Miracle-dz/UniFAR-FTUs huggingface dataset:
Blunted Brain Energy Consumption Relates to Insula Atrophy and Impaired Glucose Tolerance in Obesity

Brain energy consumption induced by electrical stimulation increases systemic glucose tolerance in normal-weight men. In obesity, fundamental reductions in brain energy levels, gray matter density, and cortical metabolism, as well as chronically impaired glucose tolerance, suggest that disturbed neuroenergetic regulation may be involved in the development of overweight and obesity. Here, we induced neuronal excitation by anodal transcranial direct current stimulation versus sham, examined cerebral energy consumption with 31P magnetic resonance spectroscopy, and determined systemic glucose uptake by euglycemic-hyperinsulinemic glucose clamp in 15 normal-weight and 15 obese participants. We demonstrate blunted brain energy consumption and impaired systemic glucose uptake in obese compared with normal-weight volunteers, indicating neuroenergetic dysregulation in obese humans. Broadening our understanding of reduced multifocal gray matter volumes in obesity, our findings show that reduced appetite- and taste-processing area morphometry is associated with decreased brain energy levels. Specifically, gray matter volumes of the insula relate to brain energy content in obese participants. Overall, our results imply that a diminished cerebral energy supply may underlie the decline in brain areas assigned to food intake regulation and therefore the development of obesity.
Outcomes in a Cohort of Patients Started on Antiretroviral Treatment and Followed up for a Decade in an Urban Clinic in Uganda

Background Short-medium term studies from sub-Saharan Africa show that, despite high early mortality, substantial loss to program, and high rates toxicity, patients on antiretroviral treatment have achieved outcomes comparable to those in developed settings. However, these studies were unable to account for long term outcomes of patients as they stayed longer on treatment. Objectives We aim to describe ten years outcomes of one of the first cohort of HIV positive patients started on antiretroviral treatment (ART) in Sub-Saharan Africa. Methods We report 10-years outcomes including mortality, retention, CD4-count response, virological outcomes, ART regimens change from a prospective cohort of 559 patients initiating ART and followed up for 10 years Uganda. Results Of 559 patients, 69.1% were female, median age (IQR) was 38 (33–44) years, median CD4-count (IQR) 98 (21–163) cell/μL; 74% were started on stavudine, lamivudine and nevirapine, 26% on zidovudine, lamivudine and efavirenz. After 10 years 361 (65%) patients were still in the study; 127 (22.7%) had died; 30 (5%) were lost to follow-up; 27 (5%) transferred; 18 (3%) withdrew consent. The probability of death was high in the first year (0.15, 95%, CI 0.12–0.18). The median CD4 count increased from 98 to 589 cell/μL (IQR: 450–739 cell/μL) with a median increase of 357 cells/μL (IQR: 128–600 cells/μL); 7.4% never attained initial viral suppression and of those who did 31.7% experienced viral failure. Three hundred and two patients had at least one drug substitution while on first line after a median of 40 months; 66 (11.9%) of the patients were switched to a second line PI-based regimen due to confirmed treatment failure. Conclusions Despite the high rate of early mortality due to advanced disease at presentation the outcomes from this cohort are encouraging, particularly the remarkable and incremental immune-recovery and a satisfactory rate of virologic suppression.
Development of an eight-subtest short form of the WISC-IV and evaluation of its clinical utility in children with traumatic brain injury

This study evaluated the degree to which an 8-subtest short form of the Wechsler Intelligence Scale for Children—Fourth Edition would yield acceptable estimates of the long-form Full-Scale IQ index while clarifying the underlying factor structure in a sample of 100 children and adolescents with traumatic brain injury. The short-form Full-Scale IQ had sufficient (i.e., at least two thirds) nonerror covariance with its full-length counterpart. In addition, a sufficient proportion (i.e., > 80%) of these short-form estimates fell within the 90% confidence interval of the respective full-length scores. Importantly, the elimination of 2 subtests, and in particular the Picture Concepts subtest, resulted in a factor structure where each remaining subtest was fairly specifically associated with its intended scale. It is concluded that this short form can be used clinically in children with traumatic brain injury without sacrificing reliability and with more straightforward interpretability at the level of the factor index scores.
TBX1 Mutation Identified by Exome Sequencing in a Japanese Family with 22q11.2 Deletion Syndrome-Like Craniofacial Features and Hypocalcemia

Background Although TBX1 mutations have been identified in patients with 22q11.2 deletion syndrome (22q11.2DS)-like phenotypes including characteristic craniofacial features, cardiovascular anomalies, hypoparathyroidism, and thymic hypoplasia, the frequency of TBX1 mutations remains rare in deletion-negative patients. Thus, it would be reasonable to perform a comprehensive genetic analysis in deletion-negative patients with 22q11.2DS-like phenotypes. Methodology/Principal Findings We studied three subjects with craniofacial features and hypocalcemia (group 1), two subjects with craniofacial features alone (group 2), and three subjects with normal phenotype within a single Japanese family. Fluorescence in situ hybridization analysis excluded chromosome 22q11.2 deletion, and genomewide array comparative genomic hybridization analysis revealed no copy number change specific to group 1 or groups 1+2. However, exome sequencing identified a heterozygous TBX1 frameshift mutation (c.1253delA, p.Y418fsX459) specific to groups 1+2, as well as six missense variants and two in-frame microdeletions specific to groups 1+2 and two missense variants specific to group 1. The TBX1 mutation resided at exon 9C and was predicted to produce a non-functional truncated protein missing the nuclear localization signal and most of the transactivation domain. Conclusions/Significance Clinical features in groups 1+2 are well explained by the TBX1 mutation, while the clinical effects of the remaining variants are largely unknown. Thus, the results exemplify the usefulness of exome sequencing in the identification of disease-causing mutations in familial disorders. Furthermore, the results, in conjunction with the previous data, imply that TBX1 isoform C is the biologically essential variant and that TBX1 mutations are associated with a wide phenotypic spectrum, including most of 22q11.2DS phenotypes.
Drug, Healthcare and Patient Safety Dovepress Safety and Tolerability of Antipsychotics: Focus on Amisulpride

The introduction of the atypical antipsychotic drugs represents an important advance in the treatment of schizophrenia, because the therapeutic efficacy, tolerability, and safety profiles of these agents seem to be superior to that of the classical neuroleptics. As would be predicted from the pharmacologic profile of a pure D 2 /D 3 receptor blocker, amisulpride is an atypical antipsychotic agent, effective for positive and negative symptoms, which can bring about additional improvement in the social functioning and quality of life of patients with schizophrenia. Amisulpride is effective in acute schizophrenia as determined by Clinical Global Impression scores. The major concern regarding the safety of the atypical antipsychotics is related to their propensity to induce weight gain and alter glucose and lipid metabolism. Amisulpride has one of the lowest potentials for weight gain of all the antipsychotic agents, and is associated with clearly lower use of antiparkinsonian medication and with fewer dropouts due to adverse events than conventional antipsychotics. Amisulpride is well tolerated with regard to anxiety and insomnia, and not notably different from placebo. Amisulpride has a pronounced prolactin-elevating effect which appears to be independent of dosage and duration of administration. Hyperprolactinemia rapidly reverses following amisulpride discontinuation. Amisulpride benefits patients with negative symptoms, and is the only antipsychotic to demonstrate efficacy in patients with predominantly negative symptoms. Amisulpride maintains its efficacy when used for medium/ long-term treatment, as demonstrated in studies of up to 12 months. In terms of relevance of the effects, superiority is observed for quality of life, social adaptation, and functioning, as measured by the Quality of Life and Functional Status Questionnaire scales. In conclusion, amisulpride is an antipsychotic agent with proven efficacy and good tolerability. Moreover, this drug can help people with schizophrenia to attain social reinsertion.
Supporting exploratory search tasks with interactive user modeling

This paper presents the design and study of interactive user modeling to support exploratory search tasks. Contrary to traditional interactions, such as query based search, query suggestions, or relevance feedback, interactive user modeling allows a user to perceive the state of the user model at all times and provide feedback that directly rewards or penalizes it. The technique allows the user to continuously tune the system's belief about the user's evolving information needs. We demonstrate that such functionality is useful in exploratory search where users need to get accustomed to a body of literature in a domain. We conducted two experiments where scientists carried out exploratory search tasks with our implementation of an interactive user modeling and retrieval system (SciNet) and two baselines: SciNet from which interactive user modeling was excluded and a real-world baseline (Google Scholar). The results show that interactive user modeling can help users to more effectively find relevant, novel and diverse information without compromises in task execution time.
Nuclear translocation of the transcription factor STAT3 in the guinea pig brain during systemic or localized inflammation

The purpose of the present study was to investigate a possible lipopolysaccharide (LPS)‐induced activation of brain cells that is mediated by the pleiotropic cytokine interleukin‐6 (IL‐6) and its transcription factor STAT3 during systemic or localized inflammation. In guinea pigs, intra‐arterial (i.a., 10 μg kg−1) or intraperitoneal (i.p., 30 μg kg−1) injections of bacterial LPS cause a systemic inflammatory response which is accompanied by a robust fever. A febrile response can also be induced by administration of LPS into artificial subcutaneously implanted Teflon chambers (s.c. 100 or 10 μg kg−1), which reflects an experimental model that mimics local tissue inflammation. Baseline plasma levels of bioactive IL‐6 determined 60 min prior to injections of LPS or vehicle amounted to 35–80 international units (i.u.) ml−1. Within 90 min of LPS injection, plasma IL‐6 rose about 1000‐fold in the groups injected i.a. or i.p., about 50‐fold in the group injected s.c. with 100 μg kg−1 LPS, and only 5‐fold in guinea pigs injected with the lower dose of LPS (10 μg kg−1). At this time point, a distinct nuclear translocation pattern of the transcription factor STAT3 became evident in several brain structures. Amongst those, the sensory circumventricular organs known to lack a tight blood–brain barrier such as the area postrema, the vascular organ of the lamina terminalis and the subfornical organ, as well as the hypothalamic supraoptic nucleus showed intense nuclear STAT3 signals in the i.a. or i.p. injected groups. In contrast a moderate (s.c. group, 100 μg kg−1), or even no (s.c. group, 10 μg kg−1), nuclear STAT3 translocation occurred in response to s.c. injections of LPS. These results suggest that STAT3‐mediated genomic activation of target gene transcription in brain cells occurred only in those cases in which sufficiently high concentrations of circulating IL‐6 were formed during systemic (i.a. and i.p. groups) or localized (s.c. group, 100 μg kg−1) inflammation.
Bilateral “Carotico-clinoid Foramen” With “Sella Turcica Bridge”- A Case Report

Introduction: The Carotico-clinoid foramen is the result of ossification of carotico-clinoid ligament between anterior and middle clinoid process. Whereas bony bridge between anterior and posterior clinoid processes formed by ossified dural extension connecting these two processes, is called Sella Turcica Bridge. They can be developed unilaterally or bilaterally and vary in frequency. Both these foramina may cause different presentations, i.e. compression, tightness or stretching of internal carotid artery as well as endocrinological problems affecting hypothalamus or hypophysis cerebri or neurological problems through Oculomotor or optic nerve, pituitary gland, which manifest as headache, behavioral changes, hormonal, visual, epileptic, craniofacial deviation and tooth anomalies, etc. That’s why thorough anatomical knowledge is a great clinical help for neurosurgeons, neurophysicians, endocrinologists, radiologists, anatomists and biological anthropologists. Case report: Recently during teaching medical students one dry skull having bilateral ossified interclinoid ligaments (carotico-clinoid foramen and sella Turcica Bridge) is found which is relatively very rare as per literatures. The morphologic analysis has been done.
Targeting the BCR-ABL Signaling Pathway in Therapy-Resistant Philadelphia Chromosome-Positive Leukemia

Beginning with imatinib a decade ago, therapy based on targeted inhibition of the BCR-ABL kinase has greatly improved the prognosis for chronic myeloid leukemia (CML) patients. The recognition that some patients experience relapse due to resistance-conferring point mutations within BCR-ABL sparked the development of the second-generation ABL kinase inhibitors nilotinib and dasatinib. Collectively, these drugs target most resistant BCR-ABL mutants, with the exception of BCR-ABLT315I. A third wave of advances is now cresting in the form of ABL kinase inhibitors whose target profile encompasses BCR-ABLT315I. The leading third-generation clinical candidate for treatment-refractory CML, including patients with the T315I mutation, is ponatinib (AP24534), a pan-BCR-ABL inhibitor that has entered pivotal phase 2 testing. A second inhibitor with activity against the BCR-ABLT315I mutant, DCC-2036, is in phase 1 clinical evaluation. We provide an up-to-date synopsis of BCR-ABL signaling pathways, highlight new findings on mechanisms underlying BCR-ABL mutation acquisition and disease progression, discuss the use of nilotinib and dasatinib in a first-line capacity, and evaluate ponatinib, DCC-2036, and other ABL kinase inhibitors with activity against BCR-ABLT315I in the development pipeline. Clin Cancer Res; 17(2); 212–21. ©2010 AACR.
Pharmacological properties of JDTic: a novel kappa-opioid receptor antagonist.

Biological studies were conducted on (3R)-7-Hydroxy-N-[(1S)-1-[[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperidinyl]methyl]-2-methylpropyl]-1,2,3,4-tetrahydro-3-isoquinoline-carboxamide (JDTic), the first potent kappa-selective opioid receptor antagonist not derived from an opiate class of compounds. In the mouse tail-flick test, JDTic, administered subcutaneously (s.c.), blocked anticociceptive activity for up to 2 weeks. When JDTic was administered either s.c. or p.o. 24 h before the selective KOP (kappa)-opioid receptor agonist, enadoline, AD(50s) of 4.1 and 27.3, respectively, were obtained. A time-course study of JDTic versus enadoline indicated significant antagonist p.o. activity up to 28 days. In contrast, JDTic, s.c. , failed to antagonize the analgesic effects of the selective MOP mu-opioid receptor agonist, sufentanil. In the squirrel monkey shock titration antinociception test, JDTic given intramuscularly (i.m.) shifted the trans-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide (U50,488) dose-effect curve to the right. In the U50,488-induced diuresis rat test, JDTic, s.c. , suppressed diuretic activity with a greater potency than that of nor-binaltorphimine (nor-BNI). Thus, JDTic is a potent long- and orally acting selective kappa-opioid antagonist.
Implicit Acquisition of Grammars With Crossed and Nested Non-Adjacent Dependencies: Investigating the Push-Down Stack Model

A recent hypothesis in empirical brain research on language is that the fundamental difference between animal and human communication systems is captured by the distinction between finite-state and more complex phrase-structure grammars, such as context-free and context-sensitive grammars. However, the relevance of this distinction for the study of language as a neurobiological system has been questioned and it has been suggested that a more relevant and partly analogous distinction is that between non-adjacent and adjacent dependencies. Online memory resources are central to the processing of non-adjacent dependencies as information has to be maintained across intervening material. One proposal is that an external memory device in the form of a limited push-down stack is used to process non-adjacent dependencies. We tested this hypothesis in an artificial grammar learning paradigm where subjects acquired non-adjacent dependencies implicitly. Generally, we found no qualitative differences between the acquisition of non-adjacent dependencies and adjacent dependencies. This suggests that although the acquisition of non-adjacent dependencies requires more exposure to the acquisition material, it utilizes the same mechanisms used for acquiring adjacent dependencies. We challenge the push-down stack model further by testing its processing predictions for nested and crossed multiple non-adjacent dependencies. The push-down stack model is partly supported by the results, and we suggest that stack-like properties are some among many natural properties characterizing the underlying neurophysiological mechanisms that implement the online memory resources used in language and structured sequence processing.
Ferroelectric phase transition in nanostructured BaTiO3 studied by Raman scattering and second harmonic generation

It is widely known that the ferroelectric phase transition from tetragonal to cubic phase in BaTiO3 ceramics and powders is strongly suppressed compared with the crystals. In our study the features of this transition were investigated by low-frequency Raman scattering and second harmonic generation (SHG) techniques. The obtained results of Raman and SHG experiments are interpreted as a relaxor-like behavior of BaTiO3 pressed powder.
A geometrically constraining bis(benzimidazole) ligand and its nearly tetrahedral complexes with Fe(II) and Mn(II).

2,2'-Bis[2-(1-propylbenzimidazol-2-yl)]biphenyl), 4, and its bis complexes with Fe(II) and Mn(II) have been prepared and characterized structurally and spectroscopically. Ligand 4 adopts an open, "trans" conformation in the solid state with the benzimidazole (BzIm) groups on opposite sides of the biphenyl unit. In its complexes with metal ions, a "cis" conformation is observed, and 4 behaves as a geometrically constraining bidentate ligand with four planar groups connected by three "hinges". Reaction of 4 with Fe(II) or Mn(II) yielded isomorphous crystals (space group Pnn2) of Fe(II)(4)2. (ClO4)2 and Mn(II)(4)2. (ClO4)2, in which the M(II)(4)2 cations exhibit distorted-tetrahedral coordination geometries (N-M-N angles, 109 +/- 11 degrees ) enforced by rigid, chiral nine-membered M(4) rings in the twist-boat-boat conformation. Individually, the cations show R,R or S,S stereochemistry, and the crystals are racemates. Mn(II)(4)2. (ClO4)2 exhibits a quasi-reversible Mn(II) --> Mn(III) oxidation at E(1/2) = 0.64 V; the corresponding Fe(II) --> Fe(III) oxidation occurs at E(1/2) = 1.76 V. The electrochemical stability of the Fe(III) oxidation state in this system suggests the possibility of isolating an unusual pseudotetrahedral Fe(III)N(BzIm)(4) species. Ultraviolet spectra of the iron and manganese complexes are dominated by absorptions of the ligand 4 blue-shifted by approximately 2000-3000 cm(-1). Ligand-field absorptions were observed for the Fe(II) complex; those for the Mn(II) complex were obscured by tailing ultraviolet absorptions. Electron paramagnetic resonance and magnetic susceptibility measurements are consistent with a high-spin Mn(II) complex, while for the Fe(II) complex, the falloff of the magnetic moment with decreasing temperature is indicative of zero-field splitting with D approximately 4 cm(-1).
THE PROPAGATION OF LIGHT IN CAUSAL SET THEORY

This is a report based on a student research project conducted at San José State University in the Spring of 2009, which was a continuation of a similar project conducted in the Spring 2008. The goal of both projects was to investigate the possibility that the speed of a photon depends on its energy and thus that the speed of light is not an absolute constant. Both projects were motivated and inspired by the launch of the FERMI Gamma Ray Space Telescope in June 2008, which detects high energy photons coming from Gamma ray bursts. The investigation was done in the context of causal sets implemented in MATLAB. The probability amplitudes were computed using a variant of the Feynman path integral approach. Our work indicates that there is a relationship between a photon’s energy and the standard deviation of its velocity.
Monetary Policy by Committee : Consensus, Chairman Dominance or Simple Majority ?

This paper studies the theoretical and empirical implications of monetary policy making by committee under four different voting protocols. The protocols are a consensus model, where a supermajority is required for a policy change; an agenda-setting model, where the chairman controls the agenda; a dictator model, where the chairman has absolute power over the committee; and a simple majority model, where policy is determined by the median member. These protocols give preeminence to different aspects of the actual decision-making process and capture the observed heterogeneity in formal procedures across central banks. The models are estimated by maximum likelihood using interest rate decisions by the committees of five central banks, namely the Bank of Canada, the Bank of England, the European Central Bank, the Swedish Riksbank, and the U.S. Federal Reserve. For all central banks, results indicate that the consensus model fits actual policy decisions better than the alternative models. This suggests that despite institutional differences, committees share unwritten rules and informal procedures that deliver observationally equivalent policy decisions.