Miracle-dz/UniFAR-FTUs huggingface dataset:
NOVEL OVINE MODEL OF METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS-INDUCED PNEUMONIA AND SEPSIS

Methicillin-resistant Staphylococcus aureus (MRSA)-related pneumonia and/or sepsis are a frequent serious menace. The aim of the study was to establish a standardized and reproducible model of MRSA-induced septic pneumonia to evaluate new therapies. Sheep were operatively prepared for chronic study. After 5 days' recovery, tracheostomy was performed under anesthesia, and smoke injury was induced by inhalation of cotton smoke (48 breaths, <40°C). Methicillin-resistant S. aureus (AW6) (~2.5 × 1011 colony-forming units) was instilled into the airway by a bronchoscope. After the injury, animals were awakened and maintained on mechanical ventilation by 100% oxygen for first 3 h, and thereafter, oxygen concentration was adjusted according to blood gases. The sheep were resuscitated by lactated Ringer solution with an initial rate of 2 mL kg−1 h−1 that was further adjusted according to hematocrit. Study groups include (1) sham (noninjured, nontreated; n = 6), (2) S + MRSA (exposed to smoke inhalation and MRSA, nontreated; n = 6), and (3) smoke (exposed to smoke inhalation alone; n = 6). Injured (S + MRSA) animals showed the signs of severe sepsis-related multiple organ failure 3 h after insult. Cardiovascular morbidity was evidenced by severe hypotension, with increased heart rate, cardiac output, left atrial pressure and severely decreased systemic vascular resistance index, and left ventricle stroke work index. Pulmonary dysfunction was characterized by deteriorated gas exchange (PaO2/FIO2 and pulmonary shunt) and increased ventilatory pressures. The S + MRSA group showed significantly greater lung tissue water content, myeloperoxidase activity, and cytokine production compared with uninjured sham animals. Microvascular hyperpermeability was evidenced by marked fluid retention (fluid net balance), decreased plasma protein with decreased plasma oncotic pressure, and increased pulmonary microvascular pressure. All these changes were accompanied by 6- to 7-fold increase in plasma nitrite/nitrate and increased production of reactive nitrogen species in lung. The smoke inhalation alone had a little or no effect on these variables. This model closely mimics hyperdynamic human sepsis. The excessive production of NO may be extensively involved in the pathogenic process.
Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons

Significance The olfactory bulb (OB) receives newly born neurons through adulthood. This process constitutes another means, in addition to molecular or synaptic changes within individual neurons, by which the OB can make changes to its functional circuitry. In this study, we show that adult-born OB neurons display adaptive changes in response to the sensory context. In a restricted domain of the dendritic arbor of adult-born neurons, we found that structural and functional changes are strongest when olfactory cues are associated with a reward. Thus, the recruitment of adult-born neurons should be seen as a form of metaplasticity that strengthens long-range functional connectivity in the olfactory system during learning. The production of new neurons in the olfactory bulb (OB) through adulthood is a major mechanism of structural and functional plasticity underlying learning-induced circuit remodeling. The recruitment of adult-born OB neurons depends not only on sensory input but also on the context in which the olfactory stimulus is received. Among the multiple steps of adult neurogenesis, the integration and survival of adult-born neurons are both strongly influenced by olfactory learning. Conversely, optogenetic stimulation of adult-born neurons has been shown to specifically improve olfactory learning and long-term memory. However, the nature of the circuit and the synaptic mechanisms underlying this reciprocal influence are not yet known. Here, we showed that olfactory learning increases the spine density in a region-restricted manner along the dendritic tree of adult-born granule cells (GCs). Anatomical and electrophysiological analysis of adult-born GCs showed that olfactory learning promotes a remodeling of both excitatory and inhibitory inputs selectively in the deep dendritic domain. Circuit mapping revealed that the malleable dendritic portion of adult-born neurons receives excitatory inputs mostly from the regions of the olfactory cortex that project back to the OB. Finally, selective optogenetic stimulation of olfactory cortical projections to the OB showed that learning strengthens these inputs onto adult-born GCs. We conclude that learning promotes input-specific synaptic plasticity in adult-born neurons, which reinforces the top-down influence from the olfactory cortex to early stages of olfactory information processing.
Cytotoxin-Associated Gene A-Negative Strains of Helicobacter pylori as a Potential Risk Factor of Pancreatic Cancer: A Meta-Analysis Based on Nested Case-Control Studies

Objectives Risk of pancreatic cancer between Helicobacter pylori infected and noninfected persons is controversial, and therefore a meta-analysis was performed. Methods PubMed was searched up to September 2014. Only population-based nested case-control studies comparing the serological prevalence of Helicobacter pylori between pancreatic cancer cases and cancer-free controls were eligible. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer risk between Helicobacter pylori infected and noninfected persons were estimated. Results Five eligible nested case-control studies were included, with 1446 pancreatic cancer cases and 2235 cancer-free controls. On the whole, the proportion of pancreatic cancer cases among those infected with Helicobacter pylori was not significant different from those noninfected (OR, 0.99; 95% CI, 0.65–1.50; P = 0.96). Likewise, seropositivity of cytotoxin-associated gene A (CagA) showed nonsignificant association with pancreatic cancer (OR, 0.92; 95% CI, 0.65–1.30; P = 0.63). The CagA-positive virulent strains of Helicobacter pylori did not increase the risk of pancreatic cancer (OR, 0.97; 95% CI, 0.50–1.89; P = 0.93). However, CagA-negative nonvirulent strains of Helicobacter pylori had a significant increased risk for pancreatic cancer (OR, 1.47; 95% CI, 1.11–1.96; P = 0.008). Conclusions The CagA-negative non-virulent strains of Helicobacter pylori may be a potential risk factor of pancreatic cancer. High-quality prospective large-scaled studies are required for more conclusive results.
Cognitive models of medical decision-making capacity in patients with mild cognitive impairment

This study investigated cognitive predictors of medical decision-making capacity (MDC) in patients with amnestic mild cognitive impairment (MCI). A total of 56 healthy controls, 60 patients with MCI, and 31 patients with mild Alzheimer's disease (AD) were administered the Capacity to Consent to Treatment Instrument (CCTI) and a neuropsychological test battery. The CCTI assesses MDC across four established treatment consent standards—S1 (expressing choice), S3 (appreciation), S4 (reasoning), and S5 (understanding)—and one experimental standard [S2] (reasonable choice). Scores on neuropsychological measures were correlated with scores on each CCTI standard. Significant bivariate correlates were subsequently entered into stepwise regression analyses to identity group-specific multivariable predictors of MDC across CCTI standards. Different multivariable cognitive models emerged across groups and consent standards. For the MCI group, measures of short-term verbal memory were key predictors of MDC for each of the three clinically relevant standards (S3, S4, and S5). Secondary predictors were measures of executive function. In contrast, in the mild AD group, measures tapping executive function and processing speed were primary predictors of S3, S4, and S5. MDC in patients with MCI is supported primarily by short-term verbal memory. The findings demonstrate the impact of amnestic deficits on MDC in patients with MCI. (JINS, 2008, 14, 297–308.)Disclosure: The capacity outcome measure used in the study is owned by the UAB Research Foundation (UABRF). Dr. Marson and Dr. Harrell receive royalty income through UABRF. Statistical analyses were carried out by Mr. Okonkwo, and statistical consultation was provided by Dr. Raman.
Binding of the sphingolipid S1P to hTERT stabilizes telomerase at the nuclear periphery by allosterically mimicking protein phosphorylation

Sphingosine 1-phosphate binds and stabilizes telomerase, a process that could be targeted to promote senescence and reduce cancer growth. Telomerase stabilized by a sphingolipid In normal adult cells, the structure at the ends of chromosomes, called the telomere, becomes progressively shorter with each replication cycle. When telomeres get too short or damaged, the cell stops dividing and becomes senescent. The enzyme telomerase maintains the integrity of telomeres, and phosphorylation stabilizes the catalytic subunit (called TERT) of this enzyme. In both normal fibroblasts and lung cancer cells, Panneer Selvam et al. found that binding of the phospholipid S1P to TERT mimicked protein phosphorylation and prevented TERT degration. Disrupting the interaction between S1P and TERT by either depleting S1P or mutating the interaction site in TERT impaired telomere maintenance and promoted senescence in cultured cells and decreased the growth of lung cancer cell xenografts in mice. During DNA replication, the enzyme telomerase maintains the ends of chromosomes, called telomeres. Shortened telomeres trigger cell senescence, and cancer cells often have increased telomerase activity to promote their ability to proliferate indefinitely. The catalytic subunit, human telomerase reverse transcriptase (hTERT), is stabilized by phosphorylation. We found that the lysophospholipid sphingosine 1-phosphate (S1P), generated by sphingosine kinase 2 (SK2), bound hTERT at the nuclear periphery in human and mouse fibroblasts. Docking predictions and mutational analyses revealed that binding occurred between a hydroxyl group (C′3-OH) in S1P and Asp684 in hTERT. Inhibiting or depleting SK2 or mutating the S1P binding site decreased the stability of hTERT in cultured cells and promoted senescence and loss of telomere integrity. S1P binding inhibited the interaction of hTERT with makorin ring finger protein 1 (MKRN1), an E3 ubiquitin ligase that tags hTERT for degradation. Murine Lewis lung carcinoma (LLC) cells formed smaller tumors in mice lacking SK2 than in wild-type mice, and knocking down SK2 in LLC cells before implantation into mice suppressed their growth. Pharmacologically inhibiting SK2 decreased the growth of subcutaneous A549 lung cancer cell–derived xenografts in mice, and expression of wild-type hTERT, but not an S1P-binding mutant, restored tumor growth. Thus, our data suggest that S1P binding to hTERT allosterically mimicks phosphorylation, promoting telomerase stability and hence telomere maintenance, cell proliferation, and tumor growth.
Effect of surface polarity on water contact angle and interfacial hydration structure.

We perform molecular dynamics simulations of water in the presence of hydrophobic/hydrophilic walls at T = 300 K and P = 0 GPa. For the hydrophilic walls, we use a hydroxylated silica model introduced in previous simulations [Lee, S. H. ; Rossky, P. J. J. Chem. Phys. 1994, 100, 3334. Giovambattista, N. ; Rossky, P. J.; Debenedetti, P. G. ; Phys. Rev. E 2006, 73, 041604. ]. By rescaling the physical partial atomic charges by a parameter 0 <or= k <or= 1, we can continuously transform the hydrophilic walls (hydroxylated silica, k = 1) into hydrophobic apolar surfaces (k = 0). From a physical point of view, k is the normalized magnitude of a surface dipole moment, and thus it quantifies the polarity of the surface. We calculate the contact angle of water for 0 <or= k <or= 1. We find that, at least for the present homogeneous, atomically flat, and defect-free surface model, the magnitude of the surface dipole correlates with the contact angle in a one-to-one correspondence. In particular, we find that polar surfaces with 0 < k <or= kc = 0.4 are macroscopically hydrophobic; that is, the contact angle is larger than 90 degrees . For the cutoff value k = kc, the magnitude of the dipole moment of the polar silica surface unit is 41% that of the water molecule dipole moment. We also study the water orientation distributions next to the walls (a microscopic property). We find that these distributions also correlate with the contact angle in a one-to-one correspondence. Thus, the structure of confined water, the surface polarity, and the contact angle are in a direct correspondence to each other, and therefore, each quantifies the hydrophobicity/hydrophilicity of the surface.
Antigen exposure shapes the ratio between antigen-specific Tregs and conventional T cells in human peripheral blood

Significance Herein we used peptide–MHC tetramer staining and enrichment to identify antigen-specific Tregs directly ex vivo and found that most CD4+ T-cell specificities, self or foreign, contain 5–15% Tregs. A notable exception is that two dominant influenza specificities contain very small proportions of Tregs. We demonstrated using human cord blood cells and murine lymphocytic choriomeningitis virus infection that antigen exposure can alter the balance between Tregs and conventional T cells in an antigen-specific and context-dependent manner. The ratio between specific Tregs and cognate effectors correlates with protective immunity in mice and T-cell dominance hierarchy in humans. Our finding provides insight into Treg specificity and highlights the importance of Treg and effector balance in an antigen-specific context. The T-cell receptor (TCR) is required for maturation and function of regulatory T cells (Tregs), but the ligand specificities of Tregs outside the context of transgenic TCRs are largely unknown. Using peptide–MHC tetramers, we isolated rare specific Foxp3+ cells directly ex vivo from adult peripheral blood and defined their frequency and phenotype. We find that a proportion of circulating Tregs recognize foreign antigens and the frequency of these cells are similar to that of self-reactive Tregs in the absence of cognate infection. In contrast, the frequencies of Tregs that recognize some common microbial antigens are significantly reduced in the blood of most adults. Exposure to peripheral antigens likely has a major influence on the balance between Tregs and conventional T-cell subsets because a larger proportion of flu-specific T cells has a regulatory cell phenotype in the cord blood. Consistent with this finding, we show that lymphocytic choriomeningitis virus infection can directly modulate the ratio of virus-specific effectors and Tregs in mice. The resulting change in the balance within an antigen-specific T-cell population further correlates with the magnitude of effector response and the chronicity of infection. Taken together, our data highlight the importance of antigen specificity in the functional dynamics of the T-cell repertoire. Each specific population of CD4+ T cells in human peripheral blood contains a subset of Tregs at birth, but the balance between regulatory and effector subsets changes in response to peripheral antigen exposure and this could impact the robustness of antipathogen immunity.
Alginate microparticles for Polymyxin B Peyer's patches uptake: microparticles for antibiotic oral administration

Microparticles with size less than 3 µm, able to be taken up by M cell of Peyer's patches for the drug delivery to the Gut Associated Limphoid Tissue (GALT), were developed in order to improve oral bioavailability of Polymyxin B (PMB). Less than 3 µm alginate microparticles resistant to gastro-intestinal media were prepared by spray-drying technique and cross-linking by calcium ions and chitosan. The cross-linked microparticles were evaluated for PMB content by spectrophotometric method, alginate/PMB interaction by rheological study, cross-linking degree by EDS analysis and PMB activity by microbiological assay. By modulating the polymer cross-linking degree, cationic PMB interacted on alginate chains leading to a proper PMB loading as well as antibiotic retention in gastric environment and sustained delivery in intestinal fluid. Moreover, the procedure resulted suitable for PMB biological activity preservation.
A meta-analytic review of the effects of psychotherapy control conditions for anxiety disorders

Background Little is known about the magnitude of improvement associated with psychotherapy control conditions for adult anxiety disorders. This information is important for the design of psychosocial treatment efficacy studies. Method We performed a computerized search of treatment outcome studies of anxiety disorders conducted between the first available year and 1 March 2007. In addition, we examined the reference lists from identified articles and asked international experts to identify eligible studies. We included studies that randomly assigned adult patients suffering from anxiety disorders to either cognitive–behavioral treatment or psychotherapy control condition. For each study, the two authors independently selected psychometrically sound measures of anxiety disorder severity. In addition, we collected data on attrition and treatment response. Results Of the 1165 studies that were initially identified, 19 studies (454 patients) met inclusion criteria and were included in the analyses. The random effects analysis yielded a pre- to post-treatment Hedges' g effect size of 0.45 (95% confidence interval 0.35–0.46, z=8.50, p<0.001). The mean weighted response and attrition rates were 25.0% and 14.2%, respectively. There was no evidence for publication bias, nor was there a significant relationship between the effect size and diagnostic group, study year or number of treatment sessions. Conclusions Psychotherapy control conditions are associated with significant improvements when administered to adults suffering from anxiety disorders. In addition, they are associated with a relatively low attrition rate. These findings can inform the design of future psychotherapy outcome studies.
Transforming growth factor alpha in arterioles: cell surface processing of its precursor by elastases

Analysis of the transforming growth factor alpha (TGF alpha) cDNA predicts that the mature TGF alpha polypeptide is cleaved from the extracellular domain of its precursor, which is an integral membrane protein. Furthermore, the cleavage sites for the release of this mitogen are compatible with the participation of an elastaselike protease. We have immunohistochemically localized TGF alpha to the vascular smooth muscle cells in the arterioles. To investigate whether polymorphonuclear (PMN) leukocytic elastase, a blood-borne protease, could process the cell surface TGF alpha, NR6 cells were transfected with the rat TGF alpha cDNA. The cDNA encoded the entire open reading frame, and its expression was under the control of the mouse metallothionein I promoter. A cloned transfectant, termed 1B2, synthesized the TGF alpha precursor in a zinc-inducible manner, and the precursor was localized to the cell surface. Western blot (immunoblot) analysis indicated that treatment of the zinc-induced 1B2 cells with either PMN leukocytic or pancreatic elastase resulted in the release of the mature TGF alpha polypeptide. The released TGF alpha was bioactive, as it was capable of both competing with epidermal growth factor for binding to its receptor and stimulating [3H]thymidine incorporation in the mitogenic assay. Formaldehyde fixation of the 1B2 cells eliminated basal release of TGF alpha but allowed normal processing by both PMN leukocytic and pancreatic elastase to occur. However, human cathepsin G, bovine pancreatic alpha 1-chymotrypsin, collagenase, trypsin, subtilisin, and plasmin failed to release any detectable fragments of the TGF alpha precursor from the fixed cells. The location of TGF alpha in the arterioles and ability of PMN leukocytic elastase to process the membrane-bound TGF alpha precursor suggests a novel role for this elastase at the wound site.
Improved approximate near neighbor search without false negatives for $l_2$

We present a new algorithm for the $c$--approximate nearest neighbor search without false negatives for $l_2^d$. We enhance the dimension reduction method presented in \cite{wygos_red} and combine it with the standard results of Indyk and Motwani~\cite{motwani}. We present an efficient algorithm with Las Vegas guaranties for any $c>1$. This improves over the previous results, which require $c=\omega(\log\log{n})$ \cite{wygos_red}, where $n$ is the number of the input points. Moreover, we improve both the query time and the pre-processing time. Our algorithm is tunable, which allows for different compromises between the query and the pre-processing times. In order to illustrate this flexibility, we present two variants of the algorithm. The "efficient query" variant involves the query time of $O(d^2)$ and the polynomial pre-processing time. The "efficient pre-processing" variant involves the pre-processing time equal to $O(d^{\omega-1} n)$ and the query time sub-linear in $n$, where $\omega$ is the exponent in the complexity of the fast matrix multiplication. In addition, we introduce batch versions of the mentioned algorithms, where the queries come in batches of size $d$. In this case, the amortized query time of the "efficient query" algorithm is reduced to $O(d^{\omega -1})$.
Thermal and 3D Kinect Sensor Fusion for Robust People Detection using Evolutionary Selection of Supervised Classifiers

In this paper we propose a novel approach for combining information from low cost multiple sensors for people detection on a mobile robot. Robustly detecting people is a key capability needed for robots that operate in populated environments. Several works show the advantages of fusing data coming from complementary sensors. Kinect sensor offers a rich data set at a significantly low cost, however, there are some limitations using it in a mobile platform, mainly that Kinect relies on images captured by a static camera. To cope with these limitations, this work is based on the fusion of Kinect and thermopile array sensor mounted on top of a mobile platform. We propose the implementation of evolutionary selection of people detection supervised classifiers built using several computer vision transformation. Experimental results carried out with a mobile platform in a manufacturing shop floor show that the percentage of wrong classified using only Kinect is drastically reduced with the classification algorithms and with the combination of the three information sources.