Miracle-dz/UniFAR-FTUs huggingface dataset:
Tumor-infiltrating T lymphocytes improve clinical outcome of therapy-resistant neuroblastoma

Neuroblastoma grows within an intricate network of different cell types including epithelial, stromal and immune cells. The presence of tumor-infiltrating T cells is considered an important prognostic indicator in many cancers, but the role of these cells in neuroblastoma remains to be elucidated. Herein, we examined the relationship between the type, density and organization of infiltrating T cells and clinical outcome within a large collection of neuroblastoma samples by quantitative analysis of immunohistochemical staining. We found that infiltrating T cells have a prognostic value greater than, and independent of, the criteria currently used to stage neuroblastoma. A variable in situ structural organization and different concurrent infiltration of T-cell subsets were detected in tumors with various outcomes. Low-risk neuroblastomas were characterized by a higher number of proliferating T cells and a more structured T-cell organization, which was gradually lost in tumors with poor prognosis. We defined an immunoscore based on the presence of CD3+, CD4+ and CD8+ infiltrating T cells that associates with favorable clinical outcome in MYCN-amplified tumors, improving patient survival when combined with the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) status. These findings support the hypothesis that infiltrating T cells influence the behavior of neuroblastoma and might be of clinical importance for the treatment of patients.
Are Medical Students Comfortable with Practicing Physical Examinations on Each Other?

Purpose To assess medical student attitudes toward, and comfort with, taking turns practicing peer physical examinations (PPEs) on fellow classmates. Method A questionnaire with 25 Likert-scaled questions was administered to 164 end-first-year medical students at the University of Minnesota, Minneapolis. Topics assessed included: (1) comfort with various aspects of PPEs; (2) attitudes regarding the professionalism, appropriateness, and perceived value of PPEs; (3) attitudes toward peer breast, genital, and rectal exams; and (4) the effects of age and gender on response. Results Of the 164 students surveyed, 124 (76%) responded. Almost all (98%) agreed that PPEs are appropriate, valuable, and a comfortable experience. Fewer students were comfortable with performing inguinal examinations and conducting PPEs with students of the opposite gender. Twelve percent of the students expressed difficulty in setting limits with peers, and 48% felt exposed when undressed as an examination model in front of a group of peers. The majority of students were opposed to peer breast, genital, and rectal examinations. Some statistically significant gender differences and age/gender interactions were observed. Conclusion Results suggest that this sample of medical students was very comfortable with PPEs and willing to participate in PPEs, although a few students were uncomfortable with these examinations. No extensive curricular change appears warranted, though steps can be taken to maximize overall student comfort and to accommodate the few students who do not favor PPEs.
Transcriptional regulation by Fos and Jun in vitro: interaction among multiple activator and regulatory domains

The proteins encoded by the proto-oncogenes c-fos and c-jun (Fos and Jun, respectively) form a heterodimeric complex that regulates transcription by interacting with the DNA-regulatory element known as the activator protein 1 (AP-1) binding site. Fos and Jun are members of a family of related transcription factors that dimerize via a leucine zipper structure and interact with DNA through a bipartite domain formed between regions of each protein that are rich in basic amino acids. Here we have defined other domains in the Fos-Jun heterodimer that contribute to transcriptional function in vitro. Although DNA-binding specificity is mediated by the leucine zipper and basic regions, Jun also contains a proline- and glutamine-rich region that functions as an ancillary DNA-binding domain but does not contribute directly to transcriptional activation. Transcriptional stimulation in vitro was associated with two regions in Fos and a single N-terminal activation domain in Jun. These activator regions were capable of operating independently; however, they appear to function cooperatively in the heterodimeric complex. The activity of these domains was modulated by inhibitory regions in Fos and Jun that repressed transcription in vitro. In the context of the heterodimer, the Jun activation domain was the major contributor to transcriptional stimulation and the inhibitory regions in Fos were the major contributors to transcriptional repression in vitro. Potentially, the inhibitory domains could serve a regulatory function in vivo. Thus, transcriptional regulation by the Fos-Jun heterodimer results from a complex integration of multiple activator and regulatory domains.
Biomechanical Responses to Repeated Stretches in Human Hamstring Muscle In Vivo

To examine stiffness, energy, and passive torque in the dynamic and static phases of a stretch maneuver in the human hamstring muscle in vivo we used a test- retest protocol and a repeated stretches protocol. Re sistance to stretch was defined as passive torque (in newton-meters) offered by the hamstring muscle group during passive knee extension as measured using an isokinetic dynamometer with a modified thigh pad. In 13 uninjured subjects, the knee was passively ex tended to a predetermined final position (0.0875 rad/ sec, dynamic phase) where it remained stationary for 90 seconds (static phase). The test-retest protocol in cluded two tests administered 1 hour apart. On a sep arate occasion, five consecutive static stretches were administered separated by 30 seconds and followed by a sixth stretch 1 hour later. For the test-retest phase, stiffness and energy in the dynamic phase and passive torque in the static phase did not differ and yielded correlations of r = 0.91 to 0.99. During the static phase, passive torque declined in both tests (P < 0.0001). For the repeated stretches, decreases were observed for energy (P < 0.01) and stiffness (P < 0.05) in the dynamic phase and for passive torque (P < 0.0001) in the static phase. However, the decline in the variables returned to baseline within 1 hour. The data show that the method employed is a useful tool for measuring biomechanical variables during a stretch maneuver. This may provide a more detailed method to examine skeletal muscle flexibility.
Cokeromyces recurvatus, a mucoraceous zygomycete rarely isolated in clinical laboratories

Cokeromyces recurvatus Poitras was isolated from an endocervical specimen obtained from a 37-year-old, insulin-dependent diabetic. The patient's diabetic condition had been well controlled for 10 years, and she had no other known medical problem. This is only the fourth time that this zygomycete has been recovered from a human source. While there was no evidence of tissue invasion in the present patient, the observation of fungus-like structures in two separate Papanicolaou-stained cervical smears prepared 1 year apart suggests that C. recurvatus may be capable of colonizing endocervical tissue.
Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets.

RATIONALE The pathophysiologic causes of obstructive sleep apnea (OSA) likely vary among patients but have not been well characterized. OBJECTIVES To define carefully the proportion of key anatomic and nonanatomic contributions in a relatively large cohort of patients with OSA and control subjects to identify pathophysiologic targets for future novel therapies for OSA. METHODS Seventy-five men and women with and without OSA aged 20-65 years were studied on three separate nights. Initially, the apnea-hypopnea index was determined by polysomnography followed by determination of anatomic (passive critical closing pressure of the upper airway [Pcrit]) and nonanatomic (genioglossus muscle responsiveness, arousal threshold, and respiratory control stability; loop gain) contributions to OSA. MEASUREMENTS AND MAIN RESULTS Pathophysiologic traits varied substantially among participants. A total of 36% of patients with OSA had minimal genioglossus muscle responsiveness during sleep, 37% had a low arousal threshold, and 36% had high loop gain. A total of 28% had multiple nonanatomic features. Although overall the upper airway was more collapsible in patients with OSA (Pcrit, 0.3 [-1.5 to 1.9] vs. -6.2 [-12.4 to -3.6] cm H2O; P <0.01), 19% had a relatively noncollapsible upper airway similar to many of the control subjects (Pcrit, -2 to -5 cm H2O). In these patients, loop gain was almost twice as high as patients with a Pcrit greater than -2 cm H2O (-5.9 [-8.8 to -4.5] vs. -3.2 [-4.8 to -2.4] dimensionless; P = 0.01). A three-point scale for weighting the relative contribution of the traits is proposed. It suggests that nonanatomic features play an important role in 56% of patients with OSA. CONCLUSIONS This study confirms that OSA is a heterogeneous disorder. Although Pcrit-anatomy is an important determinant, abnormalities in nonanatomic traits are also present in most patients with OSA.
The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease

Background and design The recent introduction of sensitive markers of myocardial injury is likely to affect the epidemiology of coronary heart disease (CHD). The American Heart Association together with other societies and research agencies have recently published a new definition on acute CHD to improve consistency in epidemiological and clinical studies (referred here as the ‘2003 definition'). Methods In this study we compare the data on CHD events in the Finnish National Hospital Discharge Register (HDR) and the Causes of Death Register (CDR) with the population-based myocardial infarction (MI) register, FINMONICA/FINAMI. The FINMONICA/FINAMI events were classified according to the 2003 definition. The relevant International Classification of Diseases (ICD) codes from the HDR and CDR were used. Results Using the 2003 definition as the reference, the overall sensitivity of the ICD codes for MI in the combined HDR and CDR was 83% and the positive predictive value (PPV) was 90%. When the ICD codes for unstable angina were added to the analyses, the sensitivity improved to 85% and the PPV declined to 83%. In the age group 35–74 the sensitivity of the MI codes improved over time, in men from 64% in 1988–1992 to 81% in 1998–2002, and in women from 61 to 78%, respectively. The oldest age group, 75 years or older, had sensitivity and PPV values comparable to those of the younger. Conclusion Diagnoses of fatal and non-fatal CHD events in the Finnish HDR and Causes of Death register were reasonably valid indicators for hard CHD events when compared with the FINMONICA/FINAMI register data. Eur J Cardiovasc Prev Rehabil 12: 132–137 © 2005 The European Society of Cardiology
Year-round spatiotemporal distribution of harbour porpoises within and around the Maryland wind energy area

Offshore windfarms provide renewable energy, but activities during the construction phase can affect marine mammals. To understand how the construction of an offshore windfarm in the Maryland Wind Energy Area (WEA) off Maryland, USA, might impact harbour porpoises (Phocoena phocoena), it is essential to determine their poorly understood year-round distribution. Although habitat-based models can help predict the occurrence of species in areas with limited or no sampling, they require validation to determine the accuracy of the predictions. Incorporating more than 18 months of harbour porpoise detection data from passive acoustic monitoring, generalized auto-regressive moving average and generalized additive models were used to investigate harbour porpoise occurrence within and around the Maryland WEA in relation to temporal and environmental variables. Acoustic detection metrics were compared to habitat-based density estimates derived from aerial and boat-based sightings to validate the model predictions. Harbour porpoises occurred significantly more frequently during January to May, and foraged significantly more often in the evenings to early mornings at sites within and outside the Maryland WEA. Harbour porpoise occurrence peaked at sea surface temperatures of 5°C and chlorophyll a concentrations of 4.5 to 7.4 mg m-3. The acoustic detections were significantly correlated with the predicted densities, except at the most inshore site. This study provides insight into previously unknown fine-scale spatial and temporal patterns in distribution of harbour porpoises offshore of Maryland. The results can be used to help inform future monitoring and mitigate the impacts of windfarm construction and other human activities.
Hypophosphatemia in Enterally Fed Patients in the Surgical Intensive Care Unit: Common but Unrelated to Timing of Initiation or Aggressiveness of Nutrition Delivery

Introduction: Hypophosphatemia has been associated with refeeding malnourished patients, but its clinical significance is unclear. We investigated the incidence of refeeding hypophosphatemia (RH) in the surgical intensive care unit (SICU) and its association with early enteral nutrition (EN) administration and clinical outcomes. Methods: We performed a retrospective review of a 2-year database of patients receiving EN in the SICU. RH was defined as a post-EN phosphorus (PHOS) level decrement of >0.5 mg/dL to a nadir <2.0 mg/dL within 8 days from EN initiation. We investigated the risk factors for RH and examined its association with clinical outcomes using multivariable regression analyses. Results: In total, 213 patients comprised our analytic cohort. Eighty-three of 213 (39%) individuals experienced RH and 43 of 130 (33%) of the remaining patients experienced non-RH hypophosphatemia (nadir PHOS level <2.0 mg/dL). Overall, there was a total 59% incidence of hypophosphatemia of any cause (N = 126). Nutrition parameters did not differ between groups; most patients were initiated on EN within 48 hours of SICU admission, and timing of EN initiation was not a significant predictor for the development of RH. The median hospital length of stay (LOS) was 21 and 24 days for those with and without RH, respectively (P = .79); RH remained a nonsignificant predictor for hospital LOS in the multivariable analysis. Conclusions: RH is common in the SICU but is not related to timing or amount of EN. Hypophosphatemia is also common in the critically ill, but regardless of etiology, it was not found to be a predictor of worse clinical outcomes.
Signal pre-distortion and bandwidth requirements for Sequential Power Amplifiers

This paper presents a linearization approach for Sequential Power Amplifiers (SPAs) through pre-distortion. The signal characteristics and pre-distortion waveforms for the main and peaking amplifiers are derived mathematically. The pre-distortion approach is validated experimentally by measurement of the reconstructed signals. It is found that the signal characteristics results in an at least three fold bandwidth of the signal. Rules for bandwidth restriction in the individual PA channels are given and the effect of a reduced bandwidth on the average efficiency of SPAs is shown.
Accelerated, Spleen-Based Titration of Variant Creutzfeldt-Jakob Disease Infectivity in Transgenic Mice Expressing Human Prion Protein with Sensitivity Comparable to That of Survival Time Bioassay

ABSTRACT The dietary exposure of the human population to the prions responsible for the bovine spongiform encephalopathy (BSE) epizooty has led to the emergence of variant Creutzfeldt-Jakob disease (vCJD). This fatal, untreatable neurodegenerative disorder is a growing public health concern because the prevalence of the infection seems much greater than the disease incidence and because secondary transmission of vCJD by blood transfusion or use of blood products has occurred. A current limitation in variant CJD risk assessment is the lack of quantitative information on the infectivity of contaminated tissues. To address this limitation, we tested the potential of a transgenic mouse line overexpressing human prion protein (PrP), which was previously reported to propagate vCJD prions. Endpoint titration of vCJD infectivity in different tissues was evaluated by two different methods: (i) the “classical” bioassay, based on the appearance of clinical symptoms and the detection of pathological prion protein in tissues of the inoculated mouse, and (ii) a shortened bioassay based on the detection of the protein in the mouse spleen at defined time points. The two methods proved equally sensitive in quantifying infectivity, even after very-low-dose inoculation of infected material, but the time schedule was shortened from ∼2.5 years to ∼1 year with the spleen bioassay. Compared to the “gold-standard” RIII model routinely used for endpoint titration of vCJD/BSE prions, either method improved the sensitivity by >2 orders of magnitude and allowed reevaluating the infectious titer of spleen from a vCJD individual at disease end stage to >1,000-fold-higher values. IMPORTANCE Here, we provide key reevaluation of the infectious titer of variant CJD brain and spleen tissues. The highly sensitive, accelerated spleen-based assay should thus constitute a key advance for variant CJD epidemiological and risk assessment purposes and should greatly facilitate future titration studies, including, for example, those aimed at validating decontamination procedures. The overlooked notion that the lymphoid tissue exhibits a higher capacity than the brain to replicate prions even after low-dose infection raises new questions about the molecular and/or cellular determinant(s) involved, a key issue regarding potent silent carriers of variant CJD in the lymphoid tissue.
El desarrollo del comercio electrónico: el efecto de la ambientación en entornos virtuales

La aplicacion de las nuevas tecnologias de la informacion y de la comunicacion (TIC) definen una nueva forma de relacion entre el comerciante y el consumidor, configurando entornos de interaccion virtuales en los que se desarrollan las relaciones de intercambio. En este articulo se plantea una serie de reflexiones relativas al marco de referencia en que se situa este entorno de interaccion virtual y sus principales componentes e influencias. Partiendo de las investigaciones sobre ambiente en entornos fisicos, se analizan los componentes del ambiente o atmosfera virtual y su influencia sobre aspectos cognitivos, afectivos y comportamentales del proceso de decision de los consumidores
Cross-cultural differences for adaptive strategies of robots in public spaces

Robots deployed in public spaces must necessarily deal with situations that demand them to engage humans in a socially and culturally appropriate manner. However, social environments are often complex and ambiguous: many queries to the robot are collaborative (e.g. a family), and in case of conflicting queries, social robots need to participate in value decisions and negotiating multi-party interactions. Given the strong influence of the people's demographic information and social schema among people, such as relationships and hierarchies, the focus of this research is to examine whether and how people exhibit socio-psychological effects with a shared robot deployed at international events or spaces (e.g. airports). With the aim to investigate who robots should adapt to (children or adults) in multi-party situations within human-robot interactions in public spaces and whether this adaptation can be influenced by culture, this paper presents a cross-cultural study conducted online. The results include a number of interesting findings based on people's relationship with a child and their parental status. In addition, a number of cross-cultural differences were identified in respondents' attitude towards robot's multi-party adaptation in various public settings.
Wide-Angle X-Ray Scattering and Solid-State Nuclear Magnetic Resonance Data Combined to Test Models for Cellulose Microfibrils in Mung Bean Cell Walls1

Peak shapes in an x-ray diffractogram of primary cell walls indicated 18-chain microfibrils with mixed cross-sectional shapes and occasional twinning, consistent with a cellulose-synthesizing complex assembled from six CESA trimers. A synchrotron wide-angle x-ray scattering study of mung bean (Vigna radiata) primary cell walls was combined with published solid-state nuclear magnetic resonance data to test models for packing of (1→4)-β-glucan chains in cellulose microfibrils. Computer-simulated peak shapes, calculated for 36-chain microfibrils with perfect order or uncorrelated disorder, were sharper than those in the experimental diffractogram. Introducing correlated disorder into the models broaden the simulated peaks but only when the disorder was increased to unrealistic magnitudes. Computer-simulated diffractograms, calculated for 24- and 18-chain models, showed good fits to experimental data. Particularly good fits to both x-ray and nuclear magnetic resonance data were obtained for collections of 18-chain models with mixed cross-sectional shapes and occasional twinning. Synthesis of 18-chain microfibrils is consistent with a model for cellulose-synthesizing complexes in which three cellulose synthase polypeptides form a particle and six particles form a rosette.
Risk of atrial fibrillation in diabetes mellitus: A nationwide cohort study

Aim Diabetes has been associated with atrial fibrillation but the current evidence is conflicting. In particular knowledge regarding young diabetes patients and the risk of developing atrial fibrillation is sparse. The aim of our study was to investigate the risk of atrial fibrillation in patients with diabetes compared to the background population in Denmark. Methods and results Through Danish nationwide registries we included persons above 18 years of age and without prior atrial fibrillation and/or diabetes from 1996 to 2012. The study cohort was divided into a background population without diabetes and a diabetes group. The absolute risk of developing atrial fibrillation was calculated and Poisson regression models adjusted for sex, age and comorbidities were used to calculate incidence rate ratios of atrial fibrillation. The total study cohort included 5,081,087 persons, 4,827,713 (95%) in the background population and 253,374 (5%) in the diabetes group. Incidence rates of atrial fibrillation per 1000 person years were stratified in four age groups from 18 to 39, 40 to 64, 65 to 74 and 75 to 100 years giving incidence rates (95% confidence intervals) of 0.02 (0.02–0.02), 0.99 (0.98–1.01), 8.89 (8.81–8.98) and 20.0 (19.9–20.2) in the background population and 0.13 (0.09–0.20), 2.10 (2.00–2.20), 8.41 (8.10–8.74) and 20.1 (19.4–20.8) in the diabetes group, respectively. The adjusted incidence rate ratios in the diabetes group with the background population as reference were 2.34 (1.52–3.60), 1.52 (1.47–1.56), 1.20 (1.18–1.23) and 0.99 (0.97–1.01) in the four age groups, respectively. Conclusion Diabetes is an independent risk factor for developing atrial fibrillation/flutter, most pronounced in young diabetes patients. Routine screening for atrial fibrillation/flutter in diabetes patients might be beneficial and have therapeutic implications, especially in younger diabetes patients. Translational perspective Diabetes increases the risk of developing atrial fibrillation and especially young diabetes patients have a high relative risk. Increased focus on detecting atrial fibrillation in young diabetes patients might prove beneficial, and both anticoagulation treatment and anti-arrhythmic treatment strategies should be considered as soon as possible.