Miracle-dz/UniFAR-FTUs huggingface dataset:
Stroke volume increase to exercise in chronic obstructive pulmonary disease is limited by increased pulmonary artery pressure

Aims: This study was designed to investigate the mechanisms by which the right ventricle is able to increase stroke volume (SV) during exercise in chronic obstructive pulmonary disease (COPD). A second aim was to determine whether resting pulmonary artery pressure (Ppa) is predictive of exercise SV. Methods: 16 COPD patients (GOLD stages II–IV) underwent right heart catheterisation at rest and during exercise. In this group and eight age-matched controls resting and exercise right ventricular SV, end-diastolic volume (RVEDV) and end-systolic volume (RVESV) were assessed by magnetic resonance imaging (MRI). The exercise protocol during both measurements consisted of 3 minutes of cycling in supine position at 40% of maximal workload. Results: In all patients mean Ppa increased significantly in response to exercise (21 (8) vs 33 (11) mm Hg, p<0.01), whereas pulmonary vascular resistance did not change. In the patient group, RVEDV (129 (42) vs 135 (42) ml, p<0.05) and SV (63 (13) vs 69 (14) ml, p<0.05) increased significantly from rest to exercise, but RVESV and RV ejection fraction remained unaltered. In contrast, in healthy controls SV is augmented (81 (22) vs 101 (28) ml, p<0.05) by both increased RVEDV (123 (33) vs 134 134) ml, p<0.05) and reduced RVESV (37 (9) vs 27 (10) ml, p<0.05). Resting mean Ppa was related to SV during exercise (r = −0.59, p<0.02). Conclusion: As a consequence of unaltered pulmonary vascular resistance to exercise in COPD patients, Ppa increases and SV response to exercise is limited and results from an increased preload only. Ppa at rest predicts exercise SV.
Trivial Connections on Discrete Surfaces

This paper presents a straightforward algorithm for constructing connections on discrete surfaces that are as smooth as possible everywhere but on a set of isolated singularities with given index. We compute these connections by solving a single linear system built from standard operators. The solution can be used to design rotationally symmetric direction fields with user‐specified singularities and directional constraints.
Identifying Young Gifted Children Using the Gifted Rating Scales—Preschool/ Kindergarten Form

This article reports on an analysis of the diagnostic accuracy of a new teacher rating scale designed to assist in the identification of gifted preschool and kindergarten students. The Gifted Rating Scales—Preschool/Kindergarten Form (GRS-P) is based on a multidimensional model of giftedness. An examination of the standardization sample using diagnostic efficiency statistics provides support for the diagnostic accuracy of the GRS-P Intellectual Ability and Academic Ability scales identifying intellectual giftedness, irrespective of the IQ cut score used to demarcate giftedness. The present findings extend the analysis of the standardization sample reported in the test manual and provide additional support for the GRS-P as a gifted screening tool.
Pathogenesis of retinopathy of prematurity

Retinopathy of prematurity (ROP) is a blinding disease, initiated by delayed retinal vascular growth after premature birth. There are both oxygen‐regulated and non‐oxygen‐regulated factors, which contribute to both normal vascular development and retinal neovascularization. One important oxygen‐regulated factor, critical to both phases of ROP, is vascular endothelial growth factor (VEGF). A critical non oxygen‐regulated growth factor is insulin‐like growth factor (IGF‐1). In knockout mice, lack of IGF‐1 prevents normal retinal vascular growth, despite the presence of VEGF, important to vessel development. In vitro, low IGF‐1 prevents vascular endothelial growth factor‐induced activation of Akt, a kinase critical for vascular endothelial cell survival. Premature infants who develop ROP have lower levels of serum IGF‐1 than age‐matched infants without disease.
Serum Phosphate Predicts Early Mortality among Underweight Adults Starting ART in Zambia: A Novel Context for Refeeding Syndrome?

Background. Low body mass index (BMI) at antiretroviral therapy (ART) initiation is associated with early mortality, but the etiology is not well understood. We hypothesized that low pretreatment serum phosphate, a critical cellular metabolism intermediate primarily stored in skeletal muscle, may predict mortality within the first 12 weeks of ART. Methods. We prospectively studied 352 HIV-infected adults initiating ART in Lusaka, Zambia to estimate the odds of death for each 0.1 mmol/L decrease in baseline phosphate after adjusting for established predictors of mortality. Results. The distribution of phosphate values was similar across BMI categories (median value 1.2 mmol/L). Among the 145 participants with BMI <18.5 kg/m2, 28 (19%) died within 12 weeks. Lower pretreatment serum phosphate was associated with increased mortality (odds ratio (OR) 1.24 per 0.1 mmol/L decrement, 95% CI: 1.05 to 1.47; P = 0.01) after adjusting for sex, age, and CD4+ lymphocyte count. A similar relationship was not observed among participants with BMI ≥18.5 kg/m2 (OR 0.96, 95% CI: 0.76 to 1.21; P = 0.74). Conclusions. The association of low pretreatment serum phosphate level and early ART mortality among undernourished individuals may represent a variant of the refeeding syndrome. Further studies of cellular metabolism in this population are needed.
Improving the Accuracy of Baha® Fittings through Measures of Direct Bone Conduction

Objectives Variability in Baha® sound processor fittings may arise from the nature of the implant-to-bone transmission as well as transcranial attenuation for patients with single-sided sensorineural deafness (SSD). One method of improving the predictability of Baha fittings is to measure the individual patient's actual bone conduction thresholds, thereby removing the influences of skin thickness and/or the implant location site. Methods Twenty adult wearers of the Baha bone conduction implant system participated in the study. Direct bone conduction thresholds were obtained through the BC Direct function of the Baha Fitting Software combined with the Cochlear Baha BP100 sound processor. For comparison, the masked and unmasked bone conduction responses of the patients were collected through standard audiometric testing techniques. Test-retest reliability measurement was performed for all participants. Data for each frequency and frequency range were analyzed separately. Results The results confirm the improved transmission of sound through the implant rather than transcutaneously through the skin. On average, the BC Direct thresholds were closer to the patient's unmasked thresholds than the masked values. In subjects with SSD, BC Direct results were poorer than contra-lateral bone conduction thresholds, most likely due to transcranial attenuation. The test-retest reliability for the BC Direct measurements was within +/-5 dB. The comparison of preferred amplification, based on direct bone conduction or bone conduction audiometry, found higher agreement for fittings based on direct bone conduction measurements. Conclusion While the transfer function between the implant and the skin can be predicted on average, there are a number of patients for whom measurement is essential to determine the required amplification. These were patients with: 1) SSD, 2) asymmetrical hearing loss, 3) unusual implant location or skull formation, and 4) users of Testband or Softband. The result for the clinician is that a fitting can take place with less fine-tuning and a greater understanding of the variability of bone conducted sound transmission.
Scalable Interconnection Network Models for Rapid Performance Prediction of HPC Applications

Performance Prediction Toolkit (PPT) is a simulator mainly developed at Los Alamos National Laboratory to facilitate rapid and accurate performance prediction of large-scale scientific applications on existing and future HPC architectures. In this paper, we present three interconnect models for performance prediction of large-scale HPC applications. They are based on interconnect topologies widely used in HPC systems: torus, dragonfly, and fat-tree. We conduct extensive validation tests of our interconnect models, in particular, using configurations of existing HPC systems. Results show that our models provide good accuracy for predicting the network behavior. We also present a performance study of a parallel computational physics application to show that our model can accurately predict the parallel behavior of large-scale applications.
Validation of a dysphagia screening tool in acute stroke patients.

BACKGROUND Although many dysphagia screening tools exist, none has high sensitivity and reliability or can be administered quickly with minimal training. OBJECTIVE To design and validate a swallowing screening tool to be used by health care professionals who are not speech language pathologists to identify dysphagia and aspiration risk in acute stroke patients. METHODS In a prospective study of 300 patients admitted to the stroke service at an urban tertiary care hospital, interrater and test-retest reliabilities of a new tool (the Acute Stroke Dysphagia Screen) were established. The tool was administered by nursing staff when patients were admitted to the stroke unit. A speech language pathologist blinded to the results with the new tool administered the Mann Assessment of Swallowing Ability, a clinical bedside evaluation, with dysphagia operationally defined by a score less than 178. RESULTS The mean time from admission to screening with the new tool was 8 hours. The mean time between administration of the new tool and the clinical bedside evaluation was 32 hours. For the new tool, interrater reliability was 93.6% and test-retest reliability was 92.5%. The new tool had a sensitivity of 91% and a specificity of 74% for detecting dysphagia and a sensitivity of 95% and a specificity of 68% for detecting aspiration risk. CONCLUSIONS The Acute Stroke Dysphagia Screen is an easily administered and reliable tool that has sufficient sensitivity to detect both dysphagia and aspiration risk in acute stroke patients.
Uniparental Markers in Italy Reveal a Sex-Biased Genetic Structure and Different Historical Strata

Located in the center of the Mediterranean landscape and with an extensive coastal line, the territory of what is today Italy has played an important role in the history of human settlements and movements of Southern Europe and the Mediterranean Basin. Populated since Paleolithic times, the complexity of human movements during the Neolithic, the Metal Ages and the most recent history of the two last millennia (involving the overlapping of different cultural and demic strata) has shaped the pattern of the modern Italian genetic structure. With the aim of disentangling this pattern and understanding which processes more importantly shaped the distribution of diversity, we have analyzed the uniparentally-inherited markers in ∼900 individuals from an extensive sampling across the Italian peninsula, Sardinia and Sicily. Spatial PCAs and DAPCs revealed a sex-biased pattern indicating different demographic histories for males and females. Besides the genetic outlier position of Sardinians, a North West–South East Y-chromosome structure is found in continental Italy. Such structure is in agreement with recent archeological syntheses indicating two independent and parallel processes of Neolithisation. In addition, date estimates pinpoint the importance of the cultural and demographic events during the late Neolithic and Metal Ages. On the other hand, mitochondrial diversity is distributed more homogeneously in agreement with older population events that might be related to the presence of an Italian Refugium during the last glacial period in Europe.
Suggestive interviewing in the McMartin Preschool and Kelly Michaels daycare abuse cases: A case study

In the 1980s and early 1990s the United States witnessed an outbreak of bizarre “daycare abuse” cases in which groups of young children levelled allegations of sexual and Satanic abuse against their teachers. In the present study, quantitative analyses were performed on a total of 54 interview transcripts from two highly publicised daycare cases (McMartin Preschool and Kelly Michaels) and a comparison group of child sexual abuse cases from a Child Protection Service (CPS). Confirming the impression of prior commentators, systematic analyses showed that interviews from the two daycare cases were highly suggestive. Compared with the CPS interviews, the McMartin and/or Michaels interviewers were significantly more likely to (a) introduce new suggestive information into the interview, (b) provide praise, promises, and positive reinforcement, (c) express disapproval, disbelief, or disagreement with children, (d) exert conformity pressure, and (e) invite children to pretend or speculate about supposed events. Renata Strok is now at the Pacific School of Psychology, Palo Alto, CA. Lisa D. Bellah (formerly Lisa D. Velarde) is at the Federal Medical Center, Federal Bureau of Prisons, in Fort Worth, Texas. Yolanda Martinez is at Rio Vista Rehabilitation Center in El Paso, TX. Kristin McLaurin is at Porter and Hedges law firm in Houston, TX. Sena Garven is at the US Army Leadership School in Fort Leavenworth, KS. We wish to thank the following members of Por Ninos y Familias for transcribing and scoring the interviews in this study: Damian Aguilar, Gabriela Bernal, Eunice Buendia, Jennifer Carrasco, Gustavo Correa, Diana Martinez, Linda Mollinary, Gabriel Nevarez, Lucia Ramirez, Regina White, LeeAnne Williams, Betty Urquidi, and Zandra Zamora.
The Nature of Surround-Induced Depolarizing Responses in Goldfish Cones

Cones in the vertebrate retina project to horizontal and bipolar cells and the horizontal cells feedback negatively to cones. This organization forms the basis for the center/surround organization of the bipolar cells, a fundamental step in the visual signal processing. Although the surround responses of bipolar cells have been recorded on many occasions, surprisingly, the underlying surround-induced responses in cones are not easily detected. In this paper, the nature of the surround-induced responses in cones is studied. Horizontal cells feed back to cones by shifting the activation function of the calcium current in cones to more negative potentials. This shift increases the calcium influx, which increases the neurotransmitter release of the cone. In this paper, we will show that under certain conditions, in addition to this increase of neurotransmitter release, a calcium-dependent chloride current will be activated, which polarizes the cone membrane potential. The question is, whether the modulation of the calcium current or the polarization of the cone membrane potential is the major determinant for feedback-mediated responses in second-order neurons. Depolarizing light responses of biphasic horizontal cells are generated by feedback from monophasic horizontal cells to cones. It was found that niflumic acid blocks the feedback-induced depolarizing responses in cones, while the shift of the calcium current activation function and the depolarizing biphasic horizontal cell responses remain intact. This shows that horizontal cells can feed back to cones, without inducing major changes in the cone membrane potential. This makes the feedback synapse from horizontal cells to cones a unique synapse. Polarization of the presynaptic (horizontal) cell leads to calcium influx in the postsynaptic cell (cone), but due to the combined activity of the calcium current and the calcium-dependent chloride current, the membrane potential of the postsynaptic cell will be hardly modulated, whereas the output of the postsynaptic cell will be strongly modulated. Since no polarization of the postsynaptic cell is needed for these feedback-mediated responses, this mechanism of synaptic transmission can modulate the neurotransmitter release in single synaptic terminals without affecting the membrane potential of the entire cell.
Improved Innate and Adaptive Immunostimulation by Genetically Modified HIV-1 Protein Expressing NYVAC Vectors

Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.
HIV Traffics through a Specialized, Surface-Accessible Intracellular Compartment during trans-Infection of T Cells by Mature Dendritic Cells

In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC–T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate that HIV resides in an invaginated domain within DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection.
Music training alters the course of adolescent auditory development

Significance We show that in-school music training changes the course of adolescent brain development. Relative to an active control group that shows the expected wane in subcortical response consistency, adolescents undertaking in-school music training maintained heightened neural consistency throughout high school. The music training group also exhibited earlier emergence of the adult cortical response, suggesting that in-school music accelerates neurodevelopment. These changes seem to benefit literacy skills: both groups improved in phonological awareness relative to the general population, but the music training group improved more compared with the active controls. Our results support the notion that the adolescent brain remains receptive to training, underscoring the importance of enrichment during teenage years. Fundamental changes in brain structure and function during adolescence are well-characterized, but the extent to which experience modulates adolescent neurodevelopment is not. Musical experience provides an ideal case for examining this question because the influence of music training begun early in life is well-known. We investigated the effects of in-school music training, previously shown to enhance auditory skills, versus another in-school training program that did not focus on development of auditory skills (active control). We tested adolescents on neural responses to sound and language skills before they entered high school (pretraining) and again 3 y later. Here, we show that in-school music training begun in high school prolongs the stability of subcortical sound processing and accelerates maturation of cortical auditory responses. Although phonological processing improved in both the music training and active control groups, the enhancement was greater in adolescents who underwent music training. Thus, music training initiated as late as adolescence can enhance neural processing of sound and confer benefits for language skills. These results establish the potential for experience-driven brain plasticity during adolescence and demonstrate that in-school programs can engender these changes.
Intratumor Heterogeneity Affects Gene Expression Profile Test Prognostic Risk Stratification in Early Breast Cancer

Purpose: To examine the effect of intratumor heterogeneity (ITH) on detection of genes within gene expression panels (GEPs) and the subsequent ability to predict prognostic risk. Experimental Design: Multiplexed barcoded RNA analysis was used to measure the expression of 141 genes from five GEPs (Oncotype Dx, MammaPrint, PAM50, EndoPredict, and Breast Cancer Index) in breast cancer tissue sections and tumor-rich cores from 71 estrogen receptor (ER)-positive node-negative tumors, on which clinical Oncotype Dx testing was previously performed. If the tumor had foci of high Ki67 (n = 26), low/negative progesterone receptor (PR; n = 13), or both (n = 5), additional cores were obtained. In total, 181 samples were processed. Oncotype Dx recurrence scores were calculated from NanoString nCounter gene expression data. Results: Hierarchical clustering using all GEP genes showed that majority (61 of 71) of tumor samples clustered by patient, indicating greater interpatient heterogeneity (IPH) than ITH. We found a strikingly high correlation between Oncotype Dx recurrence scores obtained from whole sections versus tumor-rich cores (r = 0.94). However, high Ki67 and low PR cores had slightly higher but not statistically significant recurrence scores. For 18 of 71 (25%) patients, scores were divergent between sections and cores and crossed the boundaries for low, intermediate, and high risk. Conclusions: Our study indicates that in patients with highly heterogeneous tumors, GEP recurrence scores from a single core could under- or overestimate prognostic risk. Hence, it may be a useful strategy to assess multiple samples (both representative and atypical cores) to fully account for the ITH-driven variation in risk prediction. Clin Cancer Res; 22(21); 5362–9. ©2016 AACR.