Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Metapneumovirus and Chronic Obstructive Pulmonary Disease

To the Editor: We read with interest an article, Human Metapneumovirus Detection in Patients with Severe Acute Respiratory Syndrome, in your journal (1). In the report, Chan et al., did not question that SARS-CoV is the etiologic agent of severe acute respiratory syndrome (SARS); however, human metapneumovirus (HMPV) was found in 25 (52%) of 48 probable SARS cases that were investigated, and SARS-CoV was detected in 11 (22.9%) of them. Another recent article reported HMPV in five of six patients in whom SARS was diagnosed in Canada (2); four of the six were coinfected with SARS-CoV. The prevalence of HMPV infection in SARS patients validates the interest in HMPV’s possible role in SARS etiology. From November 2001 to February 2002, 1 year before the first cases of SARS appeared, we tested the sputum of patients >64 years of age who had experienced exacerbation of chronic obstructive pulmonary disease, for HMPV. Investigations were conducted on 90 episodes in 89 elderly patients, 62 males and 27 females, in which we found no other microorganisms that could have been related to the exacerbation of chronic obstructive pulmonary disease. RNA was extracted from the sputum samples and amplified by reverse transcriptase–polymerase chain reaction (RT-PCR) to detect HMPV as previously described (3). Results of bacterial culture and culture and PCR to detect respiratory syncytial virus and influenza virus types A and B were negative, whereas HMPV was found in the sputum of five (three men and two women) immunocompetent patients, 77–87 years of age. The prevalence of HMPV infection was 5.5%, similar to the percentage obtained by Chan et al., when HMPV RT-PCR was conducted on the respiratory samples. Fever (temperature >38°C) was not present in any of the five patients infected with HMPV. Two patients were admitted to a hospital. Both patients had bronchial infection and cough with bronchospasm and moderate respiratory insufficiency (oxygen saturation rate: 90.3% and 88%, respectively) for >1 week. Sputum samples from an additional 70 elderly patients with exacerbation of chronic obstructive pulmonary disease with positive detection for influenza virus (n = 50) or respiratory syncytial virus (n = 20) were tested for HMPV infection. None of the samples showed HMPV infection. Sequence analysis of amplicons from the five samples positive for HMPV infection showed >95% similarity with HMPV sequences found in other parts of the world (4,5). Additional studies should be conducted to confirm that HMPV exacerbates chronic obstructive pulmonary disease. However, by performing an RT-PCR directly on the sample instead of the more efficient RT-PCR after viral culture used by Chan et al., these findings suggest that HMPV is a frequently undetected agent in acute respiratory infection unrelated to SARS. The important questions are whether HMPV and SARS-CoV coinfection would facilitate more severe SARS, or whether HMPV infection would facilitate a more efficient transmission of SARS-CoV.
Neurones in the ventrolateral pons are required for post‐hypoxic frequency decline in rats.

1. The breathing pattern following acute hypoxia (arterial O2 pressure (Pa,O2), 27.4 +/‐ 7.7 mmHg) was measured in intact, anaesthetized and spontaneously breathing adult rats (n = 4) and in anaesthetized, vagotomized, paralysed and ventilated animals (n = 14). Measurements were made both before and after bilateral lesions or chemical inactivation of neurones in the lateral pons. Respiratory motor activity was recorded as an index of the respiratory cycle. We tested the hypothesis that the ventrolateral pons is required for expression of post‐hypoxic frequency decline, defined as a decrease in respiratory frequency below steady‐state baseline levels following brief exposures to hypoxia. 2. We identified an area in the ventrolateral pons where brief (1 ms) low current (< or = 20 microA) pulses evoked a short‐latency inhibitor of phrenic nerve activity. At this site, bilateral electrical or chemical lesions (n = 3) were performed, or neural activity was inhibited by focal injections of 10 mM muscimol (n = 9). In six control animals, neural activity was inhibited by muscimol injections into the lateral pons, dorsal to the target site. 3. Prior to pontine intervention, respiratory frequency decreased below baseline levels following 20‐110 s of 8% O2. The decrease in frequency resulted from a prolongation of expiration (up to 276%), which gradually returned to baseline levels (tau = 45 s). 4. Following lesions or inhibition of neural activity in the ventrolateral pons, baseline inspiratory (TI) and expiratory (TE) durations were altered, albeit minimally, in the animals with intact vagus nerves. Expiratory duration following hypoxia was not different from baseline levels either in vagotomized (P = 0.18) or intact (P > 0.05) animals. In contrast, injections of muscimol at more dorsal sites did not alter the decrease in frequency normally seen following hypoxia. 5. Histological examination revealed that effective lesion or injection sites were within the lateral pontine tegmental field and included portions of the noradrenergic A5 cell group. 6. We conclude that the mechanism responsible for post‐hypoxic frequency decline involves an active neural process that depends on the integrity of the ventrolateral pons.
Influence of the model for random birefringence on the differential group delay of periodically spun fibers

We consider the two Wai-Menyuk models of birefringence in periodically spun fibers, and we show that the differential group delay differs significantly for the two models when the spin period approaches or exceeds the fiber beat length. When the fiber correlation length is large, we explain this difference quantitatively, and we explain it qualitatively for any fiber correlation length.
Communication with the seriously ill: physicians' attitudes in Saudi Arabia.

OBJECTIVES: To study some ethical problems created by accession of a previously nomadic and traditional society to modern invasive medicine, by assessment of physicians' attitudes towards sharing information and decision-making with patients in the setting of a serious illness. DESIGN: Self-completion questionnaire administered in 1993. SETTING: Riyadh, Jeddah, and Buraidah, three of the largest cities in Saudi Arabia. SURVEY SAMPLE: Senior and junior physicians from departments of internal medicine and critical care in six hospitals in the above cities. RESULTS: A total of 249 physicians participated in the study. Less than half (47%) indicated they provided information on diagnosis and prognosis of serious illnesses all the time. Physicians who were more senior and those who spoke Arabic fared better than other groups. The majority (75%) preferred to discuss information with close relatives rather than patients, even when the patients were mentally competent. Most of the physicians (72%) felt patients had the right to refuse a specific treatment modality, and 68% denied patients the right to demand such a treatment if considered futile. Further analysis showed that physicians' attitudes varied along a spectrum from passive (25%) to paternalistic (21%) with the largest group (47%) in a balanced position. CONCLUSIONS: In traditional societies where physicians are regarded as figures of authority and family ties are important, there is a considerable shift of access to information and decision-making from patients to their physicians and relatives in a manner that threatens patients' autonomy. Ethical principles, wider availability of invasive medical technology and a rise in public awareness dictate an attitude change.
Mode of delivery and development of atopic disease during the first 2 years of life

It has been hypothesized that cesarean delivery might have an impact on the development of atopic diseases because of its gut flora modulating properties. In the present study, we analysed the association between cesarean delivery and atopic diseases using data of 2500 infants enrolled in the LISA‐Study, a German prospective multicenter birth cohort study. Data on symptoms and physician‐diagnosed atopic diseases were gathered by questionnaires shortly after birth and at infant's age 6, 12, 18, and 24 months. In addition, sensitization to common food and inhalant allergens was assessed by measuring specific immunoglobulin E (IgE) using the CAP‐RAST FEIA method at the age of 2 yr. Confounder‐adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated by multiple logistic regression. We found a positive association between cesarean delivery and occurrence of at least one episode of wheezing [aOR 1.31 (95% CI 1.02–1.68)] and of recurrent wheezing [1.41 (1.02–1.96)] during the first 2 yr of life. Furthermore, effect estimates for allergic sensitization defined as at least one specific IgE ≥0.70 kU/l against any allergen [1.48 (0.98–2.24)], against food allergens [1.64 (1.03–2.63)], and against inhalant allergens [1.75 (0.98–3.12)] were increased. Symptoms of atopic dermatitis [1.21 (0.92–1.59)], physician‐diagnosed atopic dermatitis [1.04 (0.79–1.39)], and symptoms of allergic rhinoconjunctivitis [1.40 (0.80–2.44)] were only marginally increased in children delivered by cesarean section. In conclusion, our results suggest that cesarean delivery may be an additional risk factor for wheezing and allergic sensitization at least to food allergens up to the age of 2 yr. This should be considered when cesarean section is done for other than medical reasons.
Training Pediatric Residents and Pediatricians About Adolescent Mental Health Problems: A Proof-of-Concept Pilot for a Proposed National Curriculum

ObjectiveThis article presents a DVD-based educational program intended to help pediatric residents and practicing pediatricians recognize and respond to adolescent depression in busy primary care settings.MethodsRepresentatives from pediatrics and adolescent medicine, child and adolescent psychiatry and psychology, and experts in the creation of educational mental health programs met to design a multimedia approach to improving the mental health diagnostic skills among pediatric residents. The authors chose depression as the initial topic because of its relatively high prevalence among children and adolescents, and evidence suggesting that pediatricians may have difficulty diagnosing this disorder in the primary care setting. The authors created a 30-minute DVD program featuring depressed adolescents and experts in child psychiatry and adolescent medicine. After viewing the DVD, residents in the training program, as well as practicing pediatricians, completed a standardized survey to assess the usefulness and attractiveness of this approach to pediatric education.ResultsThe survey results support the potential value of this type of material and the feasibility of similar programs in addressing an array of mental health concerns in pediatric residencies. Participants found the program useful and indicated interest in receiving more educational programs in this format.ConclusionThe authors suggest that the relative ease with which initiatives such as this media-based approach can be implemented make this educational technique appropriate and feasible on a large scale for programs throughout the nation and for a variety of mental health concerns.
Increased Levels of Oxidative Stress Markers, Soluble CD40 Ligand, and Carotid Intima-Media Thickness Reflect Acceleration of Atherosclerosis in Male Patients with Ankylosing Spondylitis in Active Phase and without the Classical Cardiovascular Risk Factors

Objective The primary aim of the study was to assess levels of oxidative stress markers, soluble CD40 ligand (sCD40L), serum pregnancy-associated plasma protein-A (PAPP-A), and placental growth factor (PlGF) as well as carotid intima-media thickness (IMT) in patients with ankylosing spondylitis (AS) with active phase without concomitant classical cardiovascular risk factors. Material and methods The observational study involved 96 male subjects: 48 AS patients and 48 healthy ones, who did not differ significantly regarding age, BMI, comorbid disorders, and distribution of classical cardiovascular risk factors. In both groups, we estimated levels of oxidative stress markers, lipid profile, and inflammation parameters as well as sCD40L, serum PAPP-A, and PlGF. In addition, we estimated carotid IMT in each subject. Results The study showed that markers of oxidative stress, lipid profile, and inflammation, as well as sCD40L, PlGF, and IMT, were significantly higher in the AS group compared to the healthy group. Conclusion Our results demonstrate that ankylosing spondylitis may be associated with increased risk for atherosclerosis.
Particle–Fluid–Structure Interaction for Debris Flow Impact on Flexible Barriers

Flexible barriers are increasingly used for the protection from debris flow in mountainous terrain due to their low cost and environmental impact. However, the development of a numerical tool for the rational design of such structures is still a challenge. In this work, a hybrid computational framework is presented, using a total Lagrangian formulation of the finite element method to represent a flexible barrier. The actions exerted on the structure by a debris flow are obtained from simultaneous simulations of the flow of a fluid‐grain mixture, using two conveniently coupled solvers: the discrete element method governs the motion of the grains, while the free‐surface non‐Newtonian fluid phase is solved using the lattice Boltzmann method. Simulations on realistic geometries show the dependence of the momentum transfer on the barrier on the composition of the debris flow, challenging typical assumptions made during the design process today. In particular, we demonstrate that both grains and fluid contribute in a nonnegligible way to the momentum transfer. Moreover, we show how the flexibility of the barrier reduces its vulnerability to structural collapse, and how the stress is distributed on its fabric, highlighting potential weak points.
The Cell Adhesion Molecule Necl-4/CADM4 Serves as a Novel Regulator for Contact Inhibition of Cell Movement and Proliferation

Contact inhibition of cell movement and proliferation is critical for proper organogenesis and tissue remodeling. We show here a novel regulatory mechanism for this contact inhibition using cultured vascular endothelial cells. When the cells were confluently cultured, Necl-4 was up-regulated and localized at cell–cell contact sites where it cis-interacted with the vascular endothelial growth factor (VEGF) receptor. This interaction inhibited the tyrosine-phosphorylation of the VEGF receptor through protein-tyrosine phosphatase, non-receptor type 13 (PTPN13), eventually reducing cell movement and proliferation. When the cells were sparsely cultured, Necl-4 was down-regulated but accumulated at leading edges where it inhibited the activation of Rho-associated protein kinase through PTPN13, eventually facilitating the VEGF-induced activation of Rac1 and enhancing cell movement. Necl-4 further facilitated the activation of extracellular signal-regulated kinase 1/2, eventually enhancing cell proliferation. Thus, Necl-4 serves as a novel regulator for contact inhibition of cell movement and proliferation cooperatively with the VEGF receptor and PTPN13.
Planar polarity in the Drosophila eye: a multifaceted view of signaling specificity and cross‐talk

Functional tissues not only polarize their epithelia in the apical–basolateral axis, but also often display a polarity within the plane of the epithelium. In Drosophila, all adult structures are derived from epithelia called imaginal discs and display planar polarization; the eye and the wing are particularly well suited for analysis. Studies of their polarization have identified several conserved genes that regulate both nuclear signaling and cytoskeletal architecture. In particular, the Frizzled (Fz) receptor has been identified as a key component of polarity establishment in all tissues. The Fz signaling pathway and associated events are beginning to be unraveled, shedding light on a novel Wnt/Fz signaling cascade.
Efficacy of Ceftriaxone and Gentamicin Given Once a Day by Using Human-Like Pharmacokinetics in Treatment of Experimental Staphylococcal Endocarditis

ABSTRACT We compared the efficacy of ceftriaxone combined with gentamicin, both given once a day, with that of cloxacillin given every 4 h plus gentamicin given once a day or in three daily doses (t.i.d.) for the treatment of experimental methicillin-susceptible staphylococcal endocarditis. The antibiotics were administered by using human-like (H-L) pharmacokinetics that simulated the profiles of these drugs in human serum. Animals with catheter-induced endocarditis were infected intravenously with 105 CFU of Staphylococcus aureus S5 (MICs and minimal bactericidal concentrations of cloxacillin, ceftriaxone, and gentamicin, 0.5 and 2 μg/ml, 4 and 8 μg/ml, and 0.5 and 1 μg/ml, respectively). The animals were then treated for 24 h with cloxacillin at a dose of 2 g that simulated H-L pharmacokinetics (H-L 2 g) every 4 h alone or combined with gentamicin (administered at doses of H-L 1 mg/kg of body weight every 8 h or H-L 4.5 mg/kg every 24 h) or with ceftriaxone at H-L 2 g every 24 h alone or combined with gentamicin (administered at doses of H-L 1 mg/kg every 8 h or H-L 4.5 mg/kg every 24 h). The results of therapy for experimental endocarditis due to the S5 strain showed that (i) cloxacillin alone is more effective than ceftriaxone alone in reducing the bacterial load (P < 0.01), (ii) the combination of cloxacillin or ceftriaxone with gentamicin is more effective than each of these drugs alone (P < 0.01), and (iii) Ceftriaxone H-L plus gentamicin H-L 4.5 mg/kg, both administered every 24 h, showed efficacy similar to that of the “gold standard,” cloxacillin H-L plus gentamicin H-L 1 mg/kg t.i. d. (P > 0.05). An increase in the interval of administration of gentamicin to once daily resulted in a reduction in the numbers of bacteria in the vegetations equivalent to that achieved with the recommended regimen of cloxacillin plus gentamicin t.i. d. in the treatment of experimental endocarditis due to methicillin-susceptible S. aureus. Ceftriaxone plus gentamicin, both administered once a day, may be useful for home-based therapy for selected cases of staphylococcal endocarditis.
Experimental evolution of field populations of Daphnia magna in response to parasite treatment

Although there is little doubt that hosts evolve to reduce parasite damage, little is known about the evolutionary time scale on which host populations may adapt under natural conditions. Here we study the effects of selection by the microsporidian parasite Octosporea bayeri on populations of Daphnia magna. In a field study, we infected replicated populations of D. magna with the parasite, leaving control populations uninfected. After two summer seasons of experimental evolution (about 15 generations), the genetic composition of infected host populations differed significantly from the control populations. Experiments revealed that hosts from the populations that had evolved with the parasite had lower mortality on exposure to parasite spores and a higher competitive ability than hosts that had evolved without the parasite. In contrast, the susceptibility of the two treatment groups to another parasite, the bacterium Pasteuria ramosa, which was not present during experimental evolution of the populations, did not differ. Fitness assays in the absence of parasites revealed a higher fitness for the control populations, but only under low population density with high resource availability. Overall, our results show that, under natural conditions, Daphnia populations are able to adapt rapidly to the prevailing conditions and that this evolutionary change is specific to the environment.
Necessary Contributions of Human Frontal Lobe Subregions to Reward Learning in a Dynamic, Multidimensional Environment

Real-world decisions are typically made between options that vary along multiple dimensions, requiring prioritization of the important dimensions to support optimal choice. Learning in this setting depends on attributing decision outcomes to the dimensions with predictive relevance rather than to dimensions that are irrelevant and nonpredictive. This attribution problem is computationally challenging, and likely requires an interplay between selective attention and reward learning. Both these processes have been separately linked to the prefrontal cortex, but little is known about how they combine to support learning the reward value of multidimensional stimuli. Here, we examined the necessary contributions of frontal lobe subregions in attributing feedback to relevant and irrelevant dimensions on a trial-by-trial basis in humans. Patients with focal frontal lobe damage completed a demanding reward learning task where options varied on three dimensions, only one of which predicted reward. Participants with left lateral frontal lobe damage attributed rewards to irrelevant dimensions, rather than the relevant dimension. Damage to the ventromedial frontal lobe also impaired learning about the relevant dimension, but did not increase reward attribution to irrelevant dimensions. The results argue for distinct roles for these two regions in learning the value of multidimensional decision options under dynamic conditions, with the lateral frontal lobe required for selecting the relevant dimension to associate with reward, and the ventromedial frontal lobe required to learn the reward association itself. SIGNIFICANCE STATEMENT The real world is complex and multidimensional; how do we attribute rewards to predictive features when surrounded by competing cues? Here, we tested the critical involvement of human frontal lobe subregions in a probabilistic, multidimensional learning environment, asking whether focal lesions affected trial-by-trial attribution of feedback to relevant and irrelevant dimensions. The left lateral frontal lobe was required for filtering option dimensions to allow appropriate feedback attribution, while the ventromedial frontal lobe was necessary for learning the value of features in the relevant dimension. These findings argue that selective attention and associative learning processes mediated by anatomically distinct frontal lobe subregions are both critical for adaptive choice in more complex, ecologically valid settings.
Evidence for the Correcting-Mechanism Explanation of the Kanizsa Amodal Shrinkage

An object phenomenally shrinks in its horizontal dimension when shown on a 2-D plane as if the central portion of the object were partially occluded by another vertical one in 3-D space (the Kanizsa amodal shrinkage). We examined the predictions of the correcting-mechanism hypothesis proposed by Ohtsuka and Ono (2002, Proceedings of SPIE 4864 167 – 174), which states that an inappropriate operation of the mechanism that corrects a phenomenal increase in monocularly visible areas accompanied by a stereoscopic occluder gives rise to the illusion. In this study we measured the perceived width (or height in experiment 3) of a square seen behind a rectangle, while controlling other factors which potentially influence the illusion, such as the division of space or depth stratification. The results of five experiments showed that (a) the perceived width was not influenced when the occluder had a relatively large binocular disparity, but was underestimated when the occluder did not have disparity, and (b) the shrinkage diminished when the foreground rectangle was transparent, was horizontally oriented, or contained no pictorial occlusion cues. These results support the hypothesis that the correcting mechanism, triggered by pictorial occlusion cues, contributes to the Kanizsa shrinkage.