Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved glioblastoma treatment with Ad5/35 fiber chimeric conditionally replicating adenoviruses

Adenovirus type 5 (Ad5)‐based vectors have been used in clinical trials for glioblastoma treatment, but the capacity of Ad5 to infect human glioma cells was questioned. Seeking to improve the adenovirus transduction, we tested four Ad5‐based vectors differing only in their fiber gene on permanent and short‐term cultures of glioblastoma cells. A wild‐type fiber Ad5 vector (Ad5.Luc) was compared to an RGD integrin‐binding motif‐containing fiber adenovirus (AdlucRGD) and the two fiber chimeras Ad5/3 and Ad5/35, with vector binding redirected to the Ad3 or Ad35 receptor, respectively. Compared to Ad5, the transduction of the tested short‐term glioblastoma cultures with the vector Ad5/35.Luc, AdlucRGD and Ad5/3.Luc was enhanced by ∼72%, ∼13% and ∼2%, respectively. To limit adenovirus spread, we aimed to develop conditionally replicative Ad5/35 vectors by targeting the expression of the essential E1 and E4 genes; in addition, some vectors had the E1Δ24 deletion. We analyzed eleven promoters for their activity in glioblastoma cells and determined the specificity of eight replicative adenovirus vectors in vitro. We evaluated the most promising vectors with E1/E4 under the control of the GFAP/Ki67 or E2F‐1/COX‐2 promoters, and the native Ad5 or the chimeric Ad5/35 fiber for their antineoplastic activity in a subcutaneous and intracranial glioblastoma xenograft model. Animals treated with the Ad5/35‐based vectors showed significantly smaller tumors and longer survival than those treated with the homologous Ad5 vectors; no significant toxicity was observed in the intracranial model. Our data suggest that Ad5/35‐based vectors are promising tools for glioblastoma treatment. Copyright © 2007 John Wiley & Sons, Ltd.
Highly Efficient Regression for Scalable Person Re-Identification

Existing person re-identification models are poor for scaling up to large data required in real-world applications due to: (1) Complexity: They employ complex models for optimal performance resulting in high computational cost for training at a large scale; (2) Inadaptability: Once trained, they are unsuitable for incremental update to incorporate any new data available. This work proposes a truly scalable solution to re-id by addressing both problems. Specifically, a Highly Efficient Regression (HER) model is formulated by embedding the Fisher's criterion to a ridge regression model for very fast re-id model learning with scalable memory/storage usage. Importantly, this new HER model supports faster than real-time incremental model updates therefore making real-time active learning feasible in re-id with human-in-the-loop. Extensive experiments show that such a simple and fast model not only outperforms notably the state-of-the-art re-id methods, but also is more scalable to large data with additional benefits to active learning for reducing human labelling effort in re-id deployment.
Drugging the addict: non‐oncogene addiction as a target for cancer therapy

Historically, cancers have been treated with chemotherapeutics aimed to have profound effects on tumor cells with only limited effects on normal tissue. This approach was followed by the development of small‐molecule inhibitors that can target oncogenic pathways critical for the survival of tumor cells. The clinical targeting of these so‐called oncogene addictions, however, is in many instances hampered by the outgrowth of resistant clones. More recently, the proper functioning of non‐mutated genes has been shown to enhance the survival of many cancers, a phenomenon called non‐oncogene addiction. In the current review, we will focus on the distinct non‐oncogenic addictions found in cancer cells, including synthetic lethal interactions, the underlying stress phenotypes, and arising therapeutic opportunities.
Early Elevation of Cochlear Reactive Oxygen Species following Noise Exposure

Reactive oxygen species (ROS) have been implicated in a growing number of neurological disease states, from acute traumatic injury to neurodegenerative conditions such as Alzheimer’s disease. Considerable evidence suggests that ROS also mediate ototoxicant- and noise-induced cochlear injury, although most of this evidence is indirect. To obtain real-time assessment of noise-induced cochlear ROS production in vivo, we adapted a technique which uses the oxidation of salicylate to 2,3-dihydroxybenzoic acid as a probe for the generation of hydroxyl radical. In a companion paper we described the development and characterization of this method in cochlear ischemia-reperfusion. In the present paper we use this method to demonstrate early elevations in ROS production following acute noise exposure. C57BL/6J mice were exposed for 1 h to intense broad-band noise sufficient to cause permanent threshold shift (PTS), as verified by auditory brainstem responses. Comparison of noise-exposed animals with unexposed controls indicated that ROS levels increase nearly 4-fold in the period 1–2 h following exposure and do not decline over that time. Our ROS measures extend previous results indicating that noise-induced PTS is associated with elevated cochlear ROS production and ROS-mediated injury. Persistent cochlear ROS elevation following noise exposure suggests a sustained process of oxidative stress which might be amenable to intervention with chronic antioxidant therapy.
Urinary and fecal incontinence during levetiracetam therapy

1. Chauhan D, Mokta K, Kanga A, Grover N, Singh D, Bhagra S. Group B streptococcal meningitis in children beyond the neonatal period in sub-Himalayan India. Ann Indian Acad Neurol 2015;18:71-3. 2. Mohammadi SF, Pati l AB, Nadagir SD, Nandihal N, Lakshminarayana SA. Diagnostic value of latex agglutination test in diagnosis of acute bacterial meningitis. Ann Indian Acad Neurol 2013;16:645-9. 3. Yadhav Ml K. Study of bacterial meningitis in children below 5 years with comparative evaluation of gram staining, culture and bacterial antigen detection. J Clin Diagn Res 2014;8: DC04-6. 4. de Zoysa A, Edwards K, Gharbia S, Underwood A, Charlett A, Efstratiou A. Non-culture detection of Streptococcus agalactiae (Lancefield group B Streptococcus) in clinical samples by real-time PCR. J Med Microbiol 2012;61:1086-90. 5. Schrag SJ, Verani JR. Intrapartum antibiotic prophylaxis for the prevention of perinatal group B streptococcal disease: Experience in the United States and implications for a potential group B streptococcal vaccine. Vaccine 2013;31: D20-6. Sir, I presume that the actual prevalence of group B streptococcus (GBS) meningitis is higher than 16% reported by Chauhan et al.[1] This is based on the presence of an important methodological limitation. Chauhan et al.,[1] stated in their interesting study that 92.5% had received prior antibiotic treatment from some peripheral institutions before being referred to the tertiary care hospital. The gram staining and culture reports were negative in all their studied cases. Moreover, polymerase chain reaction (PCR) was not available for GBS. Ultimately, Chauhan et al.,[1] totally relied upon latex particle agglutination test (LPAT) to establish the diagnosis of GBS meningitis in their studied cohort. It is worthy to mention that the sensitivity and specificity of LPAT has been found to be 66.66 and 87.91%, respectively. [2] Moreover, gram staining and LPAT could detect 85% of cases of acute bacterial meningitis (ABM). [3] With the combination of gram staining, culture, and LPAT; 100% sensitivity and specificity could be achieved and they are more productive than any single test. [2,3] With the history of prior antibiotic administration, real-time PCR assay remains superior and the golden standard to firm diagnosis of ABM. [4] Considering that limitation, I presume that the actual magnitude of GBS meningitis was underestimated. Despite that limitation, Chauhan et al.,’s study[1] highlighted the importance of ongoing surveillance of GBS and triggered the need to delineate molecular characterization of GBS strains that might have implications for vaccine development strategies. With the absence of effective GBS vaccine currently, the protocol of universal culture-based screening at 35-37 weeks gestational age and intrapartum antimicrobial prophylaxis for GBS-colonized women has been recently proved in view of US experience to comprise a highly effective strategy to decrease the burden of subsequent infants’ GBS infections. [5] The implementation of such protocol need to be considered in India.
From Local Patterns to Global Models: The LeGo Approach to Data Mining

In this paper we present LeGo, a generic framework that utilizes existing local pattern mining techniques for global modeling in a variety of diverse data mining tasks. In the spirit of well known KDD process models, our work identifies different phases within the data mining step, each of which is formulated in terms of different formal constraints. It starts with a phase of mining patterns that are individually promising. Later phases establish the context given by the global data mining task by selecting groups of diverse and highly informative patterns, which are finally combined to one or more global models that address the overall data mining task(s). The paper discusses the connection to various learning techniques, and illustrates that our framework is broad enough to cover and leverage frequent pattern mining, subgroup discovery, pattern teams, multi-view learning, and several other popular algorithms. The Safarii learning toolbox serves as a proof-of-concept of its high potential for practical data mining applications. Finally, we point out several challenging open research questions that naturally emerge in a constraint-based local-to-global pattern mining, selection, and combination framework.
Respiratory syncytial virus infection in hospitalized children older than 2 years with community-acquired pneumonia.

BACKGROUND/AIM Respiratory syncytial virus (RSV) is one of the main causes of bronchiolitis and pneumonia in infants and young children. The aims of the present study were to evaluate the role of RSV in children >2 years old hospitalized with community-acquired pneumonia (CAP) and to type the circulating RSV strains. MATERIALS AND METHODS Serum and throat swab samples were taken upon admission from Greek children aged > 2 years, hospitalized with atypical CAP, and when possible, a second serum sample was also taken. RSV IgG and IgM antibodies were determined by Enzyme Linked Immunosorbent Assay (ELISA), while throat swab samples were tested by nested RT-PCR. Additional serological testing was performed to find out probable co-infections. RESULTS A total of 101 children with atypical CAP were included in the study, aged 2.5-14 years (median 8.25). RSV IgM antibodies were detected in 21 (20.7%) cases, either in the first or/and in the second serum sample, while RSV genome was detected in 11 out of 15 (73%) IgM-positive patients, which were further tested by PCR. PCR-positive results were obtained up to the 7(th) day of illness. Among the 11 cases, one was of type B, and all the rest were of type A. The median age of the RSV-positive children was 4 years (range 3-13 years). Although RSV was detected in all seasons, the majority of cases (31%) were detected in winter. Co-infection was detected in 3 cases (two with Mycoplasma pneumoniae and one with adenovirus). CONCLUSIONS Apart from the known role of RSV as the most important pathogen causing acute respiratory disease in infants and young children, it is also a significant viral pathogen in older children hospitalized because of CAP. Genetic typing provides further insight into the epidemiology of the disease.
Intrinsically Disordered Regions May Lower the Hydration Free Energy in Proteins: A Case Study of Nudix Hydrolase in the Bacterium Deinococcus radiodurans

The proteome of the radiation- and desiccation-resistant bacterium D. radiodurans features a group of proteins that contain significant intrinsically disordered regions that are not present in non-extremophile homologues. Interestingly, this group includes a number of housekeeping and repair proteins such as DNA polymerase III, nudix hydrolase and rotamase. Here, we focus on a member of the nudix hydrolase family from D. radiodurans possessing low-complexity N- and C-terminal tails, which exhibit sequence signatures of intrinsic disorder and have unknown function. The enzyme catalyzes the hydrolysis of oxidatively damaged and mutagenic nucleotides, and it is thought to play an important role in D. radiodurans during the recovery phase after exposure to ionizing radiation or desiccation. We use molecular dynamics simulations to study the dynamics of the protein, and study its hydration free energy using the GB/SA formalism. We show that the presence of disordered tails significantly decreases the hydration free energy of the whole protein. We hypothesize that the tails increase the chances of the protein to be located in the remaining water patches in the desiccated cell, where it is protected from the desiccation effects and can function normally. We extrapolate this to other intrinsically disordered regions in proteins, and propose a novel function for them: intrinsically disordered regions increase the “surface-properties” of the folded domains they are attached to, making them on the whole more hydrophilic and potentially influencing, in this way, their localization and cellular activity.
Segmentation-verification based on fuzzy integral for connected handwritten digit recognition

This paper investigates a number of verification rules to validate the segmentation of connected handwritten digits. The verification technique based on statistical reasoning and fuzzy integrals is employed to verify the segmentation through decision functions produced by multiclass SVM based recognizers. The segmentation relies on an oriented sliding window which identifies potential cut points. The resulting segmented digits are fed to recognizers and the best segmentation is identified by the verification module that combines the recognizer outputs using fuzzy integrals. The proposed methodology is evaluated on a database of handwritten digits with single as well as multiple connections. Comparative analysis shows that the use of the fuzzy integral allows providing high recognition rates comparatively to the state of the art.
Kinesthetic imagery of musical performance

Musicians use different kinds of imagery. This review focuses on kinesthetic imagery, which has been shown to be an effective complement to actively playing an instrument. However, experience in actual movement performance seems to be a requirement for a recruitment of those brain areas representing movement ideation during imagery. An internal model of movement performance might be more differentiated when training has been more intense or simply performed more often. Therefore, with respect to kinesthetic imagery, these strategies are predominantly found in professional musicians. There are a few possible reasons as to why kinesthetic imagery is used in addition to active training; one example is the need for mental rehearsal of the technically most difficult passages. Another reason for mental practice is that mental rehearsal of the piece helps to improve performance if the instrument is not available for actual training as is the case for professional musicians when they are traveling to various appearances. Overall, mental imagery in musicians is not necessarily specific to motor, somatosensory, auditory, or visual aspects of imagery, but integrates them all. In particular, the audiomotor loop is highly important, since auditory aspects are crucial for guiding motor performance. All these aspects result in a distinctive representation map for the mental imagery of musical performance. This review summarizes behavioral data, and findings from functional brain imaging studies of mental imagery of musical performance.
Akt Signals through the Mammalian Target of Rapamycin Pathway to Regulate CNS Myelination

Mammalian target of rapamycin (mTOR), a well known Akt substrate, regulates multiple cellular functions including cell growth and protein synthesis. The current study identifies a novel role of the Akt/mTOR pathway as a regulator of CNS myelination. Previously, we showed that overexpressing constitutively active Akt in oligodendrocytes in a transgenic mouse model induces enhanced CNS myelination, with no changes in the proliferation or survival of oligodendrocyte progenitor or mature cells. The present study focused on the signaling mechanisms regulating this hypermyelination induced by Akt. Activation of mTOR and its downstream substrates (p70S6 kinase and S6 ribosomal protein) was observed in Akt-overexpressing oligodendrocytes. When mTOR signaling was inhibited chronically in vivo with rapamycin starting at 6 weeks of age, the observed hypermyelination was reduced to approximately the amount of myelin seen in wild-type mice. mTOR inhibition had little impact on wild-type myelination between 6 and 12 weeks of age, suggesting that, in normal adults, myelination is relatively complete and is no longer regulated by mTOR signaling. However, when mTOR was chronically inhibited in young adult wild-type mice, myelination was reduced. These results suggest that, during active myelination, the major Akt signal regulating CNS myelination is the mTOR pathway.
Cell-Penetrating Peptides: Design Strategies beyond Primary Structure and Amphipathicity

Efficient intracellular drug delivery and target specificity are often hampered by the presence of biological barriers. Thus, compounds that efficiently cross cell membranes are the key to improving the therapeutic value and on-target specificity of non-permeable drugs. The discovery of cell-penetrating peptides (CPPs) and the early design approaches through mimicking the natural penetration domains used by viruses have led to greater efficiency of intracellular delivery. Following these nature-inspired examples, a number of rationally designed CPPs has been developed. In this review, a variety of CPP designs will be described, including linear and flexible, positively charged and often amphipathic CPPs, and more rigid versions comprising cyclic, stapled, or dimeric and/or multivalent, self-assembled peptides or peptido-mimetics. The application of distinct design strategies to known physico-chemical properties of CPPs offers the opportunity to improve their penetration efficiency and/or internalization kinetics. This led to increased design complexity of new CPPs that does not always result in greater CPP activity. Therefore, the transition of CPPs to a clinical setting remains a challenge also due to the concomitant involvement of various internalization routes and heterogeneity of cells used in the in vitro studies.
Everyday Functioning in Huntington’s Disease: A Laboratory-Based Study of Financial Management Capacity

ABSTRACT One important limitation of prior studies examining functional decline in Huntington’s disease (HD) has been the reliance on self-reported measures of ability. Since report-based methods can be biased by lack of insight, depression, and cognitive impairment, contrasting self-reported ability with measures that assess capacity may lead to a more comprehensive estimation of real-world functioning. The present study examined self-reported ability to perform instrumental activities of daily living (iADLs) and performance-based financial management capacity in 20 patients diagnosed with mild-moderate Huntington’s disease (HD) and 20 demographically similar healthy adults. HD patients reported significantly greater declines in their ability to manage finances. On the capacity measure of financial management, HD patients performed significantly below healthy adults. Additionally, in the HD group there were no significant correlations between self-reported ability and capacity measures of financial management. HD patients endorsed declines in global iADL ability and exhibited deficits in functional capacity when performing a financial management task. Capacity measures may aid in assessing the extent to which HD patients accurately estimate real-world iADL performance, and the present findings suggest that such measures of capacity may be related to the cognitive, but not motor or affective, symptoms of HD.
Flexibility of habitat use in novel environments: insights from a translocation experiment with lesser black-backed gulls

Being faced with unknown environments is a concomitant challenge of species' range expansions. Strategies to cope with this challenge include the adaptation to local conditions and a flexibility in resource exploitation. The gulls of the Larus argentatus-fuscus-cachinnans group form a system in which ecological flexibility might have enabled them to expand their range considerably, and to colonize urban environments. However, on a population level both flexibility and local adaptation lead to signatures of differential habitat use in different environments, and these processes are not easily distinguished. Using the lesser black-backed gull (Larus fuscus) as a system, we put both flexibility and local adaptation to a test. We compare habitat use between two spatially separated populations, and use a translocation experiment during which individuals were released into novel environment. The experiment revealed that on a population-level flexibility best explains the differences in habitat use between the two populations. We think that our results suggest that the range expansion and huge success of this species complex could be a result of its broad ecological niche and flexibility in the exploitation of resources. However, this also advises caution when using species distribution models to extrapolate habitat use across space.
NKG2H-Expressing T Cells Negatively Regulate Immune Responses

The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb), we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC) and is found more frequently on T cells, rather than NK cells. Moreover, although NKG2H is likely to trigger activation, co-cross-linking of this receptor with an NKG2H-specific mAb led to decreased T cell activation and proliferation in polyclonal PBMC cultures stimulated by anti-CD3 mAbs. This negative regulatory activity was seen only after cross-linking with NKG2H, but not NKG2A- or NKG2C-specific monoclonal antibodies. The mechanism underlying this negative effect is as yet unclear, but did not depend on the release of soluble factors or recognition of MHC class I molecules. These observations raise the intriguing possibility that NKG2H may be a novel marker for T cells able to negatively regulate T cell responses.
Biological activity of selenium: Revisited

Selenium (Se) is an essential micronutrient that exerts multiple and complex effects on human health. Se is essential for human well‐being largely due to its potent antioxidant, anti‐inflammatory, and antiviral properties. The physiological functions of Se are carried out by selenoproteins, in which Se is specifically incorporated as the amino acid, selenocysteine. Importantly, both beneficial and toxic effects of Se have been reported suggesting that the mode of action of Se is strictly chemical form and concentration dependent. Additionally, there is a relatively narrow window between Se deficiency and toxicity and growing evidence suggests that Se health effects depend greatly on the baseline level of this micronutrient. Thus, Se supplementation is not an easy task and requires an individualized approach. It is essential that we continue to explore and better characterize Se containing compounds and mechanisms of action, which could be crucial for disease prevention and treatment. © 2015 IUBMB Life, 68(2):97–105, 2016