Miracle-dz/UniFAR-FTUs huggingface dataset:
CONFLICTS OF INTEREST FOR AUTHORS OF AMERICAN ACADEMY OF NEUROLOGY CLINICAL PRACTICE GUIDELINES

In their invited article, Holloway et al.1 provided an excellent description of conflicts of interest (COI) as they relate to American Academy of Neurology (AAN) clinical practice guidelines. Their thoughtful discussion addressed complicated issues surrounding COI and identified areas for improvement. Both research and clinical practice were more common COI than personal income from industry. This finding occurred despite the fact that the AAN requires reporting of all industry-related COI, but leaves the reporting of non-industry related COI to the opinion of the individual as to whether it constitutes a COI. This dichotomy is surprising given that there are psychological barriers to recognizing one’s own COI, which as the authors point out has been termed “COI anosognosia. ” Holloway et al. also noted that the approach to COI is evolving. As a result, there is a hodgepodge of reporting …
Linear Time Recognition and Optimizations for Weak-Bisplit Graphs, Bi-Cographs and Bipartite P6-Free Graphs

In [7] was introduced a new decomposition scheme for bipartite graphs that was called canonical decomposition. Weak-bisplit graphs are totally decomposable following this decomposition. We give here linear time algorithms for the recognition of weak-bisplit graphs as well as for two subclasses of this class, the P6-free bipartite graphs and the bi-cographs. Our algorithms extends the technics developped in [2] for cographs's recognition. We conclude by presenting efficient solutions for some optimization problems when dealing with weak-bisplit graphs.
Adaptación lingüística y validación al castellano de la escala LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) para el diagnóstico diferencial del dolor neuropático

Fundamento y objetivo: Adaptacion linguistica y validacion al castellano de la escala LANSS (Leeds Assessment of Neuropathic Symptoms and Signs) para el diagnostico diferencial del dolor neuropatico. Material y metodo: Estudio transversal de validacion en 2 fases: a) adaptacion cultural al castellano mediante equivalencia conceptual con traduccion y retrotraduccion, por duplicado, y revision por panel de expertos, y b) estudio de validacion de la escala en pacientes con dolor neuropatico, nociceptivo y mixto, en el que se evaluaron las propiedades de fiabilidad (consistencia interna y acuerdo entre jueces, con coeficiente kappa y coeficiente de correlacion intraclase) y validez (analisis de curvas COR, concordancia con el diagnostico de referencia y determinacion de la sensibilidad, la especificidad y los valores predictivos positivo y negativo). Resultados: El estudio incluyo a 156 sujetos (90 mujeres; el 58,4%); 89 con dolor con un componente neuropatico (con una edad media [desviacion estandar] de 59,6 [19,4] anos, 22 de ellos con dolor mixto debido a radiculopatia) y 67 con dolor nociceptivo (de edad media, 66,6 [11,8] anos). El diagnostico del tipo de dolor se realizo por criterios clinicos habituales. Entrevistadores entrenados aplicaron la escala por duplicado y a ciegas sobre el diagnostico de referencia. La escala mostro buena fiabilidad (consistencia interna, * de Cronbach y coeficiente de Guttman de las 2 mitades entre 0,68 y 0,71; concordancia entre jueces, * = 0,70; y coeficientes de correlacion intraclase, 0,77 y 0,92) y validez para un punto de corte e 12 puntos, que fue el que mejor discrimino a los pacientes con dolor de componente neuropatico de aquellos con dolor nociceptivo; coeficiente * = 0,70 (intervalo de confianza [IC] del 95%, 0,59-0,81; p < 0,0001), area bajo la curva, 0,929 (p < 0,0001), especificidad del 89,4% (IC del 95%, 79,4%-95,6%) y valor predictivo positivo del 91,1% (IC del 95%, 82,6%-96,4%). Conclusiones: La version espanola de la escala LANSS es fiable y valida para el diagnostico diferencial de dolor neuropatico en Espana.
State complexity of concatenation and complementation

We investigate the state complexity of concatenation and the nondeterministic state complexity of complementation of regular languages. We show that the upper bounds on the state complexity of concatenation are also tight in the case that the first automaton has more than one accepting state. In the case of nondeterministic state complexity of complementation, we show that the entire range of complexities, up to the known upper bound can be produced.
Clinical Examination of the Hip

The hip history involves the standard medical history review components in addition to screening for hip related complaints with emphasis on function and activity. Primary systems of diagnosis have direct correlation of historical relevance, requiring a systematic approach to the history. The patient's function status can be defined by symptoms reported during rotation with load. Rotation sports commonly have been associated with injuries to the intra-articular structures, including the acetabular labrum and ligamentum teres. The twenty-point examination is a tool to help organize the structure of the physical examination. It will aid in the diagnosis or screening of the osseous, ligamentous, and musculotendonous pathological conditions. The physical exam is performed in three positions: the standing, sitting, lateral and supine examinations. A thorough evaluation takes time and thorough understanding of the anatomy.
Conformational Adaptation Drives Potent, Selective and Durable Inhibition of the Human Protein Methyltransferase DOT1L

DOT1L is the human protein methyltransferase responsible for catalyzing the methylation of histone H3 on lysine 79 (H3K79). The ectopic activity of DOT1L, associated with the chromosomal translocation that is a universal hallmark of MLL‐rearranged leukemia, is a required driver of leukemogenesis in this malignancy. Here, we present studies on the structure–activity relationship of aminonucleoside‐based DOT1L inhibitors. Within this series, we find that improvements in target enzyme affinity and selectivity are driven entirely by diminution of the dissociation rate constant for the enzyme–inhibitor complex, leading to long residence times for the binary complex. The biochemical Ki and residence times measured for these inhibitors correlate well with their effects on intracellular H3K79 methylation and MLL‐rearranged leukemic cell killing. Crystallographic studies reveal a conformational adaptation mechanism associated with high‐affinity inhibitor binding and prolonged residence time; these studies also suggest that conformational adaptation likewise plays a critical role in natural ligand interactions with the enzyme, hence, facilitating enzyme turnover. These results provide critical insights into the role of conformational adaptation in the enzymatic mechanism of catalysis and in pharmacologic intervention for DOT1L and other members of this enzyme class.
Proteinuria inducing tubulointerstitial damage

Introduction Glomerular basal membrane represents a mechanical and electric barrier for plasma proteins. In physiological conditions only plasma proteins of low molecular weight are completely filtered through basal membrane. Due to damages of glomerular basal membrane there is an increase in filtration of plasma proteins of moderate and high molecular weight. Proteinuria In regard to its etiology proteinuria can be prerenal, renal and postrenal. By analyzing albumin, 1-microglobulin, immunoglobulin G and 2-macroglobulin, together with total protein in urine, it is possible to detect and differentiate causes of prerenal, glomerular, tubular and postrenal proteinuria. Abnormal glomerular permeability to macromolecules results in excessive protein delivery and reabsorption in proximal tubules. Excessive reabsorption in turn may cause congestion of intracellular endocytic and biosynthetic compartments leading to NFkB-dependent and -independent gene upregulation. Among those genes, monocyte chemoattractant protein-1 (MCP-1), cytokines, osteopontin and endothelin stimulate processes of interstitial inflammation and fibroblast proliferation and are ultimately responsible for enhanced extracellular matrix deposition and renal scarring. Human tubular cells exposed to albumin and HDL increase production of endothelin-1. Endothelin-1 affects microcirculation and fibroblasts and is a monocyte chemoattractant. Specific proteins that are cytotoxic are transferrin/iron, low-density lipoprotein, and complement components, all of which appear in urine in proteinuric states. Adequate and early diagnosis and differentiation of proteinuria are of immense therapeutic importance.
Proper Use of Insecticides

The only possible conclusion is that there is no significant mean difference between "Before " and " After," in either the sweat, rate or the rectal temperature, either over the whole of the experiment or over the latter half. Thus no change in either sweat rate or body temperature has been demonstrated, and, as Dr. Ladell points out, the relation between arm sweat chloride and total body sweat chloride values is still under discussion. -We are, etc.,
Adams and Victor’s Principles of Neurology

Adams and Victor's Principles of Neurology provides all the information you will need to confidently handle any neurologic problem, from disorders of motility, and derangements of intellect, behavior, and language, to the degenerative and neuromuscular diseases. Having this gold standard text on your reference shelf is like being able to consult with skilled clinicians on a daily basis. More than a compilation of facts, Adams and Victor's delivers expert insights not found in any other resource that help you understand every aspect of neurological disease.
Design, Synthesis, and Antimicrobial Evaluation of Hexadentate Hydroxypyridinones with High Iron(III) Affinity

A range of hexadentate 3‐hydroxypyridin‐4‐ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO–iron complexes (logK1) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram‐positive and Gram‐negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 μg/mL, respectively. These results indicate that hexadentate 3‐hydroxypyridin‐4‐ones have potential application as antimicrobial agents, especially in the treatment of wound infection.
The Pyrazolobenzothiazine Core as a New Chemotype of p38 Alpha Mitogen‐Activated Protein Kinase Inhibitors

The identification, synthesis, biological activity, and binding mode prediction of a series of pyrazolobenzothiazines as novel p38α MAPK inhibitors are reported. Some of these compounds showed interesting activity in both p38α MAPK and TNF‐α release assays. Derivative 6 emerged as the most interesting compound with IC50 (p38α) = 0.457 μm, IC50 (TNF‐α) = 0.5 μm and a promising kinase selectivity profile. The obtained results strongly indicate the pyrazolobenzothiazine core as a new p38α inhibitor chemotype worthy of future chemical optimization efforts directed toward identifying a new generation of anti‐inflammatory agents.
Solid‐Supported Synthesis and 5‐HT7/5‐HT1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6‐(1H)‐one

A series of arylpiperazinylbutyl derivatives of 4,5‐dihydro‐1,2,4‐triazine‐6(1H)‐ones was designed and synthesized according to the new solid‐supported methodology. In this approach, triazinone scaffold was constructed from the Fmoc‐protected glycine. The library representatives showed different levels of affinity for 5‐HT7 and 5‐HT1A receptors; compounds 13, 14 and 18–20 were classified as dual 5‐HT7/5‐HT1A receptors ligands. The structure–affinity relationship analysis revealed that the receptor affinity and selectivity of the tested compounds depended on the kind of substituent in position 3 of triazinone fragment as well as substitution pattern of the phenylpiperazine moiety.
Rare disease clinical trials

The limb-girdle muscular dystrophies (LGMDs) encompass a collection of genetic muscle diseases with proximal-predominant weakness of the limbs. Thirty-two of these disorders are named via the common nomenclature, including 8 autosomal-dominant (LGMD1A-H) and 24 autosomal-recessive (LGMD2A-X) disorders.1 In addition, numerous other genetic muscle diseases, including Bethlem myopathy, dystrophinopathies, ryanodine receptor–associated myopathies, and many more, may clinically present with similar proximal-predominant weakness.2 Therefore, current genetic testing panels targeting neuromuscular weakness frequently encompass >75 genes. These disorders are quite rare, each with minimum prevalence estimates of 0.01–0.60 cases per 100,000 persons.3 LGMD2A (attributable to mutations in the gene for calpain-3) and LGMD2B (attributable to mutations in the gene for dysferlin) consistently are the 2 most prevalent LGMD subtypes in a variety of ethnic cohorts.
Neuronal Dynamics Under Periodic Stimuli

The convergence characteristics of a single dissipative Hopfield-type neuron with self-interaction under periodic external stimuli are considered. Sufficient conditions are established for associative encoding and recall of the periodic patterns associated with the external stimuli. Both continuous-time-continuous-state and discrete-time-continuous-state models are discussed. It is shown that when the neuronal gain is dominated by the neuronal dissipation on average, associative recall of the encoded temporal pattern is guaranteed and this is achieved by the global asymptotic stability of the encoded pattern.
Application of the balanced score‐card concept to develop a conceptual framework to measure facilities management performance within NHS facilities

This paper discusses the application of the balanced score‐card (BSC) concept as a widely used management framework for optimal measurement of organisational performance within NHS facilities directorates and discusses the fundamental points to cover in its implementation. Thereby, the paper identifies this framework as a strategic measurement and management system for facilities management. BSC formulation within NHS estates and facilities is described as a case study based on a facilities directorate situated in the north west of England, and discussion covers its implementation procedures, evaluation standards and reporting process. The paper further establishes the conceptual framework for performance management for the facilities directorate, as well as consistent techniques useful in undertaking the performance management administration and system oversight functions.
Synthesis and Protective Effects of Kaempferol‐3′‐sulfonate on Hydrogen Peroxide‐induced injury in Vascular Smooth Muscle Cells

A novel water‐soluble sulfated derivative, kaempferol‐3′‐sulfonate acid sodium (KS) with the composition of [C15H9O9SNa]·2.5H2O, was synthesized and characterized by elemental analysis, IR, 1H NMR, 13C NMR, and HRMS. Its protective effects on human vascular smooth muscle cells injured by hydrogen peroxide were evaluated by CCK‐8 method, flow cytometry, and Western blotting. The experimental results indicated that the KS can significantly increase cell viability and reduce apoptosis on H2O2‐injured VSMCs, as well as reverse the effects of H2O2 on Bcl‐2, Bad, and caspase‐3 expressions. In addition, LDH leakage, MDA levels, and SOD and GSH activities were also measured with spectrophotometry. The results indicated that the KS acted as antioxidant preventing LDH leakage and MDA production, while increasing intracellular SOD and GSH activities. These findings revealed that KS might potentially serve as an effective antioxidant agent for prevention and treatment of vascular disease caused by H2O2‐injured VSMCs.
Progression types after antiangiogenic therapy are related to outcome in recurrent glioblastoma

Objective: This retrospective study analyzed whether the type of radiologic progression, classified according to contrast enhancement on MRI T1-weighted sequences and changes in T2-hyperintense signal, is relevant for outcome in patients with progressive glioblastoma (pGB) treated with bevacizumab. Methods: MRI scans of 83 patients with pGB treated with bevacizumab were evaluated prior to and at disease progression. Based on initial decrease in and subsequent flare-up of contrast enhancement in T1 and 2 patterns of T2-hyperintense tumor progression, progression types (PTs) were categorized as cT1 flare-up, T2-diffuse, T2-circumscribed, or primary nonresponder. Overall survival (OS), survival from start of bevacizumab therapy (OS_Bev), survival after bevacizumab failure (OS_PostBev), time from initial diagnosis until initiation of bevacizumab therapy (StartBevT), and time to bevacizumab progression were evaluated using Kaplan-Meier curves, log-rank test, and Cox regression analyses. Results: The time observed for development of a T2-diffuse (n = 15) or a cT1 flare-up (n = 35) progression was longer than for progression in primary nonresponders (n = 16) or T2-circumscribed progression (n = 17). The T2-diffuse PT showed longer OS, OS_Bev, OS_PostBev, and StartBevT compared to the other PTs. Postprogression therapy tended to be relevant only for patients with a T2-circumscribed PT. Conclusions: Radiologic PTs following bevacizumab treatment failure show differences in time to development and are related to outcome. We therefore hypothesize that these PTs reflect a different glioma biology, including differential resistance mechanisms to bevacizumab, and may be associated with different responses to postprogression therapy.
β-Amyloidosis and neurodegeneration in Alzheimer disease

Over the past decade, there has been an explosion of research describing the relationship between brain β-amyloidosis as measured by PET imaging using 11C–Pittsburgh compound B1 or florbetapir.2 Two articles3,4 in this issue of Neurology® add additional observations. The purpose of this editorial is to describe a conceptual model of Alzheimer disease (AD) pathophysiology that enables the reader to put the current findings into perspective.
Healthcare providers’ use of brief clinical interventions for adolescent smokers

Aims: Numerous studies document the effectiveness of intensive clinical interventions to treat tobacco dependence in adult smokers. Empirical studies have provided limited support for the efficacy of such interventions among adolescent smokers, yet participation, retention, and quit rates associated with these interventions tend to be relatively low. Brief clinical interventions may be a promising alternative for promoting smoking cessation in adolescents. The purpose of this paper is to examine the efficacy and use of brief clinical interventions for adolescent smokers, healthcare providers’ provision of such treatment, barriers to adoption, and policies to increase brief clinical intervention provision. Methods: Studies were collected from the Centers for Disease Control and Prevention's Office of Smoking and Health, Medline, Psychinfo, PubMed, and the Cochrane Library. We also examined references identified from pertinent articles and books and elicited suggestions from experts in the field of tobacco control. Investigations were primarily confined to those conducted in the USA to allow ease of comparisons among studies. In addition, we chose to concentrate on research conducted in the USA because differences between the USA healthcare system and that of other countries would result in different barriers to adoption and policy recommendations. Findings: Results showed that, although healthcare professionals appear to be screening adolescents for their smoking status, rates of counseling and follow-up are disappointingly low. Obstacles to brief clinical intervention adoption include clinicians’ lack of knowledge and confidence regarding brief intervention delivery, lack of understanding regarding the unique use patterns of adolescent smokers, and focus on prevention instead of treatment. Clinician training can increase the confidence with which healthcare providers interact with their adolescent patients. Organizational changes include chart reminders, reimbursement for counseling, and staff behavior monitoring. Conclusions: Additional studies on efficacious methods to help adolescent smokers quit smoking are critically needed. Research on ways in which to increase brief clinical intervention provision are also warranted to prevent teenage smokers from carrying this habit, along with its associated morbidity and mortality risks, into adulthood.
Epidemia de displasia broncopulmonar: incidencia y factores asociados en una cohorte de niños prematuros en Bogotá, Colombia

Introduction: There is a perception that bronchopulmonary dysplasia incidence has increased in Bogota since 2000. This study estimates its incidence, compares it with historical data and describes associated factors. Materials and methods: We carried out a prospective analytical cohort of preterm newborns ≤34 weeks of gestational age without major malformations from 12 health facilities from Bogota in 2004. The main outcomes were incidence and severity of bronchopulmonary dysplasia, which were compared with an historical cohort (1994-1999). Results: Neonatal mortality was 80/496, and the bronchopulmonary dysplasia incidence was 54.3% (95% CI, 49.4–59.1). When controlling for type of institution (low and high mortality) it appeared that being born in an institution with low mortality decreased the risk for death (OR=0.308; 95% CI, 0.129-0.736) but increased the odds for moderate-severe bronchopulmonary dysplasia (OR=1.797; 95% CI, 1.046-3.088). The risk for bronchopulmonary dysplasia was higher than for the historical control cohort (RR=1.924; 95% CI, 1.686-2.196). Weight and gestational age at birth, mechanical ventilation, intrauterine growth restriction and type of institution (low vs. intermediate-high mortality) were independently associated with bronchopulmonary dysplasia of increasing severity or even death. Conclusions: The frequency of bronchopulmonary dysplasia in Bogota has increased markedly, and this cannot be explained solely by better survival of more fragile infants. Survivors–irrespective from gestational age– have more frequent and more severe respiratory sequels. Probably suboptimal aggressive respiratory care practices associated with a recent transition from restricted to almost universal access to mechanical ventilation in neonatal intensive care units in Bogota might be compromising the quality of neonatal respiratory care.
Gap Junctions as Common Cause of High-Frequency Oscillations and Epileptic Seizures in a Computational Cascade of Neuronal Mass and Compartmental Modeling

High frequency oscillations (HFO) appear to be a promising marker for delineating the seizure onset zone (SOZ) in patients with localization related epilepsy. It remains, however, a purely observational phenomenon and no common mechanism has been proposed to relate HFOs and seizure generation. In this work we show that a cascade of two computational models, one on detailed compartmental scale and a second one on neural mass scale can explain both the autonomous generation of HFOs and the presence of epileptic seizures as emergent properties. To this end we introduce axonal-axonal gap junctions on a microscopic level and explore their impact on the higher level neural mass model (NMM). We show that the addition of gap junctions can generate HFOs and simultaneously shift the operational point of the NMM from a steady state network into bistable behavior that can autonomously generate epileptic seizures. The epileptic properties of the system, or the probability to generate epileptic type of activity, increases gradually with the increase of the density of axonal-axonal gap junctions. We further demonstrate that ad hoc HFO detectors used in previous studies are applicable to our simulated data.