Miracle-dz/UniFAR-FTUs huggingface dataset:
Microglial Activation and β-Amyloid Deposit Reduction Caused by a Nitric Oxide-Releasing Nonsteroidal Anti-Inflammatory Drug in Amyloid Precursor Protein Plus Presenilin-1 Transgenic Mice

3-4-(2-Fluoro-α-methyl-[1,1′-biphenyl]-4-acetyloxy)-3-methoxyphenyl]-2-propenoic acid 4-nitrooxy butyl ester (NCX-2216), a nitric oxide (NO)-releasing derivative of the cyclooxygenase-1-preferring nonsteroidal anti-inflammatory drug (NSAID) flurbiprofen, dramatically reduced both β-amyloid (Aβ) loads and Congo red staining in doubly transgenic (Tg) amyloid precursor protein plus presenilin-1 mice when administered at 375 ppm in diet between 7 and 12 months of age. This reduction was associated with a dramatic increase in the number of microglia expressing major histocompatibility complex-II antigen, a marker for microglial activation. In contrast, ibuprofen at 375 ppm in diet caused modest reductions in Aβ load but not Congo red staining, suggesting that the effects of this nonselective NSAID were restricted primarily to nonfibrillar deposits. We detected no effects of the cyclooxygenase-2-selective NSAID celecoxib at 175 ppm on amyloid deposition. In short-term studies of 12-month-old Tg mice, we found that the microglia-activating properties of NCX-2216 (7.5 mg · kg−1 · d−1, s.c.) were present after 2 weeks of treatment. Microglia were not activated by NCX-2216 in non-Tg mice lacking Aβ deposits, nor were microglia activated in Tg animals by flurbiprofen (5 mg · kg−1 · d−1) alone. These data are consistent with the argument that activated microglia can clear Aβ deposits. We conclude that the NO-generating component of NCX-2216 confers biological actions that go beyond those of typical NSAIDs. In conclusion, NCX-2216 is more efficacious than ibuprofen or celecoxib in clearing Aβ deposits from the brains of Tg mice, implying potential benefit in the treatment of Alzheimer's dementia.
Potent antitumor activity of oncolytic adenovirus expressing Beclin-1 via induction of autophagic cell death in leukemia

An attractive strategy among adenovirus-based oncolytic systems is to design adenoviral vectors to express pro-apoptotic genes, in which this gene-virotherapy approach significantly enhances tumor cell death by activating apoptotic pathways. However, the existence of cancer cells with apoptotic defects is one of the major obstacles in gene-virotherapy. Here, we investigated whether a strategy that combines the oncolytic effects of an adenoviral vector with simultaneous expression of Beclin-1, an autophagy gene, offers a therapeutic advantage for leukemia. A Beclin-1 cDNA was cloned in an oncolytic adenovirus with chimeric Ad5/11 fiber (SG511-BECN). SG511-BECN treatment induced significant autophagic cell death, and resulted in enhanced cell killing in a variety of leukemic cell lines and primary leukemic blasts. SG511-BECN effects were seen in chronic myeloid leukemia and acute myeloid leukemia with resistance to imatinib or chemotherapy, but exhibited much less cytotoxicity on normal cells. The SG511-BECN-induced autophagic cell death could be partially reversed by RNA interference knockdown of UVRAG, ATG5, and ATG7. We also showed that SG511-BECN strongly inhibited the growth of leukemic progenitors in vitro. In murine leukemia models, SG511-BECN prolonged the survival and decreased the xenograft tumor size by inducing autophagic cell death. Our results suggest that infection of leukemia cells with an oncolytic adenovirus overexpressing Beclin-1 can induce significant autophagic cell death and provide a new strategy for the elimination of leukemic cells via a unique mechanism of action distinct from apoptosis.
Semiparametric Regression Models for RepeatedEvents with Random E ects and Measurement

Statistical methodology is presented for the regression analysis of multiple events in the presence of random eeects and measurement error. Omitted covariates are modeled as random eeects. Our approach to parameter estimation and signiicance testing is to start with a naive model of semi-parametric Poisson process regression, and then to adjust for random eeects and any possible covariate measurement error. We illustrate the techniques with data from a randomized clinical trial for the prevention of recurrent skin tumors.
Grassland to shrubland state transitions enhance carbon sequestration in the northern Chihuahuan Desert

The replacement of native C4‐dominated grassland by C3‐dominated shrubland is considered an ecological state transition where different ecological communities can exist under similar environmental conditions. These state transitions are occurring globally, and may be exacerbated by climate change. One consequence of the global increase in woody vegetation may be enhanced ecosystem carbon sequestration, although the responses of arid and semiarid ecosystems may be highly variable. During a drier than average period from 2007 to 2011 in the northern Chihuahuan Desert, we found established shrubland to sequester 49 g C m−2 yr−1 on average, while nearby native C4 grassland was a net source of 31 g C m−2 yr−1 over this same period. Differences in C exchange between these ecosystems were pronounced – grassland had similar productivity compared to shrubland but experienced higher C efflux via ecosystem respiration, while shrubland was a consistent C sink because of a longer growing season and lower ecosystem respiration. At daily timescales, rates of carbon exchange were more sensitive to soil moisture variation in grassland than shrubland, such that grassland had a net uptake of C when wet but lost C when dry. Thus, even under unfavorable, drier than average climate conditions, the state transition from grassland to shrubland resulted in a substantial increase in terrestrial C sequestration. These results illustrate the inherent tradeoffs in quantifying ecosystem services that result from ecological state transitions, such as shrub encroachment. In this case, the deleterious changes to ecosystem services often linked to grassland to shrubland state transitions may at least be partially offset by increased ecosystem carbon sequestration.
Father involvement in Latino families: The influence of acculturation, gender attitudes, and parenting style

FATHER INVOLVEMENT IN LATINO FAMILIES: THE INFLUENCE OF ACCULTURATION, GENDER ATTITUDES, AND PARENTING STYLE by Angela D. Ledgerwood Latinos are a sizeable and growing population within the United States. Despite this, the majority of empirical research on parenting and father involvement has been conducted with White, middle-class, European American families, the results of which cannot be generalized to Latinos. The primary aim of the current study was to examine how acculturation, gender attitudes, and parenting style influence father involvement in Latino families. Although fathers may have a choice in their level of involvement in the everyday lives of their children, mothers also exert influence on father involvement by conscious or unconscious encouragement or discouragement. Data were collected and independently analyzed from both Latino fathers (n = 90) and Latina mothers (n = 112) in the Midwest. Participants were asked to independently selfreport on acculturation, gender attitudes, parenting style, and father involvement. It was hypothesized that acculturation to the U.S. majority culture, egalitarian gender attitudes and an authoritarian parenting style would predict increased father involvement for fathers. This hypothesis was partially supported with parenting style predicting father involvement. Acculturation to the U.S. majority culture, egalitarian gender attitudes, and a permissive parenting style by mothers was hypothesized to predict increased father involvement. This hypothesis was not supported. However, results suggest that both fathers’ and mothers’ acculturation to the dominant U.S. majority culture may be indirectly related to father involvement. Additional research is needed to explore this potential indirect relationship. A secondary aim of this study was an exploratory examination of the relationship between gender attitudes and parenting style within this population. For both fathers and mothers, an authoritative parenting style predicted gender attitudes. Implications and applications of the results of this study are discussed for practitioners working directly with Latino parents, including utility for cultural adaptation of parenting education programs. FATHER INVOLVEMENT IN LATINO FAMILIES: THE INFLUENCE OF ACCULTURATION, GENDER ATTITUDES, AND PARENTING STYLE
Barriers to cervical cancer screening among ethnic minority women: a qualitative study

Background Ethnic minority women are less likely to attend cervical screening. Aim To explore self-perceived barriers to cervical screening attendance among ethnic minority women compared to white British women. Design Qualitative interview study. Setting Community groups in ethnically diverse London boroughs. Methods Interviews were carried out with 43 women from a range of ethnic minority backgrounds (Indian, Pakistani, Bangladeshi, Caribbean, African, Black British, Black other, White other) and 11 White British women. Interviews were recorded, transcribed verbatim and analysed using Framework analysis. Results Fifteen women had delayed screening/had never been screened. Ethnic minority women felt that there was a lack of awareness about cervical cancer in their community, and several did not recognise the terms ‘cervical screening’ or ‘smear test’. Barriers to cervical screening raised by all women were emotional (fear, embarrassment, shame), practical (lack of time) and cognitive (low perceived risk, absence of symptoms). Emotional barriers seemed to be more prominent among Asian women. Low perceived risk of cervical cancer was influenced by beliefs about having sex outside of marriage and some women felt a diagnosis of cervical cancer might be considered shameful. Negative experiences were well remembered by all women and could be a barrier to repeat attendance. Conclusions Emotional barriers (fear, embarrassment and anticipated shame) and low perceived risk might contribute to explaining lower cervical screening coverage for some ethnic groups. Interventions to improve knowledge and understanding of cervical cancer are needed in ethnic minority communities, and investment in training for health professionals may improve experiences and encourage repeat attendance for all women.
Soft Part 3D visualization by serial sectioning and computer reconstruction

Recent increases in performance of personal computer hard- and software enabled a variety of 3D graphical applications, such as surface visualizations of biological specimens. This indirectly recalled an old morphological method back to life, the investigation of soft part anatomy by light microscopical serial section analysis. A practical guide covering all procession steps beginning with anesthetization leading to the fi nal goal, 3D visualization of specimens, is provided. Most useful for 3D procession—of particularly small specimens—are ribbon-forming serial resin (= “semithin”) sections. A reliable method for achievement of ribbon formation is described in detail for the fi rst time. Contact cement is applied only to the cutting surface of the block, which represents a modifi cation of an old protocol. Details on the materials and tools, such as embedding media (epoxy resins) and knives (Ralph glass or special diamond knife) used and general handling for the entire procedure are given and critically evaluated. 3D procession is explained for the software AMIRA® . The major processing steps, from section image capturing until refi ning of surfaces, are explained. Based on the experience of the author, practical aids that cannot be found in the user’s guide of the software or elsewhere for facilitating the process are given. These include preliminary calculation of resolution, calibration and strategies for facilitating the process and improvement of results. The interpolate function is emphasized as most useful for completion of segmentation and also correction works. Visualization examples are followed by an estimate of work expenditure for graphical processes involved
A large receptive–expressive gap in bilingual children

The present study focuses on the discrepancy between receptive and expressive language competence among bilingual children and tests possible explanatory factors of this gap. The sample consisted of 406 bilingual children with German as their second language (L2) and 46 different first languages. Receptive and expressive German language competence (L2) were measured with a standardized language development test at the age of 43 months. As expected, a significant gap in receptive and expressive German language competence (L2) emerged in all language groups. The size of the gap reached 1 SD and correlated with the amount of language contact and thus provides support for the language exposure hypothesis. However, we found no evidence for the language familiarity hypothesis. The present study contributes to the understanding of mechanisms in bilingual language development and, hence, is consequential for both basic research and language assessment practice.
Increased prevalence of Listeria monocytogenes in the faeces of patients receiving long-term H2-antagonists

Background: Human listeriosis is an uncommon infection caused by the Grampositive organism Listeria rnonocytogenes. Objective: To investigate the effects of therapeutic gastric acid suppression on faecal isolation of L. monocytogenes and the incidence of human listeriosis. Methods: Five stool specimens from each of 20 patients on continuous H2-antagonist therapy and two faecal samples from each of 47 healthy controls were investigated for the presence of Listeria spp. Results: A higher faecal isolation rate of L. monocytogenes was detected amongst the patients (20%) compared with the controls (2.1%) (P<0.025). All subjects with stools positive for Listeria spp. were female, this sex difference being significant in the patient group (P<0.0036) compared with controls. No patient, however, developed listeriosis. Conclusion: Patients on long-term gastric acid suppressive therapy may be at increased risk of faecal carriage of L. monocytogenes. European Journal of Gastroenterology & Hepatology 1996, 8:1071–1074
Role of a Hydrophobic Pocket in Polyamine Interactions with the Polyspecific Organic Cation Transporter OCT3*

Background: OCT3 pharmacology is distinct from that of other OCTs, which may relate to non-conserved residues in a putative binding pocket. Results: Mutating pocket residues to their OCT1 counterparts shifts OCT3 polyamine-like blocker sensitivity toward that of OCT1, and vice versa. Conclusion: OCT substrate-recognition mechanisms are fine-tuned by the makeup of the binding cleft. Significance: A mechanism has not yet been proposed. Organic cation transporter 3 (OCT3, SLC22A3) is a polyspecific, facilitative transporter expressed in astrocytes and in placental, intestinal, and blood-brain barrier epithelia, and thus elucidating the molecular mechanisms underlying OCT3 substrate recognition is critical for the rational design of drugs targeting these tissues. The pharmacology of OCT3 is distinct from that of other OCTs, and here we investigated the role of a hydrophobic cavity tucked within the translocation pathway in OCT3 transport properties. Replacement of an absolutely conserved Asp by charge reversal (D478E), neutralization (D478N), or even exchange (D478E) abolished MPP+ uptake, demonstrating this residue to be obligatory for OCT3-mediated transport. Mutations at non-conserved residues lining the putative binding pocket of OCT3 to the corresponding residue in OCT1 (L166F, F450L, and E451Q) reduced the rate of MPP+ transport, but recapitulated the higher sensitivity pharmacological profile of OCT1. Thus, interactions of natural polyamines (putrescine, spermidine, spermine) and polyamine-like potent OCT1 blockers (1,10-diaminodecane, decamethonium, bistriethylaminodecane, and 1,10-bisquinuclidinedecane) with wild-type OCT3 were weak, but were significantly potentiated in the mutant OCT3s. Conversely, a reciprocal mutation in OCT1 (F161L) shifted the polyamine-sensitivity phenotype toward that of OCT3. Further analysis indicated that OCT1 and OCT3 can recognize essentially the same substrates, but the strength of substrate-transporter interactions is weaker in OCT3, as informed by the distinct makeup of the hydrophobic cleft. The residues identified here are key contributors to both the observed differences between OCT3 and OCT1 and to the mechanisms of substrate recognition by OCTs in general.
Algorithms for Skin Permeability Using Hydrogen Bond Descriptors: the Problem of Steroids *

Several algorithms that use hydrogen bond descriptors have been published for the permeation of compounds from aqueous solution through human stratum corneum. In the present work, all the skin permeability coefficients, Kp in cm s−, used in these algorithms for non‐steroids have been correlated through the Abraham equation to give a new algorithm:
ECONOMIC EVALUATION OF A NURSING-LED INTERMEDIATE CARE UNIT

Objective: The aim of this paper is to examine the costs of introducing a nursing-led ward program together with examining the impact this may have on patients' outcomes. Methods: The study had a sample size of 177 patients with a mean age of 77, and randomized to either a treatment group (care on a nursing-led ward, n = 97) or a control group (standard care usually on a consultant-led acute ward, n = 80). Resource use data including length of stay, tests and investigations performed, and multidisciplinary involvement in care were collected. Results: There were no significant differences in outcome between the two groups. The inpatient costs for the treatment group were significantly higher, due to the longer length of stay in this group. However, the postdischarge costs were significantly lower for the treatment group. Conclusions: The provision of nursing-led intermediate care units has been proposed as a solution to inappropriate use of acute medical wards by patients who require additional nursing rather than medical care. Whether the treatment group is ultimately cost-additive is dependent on how long reductions in postdischarge resource use are maintained.
Serotonergic and noradrenergic function in depression: clinical correlates

The present study was conducted in order to investigate the relationships between central noradrenergic (NA) and serotonergic (5-HT) function and clinical characteristics of a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. We measured growth hormone response (ΔGH) to clonidine (CLO) (an α2 NA agonist), as an index of central NA function, and prolactin response (APRL) to d-fenfluramine (d-FEN) (a specific 5-HT releaser/uptake inhibitor), as an index of central 5-HT function, in 53 medication-free depressed inpatients. On the basis of their CLO and d-FEN test responses, patients were classified into 4 groups. Group 1 (blunted ΔPRLd-FEN alone [11 %]) was characterized by a recent violent suicide attempt, a high degree of medical damage, and mild anxiety. Group 2 (blunted ΔGHCLO alone [32%]) was characterized by an absence of a history of suicide attempt and by severe anxiety. Group 3 (combination of blunted ΔGHCLO and APRLd-FEN [18%]) was characterized by a history of suicide attempts, total duration of the illness of over W years, age over 40 years, and more than 3 previous hospitalizations. Group 4 (no abnormality [39%]) had no specific clinical profile. These results suggest that, in depression, specific psychopathological features may be linked to 5-HT and/or NA dysfunction. However, our results also suggest that NA and/or 5-HT dysfunction are less likely to be the primary cause of mood disorders but are more indicative of failure of compensatory mechanisms involved in affective homeostatic processes.
The Diagnosis of Invasive and Noninvasive Pulmonary Aspergillosis by Serum and Bronchoalveolar Lavage Fluid Galactomannan Assay

The incidence and mortality of invasive pulmonary aspergillosis (IPA) are rising, particularly in critically ill patients and patients with severe chronic obstructive pulmonary disease (COPD). Noninvasive aspergillosis occurring in these patients requires special attention because of the possibility of developing subsequent IPA, given the poor health and worsened immune state of these patients. We compared the performance of the Platelia galactomannan (GM) enzyme immunoassay in the bronchoalveolar lavage fluid (BALF) and serum. The sensitivity, and specificity of BALF-GM were 85.4% and 62.4%, and those of serum-GM were 67.9% and 93.5% at the cutoff index of 0.5. As the cutoff index increased, the specificity of BALF-GM detection was increased with the detriment of sensitivity. The area under the ROC curves was 0.817 (95% CI: 0.718–0.916) for BALF-GM and 0.819 (95% CI: 0.712–0.926) for serum-GM. The optimal cutoff index was 1.19 for BALF-GM, and the sensitivity and specificity were 67.9% and 89.2%. The BALF-GM assay is more sensitive in detecting pulmonary aspergillosis than serum-GM assay and fungal cultures. However, BALF-GM assay has a high false-positive rate at the cutoff index of 0.5. Hence, the diagnostic cutoff index of the BALF-GM assay should be improved to avoid the overdiagnosis of pulmonary aspergillosis in clinic.
What Is the Position of an Arm Relative to the Body? Neural Correlates of Body Schema and Body Structural Description

Neuropsychological studies suggest that the human brain is endowed with two body representations: the body schema (BS), coding the orientation of one's body parts in space, and the body structural description (BSD), coding the location of body parts relative to a standard body. We used fMRI to disentangle the neural mechanisms underlying these putatively distinct body representations. Participants saw an arm or a pot's handle (stimulus: arm, handle) rotated at different angles (angle: 30–150°). If the stimulus was an arm, subjects were instructed to imagine (1) rotating their own arm until it matched the stimulus orientation (comparing the seen arm to their own) or (2) seeing the stimulus moving toward its appropriate position on a simultaneously presented human body [comparing the arm to the one of a standard body (strategy: motor, visual imagery)]. If the stimulus was a handle, subjects were instructed to imagine (1) placing the handle on its appropriate position on a simultaneously presented pot or (2) seeing it moving toward its pot's position. The analysis of the interaction stimulus × strategy revealed activation of left secondary somatosensory cortex (SII), specifically when comparing the stimulus arm to one's own. The analysis of the parameters describing the linear effect of angle revealed that neural activity of left posterior intraparietal sulcus was modulated by the stimulus's rotation, but only when relating the arm to a standard body. The results associate BS and BSD with differential neural substrates, thereby suggesting that these are independent body representations, and furthermore extend current concepts of SII function.