Miracle-dz/UniFAR-FTUs huggingface dataset:
Interleukin-4 Diminishes CD8+ Respiratory Syncytial Virus-Specific Cytotoxic T-Lymphocyte Activity In Vivo

ABSTRACT Although interleukin-4 (IL-4) has been implicated in respiratory syncytial virus (RSV)-enhanced disease, the mechanism by which it modulates immune responses to primary RSV infection remains unclear. We have developed a system to investigate the effect of IL-4 on RSV epitope-specific cytotoxic T-lymphocyte (CTL) effector function in vivo, using an H-2Kd -restricted RSV M2 epitope. BALB/c mice were infected with recombinant vaccinia virus (rVV) constructed to express RSV M2 protein (vvM2) alone or coexpress M2 and IL-4 (vvM2/IL-4). Splenocytes were assessed for M2-specific CTL activity in a direct 51Cr release assay and intracellular gamma interferon (IFN-γ) production by fluorescence-activated cell sorting analysis. Mice infected with vvM2/IL-4 had less M2-specific primary CTL activity than those infected with vvM2. M2-specific CTL frequency, as measured by M2 peptide-induced intracellular IFN-γ production, was diminished in the vvM2/IL-4 group, partially accounting for the reduction of CTL activity. Mice immunized with either construct were challenged intravenously with RSV 4 weeks postimmunization, and direct CTL were measured. These results demonstrate that local expression of IL-4, at the time of antigen presentation, diminishes the cytolytic activity of primary and memory CD8+ RSV-specific CTL responses in vivo.
Conscious updating is a rhythmic process

As the visual world changes, its representation in our consciousness must be constantly updated. Given that the external changes are continuous, it appears plausible that conscious updating is continuous as well. Alternatively, this updating could be periodic, if, for example, its implementation at the neural level relies on oscillatory activity. The flash-lag illusion, where a briefly presented flash in the vicinity of a moving object is misperceived to lag behind the moving object, is a useful tool for studying the dynamics of conscious updating. Here, we show that the trial-by-trial variability in updating, measured by the flash-lag effect (FLE), is highly correlated with the phase of spontaneous EEG oscillations in occipital (5–10 Hz) and frontocentral (12–20 Hz) cortices just around the reference event (flash onset). Further, the periodicity in each region independently influences the updating process, suggesting a two-stage periodic mechanism. We conclude that conscious updating is not continuous; rather, it follows a rhythmic pattern.
Consecutive microscopic anatomical characteristics of the lacrimal sac and nasolacrimal duct: cases with or without inflammation.

PURPOSE We examined the consecutive microscopic anatomy of the lacrimal sac and nasolacrimal duct with or without conspicuous inflammation. METHODS We used 18 postmortem lacrimal sacs and nasolacrimal ducts of 12 Japanese subjects (5 males, 7 females, aged 75-98 years at death). The removed mucosal wall was transversely sectioned. The first slice was cut around the internal canalicular punctum, the second slice was at the superior opening of the bony nasolacrimal canal, and the other four were harvested from the nasolacrimal duct. All specimens were dehydrated and embedded in paraffin, cut into 7-μm thick sections, and stained with Masson's trichrome. RESULTS The lumen was larger in the lacrimal sac than in the nasolacrimal duct. The lacrimal sac wall was less developed than the nasolacrimal duct wall. All specimens but two showed a narrowed area in the nasolacrimal duct. Specimens without conspicuous inflammation showed some subepithelial inflammatory cell infiltration. Goblet cells were smaller in number in the lacrimal sac with an increasing tendency in the inferior direction. Specimens with conspicuous inflammation showed narrowed portions in the nasolacrimal duct, in which severe inflammation and exudate in the lumen was observed. The epithelium was denuded and goblet cells were lost. A specimen with focal inflammation illustrated similar findings in the inflammatory part, but the other parts were similar to the specimens without inflammation. CONCLUSIONS Consecutive microscopic anatomical characteristics of the lacrimal sac and nasolacrimal duct were different from each other. A narrowed part of the nasolacrimal duct lumen is speculated to be a risk for obstruction.
Optimal power allocation and joint source-channel coding for wireless DS-CDMA visual sensor networks using the Nash Bargaining Solution

We consider the problem of resource allocation for a Direct Sequence Code Division Multiple Access (DS-CDMA) wireless visual sensor network (VSN). We use the Nash Bargaining Solution (NBS) from game theory in order to determine the transmission power and source and channel coding rate for each node. The NBS assumes that the nodes negotiate (using the help of a centralized control unit) in order to jointly determine their transmission parameters. The transmission powers are allowed to take continuous values, whereas the source and channel coding rate combination can only assume discrete values. Thus, the resulting optimization problem is a mixed-integer optimization task and is solved using Particle Swarm Optimization (PSO). Experimental results are provided and conclusions are drawn.
Antenatal maternal serum screening for Down's syndrome: results of a demonstration project.

OBJECTIVES--To assess the implementation of antenatal screening for Down's syndrome in practice, using individual risk estimates based on maternal age and the three serum markers: alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin. DESIGN--Demonstration project of Down's syndrome screening; women with a risk estimate at term of 1 in 250 or greater were classified as "screen positive" and offered diagnostic amniocentesis. SETTING--Hospital and community antenatal clinics in four health districts in London. SUBJECTS--12,603 women of all ages with singleton pregnancies seen between February 1989 and the end of May 1991, with follow up of the outcome of pregnancy completed to the end of 1991. MAIN OUTCOME MEASURES--Uptake of screening, detection rate for Down's syndrome, false positive rate, odds of being affected given a positive result, and uptake of amniocentesis in women with positive screening results, together with the costs of the screening programme. RESULTS--The uptake of screening was 74%. The detection rate was 48% (12/25), and the false positive rate was 4.1%, consistent with results expected from previous work based on observational studies. There was a loss of detection due to the selective use of ultrasound scans among women with positive screening results. One affected pregnancy occurred among 205 reclassified as negative; this illustrated the danger of false negatives occurring in this group and lends weight to the view that if an ultrasound estimate of gestational age is used it should be carried out routinely on all women rather than selectively among those with positive results. The estimated cost of avoiding the birth of a baby with Down's syndrome was about 38,000 pounds, substantially less than the lifetime costs of care. CONCLUSION--Antenatal maternal serum screening for Down's syndrome is effective in practice and can be readily integrated into routine antenatal care. It is cost effective and performs better than selection for amniocentesis on the basis of maternal age alone.
Diabetes and Change in Bone Mineral Density at the Hip, Calcaneus, Spine, and Radius in Older Women

Older women with type 2 diabetes mellitus (DM) have higher bone mineral density (BMD) but also have higher rates of fracture compared to those without DM. Limited evidence suggests that DM may also be associated with more rapid bone loss. To determine if bone loss rates differ by DM status in older women, we analyzed BMD data in the Study of Osteoporotic Fractures (SOF) between 1986 and 1998. SOF participants were women ≥65 years at baseline who were recruited from four regions in the U.S. DM was ascertained by self-report. BMD was measured with dual-energy x-ray absorptiometry (DXA) at baseline and at least one follow-up visit at the hip (N = 6624) and calcaneus (N = 6700) and, on a subset of women, at the spine (N = 396) and distal radius (N = 306). Annualized percent change in BMD was compared by DM status, using random effects models. Of 6,867 women with at least one follow-up DXA scan, 409 had DM at baseline. Mean age was 70.8 (SD 4.7) years. Baseline BMD was higher in women with DM at all measured sites. In models adjusted for age and clinic, women with prevalent DM lost bone more rapidly than those without DM at the femoral neck (−0.96 vs. −0.59%/year, p < 0.001), total hip (−0.98 vs. −0.70%/year, p < 0.001), calcaneus (−1.64 vs. −1.40%/year, p = 0.005), and spine (−0.33 vs. +0.33%/year, p = 0.033), but not at the distal radius (−0.97 vs. −0.90%/year, p = 0.91). These findings suggest that despite higher baseline BMD, older women with DM experience more rapid bone loss than those without DM at the hip, spine, and calcaneus, but not the radius. Higher rates of bone loss may partially explain higher fracture rates in older women with DM.
The Contribution of Extramedullary Hematopoiesis to Hepatomegaly in Anemic Hydrops Fetalis: A Study in Alpha-Thalassemia Hydrops Fetalis

Massive hepatomegaly is a common finding in hydrops fetalis (HF) arising from hemoglobinopathies. It has been suggested that extramedullary hematopoiesis, which is markedly increased in response to anemia, plays a principal role in hepatomegaly via sinusoidal obstruction and distortion of the intrahepatic architecture. To test this concept, the authors compared 20 cases of α-thalassemia (hemoglobin Bart, 15 cases; hemoglobin H, 5 cases) with 19 cases of HF arising from other causes and 39 control nonhydrops cases. The mean liver weight in α-thalassemia cases was significantly heavier than in control cases and in hydrops fetalis cases due to other causes (P < 0.01). This was not explainable on the basis of extramedullary hematopoiesis (erythropoiesis or myelopoiesis) or hemosiderin deposition, since cases of HF from other causes, especially related to anemia, showed similar findings to α-thalassemia cases. While these processes no doubt contribute to hepatic weight, the major factor would still be high-output cardiac failure causing hepatic congestion.
Diagnostic concordance of the interview and questionnaire versions of the eating disorder examination.

OBJECTIVE The diagnostic concordance of the interview (EDE) and questionnaire (EDE-Q) versions of the Eating Disorder Examination was examined. METHOD Two-hundred seventeen patients seeking eating disorder treatment completed the EDE and EDE-Q before beginning treatment. Diagnostic algorithms were generated for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision (DSM-IV-TR) and proposed Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria using data first from the EDE and then from the EDE-Q; thus, each participant received four diagnoses. RESULTS The sensitivity of the EDE-Q for individual diagnoses ranged from 27.8% to 84.3% (DSM-IV-TR) and from 36.8% to 80.8% (DSM-5). The specificity of the EDE-Q for individual diagnoses ranged from 71.1% to 98.5% (DSM-IV-TR) and from 77.3% to 98.0% (DSM-5). The overall diagnostic concordance was moderate (κ = .57-.60). DISCUSSION The proposed DSM-5 criteria improved the diagnostic concordance of the two instruments and reduced the prevalence of Eating Disorder Not Otherwise Specified (EDNOS). However, concordance improvement was modest and both instruments still diagnosed most respondents with EDNOS.
Critical review.

This critical review examines the efficacy of communication interventions for improving communication outcomes in adolescents with acquired brain injury. Five articles were included in this review. Studies included four Level 1 designs (i.e., one randomized controlled trial (RCT), one single subject crossover design, one single subject multiple baseline design, one single subject design), and one Level 3 design (i.e., single group preposttest design). Overall, the results of this review revealed suggestive evidence that communication interventions are effective at improving communication outcomes for adolescents with acquired brain injury. Clinical implications and future research recommendations are also discussed.
An intercomparison of WRF-ARW and JMA-NHM performance in prediction of tropical cyclones over the South China Sea in 2008

Hong Kong is located in the sub-tropics region on the southeastern coast of China. During July to September every year, Hong Kong is most likely to be affected by tropical cyclones (TCs). On average, about 30 TCs form in the western North Pacific including the South China Sea every year, and about half of them reach typhoon strength (maximum winds of 118 kilometers per hour or more). Climatologically, Hong Kong is normally affected by around six TCs per year.
Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer

The immune suppressive molecule programmed death-1 (PD-1) is upregulated in activated T lymphocytes and inhibits T-cell function upon binding to its ligands B7-H1 (PD-L1, CD274) and B7-DC (PD-L2, CD273). Substantial experimental data from in vitro cell culture systems and animal models, and more recently from clinical trials, indicate that PD-1/PD-1-ligand interactions are a major mechanism of immune suppression within the tumor microenvironment. Initial clinical studies of antibodies directed against PD-1 and B7-H1 showed both an encouraging safety profile and remarkable antitumor activity in subsets of patients with metastatic disease, including malignancies—such as lung cancer—which were previously thought to be unresponsive to immunotherapy. Preliminary data have suggested a correlation between tumor membrane B7-H1 expression and clinical response to anti-PD-1 antibodies. Several key challenges remain to optimize development of PD-1/B7-H1 pathway blockade, including defining the biologic significance of all potential ligand–receptor interactions in the tumor microenvironment, developing more accurate predictive biomarkers of response, determining the breadth of activity in human malignancies, and developing rational combinations of therapy that address key mechanisms involved in positive and negative regulation of antitumor immune responses. Clin Cancer Res; 19(5); 1021–34. ©2013 AACR.
Cardiac LXRα protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization

Pathological cardiac hypertrophy is characterized by a shift in metabolic substrate utilization from fatty acids to glucose, but the molecular events underlying the metabolic remodeling remain poorly understood. Here, we investigated the role of liver X receptors (LXRs), which are key regulators of glucose and lipid metabolism, in cardiac hypertrophic pathogenesis. Using a transgenic approach in mice, we show that overexpression of LXRα acts to protect the heart against hypertrophy, fibrosis, and dysfunction. Gene expression profiling studies revealed that genes regulating metabolic pathways were differentially expressed in hearts with elevated LXRα. Functionally, LXRα overexpression in isolated cardiomyocytes and murine hearts markedly enhanced the capacity for myocardial glucose uptake following hypertrophic stress. Conversely, this adaptive response was diminished in LXRα‐deficient mice. Transcriptional changes induced by LXRα overexpression promoted energy‐independent utilization of glucose via the hexosamine biosynthesis pathway, resulting in O‐GlcNAc modification of GATA4 and Mef2c and the induction of cytoprotective natriuretic peptide expression. Our results identify LXRα as a key cardiac transcriptional regulator that helps orchestrate an adaptive metabolic response to chronic cardiac stress, and suggest that modulating LXRα may provide a unique opportunity for intervening in myocyte metabolism.
The Use of Mouse Models of Breast Cancer and Quantitative Image Analysis to Evaluate Hormone Receptor Antigenicity after Microwave-assisted Formalin Fixation

Microwave methods of fixation can dramatically shorten fixation times while preserving tissue structure; however, it remains unclear if adequate tissue antigenicity is preserved. To assess and validate antigenicity, robust quantitative methods and animal disease models are needed. We used two mouse mammary models of human breast cancer to evaluate microwave-assisted and standard 24-hr formalin fixation. The mouse models expressed four antigens prognostic for breast cancer outcome: estrogen receptor, progesterone receptor, Ki67, and human epidermal growth factor receptor 2. Using pathologist evaluation and novel methods of quantitative image analysis, we measured and compared the quality of antigen preservation, percentage of positive cells, and line plots of cell intensity. Visual evaluations by pathologists established that the amounts and patterns of staining were similar in tissues fixed by the different methods. The results of the quantitative image analysis provided a fine-grained evaluation, demonstrating that tissue antigenicity is preserved in tissues fixed using microwave methods. Evaluation of the results demonstrated that a 1-hr, 150-W fixation is better than a 45-min, 150-W fixation followed by a 15-min, 650-W fixation. The results demonstrated that microwave-assisted formalin fixation can standardize fixation times to 1 hr and produce immunohistochemistry that is in every way commensurate with longer conventional fixation methods.
Epidemiology of bronchial asthma and chronic rhinitis in schoolchildren of different ethnic origins from two neighboring towns in Israel

Allergic diseases have increased significantly in developed countries for reasons yet to be determined. We studied the epidemiology of bronchial asthma (B.A.) and chronic rhinitis (Ch.R.) among Israeli school children from two neighboring towns, one Jewish (Zichron Yaakov, school population = 585) and the other Arab (Paradis, school population = 658). The children (age range 8–17 years, 567 males, 676 females) shared the same climate and had similar demographic characteristics. They received similar medical care and had the same rates of hospitalization and emergency room visits.
Snow Failure Modes Under Mixed Loading

The mechanical response of snow to mixed‐mode shear and normal loading is the key ingredient for snow avalanche modeling and strongly depends on microstructural characteristics. A discrete element numerical model was developed, which enables the simulation of large‐strain response of snow samples directly described by their full microstructure obtained through X‐ray microtomography. The model offers new insights into the failure mechanism as well as postfailure response of snow in mixed‐mode loading. Three distinct failure modes are identified, depending on the value of applied normal stress. Above a certain threshold normal stress, the failure is characterized by a structural collapse that decomposes the snow sample into a set of cohesionless grains. It is shown that the collapse is a dynamic process, which, once initiated, develops independently of shearing. This behavior was consistently observed for different snow types, including faceted crystals typically composing weak layers.
Self‐care in Medical Education: Effectiveness of Health‐habits Interventions for First‐year Medical Students

Purpose To examine changes in health habits (sleep, alcohol, and exercise) and the effects of an educational intervention promoting self-care on the emotional and academic adjustment of first-year medical students. Method Fifty-four medical students completed questionnaires that assessed various health habits, alcohol use, depression severity, and areas of life satisfaction at the beginning of the semester, at mid-term, and at finals. Approximately half of the students received written feedback or participated in an educational discussion group at mid-term. Results The students demonstrated significant changes in health habits, with increases in alcohol consumption and decreases in exercise and socialization. The changes in health habits were predictive of both emotional and academic adjustment, with students who decreased in positive health habits, particularly socialization, being more depressed at finals. The feedback and educational interventions influenced some sleep and exercise behaviors, but the groups did not differ in overall emotional or academic adjustment. Conclusions First-year medical students show significant changes in health habits as they adjust to medical school. An educational intervention demonstrated promising effects in changing these patterns, but self-care needs to be further elaborated to address the specific challenges associated with acute adjustment as well as with long-term stressors.
A path of perpetual resilience: Exploring the experience of a diabetes-related amputation through grounded theory

Abstract Little research has been done on the experience of diabetes-related amputation. The aim of this study was to allow amputees to describe their experiences of amputation and to generate grounded theory that will lead health professionals towards a more comprehensive understanding of the realities of post-amputation life. Unstructured interviews were conducted with five participants with a diabetes-related amputation living in a rural setting, and their respective carers. The interviews were analysed using Grounded Theory methods. Data analysis revealed three categories: ‘imposed powerlessness’, ‘adaptive functionality’ and ‘endurance’. The impact of participant’s amputations were influenced by continuing limb problems post-amputation and co-existing complications affecting their physical function. Medical errors and lack of awareness of the risks for diabetic amputations resulted in uncertainty and fear. The participants’ sense of grief, loss and shock post operatively continued later as they came to terms with their awkwardness of movement, yet they moved forward developing their own sense of hope through a coping process that revealed remarkable ability to endure and exert control over lives that seemed to be at the whim of an ongoing disease process. The substantive theory resulting from this grounded theory study was conceptualised as ‘A Path of Perpetual Resilience’. It is important that psychosocial and not just physical adjustment is considered an indicator for determining outcomes for these people, and that future care involves strategies to promote this. A greater sample size is required to determine if these findings are transferable to the general diabetes-related amputation population.
Mannosylated Lipoarabinomannans Inhibit IL-12 Production by Human Dendritic Cells: Evidence for a Negative Signal Delivered Through the Mannose Receptor1

IL-12 is a key cytokine in directing the development of type 1 Th cells, which are critical to eradicate intracellular pathogens such as Mycobacterium tuberculosis. Here, we report that mannose-capped lipoarabinomannans (ManLAMs) from Mycobacterium bovis bacillus Calmette-Guérin and Mycobacterium tuberculosis inhibited, in a dose-dependant manner, the LPS-induced IL-12 production by human dendritic cells. The inhibitory activity was abolished by the loss of the mannose caps or the GPI acyl residues. Mannan, which is a ligand for the mannose receptor (MR) as well as an mAb specific for the MR, also inhibited the LPS-induced IL-12 production by dendritic cells. Our results indicate that ManLAMs may act as virulence factors that contribute to the persistence of M. bovis bacillus Calmette-Guérin and M. tuberculosis within phagocytic cells by suppressing IL-12 responses. Our data also suggest that engagement of the MR by ManLAMs delivers a negative signal that interferes with the LPS-induced positive signals delivered by the Toll-like receptors.