Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychometrics of the Youth Internalizing Problems Screener with Turkish adolescents

ABSTRACT This study presents initial evidence supporting the language adaptation of a brief measure of youths’ internalizing problems—the Youth Internalizing Problems Screener (YIPS)—for use with Turkish adolescents within the context of school mental health screening. Results showed that responses to the Turkish version of the YIPS were characterized by a psychometrically sound, single-factor measurement model, and that scores derived from this measure were moderately negatively associated with scores from several school-specific and domain-general well-being measures. Overall, results suggest that responses to the Turkish version of the YIPS may be useful in schools to identify youth with elevated levels of internalizing problems and concurrently poor quality-of-life outcomes, providing a warrant for school-based intervention. Yet further research is needed to probe the direct utility of this measure for classification and treatment purposes in schools.
ASAP1, a Phospholipid-Dependent Arf GTPase-Activating Protein That Associates with and Is Phosphorylated by Src

ABSTRACT Membrane trafficking is regulated in part by small GTP-binding proteins of the ADP-ribosylation factor (Arf) family. Arf function depends on the controlled exchange and hydrolysis of GTP. We have purified and cloned two variants of a 130-kDa phosphatidylinositol 4,5-biphosphate (PIP2)-dependent Arf1 GTPase-activating protein (GAP), which we call ASAP1a and ASAP1b. Both contain a pleckstrin homology (PH) domain, a zinc finger similar to that found in another Arf GAP, three ankyrin (ANK) repeats, a proline-rich region with alternative splicing and SH3 binding motifs, eight repeats of the sequence E/DLPPKP, and an SH3 domain. Together, the PH, zinc finger, and ANK repeat regions possess PIP2-dependent GAP activity on Arf1 and Arf5, less activity on Arf6, and no detectable activity on Arl2 in vitro. The cDNA for ASAP1 was independently identified in a screen for proteins that interact with the SH3 domain of the tyrosine kinase Src. ASAP1 associates in vitro with the SH3 domains of Src family members and with the Crk adapter protein. ASAP1 coprecipitates with Src from cell lysates and is phosphorylated on tyrosine residues in cells expressing activated Src. Both coimmunoprecipitation and tyrosine phosphorylation depend on the same proline-rich class II Src SH3 binding site required for in vitro association. By directly interacting with both Arfs and tyrosine kinases involved in regulating cell growth and cytoskeletal organization, ASAP1 could coordinate membrane remodeling events with these processes.
Improved Safety, Bioavailability and Pharmacokinetics of Zidovudine through Lactoferrin Nanoparticles during Oral Administration in Rats

Zidovudine (AZT) is one of the most referred antiretroviral drug. In spite of its higher bioavailability (50–75%) the most important reason of its cessation are bone marrow suppression, anemia, neutropenia and various organs related toxicities. This study aims at the improvement of oral delivery of AZT through its encapsulation in lactoferrin nanoparticles (AZT-lactonano). The nanoparticles (NPs) are of 50–60 nm in size and exhibit 67% encapsulation of the AZT. They are stable in simulated gastric and intestinal fluids. Anti-HIV-1 activity of AZT remains unaltered in nanoformulation in acute infection. The bioavailability and tissue distribution of AZT is higher in blood followed by liver and kidney. AZT-lactonano causes the improvement of pharmacokinetic profile as compared to soluble AZT; a more than 4 fold increase in AUC and AUMC in male and female rats. The serum Cmax for AZT-lactonano was increased by 30%. Similarly there was nearly 2-fold increase in Tmax and t1/2. Our in vitro study confirms that, the endosomal pH is ideal for drug release from NPs and shows constant release from up to 96h. Bone marrow micronucleus assay show that nanoformulation exhibits approximately 2fold lower toxicity than soluble form. Histopathological and biochemical analysis further confirms that less or no significant organ toxicities when nanoparticles were used. AZT-lactonano has shown its higher efficacy, low organs related toxicities, improved pharmacokinetics parameter while keeping the antiviral activity intact. Thus, the nanoformulation are safe for the target specific drug delivery.
The vestibular contribution to the head direction signal and navigation

Spatial learning and navigation depend on neural representations of location and direction within the environment. These representations, encoded by place cells and head direction (HD) cells, respectively, are dominantly controlled by visual cues, but require input from the vestibular system. Vestibular signals play an important role in forming spatial representations in both visual and non-visual environments, but the details of this vestibular contribution are not fully understood. Here, we review the role of the vestibular system in generating various spatial signals in rodents, focusing primarily on HD cells. We also examine the vestibular system’s role in navigation and the possible pathways by which vestibular information is conveyed to higher navigation centers.
Pulmonary Sarcoidosis

Sarcoidosis, a granulomatous disorder of unknown etiology, characteristically involves multiple organs. However, pulmonary manifestations typically dominate. Chest radiographs are abnormal in 85 to 95% of patients. Abnormalities in pulmonary function tests are common and may be associated with cough, dyspnea, and exercise limitation. However, one third or more of patients are asymptomatic, with incidental abnormalities on chest radiographs. The clinical course and expression of pulmonary sarcoidosis are variable. Spontaneous remissions occur in nearly two thirds of patients. The course is chronic in up to 30% of patients. Chronic pulmonary sarcoidosis may result in progressive (sometimes life-threatening) loss of lung function. Fatalities ascribed to sarcoidosis occur in 1 to 4% of patients. Although the impact of treatment is controversial, corticosteroids may be highly effective in some patients. Immunosuppressive, cytotoxic, or immunomodulatory agents are reserved for patients failing or experiencing adverse effects from corticosteroids. Lung transplantation is a viable option for patients with life-threatening disease failing medical therapy.
Near-Infrared Spectroscopy for the Evaluation of Anesthetic Depth

The standard-of-care guidelines published by the American Society of Anesthesiologists (ASA) recommend monitoring of pulse oximetry, blood pressure, heart rate, and end tidal CO2 during the use of anesthesia and sedation. This information can help to identify adverse events that may occur during procedures. However, these parameters are not specific to the effects of anesthetics or sedatives, and therefore they offer little, to no, real time information regarding the effects of those agents and do not give the clinician the lead-time necessary to prevent patient “awareness. ” Since no “gold-standard” method is available to continuously, reliably, and effectively monitor the effects of sedatives and anesthetics, such a method is greatly needed. Investigation of the use of functional near-infrared spectroscopy (fNIRS) as a method for anesthesia or sedation monitoring and for the assessment of the effects of various anesthetic drugs on cerebral oxygenation has started to be conducted. The objective of this paper is to provide a thorough review of the currently available published scientific studies regarding the use of fNIRS in the fields of anesthesia and sedation monitoring, comment on their findings, and discuss the future work required for the translation of this technology to the clinical setting.
Tweets vs. Mendeley readers: How do these two social media metrics differ?

Abstract A set of 1.4 million biomedical papers was analyzed with regards to how often articles are mentioned on Twitter or saved by users on Mendeley. While Twitter is a microblogging platform used by a general audience to distribute information, Mendeley is a reference manager targeted at an academic user group to organize scholarly literature. Both platforms are used as sources for so-called “altmetrics” to measure a new kind of research impact. This analysis shows in how far they differ and compare to traditional citation impact metrics based on a large set of PubMed papers.
The Lobotomist: A Maverick Medical Genius and His Tragic Quest to Rid the World of Mental Illness

The Lobotomist explores one of the darkest chapters of American medicine: the desperate attempt to treat the hundreds of thousands of psychiatric patients in need of help during the middle decades of the twentieth century. Into this crisis stepped Walter Freeman, M.D., who saw a solution in lobotomy, a brain operation intended to reduce the severity of psychotic symptoms. Drawing on Freeman’s documents and interviews with Freeman's family, Jack El-Hai takes a penetrating look at the life and work of this complex scientific genius.
Fastfood: Approximate Kernel Expansions in Loglinear Time

Despite their successes, what makes kernel methods difficult to use in many large scale problems is the fact that storing and computing the decision function is typically expensive, especially at prediction time. In this paper, we overcome this difficulty by proposing Fastfood, an approximation that accelerates such computation significantly. Key to Fastfood is the observation that Hadamard matrices, when combined with diagonal Gaussian matrices, exhibit properties similar to dense Gaussian random matrices. Yet unlike the latter, Hadamard and diagonal matrices are inexpensive to multiply and store. These two matrices can be used in lieu of Gaussian matrices in Random Kitchen Sinks proposed by Rahimi and Recht (2009) and thereby speeding up the computation for a large range of kernel functions. Specifically, Fastfood requires O(n log d) time and O(n) storage to compute n non-linear basis functions in d dimensions, a significant improvement from O(nd) computation and storage, without sacrificing accuracy. Our method applies to any translation invariant and any dot-product kernel, such as the popular RBF kernels and polynomial kernels. We prove that the approximation is unbiased and has low variance. Experiments show that we achieve similar accuracy to full kernel expansions and Random Kitchen Sinks while being 100x faster and using 1000x less memory. These improvements, especially in terms of memory usage, make kernel methods more practical for applications that have large training sets and/or require real-time prediction.
Reply: Complexities in the association of human blood^brain barrier disruption with seizures: importance of patient population and method of disruption

We recently reported that epileptic seizures might be facilitated through the action of blood–proteins that leak into the CNS during the chronic epileptic phase in rats (Van Vliet et al ., 2007). This was further supported by our mannitol experiments in epileptic rats which showed increased seizure progression in a subgroup of rats. Mannitol can be used to open the blood–brain barrier (BBB) by producing osmotic shrinking of the endothelial cells and mechanical separation of the tight junctions that form the BBB. Therefore mannitol can be used to deliver various drugs directly to the brain. Previous studies by Neuwelt et al . (Neuwelt et al ., 1983, 1986; Roman-Goldstein et al ., 1994) pointed to the fact that seizures could be one of the complicating factors when patients with brain tumours were treated with …
mTOR inhibition as an adjuvant therapy in a metastatic model of HPV+ HNSCC

Effective treatments for recurrent/metastatic human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) are limited. To aid treatment development, we characterized a novel murine model of recurrent/metastatic HPV+ HNSCC. Further analysis of the parental tumor cell line and its four recurrent/metastatic derivatives led to preclinical testing of an effective treatment option for this otherwise fatal disease. Reverse phase protein arrays identified key signaling cascades in the parental and recurrent/metastatic cell lines. While protein expression profiles differed among the recurrent/metastatic cell lines, activated proteins associated with the mTOR signaling cascade were a commonality. Based on these data, mTOR inhibition was evaluated as an adjuvant treatment for recurrent/metastatic disease. mTOR activity and treatment response were assessed in vitro by western blot, Seahorse, proliferation, clonogenic, and migration assays. Standard-of-care cisplatin/radiation therapy (CRT) versus CRT/rapamycin were compared in vivo. Low-dose rapamycin inhibited mTOR signaling, decreasing proliferation (43%) and migration (62%) while it enhanced CRT-induced cytotoxicity (3.3 fold) in clonogenic assays. Furthermore, rapamycin re-sensitized CRT-resistant, metastatic tumors to treatment in vivo, improving long-term cures (0–30% improved to 78–100%, depending on the recurrent/metastatic cell line) and limiting lymph node metastasis (32%) and lung metastatic burden (30 fold). Studies using immune compromised mice suggested rapamycin's effect on metastasis is independent of the adaptive immune response. These data suggest a role of mTOR activation in HPV+ HNSCC recurrent/metastatic disease and that adjuvant mTOR inhibition may enhance treatment of resistant, metastatic cell populations at the primary site and limit distant metastasis.
What Influences Employees to Use Enterprise Social Networks? A Socio-Technical Perspective

The adoption of enterprise social network (ESN) for greater employee engagement and knowledge sharing practices within organisations is proliferating. However, ESN investments have thus far not resulted in expected gains in organisational benefits due to underutilisation by employees. Limited understanding of the implications of ESN use leads to a paucity of recommendations for effective use within an organisation. This research-in-progress paper seeks to determine the factors influencing the use of ESN among employees in a large Australian utility organisation, with the aim of contributing to a practical understanding of the key success factors of the use of this new workplace social platform. Our preliminary findings indicated that the employees’ ESN behaviour tends to be influenced by socio-technical factors, including technological (i.e. platform and content quality), organisational (i.e. top management support and ESN facilitating conditions), social (i.e. critical mass and communication climate), individual (i.e. perceived benefits, knowledge self-efficacy and time commitment) and task (i.e. task characteristics) factors. This paper concludes that a successful implementation of ESN in an organisation involves the nexus between these five factors and provides several recommendations about how ESN use can be enhanced.
Symmetries of supergravity black holes

We investigate Killing tensors for various black hole solutions of supergravity theories. Rotating black holes of an ungauged theory, toroidally compactified heterotic supergravity, with NUT parameters and two U(1) gauge fields are constructed. If both charges are set equal, then the solutions simplify, and then there are concise expressions for rank-2 conformal Killing–Stäckel tensors. These are induced by rank-2 Killing–Stäckel tensors of a conformally related metric that possesses a separability structure. We directly verify the separation of the Hamilton–Jacobi equation on this conformally related metric and of the null Hamilton–Jacobi and massless Klein–Gordon equations on the ‘physical’ metric. Similar results are found for more general solutions; we mainly focus on those with certain charge combinations equal in gauged supergravity but also consider some other solutions.
D1- Versus D2-Receptor Modulation of Visuospatial Working Memory in Humans

The effects of pergolide, a mixed D1/D2 receptor agonist, and bromocriptine, a selective D2 receptor agonist, were assessed in a visual delay task to further investigate the “dopamine link” of working memory in humans and to look for differential D1 versus D2 receptor contributions. Two groups of 32 healthy young adults (16 female) received either 0.1 mg of pergolide or 2.5 mg of bromocriptine in a placebo-controlled cross-over design. A pretreatment with domperidone, a peripherally active D2 antagonist, was performed in both groups to reduce side effects. Interindividual differences in pharmacokinetics were controlled by the time course of serum prolactin inhibition. The working memory paradigm was a visuospatial delayed matching task; the location of a randomly generated seven-point pattern had to be memorized and compared after 2, 8, or 16 sec with a second pattern that was either identical or slightly shifted within a reference frame. The task was designed with the intention to present unique stimuli at each trial and to require minimal motor demands. Practice effects between the two pharmacological test days were minimized by training sessions that preceded the tests. The paradigm showed significant error and reaction time increases with longer delays. After comparable doses, only pergolide, but not bromocriptine, facilitated visuospatial working memory performance as demonstrated by a significant drug-by-delay interaction. These findings are in accordance with the monkey literature as well as with neuroanatomical findings, and they confirm a preferential role of prefrontal D1 receptors for working memory modulation in humans.
Personality correlates of physical activity: a review and meta-analysis

This review aimed to combine the literature on major personality traits and physical activity alongside providing some meta-analytic summaries of the findings. Overall, 33 studies containing 35 independent samples, ranging from 1969 to 2006, met the inclusion criteria. Extraversion (r = 0.23), neuroticism (r = −0.11) and conscientiousness (r = 0.20) were identified as correlates of physical activity using random effects meta-analytic procedures correcting for sampling bias and attenuation of measurement error. The five-factor model traits of openness to experience/intellect and agreeableness, as well as Eysenck’s psychoticism trait, were not associated with physical activity. Potential moderators of personality and physical activity relationships such as sex, age, culture/country, design and instrumentation were inconclusive given the small number of studies. Still, the existing evidence was suggestive that personality and physical activity relationships are relatively invariant to these factors. Studies examining personality and different physical activity modes suggested differences by traits such as extraversion, but more research is needed to make any conclusions. Future research using multivariate analyses, personality-channelled physical activity interventions, longitudinal designs and objective physical activity measurement is recommended.
Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field. Indeed, the human TP53 gene encodes not only one but at least twelve p53 protein isoforms, which are produced in normal tissues through alternative initiation of translation, usage of alternative promoters, and alternative splicing. In recent years, it became obvious that the different p53 isoforms play an important role in regulating cell fate in response to different stresses in normal cells by differentially regulating gene expression. In cancer cells, abnormal expression of p53 isoforms contributes actively to cancer formation and progression, regardless of TP53 mutation status. They can also be associated with response to treatment, depending on the cell context. The determination of p53 isoform expression and p53 mutation status helps to define different subtypes within a particular cancer type, which would have different responses to treatment. Thus, the understanding of the regulation of p53 isoform expression and their biological activities in relation to the cellular context would constitute an important step toward the improvement of the diagnostic, prognostic, and predictive values of p53 in cancer treatment. This review aims to summarize the involvement of p53 isoforms in cancer and to highlight novel potential therapeutic targets.
Effectiveness of passive ultrasonic irrigation in improving elimination of smear layer and opening dentinal tubules

Objective: To compare the ability to eliminate debris and open dentinal tubules of different ultrasound irrigation procedures. Study Design: Forty extracted single-rooted human teeth were instrumented with mechanical rotatory instrumentation, and divided into four groups: (n=10) according to the final irrigation technique: group A (control), 2.5% NaOCl irrigation with the Miraject needle and no ultrasonic agitation; group B, passive ultrasonic irrigation (PUI) with 2.5% NaOCl and Irrisafe 20 tips; group C, PUI with 2.5% NaOCl and Irrisafe 25 tips; group D, PUI with 2.5% NaOCl and K 25 tips. The amount of debris and the number of opened dentinal tubules was established by scanning electronic microscope. Data were compared using the Kruskal Wallis test. Results: Irrisafe tips (groups B and C) opened up more dentinal tubules and eliminated more debris than conventional irrigation (p<0.05) in the apical third. The middle third shows no significant differences between groups. Irrisafe 25 was more effective than conventional irrigation and K tips (p<0.05) in the coronal third. Conclusions: Ultrasonic activation of the irrigation with Irrisafe tips was the most effective procedure for eliminating the debris and opening up dentinal tubules, especially in the apical third. Key words:Pasive ultrasonic irrigation, irrigation, sodium hypochlorite.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyride Neurotoxicity Is Attenuated in Mice Overexpressing Bcl-2

The proto-oncogene Bcl-2 rescues cells from a wide variety of insults. Recent evidence suggests that Bcl-2 protects against free radicals and that it increases mitochondrial calcium-buffering capacity. The neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyride (MPTP) is thought to involve both mitochondrial dysfunction and free radical generation. We therefore investigated MPTP neurotoxicity in both Bcl-2 overexpressing mice and littermate controls. MPTP-induced depletion of dopamine and loss of [3H]mazindol binding were significantly attenuated in Bcl-2 overexpressing mice. Protection was more profound with an acute dosing regimen than with daily MPTP administration over 5 d. 1-Methyl-4-phenylpyridinium (MPP+) levels after MPTP administration were similar in Bcl-2 overexpressing mice and littermates. Bcl-2 blocked MPP+-induced activation of caspases. MPTP-induced increases in free 3-nitrotyrosine levels were blocked in Bcl-2 overexpressing mice. These results indicate that Bcl-2 overexpression protects against MPTP neurotoxicity by mechanisms that may involve both antioxidant activity and inhibition of apoptotic pathways.