Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of GATA2 Deficiency With Severe Primary Epstein-Barr Virus (EBV) Infection and EBV-associated Cancers.

BACKGROUND Most patients infected with Epstein-Barr virus (EBV) are asymptomatic, have nonspecific symptoms, or have self-limiting infectious mononucleosis. EBV, however, may result in severe primary disease or cancer. METHODS We report EBV diseases associated with GATA2 deficiency at one institution and describe the hematology, virology, and cytokine findings. RESULTS Seven patients with GATA2 deficiency developed severe EBV disease. Three presented with EBV infectious mononucleosis requiring hospitalization, 1 had chronic active EBV disease (B-cell type), 1 had EBV-associated hydroa vacciniforme-like lymphoma with hemophagocytic lymphohistiocytosis, and 2 had EBV-positive smooth muscle tumors. Four of the 7 patients had severe warts and 3 had disseminated nontuberculous mycobacterial infections. All of the patients had low numbers of monocytes, B cells, CD4 T cells, and natural killer cells. All had elevated levels of EBV in the blood; 2 of 3 patients tested had expression of the EBV major immediate-early gene in the blood indicative of active EBV lytic infection. Mean plasma levels of tumor necrosis factor α, interferon γ, and interferon gamma-induced protein 10 were higher in patients with GATA2 deficiency than in controls. CONCLUSIONS GATA2 is the first gene associated with EBV hydroa vacciniforme-like lymphoma. GATA2 deficiency should be considered in patients with severe primary EBV infection or EBV-associated cancer, especially in those with disseminated nontuberculous mycobacterial disease and warts.
Efficiency of spinal anesthesia versus general anesthesia for lumbar spinal surgery: a retrospective analysis of 544 patients

Background Previous studies have shown varying results in selected outcomes when directly comparing spinal anesthesia to general in lumbar surgery. Some studies have shown reduced surgical time, postoperative pain, time in the postanesthesia care unit (PACU), incidence of urinary retention, postoperative nausea, and more favorable cost-effectiveness with spinal anesthesia. Despite these results, the current literature has also shown contradictory results in between-group comparisons. Materials and methods A retrospective analysis was performed by querying the electronic medical record database for surgeries performed by a single surgeon between 2007 and 2011 using procedural codes 63030 for diskectomy and 63047 for laminectomy: 544 lumbar laminectomy and diskectomy surgeries were identified, with 183 undergoing general anesthesia and 361 undergoing spinal anesthesia (SA). Linear and multivariate regression analyses were performed to identify differences in blood loss, operative time, time from entering the operating room (OR) until incision, time from bandage placement to exiting the OR, total anesthesia time, PACU time, and total hospital stay. Secondary outcomes of interest included incidence of postoperative spinal hematoma and death, incidence of paraparesis, plegia, post-dural puncture headache, and paresthesia, among the SA patients. Results SA was associated with significantly lower operative time, blood loss, total anesthesia time, time from entering the OR until incision, time from bandage placement until exiting the OR, and total duration of hospital stay, but a longer stay in the PACU. The SA group experienced one spinal hematoma, which was evacuated without any long-term neurological deficits, and neither group experienced a death. The SA group had no episodes of paraparesis or plegia, post-dural puncture headaches, or episodes of persistent postoperative paresthesia or weakness. Conclusion SA is effective for use in patients undergoing elective lumbar laminectomy and/or diskectomy spinal surgery, and was shown to be the more expedient anesthetic choice in the perioperative setting.
Multi‐modality of pI distribution in whole proteome

Multi‐modality of pI distribution is a common feature in different whole proteomes. Some researchers considered it relate to the proteins with different subcellular locations, indicating the result of natural selection. We explored the pI distribution of predicted proteomes (including animals, plants, bacterium, archaeans) and random proteome [random protein sequences constructed according to the special amino acid composition and molecular weight (MW) distribution of human predicted proteome]. Our results suggest that the multi‐modality is the result of discrete pKR values for different amino acids. Amino acid composition and MW distribution of a proteome also contributes to the specific pI distribution. Although protein subcellular location was related to pI value, our analyses revealed that comparing with the random proteome, neither the multi‐modality phenomenon nor the distribution bias of pI values is caused by subcellular location. It seems that the multi‐modality distribution is just a mathematical fun. The blank region near the neutral pI was caused by the absence of amino acids with neutral pKR, and suggests that the selection of amino acids with ionizable side chain might be restricted by the requirement for a special pH environment during the origin of life. From this point of view, the special distribution was the result of natural selection.
The FAS‐670 AA genotype is associated with high proviral load in peruvian HAM/TSP patients

Human T‐lymphotropic virus 1 (HTLV‐1) is the etiologic agent of the HTLV‐1‐associated myelopathy/tropical spastic paraparesis (HAM/TSP). Apoptosis is a mechanism of defense elicited by many triggers, including cross‐linking of the FAS receptor expressed in viruses‐infected cells, and the ligand FASL presented by T‐cytotoxic cells. As HAM/TSP has been associated with high levels of proviral load (PVL), we hypothesized that certain genotypes of single‐nucleotide polymorphisms (SNPs) associated with a decreased protein expression of FAS and FASL could be risk factors for this disease. Three SNPs: FAS‐670A/G (rs1800682), FAS‐1377G/A (rs2234767), and FASL‐844C/T (rs763110) were analyzed in 73 HAM/TSP patients and 143 HTLV‐1 asymptomatic carriers. Ancestry informative markers were used to adjust for ethnicity through a principal component analysis. Gender, age, PVL, and the first three principal components were used as covariates. The FAS/FASL genotype distribution was not associated with HAM/TSP presence (P–> 0.05). The FAS‐670 AA genotype was associated with high PVL in comparison to FAS‐670 GG in HAM/TSP patients (P = 0.015), while in asymptomatic carriers low levels of PVL were observed (P > 0.05). Our findings suggest that rs1800682, rs2234767, and rs763110 genotypes are not associated with the presence of HAM/TSP, but that the FAS‐670 AA genotype can promote higher PVL values in HAM/TSP patients. J. Med. Virol. 89:726–731, 2017. © 2016 Wiley Periodicals, Inc.
Computer-Detected Patterns of Electroencephalographic Delta Activity During and After Extended Sleep

Delta (0.5 to 3 hertz) waves are the electroencephalographic hallmark of human sleep. We measured their rate of production during and following an extended night of sleep. On the extended night, we confirmed previous observations of a linear decline in delta wave production across the first four periods of non-rapid-eye-movement (non-REM) sleep. An asymptote was reached in the fifth non-REM period, perhaps signifying that sleep processes reached completion. On the day after the extended night, subjects were allowed to remain awake 3.6 hours less than normal. During the next sleep session, amplitude and number of delta waves in non-REM periods 1 and 3 were significantly reduced. These findings illustrate the value of computer analysis of electroencephalographic waveforms in sleep. Systematic measurement of the amount and distribution of these waveforms as a function of preceding waking duration should provide clues to the kinetics of the metabolic processes underlying sleep.
Robustness of IMPT treatment plans with respect to inter-fractional set-up uncertainties: Impact of various beam arrangements for cranial targets

Abstract In the current study IMPT plan robustness was evaluated with respect to inter-fractional patient positioning for various beam arrangements and two tumor indications in the cranial region. Material and methods. For 14 patients suffering from tumors in the cranial region [skull base (SB; n = 7) and paranasal sinus (PS; n = 7)] the CTV and OARs were delineated. A safety margin of 3 mm was applied to the CTV. A prescribed dose of 2 GyE was planned via three beam arrangements (α, β, γ). Beam arrangement α consisted of lateral opposed fields for both tumor groups while beam arrangement β was optimized according to respective tumor and OAR locations, using two beams only. Beam arrangement γ applied four beams in the SB group and three beams in the PS group. Dose distributions were recalculated subjected to virtual patient translations along the major anatomical axes. The following dosimetric indices were evaluated and compared to original plans: target coverage (TC), target dose homogeneity (HI), CTV median and average dose (Dmedian, Dmean). For OARs near maximum dose and average dose (D2%, Dmean) were evaluated. Results. Dose distributions were distorted after introducing shifts. In the SB group, TC and HI were significantly different for caudal, cranial and anterior shifts for all beam arrangements. For PS patients, all but right shifts differed significantly from the original plans for all beam arrangements, although clinical relevance was not reached for arrangement γ (ΔTC < 1.5%). In general, beam arrangement γ exhibited the least spread of data regarding target indices and was consequently considered the most robust. Dosimetric parameters regarding the brainstem were mostly influenced by shifts along the anterio-posterior axis. Conclusion. For cranial IMPT, set-up uncertainties may lead to pronounced deterioration of dose distributions. According to our investigations, multi-beam arrangements were dosimetrically more robust and hence preferable over two beam arrangements.
A Review of the Concept of Culture in Holistic Nursing Literature

Core Value IV of the American Holistic Nurses’ Association includes valuing the client’s cultural background. The authors reviewed all article abstracts from two major holistic nursing journals for a 3-year period (N=198). References to concepts of culture or ethnicity were found in only 9.6% of abstracts. Many theorists and researchers did not discuss how the theory or research findings varied between culturally or ethnically diverse samples. When culture is a core value, practitioners and researchers cannot assume that culture has been considered without stating what was the interaction of culture with the phenomenon of concern. The authors recommend that nurses develop cultural competence in caring for clients from differing cultural orientations by (a) committing to improve their knowledge of multiple cultures; (b) exploring their own cultural background; (c) seeking exposure to cultures other than their own; and (d) regularly discussing culture and ethnicity in nursing theory, research, and practice.
Blood pressure control according to new guidelines targets in low- to high-risk hypertensives managed in specialist practice

Objective It is well established that adequate blood pressure (BP) control characterizes only a fraction of treated hypertensive patients. Few reports are available on BP control in relation to the cardiovascular risk profile in patients followed by specialist physicians. Methods We evaluated the cardiovascular risk profile (according to recent ESH/ESC Guidelines), antihypertensive drug treatment and systolic and diastolic blood pressure values (SBP/DBP) by semi-automatic BP monitoring in 2775 hypertensive patients, aged 60.6 ± 16.1 years (mean ± SD), followed by 131 specialist centres in northern (34.5%), central (28.1%) and southern (37.4%) Italy. Of these patients, 94.6% received antihypertensive treatment with one (36.9%) or more (57.7%) drugs. Results Optimal SBP and DBP control (< 140/90 mmHg) was shown by 37.5% of the patients, the rate of controlled values being much greater for DBP (64.4%) than for SBP (40.2%). About one-third of patients displayed BP values in the higher range (⩾ 160/95 mmHg). No difference in BP control was found in relation to different geographic areas, patient's gender, occupational activity and attitude to the use of home blood pressure monitoring. BP control was inversely related to patient's age and directly related to educational level. It was more manifest in low- or medium-risk categories than in higher-risk patients (43.2 versus 34.9%). Follow-up visits performed after 6 and 12 months after patient enrolment have shown an improvement in blood pressure control (from 40.7 to 51.8%), related to therapeutic modifications and better compliance. Conclusions These data provide evidence that BP control in different Italian geographic areas remains largely inadequate, particularly for SBP and high-risk patients. They also suggest that an improvement in treatment compliance may produce favourable therapeutic effects.
The outer membranes of Brucella spp. are resistant to bactericidal cationic peptides

The actions of polymyxin B, rabbit polymorphonuclear lysosome extracts, 14 polycationic peptides (including defensin NP-2, cecropin P1, lactoferricin B, and active peptides from cationic protein 18 and bactenecin), EDTA, and Tris on Brucella spp. were studied, with other gram-negative bacteria as controls. Brucella spp. were comparatively resistant to all of the agents listed above and bound less polymyxin B, and their outer membranes (OMs) were neither morphologically altered nor permeabilized to lysozyme by polymyxin B concentrations, although both effects were observed for controls. EDTA and peptides increased or accelerated the partition of the hydrophobic probe N-phenyl-naphthylamine into Escherichia coli and Haemophilus influenzae OMs but had no effect on Brucella OMs. Since Brucella and H. influenzae OMs are permeable to hydrophobic compounds (G. Martínez de Tejada and I. Moriyón, J. Bacteriol. 175:5273-5275, 1993), the results show that such unusual permeability is not necessarily related to resistance to polycations. Although rough (R) B. abortus and B. ovis were more resistant than the controls were, there were qualitative and quantitative differences with smooth (S) brucellae; this may explain known host range and virulence differences. Brucella S-lipopolysaccharides (LPSs) had reduced affinities for polycations, and insertion of Brucella and Salmonella montevideo S-LPSs into the OM of a Brucella R-LPS mutant increased and decreased, respectively, its resistance to cationic peptides. The results show that the core lipid A of Brucella LPS plays a major role in polycation resistance and that O-chain density also contributes significantly. It is proposed that the features described above contribute to Brucella resistance to the oxygen-independent systems of phagocytes.
Neuroimaging of the Child With Developmental Delay

Developmental delay (DD) affects approximately 1% to 3% of all children in the United States. This diagnosis significantly impedes quality of life and full participation in the life of the family, school, and community. In this setting, the clinician's ability to detect, diagnose, and possibly treat the cause for DD in a timely manner depends on a multimodality approach to neuroimaging and a robust understanding of the various imaging algorithms aimed at determining the etiology of disease, structural and/or anatomic defects, functional activity, metabolic profiles, and genetic characteristics. Taken separately and in combination, these features are effectively depicted and analyzed using an array of brain imaging modalities: ultrasound, computed tomography, nuclear medicine, magnetic resonance (MR) spectroscopy, and a growing mix of sophisticated MR imaging (MRI) techniques, including diffusion-weighted imaging, diffusion tensor imaging, perfusion MRI, and functional MRI. Thus, equipped with these advanced imaging capabilities, pediatric neurologists and neuroradiologists are now positioned to diagnose with greater accuracy and speed; this, in turn, results in more effective treatment plans and improved patient outcomes as measured by progress in reaching developmental milestones and in ameliorating secondary conditions such as seizures, poor motor control, incontinence, and impulsivity. The purpose of this article is to present the numerous causes of pediatric DD, describe their respective neuroimaging findings, discuss various neuroimaging approaches for elucidating etiology, and offer specific guidelines for optimizing imaging results in the setting of multimodality imaging capabilities.
Human monocytes/macrophages are a target of Neisseria meningitidis Adhesin A (NadA)

Specific surface proteins of Neisseria meningitidis have been proposed to stimulate leukocytes during tissue invasion and septic shock. In this study, we demonstrate that the adhesin N. meningitidis Adhesin A (NadA) involved in the colonization of the respiratory epithelium by hypervirulent N. meningitidis B strains also binds to and activates human monocytes/macrophages. Expression of NadA on the surface on Escherichia coli does not increase bacterial‐monocyte association, but a NadA‐positive strain induced a significantly higher amount of TNF‐α and IL‐8 compared with the parental NadA‐negative strain, suggesting that NadA has an intrinsic stimulatory action on these cells. Consistently, highly pure, soluble NadAΔ351–405, a proposed component of an antimeningococcal vaccine, efficiently stimulates monocytes/macrophages to secrete a selected pattern of cytokines and chemotactic factors characterized by high levels of IL‐8, IL‐6, MCP‐1, and MIP‐1α and low levels of the main vasoactive mediators TNF‐α and IL‐1. NadAΔ351–405 also inhibited monocyte apoptosis and determined its differentiation into a macrophage‐like phenotype.
Application of PILATUS II Detector Modules for High Resolution X-Ray Imaging Crystal Spectrometers on the Alcator C-Mod Tokamak

A new type of X-ray imaging crystal spectrometer for Doppler measurements of the radial profiles of the ion temperature and plasma rotation velocity in tokamak plasmas is presently being developed in a collaboration between various laboratories. The spectrometer will consist of a spherically bent crystal and a two-dimensional position sensitive detector; and it will record temporally and spatially resolved X-ray line spectra from highly-charged ions. The detector must satisfy challenging requirements with respect to count rate and spatial resolution. The paper presents the results from a recent test of a PILATUS II detector module on Alcator C-Mod, which demonstrate that the PILATUS II detector modules will satisfy these requirements.
Assessment of Degree of Disorder (Amorphicity) of Lyophilized Formulations of Growth Hormone Using Isothermal Microcalorimetry

When determining the degree of disorder of a lyophilized cake of a protein, it is important to use an appropriate analytical technique. Differential scanning calorimetry (DSC) and X‐ray powder diffraction (XRPD) are the most commonly used thermo‐analytical techniques for characterizing freeze‐dried protein formulations. Unfortunately, these methods are unable to detect solid‐state disorder at levels < 10%. Also, interpretation of DSC results for freeze‐dried protein formulations can be difficult, as a result of the more complex thermal events occurring with this technique. For example, proteins can inhibit the thermally induced recrystallization of the lyophilized cake, resulting in potential misinterpretation of DSC degree of disorder results. The aim of this investigation was to study the use of isothermal microcalorimetry (IMC) in the assessment of degree of solid‐state disorder (amorphicity) of lyophilized formulations of proteins. For this purpose, two formulations of growth hormone were prepared by lyophilization. These formulations consisted of the same amounts of protein, mannitol, glycine, and phosphate buffer, but differed in the freeze‐drying procedure. After lyophilization, the recrystallization of the samples was studied using IMC at 25°C under different relative humidities (58–75%). The effect of available surface area was studied by determining the heat of recrystallization (Q) of the samples before and after disintegration of the cakes. The results showed that, in contrast to DSC, IMC allowed detection of the recrystallization event in the formulations. Although both formulations were completely disordered and indistinguishable according to XRPD method, IMC revealed that formulation B had a different solid‐sate structure than formulation A. This difference was the result of differences in the freeze‐drying parameters, demonstrating the importance of choosing appropriate analytical methodology.
Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate

The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non‐cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N‐methyl‐D‐aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G‐saporin. In eight Han–Wistar rats with implanted electroencephalogram/electromyogram (EEG/EMG) electrodes and guide cannulas for microdialysis probes, 0.23 μg 192 IgG‐saporin was administered into the basal forebrain, while the eight control animals received artificial cerebrospinal fluid. Two weeks later, a microdialysis probe targeted into the basal forebrain was perfused with cerebrospinal fluid on the baseline day and for 3 h with 0.3 mmNMDA on the subsequent day. Sleep–wake activity was recorded for 24 h on both days. NMDA exhibited a robust arousing effect in both the intact and the lesioned rats. Wakefulness was increased and both non‐REM and REM sleep were decreased significantly during the 3‐h NMDA perfusion. Destruction of the basal forebrain cholinergic neurones did not abolish the wake‐enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate.
Economic consequences of the Home Appliance Eco-Point Program in Japan: a dynamic discrete choice approach

ABSTRACT This study combined a dynamic discrete choice model for air conditioner replacement decisions with an inter-industry model in order to evaluate the economic impact of Japan’s Home Appliance Eco-Point Program, an appliance replacement program that was in effect from May 2009 to March 2011. Focusing on air conditioners produced from 1995 to 1999 and replaced during the period from 2005 to 2013, we found that the eco-point program increased replacement probabilities by 1.5% to 1.9% in 2009. Moreover, the program produced an additional output of 31,337 million yen and a total value added of 21,259 million yen. However, the benefit–cost ratio – determined by dividing the increase in value added by the monetary value of the points awarded for appliance replacement – was only 0.68. From a cost-benefit perspective, the program can be judged not to have been an effective policy measure.