cell death. We review recent developments about the molecular basis of these actions and suggest a novel mechanism by which aspirin promotes resolution of acute inflammation and tissue injury.
Can fluorodeoxyglucose positron emission tomography/computed tomography avoid negative iliac crest biopsies in evaluation of marrow involvement by lymphoma at time of initial staging?

Abstract The assessment of bone marrow involvement (BMI) is important for accurate prognostication and deciding the appropriate therapy in patients with lymphoma. Conventional bilateral iliac crest biopsies (ILBMBs) have many limitations. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) is a useful investigative tool for detecting BMI. F-18 FDG PET/CT data for 97 patients with either non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) were analyzed. ILBMB was performed 7–10 days later. A final diagnosis of BMI was made in 38/97 patients on the basis of composite criteria derived from both FDG PET/CT and ILBMB results. ILBMB detected BMI in 29/38 patients, 2/5 patients with HL, 27/33 patients with NHL, 19/25 patients with aggressive NHL, and 8/8 patients with indolent NHL with a sensitivity of 76%, 40%, 82%, 76%, and 100%, respectively. FDG PET/CT was true positive for BMI in 5/5 patients with HL and 29/33 patients with NHL, comprising 25/25 patients with aggressive NHL and 4/8 patients with indolent NHL, with a sensitivity of 100%, 88%, 100%, and 50%, respectively. FDG PET/CT performed better than ILBMB in cases of HL and aggressive NHL, but its sensitivity was poor in cases of indolent lymphoma. In addition, FDG PET/CT had a very high negative predictive value approaching 100% in HL and aggressive NHL, which might help in avoiding negative ILBMBs.
Patterns of Cognitive Decline, Conversion Rates, and Predictive Validity for 3 Models of MCI

Our objective was to compare the predictive ability of different models of mild cognitive impairment (MCI) as a marker of incipient dementia in a longitudinal population-based Canadian sample. We examined the use of existing, well-documented MCI criteria using data from persons who underwent a clinical examination in the second wave of the Canadian Study of Health and Aging (CSHA). Demographic characteristics, average neuropsychological test performance, and sample frequencies and conversion rates were calculated for each classification. Receiver operating characteristic (ROC) analyses were employed to assess the predictive power of each cognitive classification. The highest sample frequencies and conversion rates were associated with case definitions of multiple-domain MCI. The only diagnostic criteria to significantly predict dementia 5 years later was the cognitive impairment no dementia (CIND)-2 case definition. More restrictive MCI case definitions fail to address the varying temporal increases in decline across different cognitive domains in the progression from normal cognitive functioning and dementia.
Estimating covariate‐adjusted measures of diagnostic accuracy based on pooled biomarker assessments

There is a need for epidemiological and medical researchers to identify new biomarkers (biological markers) that are useful in determining exposure levels and/or for the purposes of disease detection. Often this process is stunted by high testing costs associated with evaluating new biomarkers. Traditionally, biomarker assessments are individually tested within a target population. Pooling has been proposed to help alleviate the testing costs, where pools are formed by combining several individual specimens. Methods for using pooled biomarker assessments to estimate discriminatory ability have been developed. However, all these procedures have failed to acknowledge confounding factors. In this paper, we propose a regression methodology based on pooled biomarker measurements that allow the assessment of the discriminatory ability of a biomarker of interest. In particular, we develop covariate‐adjusted estimators of the receiver‐operating characteristic curve, the area under the curve, and Youden's index. We establish the asymptotic properties of these estimators and develop inferential techniques that allow one to assess whether a biomarker is a good discriminator between cases and controls, while controlling for confounders. The finite sample performance of the proposed methodology is illustrated through simulation. We apply our methods to analyze myocardial infarction (MI) data, with the goal of determining whether the pro‐inflammatory cytokine interleukin‐6 is a good predictor of MI after controlling for the subjects' cholesterol levels.
Polyamine‐mediated regulation of protein acetylation in murine skin and tumors

Overexpression of ornithine decarboxylase (ODC), resulting in increased polyamine metabolism, is a common feature of epithelial tumors. Polyamines play a complex role in promoting tumor development, affecting diverse cellular processes, including gene expression. One way polyamines may affect gene expression is to modulate the multiprotein complexes comprised of transcription factors and coregulatory factors that alter chromatin structure by acetylating/deacetylating nearby histones. We have capitalized on ODC‐overexpressing cultured cells and K6/ODC and ODC/Ras transgenic mouse models, in which ODC overexpression is targeted to hair follicles, to evaluate the influence of polyamines on the acetylation of histones and other proteins. ODC overexpression was found to alter intrinsic histone acetyltransferase (HAT) and deacetylase activities and histone acetylation patterns. The high HAT activity exhibited by ODC transgenic mouse skin and tumors might be partly attributed to enhanced p300/creb‐binding protein (CBP)‐associated HAT activity and increased levels of Tat interactive protein, 60 kDa (Tip60) HAT protein isoforms. Altered association of Tip60 with E2F1 and a subset of newly identified Tip60‐interacting transcription factors was detected in ODC mouse skin and tumors, implying novel polyamine modulation of Tip60‐regulated gene expression. Polyamine effects on HAT enzymes also influence the acetylation status of nonhistone proteins. Overexpression of ODC in skin serves as a novel stimulus for acetylation of the tumor suppressor protein, p53—a target of both p300/CBP and Tip60—with concomitant increased binding to, and increased transcription of, a downstream target gene. The future challenge will be to elucidate the multiple mechanisms by which polyamines influence enzymes that regulate protein acetylation and gene transcription to promote cancer. © 2007 Wiley‐Liss, Inc.
Pharmacokinetic evaluation of losartan

Introduction: Blockade of the renin-angiotensin system is one of the major therapeutic strategies in the management of patients with essential hypertension, congestive heart failure and diabetic as well as non-diabetic renal diseases. As the first angiotensin II receptor blocker (ARB) on the market, losartan belongs to the most frequently prescribed ARB. Area covered : The present review examines the pharmacokinetics of losartan with a special discussion on the dose of losartan that should be used in clinical practice to obtain the maximal benefits of the drug. Readers are provided with arguments suggesting that the dose of 50 mg losartan is probably too low and that losartan should preferably be prescribed at the dose of 100 mg/day or higher. Expert opinion : Losartan is an effective antagonist of angiotensin II AT1 receptors which has been shown to provide important clinical benefits in patients with hypertension, congestive heart failure and renal diseases. Losartan should be prescribed at the dose of 100 mg/day and the use of higher doses should be reconsidered in future studies to improve its clinical efficacy.