Miracle-dz/UniFAR-FTUs huggingface dataset:
Cytomegalovirus DNA Detection by Polymerase Chain Reaction in Cerebrospinal Fluid of Infants With Congenital Infection: Associations With Clinical Evaluation at Birth and Implications for Follow-up

Background DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. Methods A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. Results A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P = .01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P = .04), although no association was found at 6 months of age. Conclusions A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV.
Dose optimization of piperacillin/tazobactam in critically ill children

Objectives To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen. Patients and methods This pharmacokinetic study enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg every 6 h based on piperacillin). Piperacillin/tazobactam concentrations were measured by an LC-MS/MS method. Pharmacokinetic data were analysed using non-linear mixed effects modelling. Results Piperacillin and tazobactam blood samples were collected from 47 patients (median age 2.83 years; range 2 months to 15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model that included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) every 4 h over 2 h, 100 mg/kg every 4 h given over 1 h or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24 h were the minimal requirements to achieve the therapeutic targets for piperacillin (60% f T >MIC >16 mg/L). Conclusions Standard intermittent dosing regimens do not ensure optimal piperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.
Automated Extraction Improves Multiplex Molecular Detection of Infection in Septic Patients

Sepsis is one of the leading causes of morbidity and mortality in hospitalized patients worldwide. Molecular technologies for rapid detection of microorganisms in patients with sepsis have only recently become available. LightCycler SeptiFast test Mgrade (Roche Diagnostics GmbH) is a multiplex PCR analysis able to detect DNA of the 25 most frequent pathogens in bloodstream infections. The time and labor saved while avoiding excessive laboratory manipulation is the rationale for selecting the automated MagNA Pure compact nucleic acid isolation kit-I (Roche Applied Science, GmbH) as an alternative to conventional SeptiFast extraction. For the purposes of this study, we evaluate extraction in order to demonstrate the feasibility of automation. Finally, a prospective observational study was done using 106 clinical samples obtained from 76 patients in our ICU. Both extraction methods were used in parallel to test the samples. When molecular detection test results using both manual and automated extraction were compared with the data from blood cultures obtained at the same time, the results show that SeptiFast with the alternative MagNA Pure compact extraction not only shortens the complete workflow to 3.57 hrs. , but also increases sensitivity of the molecular assay for detecting infection as defined by positive blood culture confirmation.
Objective assessment of envelope enhancement algorithms for assistive hearing devices

Individuals with auditory neuropathy spectrum disorder (ANSD) or auditory processing disorders (APDs) often suffer from temporal processing deficits leading to degraded speech perception. The situation becomes worse in the presence of background noise. Evidence exists that the exaggeration of speech envelope may enhance intelligibility, although a comprehensive evaluation of envelope enhancement algorithms is lacking. In the present study, two schemes of envelope enhancement algorithms, with and without an additional noise reduction algorithm, were applied to sentence-level-stimuli in different background noise conditions. The algorithms were assessed objectively using the Hearing Aid Speech Perception Index (HASPI). Results showed that the envelope enhancement algorithms are effective in improving the predicted speech intelligibility score under certain Signal-to-Noise Ratio (SNR) conditions.
Allelic expression imbalance polymorphisms in susceptibility chromosome regions and the risk and survival of breast cancer

Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele‐specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age‐frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal‐weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.
Anti-microRNA-222 (Anti-miR-222) and -181B Suppress Growth of Tamoxifen-resistant Xenografts in Mouse by Targeting TIMP3 Protein and Modulating Mitogenic Signal*

Background: MicroRNAs-221/222 and 181b are up-regulated in tamoxifen-resistant breast cancer. Results: Anti-miRs-222/181b regressed tamoxifen-resistant xenografts. Down-regulation of TIMP3, a common target of these miRs, facilitated growth factor signaling by regulating metalloproteases. Conclusion: Survival of tamoxifen-resistant breast cancer is dependent on miR-mediated suppression of TIMP3. Significance: Anti-miRs-222/221 and -181b can be used to render tamoxifen-resistant tumors responsive to the drug. We have shown earlier that miR-221 and -222 are up-regulated in tamoxifen-resistant MCF-7 (OHTR) cells and Her2-positive human breast tumors when compared with Her2 negative tumors. In this study, we report markedly enhanced expression of miR-181b in OHTR cells and endocrine-resistant tumors. Further, anti-miR-222 or -181b in combination with tamoxifen suppressed growth of tamoxifen-resistant xenografts in mice. Luciferase reporter assay and expression analysis showed that TIMP3, a tissue metalloproteinase inhibitor, is a common target of miR-221/222 and -181b. In situ hybridization and immunohistochemical analysis demonstrated reciprocal relationships between TIMP3 and miR-221/222/181b expression in primary human breast carcinomas. Ectopic expression of TIMP3 inhibited growth of the OHTR cells, and its depletion in MCF-7 cells reduced sensitivity to tamoxifen in vitro and in vivo. EGF-induced MAPK and AKT phosphorylation were significantly higher in OHTR cells and miR-221/222-overexpressing MCF-7 cells than in control cells, which suggests modulation of mitogenic signaling by TIMP3 and the miRs. On the contrary, phosphoMAPK and phosphoAKT levels were diminished in TIMP3-overexpressing OHTR cells and increased in TIMP3-depleted MCF-7 cells. Low levels of estrogen or tamoxifen elicited similar differences in phosphoMAPK levels in these cells. Reduced levels of TIMP3 facilitated growth of tamoxifen-resistant cells by alleviating its inhibitory effect on ADAM10 and ADAM17, which are critical for OHTR cell growth. In conclusion, miR-221/222 and -181b facilitate growth factor signaling in tamoxifen-resistant breast cancer by down-regulating TIMP3, and corresponding anti-miRs can be used to render these tumors responsive to tamoxifen.
Multi-shot person re-identification approach based key frame selection

This paper presents a novel approach to solve the problem of person re-identification in non-overlapping camera views. We propose an appearance based method for person re-identification that condenses a set of frames of the same individual into the multi-class classifier SVM (Support Vector Machine). Still, the choice of different and most expressive frames for each target is very challenging. Besides, efficient person re-identification algorithms are computationally expensive due to the big amount of data used. One of the originalities of our method is how to select different shots during person tracking within each camera to guaranty efficient person re-identification. We evaluate our approach on the publicly available PRID 2011 multi-shot re-identification dataset and demonstrate some performance in comparison with the elimination of the proposed key frames selection.
Antibiotics‐induced modulation of large intestinal microbiota altered aromatic amino acid profile and expression of neurotransmitters in the hypothalamus of piglets

The evidence of gut microbiota‐mediated modulation of brain function has been widely recognized from studies using germ‐free rodents or animals with oral antibiotic‐induced microbiota depletion. Since the large intestine harbors greater numbers and more diverse of microbes than in the small intestine, large intestinal microbiota may play a crucial role in the modulation of brain function. In this study, a large intestinal microbiota‐targeted strategy was used to investigate the impact of large intestinal microbiota on brain function. Twelve piglets (12.08 ± 0.28 kg) fitted with a T‐cannula at the distal ileum were fed a standard diet and randomly assigned to two groups (n = 6) for ileal infusion of either saline or antibiotics. After 25 days of infusion, ileal and fecal microbiota, serum amino acids and neurotransmitters, and hypothalamic transcriptomics were analyzed. While the antibiotic infusion did not change the proximal ileal microbial composition, it markedly altered the fecal microbial composition and increased aromatic amino acid (AAAs) metabolism (p < 0.05), suggesting the infusion specifically targeted large intestinal microbes. Concentrations of AAAs were likewise decreased in the blood and hypothalamus (p < 0.05) by antibiotic infusion. Antibiotic infusion further decreased concentrations of hypothalamic 5‐hydroxytryptamine (5‐HT) and dopamine, in line with AAAs being their precursors. An up‐regulation in gene expressions of neurotransmitter transporters and synthetases was observed (q < 0.001). In conclusion, the distalileal‐antibiotic infusion altered neurotransmitter expression in the porcine hypothalamus and this effect occurred simultaneously with changes in both the large intestinal microbiota, and AAAs in the large intestine, blood and hypothalamus. These findings indirectly indicate that large intestinal microbiota affects hypothalamic neurotransmitter expressions.
Nasopharyngeal Pneumococcal Carriage During Childhood Community-Acquired Alveolar Pneumonia: Relationship Between Specific Serotypes and Coinfecting Viruses

Background Respiratory viruses and Streptococcus pneumoniae are known to be copathogens in childhood pneumonia. However, it is unclear whether all pneumococcal serotypes are equally prone to such interaction. We attempted to determine association between carried pneumococcal serotypes and respiratory viruses during childhood community-acquired alveolar pneumonia (CAAP). Methods The study was conducted during respiratory syncytial virus (RSV) seasons, before pneumococcal vaccine introduction. Children aged <5 years diagnosed with CAAP with positive pneumococcal nasopharyngeal cultures from whom viral diagnostic tests were obtained were enrolled. Viral detection was done by culture, direct immunofluorescence assay (DFA) or polymerase chain reaction. Adjusted odd ratios (ORs) for serotype-specific carriage rates by presence of specific viruses were calculated: single RSV-positive (RSV[+]); other respiratory viruses (ORspVs[+]); and no respiratory virus (RspVs[-]). We compared invasive and noninvasive pneumococcal serotypes according to previous publications. Results Invasive serotype colonization was significantly lower in RSV(+) versus RspVs(-) CAAP (OR = 0.18; 95% confidence interval [CI] = .05-.60), whereas colonization with noninvasive serotypes tended to be higher in RSV(+) (OR = 2.39; 95% CI = .98-5.79). Conclusions We found an inverse relationship between pneumonia-associated invasive pneumococcal serotypes and RSV detection during CAAP. This finding may lead to better understanding of the interaction between respiratory viruses and S. pneumoniae in CAAP pathogenesis.
An Ontology-Based Approach for Mobile Personalized Recommendation

Mobile devices are in a widespread use today. Restricted by the features of mobile devices, such as mobility, low communication bandwidth, small capacity of memory, limited power and inconvenient interaction, mobile services are required to recommend items adapting to the user need and location. Much existing research on recommendations ignores semantic information of user dynamic historical preferences which is vital to the quality of recommendation. In this paper, an ontology-based approach for mobile personalized recommendation is proposed. This paper gives weight values to historical preferences using a decay factor and a time window. Then, historical preferences are mapped into the domain ontology and generate the User Dynamic Preference Ontology (UDPO), which is stored in mobile devices to reduce the load of bandwidth. After building UDPO, the user profile, the domain ontology and UDPO are combined to calculate the set of recommended items. Here, the user profile involves the user location and the user interests. The experimental results show that our approach can provide Points of Interest which the user likes better.
Multiple sources identification in networks with partial timestamps

We study the problem of identifying multiple infection sources in a network based on the network topology, diffusion model and a stream of infection timestamps. We first propose a multiple sources reduction algorithm (MSR) to obtain a set of source candidate clusters, which reduces the multiple sources estimation problem to the single source estimation problem. The problem is then solved using a proposed single source estimation algorithm (SSE) based on a Gaussian diffusion model with unknown diffusion parameters, which we estimate jointly. We show that if the graph is a tree, then each source candidate cluster we found in the MSR step contains at least one source. Simulations using synthetic and real networks suggest that our algorithm is able to estimate the true infection sources to within a small number of hops with a small portion of the infection timestamps being observed.
Comparative transcriptome analysis reveals distinct genetic modules associated with Helios expression in intratumoral regulatory T cells

Significance Regulatory T cells (Tregs) play a critical role in inflammatory, autoimmune, and antitumor immune responses. Increased expression of transcription factor Helios by tumor-infiltrating Tregs can enhance immune-suppressive activity, while deletion of Helios promotes an effector T helper (Th) cell phenotype that can contribute to the host antitumor immune response. We report that chronic inflammatory conditions of tumors induce Helios-deficient Tregs to express increased levels of genes associated with T cell activation and Th cell differentiation. Helios-dependent changes in gene expression are restricted to tumor sites and not observed in peripheral lymphoid tissues. We suggest that Helios-deficient Tregs that recognize tumor-associated self-antigens may become unstable in the tumor microenvironment and undergo reprogramming into effector T cells that can inhibit tumor growth. Regulatory T cells (Tregs) are key modulators of immune tolerance, capable of suppressing inflammatory immune responses and promoting nonlymphoid tissue homeostasis. Helios, a transcription factor (TF) that is selectively expressed by Tregs, has been shown to be essential for the maintenance of Treg lineage stability in the face of inflammatory conditions that include autoimmune disease and cancer. Helios-deficient Tregs within tumors acquire effector T cell function and contribute to immune responses against cancer. However, the underlying genetic basis of this Treg reprogramming is not well understood. Here, we report that Helios-deficient Tregs within the chronic inflammatory tumor microenvironment (TME) derepress genetic programs associated with T helper (Th) cell differentiation by up-regulating Th cell-associated TFs and effector cytokines. These genetic changes of Helios-deficient Tregs are most apparent in a Treg subpopulation with high affinity for self-antigens, as detected by both increased GITR/PD-1 expression and increased responsiveness to self-antigens. Their combined effects may promote a phenotype conversion of Tregs into effector T cells within the TME, where TCR engagement and costimulatory receptor expression by Tregs are increased. These data provide a genetic basis for the unstable phenotype of Helios-deficient Tregs within the inflammatory environment of tumors and suggest that immune milieu-dependent alterations in gene expression are a central feature of Treg conversion.
The lysophosphatidic acid acyltransferases (acylglycerophosphate acyltransferases) family: one reaction, five enzymes, many roles

Purpose of review Lysophosphatidic acid acyltransferases (LPAATs)/acylglycerophosphate acyltransferases (AGPATs) are a homologous group of enzymes that all catalyze the de novo formation of phosphatidic acid from lysophosphatidic acid (LPA) and a fatty acyl-CoA. This review seeks to resolve the apparent redundancy of LPAATs through examination of recent literature. Recent findings Recent molecular studies suggest that individual LPAAT homologues produce functionally distinct pools of phosphatidic acid, whereas gene ablation studies demonstrate unique roles despite a similar biochemical function. Loss of the individual enzymes not only causes diverse effects on down-stream lipid metabolism, which can vary even for a single enzyme from one tissue to the next, but also results in a wide array of physiological consequences, ranging from cognitive impairment, to lipodystrophy, to embryonic lethality. Summary LPAATs are critical mediators of cell membrane phospholipid synthesis, regulating the production of specific down-stream glycerophospholipid species through generation of distinct pools of phosphatidic acid that feed into dedicated biosynthetic pathways. Loss of any specific LPAAT can lead to alterations in cellular and organellar membrane phospholipid composition that can vary for a single enzyme in different tissues, with unique pathophysiological implications.
Effect of layering pattern on thermal and mechanical properties of lyocell/rayon fabric reinforced textile composites

The influence of different layering pattern on the thermal and mechanical properties of the hybrid lyocell/rayon woven fabric reinforced polyester composites is demonstrated in this research work. The effect of different layering pattern was studied and characterized with tensile, open hole tensile, flexural, and impact testing. Composites manufacture with rayon/rayon/lyocell pattern reinforcement has the best tensile and flexural properties. The tensile and flexural strength increased by 36.5% and 43.79%, respectively, with reference to neat resin. It is also noted that the tensile modulus reduced by 31.1% when compared to neat resin. This represents an increase of material ductility in comparison with neat resin. It is observed that placing of high strength lyocell fabric at the extreme layer as reinforcement would result in enhanced properties. In case of rayon/lyocell/rayon hybrid tensile composites it can be seen that there is only 8% increase in tensile properties in comparison with neat resin due to rayon fabric placed as a skin rather than core. A negative effect of 6–26% reduced tensile strength was observed for the open hole (6 mm diameter) samples of all pattern of textile composites. This was due to fiber and inter fiber (matrix) fracture. A more detailed microfractography analysis was used to determine the crack growth direction and initiation. While in impact properties the lyocell/lyocell/lyocell pattern reinforcement showed the best impact strength of 3.36 kJ/m2 compared to rayon/rayon/rayon and other tri-layer composites. Thermal analysis showed higher thermal stability for the rayon/rayon/lyocell pattern reinforcement.
MIKE: A Distributed object-oriented programming platform on top of the Mach micro-kernel

This paper describes the architecture and implementation of MIKE - a version of the IK distributed persistent object-oriented programming platform built on top of the Mach microkernel. MIKE's primary goal is to offer a single object-oriented programming paradigm for writing distributed applications. In MIKE an application programmer can use C++ almost as he would in a non-distributed system. The platform supports fine grained objects which can be invoked in a location transparent way and whose references can be exchanged freely as invocation parameters. These objects are potentially persistent. MIKE supports the abstraction of one-level store, persistent objects are transparently loaded on demand when first invoked and saved to disk when the application terminates. Class objects are special persistent objects which are dynamically linked when needed. The platform also offers distributed garbage collection of non-persistent objects. This paper discusses how MIKE makes use of Mach's features to offer the functionality described above and the techniques used to achieve good performance. MIKE is compared with the Unix versions of IK to evaluate the benefits of using Mach abstractions.